ASSOCIATION OF AVIAN VETERINARIANS

EUROPEAN COLLEGE OF ZOOLOGICAL MEDICINE

MADRID, SPAIN. 26-30 of APRIL, 2011

Association of Avian Veterinarians European committee (EAAV) www.eaav.org and www.aav.org

European Collage of Zoological Medicine (ECZM)

www.eczm.org

11th European AAV conference 1st Scientific ECZM Meeting

Madrid, 26th – 30th April 2011

EAAV Conference Chairman Andres Montesinos, LV, Madrid, Spain

EAAV Scientific Committee Chairman Jaime Samour, MVZ, phD, Dipl ECZM (Avian), Abu-Dhabi, UAE

ECZM Scientific Committee Chairman Brian Speer, DVM, Dial ABVP (Avian), Dipl ECZM (Avian), Oakland, USA

Proceedings Editor in Chief

Jaime SAMOUR, MVZ, phD, Dipl ECZM (Avian), Abu-Dhabi, UAE

http://www.eaav.org/http://www.aav.org/http://www.eczm.org/

EAAV 2011 Conference Committees

EAAV Board Andres MONTESINOS (Spain), Conference Chairman

Peter COUTTEEL (Belgium), EAAV president Peter SANDMEIER (Switzerland), EAAV past president

John CHITTY (United Kingdom), Secretary Helene PENDL (Switzerland), Treasurer

Maria ARDIACA (Spain), EAAV Web Master Brian SPEER (USA), ECZM Delegate

Michael LIERZ (Germany), Conference Chairman EAAV Conference 2013

Scientific Committee Jaime SAMOUR (UAE), Chairman Scientific Committee

John CHITTY (United Kingdom), Vice chairman Scientific Committee Michael LIERZ (Germany), Vice chairman Scientific Committee

Lorenzo CROSTA (Italy) Michael P JONES (USA)

Tom BAILEY (UAE) Michael PEES (Germany)

Deborah MONKS (Australia) Paolo ZUCCA (Italy)

Susan OROSZ (USA) Petra ZSIVANOVITS (Germany)

Brian SPEER (USA)

Proceedings Editors Jaime SAMOUR (UAE), (Editor in chief)

Andres MONTESINOS (Spain)

Local Organizing Committee Andres MONTESINOS, Conference Chairman

María ARDIACA, Conference Co-Chairman & EAAV 2011 Web Master Fernando GONZALEZ, Practical Labs Coordinator

Elena RODRIGUEZ, Social Programme Coordinator Verena VALENZUELA

Irene LOPEZ Marcia VIANA

Cristina BONVEHÍ Sara BARRERA

Miriam RODRIGUEZ Pilar TAVARES

Virginia MORALEDA

Coordinators of Helga Gerlach Award and Student Grant Helene PENDL (Switzerland)

Jaime SAMOUR (UAE)

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Disclaimer The material appearing in this publication comes exclusively from the authors and contributors identified in each manuscript. The techniques and procedures discussed reflect the personal knowledge and experience of the authors and contributors, and demonstrate their views of the methods that may be used for these medical procedures. The procedures demonstrated do not incorporate all known techniques, are not exclusive, and other techniques and technology are also available. Any questions or request for additional information concerning any of the manuscript should be addressed directly to the authors. The European Association of Avian veterinarians (EAAV) does not research, review, or otherwise verified any of the information contained in this publication. Opinions expressed in this publication are those of the authors and contributors and not necessarily those of EAAV. EAAV is not responsible for errors or for opinions expressed in this publication. EAAV expressly disclaim any warranties or guarantees, expressed or implied, and shall not be liable for damages of any kind in connection with the material, information, techniques, or procedures set forth this publication. All right are reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, or otherwise, without the prior written permission of the author. To order copies of this publication contact Andres Montesinos, Centro Veterinario Los Sauces, Madrid, Spain (cvsauces@cvsauces.com)

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mailto:cvsauces@cvsauces.com

WELCOME TO 11TH EAAV and 1st ECZM Conference There is a first for everything In 1995 the first joint conference between the ECAMS and the EAAV was held. After that date, 7 more successful conferences followed throughout Europe. Since our last conference in Antwerp, much has changed with regard to specialization in zoological medicine in Europe. In 2007, the ECAMS took an initiative to strengthen the College by providing the opportunity for those working at a Specialist level within allied zoological fields to gain recognition within veterinary academia, by governments and by the public. As a result, ECAMS changed to the ECZM (European College of Zoological Medicine). In addition to the fully recognized specialist area Avian Medicine, the following new specialist areas were provisionally recognized in 2009 by the EBVS: Small Mammal Medicine, Herpetological Medicine and Wildlife Population Health. The term Zoological Medicine was chosen for the title of this College based on a publication in the Journal of the American Veterinary Medical Association (2001;219:1532-1535) which recommends the following definition: “Zoological Medicine integrates veterinary medicine and the principles of ecology and conservation as applied in both natural and artificial environments.” Since the recognition of the ECZM veterinarians have been de facto recognized as diplomates in Small Mammal Medicine (n=10), in Herpetological Medicine (n=13) and in Wildlife Population Health (n=22). The period for de facto recognition will last until April 2014 and every veterinarian who thinks he/she qualifies for recognition can apply through the website of the ECZM (www.eczm.eu). In the mean time, training programs have been developed in Small Mammal and Herpetological Medicine, and 3 residents are currently being trained in one of these specialties. The specialists in Wildlife Population Health are working on setting up a residency program as well. This scientific meeting will be the first organized by the ECZM. It will also be the first in which two concurrent programs will be provided. I hope that you agree with me that a step forward is made to advance the field of zoological medicine and that this conference will contribute to that. Any feedback on the current developments and this conference are highly appreciated. I wish everyone a great conference among old and new friends. Nico J. Schoemaker, DVM, PhD Dip ECZM (small mammal & avian); Dipl. ABVP-certified in avian practice President ECZM

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http://www.eczm.eu/

Welcome address Dear colleagues, As chairman of the European Committee of the Association of Avian Veterinarians (EAAV) I like to welcome all colleagues from throughout Europe and around the world to join this very promising conference. It is already the 11th conference organized by the EAAV and this time it will be the first joint meeting with the European College of Zoological Medicine (EZCM). Last conference in Belgium, two years ago, the board of EAAV has decided to create a legal structure by establishing a Non Profit Organisation with his own bylaws. The purpose of the association is to support scientific research, teaching and education in aviary, zoo, and wild birds medicine and related fields. The activities of this new organisation are guided by the objectives of the U.S. American association called “Association of Avian Veterinarians“, from which the association developed and to which it feels a strong commitment. Today this NPO is a fact and the seat is settled in Switzerland since December 10th 2010. I like to thank both the organizing and the scientific committee for the enormous work they have done during months to let us be part of this conference. It will be a unique opportunity to update your clinical and scientific knowledge and of course it will be the place to meet avian practitioners from all over the world. I hope you will take advantage of this big opportunity to enjoy, not only the gathering of knowledge, but also the great hospitality of Spain and I am really looking forward to see you all again in Giessen, Germany in 2013. Peter Coutteel, Chairman of the European Committee of the Association of Avian Veterinarians.

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TABLE OF CONTENTS SECTION 1: SCIENTIFIC MEETING OF THE EUROPEAN COLLEGE OF ZOOLOGICAL MEDICINE SECTION 1.1 : AVIAN MEDICINE

Form and function of the Avian Endocrine System 14

Disease of the Avian Endocrine System 24

Diagnoses and Treatment of Avian Endocrine Disease 41

Comparison of quantitative image analysis, quantitative chemical analysis and magnetic resonance imaging for monitoring liver iron content in hornbills 56

Repair techniques in case of intertarsal joint luxation: two case reports 58

Electrocardiographic changes in a galah (Eolophus roseicapilli) with lead poisoning 59

Management of extensive skin wounds in two raptors using vacuum assisted wound closure 61

ABV and PDD: A controled experimental approach 63

Radiographic evaluation of cardiac size in birds 65

The effects of adrenergic agonists as a treatment for isoflurane-induced hypotension in Hispaniolan amazon parrots (Amazona ventralis) 67

SECTION 1.2: REPTILE MEDICINE

Alfaxalan anesthesia in green iguanas (Iguana iguana) 68

Some cases of confirmed and suspected ranavirus infection in amphibians and reptiles 70

Comparative radiography of the respiratory tract of snakes using conventional mammography and a digital detector system 73 SECTION 1.3: WILDLIFE POPULATION HEALTH

Disease risk analysis for avian reintroduction programmes 74

Increase of Cathaemasia hians (Rud, 1809) (Trematoda: cathaemasiidae) in black stork nestlings (Ciconia nigra) from Central Spain 78

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Role of mycoplasmas in free-ranging white stork (Ciconia ciconia) and nightengale (Luscinia megarhynchos) populations 80

Emergence and impact of trichomonosis on british finch populations and subsequent spread to continental Europe. 83

SECTION 1.4: SMALL MAMMALS MEDICINE

Aetiology of dental disease in degus: improper wear, or metabolic bone disease? 85

Cushing’s syndrome in guinea pigs 87

Novel coryneform bacterium involved in pet rat (Rattus norvegicus) abscesses 89

Update on E. cuniculi diagnostics in rabbits 91

Blood glucose measurement in pet rabbits 93

SECTION 2: SCIENTIFIC MEETING OF THE EAAV SECTION 2.1: ANESTHESIA AND SURGERY Intranasal midazolam causes conscious sedation in hispaniolan amazon parrots (Amazona ventralis) 95

Use of polypropylene shuttle pins for the repair of various fractures in birds of prey 97

Endoscopic partial pericardectomy for resolution of pericardial effusion in a jenday conure 103

Surgical technique to correct alula malposition in falcons 105

Return to flight after a radical resection of the propatagium in the great-horned owl (Bubo virginianus) 108

SECTION 2.2: THERAPEUTICS AND GENERAL MEDICINE 1

Medical treatment of avipoxvirus infections in birds of prey 111

Deslorelin acetate long term suppression of ovarian carcinoma in a cockatiel (Nymphicus hollandicus)

114

The use of sertraline hydrochloride to prevent feather destructive behavior in two peregrine falcons (Falco peregrinus) 121

Comparison of analgesic efficacy of preoperative administration of tramadol and butorphanol in Columba livia 125

Use of a butorphanol constant rate infusion in cockatoos 127

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SECTION 2.3: THERAPEUTICS AND GENERAL MEDICINE 2 Pharmacokinetics of parenteral and oral meloxicam in African grey parrots (Psittacus erithacus erithacus) 129

Pharmacokinetics of cefovecin in grey parrots (Psittacus erithacus) and red kites (Milvus milvus) after intramuscular administration of Convenia™ 135

Reference values of serum insulin and plasma fructosamine in African grey parrots (Psittacus erithacus erithacus) 140

Thyroid endocrinal activity evaluation in yellow legged gull (Larus michahellis) 144

Radiation therapy of uropygial gland carcinoma in psittacines 147

Dental posts used in the correction of mandibular prognathism 149

SECTION 2.4: INFECTIOUS DISEASES 1

Avian simuliotoxicosis in Southern Louisiana, USA 155

Comparative examination of atoxoplasmosis and other systemic coccidioses in pet, zoo and wild birds 157

Malassezia-like infection in passerines with feather loss and hyperkeratosis: 10 cases 159

Unusual ophthalmitis and encephalitis due to Tenotrophomonas maltophilia in passerines 162

Cryptosporidial proliferative cloacitis and bursitis in a eurasian eagle-owl (Bubo bubo) with systemic bacterial infection 168

Salmonella typhimurium infection as a cause of mortality and morbidity in captive bred falcon chicks in the UK 171

SECTION 2.5: INFECTIOUS DISEASES 2 A new realtime-pcr for the detection of Mycobacterium avium ssp. avium and M. avium ssp. Silvaticum 175

Anti-ganglioside specific auto-antibodies in ganglia of PDD affected parrots 177

Level of antigangliosides antibodies, histology and clinical aspects during PDD 179

Molecular epidemiology, virulence and climate impact assessment in aspergillosis of white stork chicks 181

Development of various diagnostic tests for avian bornavirus in psittacine birds 185

Comparison of anti-ganglioside antibodies and anti-abv antibodies in psittacines 187

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SECTION 2.6: CLINICAL IMAGING AND OPHTALMOLOGY

Application of 3d ultrasonography in clinical avian ophthalmology 190

Ohthalmological findings in birds affected with PDD 193

Ocular ultrasonography in wild raptors 194

Gonioscopy in birds 195

Magnetic resonance imaging findings in four cases of neurologic disease in psittacine birds 196

Radiographic evaluation of demineralized bone matrix in the repair of avian osseous defects 200

SECTION 2.7: STUDENT SESSION 1 Characterization and classification of psittacine atherosclerotic lesions by histopathology, digital image analysis, and electron microscopy 203

Experimental trial of avian interferon gamma in chickens challenged with H7N1, in healthy falcons and in clinical cases with suspected viral aetiology 205

Evaluation of a novel vaccine against budgerigar fledgling disease polyomavirus (BFDyV) 207

Pharyngostomy tube as a method of nutritional management in raptors: case series 209

Pathogenesis of avian bornavirus (abv) in experimentally infected cockatiels (Nymphicus hollandicus) 211

SECTION 2.8: STUDENT SESSION 2 Radiographic assessment of spleen size in african grey parrots (Psittacus erithacus erIthacus) 214

Ejaculate characteristics and semen quality of falcons with special emphasis on fertility rate after artificial insemination 216

SECTION 2.9: GENERAL MEDICINE

Semen collection and artificial insemination in large psittacine species 219

Avian herpes viruses: an update and literature review 221

The situation of ABV in endangered psittacines like the Spix’s macaw 228

Monitoring of exposure to contaminants in the griffon vulture (Gyps fulvus) using dried blood spots in the Dabse project 230

Stress lines – gaps in our feather knowledge 232

Challenges facing an Indonesian bird market 238

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A case of congenital atrial communication and dilated cardiomyopathy on a griffon vulture (Gyps fulvus) 244

Sedation as an alternative to general anaesthesia in birds 250

SECTION 2.10: BEHAVIOUR

Social influence in birds: avian welfare is a matter of group 255

Practical application of behavioural science in daily practice settings 257

The importance of the early life of psittacines (or which pet parrot do we want?) 263

SECTION 2.11: MASTER CLASSES

Passerines bird medicine 270

Artificial incubation 285

Iron storage disease 289

Renal disease in psittacine birds 303

The avian cardiovascular system: anatomy and physiology for the clinician 319

Avian neuroanatomy and neurology 328

Practical aspects of avian immunology 340

Avian rehabilitation and flight reconditioning 349

Optimization of fluid therapy and critical care 361

Newest imaging techniques in avian medicine 373

SECTION 2.12: POSTER PRESENTATIONS Histological evaluation on osteogenesis of tubular and chipped avian demineralized bone matrix in pigeons 384

Transesophageal echocardiography in the normal bird 386

Medical treatment of wild birds in Germany: a statistical overview over a two-year-period 388

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Clinical neuroanatomy of the wing of the hispaniolan amazon parrot (Amazona ventralis) 389

Presence of Neospora caninum dna in brain tissue of wild birds from Spain 392

Combination of fentanyl and lidocaine for brachial plexus block in a peregrine falcon 394

Motivation of avian medicine personnel in wildlife rehabilitation centers in Spain: creating the conditions for happy and productive staff 397

Surgical debridment of adherencesand physiothera py in a specimen of white stork(Ciconia ciconia) 399

Congenital glandular atrophy of the proventriculus in Cacatua leadbeateri 402

Preliminary results on the use of a neopterin elisa in red-legged partridges (Alectoris rufa) 404

Cryptosporidiosis – a new fatal disease in falcons in Dubai 406

Investigation of cestode parasitism (Flamingolepis spp.) in brine shrimp (Artemia salina) in DubaI 409

Lymphoid leukosis in Houbara bustard in UAE 412

Effect of alfaxalone in raptors: pilot study in common kestrels (Falco tinnunculus) 415

I llegal capture of finches (fam. Fringillidae) in Catalonia (Spain): a 14 year experience 417

Prevalence of toxoplasma gondii antibodies in wild birds from Spain 419

Natural infection of H5N1 avian influenza in pet birds 421

Reovirus infection in an american crow (Corvus brachyrhynchos) 425

Serosurvey of Chlamydophila psittaci in brazilian wild birds 428

Plasma protein el ectrophoresis in clinically healthy falcons usinghigh resolution agarose gel electrophoresis 431

Herpesvirus in a trumpeter hornbill (Bycanistes bucinator) 433

Cloacal and pharyngeal bacterial flora in wild birds 435

Blood parameters and haemoparasites ocurrence in birds of prey in a rehabilitation center in Spain 437

Effects of formalin fixation on avian eye 440

Comparative tissues distribution of pcbs and metals in peregrine falcons and chamois in the Dolomiti Friulane Park, North East Italy 443

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SECTION 2.13: PRACTICAL LABS

Avian soft tissue surgery 446

Parrot behaviour, handling parrots, dealing with behaviour problems 452

Raptor medicine and management 462

Avian necropsy technique and sampling with interactive gross pathology seminar of common clinical presentations/gross lesions 476

Ultrasonographic examination in birds 487

Avian emergency and critical care procedures 495

Endoscopy 504

Traumatology: management of fractures, pain, and associated trauma in raptors 506

Clinical chemistries in birds 520

Basic techniques in avian medicine 527

Surgical procedures of the psittacine skull 537

Avian and reptilian haematology 550

Avian ophthalmology 565

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SECTION 1

SCIENTIFIC MEETING OF THE EUROPEAN COLLEGE OF ZOOLOGICAL MEDICINE

Moderator: B.SPEER, DVM,

Dip ECZM (Avian); Dipl. ABVP-certified in avian practice

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ANATOMY AND PHYSIOLOGY OF THE PROTEIN HORMONES AND THE GLANDS THAT PRODUCE THEM

S. E. Orosz, PhD, DVM, Dipl ABVP (Avian), Dipl ECZM (Avian)

Bird and Exotic Pet Wellness Center Toledo, Ohio, United States

Master Class Manuscript

KEYWORDS Birds – Endocrine system– Insulin – Protein hormones – Pancreas – Adrenal gland – Thyroid – Ultimobranchial glands – Pineal gland ABSTRACT Avian endocrine organs include the hypothalamo-pituitary complex, gonads, pancreatic islets, adrenal glands, thyroid glands, ultimobranchial glands, and the endocrine glands of the GI tract. Hormones are also produced in the pineal gland (melatonin), liver (insulin-like growth factor I) and the kidney (renin, 1, 25-dihydroxyvitamind D3, erythropoietin). The anatomy and physiology of protein hormones are emphasized is this presentation, with special consideration to how these hormones regulate vital physiologic processes such as glomerular filtration, metabolism, development, reproduction, calcium regulation, oviposition, nutrient regulation, protein synthesis, and circadian rhythms. 1 INTRODUCTION Birds have a similar group of endocrine organs as in mammals—the hypothalamo-pituitary complex, gonads, pancreatic islets, adrenal glands, thyroid glands, ultimobranchial glands that produce calcitonin, and the endocrine glands of the GI tract. These endocrine glands are ductless glands that release their hormone product into the blood vascular space to be transported to another location to act on specific target tissues, cells or organs. Each hormone interacts with receptors on the surface of the cells (protein and polypeptides) or within the cytoplasm and nucleus (steroids, thyroid hormones). Hormones are also produced in glands other than those classical endocrine glands: pineal (melatonin), liver (insulin-like growth factor I) and the kidney (renin, 1, 25-dihydroxyvitamind D3, erythropoietin). This manuscript and discussion concentrate on the protein hormones and the glands that produce them. 2 ANATOMY OF THE HYPOTHALAMIC-HYPOPHYSEAL COMPLEX The hypothalamus connects with the pituitary which is divided into the adenohyphophysis and the neurohypophysis. The adenohypophysis is derived from Rathke’s pouch which is ectodermal in origin from the roof of the mouth. The neurohypophysis originates from the infundibulum of the brain, also of ectodermal origin. In birds, there is no pars intermedia, so there is only an anterior

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pituitary or adenohypophysis, or pars distalis. The neurohypophysis forms the pars nervosa which in birds is called the posterior pituitary gland. The avian pars distalis produces the gonadotrophins:LH/ FHS; lactotrophin, prolactin; and the corticotrophin ACTH in the cephalic or cranial lobe. The caudal portion of the pars distalis produces the gonadotrophins LH/FSH and the somatotrophin : growth hormone. Like in mammals, there is a hypophyseal portal system that transports releasing factors from the median eminence. The posterior pituitary consists of neurosecretory terminals that release either mesotocin or arginine vasotocin. These protein hormones are synthesized in separate cell bodies of nuclei in the hypothalamus and are transported via specialized axons to the posterior pituitary. They are transported bound to carrier proteins or neurophysins by axoplasmic transport to the pars nervosa or the neurohypophysis. The avian equivalent to the antidiuretic hormone is arginine vasotocin or AVT and the one that has an oxytocic function is mesotocin. Each differs from their mammalian counter part by one amino acid sequence. Arginine vasotocin when administered to hydrated chickens using a hypotonic glucose solution, depresses urine flow while increasing osmolality (AMES et al. 1971). At low doses, AVT effects tubular reabsorption as it reduced clearance of water. At higher levels it reduces glomerular filtration, GFR. In desert quail, AVT reduces GFR by decreasing filtration of both the reptilian type and the mammalian type nephrons. It is unclear what role it plays in blood pressure changes as it has shown to increase and decrease blood pressure and heart rate (SCANES 2000). Oviposition is also controlled by AVT not oxytocin or mesotocin. It may provoke premature oviposition by the local production of prostaglandins which in turn causes uterine contraction (RZASA 1978, 1984). Normally, during the time of oviposition, there are increased circulating levels of AVT. The pars nervosa may contribute the majority of the AVT but ovarian AVT may also play a role in oviposition. During oviposition, the uterine musculature has an increased sensitivity to AVT. The role of mestocin is not well established in birds. 3 THYROID GLANDS The avian thyroid glands are paired oval glands located ventrolateral to the trachea caudal to the junction of the subclavian and the common carotid arteries. The architecture is like that of mammals with the spherically arranged follicles. The follicles are lined by an epithelium that secretes thyroglobulin, the storage form of thyroid hormone. This extracellular storage of a hormone is unique when compared to other endocrine glands and is thought to be due to the scarcity of iodine (McNABB 1992). The thyroid glands are well vascularized by the thyroid arteries, branches off of the carotids. Venous drainage is via veins that drain into the jugular veins. Calcitonin secreting cells, which are parafollicular cells in mammals, are not observed in avian species. Birds have separate glands, the ultimobranchial glands which contain calcitonin secreting cells. Thyroid growth is proportional to body growth in galliforms both embryologically and post hatch however altricial birds may be different. As in mammals, birds have thyroxine or T4 along with triiodothyronine or T3. It appears that the mechanism for hormone synthesis and release by the glands is similar to that of mammals. Endocytosis of droplets of colloid by the follicular cells with the subsequent digestion of thyroglobulin by lysosomal enzymes causes the release of T3 and T4 into the surrounding capillaries. Thyroid secretion rates, TSR, range for m 1-3 ug T4/100 g BW per day in chickens, quail and pigeons (WENTWORTH and RINGER 1986). Cold temperatures increase TSR where as iodine deficiency and aging tend to decrease it. Circulating levels of thyroid hormones are often determined by radioimmunoassay as studies suggest that this technique is the most accurate currently. Concentrations of T4 exceed those of T3 several fold. Adult birds of many species had plasma or serum T4 concentrations in the range of 5-15 ng T4/ml (6-19 pmol/ml) and T3 levels in the range of 0.5-4 ng/ml(0.7 –1.5 pmol/ml). In

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comparison to mammals, birds, in general, contain less T4 but similar levels of T3. Factors that influence thyroid function include dietary iodine availability, food availability, food composition, seasonality, age, time of day for the blood collection. To have confidence in interspecies comparisons and classifications of hypo function, plasma samples need to be compared in the same lab with the same validated RIA for each species. There are diurnal patterns of plasma thyroid hormone concentrations. Plasma T4 concentrations rise and peak during the dark hours and T3 levels rise and are highest during the light period. Extrathyroidal conversion of T4 to T3 is highest during the light period. Cold temperatures increase T3 concentrations while warm temperatures depress T3 within the diurnal pattern. In terms of potency of T4 vs T3, early studies suggested that they are equipotent but more recent studies of receptors indicate that these thyroid receptors are T3 receptors. The apparent T4 effects are due to deiodination to T3 and T3 is responsible for most the thyroid action in birds. The apparent greater potency of T4 that triggers some physiologic actions is unknown. Birds appear to possess identical deiodination pathways as in mammals. This also suggests that T3 production is mostly extra thyroidal in birds as well as mammals. T3 levels measured in blood reflect the production and deiodination of T4 in the peripheral tissues of the avian patient. It is interesting to note that deiodination enzymes may be important to understand from a clinical perspective. Apparently the brain is dependent on adequate levels of T3. Type II 5 D activity, a deiodination enzyme, plays an important role in protecting the T3 supply to the CNS when plasma levels of thyroid concentrations are low (RUDDAS et al. 1994, 1993). The avian thyroid gland is under the control of the hypothalamic-pituitary-thyroid (HPT) axis. The avian hypothalamus produces 2 hormones, thyrotropin releasing hormone (TRH) and somatostatin. The former is stimulatory and the latter is inhibitory to thyroid stimulating hormone release in the anterior or cranial adenohypophysis. Thyroid stimulating hormone (TSH) or thyrotropin is the major controller of production and release of thyroid hormones of the thyroid gland. Negative feedback to the hypothalamus and pituitary is exerted by the levels of circulating thyroid hormones. TRH, a tripeptide, appears to have an identical structure in mammals when compared to birds so can be used in stimulation studies. TSH is a glycoprotein. Its beta chain differs from that in mammals when compared to birds but heterologous TSHs stimulate thyroid function in birds. Thyroid hormones exert their actions through nuclear receptors that are members of the steroid superfamily (LAZAR 1993 ) They have one of 2 basic effects – metabolic or developmental. From a metabolic perspective, thyroid hormones are key controllers of heat production, necessary for maintaining body temperature. Administration of exogenous thyroid hormones causes an increase in oxygen production. Altered thyroid hormone concentrations influence metabolic energy supply. Storage of glycogen in the liver is facilitated by increases in thyroid hormone levels. Glycogen is depleted and plasma glucose decreases with decreases in hormones. Thyroid hormones influence growth apparently indirectly (MCNABB and KING 1993). Body growth stimulation appears to result from growth factors including insulin like growth factor-1 IGF1 that is under the control of growth hormone (GH). Thyroid hormones appear to be important for triggering tissue specific differentiation and maturation. Thyroid hormones induce molt in birds and inhibition of reproductive activity as high concentrations have antigonadal effects. Estrogen decreases appear to initiate molt whereas an increase in the thyroid hormone/estrogen ratio appears to be important for feather formation (DECUYPERE et al. 1986). 4 PARATHYROIDS Since birds need to mobilize calcium at a rate much faster than mammals, those hormones that regulate calcium include parathyroid hormone (PTH), calcitonin (CT), and 1,25 dihydroxy vitamin D3 (1,25-(OH)2 D3) along with prostaglandin (PGs) (DACKE 1979) and calcitonin gene-related

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peptide (CGRP). These later 2 hormones affect avian Ca metabolism differently from mammals. This may be due in part to the laying of a shelled egg, which uses about 10% of the total body store of Ca (KENNY 1986). Egg laying hens possess a labile pool of calcium in medullary bone that is uniquely avian. This bone develops in the long bones as a response to gonadal steroids. It is influenced by the need to have a skeleton that can respond to egg laying and allow a skeleton that is rigid enough for flight. Ca metabolism is much faster in birds than in mammals. Calcium uptake in the chick femur is less than 10 minutes while that of dogs, rabbits and rats are approximately 30 minutes (SHAW 1989). The parathyroid glands vary between 2 and 4 depending on the species. They often sit caudal to the thyroid glands in birds and encapsulated in connective tissue. The gland consists primarily of chief cells and does not contain oxyphil cells as in mammals. The low granular content of the organelles is consistent with the low levels of PTH that are secreted. PTH is an 88 amino acid polypeptide in the chicken and 84 in mammals. The first 34 sequences are similar between mammals and birds. Studies are extremely limited regarding circulating PTH levels in birds as normally the concentrations are thought to be lower and pure avian PTH has not been available for study. Bioassay studies show that the levels increase during egg shell calcification and there is a secondary but a lower spike with oviposition. Levels of PTH were inversely related to plasma ionized Ca levels. PTH injections in Japanese quail caused Ca levels in the plasma to increase. The primary targets for PTH in birds are bone and kidneys. The major stimulus for PTH release from the chief cells is a fall in Ca while a rise in Ca will suppress its release. Since birds respond to PTH in less than 8 minutes, it seems unlikely that osteoclastic activity causes the response. Instead, it has been shown to be from the inhibition of Ca clearance from the plasma. In addition, there is an inhibition of Ca into the skeleton as well. There are PTH receptors on the osteoblastic surfaces but may be absent in osteoclasts. The osteoclasts, if they have PTH receptors and blasts may alter their size and shape and migrate to and from areas with high or low Ca binding sites in order to regulate quick changes in plasma calcium levels. It appears that there is a proton pumping of Ca and the mechanism involves adenylate cyclase activity. Estradiol appears to block this enzyme activity in micromolar but not nanomolar levels. In the kidney, PTH causes increases in glomerular filtration, urine flow and clearance of Ca and P. 5 CALCITONIN IN THE ULTIMOBRANCHIAL GLANDS Birds have anatomically distinct asymmetrically paired ultimobranchial glands that sit caudal to the parathyroid glands. In chickens, they are caudodorsal to the base of the brachiocephalic artery and at the bifurcation of the common carotids and the subclavian arteries. The cells that secrete calcitonin or CT are C cells. These cells are derived from the 6th branchial pouch but the cells that invade the pouch are ultimately of neural crest origin. CT is a polypeptide hormone of 32 amino acids and has a 7 membered N terminal ring. The entire chain is required for biologic activity. Most often, CT levels are determined by bioassay as it is a protein hormone. The role of CT in bone and Ca metabolism is not well understood. In mammals, CT has been shown to regulate plasma levels of Ca by its hypocalcemic action inhibiting osteoclastic bone resorption. CT is secreted primarily by rising plasma Ca levels. However, in submammalian species including birds, plasma Ca levels are refractory to dosing with CT. High circulating CT concentrations are present in submammalian species including birds. Studies do not show a clear link to Ca metabolism but they do suggest that CT receptors are down regulated under normal physiological conditions and this may be the reason that this direct link has not been determined. When long-term hypocalcemic chicks are injected with CT, Ca levels do rise abruptly thereby suggesting that under normal conditions receptors are down regulated. In these studies, it is interesting to note that when CT of salmon origin was used, as bone formation proceeded, there

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was a proportional increase in alkaline phosphatase activity in the bones in culture (FARLEY et al.1988). Studies across species lines determining the location of renal binding sites for CT showed that there were none in fish, amphibians and reptiles. There were binding sites in the renal cortex and the medulla in rats, quail and chickens (BOUIZAR et al. 1989). Binding site patterns suggested CT receptors were associated with the glomeruli and the collecting tubules. These data suggest that CT receptors appear late in evolutionary development and regulation of renal function by CT is effective in only mammals and birds. In egg laying quail hens, the levels are highest immediately after ovulation and fall as egg shell calcification proceeds. Levels rise near the end of calcification. Steroid hormones, and in particular androgens, appear to have the most influence on circulating CT levels. The levels of CT are influenced by the amount of Ca consumed. In chickens where the Ca levels are high, there is a corresponding high level of circulating CT as well. 6 THE VITAMIN D SYSTEM It was in 1931 that Hou reported that the removal of the preen gland from chicks resulted in rickets even when they were fed a normal diet and exposed to sunlight. He concluded that the preen gland produced a proVitamin D3 and that sunlight converted it to an active form. Much of the knowledge on vitamin D metabolism has been centered over the intervening years using the chicken as the model. From this original work, it has been learned that sunlight after converting the inactive form of D3 is ingested when the bird preens. Vitamin D3 is metabolized to 25-(OH)-D3 in the liver and then to 1,25-(OH)-D3 in the kidneys. There are a number of factors that stimulate the conversion to the active form in the kidneys and these include: PTH, prolactin and 1,25-(OH)-D3 itself (HENRY and NORMAN 1984). There are contradictory reports regarding the role of CT but it most likely does not stimulate its production. Birds are unable to use vitamin D2 which is the major form used in dog and cat foods. Birds are able to discriminate between D2 and D3 because the plasma vitamin D binding protein has a relatively low affinity for D2 and so it is more rapidly broken down. There appears to be a cycle for the conversion of 25 Vitamin D3 to 1,25 during the egg shell calcification cycle in the hen. This was also described by Nys et al (1986) as hens that laid shell less eggs did not show the cyclical fluctuations in 1,25-(OH)- vitamin D3 levels. Circulating levels of 1,25-(OH)-vitamin D3 increase in the prelaying period and again at the onset of egg production to prime Ca for the rapid drain in shell formation. Intestinal absorption of Ca is regulated by 1,25-(OH)-vitamin D3 by inducing RNA transcription and synthesis of proteins that promote the absorption of Ca. These proteins include 3 forms of calbindin D 28k. In vitamin D deficient chicks, intestinal calbindin mRNA is barely detectable but increases dramatically with the addition of 1,25-(OH)-vitamin D3 injection. With the onset of ovulation, there is an increase in intestinal Ca absorption. There is a calbindin in the uterus of the hen as well that is under control of 1,25-(OH)-vitamin D3. The uterus or shell gland contains receptors for 1,25-(OH)- vitamin D3. Calbindin and its mRNA concentrations increase in immature pullets that are treated with estrogen. Interestingly, those hens that lay shell-less eggs have even higher levels of calbindin. It is thought that the sex steroids have an indirect effect on the oviduct as they affect its maturation and development not the levels of Ca directly.

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Hens that are fed a vitamin D deficient diet that are laying causes the resorption of medullary bone. This has also been observed clinically in seed only fed cockatiel hens from a clinical perspective. Those nonlaying hens that are fed a vitamin D deficient diet cause osteodystrophy. Bone formation is facilitated but 1,25-(OH)- vitamin D3 stimulating the biosynthesis of osteocalcin. It appears to bind Ca and has an affinity for hydroxyapatite, suggesting that it has a mineral dynamics function. It is released into the systemic circulation and may be markers for new bone formation as an index for bone turnover not bone resorption. About 30-40% of the calcium in the egg shell is derived from medullary bone. But medullary bone is induced by sex steroids and not by vitamin D levels. However, in order for the bone to be fully mineralized, both vitamin D and the sex steroids need to be present at normal levels. Cultures of medullary bone cells responded to increasing levels of 1,25-(OH)-vitamin D3. Renal functions of Ca metabolism are unaltered by a deficiency of vitamin D after Ca loading or PTH administration. When they are deficient in vitamin D, they do no increase P excretion in response to PTH stimulus (CLARK 1991). 7 PROSTAGLANDINS WITH CA METABOLISM The effects of prostaglandins is similar to those of PTH in birds as they stimulate cAMP production, cause a transient increase in Ca influx, activate carbonic anhydrase, release lysosomal enzymes and in inhibit collagen synthesis.They affect osteoclasts and osteoblasts. For example, 16,16 dimethyl PGE2 is hypercalcemic in chicks. PGE2 and other eicosanoids have a similar function and efficacy to PTH ans 1,25-(OH)- vitamin D3 as powerful stimulators of bone resorption (DACKE1989). Medullary bone of the bird is the most estrogen sensitive of all vertebrate bone types. It can form in male birds that are dosed with estrogens within a matter of days. It can be blocked from forming in these males with the addition of tamoxifen which is antiestrogenic (WILLIAMS et al. 1991). When estrogen is withdrawn, medullary bone rapidly resorbs as can be observed clinically with depo lupron. 8 PANCREATIC HORMONES The liver and pancreas play a major role in the distribution and utilization of nutrients that are absorbed from the gastrointestinal tract. Both organs are strategically placed for glucoregulation. It is interesting to note that it is glucose that is tightly regulated by the body in both mammals and birds, not protein or lipid metabolism. Several factors are involved that allow glucose to trump proteins and lipids. Glucose is the easiest substrate for cells to utilize to release energy. It can be synthesized from noncarbohydrate sources. Some tissues, including the cells of the retina and adrenal medullary and neurons, require glucose as their only substrate to maintain normal function. Effective homeostatic regulation of glucose metabolism therefore adjusts protein and lipid metabolism to normalcy. The avian liver, like that of mammals, play a central role in the regulation of carbohydrate metabolism. Nutrients from the gut ascend to the liver where they can be metabolized before moving through the caudal vena cava to be distributed systematically. The nutrients are transported by the portal veins to the hepatocytes. From there, the nutrients or their metabolites move through the hepatic veins to the vena cava, and then to the right heart. The histologic architecture of the liver in birds is similar to that of mammals. It does, however, receive blood from the renal portal system directly from the portal veins. This bypass of the caudal vena cava acts to dilute the nutrient-rich perfusate from the gut before entering the liver.

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The liver of birds appears to have similar enzyme systems for metabolism of nutrients. Unlike the case in mammals, most triglycerides are synthesized in the avian liver. High levels of glucose in the blood stream of birds trigger the release of insulin from the B cells of the pancreas. Insulin aids the enzymatic machinery of the liver to carry out the anabolic processes in the liver carry out anabolic processes in the liver and in muscle and adipose tissue to reduce the glucose load and maintain it in its narrow functional range. During periods of fasting, nutrients must be retrieved from deposits in the body. During these periods, insulin levels are low while glucagon levels are high, resulting in catabolism. The enzymatic machinery activated by glucagon during a catabolic state is directed toward producing glucose to be released into the system circulation for the tissues have an absolute requirement for glucose. These pathways include glycogenolysis gluconeogenesis, the glucose 6 phosphatase system, and lipolytic pathways. Lipid degradation in adipose tissue and muscle protein and glycogen provides substrates for the liver to make glucose. The avian pancreas is suspended by vascular components between the descending and ascending duodenum portal veins of the liver. It is lobulated and consists of dorsal, ventral and splenic lobes. One of its major functions is to provide digestive enzymes to aid in digestion within the small intestine. The other role is its endocrine function. The endocrine portion of the pancreas occupies more tissues mass in birds than in mammals. The distribution of cells types that includes A, B, D and F or PP cells appears more random. A cells synthesize and release glucagon; B cells synthesize and release insulin; D cells synthesize and releases somatostatin; F cells make and releases pancreatic polypeptide (PP). Increasing blood glucose stimulates B cell activity to release insulin while decreasing blood glucose, causing the release of glucagon. Absorbed nutrients stimulate D cells along with A cells. Gastrointestinal tract peptides, including cholegstokinin (CCK), secretin, gastrin, and absorbed amino acids stimulate F cell release of somatostatin. The close anatomic and physiologic relationship of these cells in an islet allows them to share extracellular fluid. The A cells stimulate both B and D cell activities, thereby closing a short negative feedback loop. The D cells appear to inhibit all other islet cells and may regulate the proportion of insulin (I) and glucagon (G) simultaneously—thereby adjusting the I/G molar ratio on a moment-to-moment basis. The intra-islet ECF link allows for communication with each of the islet in a more contiguous fashion than was previously thought. This would allow an easier and a more fine control of glucose metabolism in the body. Avian pancreatic insulin is many times more potent than equal concentrations of mammalian insulin to produce glycogenesis, hypoglycemia and lipid formation. Glucagon differs by two amino acids in birds, compared with mammals. It is a powerful catabolic hormone and circulates at levels 6-8 times higher in birds than in mammals. Somatostatin concentrations in the pancreatic tissue of birds are 2-150 times greater than in mammalian tissue. Pancreatic polypeptide hormones (PP) circulate at levels that are 20-40 times that of humans. It appears to inhibit gastrointestinal tract mobility and secretion, inhibits gall bladder and exocrine pancreatic secretion and induces a sense of satiety in the central nervous system. All protein hormones are synthesized in a similar manner. Insulin and glucagon have been used as a model for hormone synthesis. Most are synthesized as giant molecules that lack biologic activity. After these are manufactured from the rough endoplasmic reticulum, each is conveyed as a prohormone in a membrane lined vesicle to the golgi apparatus. It is here where the cleaving, insertions, folding and final conformational changes take place to form the biologically active hormone. This active hormone is packaged into secretory granules that move to the plasma membrane. The secretory vesicle membrane fuses with the plasma membrane and the contents are extruded into the ECF and then into the adjacent blood vascular space for release into the systemic circulation.

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Just as in mammals, the pancreatic islet hormones exert their effects on the actions of the cells of muscle, adipose tissue, liver and to a lesser extent, the erythrocyte, chondrocyte, thymocyte and other tissues (HAZELWOOD 2000). Insulin is a powerful hypoglycemic agent in mammals but is less so in birds although it varies between species. Doses that would be convulsive to a mammal were found to be moderately hypoglycemic in Aves. Chickens appear to be extremely resistant to insulin induced convulsions while the pigeon are more sensitive to insulin. Fasting tends to increase the sensitivity to insulin in birds. With increased circulating insulin, there is uptake of glucose in the liver, muscle and adipose tissue primarily to exert its hypoglycemic effect. In addition to its effects on plasma glucose, insulin aids in the transport of metabolizable and nonmetabolizable amino acids into cells of a wide variety of tissues from mycocardial cells to osteoblasts. Insulin can be thought of as in influx hormone as it causes glucose and amino acids to move into cells. It can reduce amino acid levels by about 30-40%, thereby inducing a positive nitrogen balance (SIMON 1989). There appears to be a delayed response with insulin as it this delay causes an increase in free fatty acids but is appears to be from glucagon release. It appears that insulin directly removes glucose and amino acids from circulation and indirectly adds lipids to the plasma (HAZELWOOD 2000). The liver in mammals and birds does not depend on insulin to move glucose across the cell membrane. Instead, insulin exerts its major effect on the liver by increasing the activity of glucokinase not hexokinase. Glucokinase phosphorylates glucose thereby steepening the downhill concentration of free glucose from outside to inside the cell. This favors glycogen synthesis and storage by its influence on glycogen synthase. Insulin appears to exert its effect on the liver by shutting down glucose formation in favor of glycogenesis. On the other hand, glucagon favors the formation of glucose as it inhibits glycogen synthase and glucokinase activities. This promotes hyperglycemia by its action on the liver. Insulin in mammals reduces gluconeogenesis but it is not clear if it does in birds. It is assumed that it does as well. It does increase the activity of liver phosphofructokinase. Glucagon decreases the flux through this pathway thereby flavoring the formation of glucose and releasing it to the systemic circulation. In the liver of a bird after hatching, it appears that insulin induces lipogenic hormones and maintenance of lipogenesis. As expected the opposite function can be ascribed to glucagon as it controls lipolysis especially after fasting. Glucagon blocks the synthesis of malic enzyme mRNA, while it activates hormone sensitive lipase (HAZELWOOD 2000). Adipose tissue of birds is under extreme metabolic pressure to assist the liver to make lipids available as an energy substrate. With their high metabolic rate, birds also need energy for egg laying, migratory flight and flight in general along with fasting at the minimum overnight. Insulin appears to have only a mild stimulatory effect of lipogenesis particularly when compared with mammals. Epinephrine in mammals also has a major stimulatory role for lipolysis but is weakly lipolytic in birds. It appears that glucagon plays the main role in fat metabolism in birds particularly with during metabolic stress and irrespective of insulin levels. Prolonged flight releases free fatty acids, epinephrine and norepinephrine along with glucagon and growth hormone (GEORGE et al 1989). The mobilized fatty acids are used as the energy source for flight and because the catecholamines are not lipolytic in birds, their role may be to stimulate glucagon release. Growth hormone, as a stress hormone, would support the lipolytic action of glucagon as well. Muscle metabolism is influenced by insulin levels but the extent of involvement is not well known due to problems of grappling with it experimentally. Insulin enhances the uptake of amino acids in the gut and is responsible for rapid myogenesis in the embryo and muscle structural protein formation in the adult. Protein synthesis is stimulated by insulin while the degradation of protein is inhibited. Insulin at low concentrations has been shown to increase hepatic production of albumen, alpha1globulin, fibrinogen, and lipoproteins. 9 PINEAL GLAND

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The pineal gland is formed from the evagination of neuroepithelial tissue from the diencephalic roof. In fish and amphibians it has both a secretory function and is photosensitive. In mammals, it is purely neuroendocrine as it relays light information only indirectly through neuronal pathways. There is a dichotomy in birds as diurnal birds have a well developed pineal organ. Some of the nocturnal species examined have rudimentary organs. The avian pineal glands are enlarged distally which is the pineal vesicle. This vesicle adheres to the dura mater and is exposed to the skull. Proximally, it has a slender stalk that is connected to the wall to the third ventricle. The pineal glands in birds have 3 morphological forms; saccular in passerines; tubulofollicular in pigeons and ducks and lobular in chickens and quail. In birds, the gland contains photoreceptor like cells, ependymal or interstitial cells and neurons. The photoreceptor cells while modified have in their outer segments, pinopsin which is structurally related to rhodopsin. Melatonin which is produced in the gland is highly light dependent. The pinealocytes contain secretory granules. The nerve cells are mainly bipolar cells and connect with the brain. Melatonin is produced in the pineal gland but not exclusively. A characteristic feature of pineal melatonin is that it has a 24 hour secretion rhythm with levels high at night and low during daylight. IT binds to high affinity membrane bound receptors in the retina, tectofugal , thalamofugal and accessory optic pathways in the brain. In passerines examined, it has been found in the song nucleus of the brain and in the auditory relay nuclei and structures in the limbic system that are associated with arousal and vocalization. It appears that the pineal gland is a component of the circadian pacemaker. 10 CITATION INDEX

1. AMES E, STEVEN K, SKADHAUGE E. Effect of arginine vasotocin on renal excretion of NA+, K+, Cl-, and urea in the hydrated chicken. Am J Physiol 1971; 221:1223 – 8.

2. BOUIZAR Z, KHATTAB M, TABOULET J, et al. Distribution of renal calcitonin binding sites in mammalian and nonmammalian vertebrates. Gen Comp Endocrinol 1989; 76: 364 – 70.

3. CLARK NB. Renal clearance of phosphate and calcium in vitamin D-deficient chicks: Effect of calcium loading, parthyroidectomy, and parathyroid hormone administration. 1991; 259: 188 – 95.

4. DACKE CG. Calcium Regulation in Submammalian Vertebrates. London, UK: Academic Press 1979.

5. DACKE CG. Eicosanoids, steroids and miscellaneous hormones. In: PANG PKT, SCHREIBMAN MP (eds): Vertebrate Endocrinology: Fundamentals and Biomedical Implications. Vol. 3. New York, NY: Academic Press 1989; 171 – 210.

6. DECUYPERE E, KÜHN ER, CHADWICK A. Physiological basis of induced moulting and tissue regeneration in fowls. World’s Poult Sci J 1986; 42: 55 – 6.

7. FARLEY JR, TARBAUX NM, HALL SL, et al. The anti-bone-resorptive agent calcitonin also acts in vitro to directly increase bone formation and bone cell proliferation. Endocrinology. 1988; 123: 159 – 67.

8. GEORGE JC, JOHN TM, MITCHELL MA. Flight effects on plasma levels of lipid, glucagon, and thyroid hormones in homing pigeons. Horm Metab Res 1989; 21: 542 – 5.

9. HAZELWOOD RL. Pancreas. In: WHITTOW GC (ed): Sturkies Avian Physiology. 5th ed. San Diego, CA: Academic Press; 2000; 539 – 56.

10. HENRY HL and NORMAN AW. Vitamin D: metabolism and biological actions. Ann Rev Nutr 1984; 4: 493 – 520.

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11. HOU HC. Relation of preen gland of birds to rickets. III. Site of activation during irradiation. Chin J Physiol 1931; 5: 11 – 8.

12. KENNY AD. Parathyroid and ultimobranchial glands. In: Sturkie PD (ed): Avian Physiology. 4th ed. New York, NY: Springer-Verlag 1986; 466 – 78.

13. LAZAR MA. Thyroid hormone receptors: Multiple forms, multiple possibilities. Endocr Rev 1993; 14: 184 – 92.

14. MCNABB FMA. Thyroid Hormones. Eaglewood Cliffs, NJ: Prentice Hall 1992. 15. MCNABB FMA and KING DB. Thyroid hormone effects on growth, development and

metabolism. In: SCHREIBMAN MP, SCANES CG, PANG PKT (eds): The Endocrinology of Growth, Development, and Metabolism of Vertebrates. New York, NY: Academic Press 393 – 417.

16. NYS Y, N’GUYEN TM, WILLIAMS J, ETCHES RJ. Blood levels of ionized calcium, inorganic phosphorus, 1,25-dihydroxy-cholecalciferol and gonadal hormones in hens laying hard shelled or shell-less eggs. J Endocrinol 1986; 111: 151 – 7.

17. RUDAS P, BARTHA T, FRENYO VL. Elimination and metabolism of triiodothyronine depend on the thyroid status in the brain of young chickens. Acta vet Hung 1994; 42: 218 – 30.

18. RUDAS P, BARTHA T, FRENYO VL. Thyroid hormone deiodination in the brain of young chickens acutely adapts to changes in thyroid status. Acta vet Hung 1993; 41: 381 – 93.

19. RZASA J. Effects of arginine vasotocin and prostaglandin E1 on the hen uterus. Prostaglandins 1978; 16: 357 – 72.

20. RZASA J. The effect of arginine vasotocin on prostaglandin production of the hen uterus. Gen Comp Endocrinol 1984; 53; 260-3.

21. SCANES CG. Pituitary gland. In: WHITTOW GC (ed): Sturkies Avian Physiology. 5th ed. San Diego, CA: Academic Press 2000; 437 – 60.

22. SHAW AJ, WHITAKER G, DACKE CG. Kinetics of rapid 45Ca uptake into chicken skeleton in vivo: Effects of microwave fixation. Quart J Exp Physiol 1989; 74: 907 – 15.

23. SIMON J. Chicken as a useful species for the comprehension of insulin action. In: CRC Critical Reviews in Poultry Biology. Vol 2. Boca Raton, FL: CRC Publ 1989; 121 – 48.

24. WENTWORTH BC and RINGER RK. Thyroids. In: STURKE PD (ed): Avian Physiology. New York, NY: Springer-Verlag. 1986; 452 – 65

25. WILLIAMS DC, PAUL DC, HERRING JR. Effects of antiestrogenic compounds on avian medullary bone formation. J Bone Miner Res 1991; 6: 1249 – 56.

AUTHOR ADDRESS: S. E. Orosz, PhD, DVM, Dipl ABVP (Avian), Dipl ECZM (Avian) Bird and Exotic Pet Wellness Center 5166 Monroe Street, Ste. 305 Toledo, 43623 OH United States. E-mail: DrSusanOrosz@aol.com

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mailto:DrSusanOrosz@aol.com

ENDOCRINOLOGY OF THE PROTEIN HORMONES IN AVIAN SPECIES: DISEASES

Deborah Monks BVSc (Hons) CertZooMed FACVSc (Avian Medicine) DipECZM (Avian)

Brisbane Bird and Exotics Veterinary Service Macgregor, Queensland, Australia

KEYWORDS Endocrinology – Avian – Diabetes mellitus – Diabetes insipidus – Hyperthyroidism – Hypothyroidism – Pituitary – Hypothalamus – Thyroid – Parathyroid – Pancreas – Pineal Gland – Ultimobranchial Gland – Dwarfism – Protein Hormones

INTRODUCTION

This component of the presentation series aims to give a thorough description of documented diseases involving protein hormone endocrinology. In many cases, in depth information is not available in peer reviewed format; in other cases, absolute confirmation of diagnosis are lacking. Nonetheless, this presentation aims to draw together current information into a useful format for the avian practitioner. Summary information is positioned in text boxes for ease of reference.

DISEASES OF THE PROTEIN HORMONES

Hypothalamus The hypothalamus secretes several hormones which act on the avian pituitary gland. These include; gonadotropin releasing hormone (GnRH) which causes secretion of follicle stimulating hormone (FSH) and luteinising hormone (LH); thyrotropin releasing hormone (TRH) which causes the release of thyroid stimulating hormone (TSH); growth hormone releasing hormone (GHRH) which causes the release of growth hormone (GH); somatostatin (growth hormone inhibitory hormone or GHIH) which inhibits secrection of GH; vasoactive intestinal peptide (VIP) which stimulates prolactin secretion; dopamine (prolactin inhibiting hormone) inhibits prolactin secretion; and corticotropin releasing factor (CRF) which stimulates ACTH release (RITCHIE and PILNY, 2008). Note that somatostatin is also produced in the pancreas and the intestinal cells (SITBON et al., 1980). Given the regulatory action of the hypothalamus, clinical signs of primary hypothalamic endocrine dysfunction will likely be due to secondary or tertiary gland malfunction. Additionally, hypothalamic pathology may simultaneously affect several endocrine systems, confusing accurate discrimination of individual hormone systems. Lumeij (1994) lists trauma, congenital abnormalities and lesions, granulomatous lesions and neoplasia as possible hypothalamic pathologies. However, there are few or no records of primary hypothalamic pathology inducing endocrinologic disturbance in avian species.

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Pituitary Gland The avian pituitary gland produces hormones from two distinct areas – the adenohypophysis and the neurohypophysis. The anterior pituitary (adenohypophysis) receives hormonal stimulation from the hypothalamus, which directs the production of adenohypophyseal hormones for systemic circulation. These hormones are FSH, LH, TSH, GH, prolactin and ACTH. The posterior pituitary (neurohypophysis) releases arginine vasotocin (AVT) and mesotocin in response to neural signals. Pituitary endocrine dysfunction can occur via a number of pathways; a primary pituitary cell neoplasm over-secreting a specific hormone (either adenohypophyseal or neurohypophyseal); pathologic stimulation or inhibition of adenohypophyseal cells by hypothalamic hormones (ie, hypothalamic pathology inducing effects on the adenohypophysis as a secondary gland ); a mass effect preventing passage of hypothalamic hormones to the adenohypophysis; and finally, congenital, developmental or granulomatous processes of surrounding tissue causing mass effects on pituitary cells, and preventing hormone production by causing atrophy or necrosis of adenohypophyseal and/or neurohypophyseal cells.

Specific Pituitary Diseases

Reports of pituitary disease affecting only one endocrine system are rare. More commonly, pituitary diseases affect multiple systems and cause a constellation of clinical signs.

FSH and LH are crucial for gonadal function, and at specific times are significantly involved in other endocrine systems, such as calcium regulation. In Japanese Quail, embryonic exposure to endocrine disrupting chemicals can cause alterations in GnRH production that may have lifelong ramifications. Intramuscular injection of diesel exhaust derivative has caused decreases in LH and testosterone levels in the same species (LI et al., 2006);(OTTINGER et al., 2009). TSH stimulates thyroid growth and increases the release of thyroxine (T4) from the thyroid gland (RITCHIE and PILNY, 2008). TSH release is stimulated by dropping levels of circulating T3, which also stimulate TRH release from the hypothalamus. TRH stimulates GH release from the adenohypophysis, which then increases de-iodination of T4 to form T3 (SCHMIDT and REAVILL, 2008). There are few documented cases of hyper or hypothyroidism in avian species, and absolutely none in which the dysfunction was due to hypothalamic or pituitary dysfunction. Signs of hyperthyroidism include polydipsia, polyuria, regurgitation, tachycardia, weight loss, plumage changes, convulsions and death (RAE, 1995). Clinical signs of hypothyroidism can include feather loss, epidermal atrophy, and non inflammatory skin changes, hypercholesterolaemia, nonregenerative anaemia and obesity (SCHMIDT and REAVILL, 2008; OGLESBEE, 1992). GH causes generalized growth of all body tissues, although it also has some effects on metabolism as well as T4 and corticosterone levels (RITCHIE and PILNY, 2008). GH exerts its effects through direct action on the majority of body tissues which contrasts with other pituitary hormones which act on target glands (RITCHIE and PILNY, 2008{Carsia, 2000 #21; CARSIA and HARVEY, 2000). As yet, there are no reports of pathologic levels of GH, although two acidophilic adenohypophyseal carcinomas in budgerigars demonstrated immunoreactivity with GH histologically. Unfortunately, there was no information available regarding clinical signs (SUCHY, 1999). Pituitary dwarfism has been reported in chickens as a sex linked recessive condition. In these birds, there are adequate levels of GH, but there appears to be impaired GH function, stemming from deletions in the GH protein coding (HULL et al., 1999). Dwarfism has also been reported in a pheasant, a Black-headed Gull and a Great Crested Flycatcher (LUMEIJ, 1994). Prolactin promotes incubation behaviour, and usually reduces gonadotropin levels. It is likely to be involved in the development of photorefractoriness inhibiting further breeding, and stimulates the

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production of crop milk in columbiformes (RITCHIE and PILNY, 2008). Naturally occurring dysfunction of this system has not been reported in avian species although reproductive failure is a likely manifestation. Avian adrenocorticotropic hormone (ACTH) causes release of corticosterone, aldosterone and deoxycorticosterone from the adrenal cortical cells (RITCHIE and PILNY, 2008). Functional neoplasia of corticotrophin (ACTH) producing cells of the pituitary will produce clinical signs of hyperadrenocorticism, arising from bilateral adrenal hyperfunction. These include weight change, hepatic lipidosis, polyuria, polydipsia, polyphagia, delayed wound healing, muscular weakness and atrophy, hyperglycaemia, hypophosphataemia, increased serum cholesterol and triglyceride levels and glucosuria (DE MATOS, 2008a) A Moluccan cockatoo with a pituitary adenoma had bilateral adrenal hyperplasia and clinical signs suggestive of hyperadrenocorticism. Although pre-mortem diagnostic testing was not conclusive, the presence of ACTH immunoreactive tissue within the neoplasm was supportive of the authors’ assertion that the most likely aetiology was increased levels of ACTH arising from the pituitary adenoma (STARKEY et al., 2008).

Pituitary dependent hyperadrenocorticism is characterized by polyuria, polydipsia, impaired wound healing, abdominal muscle weakness, hepatomegaly, hepatic lipidosis, weight gain, hyperglycaemia, hypophosphataemia, and lymphopaenia with a relative heterophilia (Starkey et al., 2008).

AVT is the avian antidiuretic hormone and acts on renal tubular function and glomerular filtration rate (RITCHIE and PILNY, 2008). It is also involved in oviposition (RITCHIE and PILNY, 2008). The role of mesotocin is still being elucidated (RITCHIE and PILNY, 2008). Diabetes insipidus has been reported in an African Grey Parrot, chickens, Japanese Quail and a budgerigar (STARKEY et al., 2010; BRUMMERMANN and BRAUN, 1995; MACWHIRTER, 1999); (BRAUN and STALLONE, 1989; MINVIELLE et al., 2007). In the African Grey Parrot, clinical signs included mild depression, bilateral mydriasis, decreased pupillary light reflexes bilaterally and profound polyuria and polydipsia. The urine was hyposthenuric. Following a water deprivation test, over 6% of bodyweight was lost, and the bird failed to concentrate urine. The disease was confirmed by resolution of polyuria, polydipsia and mydriasis after intramuscular (but not oral) desmopressin. Plasma AVT levels were not done, so absolute confirmation of this case as central diabetes insipidus did not occur. The signs progressed over the next 16 months, requiring an increased dose of desmopressin. Unilateral mydriasis with reduced papillary light reflex, unresponsive to desmopressin also developed. Although cranial imaging was not done, the authors postulate that an enlarging cranial neoplasm could have been the cause (STARKEY et al., 2010). In strains of chickens and quail with autosomal recessive nephrogenic diabetes insipidus, baseline plasma AVT exceeds those of normal birds, thus supporting the diagnosis of nephrogenic diabetes insipidus (MINVIELLE et al., 2007; BRAUN and STALLONE, 1989).

Diabetes insipidus is characterized by polydipsia, slight hypernatraemia and extreme polyuria with hyposmotic urine (BRAUN and STALLONE, 1989).

Generalised pituitary dysfunction Although there are many reports of pituitary neoplasia in avian species, neoplasms have rarely been differentiated into cell types, or functionality. This makes it difficult to confidently ascribe clinical signs to one endocrinologic system alone. Additionally, many of the clinical signs of pituitary neoplasia (including blindness, depression, ataxia, seizures, convulsions and exophthalmia) can be referable to the space occupying nature of the mass rather than endocrinologic derangement (DE MATOS, 2008a).

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The most common clinical signs of functional pituitary neoplasm are polydipsia and polyuria. However, this could be caused by excess ACTH, excess GH or hyposecretion of AVT, or even cerebral compression alone (ROMAGNANO et al., 1995; STARKEY et al., 2008). Many birds with pituitary neoplasia show changes in plumage colour and quality, cere colour, and weight which could relate to either dysfunctional thyroid and sex hormone production (DE MATOS, 2008a; ROMAGNANO et al., 1995; SCHLUMBERGER, 1954). Other signs of pituitary neoplasia include reproductive failure and hyperglycaemia (ROMAGNANO et al., 1995). Unfortunately, none of these clinical signs are pathognomonic for a specific hormone system. The most commonly diagnosed pituitary neoplasm is adenoma, although carcinomas are also diagnosed (DE MATOS, 2008a). Both are diagnosed most frequently in budgerigars (LUMEIJ, 1994). A specific transmissible pituitary adenoma has been described in budgerigars (ROMAGNANO et al., 1995). Adenomas have been described in cockatiels, a Moluccan cockatoo, an Amazon Parrot, a lovebird, a canary and chickens (DE MATOS, 2008a; ROMAGNANO et al., 1995; STARKEY et al., 2008; LUMEIJ, 1994; LATIMER, 1994). A carcinoma and adenocarcinoma of the pituitary have been reported in a budgerigar and a cockatiel, respectively (DE MATOS, 2008a; LUMEIJ, 1994; LATIMER and GREENACRE, 1995; CURTIS-VELASCO, 1992; SUCHY, 1999).

Pineal gland The pineal gland secretes melatonin. In other species, melatonin has been proven to have multiple functions. In birds, however, only thermoregulation, sleep regulation and circadian function have been proven to be linked to melatonin (RITCHIE and PILNY, 2008). There are scattered reports of pineal neoplasia. A cockatiel with unilateral head tilt, loss of grip, depression and polydipsia was diagnosed with a pineoblastoma while two chickens and a dove were incidentally diagnosed with pinealoma (WILSON et al., 1988; SWAYNE et al., 1986; LATIMER, 1994).

Thyroid Gland The hypothalamic-pituitary-thyroid axis controls the production and release of T4 (thyroxine) and T3 (triiodothyronine). Acting on the adenohypophysis, which produces TSH are two hypothalamic hormones - TRH which is stimulatory, and somatostatin which is inhibitory (RITCHIE and PILNY, 2008; SCHMIDT and REAVILL, 2008). Thyroid hormone stimulates carbohydrate metabolism (glucose uptake, glycolysis, gluconeogenesis, insulin secretion), facilitates metabolic heat production (and thus thermoregulation), controls growth and cellular differentiation and maturation, and augments moulting (RITCHIE and PILNY, 2008).

The avian thyroid secretes mainly T4, although T3 is the active metabolite. The conversion from T4 to T3 occurs mainly in peripheral tissues, which makes avian thyroid function susceptible to nonthyroidal effects (RITCHIE and PILNY, 2008); (SCHMIDT and REAVILL, 2008).

Non-thyroid conditions that can affect thyroid function include nutrition, temperature, light, toxins, photoperiod, light intensity and deficiencies in certain amino acids and trace elements (SCHMIDT and REAVILL, 2008).

Diseases of the Thyroid Thyroid gland pathology includes hyperplasia, neoplasia, infection, inflammation and atrophy. In nonfunctional enlargement - aetiologies of which include cystic changes, plant goitrogens, toxins,

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congenital abnormalities, amyloidosis and some neoplasia - the clinical signs often relate to those of a spaceoccupying mass (LUMEIJ, 1994) Thyroid gland hyperplasia and enlargement (goiter) is most often due to iodine deficiency. Although most commonly reported in budgerigars, that species rarely appears to suffer from thyroid endocrinopathy (SCHMIDT, 2002; LUMEIJ, 1994). At necropsy, Blue and Gold Macaws also seem to have an increased incidence of hyperplastic goiter although concomitant thyroid dysfunction has been described in that species (SCHMIDT, 2002). Histiocytic thyroiditis has been described in passerines with atypical, disseminated, mycobacteriosis, although there was no clinical evidence of hypothyroidism (RAE, 1995). Thyroiditis can also be caused by infection with viruses and pyogenic bacteria (LUMEIJ, 1994).

Thyroid pathology often fails to result in functional symptoms of hyper or hypothyroidism.

In certain strains of pigeons hyperplastic goiter can be functional, leading to clinical signs of hypothyroidism, including lethargy, obesity, reduced reproductive parameters, myxoedema and feather abnormalities (LUMEIJ, 1994). The birds are usually on fat rich, iodine deficient diets (LUMEIJ, 1994). There is also a report of an iodine responsive goiter in captive reared black stilts, causing decreased survivability after release (ALLEY et al., 2008). This syndrome responded to prerelease iodine supplementation. In chickens with spontaneous autoimmune thyroiditis, classic signs of hypothyroidism first develop 2-3 weeks after hatch, although histologic evidence of thyroid pathology is present earlier (SCHMIDT and REAVILL, 2008; WICK et al., 2006). The clinical signs can be reversed by supplementation with thyroxine, and include small body size and comb size, cold sensitivity, low fertility, poor hatchability, lipaemia and weight gain (WICK et al., 2006). Histologically, there appears to be a similar condition in African Grey Parrots (SCHMIDT and REAVILL, 2008). Japanese Quail with chemically induced hypothyroidism exhibit gondal and adrenal disturbances (WENG et al., 2007). Thyroidectomised ducks become hypoglycaemic, with large hepatic glycogen stores (MERRYMAN and BUCKLES, 1998).

Clinical signs of hypothyroidism can include severe feather loss, epidermal atrophy, orthokeratotic and parakeratotic hyperkeratotis, hypercholesterolaemia, non-regenerative anaemia and obesity. Narrowing of primary feathers, poor quality and discoloured plumage, small body and comb sizes, cold sensitivity, low fertility and poor hatchability can be seen as well. Gonadal and adrenal dysfunction, and hypoglycaemia can be seen (OGLESBEE, 1992; LUMEIJ, 1994; WICK et al., 2006; SCHMIDT and REAVILL, 2008).

An experimental model of hypothyroidism was developed using radiothyroidectomy in cockatiels, although clinical signs were absent or merely mild after 48 days [referenced in (SCHMIDT, 2002)]. There has been one confirmed case of hypothyroidism in a Scarlet Macaw, which presented with feather loss, obesity, hypercholesterolaemia, noneregenerative anaemia, low baseline T4 levels and a low TSH stimulation response (OGLESBEE, 1992). The bird responded to supplementation with thyroxine, both clinically and on laboratory testing. No thyroid biopsy was done, so the precise aetiology was not elucidated. Schmidt and Reavill briefly describe a case of hypothyroidism, but with no specific details (SCHMIDT and REAVILL, 2008). Clinical signs included severe feather loss, epidermal atrophy, and non inflammatory skin changes (SCHMIDT and REAVILL, 2008). Rae also attests to several cases in older, obese Amazon Parrots in which histologic findings were consistent with hypothyroidism, and the cause of death was attributed to secondary complications from hypothyroidism (infarction and atherosclerosis) (RAE, 1995). Thyroid neoplasia is frequently reported, but is not usually functional (RAE, 1995). However, one report (not peer reviewed) on Veterinary Information Network

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(http://www.vin.com/Members/boards/discussionviewer.aspx?DocumentId=3712562, accessed 30/12/2010) describes a parrot, eventually diagnosed with thyroid adenocarcinoma, that exhibited poor plumage, emaciation and had high baseline T4 levels. There are reports of hyperthyroidism attributed to overdose of exogenous thyroxine (RAE, 1995).

Signs of hyperthyroidism can include polydipsia, polyuria, regurgitation, tachycardia, weight loss, plumage changes, convulsions and death (RAE, 1995).

The Parathyroid Calcium is a crucial element, and is utilised in the protection of the embryo (egg shell), the maintenance of body structure and capacity for movement (bones), and many critical biochemical processes (for example, muscle contraction, blood coagulation, nerve conduction). The parathyroid gland produces parathyroid hormone (PTH) in response to ionized hypocalcaemia. PTH secretion is suppressed by rising blood levels of ionized calcium. Parathyroid hormone increases tubular resorption of calcium; increases bone resorption and increases the formation of calcitriol by the kidney (DE MATOS, 2008b) Sex hormones and prostaglandins are also involved in calcium metabolism (DE MATOS, 2008b).

Diseases of the Parathyroid Gland

Hyperparathyroidism can be classified as primary, secondary or tertiary. Primary hyperparathyroidism occurs due to excessive production of PTH, due to a genetic abnormality or to neoplasia (BLACKBURN and DIAMOND, 2007). Primary hyperparathyroidism has not been diagnosed in avian species.

Thus far, all reports of hyperparathyroidism reported in birds have been secondary, appropriate physiologic responses to other conditions.

Although not reported in birds, signs of primary hyperparathyroidism in other species include persistent hypercalcaemia, fractures, renal calculi, pancreatitis and neuropsychiatric abnormalities (BLACKBURN and DIAMOND, 2007).

Secondary hyperparathyroidism occurs when there are elevated levels of PTH, associated with normal or decreased ionized calcium levels. This is then a normal parathyroid response to abnormal calcium levels, and can be caused by chronic renal failure and nutritional deficiencies (BLACKBURN and DIAMOND, 2007; PHALEN et al., 2005). Ultrastructurally, the parathyroid is hypertrophic or hyperplastic (RAE, 1995). This condition has been seen in avian species.

Hypocalcaemia due to dietary calcium deficiency or lack of environmental ultraviolet light is common in African Grey Parrots. Clinical signs include muscular weakness, ataxia, osteodystrophy, depression, lethargy, tremors, seizures, and death (STANFORD, 2006).

African Grey Parrots in particular, seem predisposed to hypocalcaemia causing muscular weakness, ataxia, seizures, osteodystrophy, poor reproductive performance and even death (STANFORD, 2006). It is though that from an ecological viewpoint, this species depends more on ultraviolet light for calcium metabolism than other species (STANFORD, 2006). However, in cases of severe enough calcium or vitamin D deficiency, even ‘hardier’ species such as Amazon parrots can develop clinical hypocalcaemia (RANDELL, 1981). In either case, the endocrine system is competently responding to environmental deficit. That is, it is not a case of endocrine dysfunction per se.

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http://www.vin.com/Members/boards/discussionviewer.aspx?DocumentId=3712562

Tertiary hyperparathyroidism occurs in humans when functional adenomas develop within chronically hyperplastic parathyroid glands, and is associated elevated PTH, calcium and phosphorous levels (RAE, 1995). This has not yet been diagnosed in birds. Environmental pollutants such as chlorinated hydrocarbons can exert effects on parathyroid function, although these may differ with the dose and affected species (RATTNER et al., 1984). Some drugs, such as omeprazole, appear to cause hypertrophy and hyperplasia of the parathyroid gland (GAGNEMO-PERSSON et al., 1997).

Although not reported in birds, signs of primary parathyroid gland hypofunction would be congruent with hypocalcaemia – ataxia, depression, tremors, seizures, reproductive failure, egg binding and death (STANFORD, 2006; COLE et al., 1989).

Ultimobranchial Bodies In mammals, the ultimobranchial bodies produce calcitonin, which induces hypocalcaemia and hypophosphataemia (JOHNSTON and IVEY, 2002). Unfortunately, as the role of calcitonin in avian species is unclear, it is not possible to posit clinical signs due to hyper or hypofunction, nor to report any documented diseases (RITCHIE and PILNY, 2008).

Pancreas The endocrine pancreas, positioned within the pancreatic islet tissue, is primarily responsible for blood glucose regulation. Islet tissue is spread throughout the pancreas, although species variations exist in distribution (HAZELWOOD, 2000). There are four pancreatic produced hormones – glucagon, insulin, somatostatin and pancreatic polypeptide (PILNY, 2008; HAZELWOOD, 1984). These hormones are secreted by the A cells, the B cells, the D cells and the F (or PP) cells, respectively. These cells interact via local and systemic endocrine feedback processes. Somatostatin is also produced in the hypothalamus and the intestines (PILNY, 2008; HAZELWOOD, 2000). Glucagon increases blood glucose levels, using gluconeogenesis, glycogenolysis and lipolysis, and is the major glucose regulator in avian species (RAE, 1995; HAZELWOOD, 2000). Glucagon is a strong catabolic hormone (HAZELWOOD, 2000). Secretion of glucagon is triggered by increased levels of free fatty acids and cholecystokinin and is inhibited by high blood glucose levels (PILNY, 2008). Insulin lowers blood glucose levels in avian species and is a strong anabolic agent, but does not appear to be the major avian blood glucose regulator (RAE, 1995; HAZELWOOD, 2000). Release of insulin is modulated via multiple interactions, including endocrine, exocrine, neural, humoral and paracrine processes, although low blood glucose levels alone are not a major stimulus in birds (PILNY, 2008; HAZELWOOD, 2000). Somatostatin regulates the insulin:glucagon ratio via its direct action on the other islet cells, although the intricacies of this action are poorly understood. It differentially suppresses secretion of the other cell types - glucagon secretion is significantly depressed while insulin secretion is moderately suppressed (HAZELWOOD, 2000; PILNY, 2008). Pancreatic polypeptide slows gastrointestinal motility and secretion (and thus the degree of increase of glucose absorption from the gut) (PILNY, 2008).

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It has been said that the normal bird resembles an uncontrolled mammalian diabetic, in that the basal blood levels of glucose, glucagon and somatostatin are much higher than a mammal, as are pancreatic somatostatin levels (Hazelwood, 2000; (HAZELWOOD, 1984). However, it appears that the ratio of insulin and glucagon, regulated in part by somatostatin, is the crucial component of blood glucose regulation rather than any one hormone in isolation (SITBON et al., 1980).

Pancreatic Diseases Endocrine pancreatic dysfunction manifests as either hyper or hypoglycaemia. The most common syndrome in birds is diabetes mellitus (DM) – the failure to adequately constrain blood glucose levels. Sitbon (1980) defines diabetes mellitus as a ‘pathological or experimental dysfunction of the islets of Langerhans as a whole’. This definition allows for differing aetiologies, involving any or all of insulin, glucagon and somatostatin, which could all lead to hyperglycaemia. One of the difficulties in the avian literature is that many cases of diabetes mellitus have not had hormone analyses, but have been diagnosed clinically, leaving the pathophysiology opaque. In mammalian species, diabetes mellitus is divided into Type 1 (insulin dependent) and Type 2 (noninsulin dependent). Type 1 diabetes mellitus is associated with destruction of pancreatic B cells, whereas type 2 diabetes is caused by either a relative insulin deficiency or a peripheral cellular resistance to the effects of insulin (HAZELWOOD, 2000; RAE, 1995). This classification system is not entirely useful in birds, in which the insulin:glucagon ratio is so important. In fact, even in humans, Expert Committee for the Diagnosis and Classification of Diabetes Mellitus states that it is more important to understand the pathogenesis of hyperglycaemia in the particular individual than it is to classify it (http://care.diabetesjournals.org/content/25/suppl_1/s5.full accessed 15/12/10). Histologically visible destruction of B cells within pancreatic islets (which would be consistent with human Type 1 diabetes), has been documented in avian species (PILNY, 2008). Aetiologies include those diseases only afflicting the pancreas, such as chronic lymphocytic pancreatitis, and those affecting multiple organs but also causing pancreatic inflammation or destruction, including iron storage disease and peritonitis (especially reproductively related in hen birds) (PILNY, 2008; HAZELWOOD, 2000; GANCZ et al., 2007). It is not uncommon to see nonspecific islet cell degeneration at necropsy ((SCHMIDT and REAVILL, 2006). However, this does not necessarily correlate with clinical signs of glucose dysfunction. Causes of peripheral insulin resistance (consistent with human Type 2 diabetes) have been identified including obesity; high circulating levels of endogenous or exogenous corticosteroids; high circulating levels of diabetogenic hormones such as glucagon, growth hormone or epinephrine; and high levels of circulating iron (PILNY, 2008; GANCZ et al., 2007; CANDALETTA et al., 1993).

Signs of diabetes mellitus include polyuria, polydipsia, polyphagia, ketonuria, ketonaemia, glucosuria, lethargy, depression, weight loss and death. Birds will invariably demonstrate hyperglycaemia (HAZELWOOD, 2000).

Table 1 gives a summary of the peer reviewed and conference literature relating to avian diabetes mellitus. Of these cases, a number lack documented hormone levels, making it impossible to identify the exact pathophysiology of hyperglycaemia. For instance, in one case involving a Toco Toucan, insulin was only required temporarily (MURPHY, 1992). This also corresponded to a change to a lower iron diet, so it is possible that iron storage disease was the primary disease, with diabetes mellitus being a secondary problem. It has been stated that toucans are overrepresented with diabetes mellitus, but the link between that and iron storage disease needs to be further elucidated (MURPHY, 1992; GANCZ et al., 2007).

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http://care.diabetesjournals.org/content/25/suppl_1/s5.full

There is also some confusion regarding the differential effects of glucagon and insulin within the Aves class. For instance, there is the belief that carnivorous birds are more predisposed to diabetes mellitus while granivorous birds are more glucagon dependent. Regardless of the species, after a complete pancreatectomy, any bird will die from severe hypoglycaemia unless given glucagon or glucose infusions (HAZELWOOD, 2000). It is likely, given the difficulty of total pancreatectomy in some avian species, that several experiments have reported the results of inadvertent subtotal pancreatectomy (Hazelwood, 2000). Responses to subtotal pancreatectomy vary. For instance, ducks will become transiently diabetic, but geese will become permanently diabetic (HAZELWOOD, 2000). It is assumed that these differences relate to a difference in the distribution and proportion of islet cell types in the remnant pancreas. Neoplasia affecting the pancreatic islet cells has been seen, although rarely (SCHMIDT and REAVILL, 2006; RYAN et al., 1982). There has been one reported case of pancreatic islet carcinoma associated with diabetes mellitus in a budgerigar (RYAN et al., 1982). The author could find no documented reports of an insulinoma in an avian species.

Signs of an insulinoma would be persistent hypoglycaemia, causing weakness, depression, collapse, seizures and possibly death.

Gastrointestinal Endocrine System This author could find no reports of disease affecting the gastrointestinal neuroendocrine system in avian species. In humans, gastroentericpancreatic neuroendocrine tumours (GEP-NET) are a very rare, diverse group of neoplasias. Approximately 90% are nonfunctional, which leads to very late diagnosis, and associated poor prognosis. In humans, over three quarters of functional tumours secrete somatostatin (APPETECCHIA and BALDELLI, 2010). It is possible, given the importance of somatostatin in avian species, that disorders of glucose metabolism may be a presenting sign.

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CITATION INDEX

1. ALLEY, M. R., TWENTYMAN, C. M., SANCHA, S. E., CLARK, P. & MALONEY, R. F. 2008. Hyperplastic goitre and mortality in captive-reared black stilts ( Himantopus novaezelandiae ). N Z Vet J, 56, 139-144.

2. ALTMAN, R. & KIRMAYER, A. 1976. Diabetes mellitus in the Avian Species. J American Animal Hospital Association, 12, 531-537.

3. APPETECCHIA, M. & BALDELLI, R. 2010. Somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine tumours, current aspects and new perspectives. J