STUDENTS GUIDANCE

INTRODUCTION TO ENDOCRINOLOGY

ANATOMY OF ENDOCRINE ORGAN

BIOCHEMISTRY OF HORMONE

HORMONE ACTION

DIAGNOSTIC TESTING APPROACH TO THE PATIENT WITH ENDOCRINE DISEASE

FACULTY OF MEDICINE

BRAWIJAYA UNIVERSITY

MALANG

2014(1)

INTRODUCTION TO ENDOCRINOLOGYEndocrinology is concerned with the study of the biosynthesis, storage, chemistry, and physiological function of hormones and with the cells of the endocrine glands and tissues that secrete them. The endocrine system consists of several glands, in different parts of the body, that secrete hormones directly into the blood rather than into a duct system. Hormones have many different functions and modes of action; one hormone may have several effects on different target organs, and, conversely, one target organ may be affected by more than one hormone.In the original 1902 definition by Bayliss and Starling, they specified that, to be classified as a hormone (derived from Greek phrase meaning to set in motion), a chemical must be produced by an organ, be released (in small amounts) into the blood, and be transported by the blood to a distant organ to exert its specific function. This definition holds for most "classical" hormones, but there are also paracrine mechanisms (chemical communication between cells within a tissue or organ), autocrine signals (a chemical that acts on the same cell), and intracrine signals (a chemical that acts within the same cell). A neuroendocrine signal is a "classical" hormone that is released into the blood by a neurosecretory neuron.

The classic endocrine glands-pituitary, thyroid, parathyroid, pancreatic islets, adrenal, and gonads-communicate broadly with other organs through the nervous system, hormones, cytokines, and growth factors. Hormones act by binding to specific receptors in the target organ. As Baulieu notes, a receptor has at least two basic constituents: 1) a recognition site, to which the hormone binds, and 2) an effector site, which precipitates the modification of cellular function. Between these is a "transduction mechanism" in which hormone binding induces allosteric modification that, in turn, produces the appropriate response.The interdigitation of endocrinology with physiology processes in other specialties sometimes blurs the roles of hormones. For example, hormones play an important role of hormones. For example, hormones play an important role in maintanance of blood pressure, intravascular volume, and peripheral resistance in the cardiovascular system. Vasoactive substances such as catecholamines, angiotensin II, endothelin, and nitric oxide are involved in dynamic changes of vascular tone, in addition to their multiple roles in other tissues. The heart is the principal source of atrial natriuretic peptide, which acts in classic endocrine fashion to induce natriuresis at a distant target organ (the kidney).References

1. Fauci AS, Braunwauld E, Jameson JL et al, Harrisons Endocrinology. 2nd Edition, China: McGraw-Hill, 2010.2. Gardner DG and Shoback D. Basic and Clinical Endocrinology 9th edition, China : McGraw-Hill, 20113. H.M. Kronenberg, Melmed S, Larsen PR, Polonsky KS. Williams Textbook of Endocrinology 12th edition, Philadelphia : Elsevier, 2011.( 2 )

ANATOMY OF ENDOCRINE ORGANS

Histogenesis kelenjar berasal dari invaginasi sel2 epithel. Bila sel2 dibagian bawah lapisan permukaan tetap ada, akan menjadi ductus excretorius (saluran pengeluaran) dan menjadi kelenjar eksokrin yang bekerja lokal. Bila sel2 ini menghilang (disappearance) akan menjadi kelenjar endokrin, yang tidak memiliki saluran pengeluaran, dan sebagai gantinya disitu banyak pembuluh darah untuk menyalurkan hasil sekresi kelenjar yaitu hormone menuju ke target organ yang letaknya bisa jauh dri kelenjarnya.

Sistem endokrin adalah sistem kontrol kelenjar tanpa saluran yang hasilnya yaitu hormone, sebagai pembawa pesan dibawa oleh darah menuju ke target organ yang melaksanakan pesan tadi sebagai tindakan.

Macam2 kelenjar endokrin :

1. Hypophyse

2. Thyroid

3. Parathyroid

4. Suprarenalis

5. Pulau Langerhans pancreas

6. Testis

7. Ovarium

Kelenjar hipofise lokasinya didalam canium, dibasis cranii, ukuranya sebesar buah anggur lokal, terdiri dari 3 bagian yaitu lobus anterior, pars intermedia dan lobus posterior. Masing2 bagian menghasilkan hormone yang berbeda ; misalnya lobus anterior menghasilkan macam2 hormon, antara lain growth hormon yang bekerja pada tulang, otot dan lemak yang mengontrol pertumbuhan badan. Bila hormon pertumbuhan ini sangat berlebihan akan terjadi pertumbuhan raksasa dan bila sangat kurang akan terjadi kerdil. Lobus posterior menghasilkan oxitocin untuk kontraksi uterus, sehingga bayi bisa lahir, serta ADH untuk mengontrol pengeluaran urine, bila ada gangguan bisa terjadi diabetes incipidus dimana pengeluaran urine sangat banyak.

Kelenjar thyroid lokasinya didaerah leher setinggi os thyroid, terdiri dari dua lobus kanan dan kiri yang dihubungkan oleh bagian yang sempit yaitu isthmus, sehingga bentuknya seperti huruf H , fungsinya menghasilkan hormon thyroxin untuk mengatur metabolisme tubuh. Bila membesar disebut struma tanpa melihat fungsinya dan tampak sebagai benjolan didaerah leher yang ikut bergerak saat orang menelan. Bila fungsi berlebihan disebut hyperthyroid dengan gejala orang merasa selalu lapar, berkeringat, jantung berdebar, bahkan bisa terjadi tremor. Bila fungsi berkurang disebut hypothyroid : orang lemah, gemuk dan kulit kasar. Dipermukaan posterior masing2 lobus kelenjar thyroid, dibagian atas dan agak bawah terdapat kelenjar parathyroid, jadi ada empat kelenjar parathyroid, ukuran sebesar biji kacang hijau. Menghasilkan parathyroid hormon untuk mengatur keseimbangan kadar kalcium dalam darah dan tulang. Bila parathyroid hormon berlebihan (hiperparathyroid), kadar kalcium dalam darah menjadi tinggi dan kacium dalam tulang turun sehingga tulang menjadi keropos (osteoporosis), dengan akibat mudah terjadi fraktur (fraktura spontanea). Bila kadar kalcium dalam darah turun bisa terjadi tetani (kejang otot). Kelenjar suprarenalis, lokasinya pada kutub atas masing2 ren, bentuk agak segitiga. Terdiri dari dua bagian yaitu cortex yang lebih luas, dan medula yang lebih sempit.Bagian cortex ini essential untuk kehidupan, karena menghasilkan hormon yang mengatur keseimbangan cairan dan elektrolit (ACTH). Bentuk dan susunan sel2 dicortex ini berbeda2 sehingga menyebabkan cortex terbagi menjadi 3 zona : zona glomerulosa, zona fasciculata dan zona reticularis. Cortex suprarenalis menghasilkan steroid (glucocorticoid dan mineralocorticoid). Medula suprarenalis menghasilkan adrenalin.

Kelenjar pancreas mempunyai dua bagian yaitu bagian eksokrin yang berupa sel2 acini pancreas, dan bagian endokrin yaitu pulau2 Langerhans yang terletak diantara acini2 pancreas. Pulau Langerhans ini mempunyai sel alfa, sel beta dan sel delta. Sel2 beta pancreas ini memnghasilkan hormon insulin untuk mengatur penurunan kadar glucosa dalam darah. Bila produksi insulin kurang bisa terjadi diabetes mellitus, akibatnya kadar gula dalam menjadi darah tinggi dan keluar bersama urine ( sakit kencing gula), dengan gejala orang banyak makan, banyak minum dan banyak kencing.

Untuk testis dan ovarium dibicarakan bersama sistem genetalia.

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BIOCHEMISTRY OF HORMONE

Module Tasks :

1. Terangkan mengenai klasifikasi hormon

2. Hormon apa saja yang merupakan turunan steroid, jelaskan strukturnya, cara sintesisnya dan fungsi dari hormon tersebut.3. Hormon apa saja yang memerlukan asam amino tyrosin untuk sintesisnya, jelaskan proses sintesis dan fungsinya.

4. Jelaskan tentang sintesis insulin, struktur insulin dan efek ssertacara kerja insulin di dalam sel

5. Jelaskan tentang hormone angiotensin, struktur , sintesisnya dan efeknya terhadap sel

6. Jelaskan tentang POMC family, sistem sintesisnya, dan efek tiap hormon pada tubuh

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MECHANISM OF HORMONE ACTION

By:

dr. Dian Hasanah, M.Biomed

1. Several types of chemical messenger systems:

a. Neurotransmitters are released by axon terminals of neurons into the synaptic junctions and act locally to control nerve cell functions.

b. Endocrine hormones are released by glands or specialized cells into the circulating blood and inuence the function of cells at another location in the body.

c. Neuroendocrine hormones are secreted by neurons into the circulating blood and inuence the function of cells at another location in the body.

d. Paracrines are secreted by cells into the extracellular uid and affect neighboring cells of a different type.

e. Autocrines are secreted by cells into the extracellular uid and affect the function of the same cells that produced them by binding to cell surface receptors.

f. Cytokines are peptides secreted by cells into the extracellular uid and can function as autocrines, paracrines, or endocrine hormones. Examples of cytokines include the interleukins and other lymphokines that are secreted by helper cells and act on other cells of the immune system. Cytokine hormones (e.g., leptin) produced by adipocytes are sometimes called adipokines.

2. The principle differences between endocrine system and nervous system:

The nervous system coordinates rapid, precise responses and is especially important in mediating the bodys interaction with the external environment.

The endocrine system, by contrast, primarily controls activities that require duration rather than speed. It regulates, coordinates, and integrates cellular and organ function at distance.3. The functions of endocrine system:

a. Regulating organic metabolism and H2O and electrolyte balance, which are important collectively in maintaining a constant internal environment.

b. Inducing adaptive changes to help the body cope with stressful situations.

c. Promoting smooth, sequential growth and development.

d. Controlling reproduction.

e. Regulating red blood cell production.

f. Along with the autonomic nervous system, controlling and integrating activities of both the circulatory and digestive systems.

4. Definition of hormone:Hormone is a blood-borne chemical messenger synthesized and released by endocrine gland that act on target cells located a long distance from the location it released.

5. Definition of tropic hormone:Tropic hormone is a hormone that its primary function is to regulate hormone secretion by another endocrine gland.

6. Three general classes of hormones based on their chemical structure:

a. Proteins and polypeptides, including hormones secreted by the anterior and posterior pituitary gland, the pancreas (insulin and glucagon), the parathyroid gland (parathyroid hormone), and many others.

b. Steroids secreted by the adrenal cortex (cortisol and aldosterone), the ovaries (estrogen and progesterone), the testes (testosterone), and the placenta (estrogen and progesterone).

c. Derivatives of the amino acid tyrosine, secreted by the thyroid (thyroxine and triiodothyronine) and the adrenal medullae (epinephrine and norepinephrine). There are no known polysaccharides or nucleic acid hormones.

7. Two classes of hormones based on their solubility in water or lipid:a. Water-soluble hormones (hydrophilic): peptides and catecholamines.

b. Lipid-soluble hormones (lipophilic): steroid and thyroid hormones.

8. The principle differences of synthesis, storage, secretion, and transport of hormones:

a. Protein and Peptide Hormones

Synthesis: Protein and peptide hormones are synthesized on the rough end of the endoplasmic reticulum of the different endocrine cells. They are usually synthesized rst as larger proteins that are not biologically active (preprohormones) and are cleaved to form smaller prohormones in the endoplasmic reticulum. These are then transferred to the Golgi apparatus for packaging into secretory vesicles. In this process, enzymes in the vesicles cleave the prohormones to produce smaller, biologically active hormones and inactive fragments.

Storage: The vesicles are stored within the cytoplasm, and many are bound to the cell membrane until their secretion is needed.

Secretion: Secretion of the hormones (as well as the inactive fragments) occurs when the secretory vesicles fuse with the cell membrane and the granular contents are extruded into the interstitial uid or directly into the blood stream by exocytosis. In many cases, the stimulus for exocytosis is an increase in cytosolic calcium concentration caused by depolarization of the plasma membrane. In other instances, stimulation of an endocrine cell surface receptor causes increased cyclic adenosine monophosphate (cAMP) and subsequently activation of protein kinases that initiate secretion of the hormone.

Transport: The peptide hormones are water soluble. Water-soluble hormones are dissolved in the plasma and transported from their sites of synthesis to target tissues, where they diffuse out of the capillaries, into the interstitial uid, and ultimately to target cells.b. Steroid Hormones Synthesis: The chemical structure of steroid hormones is similar to that of cholesterol, and in most instances they are synthesized from cholesterol itself. Large stores of cholesterol esters in cytoplasm vacuoles can be rapidly mobilized for steroid synthesis after a stimulus. Much of the cholesterol in steroid-producing cells comes from the plasma, but there is also de novo synthesis of cholesterol in steroid-producing cells.

Storage: Steroid hormones are usually not stored.

Secretion: Because the steroids are highly lipid soluble, once they are synthesized, they simply diffuse across the cell membrane and enter the interstitial uid and then the blood. Transport: Steroid hormones are not water soluble, circulate in the blood mainly bound to plasma proteins. Usually less than 10 per cent of steroid hormones in the plasma exist free in solution. Protein-bound hormones cannot easily diffuse across the capillaries and gain access to their target cells and are therefore biologically inactive until they dissociate from plasma proteins.c. Amine Hormones

The two groups of hormones derived from tyrosine, the thyroid and the adrenal medullary hormones, are formed by the actions of enzymes in the cytoplasmic compartments of the glandular cells. i. Thyroid

Synthesis: The thyroid hormones are synthesized in the thyroid gland by the actions of enzymes in the cytoplasmic compartments and incorporated into macromolecules of the protein thyroglobulin. Storage: The thyroid hormone is stored in large follicles within the thyroid gland.

Secretion: Hormone secretion occurs when the amines are split from thyroglobulin, and the free hormones are then released into the blood stream.

Transport: Thyroid hormones are not water soluble. After entering the blood, most of the thyroid hormones combine with plasma proteins, especially thyroxine-binding globulin, which slowly releases the hormones to the target tissues. Protein-bound hormones cannot easily diffuse across the capillaries and gain access to their target cells and are therefore biologically inactive until they dissociate from plasma proteins.

ii. Epinephrine and Norepinephrine

Synthesis: Epinephrine and norepinephrine are formed in the adrenal medulla by the actions of enzymes in the cytoplasmic compartments, which normally secretes about four times more epinephrine than norepinephrine.

Storage: Catecholamines are taken up into preformed vesicles and stored until secreted.

Secretion: Similar to the protein hormones stored in secretory granules, catecholamines are also released from adrenal medullary cells by exocytosis.

Transport: Once the catecholamines enter the circulation, they can exist in the plasma in free form or in conjugation with other substances. Catecholamines are dissolved in the plasma and transported from their sites of synthesis to target tissues, where they diffuse out of the capillaries, into the interstitial uid, and ultimately to target cells. 9. Plasma concentration of a hormone is influenced by:a. Hormone secretion.b. Peripheral hormone conversion.c. Hormone transport.d. Hormone inactivation.e. Hormone excretion.

10. Hormones are cleared from the plasma in several ways, including:

a. Metabolic destruction by the tissues.

b. Binding with the tissues.

c. Excretion by the liver into the bile.

d. Excretion by the kidneys into the urine.

11. Negative feedback:After a stimulus causes release of the hormone, conditions or products resulting from the action of the hormone tend to suppress its further release. In other words, the hormone (or one of its products) has a negative feedback effect to prevent oversecretion of the hormone or overactivity at the target tissue.Positive feedback:

In a few instances, positive feedback occurs when the biological action of the hormone causes additional secretion of the hormone. One example of this is the surge of luteinizing hormone (LH) that occurs as a result of the stimulatory effect of estrogen on the anterior pituitary before ovulation. The secreted LH then acts on the ovaries to stimulate additional secretion of estrogen, which in turn causes more secretion of LH. 12. Hormones in human and their functions:

Thymus Thymosin Enhances T lymphocyte proliferation and function

Skin Vitamin DIncreases absorption of ingested calcium and phosphate

Liver Insulin-like growth factor I (IGF-I)

Thrombopoietin

Hepcidin Promotes growth

Stimulates platelet production

Inhibit absorption of iron into blood

Pineal Melatonin Entrains bodys biological rhythm with external cues; inhibit gonadotropins; its reduction likely initiate puberty; acts as an antioxidant; enhances immunity

References

1. Guyton AC, Hall JE. Textbook of Medical Physiology. 11th Edition. Philadelphia: Elsevier Inc., 2006.2. Sherwood L. Human Physiology From Cells to Systems. 7th Edition. Canada: Brooks/Cole Cengage Learning, 2010.( 5 )

DIAGNOSTIC TESTINGTopik 1: Pemeriksaan laboratorium untuk diabetes mellitus

Pendahuluan: definisi, epidemiologi, klasifikasi DM

Gambaran klinis

Pemeriksaan laboratorium untuk DM:

Diagnostik

Monitoring

Komplikasi

Lain-lain

Pemeriksaan untuk diagnostik: FPG, OGTT, C-peptide

Tes untuk pre-DM dan DM asimptomatik: FPG, OGTT

DM pada anak

GDM

Kontrol glikemik pada DM: HbA1c, fruktosamin, 1,5-AG

Tes untuk komplikasi: CVD, nefropati, koma diabetik, infeksi, ketoasidosis

C peptide, insulin, autoantibodi

POCT-SMBGTopik 2: Pemeriksaan laboratorium hormon tiroid

Rutin: T3, T4, TSH

Algoritma evaluasi hormon tiroid

Pemeriksaan TSH

Tiroiditis autoimun: anti TPO, AIT

Tiroglobulin

Buku acuan:

Burtis CA, Ashwood ER, Bruns DE, Tietz Fundamentals of Clinical Chemistry, Sunders Elsevier, 2008

Kaplan & Pesce, Methods of Clinical Chemistry, 5th ed, 2010

McPherson & Pincus: Henry's Clinical Diagnosis and Management by Laboratory Methods, 21st ed., 2006

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APPROACH TO THE PATIENT WITH ENDOCRINE DISEASE

Endocrine diseases are easily recognizable in their more extreme forms. It is hoped that most patients will be diagnosed well before they progress to that stage; endocrinologists hope to prevent diseases and their sequelae or detect and treat disease at an early stage.Several principles should be considered in evaluating endocrine diseases. Symptoms are often vague and attributable to anxiety or depression or to non-endocrine causes. Early presentation of these disorders can be masked further by compensatory responses. The clinical presentation of a given condition can differ depending on its chronicity, and a severe deficiency state can present as an acute and severe problem in a patient. The clinician must decide whether treatment should be instituted immediately, before time-consuming tests leading to definitive diagnosis have been completed. It is sometimes difficult to arrive at a clear diagnosis, and the procedures needed for definitive diagnosis may impose more risk than the disease over a short period of time, especially if disease manifestations can be managed symptomatically.Efficiency and accuracy of diagnosis are priorities. Modern endocrine testing (including genotyping) often involves considerable cost, but its goal is enhanced efficiency and accuracy of diagnosis. By combining targeted endocrine testing and imaging with a careful history and physical examination and sound clinical judgment, the clinician should be able to diagnose and manage most endocrine diseases.

History & Physical Examination

A carefully performed history and physical examination is critically important. Some diagnoses, such as hypertension, are based on physical examination findings alone. Clinical data gathering should focus on issues that will lead to the diagnosis, help determine how much tissue damage or physical deformity has occurred, and aid in developing a therapeutic plan. Clinical evaluations should help define how long the disease has been present and provide relevant data from the social, family, and past medical histories that will facilitate evaluation and management.

Signs and symptoms of endocrine disorders span the entire clinical spectrum. Manifestations of endocrine disease that are frequently due to non-endocrine or unknown causes (Table 11) include fatigue, malaise, weakness, headache, anorexia, depression, weight gain or loss, bruising, and constipation, and many others.Table 11. Examples of Manifestations of Endocrine Disease. (The Manifestations Do Not Occur in All Cases, and the Severity Can Vary Markedly.)Abdominal painAddisonian crisis; diabetic ketoacidosis; hyperparathyroidism

Amenorrhea or oligomenorrheaAdrenal insufficiency, adrenogenital syndrome, anorexia nervosa, Cushing's syndrome, hyperprolactinemic states, hypopituitarism, hypothyroidism, menopause, ovarian failure, polycystic ovaries, pseudohermaphroditic syndromes

AnemiaAdrenal insufficiency, gonadal insufficiency, hypothyroidism, hyperparathyroidism, panhypopituitarism

AnorexiaAddison's disease, diabetic ketoacidosis, hypercalcemia (eg, hyperparathyroidism), hypothyroidism

ConstipationDiabetic neuropathy, hypercalcemia, hypothyroidism, pheochromocytoma

DepressionAdrenal insufficiency, Cushing's syndrome, hypercalcemic states, hypoglycemia, hypothyroidism

DiarrheaHyperthyroidism, metastatic carcinoid tumors, metastatic medullary thyroid carcinoma

FeverAdrenal insufficiency, hyperthyroidism (severe-thyroid storm), hypothalamic disease

Hair changesDecreased body hair (hypothyroidism, hypopituitarism, thyrotoxicosis); hirsutism (androgen excess states, Cushing's syndrome, acromegaly)

HeadacheHypertensive episodes with pheochromocytoma, hypoglycemia, pituitary tumors

HypothermiaHypoglycemia, hypothyroidism

Libido changesAdrenal insufficiency, Cushing's syndrome, hypercalcemia, hyperprolactinemia, hyperthyroidism, hypokalemia, hypopituitarism, hypothyroidism, poorly controlled diabetes mellitus

NervousnessCushing's syndrome, hyperthyroidism

PolyuriaDiabetes insipidus, diabetes mellitus, hypercalcemia, hypokalemia

Skin changesAcanthosis nigricans (obesity, polycystic ovaries, severe insulin resistance, Cushing's syndrome, acromegaly), acne (androgen excess), hyperpigmentation (adrenal insufficiency, Nelson's syndrome), dry (hypothyroidism), hypopigmentation (panhypopituitarism), striae, plethora, bruising, ecchymoses (Cushing's syndrome), vitiligo (autoimmune thyroid disease, Addison's disease)

Weakness and fatigueAddison's disease, Cushing's syndrome, diabetes mellitus, hypokalemia (eg, primary aldosteronism, Bartter's syndrome), hypothyroidism, hyperthyroidism, hypercalcemia (eg, hyperparathyroidism, panhypopituitarism, pheochromocytoma)

Weight gainCentral nervous system disease, Cushing's syndrome, hypothyroidism, insulinoma, pituitary tumors

Weight lossAdrenal insufficiency, anorexia nervosa, cancer of endocrine glands, hyperthyroidism, type 1 DM , panhypopituitarism, pheochromocytoma

Laboratory Studies

Laboratory tests in endocrine diagnosis are performed to measure hormone levels in body fluids, the effects of the hormone on target cells, or the systemic sequelae of the underlying process. Tests can be done under random or basal conditions, precisely defined conditions, or in response to provocative or suppressive maneuvers. In measuring hormone levels, the sensitivity of the assay refers to the lowest concentration of the hormone that can be accurately detected, and the specificity refers to the extent to which cross-reacting species are scored inappropriately in the assay.

Measurements of Hormone Levels: Basal Levels Plasma & Urine Assays Free Hormone Levels Indirect Measurements of Hormonal Status Provocative & Supression Tests Imaging Studies. these procedures are especially useful for evaluation of tumors of the pituitary and adrenals. Biopsy Procedures

Diagnosis of Genetic Disease

Diagnosis of genetic diseases is facilitated greatly using DNA analyses. Thus, DNA can be obtained from peripheral blood cells, the region of interest can be amplified by PCR, and the gene can be rapidly sequenced. In cases where the mutation is known, these procedures can lead to rapid and accurate diagnosis in the general population or in kind reds with known mutations, such as those with maturity-onset diabetes of the young (MODY), glucocorticoid remediable aldosteronism, or medullary carcinoma of the thyroid.Large-scale sequencing of genes that contribute to a particular disease phenotype can improve diagnosis. For example, MODY is caused by monogenic defects in several different genes (including glucokinase or pancreatic transcription factors) that lead to glucose intolerance and diabetes-like symptoms. Sequencing of possible MODY genes in patientsalong with analysis of other family memberscan distinguish subsets of patients with MODY from those with type 1 diabetes and guide treatment.Treatment of Endocrine Diseases

Hormone deficiency states are usually treated with hormone replacement. In many cases, a reasonable approximation of the normal physiologic status can be achieved by administering the hormone itself or an analog. This approach is effective for treatment of hypothyroidism with thyroxine, adrenal insufficiency with hydrocortisone, and menopausal symptoms with estrogens.

In other cases, there are problems relating to management of replacement hormone levels. Insulin therapy controls hyperglycemia and prevents ketoacidosis in most patients with diabetes mellitus, but long-term complications still occur with most regimens. This results from the fact that we do not replace insulin in an ideal manner. When the hormone is injected subcutaneously, it is not delivered first to the liver, and the kinetics of the injected hormone do not accurately mimic the physiologic release of insulin. Other problems relate to ease of delivery and cost. Recombinant GH is available to treat GH deficiency, but it must be injected and is expensive.

Because many cases of type 1 diabetes mellitus, Addison's disease, hypothyroidism, and several other endocrine deficiency states result from autoimmune destruction of the gland, there is a need to predict the emergence of the condition and to prevent or limit the damage. Measuring the levels of certain antibodies associated with type 1 diabetes mellitus, thyroid disease, and other endocrine deficiency states can predict development of the disorder before major destruction of the gland occurs.

For hormone excess, treatment is ordinarily directed at the primary cause, usually a tumor, autoimmune condition, or hyperplasia. Tumors are removed when possible. It is not possible to halt the autoimmune process that results in hyperthyroidism, so therapy is directed at reducing the secretion of thyroid hormone with pharmacologic blockade, radioiodine therapy, or surgical removal. Hormone production may also be blocked by pharmacologic means in many other instances. For example, with PRL hypersecretion, use of the dopamine receptor agonist bromocriptine is preferred to surgical removal of a small prolactinoma. Octreotide acetate, a somatostatin analog, is sometimes used to block GH hypersecretion. Inhibitors of steroid production such as ketoconazole are sometimes used as an alternative to surgical removal of the steroid-producing tissue. Mineralocorticoid receptor antagonists (Table 12) are used to treat primary aldosteronism, especially when the disorder is due to hyperplasia.Table 12. Examples of Hormone Antagonists Used in Therapy

Antagonist to

Use

Progesterone

Contraceptive, abortifacient

Glucocorticoid

Spontaneous Cushing's syndrome

Mineralocorticoid

Primary and secondary mineralocorticoid excess, hypertension, heart failure

Androgen

Prostate cancer

Estrogen

Breast cancer

GnRH

Prostate cancer

Adrenergic receptor

Hypertension, hyperthyroidism

Prostaglandin

Acute and chronic inflammatory disease

Angiotensin II

Hypertension, heart failure

In many cases, it is necessary to control sequelae of hormone excess by alternative means. Thus, adrenergic receptor blockers are useful to control sequelae of hyperthyroidism, adrenergic blockers to control sequelae of pheochromocytoma, mineralocorticoid antagonists to control blood pressure and hypokalemia in primary aldosteronism, and inhibitors of cholesterol biosynthesis to treat hypercholesterolemia. With hypertension, a number of modalities are available. Examples are angiotensin-converting enzyme inhibitors to block the renin-angiotensin system, calcium channel or adrenergic blockers to inhibit second-messenger signaling, and diuretics to lower blood volume.Dikutip dari : Greenspans Basic and Clinical Endocrinology. Editors : Gardner DG and Shoback D, 9th edition, China : McGraw-Hill, 2011

MODUL TASKS1. Define the term hormone and briefly outline how the endocrine system contributes to homeostasis. 2. Describe how both the anterior pituitary and posterior pituitary glands are regulated by the hypothalamus. 3. Table: The major hormones synthesized and secreted by the pituitary gland.

HormonesMajor target organ(s)Major physiologic effects

Anterior

pituitary

Posterior

pituitary

4. Feedback mechanisms are of major importance in controlling the various body systems and maintaining homeostasis. Describe both positive and negative feedback and discuss one example of each from the endocrine system.5. The adrenal cortex consists of three distinct zones :

Zona glomerulosa Zona fasciculata Zona reticularis Each zone has a characteristic histology and secretes different types of hormones :

LayerNamePrimary Product

Most superficial cortical layer

Middle cortical layer

Deepest cortical layer

6. Hormones secreted by adrenal cortex :

Mineralocorticoid Glucocorticoid and

AndrogenDescribe the metabolic effects of glucocorticoid.

7. Clinical cases and Correlations

A 35-year-old man was admitted to the hospital because of irritability and emotional lability together with muscle weakness and easy fatigability. Physical examination revealed that his trunk was obese but his arms and legs were quite lean. He had a rounded facial appearance and a small, nontender hump at the junction of his neck and back. Fullness was noted in the supraclavicular regions, and purple striae were present in the subaxillary areas. Laboratory examination revealed that the plasma cortisol concentration was elevated (0.55 mmol/L), the fasting blood glucose was 150 mg/dL, and the urinary excretion of 11-hydroxyandrosterone and 11-hydroxyetiocholanolone were greatly increased. A diagnosis of Cushing's syndrome was made. Questions :

a. From what substance is cortisol synthesized? b. How is cortisol synthesis regulated? c. How is cortisol transported in the blood plasma? d. What are the metabolic effects of cortisol in humans?8. Descibe the differences between Cushing disease and Addison disease.