HYPOPITUITARISM

Dr. RasikapriyaFirst year paediatrics

OBJECTIVES

• Introduction• Classification• Pathophysiology• Clinical features• Investigation • Management

PITUITARY GLANDThe pituitary is located at the base of the brain, in a small depression of the sphenoid bone (sella turcica).• Purpose: control the activity of many other endocrine glands.“ Master gland”• Has two lobes, the anterior & posterior lobes.

HYPOPITUITARISM

• Hypopituitarism- denotes 1. Underproduction of GH alone 2. In combination with deficiencies of other

pituitary hormones.• Incidence – 1 in 4000- 1 in 10000 live births

( as per Nelson).

Contd…

• Hypopituitarism occurs when the anterior (front) and posterior lobes of the pituitary gland loses its ability to make hormones, resulting in multiple pituitary hormone deficiencies. Physical symptoms depend on which hormones are no longer being produced by the gland.

GH Dwarfism, Lethargy, Premature aging

ACTH Addison’s disease

TSH Decrease in BMR,HR,CO,BP.Cretinism

PROLACTIN Too little milk

FSH Late puberty, Infertility

LH Amenorrhea, Impotence

OXYTOCIN Prolonged labour, Diminished milk

ADH(VASSOPRESSIN) Diabetes insipidus, Dilute urine and Increased urine output.

ETIOLOGY

HYPOPITUITARISM

1. CONGENITAL2. ACQUIRED

CONGENITAL

• Perinatal insults (eg, traumatic delivery, birth asphyxia)

• Interrupted pituitary stalk • Absent or ectopic neurohypophysis

CONTD..

Genetic disorders:• Isolated GH deficiency types IA, IB, II, III• MPHD (eg, from PIT1 and PROP1 mutations)• Septo-optic dysplasia• Isolated gonadotropin deficiency (eg,

fromKAL and KISS1R mutations)

CONTD..

Developmental central nervous system (CNS) defects:

• Anencephaly• Holoprosencephaly• Pituitary aplasia or hypoplasia

IDIOPATHIC

ACQUIRED CAUSES

• Any lesion that damages hypothalamus, pituitary stalk or anterior pituitary hormone deficiency .

• Most common lesion- craniopharyngioma• Diabetes insipidus- most frequently seen.

BRAIN DAMAGE Traumatic brain injurySubarachnoid hemorrhageNeurosurgeryIrradiationStroke

PITUITARY TUMORS Adenomas

NON PITUITARY TUMORS CraniopharyngiomaMeningiomasGliomas Chordomas Metastases

INFECTION Abscess, Hypophysitis, Meningitis, Encephalitis.

INFARCTION Apoplexy, sheehan syndrome

AUTOIMMUNE DISORDER Lymphocytic hypophysitis

OTHERS Hemochromatosis, Histiocytosis, Empty sella, Perinatal insults

Clinical featuresCongenital :Growth and development:• Birthweight: near-normal• Birth length: may be slightly decreased• Postnatal growth: severe growth failure• Bone age: delayed, but may be advanced relative to

height age• Genitalia: micropenis in childhood; normal for body

size in adults• Puberty: delayed 3-7 yr• Sexual function and fertility: normal• Craniofacies

• Hair: sparse before the age of 7 yr• Forehead: prominent; frontal bossing• Skull: normal head circumference; craniofacial

disproportion due to small facies• Facies: small• Nasal bridge: hypoplastic• Orbits: shallow• Dentition: delayed eruption• Sclerae: blue• Voice: high pitched

• Musculoskeletal/metabolic/miscellaneous• Hypoglycemia: in infants and children; fasting

symptoms in some• adults• Walking and motor milestones: delayed• Hips: dysplasia; avascular necrosis of femoral

head• Elbow: limited extensibility• Skin: thin, prematurely aged• Osteopenia

• Common presentation- Hypoglycemia.• Jaundice • Electrolyte disturbances

ACQUIRED• TUMORS- headache, vomiting, visual

disturbance, pathologic sleep patterns, decreased school performance, seizures, polyuria and growth failure.

• Craniopharyngioma- visual field defects, optic atrophy, papilledema and cranial nerve palsy.

• Loss of weight, asthenia, sensitivity to cold, mental torpor and absence of sweating.

Contd..

• Sexual maturation fails or regression• Atropy of gonads with amenorrhea and loss of

pubic hair. • Growth slows dramatically.

INVESTIGATION

• CRITERIA FOR GROWTH FAILURE:1. Height < 1 percentile for age and sex2. Height > 2 SD below sex adjusted mid parent

height.

Evaluation Growth related history and patient physical exam

Growth failureShort stature

Imaging CT and MRI

Laboratory Measurement of GH, IGF-1 and IGF-1 binding protein levels.Determination of peak GH levels after stimulation test

Special testing Family history and genetic analyses

Other functions Levels TSH, free thyroxin, ACTH, Cortisol, Gonadotropines, Gonadal steriods.

GH stimulation test

Contd..TEST PROTOCOL LEVELS SPECIFICITY

Exercise 10 mins 0,10,20, mins 50%

Insulin 0.05-0.1 U/kg 0,30,60,90 mins 85%

Clonidine 0.15mg/m2 0,30,60,90 mins 80%

GHRH 1mcg/kg -30,0,30,45 mins 95%

PREREQUISITES FOR GH STIMULATION:1. Normal thyroid profile2. Priming in childern with bone age <10 yrs and delayed pubertyBOYS- Testosterone enanthate 100mcg IM 5 days prior to testGIRLS- Ethinyl estradiol 100mcg/day -3 days.INTERPRETATION:<5 ng/ml-Growth hormone deficiency5-10ng/ml- Indeterminate>10ng.ml- Growth hormone deficiency excluded.

MRI

MPHDTriad- small anterior pituitary, missing or attenuated pituitary stalk and ectopic posterior pituitary bright spot at base of hypothalamus

TREATMENT

• Recombinant h GH- 0.18-0.3 mg/kg/week• Higher dose – puberty.• Subcutaneously 6 to 7 divided doses.• Maximum response- 1st year treatment.

Contd..

• Recombinant IGF-1 – SC , 2 divided doses.• In MPHD- other hormonal deficiencies• TSH deficiencies- thyroxin• ACTH deficiencies- hydrocortisone • Infant with micropenis- 1 -2 (3 months course)

25 mg testosterone cypionate or testosterone enanthate.

FOLLOW UP

• CLINICAL- Height velocity and Z score for height.

• Blood sugar, TSH, bone age- yearly• After puberty- bone age 6 monthly

• DISCONTINUATION OF TREATMENT:Target height is achievedBone age- boys-16years, girls- 14 years.

Diabetes Insipitus

• DI is usually insidious but can occur with damage to the hypothalamus or the pituitary. (neurogenic DI)

• May be a result of defect in renal tubules, do not respond to ADH (nephrogenic DI)

• Decreased production or release of ADH results in massive water loss

• Leads to hypovolemic & dehydration

CLINICAL FEATURES

PolyuriaUrine specific gravity lowPolydipsia (excessive drinking)Weight lossDry skin & mucous membranesPossible hypervolemia, hypotension, electrolyte imbalance

DIAGNOSTIC TESTS

• Serum sodium • Urine specific gravity • Serum osmolality • Urine osmolality • Serum ADH levels• Vasopressin test and water deprivation test:

increased hyperosmolality is diagnostic for DI.

TREATMENT

Medical management includes• Rehydration IV fluids (hypotonic)• Symptom management• ADH replacement (vasopressin)• For nephrogenic DI: thiazide diuretics,

mild salt depletion, prostaglandin inhibitors (i.e. ibuprophen)

THANK YOU