Hypopituitarism

HYPOPITUITARISM

1. HYPOPITUITARISM Dr . Rasikapriya First year paediatrics

2. OBJECTIVES Introduction Classification Pathophysiology Clinical features Investigation Management

3. PITUITARY GLAND The 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.

4. 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).

5. 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.

6. 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.

7. ETIOLOGY HYPOPITUITARISM CONGENITAL ACQUIRED

8. CONGENITAL Perinatal insults ( eg , traumatic delivery, birth asphyxia) Interrupted pituitary stalk  Absent or ectopic neurohypophysis

9. 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 , from KAL  and  KISS1R  mutations)

10. CONTD.. Developmental central nervous system (CNS) defects: Anencephaly Holoprosencephaly Pituitary aplasia or hypoplasia IDIOPATHIC

11. ACQUIRED CAUSES Any lesion that damages hypothalamus, pituitary stalk or anterior pituitary hormone deficiency . Most common lesion- craniopharyngioma Diabetes insipidus- most frequently seen.

12. BRAIN DAMAGE Traumatic brain injury Subarachnoid hemorrhage Neurosurgery Irradiation Stroke PITUITARY TUMORS Adenomas NON PITUITARY TUMORS Craniopharyngioma Meningiomas Gliomas Chordomas Metastases INFECTION Abscess, Hypophysitis, Meningitis, Encephalitis. INFARCTION Apoplexy, sheehan syndrome AUTOIMMUNE DISORDER Lymphocytic hypophysitis OTHERS Hemochromatosis , Histiocytosis , Empty sella , Perinatal insults

13. Clinical features Congenita l : 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

14. 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

15. 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

16. Common presentation- Hypoglycemia. Jaundice Electrolyte disturbances

17. 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.

18. Contd.. Sexual maturation fails or regression Atropy of gonads with amenorrhea and loss of pubic hair. Growth slows dramatically.

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

20. Evaluation Growth related history and patient physical exam Growth failure Short 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 .

21. GH stimulation test

22. 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: Normal thyroid profile Priming in childern with bone age <10 yrs and delayed puberty BOYS- Testosterone enanthate 100mcg IM 5 days prior to test GIRLS- Ethinyl estradiol 100mcg/day -3 days. INTERPRETATION : <5 ng /ml-Growth hormone deficiency 5-10ng/ml- Indeterminate >10ng.ml- Growth hormone deficiency excluded.

23. MRI MPHD Triad- small anterior pituitary, missing or attenuated pituitary stalk and ectopic posterior pituitary bright spot at base of hypothalamus

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

25. 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.

26. 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 achieved Bone age- boys-16years, girls- 14 years.

27. 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

28. CLINICAL FEATURES Polyuria Urine specific gravity low Polydipsia (excessive drinking) Weight loss Dry skin & mucous membranes Possible hypervolemia, hypotension, electrolyte imbalance

29. 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.

30. 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 )

31. THANK YOU