Hypopituitarism

1. Hypopituitarism Hasan AYDIN, MD Endocrinology and Metabolism Yeditepe University Medical Faculty

2. Definition • The deficiency (hypo) of one or more hormones of the pituitary gland • Deficiency of oneormultiplehormones of theanteriorpituitary …….-hypopituitarism • Deficiency of theposteriorlobe …..-centraldiabetesinsipitus • Deficiency of allpituitaryhormones….- panhypopituitarism

3. Hypopituitarism • Either result from hypothalamus or pituitary • Symptoms and signs frequently protean and nonspecific • Abnormalities in electrolyte levels, • Altered mental status, • Abnormal glucose levels, • Altered body temperature, • Increased heart rate • Patients at risk of developing hypopituitarism • Traumatic brain injury (TBI), • Cocaine use, • Subarachnoid hemorrhage, • Postpartum hypotension (Sheehan syndrome).

4. Hypopituitarism • 76% tumor or treatment of tumor • Mass effect of adenoma on other hormones • Surgical resection of non-adenomatous tissue • Radiation of pituitary • 13% extrapituitary tumor • Craniopharyngioma • 8% unknown • 1% sarcoidosis • 0.5% Sheehan’s syndrome

5. Numbers • In US • Prevelance of pituitary adenoma 10-20% • Hypopituitarism 2-8/100,000 persons/year • World • Incidence of 4.2 cases per 100,000 per year • Prevalence of 45.5 per 100,000 without gender difference

6. Mortality/Morbidity • Missed or delayed diagnosis could potentially lead to permanent disability or death • Female patients with hypopituitarism have more than a 2-fold increase in cardiovascular mortality • Cardiovascular disease is significantly higher among hypopituitary patients (incidence ratio, 3.7; 95% confidence interval) • Hypopituitary patients have lower high-density lipoprotein cholesterol and higher low-density/high-density lipoprotein ratio

7. Hypopituitarism • Primary pituitary disease • Tumors • Pituitary surgery • Radiation treatment • Hypothalamic disease • Functional suppression of axis • Exogenous steroid use • Extreme weight loss • Exercise • Systemic Illness • Interruption of the pituitary stalk • Extrasellar disorders • Craniopharyngioma • Rathke pouch

8. Hypopituitarism • Developmental and genetic causes • Dysplasia • Septo-Optic dysplasia • Developmental hypothalamic dysfunction • Kallman Syndrome • Laurence-Moon-Bardet-Biedl Syndrome • Frohlich Syndrome (Adipose Genital Dystrophy) • Acquired causes: • Infiltrative disorders • Cranial irradiation • Lymphocytic hypophysitis • Pituitary Apoplexy • Empty Sella syndrome

9. Septo-Optic Dysplasia • Hypothalamic dysfunction and hypopituitarism • may result from dysgenesis of the septum pellucidum or corpus callosum • Affected children have mutations in the HESX1 gene • These children exhibit variable combinations of: • cleft palate • syndactyly • ear deformities • optic atrophy • micropenis • anosmia • Pituitary dysfunction • Diabetes insipidus • GH deficiency and short stature • Occasionally TSH deficiency

10. Kallman Syndrome • Defective hypothalamic gonadotropin-releasing hormone (GnRH) synthesis • Associated with anosmia or hyposmia due to olfactory bulb agenesis or hypoplasia • May also be associated with: color blindness, optic atrophy, nerve deafness, cleft palate, renal abnormalities, cryptorchidism • GnRH deficiency prevents progression through puberty • Characterized by • low LH and FSH levels • low concentrations of sex steroids

11. Kallman Syndrome • Males patients • Delayed puberty and hypogonadism, including micropenis • Long-term treatment: • human chorionic gonadotropin (hCG) or testosterone • Female patients • Primary amenorrhea and failure of secondary sexual development • Long-term treatment: • cyclic estrogen and progestin • Repetitive GnRH administration restores normal puberty • Fertility may also be restored by the administration of gonadotropins or by using a portable infusion pump to deliver subcutaneous, pulsatile GnRH

12. Laurence-Moon-Bardet-Biedl Syndrome • Rare autosomal recessive disorder • Characterized by mental retardation; obesity; hexadactyly, brachydactyly, or syndactyly • Central diabetes insipidus may or may not be associated • GnRH deficiency occurs in 75% of males and half of affected females • Retinal degeneration begins in early childhood • most patients are blind by age 30

13. Frohlich Syndrome (Adipose Genital Dystrophy) • A broad spectrum of hypothalamic lesions • hyperphagia, obesity, and central hypogonadism • Decreased GnRH production in these patients results in • attenuated pituitary FSH and LH synthesis and release • Deficiencies of leptin, or its receptor, cause these clinical features

14. Hypopituitarism(Acquired Causes) • Infiltrative disorders • Cranial irradiation • Lymphocytic hypophysitis • Pituitary Apoplexy • Empty Sella syndrome

15. Lymphocytic Hypophysitis • Etiology • Presumed to be autoimmune • Clinical Presentation • Women, during postpartum period • Mass effect (sellar mass) • Deficiency of one or more anterior pituitary hormones • ACTH deficiency is the most common • Diagnosis • MRI - may be indistinguishable from pituitary adenoma • Treatment • Corticosteroids – often not effective • Hormone replacement

16. Lymphocytic Hypophysitis Patoloji Radyoloji

17. Pituitary Apoplexy • Hemorrhagic infarction of a pituitary adenoma/tumor • Considered a neurosurgical emergency • Presentation: • Variable onset of severe headache • Nausea and vomiting • Meningismus • Vertigo • +/ - Visual defects • +/ - Altered consciousness • Symptoms may occur immediately or may develop over 1-2 days

18. Pituitary Apoplexy • Risk factors: • Diabetes • Radiation treatment • Warfarin use • Usually resolve completely • Transient or permanent hypopituitarism is possible • undiagnosed acute adrenal insufficiency • Diagnose with CT/MRI • Differentiate from leaking aneurysm • Treatment: • Surgical - Transsphenoid decompression • Visual defects and altered consciousness • Medical therapy – if symptoms are mild • Corticosteroids

19. Pituitary Apoplexy Radiology

20. Sheehan’s Syndrome • Infarction of pituitary after substantial blood loss during childbirth • Incidence: 3.6% • No correlation between severity of hemorrhage and symptoms • Severe: recognised days to weeks PP • Lethargy, anorexia, weight loss, unable to breast feeding

21. Sheehan’s Syndrome • Typically long interval between obstetric event and diagnosis • Of 25 cases studied: • 50% permanent amenorrhea • The rest had scanty-rare menses • Most lactation was poor to absent • Dx: MRI empty sella turcica

22. Empty Sella Syndrome • Often an incidental MRI finding

23. Empty Sella Syndrome •  Usually have normal pituitary function • Implying that the surrounding rim of pituitary tissue is fully functional • Hypopituitarism may develop insidiously • Pituitary masses may undergo clinically silent infarction with development of a partial or totally empty sella by cerebrospinal fluid (CSF) filling the dural herniation. • Rarely, functional pituitary adenomas may arise within the rim of pituitary tissue, and these are not always visible on MRI

24. Clinical Presentation • Can present with features of deficiency of one or more anterior pituitary hormones • Clinical presentation depends on: • Age at onset • Hormone affected, extent • Speed of onset • Duration of the deficiency

25. Empty Sella Syndrome Radiology

26. SpecificHormoneDeficiencies

27. Gonadotropin Deficiency Women • Oligomenorrhea or amenorrhea • Loss of libido • Vaginal dryness or dyspareunia • Loss of secondary sex characteristics (estrogen deficiency) Men • Loss of libido • Erectile dysfunction • Infertility • Loss of secondary sex characteristics • Atrophy of the testes • Gynecomastia (testosterone deficiency)

28. ACTH Deficiency • Results in hypocortisolism • Malaise • Anorexia • Weight-loss • Gastrointestinal disturbances • Hyponatremia • Pale complexion • Unable to tan or maintain a tan • No features of mineralocorticoid deficiency • Aldosterone secretion unaffected

29. TSH Deficiency • Hypothyroidism • Atrophic thyroid gland

30. Prolactin Deficiency • Inability to lactate postpartum • Often 1st manifestation of Sheehan syndrome

31. Growth Hormone Deficiency • Adults • Often asymptomatic • May complain of • Fatigue • Degrees exercise tolerance • Abdominal obesity • Loss of muscle mass • Children • GH Deficiency • Constitutional growth delay

32. Diagnosis • Biochemical diagnosis of pituitary insufficiency • Demonstrating low levels of trophic hormones in the setting of low target hormone levels • Provocative tests may be required to assess pituitary reserve

33. Diagnosis of Hypocortisolism • Basal ACTH secretion • Cortisol < 3 μg/dL, cortisol deficiency • Cortisol > 18μg/dL, sufficient ACTH • Cortisol > 3 μd/dL but < 18 μg/dL - test ACTH reserve • ACTH reserve • Metyrapone test (750 mg q 4hr for 24 hrs) • Cortisol < 7 μg/dL, 11-deoxycortisol > 10 μg/dL • ITT ( 0.1 U/kg BW) • Cortisol > 18 μg/dL, normal • Cosyntropin stimulation test • Cortisol > 18 μg/dL, normal

34. Diagnosis of Hypothyroidism • Serum T4 should be measured • TSH may not be helpful

35. Diagnosis of Hypogonadism • MEN • Testosterone low, LH normal or low • Sperm count • WOMEN • LH-FSH, E2, vaginal cytology, response to medroxyprogesterone 10 mg qd for 10 days

36. Diagnosis of GH Deficiency • Peak GH response < 5 ng/ml • ITT • Arginine ( 0.5 g/ kgBW i.v.) • L-DOPA ( 0.5 g orally ) • Clonidine ( 0.15 mg orally ) • Glucagon ( 0.03 μg/kg BW s.c. + 40 mg propranolol )

37. Treatment of Hypopituitarism • Cortisol deficiency ( 5 - 2.5 mg prednisone qd) • Levothyroxine ( 0.075 -0.15 mg qd ) • Gonadal steroids (E2 ,P, Testosterone) • Growth hormone • Vasopressin (desmopressin 10 μg x 2)

38. Treatment • Hormone replacement therapy • usually free of complications • Treatment regimens that mimic physiologic hormone production • allow for maintenance of satisfactory clinical homeostasis

39. Hormone Replacement