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

2.  The deficiency (hypo) of one or more hormones of the pituitary gland  Deficiency of one or multiple hormones of the anterior pituitary …….-hypopituitarism  Deficiency of the posterior lobe …..-central diabetes insipitus  Deficiency of all pituitary hormones….- panhypopituitarism

3.  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.  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.  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.  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.  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.  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.  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.  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.  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.  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. 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.  Infiltrative disorders  Cranial irradiation  Lymphocytic hypophysitis  Pituitary Apoplexy  Empty Sella syndrome

15.  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. Patoloji Radyoloji

17.  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.  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. Radiology

20.  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.  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. Often an incidental MRI finding

23.  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.  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. Radiology

27. 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.  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.  Hypothyroidism  Atrophic thyroid gland

30.  Inability to lactate postpartum  Often 1 st manifestation of Sheehan syndrome

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

32.  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.  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 10 μg/dL  ITT ( 0.1 U/kg BW) Cortisol > 18 μg/dL, normal  Cosyntropin stimulation test Cortisol > 18 μg/dL, normal

34.  Serum T 4 should be measured  TSH may not be helpful

35.  MEN  Testosterone low, LH normal or low  Sperm count  WOMEN  LH-FSH, E 2, vaginal cytology, response to medroxyprogesterone 10 mg qd for 10 days

36.  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.  Cortisol deficiency ( 5 - 2.5 mg prednisone qd)  Levothyroxine ( 0.075 -0.15 mg qd )  Gonadal steroids (E 2,P, Testosterone)  Growth hormone  Vasopressin (desmopressin 10 μg x 2)

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