6 causes of acquired hypopituitarism?
1. Pit/hypothal neoplasm 2. trauma 3. cranial radiation 4. sheehan's syndrome 5. infiltrative process 6. pit. apoplexy
what is the most common cause of hypopituitarim in adults?
Why Pituitary Adenomas cause hyposecretion of pituitary hormones in adults?
they exert pressure on pituitary cells; surgical removal can relieve pressure and restore cell function, but may also remove normal pituitary tissue causing more dysfunction
2 exmaples of trauma?
1. neurosurgery done to remove pituitary or hypothalamic tumor 2. fracture at skull base: severs hypothalamic- pituitary stalk
2 facts on cranial radiation?
1. children more readily affected, but adults also 2.pituitary deficiencies may present years after radiation treatment
what is SHEEHAN’S SYNDROME?
infarction of pituitary tissue following post partum bleeding which is so severe that hypotension develops, requiring need for blood transfusions
clinical presentation of sheehan sundrome
most commonly, women have: 1. absence of lactation (causing inability to breast feed) 2. difficulty with breast feeding 3. develop oligo 4. amenorrhea (little or no menses) 5. hyponatremia acutely after delivery ** women may not present with sx until years later
clinical presentation of a pt with lymphocytic hypophysitis
pregnant or postpartum female with severe headache ** means inflammation of the pituitary
Dx of lymphocytic hypophysitis
MRI and head CT scan reveal a pituitary mass
What is pituitary apoplexy?
acute expansion of pituitary gland from hemorrhage
clinical presentation of pituitary apoplexy
1. patients have sudden onset of very severe headache; they also may have visual deficit, and altered mental status 2. patients may have shock because of an abrupt decrease in ACTH which leads to an abrupt decrease in cortisol (cortisol maintains BP by maintaining peripheral vascular tone) 3. surgical decompression is needed
What is seen on imagaing of pituitary apoplexy?
pituitary mass; enlargement
what is the most common presenting feature in adults with pit insufficiency?
hypogonadism-- decreased FSH/LH
hypogonadism causes what in females?
- leads to ovarian hypofunction and decreased estradiol - oligo or amenorrhea (little or no menses); infertility
hypogonadism causes what in males?
- leads to testicular hypofunction and decreased testosterone - decreased libido; infertility
What does growth hormon def. cause in adults?
it is thought that patients develop abnormal body composition with increased fat and decreased muscle and have dyslipidemia with cardiac complications
What clinical features are present with a def in thyroid
- decreased basal metabolic rate - decreased activity of sympathetic nervous system (weight gain; decreased heart rate; cold intolerance; thin, coarse hair; dry skin; mental slowing and depression) children: growth retardation
clinical presentation with Deficiency of prolactin?
inability to lactate after delivery of baby (isolated prolactin deficiency is rare)
Deficiency of adrenocorticotrophic hormone (ACTH)?
- (ACTH): effects result from decreased cortisol release from adrenal cortex - mild, chronic decrease in cortisol level (from chronic deficiency of ACTH): fatigue, weakness, anorexia, weight loss; nausea, occasional hypoglycemia severe, acute decrease in cortisol level (from acute decrease in ACTH: e.g. pituitary apoplexy) shock (cortisol is needed to maintain peripheral vascular tone)
Causes of GH and other pituitary hormones deficient?
tumors that destroy pituitary gland tissue; congenital syndromes ( e.g. Prader-Willi)
causes of isolated GH deficiency?
a. often results from deficiency of growth hormone- releasing hormone (GHRH) b. hereditary: (e.g. abnormal GH gene or GHRH receptor; Laron’s syndrome: failure of response to GH due to abnormal GH receptor) c. unknown cause (idiopathic)
clinical features of growth hormone def in children?
1. marked short stature; hypoglycemia in infancy ( and later tendency toward hypoglycemia); increased truncal fat; delayed bone age (bone age to be discussed) 2. delicate facial features (“Kewpie-doll” appearance); high pitched voice ( compared to other children their age) 3. microphallus in males ( if congenital deficiency in gonadotropin-releasing hormone also exists)
lab testing of severe, congenital GH deficiency
1. decreased insulin-like growth factor 1 (IGF-1): IGF-1 is decreased because GH normally stimulates its production by liver 2. decreased IGF binding protein 3
lab tests for less severe cases of GH deficiency?
1. screening: serum levels of IGF-1 and IGF binding protein 3 are decreased 2. GH stimulation tests with drugs (e.g. insulin, glucagon and clonidine)- recommended to do more than 1 test for increased accuracy of diagnosis these drugs fail to increase GH level as expected (serum GH should be > 10 ug/L) 3. look for deficiency of other pituitary hormones
3 types of GROWTH HORMONE STIMULATION TESTS
Insulin: effectively causes hypoglycemia to stimulate release of growth hormone, but is less commonly used currently due to safety concerns Glucagon: causes transient hyperglycemia, which in turn stimulates endogenous insulin secretion followed by controlled hypoglycemia (safer than insulin test) Clonidine: stimulates GH releasing hormone
other diagnostic tests for growth hormone def?
1. MRI of pituitary and hypothalamus: to look for structural abnormalities/masses as cause for GH deficiency 2. Bone age: a. X-ray of pt L hand & wrist is compared with comparable X-ray in atlas b. if patient’s bone age (determined by atlas) is less then chronological age, this shows: patient’s bone age is delayed; supports lab testing results
GROWTH HORMONE DEFICIENCY: CHILDREN treatment?
- recombinant (biosynthetic) growth hormone treatment is effective especially if given at an early age
clinical presentation of gonad. def in pre-meno adult women?
oligo or amenorrhea( little or no menses ); infertility; decreased vaginal secretions; decreased libido; breast atrophy (which occurs after several years)
clinical presentation of gonad. def in adult males?
decreased libido; infertility; decreased muscle mass (which occurs after several years)
In gonad. def, both females and males will have....
decreased bone mineral density
causes of various hypothalamic/pituitary hormones deficient
1. tumors (destroy or compress pituitary and/or hypothalamic tissue) also: treatment of tumors- surgery; radiation therapy 2. infiltrative lesions: sarcoidosis; hereditary hemochromatosis (iron deposition in pituitary) 3. trauma: fracture of base of skull 4. pituitary infarction (e.g. Sheehan’s syndrome) or hemorrhage into preexisting pituitary adenoma (pituitary apoplexy)
causes: isolated gonadotropin deficiency?
1. excessive prolactin secretion: suppresses LH and FSH release (causes of hyperprolactinemia to be discussed)- elevated prolactin inhibits GnRH 2.hypothalamic dysfunction (decreased gonadotropin-releasing hormone by hypothalamus) ****no structural abnormality of hypothalamus or pituitary note: greater then 1 cause of hypothalamic dysfunction may be present; affected individuals may have a genetic predisposition
diagnosis of decreased FSH/LH?
1. LH, FSH, testosterone, estradiol, and prolactin levels females: low estradiol level with normal or low levels of LH/FSH males: low testosterone level with normal or low levels of LH/FSH note: with normal pituitary function, if the estradiol or testosterone levels are low because of a primary problem in gonads (primary hypogonadism), the LH/FSH levels should be high 2. check for deficiency of other pituitary hormones 3. order MRI to look for tumors
causes of hyperprolactinemia?
1. physiologic: pregnancy and lactation 2. PATHOLOGIC: B. prolactinoma: prolactin secreting pituitary tumor (adenoma) C. hypothalamic-pituitary lesions disrupting stalk: decrease prolactin inhibiting factor (PIF) secreted by hypothalamus D. hypothyroidism E. drugs: certain antipsychotic and antidepressant drugs; cimetidine mechanism: decrease/block binding of prolactin inhibiting factor ( dopamine ) to dopaminergic receptors) F. renal failure
Whata re the sizes of prolactinoma?
1. macroadenoma: equal or greater then 1cm ( in diameter )may have mass effect e.g. decreased vision- bitemporal hemianopsia; headache female: male ratio = 1:1 2. microadenoma: less then 1cm; female:male ratio = 20:1
clinical presentation of hyperprolactinemia in women?
- amenorrhea; infertility; galactorrhea - breast d/c - vaginal dryness; pain on intercourse (dyspareunia); loss of libido; hot flashes; decreased vertebral bone mineral density *post menopausal women often have symptoms related to mass effect like males
Clinical presentation of hyperprolactinemia in men?
impotence; loss of libido; infertility; more likely to have mass effects ( headaches and visual deficit ) due to larger size of tumors at presentation
labs to order to dx hyperprolactnemia?
- serum prolactin (20-200-- any cause is possible; greater then 200-- prolactinoma) - serum TSH and free T4 - metabolic panel (assess for chronic renal failure) - MRI
What is the cuase of hyperceretion of GH?
most cases due to pituitary adenomas: most only secrete GH; some secrete both GH and prolactin
clinical findings of hypersecretion of GH?
1. gigantism 2. acromegaly
What is gigantism?
children and adolescents (is very rare). GH hypersecretion occurs before epiphyseal closure in long bones Clinical Features: 1. increased height (may be 8 feet or more as adults) 2. prominent jaw; enlarged hands and feet 3. behavioral and visual problems (in some patients)
What is acromegaly?
Clinical Features A. soft tissue swelling (coarse facial features with prominent forehead and jaw; large fleshy nose; increased shoe and glove size; ring tightening; swelling in pharynx and larynx can cause sleep apnea) B. carpal tunnel syndrome C. joint symptoms due to enlargement of synovial tissue and cartilage (e.g. at knees, ankles, hips, spine): back pain D. kyphosis E. enlargement of heart F. symptoms associated with hyperprolactinemia if pituitary adenoma secretes both GH and prolactin
What is the life expentancy of a pt wth acromegaly?
life expectancy is 10 years less than age matched control population unless GH levels are controlled
major causes of morbidity and mortality in a pt wth acromegaly?
cardiovascular- cardiomyopathy; left ventricular hypertrophy; hypertension; arrhythmias; congestive heart failure other complications: diabetes and cancer
lab testing for acromegaly?
Laboratory testing A. screening: increased insulin-like-growth factor - 1 ( IGF- 1 ) level because GH stimulates production of IGF-1 B. confirmation test: oral glucose load ( 75gm ) should suppress GH secretion pos. test if GH fails to be suppressed (GH level fails to decrease to 1ng/mL or less within 2 hours)
What is a pituitary cause of increased ACTH release?
ACTH secreting pituitary adenoma (50 perc are microadenomas and cause b/l hyperplasia)
clinical signs and sx of cushings syndrome?
A. protein breakdown within peripheral supportive tissue results in the following (1.muscle weakness ( proximal ) 2. easy bruising ( due to thin skin and increased capillary fragility )3. wide, depressed, red skin striae (“stripes”) 4. osteoporosis---bone fractures B. abnormal fat distribution (1. truncal obesity (increased mesenteric fat) 2. "buffalo hump" (increased interscapular fat) 3. "moon facies" (fat in upper face) C. hypertension D. signs related to increased level of adrenal androgens: amenorrhea; hirsuitism (only in some patients) E. fatiguability and weakness F. plethora ( redness of face ) G. personality changes ( emotional disturbances; psychoses ) H. diabetes mellitus (