Disorders of Ant. Pituitary (Fisher) Flashcards
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What is monotropic hypopituitarism?
isolated deficiency of GH, LH/FSH, ACTH or TSH
What is polytropic hypopituitarism?
deficiency of GH, LH/FSH, ACTH and TSH in various combinations
What is panhypopituitarism?
anterior and posterior pituitary failure
What is the sequence of hormonal deficiencies following pituitary destruction?
Gonadotropic + GH → PRL + TSH → ACTH
Loss of ___% of the pituitary results in moderate effects.
Loss of ___% of the pituitary results in severe effects.
65-75%
90%
What 4 types of tumors cause hypopituitarism?
- Hypothalamic
- Pituitary
- Parasellar
- Metastatic
What do hypothalamic tumors cause?
secondary hypopituitarism
How do parasellar tumors cause hypopituitarism?
- -may directly compress median eminence or stalk
- -may invade hypothalamus or pituitary
What are 2 causes of Vascular Infarction which cause hypopituitarism?
Sheehan’s Syndrome
Pituitary apoplexy
What is Sheehan’s Syndrome?
Intra- or post-partum pituitary necrosis due to severe blood loss → shock
What is pituitary apoplexy?
intrapituitary hemorrhage caused by tumor compression of vessel walls + redistribution of blood flow
(this results in hypoxic injury, damage to capillary integrity + extravasation of blood from capillaries into tumor)
What are possible outcomes of pituitary apoplexy?
Tumor +/- normal tissue may be completely destroyed, which leads to autocure +/- hypopituitarism
What can occur if bleeding extends superiorly in pituitary apoplexy?
subarachnoid hemorrhage
Sarcoidosis, tuberculosis and post-meningitic fibrosis cause destruction of:
median eminence
Encephalitis can (occasionally) destroy:
hypothalamic nuclei
What types of infiltration may directly damage pituitary cells?
Amyloidosis
hemochromotosis
How can head trauma cause hypopituitarism?
damage to median eminence or stalk
When does idiopathic hypopituitarism occur, and what causes it?
pre-puberty
genetic defects in transcription factors needed for differentiation of anterior pituitary cells
What causes autoimmune hypopituitarism?
chronic inflammation causes pituitary cell destruction from lymphoid infiltrate
What causes primary Empty Sella hypopituitarism?
defect in diaphragm sella, which allows CSF pressure to enlarge sella
What causes Secondary Empty Sella hypopituitarism?
mass (e.g. adenoma) which has been removed by operation, radiation or infarction
What are the hormonal effects of deficient TSH?
↓ T3/T4
What are the hormonal effects of deficient ACTH?
↓ Cortisol
↓ androgens
What are the hormonal effects of deficient LH/FSH?
↓ T
↓estradiol/progesterone (females)
What are the hormonal effects of deficient GH?
↓ somatomedin-C (IgF1)
What is the clinical consequence of deficient TSH?
hypothyroidism
What is the clinical consequence of deficient ACTH?
Hypoadrenalism
What is the clinical consequence of deficient LH/FSH?
Hypogonadism
What is the clinical consequence of deficient GH?
Growth failure
What is the clinical consequence of deficient PRL?
Failed lactation
What are 5 general causes of hypothalamic disorders?
i. Infiltrative Disorders
ii. Mass lesions
iii. Radiation
iv. Infection
v. Trauma
What are the results of pituitary stalk section?
- -DI
- -pituitary hormone deficiency except PL (↑ due to loss of tonic inhibition by dopamine)
What 3 conditions result from hypothalamic lesions, and cause hyperpituitarism?
i. Precocious puberty
ii. Acromegaly
iii. Cushing’s Syndrome
What conditions do prolactinomas cause?
amenorrhea/galactorrhea (women)
impotence/↓libido (men)
What are the hormonal effects of prolactinomas?
↓GnRH ↓LH/FSH ↓T (men) ↓estradiol/progesterone (women) ↑adrenal androgens
What conditions do GH adenomas cause?
acromegaly (adults)
gigantism (children)
What conditions do ACTH adenomas cause?
Cushing’s disease
Nelson’s syndrome
What conditions do mixed GH-PRL cell adenoma cause?
acromegaly
hyperprolactinemia
What conditions do gonadotropin cell adenomas cause?
hypogonadism visual impairment (when large enough due to compression of optic chiasm)
What conditions do TSH adenomas cause?
- -hyperthyroidism
- -thyrotoxicosis
- -acromegaly or hyperprolactinemia (1/3 of cases)
How do TSH adenomas respond to TRH? TSH?
TRH = no response TSH = no suppression
What suppresses TSH adenomas?
glucocorticoids
What is elevated in 85% of patients with TSH adenomas?
alpha subunits
What conditions does pituitary hyperplasia cause?
i. Cushing’s disease
ii. Hyperprolactinemia
What types of ectopic tumors cause Cushing’s?
- ACTH-secreting lung carcinoma
2. CRH-Secreting bronchial adenoma or carcinoids
What type of ectopic tumors causes acromegaly?
GHRH-secreting pancreatic islet tumor or carcinoids
due to secondary GH cell hyperplasia
What hormone increases when GH levels increase?
IgF1
What results from increased levels of IgF1?
- ↑ growth of cartilaginous bones (resulting in prognathism; splaying of teeth; large nose, nasal sinuses, hands/feet)
- ↑ soft tissue mass (resulting in thickened skin + subQ tissue, skin tags)
- sweat gland hypertrophy (↑ sweating)
What results from increased levels of ↑GH and ↑IgF1
- Visceral enlargement (liver, spleen, kidney)
2. Insulin resistance (glu intolerance or DM)
What results from increased levels of ↑GH and ↑PRL
- Galactorhhea
- Hypogonadiam (infertility)
- Acromegaly
What hormones are elevated in and cause Cushing’s?
ACTH
Cortisol
Adrenal Androgen
What are the effects of increased ACTH in Cushing’s?
- Bilateral adrenal hyperplasia with increased plasma cortisol and adrenal androgen
- Loss of diurnal rhythm of ACTH and cortisol
- Increased urinary cortisol
What are the effects of increased cortisol in Cushing’s?
Salt retention Insulin resistance ↑ fat deposits ↓ skin collagen Proximal myopathy Cerebral effects
What are the effects of increased adrenal androgens in Cushing’s?
↓LH/FSH
↑ hair growth + sebum production
↓ libido
Signs/Symptoms of Cushing’s?
obesity HTN glu intolerance menstrual irregularity hirsutism striae dorsal fat pad (hump)
Most common cause of Cushing’s syndrome?
exogenous glucocorticoid ingestion
How is Cushing’s diagnosed?
dexamethasone suppression tests, which evaluate ACTH secretion in response to potent synthetic glucocorticoid
(nml = negative feedback)
When diagnosing Cushing’s, what can low doses of drug distinguish between?
Cushing’s syndrome versus normal hypothalamus/pituitary/adrenal function
When diagnosing Cushing’s, what can high doses of drug distinguish between?
Cushing’s disease versus Ectopic ACTH Syndrome and adrenal tumors
