Pituitary excess syndromes Flashcards
What hormones work on the hypothalamus by negative feedback regulation?
hormones from target glands, ex estrogen, testosterone, thyroxine, cortisol
What hormones are “releasing” hypothalamic hormones?
TRH, GnRH, CRH, GHRH
What hormones are “inhibiting” hypothalamic hormones
somatostatin, dopamine
List the anterior pituitary hormones
ACTH, GH, PRL, FSH, LH, TSH
List the posterior pituitary hormones
vasopressin/ ADH and oxytocin
Describe in general the mechanisms of syndromes of excess pituitary hormones
- hypersecretion by pituitary
- ectopic secretion of pituitary hormones
- disruption of inhibitory signals (ex stalk effect)
- excess stimulatory signals for pituitary hormone release
- impaired renal clearance
Prolactin is secreted in a ____ and ____ fashion, with highs around 5 am and lows around noon
bimodal, pulsatile
Prolactin is under tonic _____ control
inhibitory control by dopamine
How does dopamine inhibit prolactin secretion
- syntehsized in tuberoinfundibular neurons, transported into hypophyseal portal circulation
- reaches anterior pituitary, interacts with inhibitory G protein coupled receptors on lactotrophs
What factors stimulate prolactin release?
- TRH- ex the cause of hyperprolactinemia in people with primary hypothyroidism
- estrogen: lowers lactotroph sensitivity to inhibition by dopamine, decreases dopamine secretion, increases sensitivity to TRH stimulation
List physiologic effects of prolactin
- inhibits GnRH, thus leading to decreased LH/FSH and decreased gonadal function
- stimulates milk production
List physiologic causes of hyperprolactinemia
pregnancy lactation nipple stimulation stress REM sleep sex exercise
List pharmacologic causes of hyperprolactinemia
dopamine receptor antagonists
antidepressants
estrogen
List pathologic causes of hyperprolactinemia
prolactinoma pituitary stalk disruption- stalk effect primary hypothyroidism renal failure intercostal nerve stimulation ex chest wall injury
A prolactin level of greater than 200 is almost always indicative of a __________
prolactin secreting tumor
List the major symptoms of hyperprolactinemia
- gonadal dysfunction: infertility, amenorrhea, decreased libido, ED, loss of body hair, reduced muscle mass, gynecomastia
- galactorrhea- most common in pre-menopausal women
- mass effect: headaches, visual changes
Why are do men and post-menopausal women not usually experience galactorrhea in hyperprolactinemia?
need estrogen to sensitize breast tissue to the effects of prolactin
Prolactinomas arise from monoclonal expansion of a single ________ after having undergone mutation
lactotroph
Up to 10% of prolactinomas co-secrete GH because they are made up of lactotrophs and _______
somatotrophs
What is first line treatment of prolactinomas?
dopamine agonists such as bromocriptine or cabergoline
What are the side effects of dopamine agonist therapy?
NV, headache, congestion, orthostasis
______ is reserved for patients with prolactinomas that are refractory to dopamine agonist treatment
surgery, radiation
Describe the major physiological functions of growth hormone
- linear growth in children
- lipid, protein, carb metabolism in adults; protein sparing effects- increased protein synthesis and lipolysis
Many GH effects are mediated by _____
IGF-1
Contrast the effects of GH vs IGF-1 on carbohydrate metabolism
IGF-1 increases glucose uptake peripherally, decreases hepatic glucose output, and decreases lipolysis.
GH increases insulin resistance, decreases peripheral glucose utilization, and increases hepatic glucose output.
Both GH and GHRH stimulate _____ release
somatostatin
List physiologic causes of GH excess
stress
exercise
REM sleep
fasting
List pharmacologic causes of GH excess
insulin induced hypoglycemia
norepinephrine
clonidine
estrogen
List pathologic causes of GH excess
pituitary adenomas ectopic GHRH secreting tumors anorexia nervosa hepatic/ renal failure cachexia
Pituitary adenoma is the most common cause of ______ and _______
acromegaly, gigantism
Describe the pattern of GH secretion in acromegaly
still episodic but increased number, duration, frequency, amplitude of spikes
loss of response to hypoglycemia/ hyperglycemia
List the clinical manifestations of GH excess
acral enlargement soft tissue overgrowth hyperhidrosis fatigue arthralgias weight gain paresthesias acanthosis nigricans HTN renal stones cardiomegaly impaired glucose tolerance
_____ is a good screening test for GH excess because its levels are not affected by food intake or time of testing
IGF-1
What treatments are used for GH secreting pituitary adenomas?
- trans-sphenoidal surgery
- somatostatin analogue ex octreotide
- dopamine agonists (generally less effective)
- GH receptor antagonists- still high body level of GH but decrease in GH mediated actions
