Pituitary Prolactin and GH Flashcards
Describe the endocrine and non-endocrine roles of the hypothalamus.
non-endocrine functions: regulates temperature, control of autonomic nervous system and appetite by integrating input from higher centers of the brain, ANS and peripheral endocrine feedback
endocrine: serves as a coordinating center for endocrine system, produces hormones that are either stored in the pituitary or regulate activity of the pituitary
Describe the endocrine and non-endocrine roles of the hypothalamus.
non-endocrine functions: regulates temperature, control of autonomic nervous system and appetite by integrating input from higher centers of the brain, ANS and peripheral endocrine feedback
endocrine: serves as a coordinating center for endocrine system, produces hormones that are either stored in the pituitary or regulate activity of the pituitary
What is the role of the hypothalamus? (two differing roles)
non-endocrine functions
List the releasing hormones and inhibiting hormones released by the hypothalamus.
releasing hormones: CRH, GHRH, GnRH, TRH
inhibiting hormones: somatostatin (GH) and dopamine (prolactin)
posterior pituitary: vasopressin, oxytocin
List the releasing hormones and inhibiting hormones released by the hypothalamus.
releasing hormones: CRH, GHRH, GnRH, TRH
inhibiting hormones: somatostatin (GH) and dopamine (prolactin)
posterior pituitary: vasopressin, oxytocin
List the hormones that are released from the anterior pituitary hormones and their respective actions.
FSH and LH -gonad function and hormone production GH: bone and tissue growth PRL: mammary glands ACTH: adrenal cortex TSH: production of thyroid hormones
(posterior pituitary: oxytocin for milk let down and SM in uterus, ADH for kidney tubules)
List the hormones that are released from the anterior pituitary hormones and their respective actions.
FSH and LH -gonad function and hormone production GH: bone and tissue growth PRL: mammary glands ACTH: adrenal cortex TSH: production of thyroid hormones
(posterior pituitary: oxytocin for milk let down and SM in uterus, ADH for kidney tubules)
What are the 5 mechanisms of pituitary hormone excess?
excess stimulation from hypothalamus disruption of inhibition from hypothalamus hyper secretion from pituitary ectopic secretion of pituitary hormones impaired clearance of pituitary hormones
What is the disease conditions associated with each of the anterior pituitary hormones in excess?
prolactin- hyperprolactinemia
GH- gigantism and acromegaly
TSH- TSH secreting tumors (hyperthyroidism?)
FSH/LH- gondotropin-secreting tumors (infertility?)
Lactotrophs and somatotrophs arise from which precursor cell?
lactotrophs and somatotrophs both aries from somatomammotroph (explains why some tumors invovling either cell type are known to secrete both hormones
What effect does prolactin have on gonadal function?
prolactin shuts off ovarian and testicular function producing hypogonadism
What effect does prolactin have on gonadal function?
prolactin shuts off ovarian and testicular function producing hypogonadism by inhibiting the pulsatile release of GnRH from the hypothalamus (inhibiting LH and FSH release)
Describe the secretion of prolactin. When and how is it typically released?
prolactin secretion is pulsatile, 4-14 pulses /24h
secretion also has a bimodal distribution, increasing 60-90 min after onset of sleep with peak levels around 4-7a and lowest around noon
What are the different ways in which prolactin release is inhibited?
*predominant signal from the hypothalamus is inhibitory mediated by DA release
any disruption of the pituitary stalk or blockade of DA receptors will increase prolactin release
What are the different ways in which prolactin release is stimulated?
release is stimulated by thyrotropin releasing hormone (hyperprolactinemia may be seen in hyperthyroidism when TRH levels are high)
estrogen also promotes prolactin release by reducing DA secretion
What are the different ways in which prolactin release is stimulated?
release is stimulated by thyrotropin releasing hormone (hyperprolactinemia may be seen in hyperthyroidism when TRH levels are high)
estrogen also promotes prolactin release by reducing DA secretion, reducing lactotroph sensitivity to DA and increasing lactotroph sensitivity to TRH
What are the different ways in which prolactin release is stimulated?
release is stimulated by thyrotropin releasing hormone (hyperprolactinemia may be seen in hyperthyroidism when TRH levels are high)
estrogen also promotes prolactin release by reducing DA secretion, reducing lactotroph sensitivity to DA and increasing lactotroph sensitivity to TRH
What is a normal prolactin level?
What are physiologic cases of hyperprolactinemia?
++ pregnancy, lactation
nipple stimulation, REM sleep, stress, sexual intercourse, exercise
What are pharmacologic cases of hyperprolactinemia?
DA receptor blockers
antidepressants
estrogen (OC or replacement treatment)
What are pathologic cases of hyperprolactinemia?
prolactinomas, pituitary stalk distruption, primary hypothyroidism, renal failure, intercostal nerve stimulation or chest wall injury
Describe the most common cause of prolactemia.
prolactinoma, a benign tumor (adenoma) of lactroph cells that overproduce prolactin
a secondary cause in any lesion that compresses or damages the hypothalamus or pituitary stalk (interrupts delivery of DA) “stalk effect”
What are the symptoms of prolactinemia? (both direct effects of prolactin and due to hypogonadism)
galactorrhea: mostly in PRE-menopausal women
women: irregular menses, amenorrhea, low libido, infertility due to inoculation, low bone density
men: erectile dysfunction, libido, less muscle mass, less body hair, gynecomastia, infertility due to decreased sperm count and low bone density
mass effect: headache, visual field defects (tunnel vision), cranial neuropathies, hypopituitarism
Describe the most common cause of prolactemia.
prolactinoma, a benign tumor (adenoma) of lactroph cells that overproduce prolactin (accounts for 30% of pituitary tumors and can occur as part of MEN type 1)
a secondary cause in any lesion that compresses or damages the hypothalamus or pituitary stalk (interrupts delivery of DA) “stalk effect”
What are the symptoms of prolactinemia? (both direct effects of prolactin and due to hypogonadism)
galactorrhea: mostly in PRE-menopausal women
women: irregular menses, amenorrhea, low libido, infertility due to inoculation, low bone density
men: erectile dysfunction, libido, less muscle mass, less body hair, gynecomastia, infertility due to decreased sperm count and low bone density
mass effect: headache, visual field defects (tunnel vision), cranial neuropathies, hypopituitarism
How would a pituitary tumor appear on MRI?
hypodense region that often causes the pituitary to swing contralateral to the mass, tumors can also infiltrate laterally or up towards the hypothalamus/ optic chiasm
What level of prolactin secretion would correlate with a microadenoma v. a macroadenoma?
micro adenoma 100-200 ng/mL
macro adenoma >200 ng/mL
(typically)
a prolactin level >200 is almost always indicative of a prolactinoma
What are the first line and secondary treatments available for prolactinomas?
90% of prolactinomas (even giant ones) respond well to DA ANGONists including bromocriptine and carbergoline
20% cases may be cured after 2-5 years of tx.
surgery and radiation is reserved for only refractory cases
What are the first line and secondary treatments available for prolactinomas?
90% of prolactinomas (even giant ones) respond well to DA ANGONists including bromocriptine and carbergoline
20% cases may be cured after 2-5 years of tx.
surgery and radiation is reserved for only refractory cases
What are the potential side effects of dopamin agonists?
generally well tolerated treatment, suggest that patients take before bed due to the possibility of the following adverse effects:
nausea, vomiting, headache, nasal congestion, orthostasis
How does growth hormone act on tissue and bone?
GH stimulates liver to produce insulin-like growth factor (IGF-1) and this is the way that most effects of GH are mediated
How does growth hormone act on tissue and bone?
GH stimulates liver to produce insulin-like growth factor (IGF-1) and this is the way that most effects of GH are mediated
What is the action of GH in children?
GH is an anabolic hormone (remember builds like anabolic steroids)
increases protein synthesis to be used as building blocks
increase lipolysis so lipids can be used as fuel
decreases carb utilization by causing an insulin resistant state
Discuss the effects of GH and IGF-1 on cartilage, bone, visceral organs and skin.
increases bone length or width depending on closure of epiphyseal closure
organomegaly
increased hair growth, sweat gland hyperplasia, thickening of dermis
Discuss the effects of GH and IGF-1 on cartilage, bone, visceral organs and skin.
increases bone length or width depending on closure of epiphyseal closure
organomegaly
increased hair growth, sweat gland hyperplasia, thickening of dermis
Describe how and when growth hormone is secreted.
secretion is pulsatile, 4-11 pulses/hr, esp. at night
**extremely low or undetectable levels between pulses due to short half life (important for diagnostic tests)
Describe how and when growth hormone is secreted.
secretion is pulsatile, 4-11 pulses/hr, esp. at night
**extremely low or undetectable levels between pulses due to short half life (important for diagnostic tests)
What should be measured to gauge GH activity?
IGF-1 levels are relatively stable, having a longer half-life and random sampling is a good way to access GH status
What are the potential side effects of dopamine agonists?
generally well tolerated treatment, suggest that patients take before bed due to the possibility of the following adverse effects:
nausea, vomiting, headache, nasal congestion, orthostasis
What should be measured to gauge GH activity?
IGF-1 levels are relatively stable, having a longer half-life and random sampling is a good way to access GH status
What hormones encourage GH secretion and which inhibit?
GHRH increases secretion, somatostatin decreases secretion
IGF-1 also feeds back to decrease GHRH and GH secretion
Contrast physiologic, pharmacological and pathologic reasons for increased GH.
.
Contrast physiologic and pharmacological reasons for increased GH.
physiological (stress, exercise, REM sleep, fasting)
pharmacologic: anything that decreases blood glucose (insulin induced hypoglycemia, NE, clonidine, estrogen)
What pathological conditions cause increased GH secretion?
pituitary adenomas** or ectopic GHRH secreting tumors (primary excess secretion)
anorexia nervosa, cachexia (low blood sugar)
hepatic/renal failure (clearance)
**most common
How does a GH-secreting pituitary adenoma change the rate at which GH is secreted?
GH remains episodic but frequency, duration and amplitude of GH pulses are random and increased
nocturnal rise in GH and GH response to hypoglycemia is lost
Why is acromegaly difficult to diagnose?
signs and symptoms have insidious onset, official diagnosis is often delayed by at least 5-10 years (by the time disease is physically apparent)
Why is acromegaly difficult to diagnose?
signs and symptoms have insidious onset, official diagnosis is often delayed by at least 5-10 years (by the time disease is physically apparent)
What are the signs and symptoms of acromegaly?
acral enlargement frontal bossing thickening of nasolabial folds large lips and elongated chin widening of digits causing spade-like appearance soft tissue overgrowth hyperhidrosis- sweat/oily skin fatigue arthralgia weight gain parathesias/carpal tunnel hypertrichosifs acanthuses nigricans (sign of insulin resistance) headaches kidney stones (excess Ca++) cardiomegaly
What are the signs and symptoms of acromegaly?
acral enlargement frontal bossing thickening of nasolabial folds large lips and elongated chin widening of digits causing spade-like appearance soft tissue overgrowth hyperhidrosis- sweat/oily skin fatigue arthralgia weight gain parathesias/carpal tunnel hypertrichosifs acanthuses nigricans (sign of insulin resistance) headaches kidney stones (excess Ca++) cardiomegaly
Acromegaly can lead to what other (mostly metabolic) pathologies?
impaired glucose tolerance/diabetes hypertriglyceridemia hypercalciuria cardiac disease/ heart failure sleep apnea (hypertrophy of throat muscles) cooling polyps/colon cancer
What are the best tests for excess GH?
elevated IGF-1 is the best SCREENing test
gold standard diagnostic test is a glucose tolerance test with measurement of GH (normally glucose surprises GH to
What are the best tests for excess GH?
elevated IGF-1 is the best SCREENing test
gold standard diagnostic test is a glucose tolerance test with measurement of GH (normally glucose surprises GH to
What is the initial and second line treatments of GH excess due to pituitary adenoma?
** transsphenoidal surgery
pharmacologic treatment is an option for patients with persistent GH excess after TSS
radiation is only for patients that are refractory to surgical and medical therapies
What are some of the second line pharmacologic treatments available for excess GH?
somatostatin analogs (octreotide and lanreotide) dopamine agonists for co-secretors (bromocriptine and cabergoline GH-receptor antagonist: pegvisomant, drop in IGF-1
