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ant pituitary agents
lecture 5 hutchison
| Question | Answer |
|---|---|
| metabolic effects of GH | opposes insulin's action & synergistic with cortisol & promotes lipolysis in order to keep glucose levels elevated in serum. some pts with GH deficiency are thus prone to hypoglycemia |
| Laron's dwarfism | severe form of dwarfism where pts have an inactivating mutation of the GH-R. they can achieve improved growth with direct IGF-1 therapy |
| GHRH, produced by the arcuate nucleus | the only hormone that results in the synthesis AND storage of GH. all other agents will only regulate secretion |
| receptor and intracellular signaling mechanism of GH and prolactin | cytokine receptor links to JAK2 kinase/STAT5 signaling system. those with STAT5b mutations will have short stature |
| metabolic effects of IGF-1 | IGF-1 is very similar to proinsulin and can bind the insulin receptor = lowering of plasma glucose levels |
| the single most common pituitary hormone deficiency | GH deficiency b/c the somatotropes are wimpy and the easiest cells to insult/not mature for whatever reason |
| action of somatostatin | inhibits TSH and GH |
| stimulants and inhibitors of GH secretion | stimulants: protein-rich meals, hypoglycemia, stress, exercise, sleep & alpha-adrenergic agents // inhibitors: beta-adrenergic agents, glucose loads, FAs |
| effect of estradiol on the hypothalamus during puberty | stimulates GHRH to be secreted |
| 3 things that essentially make the clinical dx of GH deficiency | low IGF-1 levels, short stature and low growth velocity |
| GH excess is most often caused by: | somatotrope adenoma (that still maintains some of its nl regulation) |
| surgical success rate is < 50% for which type of somatotrope tumors? | macroadenomas. they need adjunct radiation and/or medical therapy to reverse residual GH excess |
| adverse effects of rGH (somatropin aka Genotropin, Humatrope, etc.) | kids: rare and include H/A, slipped capital epiphyses and inc ICP // adults: edema, arthralgias, carpal tunnel syndrome |
| indications for rGH | kids with growth failure from GH def.; long term for Prader-Willi, Turner & Noonan syndromes, CKD, idiopathic short stature, etc.; adults with endogenous GH def. |
| contraindications for rGH administration | having any active malignancy, critically ill pts in ICU setting |
| mecasermin (Increlex) | IGF-1 peptide hormone given SQ BID. approved for GHR mutations in Laron's dwarfism or those with STAT5b mutations. adverse effects: lipohyptertrophy & hypoglycemia. contraindications: neoplasia, adrenal insufficiency |
| octeotride (Sandostatin, Lanreotide) | somatostatin analog with longer half-life, approved for treating acromegaly, portal HTN and GI bleeding. follow with GH, serial IGF-1s and MRIs |
| pegvisomant (Somavert) | PEGylated rGH that blocks GH-R, indicated for pts with acromegaly who haven't responded to surg or octeotride. must watch LFTs, may cause growth of adenoma from loss of feedback inhibition. follow with serial IGF-1s |
| role of dopamine agonists in acromegaly | may paradoxically inhibit GH secretion when the adenoma is of a mixed somatotrope and lactotrope type |
| stimulants for prolactin secretion | estrogen during preg, post-partum state, suckling and breast manipulation by a newborn |
| common etiologies of hyperprolactinemia | pituitary lactotropic adenoma, drugs like Reglan that are D2R antagonists, primary hypothyroidism with elevated TRH |
| indications for bromocriptine (Parlodel) | dopamine agonist used for acromegaly, Parkinson dz, hyperprolactinemia |
| adverse effects of bromocriptine | blunted effects of drugs like Reglan, GI discomfort, n/v, orthostasis & syncope with 1st dose (can be avoided by dosing low then titrating up) |
| cabergoline (Dostinex) | dopamine agonist with better D2R affinity and half-life than bromocriptine |
| heterodimeric glycoprotein hormones | FSH, LH, hCG and TSH all have diff beta subunits that confer specificity for GPCRs that signal using Gs and ad. cyclase/cAMP. LH and hCG have the same receptor |
| action of GnRH | stimulates FSH and LH synthesis and secretion. constant GnRH downregulates the receptor and dec gonadotropin secretion. |
| follicular phase | gonadotropins stimulate follicle growth and estrogen secretion, which stimulates endometrial growth and inhibits gonadotropins. FSH/LH pulses are freq and of small amplitude |
| role of estrogen in ovulation | exerts (+) feedback on the gonadotrope and mid-cycle results in an LH surge |
| luteal phase | progesterone is high & prepares the endometrium for implantation. it feeds back on the pituitary to make gonadotropin surges have inc amplitude but less freq |
| use of LH measurement clinically | measured in urine to detect LH surge that indicates optimal fertilization time |
| use of FSH & LH clinically | precocious or delayed puberty in kids |
| cryptorchidism | testosterone usually direct latter stages of testes descent, hCG can be used to induce descent if there is no anatomical barrier |
| synthetic GnRH | gonadorelin (Factrel) can be used to distinguish btwn GnRH-dependent or independent precocious puberty. Lutrepulse is used for hypogonadotropic hypogonadism, must be delivered in a pulsatile manner |
| leuprolide (Leupron) | GnRH agonist given as depot IM formulation. constant stimulation causes cessation of gonadotropin secretion. indications: chemical castration for breast & prostate ca, endometriosis, central precocious puberty |
| ganirelix (Antagon) | GnRH-R antagonist that shuts off gonadotropin release immediately without the transient inc seen with leuprolide |
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sirprakes
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