Growth hormone and somatostatin

Recombinant growth hormone

-GH= somatotropin -recombinant hGH are called *somatotropins* -SC given daily at bedtime -IGF-1 used for patients with GH receptor mutations or antibodies against rhGH

Growth hormone regulation

-GHRH increases release of GH -somatostatin inhibits it -GH goes to bone, liver, adipocyte and muscle and activates IGF-1 -IGF1 goes back and inhibits GH & GHRH -ghrelin from stomach increases GH and inhibits SST >ghrelin elevated in fasting and hypoglycemia, stimulates appetite and food intake

Adverse effects of somatostatin analogs

-diarrhea, nausea, abdominal pain -cholelithiasis and gallbladder sludge -minor adverse effects (reduced insulin secretion and reduced TSH secretion, both mro with pasireotide)

rhGH uses adults

-for most severely affected GH deficiency adults -AIDS associated wasting -malabsorption associated with short bowel syndrome

Excess growth hormone causes Insufficient growth hormone

-gigantism (pre plate closure) -acromegaly (post plate closure) -reduced stature, decreased muscle mass, decreased exercise capacity, decreased bone density, increased cv mortality

rhGH uses

-kids with GH deficiency -has been extended to kids with other conditions associated with short stature (turner, prader willi, idiopathic short stature)

GH function

-multiple diff size proteins -pulsatile release with greatest peak amplitude at night just after onset of deep sleep -circulating GH pulse troughs are undetectable

Insulin like growth factor (IGF 1)

-rhIGF-1 known as mecasermin -used for patients with mutation in GH receptor or antibodies to GH -not as effective as rhGH Side effects: hypoglycemia due to activation of the insulin receptor

end organ effects of GH

-skeletal: increased cartilage formation and skeletal growth -extraskeletal: increased protein synthesis and cell growth and proliferation -fat metabolism: increased fat breakdown and release -carb metabolism: increased blood glucose and other anti insulin effects

Tx for -excess GH -deficient GH

-somatostatin analogs, GH receptor antagonist -recombinant hGH, recombinant hIGF-1

Physiological effects of GH

-stimulates longitudinal bone growth up to time of epiphyseal plate closure -increases bone density after plate closure (prompts differentiation of prechondrocytes to chondrocytes, stimulation of osteoclasts and osteoblasts) -increased muscle mass -increased GFR -potent anti insulin effect to increase glucose utilization (acts on adipocytes to increase lipolysis and on hepatocytes to stimulate gluconeogenesis

Octreotide use Lanreotide

-subcutaneously, 90 min halflife, 12 hour duration -controls acromegaly symptoms -IM injections that last 2 weeks

Other use for somatostatin analogs

-treating symptoms from : metastatic carcinoid tumors (diarrhea/ flushing), vasoactive intestinal peptide secreting adenoma (Diarrrhea) -TSH refuction in patients with thyrotrope adenomas -octreotide coupled to indium or technetium to image neuroendocrine tumors -octreotide coupled to 90Y to destroy SST2 receptor positive tumors

Somatostatin analogs

-used for primary GH suppression -after transphenoidal surfer to suppress activity -octapeptides, octreotide, lanreotide, bind to SST subtypes with selectivity: SST2> SST5> SST3>>> SST1 and SST4 -Pasireotide binds with high affinity to all but SST4 receptor -others non selective

Side effects of growth hormone

-very few in kids -adults: peripheral edema, carpal tunnel syndrome, arthralgias, myalgias

Pegvisomant

GH antagonist -binds to GH receptor, prevents JAK activation and IGF 1 secretion

Octapeptides, octreotide, lanreotide Pasireotide

somatostatin analogs -SST2> SST5> SST3>>> SST1 and SST4 -binds with high affinity to all but SST4 receptor