Pituitary Phys/Pharm [TRH] Flashcards
What is a sommatotrophic hormone?
A mammotrophic hormone?
Sommatotrophic= growth hormone
mammotrophic= prolactin
Describe the Prolactin axis
- releasing/inhibiting H’s
- final H
- target cells
PROLACTIN
releasing H: prolactin releasing [PRH]
inhibitory H’s: dopamine, GHIH, maybe TRH?
target cells: breast tissue
Describe the Growth H axis
- releasing/inhibiting H’s
- final H
- target cells
GH= somatotropin
releasing: growth H releasing H [GHRH]
inhibitory: GHIH = **somatostatin, **and dopamine
final hormone/3rd endocrine organ: liver–> IGF’s
target cells: many tissues
Somatostatin [side note] acts on what cellular pathway?
[hint: cAMP levels]
SS binds 1 of the 5 SS R’s [SSTR1-5]
- GPCR’s decrease cAMP & activate K+ channels
insulin resistance is observed in which patients?
acromegaly!!!
-and of course, DM2
What does GH deficiency cause in children?
-
proportional dwarfism
- laron syn: autoR GHR variant is insensitive to insulin
- SHOX syn: loss of 1 SHOX copy= in turner syn [short stature girls w/ 45,XO]
- poor nutrition
- stress –> psychogenic dwarfism
- disproportional dwarfism [diff mutations than proportional]
What would you see with GH deficiency in adults?
- generalized obesity
- reduced muscle mass
- asthenia [reduced energy/weakness]
- reduced CO
How do we test for GH deficiencies?
remember GH secretion is pulsatile–> testing is not useful
- measure IGF1 instead
- insulin tolerance test
- glucagon test
- GHRH analog & arginine co-stim test
WHat are the IGF1 test?
and the INsulin test for hyposecretion of GH?
- measure **IGF1 **instead:
- halflife is 12-16hrs, nonpulsatile
- low levels can indicate other DO’s [esp. liver/nutrition]
- levels <2.5th % for age = GH deficit/resistance
-
insulin tolerance test
- give insulin to induce hypoglycemia
- should trigger adrenals to secrete cortisol and ant pit to secrete GH
- failure to respond = may need GH replacement
What is the glucagon test….
and the GHRH analog/arginine co-stimulation test for low GH ?
-
glucagon test:
- give glucagon–> triggers transient hyperglycemia
- triggers subsequent hypoglycemia
- triggers GH release
- **safer **than insulin test
- failure to respond = mayb GH replacement & corticosteroid therapy
-
GHRH analog/arginine co-stim test
- sermoreline is GHRH analog–> triggers GH release
- IV arginine does same thing
- fail to respond w/ elevated GH = ant.pit problem
When would we use GH therapeutically in kids?
What is the goal of this Tx?
- hypopituitarism
- idiopathic short stature
- Turner syndrome growth deficiency
- other SHOX mutations
- trauma
goal= give GH to maintain IGF1 & IGFBP3 levels in normal range for age & gender
WHen would we use GH as a Tx in adults?
What is the goal of this therapy?
- structural hypothalmic/pit
- irradiation/surgery
- trauma
goal= same as w/ kids [maintain normal levels of IGF1 & IGFBP3 appropriate for age & gender]
What things do we monitor when Tx’ing with recombinant human GH [rhGH]?
(Omnitrope, Nutropin, Norditropin, Genotropin, Siazen)
what are some side effects?
monitor:
- IGF1 & IGFBP3 levels
- kids= growth
- adults = lipid profile, fasting glu, bone density
Side effects:
- some pts make antibodies to GH- 30% [lil’ consequence]
- scoliosis during rapid growth
- diabetogenic
If GH Tx fails, what can we try next?
rhIGF!!!
- typically seen in laron-type dwarfism:
- autoR
- GHR variant binds weakly with GH–> low IGF levels
What are low levels of IGF and GH associated with?
longevity
lack of cancer
