Hypothalamus & Pituitary Flashcards
What hormones does the anterior pituitary release
FSH, LH, ACTH, TSH, PRL, GH Those hormones (EXCEPT PRL) go on to stimulate production of hormones from peripheral endocrine glands, liver, or other tissues
What hormones does the posterior pituitary release
Oxytocin, ADH/vasopressin Those hormones (along with PRL) act directly on tissues
What hormones are released from the hypothalamus and what are their funcitons
- GHRH: rarely used as GH/GHRH sufficiency test
- TRH: can dx TRH/TSH deficiency
- CRH: rarely used to dx Cushing
- GnRH: treats infertility caused by deficiency, stops gonad fxn in precocious puberty, men w/ prostate cancer, women undergoing ART, and ovarian suppression for women w/ gyno d/o
- Dopamine: Tx hyperprolactinemia
What is Growth Hormone’s primary target organ hormone
IGF-1
target organs are liver, bone, muscle, kidney, etc.
What provocative pharm GH stimulation tests can you do for GH deficiency
Insulin induced hypoglycemia Clonidine L-dopa Arginine Glucagon GHRH -You expect GH to increase. If GH increases <10 in 2 hours, you have a GH deficiency
What will you likely see along with GH deficiency
reduced IGF-1
hypoglycemia
hypothyroidism
loss of other pituitary hormones
Who should get GH treatment
kids with idiopathic short stature (<2.25 SD below mean height for age)
subnormal growth for age
delayed bone age
low serum IGF-1
*>50% of kids with GH deficiency secrete normal GH and IGF1 as adults
What are treatments for GH deficiency
Somatotropin (Genotropin)
Mecasermin (Increlex)
*Needed for normal growth to regulate lipid and carb metabolism and LBM ; also to regulate production of IGF-1 in peripheral tissues
-CAN switch formulations during Tx w/o negative impacting growth trajectory
Child indications for GH treatment
Short stature (turner, Noonan, or Prader-Willi syndrome)
FTT (2/2 chronic renal failure)
small for gestational age
*Will only add appx 1.5-3 inches if w/ idiopathic short stature
Indications for GH treatment in adulthood
GH deficiency (will improve metabolism, LBM, and well being)
Wasting 2/2 HIV (increase LBM, weight, endurance)
Short bowel syndrome (improve GI fxn)
ADE of Somatotropin (genotropin)
Kids: pseudotumor cerebri (HA, blurred vision, diplopia, n/v), slipped capital femoral epiphysis, scoliosis progression, hyperglycemia
Adults: rarely peripheral edema, myalgia, arthralgia
If a child is taking Somatotropin (genotropin) always monitor
concurrent deficiency of other ant pit hormones
Drug interactions when taking Somatotropin (genotropin) include
glucocorticoids (inhibit growth promoting effects)
Other hormones; androgens, estrogens, thyroid hormones, anabolic steroids (speed up epiphyseal closure, compromising final height)
What is Mecasermin
Recombinant human IGF-1 for kids with growth failure that DON’T respond to GH therapy and are deficient in IGF-1
ADE of Mecasermin include
Hypoglycemia (eat before taking dose!)
Tonsillar/adenoidal hypertrophy
Lymphoid hypertrophy
Coarse facial features
GH secreting pituitary adenomas cause
Acromegaly in adults
Gigantism in kids and teens
TOC for acromegaly is
Pituitary transsphenoidal microsurgery
What diagnostic test is preferred for excess GH
OGTT;
postprandial hyperglycemia inhibits secretion of GH for 1-2 hours
if you give an oral glucose load, GH should decrease
Secondary testing for GH excess is
Serum IGF; GH stimulates IGF-1 production
What pharm treatment options are available for GH excess
Dopamine agonists (bromocriptine, cabergoline) Somatostatin analogs (Octreotide, Lanreotide, Pasireotide)- more effective than dop. ag GH receptor antagonist (Pegvisomant)
Pegvisomant is highly effective at
normalizing IGF-1 in 97% in one year, 60% in 5 years
Dopamine agonists are used mainly to treat
Acromegaly;
they normally cause an increase in GH production. In Acromegaly, they cause a paradoxical DECREASE in GH production
*They also normalize IGF-1 concentrations (cabergoline>bromocriptine)
*Cabergoline can be added to a somatostatin analog
ADE of Dopamine Agonists are
CNS: HA, light headed, dizziness, nervous, fatigue
GI: nausea, abd pain, diarrhea
Resp: nasal congestion, thick bronchial secretions
How do somatostatin analogs (octreotide) work
inhibit release of GH, glucagon, insulin, and gastrin
Tx acromegaly and other neuroendocrine tumors
*long acting forms available; 4-6 wk duration
ADE of Somatostatin analogs (octreotide) are
gallstones (inhibit release of CCK)
cardiac conduction abn
HTN
Abnormalities in glucose metabolism (decrease insulin, inhibits IGF-1)
Subclinical hypothyroid (TSH high, T4 normal)
How does Pegvisomant work
Inhibits IGF-1 production
blocks physiologic effect of GH on tissues
Treats acromegaly in pts who failed to achieve normal IGF-1 with other Tx
ADE of Pegvisomant include
Increased liver enzymes
edema
nausea
diarrhea
What are Raloxifene and Tamoxifen used for
Selective estrogen receptor modulators
Treat persistent acromegaly in men and post-menopausal women with Hx of breast cancer
Reduces and normalizes IGF-1 levels (does not reduce GH)
*Serum testosterone in men increases
What are prolactinomas
benign prolactin secreting pituitary tumors
What can cause hyperprolactinemia
Prolactinomas or Medications (increase PRL or antagonize Dopamine)
What are some drugs that cause hyperprolactinemia
Increase PRL: methyldopa, reserpine; estrogen, benzos, TCA, MAOI, SSRI, opioids, cocaine
Dopamine antag: antipsychotics, phenothiazine, metoclopramide
Verapamil
How do you treat hyperprolactinemia
#1: Dopamine agonist (better than surgery!) Radiation therapy (W/ surgery to shrink tumor and decrease PRL) TSS (if refractory or cant tolerate meds; if very large tumor)
What are the dopamine agonists
Cabergoline (pref), bromocriptine
Inhibit release of PRL (Dop inhibits PRL)
ADE of bromocriptine are
Infertility! HA, dizzy, fatigue, diarrhea, nausea, abd pain
give with food
ADE of cabergoline are
decrease in BP; constipation, n/v, fatigue, anxiety, depression
(rare) HA, dizzy
What is Panhypopituitarism
complete (or partial) loss of pituitary fxn; involves ant and post pit
-ACTH/ Gonadotropin/ GH deficiency, hypothyroidism, hyperprolactinemia
How do you treat panhypopituitarism
Replace glucocorticoids, thyroid hormones, and sex steroids
+/- recombinant GH
**Tx is lifelong w/ constant monitoring!
