Hypothalamic & Pit Hormones - DONE Flashcards
Release of pituitary hormones is mediated by _____.
hypothalamic control and feedback regulation
Hypothalamic-pituitary-endocrine gland systems governs systmic functions such as…..
metabolism, growth, and reproduction
Which pituitary hormone is NOT influenced by the hypothalamus?
prolactin
What inhibits GnRH, LH, & FSH via feedback inhibition?
estrogen and progesterone in women
androgens in men
What negatively regulates both TRH & TSH?
T4 & T3
____ negatively regulates both CRH and ACTH
cortisol
Release of GH is prevented by…..
somatostatin, GH, & IGF-1
Release of PRL is inhibited by ____
dopamine (D2 receptors)
Which hormone is a 191 amino acid peptide with 2 disulfide bridges?
GH
Endogenous GH has a half life of _______ and is metabolized by the ____.
20-25 min
liver
What is the primary peripheral effecto required during childhood and adolescence for normal growth?
IGF-1
Where is IGF-1 produced?
bone, cartlage, muscle, and kidney
what promate longitudinal bone growth until epiphyses close at the end of puberty?
IGF-1
What does a deficiency in GH during development (childhood to adolescence) result in?
- short stature
- increased body fat mass
- decreased lean muscle mass
Where does GH have catabolic effects?
in lipids (decreases adiposity)
What are the effects of GH on insulin?
- GH reduces insulin sensitivity
- IGF-1 has insulin-like effects
- Defective GH receptors shift balance to IGF-1 dominated effects (decreased insulin and lower serum glucose)
How is GH deficiency diagnosed?
- growth rate <4 cm per year
2. NO serum GH response to 2 secretagogues
A 35 year old male come to the clinic of feeling tired all the time. Upon physical exam you find he has generalized obesity, reduced muscle mass, asthenia, and reduced cardiac output. What do you suspect is wrong with this patient and how would you treat it?
Adult GH deficiency
tx: GH
autosomal dominant disease associated with growth failure, obesity, and carbohydrate intolerance
Prader-Willi syndrome
What are some toxicity and contraindications for GH?
- hypothyroidism (common)
- pancreatitis
- gynecomastia
What are the major side effects of GH in children?
intracranial HTN (vision changes, HA, N/V)
What are side effects of GH therapy that are more common in adults?
- edema
- myalgia
- arthralgia (hands & wrists)
What is rarely used in critically ill patients because it can increase mortality?
GH
GH producing cells in the ant. pit. tend to form ______.
secreting tumors (leads to acromegaly most commonly)
A 40 yr old female comes to the clinic presenting with abnormal growth of cartilage and bone, with complaints of noticing her shoe size and ring size getting larger. Upon further investigation you notice she also has cardiomegaly and hepatomegaly. You determine she has…..
acromegaly
What inhibits the release of GH, glucagon, insulin, and gastrin?
somatostatin
what is the half life of somatostatin?
1-3 minutes
What is the most widely used somatostatin analog?
octreotide
What is octreotide indicated use for?
acromegaly, carcinoid syndrome, gastrinoma, glucagonoma, watery diarrhea, hypokalemia, achlorhydria syndrome, diabetic diarrhea
what is the half life of octreotide?
80 min
This medication is a long acting somatostatin analog, approved for treatment of acromegaly, and has a similar profile to octreotide.
lanreotide
This hormone directs ovarian follicular development.
FSH
Which hormones re needed for ovarian steroidogenesis?
FSH & LH
What stimulates androgen production by the theca cells of the ovary during the follicular stage of the menstrual cycle?
LH
Which hormone stimulates the conversion of androgens to estrogens in granulosa cells?
FSH
What is the primary regulator of spermatogenesis?
FSH
What hormone is the main stimulus of testosterone production by Leydig cells?
LH
purified human FSH from urine of postmenopausal women
urofollitropin
recombinant FSH preparations that are identical in AA sequence to human FSH and has a shorter half life than purified FSH and more expensive.
folitropin alpha or beta
recombinant form of human LH that has been approved for used wth follitropin alpha for follicular development in infertile women with extreme LH deficiency
Lutropin alpha (it was withdrawn in July 2012)
recominant hCG = _____
choriogonadotrpin alpha
Hypogonadal infertility in men requires administration ______
gonadotropins for sperm maturation
what is the primary adverse affect women have to worry about with the use of gonadotropins and hCG?
ovarian hyperstimulation syndrome
describe the dual regulation of gonadotropin release.
- stimulation - caused by PULSATILE release of GnRH
2. inhibition - caused by SUSTAINED, NONPULSATILE release of GnRH
____ = acetate salt of synthetic human GnRH
Gonadorelin
Name the 5 synthetic GnRH analogs
- Goserelin (sq or iv)
- histrelin (sq or iv)
- Leuprolide (sq or iv)
- nafarelin (intranasally)
- Triptorelin (sq or iv)
Describe the biphasic response to constant GnRH analog administration.
- first 7-10 days - initial “flare” where LH & FSH release is increased.
- sustained response - after “flare” the serum concentrations of gonadotropin and gonadal steroids decreases.
What are the adverse side effects of GnRH and its analogs?
induces menopause like symptoms (hot flashes, sweats, HA), depression, diminished libido, generalized pain, vaginal dryness, breast atrophy, decreased bone density
How do GnRH agonists aid in overcoming female infertility?
it can be used to initiate LH surge and ovulation in women undergoing IVF
What can pulsatile administration of GnRH agonist treat in men?
hypothalamic hypogonadotrophic hypogonadism (though not common)
How can the use of GnRH agonists be helpful in the diagnosis of LH responsiveness?
- Admin of GnRH can distinguish if hypogonadotropic adolescence is due to hypothalamic or pit. dz.
- admin should increase serum LH >15.6 miU/ml is suggest of dz
What are GnRH agonists useful for in the inhibition of gonadotropin production?
- controlled ovarian hyperstimulation
- endometriosis
- uterine fibrosis
- prostate cancer
- central precocious puberty
- ovarian & breast cancer
How is ovarian hyperstimulation controlled by GnRH agonists?
the use of leuprolide or nafarelin to suppress endogenous LH surge in IVF procedures
Which GnRH agonists are approved to suppress ovarian steroidogensis?
leuprolide, goserelin, & nafrelin (limited to 6 mth use due to decrease in bone density)
How are GnRH agonists used clinically for prostate cancer?
used in combination with an androgen receptor antagonist to “chemically castrate” and to reduce testosterone production
What are the 3 GnRH antagonists?
- ganirelix
- cetrorelix
- degarelix
GnRH antagonists ____ gonadotropin production
suppress
What are the effect of GnRH antagonists similar to?
sustained administration of a GnRH agonist
In patients with advanced prostate cancer where GnRH agonist was not appropriate, what drug can be used?
degarelix
Which hormone is produced in the ant. pit. and mediate lactation?
PRL
PRL elevation is caused by…..
PRL secreting tumors (hyperprolactinemia)
PRL release is inhibited by….
dopamine receptor agonists
What are two dopamine receptor agonists that are used to treat hyperprolactinemia?
bromocriptine and cabergoline
what causes contraction of uterine smooth muscle and milk ejection in lactating women?
oxytocin
what is administered IV for initiation and augmentation of labor?
oxytocin
How do variations in dose of oxytocin affect labor?
- small doses increase frequency and force of contraction
- large doses produce a sustained contraction
What is administered IM or IV for postpartum bleeding?
oxytocin
What are contraindications of the use of oxytocin?
- fetal distress
- prematurity
- abnormal fetal presentation
- cephalopelvic disproportion
- predisposition to uterine rupture
what is release in response to increased plasma tonicity or decreased BP?
ADH
lack of ADH production or renal insensitivity resulting in excretion of large amounts of dilute urine
DI
What are the vasopressin receptors and where are they located and what is there fxn?
V1 - vascular sm. muscle cells and mediate constriction
V2 - renal tubule cells, increase water permeability and increase water resorption in collecting tubules (reduce diuresis)
long acting synthetic analog of vasopressin with minimal V1 activity and antidiuretic
desmopressin
What are the TOC for pituitary DI?
vasopressin and desmospressin
What are the adverse effects of vasopressin and desmopressin?
HA, nausea, abdominal cramps, agitation, allergic rxn (rare)
What are the vasopressin antagonists?
conivaptan (IV) and tolvaptan (PO)
conivaptan and tovaptan are approved for use in ______
hyponatremia