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Flashcards in Hypothalamic & Pituitary Hormones Deck (51)
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1

GH / ____, predominantly required during ___ 

its effects are medated by ____ 

GH / somatotropin, predominantly required during childhood 

its effects are medated by IGF-1 

 

 

 

2

GH mediates effects via cell surface receptors that activate ____ signaling cascades

GH mediates effects via cell surface receptors that activate JAK/STAT signaling cascades

3

GH Physiological effects 

  • Stimulation of longitudinal growth of bones
  • Increased bone mineral density
  • Increased muscle mass (in GH deficient people)
  • Increased GFR
  • Stimulation of preadipocyte differentiation into adipocytes
  • Anti-insulin actions (hyperglycemia) (decreased glucose utilization & increased lipolysis)
  • Development & increased function of immune system

4

GH deficiency 

  • Genetic or damage to pituitary or hypothalamus
  • Short stature and adiposity (in children)
  • Hypoglycemia (unopposed insulin action)
  • Criteria for Dx
    • A growth rate < 4cm per year, and
    • the absence of a serum GH response to two GH secretagogues

5

Recombinant GH = ____ 

GH analog = ____

Recombinant GH = Somatropin 

GH analog = Somatrem

6

Clinical use of Somatropin

  • Growth failure in children (turner XO, Prader Wili) 
  • GH deficiency in adults
    • improves metabolic state, increased lean body mass, sense of well-being
  • Hasting in HIV+ pts
    • increased lean body mass, weight, physical endurance 
  • Short bowel syndrome in pts receiving specialized nutrional support 
    • improved GI function

7

Somatotropin/Somatrem AEs in children 

  • Generally well tolerated
  • Scoliosis (during rapid growth)
  • Hypothyroidism
  • Intracranial hypertension (rare)
  • Otitis media (increased risk for Turner Syndrome patients)
  • Pancreatitis, gynecomastia & nevus growth
  • Diabetic syndrome (chronic use)

8

Somatotropin/Somatrem AEs in adults 

  • Peripheral edema, myalgias & arthralgias (hands & wrists especially)
  • Carpal tunnel syndrome
  • Proliferative retinopathy (rare)

9

Somatotropin/Somatrem contraindications

  • Cytochrome P450 inducer
  • Patients with a known malignancy
    • can increase tumor growth 

10

Small number of children with growth failure have ____deficiency

Analog of this? 

Small number of children with growth failure have IGF-1 deficiency 

Analog: Mecasermin

11

Mecasermin AEs

  • Hypoglycemia (eat 20 min before or after admin.)
  • Intracranial hypertension (rare)
  • Asymptomatic elevation of liver enzymes (rare)

12

Small GH-secreting adenomas can be treated with GH antagonists (3) 

 

  • GH receptor antagonist → Pegvisomant
  • Somatostatin analogs → Octreotide
  • Dopamine receptor agonists → Bromocriptine, Cabergoline

(Larger pituitary adenomas require surgery or radiation)

13

JAK/STAT inhibitor 

Pegvisomant (GH receptor antagonist) 

14

describe the somatostain analog

Octreotide

t1/2: 30 x Somatostatin

(inhibits release of GH, TSH, glucagon, insulin, gastrin)

15

Octreotide clinical applications

  • Reduces symptoms from hormone-secreting tumors: acromegaly, carcinoid syndrome, gastrinoma, glucagonoma, nesidioblastosis, watery diarrhea, hypokalemia, achlorhydria syndrome & diabetic diarrhea.
  • Localizing neuroendocrine tumors
  • Controls bleeding from esophageal varices (vasoconstriction) 

16

Octreotide AEs

  • Nausea, vomiting, abdominal cramps, flatulence, steatorrhea (with bulky bowel movements)
  • Constipation
  • Biliary sludge & gallstones (20-30% pts after 6mo use)
  • Sinus bradycardia (25%) & conduction disturbances (10%)
  • Vitamin B12 deficiency (long-term use)
  • Pain at injection site = common (esp. with long-acting)

17

Dopamine agonists

which drug has longer half-life? 

Bromocriptine, Capergoline

Capergoline t1/2 ~65 h (preferred drug)

18

Bromocriptine, Capergoline Clinical use

 

  • Hyperprolactinemia
    • Standard treatment. Dopamine agonists shrink pituitary prolactin-secreting tumors, lower circulating prolactin levels, and restore ovulation in ~70% women with microadenomas & ~30% with macroadenomas
  • Acromegaly
    • Alone or in addition to surgery, radiation or octreotide admin

19

Bromocriptine, Capergoline AEs

  • Nausea (bromocriptine>cabergoline), headache, light- headedness, orthostatic hypotension, fatigue
  • Psychiatric manifestations
  • High doses = cold-induced peripheral digital vasospasm
  • Chronic high-dosage therapy = pulmonary infiltrates

20

Effects of Gonadotropins on females 

FSH: ovarian follicle development

FSH & LH: ovarian steroidogenesis

Luteal stage of menstrual cycle: estrogen & progesterone production is primarily under control of LH. During pregnancy hCG takes over.

21

Effects of Gonadotropins on males 

FSH: Spermatogenesis, conversion of testosterone to estrogen. Maintains high local androgen concentrations in vicinity of developing cells

LH: Stimulates testosterone production

22

clinical application of gonadotropins

Infertility

  • induce spermatogenesis (men)
  • induce ovulation (women)

23

Follitropin and Urofollitropin

Purified FSH

24

Lutropin alfa

Recombinant LH

25

Menotropins

purified FSH and LH extract 

26

Gonadotropins clinical application

  • Male Infertility
    • d/t hypogonadism, requires both FSH and LH
  • Induce Ovulation
    • Expensive and complicated so reserved for when other treatments don’t work

27

Gonadotropin AEs

  • Women
    • Ovarian hyperstimulation syndrome
    • Multiple pregnancies (15-20%)
    • Headache, depression, edema, precocious puberty
  • Men
    • Gynecomastia

28

Gonadorelin = ____

Goserelin, Leuprolide, Nafarelin = ____

analogs are more ___ and __-lasting

GnRH: Gonadorelin (4 min)

GnRH Analogs: Goserelin, Leuprolide, Nafarelin (3 hrs)

analogs are more potent and longer-lasting

29

____ GnRH secretion is required to stimulate release of LH/FSH 

Sustained nonpulsatile admin. of GnRH ___ FSH/LH release leading to ____

Pulsatile GnRH secretion is required to stimulate release of LH/FSH

Sustained nonpulsatile admin. of GnRH inhibits FSH/LH release leading to hypogonadism

30

Continuous administration of GnRH hormone/analog gives ___ response:

First 7 days = 

Chronic effects (> 1 week) = 

Continuous administration of GnRH hormone/analog gives biphasic response:

First 7 days = agonist response ‘flare’

Chronic effects (> 1 week) = inhibitory action (receptor down-regulation & changes in signaling pathways)