Hypothalamic and Pituitary Hormones Flashcards
What hormones are released by the posterior pituitary?
ADH
Oxytocin
Both are made in hypothalamus, then stored and released in post pituitary
What hormones are released by the anterior pituitary?
TSH ACTH LH FSH GH Prolactin
What is the main target organ for GH?
Liver (stimulates production of IGF-1)
What inhibits GH production in anterior pituitary?
Somatostatin, released by hypothalamus, inhibits GH production in ant pituitary
What inhibits prolactin production in anterior pituitary?
Dopamine from the hypothalamus inhibits prolactin production in the anterior pituitary
How does GH affect both muscle cells and adipose tissue?
Muscle cells – increase glucose and AAs uptake, stimulating production of proteins
Adipose tissue – decrease glucose uptake; Lipolysis is stimulated
GH Physiological Actions in Children and Adults
Children: promotes linear growth of long bones, cartilage, muscles, organs
Adults: Increase protein synthesis in muscle, Lipolysis, opposes glucose uptake into adipose tissue
Features of GH Deficiency in Children and Adults
Children: Short stature, adiposity, hypoglycemia
Adults: Adiposity, Decreased skeletal muscle mass, decreased bone density, CV changes, Fatigue
Sermorelin
MOA and Indication
Synthetic GHRH
Used when there is defective release of GHRH but normally functioning ant pituitary somatotrophs
Somatotropin and Somatrem
MOA
Recombinant human GH
Mecasermin
MOA and Indication
Recombinant IGF-1
Used in children where IGF-1 deficiency is caused by mutation of GH receptor (Laron dwarfism or development of Abs against GH)
Somatotropin and Somatrem
Indications
Documented growth failure in patients with GH deficiency
Prader-Willi Syndrome (mutation in GH)
Turner Syndrome (XO)
GH deficiency in adults
Wasting in AIDs pts
Short bowel syndrome
Somatotropin and Somatrem
Adverse Effects
Leukemia, rapid growth of melanocytic lesions Hypothyroidism Insulin resistance Arthralgia Increase in CYP450 activity
Somatotropin and Somatrem
Contraindications
Pediatric pts with closed epiphyses
Active underlying intracranial lesion
Active malignancy
Progressive diabetic retinopathy
Features of GH Excess in Children and Adults
Children: Gigantism
Adults: Acromegaly
Large facial structures, thickened bones, macroglossia, hepatomegaly, increased risk of CV disease and GI cancers
Octreotide
MOA
Somatostatin analog, inhibits GH secretion
Lanreotide is another somatostatin analog used in Europe
Octreotide
Indications
Controlling pituitary adenoma growth in acromegaly pts
Carcinoid crisis
secretory diarrhea from VIP secreting tumors
Control acute bleeding
Octreotide
Adverse Effects
GI effects (nausea, vomiting, abd cramp)
Sinus bradycardia and conduction disturbances
Hypoglycemia
Gallstones
Pegvisomant
MOA
GH receptor antagonist
Prevents dimerization of the GH receptors, cuaisng competitive inhibition of the GH receptor
Has many polyethylene glycol residues to prolong its half life
Pegvisomant
Indications
Tx of acromegaly that is refractory to other surgical, radiologic, and pharm intervention
Pegvisomant
Side Effects
Increased pituitary adenoma size (need annual MRI to ensure the adenoma does not grow)
Elevated serum aminotransferase levels (MUST monitor the patient’s LFTs on this drug)
Describe the relationship of half lives with GnRH analogues and their ultimate effects on the Gonadal axis
GnRH analogs with short half lives are used to stimulate the reproductive axis
GnRH analogs with long half lives are used to inhibit the reproductive axis
What drugs may be used to stimulate the gonadal axis?
Human menopausal gonadotropins or menotropins
hCG
Urofollitropin (purified FSH from urine)
Follitropin (recombinant FSH)
GnRH or its analogue Gonadorelin with SHORT half life
What drugs may be used to inhibit the gonadal axis?
Synthetic analogs of GnRH with LONG half lives (Goserelin)
GnRH receptor antagonists (Ganirelix, Cetrorelix, Abarelix)
Indications for drugs to stimulate the gonadal axis
Hypogonadotropic hypogonadism (anovulation in females, infertility in males)
PCOS
Obesity
Controlled ovarian hyperstimulation in IVF
Drugs to stimulate the gonadal axis
Side effects
Ovarian hyperstimulation syndrome
Increase in multiple pregnancies
Gynecomastia in men
Ovarian cancer and ovarian cysts
Drugs to stimulate the gonadal axis
Contraindications
Endocrine disorders other than anovulation
Primary gonadal failure
Ovarian cysts or enlargement
Pregnancy
GnRH Agonists (GnRH or Gonadorelin) MOA and Indications
Both have short half lives and are used to stimulate release of LH and FSH
Indications: Hypogonadism
Stimulating Ovulation
Infertility in men with hypogonadotrophic hypogonadism
Goserelin
MOA
Sustained, nonpulsatile inhibition of release of LH and FSH in men and women
Desensitizes GnRH receptors
Get an agonist effect for 7-10 days, then long term antagonist effect
Goserelin
Indications
Keep LH surge low in controlled ovarian hypersimtulation
Endometriosis and Uterine fibroids
Adjunct in prostate cancer
Central precocious puberty
Goserelin
Adverse Effects
Hot flashes (lack of estrogen, like menopause)
Osteoporosis
Urogenital atrophy
Worsening of precocious puberty during initial week of treatment
What are the GnRH receptor antagonists?
Ganirelix, Cetrorelix, Abarelix
GnRH Receptor antagonists
Indications
Keep LH surge low in controlled ovarian hyperstimulation
Metastatic prostate cancer
