Hypothalamus and Pituitary Flashcards
Where are the hormones of the posterior pituitary synthesized?
Hypothalamus
What pathway do GH and prolactin act through?
JAK/STAT Pathway
What pathway does LH, FSH, TSH and ACTH act through?
G-protein Coupled Receptors
What are the 5 releasing hormone axes?
- GnRH
- GHRH (activation) and Somatostatin (inhibition)
- TRH
- CRH
- DOPA (inhibition)
What is long loop feedback?
Organ mediator (ex. cortisol) acts to inhibit hypothalamic release of CRH or to inhibit release of hormone from the anterior pituitary (ex. cortisol acting on ACTH)
What is short loop feedback?
Anterior pituitary hormone feeds back to hypothalamus
Ex. ACTH negative feedback on CRH
What is the major target organ of the GH axis?
Liver - IGF-1 mediates the effects of GH
Metabolic effects: increases protein synthesis and bone density; promotes lipolysis and inhibits lipogenesis; promotes gluconeogenesis and glucose release; opposes insulin-induced glucose uptake in adipose tissue, reduces insulin sensitivity.
Growth Hormone
What can be used to treat GH deficiency?
Sermorelin - synthetic GHRH
What are Somatropin and Somatrem examples of?
Recombinant human GH - used to replaced GH
Mecasermin
Recombinant IGF-1
Mecasermin Indications
Used in children where IGF1 deficiency is due to mutations of GH receptor (Laron dwarfism) or development of neutralizing antibodies against GH
Somatropin and Somatrem Indications
- Documented growth failure in pediatric patients associated with: GH deficiency, chronic renal failure, Prader-Willi syndrome, Turner syndrome
- Small-for-gestational-age condition with failure to catch up by age 2
Somatropin and Somatrem SE
- Leukemia, rapid growth of melanocytic lesions
- Hypothyroidism
- Insulin resistance
- Arthralgia (joint pain)
Somatropin and Somatrem Contraindications
- Pediatric patients with closed epiphyses
- Active underlying intracranial lesion
- Active malignancy
- Proliferative diabetic retinopathy
What is Octreotide used for?
It is a somatostatin analog and used to treat excess of GH
Pegvisomant MOA
GH antagonist
Octerotide Indications
- Acromegaly
- Pituitary Adenoma
- Secretory diarrhea from VIPomas
Octreotide SE
- GI effects
- Hypoglycemia
- Gallstones
Pegvisomant Indications
- Used for the treatment of acromegaly that is refractory
Pegvisomant SE
- Increased pituitary adenoma size
- Elevated serum aminotransferase levels
What drug has the following considerations?
- Patients should have yearly MRI to exclude enlarging adenoma
- Liver function tests should be performed periodically
Pegvisomant
Gonadotropin MOA
Replaces FSH and LH
Gonadotropin SE
- Ovarian hyperstimulation syndrome (associated with ovarian enlargement, ascites, hydrothorax, hypovolemia, sometimes resulting in shock)
- Increase in multiple pregnancies
- Increased risk of gynecomastia in men
- Ovarian cancer
What is the effect of a sustained GnRH agonist?
- There is a transient (7-10 days) increase in gonadal hormone levels (flare) – agonist effect
- Followed by a long-lasting suppression of gonadotropins and gonadal hormones – inhibitory action
What drugs are used to treat hyperprolactinemia?
Dopamine Receptor Agonists
DOPA Agonist MOA
They inhibit pituitary prolactin release by increasing DOPA
What drug class are Ganirelix, Cetrorelix and Abarelix?
GnRH Receptor Antagonist
How does GH affect response to insulin?
It increases insulin resistance
What is a somatostatin analog?
Octreotide
