Endocrine Flashcards
What are notable sites of extragonadal production of testosterone and other androgens?
Skin, adipose tissue, adrenals
What can testosterone be converted into?
Androstenedione (reverse rxn! This is a testosterone precursor), estradiol, and DHT
What enzyme converts testosterone to DHT?
5α-reductase
The hypothalamus secretes ______, which acts on gonadotrophs in the anterior pituitary
GnRH
GnRH stimulates the release of ________ from the gonadotrophs of the anterior pituitary
LH and FSH
GnRH secretion is _______
pulsatile
Continuous secretion of GnRH does what?
Suppresses the release of LH and FSH
LH acts on _______ cells
Leydig
What are Leydig cells? What do they do?
Interstitial cells in the testes
Produces testosterone
FSH acts on _______ cells
Sertoli
What are Sertoli cells? What do they do?
Cells in the testes in direct contact with the seminiferous tubules
Functions:
- synthesis of P450 aromatase (converts testosterone to estradiol)
- production of growth factors that support spermatogenesis
- synthesis of inhibins
What does aromatase do?
Converts testosterone to estradiol
20,22-desmolase
Enzyme that converts cholesterol into pregnenolone
Rate limiting step
LH stimulates this rxn
What type of G protein receptor does GnRH bind to in the anterior pituitary?
Gq –> PLC –> IP3 + DAG
Theca cells have receptors for what hormone?
LH
Granulosa cells have receptors for what hormone?
LH and FSH
Which hormone decreases the release of GH?
Somatostatin
Mecasermin
Recombinant IGF (insulin-like growth factor)
Used to treat pts w/ growth hormone insensitivity
Ex: Laron dwarves
Concern for hypoglycemia, so ingest carbs prior to taking
Recombinant GH
Replacement tx in children w/ deficiency
Octreotide
Somatostatin analogue
Uses:
- excess GH 2/2 pituitary adenoma
Pegvisomant
GH receptor antagonist
1x daily dose, SQ
What molecule directly controls the release of prolactin?
Dopamine at D2 receptors in the hypothalamus
Dopamine INHIBITS prolactin release
Cabergoline
Dopamine agonist used to treat hyperprolactinemia (prolactinomas)
Preferred agent; more selective for D2 receptors and more effective
May cause hypotension, dizziness; valvular HD at higher doses
May inhibit GH secretion in some pts, but not as effective as SST analogues.
Bromocriptine
Dopamine agonist
Used to treat hyperprolactinemia
Also activates D1 receptors
Frequent side effects include N/V, headache, and postural hypotension; less frequently can see psychosis or insomnia
Vasopressin
= ADH
Tx parenteral admin, t1/2 = 20 min
Endogenous release occurs w/ rising blood osmolality –> retain water in body via adding water channels (aquaporins) in luminal membrane
Desmopressin (DDAVP)
ADH analogue that is more stable; t1/2 = 1.5-2.5 hours
No vasopressor effect
Central diabetes insipidus
Can result from head injury, pituitary tumors, cerebral aneurysm, or ischemia = inadequate secretion of ADH from posterior pituitary
Tx: desmopressin, chlorpropamide (1st gen sulfonylurea)
Nephrogenic diabetes insipidus
Congenital or drug-induced (lithium) = inadequate ADH action
Tx: fluids, low salt/protein diet, thiazide diuretics (paradoxical mechanism), NSAIDs like indomethicin (inhibit PGs, which lower ADH effects)
Syndrome of Inappropriate Secretion of ADH (SIADH)
Incomplete suppression of ADH secretion under hypoosmolar conditions. Thus, people retain water & urine is inappropriately concentrated.
Causes: malignancy, pulmonary diseases, trauma, infections
One of the most common causes of hyponatremia; occurs in 15-22% of hospitalized pts
Tx: restrict free water intake, V2 receptor antagonists, demeclocyline
What drugs induce SIADH?
SSRIs, haloperidol, TCADs
Demeclocyline
Inhibits ADH effect on distal tubule
Treats hyponatremia in SIADH
Tolvaptan or Conivaptan
V2 receptor antagonists
Tx for hyponatremia in SIADH
Warning against rapid correction of hyponatremia: cerebellar pontine myelinolysis!!!
What is an example of an adrenal glucocorticoid?
Cortisol
What is an example of an adrenal mineralocorticoid?
Aldosterone
What controls the release of ACTH? Where is it released from?
CRF (from hypothalamus) controls release of ACTH
ACTH is released from the anterior pituitary
If there’s an -OH group at 11 in corticosteroids, it’s _____.
active
Ex: cortisol, prednisolone
Liver does this
If there’s a ketone group at 11, it’s ______.
inactive
Ex: prednisone, cortisone
Kidney does this
When using corticosteroids to treat Addison’s Disease (physiologic use), what drug(s) should be used and why?
Cortisol (aka hydrocortisone)
It’s necessary to use an agent with both glucocorticoid and mineralocorticoid properties (cortisol is 1:1) to mimic the physiologic effects of the adrenals.
Unless the disease is mild, fludrocortisone (high mineralocorticoid activity) is usually required for sufficient salt-retaining effect.
When using corticosteroids to treat inflammation (pharmacologic use), what drug(s) should be used and why?
Prednisone, triamcinolone, dexamethasone
All have significantly higher glucocorticoid properties, which = anti-inflammatory properties
Which hormones are produced by the adrenal cortex?
- Cortisol
- Aldosterone
- Sex hormones (small amounts)
Which hormones are produced by the adrenal medulla?
Epinephrine and norepinephrine
Which one is active, prednisone or prednisolone?
Prednisolone is the active form
Prednisone gets converted by liver into active form
Ketoconazole
Inhibits downstream conversion of cholesterol into other hormones. Blocks 17α-hydroxylase and 17,20-lyase.
Used to treat Cushing’s Syndrome (hypercortisolism)
May inhibit androgen synthesis, leading to gynecomastia & impotence
Mifepristone
Glucocorticoid receptor antagonist
Used in Cushing’s Syndrome
Not a first-line drug - approved to control hyperglycemia secondary to hypercortisolism
Contraindicated for use during pregnancy - women of child-bearing age should use contraception
“My wife has pristine cushions”
Congenital adrenal hyperplasia
Due to congenital enzyme defects, the production of cortisol is severely diminished
Cortisol normally has negative feedback effect on ACTH levels; thus, here, ACTH levels are extremely high
Increased ACTH leads to overstimulation of adrenal gland and adrenal hyperplasia
How is congenital adrenal hyperplasia treated in children vs. adults?
Children - hydrocortisone
Adults - prednisone or dexamethasone
The goal of therapy is to replace deficient steroids while minimizing adrenal sex hormone (overproduction) and glucocorticoid excess (via overtreatment).
Pheochromocytoma
Excess epinephrine/norepinephrine production due to a tumor in the adrenal medulla
What does the pharmacological preparation for pheochromocytoma surgery consist of?
Prep w/ α-blockers for several days to control blood pressure
THEN, beta-blockade to control tachycardia and arrhythmias
Can supplement with CCBs (nefidipine) if blood pressure control is inadequate or side effects are not tolerated
Phenoxybenzamine
Irreversible α1-α2 receptor antagonist
Initial step of pheochromocytoma surgery prep