Adrenal (book)

• Hyperaldosteronism - hypertension, hypokalemia, and metabolic alkalosis
• Pheochromocytoma - hypertension, anxiety, palpitations, dizziness, and diaphoresis
• Cushing’s syndrome - hypertension, rapid unexplained weight gain, red/purple stretch marks, and proximal muscle weakness
• Congenital adrenal hyperplasia - inappropriate hirsutism/virilization and inability to conceive
• Primary adrenal insufficiency - loss of appetite, unintentional weight loss, and pigmented skin
• Hypofunction - reated with hormone replacement
• Hyperfunction - treated with pharmacologic suppression and/or surgery
• Adrenal gland is composed of two distinct tissues - adrenal cortex and adrenal medulla
• Cortex - derived from mesenchymal cells

  -yellow
• Medulla - from neural crest cells

  -dark mahogany
• Major adrenal cortical hormones - aldosterone, cortisol, and dehydroepiandrosterone sulfate (DHEA-S)
• Zona glomerulosa

  -salt (15% of cortex)

  -produces mineralocorticoids

  -main steroid: aldosterone

  -regulator: RAAS

  -Function: blood pressure and potassium homeostasis

  -Syndromes: hypoaldosteronism and hyperaldosteronism
• Zona Fasciculata

  -Sugar (75% of cortext)
• Zona Fasciculata

  -Sugar (75% of cortex)

  -produces glucocorticoids

  -main steroid: cortisol

  -regulator: Adrenocorticotropic hormone

  -blood pressure and glucose homeostasis

  -syndrome: adrenal insufficiency and hypercortisolism
• Zona reticularis

  -sex (10% of cortex)

  -produces mineralocorticoids

  -main steroid: DHEA and DHEAS (androgen precursor)

  -syndrome: androgen excess
• Cortricotropin-releasing hormones - secreted from the hypothalamus in response to diurnal variations, low serum cortisol levels, and stress
• ACTH - released in response to CRH

  -stimulates transport of free cholesterol into adrenal mitochondria
• Conversion of cholesterol to pregnenolone - the first step and rate-limiting step in steroid biosynthesis
• Cytochrome P450 - cholesterol is converted into pregnenolone through this enzyme
• 6-8am - rise of cortisol - results to low acth and crh

  10-12am - low cortisol - results to high acth and crh
• Congenital adrenal hyperplasia

  -can be detected with newborn screening

  -most common enzyme affected is 21-hydroxylase
• Diagnostic of classic 21-hydroxylase deficiency

  -high serum concentration of 17-hydroxyprogesterone
• Primary aldosteronism

  -excessive secretion of aldosterone

  -cannot be suppressed with salt or volume replacement

  -increased risk in stroke

  -may be caused by adrenal adenoma, adrenal hyperplasia, GRA, carcinomas, and ectopic aldosterone secretion

  -diagnosis: blood drawn in the morning (patient should be up for atleast 2 hours and seated for 5-15 mins before draw)

  -treatment: surgical
• Adrenal insufficiency

  -inadequate hormone secretion from adrenal cortex

  -primary: adrenal - reduced adrenal hormones, adequate stimulation

  -secondary: pituitary - stimulus is insufficient or absent

  -tertiary: hypothalamic - interferes with CRH secretion

  -most common cause of primary: autoimmune destruction of adrenal gland

  -diagnosis: primary - ACTH stimulation test

  -diagnosis: secondary - metyrapone suppression testing

  -alternative diagnosis - insulin tolerance test
• Isolated Hypoaldosteronism

  -adrenal gland destruction with chronic heparin therapy

  -G zone enzyme deficiency

  -treatment: dietary changes and fludrocortisone
• Hypercortisolism

  -Cushing's syndrome

  -high cortisol, high acth, low aldosterone, low renin

  -hypercortisolism with high acth - secondary/pituitary

  -hypercortisolism with low/zero acth - adrenal
• liddle's syndrome

  -pseudohyperaldosteronism

  -high enac
• adrenal medulla

  -produces catecholamines from tyrosine (1-2 mins half life, first stress responders)

  -cortisol (20 minutes to respond)
• Phenylethanolamine N-Methyltransferase

  -converts norepinephrine to epinephrin

  -stimulated by cortisol

  -in the cytosol
• Vesicular monoamine transporters (VMATs)

  -enzyme that lets epinephrine and norepinephrine re-enter the vesicles
• Pheochromocytomas

  -increased production of catecholamines

  -Screening: plasma metanephrines and normetanephrines by HPLC

  -arise from adrenal medulla
• Norepinephrine

  -primary amine

  -highest in CNS

  -VMA
• Epinephrine

  -secondary amine

  -fight or flight

  -VMA
• Pheochromocytoma screening test negative result

  -24 hr urine metanephrines

  -<1ug or 5.5 umol/mg creatinine
• Cushing's syndrome screening test negative results

  -1mg bedtime dexamethasone

  -8am cortisol <3.6 ug/dL

  -24hr urine free cortisol normal
• Primary aldosteronism screening tests negative results

  -serum potassium if low

  -urine K+ excretion (<30 mmol)
• Adrenocarcinoma screening tests negative results

  -plasma renin:aldosterone ratio <30

  -plasma DHEAS (<9.2 umol/L)

  -urine 17 ketosteroid <20mg
• Enzyme defect @ 3B-hydroxysteroid dehydrogenase

  -no aldosterone, no cortisone, no estradiol
• Enzyme defect @ 17a-hydroxylase

  -no cortisone, no estradiol
• Enzyme defect @ 21B-hydroxylase

  -no aldosterone, no cortisone