Adrenal Pathophysiology (5/16) Flashcards
List diseases of the Zona Fasciculata
Cortisol Xs: Cushings
Cortisol Deficiency: Addison’s
List disease of Zona Glomerulosa
Primary Hyperaldosteronism
List disease of the Zona Reticularis
Androgen Excess
List disease of the adrenal medulla
Pheochromocytoma (tumor that secrete XS catecholamines)
Dfine Cushing’s Syndrome
Having excess cortisol secretion (regardless of cause/source)
What is the most common cause of cushings syndrome?
Iatrogenic from exogenous glucocorticoid use
What are the pathophys changes in HPA axis with cushings?
- Loss of diurnal variation of cortisol secretion (cortisol peaks are higher and taller)
- Autonomy from ACTH control (ie loss of feedback regulation)
- XS cortisol secretion
What is Cushing’s Disease?
Pituitary adenoma that secretes too much ACTH
What is ectopic ACTH syndrome
Ectopic ACTH is being produced by a tumor outside the pituitary. Most common in lung and bronchi. Very severe
What are some basic metabolic derangements due to XS corticosteroids?
- Carb metab: stimulates gluconeogenesis leading to hyperglycemia
- Fat metab: inc lipgenesis leads to inc FFAs and insulin resistance (obesity is the most common finding in Cushings)
- Protein metab: Inc gluconeo–>catabolism (uses muscle)
What is the most common finding in cushings?
Obesity (also diabetes, hypertension, menstrual abnormalities, muscle weakness etc)
What are some phyiscal effects of fat metab?
Dewlap (double chin), Buffalo hump (fat bad at back of neck), supraclavicular fat pads
What are some effects of cortisol excess?
- Impaired immunity
- Inc clotting factors
- Cataract formation
- Proximal myopathy
- Osteoporosis
- Redistribution of body fat
- Hypertension, cardiomyopathy, inc thromboemobolic events
- Thin skin, easy brusing, striae, acne, hyperpigmentation, hirsutism
- Psychiatric disturbances
- Hypokalemia
- Inc testosterone in females
- Menses abnormalities
- Marked virillization in women worrisome for malginant adnreal tumor
Describe ACTh dependent cushings
Characterized by bilateral adrenal hyperplasia
Describe ACTH independent cushings
Adenoma makes cortisol
What do you measure if there is loss of diurnal variation cortisol secretion?
Measure late night salivary cortisol. Measures free cortisol. Beware of pts with night shift/disturbed sleep/wake cycle
What do you measure if there is autonomy from ACTH control?
1mg dexamethasone suppression test. DST measures loss of feedback inhibition. Dex is a synthetic glucocorticoid so it should suppress ACTH and cortisol levels. If it doesn’t, then you have ACTH being produced elsewhere or from an ACTH producing adenoma.
- indicates inappropriate secretion, does not indicate source of cortisol
- Dex is taken at 11pm and cortisol is measured at 8am
- Normal: cortisol <2mcg/dL after dex
What do you measure if there is an excess of cortisol?
24 hr urinary free cortisol measurements. Cushings is more likely if cortisol >3x upper limit of normal
If a pts urine cortisol is markedly elevated and cortisol is elevated after DSH. ACTH is also elevated. What is the source of cushings?
Pituitary adenoma (inc ACTH, cortisol despite DST)
If ACTH is low
Cushings from adrenal source
If ACTH is normal or elevated
Pituitary or ectopic source
ACTH is suppressed
Source is exogenous glucocorticoids
How do we localize the source?
imaging
How do we treat cushings?
Depends on source
- Cure unilateral adrenal adenoma with adrenalectomy
- Use ketoconazole, metyrapone or bilateral adrenalectomy if required
How long does it take for symptoms to go away post treatment?
Up to 12 mo, not all sequelae completely resolve, esp psychiatric complications
Name a disease of cortisol deficiency
Addison’s (adrenal cortical failure)
How much of cortex is destroyed prior to presentation in addisons?
90%
What hormone is elevated in addisons?
ACTH
What ion deficiencies can you have?
Hyponatremia and hyperkalemia
What bp abnormality will you have?
Hypotension
What are the clinical characteristics of addison;s?
Hyperpigmentation from increased ACTH Weight loss Muscle or joint pains Fatigue Nausea, abdominal pain Hypoglycemia can occur
What is the etiology of primary adrenal insufficiency (aka Addison’s)
- Autoimmune destruction of 60% of the adrenal cortex
- Infectious from TB, fungus, HIV etc
- Bilateral hemorrhage/infarction: anticoag, trauma, embolic, meningococcemia etc=waterhouse-friderichsen syndrome
- Metastatic cancer
- Drugs, including those that inc cortisol metab
How do we diagnose Addison’s?
-Early AM cortisol 20mcg/dL excludes adrenal failure.
What is a good initial short term treatment?
Dexamethasone because it will not interfere with cortisol assay. If pt is hypotensive with a strong clinical suspicion, treat with glucocorticoids first and make the diagnosis later
What is an adrenal crisis
Acute deficiency in cortisol and mineralocorticoids. CAn be life threatening and masquerade as other conditions
What are the clinical characteristics of an adrenal crisis?
Hypotension, shock, fatigue, weakness, fever, lethargy, abdominal pain, anorexia, hypoglycemia
What are some causes of adrenal crisis?
- New primary adrenal failure
- Known adrenal insufficiency with acute illness or under-replacement of meds
- Acute withdrawal of high dose glucocorticoids
- Pituitary apoplexy
How do we treat adrenal crisis (short term)?
- 1-3 liters saline IV over 12-24 hrs
- Dexamethasone 4mg IV
- Monitor electrolytes
- Monitor bP
What are the two types of polyglandular syndromes and why do we care?
- We care because addisons can be associated with polyglandular syndromes
- Type 1: hypoparathyroidism, mucocutaneous candidiasis, primary hypogonadism
- Type 2: T1D, autoimmune thyroiditis, vitiligo, hypogonadism
What is primary hyperaldosteronism?
Mineralocorticoid excess
What are the associated issues with hyperaldosteronism?
Hypertension, hypokalemia (though it is possible that this is normal…still aldosterone causes the collecting duct transporters to secrete k+ in exchange for Na+), mild hyernatremia, metabolic alkalosis, muscle weakness
What causes hyperaldosteronism?
Adrenal adenoma producing aldosterone or bilateral adrenal hyperplasia
Who should be screened for primary hyperaldosteronism?
- <30 y.o with hyperT, no obesity or fam hx
- Persons with unexplained hypokalemia and hyperT
- Persons with resistant hyperT
- Persons with an adrenal incidentaloma and hyperT (ie find it accidentally)
How do we diagnose hyperaldosteronism?
- Early morning aldosterone:renin ratio
- Ratio >20 suggestive, but not diagnostic
- Aldosterone >15 and suppressed renin suggestive
- Once biochemical diag is certain, do CT or MRI
- If pos imaging, further testing req: salt loading to demonstrate inappropriate aldosterone secretion, *adrenal vein sampling prior to surgery
What is adrenal vein sampling
- MEasure aldo and cortisol concentrations in each vein and IVC
- Distinguishes between uni adenoma and bilateral adrenal hyperplasia
- For lateral dis, the aldosterone concentration needs to be 4x greater than the contralateral side
What is the treatment of primary hyperaldosteronism?
- Unilateral aldosterone secreting adenoma: surgical resection
- Bilateral adrenal hyperplasia: mineralocorticoid antag
What are the symp of androgen excess?
- Woman: hirsutism, male pattern baldness, menstrual irreg
- Men: Gonadotrophin sec disrupted
What is an adrenal adenoma relationship to androgen excess?
Adrenal adenomas rarely cause androgen xs, they usually cause cortisol xs
What can cause androgen excess?
- ACTH dependent cushings can cause elevation in testosterone and DHEAS
- If you see a woman with acute onset virilization–>think this
What does the adrenal medulla secrete?
Catecholamines
