15.10-11 Adrenal Cortex + Medulla Flashcards
You do adrenal imaging on pt with Cushing’s syndrome to determine cause. Think what in these results? How to differentiate btwn similar presentations?
- one enlarged adrenal, one atrophied
- bilateral hypertrophy
- bilateral atrophy
- adrenal adenoma/carcinoma/
- high ACTH (may be Cushing’s disease or paraneoplastic ACTH tumor)
- in order to distinguish btwn both, do a high-dose dexamethasone test. Pituitary tumor will respond, but ectopic will not - exogenous glucocorticoids
Low and high dose dexamethasone test results in these Cushing syndrome causes:
- exogenous glucocorticoids
- Cushing’s disease (ACTH secreting pit adenoma)
- ectopic ACTH secretion (paraneoplastic)
- primary adrenal adenoma, hyperplasia, carcinoma
Low:
all: no suppression
high dose:
- N/A
- suppression
- no suppression
- N/A
Acute adrenal insufficiency
- most common cause
- another important cause
- clinical presentation
- abrupt withdrawal of glucocorticoids (must wean pt off of it)
- Waterhouse -Friedrichsen syndrome
- presents as weakness and hypotension (shock)
Cortisol effect on immune function (3)
- block phospholipase A2 (decrease prostaglandins, LTs)
- block IL-2 (block T cell activation)
- block histamine release from mast cells
ACTH levels in these causes of Cushing syndrome
- exogenous glucocorticoids
- Cushing’s disease (ACTH secreting pit adenoma)
- ectopic ACTH secretion (paraneoplastic)
- primary adrenal adenoma, hyperplasia, carcinoma
- low
- high (androgen excess may be present)
- very high (androgen excess and hyperpigmentation may be present)
- low
Addison’s disease
- clinical presentation (3 mechs)
- mnemonic
- low aldo–hypotension, hyponatremia, hypovolemia, hyperkalemia, met acidosis
- low cortisol–hypotension, vomiting, diarrhea, weakness
- increased ACTH–hyperpigmentation
“A3”– Adrenal Atrophy with Absence of hormone production.
All 3 cortical divisions (medulla spared)
Primary hyperaldosteronism
-tx
Aldosterone blocker
- spironolactone, eplerenone
- surgery for adenoma
17 OHlase deficiency
- clinical presentation
- Tx
- HTN and mild hypokalemia:
excess mineralocorticoids, resulting in low renin and therefore low Aldo. buildup of mineralocorticoid activity with 11-DOC and corticosterone
- Primary amenorrhea, lack of female pubic hair. pseudohermaphroditism in males.
- loss of androgens - still have glucocorticoid activity with corticosterone
Tx: glucocorticoids, also sex steroids
Cushing syndrome
-dx tests (3)
- 24 hr urine cortisol (increased in Cushing syndrome)
- late night salivary level (increased)
- low-dose dexamethasone suppression test. (fails to suppress cort in all cases of Cushing syndrome)
- In primary Cushing syndrome, high dexamethasone has no suppression effect. In Cushing disease (pituitary), high dexamethasone has suppression effect
In Cushing syndrome, pt presents with HTN, hypokalemia, and met alkalosis
-mechs (2)
- high cortisol has mineralocort activity
- cort upregulates alpha 1 receptors in vasculature, causing vasoconstriction
Imaging reveals what in each cause of Cushing’s syndrome?
- exogenous glucocorticoids
- Cushing’s disease (ACTH secreting pit adenoma)
- ectopic ACTH secretion (paraneoplastic)
- primary adrenal adenoma, hyperplasia, carcinoma
- bilateral adrenal atrophy
- bilateral adrenal hypertrophy
- bilateral adrenal hypertrophy
- one adrenal is hypertrophied, other atrophies
Adrenal medulla
-composed of what embryologic cells?
neural crest-derived chromaffin cells
causes of renovascular HTN (2)
- fibromuscular dysplasia (young women)
- atherosclerosis (elderly)
Neonate presents with life-threatening hypotension. Also has hyponatremia and hyperkalemia.
think what?
- Think lack of mineralocorticoid and glucocorticoids
- So, think CAH (21 OHlase deficiency)
Addison’s disease
-causes (3)
chronic adrenal insufficiency
- progressive destruction of adrenal glands
1. autoimmune (most common in west)
2. TB (most common in developing world)
3. metastatic cancer (esp from lung!)
Glucocorticoid-remediable aldosteronism (GRA)
- mech
- clinical presentation
- rare cause of familial hyperaldosteronism
- aberrant expression of aldosterone synthase in fasciculata (normally only in glomerulosa)
- presents in children as HTN, hypokalemia, high Aldo, low renin (secondary hyperaldosteronism)
Cushing syndrome
-causes (4)
think source of cort/ACTH
- exogenous glucocorticoids
- Cushing’s disease (ACTH secreting pit adenoma)
- ectopic ACTH secretion (paraneoplastic)
- primary adrenal adenoma, hyperplasia, carcinoma
Primary hyperaldosteronism
- most common cause
- other causes (2)
- bilateral adrenal hyperplasia
1. Conn’s syndrome (adrenal adenoma)
2. Adrenal carcinoma
Waterhouse-Friderichsen syndrome
- mech
- classic cause
- classic cause of acute adrenal insufficiency
- hemorrhagic necrosis of adrenal glands, classically due to DIC in young children with Neisseria meningitidis infection
- lack of cortisol exacerbates hypotension, leading to death
metastic carcinoma in adrenal gland.
-What organ source is highly assoc with adrenal metastasis?
Lung cancer
How to differentiate intra-adrenal pheochromocytoma from extra-adrenal catecholamine secreting tumor?
Intra-adrenal will have serum metanephrine and normetanephrine, while extra-adrenal secretes mainly normetanephrine.
NE is converted to Epi mainly inside the medulla because of the enzyme PNMT, which is stimulated by Cortisol present in medulla
Pheochromocytoma
- tumor of what specific cell type?
- how to dx? (2)
- chromaffin cells of the adrenal medulla
- dx with:
1. increased serum metanephrines
2. increased 24 hr urine metanephrines and VMA
Pheochromocytoma
- tx
- what to be aware about in tx
- Surgery
- Must use alpha-blocker (phenoxybenzamine) before surgery to prevent deadly release of catecholamines. (HTN crisis)
phenoxybenzamine
alpha blocker, used before pheochromocytoma surgery
How can TB affect the adrenal gland?
-destruction of adrenal glands leads to Addison’s disease (chronic adrenal insufficiency)
Pheochromocytoma
-rule of 10s (4)
- 10% bilateral
- 10% familial
- 10% malignant
- 10% located outside the adrenal medulla (eg bladder wall or organ of Zuckerkandl)
21 OHlase deficiency vs 11 OHlase deficiency
-how do symptoms and tx compare
Both lead to CAH.
11 OHlase deficiency has weak mineralocorticoid production with 11-DOC, while 21 OHlase has no mineralocorticoid activity.
So, there is HTN and mild hypokalemia in 11 OHlase deficiency, whereas there is hypotension and hyperkalemia in 21 OHlase deficiency.
Tx: glucocorticoids for both, mineralocorticoids for 21 OHlase
Pheochromocytoma
-clinical presentation (5)
symptoms due to increased catecholamines
5 P’s:
Pressure (high BP)
Pain (headache)
Perspiration
Palpitations
Pallor
Neonatal female patient has clitoral enlargement, HTN, and hyperkalemia. Aldosterone is low.
think what?
Think CAH caused by 11 OHlase deficiency.
- similar to CAH from 21 OHlase deficiency, except there is mineralocorticoid activity from 11-DOC.
- Low Aldosterone b/c renin is low
Congenital Adrenal Hyperplasia
- most common enzyme deficiency?
- how does it present? (classic (4) and nonclassic)
- 21 OHlase deficiency
- classic form presents in neonates:
1. hyponatremia
2. hyperkalemia
3. hypovolemia (life threatening hypotension)
4. clitoral enlargement in females - nonclassic form presents later in life: precocious puberty in males, hirsuitism with menstrual irregulaties in females
describe metabolism of catecholamines
Tyr –> DOPA –> DA –> NE –> Epi
NE –> normetanephrine —MAO–> VMA
Epi –> metanephrine —MAO–> VMA
metanephrines and VMA (vanillylmandelic acid) excreted in urine
Pheochromocytoma
-assoc with what syndromes? (4)
- MEN 2A (MPP–medullary thyroid carcinoma, pheo, parathyroid)
- MEN 2B (MPN–medullary thyroid carcinoma, pheo, neuroma)
- Hippel-Lindau disease
- neurofibromatosis type 1
Congenital Adrenal hyperplasia
-how to screen
- look at 17 OH-progesterone levels
- increased in 21 OHlase and 11 OHlase deficiencies
- decreased in 17 OHlase deficiency
Secondary hyperaldosteronism
-causes
-activation of RAAS
(eg CHF, renovascular HTN)
Aldosterone
-fxn in nephron
Principal cells: reabsorb Na, secrete K
alpha-intercalated cells: secrete H+
Primary hyperaldosteronism vs Secondary hyperaldosteronism
-renin levels
Primary: low renin levels
secondary: high renin
Cushing syndrome–mech of each:
- muscle weakness, thin extremities (muscle wasting)
- moon facies, buffalo hump, truncal obesity
- abdominal striae
- HTN, hypokalemia, met alkalosis
- osteoporosis
- cortisol promotes proteolysis for gluconeogenesis
- high insulin (from hyperglycemia) deposits fat cenrally
- lower fibroblast activity
- high cortisol acts on mineralocorticoid receptors. also, cortisol upregulates A1 receptors
- cort decreases osteoblast activity
Child pt presents with HTN, hypokalemia, and metabolic alkalosis
- think what?
- how to dx?
- Tx
Looks like hyperaldosteronism, probably genetic since child.
- GRA–glucocorticoid remediable aldosteronism (aberrant expression of Aldo synthase in fasciculata)
- Liddle syndrome (decreased degradation of tubular Na channels)
So, measure Aldo levels! In Liddle, there is low aldo b/c it has nothing to do with Aldo.
- GRA: Tx with Aldo blockers (spironolactone, eplerenone)
- Liddle: Tx with tubular Na channel blockers (amiloride, triamterene) NOT aldo blockers
Child with meningitis:
-what adrenal gland problem to be concerned about?
Waterhouse-Friedrichsen syndrome
- classically presents as young child due to DIC with Neiserria meningitidis infection
- hemorrhagic necrosis of adrenal glands. Loss of cortisol exacerbates the hypotension, leading to death
Liddle syndrome
- mech
- clinical presentation
- Tx
- decreased degradation of sodium channels in collecting ducts
- (mimics hyperaldosteronism) presents as HTN, hypokalemia, met alkalosis in a young pt
- tx: (tubular Na channel blockers) Amiloride/triamterene
Note: Aldo blockers (spironolactone) NOT EFFECTIVE
How to distinguish primary from secondary adrenal insufficiency?
(2)
In primary:
- hyperpigmentation (MSH from POMC)
- hyperkalemia (aldo still governed by RAAS system)
Conn syndrome
primary hyperaldosteronism, from aldosterone secreting tumor
