| What are the principal adrenal pathologies? | Hypercortisolism, Pheochromocytoma, Primary Hypermineralocorticism |
| What is hypercortisolism? | Can be ACTH dependent (Cushing's syndrome) or Independent
Cushing's syndrome caused by: pituitary adenoma (Cushing's disease - 70%), Ectopic ACTH production (SCLC - 10%), CRH ectopic secretion
ACTH independent Cushing's syndrome: Either by primary adrenal secretion or exogenous admin, due to adenoma (10%) carcinoma (8%), bilateral micronodular adrenal hyperplasia (Carney syndrome: Schwanoma, testicular, vertebral, skin lesions in addition to adrenal hyperplasia, familial or sporadic))
Massive macronodular adrenal hyperplasia (Fasicular zone excess receptor formation - GIP, LH, AVP)
Exogenous admin of cortisone (inactive cortisol- activated by B HSD 2 enzyme) |
| What is pheochromocytoma? | It is a tumor in neuroectoderm (chromaffin cells), benign in adrenal medulla (catecholamines (NE and EPI)) and can be big tumors, involving extraadrenal (10% called paraganglioma- 35% in children 80% around aorta at IMA, 15% thoracic and 5% cervical)
10% bilateral (familial multiple endocrine neoplasia
10% malignant
10% for children
Can be associated with other syndromes like thyroid medullary cancer (protooncogene) |
| What are the two types of bilateral pheochromocytoma? | MEN1 and MEN2
MEN1: 3 Ps (hyperPTH, hyperPituitarism, Pancreatic lesions
MEN2: A: pheochromocytoma, hyperPTH and MTC
B: Pheochromocytoma, MTC and other presentations (Marfan for example) |
| What are the symptoms of pheochromocytoma? | 95% HTN (however it is considered as a rare cause of HTN (only 0.1% of all HTN))
Episodic symptoms (catecholamine crisis) typical triad is headache, sweating and palpitation + HTN (If all positive -->90% sensitivity and 70% specificity)
Other symptoms include heat, nausea, tremor, anxiety, abdominal pain, thoracic pain (due to vaso spasm) fatigue, flush (due to secretion of VIP other than NE and Epi), visual disorder. |
| What are signs seen between episodes of catecholamine crisis? | Profuse sweating, cold extremities, weight loss, constipation, hypovolemia, diabetes. |
| What are the biomarkers used in dx of pheochromocytoma? | Vanylmandelic acid (VMA): low sensitivity but highly specific, normal <8, between 8-11 sus, >11 high)
Metanephrines (urinary and plasma) (Highly sensitive and specific, pt fastest on certain food before the test, first line test is urinary metanephrines)
Catecholamines (urinary and plasma, very specific and sensitive, normal <400, sus btw 400 and 2000, >2000 high)
Chromogranin A (CGA, granules of catecholamines, sensitive not specific in presence of renal failure and PPI)
Pharmacological test (doubtful stimulation by glucagon and inhibition by clonidine) |
| How do we localize the tumors of pheochromocytoma? | Ideal scan is MRI (hyperintensity on T2 sequence typical pheo/ but not pathogneominc)
CT scan (seen if MRI negative)
Scintigraphy with MIBG (costly, in case of bilateral pheo or paraganglioma and MRI and CT and negative but still sus) |
| What are the tx options of pheochromocytoma? | It is a therapeutic emergency.
Surgical: median anterior incision, has a risk of HTN crisis in intubation or anesthesia, IV phentolamine or nitroprusside administered to decrease bp
Preop measures: 7 days preop start a blockers, and beta 3 days preop, Calcium Channel Blockers can be used (CCB) to minimize the possibility of HTN crisis
In addition we should avoid palpating abdomen to not induce HTN crisis. |
| What is hypermineralocorticism? | Excess mineralocorticoid, may be primary (with low renin production by adrenal glands blocking renin)
or Secondary (caused by hypersecretion of Renin. |
| What are the etiologies of primary hypermineralocorticism? | Adenoma producing aldosterone (APA) (~ 65%)
Bilateral Adrenal hyperplasia (BAH) (30-40%): lead to overproduction of aldosterone
Unilateral adrenal hyperplasia (UAH)
Glucocorticoid remediable hyperaldosteronism (GRA) (Known by aldosterone synthase hyperactivity that is ACTH sensetive; steroid therapy blocks ACTH and thus aldosterone production)
Corticoadrenaloma: malignant tumor |
| What is apparent hypermineralocorticism (AME)? | Autorecssive disorder, 11 b HSD 2 deficiency -->cortisol deactivation
Presents with: growth delay, low birth weight, severe HTN in childhood and hypercalciuria and nephrocalcinosis due to renal failure. |
| What is liddle syndrome? | Activating mutation of the sodium channel of the collecting tubules leading to water and sodium retention and HTA.. We have decrease in aldosterone by a negative feedback. This is a pseudohypoaldosteronism. |
| What are the etiologies of secondary hyperME with HTN? | Renovascular pathologies (Stenosis of the renal arteries caused by atherosclerosis, fibromuscular dysplasia)
Coarctation of the aorta
Renin-secreting tumor |
| What are the etiologies of hyperME without HTN? | Hypovolemia:
Bartter's syndrome (lack of NaCl re-absorption in ascending Henlee)
Pseudohypoaldosteronism Type I (Resistance to Aldosterone), high levels of aldo.
Diuretics
"Efficient" or "circulating" hypovolemia: (3rd compartment): excessive volemia leading to edema, ascites…
Heart failure
Hepatic Cirrhosis
Nephrotic syndrome |
| What are the clinical manifestations of primary hyperaldosteronism? | HTN (variable degree, not obligatory)
Hypokalemia (Severe with hyperkaliuria, but 20% have normal potassium)
Moderate Hypervolemia (Due to increased water absorption in distal tubule)
Metabolic acidosis (Na+ retension, H+ and K+ excretion)
Due to HTN (headache, retinopathy -rare)
Due to hypokalemia and acidosis (neuromuscular symptoms,DI, ECG disorder, orthostatic HTN, glucose intolerance...
Due to aldosterone action on CV (cardiac hypertrophy/fibrosis, vascular muscular hypertrophy |
| What are the measures done before starting testing for primary hyperaldosteronism? | Correct hypokalemia (hypoK inhibit RAAS), correct hypovolemia, specify position of dosing (lying/sitting), discontinuation of meds disrupting aldosterone action (spironolactone -4 weeks prior/ diuretics -15 days prior) |
| What are the tests done for dx of primary hyperaldosteronism? | Plasma potassium (not constant)
24-hour urinary potassium (increased excretion >30 with high salt diet )
Screening test (morning stimulation of aldosterone and renin and see PA/PRA ratio done twice (PA/PRA >30 strongly primary hyperaldo with 90% spec and sens, >70 is diagnostic)
Confirmation required if PA/PRA btw 30-70, either measure PA after suppression with IV saline or fludrocortisone , if aldo >10 --> primary hyperaldo
Or Urine aldo after high salt diet, if >14 confirmed
Be cautious of giving salt IV with heart issues |
| What are the characteristics in favor of adenoma over bilateral hyperplasia? | Young age (<50 years)
Severe hypokalaemia (<3.0 meq / L)
Very high aldosterone levels: Aldosterone plasma> 25ng / dl, urinary aldosterone > 30μg / 24hr
Absence of elevation of plasma aldosterone to the orthostatism test
Bilateral hyperplasia appears to be due to hypersensitivity to angiotensin II therefore when going to orthostatism, angio II increases or aldosterone increases. This is not observed in the adenoma. .
18-OH-B (18-OH-corticosterone)> 100ng / dl |
| How to differentiate adenoma from bilateral hyperplasia on screening, scintigraphy and catheterization? | CT or MRI (Spiral CT with fine section is gold standard for adenoma, if >1cm mass)
Iodocholesterol Scintigraphy (not used only in centers)
Catheterization (reference, invasive test, post ACTH stimulation measures cortisol and aldo together, gradient >4 -->adenoma, similar gradient btw both sides -->hyperplasia, not indicated in case of adenoma >1cm and age <35 with hypokalemia |
| What is treatment of primary hyperaldosteronism? | Adenoma: surgery (resolve hypokalemia and HTN) and meds (preop measures and if refute of operation)
Bilateral hyperplasia (no surgery, meds (spironolactone Aldo antagonist, AntiHTN tx (ACE inhibitors, amiloride)
Adrenal Carcinoma (surgery and chemo) |
| What are other causes of endocrine HTN? | Hyperparathyroidism (through hypercalcemia)
Hyperthyroidism (increased CO and heart rate) |
