Transcript Case
Case A 40 y.o. male presents with Rt flank pain radiating to his groin that started acutely last night. He has noted some hematuria as well. On physical exam you note Rt sided CVA tenderness. Given concerns for abdominal pathology you order a CT A/P Case Jason Haag Intern Conference Adrenal Incidentaloma Lesion > 1 cm in diameter Found in 4-6% on CT scans Functioning or nonfunctioning Adrenal Masses Differential Diagnosis Cold (nonsecreting) adenoma Cortisol secreting adenoma Aldosterone secreting adenoma Adrenocortical Carcinoma Metastatic Carcinoma Pheochromocytoma (medullary) Work-up Step 1 ○ Does the patient have an adrenal syndrome Step 2 ○ Screening tests Step 3 ○ Repeat imaging Cushing’s Syndrome Symptoms: weight gain, central obesity, rounded facies, dorsocervical (back of the neck) fat pad, easy bruising, thin skin, poor wound healing, purple abdominal striae, acne, hirsutism, infertility, depression, irritability, opportunistic infections Signs: hypertension, diabetes, impaired glucose tolerance, osteoporosis, osteopenia, hypokalemia, leukocytosis with relative lymphopenia Cushing’s Syndrome Screening tests *24 hour urine cortisol ○ Values higher than 3-4 times normal are highly suggestive of autonomous cortisol secretion. Values above normal but less than 3-4 times normal are inconclusive. *Overnight 1-mg dexamethasone suppression test ○ Patient takes 1 mg dex pill at 11 PM, then fasts, then presents to lab at 8:00 AM for measurement of serum cortisol. Serum cortisol level > 5 mcg/dl is highly suggestive of autonomous cortisol secretion. Serum cortisol level < 1.8 mcg/dl excludes Cushing’s syndrome. Primary Aldosteronism Symptoms: Nocturia, polyuria, muscle cramps, palpitations Signs: Hypertension, hypernatremia, hypokalemia Primary Aldosteronism Plasma renin activity (PRA) and plasma aldosterone concentration Should be measured in the AM. Can be performed with patient on any medicines except spironolactone, eplerenone, or amiloride. *Aldo/PRA ratio of 20 with aldo level of 15 ng/dl is positive result ○ * This test is highly dependent on the denominator. Consider the level of aldosterone required to achieve a ratio of 20:1 in the case where renin level is measured to be “1”, versus when the renin level is measured to be “0.1”. Different labs have different sensitivities for measuring renin activity, thus the requirement of not only a ratio of 20: 1 but also an aldosterone level of 15 ng/dl for a positive test. Pheochromocytoma Symptoms: (in paroxysms) tachycardia, palpitations, pallor, tremor, headache, diaphoresis. May be precipitated by maneuvers that increase intra-abdominal pressure (Valsalva, lifting, pregnancy, postural), or by anxiety, or by medicines such as reglan. Signs: Hypertension, orthostatic hypotension, pallor, retinopathy, fever, tremor Pheochromocytoma Pheos may be Benign or malignant (10%) Inherited (25%) or de novo In the adrenal gland or in other sympathetic chain/ganglia cells outside the adrenal gland (10%). Typically pheos are adrenal medullary tumors that secrete catecholamines. Pheochromocytoma Catecholamines: epinephrine, norepinephrine, dopamine ○ - Problem with measuring spot serum catecholamines? Episodic secretion ○ - To enhance sensitivity, can measure 24 hr urine catecholamines. ○ - However, measuring catecholamines can yield false positives (too many substances – both endogenous and exogenous – cross react w/ the catecholamine assay). Metanephrines: metanephrine, normetanephrine ○ - More specific than measuring catecholamines is measuring 24 hr urine metanephrines, which are the breakdown products of catecholamines Pheochromocytoma What about measuring spot plasma free metanephrines? Very high sensitivity (~98%). Appealing because it is just a simple blood draw. May be too sensitive at the expense of specificity. Of patients over 60 with hypertension and elevated plasma free metanephrines, 97% will NOT have pheochromocytoma. Pheochromocytoma Recommendation 24 hr urine fractionated catecholamines and 24 hr urine fractionated metanephrines. ○ Always fractionate; pheos typically secrete norepinephrine (and normetanephrine) out of proportion to epinephrine (and metanephrine). (Consider) Plasma free metanephrines ○ Must understand the test properties; high sensitivity, low specificity – thus may lead to excessive testing, procedures, surgeries and health care expenditures. Adrenocortical Carcinoma Symptoms/Signs: “Salt” – c/w Aldosteronsim “Sugar” – c/w Cushing’s syndrome “Sex” ○ androgens: hirsutism, acne, oily skin, amenorrhea, oligomenorrhea, increased libido ○ estrogens: gynecomastia, testicular atrophy > 4 cm in size worrisome for carcinoma Consider excision of mass Follow-Up If functional studies are normal Recommend repeat imaging at 6-12 months Recommend repeat adrenal screening annually for 4 years If concern for malignant potential based on imaging the biopsy or excision Take Home Points 1. If there is no adrenal syndrome on history and physical, and the adrenal incidentaloma is less than 1 cm, don’t worry about it. 2. Of adrenal incidentalomas (>1 cm) without a clinical syndrome: 5.3% subclinical Cushing’s 5% subclinical pheo 4.7% adrenocortical carcinoma 2.5% metastatic carcinoma 1% subclinical aldo 3. Treating patients (the treatment is usually surgical) with subclinical adrenal syndromes usually results in easier to control HTN, weight loss, better DM control, lower risk of osteoporosis, etc. ○ However, the major concern with discovery of an adrenal incidentaloma is the possibility of malignant disease! 4. Of the adrenal syndromes mentioned above, the only one which presents with signs and symptoms of hyperandrogenism or estroginism is adrenocortical carcinoma.