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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.

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    1. 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

    2. Case

    3. Jason Haag Intern Conference Adrenal Incidentaloma

    4. Adrenal Incidentaloma • Lesion > 1 cm in diameter • Found in 4-6% on CT scans • Functioning or nonfunctioning

    5. Adrenal Masses

    6. Differential Diagnosis • Cold (nonsecreting) adenoma • Cortisol secreting adenoma • Aldosterone secreting adenoma • Adrenocortical Carcinoma • Metastatic Carcinoma • Pheochromocytoma (medullary)

    7. Work-up • Step 1 • Does the patient have an adrenal syndrome • Step 2 • Screening tests • Step 3 • Repeat imaging

    8. 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

    9. 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.

    10. Primary Aldosteronism • Symptoms: Nocturia, polyuria, muscle cramps, palpitations • Signs: Hypertension, hypernatremia, hypokalemia

    11. 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.

    12. 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

    13. 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.

    14. 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

    15. 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.

    16. Pheochromocytoma • Recommendation • 24 hr urinefractionated 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.

    17. 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

    18. 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

    19. 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.