Adrenal Disorders - Some Common Questions Family Practice Refresher Course April 20, 2017 Janet A. Schlechte, M.D.

Disclosure of Financial Relationships Janet A. Schlechte, M.D. has no relationships with any proprietary entity producing health care goods or services consumed by or used on patients.

How do I rule-out Cushing’s? How do I check for hyperaldosteronism? What is the best replacement therapy for adrenal insufficiency? How to evaluate an adrenal incidentaloma. When to use stress doses of steroids. Adrenal fatigue?!?

“I think I have Cushing's” A 40 y.o. has gained 40 lbs in the last year. She has type 2 DM and irregular menses. She is 64 in. tall, weighs 200 lbs, has a buffalo hump, pink striae on her abdomen, a BP of 160/100 and bruises on her legs.

Common Features of Cushing's Centripetal obesity Violaceous striae Proximal muscle weakness Amenorrhea Thin skin Bruising Hypertension Glucose intolerance Diabetes Hypokalemia Bone loss

Many of your patients will have striae, weight gain and bruises but only a few will have Cushing’s. Because symptoms and weight gain are so prevalent, need a screening test to rule out glucocorticoid excess. Don’t do random cortisol, random ACTH, adrenal CT or pituitary MRI.

Screening Tests For Cushing’s A screening test will answer the question “does the patient have cortisol excess?” 24 hour urine cortisol (UFC). 1 mg (overnight) dexamethasone suppression test. 11 PM salivary cortisol(?)

24 hour UFC - few false positives - if UFC is normal Cushing’s is excluded Overnight DST - 1 mg Dex at 11 PM and 8 AM cortisol the next day - cortisol <1.8 after Dex excludes Cushing’s - false positives (estrogen, obesity, depression)

A 30 y. o. woman has gained 20 pounds over the last six months A 30 y.o. woman has gained 20 pounds over the last six months. She has also noted leg swelling and her blood pressure is harder to control. She takes HCTZ and a BCP. B/P 140/100, BMI 35, bruises on legs, buffalo hump, pale pink striae.

You give 1 mg of dex at 11 p. m. and an 8 a. m You give 1 mg of dex at 11 p.m. and an 8 a.m. cortisol the next day is 10 (<1.8). Does she have Cushing’s? No – BCP has increased corticosteroid binding globulin leading to increased cortisol. She needs a different screening test.

She then collects a 24 hour UFC and the result is 25 (<50). Does she have Cushing's? When screening test is negative Cushing’s is ruled out. When screening test is positive refer to Endocrine.

CLASSIC PRIMARY ADRENAL INSUFFICIENCY A 41 y.o. collapsed on the golf course in August. For 6 months he has had fatigue, nausea, and abdominal pain. His BP is 60/-, pulse 130. He has a deep tan, pigmented buccal mucosa, and small thyroid. Sodium 125, potassium 6.4, glucose 65. CLASSIC PRIMARY ADRENAL INSUFFICIENCY

CLASSIC SECONDARY ADRENAL INSUFFICIENCY A 40 y.o. with chronic back pain is complaining of fatigue and abdominal pain. She receives occasional injections of triamcinolone and requires chronic opiate therapy. In the ER her BP is 90/- and they call to let you know that her cortisol is 1.2!!! CLASSIC SECONDARY ADRENAL INSUFFICIENCY

Cortrosyn Stimulation (250 µg) 30 baseline 25 20 1 hour Cortisol 15 10 5 Primary Secondary Normal

Primary Adrenal Insufficiency Autoimmune Adrenal hemorrhage Granulomatous disease Mineralocorticoid and glucocorticoid replacement

Secondary Adrenal Insufficiency Glucocorticoid therapy Opiates, psychotropic meds, narcotics Medroxyprogesterone Pituitary tumor Adrenals are intact so mineralocorticoid rarely necessary

Glucocorticoid Equivalencies 5 mg Prednisone* 10-15 mg Hydrocortisone 0.75 mg Dexamethasone* * little or no mineralocorticoid activity

A 40 y. o. woman has an abdominal CT as work-up for abdominal pain A 40 y.o. woman has an abdominal CT as work-up for abdominal pain. The pain subsides but the CT scan shows a 2.5 cm adrenal mass. She has no complaints and her exam is normal.

Adrenal Incidentaloma First ask “is the mass hormonally active?” Are there clinical signs of glucocorticoid, mineralocorticoid or adrenal androgen excess? Is there evidence of increased epinephrine or norepinephrine?

Screen for pheochromocytoma - urine or plasma catecholamines/metanephrines Screen for subclinical Cushing’s - 1 mg DST (cut-off is <5) If patient is hypertensive and K is low check - plasma renin activity - aldosterone With hirsutism or virilization - DHEA-S

Refer to surgery if incidentaloma is > 4 cm FNA not helpful If Dex test, DHEA-S or aldosterone are abnormal refer to Endocrine

Long Term Follow-Up of the Adrenal Incidentaloma Controversial If mass is not hormonally active repeat CT in 12 months Growth uncommon

Hyperaldosteronism Hard to control blood pressure or patient on multiple agents with poor control Bilateral adrenal hyperplasia or single adenoma ↑ aldosterone, ↓ plasma renin activity Renin aldosterone ratio >20 when aldosterone is >15.

Hyperaldosteronism If screening test is abnormal – i.e., PRA >20, refer to Endocrine or Renal for salt suppression test If aldosterone suppresses after salt, hyperaldosteronism has been ruled out

The 21st Century Stress Syndrome Adrenal Fatigue Not an accepted medical diagnosis The idea is that existing blood tests are too insensitive to recognize diminished adrenal function The 21st Century Stress Syndrome

A 45 y.o. woman with rheumatoid arthritis has been treated with 10 mg of prednisone for 3 years. She will undergo laparoscopic surgery in 2 days. Her surgeon asks you to write pre-op orders.

Peri-Operative Corticosteroid Coverage Minor surgical stress - usual dose day of procedure Moderate surgical stress - 50 mg HC day of procedure then resume usual dose Major surgical stress - 100 mg HC on day of procedure - 50 mg HC on post-op day 1 Resume usual dose unless clinical condition deteriorates Ann Surg 219:416, 1994

In patients taking glucocorticoids who needs a stress dose? Pulling wisdom teeth Colonoscopy Endometrial biopsy Flu with aches and pains CABG Hip replacement Final exams Death in the family

Always try to avoid too much glucocorticoid, remember the equivalencies After a stress dose rapidly resume the usual replacement dose Don’t use cortisol or ACTH to monitor therapy

KEEP CALM AND TRUST YOUR ENDOCRINOLOGIST