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Fayetteville VA Medical Center Grand Rounds July 10, 2015 Adrenal Update Stanley A. Tan MD, PhD, MPH, DTM&H, FACE, FACC, FCCP Endocrinologist Objectives After this presentation, audience should be able to: • Evaluate and manage adrenal mass • Evaluate and manage adrenal insufficiency • Evaluate and manage adrenal excess diseases: hypercortisolemia (Cushing) and hyperaldosteronism • Evaluate and manage pheochromocytoma Adrenal Mass Evaluation • Functional Evaluation – Overnight dexamethasone suppression test – Aldosterone level – Fractionated catecholamines or metanephrines • “Incidentaloma” – Under 4 cm – Non secreting/functioning – Stable/non growing Adrenal Mass Surgery Indication • • • • Functioning Mass Over 4 cm Growing Mass Malignancy Laparoscopic Adrenalectomy • • • • • Tumor < 10 cm Secreting/functioning mass Pheochromocytoma Non secreting mass > 4 cm Non malignant mass Adrenal Cortical Layers • Zona glomerulosa: mineralocorticoids (eg aldosterone) • Zona fasciculata: glucocorticoids (eg cortisol) • Zona reticularis: adrenal sex steroids/weak androgens (eg dehydroepiandrosterone-DHEA) Adrenal Insufficiency Addison’s Disease • Addison's disease is the result of an underactive adrenal gland (adrenal insufficiency). • Four in every 100,000 people have Addison's disease. Etiology of Addison’s Disease • 1/2 idiopathic • 1/3 are caused by the actual destruction of the adrenal glands through cancer, infection (TB), or other diseases. • 10% auto-immune, may be associated with other auto-immune diseases (Schmidt’s Syndrome: polyglandular auto-immune disease) • Prolonged use of corticosteroids as a treatment • Certain drugs, e.g. ketoconazole, may block production of corticosteroids in the adrenal glands. Addison’s Disease Presentations • • • • Hyponatremia and hyperkalemia, which cause leads to the inability to produce concentrated urine by the kidneys, leading to polyuria, hypotension, NVD, abdominal pain and dehydration Increased insulin sensitivity and decreased gluconeogenesis, leading to hypoglycemia Decreased body’s ability to fight infection, and to heal Patient is at increased risk during stressful periods, such as surgery, infection, or injury, which may lead to Addisonian Crisis Addison’s Disease Symptoms • • • • • • • • • • • Weakness Fatigue Dizziness Dark skin Bluish-black discoloration around the nipples, mouth, rectum, scrotum, or vagina Weight loss Dehydration Lack of appetite Muscle aches Nausea, vomiting, diarrhea Cold intolerance Diagnostic Test for Addison’s • Cosyntropin stimulation test: –Basal cortisol –0.25 mg cosyntropin IV or IM –1-hr post cortisol level –Rise of 7 mg/dl above basal with final value of > 15 mg/dl Laboratory Tests for Addison’s • Blood sugar • Electrolytes (sodium & potassium) and Osmolarity: – Serum Na, K, Osm – Urine Na, K, Osm • Increased creatinine • TSH & free T4 Management of Addison’s • Corticosteroids: – Acute full stress dose: Hydrocortisone 100 mg IV q8h – Physiologic replacement equivalents: • • • • • • Cortisone acetate 25 mg qAM 12.5 mg qPM Hydrocortisone 20-10 Prednisone 5-2.5* Methylprednisolone 4-2* Dexamethasone 0.75-0.375* *+ Fludrocortisone • Fluid/electrolytes replacement • Glucose • Treat underlying diseases Over-active Adrenal Glands • Excess glucocorticoids • Excess mineralocorticoids • Excess adrenal androgens Excess Glucocorticoids • Cushing Disease: – ACTH producing pituitary tumor – Adrenal hyperplasia – Ectopic ACTH • Cushing Syndrome – Adrenal tumors – Adrenal hyperplasia – Exogenous corticosteroids Excess Mineralocorticoids • Conn disease: Aldosteronoma • Certain salt-retaining adrogenital syndrome • Exogenous mineralocorticoids Cushing’s Symptoms-1 • • • • • • Upper body obesity Round face Increased fat around neck Thinning arms and legs Fragile and thin skin Stretch marks on abdomen, thighs, buttocks, arms, and breasts • Bone and muscle weakness Cushing’s Symptoms-2 • • • • • • Severe fatigue High blood pressure High blood sugar Irritability and anxiety Excess hair growth in women Irregular or stopped menstrual cycles in women • Reduced sex drive and fertility in men Diagnostic Tests for Cushing • Screening – 24-h urinary Free Cortisol – Overnight dexamethasone suppression test: • Dexamethasone 1 mg (2x0.5 mg) po at 11PM • Cortisol at 8 AM the next morning: normal <5 mg/dl • Specific steroids assay – Serum & urine • CRH stimulation test • Imaging – CT and MRI Treatment for Cushing • Depends upon etiology • Surgery to remove tumors or the adrenal glands. • Other treatment may include radiation, chemotherapy, and use of certain hormone-inhibiting drugs (opDDD, mitotane, metyrosine) Excess Mineralocorticoids • Conn’s Syndrome—hyperaldosteronism – Aldosteronoma • Secondary hyperaldosteronism—Renal artery stenosis (hyper-reninemia) – Increased PRA • Certain salt retaining andrenogenital syndrome • Exogenous Hyperaldosteronism • Conn’s Syndrome (Primary Hyperaldosteronism): – Elevated serum or urine aldosterone level – Suppressed plasma renin activity (PRA) – Not suppressed by captopril: • Captopril 25 mg po • Aldosterone level 2 h later • Secondary hyperaldosteronism – Increased PRA – Aldosterone suppressed by captopril Hyperaldosteronism • • • • • • • Hypertension Hypernatremia Hypokalemia Normal blood sugar No Cushingoid features No hyperpigmentation or striae No hirsutism or virilization Hyperaldosteronism • Aldosteronoma – Adrenal tumor on MRI or CT – Adrenal vein sampling for aldosterone & PRA • Right & left adrenal veins • Superior & inferior vena cava • Renal artery stenosis—secondary hyperaldosteronoma – Adrenal arteriogram – Adrenal vein sampling for PRA & aldosterone Treatment for Hyperaldosteronism • Medical: – Spironolactone – ACE inhibitor – ARB – Eplerenone • Surgical: – Aldosteronoma resection – Renal artery angioplasty/stent Pheochromocytoma • Catecholamine producing tumors: – Adrenal medulla pheo: Excess epinephrine – Ganglion tumor: Excess norepinephrine • Associated with other neuro-ectoderm tumors: – MEN type II (Sipple Syndrome) – PTC: Pheochromocytoma, Thyroid medullary CA, Parathyroid tumor – Neurofibromatosis Pheochromocytoma Sign/Symptom • • • • • • • • • Headaches (severe) Excess sweating (generalized) Racing heart (tachycardia and palpitations) Anxiety / nervousness (feelings of impending death) Nervous shaking (tremors) Pain in the lower chest or upper abdomen Nausea (with or without nausea) Weight loss Heat intolerance Who should be evaluated for Pheochromocytoma? • Patients with very difficult to control hypertension • Patients requiring more than 4 blood pressure medications • Patients with onset of hypertension before the age of 35 • Patients with onset of hypertension after the age of 60 • Patients with signs or symptoms of pheochromocytoma Diagnosing Pheochromocytoma • 24-h urinary fractionated metanephrines & catecholamines • Plasma fractionated catecholamines (epinephrine, norepinephrine, dopamine) • Phentolamine test • Clonidine suppression test – Basal fractionated catecholamines – Clonidine 0.3 mg po – 2-h later: Another (suppressed) fractionated catecholamines • MRI • Octreoscan/MIBG Treatment for Pheochromocytoma • Medical – Dibenzylin – Clonidine – Alpha and beta blockers • Surgical – – – – – Standard trans-abdominal Thoraco-abdominal Posterior Retroperitoneal Laparoscopic