Adrenal Disorders PDF

Adrenal Gland Disorders Emily Bodfish, MPAS, PA-C PA 511- Clincial Medicine I Emory and Henry School of Health Sciences Objectives 1. Compare and contrast Addison Disease and Cushing Syndrome. 2. List causes for patients with adrenal diseases. 3. Describe signs...

Adrenal Gland Disorders Emily Bodfish, MPAS, PA-C PA 511- Clincial Medicine I Emory and Henry School of Health Sciences Objectives 1. Compare and contrast Addison Disease and Cushing Syndrome. 2. List causes for patients with adrenal diseases. 3. Describe signs and symptoms for patients with adrenal diseases. 4. Review abnormal laboratory and diagnostic findings in patients with adrenal diseases. 5. Discuss treatment options for patients with adrenal diseases. Adrenal Gland Anatomy Adrenal Gland Adrenal Gland Cortisol A BIG FIB Aldosterone  Adrenal Insufficiency  Primary (Addison Disease): ↓adrenal gland function = ↓ adrenocortical hormones (cortisol, aldosterone, DHEA) Types of Secondary: ↓ACTH (pituitary) = ↓Cortisol (adrenal gland) Adrenal Tertiary: ↓CRH (hypothalamus) = ↓ACTH Insufficiency (pituitary) Seen in patients with chronic exogenous steroid use Aldosterone synthesis Precipitated by abrupt withdrawal unaffected since adrenal gland is intact!  Primary Adrenal Insufficiency (Addison’s Disease) Definition: Adrenal gland abnormality = ↓cortisol, ↓aldosterone, ↓dehydroepiandrosterone (DHEA) 90% of adrenal cortex must be destroyed to cause adrenal insufficiency Acute Addison disease = Adrenal Crisis Addison disease untreated = life-threatening 90% female Incidence of 5 cases per million in the U.S.  In developed countries: 90% → Autoimmunity = Most common cause Autoimmune polyglandular syndromes Leading to atrophy of the adrenal cortex Addison’s The remaining 10%: Disease: Bilateral adrenal hemorrhage: Sepsis, HIT, anticoagulation, Antiphospholipid syndrome Genetic conditions Etiology Medications – mitotane, abiraterone acetate (chemotherapy drugs) Adrenal suppression following steroid therapy can persist up to a year (more so in SECONDARY Tuberculosis - #1 in the world-may involve the adrenals & destroy them Addison Disease Signs & symptoms are usually gradual Addison Disease: Hyperpigmentation Knuckles, elbows Nipple area Around pressure areas Skin folds Scars  Addison Disease Hyperpigmentation Addison’s Signs & Symptoms Neuro/Psych: Anxiety, irritability, depression, confusion Endo: Hypoglycemic Hypovolemia: Due to decreased cardiac output & increased renal blood flow with azotemia Intolerance to stress: In times of stress they cannot increase cortisol levels→ can result in life-threatening vascular collapse  Addison’s Labs & Diagnostics Basic Metabolic Panel Hyponatremia: Due to reduced aldosterone-mediated reabsorption of sodium in the distal renal tubules Hypoglycemia Hyperkalemia CBC: +/- moderate neutropenia, lymphocytosis, & eosinophilia AM Serum Cortisol (test of exclusion) < 3 mcg/dl = Adrenal insufficiency (Addison Disease) Diagnostic if accompanied by elevation of plasma ACTH 3-18 mcg/dl → perform ACTH Stimulation Test > 18 mcg/dl = Excludes Addison Disease Addison’s Labs & Diagnostics Cosyntropin (ACTH) Stimulation Test – confirmatory test 1.) Synthetic ACTH (cosyntropin) is given IM/IV 2.) Serum cortisol is obtained 45 minutes after Normal: serum cortisol ≥ 20 mcg/dL Adrenal insufficiency: Serum cortisol < 20 mcg/d Serum ACTH Perform to determine type of adrenal insufficiency If ↑ = Addison disease If ↓ = Secondary adrenal insufficiency  Additional Addison's Labs Overnight Metyrapone Test Measure cortisol response to metyrapone stimulation Plasma Renin Activity May distinguish Addison Disease & secondary adrenal insufficiency DHEA & DHEA-S Suppressed ( 50 mcg/day = Confirms Cushing syndrome Cushing Disease Diagnostic Testing To determine source of hypercortisolism Plasma ACTH & DHEAS High ACTH & high DHEAS = Pituitary or ectopic sources Low ACTH & low DHEAS = Probable adrenal tumor High-dose dexamethasone suppression test Suppression of cortisol and ACTH secretion = Pituitary etiology Imaging MRI head → Pituitary lesion (more common) CT abdomen → Adrenal lesion (less common) Whole body imaging (68Ga-somatostatin receptor-PET/CT) → For ectopic causes Cushing Disease Cushing Syndrome Cushing Syndrome Cushing Disease Treatment Surgical Therapy Pituitary Adenoma (ACTH-secreting) - transsphenoidal resection Ectopic ACTH-secreting tumors - resection of tumor & metastases +/- medical therapy of Adrenal enzyme inhibitors (Mitotane, ketoconazole, metyrapone) Medical therapy: Often required when surgery is delayed, contraindicated, unsuccessful or the tumor cannot be located or resected Adrenal enzyme inhibitors are the most commonly used drugs Pituitary irradiation — For patients in whom fertility is an important concern Nonresectable tumor → Adrenal enzyme inhibitors Cushing Disease Treatment If treatment continues to be refractory, the final definitive cure: Bilateral Adrenalectomy PLUS Lifelong daily glucocorticoid & mineralocorticoid replacement therapy May be preferred by some patients instead of radiation therapy Cushing Syndrome Treatment Surgical Therapy Benign adrenal adenomas Are usually resected laparoscopically if smaller than 6 cm Adrenocortical carcinomas Usually resected surgically and treated with mitotane postoperatively for 2-5 years Medical Therapy Mineralocorticoid Hypertension Spironolactone, eplerenone, dihydropyridine calcium channel blockers Hyperandrogenism Flutamide Other agents Cabergoline Patient Education Surgical treatment has an approximate 90% 10-year survival Complete remission after surgery has about a 15-20% chance of recurrence over the next 10 years Patients should be referred to Endocrinology with an abnormal dexamethasone suppression test Transsphenoidal Surgery Transsphenoidal surgery Adrenal Tumors  Adrenal Tumors Tumors of the Adrenal Cortex Adrenocortical adenoma (MC) Adrenocortical carcinoma (v. rare, highly aggressive) Tumors of the Adrenal Medulla Neuroblastoma Pheochromocytoma Incidentalomas Adrenal Tumors Adrenocortical adenoma Common, 1-10% of persons at autopsy Only 15% are “functional” (hormone producing) These are often treated surgically Adrenocortical carcinoma Rare, highly aggressive cancer These may grow quite large and may be “functional” Often treated with surgery Adrenal Tumors Incidentaloma One of the more common unexpected findings on a CT scan or MRI Tumors under 3 cm are generally considered benign & are only treated if there is evidence of Cushing’s syndrome or pheochromocytoma Adrenal Tumors Neuroblastoma Aggressive cancer of immature neuroblastic cells One of the most common pediatric cancers Often produce elevated levels of catecholamine hormone metabolites Neuroblastoma Presentation Most common: Abdominal distention and a firm, irregular mass that can cross the midline Severe watery diarrhea through production of vasoactive intestinal peptide Less likely to develop hypertension than with pheochromocytoma (Neuroblastoma is Normotensive) Opsoclonus-myoclonus syndrome ("dancing eyes- dancing feet") https://youtu.be/OatItXWkWUE Treatment: Surgery & radiation therapy (& chemotherapy for metastatic disease) Laproscopic Adrenal surgery Hyperaldosteronism Aldosterone Actions Primary Hyperaldosteronism Definition = Excessive Production of aldosterone MC cause: Bilateral adrenal cortical hyperplasia (75%) M:F→ 4:1 Peaking between ages 50 and 60 Unilateral aldosterone-producing adrenocortical adenoma (aka Conn syndrome, 25%) M:F→ 1:2 Peaking between ages 30 & 50  Renin & Primary Hyperaldosteronism In primary hyperaldosteronism, the increased aldosterone production is caused by an adrenal abnormality The volume expansion that results decreases renin production Primary Hyperaldosteronism causes increased aldosterone production & reduced renin activity Hyperaldosteronism Clinical Features Hallmark = Hypokalemic hypertension Sodium retention → Blood pressure elevation Potassium loss → Hypokalemia→ Symptoms include muscle weakness, paresthesias, & tetany, headache, polyuria Metabolic Alkalosis: Result of renal potassium & hydrogen ion depletion What Should Clue You In to Hyperaldosteronism? Difficult to control Onset of disease Patient has hypertensive Adrenal mass before the age of hypokalemia patient 40 years Diagnosis of Hyperaldosteronism Measurement of plasma renin & aldosterone with subsequent calculation of the aldosterone-renin ratio (ARR) = Most reliable screening test Must discontinue diuretics and vasodilators 2 weeks prior & have any hypokalemia corrected ARR of 24-64- indeterminate/suspicious ARR>64 = Confirms primary aldosteronism Diagnostic confirmation: Saline infusion test: Measure plasma aldosterone after 2 L of NS has been infused over 4 hours Failure of aldosterone to suppress