Adrenal hyperfunction Notes

NOTES NOTES ADRENAL HYPERFUNCTION GENERALLY, WHAT IS IT? PATHOLOGY & CAUSES ▪ Overproduction of ≥ one adrenal hormones → complex systemic disorders CAUSES ▪ Pituitary/adrenal endocrine tumors ▪ Idiopathic, iatrogenic ▪ Increased aldosterone → hyperaldosteronism ▪ Increased cortisol → Cushing syndrome SIGNS & SYMPTOMS DIAGNOSIS DIAGNOSTIC IMAGING CT scan/MRI ▪ Image tumors LAB RESULTS ▪ Blood/urine tests; measure hormone levels TREATMENT ▪ See individual disorders ▪ Diffuse systemic symptoms due to systemic endocrine effects CONN'S SYNDROME osms.it/conns-syndrome PATHOLOGY & CAUSES ▪ Type of primary hyperaldosteronism CAUSES ▪ Adrenal glands produce too much aldosterone due to benign tumor (adrenal adenoma) ▫ Forms in zona glomerulosa in adrenal gland RISK FACTORS ▪ Individuals who are biologically female, 20–60 years old, with family history 68 OSMOSIS.ORG SIGNS & SYMPTOMS ▪ Headache, facial flushing (due to hypertension) ▪ Constipation, muscle weakness, arrhythmias (if severe, due to hypokalemia) ▫ Low potassium, high blood pressure (BP); unresponsive to treatment

Chapter 11 Adrenal Hyperfunction DIAGNOSIS DIAGNOSTIC IMAGING CT scan ▪ Abdominal CT scan to differentiate tumor from idiopathic hyperaldosteronism LAB RESULTS ▪ Adrenal vein sampling (CT scans do not detect lesions < 1cm/0.39in) TREATMENT SURGERY ▪ Unilateral adrenalectomy Figure 11.1 The gross pathological appearance of an adrenal cortical adenoma in an individual with Conn’s syndrome. CUSHING'S SYNDROME osms.it/cushings-syndrome PATHOLOGY & CAUSES ▪ Endocrine disorder caused by increased cortisol ▪ Can be endogenous (caused by cortisol production inside body)/exogenous (iatrogenic) ▪ Pseudo Cushing’s syndrome: estrogencontaining oral contraceptive pills → increased cortisol-binding globulin → increased total cortisol ▫ Active hormone total free cortisol levels found in a 24-hour urine sample normal CAUSES Primary ▪ Tumor in zona fasciculata of adrenal gland secretes cortisol ▪ Adenoma (benign)/adenocarcinoma (malignant) Secondary ▪ Iatrogenic ▫ Glucocorticoid steroid medications to treat inflammatory, autoimmune disorders (e.g. asthma, rheumatoid arthritis, eczema, immunosuppression); most common ▪ Pituitary adenoma (benign) ▫ Leads to excess adrenocorticotropic hormone (ACTH), adrenal cortisol secretion ▪ Adrenal Cushing’s disease ▫ Adrenal gland tumors/hyperplastic adrenal glands/nodular adrenal hyperplasia of adrenal glands produce excess cortisol ▪ Ectopic ACTH ▫ Increased ACTH secreted from benign bronchial carcinoid tumors/malignant oat-cell carcinoma COMPLICATIONS ▪ Metabolic syndrome, diabetes, infection due to immunosuppression, fragility fractures due to osteoporosis OSMOSIS.ORG 69

SIGNS & SYMPTOMS ▪ Fat redistribution due to glucose release → insulin release ▪ Muscle, bone, skin breakdown due to protein breakdown ▪ Hypertension due to corticosteroids crossreacting with mineralocorticoid receptors ▪ High cortisol → feedback inhibition of GH-releasing hormone (GRH) → disrupts ovarian, testicular function DIAGNOSIS DIAGNOSTIC IMAGING CT scan ▪ Adrenal glands (primary Cushing’s) ▪ Chest, abdomen, pelvis (ectopic ACTH production) MRI ▪ Pituitary gland (Cushing’s disease) LAB RESULTS ▪ ↑ free cortisol in 24-hour urine sample ▪ Cortisol blood/saliva test: ↑ cortisol ▫ Performed in evening when cortisol levels are normally low OTHER DIAGNOSTICS Figure 11.2 Abdominal striae in an individual with Cushing’s syndrome. MNEMONIC: BAM CUSHINGOID Signs & symptoms of Cushing’s syndrome Buffalo hump: fat redistribution Amenorrhea Moon face: fat redistribution Psychosis/agitation: previously, Crazed Ulcers Skin changes: acne, purple striae/stretch marks Hypertension Infection: due to immunosuppression Necrosis of femoral head Glaucoma Osteoporosis: causing fragility fractures Immunosuppression Diabetes 70 OSMOSIS.ORG Dexamethasone suppression test ▪ Differentiates endogenous, exogenous Cushing’s syndrome ▪ Measure cortisol change after dexamethasone (exogenous steroid) ▪ Endogenous Cushing’s syndrome: cortisol unchanged, negative feedback cycle broken by autonomous endocrine tumor in pituitary, adrenal, etc. (ectopic ACTH) ▪ Positive dexamethasone test ▫ High ACTH: ACTH-producing tumor ▫ Low ACTH: adrenal tumor, causing pituitary ACTH suppression Long dexamethasone suppression test ▪ If high ACTH ▪ Differentiates ACTH-producing pituitary tumor, ectopic ACTH-producing tumor (e.g. small cell lung cancer) ▫ Cushing’s disease (pituitary adenoma): cells partly responsive to negative feedback → cortisol decrease ▫ Ectopic ACTH-producing tumor: no negative feedback → cortisol unchanged

Chapter 11 Adrenal Hyperfunction TREATMENT MEDICATIONS ▪ Cortisol inhibitors ▫ Esp. if surgery ruled out by ectopic ACTH production/metastatic adrenal carcinoma ▪ Wean steroid medications ▫ For Iatrogenic Cushing’s ▫ Sudden withdrawal → adrenal crisis SURGERY ▪ Transphenoidal resection of pituitary gland ▫ For Cushing disease ▪ Surgical resection ▫ For adrenal adenoma Figure 11.3 A large fat deposit at the upper back in an individual with Cushing’s syndrome. HYPERALDOSTERONISM osms.it/hyperaldosteronism PATHOLOGY & CAUSES ▪ Adrenal gland produces excess aldosterone → hypertension (high blood pressure), hypokalemia (decreased blood potassium) ▪ Increased aldosterone → sodium, water retention → increased blood volume → hypertension TYPES Primary ▪ Idiopathic (2/3 of cases): overproduction from both adrenal glands ▪ Conn’s syndrome (1/3 of cases): benign adrenal tumor → excess aldosterone ▪ Familial hyperaldosteronism: rare genetic condition, adrenocorticotropic hormone (ACTH) → adrenal aldosterone, renin secretion angiotensin-aldosterone axis activation → hyperaldosteronism ▪ Decreased blood flow to kidneys (e.g. renal stenosis) ▪ Renal-secreting neoplasms COMPLICATIONS ▪ Hypertension, hypokalemia ▫ Heart disease (ischemic heart disease, arrhythmias), vascular disease, renal disease, stroke, alkalosis (due to increased hydrogen ion excretion) SIGNS & SYMPTOMS ▪ Headache, facial flushing (due to hypertension) ▪ Constipation, muscle weakness, arrhythmias (if severe, due to hypokalemia) Secondary ▪ Hypotension (e.g. congestive heart failure, cor pulmonale, hypoalbuminemia, cirrhosis, ascites, coarctation of aorta) → renin- OSMOSIS.ORG 71

DIAGNOSIS LAB RESULTS ▪ Renin, aldosterone levels in blood and urine ▪ Primary ▫ Increased aldosterone, decreased renin; potassium decreased/normal ▫ Metabolic acidosis secondary to hypokalemia ▪ Secondary ▫ Increased renin, aldosterone in blood OTHER DIAGNOSTICS ▪ Increased blood pressure TREATMENT ▪ Goal: prevent complications of hyperaldosteronism on organs (e.g. ventricular hypertrophy, heart failure, stroke, myocardial infarction, atrial fibrillation, metabolic syndrome) MEDICATIONS ▪ Potassium-sparing diuretic/aldosterone antagonist ▫ Spironolactone ▪ Additionally ▫ Thiazide diuretics, angiotensin converting enzyme inhibitors (ACE) inhibitors, calcium channel antagonists, angiotensin II blockers OTHER INTERVENTIONS ▪ Control BP via lifestyle ▫ Sodium restriction, weight management, regular exercise ▪ Second-line ▫ Thiazide diuretics, ACE inhibitors, calcium channel antagonists, angiotensin II blockers 72 OSMOSIS.ORG