Clin Med - Pituitary Adrenal Disorders PDF

Endocrinology Pituitary & Adrenal Disorders Matthew J. Kesic, PhD, PA-C Lecture & Slide Credits Course Coordinator: Ian Ward, PA-C Some slides were edited for use with permission from Ian Ward, PA-C Adrenal and Pituitary “Instructional Objectives” At the conclusion of this lecture and completion of...

Endocrinology Pituitary & Adrenal Disorders Matthew J. Kesic, PhD, PA-C Lecture & Slide Credits Course Coordinator: Ian Ward, PA-C Some slides were edited for use with permission from Ian Ward, PA-C Adrenal and Pituitary “Instructional Objectives” At the conclusion of this lecture and completion of required readings, the student will be able to: 1. Describe the functions of the hormones secreted by the hypothalamus, the anterior pituitary gland, and the posterior pituitary gland. 2. Describe the causes of hypo/hyperpituitarism. 3. Discuss the clinical presentation and evaluation of deficiencies and excess of the following pituitary hormones: Growth hormone (GH) Thyroid Stimulating Hormone (TSH) Adrenocorticotropic Hormone (ACTH) Gonadotropins (LH/FSH) 4. Compare the different types of pituitary tumors, and associated conditions such as gigantism and acromegaly. 5. Identify the imaging studies of choice in the evaluation of hypo/hyperpituitarism. 6. Describe the etiology, presentation, laboratory evaluation, differential diagnosis, and treatment for diabetes insipidus. 7. Discuss the causes and clinical presentation of Syndrome of inappropriate antidiuretic hormone secretion (SIADH). A&P Review for Hematology “Instructional Objectives” At the conclusion of this lecture and completion of required readings, the student will be able to: 8. Discuss the common etiologies, presentation, diagnosis and management of hyperprolactinemia. 9. Describe the functions of the hormones of the adrenal cortex. 10. Explain the pathophysiology, clinical findings, laboratory evaluation, and treatment approach for the following disorders of the adrenal cortex: a. Conditions of adrenal corticosteroid excess (hypercortisolism) 11. Describe the clinical findings, laboratory evaluation, and treatment of pheochromocytoma. Hypothalamic-Pituitary Pathway Hypothalamus Releasing hormone (RH) Hormone 1 (from pituitary) Endocrine target organ Hormone 2 (from target organ) TRH TSH Thyroid gland Thyroid hormones CRH ACTH Adrenal cortex Glucocorticoids Testes Inhibin Ovaries Inhibin Estrogens Ovaries Progestins Estrogens Testes Androgens RH Pituitary gland FSH Anterior lobe GnRH LH Hormone 1 Negative feedback Endocrine organ KEY Stimulation Hormone 2 Inhibition Target cells Hormones of the Hypothalamus Releasing Hormones CRH (Corticotropin-releasing hormone) ACTH Stimulation Hypothalamus TRH (Thyrotropin-releasing hormone) TSH Stimulation RH Pituitary gland GnRH (Gonadotropin-releasing hormone) LH/FSH Stimulation PRH (Prolactin-releasing hormone) PRL Stimulation releasing hormones are always on they need to be inhibited to be stopped from producing Anterior lobe Hormone 1 GHRH (Growth hormone-releasing hormone) GH Stimulation Inhibiting Hormones GHIH (Growth hormone-inhibiting hormone) GH Inhibition (aka Somatostatin) PIF (Prolactin inhibiting factor) PRL Inhibition (aka dopamine) Negative feedback Endocrine organ Hormone 2 Target cells Hormones of the Pituitary Gland Anterior Pituitary ACTH (Adrenocorticotropic hormone) GH (Growth hormone) LH/FSH (Luteinizing hormone / Follicle-stimulating hormone) PRL (Prolactin) TSH (Thyroid stimulating hormone) Posterior Pituitary ADH (Anti-diuretic hormone) Oxytocin Pituitary Hormones & Disease Important terminology! Primary Disease Problem at the level of the end organ Thyroid Adrenals Ovaries Testes Secondary Disease Problem at the level of the pituitary Tertiary Disease Problem at the level of the hypothalamus Pituitary Adenoma Adenoma: What is it???? gland cancer - derived from glandular tissue Discovered due to signs & symptoms related to size (mass effect) Increased size of pituitary can lead to impingement on: Pituitary itself Panhypopituitarism (multiple pituitary hormone deficiencies) pan = meaning all hormones Optic chiasm Bitemporal hemianopsia (loss of peripheral vision) c/o no vision “black” Cavernous sinus CN 3, 4, 5, 6 palsy CSF Headache impacts everything but oxytocin and ADH hormone wise Pituitary Microadenoma if the size is less than 1 cm or 10 mm, then is is a MICRO adenoma ✓ < 1 cm (< 10 mm) size for this matters! 1 cm is 10 mm ~50% of all pituitary adenomas are nonfunctional Non-secreting (No hormone produced) May be found as an incidentaloma in up to 10% of cases Non-symptomatic Microadenoma Pituitary Macroadenoma ✓ > 1 cm (> 10 mm) MRI is the initial imaging study for all suspected adenomas: Superior resolution Ability to demonstrate the optic chiasm Distinction from an aneurysm or other intrasellar lesions Hypopituitarism Underproduction of hormones released by the pituitary gland….Symptoms based on which hormone(s) are undersecreted Congenital Tumor Pituitary adenoma Cancers (glioma / metastases) Vascular Aneurysm Sheehan’s syndrome (post-partum pituitary infarction) Infection TB Syphilis HIV Miscellaneous Traumatic brain injury post-irradiation increase in CSF Hypopituitarism “Clinical Presentation” Symptoms from mass effect Pituitary itself = Panhypopituitarism (multiple pituitary hormone deficiencies) Optic chiasm = Bitemporal hemianopsia (loss of peripheral vision) Cavernous sinus = CN 3, 4, 5, 6 palsy CSF = headache Symptoms from anterior pituitary hormone deficiencies LH/FSH = Secondary Hypogonadism TSH = Secondary Hypothyroidism ACTH = Secondary Adrenal Insufficiency GH = Growth Deficiency PRL = Lactation Difficulties Symptoms from posterior pituitary hormone deficiencies ADH = Diabetes Insipidus OXY = Possible parturition difficulties Hypopituitarism “EVALUATION & MANAGEMENT” Blood work and Labs!!!! If deficient, then replace the necessary hormones: Secondary Hypogonadism Testosterone / Estrogen replacement, fertility Tx Secondary Hypothyroidism Thyroid hormone replacement Secondary Adrenal Insufficiency Cortisol replacement GH Deficiency Growth hormone replacement (mostly, in children) Clinical Pearls ✓ If you find a deficit in one pituitary hormone, check them all ✓ If there is a problem with the pituitary, you must also check end organ hormone results Hyperprolactinemia Hyperprolactinemia “Clinical Presentation” Can be present in both males and females Galactorrhea (milk production) Gynecomastia (enlargement of breast tissue) The Big Three: 1. Iatrogenic 2. Tumor 3. Hypothyroidism Hyperprolactinemia “Clinical Presentation” Galactorrhea (milk production) and/or Gynecomastia Females: Secondary amenorrhea, infertility Males: Testosterone Deficiency Decreased libido Depression Fatigue Loss of secondary male sex characteristics Hyperprolactinemia Prolactinoma: Most common functional tumor of anterior pituitary Markedly elevated prolactin (100s -1000s ng/mL) Prolactin feedback at the level of the hypothalamus inhibits GnRH release: Leading to LH/FSH suppression Rule out other causes first: Medications, pregnancy Antipsychotics…..dopamine….. Haloperidol Blocks the D2 receptor, which is sensitive to dopamine MRI of pituitary gland Hyperprolactinemia Antipsychotics:(Haloperidol) Blocks the D2 receptor, which is where dopamine binds Dopamine binds to the dopamine D2 receptors on surface of the lactotroph Diminish intracellular cyclic AMP (cAMP), decreasing prolactin secretion Any factor disrupting delivery of dopamine to anterior pituitary or disturbing signal transduction may result in hyperprolactinemia Interference with dopamine inhibition of the lactotrophs results in an elevated prolactin level Other Causes of Hyperprolactinemia Source: Nature, Clinical Practice Endocrinology & Metabolism Prolactinoma Treatment Medical Treatment Indicated for: ✓ Microprolactinomas causing symptoms ✓ Infertility in women Surgical Treatment Indicated for: ✓ Macroprolactinomas Transsphenoidal surgery is the preferred approach First line treatment: Dopamine agonists Cabergoline Bromocriptine Inhibit prolactin Reduce tumor size Restore gonadal function Source: Mayo Foundation Growth Hormone EXCESS / DEFICIENCY _ Hypothalamus + GHRH Somatostatin _ + _ Somatotrope Growth hormone + Liver IGF-I GH - Promotion of Growth Gigantism Occurs in children before closure of epiphyses Rare Stimulation of epiphyseal cartilage growth plates Before late adolescence, the new cartilage translates into height and length Acromegaly After adolescence After growth plates have closed, GH’s effect on osteoblastic activity increased bone mass Especially true for membranous bones Enlarged bones of hands, feet, cranium, nose, supraorbital ridges, lower jawbone Vertebrae “hunch back” kyphosis Soft tissue involvement …….. tongue, liver, kidney Increased risk of: Diabetes Mellitus Hypertension CAD Acromegaly / Gigantism Etiology: GH secreting pituitary adenoma Less common: Excess GHRH from hypothalamic tumor Ectopic GHRH GH from neuroendocrine tumors (e.g. MEN-1) Labs Increased IGF1 Benign pituitary tumor on MRI in 90% of cases Glucose tolerance test shows failure of lowering of GH Treatment Pituitary tumor removed by transsphenoidal surgery Somatostatin analogs Dopamine agonists GH Deficiency Children: Short-stature Adults: Metabolic changes (increased fat, decreased lean mass, decreased BMD), fatigue, decreased quality of life Acquired GH deficiency Pituitary tumor, or consequence of treatment of the tumor (surgery and/or radiation therapy)- 75% Extra-pituitary tumor (e.g. craniopharyngioma)- 13% Unknown cause- 8% Sarcoidosis- 1% Treatment: Growth hormone! DWARFISM Most common type is achondroplastic Mutation in FGFR3 gene Normal intelligence Delayed physical developmental milestones Shortened limbs Pituitary dwarfism may present in male infants Lack of growth hormone (GH) Diabetes Insipidus Diabetes Insipidus Although they have a common name, diabetes mellitus and diabetes insipidus Are two entirely separate conditions with unrelated mechanisms Diabetes insipidus ….Think ADH!!!! Problem with the production of antidiuretic hormone (Central Diabetes Insipidus) Kidney's response to antidiuretic hormone (Nephrogenic Diabetes Insipidus) Diabetes mellitus …..Think Insulin Causes polyuria via a process called osmotic diuresis Due to the high blood sugar leaking into the urine and taking excess water along with it Diabetes Insipidus A condition characterized by excessive thirst and excretion of large amounts of severely diluted urine The thirst mechanism allows replacement of water lost but if access to free water is denied, They can rapidly become hypovolemic and hypotensive Different types of DI, each with a different set of causes Most common type in humans is the neurological form, called Central DI (CDI) Involves a deficiency of ADH “Production” The second common type of DI is nephrogenic diabetes insipidus (NDI) Due to kidney or nephron dysfunction caused by an insensitivity of the kidneys or nephrons to ADH “Response” Diabetes Insipidus Deficiency of (or) resistance to ADH (vasopressin) Polydipsia, polyuria, dilute urine, dehydration ( hypernatremia) Central DI Hypothalamic or pituitary or head injury Reduced ability to produce ADH ADH is Low Responds to treatment with desmopressin (synthetic ADH) Nephrogenic DI Reduced kidney response to vasopressin No response to desmopressin HCTZ may help ADH is High Central Diabetes Insipidus Etiology Idiopathic (most common,30-50%) Prior brain surgery, radiation, or trauma Primary or secondary tumors of pituitary or sellar region Diagnosis Urine volume – increased (often > 3 L/d) Urine osmolality - low Serum osmolality - normal or high Serum sodium - normal or high Water deprivation test Patients are deprived of fluids for several hours…… 1. Measure urine osmolarity…..If corrected/elevated, most likely psychogenic polydipsia…tell them stop drinking water! 2. Measure urine osmolarity….. If still low give a dose of ADH and wait 3. Measure urine osmolarity…..is correct (Central)…..if still low....(Nephrogenic) Treatment Desmopressin (DDAVP) Syndrome of Inappropriate Antidiuretic Hormone Secretion “SIADH” SIADH Increased secretion of antidiuretic hormone………..Impaired water excretion Hyponatremia Due to excess water rather than sodium deficiency Main causes: CNS disorders Meningitis, Encephalitis Pulmonary lesions Tuberculosis, Bacterial pneumonia, cancer Malignancies Almost any cancer Medications Antidepressants Antipsychotics DX: Urine sodium (UNa ) = Elevated Urine Osmolarity (Uosm) = Elevated/Concentrated Serum Osmolarity (Sosm) = Decreased / “hyponatremia” SIADH Increased secretion of antidiuretic hormone………..Impaired water excretion Hyponatremia Due to excess water rather than sodium deficiency Treatment Water Restriction Correct/reverse underlying condition (Cancer) Vasopressin antagonists (tolvaptan) Diabetes Insipidus vs SIADH Adrenal Glands Capsule Cortex Adrenal Glands Lie along superior border of each kidney Subdivided into: Superficial adrenal cortex Stores lipids, especially cholesterol and fatty acids Manufactures steroid hormones (corticosteroids) Metabolic changes persist for several days/weeks Inner adrenal medulla Secretory activities controlled by sympathetic division of ANS Produces epinephrine (adrenaline) and norepinephrine Metabolic changes persist for several minutes Medulla Adrenal Glands Adrenal Cortex Subdivided into three regions/zones 1. Zona glomerulosa (Salt) 2. Zona fasciculate (Sugar) 3. Zona reticularis (Sex) Adrenal medulla Zona reticularis Each zone produces synthesis specific steroid hormones Adrenal cortex Zona fasciculata Zona glomerulosa Capsule Adrenal gland LM × 140 The major regions of an adrenal gland Hypothalamohypophyseal-Adrenal Axis Hypothalamus _ CRH + _ Corticotrope ACTH + Adrenal Cortex Glucocorticoids & Mineralocorticoids Primary Adrenal Insufficiency “Addison’s disease” Causes of cortical destruction include: Autoimmune inflammation of adrenals (Most common in the US 80%) TB (Most common worldwide) Cancer Disseminated intravascular coagulation (DIC) Drugs that can cause Adrenal Insufficiency: Ketoconazole, Fluconazole Rifampin Phenytoin JFK had auto-immune Addison’s Disease…. but kept it hidden Secondary Adrenal Insufficiency Causes: Pituitary or hypothalamic tumors Pituitary adenomas, craniopharyngiomas Iatrogenic hypothalamic or pituitary disease Surgery, radiation Chronic high dose corticosteroid therapy Pituitary infarction (Sheehan’s syndrome) Acute infarct Granulomatous diseases Sarcoidosis Histiocytosis Idiopathic Children Adrenal Insufficiency “Signs & Symptoms” Most common: Fatigue ** Anorexia** Weight loss ** GI symptoms (N/V) Orthostatic hypotension Hyperpigmentation Hyponatremia, hyperkalemia….WHY?? Adrenal insufficiency becomes clinically apparent only after at least 90% of the cortex has been destroyed. Addison’s Disease ✓ Low cortisol ✓ Primary adrenal insufficiency due to autoimmune destruction of adrenal cortex Antibodies that react with several steroid enzymes 57-year-old woman presented with symptoms of primary adrenal insufficiency “autoimmune Addison's disease” Diffuse skin hyperpigmentation developed during last year, as illustrated by her facial appearance (A) Hands demonstrate increased pigmentation of palmar creases and wrists compared to a normal female(B) Long-term glucocorticoid and mineralocorticoid therapy, her hyperpigmentation resolved (C) She wears a medical bracelet indicating her requirement for glucocorticoids in case of severe illness Source: UpToDate. Initial Laboratory Evaluation ✓ Morning cortisol (8 AM) Cortisol < 3 ug/dL is diagnostic _ Hypothalamus ❖ Then the question is…Pituitary or adrenal problem?? So we do another test ✓ Cosyntropin (Cortrosyn) Stimulation Test (250 mcg synthetic ACTH IM) Generally, need to see cortisol rise > 20 ug/dL at 45 minutes If it rises…it is a pituitary problem (no ACTH was being made, get MRI) Those with adrenal insufficiency see < 20 ug/dL rise at 45 minutes No rise….adrenal problem (Addison’s disease CT or MRI) Anti- adrenal antibodies / Anti-21 hydroxylase antibodies CRH + _ Corticotrope ACTH + Adrenal Cortex Remember: Pituitary problem….Just need to replace ACTH Adrenal problem…. Need Cortisol and Aldosterone Glucocorticoids & Mineralocorticoids Adrenal Insufficiency: Management Corticosteroids Hydrocortisone – 15-30 mg daily (2/3 morning, 1/3 afternoon) Prednisone 5 mg daily Mineralocorticoids (for Primary AI) Fludrocortisone 0.05- 0.1 mg/d “Stress dose” – usually 2-3 x maintenance dose Monitor: blood pressure, electrolytes, weight, symptoms Medic alert bracelet ADRENAL CRISIS Acute adrenal insufficiency Medical emergency Precipitating event Major surgery, acute illness, infection or stress Patients who are abruptly withdrawn from high dose corticosteroids Clinical features Shock, dehydration, hypotension Nausea, vomiting “Acute abdomen” without apparent cause Unexplained fever Hyponatremia, hyperkalemia, hypoglycemia Treatment IV steroids (hydrocortisone) every 6 hours on first day, taper to be determine based on clinical course IV fluids Syndrome vs Disease Cushing's disease and Cushing's syndrome are not the same condition, but they are often confused with one another Cushing's syndrome When the body produces too much cortisol Can happen for many reasons, it often occurs when the patient uses corticosteroid medication Iatrogenic administration of steroids Physician induced Cushing's disease Medical cause of Cushing's syndrome Occurs when a tumor on the pituitary gland causes the gland to produce too much ACTH Increased ACTH in the system makes the adrenal glands produce cortisol in high levels Both Cushing's syndrome and Cushing's disease cause the same symptoms Hypercortisolism Cushing’s Syndrome High levels of cortisol 4 potential causes: 1. Adenomas/tumors of Anterior Pituitary Producing large amounts ACTH and resultant bilateral adrenal hyperplasia 2. Ectopic production of ACTH from tumor(s) elsewhere in the body Lung small cell 3. Iatrogenic administration of steroids Physician induced 4. Adenoma of adrenal cortex “zona fasciculate” Symptoms of Cushing’s Centripetal fat distribution “Cushingoid” Mobilization of fat from the extremities to the Abdomen Face (“Moon face”) Supraclavicular areas Fat in the upper back/lower neck gives a characteristic “buffalo hump” Image: UpToDate Cushing’s Syndrome: Evaluation 24 hr urine cortisol Random cortisol and ACTH not helpful Late night salivary cortisol In normal individuals should be low In Cushing’s will be elevated Once you confirm it is elevated you do a suppression test: Dexamethasone suppression test (Give med at night test blood in the morning) Definitive diagnosis 8 AM cortisol < 5 mcg/dL usually excludes Cushing’s Dexamethasone Long-acting steroid, does NOT interfere with the assay to measure cortisol, but should still suppress the ACTH and cortisol of a functioning HPA axis. Low-dose test can help tell whether your body is producing too much ACTH High-dose test can help determine whether the problem is in the pituitary gland (Cushing disease) or from a different site in the body (ectopic). CUSHING’S MANAGEMENT Surgical removal of tumor ACTH-secreting pituitary tumor Primary adrenal tumor Ectopic Tumor Drug therapy Blockers of steroid biosynthesis, adrenolytic drugs (mitotane) In some cases: Bilateral adrenalectomy Replace steroids using combination of glucocorticoids and mineralocorticoids Pheochromocytoma Pheochromocytoma tumor of the INSIDE adrenal medulla Very rare (< 0.2%) Catecholamine-secreting tumor 90% adrenal 10% extra-adrenal About 40% of cases due to a genetic condition: MEN (multiple endocrine neoplasia) type 2A or 2B Von Hippel-Lindau NF (neurofibromatosis) Clinical Presentation Treatment-resistant hypertension looks like a heart attack but you can’t control the hypertension Triad of symptomatic attacks: Palpitations / Tachycardia Headache Episodic sweating (diaphoresis) Pheochromocytoma Diagnosis: 24-hr Fractionated metanephrines & catecholamines Plasma metanephrine If elevated…..look for tumor ✓ CT or MRI imaging to identify tumor Sagittal Coronal Pheochromocytoma Treatment: Surgical resection Usually laparoscopic if mass < 8 cm, and no known metastasis Prior to surgery: Alpha blockers Phenoxybenzamine (Dibenzyline) Long-acting non-specific alpha blocking agent Beta blockers Propranolol (B1 and B2 blocker) Aggressive hydration (if tolerated) Aldosterone Stimulation Secretion of Aldosterone is under the control of: Drop in blood Na+, blood volume, or blood pressure Rise in blood K+ concentration Presence of Angiotensin II ACTH from anterior pituitary Aldosterone – Mechanism of Action Anatomical site of action: Distal nephrons (principal cells of the distal tubule and collecting duct) Very similar effects on sodium & potassium transport in sweat glands, salivary glands and intestinal epithelial cells (colon) Biochemical site of action: Sodium and potassium channel proteins (apical) Sodium is also reabsorbed (due to the aldosterone) and the K+ and H+ ions are secreted from the tubules Take home message…. Keeps Sodium and Water Lose Potassium and Hydrogen Primary Hyperaldosteronism “Conn Syndrome” Primary Hyperaldosteronism Non-suppressible hypersecretion of aldosterone Estimated to contribute to ~10% of cases of HTN, ~ 20% cases of resistant HTN Peak incidence in 3rd-5th decade of life Females > males Causes: Conn’s syndrome (~40%) Adrenal adenoma secreting aldosterone Bilateral adrenal hyperplasia (~60%) Idiopathic Rarely (~1%) Carcinoma or congenital Primary Hyperaldosteronism Clinical findings: Signs/Symptoms Resistant hypertension Hypokalemia Metabolic alkalosis Kidney…sodium/proton pump Sodium in and H+ out Headache / Dizziness Muscle weakness (result of hypokalemia) Diagnostic studies / Labs: Metabolic alkalosis Hypernatremia Unexplained hypokalemia Primary Hyperaldosteronism Treatment depends on cause: Adenomas: Best treated surgically- laparoscopic adrenalectomy 20-30% of patients remain hypertensive (due to nephrosclerosis) Bilateral (Idiopathic) Adrenal Hyperplasia: Best treated medically Surgical cure is uncommon, results in primary adrenal insufficiency Treatment of choice: Aldosterone receptor antagonist Spironolactone Alternative- Eplerenone Hirsutism & Virilization N Engl J Med 2005; 353:2578-2588 DOI: 10.1056/NEJMcp033496 Hirsutism Excessive male-pattern hair growth in a female 5-10% of premenopausal females 50% of those with polycystic ovarian syndrome (PCOS) Associated with elevated testosterone levels Amenorrhea/oligomenorrhea, infertility, obesity/insulin resistance Other findings: Acne Irregular menses Acanthosis nigricans (insulin resistance) Other symptoms of virilization – if present, look for androgen secreting tumor Male pattern hair loss Deepening of voice Increased muscle mass Clitoromegaly Abdominal & pelvic exam Adrenal or ovarian masses Hirsutism Common causes: PCOS (Most common cause) Idiopathic Congenital adrenal hyperplasia Less common causes Adrenal carcinoma Ovarian tumors Medications Minoxidil Cyclosporine Phenytoin Anabolic steroids Laboratory studies Serum testosterone DHEA-S 17-hydroxyprogesterone Hemoglobin A1C +/- test for Cushing’s +/- Prolactin, LH, FSH, estradiol Imaging studies Pelvic ultrasound Abdominal CT Hirsutism: Treatment Pharmacologic Topical Vaniqa Facial hair remover Oral contraceptives Clomiphene (PCOS, if fertility desired) Anti-androgen therapy Spironolactone Non-pharmacologic Cosmetic Shaving, plucking, waxing Mechanical (“permanent”) Electrolysis Laser therapy Surgery Oophorectomy or adrenalectomy if severe virilization +/- adrenal or ovarian mass, or hyperplasia present ADRENAL CANCER Adenoma Benign (noncancerous) tumor Start in the epithelial tissue Carcinoma Malignant (Cancerous) tumor Starts in cells that make up the skin or the tissue lining organs Liver Kidneys Adenocarcinomas Malignant (Cancerous) tumor Starts in the glandular cells Adrenocortical Carcinoma (ACC) Malignant cells that form from the outer layer of the adrenal gland Rare ( ~ 1-2 per million population/yr) 10-fold increased incidence in children in southern Brazil Bimodal distribution Peak prior to age 5 and 4-5th decade of life Women > Men (1.5-2.5:1) 60% of ACC’s are functioning masses 45% with Cushing’s syndrome (with rapid progression of sx in 3-6 months) 25% with Cushing’s & virilization 10% virilization alone < 10% feminization & hyperaldosteronism Adrenal Incidentaloma Benign Found in ~4-5% of chest/abdominal CT scans Increasing frequency due to widespread use of high-resolution imaging (we CT everything!) Important questions: Is it malignancy? Is it functional? There are algorithms Help with clinical decision making References Papadakis, M. A. & McPhee, S. J. (2018). Current Medical Diagnosis and Treatment 2018. Ch. 26. New York, NY: McGraw Hill. Andreoli, T. E. et al. (2015). Cecil Essentials of Medicine, 9th ed. Philadelphia, PA: Elsevier Felner, E. I. & Umpierrez, G. E. (2014). Endocrine Pathophysiology. Philadelphia, PA: Wolters Kluwer UpToDate. (2019). www.uptodate.com Rosh Review N Engl J Med 2005; 353:2578-2588. DOI: 10.1056/NEJMcp033496