21s - Adrenal Gland Pathology (McCormick Baw) - Copy.pdf

Adrenal Gland Pathology Endo, Energy, and Repro 2024-2025 ADRENAL GLAND PATHOLOGY Clare McCormick-Baw, MD, PhD Phone: 469-419-3401 Email: [email protected] **Note: Thank you to Dr. Oliver for sharing his syllabus! LEARNING OBJEC...

Adrenal Gland Pathology Endo, Energy, and Repro 2024-2025 ADRENAL GLAND PATHOLOGY Clare McCormick-Baw, MD, PhD Phone: 469-419-3401 Email: [email protected] **Note: Thank you to Dr. Oliver for sharing his syllabus! LEARNING OBJECTIVES: Name the compartments of the adrenal gland and list their functions Exemplify common causes of hypercortisolism, hyperaldosteronism, and adrenogenital syndromes and name common disease manifestations, clinical presentations and patterns of gross and histopathology observed in each. Analyze why histology alone may not differentiate benign from malignant adrenal tumors Distinguish the histology of adrenal hyperfunction and adrenal insufficiency List the histologic and clinical characteristics of pheochromocytoma List some commonly observed molecular drivers of adrenal medullary tumors ADRENAL GLAND I. Normal Histology and Physiology of the Adrenal Cortex a. The adrenals are pyramid-shaped and perch atop the kidney, bilaterally. b. The cut surface of the adrenals is yellow, due to the lipids in their cells. c. Sections of the Adrenal Gland: i. Zona glomerulosa is just under the capsule, has pink vacuolated cells arranged in homogeneous small clusters, and makes aldosterone. ii. Zona fasciculata, just deep to the glomerulosa, has larger vacuolated clear corticosteroid-producing cells arranged in cords. 1. Glucocorticoids have a major role in intermediary metabolism by controlling protein, carbohydrate, glucose, and lipid metabolism. They are also anti-inflammatory and protect patients under stress by a poorly understood mechanism. iii. Zona reticularis is deep to the fasciculata, just outside the adrenal medulla. Its cells are pink, granular, arranged in a meshwork, and make androgens. II. Adrenocortical Hyperfunction (Hyperadrenalism) a. Cushing Syndrome (Hypercortisolism) i. Today most cases of Cushing Syndrome (too much cortisol, but not necessarily too much ACTH) are iatrogenic, ie cortisol-like drugs prescribed to treat one of many diseases which results in similar symptoms to those seen in the endogenous hypercortisolism cases. Exogenous steroids, however, force the pituitary, through negative feedback, to reduce the levels of serum ACTH. Consequently, the adrenals atrophy (mainly the fasciculata and reticularis). ii. 3 main endogenous causes of Cushing syndrome are 1. Cushing disease a. Primary hypothalamic/pituitary disease that over secretes ACTH, and is the most common cause of sporadic endogenous Cushing Syndrome. b. More common in women (5:1) usually in the 20-40 year old range, Adrenal Gland Pathology Endo, Energy, and Repro 2024-2025 c. Cushing disease is usually due to a pituitary microadenoma (3mm) or micronodular (= 3.0cm, encapsulated, yellow to black and weigh up to 60g. 3.Non-endocrine neoplasms that make ACTH a. Extra-adrenal tumors that produce ACTH account for approximately 15% of Cushing syndrome cases. b. Paraneoplastic syndrome most commonly associated with: i. Pulmonary small cell carcinoma> medullary thyroid carcinoma, pancreatic islet cell tumor, carcinoid tumors, ovarian tumors or thymic carcinoma Adrenal Gland Pathology Endo, Energy, and Repro 2024-2025 1. Create ACTH, corticotropin-releasing hormone or biologically equivalent mimics. 2. Result in excessive cortisol release and adrenal hyperplasia iii. Clinical manifestations of Hypercortisolism 1. Hypertension – due to aldosterone-like effects of cortisol 2. Weight gain – due to aldosterone-like effect 3. Truncal obesity 4. Fat deposition in the neck and back 5. Moon facies 6. Atrophy of fast-twitch muscles with resultant proximal limb weakness 7. Gluconeogenesis and inhibition of glucose uptake which can mimic diabetes 8. Protein catabolism – collagen loss, bone loss resulting in osteoporosis, fractures 9. Cutaneous stria, easy bruising due to the weakened collagen 10. Immunosuppression 11. Hirsutism and menstrual abnormalities due to the androgen-like effects 12. Depression, mood swings, psychosis 13. Hyperpigmentation in some cases of Cushings disease b. Hyperaldosteronism i. Primary Hyperaldosteronism (adrenal origin) 1. Autonomous overproduction of aldosterone 2. Clinical manifestations: volume overload and hypokalemic (too much sodium retained and potassium excreted) 3. Renin and angiotensin levels are LOW because of negative feedback to the renal juxtaglomerular complex by the increased renal perfusion pressure. 4. Caused by adrenal tumors (80% adenomas/20% carcinomas), adrenal hyperplasia or can be idiopathic 5. Aldosterone secreting Adenoma causes Conn’s syndrome a. figure on left with normal adrenal in upper left being compressed by unencapsulated adenoma; figure on right with cells resembling fasciculata and glomerulosa a. Conn’s is more common in women, usually in the 30-50 year-old range b. Conn’s adenomas do not usually suppress ACTH secretion, thus there is no adrenal hypoplasia/atrophy. a. Clinicians must always consider a cortical aldosterone- secreting adenoma in patients with new onset hypertension, as the high blood pressure in these patients can be treated simply by unilateral adrenalectomy Adrenal Gland Pathology Endo, Energy, and Repro 2024-2025 6. Primary adrenocortical hyperplasia. a. This is most often seen in children and young adults b. Bilateral hyperplasia of the zona glomerulosa or bilateral nodular hyperplasia by cells resembling zona fasciculata ii. Secondary hyperaldosteronism (outside of the adrenal) 1. occurs due to stimulation of the kidney’s renin-angiotensin system (angiotensin II stimulates zona glomerulosa production of aldosterone). 2. The etiologies of the elevated renin include decreased renal blood flow and systemic hypovolemia. iii. Adrenogenital Syndromes 1. Syndromes associated with androgen excess may result from adrenal adenoma such as the figure shown a. Cells in a solid pattern with eosinophilic cytoplasm and some irregular nuclei. b. The adenomas associated with adrenogenital syndrome can be large (up to 500 g). 2. Androgen excess can also be seen with adrenal carcinoma or hyperplasia. a. Adrenal carcinomas cause virilization and feminization more often than adrenal adenomas. III. Adrenal Insufficiency -- can affect all or part of the adrenal and can be primary (acute or chronic), or secondary due to reduced ACTH secretion. a. Primary Adrenal Insufficiency i. Acute primary adrenal insufficiency can be due to massive hemorrhage of the adrenals, excessive stress (surgery, infection, trauma, long lectures) in a setting of chronic adrenal insufficiency, or sudden cessation of prescribed cortisol. ii. A well-known cause of massive adrenal hemorrhage, especially in children, is Waterhouse-Friderichsen syndrome (figure), secondary to meningococcal (classically) sepsis, but other organisms including Pseudomonas, Streptococcus, and Staphylococcus can be responsible. iii. Chronic primary adrenocortical insufficiency (Addisons disease) due to ongoing destruction of the gland may be asymptomatic until a full 90% of the gland is destroyed, and ACTH levels remain near normal through much of the course of the disease. 1. It has 4 main causes: a. Autoimmune – the most common cause i. Thought to be due to autoantibodies to 21-hydroxylase and possibly the ACTH receptor in some cases, while others appear to be part of an autoimmune polyendocrinopathy syndrome. Adrenal Gland Pathology Endo, Energy, and Repro 2024-2025 ii. These APS cases are thought to be due mutations in autoimmune regulator genes (AIRE) and cause multi-organ damage. iii. Microscopically: Histologic examination in the autoimmune disorders shows lymphocytic infiltration of the adrenal gland. b. Infections – TB, fungal damage with granulomatous inflammation c. AIDS – CMV, MAI, Kaposi sarcoma d. Metastases - most frequently from bronchogenic carcinoma, breast carcinoma iv. Clinical manifestations of Primary Adrenal Insufficiency 1. Progressive loss of glucocorticoid and mineralcorticoids results in increasing weakness and fatigue 2. Hyperpigmentation of the skin and mucous membranes (because the anterior pituitary releases a melanotropic factor simultaneously with ACTH) 3. GI disturbances including nausea, anorexia, weight loss 4. Hyperkalemia, volume loss, and hypotension due to the salt wasting from the loss of aldosterone 5. There may be hypoglycemia due to impaired gluconeogenesis because of the low cortisol 6. Patients cannot handle stress without cortisol, leading to an adrenal crisis that can result in hypotension, coma, and death IV. Benign Adrenal Tumors a. Adrenal adenomas i. derived from any of the cortical layers and are associated with production of glucocorticoids, mineralcorticoids, androgens, and estrogens. ii. Rare adenomas do not secrete hormones, i.e. they are non-functional. iii. Others are responsible for “mixed” syndromes. iv. Adenomas associated with Cushing syndrome (pictured below grossly (left) and microscopically (right)) 1. Grossly: are usually