USMLE/COMLEX 2 - Cortisol Physiology & Pathology

Here are key facts for USMLE Step 2 & COMLEX-USA Level 2 from the Cortisol Physiology & Pathology tutorial, as well as points of interest at the end of this document that are not directly addressed in this tutorial but should help you prepare for the boards. See the tutorial notes for further details and relevant links.

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1. Classic features: "Moon facies" (rounded shape of face/neck from fat accumulation), central/truncal obesity with "buffalo hump," and red/purple striae on abdomen, breasts, thighs, and buttocks. 2. Muscle and skin changes: Patients show muscle atrophy particularly in extremities making limbs appear thin, and may bruise more easily. 3. Metabolic manifestations: Hypertension (via increased cardiac contractility and extracellular fluid volume) and hyperglycemia that may progress to diabetes mellitus. 4. Key screening tests: 24-hour urine samples, midnight salivary samples, or dexamethasone suppression test are used for initial screening. 5. Diagnostic approach: If cortisol levels are elevated and/or not suppressed by dexamethasone, Cushing's syndrome is likely, followed by measuring plasma ACTH levels to determine etiology. 1. ACTH-dependent vs. ACTH-independent: Hypercortisolism is either ACTH-dependent (elevated cortisol caused by elevated ACTH) or ACTH-independent (elevated cortisol not caused by elevated ACTH). 2. Exogenous Cushing's: Exogenous glucocorticoids are responsible for most cases of ACTH-independent hypercortisolism. 3. Endogenous causes: When ACTH is elevated, either Cushing's Disease (pituitary adenoma) or ectopic ACTH production (small cell lung cancer, bronchial tumors). 4. Conditions to rule out: Physiologic causes to exclude are pregnancy, alcoholism, anorexia, obesity, depression, and uncontrolled diabetes. 5. Adrenal causes: With low/suppressed ACTH adrenal tumors (adenomas more common than carcinomas) should be considered. 1. ACTH measurement: After confirming hypercortisolism, measuring plasma ACTH levels helps determine the cause. 2. Inferior petrosal sampling: Describes this technique to determine source of excess ACTH (central ACTH > peripheral suggests pituitary tumor; central ACTH ≤ peripheral suggests ectopic tumor). 3. Imaging studies: Imaging tests to investigate potential adrenal tumors when ACTH is suppressed. 4. Pattern recognition: In adrenal tumor cases, we see a tumor in one adrenal gland and atrophy of the other due to lack of ACTH stimulation. 5. Androgen co-secretion: Carcinomas are more likely than adenomas to secrete androgens along with cortisol.

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1. Immunosuppression: Increases vulnerability to infectious diseases requiring robust B- and T-cell-mediated immune responses (TB, fungal infections). 2. Psychiatric effects: Patients may experience emotional or psychiatric disturbances, such as irritability or impaired memory. 3. Bone effects: TCchronic exposure to elevated cortisol can result in osteoporosis and increased vulnerability to bone fractures. 4. Sex hormone effects: Excess androgen secretion associated with some forms (adrenal tumors) can cause hirsutism and menstrual irregularities. 5. Pediatric impact: In children, hypercortisolism can impair linear growth via effects on bone and reduced growth hormone/TSH secretion. 1. Circadian considerations: Cortisol secretion is pulsatile and circadian with highest levels upon waking - requiring awareness of sleep schedule when assessing hormone levels. 2. Protein binding: Approximately 85% of cortisol is bound to plasma proteins, giving it a long half-life, while urine and salivary measurements detect unbound cortisol. 3. HPA dysfunction: In Cushing's Disease, the HPA axis becomes dysfunctional, no longer responsive to negative feedback from cortisol or stress stimuli. 4. Hormonal suppression: Secretion of thyrotropin, gonadotropin, and growth hormone are suppressed in Cushing's Disease. 5. Nelson syndrome: A potential complication after bilateral adrenalectomy, characterized by pituitary tumor development, headaches, elevated ACTH, and hyperpigmentation. 1. Surgical approach: Treatment of Cushing's Disease involves removal of the pituitary tumor. 2. Treatment limitations: Pituitary tumor removal can reverse effects in many, but not all patients. 3. Alternative surgery: Some patients may require bilateral adrenalectomy. 4. Rare adrenal causes: Bilateral macro- and micro-nodular adrenal hyperplasias, though rare, can cause ACTH-independent Cushing's syndrome. 5. Multiple endocrine workup: A comprehensive endocrine evaluation is warranted.

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1. Medical therapy options: Ketoconazole, metyrapone, and mitotane can block cortisol synthesis as adjunctive or primary therapy. 2. Receptor antagonism: Mifepristone (glucocorticoid receptor antagonist) may help manage hyperglycemia in patients with Cushing's syndrome. 3. Radiation therapy: Stereotactic radiosurgery may be used for pituitary tumors when surgery is incomplete or contraindicated. 4. Somatostatin analogs: Pasireotide specifically targets corticotroph adenomas in Cushing's Disease. 5. Adrenal insufficiency management: After treatment, patients often require glucocorticoid replacement therapy during stress or illness. 1. Recurrence monitoring: Regular biochemical screening is needed as recurrence is common, especially for ectopic ACTH sources. 2. Cardiovascular risk management: Aggressive treatment of comorbidities (hypertension, diabetes, dyslipidemia) is essential. 3. Bone health: Osteoporosis prevention and treatment with calcium, vitamin D, and bisphosphonates may be necessary. 4. Pregnancy considerations: Management differs during pregnancy, with altered diagnostic criteria and treatment limitations. 5. Quality of life assessment: Persistent cognitive, psychological, and physical symptoms may require specific interventions.