PANCE - Cortisol Physiology & Pathology

Here are key facts for PANCE 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. Basic mechanism: Cortisol is the primary glucocorticoid secreted by the zona fasciculata of the adrenal cortex, with secretion triggered by ACTH from the anterior pituitary. 2. Classification: Hypercortisolism (Cushing's Syndrome) can be ACTH-dependent (elevated cortisol caused by elevated ACTH) or ACTH-independent (elevated cortisol not caused by elevated ACTH). 3. Common causes: Exogenous glucocorticoids are responsible for most cases of ACTH-independent hypercortisolism (iatrogenic Cushing's syndrome). 4. HPA axis: Cortisol regulates its own production through negative feedback at both the hypothalamus and pituitary, inhibiting CRH and ACTH release. 5. Endogenous sources: When ACTH-dependent, causes include pituitary adenoma (Cushing's Disease) or ectopic ACTH production (small cell lung cancer, bronchial tumors). 1. Classic features: "Moon facies" (rounded face/neck due to fat accumulation), central/truncal obesity with "buffalo hump," and red/purple striae on abdomen, breasts, thighs, and buttocks. 2. Musculoskeletal: Muscle atrophy particularly in extremities making limbs appear thin, with increased risk of osteoporosis and fractures. 3. Cardiovascular: Hypertension develops via increased cardiac contractility and extracellular fluid volume. 4. Metabolic: Hyperglycemia may progress to diabetes mellitus due to increased gluconeogenesis and insulin resistance. 5. Immune function: Immunosuppression increases vulnerability to infections, particularly tuberculosis and fungal infections. 1. Initial screening: 24-hour urine samples, midnight salivary samples, or dexamethasone suppression test can be used. 2. Confirmatory testing: If cortisol levels are elevated and/or not suppressed by dexamethasone, Cushing's syndrome is likely. 3. Etiology determination: Measure plasma ACTH levels to distinguish between ACTH-dependent and ACTH-independent hypercortisolism. 4. Differential considerations: Rule out physiologic causes and medical conditions that raise cortisol: pregnancy, alcoholism, anorexia, obesity, depression, and uncontrolled diabetes. 5. Localization studies: For ACTH-dependent disease, inferior petrosal sampling helps determine if source is pituitary (central ACTH > peripheral) or ectopic (central ACTH ≤ peripheral).

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1. Skin changes: Red or purple striae particularly on abdomen, breasts, thighs, and buttocks; patients may bruise more easily due to skin atrophy. 2. Psychiatric symptoms: Patients may experience emotional or psychiatric disturbances, such as irritability or impaired memory. 3. Reproductive effects: Excess androgen secretion (especially with adrenal tumors) can cause hirsutism and menstrual irregularities. 4. Pediatric impact: Hypercortisolism can impair linear growth in children via negative effects on bone growth and impaired secretion of growth hormone and TSH. 5. Immunologic effects: Suppression of inflammatory and immune responses occurs via inhibition of pro-inflammatory mediators such as monocytes, neutrophils, and cytokines. 1. Cortisol patterns: Secretion is pulsatile and circadian; levels are highest upon waking and decline to lowest levels around bedtime, requiring consideration of sleep schedule when assessing. 2. Protein binding: Approximately 85% of cortisol in blood is bound to plasma proteins giving it a long half-life, while urine and salivary measurements reflect unbound cortisol. 3. Adrenal imaging: With adrenal tumors, expect to find a tumor in one adrenal gland and atrophy of the other due to lack of ACTH stimulation. 4. Tumor characteristics: Adenomas are more common than carcinomas, and carcinomas are more likely to secrete androgens along with cortisol. 5. HPA dysfunction: In Cushing's Disease, the HPA axis becomes dysfunctional, no longer responsive to negative feedback from cortisol or stress stimuli. 1. Treatment approach: For Cushing's Disease, treatment involves removal of the pituitary tumor, which can reverse effects in many, but not all, patients. 2. Surgical alternatives: Some patients may require bilateral adrenalectomy when pituitary surgery is insufficient. 3. Post-surgical complications: After bilateral adrenalectomy, be alert for Nelson syndrome with headaches, elevated ACTH, and hyperpigmentation. 4. Rare causes: Bilateral macro- and micro-nodular adrenal hyperplasias, though rare, can cause ACTH-independent Cushing's syndrome. 5. Hormone disruption: Secretion of thyrotropin, gonadotropin, and growth hormone are suppressed in Cushing's Disease, potentially requiring additional management.

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1. Steroidogenesis inhibitors: Medications like ketoconazole and metyrapone may be used when surgery is contraindicated or as bridge therapy. 2. Receptor antagonists: Mifepristone blocks glucocorticoid receptor action and may improve glucose metabolism in patients with diabetes mellitus secondary to Cushing's syndrome. 3. Targeted therapies: Pasireotide, a somatostatin analog, may be effective for persistent/recurrent Cushing's Disease. 4. Radiation therapy: Various radiation modalities may be used for pituitary tumors when surgical resection is incomplete. 5. Combination approaches: Multiple modality treatment may be necessary for refractory cases. 1. Adrenal insufficiency: Post-treatment monitoring for adrenal insufficiency is critical, with education about stress dosing of replacement steroids. 2. Cardiovascular risk management: Long-term monitoring and treatment of hypertension, hyperglycemia, and dyslipidemia even after biochemical cure. 3. Bone health: Assessment and management of osteoporosis with calcium, vitamin D, and possibly bisphosphonates. 4. Recurrence surveillance: Regular biochemical monitoring is needed as recurrence is common, especially with certain subtypes. 5. Patient education: Comprehensive teaching about chronic condition management, medication adherence, and recognition of complications.