Adrenal Disorders for the USMLE, Step One: Abnormalities of the Fasciculata: Hypercortisolism
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1 Adrenal Disorders for the USMLE, Step One: Abnormalities of the Fasciculata: Hypercortisolism Howard Sachs, MD Patients Course, 2017 Associate Professor of Clinical Medicine UMass Medical School
2 Adrenal Disorders for the USMLE, Step One: Abnormalities of the Fasciculata The Official Winter Storm of the Class of 2019
3 Manifestations Aldosterone Cortisol Response Anything else Etiologies Normal Physiology
4 Manifestions: Hypercortisolism Cardiovascular Permissive effects with NE; upregulates -1 receptors Renal Endo MSK Mineralocorticoid-like properties HTN, K, HCO3 Hyperglycemia Appearance: Facies/hump/striae Osteoporosis: osteoblast/ osteoclast Avascular necrosis Myopathy Heme Leukocytosis Cause-specific ACTH: hirsutism, pigmentation
5 Manifestions: Hypercortisolism Cardiovascular Permissive effects with NE; upregulates -1 receptors Renal Endo MSK Mineralocorticoid-like properties HTN, K, HCO3 Hyperglycemia Appearance: Facies/hump/striae Osteoporosis: osteoblast/ osteoclast Avascular necrosis Myopathy Heme Leukocytosis Cause-specific ACTH: hirsutism, pigmentation
6 Collecting Tubules Lumen Na+ Reabsorption Peritubular Capillary - 50 mv Na+ K+ Cl- K+ ATP Na+ Aldosterone Aldosterone Cushing s Cortisol Cortisol 11 -hydroxylase Normal Cortisone
7 Manifestions: Hypercortisolism Cardiovascular Permissive effects with NE; upregulates -1 receptors Renal Endo MSK Mineralocorticoid-like properties HTN, K, HCO3 Hyperglycemia Appearance: Facies/hump/striae Osteoporosis: osteoblast/ osteoclast Avascular necrosis Myopathy Heme Leukocytosis Cause-specific ACTH: hirsutism, pigmentation
8 Steroids Flat Head Avascular Necrosis: Collapse (flattening) of the Femoral Head
9 Manifestions: Hypercortisolism Cardiovascular Permissive effects with NE; upregulates -1 receptors Renal Endo MSK Mineralocorticoid-like properties HTN, K, HCO3 Hyperglycemia Appearance: Facies/hump/striae Osteoporosis: osteoblast/ osteoclast Avascular necrosis Myopathy Heme Leukocytosis Cause-specific ACTH: hirsutism, pigmentation
10 Manifestions: Hypercortisolism Cardiovascular Permissive effects with NE; upregulates -1 receptors Renal Endo MSK Mineralocorticoid-like properties HTN, K, HCO3 Hyperglycemia Appearance: Facies/hump/striae Osteoporosis: osteoblast/ osteoclast Avascular necrosis Myopathy Heme Leukocytosis Cause-specific ACTH: hirsutism, pigmentation ACTH stimulates reticularis with androgen synthesis. ACTH has homology with MSH.
11 Response to Hypercortisolism based on Etiologies Cushing s Disease Hypothalamus CRH suppressed (all causes) Pituitary Adenoma, Ectopic ACTH is elevated Adrenal Adenoma, Exogenous ACTH is suppressed
12 Response to Hypercortisolism based on Etiologies Cushing s Disease Hypothalamus CRH suppressed (all causes) Pituitary Adenoma, Ectopic ACTH is elevated Adrenal Adenoma, Exogenous ACTH is suppressed Rheumatoid Arthritis
13 Diagnostics Part One Confirm hypercortisolism (based upon clinical suspicion) 24 hr urinary free cortisol Overnight dexamethasone suppression test Don t be ascared! 1 mg at midnight; cortisol level at 0800 Cortisol should be <5 g/dl HTN Glu OP Myopathy
14 Diagnostics Part One Confirm hypercortisolism (based upon clinical suspicion) 24 hr urinary free cortisol Overnight dexamethasone suppression test Don t be ascared! 1 mg at midnight; cortisol level at 0800 Cortisol should be <5 g/dl HTN Glu OP Myopathy These are initial screening studies
15 Diagnostics Part One Confirm hypercortisolism (based upon clinical suspicion) 24 hr urinary free cortisol Overnight dexamethasone suppression test Don t be ascared! 1 mg at midnight; cortisol level at 0800 Cortisol should be <5 g/dl HTN Glu OP Myopathy Note: exogenous glucocorticoids are NOT measured. Cortisol level will be low due to suppression of HPA axis.
16 Diagnostics Part One Confirm hypercortisolism (based upon clinical suspicion) 24 hr urinary free cortisol Overnight dexamethasone suppression test Part Two ACTH level suppressed (negative feedback) If suppressed, adrenal adenoma you nailed it! Grab an imaging study so you can admire your work.
17 Diagnostics Part One Confirm hypercortisolism (based upon clinical suspicion) 24 hr urinary free cortisol Overnight dexamethasone suppression test Part Two ACTH level suppressed (negative feedback) If suppressed, adrenal adenoma you nailed it! Grab an imaging study so you can admire your work. Adrenocortical Carcinoma
18 Diagnostics Part Two ACTH : suppressed adrenal adenoma ACTH: elevated ( ACTH-dependent ) But what if ACTH level is elevated? How can you distinguish between a tumor pouring out ACTH (due to some major mutations) and a misguided pituitary adenoma that has simply lost its way? Small Cell Carcinoma Pituitary Adenoma
19 Diagnostics Part Two ACTH : suppressed adrenal adenoma ACTH: elevated ( ACTH-dependent ) High Dose Dexamethasone Suppression 2 mg q6h x 48h Assess cortisol I don t suppress Chest imaging Pituitary imaging I (partially) suppress
20 Loose Ends If this guy is making lots of cortisol, what is going on across the street? ACTH, suppressed Glomerulosa? Fasciculata? Reticularis?
21 Loose Ends If this guy is making lots of cortisol, what is going on across the street? Glomerulosa: No change ACTH, suppressed Fasciculata, Reticularis: Atrophy of contralateral gland
22 Loose Ends ACTH, suppressed Glomerulosa: No change Fasciculata & Reticularis: Atrophy
23 Loose Ends If this guy is making lots of ACTH, what is going on downstream? ACTH elevated Glomerulosa: No change Fasciculata Reticularis: Hyperplasia
24 Manifestations Aldosterone Cortisol Response Anything else Etiologies Normal Physiology Questions follow the next presentation
25 Adrenal Disorders for the USMLE, Step One: Abnormalities of the Fasciculata Winter Storm Stella
Adrenal Disorders for the USMLE, Step One: Abnormalities of the Fasciculata: Hypocortisolism
Adrenal Disorders for the USMLE, Step One: Abnormalities of the Fasciculata: Hypocortisolism Howard Sachs, MD Patients Course, 2017 Associate Professor of Clinical Medicine UMass Medical School Manifestations
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