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Hypercortisolemia

Hypercortisolemia (Cushing’s Syndrome): Clinical Findings Cortisol is a net catabolic hormone affecting many body systems, serving to release energy into the blood in response to stress. Excess cortisol also impacts circulation and impairs immune function. Excess Serum Cortisol affects: Authors: Samin Dolatabadi, Yan Yu* Reviewers: Meena Assad, Amanda Henderson, Brooke Fallis, David Campbell* * MD at time of publication Bone and Calcium Metabolism Kidney and vasculature Excess cortisol in the renal tubule saturates the enzyme 11β- HSD2, which converts cortisol to cortisone Capacity of body to convert cortisol to cortisone is exceeded Excess cortisol can mimic aldosterone and bind to mineralocorticoid receptors (cortisone can’t bind to these receptors) ↑ Aldosterone effect → ↑ Na+ reabsorption from the cortical collecting duct into blood vessels Liver and Peripheral Tissue Cortisol ↑ gluco- neogenesis in liver, and ↑ insulin resistance by body tissue (unclear mechanisms) Hyper- glycemia Reproductive System Cortisol exerts negative feedback on hypothalamus à↓ gonadotropin releasing hormone (GnRH) secretion ↓ GnRH → ↓ LH/FSH → ↓ estrogen and testosterone production (especially important in females) Infertility, ↓ Libido, Irregular Menses Adipose Tissue Cortisol ↑ fat breakdown (lipolysis) Selective expression of cortisol receptor on different adipose tissuesàcentral, facial, dorsal fat is less broken down than in other areas (mechanism unclear) Combined with cortisol ↑ appetite: Skin & Connective Tissue ↑ Serum cortisol à↓ Fibroblast proliferation → ↓ Collagen synthesis Skin atrophy with loss of connective tissue Muscle ↑ Proteolysis & ↓ Protein synthesisà↓ muscle growth and function Immune System Normal serum cortisol protects against damaging effects of uncontrolled inflammatory and immune responses ↑ Serum cortisolà over-suppression of inflammation and impaired cell- mediated immunity ↑ Serum cortisol leads to ↓ Intestinal Ca2+ absorption and ↓ renal Ca2+ reabsorption ↓ Serum Ca2+ ↑ PTH secretion ↑ Serum cortisolà↑ RANKL:OPG ratio ↓ Osteoblast activity & ↑ Osteoclast activity Cardiac muscle Cardio- myopathy, Heart Failure Skeletal muscle, especially upper arms & thighs (for unclear reasons) Proximal Muscle Weakness Easy Bruising ↑ abdominal size stretches the fragile skin to become thinneràvenous blood of the underlying dermis becomes visible Purple Striae If hypertension is chronic Ca2+ resorption from bone into the blood Osteoporosis Supraclavicular & Dorsal Fat Pads Central Obesity Poor Wound Healing Susceptibility to infection Round Face (Moon Face) Abbreviations: • RANKL – Receptor activator of nuclear factor kappa-Β ligand • OPG – Osteoprotegerin • 11β-HSD2 – 11β-hydroxysteroid dehydrogenase type 2 Water follows Na+ into blood vessels to balance the osmotic pressure between the blood and renal tubules Water reabsorption → Expansion of blood volume Hypertension Both primary Cushing’s (e.g. adenomas that extend into zona reticularis of the adrenal cortex) and central/secondary Cushing’s (e.g. ↑ ACTH stimulation of zona reticularis) are associated with ↑ adrenal androgen secretion Removal of positively charged Na+ from tubular lumen creates a negative luminal environment K+ follows the electrical gradient and is secreted into tubular lumen ↓ Serum K+ concentration Hypokalemia Arrhythmia, Paralysis, Cramps (see Hypokalemia: Clinical Findings slide) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 17, 2021 on www.thecalgaryguide.com Hirsutism, Acne