W7 Cushing Syndrome PDF - Applied Pathophysiology

Lecture Material is adapted from © 2017 Wolters Kluwer Health, Lippincott Williams & Wilkins Applied Pathophysiology: A Conceptual Approach to the Mechanisms of Disease Chapter 13: Altered Hormonal and Metabolic Regulation Module 4: Clinical Models Dr. Romeo Batacan Jr. MPAT12001 Medical Pathoph...

Lecture Material is adapted from © 2017 Wolters Kluwer Health, Lippincott Williams & Wilkins Applied Pathophysiology: A Conceptual Approach to the Mechanisms of Disease Chapter 13: Altered Hormonal and Metabolic Regulation Module 4: Clinical Models Dr. Romeo Batacan Jr. MPAT12001 Medical Pathophysiology Lecture Series Copyright © 2017 Wolters Kluwer Health | Lippincott Williams &Wilkins  Adrenal Cortical Hormone Excess - Cushing Syndrome Pathophysiology Clinical manifestations Diagnostic criteria Treatment  Adrenal Gland Two glands in one - structurally and functionally 1. Adrenal medulla—nervous tissue, part of sympathetic nervous system Epinephrine and norepinephrine 2. Adrenal cortex—three layers of glandular tissue: synthesize and secrete corticosteroids Zona glomerulosa (outer) —mineralocorticoids Zona fasciculata (middle) —glucocorticoids Zona reticularis (inner) —gonadocorticoids  Cushing Syndrome Pathophysiology Cushing syndrome: 1. excess endogenous glucocorticoids 2. excess exogenous glucocorticoids Cushing disease: hypercorticolism specifically related to pituitary tumor women 5x more likely to develop Cushing disease  Cushing Syndrome Pathophysiology Glucocorticoids affects metabolic function inflammatory responses immune responses Stimulate glucose production stress response Decrease tissue glucose utilization Increase breakdown and circulation of plasma proteins Increase mobilization of fats Inhibit bone formation Inhibit the immune response Prevent the release of chemical mediators that trigger the inflammatory response Decrease capillary permeability and inhibit edema formation Stimulate gastric acid secretions Contribute to emotional behavior Contribute to an effective stress response  Cushing Syndrome Pathophysiology Main causes of Cushing syndrome I. Excess production of glucocorticoids by the body: 1. Tumors of the pituitary gland that stimulate excess ACTH production (this form is called Cushing-disease and was described by Cushing) 2. Tumors of the adrenal gland that stimulate excess cortisol production 3. Ectopic production of ACTH or CRH from a tumor at a distant site (small cell carcinoma of the lung) II. Iatrogenic Cushing syndrome 1. Long-term administration of corticosteroid medications (such as prednisone) Used in wide range of chronic inflammatory and autoimmune conditions Exogenous corticoids (therapeutic doses) supress inflammatory and autoimmune response Decrease the impact of chronic inflammation Administration suppress cortisol production by the adrenal cortex Gradual withdrawal if needed  Cushing Syndrome Pathophysiology Pituitary or ectopic: Overstimulates adrenal cortex Excess cortisol production Hyperplasia This form depends on ACTH May require ACTH secreting tumor Adrenal tumors Direct hypersecretion Not directed by ACTH Strayer D, Rubin E. Rubin's Pathology: Clinicopathologic Foundations of Medicine. 7th ed. UK, Wolters Kluwer/Lippincott Williams & Wilkins; 2014  Cushing Syndrome Clinical Manifestations Metabolic alterations: obesity of trunk, face, and upper back “buffalo hump”, “moon face” striae/stretch marks from truncal obesity Protein degradation: weakness and muscle wasting Excessive circulating glucose and glucose intolerance May lead to diabetes mellitus Suppression of inflammation/immunity Increased infection rates Skin ulcerations Poor wound healing Behavioral changes Cortex overstimulation also leads to Impaired stress response Aldosterone overproduction: hypertension, hypokalemia Androgen overproduction: hirsutism (excessive body and facial hair, changes in the pattern of hair growth)  Cushing Syndrome McCance KL, Huether S. Pathophysiology. 7th ed. N.S.W, Mosby; 2015 Porth C. Pathophysiology : concepts of altered health states. 7th ed. Philadelphia, Lippincott Williams & Wilkins; 2005. Kumar, Robbins & Cotran: Pathophysiological basis of disease. 8th ed. Philadelphia: Saunders;2010 Marieb EN, Hoehn KN. Human Anatomy & Physiology. 9th ed. Boston, Pearson Education; 2013  Cushing Syndrome Diagnostic Criteria Cortisol levels in 24-hour urine Reliable and practical index of cortisol secretion Loss of diurnal pattern Midnight level can be elevated Plasma levels of ACTH Dexamethasone suppression test External hormones provides negative feedback Hormone secretion decrease http://thebrain.mcgill.ca/flash/i/i_11/i_11_p/i_11_p_hor/i_11_p_hor.html Imaging studies to detect tumors  Cushing Syndrome Treatment Untreated: produce serious morbidity Choice depends on cause Remove or correct the cause of excess cortisol secretion without permanent damage to pituitary or adrenal gland Surgery, radiotherapy: removal of tumors Pharmacologic: Block steroid synthesis