Cushing's Syndrome - Medical Lecture PDF

CUSHING’S SYNDROME Faisal AlAnazi Objectives ¨ At the end of the lecture the student should be able to discuss the following aspects regarding: ¨ Cushing syndrome: 1) Define Cushing syndrome 2) Outline various causes Cushing syndrome 3) Describe presenting features. 4)...

CUSHING’S SYNDROME Faisal AlAnazi Objectives ¨ At the end of the lecture the student should be able to discuss the following aspects regarding: ¨ Cushing syndrome: 1) Define Cushing syndrome 2) Outline various causes Cushing syndrome 3) Describe presenting features. 4) Formulate a likely diagnosis. 5) Plan relevant investigations. 6) Describe the basic principles of management. Definitions ¨ Cushing syndrome: ¤ Defined as chronic glucocorticoid excess, whatever its cause, that leads to the constellation of symptoms and physical features. ¨ Cushing disease: ¤ Defined as the specific type of Cushing syndrome due to excessive pituitary ACTH secretion from a pituitary tumor. Classification and Incidence ¨ Cushing syndrome is conveniently classified as either: 1. ACTH dependent (syndrome-ectopic ACTH syndrome and Cushing disease) 2. ACTH independent: caused by a primary adrenal neoplasm (adenoma or carcinoma) or nodular adrenal hyperplasia Classification and Incidence ¨ ACTH dependent types of Cushing’s: ¤ Characterized by chronic ACTH hypersecretion, ¤ Results in hyperplasia of the adrenal zonae fasciculata and reticularis and, therefore, increased secretion of cortisol and androgens. ¨ ACTH-independent Cushing syndrome: ¤ Caused by a primary adrenal neoplasm (adenoma or carcinoma) or nodular adrenal hyperplasia. ¤ The cortisol excess suppresses pituitary ACTH secretion. Cushing syndrome: causes and differential diagnosis ¨ ACTH-dependent 1. Pituitary adenoma (Cushing disease) 2. Non pituitary neoplasm (ectopic ACTH) ¨ ACTH-independent 1. Iatrogenic (glucocorticoid, megestrol acetate) 2. Adrenal neoplasm (adenoma, carcinoma) 3. Nodular adrenal hyperplasia: A. Primary pigmented nodular adrenal disease (PPNAD) B. Massive macronodular adrenoal hyperplasia C. Food dependent (GIP mediated) D. Factitious Clinical features of Cushing’s disease: ¨ The features are progressive and may be present for several years prior to diagnosis. ¨ May not always be florid, and clinical suspicion should be high. ¨ Facial appearance: 1. Round plethoric complexion 2. Acne and hirsutism, 3. Thinning of scalp hair. Clinical features of Cushing’s disease: ¨ Weight gain, truncal obesity, buffalo hump, supraclavicular fat pads. ¨ Skin: 1. Thin and fragile due to loss of SC tissue 2. Purple striae on abdomen, breasts, thighs, axillae (in contrast to silver, healed post-partum striae), 3. Easy bruising 4. Tinea versicolor 5. Occasionally pigmentation due to ACTH. Clinical features of Cushing’s disease: ¨ Proximal muscle weakness. ¨ Mood disturbance: labile, depression, insomnia, psychosis. ¨ Menstrual disturbance. ¨ Low libido and impotence. Clinical features of Cushing’s disease: ¨ There is a high incidence of venous thromboembolism (careful during surgery). ¨ Overall mortality greater than of general population (by a factor of 6). ¨ Growth arrest in children. Associated features: ¨ Hypertension (>50%) due to mineralocorticoid effects of cortisol ¨ Impaired glucose tolerance/diabetes mellitus (30%). ¨ Osteopenia and osteoporosis (leading to fractures of spine and ribs). ¨ Vascular disease due to metabolic syndrome. ¨ Susceptibility to infections. Moon facies and increased supraclavicular fat pads in Cushing's syndrome Buffalo hump in Cushing's syndrome Striae in Cushing's disease Easy bruisability in Cushing's disease Clinical features o f Cushing syndrome(% prevalence) General Musculoskeletal Gonadal dysfunction - Obesity 90% - Osteopenia 80% - Menstrual disorders 70% - Hypertension 85% - Weakness 65% - Impotence, decreased libido 85% Skin Neuropsychiatric 85% Metabolic - Plethora 70% - Emotional lability - Glucose intolerance 75% - Hirsutism 75% - Euphoria - Diabetes 20% - Striae 50% - Depression - Hyperlipidemia 70% - Acne 35% - Psychosis - Polyuria 30% - Bruising 35% - Kidney stones 15% Diagnosis ¨ The clinical suspicion of Cushing syndrome must be confirmed with biochemical studies. ¨ Initially, a general assessment of the patient regarding the presence of: 1. other illnesses 2. drugs, and alcohol 3. psychiatric problems must be done since these factors may confound the evaluation. Laboratory findings ¨ Routine laboratory examinations include: ¤ CBC show: n High normal hemoglobin, hematocrit, and red cell counts are usual; polycythemia is rare. n The total white count is usually normal; however, both the percentage of lymphocytes and the total lymphocyte count may be subnormal. n Eosinophils are also depressed, and a total eosinophil count less than 100/uL. ¤ Serum electrolytes, with rare exceptions, are normal in Cushing disease ¤ Hypokalemic alkalosis occurs when there is marked steroid hypersecretion with the ectopic ACTH syndrome or adrenocortical carcinoma. Laboratory findings ¤ Glucose intolerance is a relatively common finding and occurs in 60% of patients ¤ Serum calcium is normal; serum phosphorus is low normal or slightly depressed. ¤ Hypercalciuria is present in 40% of cases. Diagnostic Tests ¨ This can be confirmed as outpatient tests by either: A. 2–3x 24h urinary free cortisol: This test can be useful for outpatient screening B. Overnight dexamethasone suppression test: Administration of 1mg dexamethasone at midnight is followed by a serum cortisol measurement at 9 a.m. ¤ If Cortisol