Causes of Cushings Syndrome ACTH-dependent Cushings disease(acTH-producing pituitary adenoma)(60-70%) Ectopic ACTH syndrome(15-20%) Ectopic CRH syndrome Macronodular adrenal hyperplasia latrogenic( treatment with ACTH 1-24) ACTH-independent Adrenal adenoma(10-20%)and carcinoma (<5%) Primary pigmented nodular adrenal hyperplasia and Carney's syndrome McCune-Albright syndrome Aberrant receptor expression(gastric inhibitory polypeptide, interleukin-1B) (ACTH-independent macronodular hyperplasia latrogenic(e.g, pharmacologic doses of prednisolone, dexamethasone)
Causes of Cushing’s Syndrome • ACTH-dependent • Cushing's disease (ACTH-producing pituitary adenoma) (60-70%) • Ectopic ACTH syndrome (15-20%) • Ectopic CRH syndrome • Macronodular adrenal hyperplasia • Iatrogenic (treatment with ACTH 1-24) • ACTH-independent • Adrenal adenoma (10-20%) and carcinoma (<5%) • Primary pigmented nodular adrenal hyperplasia and Carney's syndrome • McCune-Albright syndrome • Aberrant receptor expression (gastric inhibitory polypeptide, interleukin-1β) (ACTH-independent macronodular hyperplasia ) • Iatrogenic (e.g., pharmacologic doses of prednisolone, dexamethasone)
Effects of Glucocorticoids LH. FSH release TSH release Brain/CNS ↓ GH secretion Depression glucose t Peripheral insulin resistance f Gluconeogenesis G/ tract I Free fatty acid production Peptic ulcerations Hypertension Promotes visceral obesity ne and calcium metabolism Bone formation I Bone mass and osteoporosis protein Skin/muscle/connective tissue ↓ Linear growth rotein cataboismvcollagen breakdown
Effects of Glucocorticoids glucose lipid protein
Clinical Features of Cushing's syndrome SYMPTOMS (%Patients) SIGNS (%Patients) weight gain 91 97 Menstrual irregularity 8416 Hirsutism 8128 Generalized 5508 Psychiatric dysfunction Plethora 9430 Backache Moon facies Muscle weakness 2980 Hypertension 7444 Fractures Bruising 62103 Loss of scalp hair Red-purple striae 625 Muscle weakness OTHER FINDINGS (%Patients) Ankle edema Hypertension 74 Pigmentation 4 Diabetes 13 Impaired glucose tolerance test 37 osteoporosis Renal calculi 15
Clinical Features of Cushing’s Syndrome (%Patients) (%Patients) (%Patients)
Clinical Features of Cushing's syndrome Obesity Truncal obesity Moon face Fat deposits in supraclavicular fossa and posterior neck-buffalo hump
Clinical Features of Cushing’s Syndrome • Obesity • Truncal obesity • Moon face • Fat deposits in supraclavicular fossa and posterior neck- buffalo hump
Truncal obesity FIG. 4. Case 1. The original example(1902)of basophil (u FIGS 6 AND 7, Dr. Turney,s patient at the age of 20 and five verified) obesity years later(1913)at the height of the disorder Weight gain and obesity are the most common sign, and this is invariably centripetal in nature
Truncal Obesity Weight gain and obesity are the most common sign, and this is invariably centripetal in nature