Clinical Features of Cushing

Clinical Features of Cushing’s Syndrome and Differentiation of Causative Lesions Clinical Features of Cushing’s Syndrome Cushing’s syndrome is a condition characterized by prolonged exposure to high levels of glucocorticoids, primarily cortisol. The clinical features can vary widely but typically include the following: 1. Weight Gain and Obesity: Central obesity is common, with fat deposition particularly in the face (moon face), supraclavicular area, and upper back (buffalo hump). 2. Skin Changes: o Thin, Fragile Skin: Easy bruising and delayed wound healing. o Purple Striae: Stretch marks, often on the abdomen, thighs, and breasts. o Acne and Hirsutism: Excess hair growth, especially in women. 3. Musculoskeletal Symptoms: o Muscle Weakness: Proximal myopathy, particularly affecting the hips and shoulders. o Osteoporosis: Increased risk of fractures due to bone demineralization. 4. Metabolic Disturbances: o Hyperglycemia and Diabetes: Due to cortisol’s antagonistic effect on insulin. o Hypertension: Elevated blood pressure is common. 5. Psychiatric Symptoms: o Mood Changes: Depression, anxiety, and irritability. o Cognitive Impairment: Memory problems and difficulty concentrating. 6. Reproductive System Effects: o Menstrual Irregularities: Amenorrhea or oligomenorrhea in women. o Decreased Libido and Erectile Dysfunction: In men. 7. Cardiovascular Risk: o Increased Risk of Cardiovascular Disease: Due to hypertension, hyperglycemia, and dyslipidemia. Differentiating Causative Lesions The causes of Cushing’s syndrome can be broadly categorized into ACTH-dependent and ACTH-independent sources. Pituitary Lesions (Cushing’s Disease) Cushing’s disease is the most common form of endogenous Cushing’s syndrome and results from an ACTH-secreting pituitary adenoma. Features include: 1. ACTH-Dependent: Elevated ACTH levels due to pituitary adenoma. 2. Hyperpigmentation: Due to increased melanocyte-stimulating hormone (MSH) production alongside ACTH. 3. Bilateral Adrenal Hyperplasia: Stimulation of both adrenal glands by excess ACTH. Diagnostic tests:   High-dose Dexamethasone Suppression Test: Suppression of cortisol levels indicates a pituitary source. MRI of the Pituitary: Identifies the adenoma. Adrenal Cortex Lesions Adrenal causes are ACTH-independent and include: 1. Adrenal Adenomas: Benign tumors that produce cortisol. 2. Adrenal Carcinomas: Malignant tumors that secrete cortisol. 3. Primary Pigmented Nodular Adrenocortical Disease (PPNAD): Rare cause with multiple small cortisol-secreting nodules. Features:   Low ACTH Levels: Due to negative feedback from high cortisol. Unilateral Adrenal Mass: Detected on imaging (CT or MRI). Diagnostic tests:   Low ACTH Levels: Confirms ACTH-independent Cushing’s syndrome. Adrenal Imaging: Identifies the adrenal lesion. Extra-Adrenal Sites (Ectopic ACTH Syndrome) Ectopic ACTH production is usually from non-pituitary tumors, such as: 1. Small Cell Lung Carcinoma: Common source of ectopic ACTH production. 2. Carcinoid Tumors: Often found in the lung or gastrointestinal tract. Features:    Severe and Rapid Onset: Often more pronounced symptoms than pituitary causes. Hyperpigmentation: Due to high ACTH levels. Weight Loss and Cachexia: Common with malignancy. Diagnostic tests:    High ACTH Levels: With no suppression on high-dose dexamethasone test. CT/MRI of Chest and Abdomen: To locate the ectopic source. Petrosal Sinus Sampling: Differentiates between pituitary and ectopic sources by comparing ACTH levels. Conclusion Cushing’s syndrome presents with a wide array of clinical features due to prolonged cortisol exposure. Differentiating between pituitary, adrenal, and extra-adrenal causes involves specific clinical and biochemical tests. Proper identification of the source is essential for appropriate treatment and management of this complex endocrine disorder.