### Date : 2024-06-19 18:13 ### Topic : Ectopic ACTH Syndrome #medicine #internalmedicine ---- ### Ectopic ACTH Syndrome Overview **Ectopic ACTH syndrome** is a condition where adrenocorticotropic hormone (ACTH) is produced by non-pituitary tumors, leading to excessive cortisol production by the adrenal glands. This results in a form of Cushing syndrome characterized by high levels of cortisol in the blood, with symptoms similar to those of other forms of Cushing syndrome. ### Pathophysiology In ectopic ACTH syndrome, tumors located outside the pituitary gland (most commonly in the lungs, pancreas, thymus, or other organs) produce ACTH. This ectopic production of ACTH stimulates the adrenal glands to produce excess cortisol, leading to hypercortisolism. The tumors responsible for ectopic ACTH production are often small and may be malignant. ### Common Sources of Ectopic ACTH Production 1. **Small Cell Lung Cancer (SCLC):** One of the most common sources. 2. **Carcinoid Tumors:** Often found in the lungs or gastrointestinal tract. 3. **Pancreatic Neuroendocrine Tumors:** Less common but possible source. 4. **Medullary Thyroid Carcinoma:** Rarely associated with ectopic ACTH production. 5. **Thymic Tumors:** Another possible source. ### Clinical Features **Symptoms of Hypercortisolism:** - **Weight Gain:** Particularly in the abdomen, face (moon face), and upper back (buffalo hump). - **Skin Changes:** Thin, fragile skin that bruises easily, and purple striae (stretch marks) on the abdomen, thighs, and breasts. - **Muscle Weakness:** Especially in the proximal muscles (hips and shoulders). - **Hypertension:** High blood pressure. - **Hyperglycemia:** High blood sugar levels, potentially leading to diabetes. - **Osteoporosis:** Increased risk of fractures due to bone loss. - **Electrolyte Imbalances:** Hypokalemia (low potassium levels). **Symptoms of the Underlying Tumor:** - Symptoms related to the primary tumor location, such as cough or hemoptysis in lung cancer, or gastrointestinal symptoms in pancreatic tumors. ### Diagnosis Diagnosing ectopic ACTH syndrome involves identifying hypercortisolism, confirming ectopic ACTH production, and locating the ectopic tumor: 1. **Clinical Evaluation:** - Assess symptoms of hypercortisolism and review medical history. 2. **Laboratory Tests:** - **24-Hour Urinary Free Cortisol:** Elevated cortisol levels. - **Late-Night Salivary Cortisol:** Elevated cortisol levels. - **Low-Dose Dexamethasone Suppression Test:** Lack of suppression of cortisol levels. - **Plasma ACTH Levels:** Elevated ACTH levels indicate ACTH-dependent Cushing syndrome. - **High-Dose Dexamethasone Suppression Test:** Lack of suppression suggests ectopic ACTH production rather than pituitary origin. 3. **Imaging Studies:** - **CT Scan or MRI of the Chest and Abdomen:** To locate possible ectopic tumors. - **Octreotide Scan or PET Scan:** Functional imaging to detect neuroendocrine tumors. ### Example Case Study **Patient Profile:** - **Name:** Jee Hoon Ju - **Age:** 60 - **Occupation:** Retired Factory Worker **Medical History:** - **Symptoms:** Jee Hoon Ju reports significant weight gain, particularly in his abdomen and face, with purple stretch marks on his abdomen. He also experiences high blood pressure, high blood sugar levels, and muscle weakness. He has a persistent cough and occasional hemoptysis. **Clinical Examination:** - **Facial Appearance:** Rounded face (moon face). - **Upper Back:** Fat deposition (buffalo hump). - **Skin:** Thin skin with purple striae on the abdomen. **Laboratory Tests:** - **24-Hour Urinary Free Cortisol:** Elevated cortisol levels. - **Late-Night Salivary Cortisol:** Elevated cortisol levels. - **Low-Dose Dexamethasone Suppression Test:** No suppression of cortisol levels. - **Plasma ACTH Levels:** Elevated. - **High-Dose Dexamethasone Suppression Test:** No suppression, suggesting ectopic ACTH production. **Imaging:** - **CT Scan of the Chest:** Reveals a mass in the lung suggestive of a small cell lung carcinoma. **Diagnosis:** Based on the clinical features, laboratory test results, and imaging findings, Jee Hoon Ju is diagnosed with ectopic ACTH syndrome secondary to a small cell lung carcinoma. ### Management 1. **Treat the Underlying Tumor:** - **Surgical Resection:** If the tumor is localized and resectable. - **Chemotherapy and/or Radiation Therapy:** For inoperable or metastatic tumors, particularly in cases of small cell lung cancer. 2. **Manage Hypercortisolism:** - **Medications to Control Cortisol Levels:** Steroidogenesis inhibitors such as ketoconazole, metyrapone, or mitotane. - **Pasireotide:** A somatostatin analog that can help reduce ACTH secretion from ectopic sources. 3. **Symptomatic Treatment:** - **Hypertension:** Antihypertensive medications. - **Hyperglycemia:** Management of blood sugar levels with diet, medications, or insulin. - **Osteoporosis:** Calcium and vitamin D supplements, bisphosphonates. 4. **Monitoring and Follow-Up:** - Regular monitoring of cortisol levels and clinical symptoms. - Follow-up imaging to assess tumor response to treatment and detect any recurrence. ### Prognosis - The prognosis depends on the underlying tumor type, its stage, and the response to treatment. - Early detection and effective management of the ectopic tumor and hypercortisolism are crucial for improving outcomes. ### Conclusion Ectopic ACTH syndrome is a serious condition resulting from non-pituitary tumors producing ACTH, leading to excessive cortisol production. Early diagnosis and comprehensive management, including treatment of the underlying tumor and control of hypercortisolism, are essential for improving patient outcomes. Regular monitoring and follow-up care are critical to ensure effective treatment and manage any potential complications.