bubble_chart Overview

Ectopic ACTH syndrome is caused by non-pituitary tumor cells secreting excessive amounts of ACTH. Clinically, it presents with symptoms similar to Cushing's syndrome. The primary tumors responsible for this syndrome mainly include lung cancer (47%), thymic carcinoma (20%), pancreatic cancer (15%), stony goiter (thyroid carcinoma) (5%), followed by gastrointestinal tract cancers, urinary system tumors, neuroblastoma, parathyroid adenoma, and others.

bubble_chart Pathogenesis

The primary tumor can secrete large amounts of macromolecular ACTH, which consists of more than 39 amino acids and is a low-activity form of ACTH, possibly ACTH itself. This stimulates the adrenal cortex to produce excessive cortisol. Cells that secrete high-molecular-weight ACTH are APUD (Amine Precursor Uptake and Decarboxylation) cells, such as oat cell bronchial lung cancer, carcinoids in various locations, islet cell carcinoma, medullary thyroid carcinoma, pheochromocytoma, melanoma, etc. Non-APUD tumors that secrete ACTH include lung adenocarcinoma, squamous cell carcinoma, liver cancer, etc. This syndrome is more commonly seen in males.

bubble_chart Clinical Manifestations

There are two types clinically:

The first type primarily occurs in oat cell lung cancer patients. Due to the short course and severe condition, characteristic symptoms of Cushing's syndrome such as centripetal obesity and purple striae may not appear. Instead, it mainly manifests as significant pigmentation, hypertension, edema, severe hypokalemia with muscle weakness, and diabetic symptoms such as polydipsia, polyuria, and weight loss. Plasma ACTH and cortisol levels are significantly elevated, with the former often exceeding 200 ng/L and the latter exceeding 360 μg/L. 17-hydroxycorticosteroids are markedly increased.

The second type includes low-grade malignant and benign tumors, such as carcinoids of the liver, pancreas, and intestines, as well as pheochromocytoma. These tumor diseases have a longer course and milder condition, and since carcinoids are very small in size, they may clinically present with more typical Cushing's syndrome symptoms, such as moon face, centripetal obesity, purple striae, acne, accelerated hypertension, brittle diabetes, muscle weakness, progressive muscular dystrophy, edema, and mental disorders.

bubble_chart Diagnosis

After a clear diagnosis, surgical treatment should be performed for carcinoid or benign tumors. For cases where resection is difficult, combination chemotherapy should be adopted. Inhibitors of corticosteroid synthesis can be used: ① Metyrapone: inhibits 11-hydroxylase, 500mg every 4 hours. ② Aminoglutethimide: inhibits the conversion of cholesterol to 5-pregnenolone, 250mg every 6 to 8 hours. ③ Mitotane: causes atrophy and necrosis of adrenal cortical zona fasciculata and reticularis cells, but has high toxicity, leading to nausea, vomiting, headache, vertigo, rash, etc. Use with caution. ④ Symptomatic treatment may include appropriate potassium supplementation, diabetes control, and, if necessary, small doses of prednisone to prevent crises.