Ectopic ACTH Secretion
The most likely diagnosis is D. Ectopic ACTH secretion, given the rapid 3-4 month onset of severe Cushingoid features combined with elevated ACTH and cortisol levels. 1
Diagnostic Reasoning Based on Clinical Tempo
The rapid onset over 3-4 months is the critical distinguishing feature that points away from pituitary adenoma and toward ectopic ACTH syndrome. 2
Ectopic ACTH-secreting tumors typically present with rapid onset of severe hypercortisolism, often developing over weeks to months rather than the insidious years-long progression typical of Cushing's disease. 2, 3
Pituitary adenomas (Cushing's disease) characteristically develop slowly over years, with the average diagnostic delay being 3 years from initial symptoms to diagnosis. 2
The 3-4 month timeframe in this case is far too rapid for the typical presentation of a pituitary adenoma, which accounts for 75-80% of ACTH-dependent cases but presents with gradual symptom progression. 1, 4
ACTH-Dependent vs ACTH-Independent Classification
The laboratory findings definitively establish this as ACTH-dependent Cushing's syndrome:
Both ACTH and cortisol are elevated, which rules out adrenal adenoma (option B) where ACTH would be suppressed or undetectable. 1, 5
Any detectable ACTH level (>5 ng/L) with confirmed hypercortisolism indicates ACTH-dependent disease, pointing toward either pituitary or ectopic sources. 1
Exogenous steroid use (option C) is excluded because ACTH is elevated rather than suppressed, as exogenous steroids would suppress the hypothalamic-pituitary-adrenal axis. 1, 6
Clinical Features Supporting Ectopic ACTH
The severity and rapidity of presentation favor ectopic ACTH syndrome:
Ectopic ACTH syndrome typically presents with more severe and rapidly progressive features including profound hypokalemia, severe hypertension, and marked hypercortisolism. 1, 7
The combination of facial hair (hirsutism), striae, and obesity developing over just 3-4 months suggests a particularly aggressive form of hypercortisolism more consistent with ectopic sources. 2, 6
Common Ectopic Sources
Ectopic ACTH-secreting tumors are most commonly found in the thorax or abdomen:
Small cell lung carcinoma and bronchial carcinoids are the most frequent thoracic sources. 3
Thymic carcinoids account for up to 2% of ectopic ACTH cases. 2
Gastroenteropancreatic neuroendocrine tumors and pheochromocytomas are common abdominal sources. 3
Next Diagnostic Steps
Following this clinical presentation, the diagnostic workup should proceed as follows:
Pituitary MRI should still be performed to exclude a large pituitary adenoma (≥10 mm), though the rapid onset makes this less likely. 1
If MRI is negative or shows only small lesions (<6 mm), bilateral inferior petrosal sinus sampling (BIPSS) is indicated to definitively distinguish between pituitary and ectopic sources, with central-to-peripheral ACTH ratio ≥2:1 baseline or ≥3:1 after CRH stimulation confirming pituitary source. 1, 6
Neck-to-pelvis thin-slice CT scan should be performed to search for ectopic ACTH-secreting tumors, particularly given the rapid onset and severity. 1
68Ga-DOTATATE PET imaging can be useful for localizing neuroendocrine tumors not visible on conventional imaging. 1
Important Clinical Caveat
While pituitary adenomas statistically account for 60-70% of endogenous Cushing's syndrome cases 6, the clinical tempo of 3-4 months makes ectopic ACTH syndrome the most likely diagnosis in this specific patient, despite its lower overall prevalence (approximately 15% of cases). 5, 7 The rapid onset is the key discriminating feature that overrides the statistical probability.