Diagnosis: Pituitary Adenoma (Cushing Disease)
This patient has ACTH-dependent Cushing syndrome caused by a pituitary adenoma (Cushing disease), making option A the correct diagnosis. The key diagnostic feature is the detectable ACTH level of 15 pg/mL combined with hypercortisolism and loss of diurnal cortisol rhythm 1, 2.
Diagnostic Reasoning
ACTH Level Interpretation
Any ACTH level >5 ng/L (or pg/mL) is detectable and definitively indicates ACTH-dependent Cushing syndrome 2. This patient's ACTH of 15 pg/mL clearly falls into this category, immediately excluding adrenal adenoma (option B) as the diagnosis 1, 2.
In ACTH-independent Cushing syndrome (adrenal adenoma), ACTH is always low and usually undetectable 2. The presence of a measurable ACTH level rules out option B entirely 1.
While ACTH >29 ng/L has 70% sensitivity and 100% specificity for Cushing disease, any detectable ACTH (>5 ng/L) in the setting of confirmed hypercortisolism indicates an ACTH-dependent etiology 1, 2.
Cortisol Pattern Analysis
The loss of normal diurnal cortisol rhythm is pathognomonic for Cushing syndrome 1. Normal individuals should have low cortisol at 4pm (midnight cortisol should be <50 nmol/L or <1.8 μg/dL), but this patient maintains elevated cortisol at 500 nmol/L in the afternoon 1, 3.
The 8am cortisol of 846 nmol/L (approximately 30.7 μg/dL) is significantly elevated above the normal range of 138-635 nmol/L (5-23 μg/dL) 3.
This pattern of persistently elevated cortisol throughout the day without normal circadian variation confirms endogenous hypercortisolism 1.
Why Not Ectopic ACTH (Carcinoid)?
While ectopic ACTH syndrome from carcinoid tumors (option C) would also show detectable ACTH, the clinical presentation strongly favors pituitary disease 4, 5.
Ectopic ACTH syndrome typically presents with very high urinary free cortisol levels and profound hypokalemia, which are not mentioned in this case 2.
Pituitary adenomas (Cushing disease) account for 75-80% of ACTH-dependent Cushing syndrome cases, making it statistically the most likely diagnosis 4.
The moderate ACTH elevation (15 pg/mL) is more consistent with pituitary disease than ectopic sources, which often produce much higher ACTH levels 2.
Clinical Context
The classic Cushingoid features (central obesity, moon facies, striae) combined with ACTH-dependent hypercortisolism are characteristic of Cushing disease 4, 5.
Microadenomas are the most common cause of Cushing disease, accounting for 98% of cases, and are frequently ≤2 mm in diameter 4. The absence of a visible adenoma on imaging would not exclude this diagnosis.
The TSH of 5 mIU/L is mildly elevated but not directly relevant to the Cushing syndrome diagnosis, though hypothyroidism can coexist 4.
Next Diagnostic Steps
Pituitary MRI with thin slices (3T preferred) should be performed to identify a potential pituitary adenoma 2.
If MRI shows an adenoma ≥10 mm, this strongly confirms Cushing disease 2.
If MRI is negative or shows a lesion <6 mm, bilateral inferior petrosal sinus sampling (BIPSS) should be performed to definitively distinguish pituitary from ectopic ACTH sources, with diagnostic criteria of central-to-peripheral ACTH ratio ≥2:1 before stimulation and ≥3:1 after CRH or desmopressin 1, 2.