In a patient with elevated Adrenocorticotropic hormone (ACTH) levels suspected of having a carcinoid tumor, which organ should be evaluated first?

Organ Evaluation in Elevated ACTH with Suspected Carcinoid Tumor

The lungs should be evaluated first in a patient with elevated ACTH and suspected carcinoid tumor, as bronchial carcinoids are the most common source of ectopic ACTH production among carcinoid tumors. 1

Primary Evaluation Focus

When elevated ACTH indicates ectopic production (not from the adrenal gland), the probable sources include ectopic tumors in the lung, thyroid, pancreas, or bowel. 1 However, the clinical priority differs significantly:

Bronchopulmonary Carcinoids as Primary Source

• Bronchial carcinoids are specifically associated with ACTH production and Cushing syndrome, making them the most relevant carcinoid subtype for this clinical presentation. 2
• Approximately one-third of all carcinoid tumors arise in the lungs or thymus, representing a substantial proportion of cases. 2
• Among ectopic ACTH-producing tumors, bronchial carcinoids are the most common solid tumor source. 3, 4, 5
• Bronchial carcinoids demonstrate a 15% rate of nodal metastases and 5% rate of liver metastases. 6

Diagnostic Approach for Bronchopulmonary Evaluation

• Bronchoscopy is the site-specific evaluation recommended for bronchopulmonary and thymic carcinoids. 2
• Multiphase CT or MRI scans of the chest are essential to assess disease burden and primary location. 2
• Selective pulmonary arterial sampling can successfully localize small bronchial carcinoids producing ectopic ACTH when imaging is inconclusive. 4
• Measurement of ACTH in bronchoscopic lavage fluid can confirm the diagnosis when the tumor is visualized but venous sampling is negative. 7
• Somatostatin receptor scintigraphy (octreotide scan) is useful for localizing occult carcinoid tumors producing ACTH. 5

Secondary Considerations

Thymus Evaluation

• The thymus is the second priority, as thymic carcinoids can also produce ACTH and cause Cushing syndrome. 2, 8
• Thymic carcinoids have metastatic potential and require thorough evaluation. 2
• 18-FDG-PET can be particularly useful for identifying thymic carcinoids when conventional imaging shows only nonspecific findings. 8

Gastrointestinal Sites

While the question lists intestine, pancreas, and stomach as options, these are less commonly associated with ACTH production:

• Intestinal carcinoids (particularly ileal) have the highest metastatic rates (60% nodal, 30% liver) but are more commonly associated with carcinoid syndrome from serotonin secretion rather than ACTH production. 2, 6
• Duodenal/pancreatic carcinoids can rarely produce ectopic ACTH, but this is exceptional rather than typical. 3
• Gastric carcinoids show 35% nodal and 15% liver metastases but are not characteristically ACTH-producing. 6

Clinical Algorithm

1. Confirm ectopic ACTH syndrome through lack of circadian rhythm, no suppression by high-dose dexamethasone, and no response to CRH stimulation. 4
2. Perform chest imaging (CT or MRI) as the initial anatomic evaluation. 1, 2
3. Conduct bronchoscopy for direct visualization and potential sampling. 2, 7
4. Consider octreotide scintigraphy if initial imaging is negative or equivocal. 5
5. Evaluate the thymus if bronchial sources are excluded. 2, 8
6. Image the abdomen and pelvis only after thoracic sources are thoroughly investigated. 1

Critical Pitfall

Do not proceed with broad abdominal imaging before thoroughly evaluating the chest, as this delays diagnosis of the most likely source and prolongs exposure to life-threatening hypercortisolemia. 3, 4

Answer: a. Lungs