What hormone is overproduced in a 49-year-old man with profuse diarrhea, facial flushing precipitated by alcohol, a pansystolic murmur, elevated liver enzymes (transaminases), and anemia?

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Diagnosis: Carcinoid Syndrome with Serotonin Overproduction

The answer is B. Serotonin. This patient's constellation of profuse diarrhea, facial flushing precipitated by alcohol, cardiac valvular disease (pansystolic murmur), elevated transaminases, and anemia is classic for carcinoid syndrome caused by excessive serotonin production from a neuroendocrine tumor with liver metastases.

Clinical Reasoning

Classic Carcinoid Syndrome Features Present

  • Carcinoid syndrome is characterized by flushing and diarrhea due to the release of serotonin, tachykinins, and other vasoactive compounds directly into the systemic circulation 1.

  • Approximately 70% of patients give a history of intermittent abdominal pain, 50% report diarrhea, and about 30% experience flushing at the time of diagnosis 1.

  • Alcohol is a known precipitant of flushing episodes in carcinoid syndrome, which distinguishes this from other causes of flushing 1.

Cardiac Involvement

  • Carcinoid heart disease manifests as a pansystolic murmur from tricuspid regurgitation and/or pulmonary stenosis 1.

  • Approximately 50% to 66% of patients with carcinoid syndrome develop valvular cardiac complications, typically occurring after the syndrome has been present for several years 1.

  • The pansystolic murmur loudest at the lower left sternal edge is consistent with tricuspid regurgitation, the most common cardiac manifestation 1.

Liver Metastases Indicated

  • Carcinoid syndrome usually results from metastases to the liver with subsequent release of hormones directly into the systemic circulation 1.

  • The elevated transaminases (ALT 320 U/L) strongly suggest liver involvement, which is necessary for carcinoid syndrome to manifest because intestinal NETs release metabolic products that are rapidly destroyed by liver enzymes in the portal circulation 1.

  • The classic syndrome occurs in approximately 8% to 28% of patients with NETs and is not usually observed unless liver metastases have occurred 1.

Anemia Explained

  • Anemia (Hb 10.2 g/dL) can occur from intestinal blood loss or as a consequence of pellagra-like syndrome from tryptophan depletion 1.

  • Serotonin synthesis consumes tryptophan, which can lead to niacin deficiency and contribute to anemia 1.

Why Not the Other Options?

  • Cholecystokinin (A): Does not cause flushing or diarrhea; primarily involved in gallbladder contraction and pancreatic enzyme secretion.

  • Vasoactive intestinal polypeptide/VIPoma (C): Causes profuse watery diarrhea with marked hypokalemia (Werner-Morrison syndrome) but does not typically cause flushing or cardiac valvular disease 1.

  • Gastrin/Gastrinoma (D): Presents with Zollinger-Ellison syndrome of severe peptic ulceration and diarrhea, not flushing or cardiac disease 1.

  • Somatostatin/Somatostatinoma (E): Associated with cholelithiasis, weight loss, diarrhea/steatorrhea, and diabetes mellitus, not the flushing-diarrhea-cardiac triad 1.

Diagnostic Confirmation

Biochemical evaluation with 24-hour urine collection for 5-hydroxyindoleacetic acid (5-HIAA) is the standard diagnostic test for carcinoid syndrome, as it measures serotonin metabolites 1.

Serum chromogranin A can also be measured as a general NET marker, though it may be elevated in other conditions 1.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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