Pellagra presents with dermatitis, diarrhea, and dementia (3Ds). In carcinoid syndrome, pellagra occurs despite adequate dietary niacin. What is the biochemical explanation?

• A Carcinoid tumors secrete ACTH, which stimulates cortisol production that depletes niacin via CYP3A4-mediated oxidative catabolism
• B Carcinoid tumors produce large amounts of serotonin from tryptophan, diverting tryptophan away from niacin (NAD) synthesis ✓
• C Carcinoid tumors impair intestinal absorption of niacin by secreting histamine that disrupts enterocyte tight junctions
• D Serotonin from carcinoid tumors inhibits quinolinate phosphoribosyltransferase, blocking de novo niacin synthesis from quinolinate

Explanation

Tryptophan is the dietary precursor for endogenous niacin synthesis: tryptophan → kynurenine → quinolinate → NAD (60 mg tryptophan = 1 mg niacin equivalent). In carcinoid syndrome, the tumor massively upregulates tryptophan hydroxylase to synthesise serotonin (5-HT) from tryptophan, diverting up to 60% of dietary tryptophan into the serotonin pathway. This leaves insufficient tryptophan for the kynurenine pathway and niacin biosynthesis, causing functional niacin deficiency (pellagra) even when dietary niacin is adequate. This also explains why urinary 5-HIAA is a diagnostic marker of carcinoid.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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Written and medically reviewed by the StethoPrep medical team.