Chronic cannabis use as a confounding factor in the delayed diagnosis of phaeochromocytoma

Summary

A 37-year-old man with a long-standing history of daily cannabis use was evaluated for refractory hypertension and recurrent paroxysmal episodes of palpitations, diaphoresis, tremor, and anxiety. A consistent and striking clinical pattern had been observed over several years: symptoms reliably improved during active cannabis use and worsened within days of abstinence. This bidirectional relationship had guided prior evaluations towards anxiety disorder and cannabis withdrawal syndrome, and no biochemical endocrine workup had ever been performed. After a sustained period of abstinence precipitated more frequent and severe episodes, urinary fractionated metanephrines were measured and found to be markedly elevated: normetanephrine at 6,114 μg/24 h (reference range: ≤445; 13.7-fold) and total metanephrines at 11,662 μg/24 h (reference range: ≤757; 15.4-fold). Contrast-enhanced CT identified a 6.0 × 5.0 cm left adrenal mass with imaging characteristics consistent with phaeochromocytoma. Following preoperative alpha- and beta-adrenergic blockade, laparoscopic left adrenalectomy was performed without complications. Histopathology confirmed phaeochromocytoma with a PASS of 5. Symptoms resolved completely, and blood pressure normalised without antihypertensive therapy. We propose that chronic cannabis use may have partially attenuated the tumour’s catecholamine surges through a cannabinoid receptor type 1 (CB1)-mediated presynaptic mechanism, whereby delta-9-tetrahydrocannabinol (THC) reduces acetylcholine release from cholinergic nerve terminals innervating the adrenal medulla, thereby attenuating chromaffin cell stimulation and catecholamine secretion. This hypothesis could explain the observed bidirectional symptom pattern and represents a biologically plausible, previously undescribed confounding interaction with important diagnostic implications. At 2-week postoperative follow-up, the patient was asymptomatic and normotensive. At 3 months, he remained symptom-free without antihypertensive medication.

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