Chronic cannabis use as a confounding factor in the delayed diagnosis of phaeochromocytoma
- 1Instituto Tecnológico y de Estudios Superiores de Monterrey, Campus Guadalajara, Zapopan, Jalisco, Mexico
- 2Universidad de Guadalajara, Centro Universitario de Ciencias Biológicas y Agropecuarias, Laboratory of Genetic Descriptors, Zapopan, Jalisco, Mexico
- 3Universidad de Guadalajara, Centro Universitario de Ciencias de la Salud, Guadalajara, Jalisco, Mexico
Abstract
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.
Learning points: Chronic cannabis use may pharmacologically attenuate the clinical expression of phaeochromocytoma through a biologically plausible CB1 receptor-mediated presynaptic mechanism – whereby THC reduces acetylcholine release from cholinergic nerve terminals innervating the adrenal medulla, attenuating chromaffin cell stimulation and catecholamine secretion – potentially creating a presentation indistinguishable from anxiety disorder or cannabis withdrawal. This hypothesis is supported by the observed temporal pattern but requires further investigation to establish causality.
The pattern of symptom improvement during active cannabis use and exacerbation during abstinence, particularly when combined with refractory hypertension, may prompt biochemical evaluation for catecholamine excess rather than reinforcing a substance-related or psychiatric diagnosis.
Cannabis withdrawal is associated with a significant rise in circulating epinephrine; in patients with a catecholamine-secreting tumour, withdrawal of the proposed CB1-mediated inhibitory tone could precipitate severe hyperadrenergic crises that are clinically indistinguishable from withdrawal without biochemical testing.
Measurement of plasma free or urinary fractionated metanephrines should not be deferred based on an apparently plausible psychiatric or substance-related explanation, particularly in patients with refractory hypertension and paroxysmal sympathomimetic symptoms.
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BibTeX
@article{gonzalez2026chronic,
title = {{Chronic cannabis use as a confounding factor in the delayed diagnosis of phaeochromocytoma}},
author = {Samuel González and Benito Minjarez and Luis Alfonso Piña Cedeño and Yury Rodríguez-Yáñez},
journal = {Endocrinology, Diabetes \& Metabolism Case Reports},
year = {2026},
month = oct,
doi = {10.1530/edm-26-0079},
url = {https://doi.org/10.1530/edm-26-0079},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Chronic cannabis use as a confounding factor in the delayed diagnosis of phaeochromocytoma
AU - Samuel González
AU - Benito Minjarez
AU - Luis Alfonso Piña Cedeño
AU - Yury Rodríguez-Yáñez
PY - 2026
DA - 2026/10/27
JO - Endocrinology, Diabetes & Metabolism Case Reports
DO - 10.1530/edm-26-0079
UR - https://doi.org/10.1530/edm-26-0079
AB - 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. Learning points: Chronic cannabis use may pharmacologically attenuate the clinical expression of phaeochromocytoma through a biologically plausible CB1 receptor-mediated presynaptic mechanism – whereby THC reduces acetylcholine release from cholinergic nerve terminals innervating the adrenal medulla, attenuating chromaffin cell stimulation and catecholamine secretion – potentially creating a presentation indistinguishable from anxiety disorder or cannabis withdrawal. This hypothesis is supported by the observed temporal pattern but requires further investigation to establish causality. The pattern of symptom improvement during active cannabis use and exacerbation during abstinence, particularly when combined with refractory hypertension, may prompt biochemical evaluation for catecholamine excess rather than reinforcing a substance-related or psychiatric diagnosis. Cannabis withdrawal is associated with a significant rise in circulating epinephrine; in patients with a catecholamine-secreting tumour, withdrawal of the proposed CB1-mediated inhibitory tone could precipitate severe hyperadrenergic crises that are clinically indistinguishable from withdrawal without biochemical testing. Measurement of plasma free or urinary fractionated metanephrines should not be deferred based on an apparently plausible psychiatric or substance-related explanation, particularly in patients with refractory hypertension and paroxysmal sympathomimetic symptoms.
SN - 2052-0573
ER -