SummaryA 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 pointsChronic 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.
SummaryWe report three Chinese children with central nervous system germ cell tumours (CNS GCTs) presenting as arginine vasopressin (AVP) deficiency with or without pituitary stalk thickening, initially diagnosed as lymphocytic hypophysitis (LyH) and idiopathic AVP deficiency. Case 1 showed conflicting biopsy results, suggesting hypophysitis and then germinoma. Case 2 had one negative transsphenoidal biopsy and later one biopsy finding LyH before suprasellar mass diagnosis. Case 3 had a normal initial MRI brain and was followed up as idiopathic AVP deficiency but found to have extensive tumour the next year. All patients achieved remission with chemotherapy and radiotherapy but sustained lifelong panhypopituitarism. Asia has a higher prevalence of CNS GCTs in children. Pituitary stalk thickening with risk factors including pituitary stalk thickness ≥6.5 mm, AVP deficiency, two or more pituitary hormone deficiencies at presentation, and evolving hypopituitarism mandates a high level of malignant suspicion even if prior histopathology is negative. In ethnic groups where the prevalence of CNS GCT is higher, biopsy should be offered when presented with risk factors. These cases highlight pitfalls of false-negative MRI and biopsy, emphasising epidemiology-informed diagnostic algorithms to prevent diagnostic delays. Learning pointsChildren with isolated AVP deficiency should have 3- to 6-monthly MRI brain surveillance.Central nervous system germ cell tumours (CNS GCTs) can closely mimic lymphocytic hypophysitis due to a pronounced lymphocytic inflammatory reaction, representing a major diagnostic pitfall.Taking into account that CNS GCTs are more common in the Asian paediatric population, malignancies should remain the leading differential diagnosis in thickened pituitary stalk until definitively ruled out.Prior negative biopsies should not preclude repeat sampling with clinical progression.Special risk factors and novel investigations should be taken into consideration in ambiguous findings.
SummaryGraves’ disease is common, with an estimated prevalence of 0.2–2% and multiple associated complications. We present a case of severe mitral regurgitation secondary to poorly controlled Graves’ disease for 11 years, highlighting the need for definitive treatment. A 30-year-old female attended hospital with palpitations, agitation and generalised pain. Her past medical history included Graves’ disease diagnosed in 2014, with poor compliance and engagement with secondary care and medical treatment. Biochemical investigations and clinical examination confirmed thyrotoxicosis (TSH < 0.05 mIU/L, free T3 > 30.72 pmol/L and free T4 34.7 pmol/L). Carbimazole 40 mg once daily and propranolol 40 mg three times daily were restarted. She later developed worsening dyspnoea, attributed to decompensated heart failure. An echocardiogram showed severe mitral regurgitation secondary to anterior mitral valve prolapse. She also displayed psychiatric abnormalities, including anxiety and anger outbursts. Multiple conversations were thus needed with the patient, her family and the multidisciplinary team regarding treatment options, and an inpatient thyroidectomy was agreed upon. She recovered well postoperatively and is awaiting mitral valve repair. Our case highlights two crucial complications occurring secondary to long-standing uncontrolled Graves’ thyrotoxicosis: mitral valve regurgitation with heart failure and neuropsychiatric complications with an impact on capacity for treatment decisions. We emphasise the complex support needed for these vulnerable patients to prevent end-stage complications of Graves’ disease. Learning pointsGraves’ thyrotoxicosis can lead to multiple complications, including cardiovascular and psychiatric conditions.Multiple management options exist for Graves’ thyrotoxicosis: medical management with thionamides, radioactive iodine or thyroidectomy.For complex cases, a multidisciplinary team-based approach is essential.Young patients with Graves’ disease who are lost to follow-up in secondary care need to be highlighted as vulnerable. More community resources are necessary to be dedicated to these patients to avoid critical complications.
SummaryA 54-year-old woman with primary aldosteronism caused by left adrenal adenoma underwent adrenal venous sampling (AVS) for subtype classification and unexpectedly exhibited bilateral aldosterone suppression (BAS) despite adequate selectivity. BAS on AVS is a recognized diagnostic pitfall that can obscure surgically curable unilateral diseases, particularly left-sided cases. In this case, venous anatomy was carefully reassessed considering the inconclusive AVS findings. Although adrenal arteriography is infrequently used in the diagnostic workup of primary aldosteronism, it was incorporated as an adjunct to assess venous anatomy. No additional drainage route was identified on the obtained angiographic images, and the cranial and medial superficial location of the tumor in close proximity to the left inferior phrenic vein raised the suspicion of preferential drainage into this vessel. Although the complete tumor-drainage pathway was not directly visualized, targeted venous sampling based on this anatomical hypothesis enabled accurate lateralization of a unilateral disease. This case underscores interpreting BAS within the context of venous anatomy, particularly on the left side, rather than as definitive evidence of bilateral primary aldosteronism. Learning pointsBilateral aldosterone suppression (BAS) on adrenal venous sampling can occur in unilateral primary aldosteronism and may reflect aberrant venous drainage; therefore, it should not be interpreted as definitive evidence of bilateral disease.Aberrant venous drainage, such as preferential distal drainage into the left inferior phrenic vein, should be considered when BAS occurs despite adequate selectivity.Careful reassessment of venous anatomy and anatomically guided targeted venous sampling can facilitate accurate lateralization and prevent misclassification.
SummaryAn 80-year-old female patient presented with a 10-year history of progressively worsening diarrhea and chronic hyponatremia. An abdominal computed tomography (CT) revealed a 6.8-centimeter right adrenal mass. A Ga-68 DOTATATE positron emission tomography (PET)/CT scan subsequently demonstrated a significant expression of somatostatin receptors on the tumoral shell (maximal SUV of 14.4), associated with a hypometabolic central portion. Endocrine investigation indicated elevated levels of both urinary and plasmatic normetanephrines. Given the watery diarrhea, VIP levels were measured, which were markedly elevated. Surgical resection confirmed a composite pheochromocytoma–ganglioneuroma with VIP immunoreactivity in both tumor components. In the postoperative period, the plasma levels of VIP and normetanephrines returned to normal with resolution of diarrhea, hyponatremia, and hypertension. This case illustrates a rare instance of composite pheochromocytoma–ganglioneuroma with co-secretion of catecholamines and VIP, with evidence of VIP production in both tumor components. The finding of VIP secretion in the pheochromocytoma and the ganglioneuroma suggests that both tumors might originate from the same cell of neural crest origin. Learning pointsPheochromocytomas are frequently associated with excessive catecholamine production and can rarely co-secrete VIP, leading to secretory diarrhea and electrolyte disturbances, such as hypokalemia and hyponatremia, while pheochromocytomas usually lead to constipation.Chronic watery diarrhea refractory to standard treatments should prompt evaluation for rare neuroendocrine tumors, such as VIP-secreting pheochromocytomas or composite adrenal tumors, especially when imaging reveals adrenal masses.Surgical removal of composite pheochromocytoma–ganglioneuroma with VIP co-secretion can lead to complete resolution of diarrhea, normalization of electrolytes, and stabilization of blood pressure, underscoring surgery as definitive therapy.
