Endocrine Abstracts

Section 1: Case history: A 42-year-old man was referred with a five-year history of hypertension and multiple hospital admissions for hypokalaemia. His blood pressure was 164/104 mmHg on three drugs.

Section 2: Investigations: A diagnosis of primary aldosteronism (PA) was confirmed on a saline suppression test: aldosterone 554 pmol/l at baseline, 240 pmol/l post saline infusion (normal <170). A CT adrenal revealed a 13 mm left-sided adrenal nodule. The right adrenal appeared normal. Adrenal vein sampling (AVS) indicated left-sided lateralisation (L:R ratio 42.5:1) with contralateral aldosterone secretion suppressed to 20% of peripheral. A [11C]metomidate PET-CT (MTO), undertaken as part of the MATCH study, showed high MTO tracer activity in the left adrenal nodule (SUVmax Ratio 1.86). After spironolactone 50/100 mg for 4 weeks, BP fell by only 15/3 mmHg, to 148/101 mmHg.

Section 3: Results and treatment: Following a left adrenalectomy, hypokalaemia resolved and quality of life improved (baseline Physical Component Summary (PCS) 21.75 and Mental Component Summary (MCS) 28.79; post treatment PCS 49.73, MCS 48.35). Markers of cardiac damage also improved: BNP reduced from 354 ng/l at baseline to 209 ng/l at 6 months, LVEDV on CMR reduced from 283 mls to 263 mls. Other measures were mixed. He remained hypertensive (BP 175/117 at 6 months, off treatment). Aldosterone/renin ratio reduced from 1010 (normal <1000) to 164 at 6 months, indicating biochemical success by PA Surgical Outcomes (‘PASO’) criteria, but levels of individual hormones at 6, 12 and 24 months suggested early recurrence of aldosterone excess (aldosterone 312 pmol/l at 6 months, 747 pmol/l at 12 months,725 pmol/l at 24 months). Immunohistochemistry and RNA sequencing of the adenoma were strongly positive for aldosterone synthase, as predicted by the in vivo 11C-metomidate binding, and revealed a novel somatic mutation, of DPYSL2. This abundantly expressed adrenocortical gene traffics calcium channels to the plasma membrane, and the adenoma transcriptome indeed resembled the pattern seen in CACNA1D-mutant adenomas.

Section 4: Conclusions and points for discussion: Despite convincing lateralisation, adrenalectomy achieved only partial success. The patient illustrates the MATCH trial’s finding that the strongest predictors of complete clinical success are a systolic BP on spironolactone of <135 mmHg and somatic genotype (KCNJ5). By contrast, 0/20 patients with a calcium-channel (CACNA1D) mutation were completely cured. This patient’s unique somatic genotype mimics impact of a CACNA1D mutation, both on cell function and clinical outcome. He also illustrates that reductions in plasma aldosterone and BP can under-estimate surgical impact on cardiovascular health and quality of life.