Endocrine Abstracts

Case History: A 57-year-old lady was referred with a 6-year history of hypertension and hypokalaemia necessitating hospital admission. Her medical background included breast cancer managed with chemotherapy, radiotherapy and surgery. She required Eplerenone 50 mg OD and Amlodipine 5 mg to control her hypertension, and Sando-K 2 tablets TDS to maintain normokalaemia. The patient was enrolled into the MATCH trial comparing adrenal vein sampling (AVS) with [¹¹C]-metomidate PET-CT(MTO) in predicting outcome from adrenalectomy in Primary Aldosteronism (PA). An extension to the trial investigated whether para-chloro-2-[¹⁸F]fluoroethyletomidate PET-CT(CETO) is interchangeable with MTO. The selectivity of both ligands for aldosterone-synthase is achieved by 72-hour pre-treatment with dexamethasone 0.5 mg QDS. CETO has a longer T1/2 compared with MTO (110 vs 20 minutes) and has reduced non-specific liver uptake, making it a more attractive and widely available radiotracer.

Investigations: The diagnosis of PA was evidenced by her spontaneous hypokalaemia, suppressed renin activity (0.4 nmol/l/hr), and aldosterone 1400 pmol/l (normal <550 pmol/l). Adrenal CT demonstrated a 2.5 cm right adrenal nodule with Hounsfield units typical of a benign adenoma. AVS results were as follows: right adrenal vein aldosterone 396,000 pmol/l and cortisol 10,084 nmol/l; selectivity index 12.96. Left adrenal vein aldosterone 6,670 pmol/l and cortisol 7,638 nmol/l; selectivity index 9.82. Lateralisation index 44.97 on the right, contralateral suppression index zero on the left. MTO vs CETO: tumour SUVmax 72.3 vs 57.8; left adrenal SUVmax 21.5 vs 15.6; lateralisation ratio 3.36 vs 3.71; liver SUVmax 14.4 vs 2.5. Despite the 72-hour dexamethasone suppression and ACTH<5 ng/l, her cortisol was 144 nmol/l.

Results and Treatment: The patient lateralised on both AVS and PETCT and proceeded to right adrenalectomy. 6 months post-operatively her BP was 110/75 mmHg off medication, renin 2.2 mmol/l/hr and aldosterone 209 pmol/l. Sequencing of tumour DNA revealed a KCNJ5 p.Gly151Arg mutation.

Conclusions and points for discussion: The case highlights recent developments in the management of PA:1. Radioligands targeting aldosterone-synthase offer a non-invasive alternative to AVS. 18F-CETO, is demonstrated in this, and 30 other patients, to be comparable to MTO, enabling PETCT to be undertaken in any hospital already performing 18F-FDG.2. A complete biochemical and clinical cure was observed, as per PASO criteria. The clinical presentation and response to treatment was typical of the KCNJ5 mutation.3. The pre-operative clue to this genotype was the failure of dexamethasone to suppress her cortisol. This failure is observed in ~50% of our patients with KCNJ5 mutations, without other biochemical or clinical features of cortisol excess.