Familial adenomatous polyposis and hypertension

In October, 2008, a 36-year-old man was referred to our unit with new onset of hypertension and adrenal hyperplasia. He had been diagnosed with familial adenomatous polyposis (FAP) in childhood, and had undergone a total colectomy at the age of 17 years. He had been under endoscopic surveillance since, with a recent polyp count of 50–60 (March). The next month, as part of his routine FAP screening programme, he had an abdominal CT scan, which showed bilateral macronodular adrenal hyperplasia. The largest nodule measured 4 cm by 2 cm on the right and 2·7 cm by 2·9 cm on the left (fi gure). On assessment in our unit, the patient was hypertensive at 150/100 mm Hg on lisinopril and amlodipine. Examination showed no clinical features suggestive of Cushing’s syndrome. Serum potassium concentration was normal at 3·8 mmol/L. Other biochemical investi gations excluded Cushing’s syndrome and phaeo chromocytoma. With confounding antihypertensive medications discontinued, plasma aldosterone measured 590 pmol/L, plasma renin activity (PRA) 0·2 pmol/mL·h, giving a ratio of aldosterone to PRA of 2950 (>2000 is highly suggestive of primary hyperaldosteronism). Saline infusion did not suppress aldosterone to below 280 pmol/L, further supporting this diagnosis. Selective adrenal vein sampling showed that the cortisol-corrected aldosterone ratio in the left adrenal vein was 3·05 (dominant) compared with a ratio of 0·74 in the right adrenal vein (non-dominant), with a ratio of 0·80 in the low inferior vena cava (peripheral). The dominant to non-dominant ratio at 4·15 was above the recommended cut-off of 4·0 for diagnosing unilateral aldosterone hypersecretion with 95% sensitivity and 100% specifi city. Furthermore, the non-dominant to peripheral ratio of >1 confi rmed that autonomous secretion of aldosterone was confi ned to the left. There were no radiological features of the right adrenal mass suggesting malignancy, apart from its size. With the fi nding of dominant left-sided aldosterone secretion, we decided that the patient would benefi t from laproscopic left adrenalectomy. When last seen in March, 2010, he was awaiting surgery, delayed pending investigation into duodenal polyps, another manifestation of FAP. FAP is associated with many extra-intestinal manifestations. Adrenal gland enlargement is even more common in patients with FAP than would be expected from the ascertainment bias due to frequent abdominal imaging. In a series of 738 FAP patients, 14 (7·4%) were found to have adrenal enlargement, compared with 0·6–3·4% in the general population. Of these, two were hypertensive and surgical removal of cortisol-secreting tumours was necessary. In a study of 30 FAP patients with adrenal adenomas, 3 needed adrenalectomy: one for a phaeochromocytoma; one for a non-functioning, malignant tumour; and one for an enlarging, non-functioning, benign adenoma. Thus, the majority of adrenal tumours associated with FAP are non-functioning and no treat ment is needed unless they enlarge. Diagnosis of those rare cases that are associated with hormone hypersecretion is important, because they are surgically treatable. Our case report describes aldosterone-secreting adrenal enlargement in a hypertensive patient with FAP. Recently, an association between tumour-suppressor APC (adenomatous polyposis coli) gene mutations and hyperaldosteronism has been proposed. Mice heterozygous for a truncating APC mutation had higher aldosterone concentrations than controls, with corresponding increases in urinary potassium excretion, despite the presence of hypertension and plasma volume expansion. These fi ndings suggest a potential pathophysiological link between the causative APC mutation and hyper aldosteronism in FAP. All FAP patients with incidentally discovered adrenal masses should have regular blood pressure measurements and be screened for possible Cushing’s syndrome, Conn’s syndrome, and phaeo chromo cytoma.