Journal of Human Hypertension (1999) 13, 75–78 1999 Stockton Press. All rights reserved 0950-9240/99 $12.00 http://www.stockton-press.co.uk/jhh CASE REPORT High and non-suppressible plasma renin activity in a patient with aldosterone producing adenoma: pathophysiologic and diagnostic implications E Shyong Tai and PHK Eng Department of Endocrinology, Singapore General Hospital, Singapore We describe a case of primary aldosteronism due to an possible pathophysiological causes of a rise in PRA in aldosterone producing adenoma with high and non-sup- this clinical setting and suggest that underlying arteri- pressible plasma renin activity (PRA). She had sup- olar disease due to prolonged hypertension may be the pressed PRA at initial diagnosis. This rose above the cause of increased and non-suppressible PRA in pri- reference range for normal individuals over a period of mary aldosteronism. 7 years with untreated hypertension. We discuss the Keywords: primary aldosteronism; plasma renin activity; diagnosis Introduction Case report Primary aldosteronism is classically associated with Our patient was a 34-year-old woman who was hypertension, hypokalaemia and suppressed plasma found to have hypertension during the fifteenth renin activity (PRA). Most cases are due to an aldo- week of pregnancy. Plasma aldosterone was sterone producing adenoma (APA). We present a 2039 pmol/l, PRA Ͻ0.15 ␮g/l/h and a diagnosis of case of prolonged, untreated, primary aldosteronism primary aldosteronism was made. Following the due to an APA. She had suppressed PRA at the time delivery of her child, she defaulted follow-up and of diagnosis, which became elevated and non-sup- was not treated with any antihypertensives nor pot- pressible by intravenous salt loading. While raised assium supplements. PRA has been reported previously in primary aldo- In 1997, 7 years after the original diagnosis, she steronism,1 spontaneous rise in PRA from sup- suffered a thalamic haemorrhage resulting in hemi- pressed levels in any one patient with primary aldo- plegia. On admission, there was marked hyperten- steronism is unusual. We discuss the various sion (219/141 mm Hg) and hypokalaemia (serum pathophysiological processes that may have resulted K+ 1.4 mmol/l). in this change. Her ECG showed marked left ventricular hypertro- phy but the cardiac shadow was not enlarged on a Biochemical methods plain chest radiograph. No hypertensive retinopathy was noted. Serum aldosterone and PRA were Serum aldosterone (normal range 16.6–617.7 2334.4 pmol/l and 3.26 ␮g/l/h respectively. It pmol/l) was measured by radioimmunoassay (Coat- should be noted that she was on fluid restriction and A Count Aldosterone, Diagnostic Products Corpor- sodium was undetectable in her urine at that time. ation, Los Angeles, CA, USA). PRA (normal range Twenty-four hour urinary catecholamines and cor- 0.66–3.08 ␮g/l/h) was assayed using radioimmu- tisol levels were normal. noassay (Incstar Gammacoat 1251 Plasma Renin Control of her blood pressure was achieved with Activity Radioimmunoassay kit, Incstar Corpor- prazosin 5 mg (6 hourly) and nifedipine 15 mg (8 ation, Stillwater, MN, USA). To calculate the hourly). Subsequently, she was put on an intra- aldosterone/renin ratio, the serum aldosterone was venous infusion of 2 L of normal saline and first divided by 27.75 to convert the concentration 80 mmols of potassium daily for 3 days. Biochemi- from pmol/l to ng/dl before dividing by the PRA. cal data were obtained as in Table 1. Postural studies were not possible at the time due to the right hemi- paresis. A captopril renogram was performed which Correspondence: Dr E Shyong Tai, Department of Endocrinology, Singapore General Hospital, 1, Hospital Drive, Singapore 169608 showed no evidence of renal artery stenosis. A CT Received 16 April 1998; revised 22 June 1998; accepted 4 Sep- scan of the abdomen revealed a 2 × 1 cm nodule in tember 1998 the left adrenal and normal sized kidneys. Adrenal High plasma renin in primary aldosteronism E Shyong Tai and PHK Eng 76 Table 1 Biochemistry performed after 3 days of salt loading. All presented during pregnancy with hypertension and tests were done with the patient supine hypokalaemia when we know that patients with pri- mary aldosteronism often become normotensive and 24-h urinary aldosterone 47.9 ␮g/day (6.0–25.0) 24-h urinary sodium 260 mmol/d (50–220) normokalaemic during pregnancy due to the spiro- Serum potassium 4.3 mmol/l (3.3–4.9) nolactone-like effect of progesterone. Perhaps of Plasma renin activity 4.66 ␮g/1/h (0.66–3.08) greater interest is the finding that the PRA, having (supine at 8 am) been suppressed early in the course of the disease Serum aldosterone 1023.4 pmol/l (16.6–617.7) has spontaneously risen to levels above the refer- ence range, even following salt loading. Non-sup- pressed PRA is not in itself an unusual finding in 1 vein sampling was performed 2 months after her primary aldosteronism. Bravo et al found that intracranial bleed. The results are in Table 2. 12.5% of patients with primary aldosteronism had She was subjected to laparoscopic adrenalectomy normal PRA and 15% had PRA above the 95% con- and a left adrenal cortical adenoma (confirmed on fidence intervals for normal individuals of the popu- histology) was excised. Preoperatively, she required lation. However, the lack of suppression of PRA in prazosin 4 mg t.i.d., nifedipine 20 mg q.i.d., atenolol these individuals has never been fully explained 100 mg o.m. and spironolactone 100 mg t.i.d. for and a rise in PRA from suppressed levels to above blood pressure control. Despite this treatment, she the normal range have not been described in the continued to have hypokalaemia requiring oral pot- same patient. assium supplementation of 78 mmol per day. During There are several pathophysiological reasons why this period, captopril was briefly added to her treat- the PRA may have risen. Fluid and salt restriction 3 ment regimen for poorly controlled blood pressure could cause high PRA. This is the basis of diagnos- and hypokalaemia. This resulted in an acute deterio- tic tests using the PRA after salt depletion for the ration in renal function (serum creatinine rose from diagnosis of primary aldosteronism. Although PRA 93 ␮mol/l to 202 ␮mol/l) which resolved after with- usually does not exceed 2 ng/ml/h following salt drawal of the drug. Postoperatively, her blood press- depletion in primary aldosteronism,4 it does occur ure is controlled on atenolol 100 mg om and Adalat in 36% of patients. The PRA was even higher in the LA 30 mg o.m. Her serum potassium is now normal salt replete state and this is unusual. We believe the (4.8 mmol/l) without supplementation. Repeat PRA salt load was adequate as the 24-h urinary sodium was 0.52 ␮g/l/hour and serum aldosterone was was 260 mmol/l and took place 4 days after the fluid 308.8 pmol/l. restriction was lifted. We therefore do not feel that salt or fluid depletion was responsible for the hyper- reninaemia seen in this patient. Other causes of Discussion renal hypoperfusion such as cardiac failure, liver There is little doubt that this patient had primary cirrhosis or nephrotic syndrome were not evident. aldosteronism at the time of her initial presentation This patient did not exhibit any oedema or hypo- given the presence of hypertension, hypokalaemia, albuminaemia to suggest nephrotic syndrome. very high levels of serum aldosterone and PRA sup- Drugs can give rise to hyperreninaemia and these pressed below the limits of the assay. Even allowing would include the angiotensin-converting enzyme for the rise in plasma aldosterone during normal inhibitors, the aldosterone antagonist spironolac- pregnancy, the value of 2039 pmol/l exceeds the lev- tone, or angiotensin II receptor antagonists. None of els expected in the first trimester although it could these agents were used in this patient. The calcium be considered normal in the third trimester. Further- channel blockers can raise PRA in normal indi- more, the increase in plasma aldosterone during viduals. This occurs through inhibition of calcium pregnancy is correlated with an increase in the PRA entry into juxtaglomerular apparatus cells resulting rather than suppression as seen in this case.2 Pri- in renin release. Although this patient was on nifed- mary aldosteronism is confirmed again by failure of ipine at this time, we do not feel this is sufficient to suppression of the 24-h urine aldosterone excretion explain all the current findings. below 14 ␮g/day,1 which is perhaps the most sensi- Hyperreninaemic hypertension has been reported 5 tive test for primary aldosteronism. There are sev- in association with acute pyelonephritis, unilateral 6–8 eral unusual features about this case. This patient hydronephrosis and blunt trauma to the kid- ney.9,10 It has also been reported following haemor- rhage into the perinephric space from polycystic Table 2 Results of adrenal venous sampling. The cortisol levels 11 from the right adrenal vein confirm that the right adrenal vein kidney disease. None of these conditions were evi- was not cannulated dent in this patient. This brings us to various vascular causes of hyper- Aldosterone Cortisol reninaemic hypertension. This can be due to (pmol/l) (nmol/l) decreased renal perfusion as in renal artery sternosis12 or dissecting aneurysm of the renal Supra-renal inferior veno-cava 996.9 172 artery.13,14 Involvement of smaller vessels by sys- Right adrenal vein 2227 142 temic sclerosis15,16 and necrotising vasculitis17 can Left adrenal vein 22211 354 Right renal vein 830.1 157 also cause hyperreninaemia but these were not evi- Left renal vein 914.7 139 dent in this case.