Primary aldosteronism in type 1 diabetes mellitus.

To the Editor: Alterations in the renin-angiotensin-aldosterone system have been documented in patients with diabetes mellitus. Their blood potassium levels are usually high or in normal ranges. The syndrome of hyporeninemic hypoaldosteronism or renal tubular acidosis (RTA) type IV is most frequently seen in diabetes mellitus, usually with concomitant nephropathy. It is characterized by hyperkalemia and low levels of plasma renin activity (PRA) and aldosterone without significant changes in glucocorticoid secretion. We present the case of a diabetic patient with hypokalemia and low renin levels with inappropriately high plasma aldosterone concentration, suggestive of primary aldosteronism.

A 62-year-old white male, known to have type 1 diabetes mellitus for over 30 years, was referred for persistent hypokalemia of 6 months' duration. He was an adopted child. Past medical history included paranoid schizophrenia, cataract surgery on his left eye, and hypertension. He did not smoke cigarettes or drink alcohol. His blood pressure was 150/90 mm Hg. Current medications included insulin neutral protamine Hagedorn 30 U, pioglitazone 30 mg daily, nifedipine 120 mg daily, amiodarone 100 mg daily, thiothixene 30 mg twice a day, benztropine 1 mg twice a day, and potassium chloride 20 mEq daily.

Laboratory investigations revealed the following: serum fasting glucose, 120 mg/dL (normal, 75-110); glycohemoglobin [A.sub.1C], 7.4% (normal, 4.6-6.0); serum C[O.sub.2], 33 mmol/L (normal, 22-27); serum potassium, 3.0 mEq/L (normal, 3.7-4.5); serum aldosterone, 61.8 ng/dL (normal, 4-31) and renin, 0.9 ng/mL/h. (normal, 0.5-3.3). The following were within normal limits: serum calcium, phosphate, magnesium, creatinine, thyroid-stimulating hormone, and thyroxine. Twenty-four hour urine for chlorine, potassium and sodium, were also normal. Unfortunately, the patient refused computed tomography scan of the abdomen.

The patient was treated with spironolactone 50 mg orally twice a day. His blood pressure was 130/80 mm Hg, and his pulse was regular at 80 beats per minute. Repeat laboratory examination showed serum sodium of 143 mEq/L, serum potassium of 4.6 mEq/L, serum chloride of 102 mEq/L, serum C[O.sub.2] of 31 mEq/L, aldosterone of 56.3 ng/dL, and renin of 0.7 ng/mL/h.

The coexistence of two diseases, type 1 diabetes mellitus and primary aldosteronism, suggested that diabetes mellitus may have had a role in inducing primary aldosteronism in our patient. Hyperglycemia per se may contribute to diabetic hypertensive and vascular disease by altering cellular ion content. (1) The role of glucose in the renin-angiotensin system (RAS) has been discussed in the literature. Diabetic ketoacidosis is usually associated with secondary hyperaldosteronism. (2) Plasma levels of renin and aldosterone are increased before treatment, with values falling rapidly toward normal as metabolic control is restored. Nicolis et al (3) demonstrated a normal response of aldosterone to glucose load in type 1 diabetic patients. These patients had serum aldosterone levels increased after 100 g of glucose taken orally.

Nakayama et al (4) investigated the dissociation changes in the circulating RAS and adrenal RAS. They produced a low renin status in streptozotocin-induced diabetic rats. They found that adrenal renin activity and aldosterone concentration were significantly increased in the group of rats six weeks after induction of diabetes compared with those in control rats. In another experimental study, Ustundag et al (5) noted that the plasma renin activity levels were decreased with increased time period, whereas serum aldosterone levels were increased at days 3 and 12.

In the literature, there are some reports about the coexistence of diabetes mellitus and aldosteronism. Yamamoto et al (6) reported that a diabetic patient had primary aldosteronism due to bilateral functioning adrenocortical adenomas.

The presence of primary aldosteronism in our diabetic patient suggests that glucose may have a role in inducing primary aldosteronism. However, a coincidental presence of two diseases, cannot be excluded.

References

1. Barbagallo M, Resnick LM. The role of glucose in diabetic hypertension: effects on intracellular cation metabolism. Am J Med Sci 1994;307(suppl 1):S60-S65.

2. Christlieb AR, Assal JP, Katsilambros N, et al. Plasma renin activity and blood volume in uncontrolled diabetes Ketoacidosis, a state of secondary aldosteronism. Diabetes 1975;24:190-193.

3. Nicolis GL, Kahn T, Sanchez A, et al. Glucose-induced hyperkalemia in diabetic subjects. Arch Intern Med 1981;141:49-53.

4. Nakayama T, Izumi Y, Soma M, et al. Adrenal renin-angiotensin-aldosterone system in streptozotocin-diabetic rats. Horm Metab Res 1998;30:12-15.

5. Ustundag B, Cay M, Naziroglu M, et al. The study of renin-angiotensin-aldosterone in experimental diabetes mellitus. Cell Biochem Funct 1999;17:193-198.

6. Yamamoto H, Sato t, and Kato Y. A rare case of primary aldosteronism due to bilateral functioning adrenocortical adenomas. Nippon Naibunpi Gakkai Zasshi 1993;69:125-134.

Dung Ngoc Pham Nguyen, MD, Lan Thi Hoang Nguyen, MD, and Khanh Vinh Quoc Luong, MD

Vietnamese American Medical Research Foundation, Westminster, CA Metropolitan State Hospital, Norwalk, CA

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