Vitamin D deficiency in primary aldosteronism*.

To the Editor: Alterations in calcium metabolism have been reported in hypertensive patients and animal models. However, there is no report on the presence of vitamin D deficiency in salt-sensitive hypertension of primary aldosteronism in the literature. We report a patient who presented with primary aldosteronism associated with vitamin D deficiency. We discuss the relationship between vitamin D deficiency and salt-sensitive hypertension of primary aldosteronism.

A 62-year-old Caucasian male, with a history of Type 1 diabetes mellitus for over 30 years, was referred for a 6-month history of persistent hypokalemia. He was an adopted child. Past medical history included paranoid schizophrenia, cataract surgery on the left eye, and hypertension. He did not smoke cigarettes or drink alcohol. Physical examination was remarkable for an old gunshot wound to the chest. His blood pressure was 150/90 mm Hg. Current medications included insulin NPH 30 U SC, pioglitazone 30 mg daily, nifedipine XL 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. The patient's laboratory data is listed in the Table below.

The patient's renin activity (0.4 ng/mL/h) and aldosterone level (59.7 ng/dL) were not changed with enalapril 20 mg/d, but the aldosterone/renin ratio increased to 149.25. Unfortunately, the patient refused computed tomography scan of the abdomen.

The patient was treated with spironolactone 50 mg orally twice a day, calcitriol 0.25 [micro]g and calcium gluconate 1,000 mg daily for 6 months. His blood pressure on return visit was 130/80, 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, calcium of 9.4 mg/dL, intact PTH of 50 pg/mL, 25OHD ng/mL of 15, serum chloride of 102 mEq/L, serum [CO.sub.2] of 31 mEq/L, aldosterone of 56.3 ng/dL, and a renin of 0.7 ng/mL/h.

Our patient presented with hypertension, persistent hypokalemia, metabolic alkalosis, low plasma renin activity, an inappropriately high level of serum aldosterone, and a high aldosterone/renin ratio that suggested primary aldosteronism. In addition, due to the fact that the aldosterone and renin levels did not change with angiotensin converting enzyme inhibitor and high aldosterone/renin ratio, further confirmed our diagnosis. Of interest, the presence of vitamin D deficiency in salt-sensitive hypertension of primary aldosteronism suggests that primary aldosteronism might have a role in inducing vitamin D deficiency. Several studies in animals and humans have revealed various abnormalities in calcium and vitamin D metabolism in hypertension. McCarron et al (1) demonstrated that renal calcium retention was decreased in hypertensive patients. Resnick et al (2) revealed that patients with low-renin essential hypertension had a decreased circulating level of ionized calcium and increased serum levels of PTH. Subjects with high diastolic blood pressure also had significantly higher PTH plasma concentrations than controls with low diastolic blood pressure. (3) Spontaneously hypertensive rats were reported to have a decreased serum level of ionized calcium, increased urinary calcium excretion, and an increased serum level of PTH. (4) Kotchen et al (5) also demonstrated these alterations in calcium metabolism and parathyroid hormone secretion in the "prehypertensive" salt-sensitive rats on NaCl intakes.

Clements et al (6) showed in rats that the rate of inactivation of vitamin D in the liver is increased by calcium deprivation. With deprivation of dietary calcium, the mean half-life of 25OHD decreased from 15.4 days (0.64% calcium) to 9.2 days (0.02% calcium). The accelerated loss of the 25OHD on a 0.02% calcium diet could be quantitatively accounted for by an 86% greater output of labeled vitamin D metabolites in feces of calcium-deficient rats compared with control rats. This reflected a similar increase in the output of polar vitamin D metabolites in the bile of calcium-deficient rats. The plasma 25OHD concentration of Dahl salt-sensitive rats is markedly decreased in response to the high salt intake. (7) African-Americans, who have a higher rate of hypertension and salt-sensitivity than Caucasian-Americans, have demonstrated significantly lower mean plasma 25OHD concentrations than Caucasian-Americans. (8)

The presence of vitamin D deficiency in salt-sensitive hypertension of primary aldosteronism suggests that primary aldosteronism may have a role in inducing vitamin D deficiency. However, a coincidental presence of the two diseases cannot be excluded.

Dung Ngoc Pham Nguyen, MD

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

Lan Thi Hoang Nguyen, MD

Khanh vinh quoc Luong, MD

Vietnamese American Medical Research Foundation Westminster, CA

References

1. McCarron DA, Pingree PA, Rubin RJ, et al. Enhanced parathyroid function in essentialhypertension: a homeostatic response to a urinary calcium leak. Hypertension 1980;2:162-168.

2. Resnick LM, Muller FB, Laragh JH. Calciumregulating hormones in essential hypertension: relation to plasma renin activity and sodium metabolism. Ann Intern Med 1986;105:649-654.

3. Reichel H, Liebethal R, Hense HW, et al. Disturbed calcium metabolism in subjects with elevated diastolic blood pressure. Clin Investig 1992;70:748-751.

4. McCarron DA, Yung NN, Ugoretz BA, et al. Disturbances of calcium metabolism in the spontaneously hypertensive rat. Hypertension 1981;3:1162-1167.

5. Kotchen TA, Ott CE, Whitescarver SA, et al. Calcium, parathyroid hormone, and vitamin D in the 'prehypertensive' Dahl salt-sensitive rat. Am J Hypertens 1990;3: 167S-170S.

6. Clements MR, Johnson L, Fraser DR. A new mechanism for induced vitamin D deficiency in calcium deprivation. Nature 1987;325:62-65.

7. Thierry-Palmer M, Doherty A, Bayorh MA, et al. Dahl salt-sensitive rats excrete 25-hydroxyvitamin D into urine. J Nutr 2003;133:187-190.

8. Bell NH, Greene A, Epstein S, et al. Evidence for alteration of the vitamin D-endocrine system in blacks. J Clin Invest 1985;76:470-473.

*Part of this paper was presented at the Annual Meeting of the Endocrine Society on June 16-19, 2004, at the Morial Convention Center, New Orleans, LA.

Table. Laboratory data

Laboratory             Value                  Normal parameters

Serum fasting glucose  120 mg/dL                75-110 mg/dL
Glycohemoglobin          7.4%                    4.6-6.0%
  [A.sub.1]c
Serum [CO.sub.2]        33 mmol/L               22-27 mmol/L
Serum potassium          3.0 mEq/L               3.7-4.5 mEq/L
Serum calcium            8.7 mg/dL (9.34 mg/     8.4-10.2 mg/dL
                           dL (a))
Serum phosphate          3.5 mg/dL               2.5-4.6 mg/dL
Serum magnesium          1.8 mg/dL               1.8-2.5 mg/dL
Serum creatinine         0.8 mg/dL               0.5-1.3 mg/dL
Albumin                  3.2 g/dL                3.5-5 g/dL
Intact PTH             114 pg/mL                10-65 pg/mL
1,25-dihydroxyvitamin   39 pg/mL                15-75 pg/mL
  [D.sub.3]
24-hydroxyvitamin      Less than 5 ng/mL        20-57 ng/mL
  [D.sub.3]
Serum ionized calcium    4.3 mg/dL               4.5-5.3 mg/dL
Serum aldosterone       61.8 ng/dL               4-31 ng/dL
Renin activity           0.9 ng/mL/hour          0.5-3.3 ng/mL/hour
Aldosterone/renin       68.67                 < 50
  ratio
Calcium                352 mg                  500-300 mg
Chlorine               149 mEq                 110-250 mg
Potassium              113.1 mEq                26-123 mEq
Sodium                 112 mEq                  40-220 mEq

(a) Corrected for albumin