Primary aldosteronism and secondary hyperparathyroidism of the vitamin D deficiency.

To the Editor: The relationship between vitamin D, parathyroid hormone (PTH) and hypertension has been discussed in the literature. However, to our knowledge, primary aldosteronism associated with vitamin D deficiency has not been reported. We present a patient with simultaneous hyperparathyroidism from vitamin D deficiency and aldosteronism.

Our patient, a 62-year-old Caucasian male, had a history of type 1 diabetes mellitus for over 30 years. He was referred for persistent hypokalemia for 6 months. He was an adopted child. Past medical history included paranoid schizophrenia, and hypertension. He did not smoke cigarettes or drink alcohol. Physical examination revealed a blood pressure of 150/90 mm Hg. Current medications included insulin NPH 30 U subcutaneously, 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. Laboratory data are listed in Table 1. Twenty-four hour urine collection for vanillylamandelic acid (VMA) was 4.5 mg (normal 0-7), metanephrine 129 mg (normal 30-300), normetanephrine 378 mg (normal 50-600), calcium 352 mg (normal 50-300), chlorine 149 mEq (normal 110-250), potassium 113.1 mEq (normal 26-123), and sodium 112 mEq (normal 40-220). The patient had a normal ultrasound of the adrenal gland. Unfortunately, he refused computed tomography of the abdomen.

The patient was treated with spironolactone 50 mg orally twice a day, 1,25OHD 0.25 [micro]g/d orally and a calcium supplement. His blood pressure was 120/80, and his pulse was regular at 80 beats per minute. At the patient's one month follow-up visit, spironolactone and potassium supplementation were discontinued. Laboratory values from the one month and three month follow-up visits are listed in Table 2. Unfortunately, the patient was lost to follow up.

Our patient presented with hypertension, persistent hypokalemia, metabolic alkalosis, low plasma renin activity, high levels of serum aldosterone, and a high aldosterone/renin ratio that suggested primary aldosteronism. In addition, the aldosterone and renin levels were not changed with the addition of an angiotensin-converting enzyme inhibitor and the high aldosterone/renin ratio further confirmed our diagnosis. Our patient presented with a vitamin D deficiency and a secondary hyperparathyroidism associated with a primary aldosteronism.

It has been reported that vitamin D supplementation reduces blood pressure in patients with essential hypertension, (1) and 1,25OHD treatment reduces plasma renin activity, and angiotensin levels in patients with high levels of PTH secretion. (2) Mice lacking the vitamin D receptor (VDR) maintain an elevated renin expression and plasma angiotensin II production, develop hypertension, and exhibit increased water consumption. (3) Powell et al (4) demonstrated that PTH produced a consistent rise in plasma renin activity in saline-loaded dogs when given IV, either as a single bolus or infused steadily over a number of hours. In humans, infusion PTH increased plasma renin activity without a change in serum ionized calcium, which suggested a direct effect of PTH on the juxtaglomerular apparatus. Blood pressure and plasma aldosterone levels have been reported to improve following parathyroidectomy due to primary hyperparathyroidism. (5)

The role of PTH in the production of aldosterone has been discussed in the literature. PTH-binding sites have been autoradiographically localized in the rat adrenal cortex (6) and the presence of PTH/PTH-related peptide receptor mRNA has been located in the adrenal gland. (7) Rosenberg et al (8) illustrated the response of adrenal cells of avian and bovine origin to PTH stimulation. PTH stimulates aldosterone secretion from adrenal glomerulosa cells in a dose-dependent manner, both alone and in combination with angiotensin II. (6)

The presence of primary aldosteronism in secondary hyperparathyroidism of vitamin D deficiency suggests that hyperparathyroidism might have a role in inducing primary aldosteronism. However, the coincidental presence of these 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. Kimura Y, Kawamura M, Owada M, et al. Effectiveness of 1,25-dihydroxyvitamin D supplementation on blood pressure reduction in a pseudohypoparathyroidism patient with high renin activity. Intern Med 1999;38:31-35.

2. Garcia-Palmieri MR, Costas R Jr, Cruz-Vidal M, Milk consumption, calcium intake, and decreased hypertension in Puerto Rico. Puerto Rico Heart Health Program study. Hypertension 1984;6:322-328.

3. Li YC, Kong J, Wei M, et al. 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest 2002;110:229-238.

4. Powell HR, McCrcdie DA, Rotenberg E. Renin release by parathyroid hormone in the dog. Endocrinology 1978;103:985-989.

5. Grant FD, Mandel SJ, Brown EM, et al. Interrelationships between the renin-angiotensin-aldosterone and calcium homeostatic systems. J Clin Endocrinol Metab 1992;75:988-992.

6. Isales CM, Barrett PQ, Brines M, et al. Parathyroid hormone modulates angiotensin II-induced aldosterone secretion from the adrenal glomerulosa cell. Endocrinology 1991;129:489-495.

7. Urena P, Kong XF, Abou-Samra AB, et al. Parathyroid hormone (PTH)/PTH-related peptide receptor messenger ribonucleic acids are widely distributed in rat tissues. Endocrinology 1993;133:617-623.

8. Rosenberg J, Pines M, Hurwitz S. Response of adrenal cells to parathyroid hormone stimulation. J Endocrinol 1987;112:431-437.

Table 1. Laboratory data on initial visit

                                  Normal
Laboratory           Value        range

Fasting glucose      120 mg/dL    75-110
Glycohemoglobin      7.4%          4.6-6.0
  [A.sub.1C]
C[O.sub.2]           33 mmol/L    22-27
Magnesium            1.8 mg/dL     1.8-2.5
Creatinine           0.8 mg/dl     0.5-1.3
Albumin              3.2 g/dL      3.5-5
Aspartate            20 U/L       17-59
  transaminase
1,25OHD              39 pg/mL     15-75
TSH                  1.9 mIU/L     0.5-4.5
Thyroxine (T4)       8.36 mcg/dL   4.5-12
Ratio plasma         68/67
  aldosterone/renin
Dopamine             217 pmol/L   60-400
Epinephrine          19 pg/mL     10-200
Norepinephrine       576 pg/mL    80-520

C[O.sub.2], carbon dioxide; 1,25OHD, 25-hydroxyvitamin [D.sub.3]; TSH,
thyroid stimulating hormone.

Table 2. Laboratory data before and after 1,25-dihydroxyvitamin
[D.sub.3] (1,25OHD) treatment

                                                             Alk
                          Calcium   [Ca.sup.++]  P[O.sub.4]  P[O.sub.4]
Normal value              8.4-10.2  4.5-5.3      2.5-4.6     38-126
Unit                      mg/dL     mg/dL        mg/dL       U/L

Initial                   8.7       4.3          3.5         191
1 month after treatment   9.2       4.3          3.9         133
3 months after treatment  9.4       4.7          --          113

                          K        PTH    25OHD  Renin     Aldosterone
Normal value              3.7-4.5  10-65  20-57  0.5-3.3   4-31
Unit                      mEq/L    pg/mL  ng/mL  ng/mL/hr  ng/mL

Initial                   3.0      114    <5     0.9       61.8
1 month after treatment   4.6       53    --     0.7       56.3
3 months after treatment  3.8 (a)   50    15     0.9       40.2

(a) Two months after discontinuation of spironolactone and potassium
supplement.
[Ca.sup.++], calcium ionized; P[O.sub.4], phosphate; Alk P[O.sub.4],
alkaline phosphatase; K, potassium; PTH, parathyroid hormone; 25OHD,
25-hydroxyvitamin [D.sub.3].