The Effect of Vitamin D Treatment on Clinical and Biochemical Outcomes of Primary Aldosteronism

Noor Ashikin Ismail; Nor Azmi Kamaruddin; Shamsul Azhar Shah; Norlela Sukor


Clin Endocrinol. 2020;92(6):509-517. 

In This Article

Materials and Methods

Study Design

This was a single-centre, prospective interventional study performed at the Hospital Canselor Tuanku Muhriz, National University of Malaysia Medical Centre (NUMMC), Kuala Lumpur. The study was approved by the Research Ethics Committee, National University of Malaysia and all participants gave written informed consent.


We enrolled patients with confirmed diagnosis of PA (based on the 2016 Endocrine Society Clinical Practice Guideline on the Management of Primary Aldosteronism) at our institution. Patients attending the Endocrine Hypertension clinic were screened for PA using an aldosterone-renin ratio (ARR) ≥30 (ng/dL)/(ng/mL/h), and diagnosis of PA was confirmed by the lack of aldosterone suppression either following saline suppression test (plasma aldosterone concentration more than 10 ng/dL following 2 L of 0.9% saline infusion over 4 hours) or fludrocortisone suppression test (plasma aldosterone concentration more than 6 ng/dL on day 4 of 0.1 mg fludrocortisone 6 hourly). Throughout the work-up of PA, patient's antihypertensive medications were switched to agents with the least effect on the aldosterone and renin such as verapamil, prazosin, hydralazine or moxonidine according to its correct wash-out period. The dosages of all these medications were not altered throughout the study. The use of these noninterfering antihypertensive agents specifically the nondihydropyridine calcium channel blocker does not interfere with parathyroid hormone concentrations or urinary calcium excretions as shown in a previous study.[21] Other noninterfering agents used in this study are not known to affect calcium and bone metabolism as reported by Ghosh and Majumdar.[22]

Patients with hypercalcemia, pre-existing primary hyperparathyroidism, renal failure (eGFR < 30 mL/min/m2), pregnant or lactating women and PA subjects already on definitive therapy (adrenalectomy or receiving mineralocorticoid receptor antagonist) were excluded from the study. None of the patients had taken drugs known to influence bone and calcium metabolism such as calcium supplements, vitamin D, bisphosphonates or glucocorticoids.


All eligible patients (regardless of their vitamin D levels at baseline) received 2400IU Bio-D3 capsule per day (Pharma Nord ApS, Denmark) for 3 months. They were advised to take the capsule following meals to enhance its absorption. Patients were reviewed at baseline and 3 months following treatment with Bio-D3. Two-weekly phone calls were done to enhance treatment adherence.

Outcome Measurement

Clinical Parameters. Selected participants underwent assessment of the office blood pressure (BP) measured with standard mercury sphygmomanometer using an appropriate cuff size with the subjects sitting for 15 minutes, systolic blood pressure (SBP) was taken as the first sound on the cuff (Korotkoff phase I), and diastolic blood pressure (DBP) was taken on the complete disappearance of Korotkoff sounds (phase V) from the average of 3 readings, at 1 minute interval, both at baseline and 3 months following treatment. All subjects underwent assessment of weight (kg), height (cm) and body mass index (BMI) calculated by the formula (kg/m2).

Biochemical Parameters. Biochemical variables such as renal function, corrected serum calcium-to-albumin, serum phosphate, plasma aldosterone, plasma renin activity, intact parathyroid hormone, 25-hydroxyvitamin D and 24-hour urinary calcium were measured at baseline and 3 months following treatment with Bio-D3. eGFR (ml/min/1.73 m2) was calculated by using CKD-EPI formula (see Appendix 1 for study flow chart).

Plasma aldosterone concentration (pg/mL) was determined by means of a radioimmunoassay (RIA Aldosterone IM1664; Beckman Coulter) with an intra- and interassay coefficient variation (CV) of 11.9% and 10.2%, respectively. Plasma renin activity (ng/mL/hr) was measured from EDTA plasma using angiotensin I radioimmunoassay (Angiotensin I RIA IM3518; Beckman Coulter) with intra- and interassay CV of 11.3% and 20.9%, respectively. Intact parathyroid hormone (iPTH) (pmol/L) was measured in plasma by electrochemiluminescence immunoassay on an Elecsys 2010 (Roche Diagnostics) with a normal range of 1.6–6.9 pmol/L with an intra- and interassay CV of 1.6% and 3.9%, respectively. Measurements of plasma 25-hydroxyvitamin D [25(OH)D] (ng/mL) were determined by means of electrochemiluminescence binding assay on Elecsys 2010 (Vitamin D total assay, Roche Diagnostics) The interassay CV was 6.2% at 19.9 ng/mL and 3.7% at 38.3 ng/mL, while the intra-assay CV was 4.8% at 19.9 ng/mL and 2.7% at 38.3 ng/mL.

Statistical Analysis

All statistical analyses were performed using IBM SPSS version 25.0 software. Continuous data were shown as mean with standard deviations. Categorical data were presented as percentages. Paired sample t tests or Wilcoxon signed-rank test was used where applicable to evaluate the difference in between continuous parameters before and after treatment. We calculated Pearson correlation coefficients to test for associations between continuous variables. Values of P < .05 were considered statistically significant.