Clinical Significance of Vitamin D Deficiency in Primary Hyperparathyroidism, and Safety of Vitamin D Therapy

Nasser Mikhail, MD, MSc

South Med J. 2011;104(1):29-33.

Effects of Vitamin D Supplementation in Concomitant Primary Hyperparathyroidism and Vitamin D Deficiency

Review of the literature up to July 2010 revealed five studies that evaluated vitamin D therapy in patients with concomitant hypovitaminosis D and PHPT (Table).^[15,24–27] Patients included in these trials had mild, mostly asymptomatic PHPT with serum calcium levels <12 mg/dL. Other important limitations include lack of randomization and, except in one study, absence of control subjects.^[27] The overall results suggested that vitamin D supplementation in the setting of mild PHPT was safe. Meanwhile, the most common adverse effect of vitamin D therapy appeared to be an increase in urinary calcium, which reached statistical significance in two studies.^[15,26] A fairly consistent finding after vitamin D therapy in the five studies was a mild decrease in serum PTH levels with mean reductions ranging from 3% to 25%, implying the coexistence of mild secondary hyperparathyroidism on top of PHPT.^[15]

Two of the five studies evaluated the impact of vitamin D therapy on BMD. The first did not record significant effect on BMD in the lumbar spine and femoral neck in a subgroup of 12 patients after 12 months of vitamin D administration.^[24] In the second study there was a significant increase in BMD at the lumbar spine and femoral neck in five patients who received calcium and vitamin D for five weeks.^[15] The retrospective data of Grubbs et al^[27] suggested that vitamin D replacement prior to parathyroidectomy had no significant effect on cure rates, frequency of recurrent disease, or occurrence of eucalcemic PTH elevation after parathyroidectomy.

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Abstract and Introduction
Prevalence of Vitamin D Deficiency in Primary Hyperparathyroidism
Characteristics of Primary Hyperparathyroidism Complicated by Vitamin D Deficiency
Diagnostic Importance of Normalization of Vitamin D Status
Effects of Vitamin D Supplementation in Concomitant Primary Hyperparathyroidism and Vitamin D Deficiency
Current Needs
Conclusion
References
Sidebar

Table. Overview of studies of vitamin D supplementation in patients with concomitant vitamin D deficiency and primary hyperparathyroidism^a
	Grey et al²⁴	Tucci²⁵	Isidro and Ruano²⁶	Grubbs et al²⁷	Kantorovich et al¹⁵
Design	Prospective audit study	Prospective audit study	Prospective	Retrospective, controlled	Retrospective
Follow-up	12 mo	34 wk	12 mo	6 mo	12 mo
Patient number and gender	n = 25, 23 women	n = 56, 37 women	n = 27, 24 women	n = 112, 87 women	n = 5, gender not reported
Mean age (yr)	68	30	67	58	Not reported
Regimen of vitamin D therapy	Cholecalciferol (vitamin D₃) 50,000 IU/wk for 1 mo, then 50,000 IU/mo for 12 mo	Ergocalciferol (vitamin D₂) 50,000 U/wk for 8 wk, followed by 800 U/day up to 100,000 U/mo to keep serum vitamin D ≥75 mmol/L (30 ng/mL)	Calcifediol (25OH vitamin D) 480–960 IU/d	Ergocalciferol (vitamin D2) 50,000 units two to three times/wk for four to 8 wk to keep serum vitamin D ≥75 mmol/L (30 ng/mL)	Vitamin D2 50,000 U + 1000 mg elemental calcium twice/wk for 5 wk
Mean serum levels of 25-OHD at baseline	11 ng/mL	14 ng/mL	11 ng/mL	18 ng/mL	8 ng/mL
Mean serum levels of 25-OHD after vitamin D therapy	31 ng/mL after one year	37 ng/mL after 34 wk	28 ng/mL after 12 mo	46 ng/mL after four to 8 wk	20 ng/ml after 5 wk
Mean serum levels of calcium at baseline	10.8 mg/dL	11 mg/dL	10.8 mg/dL	10.9 mg/dL	10.1 mg/dL
Mean serum levels of calcium after vitamin D therapy	10.8 mg/dL	10.8 mg/dL	10.9 mg/dL	10.7 mg/dL	10.1 mg/dL
Patients having increase in serum calcium levels	Calcium increased in one patient from 10.5 to 11.3 mg/dL	Calcium increased in two patients from 11.2 to 12.1 mg/dL, and from 11.3 to 12.2 mg/dL at 10 wk	Calcium increased in two patients from 10.8 to 12.4 mg/dL, and from 10.8 to 12 mg/dL. Vitamin D therapy was discontinued in the two patients after 3 mo	Calcium increased in six of 112 patients (5%) to a maximum levels of 11.7 mg/dL	Calcium increased in one patient from 10.5 to 10.9 mg/dL
Baseline mean serum levels of intact PTH	138 pg/mL	144 pg/mL	188 pg/mL	175 pg/mL	107 pg/mL
Serum levels of PTH after vitamin D therapy	102 pg/mL (26% significant reduction, P < 0.004)	133 pg/mL after (7% reduction, not statistically significant)	162 pg/mL (14% reduction, not statistically significant)	164 pg/mL (6% significant reduction, P < 0.01)	104 pg/mL (3% reduction, not Statistically significant)
Change in urine calcium after vitamin D therapy	Two patients had urine calcium >400 mg/24 hr	No significant change	Significant increase in the mean value from 228 to 316 mg/24 hr	Not reported	Significant increase in mean urinary calcium/creatinine ratio from 0.06 to 0.24. Three of the five patients developed hypercalciuria (urinary calcium/creatinine ratio >0.160)

^a25-OHD, 25-hydroxy vitamin D; PTH, parathyroid hormone.

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Clinical Significance of Vitamin D Deficiency in Primary Hyperparathyroidism, and Safety of Vitamin D Therapy

Effects of Vitamin D Supplementation in Concomitant Primary Hyperparathyroidism and Vitamin D Deficiency

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