Vitamin D Deficiency in Primary Hyperparathyroidism

Prevalence of Vitamin D Deficiency in Primary Hyperparathyroidism

The majority of prevalence studies of vitamin D deficiency in patients with PHPT are limited by lack of adequate control subjects, and by failure to report serum 25-OHD levels as a function of the season of the year (a factor that can significantly alter serum concentrations of 25-OHD).^[5,6] Despite these limitations, available data worldwide suggest that the prevalence of vitamin D deficiency among patients with PHPT is higher than in the general population. In one of the few controlled studies, Moosgaard et al^[5] from Denmark reported that 81% of 289 patients with PHPT had vitamin D deficiency (defined as 25-OHD serum levels <25 ng/mL) compared with 60% of age-, sex-, and season-matched subjects referred for osteoporosis evaluation, and 35% of healthy blood donors. In France, Boudou et al^[7] found that 93% of 72 patients with PHPT had serum 25-OHD values <20 ng/dL, compared with the 38% prevalence previously reported among French postmenopausal women.^[6] In the United States (US), the frequencies of patients with PHPT having serum 25-OHD levels <20 ng/mL and <25 ng/mL were 53% and 61%, respectively.^[8,9] The previous proportions are higher than the most recent statistics released by the National Health and Nutrition Examination Survey (NHANES, 2001–2004) suggesting that 36% of the US population have serum 25-OHD levels <20 ng/mL.^[10] The causes of low circulating levels of 25-OHD in patients with PHPT are not totally understood. Proposed mechanisms include accelerated conversion of 25-OHD to 1,25-dihydroxy vitamin D (1,25-(OH)₂D) by PTH, and the increased catabolism of 25-OHD by the high levels of 1,25-(OH)₂D that prevail in PHPT.^[11,12] In addition, the increased adiposity described in patients with PHPT might be a contributing factor, due in part to sequestration of vitamin D in fatty tissue.^[13,14]

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)

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

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)

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

10.9 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)

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

Prevalence of Vitamin D Deficiency in Primary Hyperparathyroidism

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Prevalence of Vitamin D Deficiency in Primary Hyperparathyroidism

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