To the Editors:
The risk of occurrence of hypercalcaemia induced by vitamin D in certain conditions has recently been summarised by Kallas et al. 1. Despite the high prevalence of vitamin D deficiency among the healthy population and observational associations with cardiovascular disease, autoimmune diseases, some types of cancer, tuberculosis and mortality 2, 3, there are currently no data to justify widespread use of vitamin D supplementation, taking into account the lack of large prospective randomised controlled trials.
We would like to share our experience with calcitriol-mediated hypercalcaemia in an apparently healthy individual. A 26-yr-old obese female with a body mass index of 48.4 kg·m−2 was transferred to the endocrinology outpatient clinic of the Medical University of Graz (Graz, Austria) for evaluation of metabolic syndrome before bariatric surgery. Severe vitamin D deficiency was noted during the routine laboratory tests, and the patient received an oral loading dose of 180,000 IU cholecalciferol followed by 2,000 IU daily.
6 weeks later, the patient was sent to the nephrology outpatient clinic for evaluation of asymptomatic hypercalcaemia and hypercalciuria. Laboratory investigation demonstrated an increased 1,25-dihydroxyvitamin D (1,25-(OH)2-D) and suppressed parathyroid hormone (PTH) level (table 1).
During the ensuing work-up, stage I sarcoidosis was diagnosed by chest radiography, with bilateral hilar lymphadenopathy. High angiotensin-converting enzyme levels (176.7 U·L−1; normal range 20–70 U·L−1) and cytological samples from bronchoscopy with typical histopathological findings confirmed the diagnosis of sarcoidosis. 5 weeks after the initial diagnosis of hypercalcaemia and withdrawal of oral cholecalciferol, calcium levels had normalised (ionised calcium 1.26 M) and the 25-hydroxyvitamin D (25-OH-D) level was in the upper normal range, whereas levels of 1,25-(OH)2-D were still elevated and of PTH remained suppressed (table 1).
Vitamin D deficiency is highly prevalent, especially in obese individuals 4, but also in respiratory disease 5, 6. Although vitamin D has a low-risk profile and a broad therapeutic window, we suggest that the use of vitamin D in healthy individuals outside of clear indications or clinical trials should be questioned for two reasons: first, there are currently no large prospective randomised controlled trials showing that vitamin D supplementation leads to beneficial outcomes; and, secondly, because of the potential risk of calcitriol-mediated hypercalcaemia that may arise from a variety of potentially unrecognised or asymptomatic conditions, as in the present patient. Asymptomatic sarcoidosis, especially in stage I, is not uncommon 7. Vitamin D and calcium metabolism is abnormal in sarcoidosis. A Japanese group reported hypercalcaemia in 7% of newly diagnosed patients 8, whereas, in the ACCESS (A Case Control Etiologic Study of Sarcoidosis) cohort, hypercalcaemia and/or hypercalciuria were found in 4% of recently diagnosed patients 9 even without concomitant vitamin D therapy. Calcitriol-induced hypercalcaemia can occur in sarcoidosis when macrophages are challenged with sudden availability of the substrate 25-OH-D because pulmonary alveolar macrophages possess a 1α-hydroxylase and are able to produce 1,25-(OH)2-D. Furthermore, the feedback mechanism seems to be less effective 6.
Although vitamin D is an important immunomodulator that may have a positive effect in patients with sarcoidosis 10, vitamin D loading doses are not recommended and vitamin D repletion must be undertaken with great care 6.
We think it is important to carefully weigh the risk/benefit ratio and consider the risk of hypercalcaemia in apparently healthy patients on vitamin D therapy. Therefore, calcium levels should be checked regularly when administering vitamin D, since hypercalcaemia is often asymptomatic.
Footnotes
Statement of Interest
None declared.
- ©ERS 2011
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