This case describes an important metabolic effect of increased thyroid hormone concentrations on calcium and bone as well as subtle T-cell defects known to occur in the setting of DiGeorge syndrome (also known as DiGeorge sequence). DiGeorge sequence is caused by chromosomal deletions at 22q11.2, which can be transmitted with an autosomal dominant pattern of inheritance; new mutations constitute 90% of cases.
Calcium metabolism is regulated by parathyroid hormone and by vitamin D. Physiological concentrations of thyroid hormone do not direct calcium homeostasis, but high concentrations often produce important perturbations.
In 1891, von Recklinghausen described bone abnormalities in hyperthyroidism. In the 1920s, investigators at Massachusetts General Hospital observed increased calcium excretion in hyperthyroidism and that it occurred independently of parathyroid hormone.
Hypercalcemia was observed in thyrotoxic patients in the 1930s and 1940s. Twenty-seven percent of hyperthyroid patients have an increased total calcium concentration, and 47% have increased ionized calcium (1). Parathyroid hormone is suppressed in these patients.
We described a patient who had hypoparathyroidism, conotruncal cardiac abnormalities, and developmental delay suggestive of DiGeorge sequence and who became hypercalcemic with Graves disease (2).
DiGeorge sequence includes congenital conotruncal cardiac defects, palate abnormalities, hypoplastic thymus, T-cell immune defects, hypoparathyroidism, and learning and psychiatric problems. Bicuspid aortic valve, which is described in the report of Meek et al., has been described in only a single patient with this condition.
T-cell deficiency is occasionally severe in DiGeorge sequence. Less severe immune defects are more common and include autoimmune diseases, which occur in 30% of patients (3). Autoimmune thyroid diseases occurring in DiGeorge sequence prominently include Graves disease.
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Authors' Disclosures or Potential Conflicts of Interest: No authors declared any potential conflicts of interest.
Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript.
- Received for publication December 12, 2010.
- Accepted for publication January 10, 2011.
- © 2011 The American Association for Clinical Chemistry