To the Editors

We read with great interest the paper by Zwermann et al. about hypercalcitoninemia and abnormal pentagastrin response in a patient with pseudohypoparathyroidism (PHP) ([Zwermann et al., 2002]). During the reviewing and publishing process of this paper, we published a 10 patient-study about this topic ([Vlaeminck-Guillem et al., 2001]). We found that the 6 patients with PHP Ia had elevated basal calcitonin levels and abnormal response to pentagastrin, whereas the 3 patients with pseudopseudohypoparathyroidism (PPHP) and the one patient with PHP Ib had normal calcitonin levels and response to pentagastrin. Medullary thyroid carcinoma was excluded by normal clinical, biological and ultrasonographical follow up over a mean follow-up exceeding 3 years, and by normal genomic screening for RET protooncogene mutations. Since this publication, we studied 4 other patients with PHP Ia (3 sisters and one sporadic case). All had elevated calcitonin levels and abnormal response to pentagastrin. The ten consecutive patients referred to our institution for PHP Ia were therefore diagnosed as having hypercalcitoninemia and abnormal response to pentagastrin. We postulate that hypercalcitoninemia should be considered as a very frequent feature in PHP Ia and support the stating of Zwermann et al. that an abnormal pentagastrin response in this setting does not imply medullary thyroid carcinoma.

A marked point of interest in the report by Zwermann et al. is that their patient presented with a PHP Ib phenotype. All other reports of hypercalcitoninemia and PHP concerned type Ia ([Fujii et al., 1984]; [Kageyama et al., 1988]; [Vlaeminck-Guillem et al., 2001]; [Wagar et al., 1980]), and we failed to demonstrate any anomaly in calcitonin levels in one PHP Ib patient ([Vlaeminck-Guillem et al., 2001]). The mechanism by which PHP Ib is associated with hypercalcitoninemia is particularly difficult to understand. We do not agree with the authors when they hypothesized that “the most likely reason for abnormal pentagastrin reponse and high basal calcitonin levels in [their] patient is long-lasting chronic hypocalcaemia”. We feel that hypocalcaemia can hardly be considered as the unique cause of hypercalcitoninemia and excessive response to pentagastrin since 1) these biological anomalies have not been reported in other long-lasting hypocalcaemic conditions (A[dachi et al., 1976]; [Deftos et al., 1973]), and 2) they were not observed in our patients with hypocalcaemia unrelated to PHP ([Vlaeminck-Guillem et al., 2001]); and 3) they were observed in our experience even in PHP Ia patients with normalized calcaemia because of efficient calcium and vitamin D3 uptake. As calcitonin receptors are members of the G protein-coupled receptors, we postulate that resistance to calcitonin is the more probable mechanism and demonstrated that a calcitonin infusion test, which induced a significant increase in plasma cAMP in 5 healthy subjects, 1 patient with PHP Ib and 3 patients with spontaneously acquired hypoparathyroidism, failed to produce significant response in 6 PHP Ia patients (A[dachi et al., 1976]; [Deftos et al., 1973]; [Vlaeminck-Guillem et al., 2001]).

Virginie Vlaeminck-Guillem, Michèle d'Herbomez, Jean-Louis Wemeau

References

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• 2 Deftos L J, Powell D, Parthemore J G, Potts J T. Secretion of calcitonin in hypocalcemic states in man.  J Clin Invest. 1973;  52 3109-3114
• 3 Fujii H, Higashi K, Morita M, Sato T. A case of pseudohypoparathyroidism (PHP) associated with multiple hormonal abnormalities.  Jpn J Med. 1984;  23 237-241
• 4 Kageyama Y, Kawamura J, Ajisawa A, Yamada T, Iikuni K. A case of pseudohypoparathyroidism type 1 associated with gonadotropin resistance and hypercalcitoninaemia.  Jpn J Med. 1988;  27 207-210
• 5 Vlaeminck-Guillem V, d'Herbomez M, Pigny P, Fayard A, Bauters C, Decoulx M, Wemeau J L. Pseudohypoparathyroidism Ia and hypercalcitoninemia.  J Clin Endocrinol Metab. 2001;  86 3091-3096
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• 7 Zwermann O, Piepkorn B, Engelbach M, Beyer J, Kann P. Abnormal pentagastrin response in a patient with pseudohypoparathyroidism.  Exp Clin Endocrinol Diabetes. 2002;  110 86-91