Correspondence

Graves' Disease, Thymus Enlargement, and Hypercalcemia

N Engl J Med 2008; 358:1078-1079March 6, 2008

Article

To the Editor:

A previously healthy 32-year-old man presented with dyspnea on exertion. Chest radiography showed mediastinal enlargement without pulmonary abnormalities. Magnetic resonance imaging (MRI) showed a mass in the anterior mediastinum with homogeneous gadolinium-diethylenetriamine pentaacetic acid enhancement. An increase in the total serum calcium level (2.98 mmol per liter [normal range, 2.10 to 2.65]) and suppression of thyrotropin (<0.01 mU per liter [normal range, 0.40 to 4.00]) were found.

The patient was referred to our thyroid unit. Increased levels of free thyroid hormones (triiodothyronine and thyroxine), anti–thyrotropin-receptor antibody (6.9 U per liter [normal value, <1.5]), and ionized calcium (1.34 mmol per liter [normal range, 1.14 to 1.29]) were found. The level of parathyroid hormone was in the low–normal range (2.1 pmol per liter [normal range, 1.7 to 9.2]), and an increase in parathyroid hormone–related peptide (3.4 pmol per liter [normal value, <1.5]) was found by immunoradiometric measurement. The thyroid gland was enlarged and hypoechoic on ultrasonography. A diffuse increase in ^99mTc-pertechnetate trapping was found on scintigraphy. Graves' disease with thymus enlargement and hypercalcemia associated with parathyroid hormone–related peptide was diagnosed.

Standard treatment with carbimazole (Neomercazole) at a daily dose of 30 mg was started. Six weeks later, the levels of thyroid hormones, total and ionized calcium, anti–thyrotropin-receptor antibody, and parathyroid hormone–related peptide had normalized (Table 1Table 1Biologic Measures before and 6 Weeks after the Initiation of Carbimazole Therapy.). Levels of thyrotropin and parathyroid hormone had increased to 0.30 mU per liter and to 4.6 pmol per liter, respectively. MRI of the mediastinum showed a dramatic decrease in the mediastinal mass.

Because the thyrotropin receptor is expressed in human thymus, overstimulation of the thyrotropin receptor by anti–thyrotropin-receptor antibody may enhance thymus growth in patients with Graves' disease.1 Accordingly, thymic hyperplasia may be expected to decrease with antithyroid treatment. A recent study showed that parathyroid hormone–related peptide is synthesized in the thymus, which suggests that stimulation of the thymus by anti–thyrotropin-receptor antibody could lead to hypercalcemia.2 However, hyperthyroidism itself is also frequently associated with mild hypercalcemia, which usually subsides after successful treatment of hyperthyroidism. Hypercalcemia in patients with thyrotoxicosis may be due to the activation of osteoclastic bone resorption by the excess thyroid hormone, but the pathogenesis of the condition has not been completely clarified.3

We report here on an increase in parathyroid hormone–related peptide associated with hypercalcemia in a patient with Graves' disease and thymus enlargement. Because levels of both anti–thyrotropin-receptor antibody and parathyroid hormone–related peptide decreased during antithyroid treatment, we hypothesize that anti–thyrotropin-receptor antibody induced the release of parathyroid hormone–related peptide in this patient. From a clinical point of view, it is important to recognize that thymus enlargement and parathyroid hormone–independent hypercalcemia may occur simultaneously in Graves' disease and that both may respond to antithyroid treatment.

Luca Giovanella, M.D.
Sergio Suriano, M.D.
Luca Ceriani, M.D.
Oncology Institute of Southern Switzerland, CH-6500 Bellinzona, Switzerland
luca.giovanella@eoc.ch

3 References

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   Budavari AI, Whitaker MD, Helmers RA. Thymic hyperplasia presenting as anterior mediastinal mass in 2 patients with Graves disease. Mayo Clin Proc 2002;77:495-499
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   Gessi M, Monego G, Lauriola L, Maggiano N, Ranelletti FO. Parathyroid hormone-related peptide (hPTHrP) and parathyroid hormone-related peptide receptor type 1 (PTHR1) expression in human thymus. J Histochem Cytochem 2005;53:955-962
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   Igbal AA, Burgess EH, Gallina DL, Nanes MS, Cook CB. Hypercalcemia in hyperthyroidism: patterns of serum calcium, parathyroid hormone, and 1,25-dihydroxyvitamin D3 levels during management of thyrotoxicosis. Endocr Pract 2003;9:517-521
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Citing Articles (3)

Citing Articles

1. 1

   V. Desforges-Bullet, G. Petit-Aubert, C. Collet-Gaudillat, R. Cerceau, B. Fraleu-Louer, R. Meckenstock, A. Greder, Y. Cordoliani, J.-P. Beressi. (2011) Hyperplasie thymique et maladie de Basedow : une association non fortuite. Cas clinique et revue de la littérature. Annales d'Endocrinologie 72:4, 304-309
   CrossRef

2. 2

   Luca Giovanella, Sergio Suriano, Franco Keller, Giorgio Borretta, Luca Ceriani. (2011) Evaluation of serum parathyroid hormone-related peptide in hyperthyroid patients. European Journal of Clinical Investigation 41:1, 93-97
   CrossRef

3. 3

   Ator Yacoub, David Y. Gaitonde, Joseph C. Wood. (2009) Thymic Hyperplasia and Graves Disease: Management of Anterior Mediastinal Masses in Patients with Graves Disease. Endocrine Practice 15:6, 534-539
   CrossRef