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Hypoparathyroidism preceding Riedel’s thyroiditis
European Journal of Internal Medicine 14 (2003) 202–204 www.elsevier.com / locate / ejim
Brief report
Hypoparathyroidism preceding Riedel’s thyroiditis ` Lefort a , Bruno Fantin a , * Eve-Marie Nazal a , Nadia Belmatoug a , Anne de Roquancourt b , Agnes a
´ ˆ ´ ´ Beaujon, 100 Boulevard du General Leclerc, 92110 Clichy, France Service de Medecine Interne, Hopital b ˆ Saint-Louis, Paris, France Service d’ Anatomie et Cytologie Pathologiques, Hopital Received 7 May 2002; received in revised form 18 November 2002; accepted 31 December 2002
Abstract We report the case of a woman who presented with primary hypoparathyroidism and who subsequently developed extensive Riedel’s thyroiditis. To our knowledge, this is the first reported case of primary hypoparathyroidism preceding Riedel’s thyroiditis. This observation suggests that Riedel’s thyroiditis is part of a diffuse fibrotic process that may involve other organs, such as the parathyroid glands. 2003 Elsevier Science B.V. All rights reserved. Keywords: Hypoparathyroidism; Thyroiditis
1. Introduction Hypoparathyroidism is most frequently related to thyroid and parathyroid surgery; non-surgical causes of hypoparathyroidism are fairly rare [1,2]. Rare cases of hypoparathyroidism secondary to Riedel’s thyroiditis (RT) have been described previously [3–11]. In this setting, hypoparathyroidism results from the extension of the fibrotic process to the parathyroid glands. We report the case of a woman who presented with primary hypoparathyroidism and who subsequently developed extensive Riedel’s thyroiditis.
2. Case report A 56-year-old Algerian woman was admitted to our hospital in May 2000 because of fatigue, paresthesias, and generalized muscle weakness. She had no personal or familial history of thyroid disease. She had not undergone *Corresponding author. Tel.: 133-1-4087-5890; fax: 133-1-40871081. E-mail address: [email protected] (B. Fantin).
radiotherapy or surgery of the neck. She denied taking any medication. No signs of hypo- or hyperparathyroidism were found. Physical examination revealed enlargement of the thyroid gland with palpable nodules in the right lobe. No cervical adenopathy was noted. Neurological findings were unremarkable. Relevant laboratory test results were as follows: ionized calcium 0.58 mmol / l (normal range: 1.15–1.32 mmol / l), phosphorus 1.96 mmol / l (normal range: 0.77–1.44 mmol / l), magnesemia 0.66 mmol / l (normal range: 0.71–1.04 mmol / l), plasma thyroid-stimulating hormone (TSH) 2.23 mU / l (normal range: 0.2–4 mU / l), plasma-free T4 8.8 pmol / l (normal range: 7.5–24 pmol / l), and plasma-free T3 5 pmol / l (normal range: 3.7–7.6 pmol / l). Parathyroid hormone (PTH) was undetectable in plasma. The plasma 1,25-(OH) 2 D 3 level was 27 pmol / l (normal range: 45–110 pmol / l). Moderate inflammation was noted, with an erythrocyte sedimentation rate of 76 mm and a C-reactive protein level of 76 mg / l (normal ,5 mg / l). Thyroid ultrasonography showed multinodular goiter. Isotopic scanning revealed three hot nodules. Cervical CT showed thyroid goiter with several nodules but no infiltration of the thyroid or surrounding organs. Fine-needle aspiration of one of the nodules revealed no malignant
0953-6205 / 03 / $ – see front matter 2003 Elsevier Science B.V. All rights reserved. doi:10.1016 / S0953-6205(03)00039-6
E.-M. Nazal et al. / European Journal of Internal Medicine 14 (2003) 202–204
cells. As hypomagnesemia can induce hypoparathyroidism, the patient received oral magnesium and calcium supplementation. However, despite resolution of the hypomagnesemia, hypocalcemia persisted and plasma PTH remained undetectable. Primary hypoparathyroidism was diagnosed, and the patient received oral calcium and 1,25(OH) 2 D 3 supplementation. In April 2001 the patient complained of dysphagia without dysphonia or dyspnea. On physical examination, the thyroid goiter, which had significantly increased in volume, had a stony consistency. Laryngoscopic examination showed paralysis of the right vocal cord. TSH was elevated to 703 mU / l, with normal free T3 and T4 serum levels. Cervical CT and MRI showed voluminous, heterogeneous nodular goiter that enveloped the trachea and the right carotid artery. Several small cervical adenopathies (,1 cm) were noted. Open-neck surgery revealed a voluminous, heterogeneous thyroid goiter with a stony consistency. Pathological examination of thyroid biopsy specimens showed an intense lymphocytic infiltrate with peripheral collagen fibrosis (Fig. 1). There was no malignant proliferation or granuloma. Riedel’s thyroiditis was diagnosed.
203
Table 1 Causes of acquired hypoparathyroidism in adults Cervical surgery Radiation therapy Metal deposition Hemochromatosis Wilson’s disease Aluminum deposition in renal osteodystrophy Infiltrative processes Metastases Amyloidosis Granulomatosis (sarcoidosis, tuberculosis, syphilis) Functional hypoparathyroidism in hypomagnesemia Idiopathic hypoparathyroidism Adapted from Ref. [2].
3. Discussion Non-surgical causes of acquired hypoparathyroidism in adults are extremely rare (Table 1). In the case we describe, functional hypoparathyroidism was first suspected on the basis of hypomagnesemia, which can inhibit PTH secretion. However, hypoparathyroidism persisted despite the correction of hypocalcemia. The initial diagnosis was idiopathic hypoparathyroidism. Hypo-
Fig. 1. Riedel’s thyroiditis. Collagen fibrosis with fibrous endarteritis (A), atrophic muscular fibers (B), and collagen fibrosis with lymphocytic infiltration (C). HES.G, 3200.
204
E.-M. Nazal et al. / European Journal of Internal Medicine 14 (2003) 202–204
parathyroidism associated with Riedel’s thyroiditis was not diagnosed until 1 year later. Riedel’s thyroiditis is a rare cause of thyroiditis, during which normal thyroid tissue is replaced by dense fibrous tissue. The pathophysiology of this thyroiditis is unclear. The main differential diagnosis is undifferentiated thyroid carcinoma. In most cases, fine-needle puncture-aspiration fails to distinguish between these two entities, and open neck surgery is often required. In Riedel’s thyroiditis, macroscopic examination typically shows a pale thyroid gland with a stony consistency. Surgical removal of the entire thyroid gland is usually impossible, as the fibrotic process frequently involves adjacent structures. Diagnostic criteria for Riedel’s thyroiditis, defined by Schwaegerle et al. [12], include: (a) a fibroinflammatory process involving all or part of the thyroid gland; (b) gross and / or histological evidence of fibrotic extension to adjacent structures; and (c) no granulomatous reaction or neoplastic cells. Endocrinology textbooks do not mention Riedel’s thyroiditis as a possible cause of hypoparathyroidism [2]. Only 10 cases of Riedel’s thyroiditis complicated by hypoparathyroidism have previously been published [3– 11]. Nine patients were women, with a mean age of 45 years (range 36–66 years). In every case, the thyroid gland was markedly and diffusely enlarged, ‘rock-hard’, and moved little during swallowing. Diagnosis was always based on pathological examination of surgical thyroid biopsies. Hypoparathyroidism and Riedel’s thyroiditis occurred simultaneously in three patients. In the other seven cases, the hypoparathyroidism occurred between 4 and 32 months after the diagnosis of Riedel’s thyroiditis. To our knowledge, the case we describe is the first case in which hypoparathyroidism preceded Riedel’s thyroiditis. In patients with Riedel’s thyroiditis, fibrotic processes can occur in various organs other than the thyroid gland, including the mediastinum, the hepatobiliary tract, the retroperitoneum, and the orbits [3,7–9,11], several years after the diagnosis of thyroiditis. Riedel’s thyroiditis was initially considered a benign, self-limited condition, but it is now thought to be part of a generalized fibrotic disorder. In the case we describe, it cannot be ruled out that Riedel’s thyroiditis was already present at the onset of hypo-
parathyroidism. However, initial radiological investigations showed no infiltrative process extending from the thyroid gland. It is conceivable that the hypoparathyroidism resulted from a fibrotic disorder of the parathyroid glands that preceded the onset of Riedel’s thyroiditis. The physiopathology of Riedel’s thyroiditis remains unclear, but the present case suggests that it may result from an inflammatory and fibrotic process that may initiate in organs other than the thyroid gland.
References [1] Crile Jr. C. Thyroiditis. Ann Surg 1948;127:640–54. [2] Strewler GJ, Rosenblatt M. Mineral metabolism. In: Felig P, Baxter JD, Frohman LA, editors, Endocrinology and Metabolism, New York: McGraw-Hill, 1995, pp. 1407–516. [3] Austoni M, Conte N, Zaccaria M, Bottazzo GF. Tiroidite di Riedel associata a ipoparatiroidismo. Folia Endocrinol 1972;25(Suppl 6):495–501. [4] Chopra D, Wool MS, Crosson A, Savin CT. Riedel’s struma associated with subacute thyroiditis, hypothyroidism and hypoparathyroidism. J Clin Endocrinol Metab 1979;46:869–71. [5] De Lange WE, Freleng WJM, Molenaar WM, Dorenbos H. Invasive fibrous thyroiditis (Riedel’s struma): a manifestation of multifocal sclerosis? A case report with a review of the literature. Q J Med 1989;268:709–17. [6] Marin F, Araujo R, Paramo C, Lucas T, Salto L. Riedel’s thyroiditis associated with hypothyroidism and hypoparathyroidism. Postgrad Med J 1989;65:381–3. [7] Malote MJ, Chonkich GD, Zuppan GW. Riedel’s thyroiditis. Arch Otolaryngal Head Neck Surg 1991;117:214–7. [8] Best TB, Munro RE, Burwell S, Volpe R. Riedel’s thyroiditis associated with Hashimoto’s thyroiditis, hypoparathyroidism and retroperitoneal fibrosis. J Endocrinol Invest 1991;14:767–72. [9] Mc Rorie ER, Chalmeras J, Campbell IW. Riedel’s thyroiditis complicated by hypoparathyroidism and hypothyroidism. Scot Med J 1993;38:27–8. [10] Lo JC, Loh KC, Rubin AL, Cha I, Greenspan FS. Riedel’s thyroiditis presenting with hypothyroidism and hypoparathyroidism: dramatic response to glucocorticoid and thyroxine therapy. Clin Endocrinol 1998;48:815–8. [11] Casoli P, Tumiati B. Hypoparathyroidism secondary to Riedel’s thyroiditis. A case report and a review of the literature. Ann Ital Med Int 1999;14:54–7. [12] Schwaegerle SM, Bauer TW, Esselstyn CR. Riedel’s thyroiditis. Am J Clin Pathol 1988;90:715–22.
Brief report
Hypoparathyroidism preceding Riedel’s thyroiditis ` Lefort a , Bruno Fantin a , * Eve-Marie Nazal a , Nadia Belmatoug a , Anne de Roquancourt b , Agnes a
´ ˆ ´ ´ Beaujon, 100 Boulevard du General Leclerc, 92110 Clichy, France Service de Medecine Interne, Hopital b ˆ Saint-Louis, Paris, France Service d’ Anatomie et Cytologie Pathologiques, Hopital Received 7 May 2002; received in revised form 18 November 2002; accepted 31 December 2002
Abstract We report the case of a woman who presented with primary hypoparathyroidism and who subsequently developed extensive Riedel’s thyroiditis. To our knowledge, this is the first reported case of primary hypoparathyroidism preceding Riedel’s thyroiditis. This observation suggests that Riedel’s thyroiditis is part of a diffuse fibrotic process that may involve other organs, such as the parathyroid glands. 2003 Elsevier Science B.V. All rights reserved. Keywords: Hypoparathyroidism; Thyroiditis
1. Introduction Hypoparathyroidism is most frequently related to thyroid and parathyroid surgery; non-surgical causes of hypoparathyroidism are fairly rare [1,2]. Rare cases of hypoparathyroidism secondary to Riedel’s thyroiditis (RT) have been described previously [3–11]. In this setting, hypoparathyroidism results from the extension of the fibrotic process to the parathyroid glands. We report the case of a woman who presented with primary hypoparathyroidism and who subsequently developed extensive Riedel’s thyroiditis.
2. Case report A 56-year-old Algerian woman was admitted to our hospital in May 2000 because of fatigue, paresthesias, and generalized muscle weakness. She had no personal or familial history of thyroid disease. She had not undergone *Corresponding author. Tel.: 133-1-4087-5890; fax: 133-1-40871081. E-mail address: [email protected] (B. Fantin).
radiotherapy or surgery of the neck. She denied taking any medication. No signs of hypo- or hyperparathyroidism were found. Physical examination revealed enlargement of the thyroid gland with palpable nodules in the right lobe. No cervical adenopathy was noted. Neurological findings were unremarkable. Relevant laboratory test results were as follows: ionized calcium 0.58 mmol / l (normal range: 1.15–1.32 mmol / l), phosphorus 1.96 mmol / l (normal range: 0.77–1.44 mmol / l), magnesemia 0.66 mmol / l (normal range: 0.71–1.04 mmol / l), plasma thyroid-stimulating hormone (TSH) 2.23 mU / l (normal range: 0.2–4 mU / l), plasma-free T4 8.8 pmol / l (normal range: 7.5–24 pmol / l), and plasma-free T3 5 pmol / l (normal range: 3.7–7.6 pmol / l). Parathyroid hormone (PTH) was undetectable in plasma. The plasma 1,25-(OH) 2 D 3 level was 27 pmol / l (normal range: 45–110 pmol / l). Moderate inflammation was noted, with an erythrocyte sedimentation rate of 76 mm and a C-reactive protein level of 76 mg / l (normal ,5 mg / l). Thyroid ultrasonography showed multinodular goiter. Isotopic scanning revealed three hot nodules. Cervical CT showed thyroid goiter with several nodules but no infiltration of the thyroid or surrounding organs. Fine-needle aspiration of one of the nodules revealed no malignant
0953-6205 / 03 / $ – see front matter 2003 Elsevier Science B.V. All rights reserved. doi:10.1016 / S0953-6205(03)00039-6
E.-M. Nazal et al. / European Journal of Internal Medicine 14 (2003) 202–204
cells. As hypomagnesemia can induce hypoparathyroidism, the patient received oral magnesium and calcium supplementation. However, despite resolution of the hypomagnesemia, hypocalcemia persisted and plasma PTH remained undetectable. Primary hypoparathyroidism was diagnosed, and the patient received oral calcium and 1,25(OH) 2 D 3 supplementation. In April 2001 the patient complained of dysphagia without dysphonia or dyspnea. On physical examination, the thyroid goiter, which had significantly increased in volume, had a stony consistency. Laryngoscopic examination showed paralysis of the right vocal cord. TSH was elevated to 703 mU / l, with normal free T3 and T4 serum levels. Cervical CT and MRI showed voluminous, heterogeneous nodular goiter that enveloped the trachea and the right carotid artery. Several small cervical adenopathies (,1 cm) were noted. Open-neck surgery revealed a voluminous, heterogeneous thyroid goiter with a stony consistency. Pathological examination of thyroid biopsy specimens showed an intense lymphocytic infiltrate with peripheral collagen fibrosis (Fig. 1). There was no malignant proliferation or granuloma. Riedel’s thyroiditis was diagnosed.
203
Table 1 Causes of acquired hypoparathyroidism in adults Cervical surgery Radiation therapy Metal deposition Hemochromatosis Wilson’s disease Aluminum deposition in renal osteodystrophy Infiltrative processes Metastases Amyloidosis Granulomatosis (sarcoidosis, tuberculosis, syphilis) Functional hypoparathyroidism in hypomagnesemia Idiopathic hypoparathyroidism Adapted from Ref. [2].
3. Discussion Non-surgical causes of acquired hypoparathyroidism in adults are extremely rare (Table 1). In the case we describe, functional hypoparathyroidism was first suspected on the basis of hypomagnesemia, which can inhibit PTH secretion. However, hypoparathyroidism persisted despite the correction of hypocalcemia. The initial diagnosis was idiopathic hypoparathyroidism. Hypo-
Fig. 1. Riedel’s thyroiditis. Collagen fibrosis with fibrous endarteritis (A), atrophic muscular fibers (B), and collagen fibrosis with lymphocytic infiltration (C). HES.G, 3200.
204
E.-M. Nazal et al. / European Journal of Internal Medicine 14 (2003) 202–204
parathyroidism associated with Riedel’s thyroiditis was not diagnosed until 1 year later. Riedel’s thyroiditis is a rare cause of thyroiditis, during which normal thyroid tissue is replaced by dense fibrous tissue. The pathophysiology of this thyroiditis is unclear. The main differential diagnosis is undifferentiated thyroid carcinoma. In most cases, fine-needle puncture-aspiration fails to distinguish between these two entities, and open neck surgery is often required. In Riedel’s thyroiditis, macroscopic examination typically shows a pale thyroid gland with a stony consistency. Surgical removal of the entire thyroid gland is usually impossible, as the fibrotic process frequently involves adjacent structures. Diagnostic criteria for Riedel’s thyroiditis, defined by Schwaegerle et al. [12], include: (a) a fibroinflammatory process involving all or part of the thyroid gland; (b) gross and / or histological evidence of fibrotic extension to adjacent structures; and (c) no granulomatous reaction or neoplastic cells. Endocrinology textbooks do not mention Riedel’s thyroiditis as a possible cause of hypoparathyroidism [2]. Only 10 cases of Riedel’s thyroiditis complicated by hypoparathyroidism have previously been published [3– 11]. Nine patients were women, with a mean age of 45 years (range 36–66 years). In every case, the thyroid gland was markedly and diffusely enlarged, ‘rock-hard’, and moved little during swallowing. Diagnosis was always based on pathological examination of surgical thyroid biopsies. Hypoparathyroidism and Riedel’s thyroiditis occurred simultaneously in three patients. In the other seven cases, the hypoparathyroidism occurred between 4 and 32 months after the diagnosis of Riedel’s thyroiditis. To our knowledge, the case we describe is the first case in which hypoparathyroidism preceded Riedel’s thyroiditis. In patients with Riedel’s thyroiditis, fibrotic processes can occur in various organs other than the thyroid gland, including the mediastinum, the hepatobiliary tract, the retroperitoneum, and the orbits [3,7–9,11], several years after the diagnosis of thyroiditis. Riedel’s thyroiditis was initially considered a benign, self-limited condition, but it is now thought to be part of a generalized fibrotic disorder. In the case we describe, it cannot be ruled out that Riedel’s thyroiditis was already present at the onset of hypo-
parathyroidism. However, initial radiological investigations showed no infiltrative process extending from the thyroid gland. It is conceivable that the hypoparathyroidism resulted from a fibrotic disorder of the parathyroid glands that preceded the onset of Riedel’s thyroiditis. The physiopathology of Riedel’s thyroiditis remains unclear, but the present case suggests that it may result from an inflammatory and fibrotic process that may initiate in organs other than the thyroid gland.
References [1] Crile Jr. C. Thyroiditis. Ann Surg 1948;127:640–54. [2] Strewler GJ, Rosenblatt M. Mineral metabolism. In: Felig P, Baxter JD, Frohman LA, editors, Endocrinology and Metabolism, New York: McGraw-Hill, 1995, pp. 1407–516. [3] Austoni M, Conte N, Zaccaria M, Bottazzo GF. Tiroidite di Riedel associata a ipoparatiroidismo. Folia Endocrinol 1972;25(Suppl 6):495–501. [4] Chopra D, Wool MS, Crosson A, Savin CT. Riedel’s struma associated with subacute thyroiditis, hypothyroidism and hypoparathyroidism. J Clin Endocrinol Metab 1979;46:869–71. [5] De Lange WE, Freleng WJM, Molenaar WM, Dorenbos H. Invasive fibrous thyroiditis (Riedel’s struma): a manifestation of multifocal sclerosis? A case report with a review of the literature. Q J Med 1989;268:709–17. [6] Marin F, Araujo R, Paramo C, Lucas T, Salto L. Riedel’s thyroiditis associated with hypothyroidism and hypoparathyroidism. Postgrad Med J 1989;65:381–3. [7] Malote MJ, Chonkich GD, Zuppan GW. Riedel’s thyroiditis. Arch Otolaryngal Head Neck Surg 1991;117:214–7. [8] Best TB, Munro RE, Burwell S, Volpe R. Riedel’s thyroiditis associated with Hashimoto’s thyroiditis, hypoparathyroidism and retroperitoneal fibrosis. J Endocrinol Invest 1991;14:767–72. [9] Mc Rorie ER, Chalmeras J, Campbell IW. Riedel’s thyroiditis complicated by hypoparathyroidism and hypothyroidism. Scot Med J 1993;38:27–8. [10] Lo JC, Loh KC, Rubin AL, Cha I, Greenspan FS. Riedel’s thyroiditis presenting with hypothyroidism and hypoparathyroidism: dramatic response to glucocorticoid and thyroxine therapy. Clin Endocrinol 1998;48:815–8. [11] Casoli P, Tumiati B. Hypoparathyroidism secondary to Riedel’s thyroiditis. A case report and a review of the literature. Ann Ital Med Int 1999;14:54–7. [12] Schwaegerle SM, Bauer TW, Esselstyn CR. Riedel’s thyroiditis. Am J Clin Pathol 1988;90:715–22.