The role of leuprolide acetate therapy in triggering auto-immune thyroiditis

Abstract

To the Editor: We read with interest the report by Eyal and Rose regarding the occurrence of autoimmune hypothyroidism in a 9-year-old girl with precocious puberty who was treated with the gonadaropin-releasing hormone (GnRH) agonist, leuprolide acetate, for approximately 8 months.1Eyal O. Rose S.R. Autoimmune thyroiditis during leuprolide acetate treatment.J Pediatr. 2004; 144: 394-396Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar From this single case report, the authors suggested an association of leuprolide acetate with autoimmune thyroiditis and recommended thyroid stimulating hormone (TSH) screening before and 6 to 8 months into treatment. We believe the authors' conclusions are overstated. The authors suggest that autoimmune disease is “related to potential immunostimmulatory properties of GnRH agonists independent of gonadal steroids,” as stated in the paper. The reference cited in support of the authors' suggestion states “there is little evidence for direct immune actions of gonadatropins” and “it appears that the studies demonstrating immunostimulatory properties of GnRH were done exclusively in female rats.”2Jacobson J.D. Gonadotropin-releasing hormone: potential role in autoimmunity.Int Immunopharmacol. 2001; 1: 1077-1083Crossref PubMed Scopus (14) Google Scholar No other accompanying organ specific or non-organ specific autoimmune disorders were reported. In the case presented, there was no documentation of autoantibody status before the start of leuoprolide therapy. In addition, the patient had a sibling with primary hypothyroidism and a family member with type I diabetes (T1DM). Clustering of autoimmune thyroid disease in families is well described.3Marwaha R.K. Sen S. Tandon N. Sahoo M. Walia R.P. Singh S. et al.Familial aggregation of autoimmune thyroiditis in first-degree relatives of patients with juvenile autoimmune thyroid disease.Thyroid. 2003; 13: 297-300Crossref PubMed Scopus (19) Google Scholar, 4Brix T.H. Hansen P.S. Kyvik K.O. Hegedus L. Aggregation of thyroid autoantibodies in first-degree relatives of patients with autoimmune thyroid disease is mainly due to genes: a twin study.Clin Endocrinol (Oxf). 2004; 60: 329-334Crossref PubMed Scopus (38) Google Scholar, 5Levin L. Tomer Y. The etiology of autoimmune diabetes and thyroiditis: evidence for common genetic susceptibility.Autoimmun Rev. 2003; 2: 377-386Crossref PubMed Scopus (62) Google Scholar Furthermore, relatives of patients with T1DM have a much higher incidence of thyroid autoimmunity (up to 25%).6Hanukoglu A. Mizrachi A. Dalal I. Admoni O. Rakover Y. Bistritzer Z. et al.Extrapancreatic autoimmune manifestations in type 1 diabetes patients and their first-degree relatives: a multicenter study.Diabetes Care. 2003; 26: 1235-1240Crossref PubMed Scopus (85) Google Scholar When added to the significant female to male predominance of thyroid disease, it is likely that these factors played a much more significant role in the patient's development of thyroid disease than leuprolide acetate therapy. Based on this single case report, we therefore disagree with the suggestion that leuprolide acetate treatment requires thyroid screening. The use of primary autoantibody screening vs primary thyroid function screening also must be addressed. Screening always involves additional cost and, often, additional stress. Well-designed studies should be conducted before such recommendations are made. Outside a research setting, patients should be screened for autoimmune thyroid disease only on the basis of well-established risk factors and clinical presentation. Autoimmune thyroiditis during leuprolide acetate treatmentThe Journal of PediatricsVol. 144Issue 3PreviewAutoimmune thyroiditis developed in a 9-year-old girl with precocious puberty approximately 8 months after initiation of Leuprolide acetate therapy. In addition, gonadotropin concentrations as measured by radioimmunoassay appeared high. Treatment with levothyroxine, in addition to continued Leuprolide acetate treatment, resolved gonadotropin elevation and hypothyroidism. Full-Text PDF ReplyThe Journal of PediatricsVol. 146Issue 2PreviewTo the Editor: Full-Text PDF