Thyroid Diseases: De Groot LJ

Abalovich M, Amino N, Barbour LA, Cobin RH, De Groot LJ, Glinoer D, Mandel SJ, Stagnaro-Green A. · Endocrinology Division, Durand Hospital, Buenos Aires, Argentina. · J Clin Endocrinol Metab. · Pubmed #17948378 links to  free full text

Abstract: OBJECTIVE: The objective is to provide clinical guidelines for the management of thyroid problems present during pregnancy and in the postpartum. PARTICIPANTS: The Chair was selected by the Clinical Guidelines Subcommittee (CGS) of The Endocrine Society. The Chair requested participation by the Latin American Thyroid Society, the Asia and Oceania Thyroid Society, the American Thyroid Association, the European Thyroid Association, and the American Association of Clinical Endocrinologists, and each organization appointed a member to the task force. Two members of The Endocrine Society were also asked to participate. The group worked on the guidelines for 2 yr and held two meetings. There was no corporate funding, and no members received remuneration. EVIDENCE: Applicable published and peer-reviewed literature of the last two decades was reviewed, with a concentration on original investigations. The grading of evidence was done using the United States Preventive Services Task Force system and, where possible, the GRADE system. CONSENSUS PROCESS: Consensus was achieved through conference calls, two group meetings, and exchange of many drafts by E-mail. The manuscript was reviewed concurrently by the Society's CGS, Clinical Affairs Committee, members of The Endocrine Society, and members of each of the collaborating societies. Many valuable suggestions were received and incorporated into the final document. Each of the societies endorsed the guidelines. CONCLUSIONS: Management of thyroid diseases during pregnancy requires special considerations because pregnancy induces major changes in thyroid function, and maternal thyroid disease can have adverse effects on the pregnancy and the fetus. Care requires coordination among several healthcare professionals. Avoiding maternal (and fetal) hypothyroidism is of major importance because of potential damage to fetal neural development, an increased incidence of miscarriage, and preterm delivery. Maternal hyperthyroidism and its treatment may be accompanied by coincident problems in fetal thyroid function. Autoimmune thyroid disease is associated with both increased rates of miscarriage, for which the appropriate medical response is uncertain at this time, and postpartum thyroiditis. Fine-needle aspiration cytology should be performed for dominant thyroid nodules discovered in pregnancy. Radioactive isotopes must be avoided during pregnancy and lactation. Universal screening of pregnant women for thyroid disease is not yet supported by adequate studies, but case finding targeted to specific groups of patients who are at increased risk is strongly supported.

De Groot LJ. · Endocrine Division, Brown University, Box G, Room E-308, 70 Ship Street, Providence, RI 02920, USA. · Crit Care Clin. · Pubmed #16399020 No free full text.

Abstract: This article documents the role of hypothalamic hypothyroidism and decreased T4-->T3 conversion as the cause of low T4 and T3 in non-thyroidal illness syndrome (NTIS). This article also presents the arguments for administration of replacement triiodothyronine (T3) and thyroxine (T4) hormone in patients who have NTIS. It is impossible to be certain at this time that it is beneficial to replace hormone, or whether this could be harmful. Only a prospective study will be adequate to prove this point, and probably this would need to involve hundreds of patients. If effective, thyroid hormone replacement will be one of many beneficial treatments given the patient, rather than a single magic bullet, which would reverse all the metabolic changes going wrong in these severely ill patients.

De Groot LJ. · Thyroid Study Unit, University of Chicago, IL 60637, USA. · J Pediatr Endocrinol Metab. · Pubmed #11964038 No free full text.

This publication has no abstract.

De Groot LJ. · Thyroid Study Unit, University of Chicago, Illinois 60637, USA. · J Clin Endocrinol Metab. · Pubmed #9920076 links to  free full text

This publication has no abstract.

De Groot LJ, Shin YH, Pan D, Gopalakrishnan G, Hennessey JV. · Division of Endocrinology, Department of Medicine, Brown University, Providence, USA. · J Endocrinol Invest. · Pubmed #19337016 No free full text.

Abstract: In Graves' disease (GD) immunized T cells reactive to TSH-receptor epitopes contribute to pathogenesis through B cell help, and cytotoxicity. We evaluated T cell responses to synthetic TSH-receptor epitopes in hyperthyroid patients with GD prior to therapy, at 6-8 weeks after radioactive iodine (RAI) administration, or 6-8 months later when euthyroid, and in control subjects. All T cell responses were relatively low as generally found in human autoimmune diseases. Responses in hyperthyroid GD patients were significantly greater than among controls, were augmented 6-8 weeks after RAI treatment, were still present after patients became euthyroid, and did not differ between DR3+ and non-DR3+ patients. Patient's T cells reacted to multiple different epitopes, and reactivity differed depending on the course of the disease and treatment.While certain epitopes most commonly cause T cell reactivity, we did not find evidence for a single or few "dominant" epitopes.

Inaba H, Martin W, De Groot AS, Qin S, De Groot LJ. · Brown University/Medicine/Endocrinology, Box G, Room E-308, 70 Ship Street, Providence, Rhode Island 02903, USA. · J Clin Endocrinol Metab. · Pubmed #16595602 links to  free full text

Abstract: CONTEXT: Graves' disease (GD) is characterized by autoimmunity to the TSH receptor (TSHR). OBJECTIVE: We sought to identify T cell epitopes in TSHR that initiate this immune response and their interaction with human histocompatibility leukocyte antigen (HLA) molecules predisposing to GD. DESIGN: We examined the affinity of 31 overlapping peptides spanning the TSHR extracellular domain for binding in vitro to five purified HLA-DR molecules; DRB1*0101 (DR1), DRB1*1501 (DR2), DRB1*0301 (DR3), DRB1*1101 (DR5), and DRB1*0701 (DR7). We scanned the TSHR extracellular domain using a T cell epitope-mapping algorithm, EpiMatrix. We compared these results with clinical studies of GD patients measuring in vitro T cell responses to the peptides. SETTING: The study was conducted at a university laboratory. PATIENTS: Patients included 200 serial adult clinic patients with GD. INTERVENTION: There were no interventions. MAIN OUTCOME MEASUREMENTS: Binding affinity of epitopes, predicted affinity, and reported T cell stimulation data were measured. RESULTS: Most peptides bound with intermediate or high affinity to one or more HLA-DR molecule. Peptides binding to HLA-DR3 and HLA-DR5, which predispose to GD, exhibited moderate binding affinities overall, whereas most peptides binding to GD-protective HLA-DR7 bound with high affinity. These differences may relate to T cell selection in the thymus. Binding affinity of peptides correlated strongly with EpiMatrix-predicted affinity for HLA-DRB1*0101, DRB1*1501, DR3, and DRB1*0701 but not HLA-DR5. Average IC(50) values correlated significantly with clinical T cell stimulation data. CONCLUSIONS: Three different methods for identifying immunogenic peptides did not provide a uniform picture of important TSHR epitopes. However, peptide 132-150 (GIFNTGLKMFPDLTKVYST) was identified by three methods as an important epitope in GD; the possible importance of peptides 145-163, 158-176, 207-222, 248-263, 272-291, and 343-362 was also identified.