Deborah Doniach: Discovering Thyroid Autoimmunity: The End of Horror Autotoxicus.

Deborah Doniach MD, FRCP was born in Geneva, Switzerland in 1912. She attended high school at the Lycée Molière and medical school at the Sorbonne in Paris. Deborah married Israel (Sonny) Doniach in 1933.

A Prospective, Randomized, Double-blind, Placebo-controlled Study of Orbital Radiotherapy for Graves' Ophthalmopathy.

Context: Although widely used for more than 85 years, the efficacy of radiotherapy for Graves' ophthalmopathy (GO) has not been established convincingly.

Objective: To evaluate the efficacy of radiotherapy for GO.

Design: Prospective, randomized, internally controlled, double-blind clinical trial in a tertiary care academic medical center.

Clinical Experience with Rituximab and Intravenous Immunoglobulin for Pretibial Myxedema: A Case Series.

Severe pretibial myxedema (PTM) can be difficult to manage, highlighting the need to investigate newer therapies. Rituximab (RTX) and intravenous immunoglobulin (IVIg) have been tried in Graves' orbitopathy. Since PTM and orbitopathy share a similar underlying pathophysiology, this study aimed to explore these therapies for progressive PTM.

Comparative Effectiveness of Treatment Choices for Graves' Hyperthyroidism: A Historical Cohort Study.

Background: The optimum therapy for Graves' disease (GD) is chosen following discussion between physician and patient regarding benefits, drawbacks, potential side effects, and logistics of the various treatment options, and it takes into account patient values and preferences. This cohort study aimed to provide useful information for this discussion regarding the usage, efficacy, and adverse-effect profile of radioactive iodine (RAI), antithyroid drugs (ATDs), and thyroidectomy in a tertiary healthcare facility.

Methods: The cohort included consecutive adults diagnosed with GD from January 2002 to December 2008, who had complete follow-up after treatment at the Mayo Clinic, Rochester, Minnesota.

Riedel's thyroiditis association with IgG4-related disease.

Context: IgG4-positive (+) plasma cells have been reported in both Riedel's thyroiditis (RT) and Hashimoto's thyroiditis (HT). These cells are the hallmark of IgG4-related disease (IgG4-RD).

Objective: We sought to determine whether RT is part of IgG4-RD spectrum.

LINGUAL THYROID: 35-YEAR EXPERIENCE AT A TERTIARY CARE REFERRAL CENTER.

Objective: Lingual thyroid (LT) results from a developmental abnormality due to failure of the thyroid gland to descend to its pretracheal position. Given the low incidence of this disease, standardized management recommendations are lacking. We aimed to describe our institution's experience in LT management and to suggest a practice algorithm.

Development and Pilot Testing of an Encounter Tool for Shared Decision Making About the Treatment of Graves' Disease.

Background: The best treatment option for patients with Graves' disease (GD) depends on each person's situation and how the differences between the treatment options matter to them in bringing resolution to their illness. The objective of this study was to develop and test an encounter decision tool (GD Choice) for patients and clinicians to engage in shared decision making about the treatment of GD.

Methods: GD Choice was developed using an iterative process based on the principles of interaction design and participatory action research.

Forkhead Transcription Factor FOXO1 Is Regulated by Both a Stimulatory Thyrotropin Receptor Antibody and Insulin-Like Growth Factor-1 in Orbital Fibroblasts from Patients with Graves' Ophthalmopathy.

Background: Activation of thyrotropin receptor (TSHR) and/or insulin-like growth factor (IGF-1) receptor (IGF-1R) enhances HA production and adipogenesis in orbital fibroblasts from patients with Graves' ophthalmopathy (GO) and recapitulates the tissue remodeling characteristic of the orbit in GO. A functional relationship between TSHR and IGF-1R has long been postulated, and recently bidirectional crosstalk between the receptors in GO fibroblasts was demonstrated. Because the transcription factor Forkhead box O-1 (FOXO1) was recently shown to be a critical downstream mediator of TSH and IGF-1 effects on thyrocyte proliferation, studies were designed to determine whether FOXO1 might similarly act as a common mediator of M22, a stimulatory TSHR antibody (TSAb), and IGF-1 in GO orbital fibroblasts.

Randomized controlled trial of rituximab in patients with Graves' orbitopathy.

Context: Graves' orbitopathy (GO) is a potentially sight-threatening disease for which available medical therapy is not uniformly successful. Multiple case series suggest that rituximab (RTX) may be effective therapy for GO patients.

Objective: To determine the efficacy of RTX in GO.

Mentoring interdisciplinary research teams for the study of sex and gender differences in health and disease.

Initiatives to hasten the translation of basic science discoveries to clinical care have necessitated the development of new approaches to interdisciplinary collaboration and training of future investigators. This has been nowhere more important than in the study of sex differences with implications for extension into areas of gender medicine. Clearly, gaining better understanding of the role that sex and gender play in health and disease is essential to the implementation of truly individualized medicine.

Amiodarone-induced thyrotoxicosis in adults with congenital heart disease--clinical presentation and response to therapy.

Objective: The development of amiodarone-induced thyrotoxicosis (AIT) can threaten the hemodynamic stability of adult patients with congenital heart disease (CHD). Here, we describe the natural history and treatment response of AIT in this at-risk population.

Methods: We studied retrospectively all cases of AIT that occurred in CHD patients at our institution after a minimum of 3 months on amiodarone.

Comparative effectiveness of therapies for Graves' hyperthyroidism: a systematic review and network meta-analysis.

Context: Several treatment options are available for Graves' disease (GD), including antithyroid drugs (ATDs), radioactive iodine (RAI), and thyroidectomy.

Objective: The primary outcome was to determine the relapse rates of various treatment options. The secondary outcome was to present data regarding adverse effects of ATDs.

A small molecule antagonist inhibits thyrotropin receptor antibody-induced orbital fibroblast functions involved in the pathogenesis of Graves ophthalmopathy.

Context: Graves ophthalmopathy (GO) is an autoimmune disorder characterized by increased adipogenesis and hyaluronan (HA) production by orbital fibroblasts. Circulating autoantibodies (thyroid-stimulating antibodies [TSAbs]) directed at the thyrotropin receptor (TSHR) on these cells stimulate or augment these cellular processes. A recently developed drug-like small molecule inverse agonist of TSHR, NCGC00229600, termed 1, binds to TSHR and blocks basal and stimulated signal transduction.

Bioidentical compounded hormones: a pharmacokinetic evaluation in a randomized clinical trial.

Objective: Bioidentical compounded hormone therapy is popular among patients, but providers do not have pharmacokinetic information or dosing guidelines for these preparations. Our objective was to compare the pharmacokinetics of the commonly used compounded preparations with conventional hormonal preparations that are considered bioequivalent in practice.

Methods: We conducted a randomized, blinded, four-arm 16-day clinical trial of forty postmenopausal women assigned to one of three doses of a compounded estrogen cream (Bi-est (80:20); 2.

Cohort study on radioactive iodine-induced hypothyroidism: implications for Graves' ophthalmopathy and optimal timing for thyroid hormone assessment.

Background: Graves' ophthalmopathy (GO) develops or worsens in up to one-third of patients treated with radioactive iodine (RAI) for Graves' hyperthyroidism. We sought to identify the prevalence of development or worsening of GO in patients treated with RAI for Graves' hyperthyroidism and to identify the risk factors associated with that outcome.

Methods: We identified a retrospective cohort of consecutive patients treated with RAI at Mayo Clinic (Rochester, MN) between 2005 and 2006.

A drug-like antagonist inhibits thyrotropin receptor-mediated stimulation of cAMP production in Graves' orbital fibroblasts.

Background: Fibroblasts (FIBs) within the retro-orbital space of patients with Graves' disease (GOFs) express thyrotropin receptors (TSHRs) and are thought to be an orbital target of TSHR-stimulating autoantibodies in Graves' ophthalmopathy (GO). Recently, we developed a low molecular weight, drug-like TSHR antagonist (NCGC00229600) that inhibited TSHR activation in a model cell system overexpressing TSHRs and in normal human thyrocytes expressing endogenous TSHRs. Herein, we test the hypothesis that NCGC00229600 will inhibit activation of TSHRs endogenously expressed in GOFs.

Genetic profiling in Graves' disease: further evidence for lack of a distinct genetic contribution to Graves' ophthalmopathy.

Background: Graves' disease (GD), including Graves' ophthalmopathy or orbitopathy (GO), is an autoimmune disease with an environmental and genetic component to its etiology. The genetic contribution to the GO clinical phenotype remains unclear. Previous data from our laboratory and others have suggested that GO has no specific genetic component distinct from GD itself, while other reports have occasionally appeared suggesting that polymorphisms in genes such as CTLA4 and IL23R specifically increase the risk for GO.

Immunopathogenesis of Graves' ophthalmopathy: the role of the TSH receptor.

Graves' ophthalmopathy is an inflammatory autoimmune disorder of the orbit. The close clinical and temporal relationships between Graves' hyperthyroidism and ophthalmopathy have long suggested that both conditions derive from a single systemic process and share the thyrotropin receptor as a common autoantigen. This receptor is expressed not only in thyroid follicular cells, but also in orbital fibroblasts with higher levels measured in orbital cells from ophthalmopathy patients than in cells from normal individuals.

A risk prediction index for amiodarone-induced thyrotoxicosis in adults with congenital heart disease.

Amiodarone therapy in adults with congenital heart disease (CHD) is associated with a significant risk of amiodarone-induced thyrotoxicosis (AIT). We developed a risk index to identify those patients being considered for amiodarone treatment who are at high risk for AIT. We reviewed the health records of adults with CHD and assessed the association between potential clinical predictors and AIT.

The evaluation and treatment of graves ophthalmopathy.

Optimum care of the patient with Graves ophthalmopathy (GO) is achieved through teamwork between the endocrinologist and ophthalmologist, with input from ancillary specialists as needed. Clinical evaluation should include determination of both the severity and the activity of the disease. It is important to assess early in the evaluation the impact of the disease on the patient's quality of life and their priorities and expectations regarding management.

A stimulatory thyrotropin receptor antibody enhances hyaluronic acid synthesis in graves' orbital fibroblasts: inhibition by an IGF-I receptor blocking antibody.

Context: Graves' ophthalmopathy (GO) is characterized by expanded volume of the orbital fat and extraocular muscle tissues and elevated levels of TSH receptor autoantibodies (TRAb). The expansion of orbital tissues involves accumulation of hyaluronic acid (HA) within the orbit.

Objective: The objective of the study was to determine whether a monoclonal stimulatory TRAb (M22) impacts HA synthesis in GO orbital cells and, if so, whether this might be blocked by an IGF-I receptor (IGF-IR)-blocking antibody (1H7) or inhibitors of various downstream signaling cascades.

Body mass index and the development of amiodarone-induced thyrotoxicosis in adults with congenital heart disease--a cohort study.

Introduction: Amiodarone-induced thyrotoxicosis (AIT) is a recognized complication of amiodarone treatment with limited management options. Its predisposing factors are incompletely defined yet a higher prevalence was reported in adults with congenital heart disease (CHD). Therefore we sought to determine the incidence and risk factors for AIT in adults with CHD.