Medically not yet explained symptoms in hypothyroidism.

Persistent symptoms are common in the general population and even more so in people with hypothyroidism. When symptoms are unexplained and brought to medical attention, they can be referred to as medically not yet explained symptoms (MNYES), a term preferred to other descriptors by patients, care-givers and experts. MNYES might be neglected by endocrinologists or misattributed to hypothyroidism.

Hypothyroidism and Somatization: Results from E-Mode Patient Self-Assessment of Thyroid Therapy, a Cross-Sectional, International Online Patient Survey.

Between 10% and 15% of hypothyroid patients experience persistent symptoms despite achieving biochemical euthyroidism. Unexplained persistent symptoms can be a sign of somatization. This is associated with distress and high health care resource use and can be classified as somatic symptom disorder (SSD).

Primary hypothyroidism and quality of life.

In the 1970s, treatment with thyroid extract was superseded by levothyroxine, a synthetic L form of tetraiodothyronine. Since then, no major innovation has emerged for the treatment of hypothyroidism. The biochemical definition of subclinical hypothyroidism is a matter of debate.

The enigma of persistent symptoms in hypothyroid patients treated with levothyroxine: A narrative review.

A significant minority of patients with hypothyroidism report persistent symptoms despite achieving normal thyroid biochemistry after levothyroxine (L-T4) replacement. Four principal lines of thinking, which are not mutually exclusive, may explain this enigma. The 'low tissue liothyronine hypothesis' emphasizes the potential imperfections of L-T4 replacement therapy that may lead to hypothyroidism in some tissues such as the brain, while others (eg hypothalamus) are euthyroid.

Autoimmune Hypercalcemia Due to Autoantibodies Against the Calcium-sensing Receptor.

Context: Autoimmune hypocalciuric hypercalcemia (AHH) is an acquired disorder caused by the presence of blocking autoantibodies against the calcium-sensing receptor (CaSR). Few cases of this condition have been described to date in the literature.

Objective: The objectives of this study were to describe 2 patients in whom the presence of AHH was suspected and to assess the patients for the presence of CaSR antibodies.

Calcium-Sensing Receptor Autoantibodies in Patients with Autoimmune Polyendocrine Syndrome Type 1: Epitopes, Specificity, Functional Affinity, IgG Subclass, and Effects on Receptor Activity.

A major manifestation of autoimmune polyendocrine syndrome type 1 (APS1) is hypoparathyroidism, which is suggested to result from aberrant immune responses against the parathyroid glands. The calcium-sensing receptor (CaSR), which plays a pivotal role in maintaining calcium homeostasis by sensing blood calcium levels and regulating release of parathyroid hormone (PTH), is an autoantibody target in APS1. In this study, the aim was to characterize the binding sites, specificity, functional affinity, IgG subclass, and functional effects of CaSR autoantibodies using phage-display technology, ELISA, and bioassays.

Immunosuppressive therapy of autoimmune hypoparathyroidism in a patient with activating autoantibodies against the calcium-sensing receptor.

Context: Activating antibodies directed at the extracellular calcium-sensing receptor (CaSR) have been described in autoimmune hypoparathyroidism in the setting of isolated hypoparathyroidism or autoimmune polyglandular syndrome type 1.

Materials And Methods: A 34-year-old female presented with hypocalcaemia (6.0 mg/dL) and hypomagnesaemia (1.

Autoantibodies against the calcium-sensing receptor and cytokines in autoimmune polyglandular syndromes types 2, 3 and 4.

Objective: The frequency of autoimmunity against the parathyroid glands in patients with polyglandular autoimmunity that is not due to autoimmune polyendocrine syndrome type 1 (APS1) is unclear. To investigate this, this study aimed to determine the prevalence of autoantibodies against parathyroid autoantigens, calcium-sensing receptor (CaSR) and NACHT leucine-rich-repeat protein 5 (NALP5), in a large group of patients with non-APS1 polyendocrine autoimmunity. Possible occult APS1 was investigated by cytokine autoantibody measurement and AIRE gene analysis.

Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants.

Vitiligo is an autoimmune disease in which depigmented skin results from the destruction of melanocytes, with epidemiological association with other autoimmune diseases. In previous linkage and genome-wide association studies (GWAS1 and GWAS2), we identified 27 vitiligo susceptibility loci in patients of European ancestry. We carried out a third GWAS (GWAS3) in European-ancestry subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication.

Early-onset hypoparathyroidism and chronic keratitis revealing APECED.

Early diagnosis of potentially life-threatening autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is crucial, but is often delayed due to the clinical heterogeneity of the disorder. Even in the absence of the classic disease triad of chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenocortical insufficiency, a diagnosis of APECED should be considered in children who have hypoparathyroidism and chronic keratitis, with a past medical history showing a mild and transient Candida infection.

Dominant Mutations in the Autoimmune Regulator AIRE Are Associated with Common Organ-Specific Autoimmune Diseases.

The autoimmune regulator (AIRE) gene is crucial for establishing central immunological tolerance and preventing autoimmunity. Mutations in AIRE cause a rare autosomal-recessive disease, autoimmune polyendocrine syndrome type 1 (APS-1), distinguished by multi-organ autoimmunity. We have identified multiple cases and families with mono-allelic mutations in the first plant homeodomain (PHD1) zinc finger of AIRE that followed dominant inheritance, typically characterized by later onset, milder phenotypes, and reduced penetrance compared to classical APS-1.

IL-14 and IL-16 are expressed in the thyroid of patients with either Graves' disease or Hashimoto's thyroiditis.

Objectives: Cytokines have an important role in orchestrating the pathophysiology in autoimmune thyroid disease. The aim of the current study was to analyse the expression of interleukin (IL)-14 and IL-16 in the thyroid tissue of patients with Graves' disease (GD), Hashimoto's thyroiditis (HT) or multinodular goitre (MNG) and in that of normal individuals, in patients' intrathyroidal CD4(+) and CD8(+) T cells, and in patient and normal cultured thyroid follicular cells.

Methods: The expression of IL-14 and IL-16 mRNA and protein was investigated using reverse transcription-polymerase chain reaction (RT-PCR) amplification, and Western blotting and ELISAs, respectively.

Regulatory T cells in vitiligo: Implications for pathogenesis and therapeutics.

Vitiligo is a hypomelanotic autoimmune skin disease arising from a breakdown in immunological self-tolerance, which leads to aberrant immune responses against melanocytes. Regulatory T cells (Tregs) are crucial to the development of self-tolerance and so are major foci in the study of autoimmune pathogenesis of vitiligo. This review will summarise recent findings concerning the role of Tregs in the pathogenesis of vitiligo.

Thyroid abnormalities.

Thyroid abnormalities and nonthyroidal illness complicate human immunodeficiency virus (HIV) infection. Among the effects that result from HIV and other opportunistic infections, distinctive features of HIV infection include early lowering of reverse tri-iodothyromine (T3) levels, with normal free T3 levels. Later, some patients develop an isolated low free thyroxine level.

Impact of month of birth on the development of autoimmune thyroid disease in the United Kingdom and Europe.

Context: Viral/bacterial infection is proposed as a trigger for the autoimmune thyroid diseases (AITD): Graves' disease (GD) and Hashimoto's thyroiditis (HT). Previous studies in European Caucasian AITD subjects found higher birth rates in the autumn/winter, suggesting those born in the autumn/winter experience increased viral/bacterial exposure after birth, impacting upon immune system development and predisposing to AITD later in life.

Objective: Month of birth effects were investigated in three independent European Caucasian AITD datasets.

Pendrin and NIS antibodies are absent in healthy individuals and are rare in autoimmune thyroid disease: evidence from a Danish twin study.

Objective: Antibodies against thyroglobulin, thyroid peroxidase and the TSH receptor are accepted as pathophysiological and diagnostic biomarkers in autoimmune thyroid disease (AITD). In contrast, the prevalence, aetiology and clinical relevance of autoantibodies against the human sodium-iodine symporter (NISAb) and pendrin (PenAb) remain unclear. The objectives of the study were to investigate the presence of NISAb and PenAb in Danish twins, with and without AITD, to study whether the published variations in NISAb and PenAb frequencies were related to differences in methodology or study populations, and to evaluate whether the presence of NISAb or PenAb most likely results from genetic or nongenetic factors.

Graves' disease following immune reconstitution or immunomodulatory treatment: should we manage it any differently?

Graves' disease and other disorders of thyroid function may occur following treatment with novel anticancer agents or during periods of lymphocyte recovery after lymphopenia. There are three main settings for such lymphocyte reconstitution: recovery after a bone marrow or haematopoietic stem cell transplant, alemtuzumab treatment and the use of highly active antiretroviral therapy (HAART) for human immunodeficiency virus infection. The available evidence suggests that Graves' disease behaves as normal in most of these cases and should be treated conventionally, but it may follow a more favourable course in those receiving alemtuzumab or HAART.

Prevalence and clinical associations of calcium-sensing receptor and NALP5 autoantibodies in Finnish APECED patients.

Context: Previous studies have identified the calcium-sensing receptor (CaSR) and NALP5 as parathyroid autoantibody targets in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). However, although NALP5 antibodies have been associated with the occurrence of hypoparathyroidism (HP) in APECED, it is unclear whether CaSR antibodies are a specific or sensitive marker for APECED-associated HP.

Objective: The objective of the study was to identify associations between the presence of CaSR and NALP5 antibodies and the disease manifestations and demographic characteristics of Finnish APECED patients.

Acquired hypocalciuric hypercalcemia in a patient with CKD.

We present a case of an 82-year-old woman with elevated parathyroid hormone (PTH) levels, hypocalciuria, hypercalcemia, and stage 3 chronic kidney disease. Hypocalciuria initially was attributed to chronic kidney disease, and hypercalcemia was attributed to primary hyperparathyroidism. Subsequent laboratory studies showed autoantibodies in the patient's serum directed against the calcium-sensing receptor (CaSR).

Low frequency of pendrin autoantibodies detected using a radioligand binding assay in patients with autoimmune thyroid disease.

Context: Pendrin is a transmembrane protein located at the apical end of the thyrocyte in which it mediates the efflux of iodide through the thyroid follicular cell. Recently pendrin was described as a significant antibody target in Japanese patients with Graves' disease (GD) or autoimmune hypothyroidism (AH) using an immunoblotting assay. However, a subsequent study failed to verify this in autoimmune thyroid disease (ATD) patients of Tunisian origin.

The immunopathogenesis of chronic autoimmune thyroiditis one century after hashimoto.

Hakaru Hashimoto described 4 patients with a hitherto unknown cause for goitre, struma lymphomatosa, a century ago. He was careful to distinguish this from Riedel thyroiditis but it has become clear that fibrosis and atrophy of the thyroid are indeed components of Hashimoto thyroiditis, and in rare cases IgG4-related sclerosing disease may be an outcome. Although the cause of the lymphocytic infiltration was unknown to Hashimoto, we now know through the pioneering studies of N.

Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo.

We previously reported a genome-wide association study (GWAS) identifying 14 susceptibility loci for generalized vitiligo. We report here a second GWAS (450 individuals with vitiligo (cases) and 3,182 controls), an independent replication study (1,440 cases and 1,316 controls) and a meta-analysis (3,187 cases and 6,723 controls) identifying 13 additional vitiligo-associated loci. These include OCA2-HERC2 (combined P = 3.

Thyroid disease in pregnancy in 2011: Thyroid function--effects on mother and baby unraveled.

The complex relationship between pregnancy and thyroid function, and its clinical effect on mother and baby, continued to stimulate research in 2011. Key advances were made on three important issues: how long maternal thyroid function affects fetal thyroid hormone levels; whether thyroid autoimmunity affects pregnancy outcome; and the prevalence of permanent hypothyroidism after postpartum thyroiditis.