OBJECTIVE: To observe the effect of wheat-grain moxibustion on behavior, 5-hydroxytryptamine (5-HT) and cortisol in the serum, mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the hippocampus in rats with hypothyroidism complicated with depression, and to explore the possible mechanism of wheat-grain moxibustion on improving depression in rats with hypothyroidism. METHODS: A total of 32 SPF SD rats were randomly divided into a blank group, a model group, a medication group and a wheat-grain moxibustion group, 8 rats in each group. Except for the blank group, the rats in the remaining groups were treated with intragastric administration of 0.1% propylthiouracil (PTU) suspension at 1 mL/100 g, once a day for 4 weeks to establish the rat model of hypothyroidism, and whether the rats were accompanied with depression-like behavior determined through behavioristics evaluation. The rats in the medication group were intervened with euthyrox at 0.9 mL/100 g, once a day, for 4 weeks; the rats in the wheat-grain moxibustion group were treated with wheat-grain moxibustion at "Dazhui" (GV 14), "Mingmen" (GV 4), "Shenshu" (BL 23) and "Pishu" (BL 20), 7 cones each acupoint, once a day, six times a week for 4 weeks. After the intervention, the depression status was observed by behavioristics test; the contents of thyroid stimulating hormone (TSH), total thyroxine (TT4), 5-HT and cortisol in the serum were detected by ELISA; the protein expressions of MR and GR in hippocampus were detected by Western blot; the expressions of MR mRNA and GR mRNA in the hippocampus were detected by real-time PCR. RESULTS: Before the intervention, compared with the blank group, the scores of open field test (OFT) were decreased and the immobility time of tail suspension test (TST) was prolonged (P<0.05); the serum TSH contents were increased and TT4 contents were decreased (P<0.01) in the other three groups. After the intervention, compared with the model group, the vertical score of OFT was increased and the immobility time of forced swimming test (FST) was prolonged in the medication group (P<0.05), while the scores of three items of OFT were increased (P<0.05, P<0.01), and the immobility time of FST and TST was shortened in the wheat-grain moxibustion group (P<0.01, P<0.05). Compared with the medication group, the immobility time of TST and FST in the wheat-grain moxibustion group was shorter (P<0.05, P<0.01). Compared with the blank group, in the model group, the contents of serum TSH and cortisol were increased (P<0.01, P<0.001), while the contents of serum TT4 and 5-HT were decreased (P<0.01, P<0.001). Compared with the model group, the contents of serum TT4 and 5-HT were increased, while the contents of serum TSH and cortisol were decreased in the medication group and wheat-grain moxibustion group (P<0.01, P<0.05). Compared with the blank group, the protein and mRNA expression of MR, GR in the hippocampus in the model group was decreased (P<0.01, P<0.05, P<0.001); compared with the model group, the protein and mRNA expression of MR in the hippocampus in the medication group were increased (P<0.05), and the protein expression of MR, GR and mRNA expression of MR in the hippocampus in the wheat-grain moxibustion group were increased (P<0.05, P<0.01). Compared with the medication group, the expression of MR mRNA in the wheat-grain moxibustion group was increased (P<0.05). CONCLUSION Wheat-grain moxibustion could significantly improve thyroid function and depression in rats with hypothyroidism. Its mechanism may be related to up-regulating the protein and mRNA expression of MR and GR in the hippocampus, and then affecting the expression of serum cortisol and 5-HT.
Acupuncture Points ; Animals ; Depression/therapy* ; Hippocampus/metabolism* ; Hydrocortisone/metabolism* ; Hypothyroidism/therapy* ; Moxibustion ; RNA, Messenger/metabolism* ; Rats ; Rats, Sprague-Dawley ; Receptors, Glucocorticoid/metabolism* ; Receptors, Mineralocorticoid/metabolism* ; Serotonin ; Thyrotropin/metabolism* ; Triticum/metabolism*

Resistance to thyroid hormone (RTH) is a condition caused by a mutation in the thyroid hormone receptor gene. It is rarely reported in individuals with no family history of RTH or in premature infants, and its clinical presentation varies. In our case, a premature infant with no family history of thyroid diseases had a thyroid stimulating hormone level of 85.0 µIU/mL and free thyroxine level of 1.64 ng/dL on a thyroid function test. The patient also presented with clinical signs of hypothyroidism, including difficulties in feeding and weight gain. The patient was treated with levothyroxine; however, only free thyroxine and triiodothyronine levels increased without a decrease in thyroid-stimulating hormone levels. Taken together with thyroid gland hypertrophy observed on a previous ultrasound examination, RTH was suspected and the diagnosis was eventually made based on a genetic test. A de novo mutation in the thyroid hormone receptor β gene in the infant was found that has not been previously reported. Other symptoms included tachycardia and pulmonary hypertension, but gradual improvement in the symptoms was observed after liothyronine administration. This report describes a case involving a premature infant with RTH and a de novo mutation, with no family history of thyroid disease.
Diagnosis ; Goiter ; Humans ; Hypertension, Pulmonary ; Hypertrophy ; Hypothyroidism ; Infant ; Infant, Newborn ; Infant, Premature ; Receptors, Thyroid Hormone ; Tachycardia ; Thyroid Diseases ; Thyroid Function Tests ; Thyroid Gland ; Thyroid Hormone Receptors beta ; Thyroid Hormone Resistance Syndrome ; Thyrotropin ; Thyroxine ; Triiodothyronine ; Ultrasonography ; Weight Gain

BACKGROUND: Graves' disease (GD) is an autoimmune thyroid disorder caused by antibodies stimulating the thyrotropin (TSH) receptor. TSH receptor antibody (TRAb) measurement is useful for predicting GD relapse after antithyroid drug (ATD) treatment. However, the association of other thyroid autoantibodies with GD relapse remains obscure. METHODS: This retrospective study enrolled patients with GD who were initially treated with ATD. TRAb, thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) were measured at the initial diagnosis and at the time of ATD discontinuation. RESULTS: A total of 55 patients were enrolled. The mean age was 49.7 years, and 39 patients (70.9%) were female. Antibody positivity at diagnosis was 90.9%, 69.1%, and 61.9% for TRAb, TPOAb, TgAb, respectively. Median ATD treatment period was 15.1 months. At the time of ATD withdrawal, TRAb titers decreased uniformly overall. Conversely, TPOAb and TgAb showed various changes. After withdrawal of ATD, 19 patients (34.5%) experienced relapse. No clinical features or laboratory results were significantly related to relapse in the overall patient group. However, in the TPOAb positive group at diagnosis, increasing titer of TPOAb or TgAb after ATD treatment was significantly and independently related to relapse free survival (TPOAb: hazard ratio [HR], 17.99; 95% confidence interval [CI], 1.66 to 195.43; P=0.02) (TgAb: HR, 5.73; 95% CI, 1.21 to 27.26; P=0.03). CONCLUSION: Changes in TPOAb or TgAb titers during treatment might be useful for predicting relapse after ATD treatment in patients with positive TPOAb at diagnosis.
Antibodies ; Autoantibodies ; Diagnosis ; Drug Therapy ; Female ; Graves Disease ; Humans ; Iodide Peroxidase ; Receptors, Thyrotropin ; Recurrence ; Retrospective Studies ; Thyroglobulin ; Thyroid Gland ; Thyrotropin

Whether or not Graves' hyperthyroidism can be really cured, depends on the definition of “cure.” If eradication of thyroid hormone excess suffices for the label “cure,” then all patients can be cured because total thyroidectomy or high doses of 1¹³¹I will abolish hyperthyroidism albeit at the expense of creating another disease (hypothyroidism) requiring lifelong medication with levothyroxine. I would not call this a “cure,” which I would like to define as a state with stable thyroid stimulating hormone (TSH), free thyroxine, and triiodothyronine serum concentrations in the normal range in the absence of any thyroid medication. Surgery and radioiodine are unlikely to result in so-defined cures, as their preferable aim as stated in guidelines is to cause permanent hypothyroidism. Discontinuation of antithyroid drugs is followed by 50% recurrences within 4 years; before starting therapy the risk of recurrences can be estimated with the Graves' Recurrent Events After Therapy (GREAT) score. At 20-year follow-up about 62% had developed recurrent hyperthyroidism, 8% had subclinical hypothyroidism, and 3% overt hypothyroidism related to TSH receptor blocking antibodies and thyroid peroxidase antibodies. Only 27% was in remission, and might be considered cured. If the definition of “cure” would also include the disappearance of thyroid antibodies in serum, the proportion of cured patients would become even lower.
Antibodies ; Antibodies, Blocking ; Antithyroid Agents ; Follow-Up Studies ; Graves Disease ; Humans ; Hyperthyroidism ; Hypothyroidism ; Iodide Peroxidase ; Receptors, Thyrotropin ; Recurrence ; Reference Values ; Thyroid Gland ; Thyroidectomy ; Thyrotropin ; Thyroxine ; Triiodothyronine

Thyroid disorders are common, affecting more than 10% of people in the US, and laboratory tests are integral in the management of these conditions. The repertoire of thyroid tests includes blood tests for thyroid-stimulating hormone (TSH), free thyroxine, free triiodothyronine, thyroglobulin (Tg), thyroglobulin antibodies (Tg-Ab), thyroid peroxidase antibodies (TPO-Ab), TSH receptor antibodies (TRAb), and calcitonin. TSH and free thyroid hormone tests are frequently used to assess the functional status of the thyroid. TPO-Ab and TRAb tests are used to diagnose Hashimoto's thyroiditis and Graves' disease, respectively. Tg and calcitonin are important tumor markers used in the management of differentiated thyroid carcinoma and medullary thyroid carcinoma (MTC), respectively. Procalcitonin may replace calcitonin as a biomarker for MTC. Apart from understanding normal thyroid physiology, it is important to be familiar with the possible pitfalls and caveats in the use of these tests so that they can be interpreted properly and accurately. When results are discordant, clinicians and laboratorians should be mindful of possible assay interferences and/or the effects of concurrent medications. In addition, thyroid function may appear abnormal in the absence of actual thyroid dysfunction during pregnancy and in critical illness. Hence, it is important to consider the clinical context when interpreting results. This review aims to describe the above-mentioned blood tests used in the diagnosis and management of thyroid disorders, as well as the pitfalls in their interpretation. With due knowledge and care, clinicians and laboratorians will be able to fully appreciate the clinical utility of these important laboratory tests.
Antibodies ; Biomarkers, Tumor ; Calcitonin ; Critical Illness ; Diagnosis ; Graves Disease ; Hematologic Tests ; Iodide Peroxidase ; Physiology ; Pregnancy ; Receptors, Thyrotropin ; Thyroglobulin ; Thyroid Function Tests ; Thyroid Gland* ; Thyroid Neoplasms ; Thyroiditis ; Thyrotropin ; Thyroxine ; Triiodothyronine

Thyroid diseases, including autoimmune thyroid diseases and thyroid cancer, are known to have high heritability. Family and twin studies have indicated that genetics plays a major role in the development of thyroid diseases. Thyroid function, represented by thyroid stimulating hormone (TSH) and free thyroxine (T4), is also known to be partly genetically determined. Before the era of genome-wide association studies (GWAS), the ability to identify genes responsible for susceptibility to thyroid disease was limited. Over the past decade, GWAS have been used to identify genes involved in many complex diseases, including various phenotypes of the thyroid gland. In GWAS of autoimmune thyroid diseases, many susceptibility loci associated with autoimmunity (human leukocyte antigen [HLA], protein tyrosine phosphatase, non-receptor type 22 [PTPN22], cytotoxic T-lymphocyte associated protein 4 [CTLA4], and interleukin 2 receptor subunit alpha [IL2RA]) or thyroid-specific genes (thyroid stimulating hormone receptor [TSHR] and forkhead box E1 [FOXE1]) have been identified. Regarding thyroid function, many susceptibility loci for levels of TSH and free T4 have been identified through genome-wide analyses. In GWAS of differentiated thyroid cancer, associations at FOXE1, MAP3K12 binding inhibitory protein 1 (MBIP)-NK2 homeobox 1 (NKX2-1), disrupted in renal carcinoma 3 (DIRC3), neuregulin 1 (NRG1), and pecanex-like 2 (PCNXL2) have been commonly identified in people of European and Korean ancestry, and many other susceptibility loci have been found in specific populations. Through GWAS of various thyroid-related phenotypes, many susceptibility loci have been found, providing insights into the pathogenesis of thyroid diseases and disease co-clustering within families and individuals.
Autoimmunity ; Genes, Homeobox ; Genetics ; Genome-Wide Association Study* ; Graves Disease ; Hashimoto Disease ; Humans ; Leukocytes ; Neuregulin-1 ; Phenotype ; Protein Tyrosine Phosphatase, Non-Receptor Type 22 ; Receptors, Interleukin-2 ; T-Lymphocytes, Cytotoxic ; Thyroid Diseases* ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyrotropin ; Thyroxine

Elephantiasis is a symptom characterized by the thickening of the skin and underlying tissues in the legs. Pretibial myxedema (PTM) is a non-frequent manifestation of autoimmune thyroiditis, particularly Graves' disease. Lesions of myxedema occur most commonly on the pretibial surfaces, also develop at sites of previous injury or scars and other areas. A 49-year-old male presented with severe elephantiasis on the both pretibial areas, dorsum of the feet, ankles and toes. Twenty years previously, he had received radioactive iodine treatment for thyrotoxicosis. Laboratory tests showed that the patient's thyroid function was normal, but the level of thyroid stimulating hormone (TSH) receptor antibodies was very high (>40 IU/L). The biopsy confirmed PTM. Interestingly, the connective tissue was stained with the TSH receptor antibodies in the deep dermis. Elephantiasic PTM is a severe form of the myxedema and there is few reported case. We report a rare case of PTM with appearance of severe elephantiasis.
Ankle ; Antibodies ; Biopsy ; Cicatrix ; Connective Tissue ; Dermis ; Elephantiasis* ; Foot ; Graves Disease ; Humans ; Iodine ; Leg ; Male ; Middle Aged ; Myxedema* ; Receptors, Thyrotropin ; Skin ; Thyroid Gland ; Thyroiditis, Autoimmune ; Thyrotoxicosis ; Thyrotropin ; Toes

Most cases of congenital hyperthyroidism are autoimmune forms caused by maternal thyroid stimulating antibodies. Nonautoimmune forms of congenital hyperthyroidism caused by activating mutations of the thyrotropin receptor (TSHR) gene are rare. A woman gave birth to a boy during an emergency cesarean section at 33 weeks of gestation due to fetal tachycardia. On the 24th day of life, thyroid function tests were performed due to persistent tachycardia, and hyperthyroidism was confirmed. Auto-antibodies to TSHR, thyroid peroxidase, and thyroglobulin were not found. The patient was treated with propylthiouracil and propranolol, but hyperthyroidism was not well controlled. At 3 months of age, the patient had craniosynostosis and hydrocephalus, and underwent a ventriculoperitoneal shunt operation. Direct sequencing of the TSHR gene showed a heterozygous mutation of c.1899C>A (p.Asp633Glu) in exon 10. No mutations were discovered in any of the parents in a familial genetic study. We have reported a case of sporadic nonautoimmune congenital hyperthyroidism, by a missense mutation of the TSHR gene, for the first time in South Korea.
Cesarean Section ; Craniosynostoses ; Emergencies ; Exons ; Female ; Germ-Line Mutation ; Humans ; Hydrocephalus ; Hyperthyroidism* ; Immunoglobulins, Thyroid-Stimulating ; Iodide Peroxidase ; Korea ; Male ; Mutation, Missense ; Parents ; Parturition ; Pregnancy ; Propranolol ; Propylthiouracil ; Receptors, Thyrotropin ; Tachycardia ; Thyroglobulin ; Thyroid Function Tests ; Ventriculoperitoneal Shunt

Congenital hypothyroidism (CH), which results from insufficient thyroid hormone biosynthesis, is one of the most common neonatal endocrine disorders. Thyroid dysgenesis and thyroid dyshormonogenesis are the two causes of CH and either one will lead to deficiencies of enzymes during thyroid hormone biosynthesis and insufficient thyroid hormone biosynthesis. Recently, researchers have performed extensive studies on genetics of CH. This paper reviews genes reported to be associated with CH in China.
Congenital Hypothyroidism ; genetics ; Humans ; Iodide Peroxidase ; genetics ; Membrane Proteins ; genetics ; PAX8 Transcription Factor ; genetics ; Receptors, Thyrotropin ; genetics ; Thyroglobulin ; genetics ; Transcription Factors ; genetics

BACKGROUND AND OBJECTIVES: The role of thyroid-stimulating hormone (TSH) signaling on osteoblastic differentiation is still undetermined. The aim of this study was to investigate the effects of 5-aza-2′-deoxycytidine (5-azacytidine) on TSH-mediated regulations of osteoblasts. MATERIALS AND METHODS: MG63, a human osteoblastic cell-line, was treated with 5-azacytidine before inducing osteogenic differentiation using osteogenic medium (OM) containing L-ascorbic acid and β-glyceophosphate. Bovine TSH or monoclonal TSH receptor stimulating antibody (TSAb) was treated. Quantitative real-time PCR analyses or measurement of alkaline phosphatase activities were performed for evaluating osteoblastic differentiation. RESULTS: Studies for osteogenic-related genes or alkaline phosphatase activity demonstrated that treatment of TSH or TSAb alone had no effects on osteoblastic differentiation in MG63 cells. However, treatment of 5-azacytidine, per se, significantly increased osteoblastic differentiation and combination treatment of 5-azacytidine and TSH or TSAb in the condition of OM showed further significant increase of osteoblastic differentiation. CONCLUSION: Stimulating TSH signaling has little effects on osteoblastic differentiation in vitro. However, in the condition of epigenetic modification using inhibitor of DNA methylation, TSH signaling positively affects osteoblastic differentiation in human osteoblasts.
Alkaline Phosphatase ; Ascorbic Acid ; Azacitidine* ; DNA Methylation ; Epigenomics ; Humans* ; In Vitro Techniques ; Osteoblasts* ; Real-Time Polymerase Chain Reaction ; Receptors, Thyrotropin ; Social Control, Formal ; Thyrotropin*