Clinical efficacy of thyroid-stimulating immunoglobulin detection for diagnosing Graves' disease and predictors of responsiveness to methimazole.

BACKGROUND: As thyroid-stimulating immunoglobulins (TSI) are a sign of Graves' disease (GD), measuring TSI titers is becoming increasingly important for GD diagnosis. This study evaluated the diagnostic accuracy of a new fully automated TSI immunoassay (Immulite™ TSI assay) in GD patients and compared it to the third generation thyroid-stimulating hormone receptor antibody (TRAb) electrochemiluminescence assay (Elecsys Anti-TSHR assay). Additionally, clinical characteristics associated with responsiveness to methimazole in patients with newly diagnosed GD were preliminarily explored. METHODS: This study involved 324 subjects, comprising patients with untreated GD (GD-UT), Graves' ophthalmopathy (GO) patients, GD patients who had been treated for > 12 months (GD-T), autoimmune thyroiditis (AIT) patients, and healthy subjects (HS). The Immulite™ TSI and Elecsys Anti-TSHR assay were performed on all samples. According to their responsiveness to methimazole, the GD-UT patients were divided into rapid and slow responder groups, and their clinical characteristics were compared. RESULTS: A receiver operating characteristic (ROC) curve analysis of GD-UT patients showed that the optimal TSI cut-off value was 0.57 IU/L. Logistic regression revealed that age and initial FT4 and TSI levels in the middle-dose methimazole group were related to a rapid response, while the initial FT4 level, but not TSI, in the high-dose group was also associated with a rapid response. CONCLUSIONS: The clinical diagnostic performance of the Immulite™ TSI assay for diagnosing GD was comparable to that of the Elecsys Anti-TSHR assay. The initial FT4 and TSI levels can be used as predictors of the responsiveness to methimazole in patients with newly diagnosed GD.

Change in newly diagnosed Graves' disease phenotype between the twentieth and the twenty-first centuries: meta-analysis and meta-regression.

PURPOSE: According to a few recent studies, the clinical phenotype of Graves' disease (GD) at onset is becoming milder in recent years, in terms of prevalence and severity of hyperthyroidism, goiter and overt eye disease. The aim of this study was to assess the change in GD phenotype across the late twentieth and the early twenty-first centuries. MATERIALS AND METHODS: We carried out a systematic search of studies published between 1/1/1980 and 12/31/2017 describing naïve GD patients at diagnosis. We collected epidemiological, clinical, biochemical and serological data reported in the selected studies, and (1) conducted a single-arm meta-analysis to compare clinical and biochemical characteristics of naïve GD patients before and after year 2000 and (2) performed a meta-regression to identify the trend of the observed clinical presentations. RESULTS: Eighty selected articles were related to the period before the year 2000, 30 to the years 2000-2017. According to demographics, the two defined populations were homogeneous at meta-analysis: overall estimated female prevalence was 81% [95% CI 79-82], mean estimated age of the entire population was 39.8 years [95% CI 38.4-41.1], with no significant differences between pre- and post-2000 groups (p > 0.05). The overall estimated prevalence of smokers was 40% [95% CI 33-46], with no significant difference between the two groups (p > 0.05). Mean estimated free thyroxine (FT4) and free triiodothyronine (FT3) levels at diagnosis were higher in the pre-2000 group: 4.7 ng/dl [95% CI 4.5-4.9] for FT4 and 14.2 pg/ml [95% CI 13.3-15.1] for FT3, as compared to the post-2000 group: 3.9 ng/dl [95% CI 3.6-4.2] for FT4 and 12.1 pg/ml [95% CI 11.0-13.3] for FT3 (all p < 0.01). Goiter estimated prevalence was higher in the pre-2000 group, 87% [95% CI 84-90], than in the post-2000 group, 56% [95% CI 45-67]. Estimated prevalence for Graves' Orbitopathy (GO) was 34% [95% CI 27-41] in the pre-2000 group and 25% [95% CI 19-30] in the post-2000 group (p = 0.03). Accordingly, meta-regression adjusted for covariates showed an average annual reduction of FT4 (- 0.040 ± 0.008 ng/dl, p < 0.0001), FT3 (- 0.316 ± 0.019 pg/ml, p < 0.0001), goiter prevalence (- 0.023 ± 0.008%, p = 0.006), and goiter size (- 0.560 ± 0.031 ml, p < 0.0001). CONCLUSIONS: Our meta-analysis and meta-regression confirmed that GD phenotype at diagnosis is nowadays milder than in the past; we hypothesize that conceivable factors involved in this change are iodoprophylaxis, worldwide decrease in smoking habits, larger use of contraceptive pill and micronutrient supplementation, as well as earlier diagnosis and management.

Predictors of euthyreosis in hyperthyroid patients treated with radioiodine 131I-: a retrospective study.

BACKGROUND: Radioiodine (RAI) treatment for hyperthyroidism is a very common modality, chosen by physicians worldwide. The outcome of the therapy, however, is not always predictable. While rendering a patient hypo- or euthyroid is meant as a therapeutic success, the latter does not require lifelong hormonal supplementation. The aim of our study is to determine predictors of euthyreosis in patients who underwent RAI treatment. METHODS: Medical records of 144 patients who had undergone RAI therapy were examined. Laboratory and clinical data were analyzed statistically. Ultrasonography findings, such as thyroid volume, nodules' size and characteristics had been collected at the beginning of treatment and 6 months after the administration of radioiodine 131I-. Moreover, scintigraphy results were taken into account. Multivariate logistic regression analysis model has been used to find predictors of euthyroidism after 12 months of follow-up. The predictors of normal thyroid function have also been analyzed separately for patients with GD (Graves' disease) and TMNG (toxic multinodular goiter). RESULTS: The analysis showed that age (OR 1,06; 95%CI 1.025-1.096, p = 0,001), thyroid gland volume (OR 1,04; 95%CI 1,02-1,06; p < 0.001) and iodine uptake level (OR 0,952; 95%CI 0,91-0,98; p = 0,004) were significant factors of achieving normal thyroid function after RAI therapy. According to multivariate logistic regression analysis, in GD patients only age has been shown to be a significant factor (OR 1,06; 95%CI 1,001-1,13; p = 0.047), while in TMNG patients' age (OR 1,04; 95%CI 1-1,09; p = 0.048), thyroid gland volume (OR 1.038; 95%CI 1.009-1.068; p = 0.009) and iodine uptake level (OR 0.95; 95%CI 0.9-0.99; p = 0.02) all have been proven to be significant predictors of achieving euthyroidism. CONCLUSIONS: The more advanced age, larger volume of thyroid gland and lower iodine uptake level are predictors of euthyreosis after RAI treatment.

The potential markers involved in newly diagnosed graves' disease and the development of active graves' orbitopathy.

BACKGROUND: Graves' disease (GD) patients experience two major issues: one is the severe hyperthyroidism associated with newly diagnosed GD, and the other involves the disfiguring and dysfunctional features of active Graves' orbitopathy (GO). Therefore, the aim of our study was to identify potential markers involved in the initial phase of GD dysfunction and the development of active GO. METHODS: Seventy-eight subjects were recruited: 40 with newly diagnosed GD, 20 with inactive GO and 18 with active GO. GO activity was evaluated by the clinical activity score (CAS, active GO = CAS ≥ 3), and severity was assessed according to the NOSPECS classification. Plasma selenium concentrations were determined by dual channel hydride generation atomic fluorescence photometry. A liquid chip assay was used to measure plasma Th1 cytokines IFN-γ and TNF-α; Th2 cytokines IL4, IL5 and IL6; Th17 cytokine IL23; Treg cytokines IL10 and TGF-ß; and two chemokines, CCL2 (Th2 chemokine) and CXCL10 (Th1 chemokine). RESULTS: Among the three groups, newly diagnosed GD patients showed significantly elevated plasma levels of CXCL10 and IL-23 (all p < 0.05). Both CXCL10 and IL23 were significantly correlated with hyperthyroidism severity, specifically, increasing FT3 and FT4 and decreasing TSH. Notably, a very strong positive relationship between IL23 and CXCL10 was revealed (adjusted R square = 0.795; p < 0.001). Moreover, the selenium level was lower, while that of CCL2 was higher, in active GO than in inactive GO (p = 0.007, p < 0.001, respectively). Likewise, we also discovered that increasing CCL2 levels and decreasing selenium levels were associated with high CAS. Remarkably, after adjusting for potential confounding factors, selenium (OR, 0.919) and CCL2 (OR, 1.042) were still independent predictors for the diagnosis of active GO, and similar conclusions were drawn by receiver operating characteristic (ROC) curve analysis. CONCLUSION: Pro-inflammatory cytokines, especially Th17-associated cytokines (e.g., IL23) and Th1 chemokines (e.g., CXCL10), appear to be involved in the initial phase of GD dysfunction. Moreover, we revealed for the first time that decreased plasma selenium levels and increased concentrations of Th2 chemokines (e.g., CCL2) may reflect GO disease activity, shedding light on the diagnosis and evaluation of active GO.

Elevated phosphatidylserine-specific phospholipase A1 level in hyperthyroidism.

OBJECTIVES: Although a single nucleotide polymorphism in a specific receptor for lysophosphatidylserine, a lysophospholipid mediator involved in the immune system, is reportedly associated with Graves' disease, the association between lysophosphatidylserine and thyroid disorders remains to be elucidated. Therefore, we aimed to investigate the association between the level of phosphatidylserine-specific phospholipase A1 (PS-PLA1), which produces lysophosphatidylserine, and thyroid disorders. METHODS: We measured serum PS-PLA1 levels in the patients with various thyroid disorders (n = 120) and normal subjects (n = 58). RESULTS: We observed that the serum PS-PLA1 levels were higher in the subjects with Graves' disease, subacute thyroiditis, or silent thyroiditis, while they were not modulated in the patients with hypothyroidism. The serum PS-PLA1 levels were strongly correlated with the levels of thyroid hormones, especially in the subjects with Graves' disease. Moreover, we found that the serum PS-PLA1 levels were lowered by treatment with anti-thyroid reagents in subjects with Graves' disease and that the changes in PS-PLA1 were strongly correlated with those in thyroid hormones. CONCLUSION: These results suggest that PS-PLA1 might be a novel target in the treatment of hyperthyroidism, especially Graves' disease, and that its measurement might be useful as a supplementary diagnostic test for thyroid function.

Best practices in mitigating the risk of biotin interference with laboratory testing.

Dietary biotin intake does not typically result in blood biotin concentrations that exceed interference thresholds for in vitro diagnostic tests. However, recent trends of high-dose biotin supplements and clinical trials of very high biotin doses for patients with multiple sclerosis have increased concerns about biotin interference with immunoassays. Estimates of the prevalence of high biotin intake vary, and patients may be unaware that they are taking biotin. Since 2016, 92 cases of suspected biotin interference have been reported to the US Food and Drug Administration. Immunoassays at greatest risk from biotin interference include thyroid and reproductive hormones, cardiac, and immunosuppressive drug tests. Several case studies have highlighted the challenge of biotin interference with thyroid hormone assays and the potential misdiagnosis of Graves' disease. Biotin interference should be suspected when immunoassay test results are inconsistent with clinical information; a clinically relevant biotin interference happens when the blood biotin concentration is high and the assay is sensitive to biotin. We propose a best practice workflow for laboratory scientists to evaluate discrepant immunoassay results, comprising: (1) serial dilution; (2) retesting after biotin clearance and/or repeat testing on an alternate platform; and (3) confirmation of the presence of biotin using depletion protocols or direct measurement of biotin concentrations. Efforts to increase awareness and avoid patient misdiagnosis should focus on improving guidance from manufacturers and educating patients, healthcare professionals, and laboratory staff. Best practice guidance for laboratory staff and healthcare professionals would also provide much-needed information on the prevention, detection, and management of biotin interference.

Serum fibroblast growth factor 23 and mineral metabolism in patients with euthyroid Graves' diseases: a case-control study.

This study investigated the alterations of mineral metabolism in patients with Graves' disease (GD) who achieved euthyroidism. They had higher fibroblast growth factor 23 (FGF23) and phosphorus as compared with healthy subjects. Serum FGF23 was negatively correlated with serum phosphorus. These indicated abnormal mineral metabolism even after 1.6 years of euthyroid status. INTRODUCTION: FGF23 is involved in the mineral homeostasis, especially the regulation of serum phosphorus. Graves' disease (GD) is associated with accelerated bone turnover, hyperphosphatemia, and elevated serum FGF23. Evidence suggested that serum FGF23 decreased after a 3-month treatment of GD. However, it remains unclear whether serum FGF23, serum phosphorus, and other markers of mineral metabolism will be normalized after euthyroid status achieved. METHODS: A total of 62 patients with euthyroid GD and 62 healthy control subjects were enrolled, and the median duration of euthyroid status was 1.6 years. Endocrine profiles including thyroid function test, autoantibodies, serum FGF23, and bone turnover markers were obtained and compared between the two groups. RESULTS: Euthyroid GD patients had significantly higher serum FGF23 and phosphorus, and lower 25-hydroxyvitamin D (25(OH)D) and intact parathyroid hormone (iPTH) levels as compared with the control group. Serum FGF23 was significantly and negatively correlated with phosphorus level after adjusted for age, gender, calcium, iPTH, and 25(OH)D in the euthyroid GD group. CONCLUSION: Serum phosphorus and FGF23 levels remain higher in GD patients even after euthyroid status has been achieved for a median of 1.6 years. Serum FGF23 was negatively correlated with serum phosphorus in euthyroid GD patients. Underlying mechanisms warrant further investigations. TRIAL REGISTRATION: Registration number: NCT01660308 and NCT02620085.

Serum Trace Elements Profile in Graves' Disease Patients with or without Orbitopathy in Northeast China.

OBJECTIVE: The purpose of the present study was to investigate serum trace elements in Graves' disease (GD) patients with or without orbitopathy in Northeast China. METHODS: Patients with newly diagnosed Graves' disease (HyGD) (n = 66), GD patients with euthyroid status or subclinical thyroidism after treatment (EUGD) (n = 55), GO patients with euthyroid status or subclinical thyroidism after treatment (GO) (n = 57), and normal controls (NC) (n = 66) were enrolled in this study. Serum trace elements were measured with ICP-MS. RESULTS: Serum selenium (Se) levels in EUGD group (median: 7.53 µg/dL), HyGD group (median: 6.76 µg/dL), and GO group (median: 7.40 µg/dL) were significantly lower than those in NC group (median: 9.20 µg/dL, all P < 0.01). Serum copper (Cu) levels in GO group (median: 95.93 µg/dL) were significantly lower than those in the NC group (median: 113.59 µg/dL, P = 0.015). After being adjusted for multivariables, thyroid-specific antibodies grade was associated with low Se levels. Hyperthyroidism and thyroid-specific antibodies grade were associated with high Cu levels. In addition, orbitopathy was associated with low Cu levels. CONCLUSIONS: Thyroid autoimmunity was associated with low Se levels. Hyperthyroidism and thyroid autoimmunity may be associated with relatively high serum Cu levels. Alternatively, ophthalmopathy may be related to low serum Cu levels.

[Apparent thyrotoxicosis in a patient with multiple sclerosis: biochemical assay interference due to high dose biotin use]. / Schijnbare thyreotoxicose door gebruik van biotine in hoge dosis.

BACKGROUND: Supraphysiological doses of biotin are being tested in patients with multiple sclerosis. Biotin can cause interference with laboratory assessment of thyroid function, and therefore give a false suggestion of thyrotoxicosis. CASE DESCRIPTION: A 64-year-old patient was referred for assessment of thyrotoxicosis, due to Graves' disease. Antithyroid medication was started, but there was no effect on laboratory results. In addition, he developed symptoms which subsequently could be attributed to iatrogenic hypothyroidism. Biotin interference, when assaying TSH and thyroxin, was suspected. Upon further investigation, the patient revealed to use high doses of biotin. After discontinuation of the biotin treatment, the thyroid function test normalized. CONCLUSION: It is expected that in the future, patients with multiple sclerosis will use biotin more often. Therefore, it is important for healthcare professionals to be aware that biotin can interfere with immunoassays for thyroid hormones, to avoid misdiagnosis and unnecessary treatment for hyperthyroidism.

Serum selenium and selenoprotein-P levels in autoimmune thyroid diseases patients in a select center: a transversal study

ABSTRACT Objective: Selenium (Se) supplementation has been used to help prevent the progression of Graves' ophthalmopathy (GO) and autoimmune thyroid diseases (AITD) patients. We investigated Se serum and selenoprotein P (SePP) levels in Graves' disease (GD) with and without GO, Hashimoto's thyroiditis (HT) patients and in 27 control individuals (C). Subjects and methods: We studied 54 female and 19 male patients: 19 with GD without GO, 21 GD with GO, 14 with HT and 19 with HT+LT4. Se values were measured using graphite furnace atomic absorption spectrophotometry. Serum SePP levels were measured by ELISA. Results: Median Se levels were similar among all groups; GD patients: 54.2 (46.5-61.1 μg/L), GO: 53.6 (43.5-60.0 μg/L), HT: 51.9 (44.6-58.5 μg/L), HT+LT4 54.4 (44-63.4) and C group patients: 56.0 (52.4-61.5 μg/L); P = 0.48. However, serum SePP was lower in GO patients: 0.30 (0.15-1.05 μg/mL) and in HT patients: 0.35 (0.2-1.17 μg/mL) compared to C group patients: 1.00 (0.564.21 μg/mL) as well as to GD patients: 1.19 (0.62-2.5 μg/mL) and HT+LT4 patients: 0.7 (0,25-1.95); P = 0.002. Linear regression analysis showed a significant relationship between SePP and TPOAb values (r = 0.445, R2 = 0.293; P < 0.0001). Multiple regression analysis found no independent variables related to Se or SePP. Conclusion: A serum Se concentration was lower than in some other countries, but not significantly among AITD patients. The low serum SePP levels in GO and HT patients seems to express inflammatory reactions with a subsequent increase in Se-dependent protein consumption remains unclear.

Impaired Metabolism of Selenomethionine in Graves' Disease: A Biokinetics Study of Soft Gel Capsule Formulation.

Patients with Graves' disease are known to have low selenium (Se) status, Se supplementation resulting in clinical and biochemical improvement. Selenomethionine (SeMet) in a new soft gel capsule formulation was used in a pilot study in 6 patients with acute Graves' disease and low selenium levels (61.3±12.9 µg/l) before and in 4/6 patients 3 months after combined treatment with methimazole and SeMet 200 µg/day (113.3±46.3 µg/l), as well as in 6 euthyroid controls (82±11.8 µg/l). The biokinetics were studied following ingestion of 200 µg SeMet (single dose) soft gel capsule, Se serum concentrations being measured at various time points within 24 h. Se levels rose variably in all patients and controls. While levels peaked in all subjects following 8 h of intake, the increase was somewhat slower in acute hyperthyroidism as compared to 3 months later when these patients had been rendered euthyroid, this possibly due to derangement of Se storage capacity by SEPP or increased requirements in the acute phase of the disease, leading to depletion of the trace element. The compound was shown to be bioavailable and safe and patients treated for 3 months exhibited higher Se levels at the different time points. These findings are of major importance for sufferers of GD since they indicate that early Se supplementation, with its beneficial antioxidant impact on inflammatory activity, could slow, or possibly even forestall, the clinical progression of the disease.

Does vitamin D play a role in autoimmune endocrine disorders? A proof of concept.

In the last few years, more attention has been given to the "non-calcemic" effect of vitamin D. Several observational studies and meta-analyses demonstrated an association between circulating levels of vitamin D and outcome of many common diseases, including endocrine diseases, chronic diseases, cancer progression, and autoimmune diseases. In particular, cells of the immune system (B cells, T cells, and antigen presenting cells), due to the expression of 1α-hydroxylase (CYP27B1), are able to synthesize the active metabolite of vitamin D, which shows immunomodulatory properties. Moreover, the expression of the vitamin D receptor (VDR) in these cells suggests a local action of vitamin D in the immune response. These findings are supported by the correlation between the polymorphisms of the VDR or the CYP27B1 gene and the pathogenesis of several autoimmune diseases. Currently, the optimal plasma 25-hydroxyvitamin D concentration that is necessary to prevent or treat autoimmune diseases is still under debate. However, experimental studies in humans have suggested beneficial effects of vitamin D supplementation in reducing the severity of disease activity. In this review, we summarize the evidence regarding the role of vitamin D in the pathogenesis of autoimmune endocrine diseases, including type 1 diabetes mellitus, Addison's disease, Hashimoto's thyroiditis, Graves' disease and autoimmune polyendocrine syndromes. Furthermore, we discuss the supplementation with vitamin D to prevent or treat autoimmune diseases.

Clinical efficacy of Yingliu mixture combined with metimazole for treating diffuse goitre with hyperthyroidism and its impact on related cytokines.

CONTEXT: Yingliu mixture was developed in 1990s by Affiliated Longhua Hospital of Shanghai University of Traditional Chinese Medicine, for treating diffuse goitre with hyperthyroidism (Graves' disease, GD). Former studies have shown Yingliu mixture combined with methimazole (Y-M) can effectively improve thyroid function and decrease thyrotropin-receptor antibody level. Furthermore, we researched its impact on related cytokines to prove that Y-M improve patients' immunity status. OBJECTIVE: To observe the clinical efficacy of Y-M for treating GD. METHODS: A total of 120 GD patients were randomly divided into two groups, the treatment and the control groups (n = 60). The treatment group's patients were treated with Y-M. The control group's patients were treated with methimazole alone. Yingliu mixture was orally administered, 25 mL three times daily. Methimazole was administered at 5-25 mg/day. After 12 weeks of the treatment, the cytokines, antibodies related to thyroid function, and Chinese medical syndromes were evaluated. RESULTS: After the treatment, the free triiodothyronine and thyroxine levels in both groups decreased. The thyroid-stimulating hormone level increased in the treatment group. The thyrotropin-receptor antibody levels and TNF-α levels decreased in both groups. In the control group, IL-6 and IFN-γ levels were lower than that before the treatment. In the treatment group, CD4+ and CD25+ levels were higher than pretreatment levels, but IL-10 levels were reduced. CLINICAL SYMPTOMS: the total CMS scores for both groups decreased. CONCLUSIONS: The Y-M combination can improve thyroid function, and decrease autoantibodies, cytokines, and clinical symptoms, so its efficacy may surpass that of methimazole alone.

Serum selenium and selenoprotein-P levels in autoimmune thyroid diseases patients in a select center: a transversal study.

OBJECTIVE: Selenium (Se) supplementation has been used to help prevent the progression of Graves' ophthalmopathy (GO) and autoimmune thyroid diseases (AITD) patients. We investigated Se serum and selenoprotein P (SePP) levels in Graves' disease (GD) with and without GO, Hashimoto's thyroiditis (HT) patients and in 27 control individuals (C). SUBJECTS AND METHODS: We studied 54 female and 19 male patients: 19 with GD without GO, 21 GD with GO, 14 with HT and 19 with HT+LT4. Se values were measured using graphite furnace atomic absorption spectrophotometry. Serum SePP levels were measured by ELISA. RESULTS: Median Se levels were similar among all groups; GD patients: 54.2 (46.5-61.1 µg/L), GO: 53.6 (43.5-60.0 µg/L), HT: 51.9 (44.6-58.5 µg/L), HT+LT4 54.4 (44-63.4) and C group patients: 56.0 (52.4-61.5 µg/L); P = 0.48. However, serum SePP was lower in GO patients: 0.30 (0.15-1.05 µg/mL) and in HT patients: 0.35 (0.2-1.17 µg/mL) compared to C group patients: 1.00 (0.564.21 µg/mL) as well as to GD patients: 1.19 (0.62-2.5 µg/mL) and HT+LT4 patients: 0.7 (0,25-1.95); P = 0.002. Linear regression analysis showed a significant relationship between SePP and TPOAb values (r = 0.445, R2 = 0.293; P < 0.0001). Multiple regression analysis found no independent variables related to Se or SePP. CONCLUSION: A serum Se concentration was lower than in some other countries, but not significantly among AITD patients. The low serum SePP levels in GO and HT patients seems to express inflammatory reactions with a subsequent increase in Se-dependent protein consumption remains unclear.

Factitious Graves' Disease Due to Biotin Immunoassay Interference-A Case and Review of the Literature.

CONTEXT: Biotin (vitamin B7) is an essential co-factor for four carboxylases involved in fatty acid metabolism, leucine degradation, and gluconeogenesis. The recommended daily intake (RDI) of biotin is approximately 30 µg per day. Low-moderate dose biotin is a common component of multivitamin preparations, and high-dose biotin (10 000 times RDI) has been reported to improve clinical outcomes and quality of life in patients with progressive multiple sclerosis. Biotin is also a component of immunoassays, and supplementation may cause interference in both thyroid and non-thyroid immunoassays. OBJECTIVE: To assess whether biotin ingestion caused abnormal thyroid function tests (TFTs) in a patient through assay interference. DESIGN: We report a patient with biotin-associated abnormal TFTs and a systematic review of the literature. SETTING: A tertiary endocrine service in Hamilton, New Zealand. RESULTS: The patient had markedly abnormal TFTs that did not match the clinical context. After biotin cessation, TFTs normalized far more rapidly than possible given the half-life of T4, consistent with assay interference by biotin. Multiple other analytes also tested abnormal in the presence of biotin. CONCLUSION: Biotin ingested in moderate to high doses can cause immunoassay interference. Depending on the assay format, biotin interference can result in either falsely high or low values. Interference is not limited to thyroid tests and has the potential to affect a wide range of analytes. It is important for clinicians to be aware of this interaction to prevent misdiagnosis and inappropriate treatment.

Misdiagnosis of Graves' Disease with Apparent Severe Hyperthyroidism in a Patient Taking Biotin Megadoses.

BACKGROUND: Accurate immunoassays measuring minute quantities of hormones are the cornerstone of the practice of endocrinology. Despite tremendous advances in this field, novel pitfalls in these tests emerge from time to time. Oral biotin can interfere with immunoassays of several hormones. The purpose of this report is to relate an extreme case of such interference. PATIENT FINDINGS: A patient with progressive multiple sclerosis was found to have extremely elevated free thyroxine, triiodothyronine, and suppressed thyrotropin (TSH) levels. His TSH receptor binding inhibiting antibody level was also elevated. This constellation of laboratory findings suggested a diagnosis of severe Graves' disease. All of the assays yielding abnormal results employed the biotin-streptavidin affinity in their design. The patient had no symptoms of hyperthyroidism, and detailed review of his medications revealed intake of megadoses of biotin. Temporary discontinuation of biotin treatment resulted in complete resolution of the biochemical abnormalities. CONCLUSIONS: Non-physiologic biotin supplementation may interfere with several immunoassays, including thyroid hormones, TSH, thyroglobulin, and TSH receptor binding inhibiting antibody, leading to erroneous diagnoses. Questioning for biotin intake should be part of the evaluation for patients undergoing endocrine tests. Interruption of biotin supplementation for at least two days prior to biotin-sensitive tests should be sufficient to avoid major misdiagnoses.

Calcium maelstrom: recalcitrant hypocalcaemia following rapid correction of thyrotoxicosis, exacerbated by pregnancy.

A 29-year-old pregnant woman with Graves' disease presented with severe persistent hypocalcaemia after thyroidectomy. Six months prior to presentation she was diagnosed with Graves' disease and remained uncontrolled with methimazole. She was confirmed pregnant prior to radioactive iodine ablation (RAI), and underwent total thyroidectomy during her second trimester. After surgery, continuous intravenous calcium infusion was required until delivery of the fetus allowed discontinuation at postoperative day 18, despite oral calcium and calcitriol administration. A total of 38 g of oral and 7.5 g of intravenous elemental calcium was administered. We report an unusual case of recalcitrant hypocalcaemia thought to be due to a combination of postoperative hypoparathyroidism, combined with thyrotoxic osteodystrophy and pregnancy, after surgical correction of Graves' disease. Increased vigilance and early calcium supplementation should be a priority in the management of these patients.

Vitamin D and thyroid disease: to D or not to D?

The main role of vitamin D is to maintain calcium and phosphorus homeostasis, thus preserving bone health. Recent evidence has demonstrated that vitamin D may also have a role in a variety of nonskeletal disorders such as endocrine diseases and in particular type 1 diabetes, type 2 diabetes, adrenal diseases and polycystic ovary syndrome. Low levels of vitamin D have also been associated with thyroid disease, such as Hashimoto's thyroiditis. Similarly, patients with new-onset Graves' disease were found to have decreased 25-hydroxyvitamin D concentrations. Impaired vitamin D signaling has been reported to encourage thyroid tumorigenesis. This review will focus on the role of vitamin D in thyroid diseases, both autoimmune diseases and thyroid cancer, and will summarize the results of vitamin D supplementation studies performed in patients with thyroid disorders. Although observational studies support a beneficial role of vitamin D in the management of thyroid disease, randomized controlled trials are required to provide insight into the efficacy and safety of vitamin D as a therapeutic tool for this dysfunction.

Mechanisms in endocrinology: vitamin D as a potential contributor in endocrine health and disease.

OBJECTIVE: It has been suggested that vitamin D may play a role in the pathogenesis of several endocrine diseases, such as hyperparathyroidism, type 1 diabetes (T1DM), type 2 diabetes (T2DM), autoimmune thyroid diseases, Addison's disease and polycystic ovary syndrome (PCOS). In this review, we debate the role of vitamin D in the pathogenesis of endocrine diseases. METHODS: Narrative overview of the literature synthesizing the current evidence retrieved from searches of computerized databases, hand searches and authoritative texts. RESULTS: Evidence from basic science supports a role for vitamin D in many endocrine conditions. In humans, inverse relationships have been reported not only between blood 25-hydroxyvitamin D and parathyroid hormone concentrations but also with risk of T1DM, T2DM, and PCOS. There is less evidence for an association with Addison's disease or autoimmune thyroid disease. Vitamin D supplementation may have a role for prevention of T2DM, but the available evidence is not consistent. CONCLUSIONS: Although observational studies support a potential role of vitamin D in endocrine disease, high quality evidence from clinical trials does not exist to establish a place for vitamin D supplementation in optimizing endocrine health. Ongoing randomized controlled trials are expected to provide insights into the efficacy and safety of vitamin D in the management of endocrine disease.

Thyrotoxic hypokalaemic periodic paralysis: a rare presentation of Graves' disease in a Hispanic patient.

A 26-year-old Hispanic man with no significant medical history presented to our emergency room with gradual onset weakness of his lower extremities. He was haemodynamically stable and examination revealed loss of motor function in his lower limbs up to the level of hips. Laboratory data revealed hypokalaemia. The patient was started on potassium supplementation and he recovered his muscle strength. Differential diagnosis included familial hypokalaemic periodic paralysis and thyrotoxic periodic paralysis (TPP). Further investigations revealed a low thyroid-stimulating hormone and high free thyroxine levels. Radio iodine 123 scan revealed an enhanced homogeneous uptake in the thyroid suggesting Graves' disease. Thyroid stimulating antibodies were also found to be elevated. The patient was started on methimazole and propranolol and he never had another attack of TPP even at 1 year follow-up.