Research on Intra-Operative Indocyanine Green Angiography of the Parathyroid for Predicting Postoperative Hypoparathyroidism: A Noninferior Randomized Controlled Trial

Objective: A noninferiority randomized controlled trial was undertaken to clarify whether the postoperative measurements of serum calcium and parathyroid hormone and oral supplementation of calcium and calcitriol could be omitted if patients had at least one well-perfused parathyroid gland evaluated by intra-operative indocyanine green (ICG) angiography.Methods: Patients with at least one parathyroid gland well-perfused by ICG angiography (ICG score >2) were randomized to the control group or test group. For the control group, oral calcium and calcitriol were systematically supplemented. For the test group, no oral calcium or calcitriol was supplemented to the patients. Levels of serum calcium and parathyroid hormone of patients on the first and 30th postoperative day were compared between the two groups.Results: Among all 68 selected patients, 56 patients had at least one well-perfused parathyroid gland evaluated by intra-operative ICG angiography. The 56 patients were randomized to the control group or test group. There were no statistically significant differences in the levels of serum calcium and parathyroid hormone between test group and control group on the first or 30th postoperative day.Conclusion: The postoperative measurements of serum calcium and parathyroid hormone and oral supplementation of calcium and calcitriol were evaluated as redundant, if patients had at least one well-perfused parathyroid gland evaluated by intra-operative ICG angiography.Abbreviations: ICG = indocyanine green; NIR = near infrared; POD = postoperative day; PTH = parathyroid hormone; SBR = signal background ratio     

American Association of Clinical Endocrinologists and American College of Endocrinology Disease State Clinical Review: Postoperative Hypoparathyroidism - Definitions and Management

Abbreviations: BID = bis in die DSPTC = diffuse sclerosing papillary thyroid cancer FNA = fine-needle aspiration HT = Hashimoto thyroiditis iPTH = intact parathyroid hormone 25OHD = 25-hydroxy vitamin D PTH = parathyroid hormone TPO = thyroid peroxidase US = ultrasonography     

Subacute thyroiditis manifesting as a thyroid mass, vocal cord paralysis, and hypercalcemia

ObjectiveTo report a case of subacute thyroiditis manifesting as a thyroid mass, vocal cord paralysis, and hypercalcemia.MethodsWe describe the clinical, laboratory, and radiologic findings in a patient with an unusual clinical course of subacute thyroiditis.ResultsA 65-year-old woman presented with a hoarse voice and an enlarging tender mass in the right side of the neck. On admission, thyroid function was consistent with thyrotoxicosis from subacute thyroiditis. Laboratory studies showed a corrected serum calcium concentration of 11.4 mg/dL, intact parathyroid hormone of 125 pg/mL, 25-hydroxyvitamin D of 12 ng/mL, and creatinine of 1.8 mg/dL. Computed tomography of the neck without use of a contrast agent showed a heterogeneous mass in the right side of the neck in conjunction with deviation of the trachea from right to left but without invasion of the trachea. Thyroid ultrasonography disclosed a heterogeneous mass in the right thyroid lobe measuring 4.7 cm by 5.5 cm by 4.5 cm. Flexible laryngoscopy revealed right vocal cord paralysis. Treatment with a course of prednisone yielded normalization of the serum calcium level, improvement in her voice, and a decrease in size of the thyroid mass. Four months after initial presentation of the patient, thyroid hormone levels became normal, she was clinically euthyroid, and she had a full recovery of her voice. Her serum calcium concentration was normal (9.8 mg/dL) in association with a near-normal parathyroid hormone level of 90 pg/mL. The 25-hydroxyvitamin D and creatinine values were also normal. Repeated thyroid ultrasonography showed a smaller right thyroid lobe with a dominant nodule measuring 2.0 cm by 1.3 cm by 1.4 cm in the right upper pole.ConclusionThis case illustrates that subacute thyroiditis can have the unusual initial manifestations of a thyroid mass, vocal cord paralysis, and hypercalcemia. In similar patients, a trial of corticosteroid therapy may be warranted in an effort to improve clinical symptoms and thus avoid unnecessary surgical treatment. (Endocr Pract. 2012;18:e17-e20)     

No Longterm Severe Thyroid Dysfunction Seen In Patients With Preexisting Reduced Serum Tt3 Concentrations After A Single Large Dose Of Iodinated Contrast

Objective: After an intravenous bolus injection of 100 mL of iodinated contrast agent (370 mgI/mL), the amount of iodine atoms entering the blood is tens of thousands of times the daily dose of iodine recommended by the World Health Organization. However, the effect of iodinated contrast in patients with nonthyroidal illness, manifested as reduced serum total triiodothyronine (TT3) concentrations, is unclear. We studied the effect of iodinated contrast on thyroid function and auto-antibodies in patients with reduced TT3 after diagnosis and treatment of coronary heart disease.Methods: This was a prospective cohort study. One hundred and fifty-four stable angina pectoris patients with reduced TT3 and normal thyroid-stimulating hormone (TSH), free thyroxine (FT4), and reverse triiodothyronine (rT3) were enrolled from January, 2017, to June, 2018. All subjects had no history of thyroid dysfunction and had no recent infections, tumors, trauma, or other critical illnesses. Fourty-one patients underwent coronary angiography and 113 patients underwent coronary intervention.Results: There were 6 patients (3.9%) with hypothyroidism and 30 patients (19.5%) developed subclinical hypothyroidism (SCHypo) on the first day after surgery. There were 6 patients (3.9%) with hypothyroidism, 6 patients (3.9%) with SCHypo, and 18 patients (11.7%) with subclinical hyperthyroidism (SCHyper) at the first month postsurgery. There were 23 patients (14.9%) with SCHyper and 6 patients (3.9%) with SCHypo at the sixth month after surgery. No patient with longterm severe thyroid dysfunction occurred during follow-up. The levels of free triiodothyronine, FT4, TT3, total thyroxine, and TSH showed statistically significant changes at 1 day, and 1, 3, and 6 months postoperative (P<.005). The level of rT3 showed no statistically significant change at 1, 3, and 6 months postoperative (P>.05). The levels of thyroglobulin antibody and thyroid peroxidase antibody decreased at 6 months postoperative (P<.001).Conclusion: The risk of subclinical thyroid dysfunction and transient hypothyroidism occurred with a single large dose of iodinated contrast in the diagnosis and treatment of coronary heart disease, but no longterm severe thyroid dysfunction occurred. Patients with preoperative thyroid antibody elevation were more likely to have subclinical thyroid dysfunction after surgery.Abbreviations: FT3 = free triiodothyronine; FT4 = free thyroxine; PCI = percutaneous coronary intervention; rT3 = reverse triiodothyronine; SCHyper = subclinical hyperthyroidism; SCHypo = subclinical hypothyroidism; TGAB = thyroglobulin antibody; TPOAB = thyroid peroxidase antibody; TT3 = total triiodothyronine; TT4 = total thyroxine; TSH = thyroid-stimulating hormone; WHO = World Health Organization     

Effect of Post-Surgical Rai Therapy on Parathyroid Function in Patients with Differentiated Thyroid Cancer

Objective: Radiotherapy with radioactive iodine (RAI) has become a common treatment for postsurgical differentiated thyroid carcinoma (DTC). The objective of this study was to determine the effect of RAI therapy following surgery on the function of the parathyroid glands in DTC patients.Methods: A total of 81 DTC patients who received RAI therapy after surgery were enrolled in the study. The size of the residual thyroid was detected by technetium-99m (^99mTc)-pertechnetate thyroid scan (^99mTc thyroid scan) before RAI therapy. The iodine uptake ability of residual thyroid was evaluated by iodine-131 (¹³¹I) whole-body scan (WBS). All patients were treated with an activity of 3.7 GBq (100 mCi) ¹³¹I. Parathyroid hormone (PTH), serum calcium, phosphorus, and magnesium were evaluated at 1 day before treatment, and at 1 month and 3 months after treatment.Results: The results show that there was no statistically significant difference in blood PTH level observed (P>.05) between 3 time points (pre-treatment, 1 month post-treatment and 3 months post-treatment). The serum calcium and phosphorus did not change significantly (P>.05), but serum magnesium level was elevated after treatment (P<.05). There were no significant differences between PTH changes and sex, age, scores of ^99mTc thyroid scan, scores of ¹³¹I WBS, Tumor (T) stage, and Node (N) stage.Conclusion: RAI therapy following surgery did not significantly affect parathyroid function in DTC patients.Abbreviations: ATA = American Thyroid Association; DTC = differentiated thyroid carcinoma; FT3 = free triiodothyronine; FT4 = free thyroxine; 131I = iodine-131; PTH = parathyroid hormone; RAI = radioiodine; 99mTc = Technetium-99m; TG = thyroglobulin; TNM = Tumor Node Metastasis; TSH = thyroid-stimulating hormone; WBS = whole-body scan     

小剂量糖皮质激素联合消炎痛治疗亚急性甲状腺炎的临床效果

目的:探讨小剂量糖皮质激素联合消炎痛治疗亚急性甲状腺炎(Subacute thyroiditis,ST)的临床效果及安全性。方法:选取我院内分泌科2012年6月-2014年7月收治的150例亚急性甲状腺炎患者,按照随机平均原则即药物治疗的不同将其分为三组,每组50例,即泼尼松与消炎痛联合治疗(A组)、泼尼松单独治疗(B组)、消炎痛单独治疗(C组),对比并分析三组的治疗效果,包括甲状腺疼痛和肿大平均消失时间,治疗1周的ESR平均水平,治疗4周后的血清TSH、FT3、FT4水平,并通过随访,观察治疗后8周患者不良反应的发生率、复发率。结果:(1)A组患者甲状腺疼痛和甲状腺肿大的消失时间与B组比较无显著差异(P0.05),A、B组均显著短于C组(P0.05)。A组患者治疗后1周、4周的ESR水平与B组对比差异不明显,无统计学意义(P0.05);A、B组患者治疗后1周的ESR水平明显低于C组(P0.05)。A、B组治疗后的血清TSH、FT3、FT4水平改善程度均优于C组,差异有统计学意义(P0.05)。(2)A组、C组的不良反应发生率、复发率均低于B组,差异具有统计学意义(P0.05)。结论:采用小剂量糖皮质激素联合消炎痛治疗亚急性甲状腺炎的临床效果显著,且不良反应和复发情况少。     

Unknown and Already Known Thyroid Abnormalities in Primary Hyperparathyroidism

Objective: Primary hyperparathyroidism (PHPT) and thyroid diseases are highly prevalent in the general population, but the putative link between the 2 conditions remains unclear.Methods: A monocentric consecutive series of 434 patients with PHPT was retrospectively evaluated by lab and ultrasonography to look for thyroid abnormalities. Patients were classified in 3 groups: without thyroid abnormalities (group 1, n = 171), with thyroid diseases not previously known (group 2a, n = 69), and thyroid diseases previously known (group 2b, n = 194).Results: In terms of thyroid disease, no significant difference was found between groups 2a and 2b, except for the significantly larger number of patients with toxic nodular goiter in group 2b. PHPT was more frequently symptomatic in group 2a than in group 2b, despite no differences in serum calcium, creatinine, parathyroid hormone (PTH), or 25-hydroxyvitamin D (25OHD) levels.Conclusion: A total of 60% of PHPT patients had a thyroid disease that was unknown prior to PHPT diagnosis in almost one-third of cases. The newly diagnosed and previously known thyroid diseases were similar, both mostly affecting postmenopausal females.Abbreviations: Ab = antibody; aPHPT = asymptomatic PHPT; 25OHD = 25-hydroxyvitamin D; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; Tg = thyroglobulin; TPO = thyroperoxidase; TSH = thyroid-stimulating hormone; US = ultrasound     

Destructive Thyroiditis Followed by Hypothyroidism Associated with Infliximab Therapy

ObjectiveTo present the rare case of a patient who developed destructive thyroiditis accompanied by transient thyrotoxicosis resulting from infliximab therapy for the treatment of psoriasis.MethodsThe clinical presentation and management of a case with infliximab-associated thyroiditis is described with a brief review of the literature.ResultsA 57-year-old male who suffered from psoriasis was treated with infliximab therapy for 4 years. Thyroid function tests were normal before infliximab therapy. When the patient presented in our clinic, he had thyrotoxicosis and was using propylthiouracil. A 99m Technetiumpertechnetate thyroid scintigraphy scan showed no visualization of either thyroid lobe or decreased thyroid iodine uptake. Thyroid-stimulating hormone (TSH) receptor antibody, thyroid peroxidase antibody (anti-TPO Ab) and thyroglobulin antibody (anti-Tg Ab) were negative. Thyroid ultrasonography revealed a heterogeneous thyroid gland without nodules. After stopping propylthiouracil therapy, we advised monitoring of his thyroid function tests in the following weeks, and infliximab therapy for psoriasis was continued. Four weeks later, his thyroid function tests showed an elevated TSH level with normal levels of free triiodothyronine and thyroxine (FT3 and FT4, respectively), and levothyroxine treatment was administered to the patient. Thyroid function tests normalized after levothyroxine treatment. One year later, infliximab therapy was stopped because of clinical remission. Simultaneously, levothyroxine treatment was also stopped. His thyroid function tests were normal 6 weeks after the cessation of levothyroxine treatment.ConclusionTo our knowledge, the present report is the third infliximab-associated thyroid disorder case. Periodic follow-up of thyroid function tests is necessary during infliximab therapy. (Endocr Pract. 2014;20:e207-e210)     

The Correlation Between Metabolic Disorders And Tpoab/Tgab: A Cross-Sectional Population-Based Study

Objective: Studies have shown that metabolic abnormalities influence the immune system. Because the prevalence of metabolic and autoimmune thyroid diseases has increased synchronously, the correlation between them was worth exploring. The study objective was to investigate the relationship between metabolic disorders and thyroid auto-antibodies in euthyroid subjects.Methods: Data were obtained from the Thyroid Diseases and Diabetes Mellitus project survey of 55,891 subjects from 31 provinces in China. The body mass index (BMI), waist circumference (WC), blood pressure, thyroid peroxidase antibodies (TPOAbs), thyroglobulin antibodies (TgAbs), thyroid-stimulating hormone (TSH), urinary iodine concentration, blood glucose, lipid profile, and uric acid levels were evaluated. Free thyroxine and free triiodothyronine levels were measured in patients with abnormal serum TSH levels.Results: In males, the BMI, WC, systolic blood pressure (SBP), diastolic blood pressure (DBP), and 2-hour post-glucose oral glucose tolerance test results of the TPOAb-/TgAb-positive group were significantly higher than those of the TPOAb-/TgAb-negative group. In females, the BMI, WC, SBP, DBP, total cholesterol, and low-density-lipoprotein cholesterol (LDL-C) in the TPOAb-/TgAb-positive group were significantly increased compared to the TPOAb-/TgAb-negative group. Multivariate analysis showed that in males, the odds ratio (OR) of positive TgAbs in the abdominal obesity group was 1.175 (95% confidence interval [CI], 1.016 to 1.359; P = .03), and the OR of positive TPOAbs in the hyperuricemia group was 1.195 (95% CI, 1.041 to 1.372; P = .011). In females, the OR of positive TgAbs was 1.19 (95% CI, 1.068 to 1.326; P = .002) in the high LDL-C group.Conclusion: Obesity, high LDL-C, and hyperuricemia were positively correlated with the prevalence of positive thyroid autoantibodies in euthyroid subjects in a gender-dependent manner. This cross-sectional survey showed that metabolic disorders are associated with increased positive thyroid autoantibody levels in euthyroid subjects in a gender-dependent manner.Abbreviations: AIT = autoimmune thyroiditis; BMI = body mass index; CI = confidence interval; DBP = diastolic blood pressure; FPG = fasting plasma glucose; FT3 = free triiodothyronine; FT4 = free thyroxine; HbA1c = glycated hemoglobin; HDL-C = high-density-lipoprotein cholesterol; LDL-C = low-density-lipoprotein cholesterol; OGTT2hPG = oral glucose tolerance test 2-hours post-glucose; OR = odds ratio; SBP = systolic blood pressure; TC = total cholesterol; TG = triglycerides; TgAb = thyroglobulin antibody; TPOAb = thyroid peroxidase antibody; TSH = thyroid-stimulating hormone; UA = uric acid; WC = waist circumference     

Baseline TSH Level is Associated with Risk of Anti–PD-1–Induced Thyroid Dysfunction

Objective: To characterize anti–programmed cell death 1 (PD-1)–induced thyroid immune-related adverse events (irAEs) in metastatic melanoma patients treated at our institution and to identify risk factors associated with their development.Methods: We reviewed the files of 154 patients with metastatic melanoma treated with PD-1 inhibitors at a single institution from November 1, 2011, to February 28, 2017. The association of thyroid irAEs within 120 days posttreatment initiation with age, gender, melanoma characteristics, treatment protocol, and baseline thyroid-stimulating hormone (TSH) was examined.Results: Overall, 42.4% developed thyroid dysfunction following treatment, including 20.2% (20/99) subclinical thyroid dysfunction, 13.1% (13/99) overt hypothyroidism, and 9.1% (9/99) overt hyperthyroidism. Of those that developed overt hyperthyroidism, 8 progressed to overt hypothyroidism, consistent with thyroiditis. Age, gender, melanoma characteristics, or treatment protocol did not modify the risk of developing thyroid irAEs. Higher baseline TSH was observed in patients who developed overt hypothyroidism versus hyperthyroidism versus those who remained euthyroid (P = .05). A pretreatment TSH >2.19 mIU/mL was associated with an increased risk of overt thyroid dysfunction (odds ratio, 3.46; 95% confidence interval, 1.2 to 9.8).Conclusion: Thyroid dysfunction following treatment with PD-1 inhibitors is common, and patients with a higher baseline TSH appear to be at increased risk. Such patients may benefit from closer monitoring of their thyroid function following initiation of anti PD-1 agents.Abbreviations: CTLA-4 = cytotoxic T-lymphocyte antigen 4; FT3 = free triiodothyronine; FT4 = free thyroxine; irAE = immune-related adverse event; PD-1 = programmed cell death 1; TFT = thyroid function test; TPO = thyroid peroxidase; TSH = thyroid-stimulating hormone     

Primary Hyperparathyroidism: Comparing Between Solid and Cystic Adenomas and the Efficacy of Ultrasound and Single-Photon Emission Computed Tomography in their Diagnosis

Objective: Primary hyperparathyroidism (PHPT) is a disorder that results from abnormal functioning of the parathyroid glands. The purpose of this study was to compare cystic and solid adenomas by analyzing different variables associated with PHPT and parathyroid adenomas (age, calcium, phosphorus, and parathyroid hormone &lsqb;PTH] levels, adenoma volume) while comparing the efficacy of ultrasound and single-photon emission computed tomography in differentiating between both types of adenoma.Methods: From 152 patients diagnosed with PHPT between January 2013 and 2014, only 109 patients who had positive ultrasonographic findings for single parathyroid adenoma were included in the study.Results: A total of 26 patients had cystic adenomas and 83 patients had solid adenomas. Sestamibi (MIBI) was negative in 50% of the cystic adenoma group and 27.7% of the solid adenoma group, with an overall technetium-MIBI efficacy of 67%. Age, phosphorus level, and adenoma volume were significantly higher in patients with cystic adenomas (P = .001, P = .02, and P = .02, respectively), whereas calcium and PTH levels were significantly higher in patients with solid adenomas (P = .02, P = .038, respectively). MIBI had a significant correlation with PTH levels (P = .031) and adenoma volume (P = .05) only in patients with solid adenomas. No significant correlation was found between sex and type of parathyroid adenoma.Conclusion: The current study is the first to compare age, PTH levels, and adenoma volume between cystic and solid adenoma patients, providing more information for the poorly understood pathology of cystic adenomas. Our findings showed that age and calcium and PTH levels are significantly higher in patients with solid adenomas, whereas adenoma volume and phosphorus levels are significantly higher in patients with cystic adenomas.Abbreviations: BMD = bone mineral density GFR = glomerular filtration rate iPTH = intact parathyroid hormone MIBI = sestamibi PHPT = primary hyperparathyroidism PTH = parathyroid hormone SPECT = single-photon emission computed tomography Tc = technetium US = ultrasound     

Management of Thyrotoxicosis: Preconception,Pregnancy, and the Postpartum Period

Objective: To review the diagnosis and management of thyrotoxicosis in women who are preconception, pregnant, and in the postpartum period.Methods: Literature review of English-language papers published between 1980 and 2018.Results: Overt thyrotoxicosis occurs in 0.2% of pregnancies and subclinical thyrotoxicosis in 2.5%. Hyperthyroidism in women of childbearing age most frequently is caused by Graves disease (GD). Gestational thyrotoxicosis, transient human chorionic gonadotropin (hCG)-mediated hyperthyroidism, may develop in the first trimester. In the first year following delivery, postpartum thyroiditis, which frequently includes a thyrotoxic phase, occurs in 5% of women. Hyperthyroidism from nodular autonomy is uncommon in women of childbearing age. It is essential to understand the underlying etiology for thyrotoxicosis in order to recommend appropriate treatment. Gestational thyrotoxicosis requires supportive care, without antithyroid drug therapy. GD may be treated with antithyroid drugs, radioactive iodine, or thyroidectomy. Pregnancy, plans for pregnancy, and lactation have important implications for the choice of GD treatment. When thyrotoxicosis presents following delivery, postpartum thyroiditis must be differentiated from GD.Conclusion: The diagnosis and management of thyrotoxicosis in the peripregnancy period present specific challenges. In making management decisions, it is essential to weigh the risks and benefits of treatments not just for the mother but also for the fetus and for breastfed infants. A team approach to management is critical, with close collaboration among endocrinologists, maternal-fetal medicine specialists, and neonatologists.Abbreviations: GD = Graves disease; hCG = human chorionic gonadotropin; MMI = methimazole; PPT = postpartum thyroiditis; PTU = propylthiouracil; T3 = triiodothyronine; T4 = thyroxine; TBG = thyroxine-binding globulin; TRAb = TSH receptor antibody; TSH = thyroid-stimulating hormone     

An Open-Label Extension Study of Parathyroid Hormone Rhpth(1-84) in Adults with Hypoparathyroidism

Objective: Hypoparathyroidism is characterized by inadequate parathyroid hormone (PTH), resulting in hypocalcemia, hyperphosphatemia, and bone abnormalities. Adults with hypoparathyroidism treated with recombinant human PTH, rhPTH(1-84), in the 24-week, phase III REPLACE study maintained serum calcium despite reductions in oral calcium and active vitamin D. This study assessed the long-term efficacy and safety of rhPTH(1-84) for hypoparathyroidism.Methods: This was a 24-week, open-label, flexible-dose extension study of REPLACE (REPEAT) conducted in 3 outpatient centers in Hungary. Patients who previously completed or enrolled in REPLACE received 50 μg/day rhPTH(1-84), escalated to 75 and then to 100 μg/day, if needed, to reduce active vitamin D and oral calcium. The primary endpoint was ≥50% reduction in oral calcium (or ≤500 mg/day) and active vitamin D (or calcitriol ≤0.25 μg/day or alfacalcidol ≤0.50 μg/day) with normocalcemia.Results: Twenty-four patients (n = 16 previously treated with rhPTH[1-84]; n = 8 rhPTH[1-84]-naïve) were enrolled and completed the study. At Week 24, 75% of patients (95% confidence interval [CI], 53.3–90.2%) achieved the study endpoint; 58% eliminated oral calcium and active vitamin D. Urinary calcium, serum phosphate, and calcium × phosphate (Ca × P) product decreased by Week 24. Mean serum bone turnover markers increased with rhPTH(1-84). Treatment-emergent adverse events (TEAEs) were reported by 92% of patients. No serious adverse events (AEs) occurred.Conclusion: This study used a simplified treatment algorithm intended to better mimic typical clinical practice and demonstrated the extended efficacy and safety of rhPTH(1-84) in patients with hypoparathyroidism and confirmed the REPLACE findings. Sustained rhPTH(1-84) efficacy up to 48 weeks was observed despite treatment interruption between studies.Abbreviations:AE = adverse eventBMD = bone mineral densityBSAP = bone-specific alkaline phosphataseBTM = bone turnover markerCa × P product = calcium × phosphate productCTX = cross-linked C-telopeptide of type 1 collagenOCN = osteocalcin25(OH)D = 25-hydroxyvitamin DP1NP = aminoterminal propeptide of type 1 collagenPTH = parathyroid hormonerhPTH(1-84) = recombinant human parathyroid hormoneTEAE = treatment-emergent adverse eventULN = upper limit of normal     

Gender Influences the Clinical Presentation and Long-Term Outcome of Graves Disease

Objective: The outcome of antithyroid drug (ATD) treatment for Graves disease (GD) is difficult to predict. In this study, we investigated whether male gender, besides other factors usually associated with a poor outcome of ATD treatment, may affect disease presentation and predict the response to medical treatment in subjects with GD.Methods: We studied 294 patients with a first diagnosis of GD. In all patients, ATD treatment was started. Clinical features, thyroid volume, and eye involvement were recorded at baseline. Serum levels of free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), and TSH-receptor antibodies (TRAb) were measured at baseline and during the follow-up. Treatment outcome (FT4, FT3, and TSH serum levels and further treatments for GD after ATD withdrawal) was evaluated.Results: When compared to women, men showed a significantly larger thyroid volume and a higher family positivity for autoimmune diseases. During ATD, the mean serum levels of TSH, FT4, FT3, and TRAb did not differ between groups. Within 1 year after ATD discontinuation, relapse of hyperthyroidism was significantly more frequent in men than in women. Within the 5-year follow-up period, the prevalence of men suffering a late relapse was higher compared with that of women. The outcome at the end of the 5-year follow-up period was significantly associated with gender and TRAb levels at disease onset.Conclusion: Male patients with GD have a poorer prognosis when submitted to medical treatment with ATDs. A larger goiter at presentation and a stronger genetic autoimmune background might explain this gender difference in patients with GD.Abbreviations:ATD = antithyroid drugFT3 = free triiodothyronineFT4 = free thyroxineGD = Graves diseaseGO = Graves orbitopathyRAI = radioiodineTRAb = thyroid-stimulating hormone-receptor antibodyTSH = thyroid-stimulating hormone     

Identifying Parathyroid Hormone Disorders and their Phenotypes through a Bone Health Screening Panel: It's not Simple Vitamin D Deficiency!

Objectives: To determine the utility of bone health screening panels in identifying disorders of parathyroid gland secretions.Methods: A retrospective analysis of biochemical parameters in a bone health screening panel (BHSP) was conducted. Low and high cutoffs were applied to determine hypofunctioning and hyperfunctioning conditions related to parathyroid hormone. Clinical phenotypes of parathyroid gland abnormalities were determined using a combination of levels of calcium, 25-hydroxyvitamin D, and intact parathyroid hormone (iPTH). A PTH nomogram was applied to calculate the maximum expected PTH for existing levels of 25-hydroxyvitamin D. Medical records of patients were reviewed for clinical validation of biochemical findings.Results: Sixty-eight percent of subjects showed abnormal PTH secretion. Primary hyper- and hypoparathyroidism were detected in 1% (n = 5) and 0.4% (n = 2) of subjects, respectively. Normocalcemic hyperparathyroidism and hypercalcemia with inappropriately high-normal PTH were identified in 8.5% (n = 37) and 2% (n = 10) of subjects, respectively. All subjects with primary and normocalcemic hyperparathyroidism had higher measured PTH than calculated maximum PTH using the PTH nomogram. Secondary hyperparathyroidism and functional hypoparathyroidism were present in 18% (n = 88) and 39% (n = 194) of subjects, respectively. High prevalence of bone pains, renal stones, and low bone mineral density were identified in patients with abnormal PTH secretion.Conclusion: Panel testing is useful in early diagnosis of metabolic bone disorders related to PTH. A BHSP helps identify normocalcemic hyperparathyroidism and hypercalcemia with inappropriately high PTH.Abbreviations:25OHD = 25-hydroxyvitamin DAKUH = Aga Khan University HospitalBHSP = bone health screening paneliPTH = intact parathyroid hormonemaxPTH = maximum parathyroid hormoneMBD = metabolic bone diseaseNCHPT = normocalcemic hyperparathyroidismPHPT = primary hyperparathyroidismPTH = parathyroid hormoneSHPT = secondary hyperparathyroidismVDD = vitamin D deficiency     

Parathyroid Function after Total Thyroidectomy: A Randomized Clinical Trial Concerning the Influence of the Surgical Technique

Objective: Thyroidectomy impairs parathyroid function, even if it does not necessarily lead to postoperative clinical hypocalcemia. This study was prospective and evaluated the parathyroid hormone (PTH) function in nonclinically symptomatic patients after total thyroidectomy performed by two different techniques.Methods: Prospective randomized clinical trial including 269 patients undergoing classic or harmonic scalpel total thyroidectomy. Pre-operatively and at 48 hours, biochemical analysis was performed. Simultaneously, a sodium bicarbonate test (SBT) was performed.Results: Calcium and PTH were altered for both groups (P<.001). During SBT at 3 minutes after infusion, PTH rose and reached its maximum for both groups (P<.001) and then decreased at 5 minutes (P<.001 and P = .004) and at 10 minutes (P = .006 and P = .043) before returning to baseline levels. At 5 and 10 minutes of the SBT, some differences were observed between the groups. The difference in clinically obvious parathyroid dysfunction between groups was not significant, but there was a difference in the peak PTH levels after bicarbonate stimulation. Similarly, total secretion during the test, as well as total secretion for the first 10 minutes, was practically the same for the two groups. Additionally, partial subclinical postoperative hypoparathyroidism was clearly more common in the harmonic scalpel thyroidectomy group (P<.001).Conclusion: SBT demonstrated more impairment in the harmonic scalpel group, as parathyroid function was altered after thyroidectomy.Abbreviations:HSTT = harmonic scalpel total thyroidectomyPTH = parathyroid hormoneSBIT = sodium bicarbonate infusion test     

A novel compound heterozygous variant Of SLC12A3 Gene in A Pedigree with Gitelman Syndrome Co-Existent with Thyroid Dysfunction

Objective: Gitelman syndrome (GS) is an autosomal recessive disorder characterized by salt wasting and hypokalemia resulting from mutations in the SLC12A3 (solute carrier family 12 member 3) gene, which encodes the thiazide-sensitive sodium-chloride cotransporter. To date, more than 488 mutations of the SLC12A3 gene have been discovered in patients with GS. In this study, we reported a GS pedigree complicated by thyroid diseases or thyroid dysfunction.Methods: Sanger sequencing and next-generation sequencing analysis were performed to determine the SLC12A3 gene mutations in a GS pedigree including the 16-year old male patient with GS and his family members within 3 generations. Chemiluminescence immunoassays were used to detect thyroid hormone and antibody concentrations.Results: Genetic analysis of the SLC12A3 gene identified 2 mutations in the 16-year old male patient with GS concomitant with Graves disease (GD) and his younger sister accompanied by abnormal thyroid function. Additionally, one mutation site (c.1456G>A) in SLC12A3 gene was found in his father, paternal uncle and elder female cousin, who were complicated by subclinical hypothyroidism or autoantibody against thyroid. The other mutation site (c.2102_2107 delACAAGA) in SLC12A3 gene, a novel mutated variant of SLC12A3 gene, was carried by his mother and maternal grandfather.Conclusion: Two mutation sites were documented in the pedigree with GS, and one has not been reported before. Moreover, we found a mutation at nucleotide c.1456 G>A in the SLC12A3 gene that may affect thyroid function. However, further studies are needed to explore the underlying molecular mechanisms.Abbreviations: FT3 = free triiodothyronine; FT4 = free tetraiodothyronine; GD = Graves disease; GS = Gitelman syndrome; SLC12A3 = solute carrier family 12 member 3; TGAb = thyroglobulin antibody; TPOAb = thyroid peroxidase antibody; TSH = thyroid-stimulating hormone; TT3 = total triiodothyronine; TT4 = total tetraiodothyronine     

The Emerging Role of Denosumab in the Long-Term Management of Parathyroid Carcinoma-Related Refractory Hypercalcemia

Objective: The main cause of death in patients with parathyroid carcinoma is parathyroid hormone (PTH)-induced hypercalcemia. To date, the management of hypercalcemia has been based on the use of bisphosphonates and calcimimetic agents. In recent reports, the use of denosumab has shown encouraging results in cases of refractory hypercalcemia of malignancy. Our objective is to present a case of successful management of resistant hypercalcemia due to parathyroid carcinoma with denosumab, to review similar cases from the literature, and to propose denosumab's use in the clinical management of PTH-induced refractory hypercalcemiaMethods: Presentation of a case report and review of the literature for cases of parathyroid carcinoma–mediated hypercalcemia successfully treated with denosumab.Results: A 71-year-old man with metastatic parathyroid carcinoma was referred to our department for uncontrolled hypercalcemia, resistant to treatment with bisphosphonates and cinacalcet. Treatment with denosumab (120 mg per month) in addition to cinacalcet (180 mg per day) resulted in normalization of calcium levels and maintenance within the normal range for an observation period of 11 months. Review of the literature revealed 4 case reports and a letter to the editor, all of which reported the successful treatment of resistant hypercalcemia associated with parathyroid carcinoma.Conclusion: Based on the above findings of the effectiveness of denosumab in controlling refractory hypercalcemia, its safety in renal failure and the fact that denosumab may reduce PTH-induced bone loss, we endorse its use in the management of hypercalcemia in patients with parathyroid carcinoma and perhaps other conditions with PTH-induced hypercalcemia.Abbreviations: CT = computed tomography IV = intravenous PTH = parathyroid hormone     

Positive Thyrotropin Receptor Antibodies in Patients with Transient Thyrotoxicosis

Objective: Thyrotropin (TSH) receptor antibody (TRAb) testing is considered accurate for the diagnosis of Graves disease (GD) and has been identified rarely in thyrotoxic patients without GD. We describe 4 patients with transient thyrotoxicosis and positive TRAb to highlight this clinical possibility.Methods: Patient demographics, symptoms, laboratory findings, and time to resolution of thyrotoxicosis are summarized. TRAb testing was performed by either a third-generation thyrotropin-binding inhibitory immunoglobulin (TBII) competitive-binding assay or a thyroid-stimulating immunoglobulin (TSI) bioassay from either Mayo Clinic Laboratory or Quest Diagnostics.Results: Four patients with transient thyrotoxicosis and positive TRAb testing were identified. Of these, three were female, and the median age was 44 years (range, 25 to 49 years). Median symptom duration at evaluation was 6.5 weeks (range, 3 to 12 weeks). No patient had any clinical manifestations unique to GD or exposure to biotin, thyroid hormone, supplements, iodine, or relevant medications. The TSH was <0.1 mIU/L in all patients. Three patients had a positive TSI, which was elevated less than twice the upper limit of the reference range in all cases, and 1 patient had a strongly positive TBII. None of the patients were treated with thionamides or radioactive iodine. Spontaneous resolution occurred in all patients at a median of 5.5 weeks (range, 2 to 14.4 weeks).Conclusion: These cases demonstrate that TSI or TBII may be present in thyrotoxic patients with transient thyrotoxicosis. For clinically stable patients presenting without pathognomonic evidence of GD, mildly elevated TRAb results may require cautious interpretation, and alterative diagnostic testing or close monitoring should be considered.Abbreviations: cAMP = cyclic adenosine monophosphate; FT4 = free thyroxine; GD = Graves disease; TBII = thyrotropin-binding inhibitory immunoglobulin (also known as TBI); TRAb = thyrotropin receptor antibody; TSH = thyrotropin; TSHR = thyrotropin receptor; TSI = thyroid-stimulating immunoglobulin; TT3 = total triiodothyronine; TT4 = total thyroxine     

Pre-Operative Localization of Parathyroid Adenoma: Performance of 4D Mri Parathyroid Protocol

Objective: Accurate pre-operative image localization is critical in the selection of minimally invasive parathyroidectomy as a surgical treatment approach in patients with primary hyperparathyroidism (PHPT). Sestamibi scan, ultrasound, computed tomography, and conventional magnetic resonance imaging (MRI) has varying accuracy in localizing parathyroid adenoma (PTA). Our group has previously shown that four-dimensional (4D) MRI is more accurate than conventional imaging in identifying single adenomas. In this study, we set out to determine if it is possible to accurately localize the quadrant of the adenoma using 4D MRI.Methods: We analyzed and matched the quadrants of PTA identified by pre-operative 4D-MRI with the operative findings during parathyroidectomy for PHPT at our institution during the study period. All resections were confirmed to be successful with an adequate decrease in intraoperative parathyroid hormone as defined by the Miami criterion.Results: A total of 26 patients with PHPT underwent pre-operative localization with the 4D MRI parathyroid protocol. Fourteen patients had true single-gland adenoma (SGA) and 12 patients had multi-gland disease (MGD). 4D MRI accurately identified all the SGA. Using this method, we were also able to localize the adenoma in the correct quadrant in 14 of the 18 patients with SGA. All 3 double adenomas were accurately identified using 4D MRI; however, MGD was only accurately identified 67% of the time. The 4D MRI had an overall 85% accuracy in distinguishing SGA from MGD.Conclusion: 4D MRI accurately identified single and double adenomas in their respective quadrants. However, accuracy was lower with MGD.Abbreviations: BNE = bilateral neck exploration; CT = computed tomography; IOPTH = intra-operative parathyroid hormone; MGD = multi-gland disease; MIBI = sestamibi; MIP = minimally invasive parathyroidectomy; MRI = magnetic resonance imaging; PHPT = primary hyperparathyroidism; PTA = parathyroid adenoma; PTH = parathyroid hormone; SGA = single-gland adenoma; SPECT = single photon emission computed tomography; 4D = four-dimensional