With the generalized use of highly sensitive thyroid stimulating hormone (TSH) and free thyroid hormone assays, most thyroid function tests (TFTs) are straightforward to interpret and confirm the clinical impressions of thyroid diseases. However, in some patients, TFT results can be perplexing because the clinical picture is not compatible with the tests or because TSH and free T4 are discordant with each other. Optimizing the interpretation of TFTs requires a complete knowledge of thyroid hormone homeostasis, an understanding of the range of tests available to the clinician, and the ability to interpret biochemical abnormalities in the context of the patient's clinical thyroid status. The common etiologic factors causing puzzling TFT results include intercurrent illness (sick euthyroid syndrome), drugs, alteration in normal physiology (pregnancy), hypothalamic-pituitary diseases, rare genetic disorders, and assay interference. Sick euthyroid syndrome is the most common cause of TFT abnormalities encountered in the hospital. In hypothalamicpituitary diseases, TSH levels are unreliable. Therefore, it is not uncommon to see marginally high TSH levels in central hypothyroidism. Drugs may be the culprit of TFT abnormalities through various mechanisms. Patients with inappropriate TSH levels need a differential diagnosis between TSH-secreting pituitary adenoma and resistance to thyroid hormone. Sellar magnetic resonance imaging, serum a-subunit levels, serum sex hormone-binding globulin levels, a thyrotropin-releasing hormone stimulation test, trial of somatostatin analogues, and TR-ss sequencing are helpful for the diagnosis, but it may be challenging. TFTs should be interpreted based on the clinical context of the patient, not just the numbers and reference ranges of the tests, to avoid various pitfalls of TFTs and unnecessary costly evaluations and therapies.

Hypocalcemia is relatively uncommon paraneoplastic syndrome. Only one case of hypocalcemia has been reported in a patient with chondrosarcoma. We herein report a case of a 32-year-old woman with metastatic chondrosarcoma with tetany. Her imaging findings revealed multiple calcific metastatic lesions in the lungs, pancreas, left atrium, and pulmonary vein. A laboratory examination showed hypocalcemia with no evidence of any other disease that could induce hypocalcemia. On the basis of the laboratory and clinical findings, we concluded the etiology of her severe hypocalcemia to be excessive calcium consumption by the tumor itself.

Objectives Higher thyroid-stimulating hormone (TSH) levels are associated with differentiated thyroid cancers (DTC). To validate this association, we compared TSH levels obtained from euthyroid patients with DTC with TSH levels from controls in the general population. Design and patients The case group included 1759 patients with DTC, who underwent thyroid surgery at Chonnam National University Hwasun Hospital. The control group (n = 1548), who had participated in the Thyroid Disease Prevalence Study were used as a healthy control group. The subjects were divided into four groups of similar size according to their TSH levels, with the first quartile used as a reference group. Results The mean TSH level of the case group was significantly higher than the mean TSH level of the control group (1.95 +/- 0.9 mIU/l vs 1.62 +/- 0.8 mIU/l, P < 0.001), and was associated with DTC risk. Multiple logistic regression, after controlling for age, gender and the presence of a family history of thyroid cancer, showed that the odds ratios and 95% confidence intervals for the second, third and fourth quartiles of TSH levels were 1.27 (1.03-1.57), 1.55 (1.25-1.92) and 2.21 (1.78-2.74) respectively. No significant differences were observed in mean TSH levels in patients with different tumour stages and tumour sizes. Conclusion Having a high TSH level within the normal range is an independent risk factor for DTC, and may contribute to the initiation of thyroid carcinogenesis. TSH levels in patients with thyroid nodules may be used as diagnostic adjuncts for the identification of high-risk patients, who require further investigation and/or surgical intervention.

Cases of metastases to the thyroid gland seem to be increasing in recent years. The clinical and ultrasonographic findings of diffuse metastases have been sparsely reported. Thirteen cases of diffuse metastases to the thyroid gland were documented by thyroid ultrasonography-guided fine needle aspiration cytology between 2004 and 2013. We retrospectively reviewed the patients with diffuse thyroid metastases. The most common primary site was the lung (n=3D9), followed by unknown origin cancers (n=3D2), cholangiocarcinoma (n=3D1), and penile cancer (n=3D1). Eleven patients were incidentally found to have thyroid metastases via surveillance or staging FDG-PET. Other 2 patients were diagnosed during work-up for hypothyroidism and palpable cervical lymph nodes. On ultrasonography, the echogenicity of the enlarged thyroid gland was heterogeneously hypoechoic or isoechoic, and reticular pattern internal hypoechoic lines were observed without increased vascularity found by power Doppler ultrasonography (3 right lobe, 2 left lobe, and 8 both lobes). In the 8 patients who had involvement of both lobes, 3 had hypothyroidism. In conclusion, ultrasonographic finding of diffuse metastasis is a diffusely enlarged heterogeneous thyroid with reticular pattern internal hypoechoic lines. Thyroid function testing should be performed in all patients with diffuse thyroid metastases, especially those with bilateral lobe involvement. =20

INTRODUCTION: Several studies have reported a high frequency of papillary thyroid cancer (PTC) in patients with acromegaly. The aim of this study was to determine the prevalence and predictors of thyroid cancer in patients with acromegaly and to investigate the frequency of the BRAFV600E mutation in PTC patients with and without acromegaly.; MATERIALS AND METHODS: We conducted a retrospective study of 60 patients with acromegaly. Thyroid ultrasonography (US) and US-guided fine needle aspiration were performed on nodules with sonographic features of malignancy. We selected 16 patients with non-acromegalic PTC as a control group. The BRAFV600E mutation was analyzed in paraffin-embedded surgical specimens of PTC by real-time polymerase chain reaction, and tumor specimens from patients with PTC were stained immunohistochemically with an antibody against insulin-like growth factor-1 receptor beta (IGF-1Rbeta).; RESULTS: Thyroid cancer was found in 15 (25.0%) patients. No differences in age, sex, initial growth hormone (GH) and IGF-1 percentage of the upper limit of normal values or treatment modalities were observed between patients with and without PTC. Acromegaly was active in 12 of 15 patients at the time of PTC diagnosis; uncontrolled acromegaly had a significantly higher frequency in the PTC group (60%) than in the non-PTC group (28.9%) (p=E2=80=8A=3D=E2=80=8A0.030). The BRAFV600E mutation was present in only 9.1% (1/11) of PTC patients with acromegaly, although 62.5% (10/16) of control patients with PTC had the mutation (p=E2=80=8A=3D=E2=80=8A0.007). IGF-1Rbeta immunostaining showed moderate-to-strong staining in all malignant PTC cells in patients with and without acromegaly. Significantly less staining for IGF-1Rbeta was observed in normal adjacent thyroid tissues of PTC patients with acromegaly compared with those without (p=E2=80=8A=3D=E2=80=8A0.014).; CONCLUSION: The prevalence of PTC in acromegalic patients was high (25%). An uncontrolled hyperactive GH-IGF-1 axis may play a dominant role in the development of PTC rather than the BRAFV600E mutation in patients with acromegaly.=20

MicroRNAs (miRNA) of approximately 22 nucleotides are fundamental molecules in cellular biology that act by modulating target gene expression. As a post-transcriptional/translational regulator, the role of miRNAs in human disease is highly expected. Recently, a rising number of miRNAs that are associated with a variety of human diseases have been reported in the literature. Aiming to provide a comprehensive of resource of miRNAs that are related to the human disease, we built the Disease miRNA Database (Disease-miRNAdb). MiRNAs from three groups of diseases including kidney disease, cancer, and metabolic disease were manually curated in the current version of database located on a user-friendly online website (http://disease-miRNAdb.hallym.ac.kr). In addition, this database also includes information regarding single nucleotide polymorphisms (SNPs) located in pre-miRNAs, miRNA flanking regions, and 3'-UTRs of miRNA target genes. The generation of genetic variation in these regions may result in a loss or gain of miRNA-target gene interactions, which may influence the development of disease. Thus, information regarding miRNA-related SNPs will be useful in the discovery of disease-associated miRNAs in human populations by employing SNP association analysis for the disease of interest. Disease-miRNAdb will be continually maintained with up-to-date information to provide a current and valuable resource for investigating the roles of miRNAs in human disease.

BACKGROUND: Medullary thyroid cancer (MTC) is a calcitonin (Ct)-secreting tumor of the parafollicular or C cells of the thyroid gland. Higher serum Ct levels are associated with larger tumor size, distant metastases, and prognosis. We report herein a case of prostate and multiple bone metastases of nonfamilial MTC with mildly elevated Ct levels.; PATIENT FINDINGS: A 73-year-old man who was found to have a 2.5 cm MTC in the left thyroid lobe with cervical lymph node metastases presented with confused mental status because of severe hypercalcemia (albumin-modified serum calcium concentration 15.2 mg/dL) associated with multiple bone metastases. Prostate biopsy was performed because the patient had frequent urination with mildly elevated serum prostate-specific antigen (5.297 ng/mL). Histologically, the prostate was diagnosed as MTC metastasis, forming a tissue architecture closely resembling the previously diagnosed MTC, and the cells were positive for Ct, carcinoembryonic antigen, and thyroid transcription factor 1. Although the patient had multiple MTC metastases, basal and calcium-stimulated serum Ct levels were not significantly elevated, measuring 22.7 pg/mL (normal <10 pg/mL) and 22.1 pg/mL, respectively.; CONCLUSIONS: A chronic hypercalcemic state may exhaust Ct reserves and diminish the Ct response to an acute intravenous calcium injection. Therefore, the Ct level of a patient in a hypercalcemic state should be carefully interpreted. To our knowledge, this is the first reported case in the literature in which serum Ct levels were not significantly increased when associated with hypercalcemia, and an MTC metastasis to the prostate.=20