Endocrine

Variants in MCT10 protein do not affect FT3 levels in athyreotic patients Abstract Purpose Several single-nucleotide polymorphisms in genes encoding for transporters have been associated with serum thyroid hormone concentrations with inconsistent results. The aim of this study was to assess the clinical significance of the rs17606253 in SLC16A10 gene alone and in combination with the DIO2 Thr92Ala variation in athyreotic patients. Methods One-hundred patients submitted to total thyroidectomy and treated with levothyroxine were included. Pre- and post surgical serum TSH levels did not differ by more than ± 0.5 mIU/l. Results Both patients carrying the wild-type allele or heterozygous for rs17606253 in SLC16A10 gene had a significant reduction in FT3 post surgical levels (p = 0.01 and p < 0.0001, respectively) while Thr92Ala in DIO2 gene was associated with reduced FT3 levels for heterozygous and rare homozygous patients (p < 0.0001 and p = 0.01, respectively). We identified two groups (“FT3 unchanged” and “FT3 reduced”) using a cutoff of at least 0.5 pg/ml as a significant variation between pre- and post surgical FT3 values. In this case, the rs17606253 was not statistically associated with reduced FT3 levels at genotype and allele levels. On the contrary, the Thr92Ala in DIO2gene was confirmed statistically associated with reduced FT3 levels after surgery with a p = 0.035 at genotype level and p = 0.014 at allele level. Conclusions We confirmed the role of DIO2 Thr92Ala polymorphism on T3 levels. On the contrary, SLC16A1 rs17606253 polymorphism did not impair hormone levels in athyreotic patients treated with levothyroxine therapy.

Effect of 9 months of vitamin D supplementation on arterial stiffness and blood pressure in Graves’ disease: a randomized clinical trial Abstract Purpose Risk of cardiovascular disease (CVD) is increased in Graves’ disease (GD). CVD is predicted by increased pulse wave velocity (PWV) and blood pressure (BP). GD and these risk factors are all associated with lower levels of vitamin D. We aimed to assess the effect of supplemental vitamin D on PWV and BP in GD. Methods In a double-blinded trial, newly diagnosed GD patients were randomized to vitamin D3 70 µg/day (n = 44) or placebo (n = 42) as add-on to anti-thyroid medication. At baseline, 3 and 9 months PWV, BP and wave analysis were performed in office and 24 h setting. Between-group differences in change at 9 months were analyzed using linear mixed modelling. In subanalysis, effect of intervention in regard to baseline vitamin D insufficiency (25(OH)D < 50 nmol/L) was investigated. (The DAGMAR study, clinicaltrials.gov ID NCT02384668). Results PWV was unaffected by intervention in main analysis. However in the subanalysis, comparing the response to intervention in the vitamin D insufficient (n = 28) and the vitamin D replete patients, supplemental vitamin D induced a significant decrease in office PWV of 1.2 (95% CI: −2.3; −0.1) m/s compared to placebo. Of notice, baseline PWV was non-significantly higher among the vitamin D insufficient as compared to the replete participants. In response to vitamin D, office central systolic BP (−3.9 (95% CI: −7.5; −0.3) and brachial mean BP (−3.3 (95% CI: −6.5; −0.3) declined whereas 24 h measurements were unaffected. Conclusions High-dose vitamin D supplementation did not affect PWV. We observed significant reduction in office but not 24 h BP. Subanalysis showed a clinically relevant PWV reduction among vitamin D insufficient participants, although regression towards the mean might contribute to findings. Further studies on supplemental vitamin D in GD should focus on patients with vitamin D insufficiency.

Differential expression of RET isoforms in normal thyroid tissues, papillary and medullary thyroid carcinomas Abstract Pourposes We investigated the expression of RET9 and RET51 isoforms in medullary (MTC), papillary (PTC) thyroid carcinoma, normal thyroid tissues, and pheochromocytoma (PHEO) to verify if these isoforms are present also in follicular thyroid cell-derived tissues, and if there is a differential expression of RET9 and RET51 in MTC. Methods Nineteen patients with MTC, 18 patients with PTC, 18 samples of contralateral normal thyroid tissues, and 5 cases of PHEO were included in this study. RET isoform expression was studied by real-time RT-PCR. Results All MTCs and PHEOs were positive for RET9 and RET51. Fourteen/eighteen (77.7%) PTC cases were positive for RET9 and/or RET51, and four were positive for only one of the genes. In normal thyroid tissues, 3/18 (16.7%) cases were negative for both isoforms, 4/18 (22.2%) were positive for both, and 11/18 (61.1%) were positive for only one. RET isoforms were expressed at different levels in MTC, PHEO, PTC, and normal thyroid tissues: RET9 expression was higher in PHEO than in MTC, PTC, and normal thyroid tissues. RET9 expression was also higher in MTC than in PTC and normal thyroid tissues. No difference was observed between PTC and normal thyroid tissues. A similar pattern of expression was observed for RET51. In addition, RET51 was significantly more expressed than RET9 in MTC, while RET9 was the predominant isoform in PHEO. Conclusions Our study documented the expression of the RET9 and RET51 isoforms in normal thyroid and PTC tissues. RET9 and RET51 isoforms were also present in MTC and PHEO. RET51 expression was higher than RET9expression in MTC, while there was no difference in the expression of these two isoforms in PTC and normal thyroid tissues. RET9 was more highly expressed than RET51 in PHEOs.

Primary adrenal schwannoma: a series of 31 cases emphasizing their clinicopathologic features and favorable prognosis Abstract Purpose Primary adrenal schwannoma (PAS) is a very rare benign tumor, and most of them have been described in case reports. This study aimed to analyze their distinct clinicopathologic features and follow-up data through the largest series yet. Methods Clinicopathologic features of 31 primary adrenal schwannomas were retrospectively studied. Imaging and histologic features were re-evaluated and summarized. Immunohistochemical markers were measured, including S100, SOX10, AE1/AE3, EMA, SMA, Desmin, HMB45, GLUT1, and Ki67. Follow-up of all cases was performed. Results All the tumors were clinically misdiagnosed as nonfunctioning adrenal adenoma (NAA; 23/31), aldosterone-producing adenoma/aldosteronoma (APA; 3/31), cortisol-producing adenoma (CPA; 3/31), or pheochromocytoma (PCC; 2/31). Some 87% (27/31) presented with adrenal incidentaloma, and 13% (4/31) had a clinical symptom or unregulated hormone levels. They comprised conventional (19/31), cellular (7/31), plexiform (2/31), ancient (1/31), epithelioid (1/31) and microcystic/reticular variants (1/31) and had various histologic features. Immunohistochemically, all tumors (31/31) were positive for S100 and Sox10, with a low Ki-67 proliferative index. In the long-term follow-up (mean, 53 mo.; median, 56 mo.), none had evidence of recurrence and metastasis. Univariate analysis showed that OS and DFS were not associated with age; sex; tumor side, size, or number; adrenal-related symptoms; gross feature (solid vs. cystic); or any histologic feature (P > 0.9999). Conclusion PAS is an extremely rare tumor and mostly appears as an incidentaloma. Clinically, it tends to be misdiagnosed as other common adrenal tumors. This tumor has a benign biologic behavior and prognosis, without correlations with clinical or histologic parameters.

Medullary thyroid carcinoma treated with percutaneous ultrasound-guided radiofrequency ablation Abstract Purpose Minimally invasive image-guided thermal ablation has been proposed as alternative to surgery for treatment of benign thyroid nodules and recurrent differentiated thyroid carcinoma. Here, we report for the first time the use of radiofrequency ablation (RFA) in a patient with non-metastatic medullary thyroid carcinoma (MTC) who did not undergo surgery due to high anesthesiological risk. Methods and results A 64-year-old woman was referred to our institution for a routine endocrinological visit. No thyroid-related symptoms were present. She had a history of metabolic, cardiovascular and neurological diseases. On clinical examination, a nodular lesion of about 10 mm was palpable in the right thyroid lobe; ultrasonography (US) confirmed the presence of a 13 mm thyroid nodule in the lower pole of the right lobe, that was hypoechoic and with regular margins. Serum calcitonin (Ctn) level was significantly high (647 pg/mL). Fine-needle aspiration (FNA) of the thyroid nodule was negative for malignant cells, but the marked increase of Ctn level in the FNA wash-out fluid confirmed the diagnostic suspicion of MTC. Since patient refused surgery due to high anesthesiological risk, percutaneous US-guided RFA in single session was performed. At 6-months follow-up the serum Ctn level decreased from the initial value of 647 pg/mL, reaching near-normal range (15 pg/mL), and neck ultrasound showed a complete necrosis of the tumour. Afterward, serum Ctn slowly increased to 49 pg/mL at 15-month follow-up. The US performed at 6 and 12 months of follow-up revealed fibrotic tissue in place of the thyroid nodule, without evidence of cervical lymph-node metastases. Conclusions This clinical case suggests that RFA may be effective and safe for treatment of MTC when surgery cannot be performed.

In children with acquired hypothyroidism levothyroxine requirements may be significantly conditioned by the etiology of thyroid failure

Human heart shifts from IGF-1 production to utilization with chronic heart failure

Lower all-cause mortality rates in patients harboring pituitary carcinoma following the introduction of temozolomide Abstract Objective To evaluate the impact of temozolomide (TMZ) introduction on the survival of patients with pituitary carcinoma (PC) compared to aggressive pituitary adenoma (APA). Methods Retrospective analysis of the Surveillance Epidemiology and End-Results database (SEER), including patients diagnosed with PC or APA between 1973 and 2015. Age-adjusted Kaplan–Meier analyses were performed, comparing all-cause mortality (ACM) rates before the year 2006, the time of TMZ introduction (“period 1”), and afterwards (“period 2”), in patients harboring PC and APA. Results Among 107 patients, 18 (16.8%) harbored PC. The prevalence of PC and APA was comparable between genders, ethnicities and age strata. Patients harboring any pituitary tumor (PC or APA) had comparable risk for ACM and disease-specific mortality between the two time periods. However, among patients harboring PC, the risk for ACM was significantly lower in period 2 vs. period 1 (p = 0.021), becoming comparable to the risk of ACM in patients diagnosed with APA (p = 0.48). Conclusions In this large cancer-database-based analysis we observed improved overall survival in patients harboring PC in the years following the introduction of TMZ.

Long-term control of Paget’s disease of bone with low-dose, once-weekly, oral bisphosphonate preparations, in a “real world” setting

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