This is the first report on MKRN3 levels in men and the sec- ond report on circulating MKRN3 levels in humans. Our results suggest that peripheral MKRN3 levels do not reflect the integrity of the hypothalamic–pituitary–testicular axis. A potential limita- tion of our study is the cross-sectional study design, and longi- tudinal studies in peripubertal and pubertal boys will further clarify the physiological and biochemical correlates of circulating MKRN3 levels. Competing interests/disclosures Nothing to declare. Tero Varimo*, Matti Hero*, Johanna K€ ans€ akoski†, Kirsi Vaaralahti†, Niina Matikainen‡ and Taneli Raivio* , † *Children’s Hospital, University of Helsinki and Helsinki University Hospital †Department of Physiology, Faculty of Medicine, University of Helsinki, ‡Endocrinology, Abdominal Center, Helsinki University Hospital and Cardiovascular Research Unit, Diabetes and Obesity Research Program, University of Helsinki, Helsinki, Finland E-mail: taneli.raivio@helsinki.fi doi: 10.1111/cen.12851 References 1 Abreu, A.P., Dauber, A., Macedo, D.B. et al. (2013) Central pre- cocious puberty caused by mutations in the imprinted gene MKRN3. New England Journal of Medicine, 368, 2467–2475. 2 Hagen, C.P., Sørensen, K., Mieritz, M.G. et al. (2015) Circulating MKRN3 levels decline prior to pubertal onset and through puberty: a longitudinal study of healthy girls. Journal of Clinical Endocrinology and Metabolism, 100, 1920–1926. 3 Laitinen, E.M., Tommiska, J., Sane, T. et al. (2012) Reversible congenital hypogonadotropic hypogonadism in patients with CHD7, FGFR1 or GNRHR mutations. PLoS ONE, 7, e39450. 4 Song, R., Peng, W., Zhang, Y. et al. (2013) Central role of E3 ubiquitin ligase MG53 in insulin resistance and metabolic disor- ders. Nature, 494, 375–379. 5 Abreu, A.P., Navarro, V.M. & Eren, A. et al. (2015) Regulation of Mkrn3 Expression by Sex Steroids. Proceedings of the 97th Annual Meeting of the Endocrine Society, San Diego, CA, 2015. 6 Li, J.J., Ferry, R.J. Jr, Diao, S. et al. (2015) Nedd4 haploinsufficient mice display moderate insulin resistance, enhanced lipolysis, and protection against high-fat diet-induced obesity. Endocrinology, 156, 1283–1291. BRAF (V600E) mutation in isthmic malignant thyroid nodules Dear Editor, Thyroid cancers occur in approximately 2–5% of all nodules, with an incidence of about 3Á8% of all new cancer diagnosis in 2014. Differentiated thyroid cancer (DTC) is the most common thyroid cancer type. Incidence has been increasing in the last few decades, mainly due to incidental detection of small, low-risk, cancers (i.e. ≤ 2 cm) by neck ultrasound. Accordingly, DTC-related mortality has not increased and, to date, it is reported at about 0Á5 cases per 100 000 persons. According to American Thyroid Association guidelines and European Thyroid Association consensus, in the absence of additional risk factors, thyroid remnant ablation (TRA) with 131-radioiodine is not indicated in patients with DTC <1 cm, while selective and tailored use is suggested for others low-risk patients (i.e. pT1b-2N0M0). However, the prevalence of lymph- node metastases in patients affected by low-risk cancer is not negligible, ranging from 10 to 30%. 1,2 Thus, the choice to per- form or to rule out TRA is based on risk factors such as age, gender, histological variants. To date, BRAF(V600E) mutation (presence or absence) and the topography of malignant thyroid nodules have not been considered amongst risk factors. We recently published that the prevalence of lymph-node metastases was significantly higher in patients with low-risk DTC located in the isthmus compared to those located in thyroid lobes. 1 We concluded that the isthmic localization of the malig- nant thyroid nodule was an independent risk factor in patients with low-risk DTC. In our series of papillary thyroid carcinoma (PTC), patients with isthmus lesion had undergone TRA by 131- radioiodine ablative activity (range 1110–3700 MBq; median 2753 MBq) oral administration and their median follow-up was 5 years (range 2–7 years). 1 All except one patients reached an ‘excellent response’ status [i.e. undetectable basal and stimulated thyroglobulin (Tg) serum levels (<1 ng/ml); negative neck ultra- sound] 3 with the first 131-radioiodine ablative therapy, as appre- ciated during the first follow-up performed 12 months after TRA. Taking into account literature on a possible negative impact of BRAF (V600E) mutation in terms of disease persistence and worse prognosis, 4 we decide to assess the presence or absence of BRAF(V600E) mutations in our series of patients with an isth- mic DTC. The BRAF (V600E) mutation was analysed as previously reported. 5 To overcome any problem due to little tumour amount and tissue heterogeneity in molecular analysis, DNA was extracted from tumour cells captured using the laser cap- ture microdissection technique. The BRAF (V600E) sequences present in the GenBank database were used for mutagenesis analysis. Overall, BRAF(V600E) mutation was identified in 4 of 27 patients with isthmic lesion (15%): one of eight (12%) meta- static patients and three of nineteen (16%) nonmetastatic patients (v 2 0Á13, P = 0Á709). Accordingly, the risk of developing lymph-node metastases in patients with isthmus lesion and posi- tive BRAF mutation is not higher than in patients with isthmus lesion and negative BRAF mutation (Odds ratio = 0Á762, CI 0Á067–8Á665). In our cohort, the small number of patient harbouring BRAF mutation does not allow to assess whether the final outcome of these patients is affected by the presence of the mutation. How- ever, the sole patient with persistent disease had BRAF mutation and lymph-node metastasis. In this patient, the intensity of 131-radioiodine uptake observed (visual analysis) in thyroid © 2015 John Wiley & Sons Ltd Clinical Endocrinology (2016), 84, 149–153 152 Letters to the Editor