In isolated TSH deficiency, the exact molecular diagnosis is mandatory for diagnosis of isolated pituitary deficiency, delineation of prognosis, and genetic counseling. Moreover, diagnosis of central hypothyroidism should be considered in the face of severe infant anemia of uncertain etiology.

Carriers of germline DICER1 mutations are predisposed to a rare cancer syndrome, the DICER1 syndrome, associated with tumours such as pleuropulmonary blastoma (PPB), ovarian Sertoli-Leydig cell tumours (SLCT), multinodular goiter (MNG), cystic nephroma (CN), embryonal rhabdomyosarcoma (ERMS) and others. Germline mutations in DICER1 cause an alteration in miRNAs processing, deregulating target oncogenes and leading to elevated risk of tumorigenesis. In most reported cases, there is a heterozygous germline mutation and a somatic second hit mutation. Aim: Analyze the presence of germline and somatic alterations in the DICER1 gene in 6 patients with paediatric tumours associated with DICER1 spectrum. Methods: Automated sequencing of DICER1 gene from gDNA extracted from blood and formalin-fixed, paraffin-embedded tumour tissues of affected subjects and relatives. Cases: 5 girls (P1-P5) and 1 boy (P6), (P1: bilateral SLCT, P2 and P3: SLCT and MNG, P4: MNG and uterine myosarcoma, P5: vaginal rhabdomyosarcoma, and P6: CN). Chronological age at diagnostic was 5, 12, 15, 16, 13 y 2, respectively. Results: We detected 5 novel heterozygous mutations: p.Trp1098* in P1, p.Phe351fs*1 in P2, p.Arg1596Glyfs*24 in P4, c.3269+1G>A in P5, p.Asp244Glyfs*27 in P6, and one previously described heterozygous deletion p.Asp1437Metfs*16 in P3.These mutations (P1-P4 and P6) predict the presence of a truncated protein losing its essential domains for the enzymatic activity and, in one P5 an alteration in the splicing process. The tissue analysis revealed p.Asp1709Glu in MNG and p.Glu1705Lys in SLCT in P2, and p.Glu1705Lys in MNG in P3,previously described as hotspot somatic mutations. Conclusions: We report five novel germinal mutations in DICER1 gene and two somatic hotspot mutations in MNG and SLCT tissue samples. These findings confirm that a second hit event is involved in the mechanism of MNG and SLCT development. Molecular analysis of DICER1 gene allows to perform genetic counselling about familial recurrence risk.

Monocarboxylate transporters (MCTs) allow the cellular entry of thyroid hormones, especially into the central nervous system (CNS), where they are crucial for neurodevelopment. MCT8 deficiency results in the combination of hypothyroidism in the CNS and peripheral hyperthyroidism, characterized by elevated T3 levels.The only treatment currently available is 3,3',5-triiodothyroacetic acid (TRIAC), a thyroid hormone analogue aimed at improving peripheral thyrotoxicosis and preventing the progression of neurological impairment.Here we assess the clinical, imaging, biochemical, and genetic characteristics of 4 patients with MCT8 deficiency who have received TRIAC to date, the doses used, and the response to treatment.

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