Chromosome 6q24-related diabetes mellitus is the most common cause of transient neonatal diabetes (TNDM), accounting for approximately two-thirds of all TNDM cases. Patients with 6q24-TNDM develop insulin-requiring diabetes soon after birth, followed by the gradual improvement and eventual remission of the disorder by 18 mo of age. The most important clinical feature of affected patients is a small-for-gestational age (SGA) birth weight, which reflects the lack of insulin in utero. It is believed that 6q24-TNDM is caused by the overexpression of the paternal allele of the imprinted locus in chromosome 6q24, which contains only two expressed genes, PLAGL1 and HYMAI. Identified mechanisms include: (1) duplication of the paternal allele, (2) paternal uniparental disomy, and (3) hypomethylation of the maternal allele. Many patients with TNDM relapse after puberty. Relapsed 6q24-related diabetes is no longer transient and typically occurs in non-obese patients who are autoantibody negative. Thus, these patients possess features indistinguishable from those of maturity-onset diabetes of the young (MODY). Conversely, it has been shown that not all patients with 6q24-related diabetes have a history of TNDM. 6q24-related diabetes should therefore be considered as one of the differential diagnoses for patients with MODY-like diabetes, especially when they are SGA at birth.

Selenium (Se) is an essential trace element that is involved in numerous biological processes in the form of a selenoprotein such as iodothyronine deiodinase (DIO). Se deficiency may prevent the conversion of T4 to T3 through reducing DIO expression and thereby affecting thyroid hormone status. However, this has not been well documented in humans. In this study, to clarify the association between Se and thyroid hormone status, we investigated the thyroid hormone levels in patients with severe Se deficiency (< 2 µg/dl). Severe Se deficiency was associated with increases in free T4 levels, but not with decreases and increases in free T3 and thyroid stimulating hormone (TSH) levels, respectively. Increases in free T4 levels during Se deficiency were reduced with Se supplementation; however, neither free T3 nor TSH levels were affected. Taken together, these findings indicate that free T4 may be a useful biomarker for Se status when serum Se levels are severely low.

Thyroid nodules have been observed in childhood cancer survivors (CCS) treated with chemotherapy and radiotherapy. We report four patients with thyroid nodules identified during the long-term follow-up of children who underwent hematopoietic stem cell transplantation (HSCT). The thyroid nodules were diagnosed as adenomatous goiter in all four patients. The interval between the primary cancer diagnosis and the occurrence of the thyroid nodules was more than 10 yr. Furthermore, all four patients underwent HSCT in conditioning with total body irradiation (TBI) before the age of 10 yr. Two of four patients commenced treatment with levothyroxine due to elevated TSH levels. Only two patients showed elevated thyroglobulin levels (> 70 µg/L). In conclusion, we suggest that CCS who have undergone HSCT in conditioning with TBI more than 10 yr previously should be followed up carefully for thyroid nodules using ultrasound.

Primary hyperparathyroidism (PHT) causes increased bone turnover, leading to reduction in bone mineral density (BMD). Parathyroidectomy is a definitive therapy and improves BMD in adult patients with PHT. However, there are no reports regarding alterations of BMD in pediatric or adolescent patients with PHT. Here, we report a case of a 13-yr-old boy with PHT who was referred to our institution for evaluation of hypercalcemia and hyperparathyroidism. Radiological investigation revealed an ectopic parathyroid adenoma below the right thyroid lobe. A minimally invasive radio-guided parathyroidectomy was successfully performed. We followed up the patient’s BMD for three years both before and after parathyroidectomy. Over the course of three years, his BMD was steadily decreased, with z-scores of +0.506 at 13 yr and 9 mo, +0.162 at 14 yr and 9 mo, and –0.411 at 15 yr and 9 mo. BMD usually increases during peak height velocity in an adolescent and improves after parathyroidectomy in adult patients with PHT. However, our patient showed decreased BMD z-scores following parathyroidectomy. Therefore, the patient had an increased risk of fracture after parathyroidectomy and was followed up closely. Both height and BMD should be carefully evaluated after parathyroidectomy in pediatric and adolescent patients with PHT.

Pheochromocytomas are catecholamine-secreting tumors. These tumors are rare in children, and they may be associated with hereditary syndromes such as von Hippel-Lindau (VHL) disease. Most pediatric patients with pheochromocytoma present with sustained hypertension, while 10% to 69% of adult patients are asymptomatic. Herein, we present the case of a 12-yr-old Japanese girl with pheochromocytoma due to a germline mutation in the VHL (Arg161Gln). The only complaint was loss of weight. Pyrexia, anemia, and increases in C-reactive protein (CRP) and ferritin were observed. Abdominal ultrasonography revealed a right adrenal gland tumor. Fractionated catecholamines and metanephrines in plasma and 24-h collected urine revealed elevated levels of norepinephrine and normetanephrine. Although hypertension and tachycardia were inapparent by an ordinary physical examination, paroxysmal mild hypertension and tachycardia were identified by a thorough examination after walking and abdominal compression. Paroxysmal hypertension and tachycardia were profound during operation. In conclusion, pheochromocytoma can be a consideration in the differential diagnosis of weight loss. Hypertension and tachycardia can be inapparent and paroxysmal in pediatric patients as well as in adults; thus, thorough assessment should be repeated.

Genetic defects in the immunoglobulin superfamily member 1(IGSF1) protein are the cause of congenital central hypothyroidism (C-CH). Here we report two Japanese siblings with C-CH due to a novel IGSF1 mutation. The youngest brother showed a failure to thrive, hypothermia, and neonatal icterus six days after birth. Further endocrine evaluations led to the diagnosis of C-CH. In addition, PRL deficiency was later detected. In contrast, the elder brother did not show symptoms of severe hypothyroidism during the neonatal period, but he had been followed up by doctors due to psychomotor developmental delays since the age of 1 yr. At the age of 3 yr, he had low thyroxine and PRL levels and was also diagnosed with C-CH. Because of the C-CH and PRL deficiency, an IGSF1 deficiency was suspected. Sequence analysis of the IGSF1 gene identified a novel hemizygous mutation of p.Trp1173GlyfsTer8 (NM_001170961.1:c.3517del) in both siblings. In conclusion, the phenotypic severity of C-CH is different, even in siblings. Importantly, an IGSF1 deficiency may result in severe hypothyroidism during the neonatal period.