Perinatal asphyxia and hypothermic treatment from the endocrine perspective.

Introduction: Perinatal asphyxia is one of the three most important causes of neonatal mortality and morbidity. Therapeutic hypothermia represents the standard treatment for infants with moderate-severe perinatal asphyxia, resulting in reduction in the mortality and major neurodevelopmental disability. So far, data in the literature focusing on the endocrine aspects of both asphyxia and hypothermia treatment at birth are scanty, and many aspects are still debated. Aim of this narrative review is to summarize the current knowledge regarding the short- and long-term effects of perinatal asphyxia and of hypothermia treatment on the endocrine system, thus providing suggestions for improving the management of asphyxiated children. Results: Involvement of the endocrine system (especially glucose and electrolyte disturbances, adrenal hemorrhage, non-thyroidal illness syndrome) can occur in a variable percentage of subjects with perinatal asphyxia, potentially affecting mortality as well as neurological outcome. Hypothermia may also affect endocrine homeostasis, leading to a decreased incidence of hypocalcemia and an increased risk of dilutional hyponatremia and hypercalcemia. Conclusions: Metabolic abnormalities in the context of perinatal asphyxia are important modifiable factors that may be associated with a worse outcome. Therefore, clinicians should be aware of the possible occurrence of endocrine complication, in order to establish appropriate screening protocols and allow timely treatment.

Influence of Hashimoto Thyroiditis on the Development of Thyroid Nodules and Cancer in Children and Adolescents.

It is unclear whether patients with Hashimoto thyroiditis (HT) are predisposed to develop thyroid nodules and/or thyroid cancer. The objective of our study was therefore to assess the prevalence of thyroid nodules and/or cancer in patients with HT and to look for possible prognostic factors. A retrospective survey of 904 children/adolescents with HT (709 females, 195 males) regularly followed in nine Italian centers of pediatric endocrinology was performed. Median period of follow-up was 4.5 years (1.2 to 12.8 years). We evaluated free T4, TSH, thyroid peroxidase antibody (TPOAb), thyroglobulin antibodies, and thyroid ultrasound yearly. One hundred seventy-four nodules were detected, with an annual incidence rate of 3.5%. Ten nodules were malignant (8 papillary and 2 papillary follicular variant), giving a 5.7% prevalence of cancer among patients with nodules. The severity of hypoechogenity at ultrasound, TPOAb, and free T4 serum concentrations were predictive for the appearance of new nodules. Furthermore, a positive correlation was observed between TPOAb titer and the development of thyroid cancer. In conclusion, HT seems to influence the development of thyroid nodules, but not cancer in children and adolescents.

Final height in Italian patients with congenital hypothyroidism detected by neonatal screening: a 20-year observational study.

BACKGROUND: Linear growth and final height are reported as normal in congenital hypothyroid patients in the neonatal screening era. METHODS: We evaluated the final height in 215 patients with congenital hypothyroidism to assess if it improved over the last 2 decades. RESULTS: Final height (-0.1 ± 1.0 SDS) was higher than target height (-0.8 ± 1.0 SDS, p < 0.001) and not different among the 4 quartiles for birthdate. It was correlated with target height (r(2) = 0.564, p < 0.001) and height at puberty onset (r(2) = 0.685, p < 0.001), but not with age at diagnosis or the starting LT4/kg/day dose. The curve fitting analysis showed that the age at diagnosis progressively decreased during the 20-year study period, while the target height and the starting LT4/kg/day increased. Final height was not affected by the birthdate, the age at diagnosis, the starting LT4 dose. CONCLUSIONS: The final height is higher than the target height, but despite the improvement in the screening and the treatment, it did not improve over the last 20 years. These findings are in keeping with the described secular trend and suggest that earlier diagnosis and replacement therapy do not significantly modify final height in these patients.

Levothyroxine requirement in congenital hypothyroidism: a 12-year longitudinal study.

The aim of the replacement therapy with levothyroxine in congenital hypothyroidism (CH) is to correct hypothyroidism and ensure normal growth and neuropsychological development. Few data are available about the appropriate dose during childhood and early adolescence; therefore, we performed a multicenter observational study in a large population of patients with CH to assess the required levothyroxine dose to obtain euthyroidism. We recruited 216 patients with permanent CH classified into three groups (agenesia, ectopia, and in situ gland) on the basis of the thyroid imaging. The levothyroxine dose was recorded at 6 and 12 months and then yearly until 12 years of age. The daily levothyroxine requirement progressively decreased during the follow-up, irrespective of etiology. It was significantly lower in patients with in situ gland than in patients with athyreosis during the entire study period and with ectopic gland from the age of 1 year. The levothyroxine requirement at 6 months of age was correlated with the requirement at each later time-point. The daily dose was modified less frequently in patients with in situ thyroid (36 %) than in patients with ectopic gland (41.4 %) or with athyreosis (43.6 %). Patients with in situ gland required a lower dose than the other two subgroups. The dose at 6 months seems predictive of the requirement until 12 years of age. Euthyroidism may be achieved in pre-school and in-school patients by 3-4 and 2-3 µg/kg/day (70-90 and 60-80 µg/m(2)/day) of levothyroxine, respectively.

Rare cases of autoimmune hypothyroidism in young children.

Acquired autoimmune hypothyroidism is common in late childhood and adolescence but is very rare in the first 3 years of life. We report on three cases of autoimmune thyroiditis (AT) in young children who presented with constipation, decreased appetite, and increased hours of sleep. Our cases highlight that AT may remain undiagnosed for a long time in young children owing to the rarity of the disease.

Asymptomatic thyrotropin-secreting pituitary macroadenoma in a 13-year-old girl: successful first-line treatment with somatostatin analogs.

BACKGROUND: Thyrotropin-secreting pituitary adenomas (TSHomas) are an extremely rare cause of hyperthyroidism. Up to now there are only few cases reported in the pediatric age range. Thefirst therapeutic option is surgical resection, whereas medical treatment with somatostatin analogs has been reported only in cases wherein surgery was unsuccessful. PATIENT FINDINGS: A 13-year-old girl was referred to our clinic for incidental finding of increased circulating free thyroid hormones in the presence of detectable TSH concentrations. She had no signs/symptoms of thyrotoxicosis. Resistance to thyroid hormone was excluded due to the lack of TSH response after thyrotropin-releasing hormone (TRH) stimulation test. Cerebral magnetic resonance imaging showed the presence of a large pituitary macroadenoma, with intra- and suprasellar extension. We decided to treat this patient with somatostatin analog as a first-line therapy because of high surgery risks due to the tumor dimensions. The response to medical treatment was excellent, with rapid and significant tumor shrinkage. No major side effects were reported. The patient developed central hypothyroidism that was corrected with L-thyroxine therapy. SUMMARY: We report the first pediatric case of TSHoma treated with somatostatin analog as a first-line therapy. The diagnosis was challenging because of the insidious and asymptomatic presentation of the tumor. CONCLUSIONS: We conclude that somatostatin analogs should be considered as first choice, bridge-to-surgery treatment in young patients, in order to reduce neurosurgical complications and prevent hypopituitarism during pubertal development.

Bulb biopsies for the diagnosis of celiac disease in pediatric patients.

BACKGROUND: Celiac disease (CD) is a gluten-dependent enteropathy. The current standard for diagnosing CD involves obtaining 4 biopsy samples from the descending duodenum. It has been suggested that duodenal bulb biopsies may also be useful. OBJECTIVE: To assess the utility of bulbar biopsies for the diagnosis of CD in pediatric patients. DESIGN: Prospective study. SETTING: Single center. PATIENTS: Forty-seven consecutively enrolled pediatric patients with celiac serologies and a clinical suspicion of CD. INTERVENTIONS: All patients underwent EGD, and 4 biopsy samples were obtained from the duodenal bulb and 4 from the descending duodenum of each child. MAIN OUTCOME MEASUREMENTS: The pathologist blindly reported the Marsh histological grade for the diagnosis of CD of the bulb and descending duodenum. RESULTS: The diagnosis of CD was histologically confirmed in 89.4% (42/47) of the cases of biopsy samples obtained from the descending duodenum and in all 47 obtained from the bulb. In 35 patients (74.5%), histology was the same in the bulb and duodenum; in 11 (23.4%) cases, the grade of atrophy was higher in the bulb than in the descending duodenum, and 5 (10.6%) had bulb histology positive for CD but negative duodenal findings. One child (2.1%) had a higher histological grade in the duodenum than in the bulb. The diagnostic gain with bulbar biopsies was 10.6%. LIMITATIONS: Small sample and absence of a comparison group (asymptomatic children with normal CD antibodies). CONCLUSIONS: We suggest examining 4 biopsy samples from the duodenal bulb and 4 from the descending duodenum to improve diagnostic accuracy of CD.