Altered growth patterns of a mountain Ok population of Papua New Guinea over 25 years of change.

CONTEXT: The Mountain Ok (Mt Ok) people of Telefomin, who live at the interior of Papua New Guinea (PNG), were documented over 25 years ago to be one of the shortest populations on record, with average adult height below the fifth percentile (US). Serum Growth Hormone was detectable, Insulin-like Growth Factor-1 and serum indicators of protein nutritional status fell within the normal range, suggesting that these were not primary factors for their relative short stature. OBJECTIVE: Since the Telefolmin people have experienced recent socioeconomic changes, they were re-evaluated in 2008, to examine height, weight, and body mass index (BMI), for insight into relative contributions of environment and other factors that modulate stature in children and adults. STUDY DESIGN AND SETTING: Cross-sectional anthropometric data were collected from 474 individuals at Telefomin in 2008, and compared with anthropometric data from 342 individuals measured in 1983. RESULTS: The height of Telefolmin subjects, below the fifth percentile in 1983, remained below the fifth percentile in 2008. Weight and BMI of peripubertal and adult age groups increased from 1983 to 2008. Male and female heights at peripubertal ages were significantly greater in 2008. Nevertheless, final adult height did not change significantly over the 25 years. CONCLUSIONS: Recent socioeconomic changes appear to contribute to increased weight, BMI, and stature at younger ages in the Mt Ok at Telefomin. In contrast, unchanging adult stature may reflect a delay in the impact of socioeconomic changes, or genetic influences that modulate responsiveness to other growth regulators.

Familial neonatal nonautoimmune hyperthyroidism due to a gain-of-function (D619G) thyrotropin-receptor mutation.

OBJECTIVES: Activating germline mutations of the thyroid-stimulating hormone receptor (TSHR) are responsible for a rare form of neonatal nonautoimmune hyperthyroidism (NAH). We report the first case of familial neonatal neonatal nonautoimmune associated with c.1856A>G (p.Asp619Gly) variant in the TSHR gene. CASE PRESENTATION: We describe an eight-year-old African-American female presenting with neonatal NAH associated with an inherited heterozygous c.1856A>G (p.Asp619Gly) variant in the TSHR gene. This variant was previously described in one patient presenting with sporadic NAH in adolescence. Our patient was diagnosed with hyperthyroidism in the neonatal period. The mother had a history of hyperthyroidism and had thyroidectomy at the age of 4 years. The patient had goiter and elevated free thyroxine (FT4) and free triiodothyronine (FT3) levels that normalized with methimazole treatment; however, TSH level remained suppressed. Thyroid antibodies were negative. The patient also had bilateral exotropia, a trait shared by the mother and may represent a new association. CONCLUSIONS: Familial neonatal NAH is associated with heterozygous c.1856A>G (p.Asp619Gly) variant of the TSHR gene.

Neonatal diabetes mellitus with pancreatic agenesis in an infant with homozygous IPF-1 Pro63fsX60 mutation.

Permanent neonatal diabetes mellitus is a rare disorder known to be caused by activating mutations in KCNJ11 or ABCC8, inactivating mutations in INS, or very rarely in GCK or insulin promotor factor-1 (IPF-1) genes. We report a patient with permanent neonatal diabetes mellitus and severe exocrine pancreatic insufficiency. Ultrasound examination revealed pancreatic agenesis with a suggestion of a small amount of tissue in the head of the pancreas. Genetic testing revealed that the neonate had a homozygous Pro63fsX60 IPF-1 mutation. This is the second reported case of neonatal diabetes mellitus secondary to a homozygous mutation in the IPF-1 gene and supports the previously proposed biological role of IPF-1 in the pancreatic development in human.

Methimazole Induced Total Myeloid Aplasia with Delayed Recovery Despite Granulocyte Colony Stimulating Factor (G-CSF): Marrow Progenitor Recovery Kinetics.

An eighteen-year-old female with Graves thyrotoxicosis presented with methimazole-induced agranulocytosis and total myeloid aplasia. The bone marrow at presentation showed complete absence of myeloid precursors and striking plasmacytosis. 16 days later, myeloid precursors were still absent morphologically; however bone marrow flow cytometry and cell culture detected an improvement in myelogenesis, which was soon followed by clinical recovery of agranulocytosis. Neutrophil recovery was delayed until day 22 after cessation of methimazole despite G-CSF use, consistent with a direct toxic effect on committed myeloid cells. Our findings suggest that cell culture and flow cytometric evaluation of bone marrow myeloid progenitors can be used as a guide to anticipate neutrophil recovery.

Development and Validation of a Pediatric Endocrine Knowledge Assessment Questionnaire: Impact of ac Pediatric Endocrine Knowledge Assessment Questionnaire Intervention Study.

OBJECTIVE: While there is general agreement that patient education is essential for compliance, no objective tools exist to assess knowledge in children and parents of children with endocrine disorders. We aimed to design and validate a Pediatric Endocrine Knowledge Assessment Questionnaire (PEKAQ) for congenital hypothyroidism, Hashimoto's thyroiditis, isolated growth hormone deficiency, Graves' disease, and congenital adrenal hyperplasia. We evaluated baseline knowledge of children and parents of children with these disorders and assessed impact of educational intervention. METHODS: At baseline, 77 children (12-18 years) and 162 parents of children 1-18 years participated in this prospective intervention study. Educational handouts for five targeted disorders were designed. Following one-on-one educational intervention, 55 children and 123 parents participated. Baseline and post-intervention knowledge scores were compared using McNemar's test. RESULTS: Adequate multi-rater Kappa measure of agreement was achieved for children's (0.70) and parent's (0.75) PEKAQs. Flesch Reading Ease Score for both PEKAQs (15 questions each) was 65. Post-intervention, significantly higher proportion of parents and children answered majority of questions correctly (p<0.05). Sixteen percent more parents and 22% more children knew their diagnosis correctly (p<0.05). Significant improvement was noted among all participants regarding reason for treatment, steps to take in a situation of missed dose, exercise and diet with these disorders, and long-term prognosis. Parent's knowledge score was an independent predictor of child's score. CONCLUSIONS: To our knowledge, this is the first validated PEKAQ that can be used widely in pediatric endocrinology clinics. We noted significant improvement in knowledge of children and parents of children with endocrine disorders.