A Novel Mutation in the TBG Gene Producing Partial Thyroxine-Binding Globulin Deficiency (Glencoe) Identified in 2 Families.

BACKGROUND: Thyroxine-binding globulin (TBG) is the major thyroid hormone transport protein in serum. Located on the long arm of the X chromosome, TBG (SERPINA7) gene mutations most commonly produce inherited partial TBG deficiency (TBG-PD). OBJECTIVE: We report a novel TBG variant associated with TBG-PD identified in 2 different families of Ashkenazi origin residing in greater Chicago. METHODS: Family 1: The proband was 12.6 years old when she presented for delayed puberty and was placed on L-T4. Although her serum TSH normalized, her serum T4 remained low. Affected family members had low total T4 and T3, but a normal free T4 index, even when serum TSH concentrations were normal. Family 2: A 71-year-old male presented with a history of a nonfunctioning pituitary adenoma and normal pituitary axes except for low total T4 and T3. His brother had a similar thyroid phenotype. RESULTS: Following direct DNA sequencing, both index patients were found to carry a missense mutation in the TBG gene (c.751T>G) producing p.V215G. The proposita of family 1 was heterozygous and the proband in family 2 was hemizygous for the mutation. Isoelectric focusing showed no alteration in the TBG isoforms and in vitro expression demonstrated a TBG with reduced affinity for T4. CONCLUSIONS: We report a novel mutation in the TBG gene in 2 unrelated families that produces a molecule with reduced affinity for T4 resulting in low serum T4. However, the physical properties of the mutant molecule remained unaltered as determined by isoelectric focusing.

Glucose control in Rwandan youth with type 1 diabetes following establishment of systematic, HbA1c based, care and education.

AIMS: To assess change in glycemic control concurrent with increased clinic visits, HbA1c testing, and education. Rates of complications were also examined. METHODS: A 1-2 year follow-up of 214 members of the Rwanda Life for a Child program (aged <26 years) with a first HbA1c between June 2009 and November 2010 was conducted. Data were analyzed for the entire cohort and by age (<18 years, ≥18 years). Trajectory analysis was performed to identify trends in HbA1c. RESULTS: Mean overall HbA1c decreased significantly from baseline (11.2 ± 2.7%; 99 ± 30 mmol/mol) to one- (10.2 ± 2.6%; 88 ± 28 mmol/mol) and two- (9.8 ± 26%; 84 ± 25 mmol/mol) year follow up visits. The prevalence of microalbuminuria did not significantly change (21.0%, 18.8%, and 19.6%), nor did nephropathy (4.7%, 7.8%, and 5.4%). However, rates of hypertension (31.8%, 44.9%, and 40.3%) were higher than expected. Five HbA1c groups were identified by trajectory analysis, and those with the worst control monitored their glucose significantly fewer times per week. CONCLUSIONS: The establishment of regular care, HbA1c testing, and increased education is associated with significant improvements in glycemic control in youth with type 1 diabetes (T1D) in sub-Saharan Africa, but the high prevalence of hypertension is of concern.

Intractable early childhood obesity as the initial sign of insulin resistant hyperinsulinism and precursor of polycystic ovary syndrome.

OBJECTIVE: We report that intractable early childhood obesity may be associated with severe insulin resistance syndromes (pseudo-Cushing's syndrome and pseudo-acromegaly) and precede polycystic ovary syndrome (PCOS). STUDY DESIGN/RESULTS: Patient 1 had prepubertal obesity followed by early puberty and was diagnosed with pseudo-Cushing's syndrome and insulin resistance at 10.3 years. Oligomenorrhea, androgen excess, and type 2 diabetes mellitus (DM2) emerged at 13.5 years. Patient 2 developed intractable prepubertal obesity followed by atypical true sexual precocity and pseudo-Cushing's syndrome in early childhood. By 11.3 years, oligomenorrhea, androgen excess, and DM2 had appeared. Patient 3 had prepubertal overgrowth in weight and height and was diagnosed with pseudo-acromegaly, menstrual irregularity, androgen excess, and impaired glucose tolerance at 14.3 years of age. Patient 4 had prepubertal overgrowth that evolved into pseudo-acromegaly, insulin resistance, secondary amenorrhea, and androgen excess at 15.6 years. CONCLUSIONS: Intractable prepubertal obesity was recognized to culminate in early childhood pseudo-Cushing's syndrome or pseudo-acromegaly, which are manifestations of insulin-resistant hyperinsulinism, and to herald adolescent PCOS.

Increasing problem solving in adolescents with type 1 diabetes: the choices diabetes program.

UNLABELLED: The purpose of this pilot study was to test the hypothesis that adolescents with type 1 diabetes can learn to become better problem solvers in diabetes self-care and thereby improve their metabolic control. METHODS: Fifty-three adolescents aged 13 to 17 with type 1 diabetes were randomly assigned to either a 6-week problem-solving diabetes education program or to a control group (usual care). A1C levels were obtained as well as assessments of problem solving, frequency of behavior, level of responsibility, and 24-hour behavior recall at baseline and 6 months. RESULTS: The experimental group participants showed significantly improved problem-solving test scores and A1C values from baseline to 6 months, changes not evident in the control group. At 6 months, the experimental group participants were doing blood glucose testing more often than those in the control group. However, there was no significant difference in problem-solving test scores or A1C values. CONCLUSIONS: This 6-week intervention for adolescents with diabetes resulted in better problem-solving skills, more frequent blood glucose testing, and improved A1C values. The results suggest that a diabetes problem-solving program for adolescents can be effective in improving metabolic control.