Longitudinal Evaluation of the Hypothalamic-Pituitary-Testicular Function in 8 Boys with Adrenal Hypoplasia Congenita (AHC) Due to NR0B1 Mutations

BACKGROUND:Boys carrying mutations in the NR0B1 gene develop adrenal hypoplasia congenita (AHC) and impaired sexual development due to the combination of hypogonadotropic hypogonadism (HH) and primary defects in spermatogenesis. METHODS:We analysed the evolution of hypothalamic-pituitary-testicular function of 8 boys with AHC due to NR0B1 mutations. Our objective was to characterize and monitor the progressive deterioration of this function. RESULTS:The first symptoms appeared in the neonatal period (n = 5) or between 6 months and 8.7 years (n = 3). Basal plasma adrenocorticotrophic hormone (ACTH) concentrations increased in all boys, whilst cortisol levels decreased in one case. The natremia was equal or below 134 mmol/L and kaliemia was over 5 mmol/L. All had increased plasma renin. In 3 of 4 patients diagnosed in the neonatal period and evaluated during the first year, the basal plasma gonadotropins concentrations, and their response to gonadotropin releasing hormone (GnRH) test (n = 2), and those of testosterone were normal. The plasma inhibin B levels were normal in the first year of life. With the exception of two cases these concentrations decreased to below the normal for age. Anti-Müllerian hormone concentrations were normal for age in all except one case, which had low concentrations before the initiation of testosterone treatment. In 3 of the 8 cases the gene was deleted and the remaining 5 cases carried frameshift mutations that are predicted to introduce a downstream nonsense mutation resulting in a truncated protein. CONCLUSIONS:The decreases in testosterone and inhibin B levels indicated a progressive loss of testicular function in boys carrying NR0B1 mutations. These non-invasive examinations can help to estimate the age of the testicular degradation and cryopreservation of semen may be considered in these cases as investigational procedure with the aim of restoring fertility

Dentists' and patients' opinions of the dental condition at moment of full clearance

Reasons for full mouth extraction in an urban and a rural area in The Netherlands (dentist‐patient ratio 1:2500 and 1:5700 respectively) have been studied. Patients who participated in this combined sociodental research project were those who received full mouth extractions over a period of 1 yr. The combined patient response was 75% and the overall dentist response 90%. In the urban and the rural areas respectively 137 and 237 cases of full mouth extraction were recorded. When comparing the dentists' diagnoses with the conditions of the dentitions there appeared to be a fair degree of agreement in most of the cases, although some striking deviations were also found. In the relationship between the patient's opinion and the condition of the dentition some unexplained discrepancies were found: 37% of the dentitions in which the teeth and attachment were in a healthy condition were perceived as bad by the patients. Dentists and patients agreed in their perceptions of the dental conditions in 60% of the cases. In 27% there was a strong disagreement. In most of the discrepancies found plausible explanations could be given. In some cases this was not possible. As this involves a substantial minority of cases, dentists should be aware of reasons other than the clinical condition in the disabling treatment of full clearanc