Androgen Receptor CAG Repeat Length in Relation to Phenotype Among Females with Nonclassical 21-Hydroxylase Deficiency.

Nonclassical 21-hydroxylase deficiency (NC21OHD) manifests with various degrees of post natal virilization. The length of CAG repeats of the androgen receptor gene (AR) is inversely correlated to activity of the human androgen receptor (AR) and affects phenotype of several androgen-dependent disorders. The aim of the study was to investigate the associations between CAG repeat length and the phenotype of females with NC21OHD. CAG repeat length and AR inactivation were assessed in females with NC21OHD, and related to their clinical presentation. CAG repeat length and AR inactivation were assessed in 119 females with NC21OHD. Biallelic mean (BAM) of the CAG repeat length and the weighted BAM (WBAM) were related to various clinical parameters. Age at diagnosis and age of menarche positively correlated with BAM (r=0.22, p=0.02, and r=0.23, p=0.01, respectively). A shorter (<25) BAM was associated with younger age at diagnosis (14.8 vs. 21.4 years, p<0.01), at adrenarche (8.1 vs. 10.2 years, p<0.01) and gonadarche (9.9 vs. 11.2 years, p<0.01), and higher corrected height standard deviation score at diagnosis (0.77 vs. 0.15, p=0.01). Precocious pubarche and precocious puberty were more frequent in these with the shorter BAM. Results of WBAM were similar. The CAG repeat length of the AR gene contributes to the clinical diversity of the phenotype in females with NC21OHD.

Improved glycaemic control with reduced hypoglycaemic episodes and without weight gain using long-term modern premixed insulins in type 2 diabetes.

OBJECTIVE: The primary goal of the study was to evaluate retrospectively efficacy of long-term modern premixed insulin (MPI) administration. The secondary aims were to monitor weight gain, hypoglycaemia and compliance during MPI therapy. RESEARCH DESIGN AND METHODS: One hundred and fifteen outpatients with type 2 diabetes (64 male patients, 51 female patients; mean age 62.4±12.2 years; mean duration of diabetes 10±8 years; mean weight 84.3±14.8 kg) were included in this study. Patients were prescribed one of three MPIs thrice-daily: biphasic insulin lispro 25, biphasic insulin lispro 50, or biphasic insulin aspart 30. Metformin was combined with MPI in 81 patients. Data prior to and during MPI treatment were retrieved from computerised patient medical files. RESULTS: After a mean treatment period of 2.9±0.9 years, mean A1C levels and fasting blood glucose decreased from 8.7±1.4% and 193±59 mg/dl to 7.3±1.1% and 141±41 mg/dl (p<0.001 for both), respectively. Thirty-six per cent of the cohort achieved target A1C level of ≤7%. Serum triglycerides decreased from 183±109 mg/dl to 151±76 mg/dl (p<0.001). Weight did not change during MPI treatment. Frequency of minor hypoglycaemic episodes decreased significantly during MPI administration. No major hypoglycaemic event was reported. Number of incompliant patients decreased significantly from 39 to 25 (p=0.001) during MPI treatment. CONCLUSIONS: Modern premixed insulins represent an effective and safe long-term therapy for patients with type 2 diabetes. Specifically, the regimen of thrice-daily injections combined with metformin is a viable treatment option.

Acquired prolactin deficiency in patients with disorders of the hypothalamic-pituitary axis.

UNLABELLED: Acquired PRL deficiency occurs when the anterior pituitary is functionally destroyed, and it usually accompanies other pituitary hormone deficiencies. We retrospectively investigated in an outpatient endocrine clinic of a major tertiary medical center the prevalence and clinical characteristics of acquired PRL deficiency in patients with diseases of the hypothalamic-pituitary axis. The study included 100 consecutive patients, 61 men and 39 women, aged 4-79 yr at diagnosis. Patients were divided by PRL level to normal (>5 ng/ml), mild (3-5 ng/ml), and severe deficiency (<3 ng/ml). Twenty-seven patients (27%) had PRL deficiency, 13 mild deficiency and 14 severe deficiency. Patients with severe PRL deficiency tend to be younger at diagnosis (mean age, 37.5+/-21.8 yr) than patients with normal PRL (46+/-18.5 yr; ns). Underlying diseases including pituitary apoplexy, non-functioning pituitary adenoma, craniopharyngioma, and idiopathic hypogonadotropic hypogonadism were associated with PRL deficiency. The incidence of severe PRL deficiency rose with an increase in the number of other pituitary hormone deficits (ACTH, TSH, gonadotropin, vasopressin), from 0 in patients with no other deficits to 38% in patients with 4 deficits (p=0.006). Patients with severe deficiency had a mean of 3 hormone deficits compared to 1.8 in the other groups (p=0.006). PRL deficiency was significantly associated with TSH, ACTH and GH deficiency. CONCLUSIONS: PRL deficiency is common in patients with hypothalamic-pituitary disorders, especially pituitary apoplexy and craniopharyngioma. Acquired severe PRL deficiency can be considered a marker for extensive pituitary damage and a more severe degree of hypopituitarism.

Invasive pneumococcal infections. A comparison between adults and children.

A similar number of adults and children had invasive pneumococcal infection. There was male predominance, and different ethnic distribution between children and adults. The majority of adults (78%), had underlying diseases, but this was less frequent in children (24%). The presenting illness differed between adults and children. Complications of invasive pneumococcal infection occurred more frequently in adults than in children. The mortality rate in adults was 21.5%; in children, only 3.8%. The rate of penicillin-resistant pneumococci at our hospital was 23%, while cefotaxime resistance was 4.2%. Penicillin-resistant pneumococci were not isolated more frequently from children than from adults. Patients with penicillin-resistant pneumococci had longer duration of hospitalization and more nosocomially acquired infections. No difference in the mortality rate was found between patients with resistant or sensitive pneumococci. Ninety-five percent of strains were included in the current vaccine, but less than 2% of patients had been vaccinated. Isolates prevalent in Europe and the United States (19, 5, 1, 14, 6, 18, 12, 4, 9, 23, 7) were also most prevalent in Jerusalem. The distribution of serotypes differed between children and adults, and between patients from whom resistant organisms were isolated as opposed to sensitive organisms.