Two siblings with the classical phenotype of complete androgen insensitivity syndrome (CAIS) and increased total cellular androgen receptor concentrations in genital skin fibroblasts (GSF) are described. Testosterone biosynthesis was normal, and there was no evidence of 5 alpha-reductase deficiency. Specific binding of [3H]dihydrotestosterone ([3H]DHT) in GSF was 7 SD above the mean value in normal fibroblast strains [maximum binding, 775 +/- 185 X 10(-18) mol/micrograms DNA (mean +/- SD)]. Binding at 40 C was stable, and the androgen-receptor complex dissociated at a normal rate (t1/2, 85 min). The androgen-receptor complex from GSF cytosol sedimented at 5-6S on sucrose density gradients in the presence of sodium molybdate. In a whole cell binding assay, the percentage of [3H]DHT that bound to a crude nuclear pellet was 60%. Preincubation of GSF with 2 nM [3H]DHT for 20 h before the standard 1-h whole cell binding assay produced a further augmentation in elevated total cellular androgen receptor concentrations. A new variant of CAIS is described which is characterized by an increased concentration of androgen receptors that appear to be quantitatively and qualitatively normal. Augmentation of the receptor by androgen suggests that the gene coding for the androgen receptor is intact and does not account for the androgen insensitivity.

This study examined the fine structure of the human endometrial glandular epithelium after the administration of a single dose of RU486 (mifepristone), given in the early luteal phase. The drug was administered on days 2, 3, 5 and 6 after the luteinizing hormone peak (LH + 0). Biopsies were performed on days LH + 5, 6, 8 and 9. These were compared with control biopsies taken on corresponding days. Qualitatively, the main cytological effect of the RU486 was on the secretory apparatus and on the polarity of the cell. The formation of the nuclear channel system was also affected by the drug. A two-way analysis of variance on cell and nuclear volume data revealed no significant effect of day of biopsy, condition or interaction. Mitochondrial volume and secretory apparatus volume data revealed a significant effect of day of biopsy and interaction term; mitochondrial volume at LH + 5 was 95.9 +/- 25.3 microm3 (mean +/- SD) for control and 57.7 +/- 31.9 microm3 for RU486-treated epithelium. The volume of the secretory apparatus in the treated group was smaller on days LH + 5 and 6 (14.6 +/- 4.2 microm3, 6.41 +/- microm3) when compared to day-matched control biopsies (35.9 +/- 10.5 microm3, 41.7 +/- 26.4 microm3). RU486 administration in the early luteal phase disrupted the secretory activity of the cells. These findings provide an insight into the cellular mechanisms of progesterone receptor blockade in the peri-implantation period.

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A 42 year-old Caribbean woman with, known type 2 diabetes, was admitted with worsening fatigue, arthritis and rashes. She was diagnosed with multisystem systemic lupus erythematosus and was initially treated with systemic steroids. During this admission, she had persistently elevated capillary glucose levels with insulin requirements over 8 U/kg/day that still did not control her blood glucose levels. Due to her profound hyperglycaemia, serum samples of fasting insulin, C-peptide, paired with blood glucose were analysed, which confirmed significant hyperinsulinaemia. Further analysis confirmed the presence of insulin receptor antibodies consistent with type B insulin resistance.She was started on intravenous cyclophosphamide (Euro-Lupus regimen) along with continuous glucose monitoring system. After completing her six cycles of cyclophosphamide, she no longer required insulin treatment. The goal of therapy for our patient with confirmed type B insulin resistance was to manage hyperglycaemia with high doses of insulin until autoantibodies were eliminated with immunosuppressive therapy.

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