Mosaic Turner syndrome shows reduced penetrance in an adult population study.

PURPOSE: Many women with X chromosome aneuploidy undergo lifetime clinical monitoring for possible complications. However, ascertainment of cases in the clinic may mean that the penetrance has been overestimated. METHODS: We characterized the prevalence and phenotypic consequences of X chromosome aneuploidy in a population of 244,848 women over 40 years of age from UK Biobank, using single-nucleotide polymorphism (SNP) array data. RESULTS: We detected 30 women with 45,X; 186 with mosaic 45,X/46,XX; and 110 with 47,XXX. The prevalence of nonmosaic 45,X (12/100,000) and 47,XXX (45/100,000) was lower than expected, but was higher for mosaic 45,X/46,XX (76/100,000). The characteristics of women with 45,X were consistent with the characteristics of a clinically recognized Turner syndrome phenotype, including short stature and primary amenorrhea. In contrast, women with mosaic 45,X/46,XX were less short, had a normal reproductive lifespan and birth rate, and no reported cardiovascular complications. The phenotype of women with 47,XXX included taller stature (5.3 cm; SD = 5.52 cm; P = 5.8 × 10-20) and earlier menopause age (5.12 years; SD = 5.1 years; P = 1.2 × 10-14). CONCLUSION: Our results suggest that the clinical management of women with 45,X/46,XX mosaicism should be minimal, particularly those identified incidentally.

Block & replace regime versus titration regime of antithyroid drugs for the treatment of Graves' disease: a retrospective observational study.

CONTEXT: Two widely used antithyroid drug (ATD) regimes for Graves' disease (GD) include the 'block & replace' (B&R) regime (a fixed high-dose of ATD combined with levothyroxine) and the 'titration' regime (a titrating dose of ATD). Anecdotally, it is believed that B&R is less prone to fluctuating thyroid function. OBJECTIVE: To study whether, in routine clinical practice, the B&R regime, compared with the titration regime, is associated with more stable thyroid function. METHODS: We retrospectively analysed case-records for 450 patients treated with ATDs for GD at a secondary care hospital. Exclusion criteria included treatment with ATDs for <6 months, thyrotoxicosis due to other causes, treatment with radioiodine or thyroidectomy and pregnancy. RESULTS: Two hundred and twenty three patients were treated with the B&R regime ('B&R group'), 149 with the titration regime ('titration group') and 78 with both regimes. The number of thyroid function tests (TFTs) performed per year (mean(SD): 3·2(1·2) vs 3·4(1·5); adjusted mean difference = -0·4; 95% CI: -0·7 to -0·1; and P = 0·008) and the number of hospital clinic visits per year (mean (SD): 2·9 (1·0) vs 3·2 (1·3); adjusted mean difference = -0·4; 95% CI: -0·7 to -0·2; and P = 0·002) were lower in the B&R group than the titration group. The number of abnormal TFT results per year was similar in the two groups (mean(SD): 1·8(1·3) vs 1·8(1·4); adjusted mean difference = 0·05; 95%CI: -0·3 to 0·4; and P = 0·74). CONCLUSIONS: In this retrospective study, there was little evidence that patients under B&R have more stable thyroid function. Further data from prospective studies, however, are needed to confirm this finding.

A novel case of a raised testosterone and LH in a young man.

A 19 year old male attended his GP with a history of "fluid retention", lack of libido and erectile dysfunction. He was found to have a high serum testosterone, and a raised luteinising hormone. After further investigations, the patient admitted to taking a supplement called ActivaTe Xtreme, obtained from an internet source, to address his low libido. ActivaTe Xtreme contains active ingredients which increase serum testosterone levels by several independent mechanisms that are not associated with luteinising hormone suppression. Urine analyses for synthetic anabolic steroids were negative, and urinary testosterone, epitestosterone and other androgens were normal. This biochemical pattern is not the same as that seen with anabolic steroids (i.e. raised testosterone, suppressed luteinising hormone and abnormal urine steroid profile). The issue of self medication with performance enhancing compounds needs to be carefully considered in order to avoid expensive and invasive investigations, missing an underlying pathology or misdiagnosing a patient. This case also raises the spectre of yet another "performance enhancing" product that may cause difficulty for those trying to ensure that sport remains on a "hormonally" equal basis.

The Ipswich Touch Test: a simple and novel method to identify inpatients with diabetes at risk of foot ulceration.

OBJECTIVE: To promote foot screening of inpatients with diabetes, we simplified sensory testing to lightly touching the tips of the first, third, and fifth toes (the Ipswich Touch Test [IpTT]). RESEARCH DESIGN AND METHODS: Respective performances of the IpTT and 10-g monofilament (MF) were compared with a vibration perception threshold of ≥25 V indicating at-risk feet in 265 individuals. The IpTT and MF were also directly compared. RESULTS: With ≥2 of 6 insensate areas signifying at-risk feet, sensitivities and specificities, respectively, were IpTT (77 and 90%), MF (81 and 91%); positive predictive values were IpTT (89%), MF (91%); and negative predictive values were IpTT (77%), MF (81%). Directly compared, agreement between the IpTT and MF was almost perfect (κ=0.88, P<0.0001). Interrater agreement for the IpTT was substantial (κ=0.68). CONCLUSIONS: The IpTT performs well against a recognized standard for ulcer prediction. Simple to teach, reliable, without expense, and always at hand, it should encourage uptake of screening and detection of high-risk inpatients requiring foot protection.

Mesangiocapillary glomerulonephritis type 2 associated with familial partial lipodystrophy (Dunnigan-Kobberling syndrome).

The lipodystrophies are a heterogeneous group of disorders of adipose tissue associated with insulin resistance. The sporadic form of partial lipodystrophy, characterised by fat loss from the face and upper body, is associated with complement abnormalities and mesangiocapillary glomerulonephritis type 2 (MCGN II) and the conditions are thought to have a shared autoimmune aetiology. We present the first case of the rare familial form of partial lipodystrophy, caused by a mutation in the LMNA gene, associated with MCGN II. This suggests that partial lipodystrophy of both the sporadic and familial subtypes may predispose to this condition and that the observed renal and complement abnormalities may be secondary to other factors associated with lipodystrophy.

Response to treatment with rosiglitazone in familial partial lipodystrophy due to a mutation in the LMNA gene.

BACKGROUND: Familial partial lipodystrophy (FPLD) is a monogenic form of diabetes characterised by a dominantly inherited disorder of adipose tissue associated with the loss of subcutaneous fat from the limbs and trunk, with excess fat deposited around the face and neck. The lipodystrophy causes severe insulin resistance, resulting in acanthosis nigricans, diabetes, dyslipidaemia, and increased risk of cardiovascular disease. Preliminary results from animals and man suggest that increasing subcutaneous fat by treatment with thiazolidinediones should improve insulin resistance and the associated features of this syndrome. CASE REPORT: We report a 24-year-old patient with FPLD caused by a mutation in the LMNA gene (R482W) treated with 12 months of rosiglitazone. Subcutaneous fat increased following rosiglitazone treatment as demonstrated by a 29% generalised increase in skin-fold thickness. Leptin levels increased from 5.8 to 11.2 ng/ml. Compared with treatment on Metformin, there was an increase in insulin sensitivity (HOMA S% 17.2-31.6) but no change in glycaemic control. The lipid profile worsened during the follow-up period. CONCLUSION: This initial case suggests that, for modification of cardiovascular risk factors, there are no clear advantages in treating patients with FPLD with rosiglitazone despite increases in subcutaneous adipose tissue. Larger series will be needed to identify moderate beneficial effects and treatment may be more effective in patients with generalised forms of lipodystrophy.