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.

Dehydroepiandrosterone (DHEA) replacement reduces growth hormone (GH) dose requirement in female hypopituitary patients on GH replacement.

OBJECTIVE: GH dose requirement is lower in ACTH replete compared with ACTH deficient hypopituitary patients suggesting that adrenal androgens may augment IGF-I generation for a given GH dose. This study aimed to determine the effect of dehydroepiandrosterone (DHEA) administration on GH dose requirements in hypopituitary adults. DESIGN: A double blind placebo controlled trial was conducted adding 50 mg DHEA to the standard replacement of hypopituitary patients, including GH, over an initial 6 months, followed by an open phase study of 6 months DHEA replacement and a final 2 month washout phase after DHEA withdrawal. The dose of GH was adjusted to achieve a constant serum IGF-I. PATIENTS: Thirty female and 21 male hypopituitary patients were enrolled. Data from 26 women and 18 men were analysed after patient withdrawal. MEASUREMENTS: The primary outcome objective was the GH dose required to achieve a stable serum IGF-I. Secondary outcome measures were lipoprotein profiles, insulin, insulin sensitivity, IGFBP-3, waist/hip ratio and indices of bone remodelling. RESULTS: DHEA replacement in female patients lead to a 14.6 +/- 20% reduction in the dose of GH for a constant serum IGF-I (P < 0.05, 95% CI: 1.8, 32.7). This was maintained for 12 months and there was a significant fall in serum IGF-I two months after withdrawal of DHEA. There was no change in the male group. CONCLUSIONS: DHEA replacement may reduce GH dose requirements in female hypopituitary patients.

Dehydroepiandrosterone improves psychological well-being in male and female hypopituitary patients on maintenance growth hormone replacement.

CONTEXT: Patients with panhypopituitarism have impaired quality of life (QoL) despite GH replacement. They are profoundly androgen deficient, and dehydroepiandrosterone (DHEA) has been shown to have a beneficial effect on well-being and mood in patients with adrenal failure and possibly in hypopituitarism. OBJECTIVE: Our objective was to determine the effect of DHEA administration on mood in hypopituitary adults on established GH replacement with a constant serum IGF-I. DESIGN: A double-blind, placebo-controlled trial was conducted over an initial 6 months followed by an open phase of 6 months of DHEA. SETTING: The study was conducted at a tertiary referral endocrinology unit. PATIENTS: Thirty female and 21 male hypopituitary patients enrolled. Data from 26 females and 18 males were analyzed after patient withdrawal. INTERVENTIONS: DHEA (50 mg) was added to maintenance replacement including GH. MAIN OUTCOME MEASURES: The primary outcome objective was the effect on QoL and libido assessed by QoL assessment in GH deficiency in adults, Short Form 36, General Health Questionnaire, EuroQol, and sexual self-efficacy scale. RESULTS: Patients had impaired QoL at baseline compared with the age-matched British population. Females showed improvement in QoL assessment in GH deficiency in adults score (-2.9 +/- 2.8 DHEA vs.-0.53 +/- 3 placebo; P < 0.05), in Short Form 36 social functioning (14.6 +/- 23.1 DHEA vs.-4.7 +/- 25 placebo; P = 0.047), and general health perception (9.6 +/- 14.2 DHEA vs.-1.2 +/- 11.6 placebo; P = 0.036) after 6 months of DHEA. Men showed improvement in self-esteem (-1.3 +/- 1.7 DHEA vs. 0.5 +/- 1.5 placebo; P = 0.03) and depression (-1.6 +/- 2.2 DHEA vs. 1.2 +/- 2.4 placebo, P = 0.02) domains of the General Health Questionnaire after 6 months of DHEA. CONCLUSIONS: DHEA replacement leads to modest improvement in psychological well-being in female and minor psychological improvement in male hypopituitary patients on GH replacement.

Do all adults with growth hormone deficiency require growth hormone treatment?

Adult growth hormone (GH) deficiency results mainly from pituitary or peri-pituitary disease and/or its treatment and is frequently accompanied by other anterior pituitary hormone deficiencies. GH deficiency (GHD) results in a number of psychological and physical symptoms and signs which in combination constitute the adult 'GHD syndrome'. The psychological symptoms include decreased energy levels, social isolation, and lack of positive well being, depressed mood and increase in anxiety. The physical symptoms and signs include abnormal body composition with reduced lean body mass, increased central adiposity, and decreased extracellular fluid volume, decreased bone mineral density with an increased risk of fracture, reduced muscle strength, reduced exercise capacity, increased LDL cholesterol and reduced insulin sensitivity. Hypopituitarism and GHD are associated with an increased standardised mortality ratio. The diagnosis of GHD is confirmed by the insulin tolerance test or alternative stimulation test in the presence of structural pituitary disease and/or additional pituitary hormone deficiencies. Replacement with synthetic growth hormone by once daily subcutaneous injection can reverse many of the symptoms and signs of growth hormone deficiency, but the long-term effects are yet to be established. Whether or not all patients with GHD should receive GH replacement remains a matter for debate: a selective approach to therapy based on psychological well being and quality of life has been adopted in many centres.