Osteoporosis and fractures are features in adults with Turner syndrome (TS). Using dual-energy x-ray absorptiometry, correcting bone mineral content (BMC) for height and lean mass (LTM) avoids misclassification of short children as osteopenic. Total body (TB), lumbar spine (LS), and femoral neck (FN) dual-energy x-ray absorptiometry scans were performed on 83 patients with TS (aged 4-24 yr). A prepubertal subgroup (n = 17) receiving GH was followed for 24 months. Age z-scores for height, TB BMC, LTM, the BMC/LTM ratio, and LS volumetric bone mineral density (vBMD) decreased significantly (P < 0.001) with age in prepubertal subjects (n = 51) but were constant in the combined pubertal and postmenarchal group (n = 32). Osteopenia was found in 14.5% (TB), 15.8% (LS), and 28.4% (FN) of patients. In the longitudinal subgroup, TB BMC z-scores decreased by -0.28 (0.31) in subjects remaining prepubertal (n = 11) but increased by 0.71 (0.56) in subjects entering puberty (n = 6; P = 0.007). The z-scores for height and LTM increased in both groups. Our results show a height-independent prepubertal decrease in bone mass accrual, which ceased with puberty. Optimizing bone mass in TS may require earlier induction of puberty than currently recommended. However, reduced FN volumetric bone mineral density and a dissociation of bone and muscle measures were age independent, suggesting an additional intrinsic bone defect.

No abstract

In children with CAI risk factors, the diagnosis can be made if unstressed 9am cortisol is < 108 nmol/l. As cortisol levels > 381 nmol/l are highly suggestive of normal hypothalamic-pituitary-adrenal (HPA) function, stimulation testing need only be performed if 9am cortisol is 108-381 nmol/l. The LDST should be interpreted cautiously because mild CAI may be missed. When stimulation results are marginal, 24-h cortisol profiles can provide reassurance of normal cortisol status.

Growth hormone deficiency (GHD) in adults and children is associated with decreased lean tissue mass (LTM), increased fat mass and reduced bone mineral density (BMD). The changes in BMD and body composition, 6 and 12 months after ceasing GH treatment, were assessed using dual‐energy X‐ray absorptiometry in eight patients with GHD (age range, 13.8–17.5 years). Seven age‐matched normal subjects who had completed growth were assessed at 0 and 12 months. Total body BMD was low at baseline (p < 0.05) in patients with GHD compared with the predicted values based on sex‐specific regression equations, with height, weight and age taken into account. Total body, lumbar spine and femoral neck BMD increased in the patients and controls at 12 months. LTM decreased significantly by a mean of 1.37 kg in the patients with GHD at 12 months whereas there was a non‐significant increase in LTM in the control group. The percentage of body fat increased in all patients with GHD at 6 and 12 months, from 27.2 ± 11% (mean ± SD) at baseline to 32 ± 9.9% at 12 months (p= 0.009). There was no significant increase in mean percentage body fat in the control group. The ratio of android (trunk):gynoid (legs) fat was calculated using default settings of dual‐energy X‐ray absorptiometry. The mean android:gynoid fat ratio increased, though non‐significantly, in patients with GHD at 12 months, with 6 of 7 showing an increase; no change was observed in the control group. These results indicate that BMD continues to increase 12 months after ceasing GH therapy in adolescents with GHD, but that unfavourable alterations in body composition occur.

Thrice-daily dosing resulted in less frequent and prolonged hypocortisolemia than twice-daily regimens, but we were unable to relate either regimen to acute clinical end points of glycemia, lethargy, or cognitive function.

It is presently unclear whether men with a history of constitutional delay (CD) of puberty are osteopenic. This study compares auxology, bone mass, size, and density of 32 men (age, 21-33 yr) with previous CD with 45 controls. Using dual-energy x-ray absorptiometry, areal bone mineral density (aBMD) and volumetric bone mineral density at the lumbar spine (LS) and femoral neck (FN), hip strength analysis, and total-body and body segment (arms, legs, trunk) measurements were determined. Auxological variables, body composition, the muscle-bone relation, and the effect of prior androgen treatment were studied. Men with previous CD were shorter (P < 0.001) and had shorter height-adjusted arms compared with controls. Height-adjusted total-body bone mineral content (BMC) (P = 0.004), aBMD (P = 0.016), and bone area (P = 0.006) but not lean tissue mass (P = 0.507) were lower in CD men compared with controls; consequently, their BMC to lean tissue mass ratio was reduced (P < 0.001). Segment length-adjusted BMC and bone area of arms (P < 0.001) and legs (P < 0.03), but not trunk were lower in CD men than in controls. They had lower LS aBMD (P = 0.044) but normal LS and FN volumetric bone mineral density. Size-adjusted LS width and the hip cross-sectional area were lower than in controls. There was no difference in anthropometric or dual-energy x-ray absorptiometry results between untreated (n = 15) and androgen-treated (n = 17) CD men.We conclude that men with previous CD have normal LS and FN volumetric density but reduced total-body bone mass, which was explained by reduced limb bone mass and size. Together with the reduced LS bone width and hip crosssectional area, these skeletal characteristics suggest impaired periosteal expansion during puberty. The skeletal phenotype of CD males may be altered by their late onset of puberty.

Modern dairy cows rely on hormonally driven mechanisms to coordinate the metabolic adaptations needed to meet the energy and nutrient deficits of early lactation. In the case of glucose, dairy cows cope with its scarcity during early lactation via reduced plasma concentrations of insulin and the insulin sensitizing hormone adiponectin and increased insulin resistance. Reduced insulin action promotes diversion of available glucose to the mammary gland but increases susceptibility to diseases if excessive. In earlier work, we reported that the insulin sensitizing hormone fibroblast growth factor-21 (FGF21) is increased in periparturient dairy cows and identified liver and adipose tissue as possible targets. These observations raised the possibility that FGF21 acts directly on these tissues to limit the insulin resistance of early lactation. To test this hypothesis, dairy cows were randomly assigned on d 12.6 ± 2.2 (± standard error) of lactation to receive either excipient (n = 6) or recombinant human FGF21 (n = 7), first as an FGF21 bolus of 3 mg/kg of body weight, followed 2 d later by a constant i.v. infusion of FGF21 at the rate of 6.3 mg/kg of metabolic body weight for 9 consecutive days. Biopsies of liver and adipose tissue were collected during the bolus phase of the experiment and used to analyze FGF21 signaling by Western blotting and expression of its receptor components by quantitative PCR. Bolus FGF21 administration caused a 4-fold increase in p44/42 MAPK (ERK1/2) activation in adipose tissue but had no effect on AKT and signal transducer and activator of transcription-3 (STAT3) signaling. The liver expressed negligible levels of the preferred FGF21 receptor FGFR1c and failed to mount any FGF21 signaling response. The FGF21 administered as a bolus had no effect on plasma glucose or insulin and did not stimulate an acute release of adiponectin from adipose tissue. Similarly, FGF21 infusion had no effect on plasma levels of glucose or insulin measured over the 9-d infusion or on glucose disposal during an i.v. glucose tolerance test performed on d 8 of infusion. Finally, the chronic FGF21 infusion had no effect on indices of adiponectin production, including plasma adiponectin and adipose tissue mRNA abundance of adiponectin and the endoplasmic reticulum chaperones ERO1A and DSBA-L involved in the assembly of adiponectin into multimeric complexes. These data show that human FGF21 does not act as an insulin sensitizer during the energy and glucose deficit of early lactation but do not rule out such a role in other physiological states.

Objective: The aim of glucocorticoid replacement therapy in ACTH-deficient patients is to mimic the normal diurnal variation of cortisol. However, current hydrocortisone (HC) replacement results in prolonged episodes of hypocortisolaemia and supraphysiological peaks. Plasma cortisol profiles are an accurate yet labour-intensive method of assessing HC replacement. Salivary and bloodspot cortisol sampling methods are less invasive and may be useful tools for assessing glucocorticoid replacement, particularly in children. Therefore, we aimed to define normal salivary and bloodspot cortisol levels in children and their correlations with the gold standard (plasma cortisol). Design: Cross-sectional study in a paediatric teaching hospital. Methods: Plasma, saliva and bloodspot cortisol profiles were performed on 30 ACTH-deficient children and 22 healthy siblings. Results: In ACTH-deficient patients taking oral HC, the bloodspot-plasma correlation (rZ0.90) was stronger than the salivary-plasma correlation (rZ0.49). Using target ranges for salivary and bloodspot cortisol levels based on normal data from control subjects, the less invasive sampling methods had low rates of agreement with plasma cortisol target ranges (saliva 65% and bloodspot 75%). Using the plasma-bloodspot correlation regression equation to convert bloodspot to calculated plasma cortisol, there was a high concordance between calculated and actual measured plasma cortisol (88%). Conclusion: Bloodspot cortisol sampling is a feasible and accurate method for monitoring oral HC replacement in paediatric patients without necessitating hospital admission, but salivary sampling is not useful. 156 471-476 European Journal of Endocrinology