Gender-specific soluble α-klotho levels as marker of GH deficiency in children: a case-control study.

PURPOSE: To evaluate circulating soluble α-klotho (sαKL) levels in GHD children before and after 12 months of GH treatment (GHT). METHODS: Auxological and basal metabolic parameters, oral glucose tolerance test for glucose and insulin levels, insulin sensitivity indices and klotho levels were evaluated before and after 12 months of follow-up in 58 GHD children and 56 healthy controls. RESULTS: At baseline, GHD children showed significantly lower growth velocity standard deviation score (SDS) (p < 0.001), bone/chronological age ratio (p < 0.001), GH peak and area under the curve (AUC) after arginine test (ARG) (both p < 0.001) and glucagon stimulation test (GST) (p < 0.001 and 0.048, respectively), IGF-1 (p < 0.001), with higher BMI (SDS) (p < 0.001), WC (SDS) (p = 0.003) and sαKL (p < 0.001) than controls. After 12 months of GHT, GHD children showed a significant increase in height (SDS) (p < 0.001), growth velocity (SDS) (p < 0.001), bone/chronological age ratio (p < 0.001) IGF-1 (p < 0.001), fasting insulin (p < 0.001), Homa-IR (p < 0.001) and sαKL (p < 0.001) with a concomitant decrease in BMI (SDS) (p = 0.002) and WC (SDS) (p = 0.038) than baseline. At ROC curve analysis, we identified a sαKL cut-off to discriminate controls and GHD children of 1764.4 pg/mL in females and 1339.4 pg/mL in males. At multivariate analysis, the independent variables significantly associated with sαKL levels after 12 months of GHT were the oral disposition index (p = 0.004, ß = 0.327) and IGF-1 (p = 0.019, ß = 0.313). CONCLUSIONS: Gender-related sαKL may be used as a marker of GHD combined to GH and IGF-1. Insulin and IGF-1 are independently associated with sαKL values after 12 months of GHT.

Levothyroxine and insulin requirement in autoimmune polyglandular type 3 syndrome: a real-life study.

PURPOSE: To evaluate factors influencing the insulin and levothyroxine requirement in patients with autoimmune polyglandular syndrome type 3 (APS-3) vs. patients with type 1 diabetes mellitus (T1DM) and autoimmune hypothyroidism (AH) alone, respectively. METHODS: Fifty patients with APS-3, 60 patients with T1DM and 40 patients with AH were included. Anthropometric, clinical and biochemical parameters were evaluated in all patients. Insulin requirement was calculated in patients with APS-3 and T1DM, while levothyroxine requirement was calculated in APS-3 and AH. RESULTS: Patients with APS-3 showed higher age (p = 0.001), age of onset of diabetes (p = 0.006) and TSH (p = 0.004) and lower total insulin as U/day (p < 0.001) and U/Kg (p = 0.001), long-acting insulin as U/day (p = 0.030) and U/kg (p = 0.038) and irisin (p = 0.002) compared to T1DM. Patients with APS-3 had higher waist circumference (p = 0.008), duration of thyroid disease (p = 0.020), levothyroxine total daily dose (p = 0.025) and mcg/kg (p = 0.006), triglycerides (p = 0.007) and VAI (p = 0.010) and lower age of onset of thyroid disease (p = 0.007) than AH. At multivariate analysis, levothyroxine treatment and VAI were associated with insulin and levothyroxine requirement in APS-3, respectively. VAI was independently associated with insulin requirement in T1DM. Circulating irisin levels were independently associated with levothyroxine requirement in AH. CONCLUSION: Patients with APS-3 show lower insulin requirement and higher levothyroxine requirement than T1DM and AH alone, respectively. Levothyroxine treatment and VAI affect insulin and levothyroxine requirement, respectively, in APS-3. In T1DM, adipose tissue dysfunction, indirectly expressed by high VAI, is associated with an increased insulin requirement, while circulating irisin levels influence the levothyroxine requirement in AH.

Efficacy of combined treatment with pasireotide, pegvisomant and cabergoline in an acromegalic patient resistant to other treatments: a case report.

BACKGROUND: The approach to acromegalic patients with persistent acromegaly after surgery and inadequate response to first-generation somatostatin receptor ligands (SRLs) should be strictly tailored. Current options include new pituitary surgery and/or radiosurgery, or alternative medical treatment with SRLs high dose regimens, pegvisomant (PEG) as monotherapy, or combined therapy with the addition of PEG or cabergoline to SRLs. A new pharmacological approach includes pasireotide, a second-generation SRL approved for patients who do not adequately respond to surgery and/or for whom surgery is not an option. No reports on efficacy and safety of combined therapy with pasireotide and pegvisomant (PEG) in acromegaly are available. CASE PRESENTATION: Here we report the case of a 41-year-old acromegalic man with a mixed GH/PRL pituitary adenoma post-surgical resistant to first-generation SRLs both alone and in combination with cabergoline and PEG who achieved biochemical and tumor control with the combined triple treatment with pasireotide, PEG and cabergoline without adverse events and with a good compliance to treatment. CONCLUSIONS: Twelve months of therapy with pasireotide, PEG and cabergoline proved to be safe and effective in this particular patient and the clinical improvement of disease resulted in an improved compliance to treatment.

Correlation between adrenal function, growth hormone secretion, and insulin sensitivity in children with idiopathic growth hormone deficiency.

PURPOSE: Patients with growth hormone deficiency (GHD) demonstrate an increased cortisol/cortisone ratio which could potentially explain the metabolic features of GHD, while GH treatment (GHT) could increase the cortisol metabolism. METHODS: In 35 children (27 M, mean age 10.1 years) with idiopathic GHD at baseline and after 12 months of GHT and in 25 controls, in addition to metabolic parameters, we assessed adrenal function by morning serum cortisol, its peak, and its area under the curve (AUCCOR) during insulin tolerance test (ITT). RESULTS: A cortisol peak <18 µg/dl was shown in 22 and 31% of GHD children at baseline and after GHT, respectively. At baseline, GHD children had lower fasting glucose (p < 0.001) and ISI-Matsuda (p = 0.042), with concomitant higher Homa-IR (p = 0.006) and morning cortisol (p = 0.012) than controls. Morning cortisol was negatively correlated with GH (p < 0.001), fasting glucose (p < 0.001) and ISI-Matsuda (p < 0.001) and positively with Homa-IR (p = 0.010). Both cortisol peak and AUCCOR were negatively correlated with GH (all p < 0.001) and ISI-Matsuda (p = 0.016 and p = 0.001, respectively). After 12 months of GHT, a significant increase in fasting glucose (p < 0.001), and Homa-IR (p = 0.011) was documented, with a concomitant decrease in morning cortisol (p = 0.002), AUCCOR (p = 0.038), total (p = 0.003) and LDL-cholesterol (p = 0.016). No significant correlations were found among cortisol levels and all parameters were investigated. CONCLUSIONS: Cortisol levels correlate with GH secretion and with many metabolic parameters in GHD children, while the metabolic effects during GHT are mainly due to GHT per se and less to cortisol reduction.

Corneal thickness in children with growth hormone deficiency: the effect of GH treatment.

OBJECTIVE: The eye represents a target site for GH action, although few data are available in patients with GH deficiency (GHD). Our aim was to evaluate central corneal thickness (CCT) and intraocular pressure (IOP) values in GHD children to assess the role played by GHD or GH treatment on these parameters. DESIGN: In 74 prepubertal GHD children (51M, 23F, aged 10.4±2.4years) we measured CCT and IOP before and after 12months of treatment. A baseline evaluation was also made in 50 healthy children matched for age, gender and body mass index. The study outcome considered CCT and IOP during treatment and their correlations with biochemical and auxological data. RESULTS: No difference in CCT and IOP between GHD children at baseline and controls was found (all p>0.005). GHD children after 12months of therapy showed greater CCT (564.7±13.1µm) than both baseline values (535.7±17µm; p<0.001) and control subjects (536.2±12.5µm; p<0.001), with a concomitantly higher corrected mean IOP (15.6±0.7mmHg; p<0.001) than both baseline (12.5±0.8mmHg; p<0.001) and controls (12.3±0.5mmHg; p<0.001), without correlation with auxological and biochemical parameters. CONCLUSIONS: 12months of GH treatment in children with GHD, regardless of auxological and biochemical data, affect CCT and IOP. Our findings suggest careful ocular evaluation in these patients to prevent undesirable side effects during the follow-up.