Claudio Paganini

Height, bone mineral density and bone markers in congenital adrenal hyperplasia

Aim: To evaluate height, bone growth, areal bone mineral density (aBMD), volumetric bone mineral density (vBMD) and markers of bone turnover in a group of patients affected by congenital adrenal hyperplasia (CAH). Patients: There were 50 patients (23 males, 27 females), aged 1–28 years, affected by CAH due to 21-hydroxylase deficiency: 27 with the salt-wasting (SW); 14 with the simple virilizing (SV), and 9 with the nonclassical (NC) forms. Methods: Bone morphometry was evaluated with the metacarpal index (MI) and lumbar aBMD and vBMD (L2–L4) by dual energy X-ray absorptiometry. Serum osteocalcin was used as a marker of bone formation, while urinary cross-linked N-telopeptides of type-I collagen and free deoxypyridinoline levels were evaluated as indexes of bone resorption. Results: The height standard deviation score (SDS) was –0.41 ± 1.4 in SW patients, –0.01 ± 1.9 in SV patients, and –0.01 ± 2.3 in NC patients. There was no significant difference among groups and against zero. The MI SDS was also not different between groups and against zero.aBMD was significantly lower in the pubertal patients compared with normal values, but only when patients with the SW and SV forms were considered together (p < 0.05). vBMD was significantly reduced in all patients with the classical form. Bone markers were not different in patients and controls. Conclusion: Our study shows that normal height can be attained in CAH patients; however, an impairment in bone growth and mineralization may be found in adolescents and young adults affected by the classical form.

Evaluation of cortical thickness and bone density by roentgen microdensitometry in growing males and females

The bone mineral content (BMC) and the cortical thickness at the distal radius and at the II metacarpal were assessed in growing individuals (167 females and 158 males) by radiometric and quantitative roentgen microdensitometric methods. BMC adjusted for age and pubertal status was significantly higher in males than in females. However, the BMC corrected for bone volume (volumetric bone density, g/cm3) and the metacarpal cortical index (cortical area/total area) were identical in males and females. BMC rose progressively with age, approaching a plateau by the end of puberty. Lower but still significant increases with age were also observed for volumetric bone density of the metacarpus and the metacarpal index. These increases were also most marked by the end of pubertal maturation and might be related to diminution of bone turnover.ConclusionThis study provides the normative data of bone mass in growing individuals by making use of a reasonably accurate and easily available technique. The results obtained indicate that most of the differences between males and females and the changes with age are related to changes in skeletal dimension rather than density.

Does Graves’ Disease during Puberty Influence Adult Bone Mineral Density?

Aim: To evaluate the bone mineral density at lumbar spine and at femoral neck in a group of young adults in whom Graves’ disease developed during childhood and adolescence. Patients and Methods: We examined 28 patients (5 male, 23 female, age 20.9 ± 3.3 years) who were 11.8 ± 2.9 years old at the onset of Graves’ disease. They were treated either with methimazole (14 patients) or with methimazole plus l-thyroxine (14 patients). At the time of the investigation, 13 patients were considered cured following antithyroid treatment, 2 were still on antithyroid drugs, 3 were on replacement therapy with l-thyroxine because of hypothyroidism, and 10, treated either surgically or with 131I, were on replacement therapy. The bone mineral density was measured at the lumbar spine (L2–L4) and at the femoral neck, using dual-energy X-ray absorptiometry. Results: The spinal bone mineral density SD score was –0.28 ± 1.02, the femoral neck bone mineral density SD score was 0.36 ± 1.02, and both were not different from zero (NS). We did not find any correlation between the bone mineral density of the femoral neck and that of the lumbar spine and the clinical parameters. Conclusion: Graves’ disease, beginning in childhood and adolescence, when appropriately treated, does not affect attainment of peak bone mass.

Cardiac Performance in Turner’s Syndrome Patients on Growth Hormone Therapy

Objectives: To investigate possible cardiac morphofunctional alterations observed in 26 Turner’s syndrome (TS) patients on prolonged high-dose growth hormone (GH) therapy. Study Design: We examined 26 TS subjects treated with rhGH (1 U/kg/week) for a mean period of 4.9 years (range 1–7.8) and 37 age-, weight- and height-matched healthy girls. Left ventricular volume, mass, systolic function, cardiac index, systemic vascular resistance and diastolic function were evaluated by two-dimensional and Doppler echocardiography. Results: Heart rate and systolic blood pressure (BP) were higher in TS patients than in controls, while diastolic BP was lower. Left ventricular volumes, ejection fraction, mass index, M/V ratio and cardiac index did not differ significantly; systemic vascular resistance was slightly decreased. Left ventricular fractional shortening and mean velocity of circumferential shortening were slightly increased while end-systolic meridional stress was decreased in TS. Contractile state was normal in TS. Diastolic function assessment showed a shortening of isovolumetric relaxation and diastolic filling times with an increased atrial contribution and a normal pulmonary venous flow. Conclusion: Cardiac morphology in TS patients on GH therapy is similar to controls. The observed changes in left ventricular systolic and diastolic function should be interpreted as an adaptation to the higher heart rate and reduced peripheral vascular resistance induced by GH therapy.

Growth hormone-binding proteins, IGF-I and IGF-binding proteins in children and adolescents with type 1 diabetes mellitus.

Growth hormone binding proteins, insulin-like growth factor I and insulin-like growth factor binding proteins were determined in 54 children and adolescents affected by type 1 diabetes mellitus (25 prepubertal and 29 pubertal) showing reduced height velocity and the results were compared to those of 104 matched controls. Growth hormone binding proteins were similar in prepubertal and pubertal subjects but were significantly lower in the prepubertal diabetic group than in controls. Insulin-like growth factor I was low both in prepubertal and pubertal diabetic subjects. Insulin-like growth factor binding protein 3 was similar to controls, while insulin-like growth factor binding protein 1 and 2 were always high in diabetic children. Insulin-like growth factor binding protein 4 was high only in the prepubertal diabetic group. In conclusion, a low insulin-like growth factor I in diabetic children seems to depend on a GH receptor and/or a postreceptor defect. A low insulin-like growth factor I together with a normal insulin-like growth factor binding protein 3 and high levels of insulin-like growth factor binding proteins 1, 2 and 4 results in a reduced bioavailability of insulin-like growth factor I to target tissues. This could be a possible contributing factor to the reduced height velocity seen in our diabetic children.

Growth hormone secretory pattern and response to treatment in children with short stature followed to adult height

objective To compare the relative utility of GH stimulation tests and assays of spontaneous GH secretion as predictors of change in height standard deviation score at the end of GH treatment in children with short stature.

Medium-Term Cardiovascular Effects of High-Dose Growth Hormone Treatment in Growth Hormone-Deficient Children

Aim: To investigate the possible cardiac morphofunctional alterations inducd by prolonged and high-dose GH therapy in a group of 14 children with isolated GH deficiency. Patients and Methods: Patients were evaluated at phase 1, after 1.1 ± 0.6 years of treatment with GH 0.93 ± 0.13 U/kg/week, and at phase 2, after 5.5 ± 2.1 years of therapy 0.89 ± 0.11 U/kg/week. At each phase left ventricular volume, mass and systolic function were evaluated by two-dimensional guided M-mode echocardiography; left ventricular diastolic function was assessed by PW-Doppler sampling of transmitral flow. Results: Phase 1: diastolic blood pressure was lower (p < 0.05) and fractional shortening was not adequate for the level of afterload (stress shortening index p < 0.05) in patients compared to controls. Phase 2: diastolic blood pressure was lower (p < 0.01) and mass and mass/volume ratio were increased (mass index p < 0.05, mass/ volume ratio p < 0.05) in patients compared to controls. The increased mass/volume ratio, together with the normal systolic blood pressure, explains the reduction in peak systolic stress (p < 0.005). Among the parameters of left ventricular diastolic function, the peak E velocity/total area under mitral valve tracing and the area under E velocity/total area under mitral value tracing ratios were significantly decreased (p < 0.05). Conclusion: After a mean period of 5 years on high-dose GH treatment in GH-deficient children, subclinical morphofunctional alterations in the left ventricle were found.

Cholelithiasis in a newborn following treatment with the somatostatin analogue octreotide

We report the case of a newborn infant affected by congenital hyperinsulinism who developed cholelithiasis associated with cholestatic jaundice following treatment with octreotide, a somatostatin analogue.

The advantage of measuring spontaneous growth hormone (GH) secretion compared with the insulin tolerance test in the diagnosis of GH deficiency in young adults

Objective  Reassessment of GH status after the attainment of adult height has important clinical implications in the diagnosis and prognosis of GH deficiency (GHD) in adulthood. The current GH threshold for biochemical definition of GHD in young adults is still a subject of debate.

Serum leptin levels are not influenced by arginine and insulin infusion and by acute changes of GH

The aim of this study was to evaluate the relationship between GH and leptin in a group of short children and adolescents. Leptin and GH serum levels were measured before and during pharmacological stimulation tests (arginine and insulin) in a group of 45 children (30 male, 15 female), mean age 8.6±3.9 yr, affected by idiopathic isolated GH deficiency (GHD), and in a group of 27 children (15 male, 12 female), age 10.9±3.3 yr, with constitutional growth delay. Results showed that basal and peak leptin levels as well as the AUC were significantly higher in GHD patients compared to controls (p<0.05) and correlated with BMI SDS (p<0.0001) in GHD patients. No change in leptin serum levels was observed during either stimulation test. No correlation was found, however, between basal leptin serum levels and basal, peak and the AUC of GH during the tests. Moreover, no correlation was found between the acute changes of serum GH concentration during both stimulation tests and leptin serum levels. The results suggest that leptin and GH secretion is not correlated and that leptin serum levels mainly reflect the amount of fat tissue, which is higher in GHD patients.