Giuseppe Perri

Effect of central precocious puberty and gonadotropin-releasing hormone analogue treatment on peak bone mass and final height in females

To evaluate the effect of central precocious puberty (CPP) and its treatment with gonadotropin-releasing hormone (GnRH) analogues on final height and peak bone mass (PBM), we measured lumbar bone mineral density (BMD) in 23 girls at final height. Patients were distributed in two groups. Group 1: 14 patients with progressive CPP were treated with GnRH analogues; seven patients received buserelin (1600 μg/daily), subsequently switched to depot triptorelin (60 μg/kg/26–28 days); seven patients were treated with depot triptorelin (60 μg/kg/26–28 days); mean age of treatment was 6.2 years (range 2.7–7.8 years); the treatment was discontinued at the mean age of 10.1 years (range 8.7–11.3 years); final height was reached at the mean age 13.4 years (range 12.0–14.9 years). Group 2: 9 patients (mean age 6.5 years, range 4.8–7.7 years) with a slowly progressing variant of CPP were followed without treatment; final height was reached at the mean age 13.6 years (range 12.5–14.8 years). Lumbar BMD (L2–L4 by dual energy X-ray absorptiometry) was measured in all patients at final height. In group 1, final height (158.9 ± 5.4 cm) was significantly greater than the pre-treatment predicted height (153.5 ± 7.2 cm, P < 0.001), but significantly lower than mid-parental height (163.2 ± 6.2 cm, P < 0.005). Subdividing the girls of group 1 according to the bone age at discontinuation of therapy (i.e. ≤11.5 years, n = 5, or ≥12.0 years, n = 9), the former patients had a final height significantly higher than the latter (163.7 ± 3.9 cm vs 156.5 ± 4.6 cm, P < 0.02). In group 2, final height (161.8 ± 4.6 cm) was similar to the pre-treatment predicted height (163.1 ± 6.2 cm, P = NS) and was not significantly different from mid-parental height (161.0 ± 5.9 cm). BMD values (group 1: 1.11 ± 0.14 g/cm2, group 2: 1.22 ± 0.08 g/cm2) were not significantly different from those of a control group (1.18 ± 0.10 g/cm2; n = 20, age 16.3–20.5 years) and the patients’ mothers (group 1: 1.16 ± 0.07 g/cm2, n = 11, age 32.9–45.1 years; group 2: 1.20 ± 0.08 g/cm2, n = 7, age 33.5–46.5 years). In group 1, the girls who stopped therapy at a bone age ≤11.5 years had significantly higher BMD (1.22 ± 0.10 g/cm2) compared to those who discontinued therapy at a bone age ≥12.0 years (1.04 ± 0.12 g/ cm2, P < 0.05).ConclusionIn girls with progressive CPP, long-term treatment with GnRH analogues improves final height. A subset of patients with CPP does not require treatment because good statural outcome (slowly progressing variant). In CPP, the abnormal onset of puberty and the long-term GnRH analogue treatment do not impair the achievement of PBM. In GnRH treated patients, the discontinuation of therapy at an appropriate bone age for pubertal onset may improve both final height and PBM.

Long-term growth hormone treatment in children with renal hypophosphatemic rickets : effects on growth, mineral metabolism, and bone density

OBJECTIVE To evaluate the effects of treatment with recombinant human growth hormone (rhGH) on growth, mineral metabolism, and bone density in children with renal hypophosphatemic rickets (RHR). DESIGN Long-term rhGH treatment combined with conventional therapy with 1,25-dihydroxyvitamin D3 plus inorganic phosphate salts. SETTING Endocrine unit, department of pediatrics, university hospital. SUBJECTS Twelve patients (5 boys; age range 4.6 to 12.5 years, median 7.0 years) were subdivided into two groups of six patients on the basis of the median of height z score (-2.41) and the median bone age/statural age (BA/SA) ratio (1.23). Group A included patients with a severe degree of short stature (height z score -3.4 +/- 0.5) (mean +/- SD) and altered BA/SA ratio (1.26 +/- 0.08); group B included patients with a lesser degree of short stature (height z score -2.1 +/- 0.6, p < 0.001 vs group A) and more normal BA/SA ratio (1.04 +/- 0.15, p < 0.01 vs group A). INTERVENTION Group A received rhGH treatment (0.6 IU/kg per week subcutaneously) combined with conventional therapy; group B received conventional therapy alone. MEASUREMENTS Height, growth velocity, predicted adult height, serum values of calcium, phosphate, bone alkaline phosphatase isoenzyme, osteocalcin, propeptides of type I and type III procollagen, intact parathyroid hormone, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and urinary calcium/urinary creatinine ratio and tubular maximum for phosphate reabsorption normalized to the glomerular filtration rate (TmP/GFR), as well as radial bone density, were measured at baseline and for 3 years. RESULTS Height z score, growth velocity z score, predicted adult height, serum values of phosphate, bone alkaline phosphatase isoenzyme, osteocalcin, propeptides of type I and type III procollagen, intact parathyroid hormone 1,25-dihydroxyvitamin D, and TmP/GFR, as well as radial bone density, improved significantly only in group A. Serum calcium and 25-hydroxyvitamin D, and urinary calcium/urinary creatinine ratio did not change in either group. CONCLUSIONS Long-term rhGH administration may benefit growth, phosphate retention, and bone density in patients with RHR, without evidence of side effects.

Growth hormone secretion in poorly growing children with renal hypophosphataemic rickets.

We evaluated growth hormone (GH) secretion and baseline serum free insulin-like growth factor-I (IGF-I) levels in 12 poorly growing patients (5 males and 7 females; age 1.6–12.5 years, median 6.4) with renal hypophosphataemic rickets treated with 1,25-dihydroxy-vitamin D3 plus inorganic oral phosphate salts. Eleven healthy normally growing children (6 males and 5 females age 3.1–10.8 years, median 6.6) were studied as control group. All patients had a normal GH response (GH peak ≥ 10 μg/l) to at least one provocative pharmacological stimulus (levodopa or insulin tolerance test), as well as all the controls. Mean growth hormone concentrations (MGHC), mean pulse amplitude, number of GH peaks above 5 μg/l, and IGF-I values overlapped between patients and controls, even though four patients had MGHC below the lower limit of MGHC of controls. In these patients, however, height-SDS, serum calcium, phosphate, alkaline phosphatase, intact parathyroid hormone, 1,25-dihydroxyvitamin D concentrations and maximum tubular phosphate reabsorption/glomerular filtration rate ratio did not differ in respect to the patients who showed MGHC in the range of controls (n = 6). MGHC, IGF-I and biochemical parameters of phospho-calcium metabolism did not differ when the patients were subdivided in two groups on the basis of the median (−2.4) of height-SDS. No relationship was found between MGHC or IGF-I and height-SDS or growth velocity-SDS. Height-SDS and years of treatment or age at which therapy was started were not related.

Association between X-linked hypophosphatemic rickets and Klinefelter's syndrome: effects on growth and body proportion

Growth failure with disproportionate short stature is the major clinical feature of patients with X-linked hypophosphatemic rickets (HYP). We studied the pattern of linear growth and body proportion in an untreated normally growing HYP child also affected by Klinefelters syndrome. Auxologic data were compared with those of a HYP half-brother who showed growth failure despite long-term treatment either with vitamin D or with vitamin-D-analog plus phosphate salt supplementation. The degree of body disproportion changed from negative values to positive values in the proband, whereas it was reduced in the half-brother. We conclude that, in the proband, the normal pattern of growth and the lack of the typical body disproportion as seen in HYP patients are attributable to the concomitant presence of Klinefelters syndrome.

Case report 393

This 56-year-old woman presented with painful swelling on the ulnar aspect of the left wrist together with slowly-increasing limitation of motion of the wrist of three years duration. The patient complained of slight erythema which was present on the back of the wrist. Clinical examination demonstrated a tender, firm, mass in the medial soft tissue of the wrist just distal to the ulnar styloid. Radiological studies (Fig. 1 A and B) confirmed the presence of the irregularly outlined, poorly-defined mass in the medial soft tissues of the wrist distal to the ulnar styloid. Widening of the prestyloid process was present; the ulnar styloid appeared shorter than normal, with a small erosion on its medial tip. No calcification or ossification in the soft tissue mass was noted. Osteopenia of the pisiform and triquetrum, with small erosions and irregularity of their subchondral margins, was noted. All laboratory studies were normal, particularly those for rheumatic diseases. An operative procedure was performed.

Widening of the radial notch of the ulna: a new articular change in haemophilia.

A new radiological sign has been observed in 14 of 236 elbows of haemophiliacs examined. This finding is a widening of the radial notch of the ulna, which may become extremely large.

X-Ray Tomography Vs Compton Scattering in the Diagnosis of Pulmonary Diseases

A comparative study in various pulmonary conditions has been carried out using the methodologies of X-Ray Tomography and Compton Scatter Imaging. This last technique is based on the detection of the photons scattered at 90° by the chest tissues, using a LFOV gamma camera. The radiation source is made up of a laminar beam of photons generated by a twin of 2Ci Ir-192 sources. (1, 2).