Persistent effect of zoledronic acid in Paget's disease.

Paget's bone disease is a disorder in which bone regions with high turnover are replaced by new, vascular, but disorganized and immature bone with excessive fibrosis, high tendency of deformity and diminished mechanical resistance. Treatment aims at the suppression of osteoclast activity and is achieved with bisphosphonates, which represent the treatment of choice for Paget's disease. Zoledronic acid, a relatively new member of this class, normalizes alkaline phosphatase in the majority of patients and has a favorable safety profile. We report the case of an asymptomatic patient who was diagnosed with Paget's disease based on typical biochemical, radiological and histological findings and was treated with a single intravenous infusion of 4 mg of zoledronic acid. No side effects were observed. Alkaline phosphatase levels normalized within four months. At the last follow up examination, three years after treatment, the patient remains asymptomatic, without significant changes in radiology imaging, and alkaline phosphatase levels are still within the normal range. In conclusion, zoledronic acid, apart from being safe and effective in Paget's disease, also appears to be able to achieve significantly prolonged remissions.

Growth hormone treatment in short children with beta-thalassemia major.

The effect of one year recombinant human growth hormone (rhGH) treatment on growth rate and bone age was studied in ten short prepubertal children with beta-thalassemia major (age range 7.10-12.03 yr) with normal GH response to provocative stimuli. rhGH was given subcutaneously every day in a dose of 28 IU/m2/week. In the 10 children who completed 12 months of treatment the growth velocity increased from 4.22+/-0.81 cm/yr (-1.38+/-0.80 SDS for CA) to 7.61+/-1.16 cm/yr (+2.27+/-1.64 SDS for CA). IGF-I was low before treatment, 138.3 +/-38.9 ng/ml, and rose significantly to 232.2+/-122.1, 243.2+/-98.4 and 227.5+/-86.2 at 3, 6 and 12 months post-treatment, respectively (p<0.01). Bone maturation was accelerated in proportion to the increase in chronological age. The mean pre-treatment bone age in the ten children was 8.20+/-1.97 and increased to 9.55+/-1.80 yr after one year of treatment. Our data demonstrate that GH treatment of thalassemic children with normal GH reserve and low serum IGF-I concentrations with supraphysiological doses of rhGH for one year can cause a significant increase in serum IGF-I levels and growth velocity, but it remains to be elucidated whether long-term administration will affect the final height.

Adrenal insufficiency with enlarged adrenals.

Five patients with adrenal insufficiency and large adrenal glands at presentation are reported. Addison's disease was due to adrenal tuberculosis in three patients, with important changes in adrenal configuration on CT reflecting the natural history of the disease. Adrenal infiltration by non-Hodgkin lymphoma and metastatic carcinoma of the lung was the cause of the disease in the fourth and fifth patients, respectively, who developed signs of adrenal insufficiency before the diagnosis of the primary lesion became apparent. Histologic confirmation was established after unilateral adrenalectomy in three patients. In two patients with adrenal tuberculosis, long clinical and laboratory follow-up confirmed the diagnosis. This report indicates that Addison's disease is not infrequently associated with adrenal enlargement. Adrenal size is related to the cause and duration of the various disease states leading to adrenal insufficiency. Moreover, adrenal insufficiency associated with enlarged adrenal glands can be the presenting manifestation of lymphoma or metastasis.

Circadian growth hormone secretion in short multitransfused prepubertal children with thalassaemia major.

UNLABELLED: Growth hormone (GH) secretion was determined by evaluating circadian GH profiles for 24 h and GH responses to clonidine stimulation test and insulin-stimulated hypoglycaemia (ITT), in nine prepubertal children with beta-thalassaemia major (TM) and 17 with non-GH deficient short stature (NGHDSS). The TM children were multitransfused and had early and intensive chelation therapy. All patients had normal hypoglycaemia to ITT, with peak GH levels of 15.71 +/- 5.86 ng/ml for children with NGHDSS and 13.91 +/- 7.20 ng/ml for children with TM. Peak GH levels during a clonidine test were 17.54 +/- 5.30 and 17.15 +/- 1.38 ng/ml, respectively. The GH peak parameters such as the number of peaks, the integrated GH concentration and the area under the curve (AUC) were similar in both groups of children and reflected the total 24-h secretion and the daily and nocturnal secretion separately. An abnormal 24-h GH profile compatible with the diagnosis of endogenous neurosecretory GH dysfunction was found in only two out of nine children with TM and in four out of seven children with NGHDSS. CONCLUSION: Our data suggest that growth hormone neurosecretory dysfunction is not a universal finding in children with thalassaemia major but might depend on the degree of iron deposit in the pituitary.