Brunetto Boscherini

Central diabetes insipidus in children and young adults

BACKGROUND Central diabetes insipidus is rare in children and young adults, and up to 50 percent of cases are idiopathic. The clinical presentation and the long-term course of this disorder are largely undefined. METHODS We studied all 79 patients with central diabetes insipidus who were seen at four pediatric endocrinology units between 1970 and 1996. There were 37 male and 42 female patients whose median age at diagnosis was 7.0 years (range, 0.1 to 24.8). All patients underwent magnetic resonance imaging (MRI) and periodic studies of anterior pituitary function. The median duration of follow-up was 7.6 years (range, 1.6 to 26.2). RESULTS The causes of the central diabetes insipidus were Langerhans-cell histiocytosis in 12 patients, an intracranial tumor in 18 patients, a skull fracture in 2 patients, and autoimmune polyendocrinopathy in 1 patient; 5 patients had familial disease. The cause was considered to be idiopathic in 41 patients (52 percent). In 74 patients (94 percent) the posterior pituitary was not hyperintense on the first MRI scan obtained, and 29 patients (37 percent) had thickening of the pituitary stalk. Eighteen patients had changes in the thickness of the pituitary stalk over time, ranging from normalization (six patients) or a decrease in thickness (one patient) to further thickening (seven patients) or thickening of a previously normal stalk (four patients). Anterior pituitary hormone deficiencies, primarily growth hormone deficiency, were documented in 48 patients (61 percent) a median of 0.6 year (range, 0.1 to 18.0) after the onset of central diabetes insipidus. CONCLUSIONS Most children and young adults with acquired central diabetes insipidus have abnormal findings on MRI scans of the head, which may change over time, and at least half have anterior pituitary hormone deficiencies during follow-up.

Is IGF binding protein-3 assessment helpful for the diagnosis of GH deficiency?

OBJECTIVE The measurement of serum immunoreactive IGFBP‐3 levels has been proposed as a screening test to Identify children with growth hormone deficiency (GHO). We tested the sensitivity and specificity of the IGFBP‐3 assessment In comparison with the measurement of IGF‐I.

Height velocity and IGF‐I assessment in the diagnosis of childhood onset GH insufficiency: do we still need a second GH stimulation test?

objective The diagnosis of GH insufficiency (GHI) in childhood is not straightforward. Our aim was to test the sensitivity and specificity of height velocity (HV), IGF‐I, IGFBP‐3 and GH stimulation tests alone or in combination in the diagnosis of GHI.

Hormone-modulated rRNA gene activity is visualized by selective staining of the NOs

The role of Growth Hormone and Dexamethasone in the regulation of rRNA gene activity was evaluated on cultured human fibroblasts by the cyto-chemical method of selective silver staining. By this method the transcriptionally active r-gene clusters can be specifically visualized in individual cells. Statistically significant increases in the rate of rRNA transcriptional activity were demonstrated after hormone administration.

Neonatal Identification of Pituitary Aplasia: A Life-Saving Diagnosis

Background: Neonatal onset hypopituitarism is a life-threatening, potentially treatable endocrine disease. A possible cause is congenital absence of the anterior pituitary gland, a condition very rarely reported in the literature. Methods: A series of 5 cases of children with pituitary aplasia referred to the Centre of Paediatric Endocrinology ‘Rina Balducci’, Tor Vergata University, Rome, is presented. Results: Major clinical features in our patients were respiratory distress on the first day of life, in spite of uneventful pregnancy, labour and delivery, metabolic acidosis, non-cholestatic jaundice, hypotonia, severe hypoglycaemia, hypogenitalism, and midline defects. Diagnosis was established by endocrine tests during hypoglycaemia and hypothalamic-pituitary MRI scan. Symptoms disappeared soon after replacement therapy was started. Conclusion: We stress the importance of performing baseline endocrine tests as soon as possible during hypoglycaemia and MRI of the brain aimed at visualizing the hypothalamic-pituitary area in neonates with hypogenitalism and severe unexplained hypoglycaemia, so that the irreversible neurological and developmental consequences of panhypopituitarism can be prevented by adequate replacement therapy.

In vitro effects of growth hormone (GH) and insulin-like growth factor I and II (IGF-I and -II) on chromosome fragility and p53 protein expression in human lymphocytes.

We have reported previously that growth hormone (GH) therapy increases cell radiosensitivity; in this study we tested whether GH itself or IGFs induce chromosome aberrations and investigated the expression of p53 protein in response to DNA damage.

A multi-centre randomized trial of two different doses of nicotinamide in patients with recent-onset Type 1 diabetes (the IMDIAB VI)

Intensive insulin therapy is the gold standard by which Type 1 diabetes is treated. In addition to this therapy, administration of nicotinamide (NA) can be beneficial. This concept is reinforced by the results of a recent meta‐analysis of the use of NA in patients with recent‐onset Type 1 diabetes.

Immune function in growth hormone-deficient children treated with biosynthetic growth hormone

Several studies have shown conflicting data regarding the immune function in children suffering from growth hormone (GH) deficiency (1). Recently Rappaport et al. (2) reported changes in several immunological parameters during human G H (hGH) therapy in GH deficiency. On the other hand, Abbassi & Bellanti (3) did not find any immunological changes during the first year of treatment with hGH. The recent disturbing reports of deaths from Creutzfeldt-Jakob disease in patients treated with hGH have halted treatment with pituitary-derived h G H in many countries. Therefore, treatment with biosynthetically obtained GH preparation is currently the only treatment in GH-deficient children. Up to now no data are available regarding the effect of recombinant G H on the immune system. We have looked at the immune function of six patients with GH deficiency 6-11 years of age. Five of the patients had isolated G H deficiency, and one had multiple pituitary hormone deficiency. None of the patients had been on h G H therapy previously. Four of the patients were on treatment with biosynthetic GH for 6 months and two for 2 months. Recombinant hGH (Biotechnology General, Israel) was given at a dose of 0.1 U/kg subcutaneously three times weekly. We found that levels of B-lymphocytes, serum immunoglobulins, total TandT-lymphocyte subsets, and the proliferative response of lymphocytes to polyclonal mitogens (phytohemagglutinin, concanavalin A, pokeweed mitogen) were all in the normal range (Table 1).

Gelastic Epilepsy and True Precocious Puberty due to Hypothalamic Hamartoma

A new case of gelastic epilepsy and precocious puberty due to hypothalamic hamartoma is reported. After long‐term medical treatment there was no observable neurological or endocrinological improvement and the clinical outcome was poor. The authors consider that early surgery for hamartoma should be reconsidered.

Expression and down-regulation by retinoic acid of IGF binding protein-2 and -4 in medium from human neuroblastoma cells

Insulin‐like growth factors (IGFs) regulate the autocrine/paracrine growth of neuroblastomas. The IGFs bind to specific binding proteins (IGFBPs) which modulate their biological activity. We investigated, by Western ligand blotting (WLB), the presence of IGFBPs and their possible modulation by retinoic acid (RA), IGF‐I, IGF‐II and truncated Des(1‐3)IGF‐l in conditioned medium (CM) of the human neuroblastoma SK‐N‐BE(2) cell line. We demonstrated the presence of two IGFBPs, with MW 37 kDa and 25 kDa. Following immunoprecipitation, they turned out to be IGFBP‐2 and ‐4, respectively. The RA‐induced differentiation in SK‐N‐BE(2) cells was accompanied by a marked reduction of the intensity of both IGFBP bands after 48 h (32% and 24% of control, respectively) and 72 h (2% and 0% of control, respectively) incubation. The addition of exogenous IGFs, which did not induce cell differentiation, did not change the IGFBP pattern significantly, except for the truncated form of IGF‐I, which induced a marked decrease in both the 37 kDa and 25kDa bands after 72 h incubation (45% and 18% of control, respectively). These findings suggest that IGFBPs have a role in RA‐induced differentiation in human neuroblastoma cells.