Shared signaling pathways between endocrine and immune system receptors: the model of gamma chain

The rapid expansion in the past two decades in the understanding of the molecular basis of a large variety of novel congenital immunodeficiencies has provided valuable information on the signal transduction general mechanisms, that goes far beyond the comprehension of the individual disease. In most cases, the altered molecules are exclusively expressed in haematopoietic cells, while in other cases they are not restricted to a certain cell type. This leads to more complex clinical phenotypes, which contribute to unravel previously unappreciated non-haematopoietic functions of signaling proteins and the mechanism of coordination and integration of several pathways. Moreover, this knowledge will help define potential new therapeutic strategies through novel molecular targets, drive stem cell development into the desired differentiation path and ameliorate our comprehension of tissue engineering. This review focuses on the multiple roles in haematopoietic and non-haematopoietic receptors of the gamma signaling element with a special attention paid to the participation of gamma to growth hormone receptor signaling, confirming the presence of an interplay between endocrine and immune syste

Liver abnormalities during growth hormone treatment.

BACKGROUND: Occasional and transient increase in liver enzymes is reported during growth hormone (GH) treatment in girls with Turner syndrome (TS). METHODS: Retrospectively, the specific role of GH treatment on liver and muscular enzymes was evaluated in 78 patients (48 boys; age range 4.0-20.8 years) affected by GH deficiency (GHD) who had been treated with GH for at least 1 year (range: 1-15 years). All patients had normal serum levels of liver and muscular enzymes before GH therapy was started. RESULTS: A clinically asymptomatic and mild increase in serum transaminase levels was observed in 6 of 78 patients with GHD during GH treatment; 3 (3.8%) of the patients showed an isolated, transitory and self-limiting increase in serum liver transaminase levels which was noticed 6 to 12 months after GH treatment was started, and normalized spontaneously within 3 to 6 months, without stopping the therapy. Three additional patients showed a transitory mild increase both in aspartate aminotransferase (AST) and creatine phosphokinase (CK) which also normalized spontaneously within 3 to 6 months. The increase in transaminase levels was not related to the brand of GH preparations nor to the dosage administered. CONCLUSIONS: A mild, transient, self-limiting increase in serum transaminase may occur during GH treatment. Concomitant determination of CK serum levels may quickly differentiate muscular from hepatic hypertransaminasemia. Except for persistent cases, this condition does not generally require further investigations

Liver abnormalities during growth hormone treatment

Background: Occasional and transient increase in liver enzymes is reported during growth hormone (GH) treatment in girls with Turner syndrome (TS). Methods: Retrospectively, the specific role of GH treatment on liver and muscular enzymes was evaluated in 78 patients (48 boys; age range 4.0-20.8 years) affected by GH deficiency (GHD) who had been treated with GH for at least 1 year (range: 1-15 years). All patients had normal serum levels of liver and muscular enzymes before GH therapy was started. Results: A clinically asymptomatic and mild increase in serum transaminase levels was observed in 6 of 78 patients with GHD during GH treatment: 3 (3.8%) of the patients showed an isolated, transitory and self-limiting increase in serum liver transaminase levels which was noticed 6 to 12 months after GH treatment was started, and normalized spontaneously within 3 to 6 months, without stopping the therapy. Three additional patients showed a transitory mild increase both in aspartate aminotransferase (AST) and creatine phosphokinase (CK) which also normalized spontaneously within 3 to 6 months. The increase in transaminase levels was not related to the brand of GH preparations nor to the dosage administered. Conclusions: A mild, transient, self-limiting increase in serum transaminase may occur during GH treatment. Concomitant determination of CK serum levels may quickly differentiate muscular from hepatic hypertransaminasemia. Except for persistent cases, this condition does not generally require further investigations

Longitudinal growth, sexual maturation and final height in patients with congenital hypothyroidism detected by neonatal screening.

To evaluate longitudinal growth, pubertal development and final height in patients with congenital hypothyroidism (CH) detected by a neonatal screening programme, and to identify factors potentially affecting growth outcome. Fifty-five patients (41 females) detected by neonatal screening and followed longitudinally from the time of diagnosis and treatment (25+/-5 days) up to the age of 17+/-0.5 years were evaluated retrospectively. Pubertal development began and progressed normally in both males and females. In boys, a testicular volume of 4 ml was reached at 11.3+/-1.0 years. In girls breast enlargement (B2) occurred at a mean age of 10.3+/-1.2 years and the mean age of menarche was 12.5+/-1.2 years. The onset and the progression of puberty were independent of the aetiology, the severity of CH and the timing of the beginning of treatment. Girls treated with an initial amount of L-thyroxine (L-T4) greater than 8 microg/kg per day showed an earlier onset of puberty (B2 9.4+/-0.9 years; menarche 11.5+/-0.8 years) compared with girls treated with a lower initial dose of L-T4 (B2 10.5+/-1.2 years; menarche 12.6+/-1.2 years; P<0.02). However, both groups attained a similar final height (-0.1+/-1.0 SDS and 0.4+/-1.0 SDS, respectively), which in both cases was above the target height (P=0.03). All the patients in the study attained a mean final height (0.1+/-1.1 SDS) within the normal range for the reference population and above the target height (-0.9+/-0.9 SDS, P<0.0001). No significant relationship was found between final height and severity of CH at diagnosis, initial L-T4 dosage or aetiology of the defect. Patients with ectopic gland, thyroid aplasia or in situ gland attained a similar mean final height (0.1+/-1.1 SDS, 0.5+/-1.0 SDS and -0.5+/-1.0 SDS, respectively), which was in all cases greater than target height (-1.0+/-0.9, -0.6+/-0.8, -0.9+/-0.8 respectively; P<0.05). Our results suggest that conventional management of children with CH detected by neonatal screening leads to normal sexual development and normal adult height, and that the major factor determining height in these children is familial genetic growth potentia