Reversible weight gain and prolactin levels--long-term follow-up in childhood.

In adult patients weight gain is a frequent complaint of hyperprolactinaemia and it has been associated with a high prevalence of obesity. Normalization of prolactin (PRL) levels result in weight loss. The nature of this link is poorly defined. In this report we describe a 14 year-old female with primary amenorrhea and persistent progressive weight gain. The patient's height, weight and BMI were 152 cm, 70 kg, and 30.3 kg/m2, respectively. Basal hormonal investigation showed normal free thyroxin, TSH, IGF-I, cortisol and ACTH values. Serum PRL level was very high (16,278 mIU/l; normal range 63-426 mIU/l). Magnetic resonance imaging scan showed the presence of a pituitary microadenoma. Treatment with the non-selective dopamine agonist pergolide caused a significant reduction of serum PRL concentration with a remarkable decrease of body weight. During follow-up, repeat MRI scan revealed disappearance of the microadenoma. The reduction of the daily dose of pergolide was associated with an increase of serum PRL with significant weight gain. A further reduction of body weight was subsequently observed with an increase of pergolide dosage. Serum PRL measurement may be useful as part of the endocrine work-up of obese children with a history of unexplained recent weight gain, especially if associated with pituitary-gonadal axis dysfunction. The relationship between PRL secretion and weight change needs to be examined in prospective larger studies.

Precocious, early and fast puberty in males with Chiari I malformation.

Type I Chiari malformation is a disorder characterized by a displacement of the cerebellar tonsils through the foramen magnum into the upper cervical spinal canal and, contrary to type II Arnold-Chiari malformation, without the presence of myelomeningocele. As described in the literature, patients suffering from Arnold-Chiari malformation with myelomeningocele can frequently present with precocious puberty, whereas only one report shows an association between Chiari I malformation and early puberty. We describe three young males--8.8, 9.4 and 10.4 years old--who were diagnosed with precocious, early and fast puberty associated with type I Chiari malformation. In patients 2 and 3, the reason for diagnostic management recommendation was a rapid progression of pubertal development over one year. None of the patients manifested hypophyseal-hypothalamic axis dysfunction other than sexual precocity. Neurological and ophthalmological examinations were normal in all patients. Our data show that type I Chiari malformation can be considered one of the possible causes for precocious, early and accelerated puberty in male patients, suggesting the need to carry out brain nuclear magnetic resonance imaging in order to investigate the presence of this malformation.

Catch-up growth in short-at-birth NICU graduates.

The statural catch-up growth, defined as reaching at least tenth length/height percentile (P10) for normal population standards (-1.28 SD score, SDS), was studied in 73 infants short at birth (length < P10 for gestational age) admitted to NICU. Mean gestational age at birth was 35.2 weeks (range 29-41) and mean birth length standard deviation score -2.31 (-4.52/-1.46). Infants were measured at birth, at 3, 6, 12, 18, and 24 months corrected age and then once a year until 6 years chronological age. Statural catch-up growth was studied, with reference both to normal population standards and to individual genetic target. With reference to normal population standards, 44% of infants had caught-up at 3 months of age, 51% at 3 years, 66% at 4 years and 73% at 6 years. In the case of individual genetic targets, a similar trend was present, but the absolute values were slightly higher from 4 to 6 years (73 vs. 66% and 78 vs. 73%, respectively). Statistically significant changes in mean standard deviations score for chronological age were present from birth to 3 months, 3 to 12 months, 3 to 4 years and 5 to 6 years (p<0.05). No differences were found in this trend of recovery when considering ponderal index (PI) at birth (symmetrical vs. asymmetrical), sex (male vs. female) or gestational age (p>0.05). In the majority of cases infants with short stature at birth admitted to a NICU had a statural catch-up growth within the first years of life. This is more evident when considered in relation to individual genetic target rather than to normal population standards.

Effect of long-term growth hormone treatment on carbohydrate metabolism in children with growth hormone deficiency.

OBJECTIVE: Growth hormone (GH) has well known effects on carbohydrate metabolism. We have evaluated the effects of long-term growth hormone (GH) therapy on carbohydrate metabolism in children with classical GH deficiency (GHD) or GH neurosecretory dysfunction (GHND). STUDY DESIGN: Glucose, insulin and C-peptide concentrations at baseline and during oral glucose tolerance test (OGTT) were measured before and after 18 and 36 months of GH therapy (0.6-0.8 IU/Kg/week in 6 evening doses) in 13 GHD and 7 GHND children (15 boys and 5 girls, 15 prepubertal and 5 early pubertal; age at diagnosis 2.11-13.1 y). RESULTS: Mean fasting insulin and C-peptide concentrations after 18 months were similar to the pretreatment values, while after 36 months they were significantly higher than before treatment. Fasting glucose concentrations were similar to pretreatment both after 18 and 36 months. The mean areas under the curve (AUC) during OGTT for glucose, insulin, and C-peptide were significantly increased after 18 and 36 months. There were no differences between GHD and GHND patients. During the treatment period 10 of the 15 prepubertal patients entered puberty. A significant increase of insulin and C-peptide concentrations occurred after 36 months of GH treatment in the patients that remained prepubertal during treatment as well as in those who were pubertal when treatment was started. In three of our patients GH treatment caused glucose intolerance, which resolved after 6-12 months of a normal calorie low-simple carbohydrate diet without requiring discontinuation of treatment. CONCLUSION: Our data show that long-term GH treatment in GH deficient children causes hyperglycaemia and increased insulin secretion. These effects may in some patients induce glucose intolerance, which is reversible with appropriate dietary measures and does not require discontinuation of treatment.

Growth hormone binding protein activity in obese children.

We evaluated growth hormone binding protein (GHBP) activity in a group of obese children (12 boys and 12 girls, age 3.1-14.7 years, BMI 21.1-33.3, 11 prepubertal and 13 early pubertal) and in 26 age-matched normal weight children (14 boys and 12 girls, age 2.1-16.0 years, BMI 14.2-21.4, 18 prepubertal and 8 early pubertal). All children were of normal stature. GHBP activity was significantly higher in the obese (39.1 +/- 1.1%) than in the control children (28.3 +/- 1.0%, p < 0.0001). Mean serum GHBP was not different between boys and girls or between prepubertal and pubertal subjects. A positive correlation was found between BMI and GHBP levels only in the normal weight children (r = 0.425, p < 0.05). Baseline insulin concentrations in the obese children were 97.6 +/- 7.9 pmol/l (normal values, 45.0 +/- 18.6 pmol/l), and the mean insulin AUC following OGTT in the obese was 811.3 +/- 160.7 pmol/l (normal values, 373.1 +/- 150.1 pmol/l). Serum GHBP activity in the obese was not correlated with baseline serum insulin concentrations or with the insulin AUC following OGTT. In conclusion, we found that obese children have elevated GHBP activity, and speculate that this phenomenon may serve to compensate for their reduced GH secretion and accelerated GH clearance.

Growth hormone (GH) response to GH-releasing hormone in short children: lack of correlation with endogenous nocturnal GH secretion.

The growth hormone (GH) response to iv administration of GH-releasing hormone (GHRH, 0.3 microgram/Kg) was evaluated in 21 short children (13 boys and 8 girls, age 6.7-13.8 yr). Fourteen had familial short stature and/or constitutional growth delay, one had coeliac disease, and 6 were ultimately diagnosed as non-classical GH deficiency or neurosecretory dysfunction on the basis of subnormal integrated spontaneous GH concentrations (ICGH). The response was compared with 12-h spontaneous GH secretion measured every 30 min from 20:00 to 08:00. Mean ICGH ranged from 2.0-17.7 micrograms/l, with a maximum nocturnal GH peak ranging from 5.4-74 micrograms/l. The maximum GH peak after GHRH ranged from 9.4-50 micrograms/l, and the area under the curve (AUC) from 406-3012 micrograms.min/l. No correlation was found between the maximum GH peak and the AUC after GHRH and the maximum overnight GH peak, the ICGH and the overnight AUC. This study confirms that the GH response to GHRH is highly variable among short children with a wide range of spontaneous GH secretion, and that this response is not correlated with the spontaneous ability to secrete GH.

[Visceral leishmaniasis in children in the province of Florence]. / La leishmaniosi viscerale in età pediatrica in provincia di Firenze.

Three cases of visceral leishmaniasis are presented: two children who got the disease in Florence and the imported case of a girl coming from Albania with her disease in act. The diagnosis was made showing Leishmania in bone marrow specimen. Therapy with melglumine antimonate was effective and well borne, leading the three children to a complete healing. In the province of Florence visceral leishmaniasis is very rare, but such protozoa and the sand flies are present as shown by the high number of dog with leishmaniasis.

[Therapy with arginine chlorohydrate in children with short constitutional stature]. / Terapia con arginina cloridrato nella bassa statura costituzionale (BSC).

It is common knowledge that the administration by mouth of chlorhydrate arginine in children with BSC is followed by an increase of plasma levels of Growth Hormone and Insulin as well as an improvement of statural growth. In order to confirm or disprove this observation we have administrated chlorhydrate arginine for six months in children affected by BSC. We have treated 20 prepubertal children (14 males, 6 females) affected by BSC (13 constitutional growth delay, and 7 familiar short stature) with chronological age ranged from 4.75 to 12.55 years, and bone age from 3 to 12 years, with height < 10 degrees centile. The chlorhydrate arginine was administered by mouth at a daily dosage of 4 g (1 phial/2) for 6 months. Height was controlled 6 months before treatment ("off" period) at the start, and after 6 months of treatment ("on" period). Before the start of treatment GH release was assessed with 3 pharmacological tests (arginine, insulin and clonidine) at last of treatment has been made only arginine test in order to investigate GH and insulin response. We have compared the "off" with "on" period and we have observed a substantial improvement (p < 0.01) of the height velocity (HC), worded in SDS-HC (standard deviation score of height velocity) that changed from -1.21 +/- 0.40 to -0.30 +/- 1.37 with a positive difference of +0.91 +/- 0.47 between the two periods. As for as GH release is concerned we have observed, after therapy, a significant increase of mean almost twice that see in the "off" period and the difference is significant p = 0.012).(ABSTRACT TRUNCATED AT 250 WORDS)

[The assessment of skeletal age in hypothyroidism during the first year of life. The features of a new method]. / La valutazione dell'età scheletrica nell'ipotiroidismo durante il primo anno di vita. Rilievi con un nuovo metodo.

Determining skeletal maturity in the first year of age with usual methods is often quite difficult. Some years ago, we investigated a new method based on the time of appearance of appreciable ossification centres in the upper limbs with the following succession: humerus head, capitate, coracoid process, hamate, humerus capitulum, greater tuberosity and radius distal epiphysis; in the first month of age it must be associated to knee and foot study. We studied with our method the skeletal maturity of 16 hypothyroid patients before and after 6 and 12 months of therapy; in the first month of age we associated the study of left knee and foot and study of left hand and wrist using Greulich and Pyle's method at 12 months of age. We compared data of hypothyroid patients to data of 399 infants hospitalized in Pediatric Clinic of Florence for infectious diseases or for neonatal hyperbilirubinemia. Our study has showed that skeletal maturity, retarded before therapy, rejoined normal values over a period of time of 12 months of substitutive treatment; it was accelerated in some patients.