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.

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.

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.

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.

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.