Romana Marini

Final height after growth hormone therapy in non-growth-hormone-deficient children with short stature

We report the effect of growth hormone (GH) treatment for 4 to 10 years in 15 prepubertal non-GH-deficient short children (10 boys, 5 girls, aged 7.4 to 13.2 years). In 7 patients, GH was administered at a dosage of 0.5 U/kg per week (group 1: 4 boys, 3 girls) and in 8 patients (group 2: 6 boys, 2 girls) at a dosage of 1.0 U/kg per week. After the first year, mean linear growth velocity had significantly increased in both groups. The increase in growth velocity was sustained during the first 4 years and then declined to pretreatment values in the majority of subjects. Treatment with GH did not induce an earlier onset of puberty, but there was a tendency toward faster skeletal maturation. The mean final height standard deviation score (SDS) was similar in the two groups and was significantly higher than the height SDS for chronologic age before treatment, but it did not differ from mean pretreatment predicted adult height SDS nor from mean target height SDS in both groups. Final height was significantly correlated with target height in both groups. These preliminary observations indicate that GH treatment does not generally increase final height over target height in short non-GH-deficient children.

Growth hormone response to growth hormone releasing hormone 1-40 in Turner's syndrome.

The response of growth hormone (GH) to acute administration of GH-releasing hormone 1-40 (GHRH) was evaluated in 12 patients with Turners syndrome and in 12 prepubertal or early pubertal girls. In 7 of 12 patients GHRH induced a definite increase (greater than 10 ng/ml) of plasma GH levels. In 5 patients there was a poor GH rise after GHRH administration (less than 10 ng/ml). Overall, the mean GH response of patients was significantly lower than that of normal girls. Five out of 7 patients with a 45 X,O karyotype had a reduced GH rise after GHRH, while all patients with non X,O karyotype (mosaicism and/or 46 X,iX) had a normal GH response to GHRH. Although the cause of short stature in patients with Turners syndrome is most likely multifactorial, a reduced pituitary GH reserve, as documented by the reduced GH response to GHRH in some of our patients, may contribute to the growth impairment in this disorder.

Clinical features suggestive of non-classical 21-hydroxylase deficiency in children presenting with precocious pubarche

Abstract Precocious pubarche (PP) is defined as the onset of pubic hair at 8 years of age in girls and at 9 years of age in boys. PP is idiopathic (IPP) in most children, but it is the earliest manifestation of non-classical congenital adrenal hyperplasia owing to steroid 21-hydroxylase deficiency (NC21OHD) in 5%–20% of cases. 17-Hydroxyprogesterone (17OHP) levels after ACTH stimulation test are used to distinguish the two forms. We studied clinical indicators of NC21OHD in 289 PP children: 14 (4.8%) showed post-ACTH 17OHP levels >30 nmol/L and NC21OHD due to CYP21A2 gene mutations was confirmed. NC21OHD children were younger (p: 0.006) and thinner (p: 0.003) than IPP children. Height standard deviation score (SDS) was not different (p: 0.97). NC21OHD girls showed more advanced bone age than IPP girls (p<0.001). Earlier PP onset and bone age advance suggest NC21OHD, which requires confirmation by an ACTH stimulation test. Later, PP appearance in overweight children suggests IPP and could merit only clinical monitoring.

Partially Reversible Hypopituitarism in an Adolescent with a Rathke Cleft Cyst

Rathke cleft cysts are remnants of the Rathke pouch. Most of them are asymptomatic, but sometimes they can grow enough to cause compression of structures within and/or close to the sella, thus eliciting symptoms such as visual disturbance, pituitary defects, and headache. Asymptomatic cysts can safely be followed up with serial imaging, while the standard treatment for symptomatic lesions is surgical removal. We describe a 14-yr-old boy, admitted for anorexia, fatigue, weight loss, recurrent headache and vomiting. Magnetic resonance imaging showed an intra- and suprasellar cystic lesion, which was surgically removed. Histology was consistent with Rathke’s cleft cyst. Diabetes insipidus and multiple anterior pituitary defects (GH, ACTH and TSH) were found preoperatively, and substitutive therapy was started. No additional hormonal defect appeared after surgery. After 4 yr of follow up, pituitary function was retested, and there were no confirmed GH or ACTH defects, allowing a partial withdrawal of replacement therapy. Our report confirms that pituitary defects, in patients with a Rathke cleft cyst, may recover even year after surgery. Thus, retesting of pituitary axes is indicated during long-term follow up.