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Aims-To define, in a prospective study, the risk of hypoglycaemia-defined as blood glucose concentration < 1.8 mmol/ l-in term infants exposed in utero to valproate and to describe the withdrawal symptoms. Methods-Twenty epileptic women were treated with valproate only during pregnancy and two were treated with valproate and carbamazepine. In the first trimester, the daily median dose of valproate was 1.0 g (range 0.3-4.2) and in the third trimester 1.2 g (range 0.3-4.8).Results-Thirteen of the 22 infants became hypoglycaemic. One infant had eight episodes of hypoglycaemia, one had three episodes, two had two episodes, and nine had one episode each. The lowest blood glucose concentration was 1.0 mmol/l. All episodes were asymptomatic. The maternal mean plasma concentration of total valproate during the third trimester correlated negatively with blood glucose concentration one hour after delivery (p < 0.0003) and with the development of hypoglycaemia (p < 0.0001). There was no evidence for hyperinsulinaemia as the cause of hypoglycaemia. Ten infants developed withdrawal symptoms, which correlated positively with the mean dose of valproate in the third trimester and the concentration of the free fraction of valproate in maternal plasma at delivery (p < 0.02). Conclusions-Infants exposed to valproate in utero had a significantly elevated risk of hypoglycaemia, and withdrawal symptoms were often observed. (Arch Dis Child Fetal Neonatal Ed 2000;83:F124-F129)

Objective: To describe three cases of Cushing's disease in children with multiple endocrine neoplasia type 1 (MEN1), as clinical manifestations of MEN1 are very rare in childhood. Design and methods: A retrospective review of three cases of Cushing's disease diagnosed between 1997 and 1999. Genetic screening for MEN1 gene mutation was performed in each patient. Results: An ACTH-secreting microadenoma was diagnosed in three children, aged 11 -13 years, presenting with growth retardation and weight gain over a period of 3-4 years. All patients had successful transsphenoidal adenomectomies. Primary hyperparathyroidism was subsequently diagnosed in two of the patients, and in the monozygotic twin of one of the patients. A new mutation in the MEN1 gene (Tyr351His) was identified in two of the patients and the affected members of their families. In the third patient a de novo MEN1 gene mutation (Leu444Pro) was found. Conclusions: MEN1 has to be considered in all children with tumours of the pituitary gland, and in those presenting with primary hyperparathyroidism. The children and their families should be advised to seek genetic counselling. We suggest that careful growth records be kept for children at risk of developing inherited MEN1 and, in the event of a decelerating growth rate, further diagnostic evaluation be undertaken with regards to ACTH-secreting pituitary tumours.European Journal of Endocrinology 151 709-715

Objective: The use of a growth hormone (GH) receptor antagonist, pegvisomant has shown great promise in adults with acromegaly, but experience in paediatric patients is lacking. We aimed to describe the results of pegvisomant therapy in a 12-year-old girl with an aggressive GH-secreting pituitary tumour. Design: To evaluate the ability of pegvisomant therapy to control the effects of peripheral GH excess in a case of pituitary gigantism. Methods: Pegvisomant was introduced at 10 mg/day, given subcutaneously, and gradually increased to 20 mg/day until serum IGF-I was normal for age. Results: A large pituitary adenoma with suprasellar extension was diagnosed in a 12-year-old girl with progressive tall stature (178 cm), GH hypersecretion without suppression during oral glucose loading (nadir serum GH, 90 mU/l), high serum IGF-I and serum prolactin levels. Surgical extirpation was not possible because tumour tissue was fibrous and adherent to the optical nerves. Histological examination showed a mixed GH-and prolactin-secreting adenoma with lymphocytic infiltration of B and T cells. Treatment with a dopamine agonist, cabergoline, normalized serum prolactin, but GH secretion was resistant to both somatostatin analogue, octreotide and cabergoline. Radiation followed by pegvisomant therapy titrated up in dose to 20 mg/day led to a marked reduction in GH secretion and normalization of IGF-I, and to growth arrest and improvement of well-being. Conclusions: We suggest that treatment in pituitary gigantism with pegvisomant is safe and may normalize IGF-I levels and effectively stop growing.