G. Van Vliet

Hypothalamo-pituitary dysfunction in congenital toxoplasmosis

Three patients with congenital toxoplasmosis and hypothalamo-pituitary dysfunction are reported. All three children were growth hormone (GH) deficient, two were gonadotropin deficient and one had precocious puberty in addition to central diabetes insipidus (DI). It is suggested that congenital toxoplasmosis might result in a neuro-endocrine disturbance and thus be an organic cause of hypopituitarism. Pituitary function and growth should be monitored in children with congenital toxoplasmosis.

THYROID DYSHORMONOGENESIS - SEVERE HYPOTHYROIDISM AFTER NORMAL NEONATAL THYROID STIMULATING HORMONE SCREENING

We report four children who presented no evidence of primary hypothyroidism in the neonatal period, either clinically (normal growth velocity) or biochemically (normal plasma levels of thyroid stimulating hormone and/or thyroid hormone). However, in early childhood, these children developed severe hypothyroidism due to dyshormonogenesis. We conclude that apparently normal thyroid function in the neonatal period does not preclude the development of severe hypothyroidism due to thyroid dyshormonogenesis later in childhood.

Treatment of central precocious puberty with an intranasal analogue of GnRH (Buserelin)

One boy and 13 girls with central precocious puberty were treated for 1 year using Buserelin, a GnRH analogue, given intranasally (0.3 mg, four times a day). After 1, 3 and 12 months of therapy, the gonadotropin responses to GnRH were abolished in all the patients whereas mean basal serum concentrations of luteinizing hormone (LH) remained similar to those of pubertal controls. During Buserelin treatment, genital development in the boy and breast development in the girls showed no further progress or some regression. In the boy, serum testosterone levels returned to prepubertal values. In the girls, serum oestradiol levels were variable and, in four of them, vaginal smears showed the persistence of a slight oestrogenic effect during therapy. Pelvic ultrasonography did not show any significant variation in ovarian and uterine lengths. Among the 14 patients, 3 had some progression of pubic hair development, irrespective of serum dehydroepiandrosterone sulphate (DHEAS) levels. In eight patients previously treated with cyproterone, elevated prolactin levels were observed before and during the first month of Buserelin administration. During treatment, mean height velocity was markedly reduced from 11.6 to 6.1 cm/year and mean bone age velocity (±1 SD) was 0.85±0.38 year/year. After 1 year of treatment, the differences in predicted adult height ranged between −0.74 and +1.04 SDS (standard deviation score). These differences were inversely related (r=−0.72) to the prognosis of adult height calculated before treatment. We conclude that, in central precocious puberty, intranasal administration of Buserelin, 1.2 mg/day, may arrest sexual development and reduce height velocity and bone maturation. Improvement of adult height prognosis may occur, especially when it was markedly impaired before treatment.

Vasopressin and gonadotropin deficiency in a boy with the ectrodactyly‐ectodermal dysplasia‐clefting syndrome

A boy presented with ectrodactyly (lobster claw deformity), bilateral cleft lip and palate, semilobar holoprosencephaly and microcephaly, associated with congenital hypogonadotropic hypogonadism and central diabetes insipidus. Other aspects of pituitary function were normal. We suggest that the ectrodactyly‐ectodermal dysplasia‐clefting syndrome can be associated with a variety of hypothalamo‐pituitary dysfunctions, in addition to the already described isolated growth hormone deficiency.

Hormonal Changes during Development in Turner's Syndrome

The hormonal changes observed during infancy, childhood and adolescence in patients with Turners syndrome are reviewed, with particular emphasis on gonadotrophins and GH. The relative roles of gonadal insufficiency, maturation of the CNS and disturbed body composition (i.e. obesity) are discussed with respect to the endocrine findings.

Growth hormone treatment of Turner syndrome patients with insufficient growth hormone response to pharmacological stimulation tests

Growth before and during treatment with biosynthetic human growth hormone (hGH) was studied in 13 patients with Turner syndrome (TS) and a growth hormone (GH) response of less than 10 μg/l to two standard provocative tests. During 1 year of treatment with hGH (0.15 IU/kg per day) height velocity (mean±SD) increased significantly (P<0.001) from 3.7±1.8 cm/year to 7.6±1.5 cm/year. The auxological data in these girls before and during treatment with hGH were similar to those observed in TS patients with a normal response of GH to pharmacological stimuli. It is concluded that in girls with Turner syndrome GH testing should only be performed when height velocity is below the Turner norm. In TS patients with residual growth potential a clinically significant growth acceleration can be obtained with a higher-than-replacement dose of hGH, i.e. 0.15 IU/kg per day, regardless of GH testing.

A neonatal form of isolated ACTH deficiency frequently associated with Tpit gene mutations.

Tpit is a T-box transcription factor involved in terminal differentiation of the pituitary POMC-expressing cells. We previously demonstrated that human and mice mutations of the highly cortico/melanotroph specific transcription factor gene Tpit cause a neonatal onset form of congenital isolated ACTH deficiency (IAD). In the absence of glucocorticoid replacement, IAD can lead to neonatal death by acute adrenal insufficiency. This clinical entity was not previously well characterized because of the small number of published cases. We investigated the Tpit gene coding sequences in 28 patients (22 unrelated families) presenting with neonatal onset IAD. We found a Tpit mutation in 17/28 patients (61%). We identified 10 different Tpit mutations with a high frequency site in exon 6, which was found in 5 unrelated families. All patients were homozygous or compound heterozygotes for Tpit mutations, and their unaffected parents were all heterozygous carriers, confirming the recessive mode of transmission. It is noteworthy that five compound heterozygotes involving different mutations were identified. We compared the clinical and biological phenotype of the 17 IAD patients carrying a Tpit mutation with the 11 remaining IAD patients and we didn’t find any

Congenital hypopituitarism: Results of pituitary stimulation tests and of magnetic resonance imaging in a newborn girl

We report the case of a newborn girl in whom hypopituitarism was diagnosed in the neonatal period. Clinical, biological and radiological evidence suggested that hypopituitarism must have existed before delivery, yet MRI findings were similar to those described in older children with hypopituitarism of later onset.