Endocrinological Abnormalities in Prader-Willi Syndrome

Ten patients with typical Prader-Willi syndrome were studied for their short stature, hypogonadism, and obesity. Tne following results were obtained.

• 1) GH secretion was variable, ranging from subnormal to normal, although all shared short stature in common.
• 2) Two of the 4 adolescent patients were diagnosed as having hypo-gonadotropic hypogonadism. The remainder disclosed normal response to LH-RH stimulation. Of the two patients with normal LH-RH stimulation test, one showed normal testosterone production.
• 3) In one child who developed overt diabetes, there remained elevated basal plasma insulin and depressed RBC-insulin binding, despite weight control. There appears to be a significant heterogeneity in endo crinological derangement of Prader-Willi syndrome.

     

Lymphoepithelioma in childhood

Nine black children with lymphoepithelioma, a rare malignancy of childhood, are the subject of this report. Unique clinical features included tender cervical lymphadenopathy with torticollis, trismus, epistaxis, and change in voice quality. A nasopharyngeal mass was demonstrable in seven children on careful examination, but none was resectable. Treatment with radiation alone or radiation plus cyclophosphamide resulted in complete tumor regression in eight of the nine children. Local recurrence or distant metastases occurred in four within 10 months, two of whom responded to additional radiation plus cyclophosphamide or adriamycin. At present, four children are alive without disease for periods of seven to 78 months, two are alive for seven to 53 months and are in remission from recurrent disease, and three have died with distant metastases. Freedom from disease for one year was associated with a favorable prognosis. Adjuvant chemotherapy appears warranted in view of the high incidence of local recurrence and distant metastases.     

Endocrine studies in cystinosis: compensated primary hypothyroidism.

Children with nephropathic cystinosis exhibit marked growth retardation. Improved medical management and renal transplantation have increased their life expectancy beyond the second decade. We have studied endocrine function in seven patients with cystinosis and reviewed autopsy findings of four patients and medical records of 24 others. One 10-year-old boy was overtly hypothyroid. The six other patients had normal studies of peripheral thyroid function but two had borderline and two had frankly elevated serum TSH levels. Stimulation tests of cortisol and growth hormone secretion and basal levels of serum NSILA-s were normal. Postmortem histology of the thyroid glands revealed extensive destruction and infiltration of the epithelium with cystine crystals. Despite the presence of cystine crystals in other endocrine tissues, there was no destruction of epithelium in glands other than in the thyroid. We conclude that in nephropathic cystinosis "compensated" primary hypothyroidism occurs frequently and early and may be diagnosed by measurement of serum TSH concentrations.     

Hydrocephalus and mental retardation in craniosynostosis

We prospectively studied craniosynostosis, regardless of neurologic status, by cranial computed tomography or psychometric testing in 56 children. None of the 27 children with simple craniosynostosis (single or multiple suture involvement) had evidence of hydrocephalus on CT scan. Of the 24 patients with simple craniosynostosis who underwent psychometric testing, 17 were of average intelligence; six were in the low average range. The single mentally retarded child had a history of severe perinatal asphyxia. Hydrocephalus occurred more frequently (five of 23 cases) in children with complex craniosynostosis syndromes, including Pfeiffer syndrome, Crouzon syndrome, and kleeblattsch?del deformity. More striking than hydrocephalus, however, was the finding of dysmorphic ventricular dilation in eight patients, including the three children with Apert syndrome and four with Crouzon syndrome. Nineteen of the 25 children with complex craniosynostosis syndromes receiving psychometric testing were of normal intelligence. Four children with borderline normal intelligence had either hydrocephalus or ventricular dilation. The two children with mental retardation were sisters with Crouzon syndrome whose family included other retarded individuals. This study indicates that the incidence of hydrocephalus and mental retardation in craniosynostosis is lower than reported previously.     

Fetal blood lead values in a rural area

Lead levels were determined from neonatal samples of blood collected at a general-care hospital. The cord blood lead values of babies from urban maternal residences were significantly higher than those from rural environments. The over-all cord blood lead value was (mean +/- S.D.) 9.4 +/- 3.7 micrograms of lead per 100 ml. of whole blood. This level represented a considerably lower value than others previously reported and suggests a lower "normal" value for our population.     

Evaluation of growth hormone release in children using arginine and L-dopa in combination.

L-Dopa in a dose ranging from 125-500 mg and arginine monochloride in a dose of 0.5 gm/kg were given simultaneously to 56 children with short stature (height less than third percentile). Sixteen of these children were subsequently diagnosed as having growth hormone deficiency. The diagnosis of hyposomatotropism was based on clinical findings and on responses to the combination test and to arginine and L-dopa administered as separate tests. All of the remaining 40 children had a normal GH response of greater than 6 ng/ml to the combination test. However, in this group, nine children were identified who responded to the combination test but who failed to respond to arginine and L-dopa in individual tests. The data suggest that a positive response to arginine and L-dopa in combination in children, who do not respond to the usual provocative tests when administered individually, may fail to identify children with partial GH deficiency who would benefit from treatment. The integrated stimulated GH response in the 31 children in whom a normal GH response to all three tests occurred suggests that the effects of L-dopa and arginine are additive.