Incidence of transient congenital hypothyroidism due to maternal thyrotropin receptor-blocking antibodies in over one million babies.

To determine the incidence of transient congenital hypothyroidism due to TSH receptor-blocking antibodies, we screened dried blood specimens obtained from 788 neonates identified as having possible congenital hypothyroidism (from a total population of 1,614,166 babies) and 121 controls. A RRA was used. The potency of blood spot TSH binding inhibitory activity was compared with the severity of congenital hypothyroidism to assess the possible etiological relationship. Maternal serum was studied to confirm the presence of blocking antibodies by both RRA and bioassay. Blood spots obtained from 9 infants contained potent TSH receptor-blocking activity. Samples from 2 additional babies, studied because of clinical suspicion of the disease, were also positive. Long term outcome was known in 8 of the 11 babies, and all had transient disease. Neonates with TSH receptor-blocking activity greater than 132 U/L had a significantly lower T4 level (P < 0.05) and higher TSH (P < 0.005) than those in whom TSH binding-inhibitory activity was less than 132 U/L. All 9 mothers had autoimmune thyroid disease, and 3 had more than 1 affected child. Potent blocking activity was present in 7 maternal serum samples as long as 7 yr after the births of their affected babies. We conclude that measurement of TSH binding-inhibitory activity in dried neonatal blood specimens is a simple and effective method to predict the occurrence of transient congenital hypothyroidism. The incidence of this disorder in North America is 1 in 180,000 normal infants, or approximately 2% of babies with congenital hypothyroidism.

Prenatal diagnosis of congenital lipoid adrenal hyperplasia.

Congenital lipoid adrenal hyperplasia (lipoid CAH) is a rare genetic disorder of adrenal and gonadal steroidogenesis of unknown cause in which cholesterol cannot be converted to pregnenolone. As a result, affected individuals can make no steroid hormones, so that all affected newborns are phenotypic females, irrespective of karyotype. We studied two pregnancies in a family with two previously affected children by examining fetal karyotype, genital ultrasonography, and amniotic fluid steroid concentrations and by performing ACTH tests on family members. Prenatal diagnosis correctly identified both an unaffected XX fetus and an affected XY fetus. In the affected pregnancy, amniotic fluid concentrations of progesterone and pregnenolone were 30% and 50% of normal, respectively, but concentrations of 17 alpha-hydroxypregnenolone, 17 alpha-hydroxyprogesterone, cortisol, dehydroepiandrosterone, androstenedione, and estriol were either extremely low or undetectable, suggesting that these detected steroids were donated by maternal steroidogenesis. Fetal cord blood obtained at the termination of pregnancy showed very low concentrations of estrogens donated by the mother's circulation. Absent fetal steroidogenesis was confirmed by gas chromatography and mass spectrometry of both fetal and maternal serum. The responses of 10 different steroids to adrenal stimulation with ACTH in the obligately heterozygous parents were normal. Thus, unlike the case with other forms of CAH, heterozygosity cannot be determined by hormonal responses to provocative testing with ACTH. Immunocytochemistry and Western blotting showed that the affected placental tissue contained P450scc protein, confirming that P450scc is intact in these patients.

Unifying heterogeneous distributed clinical data in a relational database.

Access to clinical data which are distributed among multiple satellite information systems is crucial to delivering better care and reducing costs in many hospitals and medical centers. An integrated view of these data is needed to reduce the effort of users requiring data from multiple systems. We have addressed the issue of distributed data integration while developing both production and research decision-support applications. We describe an ideal integration solution, obstacles to realizing this solution, and our integration requirements and architecture. Our focus is a description of our specific schema and data integration techniques. We conclude with an analysis of our approach.

Gonadotropin-associated psychosis in perimenstrual behavior disorder.

Sexually provocative and violent behavior have been reported as a result of excess androgens. We now report a temporal relationship between increased gonadotropin levels and behavioral changes in two adolescent girls who presented with a history of aggressive and bizarre sexual behavior coincident with the onset of menarche. We evaluated the possibility of a cyclical hormonal cause with daily measurements of gonadotropins, androgens and estradiol levels and correlated the results with periodic reports on the girls' behavior. We concluded that a correlation exists between periods of extremely violent and sexually provocative behavior and peaks of gonadotropin hormone secretion, even though androgen levels were normal. Treatment with medroxyprogesterone acetate (Depo-Provera) in one case and with leuprolide acetate (Lupron-Depot) in the other suppressed gonadotropin levels, and behavior improved markedly. Thus, the behavioral changes (or psychosis) seen in these girls might have been induced by increased levels of gonadotropins.

An object model for uniform access to heterogeneous databases.

The vast amount of patient information collected and maintained by hospitals is seldom stored in a single database. Much programming effort is wasted on formulating specific queries for each of several data sources, rather than focusing attention on developing the intended functionality of the application. This problem becomes more apparent as more data sources become available. The most obvious strategy for dealing with this multiplicity of data sources, namely storing all data in a single database, is impractical for reasons such as security and administrative control. This paper describes one possible solution to managing access to several database systems within applications. Using object-oriented techniques, the solution identifies the commonality among database management systems and provides a uniform method of communication between applications and databases. We describe a C(++)-based implementation which embodies these concepts.

Hazards of overconcentrated milk formula. Hyperosmolality, disseminated intravascular coagulation and gangrene.

Severe hypertonic dehydration with hyperglycemia developed in a 7-week-old infant girl after she was fed an overconcentrated milk formula for five days. Renal failure,disseminated intravascular coagulation, gangrene of the legs, and coma were added complications. Intravenous rehydration, peritoneal dialysis, and heparin administration corrected the metabolic and coagulation derangements, and renal function returned to normal. Bilateral below-the-knee amputations were performed and the child subsequently learned to walk with artificial limbs. The dangers of overconcentrated formulas in infant feeding should be widely publicized through warnings printed on all commercial milk preparations.