Growth hormone receptor mutations in children with idiopathic short stature.

Homozygous or compound heterozygous mutations in the GH receptor (GHR) gene result in GH insensitivity syndrome. Previous reports have shown that some heterozygous mutations may induce a partial insensitivity to GH, but others appear to have limited effect on growth. To investigate further these observations, we analyzed the GHR gene in 17 subjects with idiopathic short stature (ISS). All subjects had a height 2 SD or more below the mean and/or abnormal growth velocity. In addition, serum GH levels were 10 ng/mL or more and insulin-like growth factor I levels were normal or low. A novel heterozygous mutation resulting in a valine to isoleucine change (V144I) in exon 6 in the extracellular domain was found in one subject. His mother and one brother had significant short stature and also had the identical mutation. Affected family members also had a polymorphism in exon 6 of the GHR gene, which has been present in other subjects who had short stature and heterozygous mutations of the GHR gene. The other subjects with ISS had normal GHR genes. However, eight subjects had neutral polymorphisms distributed throughout the GHR locus. Accumulating evidence suggests that GHR gene mutations account for up to 5% of all ISS patients. These mutations should be considered when other causes of short stature have been eliminated.

Kenny-Caffey syndrome and microorchidism.

We report on two adolescent boys with Kenny-Caffey syndrome and microorchidism. The first patient had elevated levels of serum follicle-stimulating hormone, but normal levels of luteinizing hormone and testosterone. There was no evidence of a microdeletion of the Y chromosome. The second patient had Leydig cell hyperplasia with normal seminiferous tubules and spermatogenesis, and normal pituitary histologic findings at autopsy. The presence of microorchidism in these patients confirms the previous observations and suggests subfertility, but does not fully clarify the pathogenesis.

Height screening in the community. The commercialization of growth. The role of the pediatrician.

The availability of unlimited but costly supplies of biosynthetic growth hormone has led to pressure for pharmacologic use (as opposed to replacement therapy in proven deficiency states). Commercial and altruistic motives have converged to promote community height screening among individuals who have been perceived by themselves or parents as short. This does not meet accepted criteria for health screening. Height screening of large populations of children yields few unrecognized medical conditions. If the goal of community screening is to identify abnormally short individuals (less than 3%) who might benefit from growth hormone treatment and if the unproven assumption is correct that stature correlates with success and happiness, then those less likely to appear for screening need to be recruited to avoid elitist domination. The annual cost of such growth promotion would be greater than $10 billion, with no evidence for substantial health benefits. Growth monitoring of all children through improved height measurement in schools and in physicians offices, as part of health supervision, is a more sound community approach than height screening.

Oral rehydration of infants in a large urban U.S. medical center.

A prospective randomized study of 100 well-nourished infants with acute gastroenteritis resulting in dehydration and acidosis was carried out at the Jackson Memorial Hospital, Miami from 1981 to 1983. Patients were randomly assigned to receive either standard intravenous therapy or oral rehydration. Infants in the latter group first received solution A containing 75 mEq/L sodium, 30 mEq/L potassium, 75 mEq/L chloride [corrected], 30 mEq/L bicarbonate, and 2 gm/dL glucose [corrected]. After ad libitum feeding for six hours, solution B containing 50 mEq/L sodium, 30 mEq/L potassium, 50 mEq/L chlorine, 30 mEq/L bicarbonate, and 3 gm/dL [corrected] glucose was given. With three exceptions (6%), oral rehydration was comparable to the intravenous regimen in clinical estimates of improvement, although the oral group had more stools in the first day. The oral group had faster correction of acidosis and a sustained rise in serum potassium concentration, whereas in the intravenous group the potassium concentration showed first a drop with a later increase, but levels were at all times below those in the oral group. Although potassium was given from the beginning of oral rehydration, and at a higher concentration than recommended by the World Health Organization, no hyperkalemia occurred. We concluded that oral therapy is safe, less expensive for patients, and more convenient for the medical and nursing staffs.

Effects of fetal sex and weight and placental weight on maternal serum progesterone and chorionic gonadotropin concentrations.

A prospective study of 268 normal pregnant women at term was undertaken in which serum concentrations of progesterone (P) and chorionic gonadotropin (HCG) were determined zero to four days before spontaneous labor. Neither HCG nor P changed significantly during these four days, although they were not measured serially in most women. There was no correlation between the HCG level and either the placental or infant weight, infant sex, or maternal serum progesterone concentration. The maternal serum P level was slightly but significantly correlated with the weight of the placenta (r equal to 0.24; p smaller than 0.001) but not with the fetal weight or infant sex. Thus, although the mass of trophoblastic tissue contributed in part to P concentration, other intracellular factors such as the cyclic adenosine monophosphate system are probably more important regulating mechanisms.

Immunologic reconstitution in the DiGeorge syndrome by fetal thymic transplant.

An infant with idiopathic hypoparathyroidism was found to have no evidence of thymus by radiologic examinations, including pneumomediastinum. Immunoglobulin concentrations were normal but there was clear evidence of inadequate cellular immunity including gradually developing lymphopenia. The infant suffered recurrent diarrhea and pneumonia, chronic rhinorrhea and moniliasis. At age 7 months fetal thymic tissue was implanted in the rectus abdominis muscle. There was immediate increase in lymphocyte counts which have remained normal on most determinations. Other aspects of immunologic function were restored and remain intact. The child, now 6 years of age, although mentally retarded, has no unusual infections. Immunologic reconstitution was thus achieved by transplant of fetal thymus.