Marvin L. Rallison

Utah Growth Study: Growth standards and the prevalence of growth hormone deficiency

Serial measurements of elementary-school children were conducted for 2 consecutive years to assess height and growth velocity and to determine the prevalence of growth hormone deficiency (GHD) in American children. Trained volunteers measured 114,881 children the first year; 79,495 growth rates were calculated after the second measurements. The height and growth velocity curves generated were very similar to the currently used charts. We examined 555 children with short stature (< 3rd percentile) and poor growth rates (< 5 cm/yr). Five percent had an endocrine disorder. The presence of GHD (peak level, < 10 ng/dl with two provocative tests) was found in 16 previously unrecognized children; 17 children from this school population were already known to have GHD. Boys outnumbered girls 2.7:1 (p = 0.006). Six girls with Turner syndrome also were identified. We conclude that (1) the growth curves generated in the 1960s and 1970s are valid for children of the 1990s; (2) most children growing < 5 cm/yr (a commonly used threshold rate) will not have an endocrine disorder; (3) many children (48% in this study) with GHD and others with Turner syndrome may currently be unrecognized and untreated; (4) GHD appears to be more common in boys; and (5) the prevalence of GHD in the United States is at least 1:3480.

Natural history of thyroid abnormalities: Prevalence, incidence, and regression of thyroid diseases in adolescents and young adults

PURPOSE This study reports the prevalence, incidence, and regression of thyroid abnormalities in a population observed from adolescence to adulthood. PATIENTS AND METHODS Examinations for thyroid abnormalities were performed in 4,819 school-age children, ages 11 to 18, in 1965 to 1968; two thirds of this original cohort (3,121) were re-examined 20 years later (1985 to 1986). Each subject with a thyroid abnormality detected by physical examination was studied by means of a series of re-examinations, and tests of thyroid function, imaging, and biopsy to determine the exact nature of the thyroid abnormality. RESULTS In the initial examinations (1965 to 1968), 185 thyroid abnormalities were found (3.7%). Diffuse hypertrophy with normal function (adolescent goiter) was the most common abnormality (19.3/1,000); 12.7/1,000 had chronic lymphocytic thyroiditis, and 4.6/1,000 had thyroid nodules, including two papillary carcinomas. Hyperthyroidism or hypothyroidism was found in 1.9/1,000. In the follow-up examinations in 1985 to 1986, 298 subjects had thyroid abnormalities (10.5%), of whom 81 (28.7/1,000) had simple goiters, 145 (51.3/1,000) had chronic thyroiditis, 45 (15.9/1,000) had hypothyroidism, 11 (3.9/1,000) had hyperthyroidism, and 66 (23.2/1,000) had nodules, which included 10 carcinomas. Of the 92 subjects with simple or adolescent goiter in 1965 to 1968, 60% were normal by 1985 to 1986, 20% were unchanged, and a few had developed thyroiditis (10%) or colloid goiters (3.0%). Of 61 subjects with thyroiditis, 27% had become normal, 33% remained unchanged, and 33% had become hypothyroid. Of the 22 subjects with thyroid nodules, two had complete disappearance of the nodules, and three had nodules considered to be variants of normal. The others exhibited a variety of nodular pathologic conditions. CONCLUSIONS The natural history of thyroid disorders, including simple goiter, chronic thyroiditis, hyperthyroidism, hypothyroidism, and nodular diseases of the thyroid, indicates they are dynamic and changeable in form, function, appearance, and disappearance.

Infancy-onset diabetes mellitus and multiple epiphyseal dysplasia*

Summary Three siblings with onset of diabetes mellitus infancy are reported. Two (and possibly all three) of the children also had multiple epiphyseal dysplasia. Demineralization of the bone with multiple fractures, tooth discoloration, and skin abnormalities were also observed. A unifying biochemical or physiologic mechanism for the simultaneous appearance of diabetes, epiphyseal dysplasia, and possible ectodermal dysplasia has not suggested itself, but this may represent a new syndrome.

Metabolic Activity of Diabetic Monocytes

There have been several reported abnormalities in the cellular components of the acute inflammatory response in diabetes mellitus. These studies have dealt primarily with polymorphonuclear leukocytes. In the present investigations, we have examined monocyte metabolic activity in diabetic patients and controls. Following particle ingestion, the microbicidal mechanisms of the monocyte are activated and excited molecular oxygen and carboxyl groups are generated. Upon decay to the ground state, these molecules emit photons, which can be measured as chemiluminescence. Chemiluminescence production was significantly increased in 27 patients with poorly controlled diabetes (blood glucose levels from 208 to 712 mg/dl). The mean peak in the diabetics was 31.3 ± 8.2 (SD) × 103 cpm versus 25.8 ± 3.8 × 103 cpm in controls. Hexose monophosphate shunt activity as determined by 14 C-I-glucose utilization was also increased (667 ± 284 percent increase in diabetics versus 425 ± 154 in controls). Superoxide dismutase-inhibitable superoxide production was also significantly augmented in diabetic monocytes (9.77 ± 3.06 nmol/106 monocytes/20 min versus 6.36 ± 1.10 nmol). Addition of glucose to whole blood from a normal individual, or to normal or diabetic monocyte suspensions, resulted in marked enhancement of chemiluminescence production. Increasing blood sugar levels appear, therefore, to be associated with monocyte metabolic activation in diabetic patients. Such activation could conceivably be detrimental to the diabetic host by contributing to cell damage through the release of toxic oxygen products.

Thyroid disease in children. A survey of subjects potentially exposed to fallout radiation

Abstract We found no significant difference in any type of thyroid disease between children in Utah and Nevada exposed to fallout radiation in the 1950s and control groups living in Utah and Arizona at present. Of the 5,179 children surveyed, thyroid abnormalities were found in 201. Adolescent goiter was the most common disorder with a prevalence of 15 per 1,000 for boys and 20 per 1,000 for girls. There were seven cases of hyperthyroidism, and the rates for lymphocytic thyroiditis were 8 and 16 per 1,000 for boys and girls, respectively. Twenty benign neoplasms and two carcinomas of the thyroid were found. Only 6 of the 201 children with thyroid disease knew of their disease prior to our examination. The inapparent thyroid disease discovered in this group of children through meticulous examination may have its counterpart in other populations as well. This study demonstrates the need, therefore, for careful examination of thyroids even in apparently healthy children.

Defective monocyte chemotactic responses in diabetes mellitus

A variety of polymorphonuclear leukocyte (PMN) defects has been described in diabetics, but to date no investigations of monocyte (MN) function have been reported in diabetics. In the present studies, we have employed an underagarose chemotactic assay to examine directed and random motility of MNs from diabetic individuals. Among 45 diabetics and 25 controls there was no significant difference in the maximal distance migrated by the leading front of cells to zymosan-activated serum (chemotaxis) or medium alone (random migration). In contrast, many fewer diabetic MNs [293±28 (SE)] moved toward the attractant than did control MNs (446±21;P<0.001). Random motility of the diabetic MNs (121±14 SE) was also decreased compared to that of the controls (225±24;P<0.0004).In vitro incubation of the diabetic monocytes with insulin (25, 75, and 100 µU/ml) failed to improve chemotactic function. Treatment of diabetic MNs with 2,3-dihydroxybenzoic acid, a scavenger of H2O2 and O2−, increased both random motility and directed movement, however. In addition,in vivo therapy of 7 diabetic patients with α-tocopherol (vitamin E) resulted in a marked increase in the number of MNs moving toward the chemoattractant (pretherapy, 118±12; posttherapy, 246±31;P<0.05). These results indicate that diabetic individuals have defective monocyte chemotactic function which can be corrected, in part, byin vitro orin vivo treatment with antioxidants. Thus, defective function may be, at least partly, the result of autooxidative membrane damage.

Acquired von Willebrand disease in twins with autoimmune hypothyroidism: Response to desmopressin and L-thyroxine therapy

Because of menorrhagia, a 13-year-old girl was found to have type I von Willebrand disease and then chronic autoimmune thyroiditis with hypothyroidism. All clinical and laboratory evidence of von Willebrand disease resolved transiently after infusion of desmopressin, and permanently with L-thyroxine therapy. We recommend investigation for hypothyroidism in patients with newly diagnosed acquired von Willebrand disease.

Renal Anomalies in Turner's Syndrome: Types and Suggested Embryogenesis

Of 15 patients with Turners syndrome studied for renal anomalies by intravenous pyelogram, 11 had demonstrable abnormalities ; three had horseshoe kidney. None had evidence of impaired renal func tion. Four reported previous urinary tract infections. Similarities among the positional and structural abnormalities of the kidneys suggested a continuum of morphologic changes, with a possible re lationship of such changes to impaired positional information pro gramming by the developing abnormal gonad during embryogenesis.

Functional and Metabolic Abnormalities of Diabetic Monocytes

There is considerable controversy about whether diabetic individuals suffer more infections than do normal individuals1. There is no question, however, about the increased severity of infection in the diabetic patient or the fact that infection greatly complicates the diabetic state. Although numerous studies have examined the functional activity of polymorphonuclear leukocytes (PMNs) in diabetic patients, almost none have investigated monocyte activity. The present studies were undertaken to assess the functional and metabolic activity of monocytes from patients with diabetes mellitus.

Hypoglycemia and lactic acidosis associated with fructose-1,6-diphosphatase deficiency

HEREDITARY FRUCTOSE1 ,6-DIPHOSPHATASE deficiency is an inborn error of carbohydrate metabolism characterized by metabolic acidosis, hyperventilation, fasting hypoglycemia, and hepatomegaly. Acidosis is associated with elevated lactic, pyruvic, betahydroxybutyric, and acetoacetic acids. Hypoglycemia and acidosis may be induced in affected children by prolonged fasting or by infections, and by administration of fructose, glycerol, or alanine. 14. ~ Prevention of hypoglycemia and acidosis has been reported with a fructose-free diet ~ and with folic acid therapy. 7 We report a child who presented with recurrent lactic acidosis and hypoglycemia associated with fructoseol,6-diphosphatase deficiency in whom we have tried both diet and folate therapy.