Margaret H. MacGillivray

Immunoglobulin response in serum and secretions after immunization with live and inactivated poliovaccine and natural infection.

Abstract The responses of the major immunoglobulins (gamma G, gamma M and gamma A) in serum and nasal and duodenal secretions were studied in infants and children after immunization with live and inactivated poliovaccines and after natural poliomyelitis infection. The serum immunoglobulin responses to these procedures resembled each other although higher levels followed the natural infection. After immunization with live attenuated vaccine, antibody activity was found regularly in nasal and duodenal secretory gamma A immunoglobulin, but not after immunization with inactivated vaccine. To explain the alimentary immunity that follows infection with attenuated or wild poliovirus, it is proposed that orally administered live virus, which implants and replicates in the pharynx and intestinal tract, stimulates local lymphoid cells, leading to the production of immunoglobulins predominantly of the gamma A class.

Long‐term effects of cranial irradiation on endocrine function in children with brain tumors a prospective study

This study prospectively evaluated the endocrine function of 11 children treated with cranial irradiation (CRT) for brain tumors. All tumors were remote from the hypothalamic‐pituitary axis. Children were studied before treatment and at 3, 6, and 12 months after the completion of CRT. T4, thyroid‐stimulating hormone, prolactin, plasma cortisol, and urinary follicle‐stimulating hormone and lueteinizing hormone values were normal before and after treatment in all patients. Growth hormone (GH) deficiency was identified in 0 of 7 patients before treatment, in 2 of 7 patients 3 months post‐CRT, in 9 of 11 patients 6 months post‐CRT, and in 7 of 8 patients 12 months post‐CRT. Growth deceleration was identified in five of seven prepubertal patients. GH deficiency is an extremely common sequelae of CRT, beginning as early as 3 months after the completion of CRT. The deficit is progressive over time.

Pediatric Endocrinology Update: An Overview

The goals of this presentation are to review the essential roles of aromatase, estrogens and the estrogen receptor in pubertal growth. Estrogen deficiency due to mutations in the aromatase gene (CYP19) and estrogen resistance due to disruptive mutations in the estrogen receptor gene have no effect on normal male sexual maturation in puberty. However, they lead to absence of the pubertal growth spurt, delayed bone maturation, unfused epiphyses, continued growth into adulthood and very tall adult stature in both sexes. Gonadotropin and androgen levels are elevated in patients with either estrogen deficiency (aromatase deficiency) or estrogen resistance (estrogen receptor mutation). Glucose intolerance, hyperinsulinemia and lipid abnormalities are also present. Skeletal integrity is compromised. Increased bone turnover, reduced bone mineral density and osteoporosis develop in both sexes. Sexual orientation is appropriate in males and females. In females, aromatase deficiency in the ovary causes pubertal virilization and multicystic ovaries because of elevated gonadotropins and androgens. Simultaneously, secondary sexual maturation fails to occur. Placental aromatase deficiency results in virilization of the mother and her female fetus because of the accumulation of potent androgens which are not converted to estrogens. The male fetus has normal genitalia. In conclusion, estrogens are essential for normal female secondary sexual maturation, bone maturation, epiphyseal fusion, pubertal growth spurt and achievement of normal bone mineral mass. Estrogens also influence insulin sensitivity and lipid homeostasis. However, estrogens do not appear to be essential for fetal survival, placental growth, or female sexual differentiation.

Triad of Hypopituitarism, Granulomatous Hypophysitis, and Ruptured Rathke's Cleft Cyst

A 19-year-old girl with pituitary insufficiency and a large sella turcica was found to have granulomatous hypophysitis in association with a Rathkes cleft cyst. We think that the inflammatory process represents a foreign body reaction to leakage of cyst contents, with destruction of pituitary tissue.

Familial 46,XX males coexisting with familial 46,XX true hermaphrodites in same pedigree

Reported here is a family with which 46,XX males and 46,XX true hermaphrodites coexist. The propositus was a paternal uncle with 46,XX true hermaphroditism. One of his brothers fathered a 46,XX daughter with true hermaphroditism; a second brother fathered two 46,XX males. Both fathers have normal male karyotypes and phenotypes. No evidence for chromosomal mosaicism or any additional chromosomal abnormalities was obtained. We conclude that inheritance of the abnormality is most likely via paternal transmission of an autosomal testis-determining factor. This family provides evidence to support the hypothesis that 46,XX true hermaphrodites and 46,XX males represent alternative manifestations of the same genetic defect.

Quantitation of Urinary Growth Hormone in Children with Normal and Abnormal Growth

ABSTRACT. Urinary growth hormone (GH) excretion was quantitated in 12-h overnight urine collections obtained from 31 control children, ages 3 to 17 yr (group 1); 21 children, ages 5 to 19 yr with GH deficiency (group 2), and 30 subjects, ages 10 to 18 yr with idiopathic growth failure and normal GH stimulation tests (group 3). The output of urinary GH was measured in one acromegalic woman. The authenticity of urinary GH, 22 kDa, was confirmed by high-performance liquid chromatography. The elution pattern of urinary GH was identical to that of biosynthetic and pituitary-derived GH. The immunoreactive profiles characterized by monoclonal immunoradiometric GH assay and standard GH radioimmunoassay were identical. The quantity of GH (mean ± SEM per kg body weight) in group 1 (0.27 ± 0.02 ng/kg) was significantly greater than group 2 (0.08 ± 0.02 ng/kg) or group 3 (0.17 ± 0.02 ng/kg, p < 0.01). Approximately 50% of the subjects in group 3 had urinary GH measurements indistinguishable from those observed in the GH-deficient population. Twelve hypopituitary patients (group 2) excreted significantly greater amounts of urinary GH in the first 12 h after GH administration compared to the baseline period (0.41 ± 0.07 versus 0.12 ± 0.02 ng/kg, p < 0.01). Markedly elevated output of urinary GH (2.0 ng/kg) was documented in one acromegalic patient. The data suggest that measurements of urinary GH may be a useful, simple, and noninvasive screening test for identifying patients with GH deficiency or excess.

Enhanced linear growth responses in hypopituitary dwarfs treated with growth hormone plus androgen versus growth hormone alone.

Extract: Twelve hypopituitary patients ranging in age from 5 8/12 to 15 7/12 years were treated for 12 months with a standardized dose of human growth hormone (HGH), 0.1 or 0.05 U/kg three times weekly). From the 7th to 12th month inclusive, fluoxymesterone, 2.5 mg/m2/24 hr per os was given in combination with the growth hormone. From the 12th to the 18th month, no therapy was given. Heights and weights were recorded every 1 or 2 months. Bone age films were assessed at the onset and again in the 6th, 12th, and 18th month of the study.In the first 6 months of HGH therapy, the mean growth rate (centimeters per year ± SD) was 9.4 ± 2.3. During combined treatment with HGH and fluoxymesterone, the mean growth rate of 13.4 ± 3 was significantly greater (P < 0.001) than on HGH alone. Post-treatment mean growth rate from the 13th through 18th month, inclusive, was 2.7 ± 1.2. Weight gain (kilograms per year ± SD) during combined treatment (13 ± 7) was significantly greater (P < 0.001) than during HGH administration (3.4 ± 2.4). Mean advancement in bone maturation (months ± SD) during HGH (12 ± 7.7) was not significantly different from the mean gain in bone age during combined treatment (12 ± 12). In the final 6 months without any therapy, the mean gain in bone age was 8.8 ± 6.1. In the 18 months of study, the mean increase in bone age was 33 months, and the mean gain in height age (HA) was 23 months.Although final evaluation of this treatment program depends upon a longer period of observation, the immediate assessment suggests that the significant improvements in height, weight, and physical appearance were sufficient to compensate for the gains in bone maturation, especially since the patients who entered the study had markedly retarded bone ages.Speculation: HGH and androgens interact synergistically. Androgens stimulate HGH secretion in intact animals. In the hypopituitary state, androgens require the addition of HGH for optimal promotion of optimal growth and secondary sexual development.

PSYCHOSEXUAL BEHAVIOR IN HYPOPITUITARY MEN: A CONTROLLED COMPARISON OF GONADOTROPIN AND TESTOSTERONE REPLACEMENT

Nine gonadotropin-deficient hypopituitary men were cycled through periods of treatment with testosterone (T), gonadotropin (Gn), and placebo (Pl) using a blind cross-over design. Self-reports of sexual behavior, recordings of nocturnal penile tumescence (NPT), and sex steroid levels were obtained during each treatment period. Subjects had significantly higher plasma T during the T and Gn treatments than during the control periods. Similarly, self-reported frequency of ejaculation and ratings of libido as well as duration measures of NPT were significantly higher on T and Gn. Two thirds of the sample had no sociosexual experience. Behavioral differences between the T and Gn periods were minimal. These data support the hypothesis that Gn and T are equally effective in stimulating specific aspects of male psychosexual behavior.

Human Dicentric Y Chromosomes: Case Report and Review of the Literature

A phenotypic female with histological evidence of mixed gonadal dysgenesis, and 45,X/46,X,dic(Yq) mosaicism is described. A review of the literature yielded 15 additional cases of dicentric Y chromosomes. Among the cases, a wide range of variation in phenotype, external genitalia, histology, and chromosomal findings was observed. Factors possibly contributing to such variability are discussed and include: the exact site of breakage and exchange in the Y chromosome; the timing of dicentric formation (meiotic vs mitotic); the occurrence of non-disjunction; and the presence or absence of a Y chromosome in cells of the gonadal anlage during a critical ontogenic period.

Posthypoglycemic hyperglycemia in diabetic children.

Posthypoglycemic hyperglycemia was suspected in eight diabetic children who had excessive glycosuria while taking large doses of insulin. The cases of two brothers with diabetes since infancy are reported as examples. Rapid changes in levels of blood glucose with episodes of hypoglycemia were suspected; therefore glucose in blood was measured every half hour for 48 hours while the patients received their customary insulin dosage and diet. Urine was collected in two-hourly portions for measurements of glucose and tests for ketones. Hypoglycemic episodes were documented repeatedly. They lasted between one and 22 hours, occurred at varying times, and were usually followed by abrupt rises of blood sugar; blood sugar often rose or fell by 200 to 300 mg. per 100 ml. within two to four hours. Hyperglycemic phases lasted from several hours to several days. Conventional spot tests of urine and “fasting” or “postprandial” blood sugar values often failed to detect the hypoglycemia.