Robert M. Blizzard

Emotional deprivation and growth retardation simulating true idiopathic hypopituitarism

DURING the past six years we have observed and evaluated 13 children, most of whom initially were believed to have growth failure on the basis of idiopathic hypopituitarism. However, a number of unusual features were noted in the histories that suggested emotional disturbances in the children and abnormal home environments. These were not common to the histories of patients with idiopathic hypopituitarism. When these patients were placed in a convalescent hospital, they demonstrated remarkable growth acceleration without receiving growth hormone or other agents. Detailed studies were performed before and during the period of rapid growth. This paper presents the clinical .xa0.xa0.

Autoimmunity and ovarian failure.

Abstract The incidence of ovarian autoantibodies in 55 patients with various forms of complete and partial ovarian failure, including spontaneous premature menopause, gonadal agenesis, luteal phase defect, and various other forms of secondary amenorrhea was determined. In addition, antibodies against thyroglobulin and the cytoplasm of thyroid follicle cells, parietal cells, and adrenal cortical cells were investigated. Specificity was evaluated with the use of differential adsorption. Ovarian cytoplasmic antibodies were found in 8 patients, all in a group of 16 patients with premature menopause and associated immune disorders. Antiovarian antibodies against nuclei were demonstrated in a ninth patient, 1 of 11 with a luteal phase defect. These antinuclear antibodies were adsorbed out of the serum by extracts of all the tissues used. A high incidence of autoantibodies to other tissue antigens was found in patients with complete ovarian failure, even in the absence of associated overt immune disorders. A possible role of an as yet undefined generalized autoimmune diathesis is postulated as a potential factor in the development of at least some cases of premature menopause.

Growth responses to human growth hormone in patients with intrauterine growth retardation

Twelve patients with low birth weights and/or birth lengths for gestational age were treated with one or more daily doses of human growth hormone (hGH) ranging from 1.0 to 10.2 mg. per square meter of body surface area per day for five to 18 months. Significant delay in skeletal maturation was found in all but one patient. Of the eight patients aged seven years or younger at the time of treatment, the growth rates of five (62.5 per cent) during treatment with hGH were at least twice their pretreatment growth rate; in six (75 per cent) the pretreatment growth rates were exceeded by 3.5 cm. or more per year. Among those patients who received their initial course of hGH therapy in a dose of 2 mg. or more per square meter of body surface area per day, five of eight patients (62.5 per cent) more than doubled their pretreatment growth rates during hGH therapy; seven of eight (88 per cent) increased their pretreatment growth rates by more than 3.5 cm. per year during hGH therapy. In sufficient dose hGH is an effective therapeutic agent in some young patients who have had intrauterine growth retardation.

Serum luteinizing hormone by radioimmunoassay in normal children

Using a sensitive radioimmunoassay, serum luteinizing hormone (LH) levels have been determined in 249 normal children (5 to 18 years of age), 30 normal adult males, 2 normal adult females throughout a menstrual cycle, and 19 patients with pituitary deficiency. The mean levels in prepubertal boys and girls were comparable (3.4 and 2.8 m.I.U. per milliliter, respectively) and began increasing at the same age (10 to 12 years) in both sexes. An increase in serum LH was noted in the males but not in the females before beginning sexual maturation was apparent clinically. In adult males and females, the mean serum LH levels (10.9 and 10.2 m.I.U. per milliliter, respectively) were approximately 3.5 times prepubertal values. Patients with pituitary deficiency had a very low mean level (1.7 m.I.U. per mililiter), but some immunochemical LH was found in all sera. In males, the urinary excretion of 17-ketosteroids had a statistically significant correlation (correlation coefficient=0.73) with the serum LH leterminations.

Measurement of immunologically reactive follicle stimulating hormone in serum of normal male children and adults

Abstract Using a radio immunoassay serum, FSH concentrations have been determined in 97 normal male children between the ages of 5 and 18 years, in 30 normal adult males between 25 and 45 years, and in 9 adult patients who were sexually infantile, presumably because of deficient gonadotrop in secretion by the pituitary. FSH reactive material was found in all serums. In normal children serum FSH concentrations begin increasing shortly after 9.0 years of age from the low levels found in early childhood. By the age of 13 years the mean FSH determination was comparable to that of normal adults. When correlated with various stages of sexual development (1 through 5), the mean FSH concentrations found in the serums of individuals in stages 1, 2, and 3 differed significantly from each other. However, mean levels for the individuals in groups 3, 4, and 5 did not differ significantly. There was a low degree of correlation between serum FSH concentration and the excretion of urinary 17-ketosteroids. The values of immunologic FSH reported may have no specific correlation with biologically active FSH in serum, and all results are interpretable only in comparison of one group of values against another. The determination of absolute values of FSH in serum will be possible only when there is an adequately defined standard for serum and commonly available antigen and antiserum. Only then will it be possible to compare biologic and immunologically reactive FSH in sera.

Growth in patients with gonadal dysgenesis receiving fluoxymesterone

Patients with gonadal dysgenesis have been treated for 7 to 30 months with an anabolic agent, fluoxymesterone. Growth rates during the first year of treatment were significantly increased over growth rates prior to treatment. Heights of patients over 15 years of age and treated for more than 18 months were greater than heights achieved by an estrogen-treated group. Side effects were frequent, but not severe.

Sequential study of arginine monochloride and normal saline as stimuli to growth hormone release

Plasma growth hormone (GH), immunoreactive insulin (IRI), and glucose concentrate were evaluated in five normal adult females and five normal adult males following infusion of saline and 0.5 Gm./Kg. of arginine monochloride. All individuals responded to arginine infusion with an increase in the IRI concentrations. Plasma glucose usually, but not always, increased with arginine infusion. Four of the five females and two of the five males responded to the initial infusion of arginine with a significant increase in plasma GH concentration. Two of the three nonresponding males subsequently responded when infused with the same amount of arginine, even without estrogen administration. Saline infusion was not associated with an increase in GH, IRI, or glucose concentrations. It is concluded (1) that saline is not a stimulus to GH release, (2) that arginine consistently increases IRI concentration, (3) that plasma glucose levels usually, but not invariably, increase with arginine infusion and (4) that some males have a variable GH response to arginine, which is independent of estrogen replacement.