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Biomedical subjects

R M Blizzard

Publications and source records attributed to R M Blizzard.

At least 73 records · Page 4Linked to original sources
PubMed1982

Organ-specific autoantibodies in children with common endocrine diseases.

Sera from 438 children were examined for autoantibodies to thyroid microsomes, thyroglobulin, pancreatic islet cells, gastric parietal cells, and adrenocortical cells by indirect hemagglutination and immunofluorescence techniques. A modification of the indirect hemagglutination technique allowed specific detection of low titers of antithyroidal antibodies. The subjects included a control group (117) with no known autoimmune disease, and children with disorders of the thyroid (88), insulin-dependent diabetes mellitus (201), Turner's Syndrome (24), and Addison disease (8). A subject's age at the time of disease onset and the race and sex were correlated with the prevalence of autoantibodies. The coincidence of autoantibodies to components of the thyroid with autoantibodies to gastric parietal cells was increased in children with disorders of the thyroid (94%, 18/19) over that observed in diabetes (29%, 4/14), Turner syndrome (0%), or Addison disease (0%), perhaps indicating different genetic propensities for the development of parietal cell antibodies in these groups. Islet cell antibodies were not found in subjects with Turner syndrome, nor were they more prevalent in white or black subjects with diabetes. The incidence of organ-specific autoantibodies in individuals without overt clinical disease may reflect an altered immunologic state that will lead eventually to autoimmune disease. Islet cell antibodies decline in prevalence in diabetes, whereas thyroid antibodies in disorders of the thyroid do not; this may reflect differences in the pathogenesis of these common autoimmune endocrine disorders in children.

Addison Disease↗
PubMed1981

Qualitative abnormalities in insulin binding in a patient with extreme insulin resistance: decreased sensitivity to alterations in temperature and pH.

Cultured lymphocytes transformed by Epstein--Barr virus were employed to study insulin receptors from a patient with extreme insulin resistance associated with the syndrome of leprechaunism. With cultured lymphocytes from normal subjects, insulin binding to its receptor is exquisitely sensitive to changes in temperature and pH. In cells from normal subjects, insulin binding was increased by approximately 250% as the temperature was decreased from 37 degrees C to 12 degrees C. In contrast, with cells from the leprechaun, insulin binding was only approximately 30% higher at 12 degrees C than at 37 degrees C. Similarly, insulin binding to cells from the leprechaun was markedly less sensitive to changes in pH, as compared to cells from normal subjects. Binding studies suggested that the number of insulin receptors per cell was within the normal range in this patient. Despite the unusual characteristics of insulin binding in cells from this insulin-resistant patient, the receptors were typical in at least two respects: (i) binding was inhibited normally by antibodies to the receptor; and (ii) the specificity for insulin analogs was normal (chicken insulin greater than porcine insulin much greater than guinea pig insulin greater than porcine proinsulin). This patient has an inborn error affecting insulin receptor function. The receptor's binding function was abnormal in having decreased sensitivity to alterations in temperature and pH. However, the level of insulin binding to cells from the leprechaun was within normal limits. Consequently, the hormonal resistance probably results from a decreased ability of the receptor to couple insulin binding to insulin action.

Adult↗
PubMed1981

Two types of autoimmune Addison's disease associated with different polyglandular autoimmune (PGA) syndromes.

A review of 295 patients with autoimmune Addison's disease which occurred as part of a polyglandular autoimmune syndrome is presented. Information of 41 cases was obtained from our clinics and from the examination of medical records, while 254 cases were culled from the literature. We report that autoimmune Addison's disease in association with other autoimmune diseases occurs in at least two distinct types. Addison's disease occurring in Type I polyglandular autoimmune disease (PGA) is associated with chronic mucocutaneous candidiasis and/or acquired hypoparathyroidism. The age of onset is predominately in childhood or in the early adult years. Type I PGA syndrome is also frequently associated with chronic active hepatitis, malabsorption, juvenile onset pernicious anemia, alopecia and primary hypogonadism. Insulin requiring diabetes and/or autoimmune thyroid disease are infrequent. In contrast, Addison's disease in Type II PGA is associated with insulin requiring diabetes and/or autoimmune thyroid disease(s). Although the age of onset of Addison's disease in Type II PGA syndrome is not confined to any age group or any specific sex, it occurs predominately in the middle years of life in females. The associated autoimmune diseases found in Type I disease, such as chronic active hepatitis, etc. (see table II) are rare in Type II PGA disease except for a low frequency of gonadal failure. We provide evidence to support the concept that the Addison's diseases in Type I and II PGA syndromes have different genetic bases, as related to HLA haplotypes, and possibly have different underlying pathogeneses.

Addison Disease↗
PubMed1980

Micropenis. I. Criteria, etiologies and classification.

A micropenis is an abnormally small penis with a normal configuration. This finding constitues a sign not a diagnosis. The etiologies may be classified as hypogonadotropic hypogonadism, primary hypogonadism, androgen insensitivity, or idiopathic; among 45 patients, the respective percentages in these categories were 31, 24, 2 and 7% with 36% as yet undiagnosed. Various clinical syndromes may include a micropenis and can be classified in one of the etiologic categories. This paper provides the criteria for determining the presence of a micropenis. A phallic length which is 2.5 or more standard deviations below the mean should be considered as abnormal; for an infant of 0 to 5 months of age, the lower limit is 1.9 cm. The technique of penile measurement, determination of etiology, guidelines for sex of rearing and psychologic, surgical and medical management are discussed.

Counseling↗
PubMed1979

Thyroid-stimulating hormone and prolactin responses to thyrotropin-releasing hormone during infusion of epinephrine and propranolol in man.

Male volunteers were administered 100 microgram thyrotropin-releasing hormone (TRH) intravenously during control (saline) and drug (epinephrine-propranolol) infusions. There were no differences in the thyroid-stimulating hormone (TSH) or prolactin responses to TRH during the epinephrine-propranolol infusion periods. There were no significant differences in growth hormone (GH) responses to epinephrine-propranolol infusions. Epinephrine-propranolol had no detectable effect on basal TSH, prolactin and GH concentrations. We conclude that the alpha-adrenergic system does not play any role at the pituitary level in modulating the effect of TRH-stimulated TSH or prolactin secretion in male volunteers.

Adult↗
PubMed1978

Congenital lipodystrophy: An endocrine study in three siblings. I. Disorders of carbohydrate metabolism.

Three siblings with congenital lipodystrophy were studied extensively for endocrine abnormalities. A severe disturbance in carbohydrate metabolism was observed. Plasma concentrations of glucagon and insulin were markedly elevated both in the basal state and in response to provocative stimuli. In addition, marked resistance to exogenous insulin and a diabetic oral glucose tolerance test were demonstrated. Lipid metabolism, GH, and ACTH secretion were normal...

Adolescent↗
PubMed1977

Treatment of congenital virilizing adrenal hyperplasia patients with single and multiple daily doses of prednisone.

Six patients with congenital virilizing adrenal hyperplasia were evaluated on single- and multiple-dose prednisone schedules. Each of the treatment periods was for one month. Patients were evaluated by 24-hour urinary excretion of 17-ketosteroids and pregnanetriol, as well as 0900 plasma concentrations of 17-hydroxyprogesterone, progesterone, and testosterone. By the criteria of urinary excretion of KS and PNT appropriate for chronologic age, three of the six patients were adequately controlled on prednisone given once a day. Prednisone administered twice daily at 12-hourly intervals either in equally divided doses or with a larger dose in the evening, however, resulted in adequate suppression in all patients. Because of the marked diurnal variation of plasma 17-OHP, the time of day that the sample is drawn is critical. Afternoon samples are often misleadingly low. Plasma 17-OHP concentration may reflect escape from therapeutic control sooner than urinary KS and PNT excretion. There was no correlation between 17-OHP and P values. Plasma concentration of T was not a reliable indicator of good control, since T values were often at prepubertal levels when urinary KS and PNT were elevated.

17-Ketosteroids↗
PubMed1977

Glucocorticoid treatment of girls with congenital adrenal hyperplasia: effects on height, sexual maturation, and fertility.

Ninety-eight females with congenital adrenal hyperplasia due to a defect in either the 21-hydroxylase or the 11 beta-hydroxylase enzyme were evaluated to determine the effects of glucocorticoid treatment on growth, pubertal development, and fertility. When treatment was begun prior to one year of age, mean final height was 157.4 +/- 7.3 com, well within the normal adult female range, and significantly (p less than 0.001) greater than the mean final height of 150.9 +/- 4.3 cm found in untreated patients. The mean age of menarche in patients treated prior to the age of six years was 13.8 +/- 3.7 years which is significantly (p less than 0.01) delayed compared to that in the normal population of the United States. However, 92% of patients with menstrual delay had inadequate suppression of adrenal androgens and urinary excretion of 17 ketosteroids larger than 7.0 mg/24hours. The increased production of adrenal androgens was the result of poor compliance or an insufficient prescribed dose of glucocorticoids. The fertility rate in patients first treated between six and 20 years of age was 64%. The excretion of urinary 17 KS at the time of pregnancy was 2.5 to 5.3 mg/24 hours. All of the patients who delivered term infants required delivery by cesarean section because of cephalopelvic disproportion. The major problems encountered in the management of adolescent patients were patient noncompliance and physician failure to increase the glucocorticoid dose as the patient's body size increased.

17-Ketosteroids↗
PubMed1977

Antithyroid drug therapy for toxic diffuse goiter (Graves disease): thirty years experience in children and adolescents.

Since 1946 104 children and adolescents with toxic diffuse goiter have been treated. Sixty-seven were treated with a thioamide for more than 12 months. Remission occurred in 61%. Twenty-five patients had a 12-hour perchlorate discharge test to determine the least frequent dose schedule required for disease control: 68% could be controlled on a single daily dose and an additional 25% on an every 12-hour schedule. A one-hour radioiodine uptake on combined therapy and change in thyroid gland size during treatment were found to be highly correlated with the presence of a spontaneous remission. Thirty-six patients have been treated by subtotal thyroidectomy. To date 65% have developed permanent hypothyroidism. In the author's opinion, thoamides are the treatment of choice for the majority of children and adolescents.

Adolescent↗
PubMed1977

Effect of prolactin on adrenocortical and gonadal function in normal men.

Dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), androstenedione (A), testosterone (T), estrone (E1), estradiol (E2) and gonadotropins were measured in 3 normal adult men before and after administration of 50 mg ovine prolactin for 5 days. No significant change as a result of ovine prolactin administration was observed in any of the parameters examined.

Adrenal Cortex Hormones↗
PubMed1977

Pubertal progression in the presence of elevated serum gonadotropins in girls with multiple endocrine deficiencies.

Pubertal progression in the presence of abnormally elevated serum gonadotropins was followed over several years in two girls with multiple endocrine deficiencies and mucocutaneous candidiasis. Both had hypoparathyroidism and one had adrenal failure as well. A serum level of progesterone (8 ng/ml) consistent with ovulation was documented in the one girl who had regular monthly menses. High serum levels of FSH (30--60 mIU/ml) at times when serum estradiol was in the normal pubertal range (100--200 pg/ml) may indicate partial ovarian end-organ resistance or failure. Since premature menopause is associated with this syndrome, we postulate that we are observing puberty in girls whose ovaries are in the early stages of a destructive process which may eventually result in irreversible ovarian failure. A possible explanation could be the existence of increased resistance to gonadotropins at the ovarian level because of gonadotropin receptor antibodies or an inherent receptor defect.

Adolescent↗
PubMed1976

Metabolic and hormonal responses to a protein-glucose meal in normal infants and in marasmus and marasmic kwashiorkor.

Blood sugar and plasma free fatty acids (FFA), immunoreactive insulin (IRI), and growth hormone (GH) responses to a protein-glucose meal were determined in normal infants and those with marasmus and marasmic kwashiorkor. Among the normal subjects, fasting blood sugar (BS), peak BS and IRI, and the IRI/BS ratio tended to decrease as age increased. Peak IRI was at least 13muU/ml above fasting in 21 of 24 infants. Fasting GH levels were high 38.5 +/- 13.6 (SD) and 26.3 +/- 14.0 ng/ml, in the two youngest groups (under 1 year) and were comparable with those of the late newborn period. They were slightly lower, 20.8 +/- 22.1, in those 12.5-18.5 months of age. Suppressions of FFA and subsequent rebounds were in close temporal relation to BS and IRI peaks and lows, but not the GH levels. GH was promptly suppressed by the meal, and in most infants secondary elevations were seen. Untreated marasmic infants had normal or low BS, correspondingly normal or low IRI, markedly elevated FFA (1,821 +/- 588 muEq/liter), and GH levels comparable with those of the control subjects. There was some delay in BS elevation and disappearance and poor insulin release after the meal, with only two of nine having elevations of at least 13 muU /ml The BS elevations and IRI responses, however, were adequate to block FFA release. GH levels were poorly suppressed by the meal but some infants had further elevations, possibly in response to protein. After partial rehabilitation, fasting BS and FFA and BS elevations after the meal were normal. A slight improvement in insulin release was apparent. Fasting GH levels and responses to the meal were normal. Fasting, minimally treated children with marasmic kwashiorkor (MK) had normal or low BS, normal or low IRI, normal FFA, and probably normal GH levels. There was considerable delay in BS elevation, moderately delayed glucose disappearance, and very poor or unmeasurable insulin release after the test meal; FFA and GH were poorly suppressed. After partial rehabilitation, fasting BS was normal, FFA levels were (630 +/- 163 muEq/l), IRI was still low, BS elevations and disappearance improved. IRI responses modestly improved, and GH responses were normal.

Age Factors↗
PubMed1976

Integrated concentrations of luteinizing hormone and puberty.

Integrated serum concentrations of luteinizing hormone have been compared among 30-minute collections from 10 boys (6-18 years old) and 5 girls (5-11 years old). This study suggests that perpubertal as well as pubertal boys have greater mean integrated concentrations of LH during sleep than during waking. One of two pubertal girls had greater concentrations of LH during sleep, while three prepubertal girls did not.

Adolescent↗
PubMed1976

A case of male pseudohermaphroditism associated with elevated LH, normal FSH and low testosterone possibly due to the secretion of an abnormal LH molecule.

A 27 year old female is described who had 46,XY chromosome complement, ambiguous external genitalia with elevated LH, slightly above normal FSH and low testosterone. Her plasma testosterone level increased 15-20 fold after HCG stimulation (5000 IU X 3). then returned to prestimulation level 3 months later. This was possibly due to the secretion of an abnormal LH molecule which is immunoreactive but biologically inactive in the human.

Adult↗