Biomedical subjects
A W Root
Publications and source records attributed to A W Root.
Hypercalcemia associated with normal 1,25-dihydroxyvitamin D concentrations in a neonate with factor IX deficiency.
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Pooled prolactin measurements in the evaluation of short children.
PRL secretion was determined in 63 children undergoing evaluation of GH status. Children were assigned to 1 of 3 groups based on GH studies: group 1, those with abnormal GH responses to provocative testing (n = 23); group 2, children with normal GH responses to provocative testing and mean 24-h GH concentrations below 2.5 micrograms/L (n = 14); or group 3, those with normal stimulated GH secretion and mean 24-h GH concentrations of 2.5 micrograms/L or more (n = 26). Serum PRL concentrations were measured in daytime (0800-1600 h), nighttime (2200-0600 h), and 24-h pools of serum specimens obtained every 20 min over a 24-h period. Mean (+/- SD) daytime (17.5 +/- 14.3 micrograms/L) and 24-h (19.2 +/- 13.0 micrograms/L) pool PRL concentrations were significantly higher in group 1 than in group 3 (daytime, 6.7 +/- 2.3; 24 h, 10.2 +/- 2.5 micrograms/L; P less than 0.01). Mean nighttime pool PRL concentrations did not differ among groups. Mean nighttime pool PRL values were significantly higher (P less than 0.01) than daytime pool values in group 3 (nighttime pool, 13.6 +/- 3.6 micrograms/L; night to day ratio, 2.2 +/- 1.0) and group 2 (16.8 +/- 9.0 micrograms/L; night to day ratio, 2.5 +/- 1.5), but not within group 1 (21.4 +/- 13.5 micrograms/L; night to day ratio, 1.4 +/- 0.5). The mean peak and increment in PRL concentrations after an iv bolus of insulin-TSH-LHRH were not different among groups. The mean decrement in serum PRL level after L-dopa ingestion was greater in group 1 than in group 3 (P less than 0.05). Two children in group 2 and 10 in group 1 had significantly elevated daytime pool PRL concentrations (greater than 11.3 micrograms/L; 2 SD above the mean value for group 3). Two additional children in group 2 and 2 in group 1 had elevated 24-h (greater than 15.2 micrograms/L) pool PRL concentrations. One child in group 2 and 3 in group 1 had low 24-h PRL concentrations (less than 5.2 micrograms/L; less than 2 SD below the mean of group 3). Fourteen of 20 children with elevated daytime and/or 24-h pool PRL levels or low 24-h pool PRL values had structural or radiation-associated insults to the hypothalamic-pituitary axis evident in the history or with brain-imaging techniques; 1 had microphallus with panhypopituitarism and 5 children had no structural abnormalities.(ABSTRACT TRUNCATED AT 400 WORDS)
Neurophysiological regulation of the secretion of growth hormone.
The regulation of GH secretion involves the harmonious integration of factors acting at the hypothalamic and pituitary levels summating to produce the peripheral patterns of intermittent GH secretion observed in man and experimental animals under physiologic and experimental conditions. SRIH and GHRH act primarily at the pituitary to regulate the secretion of GH, while monaminergic, cholinergic and peptidergic neurotransmitters act centrally and/or at the pituitary level. In addition IGF-I, the anabolic effector of GH has inhibitory feedback effects at both the pituitary and hypothalamus. The control of GH secretion often differs between species and is dependent on the sex, nutritional state and physiologic condition being studied. In vivo and in vitro effects may differ as the complex, multilayered regulatory mechanisms of GH secretion in the intact subject override the direct effects of an individual controlling factor.
Usefulness of serum thyrotropin-binding inhibitory index measurements in infantile hypothyroidism. Relationship to serum thyrotropin concentrations.
Transplacental passage of thyrotropin (TSH)-binding inhibitory immunoglobulins may result in transient congenital hypothyroidism. We measured serum TSH-binding inhibitory index (TBII) in 11 infants with abnormal screening findings using a commercially available kit. Two of the infants, who were siblings, had markedly elevated TBII values (90% and 100%, respectively), as did their mother (89%, 100%), and had a clinical course consistent with transient antibody-mediated hypothyroidism. Four other infants had a borderline or mildly elevated TBII that was not present in maternal serum, suggesting that endogenous TSH was being measured in this assay. The TBII was measured in the sera of 18 additional children with primary hypothyroidism and in human TSH standards from 25 to 2000 mU/L. Increasing concentrations of TSH were associated with a linear increase in TBII. Measurement of TBII by this method may identify infants with transient antibody-mediated hypothyroidism, although simultaneous assessment of maternal serum is necessary.
Coronary artery disease in diabetic adolescents.
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Effect of estrogen on the growth hormone (GH) secretory response to GH-releasing factor in the castrate adult female rat in vivo.
Five groups (n = 11) of 250-g female rats were oophorectomized and immediately thereafter received daily sc injections of estradiol benzoate (EB; 0.05, 0.5, 5.0, and 50.0 micrograms) or vehicle for 28 days. A sixth group underwent sham operation and received injections of vehicle. Somatomedin-C (SmC) concentrations were determined before EB administration. After 4 weeks of EB treatment, the GH response to human GH-releasing factor (1-44) (GRF; 5 micrograms/kg, iv) was determined under pentobarbital anesthesia in seven animals from each group. Serum PRL, LH, and estradiol and plasma SmC concentrations were also measured. The GH secretory response to GRF (delta GH) was greatest in castrated animals receiving vehicle (P less than 0.05) and was significantly blunted in animals receiving 5.0 and 50.0 micrograms EB (P less than 0.05) compared to that in sham-operated animals. A significant negative correlation was observed between delta GH and serum PRL concentrations (r = -0.53; P less than 0.0001). SmC concentrations after treatment were significantly lower in animals receiving 5.0 and 50.0 micrograms EB (P less than 0.01), than in sham-operated animals and were elevated compared to those in sham-operated controls in the group receiving the lowest dose of EB (0.05 microgram; P less than 0.01). Posttreatment SmC levels correlated positively with delta GH (r = 0.58; P less than 0.001) and negatively with serum estradiol concentrations (r = -0.47; P less than 0.01). Pituitary glands from the remaining animals in each group (n = 4) were weighed and assayed for GH, PRL, and LH content. Pituitary PRL content increased with increasing doses of EB replacement and correlated strongly (r = 0.82; P less than 0.0001) with pituitary weight. In the castrated adult female rat, high doses of estrogen inhibited the GH secretory response to GRF in vivo and decreased SmC concentrations. Low dose estrogen increased SmC concentrations, although the GH secretary response to GRF in this group was similar to that in sham-operated rats. The latter observation suggests that the rise in SmC levels associated with low dose estrogen may not be mediated through a change in GH secretion.
Age-related differences in the growth hormone secretory response to hGHRH 1-44 in male rats from infancy through puberty. In vivo and in vitro studies.
The GH secretory response to varying doses (15, 30, 60 micrograms/kg) of sc administered hGHRH 1-44 (or normal saline) was measured in vivo in 10, 20, 30, 40, 50, 60 and 130 days old pentobarbital-anaesthetized, male rats. The 10-min GH level and delta GH were in general significantly greater in older rats (50, 60, 130 days old) than in younger rats (10, 20 days old) following all doses hGHRH. Ten-day-old animals had no significant GH response to any dose of hGHRH tested. delta GH correlated significantly with age (r = 0.36; P less than 0.0001) and Sm-C level (r = 0.29; P less than 0.01) but not with serum testosterone concentrations. Monolayer pituitary cell cultures were established in rats aged 10 to 130 days and were incubated with varying concentrations of hGHRH 1-44 (0.05, 0.5, 5.0, 50 nmol/l or incubation medium). Cultures from 10- and 20-day-old animals had a greater percentage increase over basal GH secretion than other groups at all concentrations of hGHRH tested (P less than 0.05). Age-related differences in the GH secretory response to hGHRH are present in male rats from 10 to 130 days. The in vitro results reported here suggest that the increase in magnitude and sensitivity of the GH response to hGHRH observed in pubertal animals in vivo under pentobarbital anaesthesia is likely due to influences above the level of the somatotrope receptor.
Isosexual precocity: current concepts and recent advances.
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Gonadotropin-independent isosexual precocity in a boy with tuberous sclerosis: effect of ketoconazole.
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Hypothalamic-pituitary dysfunction in primary empty sella syndrome in childhood.
In a series of 37 consecutive CT scans performed in children referred to our pediatric endocrine unit, an empty (eight) or partially empty (one) sella turcica was found in nine (24%) patients with short stature or delay in sexual maturation, precocious puberty, or hypoparathyroidism. The size and contour of the sella were abnormal in only three patients. Five of the nine children had evidence of decreased growth hormone secretion as determined by subnormal GH secretory responses to provocative tests (peak GH concentration less than 7 ng/ml) or assessment of endogenous 24-hour GH secretion (mean 24-hour GH concentration less than 3 ng/ml). Two children had multiple pituitary hormone deficiencies. Although primary empty sella syndrome was often associated with hypothalamic-pituitary dysfunction in this series, the prevalence of an empty sella in normal children is unknown. Further identification and evaluation of children with empty sella may provide new information regarding the cause of pituitary dysfunction in childhood.
Growth hormone (GH) provocative testing frequently does not reflect endogenous GH secretion.
GH secretion was studied in 73 children with classical GH deficiency or GH neurosecretory dysfunction (GHND), intrinsic short stature, or normal stature. The GH-deficient group was defined by a peak GH secretory response below 10 ng/ml to all provocative tests (arginine, L-dopa, insulin hypoglycemia, and clonidine). GHND was defined by a mean serum 24-h GH concentration below 3 ng/ml, with a normal response (greater than or equal to 10 ng/ml) to provocative testing. Twenty-one GH-deficient children, 21 children with GHND, and 18 short control children underwent provocative GH testing and a 24-h study with GH sampling every 20 min. A group of 13 normal stature control children also underwent 24-h GH sampling. The mean stimulated peak serum GH level [4.7 +/- 0.6 (+/- SEM) ng/ml] in the GH-deficient group was significantly below that in the GHND (19.5 +/- 1.7 ng/ml) and short control groups (24.0 +/- 3.5 ng/ml; P less than 0.01). The mean 24-h serum GH concentration was reduced in GH-deficient (1.5 +/- 0.2 ng/ml) and GHND (2.0 +/- 0.1 ng/ml) children compared to those in short (5.6 +/- 0.5 ng/ml) and normal stature (5.8 +/- 0.8 ng/ml) control children (P less than 0.01). Peak GH concentrations after provocative testing correlated poorly with 24-h mean concentrations in GH-deficient, GHND, and short control children (r = 0.38, 0.23, and 0.41, respectively; P = NS for all groups). Mean serum GH concentrations from blood sampling intervals of 12 h (day/night; 0800-2000/2000-0800 h, respectively) or even 6 h (day; 0900-1500 h) were statistically different in GHND or GH-deficient groups compared to those in control children; however, there was significantly more overlap for individual children using the 6- and 12-h daytime intervals than for the 24-h data. Plasma somatomedin-C/insulin-like growth factor I correlated with mean 24-h GH concentration endogenous secretion (r = 0.7; P less than 0.001). These data suggest that provocative GH testing frequently does not correlate with endogenous GH secretion.
Preservation of dopaminergic and alpha-adrenergic function in children with growth hormone neurosecretory dysfunction.
The integrity of dopaminergic and alpha-adrenergic neurotransmitter regulation of GH secretion was examined in children with decreased GH secretion. Children with GH neurosecretory dysfunction (GHND; n = 16) those with classical GH deficiency (n = 9), and short but otherwise normal children (n = 12) underwent 24 h GH studies (blood sampling every 20 min for 24 h) and provocative tests using arginine, insulin hypoglycemia, L-dopa (dopaminergic) and clonidine (alpha-adrenergic), and GH-releasing hormone (GHRH). GHND was defined as children with height in the first percentile or below, growth velocity of 4 cm/yr or less, low plasma somatomedin-C for age, delayed skeletal age by 2 or more yr, peak serum GH responses to any one (or more) provocative test of 10 ng/ml or more, and mean 24-h GH concentration below 3 ng/ml. GHND and GH-deficient children had reduced endogenous GH secretion, expressed as mean serum 24-h GH concentration [1.6 +/- 0.1 (+/- SEM) and 2.1 +/- 0.1 vs. 6.1 +/- 0.5 ng/ml (GH-deficient and GHND vs. normal, respectively); P less than 0.01]. the mean peak serum GH levels after arginine [8.2 +/- 2.0 vs. 20.8 +/- 6.6 ng/ml (GHND vs. normal); P less than 0.05] and insulin [9.3 +/- 1.0 vs. 16.2 +/- 1.7 ng/ml (GHND vs. normal); P less than 0.01) were lower in GHND children. The mean peak responses after L-dopa [13.4 +/- 3.4 vs. 14.6 +/- 4.7 ng/ml (GHND vs. normal); P = NS] and clonidine [19.0 +/- 2.2 vs. 23.3 +/- 3.8 ng/ml (GHND vs. normal); P = NS] were preserved in GHND children. In GH-deficient children, mean peak serum GH concentrations after all four provocative tests were low (arginine, 2.7 +/- 0.8; insulin, 2.6 +/- 0.8; L-dopa, 3.0 +/- 0.9; clonidine, 3.4 +/- 1.0 ng/ml; all P less than 0.01 vs. normal). The mean peak serum GH concentration after GHRH was blunted in GH-deficient children (9.1 +/- 1.7 ng/ml) compared to those in GHND (32.9 +/- 8.5 ng/ml) and normal (43.2 +/- 6.4 ng/ml) children (P less than 0.01). The area under the GH curve after GHRH stimulation was greater for normal than GHND children (P less than 0.05). These data demonstrate preservation of dopaminergic and alpha-adrenergic neurotransmitter pathways in GHND children. They further suggest a defect in the release of pituitary GH secondary to an abnormality in alternative neurotransmitter pathways resulting in decreased GHRH and/or increased somatostatin secretion.
The interrelationships of thyroid and growth hormones: effect of growth hormone releasing hormone in hypo- and hyperthyroid male rats.
Growth hormone (GH) and the thyroid hormones interact in the hypothalamus, pituitary and peripheral tissues. Thyroid hormone exerts a permissive effect upon the anabolic and metabolic effects of GH, and increases pituitary synthesis of this protein hormone. GH depresses the secretion of thyrotropin and the thyroid hormones and increases the peripheral conversion of thyroxine to triiodothyronine. In the adult male rat experimental hypothyroidism produced by ingestion of propylthiouracil depresses the GH secretory response to GH-releasing hormone in vivo and in vitro, reflecting the lowered pituitary stores of GH in the hypothyroid state. Short term administration of large amounts of thyroxine with induction of the hyperthyroid state does not affect the in vivo GH secretory response to GH-releasing hormone in this animal.
Hypercalciuria, hyperphosphaturia, and growth retardation in children with diabetes mellitus.
The role of hypercalciuria and hyperphosphaturia in the growth retardation of children with diabetes mellitus was investigated in 157 children with diabetes whose mean height was less than that of 37 nondiabetic siblings of similar age (P less than .025). Hyperglycemia, hypercalciuria, and hyperphosphaturia were assessed coincident with the height measurement of each child in a cross-sectional survey. The distribution of height percentiles of the children with diabetes was skewed to the left with 61% at or below the 50th percentile. Eleven percent of the insulin-dependent children with diabetes mellitus were shorter than would be anticipated by a normal distribution of the 157 children. The duration of diabetes (hyperglycemia) had the greatest influence upon the children's height. Children with diabetes were shorter than the nondiabetic subjects by the fourth year of hyperglycemia, and this difference in height became statistically significant after 7 years or more of diabetes. The degree of hypercalciuria and hyperphosphaturia was more closely associated with reduced height in children with diabetes than was the degree of hyperglycemia, although the renal wastage of calcium and phosphorus seemed to be the result of glucosuria. Because hypercalciuria and hyperphosphaturia impair growth in nondiabetic children, they may also play an important role in the poor growth of children with diabetes mellitus.
Current status of neonatal screening for congenital hypothyroidism.
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Hypothyroidism blunts the growth hormone (GH) releasing effect of human pancreatic GH releasing factor in the adult male rat in vivo and in vitro.
The effect of the 44-amino-acid peptide human pancreatic GH releasing factor (hpGRF-44) upon the secretion of GH was studied in control and hypothyroid adult male rats. In animals rendered hypothyroid by ingestion of propylthiouracil (PTU), basal and hpGRF-44-stimulated secretion of GH was depressed in vivo. Administration of T4 together with PTU prevented the decline in basal and hpGRF-provoked GH secretion in vivo. HpGRF-44-stimulated release of rat GH was also impaired in vitro, an effect partially reversed by administration of low doses of T4 in vivo. The depressed in vitro secretion of GH could not be restored in hypothyroidism pituitaries by incubation of the glands with T3. Thus, hypothyroidism blunts hpGRF-44-stimulated secretion of GH in vivo and in vitro in the hypothyroid adult male rat.
Ectopic and entopic peptide hormone secreting neoplasms of childhood.
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