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Biomedical subjects

A W Root

Publications and source records attributed to A W Root.

At least 19 recordsLinked to original sources
PubMed1991

Homozygosity for a dominant negative thyroid hormone receptor gene responsible for generalized resistance to thyroid hormone.

Generalized resistance to thyroid hormones (GRTH) commonly results from mutations in the T3-binding domain of the c-erbA beta thyroid hormone receptor gene. We have reported on a novel deletion mutation in c-erbA beta in a kindred, S, with GRTH. One patient from this kindred was the product of a consanguineous union from two affected members and was homozygous for the beta-receptor defect. This patient at 3.5 weeks of age had unprecedented elevations of TSH, free T4, and free T3 (TSH, 389 mU/L; free T4, 330.8 pmol/L; free T3, 82,719 fmol/L). He displayed a complex mixture of tissue-specific hyperthyroidism and hypothyroidism. He had delayed growth (height age, 1 3/12 yr at chronological age 2 9/12 yr) and skeletal maturation (bone age, 4 months), and developmental delay (developmental age, 8 months), but he was quite tachycardic. The homozygous patient of kindred S is markedly different from a recently reported patient with no c-erbA beta-receptor. This difference indicates that a dominant negative form of c-erbA beta in man can inhibit at least some thyroid hormone action mediated by the c-erbA alpha-receptors.

Adolescent↗
PubMed1991

The Klinefelter syndrome of testicular dysgenesis.

Klinefelter syndrome of testicular dysgenesis is the most common form of male hypogonadism. It may be suspected and identified by specific physical signs in infants, children, and adolescents as well as in adults. This review discusses the genetics, clinical manifestations, complications, and treatment of Klinefelter syndrome and its variants.

Humans↗
PubMed1990

Linear growth response to exogenous growth hormone in children with short stature.

Response to growth hormone (GH) therapy was evaluated in 38 short children (28 males and 10 females; less than 1% in height for chronologic age [CA]) who were clinically categorized into three groups based on their endogenous mean 24-hour GH concentration (mean 24-hour GH) and peak GH response to two or more provocative agents (peak GH). All patients were treated with biosynthetic somatropin (human growth hormone) (0.15 to 0.30 mg/kg per week) injected subcutaneously three to seven times per week for a mean duration of 12.5 months. Group 1 consisted of 17 subjects (CA, 12.5 +/- 2.9 years [mean +/- SD]; bone age, 9.4 +/- 2.9 years; height velocity [HV], 3.4 +/- 1.8 cm/y; peak GH, 5.8 +/- 2.6 micrograms/L; mean 24-hour GH, 1.7 +/- 0.6 micrograms/L; and insulinlike growth factor-I, 0.40 +/- 0.24 U/mL. Group 2 consisted of 10 subjects (CA, 11.7 +/- 2.7 years; bone age, 9.2 +/- 3.0 years; HV, 3.4 +/- 1.6 cm/y; peak GH, 16.4 +/- 5.2 micrograms/L; mean 24-hour GH, 1.7 +/- 0.5 micrograms/L; and insulinlike growth factor-I, 0.49 +/- 0.27 U/mL. Group 3 consisted of 11 subjects (CA, 12.7 +/- 2.2 years; bone age, 10.2 +/- 2.4 years; HV, 3.5 +/- 1.5 cm/y; peak GH, 22.5 +/- 8.6 micrograms/L; mean 24-hour GH, 3.8 +/- 1.1 micrograms/L; and insulinlike growth factor-I, 1.07 +/- 0.69 U/mL. Following administration of somatropin, an increase (delta) in HV of 2.0 cm/y or greater occurred in 94% (16/17) of the group I subjects (delta HV of 5.1 +/- 2.6 cm/y), in 90% (9/10) of the group 2 subjects (delta HV of 4.3 +/- 2.2 cm/y), and in 73% (8/11) of group 3 subjects (delta HV of 3.7 +/- 2.3 cm/y). However, regardless of provoked and/or endogenous GH secretory dynamics, 88% of the children whose pretreatment HV was 2.0 cm/y or less, 94% whose pretreatment HV was between 2.0 and 4.0 cm/y, and 79% whose pretreatment HV was greater than 4.0 cm/y increased their HVs to 2.0 cm/y or greater while they were receiving somatropin. Significant negative correlations were observed between delta HV and pretreatment HV (r = -.67), delta HV and GH concentration expressed as a 24-hour area under the curve (r = -.33), and delta HV and peak GH (r = -.34).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1989

Subhypothalamic high-intensity signals identified by magnetic resonance imaging in children with idiopathic anterior hypopituitarism. Evidence suggestive of an 'ectopic' posterior pituitary gland.

Magnetic resonance imaging in two children with idiopathic hypopituitarism demonstrated a signal of high intensity near the optic tract that was consistent with the signal produced by posterior pituitary tissue. Patient 1 was a 15-year-old girl with panhypopituitarism but intact posterior pituitary function. Computed tomography disclosed widening of the superior aspect of the pituitary stalk and a partially empty sella. Magnetic resonance imaging disclosed a 3-mm high-intensity signal abutting the optic tract in the midline just above the sella. The pituitary stalk was not clearly defined, the pituitary gland was small, and the sella was filled with cerebrospinal fluid. Patient 2 was a 12-year-old boy with isolated deficiency of growth hormone secretion. Findings from magnetic resonance imaging and computed tomography were similar to those in patient 1. These data suggest that the high-intensity magnetic resonance imaging findings represent a displaced or "ectopic" posterior pituitary gland, and that the hypopituitary state is due to an insult to the pituitary stalk.

Adolescent↗
PubMed1989

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)

Adolescent↗
PubMed1989

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.

Animals↗
PubMed1988

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.

Antibodies↗
PubMed1986

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.

Adolescent↗
PubMed1979

Changes in 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D during pregnancy.

Serum concentrations of 25-hydroxyvitamin D (25OHD) and 24,25-dihydroxyvitamin D (24,25(OH)2D) were measured in a cross-sectional study of 94 normal pregnant women at various stages of gestation in order to assess the hormonal regulation of calcium homeostasis during gestation. The 40 week gestational period was divided into four 10 weeks quarters. 25OHD concentration were significantly below control levels (32.2 +/- 3.1 (S.E.) ng/ml) by the second quarter of pregnancy and were even lower at term. Serum levels of 24,25(OH)2D did not decrease until the fourth quarter, when the mean concentration (0.8 +/- 0.1 ng/ml) was approximately one half the control values (1.5 +/- 0.3, p less than 0.025). These data suggest that the metabolic pathways of vitamin D are altered during gestation, perhaps in response to increasing mother-to-fetus transport of calcium. There is decreased 24-hydroxylation and, in view of the lowered 25OHD levels, possibly increased production of 1,25-hydroxyvitamin D (1,25(OH)2D).

Chorionic Gonadotropin↗
PubMed1979

Serum concentrations of 24,25(OH)2D in uremic children: a reflection of renal function.

The mean serum concentration of 24,25(OH)2D determined by competitive protein-binding radioassay was significantly lower in ten uremic children maintained on hemodialysis (0.82 +/- 0.43[SD] ng/ml) than in ten patients with impaired renal function not requiring hemodialysis (1.30 +/- 0.54 ng/ml, P less than 0.05), or in 12 normal children (2.98 +/- 1.57 ng/ml, P less than 0.01). The serum levels of 250HD were similar in all groups. There were significant (P less than 0.01) positive correlations between the serum concentration of 24,25(OH)2D or the ratio 24,25(OH)2D/25OHD and the creatinine clearance. The serum concentration of 24,25(OH)2D was significantly decreased also in six anephric adults relative to normal adult values. The data indicate that production of 24,25(OH)2D is impaired in subjects with compromised renal function. Inasmuch as the major active metabolite of Vitamin D, i.e., 1,25(OH)2D, is requried for renal synthesis of 24,25(OH)2D measurement of the latter metabolite may provide a convenient method for assessment of renal vitamin D metabolism. The role of this metabolite in the pathogenesis of renal osteodystrophy remains speculative.

Child↗