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Biomedical subjects

G B Cutler

Publications and source records attributed to G B Cutler.

At least 37 records · Page 2Linked to original sources
PubMed1998

Gonadotrophin and prolactin secretory dynamics in girls with normal puberty, idiopathic precocious puberty and precocious puberty due to hypothalamic hamartoma.

OBJECTIVE: This study was designed to test the hypothesis that hypothalamic hamartoma causes precocious puberty through a different neuroendocrine mechanism than that of normal puberty or of idiopathic precocious puberty. DESIGN AND PATIENTS: We compared the pattern of gonadotrophin secretion among 4 girls with precocious puberty due to hypothalamic hamartoma, 27 girls with idiopathic precocious puberty, and 14 girls with normal puberty. All subjects were breast stage 3 or 4. Blood samples were obtained every 20 min for 4 h during the day (1.000 hours to 1400 h) and night (22.00 hours to 0200 h). MEASUREMENTS: LH, FSH, and prolactin were measured in each blood sample. Girls also underwent LHRH-stimulation with measurement of LH and FSH before and after stimulation. RESULTS: There were no significant differences in mean LH level, LH peak amplitude, or LH or FSH peak frequency during either the day or the night among the three diagnostic groups. However, the mean +/- SD LHRH-stimulated peak LH levels were greater in girls with hypothalamic hamartoma than in girls with normal puberty or with idiopathic precocious puberty (194 +/- 142 vs 85 +/- 60 or 66 +/- 54 IU/l, respectively, P < 0.05). The LHRH-stimulated peak FSH level in girls with hypothalamic hamartoma exceeded the level for the normal pubertal girls (31 +/- 19 vs 17 +/- 7 IU/l, P < 0.05), but not the level for the girls with idiopathic precocious puberty (25 + 12 IU/l). The peak LH to peak FSH ratio in the girls with hypothalamic hamartoma exceeded the ratio for the girls with idiopathic precocious puberty (7.3 +/- 3.9 vs 2.6 +/- 3.0 IU/l, P < 0.05), but not the ratio for the normal pubertal girls (5.0 + 2.9). There were no significant differences in mean prolactin level, peak amplitude or frequency, or in the ratio of mean night to mean day prolactin, among the 3 diagnostic groups. CONCLUSIONS: We conclude that spontaneous gonadotrophin and prolactin secretion are similar among girls with hypothalamic hamartoma, idiopathic precocious puberty, or normal puberty. However, the increased LHRH-stimulated peak LH in the girls with hypothalamic hamartoma suggests subtle differences in neuroendocrine regulation that may underlie their more rapid pubertal maturation.

Adolescent↗
PubMed1998

Novel CYP11B1 mutations in congenital adrenal hyperplasia due to steroid 11 beta-hydroxylase deficiency.

The second most common cause of congenital adrenal hyperplasia is 11 beta-hydroxylase deficiency, an autosomal recessive disorder. We performed genetic analysis of CYP11B1, the gene encoding steroid 11 beta-hydroxylase, in three patients with classic 11 beta-hydroxylase deficiency. Herein we describe the first splice donor site mutation, a new nonsense mutation, and a new missense mutation in this disorder. An African-American patient was found to be a compound heterozygote for a codon 318 + 1G --> A substitution at the 5'-splice donor site of intron 5, in combination with Q356X, a nonsense mutation previously reported in an African-American patient. A Caucasian patient was found to be a compound heterozygote with a novel missense mutation, T318R, in combination with a previously reported 28-bp deletion in exon 2. A different mutation at codon 318 (T318M) has been described previously. A Caucasian patient was heterozygous for a novel nonsense mutation (Q19X) in exon 2. The second mutation was not identified in this patient. Multiple apparent polymorphisms were also observed. Two of these polymorphisms in CYP11B1 represent sequences from CYP11B2, suggesting that gene conversion may have occurred. In summary, we have identified three novel mutations and two previously reported mutations in CYP11B1 patients with 11 beta-hydroxylase deficiency. Our data suggest the presence of a mutational hot spot at codon 318 of CYP11B1, and the possibility of a founder effect in frequently identified mutations.

Adrenal Hyperplasia, Congenital↗
PubMed1998

A randomized, cross-over trial of once-daily versus twice-daily parathyroid hormone 1-34 in treatment of hypoparathyroidism.

Once-daily sc injection of PTH 1-34 can normalize mean serum and urine calcium levels in patients with hypoparathyroidism; however, once-daily PTH has diminishing effects on serum calcium after 12 h, such that serum calcium levels fall below the normal range in some patients. Once-daily PTH also causes a marked increase in bone turnover, with persistent increases in markers of bone formation and resorption. To test the hypothesis that a twice-daily PTH regimen can produce more physiological control than a once-daily regimen, we performed a randomized cross-over trial, lasting 28 weeks, in 17 adult subjects with hypoparathyroidism. Each 14-week study arm was divided into a 2-week inpatient dose-adjustment phase and a 12-week outpatient phase. The PTH dose (given sc once daily at 0900 h or twice daily with one dose at 0900 h and the other at 2100 h) was adjusted to maintain both serum and urine calcium within, or close to, the normal range. During the second half of the day (12-24 h), twice-daily PTH increased serum calcium and magnesium levels more effectively than once-daily PTH. In patients with calcium receptor mutations (CaR), once-daily PTH normalized urine calcium, provided that serum calcium was maintained at levels below normal range. However, twice-daily PTH treatment produced higher mean serum calcium in patients with CaR with no significant rise in urine calcium excretion, and with no significant differences in either serum or urine calcium levels between CaR and patients with acquired or idiopathic hypoparathyroidism. Thus, treatment with twice-daily PTH is the better regimen for patients with CaR to overcome their tendency to hypercalciuria while producing near-normal levels of serum calcium. The total daily PTH dose was markedly reduced with the twice-daily regimen (twice daily 46+/-52 vs. once daily 97+/-60 microg/day, P < 0.001). We conclude that a twice-daily PTH regimen provides effective treatment of hypoparathyroidism and reduces the variation in serum calcium levels at a lower total daily PTH dose.

Adult↗
PubMed1998

High fluid intake increases urine free cortisol excretion in normal subjects.

To test the hypothesis that increased fluid intake increases the urine free cortisol, we prescribed 5 liters of fluid intake per day or a normal fluid intake according to a randomized cross-over design in six normal volunteers. Each period lasted 5 days, with a 2-day washout period of normal fluid intake between the two periods. Urine free cortisol, 17-hydroxycorticosteroids, and creatinine were measured daily during each study period, and the average value over each 5-day period was calculated for each subject. High fluid intake caused a significant increase in the mean urine free cortisol [126 +/- 33 (SD) vs. 77 +/- 18 micrograms/day, P < 0.005]. The frequency of urine free cortisol results that exceeded the upper normal limit of 95 micrograms/day was also much higher during high fluid intake (23/30 vs. 6/30, P < 0.005). By contrast, urine 17-hydroxycorticosteroids (high fluid vs. normal fluid: 5.3 +/- 1.5 vs. 5.0 +/- 1.7 mg/day, respectively, P = not significant) and urine creatinine (1.51 +/- 0.48 vs. 1.45 +/- 0.37 g/day, P = not significant) did not differ between the two study periods. We conclude that high fluid intake (5 liters/day) increases free cortisol excretion without an increase in urine 17-hydroxycorticosteroids. Thus, mild to moderate increases in urine cortisol excretion may not indicate hypercortisolism in individuals who have a high fluid intake and urine volume.

17-Hydroxycorticosteroids↗
PubMed1998

The dexamethasone-suppressed corticotropin-releasing hormone stimulation test differentiates mild Cushing's disease from normal physiology.

The dexamethasone-suppressed CRH test (Dex-CRH test) differentiates patients with Cushing's syndrome (CS) from those with pseudo-Cushing states, who have decreased ACTH responses to CRH because of negative feedback exerted by chronic hypercortisolism. Normal subjects, however, have not been studied with the Dex-CRH test, raising concern that this test might not separate patients with CS from patients with normal adrenal function. To determine whether the criterion that separates CS from pseudo-Cushing states also would differentiate patients with Cushing's disease (CD) from individuals with eucortisolism, we studied 20 healthy volunteers during low-dose (2 mg/day) dexamethasone suppression, and then during the Dex-CRH test (CRH stimulation test performed 2 h after completion of low-dose dexamethasone suppression), and contrasted their results with those of 20 patients with surgically proven mild CD [urine free cortisol (UFC) < 1000 nmol/day). Basal UFC was significantly greater in patients with CD (P < 0.001) but within the normal range (55-250 nmol/day) in 4 patients. During low-dose dexamethasone suppression, a UFC less than 100 nmol/day (36 micrograms/day) was found in all but 1 volunteer subject, and a urine 17-hydroxycorticosteroid excretion less than 14.6 mumol/day (5.3 mg/day) was found in all but 2 subjects. During the Dex-CRH test, plasma cortisol less than 38 nmol/L was found in all 20 normal volunteers until 30 min after CRH administration. By contrast, the 15-min CRH-stimulated plasma cortisol exceeded 38 nmol/L in all patients with CD (P < 0.001). Plasma dexamethasone measured just before CRH administration was similar in normal volunteers (13.0 +/- 6.1 mumol/L) and patients with CD (16.4 +/- 6.4 mumol/L). We conclude that cortisol measurements obtained during the Dex-CRH test are suppressed in normal volunteers below those found in mild CD. These results suggest that the Dex-CRH test may be useful in the evaluation of CS in patients without significant hypercortisoluria. However, its value in patients with episodic hormonogenesis has not been tested.

17-Hydroxycorticosteroids↗
PubMed1998

A single midnight serum cortisol measurement distinguishes Cushing's syndrome from pseudo-Cushing states.

Cushing's syndrome (CS) may be difficult to distinguish from pseudo-Cushing states (PCS) based on physical findings or urinary glucocorticoid excretion. As the lack of diurnal variation in serum cortisol is characteristic of CS, we studied whether diurnal cortisol determinations could discriminate CS from PCS. Two hundred and sixty-three patients were evaluated: 240 had CS, and 23 had PCS. Urine was collected for 24 h for measurement of cortisol and 17-hydroxycorticosteroids (17OHCS). Blood was drawn at 2300, 2330, 0000, 0030, and 0100 h and at 0600, 0630, 0700, 0730, and 0800 h the next morning for serum cortisol determination. The main outcome measure was the sensitivity of these parameters for the diagnosis of CS at 100% specificity. A midnight cortisol value greater than 7.5 microg/dL correctly identified 225 of 234 patients with CS and all PCS patients. This sensitivity (96%) was superior to that obtained for any other measure, including urinary cortisol (45%), 17OHCS (22%), any other individual cortisol time point (10-92%), the morning (23%) or the evening (93%) cortisol mean, and the ratio (11%) of morning to evening values. We conclude that at 100% specificity, a single serum cortisol value above 7.5 microg/dL at midnight discriminates CS from PCS with higher sensitivity than 24-h urinary cortisol or 17OHCS, or other individual or combined measures of serum cortisol.

Adolescent↗
PubMed1998

Use of an ultrasensitive recombinant cell bioassay to determine estrogen levels in girls with precocious puberty treated with a luteinizing hormone-releasing hormone agonist.

Although treatment of girls with precocious puberty should ideally restore estradiol levels to the normal prepubertal range, treatment effectiveness has usually been monitored by gonadotropin levels because estradiol RIAs have lacked sufficient sensitivity to monitor treatment effectiveness. We hypothesized that a recently developed ultrasensitive recombinant cell bioassay for estradiol would have sufficient sensitivity to demonstrate a dose-dependent suppression of estradiol during LH-releasing hormone agonist treatment and to determine whether currently used doses are able to suppress estradiol levels to the normal prepubertal range. Twenty girls with central precocious puberty were assigned randomly to receive deslorelin for 9 months at a dose of 1, 2, or 4 micrograms/ kg.day. A significant dose-response relationship was observed, with mean +/- SD estradiol levels of 16.7 +/- 6.1, 7.9 +/- 1.6, and 6.5 +/- 0.7 pmol/L at the doses of 1, 2, and 4 micrograms/kg.day, respectively (P < 0.01). The highest dose suppressed estradiol levels to just above the 95% confidence limits for normal prepubertal girls (< 0.07-6.3 pmol/L). We conclude that the ultrasensitive bioassay for estradiol has sufficient sensitivity for monitoring the response to LH-releasing hormone agonist treatment of central precocious puberty. Additionally, the observation that the deslorelin dose of 4 micrograms/kg.day did not fully restore estradiol levels to the normal prepubertal range suggests that some girls with precocious puberty may require higher doses to receive the maximal benefit of treatment. We suggest that restoration of estradiol levels to the normal prepubertal range should be the ultimate biochemical measure of efficacy, as estradiol is the key hormone that accelerates growth rate, bone maturation rate, and breast development in girls with precocious puberty.

Biological Assay↗
PubMed1998

Effects of estrogen on nonverbal processing speed and motor function in girls with Turner's syndrome.

The Turner syndrome (TS) phenotype is characterized by a specific neurocognitive profile of normal verbal skills, impaired visual-spatial and/or visual-perceptual abilities, and difficulty with motor function. In the current study, we investigated motor function and nonverbal processing speed in estrogen- and placebo-treated girls (aged 10-12 years) with TS and in age-matched female controls. The goal of this study was to examine whether estrogen replacement therapy would reverse deficits in motor function and in nonverbal processing speed, a measure of the time required to perform certain disparate nonverbal tasks, in adolescent girls with TS. Children received either estrogen (ethinyl estradiol, 12.5-50 ng/kg.day), or placebo for durations of 1-7 yr (mean, 4.0 +/- 2.1 yr) in this randomized, double blind study. Cognitive and motor tasks administered included the Wechsler Intelligence Scale for Children-Revised; nonspatial, repetitive motor tasks (tapping and three tasks from the Paness); and spatially mediated motor tasks [nongrooved pegboard (Lafayette), pursuit rotor, visual-motor integration, and money street map]. Questionnaires administered included the Self-Concept Scale. The major result of this study was the positive estrogen treatment effect on nonverbal processing speed and speeded motor performance in 12-yr-old TS girls. That motor performance would be slower in estrogen-deficient TS females is consistent with previous studies of the influence of estrogen on motor function. Estrogen replacement is thus the most likely explanation for the improved motor speed and nonverbal processing time in the estrogen-treated TS girls compared to that in the placebo-treated TS girls. Whether these findings will influence the psychoeducational outcome or quality of life of females with TS is not yet known.

Child↗
PubMed1998

Inactivation of the luteinizing hormone/chorionic gonadotropin receptor by an insertional mutation in Leydig cell hypoplasia.

We previously identified a nonsense mutation (Cys545Stop) in the paternal human LH/CG receptor (hLHR) allele in a family with two 46,XY children afflicted with Leydig cell hypoplasia. This mutation abolished the signal transduction capability of the affected hLHR. We have now examined all coding exons and the transcript of both alleles of the hLHR gene of the affected children. A 33-bp in-frame insertion was found in the maternal hLHR allele. This insertion occurred between nucleotide 54 and 55 and might be the result of a partial gene duplication. Genomic DNA-PCR showed that this defective maternal hLHR allele was inherited by the two affected children. However, examination of the inheritance of the 935-A/G polymorphism of the hLHR by genomic- and RT-PCR indicated that the maternal hLHR allele was not expressed in cultured fibroblasts of the patients. The effect of the in-frame insertion on the biological activity of the hLHR was examined by expressing the mutated hLHR construct, generated by site-directed mutagenesis, in HEK 293 cells. The expression of the mRNA for the mutant hLHR in HEK 293 cells was not affected. Response of cells expressing the mutated hLHR to hCG stimulation was impaired as demonstrated by reduced intracellular cAMP biosynthesis. This change in signal transduction was the result of a profound reduction in hormone binding at the cell surface due to altered expression and processing of the mutated receptor. We conclude that Leydig cell hypoplasia in this family is the result of compound heterozygous loss-of-function mutations of the hLHR gene.

Alleles↗
PubMed1998

Prenatal diagnosis of steroid 21-hydroxylase deficiency by the modified polymerase chain reaction to detect splice site mutation in the CYP21 gene.

A splicing junction mutation at nucleotide 656 (A-> G substitution, I2G) in the steroid 21-hydroxylase gene (CYP21) is the most frequently detected mutation in patients with the salt-wasting and simple-virilizing forms of steroid 21-hydroxylase deficiency (approximately 60%). In this disease, prenatal diagnosis and treatment to minimize the effects of excess androgen in affected females has been advocated. Therefore, to detect the I2G mutation rapidly, accurately, and without the use of radioisotope, we developed a modified polymerase chain reaction (PCR) with a mismatched 3' nucleotide primer to introduce a new restriction site upon PCR amplification of the mutant allele. This allowed the mutant allele to be identified readily by restriction enzyme digestion of the PCR product, and subsequently this PCR product was subjected to restriction enzyme digestion for diagnosis. Chorionic villus biopsy samples (CVS) were obtained at 10 to 11 weeks gestation from two females carrying fetuses at risk for steroid 21-hydroxylase deficiency. Prenatal diagnosis was successful in both cases. One affected female was treated with dexamethasone to term. In the other case, treatment was withdrawn at an early stage when testing revealed a normal fetus. The results demonstrate the rapid and accurate detection of the I2G mutation by this method, thereby indicating the feasibility of for prenatal diagnosis of the I2G mutation.

Adrenal Hyperplasia, Congenital↗
PubMed1998

Mutations of the CYP21 gene in nonclassical steroid 21-hydroxylase deficiency in Japan.

To determine whether nonclassical steroid 21-hydroxylase deficiency in Japan has the same molecular basis as in western countries, we have characterized the mutations of the CYP21 gene in 7 Japanese patients with nonclassical (NC) steroid 21-hydroxylase deficiency. In the Japanese NC cases the P30L was present in one allele in 5 of the 7 patients and on both alleles in one patient. By contrast, the V281L mutation, which was present in about 60% of NC cases in western countries, was not identified in any patient. Among our 7 cases, 4 were detected through neonatal mass screening by a mild increase in serum 17-hydroxyprogesterone (without any symptoms of CAH) at birth, but the 2 cases who were diagnosed as adults were born before nationwide neonatal screening was instituted, so that the Japanese neonatal screening program does detect some cases of NC steroid 21-hydroxylase deficiency. We suggest that P30L mutation is more frequent in Japanese NC CAH than V281L and that the frequency of the mutations causing NC steroid 21-hydroxylase deficiency in Japan might be different from that in western countries.

Adrenal Hyperplasia, Congenital↗
PubMed1997

Urodynamic abnormalities in two brothers with adrenomyeloneuropathy.

Adrenoleukodystrophy is an X-linked disorder characterized by loss of adrenal function and demyelinating nervous disease. A slowly progressive form, adrenomyeloneuropathy, has been described that can mimic multiple sclerosis. Two brothers are presented whose contrasting urodynamic findings are compatible with upper and mixed (upper and lower) motor neuron disease, respectively.

Adrenoleukodystrophy↗
PubMed1997

Inferior petrosal sinus AVP in patients with Cushing's syndrome.

OBJECTIVE: In both normal volunteers and patients with Cushing's disease, one dominant inferior petrosal sinus (IPS) contains higher concentrations of AVP and ACTH than the contralateral (non-dominant) IPS, but ovine corticotrophin-releasing hormone (oCRH)-stimulated AVP in the petrosal sinuses is greater in Cushing's disease than in normal volunteers. To distinguish whether greater oCRH-releasable AVP might be specifically related to the presence of a pituitary corticotrophinoma, or be due to hypercortisolism per se, we compared IPS AVP in patients with Cushing's disease with those of patients with other causes of Cushing's syndrome. PATIENTS: Twenty-three patients with Cushing's disease, 16 patients with the syndrome of ectopic ACTH and seven patients with Cushing's syndrome of adrenal origin. MEASUREMENTS: AVP and ACTH, measured both before and 3, 5 and 10 minutes after oCRH in the petrosal sinuses, and in a peripheral vein. RESULTS: In all three groups, AVP concentrations were lateralized such that most of the AVP was found in one, dominant IPS. oCRH significantly increased IPS ACTH only in patients with Cushing's disease (p < 0.001), whereas it significantly increased dominant IPS AVP levels in all three patient groups (P < 0.01). However, neither dominant nor non-dominant IPS AVP (basal or oCRH-stimulated) were significantly different among patients with Cushing's disease, ectopic ACTH or Cushing's syndrome of adrenal origin. Basal and oCRH-stimulated IPS AVP were negatively correlated with urine free cortisol. CONCLUSIONS: Inferior petrosal sinus AVP levels are similar in all forms of Cushing's syndrome, and thus the higher inferior petrosal sinus AVP levels in patients with Cushing's disease compared with normal volunteers are unlikely to be related specifically to the presence of the pituitary corticotrophinoma. While AVP may play a role in pituitary corticotroph tumourigenesis or may be secreted by some pituitary corticotroph tumours, the observation that CRH-stimulated inferior petrosal sinus AVP levels are higher in Cushing's disease than in normal volunteers appears most likely to be related to the low endogenous CRH levels induced by hypercortisolism, rather than a consequence of Cushing's disease itself. We hypothesize that low endogenous CRH leads to increased sensitivity of central nervous system CRH receptors to exogenous CRH, and thus to greater ovine CRH-stimulated AVP.

ACTH Syndrome, Ectopic↗
PubMed1997

Effects of luteinizing hormone-releasing hormone analog-induced pubertal delay in growth hormone (GH)-deficient children treated with GH: preliminary results.

To study the effect of delaying epiphyseal fusion on the growth of GH-deficient children, we studied 14 pubertal, treatment naive, GH-deficient patients (6 girls and 8 boys) in a prospective, randomized, placebo-controlled trial. Chronological age was 14.5 +/- 0.5 yr, and bone age was 11.6 +/- 0.3 yr (mean +/- SEM) at the beginning of the study. Patients were assigned randomly to receive GH and LH-releasing hormone (LHRH) analog (n = 8) or GH and placebo (n = 6) during 3 yr, with planned continuation of GH treatment until epiphyseal fusion. Patients were measured with a stadiometer and had serum LHRH tests, serum testosterone (boys), serum estradiol (girls), and bone age performed every 6 months. Patients treated with GH and LHRH analog showed a clear suppression of their pituitary-gonadal axis and a marked delay in bone age progression. We observed a greater gain in height prediction in these patients than in the patients treated with GH and placebo after 3 yr of treatment (mean +/- SEM, 14.0 +/- 1.6 vs. 8.0 +/- 2.4 cm; P < 0.05). These preliminary findings suggest that delaying epiphyseal fusion with LHRH analog in pubertal GH-deficient children treated with GH increases height prediction and may increase final height compared to treatment with GH alone.

Adolescent↗
PubMed1997

Acute effects of bromocriptine, cyproheptadine, and valproic acid on plasma adrenocorticotropin secretion in Nelson's syndrome.

Previous studies have found that bromocriptine, cyproheptadine, and valproic acid can reduce ACTH secretion in Nelson's syndrome, but none of these agents has achieved widespread use due to their failure to normalize ACTH in most patients. The current study was undertaken to determine whether these three agents, which act through different mechanisms, decrease plasma ACTH synergistically when administered together. Six adult female patients (mean age, 41 yr) with Nelson's syndrome were studied. ACTH was measured every 20 min for 8 h, 2 h before and 6 h after each of the following six treatments: placebo, bromocriptine (2.5 mg), cyproheptadine (8 mg), valproic acid (1 g), cyproheptadine plus valproic acid, and the combination of all three drugs. The sequence of treatments was determined randomly, and there was an interval of at least 2 days between each treatment. The hourly ACTH values were averaged, and the percent maximal suppression of plasma ACTH, relative to the baseline values before drug administration, was compared among the six treatments. Basal plasma ACTH levels in the six patients ranged from 40-3324 pmol/L (normal range, 1-8). The percent maximal suppression of ACTH after administration of placebo (6 +/- 11%), cyproheptadine (17 +/- 15%), valproic acid (37 +/- 10%) or the combination of cyproheptadine and valproic acid (19 +/- 14%) did not achieve statistical significance. Bromocriptine, on the other hand, caused a significant decrease in plasma ACTH (52 +/- 8%; P < 0.05), as did the combination of bromocriptine, cyproheptadine, and valproic acid (58 +/- 12%; P < 0.05). However, the combined effect of the three drugs did not significantly exceed the effect of bromocriptine alone. We conclude that at the doses studied, bromocriptine had the greatest acute effect in suppressing ACTH secretion in Nelson's syndrome, and that combined administration with valproic acid and cyproheptadine did not further increase this acute ACTH-suppressive effect.

Adrenocorticotropic Hormone↗
PubMed1997

Absence of growth hormone effects on cognitive function in girls with Turner syndrome.

Turner syndrome (TS) is a genetic disorder characterized by short stature, gonadal dysgenesis, and a particular neurocognitive profile of normally developed language abilities (particularly verbal IQ) and impaired visual-spatial and/or visual-perceptual abilities. We have followed a large sample of girls with Turner syndrome who were enrolled in a long-term, double-blind, placebo-controlled trial of the effects of growth hormone (GH) treatment on final adult height. This study provides a unique opportunity to prospectively evaluate the effects of GH treatment on neurocognitive function in this population of girls with Turner syndrome. The GH- and placebo-treated Turner syndrome subjects were well matched for age, treatment duration, race, karyotype, and socioeconomic status. Treatment (GH or placebo) durations ranged from 1-7 yr. Whether GH deficiency and/or treatment in childhood and adolescence influences cognitive outcome in short children or GH-children is controversial. The major result of this study was the absence of GH treatment effects on cognitive function in girls with Turner syndrome. Our findings are in agreement with most of the previous studies that found no apparent growth hormone treatment effects on cognitive function in growth-hormone deficient children. We conclude that this study does not support a role for growth hormone in influencing childhood brain development in girls with Turner syndrome. Their characteristic nonverbal neurocognitive deficits were not altered with GH treatment into early adolescence.

Child↗