Biomedical subjects

G B Cutler

Publications and source records attributed to G B Cutler.

At least 163 records · Page 9Linked to original sources

PubMed1988

Glucocorticoid receptor-mediated effects on rat fibrosarcoma growth.

Glucocorticoid receptors are present in most normal and malignant mammalian cells. To examine the hypothesis that the growth of methylcholanthrene-induced malignant sarcoma is glucocorticoid dependent, we evaluated the behavior of malignant fibrosarcoma (MCA) in adrenalectomized rats treated with either normal saline or deoxycorticosterone acetate and in intact rats treated with placebo or with the glucocorticoid receptor antagonist RU 486. Survival, tumor weight, and loss of body weight (an index of cachexia) were measured. In MCA-bearing rats, neither survival nor loss of body weight was affected by bilateral adrenalectomy or by treatment with RU 486. Tumor weight and time-integrated tumor volume, however, were significantly less in bilaterally adrenalectomized rats without deoxycorticosterone acetate replacement than in animals treated with deoxycorticosterone acetate. Similarly, tumor weight and time-integrated tumor volume were less in intact animals treated with RU 486 than in intact animals treated with placebo. The glucocorticoid receptors in the tumor cells had similar binding capacity (Ro) and equilibrium dissociation constant (Kd) as in control rat fibroblasts. These results suggest that the growth of MCA sarcoma cells is partially dependent upon glucocorticoids. This effect of glucocorticoids, however, was not of sufficient magnitude to improve survival and prevent cachexia. We conclude that glucocorticoids appear to influence MCA sarcoma growth in the rat, and that glucocorticoid receptor blockade, perhaps in combination with other antitumor agents, merits future study in the treatment of malignant tumors.

Adrenalectomy↗

PubMed1988

Blood pressure and body size in precocious puberty.

Blood pressure increases with age in normal children. This increase appears to be related to body size. To assess the role of body size as a determinant of blood pressure in precocious puberty, we compared the blood pressure of 81 children with precocious puberty with the blood pressure standards for normal children from the NHLBI Task Force on Blood Pressure Control in Children. Children with precocious puberty had significantly increased blood pressure for chronologic age (p less than 0.05) but generally appropriate blood pressure for height age or weight age. These data are consistent with the hypothesis that increased body size causes the increased blood pressure for chronologic age in children with precocious puberty. Physicians who evaluate such children should assess whether blood pressure is appropriate for height age rather than chronologic age.

Age Determination by Skeleton↗

PubMed1988

Macronodular adrenal hyperplasia in Cushing disease.

Computed tomographic (CT) scans of the adrenal glands were obtained in nine patients with Cushing disease as a result of an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma and macronodular hyperplasia of the adrenal glands. The findings were compared retrospectively with those in six patients with Cushing syndrome as a result of an autonomous adrenal adenoma and 16 with Cushing syndrome as a result of ectopic ACTH production. Seven of nine patients with macronodular adrenal hyperplasia had hyperplastic adrenal glands in addition to single or multiple focal adrenal nodules. The six patients with hypercortisolism caused by an autonomous adrenal adenoma showed atrophic (four patients) or normal (two patients) ipsilateral and contralateral adrenal glands. Fourteen of 16 patients with the ectopic ACTH syndrome had hyperplasia of the adrenal glands without nodularity, and only two had focal nodules.

ACTH Syndrome, Ectopic↗

PubMed1988

Effect of gonadotropin secretion rate on the radiosensitivity of the rat luteinizing hormone-releasing hormone neuron and gonadotroph.

To test the hypothesis that the functional state of hypothalamic LHRH neurons and pituitary gonadotrophs might alter their radiosensitivity, we determined the experimental conditions under which the gonadotropin response to castration could be impaired by a single dose of cranial irradiation. Single doses of cranial irradiation greater than 2000 rads were lethal to unshielded rats. Shielding of the oropharynx and esophagus allowed the animals to survive doses up to 5000 rads. Doses between 2000 and 5000 rads had no effect on basal gonadotropin levels for as long as 3 months after irradiation. Irradiation caused a dose- and time-dependent impairment, however, in the gonadotropin response to castration. Impairment of the gonadotropin levels of castrate animals occurred in animals that were irradiated either before or after castration. However, rats irradiated in the castrate state showed a decreased susceptibility to irradiation damage. Additionally, stimulation of the pituitary by LHRH agonist (LHRHa) 3 h before irradiation significantly reduced the impairment of gonadotropin secretion 12-20 weeks after irradiation (P less than 0.05). Thus, increased functional activity of the rat hypothalamus or pituitary at the time of irradiation, induced by either castration or acute LHRHa administration, was associated with some protection against the gonadotropin-lowering effect of irradiation. Based upon these data, we hypothesize that stimulation of gonadotropin secretion at the time of therapeutic cranial irradiation in humans might protect against subsequent impairment of gonadotropin secretion.

Animals↗

PubMed1988

Dose-response relationship between thyroid hormone and growth velocity in cynomolgus monkeys.

To investigate the dose-response relationship between thyroid hormone and linear growth, we studied 10 castrated prepubertal cynomolgus monkeys. Hypothyroidism was induced by administration of methimazole (0.0125% in drinking water) and was confirmed by high serum TSH levels (greater than 40 mU/L) in all animals. Subsequently, each animal received 1, 2, 4, or 8 micrograms/kg.day T4, im, for 9 weeks. The sequence of T4 doses was random, and 6 weeks elapsed between successive T4 doses. Serum T4, T3, TSH, and insulin-like growth factor I (IGF-I) levels and lower leg length were measured every 3 weeks. Methimazole administration decreased thyroid hormone and IGF-I levels and lower leg growth rate. With increasing doses of exogenous T4, serum T4, T3, and IGF-I as well as lower leg growth rate increased significantly. Animals not given T4 had a 65% decrease in lower leg growth rate (P less than 0.01). Animals given 4 and 8 micrograms/kg.day T4 had 56% and 73% increases, respectively, in lower leg growth rate compared to baseline (P less than 0.05 and P less than 0.01, respectively). Lower leg growth rate correlated better with serum T3 (r = 0.50; P less than 0.001) than with serum T4 (r = 0.29; P less than 0.05). Lower leg growth rate also correlated with serum IGF-I levels (r = 0.53; P less than 0.001). Serum IGF-I correlated with serum T3 (r = 0.47; P less than 0.001), but not with serum T4. We conclude that increased serum T4 and T3 levels cause progressive increases in growth velocity and IGF-I levels over a range from moderate hypothyroidism to moderate hyperthyroidism. Growth velocity and IGF-I levels correlated more strongly with the serum T3 than with the serum T4 level.

Animals↗

PubMed1988

Resumption of puberty after long term luteinizing hormone-releasing hormone agonist treatment of central precocious puberty.

To determine whether puberty resumes normally after long term LHRH agonist (LHRHa) treatment, we studied 16 children with central precocious puberty treated with LHRHa (D-Trp6,Pro9,NEt-LHRH) for 1-4 yr (mean, 3.3 yr). Treatment was discontinued at a mean age of 11.6 +/- 1.3 (+/- SD) yr. Plasma hormone levels, growth velocity, rate of bone maturation, and pubertal stage were assessed at the end of treatment and 3 and 12 months later. Basal plasma sex steroid and basal and LHRH-stimulated gonadotropin levels returned to near-pretreatment levels 3 months after discontinuation of therapy and were fully restored to pretreatment levels at 12 months. Growth velocity, which had been 7.8 cm/yr before treatment, was stable after discontinuation of treatment at approximately 2.6 cm/yr. The predicted height, which had increased during treatment (P less than 0.01), remained stable at approximately 5 cm above the pretreatment predicted height. The rate of bone age advancement (delta bone age/delta chronological age) increased gradually from 0.4 at the end of treatment to the normal value of 0.9 12 months posttreatment. Breast and pubic hair pubertal stages, which were stable throughout treatment and were 4.0 +/- 0.8 (+/- SD) and 3.6 +/- 1.0 at the end of treatment, increased to 4.9 +/- 0.2 and 4.5 +/- 1.0. This approximated the normal rate of 1 stage/yr. Menses occurred in 8 of 12 girls within 1 yr after treatment and in an additional 3 by 20 months after treatment. Six of the girls had menstruated before treatment, and all of these menstruated within 14 months after discontinuing therapy. We conclude that gonadotropin and sex steroid secretion and the clinical progression through puberty appear to resume normally after discontinuation of long term LHRHa treatment of central precocious puberty. Long term follow-up will be required, however, to determine whether the improvement in predicted height of these patients will be achieved, and whether adult reproductive function will be normal.

Body Height↗

PubMed1988

Premature thelarche and central precocious puberty: the relationship between clinical presentation and the gonadotropin response to luteinizing hormone-releasing hormone.

Premature thelarche is a benign condition that affects young girls. In contrast, central precocious puberty is considered a more serious disorder that causes progressive secondary sexual development, accelerated growth and skeletal maturation, early epiphyseal fusion, and short adult stature. Differentiation between these 2 conditions is important, but may be difficult on clinical grounds, since patients with both disorders may present initially as isolated breast development. To examine the potential usefulness of gonadotropin measurements in distinguishing early central precocious puberty from premature thelarche, we measured basal and LHRH-stimulated plasma gonadotropin levels in 58 girls with idiopathic premature breast development. The girls were divided into six clinically distinct groups, based on the severity of clinical presentation, ranging from isolated breast development (group A) to complete secondary sexual development and accelerated growth and skeletal maturation (group F). The mean basal plasma LH levels and the peak LH response to LHRH stimulation were significantly less in girls with isolated thelarche (group A) than in girls with complete sexual development (group F). The mean basal plasma FSH levels did not differ between these groups, but the peak FSH response to LHRH was greater in girls with isolated thelarche than in girls with complete sexual development. Thus, girls with isolated premature thelarche had a FSH-predominant response to LHRH [mean ratio of peak LH to peak FSH, 0.29 +/- 0.10 (+/- SD)], while girls with complete sexual development had a LH-predominant response (peak LH/FSH, 4.16 +/- 1.80). All girls with isolated thelarche had peak LH/FSH ratios less than 1, and all girls with complete sexual development had a ratio greater than 1. Girls with early or intermediate manifestations of central precocious puberty, who had features of puberty in addition to breast development but lacked all of the features of group F, comprised groups B-E. These girls also had intermediate peak LH/FSH ratios, ranging from 0.29 +/- 0.10 (group B) to 3.35 +/- 2.66 (group E). We conclude that girls with early central precocious puberty frequently have LH and FSH responses to LHRH that are indistinguishable from the FSH-predominant responses of girls with isolated thelarche. These data are consistent with the hypothesis that premature thelarche and central precocious puberty may represent different positions along a continuum of hypothalamic LHRH neuron activation.

Breast↗

PubMed1988

The effect of short term treatment with growth hormone and ethinyl estradiol on lower leg growth rate in girls with Turner's syndrome.

An important consequence of Turner's syndrome is short stature. We previously reported that the optimal doses of ethinyl estradiol (EE2) and GH for the stimulation of short term growth in such patients were 100 ng/kg.day and 0.15 U/kg (administered sc three times weekly), respectively. The aim of this study was to determine whether the combination of low dose estrogen and GH would stimulate short term growth more than either agent administered alone. Thirty-nine girls with Turner's syndrome (aged 5-15 yr) underwent one to three 6-month cycles, each consisting of a 2-month baseline period, a 2-month treatment period, and a subsequent 2-month washout period. During the first 2 yr of the study, the girls were assigned to receive the three treatments in random order. The treatments were EE2 (100 ng/kg.day, orally), GH (0.15 U/kg, sc, three times weekly), or the combination of EE2 and GH. Subsequently, some of the girls were treated with reduced doses of EE2 (50 ng/kg.day) and GH [0.09 U/kg, three times weekly (tid)] according to the same protocol. Lower leg length was measured every 2 months throughout the study. EE2 increased lower leg growth rate significantly at the dose of 100 ng/kg.day, but not at the dose of 50 ng/kg.day. Similarly, the higher dose of GH (0.15 U/kg, tiw) increased lower leg growth rate significantly, whereas the lower dose (0.09 U/kg, tiw) did not. However, combined treatment with the lower doses of EE2 (50 ng/kg.day) and GH (0.09 U/kg, tiw) stimulated lower leg growth rate significantly and to a similar degree as the higher dose of GH (0.15 U/kg, tiw). This higher dose of GH appeared to cause a maximal increase in lower leg growth rate, which was not further increased by combined administration with the higher dose (100 ng/kg.day) of estrogen. Thus, addition of low dose EE2 to an optimal dose of GH did not cause any apparent increase in short term lower leg growth rate in girls with Turner's syndrome. Whether the long term outcome of GH treatment would be altered by concurrent administration of low dose estrogen will require long term clinical trials.

Adolescent↗

PubMed1988

Usefulness of inferior petrosal sinus venous endocrine markers in Cushing's disease.

Bilateral and simultaneous sampling of the inferior petrosal sinuses in patients with Cushing's disease has been used to establish the presence and laterality of adrenocorticotropic hormone (ACTH)-producing microadenomas prior to transsphenoidal surgery. Successful preoperative lateralization depends upon equivalent dilution of pituitary venous blood on the two sides since samples which are diluted by unequal amounts of non-pituitary blood may lead to erroneous results. To assure valid sampling results, the use of other pituitary hormones, measured simultaneously, has been proposed to correct the ACTH concentrations from the inferior petrosal sinuses against unequal dilution by non-pituitary venous blood. This proposal presumes that ACTH-secreting microadenomas will not cause unequal delivery of the other pituitary hormones into the two inferior petrosal sinuses. The inferior petrosal sinus concentrations of prolactin (PRL), thyrotropin (TSH), and the alpha subunit of human chorionic gonadotropin (alpha-HCG) were evaluated as indicators of pituitary venous blood dilution in 11 patients with Cushing's disease. Four patients with ectopic ACTH syndrome served as controls. Blood was withdrawn simultaneously from catheters in both inferior petrosal sinuses and from a peripheral vein for measurement of ACTH, PRL, TSH, and alpha-HCG. The ACTH concentrations were then corrected for dilution by non-pituitary blood by dividing the ACTH concentration from each side by the ratio of the inferior petrosal sinus to peripheral blood concentrations of PRL, TSH, and alpha-HCG for that side. At surgery, all 11 patients had ACTH-secreting microadenomas on the side predicted by the uncorrected ACTH concentrations. However, in three patients the corrected ACTH values would have led to erroneous results. Among the 18 sets of corrected inferior petrosal sinus measurements in these three patients, the corrected ACTH values failed to show an inferior petrosal sinus gradient in six and localized the tumor to the side opposite the adenoma in four. Incorrect lateralization was obtained with each of the hormones (PRL, TSH, and alpha-HCG) used for correction. Furthermore, the ipsilateral (side of tumor)-to-contralateral inferior petrosal sinus gradient of ACTH in patients with Cushing's disease was generally paralleled by a significant inferior petrosal sinus gradient of PRL, TSH, and alpha-HCG to the side of the tumor, whereas patients with the ectopic ACTH syndrome tended not to exhibit lateralizing (side-to-side) gradients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenoma↗

PubMed1987

Developmental processes in early adolescence. Relations among chronologic age, pubertal stage, height, weight, and serum levels of gonadotropins, sex steroids, and adrenal androgens.

Cross-sectional data are presented on 108 young adolescents (56 boys, 52 girls), ages 9 to 14 years. The measures were: for all subjects, pubertal stage (Tanner criteria for genital/breast and pubic hair stage); height and weight; serum hormone concentrations for gonadotropins (luteinizing hormone and follicle-stimulating hormone), sex steroids (testosterone, estradiol, and the computed testosterone to estradiol ratio), adrenal androgens (dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione), and testosterone-estradiol binding globulin. In addition, testicular volume for boys and menarchial status for girls are reported. The study goal was to provide interrelations among these measures, based on the same sample, and examine their interchangeability. Results suggest that it would be reasonable to compare research across as well as within studies based on different markers. Multiple regression analysis showed that the strongest hormone correlates of pubertal development were androgen levels (primarily testosterone in boys and primarily dehydroepiandrosterone sulphate and androstenedione in girls). Estradiol level in girls was the strongest correlate only for menarchial status. Level of testosterone-estradiol binding globulin, which was lower at successive pubertal stages for boys and showed no consistent differences for girls, may be a useful measure for studying the developmental processes and gender differences during puberty.

Adolescent↗

PubMed1987

Growth hormone secretory dynamics in children with precocious puberty.

We investigated whether an increase in growth hormone secretion contributed to the growth spurt in children with precocious puberty by measuring the 24-hour profile of serum growth hormone in 51 patients with central precocious puberty. Girls with central precocious puberty had significantly greater mean 24-hour levels of growth hormone in comparison with normal prepubertal girls (5.1 +/- 0.5 SEM vs 3.4 +/- 0.3 ng/mL, P less than 0.005). Mean 24-hour growth hormone levels did not differ significantly between boys with central precocious puberty and normal prepubertal boys (4.4 +/- 1.2 vs 3.0 +/- 0.4 ng/mL). Serum somatomedin C levels were significantly correlated with mean 24-hour growth hormone levels in the girls only. Height age advancement (expressed as height age/chronologic age) was significantly correlated with mean 24-hour growth hormone levels in both boys and girls with central precocious puberty. We conclude that spontaneous 24-hour growth hormone secretion in girls with precocious puberty is greater than that of normal prepubertal girls and may mediate at least in part the increased growth rate in this disorder.

Body Height↗

PubMed1987

Developmental processes in early adolescence: relationships between adolescent adjustment problems and chronologic age, pubertal stage, and puberty-related serum hormone levels.

Relations between adolescent psychosocial adjustment problems and markers of biologic development, including chronologic age, pubertal status, and serum hormone levels, were examined in 56 normal boys and 52 normal girls, ages 9 to 14 years. Adolescent psychosocial adjustment was assessed by adolescent self-ratings of various aspects of self-image (Offer Self-Image Questionnaire for Adolescents) and parent ratings of adolescent behavior problems (Child Behavior Checklist). The pubertal status measure used in the analyses was Tanner genital stage for boys and Tanner breast stage for girls. The hormone measures, determined by radioimmunoassay, were serum levels of gonadotropins (luteinizing hormone and follicle stimulating hormone), sex steroids (testosterone and estradiol), and adrenal androgens (dehydroepiandrosterone and its sulfate, and androstenedione). The testosterone/estradiol ratio also was computed. Overall, findings were stronger, more consistent, and more generalized for boys than for girls. For boys, adjustment problems typically were associated with a multivariate profile that may be characteristic for later maturers: relatively low sex steroid levels, or lower pubertal stage, and relatively high adrenal androgen (androstenedione) levels, frequently in conjunction with higher chronologic age. Univariate relations predominated for girls; that is, associated with adjustment problems for girls were relatively high levels of gonadotropins, relatively low levels of dehydroepiandrosterone sulfate, and relatively high levels of androstenedione on their own or in conjunction with lower pubertal stage. Higher levels of androstenedione, a steroid particularly responsive to stress, were associated with adjustment problems in both boys and girls. This relation may reflect the stress of later maturation, which could result from environmental factors, such as adolescent self-comparisons with same-age peers, or endogenous effects of hormones.

Adolescent↗

PubMed1987

Cushing syndrome: pituitary CT scanning.

Proper treatment of patients with Cushing syndrome depends on knowledge of whether the condition derives from a pituitary or adrenal adenoma or an ectopic tumor that secretes adrenocorticotropic hormone (ACTH). Fifty-seven patients with Cushing syndrome were prospectively evaluated to determine whether computed tomography (CT) of the pituitary gland is useful in diagnosing or excluding an ACTH-producing adenoma and in predicting the site of the adenoma within the pituitary gland. Findings on CT scans were normal in 35 of 50 patients with surgically confirmed Cushing disease and in seven patients with ectopic ACTH-producing tumors. Of the 15 patients with Cushing disease for whom CT results were abnormal, eight had macroadenomas and seven had microadenomas. This study demonstrates a low sensitivity (30%) and low diagnostic accuracy (39%) of CT in the detection of ACTH-producing pituitary tumors and indicates the need for alternative methods of confirming the pituitary origin of excessive ACTH secretion in most patients.

Adenoma↗

PubMed1987

Identification of ACTH-producing intrathoracic tumors by measuring ACTH levels in aspirated specimens.

Three patients with Cushing syndrome secondary to ectopic adrenocorticotropic hormone (ACTH) production underwent direct 22-gauge needle aspiration of bronchial (two cases) and mediastinal (one case) carcinoid tumors. High levels of ACTH were measured in all three tumors. This technique permits absolute identification of an ectopic source of ACTH before surgery.

ACTH Syndrome, Ectopic↗

PubMed1987

Pituitary adenomas in patients with Cushing disease: initial experience with Gd-DTPA-enhanced MR imaging.

To assess the role of magnetic resonance imaging in the evaluation of adrenocorticotropic-hormone (ACTH)-producing pituitary adenomas, and the effect of intravenously administered gadolinium-diethylenetriaminepentaacetic acid (DTPA) on lesion/pituitary contrast, imaging was performed in 13 patients with clinical and chemical evidence of Cushing disease. Images were obtained at 0.5 T before and after the injection of Gd-DTPA (0.1 mmol/kg). Lesions were identified in eight of 12 precontrast and ten of 12 postcontrast studies. In these 12 patients adenomas were found at transsphenoidal surgery. The other patient, with normal images, was found to have an ectopic source of ACTH. Coronal images corresponded remarkably well with the neurosurgeon's intraoperative findings. Serial T1-weighted images disclosed early enhancement of the pituitary gland and delayed enhancement of the cystic adenomas. The discrepancy in times to peak enhancement accounted for improved lesion/pituitary contrast in some early images and for reversal or diminution of lesion/pituitary contrast in later images.

ACTH Syndrome, Ectopic↗

PubMed1987

The relationship of saline-induced changes in vasopressin secretion to basal and corticotropin-releasing hormone-stimulated adrenocorticotropin and cortisol secretion in man.

To investigate the effect of endogenous arginine vasopressin (AVP) on ACTH secretion, normal subjects were given infusions of either hypertonic saline (HS) or isotonic saline (NS) combined with human corticotropin-releasing hormone (CRH) or placebo. Basal plasma AVP was 2.3 +/- 0.3 (+/- SE) pg/ml, did not change with NS treatment, and rose to 5.4 +/- 0.6 pg/ml during HS infusion (P less than 0.01). Both basal and CRH-stimulated plasma ACTH and cortisol concentrations increased during HS infusion. Peak plasma ACTH and cortisol levels were 11.4 +/- 1.5 pg/ml and 8.6 +/- 0.8 micrograms/dl, respectively, during the HS (plus placebo) infusion. During the NS (plus placebo) infusion, plasma ACTH and cortisol gradually declined to 6.8 +/- 0.5 pg/ml and 2.6 +/- 0.4 micrograms/dl. The timing of the rise in ACTH during the HS infusion paralleled the rise in AVP. When an iv dose of 1 microgram/kg CRH was administered during the saline infusions, peak plasma ACTH and cortisol levels were 27.7 +/- 6.3 pg/ml and 17.5 +/- 1.0 micrograms/dl, respectively, during the HS infusion and 15.6 +/- 1.7 pg/ml and 13.4 +/- 1.2 micrograms/dl during the NS infusion. When the areas under the hormone response curves were compared, CRH stimulated ACTH and cortisol secretion to a greater extent than did HS (P less than 0.05). The hormonal stimulation due to combined CRH and hypertonic saline was greater than that attributable to either factor alone (P less than 0.025), but was not different than the sum of the effects of the individual factors. These results indicate that increases in endogenous AVP produced by HS are associated with increases in both basal and CRH-stimulated ACTH and cortisol release. The effect of HS appears to be additive to but not consistently synergistic with the effect of CRH.

Adrenocorticotropic Hormone↗

PubMed1987

Dissociation of adrenarche and gonadarche in precocious puberty and in isolated hypogonadotropic hypogonadism.

Adrenarche is a developmental change of the adrenal gland that results in increased secretion of adrenal androgens. This maturational process generally begins several years before activation of the hypothalamic-pituitary-gonadal axis (gonadarche). To study further the relationship between adrenarche and gonadarche, we examined adrenarche in patients with precocious puberty and in patients with isolated hypogonadotropic hypogonadism. Plasma dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, and cortisol were measured basally and during an infusion of ACTH in 50 children with precocious puberty, 5 patients with isolated hypogonadotropic hypogonadism, 7 preadrenarchal children with constitutional short stature, 44 normal pubertal children, and 40 normal adults. Children with precocious puberty did not have a corresponding advance in the timing of adrenarche. Their basal and ACTH-stimulated adrenal androgen levels were markedly lower than those of normal children matched for pubertal stage (P less than 0.05) and were only slightly greater than those reported for normal children of the same age. Similarly, patients with isolated hypogonadotropic hypogonadism and delayed puberty had no corresponding delay of adrenarche. Their adrenal androgen levels were appropriate for chronological age. Thus, these data provide further support for the hypothesis that adrenarche and gonadarche are independent maturational events controlled by separate mechanisms.

Adolescent↗

PubMed1987

Dissociation between cortisol and adrenal androgen secretion in patients receiving alternate day prednisone therapy.

To evaluate the hypothesis that chronic, low dose, alternate day prednisone treatment may suppress adrenal androgen secretion without causing long term suppression of the hypothalamic-pituitary-adrenal axis we studied seven patients with systemic lupus erythematosus who had been taking low dose (5-20 mg), alternate day prednisone therapy for at least 1 yr. Basal and ovine CRH (oCRH)-stimulated plasma ACTH, cortisol, and adrenal androgen levels were measured 12 h (day on) and 36 h (day off) after the most recent dose of prednisone, and the results were compared to those in seven age- and sex-matched normal subjects. The patients' basal ACTH and cortisol levels did not differ significantly from those in the normal subjects on either the day on or the day off prednisone treatment. By contrast, their basal adrenal androgen levels were significantly decreased compared to those in normal subjects on both the day on and the day off prednisone (P less than 0.05). The patients' oCRH-stimulated ACTH and cortisol levels on the day off prednisone did not differ from normal levels, but were significantly blunted during the day on prednisone (P less than 0.05). In contrast, the patient's oCRH-stimulated adrenal androgen levels were significantly decreased during both the day off and the day on prednisone (P less than 0.05). These findings are consistent with the hypothesis that chronic alternate day prednisone therapy, at doses close to or below replacement, suppresses adrenal androgen levels without long term suppression of the hypothalamic-pituitary-adrenal axis. Based upon these findings, we postulate that an alternate day regimen of prednisone might maintain the benefits while reducing the risks of glucocorticoid therapy of adrenal hyperandrogenism.

Adrenal Glands↗