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Biomedical subjects

D L Loriaux

Publications and source records attributed to D L Loriaux.

At least 235 records · Page 13Linked to original sources
PubMed1984

Dose-response relationships for the effects of growth hormone-releasing factor-(1-44)-NH2 in young adult men and women.

Human GRF-(1-44)-NH2 (GRF-44) was administered iv in graded doses of 0.01-10 micrograms/kg to 35 normal young adult men and 38 women. GRF-44 stimulated the release of GH in a dose-dependent fashion, although the individual responses varied widely. The ED50 values for this effect were 0.4 micrograms/kg in men and 0.2 micrograms/kg in women in the midfollicular phase of the menstrual cycle. Maximal responses in men and women were not significantly different, and a dose of 1 micrograms/kg was sufficient to produce a maximal response. There was, likewise, no difference between responses of women tested in the midfollicular and midluteal phases of the cycle. There were no changes in PRL, LH, FSH, TSH, ACTH, beta-endorphin, or cortisol at doses up to 1 microgram/kg; at 10 micrograms/kg, PRL increased by an average of 7.6 ng/ml in the women. Side effects occurred in approximately 20% of both men and women at 1 microgram/kg and in nearly all subjects given 10 micrograms/kg; these consisted primarily of flushing and a sense of warmth. Thus, a dose of 1 microgram/kg GRF-44 is safe and effective, and would appear to be a reasonable choice for use in studying GH responses in normal subjects of other ages and in patients with disorders of GH secretion.

Adolescent↗
PubMed1984

Variable response to a long-acting agonist of luteinizing hormone-releasing hormone in girls with McCune-Albright syndrome.

Six girls with McCune-Albright syndrome were treated for at least 2 months with the long-acting LHRH agonist D-Trp6-Pro9-NEt-LHRH, which previously was found to be an effective treatment for true precocious puberty. Nocturnal and LHRH-stimulated serum gonadotropin levels and plasma estradiol levels were measured before treatment and after 2-3 months of treatment. Five of the six girls had no decrease in serum gonadotropin or plasma estradiol levels during therapy, and their pubertal signs were unaffected by treatment. All five of these girls had serum gonadotropin levels that were within or below the normal prepubertal range. The sixth girl, who had gonadotropin levels in the normal pubertal range before treatment, had decreased serum gonadotropin and plasma estradiol levels during 1 yr of LHRH analog therapy. This was associated with cessation of menses and regression of secondary sexual changes. The failure of LHRH analog to modify the course of precocious puberty in the five patients with prepubertal serum gonadotropin concentrations is further evidence that the mechanism of precocious puberty in most girls with McCune-Albright syndrome differs from that in patients with true precocious puberty.

Child↗
PubMed1984

Luteinizing hormone-releasing hormone analog treatment of boys with hypothalamic hamartoma and true precocious puberty.

A long-acting analog of LRH (LRHa) has been shown to suppress pituitary gonadotropin and estradiol secretion to prepubertal levels in girls with idiopathic true precocious puberty. We treated six boys, aged 1-6 yr, with true precocious puberty due to hypothalamic hamartoma for 6-24 months with daily sc injections of LRHa. The patients had enlarged testes (6-25 ml), Tanner stage II-IV pubic hair, facial and axillary hair, increased growth rate, and an advanced bone age. Frequent erections occurred in all patients. Computed tomography of the head showed abnormalities characteristic of hypothalamic hamartoma (0.5-3 cm in diameter) in each boy. Each patient had measurable LH and FSH levels, with pulsed nocturnal secretion, and pubertal LH and FSH responses to LRH. Serum testosterone was in the range for normal adult men (200-600 ng/dl). LRHa significantly decreased basal LH (P less than 0.005) and FSH levels (P less than 0.01), LRH-stimulated gonadotropin levels (P less than 0.005), and serum testosterone levels (P less than 0.005). Testis size decreased significantly (P less than 0.005). Annualized growth velocity (centimeters per yr) decreased significantly compared to the pretreatment growth rate (P less than 0.01). Bone age advancement per yr slowed significantly during the course of LRHa treatment (P less than 0.01). Pubic hair, facial hair, and erections decreased in all patients. LRHa is an effective treatment for boys with precocious puberty associated with hypothalamic hamartoma. Chronic therapy will be required, however, to assess the ultimate effect of LRHa.

Bone Development↗
PubMed1984

Vertebral body bone mineral content in hyperprolactinemic women.

Hyperprolactinemia with amenorrhea and galactorrhea generally has a benign clinical course without treatment. Prolonged amenorrhea due to early surgical castration or premature menopause is, however, associated with reduced bone mass and increased risk of fractures. Previous studies in hyperprolactinemic women suggested an association with decreased cortical bone density. To determine whether hyperprolactinemia is associated with reduced trabecular bone mineral, we studied 13 hyperprolactinemic women and matched normal women by quantitative computed tomographic scans of the vertebral bodies. No patient had taken bromocriptine and one patient had previously unsuccessful transsphenoidal surgery. Each patient was matched with a normal woman on the basis of race, age +/- 52 weeks, parity, exercise, tobacco use, oral contraceptive (OCP) use, and alcohol use. No subject was currently taking OCPs. Calcium, phosphorus, and protein intakes were estimated from a 3-day diet diary. The mean duration of amenorrhea was 98.9 +/- 79.7 (SD) months. The mean height, weight, serum 25-hydroxyvitamin D (25,OHD), serum 1,25 dihydroxyvitamin D [1,25(OH)2D] and daily intakes of calcium, phosphorus, and protein were not different. The bone mineral content for each patient fell within +/- SD of the mean of the normal subjects. The mean bone mineral content (mg K2HPO4 eq/ml) of the patients was 10% less than in the normal subjects (144.6 +/- 31.4 (SD) vs. 160.1 +/- 26.6, P less than 0.05). The slope of the regression of bone mineral content and age (mg K2HPO4 eq/ml X yr) was similar in patients (-2.4 +/- 1.1) and normal subjects (-2.3 +/- 1.0). We conclude that hyperprolactinemia is associated with reduced bone mineral content, but does not necessarily produce persistent acceleration of the age-related decline in bone density.

Adult↗
PubMed1984

Human corticotropin-releasing factor in man: pharmacokinetic properties and dose-response of plasma adrenocorticotropin and cortisol secretion.

The responses of plasma immunoreactive ACTH (IR-ACTH), cortisol, GH, PRL, and LH to a single iv injection of 0.01-5 micrograms/kg human corticotropin-releasing factor (hCRF) were investigated in healthy volunteers. The lowest effective dose of hCRF was 0.5 micrograms/kg. hCRF caused brief pulse-like elevations of plasma IR-ACTH and cortisol without any effect on the plasma concentrations of GH, PRL, and LH. By contrast, ovine CRF (oCRF), given for comparison, produced long-lasting stimulation of the human pituitary-adrenal axis. The difference in duration of effect between hCRF and oCRF may be attributed to an approximately 3-4 times higher MCR of hCRF [7.9 +/- 1.2 (+/- SE) ml/kg min; n = 14] than oCRF (1.9 +/- 0.1 ml/kg min; n = 9) in man. No serious side effects occurred at any of the doses of hCRF tested. The highest dose (5 micrograms/kg) caused a slight increase of heart rate that was not associated with significant changes in arterial blood pressure. All subjects receiving 5 micrograms/kg and one third of the subjects receiving 1 micrograms/kg hCRF experienced a transient facial flush. We conclude that hCRF causes brief plasma ACTH and cortisol secretory episodes in man, similar to the physiological plasma ACTH and cortisol secretory episodes. This is in contrast to oCRF, which causes prolonged ACTH and cortisol secretion. These differences between the two peptides may be explained by the higher MCR of hCRF than oCRF.

Adrenocorticotropic Hormone↗
PubMed1984

A comparison of two methods for detecting hormone peaks: the effect of sampling interval on gonadotropin peak frequency.

There is no consensus on the optimum method to identify gonadotropin pulses in serum. We compared two approaches for detecting gonadotropin peaks. The first employed the conventional criterion of an increment from nadir to peak of 3 times the intraassay coefficient of variation (3 CV). The second identified peaks by Student's t test to quadruplicate measurements at each time point. We obtained blood samples every 5 min for 6 h from four women in the follicular phase. We also constructed control or noise series by subdividing single serum pools into consecutively labeled aliquots. Any variations in hormone concentration in the noise series that were identified as peaks were, by definition, false positive peaks. We evaluated the effect of sampling interval on gonadotropin peak detection by omitting data to simulate sampling every 10, 15, or 20 min. The 3 CV approach identified numerous false positive peaks in the noise series and detected as many peaks in the noise series as it did in the patient series. Increasing the sampling frequency from every 20 to every 5 min nearly doubled the apparent peak frequencies in both the patient and the noise series (P less than 0.025). By contrast, the t test method detected far fewer false positive peaks and significantly more peaks in the patient series than in the noise series. Increasing the sampling frequency from every 20 to every 5 min resulted in a 50-75% increase in peak frequency by the t test method. This increase in peak frequency appeared to result from improved detection of small peaks, because samples were obtained nearer the true peaks and nadirs. The resulting increase in the nadir to peak increment made it more likely that a small peak would achieve statistical significance. We conclude that increasingly stringent criteria for pulse detection should be applied as one increase the sampling frequency, and that the t test approach is a more valid method than the 3 CV approach because it yields significantly fewer false positive peaks.

Adolescent↗
PubMed1984

Hyperprolactinemia, amenorrhea, and galactorrhea. A retrospective assessment of twenty-five cases.

The syndrome of hyperprolactinemia, galactorrhea, and amenorrhea is frequently caused by a pituitary tumor. Transsphenoidal surgical removal is often advocated for microadenomas, tumors smaller than 10 mm, to prevent the progression of these small adenomas into large tumors. Because no strong evidence indicates that microadenomas naturally progress to macroadenomas, we studied 25 women who had had hyperprolactinemia, amenorrhea, or galactorrhea for a mean duration of 11.3 years. Their mean initial prolactin level was 225 ng/mL (normal, less than 36 ng/mL). Of 22 patients presenting with amenorrhea, 7 resumed menses spontaneously. Galactorrhea resolved completely in 6 of the 19 patients with this disorder. Only 1 patient had progression of a sellar abnormality, and this was slight. Visual fields remained full in all patients, and basal adrenal and thyroid functions remained normal. The mean prolactin level was 155 ng/mL at the reevaluation (p less than 0.01, initial versus reevaluation levels). Hyperprolactinemia apparently has a benign clinical course in most women, and we advocate a conservative approach to management of this disorder.

Adenoma↗
PubMed1984

Ultrasound evaluation of female isosexual precocious puberty.

Fifty-six female children with signs of precocious puberty were examined. Adult-sized ovaries and an intermediate-sized uterus were characteristic of true sexual precocity, either idiopathic or due to a CNS lesion. Premature thelarche and premature adrenarche showed normal infantile pelvic organs, while in cases of precocious pseudopuberty, the appearances of the ovaries and uterus varied depending upon the underlying process. Large ovarian cysts and large ovaries were found in six patients with McCune-Albright syndrome. An ultrasound study is of benefit in the evaluation of female children with precocious sexual development because it can demonstrate the adult-sized ovaries of true precocious puberty, thereby distinguishing this condition from premature thelarche and premature adrenarche, and it can demonstrate specific causes of precocious sexual development, such as adrenal and ovarian tumors and ovarian cysts.

Child↗
PubMed1984

Hemodynamic and endocrine parameters in the anesthetized cynomolgus monkey: a primate model.

Hemodynamic and endocrine parameters were determined in nine anesthetized adult male cynomolgus monkeys. Simultaneous phasic and mean pressures were measured in the right atrium, pulmonary artery, and abdominal aorta. Intermittent pulmonary artery wedge pressures and mean cardiac output measured by the thermal dilution method were used to calculate stroke volume, systemic vascular resistance, and pulmonary vascular resistance. Plasma adrenocorticotropic hormone (ACTH), cortisol, and plasma renin activity were measured throughout the procedure. Technical aspects, data in the anesthetized monkey, and comparison with previously reported data are presented.

Adrenocorticotropic Hormone↗
PubMed1984

Steroid and gonadotropin secretion in a patient with a 30-year history of virilization due to lipoid-cell ovarian tumor.

A 36-year-old woman with a 30-year history of undiagnosed virilizing lipoid-cell ovarian tumor is described. The tumor was localized by the NP-59 scan. Data of extensive investigations of steroid and gonadotropin secretion are provided. The preoperative dynamics of serum dehydroepiandrosterone sulfate and its decrease after the removal of the tumor suggested that dehydroepiandrosterone sulfate was being secreted by the ovarian tumor. Ovarian-peripheral venous gradients for plasma delta 5 and delta 4 steroids were correlated with the in vitro measurements of various steroidogenic enzymatic activities in the tumor tissue. The proposed metabolic pathway of the tumor is as follows: Pregnenolone----17-hydroxypregnenolone----dehydroepiandrosterone---- androstenedione----testosterone----estradiol. Low basal gonadotropin levels with no discernible pulsatility and no response to gonadotropin-releasing hormone were observed preoperatively, and a gradual normalization in both parameters was observed during the six months after removal of the tumor.

Adosterol↗
PubMed1984

Idiopathic precocious puberty in the chimpanzee: a case report.

A female chimpanzee developed premature sex skin swelling, breast budding, advanced bone age, and moderate estrogen effect of the vaginal cytology. Extensive radiographic and hormonal studies excluded all the known causes of precocious puberty and pseudopuberty, yielding a diagnosis of idiopathic true precocious puberty. To our knowledge this is the first observation of idiopathic true precocious puberty in a chimpanzee.

Animals↗
PubMed1983

The thymus-adrenal connection: thymosin has corticotropin-releasing activity in primates.

Endotoxin-free thymosin fraction 5 elevated corticotropin, beta-endorphin, and cortisol in a dose- and time-dependent fashion when administered intravenously to prepubertal cynomolgus monkeys. Two synthetic component peptides of thymosin fraction 5 had no acute effects on pituitary function, suggesting that some other peptides in thymosin fraction 5 were responsible for its corticotropin-releasing activity. In agreement with these observations, total thymectomy of juvenile macaques was associated with decreases in plasma cortisol, corticotropin, and beta-endorphin. These findings indicate that the prepubertal primate thymus contains corticotropin-releasing activity that may contribute to a physiological immunoregulatory circuit between the developing immunological and pituitary-adrenal systems.

Adrenocorticotropic Hormone↗
PubMed1983

Effects of human pancreatic tumour growth hormone releasing factor on growth hormone and somatomedin C levels in patients with idiopathic growth hormone deficiency.

Human pancreatic tumour growth hormone releasing factor (hpGRF-40) 10 micrograms/kg was administered intravenously to 6 normal young men and 12 adult patients who had presented in childhood with growth hormone (GH) deficiency (7 patients had isolated GH deficiency, 4 had multiple anterior pituitary hormone deficiencies, and 1 had Hand-Schüller-Christian [HSC] disease). hpGRF-40 administration increased serum GH concentrations in all normal subjects and in 3 of 7 patients with isolated GH deficiency and in the 1 with HSC disease; however, the mean serum GH concentration in the patients who responded was less than that of the normal subjects. Somatomedin C concentrations were increased 24 h after a single dose of hpGRF-40 in 8 of 10 patients with GH deficiency. All subjects experienced flushing in response to hpGRF-40. A patient with isolated GH deficiency received 0.33 micrograms/kg hpGRF-40 every 3 h for 5 days. Despite the modest increase in GH in response to a subsequent dose of 10 micrograms/kg hpGRF-40, serum somatomedin C levels increased within 12 h from 0.06 to 0.1 U/ml and peaked at 0.36 U/ml at 72 h; in addition the patient with HSC disease, treated with hpGRF-40 daily for 5 days, demonstrated an increase in somatomedin C from 0.4 to 0.58 U/ml. The increase after hpGRF-40 in serum GH levels in this patient and the similar or greater responses in 3 of 7 patients suggest that at least some of these patients may have hypothalamic GH-releasing-hormone deficiency. hpGRF-40 may be useful in distinguishing pituitary disease from hypothalamic disease. After hpGRF-40 administration serum somatomedin C levels may increase without a change in serum immunoreactive GH concentrations. Further studies are needed to determine whether hpGRF-40 is useful in promoting linear growth in children with GH deficiency.

Adult↗
PubMed1983

Thermal stability of a long-acting analogue of luteinizing hormone releasing hormone (D-trp6-pro9-NEt-LHRH).

The stability of solutions of a long-acting analogue of luteinizing hormone releasing hormone (D-trp6-pro9-NEt-LHRH [LHRHa] after heating to 60C for 5 days, after repeated freezing and thawing, and after refrigeration at 4C for 8 days has been examined. None of the treatments caused a detectable alteration in the HPLC profile, and none caused a significant change in biological activity in vivo. It is concluded that D-trp6-pro9-NEt-LHRH can withstand mild heating, repeated freezing and thawing, and short-term refrigeration without apparent change in HPLC profile or biological activity. It is also concluded that the results obtained with the HPLC method correlate well with the results from the in vivo bioassay.

Animals↗
PubMed1983

Primary cortisol resistance: a familial syndrome and an animal model.

Primary cortisol resistance in man is a familial disease. It is characterized by increased plasma cortisol concentrations, high urinary free cortisol excretion, a normal circadian pattern of cortisol secretion, resistance to adrenal suppression by dexamethasone and absence of clinical stigmata of Cushing's syndrome. In its severe form, hypertension and hypokalemic alkalosis are present, owing to increased secretion of the sodium-retaining corticoids, corticosterone and deoxycorticosterone. In subjects with a less severe resistance to cortisol, there are no clinical abnormalities and the disease is revealed only by detailed examination of several parameters of cortisol metabolism. In the whole-cell assay (peripheral mononuclear leukocytes or fibroblasts) the glucocorticoid receptor shows a low affinity for dexamethasone. The receptor may be unsaturable as suggested by decreased receptor concentrations in broken-cell systems. Thus, generalized target-tissue resistance to cortisol, including the pituitary gland and the hypothalamus, is accompanied by a decreased negative feedback of the cortisol-ACTH feedback system resulting in increased ACTH secretion. This causes higher plasma cortisol to compensate for the end-organ resistance and also increases the production of adrenal mineralocorticoids, as by-products. Thus hypertension and hypokalemic alkalosis depends on the degree of the resistance. Cortisol resistance in many New World primate species is characterized by greatly increased plasma cortisol concentrations, decreased cortisol binding globulin capacity and affinity, high levels of plasma and urinary free cortisol, marked resistance of ACTH suppression by dexamethasone, and no physiologic evidence of glucocorticoid hormone excess. Target tissues have normal concentrations of glucocorticoid receptors with decreased affinity for dexamethasone. The New World primates, unlike man, have compensated for this cortisol resistance with intra-adrenal adaptations over the 50 million years of their evolutionary development. These primates also have abnormalities of other steroid hormone-receptor systems such as progesterone, estrogen, androgen and mineralocorticoid. In contrast, the human syndrome appears to be a recent mutation with pathophysiologic consequences.

Adrenal Gland Diseases↗
PubMed1983

Catechol estrogens and the control of gonadotropin and prolactin secretion in man.

The catechol estrogens, the 2- or 4-hydroxylated metabolites of estrone and estradiol, have pharmacologic properties of both estrogens and catecholamines and are formed from estrogens in peripheral tissues and in the brain. This has led to speculation that they may mediate some of the feedback effects of estrogens upon gonadotropins and prolactin (PRL). Studies testing these hypotheses are still few and have not been conclusive. There have been reports that the catechol estrogen 2-hydroxyestrone (2-OHE1) might act as a partial estrogen antagonist, stimulating gonadotropin secretion; and that it might have dopamine-like effects, suppressing the secretion of PRL. In studies testing the chronic and acute effects of catechol estrogens on LH, FSH, and PRL in men and women, we found that they behaved as estrogens, suppressing gonadotropins when given in doses high enough to compensate for their rapid clearance and degradation. We found no evidence that they suppress PRL secretion. The weight of available evidence suggests that these effects are mediated by estrogen receptor interactions; and that the formation of catechol estrogens is not an obligatory step in the feedback effects of estrogens, although it may have a modulatory role. Plasma levels of catechol estrogens are too low for them to exert circulating neuroendocrine effects.

Animals↗