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D L Loriaux

Publications and source records attributed to D L Loriaux.

At least 19 recordsLinked to original sources
PubMed1997

A double-blind study of perioperative steroid requirements in secondary adrenal insufficiency.

BACKGROUND: Patients treated long-term with supraphysiologic doses of glucocorticoids experience secondary adrenal insufficiency and are routinely given large doses of steroids in the perioperative period to prevent hypotension. Because the dose of steroids required to prevent hypotension is not known, we conducted a randomized, double-blind study to determine whether patients treated long-term with glucocorticoids actually require increased steroids in the perioperative period. METHODS: Patients who had been taking at least 7.5 mg prednisone daily for several months and had secondary adrenal insufficiency as defined by adrenocorticotropic hormone testing formed the study population. Patients were randomized to two groups. One group received perioperative injections of saline solution alone; the other received perioperative saline solution and cortisol. All patients received their usual daily prednisone dose throughout the study. RESULTS: Six patients were in the steroid-treated group and 12 were in the saline-treated group. Most subjects underwent major operations such as joint replacements, abdominal operations, and miscellaneous other procedures. Two patients had hypotension, one in each group. Hypotension resolved with volume replacement in both patients. The average pulse rates and blood pressures were similar in both groups during the perioperative period. CONCLUSIONS: Patients with secondary adrenal insufficiency do not experience hypotension or tachycardia caused by inadequate glucocorticoid levels when given only their daily dose of steroids for surgical procedures.

Adrenal Insufficiency↗
PubMed1996

A prospective controlled study of luteal and endometrial abnormalities in an infertile population.

OBJECTIVE: To investigate whether luteal and endometrial abnormalities occur more frequently in an infertile population and thus contribute to infertility. DESIGN: Prospective controlled clinical study. SETTING: Outpatient clinic in an academic research institution. PARTICIPANTS: Thirty-three fertile controls and 31 infertile women without ovulatory disorders, tubal disease, or male factors. INTERVENTIONS: All women underwent an endometrial biopsy 9 days after the LH surge followed by an IM injection of 5,000 IU hCG. Blood samples were drawn immediately before hCG administration for serum P and placental protein 14 (PP14) measurements, at 6 hours after hCG stimulation for serum P concentrations, and on day 5 after hCG administration for serum PP14 levels. MAIN OUTCOME MEASURES: Histologic dating of the endometrium and serum P and PP14 measurements. RESULTS: Abnormal endometrial biopsies occurred more frequently in infertile (43%) than in fertile women (9%). Except for one case, these specimens were not associated with low hCG-stimulated P levels. Serum PP14 measurements varied widely and did not discriminate subjects with abnormal endometrial development. CONCLUSIONS: Disruption of endometrial maturation without a concomitant defect of the corpus luteum occurs more frequently in an infertile population and thus may contribute to infertility.

Adult↗
PubMed1995

Inhibition of dexamethasone binding to human glucocorticoid receptor by New World primate cell extracts.

To determine if New World primates express an inhibitor that influences glucocorticoid receptor (GR) binding characteristics, we examined [3H]dexamethasone binding in cytosol prepared from B95-8 lymphoid cells, derived from the cotton top tamarin (Saguinus oedipus), in combination with cytosol prepared from human or rat tissues. B95-8 cytosol inhibited specific binding of [3H]dexamethasone (P < 0.01) when mixed with cytosol prepared from either a human lymphoid cell line (HL) or rat thymus. The inhibitory activity was heat labile and trypsin sensitive. Peak inhibitory activity was found in the 150-200 kd fractions after Sephacryl G-200 ultrafiltration. Scatchard analysis of [3H]dexamethasone binding using mixed cytosol showed a diminished GR apparent binding affinity when compared to HL cytosol. Kinetic studies using mixed cytosol indicated that B95-8 cytosol did not affect the apparent dissociation rate of [3H]dexamethasone. These data demonstrate that B95-8 cells contain a competitive inhibitor that prevents binding of dexamethasone to its cognate receptor.

Animals↗
PubMed1994

The antiprogestin RU486 delays the midcycle gonadotropin surge and ovulation in gonadotropin-releasing hormone-induced cycles.

OBJECTIVE: To investigate whether the antiprogestin RU486 acts primarily on the hypothalamus to delay the midcycle gonadotropin surge and thus gain insight into the site(s) of action of P in the control of ovulation. DESIGN: Prospective, crossover, single-blinded clinical study. SETTING: Outpatient clinic in an academic research environment. PATIENTS: Women with hypothalamic amenorrhea. INTERVENTIONS: RU486 or a placebo was given orally at a low dose of 1 mg/d for 5 days, starting when the dominant follicle reached 14 to 16 mm, to women with hypothalamic amenorrhea undergoing ovulation induction with GnRH pulses of unvarying frequency and dose. Blood samples and ovarian ultrasounds were obtained daily in the late follicular phase and every 3 to 4 days in the remainder of the cycle. MAIN OUTCOME MEASURES: Follicular diameter and plasma levels of LH, FSH, E2, and P. RESULTS: RU486 consistently delayed the timing of the midcycle gonadotropin surge and ovulation. Gonadotropin and steroid levels were suppressed during RU486 treatment, but follicular growth progressed normally in most patients. CONCLUSIONS: RU486 does not act primarily on the hypothalamus to delay ovulation. Rather, this compound appears to antagonize P at the pituitary level to suppress gonadotropin and steroid hormone secretion. P may thus act on the pituitary, independent of any hypothalamic effects, to regulate the timing of the midcycle gonadotropin surge and ovulation.

Adult↗
PubMed1994

Perioperative glucocorticoid coverage. A reassessment 42 years after emergence of a problem.

OBJECTIVE: The authors review the historical basis for the provision of perioperative glucocorticoid coverage, and detail the evolution in the understanding of the role of the hypothalamic-pituitary-adrenal cortical (HPA) axis in response to physical stressors. New recommendations are proposed for glucocorticoid-dependent patients who require anesthesia and surgery. SUMMARY BACKGROUND DATA: In 1952, a patient developed surgery-associated adrenal insufficiency as a result of preoperative withdrawal from glucocorticoid therapy. That case report, and one other in the ensuing 12 months, prompted the publication of recommendations for perioperative glucocorticoid coverage, which became the standard of care. The understanding of the role of the HPA axis in the stress response has been subsequently refined; however, recommendations for perioperative glucocorticoid coverage have not been altered in parallel. METHODS: Studies were identified beginning with the first reports of the physiologic actions of the adrenal glands (1855) and the description and clinical use of cortisone (1930-1993). Studies were selected for review if they were related to or evaluated the provision of stress-related glucocorticoid administration. All clinical studies were evaluated to determine the basis for the provision of perioperative glucocorticoid coverage and the validity of the data used to justify these conclusions. CONCLUSIONS: Clinical and experimental evidence support the concept that the current amount of perioperative glucocorticoid coverage is excessive and has been based on anecdotal information. New recommendations are proposed which suggest that the amount and duration of glucocorticoid coverage should be determined by: a) the preoperative dose of glucocorticoid taken by the patient, b) the preoperative duration of glucocorticoid administration, and c) the nature and anticipated duration of surgery.

Glucocorticoids↗
PubMed1994

Dexamethasone therapy for isosexual precocious pseudopuberty caused by generalized glucocorticoid resistance.

Generalized glucocorticoid resistance presents with clinical features secondary to excess production of mineralocorticoids and adrenal androgens. It is our hypothesis that these clinical and biochemical features will respond to glucocorticoid therapy. We tested this hypothesis in a boy with generalized glucocorticoid resistance and increased adrenal androgens. Dexamethasone was administered from age 7 6/12 yr until the onset of true puberty at 11 0/12 yr. Serum concentrations of cortisol and adrenal androgens decreased to the normal or near normal range. The accelerated precocity improved. Secondary sex characteristics did not progress; the difference between bone age and chronological age decreased from 3 1/2 yr to 2 yr, and the difference between height age and bone age decreased from 2 yr to 1/2 yr. We conclude that dexamethasone is effective and safe therapy for the sexual precocity of generalized glucocorticoid resistance.

Age Determination by Skeleton↗
PubMed1994

Effect of the antiglucocorticoid RU486 on adrenal steroidogenic enzyme activity and steroidogenesis.

RU486, a synthetic steroid receptor antagonist, has strong antiprogesterone and antiglucocorticoid properties. Chronic RU486 administration in two patients with ectopic secretion of adrenocorticotropin (ACTH) has been associated with decreasing plasma cortisol concentrations. One explanation of this finding is that RU486 may directly inhibit adrenal steroidogenesis. To test this hypothesis, we measured the effect of RU486 on specific steroidogenic enzymatic steps using an in vivo rat and an in vitro monkey model. Hypophysectomized-castrated-ACTH-replaced Sprague-Dawley rats were given RU486 i.p. at daily doses of 0, 0.0005, 0.005, 0.05, 0.5 and 5 mg/kg body weight per day for 7 days. The animals were sacrificed, and blood and adrenal glands collected. Adrenal cortical mitochondria and microsomes were purified from the rats and from two untreated Cynomolgus macaque monkeys. Specific steroidogenic enzyme activities were measured in the rat by the incorporation of 14C-labeled steroid substrates into products. A similar protocol was used to assay the steroidogenesis in the monkey adrenal fractions in the presence and absence of added RU486. Although rat adrenal weights decreased significantly at the highest RU486 dose, plasma levels of corticosterone were similar in control and treated rats. Rat adrenal 3 beta-hydroxysteroid dehydrogenase/isomerase (3-HSD), 21-hydroxylase (21-OH) and 11-hydroxylase (11-OH) activities decreased with increasing RU486 doses, with 21-OH and 11-OH being most severely affected. Monkey adrenal 3-HSD, 21-OH, 11-OH, 17-hydroxylase and 17,20-desmolase similarly decreased in the presence of increasing in vitro concentrations of RU486.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxysteroid Dehydrogenases↗
PubMed1994

Cushing's syndrome.

Explore the source record for details and available documents.

ACTH Syndrome, Ectopic↗
PubMed1994

Cushing's syndrome and the nodular adrenal gland.

This article examines Cushing's syndrome in four main categories as associated with nodular adrenal glands: adrenal adenoma, adrenal carcinoma, primary pigmented nodular adrenal dysplasia, and macronodular adrenal hyperplasia. A summary of clinical features of these four categories is presented.

Adenoma↗
PubMed1994

Characterization of the normal progesterone and placental protein 14 responses to human chorionic gonadotropin stimulation in the luteal phase.

OBJECTIVE: To examine whether midluteal phase administration of the luteotrophic hormone hCG can result in higher and more stable serum levels than random sampling of P and placental protein 14 (PP14). DESIGN: Prospective controlled clinical study. SETTING: Normal human volunteers in an academic research environment. PARTICIPANTS: Twenty-six fertile, regularly cycling women. INTERVENTIONS: Blood samples were drawn at 0, 3, 6, 9, 12, 18, and 24 hours and then daily for the next 6 days, after a single IM injection of 5,000 IU hCG or saline given on day 5, 7, or 9 after the LH surge, as detected by rapid plasma assays. MAIN OUTCOME MEASURES: Serum P and PP14 measurements. RESULTS: Peak P and PP14 concentrations occurred at 6 hours and 5 days, respectively, after hCG stimulation on luteal phase day 9. Progesterone but not PP14 levels were significantly higher and less variable after hCG than after saline administration on this day. Progesterone responses exceeded 11.0 ng/mL (35.0 nmol/L) in all women, suggesting that this represents the cutoff limit for normal luteal function. Because PP14 responses were highly variable and inconsistent, it was not possible to determine a threshold for normal endometrial function. CONCLUSIONS: Midluteal phase administration of hCG in normal women induces consistent serum P levels > 11.0 ng/mL (35.0 nmol/L) but highly variable PP14 responses.

Adult↗
PubMed1993

Comparative analysis of progesterone and placental protein 14 measurements in the evaluation of luteal function.

OBJECTIVE: Our purpose was to investigate the diagnostic accuracy of single or summed measurements of progesterone and placental protein 14, a progestin-dependent endometrial glycoprotein, in the evaluation of luteal function. STUDY DESIGN: Forty-five healthy women had daily blood measurements of luteinizing hormone, progesterone, and placental protein 14 during one menstrual cycle. RESULTS: Thirty-nine women had normal and six had deficient luteal function on the basis of serial progesterone determinations. Luteal insufficiency was not accurately diagnosed by single progesterone or placental protein 14 values or by integrated placental protein 14 measurements. In contrast, the condition was correctly identified in all but one cycle when the sum of progesterone on days 4 and 7 was < 49 nmol/L (15.4 ng/ml). A poor correlation was found between peak or integrated measurements of progesterone and placental protein 14. CONCLUSION: Measurement of serum progesterone, but not placental protein 14, on 2 days of the midluteal phase provides a convenient and reliable test of luteal function.

Adult↗
PubMed1993

Contraceptive choices for women with endocrine complications.

Previous confusion regarding the interference by oral contraceptives in measurements of endocrine function have been largely eliminated by the advent of improved, more sensitive assays. There are few if any contraindications to oral contraceptive use in patients with thyroid disease. Patients with prolactinoma can be treated with bromocriptine to restore fertility and prevent mineral loss. However, as a less expensive alternative, oral contraceptives can be prescribed to correct mineral loss, because there is no convincing evidence of an adverse effect on prolactinomas by the steroidal content of the pill. Oral contraceptives comprise a near ideal treatment modality for women with polycystic ovary disease because, among other effects, oral contraceptives reduce synthesis of androgen by inhibiting pituitary gonadotropin secretion.

Contraception↗
PubMed1993

The relation between clinical manifestations of polycystic ovary syndrome and beta-cell function.

OBJECTIVE: Hyperandrogenism in patients with polycystic ovary syndrome has been shown to correlate with hyperinsulinaemia of insulin resistance. We have investigated if basal levels of insulin and the response to the intravenous administration of glucagon can reveal insulin resistance in patients with polycystic ovary syndrome. PATIENTS: Nine obese (BMI > 25 kg/m2) and nine non-obese (BMI 19-25 kg/m2) women with PCOS, chosen from a population of 91 women attending the infertility clinic, and 19 normally cycling women (seven obese, 12 non-obese) were studied. Oligo or amenorrhoea, hirsutism, and 12 or more follicles in a given ovary were selection criteria. MEASUREMENTS: Glucagon, 1 mg, was given intravenously to 18 of the 91 women and to the control subjects. Blood was taken at -5, 0, 5, 10 and 15 minutes for measurements of integrated areas under the response curve for insulin, C-peptide and glucose, respectively. Basal blood samples were drawn for fasting insulin, C-peptide, glucose, testosterone, sex hormone-binding globulin (SHBG), free fatty acids and IGF-I measurements. The free androgen index was calculated according to the formula FAI = testosterone x 100/SHBG. RESULTS: There were no significant differences in maximal increment and area under the response curve for glucose, C-peptide and insulin. FAI was significantly higher in all patients with features of polycystic ovary syndrome. However, fasting insulin levels were significantly higher only in obese patients when compared with obese control subjects and lean patients. CONCLUSIONS: The administration of 1 mg glucagon i.v. did not distinguish patients with polycystic ovary syndrome from control subjects. The mild insulin resistance of polycystic ovary syndrome is related only to obesity and is therefore unlikely to play an important role in the hyperandrogenism associated with the syndrome.

Adult↗
PubMed1993

A simplified morning ovine corticotropin-releasing hormone stimulation test for the differential diagnosis of adrenocorticotropin-dependent Cushing's syndrome.

The objective of this study was to develop criteria for the interpretation of a morning ovine CRH stimulation test for the differential diagnosis of ACTH-dependent Cushing's syndrome. Its design was retrospective review, and its setting was the in-patient unit of a tertiary care center. One hundred and eighteen patients with proven Cushing's disease or ectopic ACTH secretion were studied. The percent change in plasma ACTH and cortisol levels after CRH administration (1 microgram/kg BW) was calculated for each patient using 3 combinations of pre-CRH values (-15, -10, -5, and -1 min) and 6 combinations of post-CRH values (15, 30, 45, and 60 min). The diagnostic performance of these 36 sets of response measures was compared. The mean ACTH concentrations 15 and 30 min after CRH increased by at least 35% above the mean basal value at -5 and -1 min in 93 of 100 patients with Cushing's disease, but in none of the 16 patients with ectopic ACTH secretion. This measure gave the best sensitivity (93%) and specificity (100%). The best cortisol criterion was a mean increase at 30 and 45 min of 20% or more above mean basal values at -5 and -1 min, which gave a sensitivity of 91% and a specificity of 88%. We developed a simplified diagnostic test with 100% specificity using ACTH measurements 5 and 1 min before and 15 and 30 min after CRH administration. Although all patients with ectopic ACTH secretion had less than a 35% increase in ACTH, the probability of Cushing's disease was high at all levels of response, indicating that other tests should be performed to confirm the diagnosis.

ACTH Syndrome, Ectopic↗
PubMed1993

Midluteal phase endometrial biopsy does not accurately predict luteal function.

OBJECTIVE: To investigate whether a midluteal phase endometrial biopsy accurately predicts luteal function. DESIGN: One nonpregnant menstrual cycle was evaluated in a prospective fashion. SETTING: Outpatient Clinic of the Clinical Center of the National Institutes of Health. PARTICIPANTS: Fifty healthy, normally cycling women. INTERVENTIONS: Serum progesterone (P) was measured daily throughout the luteal phase. An endometrial biopsy was performed 7 to 9 days after the luteinizing hormone (LH) surge, as detected by rapid plasma assays, and dated histologically according to Noyes' criteria. MAIN OUTCOME MEASURE: To correlate endometrial maturation with luteal P secretion. RESULTS: Mean integrated P measurements were reduced only when the lag between histologic and chronological dating was > or = 3 days or > or = 4 days, depending on whether chronological dates were assigned prospectively from the LH surge or retrospectively from the onset of next menses, respectively. However, these lags did not consistently predict deficient luteal function because subnormal integrated P secretion was seen in only 14% of women with these delays in endometrial maturation. CONCLUSIONS: Midluteal phase endometrial biopsy provides a crude test of luteal function that does not precisely distinguish luteal insufficiency.

Adult↗
PubMed1993

Serum levels of placental protein 14 do not accurately reflect histologic maturation of the endometrium.

OBJECTIVE: To determine whether serum levels of placental protein 14, a major product of the progesterone-induced secretory endometrium, accurately reflect histologic maturation of the endometrium. METHODS: Daily serum levels of placental protein 14 were compared in 50 normally cycling women with normal or delayed endometrial maturation, as assessed by histologic dating of an endometrial biopsy in the midluteal phase of the same cycle. Ten of these subjects had placental protein 14 measurements but no biopsy in an additional cycle to examine the potential effects of the biopsy on secretion of this protein. RESULTS: Serum placental protein 14 concentrations started to increase 8 days after the LH surge and peaked at similar levels on the first day of the next menses in biopsy and non-biopsy cycles. The biopsy cycles had a shorter luteal phase but a slightly faster increase in placental protein 14 concentrations. Both the integrated secretion of this protein and single measurements on the day of the biopsy or at the onset of the next menses overlapped substantially in women with different degrees of endometrial development, even when differentiation of the endometrium was severely delayed. CONCLUSION: Serum measurements of placental protein 14 do not accurately predict, and thus should not replace, histologic evaluation of the endometrium at nidation.

Abortion, Habitual↗