Effects of ovine corticotropin-releasing hormone on adrenocorticotropin secretion in the absence of glucocorticoid feedback inhibition in man

We studied 1) the nature of the plasma ACTH response to ovine CRH (oCRH) in the absence of normal glucocorticoid negative feedback inhibition and 2) the cause of the diminished circadian peak in plasma ACTH in normal men the morning after 3–30 μg/kg BW doses of oCRH. Placebo or oCRH (3 μg/kg BW, iv) was administered as iv injections to five normal men given metyrapone to produce acute glucocorticoid deficiency. Four studies were performed: 1) placebo oCRH plus placebo hydrocortisone (HC), 2) oCRH plus placebo HC, 3) placebo oCRH plus HC, and 4) oCRH plus HC. HC was given as a variable rate iv infusion to mimic the plasma cortisol response to the same dose of oCRH in normal men. Plasma cortisol levels rose only slightly after oCRH, indicating nearly complete blockade of cortisol biosynthesis. Plasma cortisol levels during the HC infusion were similar to those in normal men given 3 μg/kg oCRH. There was an exaggerated rise in both the first and second peaks of the plasma ACTH response to oCRH in the metyrapone-treated men. HC infusion did not alter the plasma ACTH response during the first 60 min after oCRH, but markedly attenuated the response thereafter; however, it did not affect the timing of the second peak. This inhibitory effect continued for up to 11 h, which was 2–3 h longer than the period that plasma cortisol levels were increased. Thus, cortisol secreted in response to ACTH released by oCRH modulates, after about a 60-min delay, the continuing release of ACTH. Despite the greater oCRH-induced release of pituitary ACTH in the metyrapone-treated men, the magnitude of their next morning’s circadian plasma ACTH peak was similar to that after they received placebo oCRH. Thus, depletion of pituitary ACTH did not appear to explain the diminished circadian peak. Its magnitude was reduced by the combination of oCRH and HC, but not by HC alone. Administration of oCRH, alone or in combination with HC, delayed the onset of the circadian rise, while oCRH, HC, or the combination thereof delayed the time of the circadian peak. Thus, it appears that both the glucocorticoid response to oCRH and direct or indirect effect(s) of oCRH are required to produce these two phenomena

Education and Phone Follow-Up in Postmenopausal Women at Risk for Osteoporosis: Effects on Calcium Intake, Exercise Frequency, and Medication Use

Introduction: Postmenopausal osteoporosis remains a substantially underdiagnosed and undertreated disease. There is a lack of knowledge among older individuals of the appropriate measures to slow or prevent bone mineral density (BMD) loss, particularly in regard to their own personal risk of osteoporosis. Bone densitometry combined with education about osteoporosis improves self-reported daily calcium intake and utilization of hormone replacement therapy (HRT). This prospective unblinded randomized controlled trial was undertaken to determine the effect of nurse education plus follow-up phone care on initiation of and persistence with antiresorptive drug therapy, increases in calcium intake, and increases in weight-bearing exercise in postmenopausal women at high risk for osteoporosis, independent of bone densitometry testing. Methods: The target study population was female patients of a large, multispecialty community practice aged >=50 years. Study participants were not on HRT or antiresorptive drug therapy, were >=5 years post menopause, had a score of >=8 on the Simple Calculated Osteoporosis Risk Estimation (SCORE) questionnaire. A total of 310 patients were enrolled and 287 (92.9%) completed the study. Participants underwent bone densitometry at study entry. They were then randomly assigned to one of two groups: (i) the usual care group who were given two educational brochures regarding osteoporosis; and (ii) the nurse education group who received these brochures plus a 15 minute one-on-one education regarding osteoporosis with a nurse. Both groups were told to follow up with their primary care physician. Those receiving nurse education also had telephone follow-up with the nurse educator at 3, 6, and 9 months. Telephone surveys of all participants were performed at 12 months after bone densitometry to assess self-reported initiation of and persistence with antiresorptive drug therapy after bone densitometry, self-reported changes in calcium intake, and weight-bearing exercise habits. Results: Nurse education plus phone care follow-up had no effect on commencement of antiresorptive drug therapy (odds ratio [OR] 1.18, 95% CI 0.69, 2.04) or persistence with antiresorptive drug therapy (OR 1.05, 95% CI 0.56, 1.97). Nurse education plus phone care follow-up was associated with improved self-reported calcium intake (OR 2.18, 95% CI 1.36, 3.49) and exercise frequency (OR 1.89, 95% CI 1.11, 3.21). Conclusion: Nurse education plus follow-up phone care does not improve utilization of drug therapy to prevent BMD loss or osteoporotic fracture, although it does improve the use of nonpharmacologic preventive measures for osteoporosis. Other strategies beyond patient education and follow-up phone care will be required to increase appropriate utilization of osteoporosis drug therapy.Calcium, Exercise, Osteoporosis, Osteoporosis-therapies, Patient-education, Postmenopausal-osteoporosis

Rapid sequential intravenous administration of four hypothalamic releasinghormones as a combined anterior pituitary function test in normal subjects

Normal subjects were studied to test the feasibility of a combined anterior pituitary function test using iv administration of four hypothalamic releasing hormones: ovine corticotropin-releasing hormone, human GH-releasing hormone, GnRH, and TRH. Initially, nine normal men were studied with various combinations of these four hormones to exclude the possibility that they might inhibit or synergize with each other in releasing the individual anterior pituitary hormones. When given in combination, the releasing hormones were administered as sequential 20-sec iv infusions in the following order and doses: ovine corticotropin-releasing hormone, 1 μg/kg; GnRH, 100 μg; human GH-releasing hormone, 1 μg/kg; and TRH, 200 μg. Plasma or serum samples were assayed for ACTH, cortisol, GH, PRL, FSH, LH, and TSH at multiple times for 120 min after injection. Compared to individual administration, combined administration of these four hypothalamic releasing hormones caused no apparent inhibition or synergism with respect to the individual hormone responses of these normal subjects. Sideeffects of the combined test were the same as those observed with individual hormone administration. No unusual or dangerous side-effects were observed. Having confirmed the efficacy of combined administration of the four releasing hormones, we administered the combination to five additional normal men and 12 normal women. Anterior pituitary hormone and cortisol responses were the same in men and women, except for a lower LH and a greater PRL response in women. There was a rapid increase in all hormones, with peak levels usually reached by 60 min. Adequate assessment of individual hormone responses can be achieved by assaying a basal and only 2 (or 3 in the case of ACTH and GH) postinfusion samples. A rapid, safe, and useful test of combined anterior pituitary function appears to be feasible using these four hypothalamic releasing hormones