Publications by authors named "Debold C"

The standard of care treatment for chronic hepatitis C viral infection (HCV) is a combination of pegylated interferon alfa and ribavirin for 24-48 weeks according to the virus genotype. This therapy is known to have multiple neuropsychiatric side effects. A major concern when evaluating a patient for HCV treatment with a known history of a psychiatric disorder is the risk that the patient's psychiatric disorder will flare or become unmanageable.

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Unlabelled: We compared SQ and ABQ diagnosis of VF imaged by radiography and X-ray absorptiometry. Mild ABQ VF had stronger associations with osteoporosis than mild SQ VF. Interobserver agreement (radiographic diagnosis) was better for ABQ.

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Absorptiometry of the thoraco-lumbar spine at the time of bone densitometry to detect vertebral deformities consistent with fracture is now available. The performance of absorptiometry in clinical practice compared to radiography has not been fully established, especially in the presence of osteoarthritis or scoliosis. Our first objective was to compare absorptiometry to radiography for detection of vertebral deformity in elderly women who were referred for bone densitometry with or without scoliosis or disc space osteoarthritis excluded.

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The presence of a vertebral compression fracture has been demonstrated to be a predictor of future fracture independent of bone mineral density in prospective cohort studies. Fan-beam densitometers are now available that can image the thoracic and lumbar spines and detect deformities consistent with fracture. We report a pilot study of 342 patients referred for bone densitometry who had lateral vertebral imaging performed.

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The CRH test may sometimes be useful in the differential diagnosis of Cushing's syndrome, because most patients with pituitary ACTH-dependent Cushing's syndrome (Cushing's disease) respond to CRH, but those with other causes of Cushing's syndrome usually do not. However, about 10% of Cushing's disease patients fail to respond to CRH. We wondered if we could eliminate these false negative results either by exploiting the potential additive or synergistic effects of another ACTH secretagogue or by reducing glucocorticoid inhibition of CRH's ACTH-releasing effect.

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ACTH secretion by tumors of nonpituitary origin is characteristically resistant to negative feedback regulation by glucocorticoids. One possible mechanism for the phenomenon could be a structural defect in the intracellular glucocorticoid receptor (GR). We studied the GR in DMS-79 cells derived from a human ACTH-secreting small cell lung cancer.

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While angina is not uncommonly seen in association with hyperthyroidism, only rare case reports have suggested that myocardial ischemia in this state may be due to coronary artery spasm. The authors review the literature and describe a case in which the repetitive occurrence of episodes of myocardial ischemia due to coronary spasm correlated with repeated transient elevations in thyroid hormone levels, thus clarifying this relationship. The importance of defining thyroid status in patients presenting with coronary vasospasm is emphasized and the effects of thyroid hormone on the heart are reviewed.

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We evaluated 20 patients with Cushing's disease (i.e., Cushing's syndrome due to ACTH-secreting pituitary microadenoma) and 20 patients with Major Depressive Disorder (MDD) using the Structured Clinical Interview for DSM-III-R (SCID) and Research Diagnostic Criteria.

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Cells of the immune system can produce and respond to peptide hormones associated with the endocrine system. However, the physiological significance of these endocrine-immune interactions is not known. It has been postulated that cells of the immune system, when stimulated with viruses that induce interferon-alpha, produce sufficient levels of ACTH to stimulate adrenal steroidogenesis and, thus, function as an auxiliary source of ACTH that may have a role in the response to stress.

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We report here a study of the plasma ACTH and corticosterone responses to synthetic ovine CRH (oCRH) in hypothyroid and hyperthyroid rats studied 7, 15, and 60 days after either thyroidectomy or the administration of pharmacological doses of T4. The purpose of this study was to further clarify the time-dependent effects of alterations in thyroid status on the functional integrity of the hypothalamic-pituitary-adrenal axis and to aid in the interpretation of the oCRH stimulation test in hypo- and hyperthyroid states. Our data demonstrate that hypothyroid rats have a significant reduction in the cerebrospinal fluid (CSF) levels of corticosterone and a significant decrease in adrenal weight in association with significant increases in the plasma ACTH response to oCRH.

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Hyperandrogenic states in women may alter hypothalamic pituitary response. The pituitary function of a 64-year-old postmenopausal woman with a testosterone-secreting (T-secreting) ovarian neoplasm was assessed with a combined infusion of ovine corticotropin releasing hormone, 1 microgram/kg; GnRH, 100 micrograms; human growth hormone releasing hormone, 1 microgram/kg; and TRH, 200 micrograms preoperatively when T and estradiol (E2) were elevated, six weeks postoperatively when T and E2 were low and 16 months postoperatively while the patient was on micronized E2 (low T, high E2). The principal findings were a reduction in luteinizing hormone response by both T and E2, no effect of either T or E2 on follicle stimulating hormone and greater growth hormone and TSH responses in an estrogenic milieu.

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Inappropriate ACTH secretion with bilateral diffuse or macronodular adrenal hyperplasia is the most common cause of Cushing's syndrome. This report describes a patient with Cushing's syndrome and feminization due to ACTH-independent bilateral macronodular adrenal hyperplasia. A 47-yr-old black man presented with Cushingoid features, diabetes mellitus, hypertension, impotence, and gynecomastia.

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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 micrograms/kg BW doses of oCRH. Placebo or oCRH (3 micrograms/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.

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The proopiomelanocortin (POMC) gene is expressed in many normal nonpituitary tissues, in addition to the pituitary. POMC-derived peptides have also been detected in many pheochromocytomas. We examined poly(A)+ RNA from 5 pheochromocytomas with a POMC exon 3 riboprobe and show that 3 tumors contained POMC-like mRNAs that were 50 to 350 bases longer than pituitary POMC mRNA.

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Immunoreactive (IR) POMC peptides have been detected in several human nonpituitary tissues and most pheochromocytomas and lung cancers, including those not associated with ectopic ACTH syndrome. We found IR-ACTH, IR-gamma MSH, IR-beta-endorphin (beta END), and IR-lipotropin in extracts from the following 10 normal human tissues, listed in order of decreasing POMC peptide concentrations: adrenal, testis, spleen, kidney, ovary, lung, thyroid, liver, colon, and duodenum. IR-ACTH, IR-gamma MSH, and IR-beta END were detected in all six pheochromocytomas and all 12 lung tumors (six squamous cell carcinomas, five adenocarcinomas, and one small cell carcinoma) we examined, as well as in a squamous cell carcinoma of the larynx.

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Immunoreactive (IR) POMC peptides have been found in several rat nonpituitary tissues. We found IR-ACTH, IR-beta-endorphin (beta END), and IR-gamma MSH in extracts from the following eight rat nonpituitary tissues, listed in order of decreasing POMC peptide concentrations: testis, duodenum, kidney, colon, liver, lung, stomach, and spleen, but not in adrenal or muscle extracts. Concentrations were very low and ranged from less than 0.

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The response of plasma immunoreactive (IR)-ACTH, IR-beta-endorphin (beta-END) and IR-cortisol to insulin-induced hypoglycaemia, an acute stimulus to the pituitary corticotrophs through the central nervous system, and to synthetic ovine corticotrophin-releasing hormone (CRH), a direct corticotroph stimulator, were studied in normal males and males with myotonic dystrophy. Myotonics had an increased IR-ACTH and IR-beta-END response to hypoglycaemia and an increased IR-ACTH response to CRH compared with normals. Plasma IR-cortisol response were not different in either group of subjects to both stimuli.

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A 15-year-old girl who presented with primary amenorrhea and virilization had an adrenocortical adenoma that secreted predominantly testosterone. To our knowledge, she is the first peripubertal and second youngest patient with a testosterone-secreting adrenal tumor described. Serum dehydroepiandrosterone sulfate and urinary 17-ketosteroid and 17-hydroxycorticosteroid levels were normal.

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To determine whether alterations in serum thyroid hormone levels affect hypothalamic-pituitary-adrenal function, we measured the plasma immunoreactive (IR) ACTH and IR-cortisol responses to 1 microgram/kg BW ovine CRH (oCRH) given iv in the late afternoon and the plasma IR-ACTH, IR-cortisol, and IR-11-deoxycortisol responses to 2 g metyrapone given orally at midnight in 10 athyreotic patients during T4 treatment and 1 month after stopping T4 when they were biochemically, but not clinically, hypothyroid. Mean serum TSH increased from 0.7 +/- 0.

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The factors that mediate the hypothalamic-pituitary response to hypoglycemia in man are unknown. To investigate the role of CRH in the plasma ACTH response to hypoglycemia, two different doses of ovine CRH (oCRH) were given to normal men during insulin-induced hypoglycemia. We hypothesized that if the endogenous CRH response to hypoglycemia were less than maximally stimulating, administration of oCRH during hypoglycemia would result in a greater peak plasma immunoreactive (IR) ACTH response.

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Synthetic ovine corticotropin-releasing hormone (oCRH) is a potent and specific ACTH secretagogue in man. Threshold and maximal i.v.

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The ability of single doses of a LHRH antagonist [Ac-delta 3Pro1, 4F-D-Phe2, D-Trp3,6]LHRH (4F-antagonist) to suppress serum gonadotropin and testosterone levels was studied in six normal men. The 4F-antagonist was given sc at four doses: 40, 80, 160, and 320 micrograms/kg body weight. Serum immunoreactive LH, FSH, and testosterone and bioactive LH were measured at intervals for the subsequent 18 h.

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To determine whether the plasma immunoreactive ACTH (IR-ACTH) and IR-cortisol responses to ovine corticotropin-releasing hormone (oCRH) depend on the time of day, we administered 1 microgram/kg BW synthetic oCRH as an iv bolus dose to five normal men at their usual time of awakening between 0530-0740 h, at 1600 h, and at 2300 h. Mean basal plasma IR-ACTH and IR-cortisol levels were highest upon awakening, intermediate at 1600 h, and lowest at 2300 h, reflecting the diurnal rhythm of ACTH secretion. There was no significant difference in the plasma IR-ACTH response to oCRH at different times of the day.

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