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G Chrousos

Publications and source records attributed to G Chrousos.

35 records · Page 2Linked to original sources
PubMed1991

Neuroendocrine tumors of the lung with proposed criteria for large-cell neuroendocrine carcinoma. An ultrastructural, immunohistochemical, and flow cytometric study of 35 cases.

Based on our review of 35 cases and the literature, we found the spectrum of pulmonary neuroendocrine (NE) tumors to be too broad to fit into the traditional three-category classification scheme of typical carcinoid (TC), atypical carcinoid (AC), and small-cell lung carcinoma (SCLC). We found that a spectrum of high- and low-grade tumors exist between TC and SCLC and that in the past many of these tumors have been called AC. We chose to adhere to Arrigoni's definition of AC, as his original criteria characterized a low-grade tumor. For the higher grade non-small-cell tumors (NSCLC), we propose a fourth category of large-cell neuroendocrine carcinoma (LCNEC), which is characterized by: (a) light microscopic NE appearance; (b) cells of large size, polygonal shape, low nuclear-cytoplasmic ratio (N:C), coarse nuclear chromatin, and frequent nucleoli; (c) high mitotic rate [greater than 10/10 high-power fields (HPF)] and frequent necrosis; and (d) NE features by immunohistochemistry (IHC) or electron microscopy (EM). Thus, after deciding that a pulmonary NE tumor is high grade, the major diagnostic issue is separation of LCNEC from SCLC. This distinction is based not only on cell size, but on a variety of morphologic features. We studied 20 TC, six AC, five LCNEC, and four SCLC and characterized the clinical, light microscopic, EM, IHC, and flow cytometric features of each type of tumor. We did not find any advantage to IHC, EM, or flow cytometry over light microscopy in the subclassification or prediction of prognosis; however, these methods were useful in characterizing these four types of pulmonary NE tumors and in demonstrating their NE properties. LCNEC must be distinguished from a fifth category pulmonary NE tumor: NSCLC with NE features in which NE differentiation is not evident by light microscopy and must be demonstrated by EM or IHC. Although the prognosis of LCNEC appears to be intermediate between AC and SCLC, larger numbers of patients will be needed to demonstrate significant differences in survival.

Adrenocorticotropic Hormone↗
PubMed1991

Corticotropin-releasing hormone is not the sole factor mediating exercise-induced adrenocorticotropin release in humans.

To determine whether CRH is the sole mediator of ACTH release during exercise, five men and five women were given, in a subject-blinded random manner at separate visits, both a 6-h infusion of ovine CRH (1 microgram/kg.h) and a saline infusion as a placebo. After the fourth hour of each infusion, when plasma concentrations of ovine CRH were sufficiently elevated to saturate the capacity of the corticotroph to respond further to CRH, each subject completed a high intensity intermittent run. Plasma ACTH and cortisol levels increased significantly during the CRH infusion from 4.6 +/- 0.8 (mean +/- SE) to 8.6 +/- 1.6 pmol/L and from 361 +/- 39 to 662 +/- 70 nmol/L, respectively (P less than 0.05). Despite elevated preexercise cortisol levels during the CRH infusion, plasma ACTH rose to 32.0 +/- 8.5 pmol/L after exercise. During the saline infusion, plasma ACTH rose from 3.4 +/- 0.6 pmol/L before exercise to 18.1 +/- 4.2 after exercise. Time-integrated responses for postexercise values of ACTH and cortisol were higher during the CRH infusion than during the saline infusion (P less than 0.05). No significant exercise-induced differences in heart rate or plasma concentrations of lactate, epinephrine, and norepinephrine were observed between the two tests. The findings suggest that some factor(s) in addition to CRH causes ACTH release during exercise. Vasopressin, produced by the magnocellular and/or parvocellular neurons of the hypothalamus, is a likely candidate.

Adrenocorticotropic Hormone↗
PubMed1990

Bilateral orbital involvement in fatal giant cell polymyositis.

The case of a young woman with giant cell polymyositis is described. She had bilateral, severe, midly painful proptosis and ophthalmoplegia. Extensive pharyngeal, laryngeal, and cardiac muscle involvement occurred 18 months later coincident with fatal cardiac arrhythmia. At autopsy, extensive muscle necrosis and giant cells were noted in extraocular, pharyngeal, laryngeal, and cardiac muscle with only minimal involvement of other striated muscles.

Adult↗
PubMed1990

The hypothalamic-pituitary-adrenal axis in infantile malnutrition.

We studied the circadian rhythm and the response of the hypothalamic-pituitary-adrenal (HPA) axis to ovine corticotrophin releasing hormone (oCRH) stimulation and dexamethasone suppression in 32 children with grade II-III marasmus. Children were studied prior to and after nutritional rehabilitation. Mean baseline plasma cortisol concentrations were elevated at admission and decreased significantly after nutritional rehabilitation. Mean +/- SEM plasma cortisol response to oCRH increased from a basal of 480 +/- 41 to a peak of 582 +/- 58 nmol/l at the time of admission, and from a basal of 234 +/- 27 to a peak of 532 +/- 41 nmol/l after caloric rehabilitation. Dexamethasone suppression in the malnourished group was associated with a decrease in the mean +/- SEM basal plasma cortisol concentration from 397 +/- 44 to 171 +/- 44 nmol/l. After caloric rehabilitation, basal cortisol levels decreased from 259 +/- 27 to 22 +/- 5 nmol/l following dexamethasone. Our results support the concept that malnutrition is associated with decreased responsiveness to oCRH and incomplete dexamethasone suppression, and that these abnormalities are restored after nutritional rehabilitation.

Child, Preschool↗
PubMed1990

Petrosal sinus sampling: discordant lateralization of ACTH-secreting pituitary microadenomas before and after stimulation with corticotropin-releasing hormone.

Petrosal sinus sampling was performed 171 times in 157 patients with known or suspected Cushing disease. In all cases, samples for measuring adrenocorticotropic hormone (ACTH) levels were obtained from both inferior petrosal sinuses and a peripheral vein, both before and after intravenous corticotropin-releasing hormone (CRH) administration. In seven examinations in seven patients, a ratio, or gradient, between the ACTH levels in the inferior petrosal sinuses existed in the samples obtained prior to CRH stimulation; however, poststimulation samples demonstrated reversal of the gradient, suggesting lateralization to the contralateral side of the pituitary gland. Data from surgical exploration of the pituitary gland were available for six of these patients, all of whom had adenomas. Prestimulation samples provided correct lateralization in three patients, and in two patients the poststimulation samples provided correct lateralization. One patient had a midline adenoma. When the results of pre- and poststimulation petrosal sinus sampling conflict, neither can be relied on uniformly to provide correct lateralization of ACTH-secreting pituitary adenomas.

Adenoma↗
PubMed1990

Recovery of the rat hypothalamic-pituitary-adrenal axis after discontinuation of prolonged treatment with the synthetic glucocorticoid agonist dexamethasone.

To evaluate the recovery of the hypothalamic-pituitary-adrenal (HPA) axis after discontinuation of prolonged exposure to glucocorticoids, we employed adult male Sprague-Dawley rats which were implanted sc with osmotic minipumps filled with saline (vehicle) or dexamethasone (DEX), 100 micrograms/day, for 7 days. At the end of the glucocorticoid treatment period, the minipumps were removed and both saline- and DEX-treated rats were randomly assigned to five different groups tested at 1, 3, 7, 14, and 21 days after removal of the minipumps. Each group was divided into two subgroups receiving either arecoline (ARE), or ovine CRH (oCRH) stimulation tests. ARE was chosen because it has been shown to selectively stimulate the hypothalamic CRH neuron, whereas oCRH was selected as a probe of the pituitary component of the HPA axis. ARE (0.2 mg/kg) and oCRH (10 micrograms/kg) were injected iv to catheterized, freely moving rats and serial blood samples for plasma ACTH and corticosterone determinations were drawn from the catheter before, and 5, 15, 30, and 60 min after the injection. The day after the tests were performed, the rats were killed by decapitation, and body, adrenal and thymus weights, as well as hypothalamic CRH and pituitary ACTH content were determined. On the day of the stimulation tests, basal plasma levels of ACTH and corticosterone were not different between saline- and DEX-treated rats at any time-point after discontinuation of treatment. The ACTH response to ARE, on the other hand, was suppressed one day after, but became normal 3 days after discontinuation of DEX treatment. ACTH response to oCRH normalized later, after 7 days. Interestingly, corticosterone responses to both ARE and oCRH normalized 7 days after discontinuation of glucocorticoid administration. Body, adrenal and thymus weights were significantly reduced by DEX treatment. They recovered slowly and only after 22 days there was no difference between DEX- and saline-treated rats in body and adrenal weight. In contrast, thymus weight was still low on day 8, began to increase after 15 days, and by day 22 did not reach the values recorded in saline-treated rats. Hypothalamic immunoreactive CRH content was not different between DEX- and saline-treated rats, whereas the content of ACTH in the pituitary gland was lower in the DEX-treated rats the second day after discontinuation of GC treatment, normalized after 4 days and increased significantly after 8 days.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Glands↗
PubMed1986

CRF-induced seizures and behavior: interaction with amygdala kindling.

Intracerebroventricular (i.c.v.) administration of ovine corticotropin-releasing factor (CRF) in doses varying from 10 to 100 micrograms has been reported to produce the late onset of seizures that resemble those observed during electrical kindling of the amygdala. We assessed the effects of repeated CRF administration on seizure development and on subsequent electrical kindling of the amygdala. Rats were administered vehicle or CRF (100 micrograms in 10 microliter of sterile water, i.c.v.) once daily for 5 consecutive days and were rated for seizures and aggressive behavior. On days 1 or 2, all animals receiving CRF developed major motor seizures of late onset (1-5 h post-injection), accompanied by spiking in the amygdala. By day 5, however, no rats had seizures, suggesting the development of tolerance. Defensive biting attacks were also observed following latencies of several hours and tolerance appeared to develop to these as well. After the CRF regimen, treated rats developed amygdala-kindled seizures following electrical stimulation approximately twice as fast as vehicle-injected controls (P less than 0.03). In a second experiment, rats were electrically kindled or sham-kindled prior to receiving i.c.v. CRF (100 micrograms). Kindled animals were significantly less sensitive to the seizure-inducing effects of CRF (P less than 0.03), but were more intensely aggressive than sham-kindled animals or naive rats receiving CRF for the first time.

Amygdala↗
PubMed1986

Benzodiazepine sensitivity in normal human subjects.

Increasing intravenous doses of diazepam or placebo were administered to ten healthy normal volunteers, and the changes in saccadic eye velocity, self-rated sedation and anxiety, and plasma cortisol and growth hormone concentrations were measured. Diazepam administration (4.4 to 140 micrograms/kg, cumulative dose) resulted in a dose-dependent decrease in saccadic eye velocity and plasma cortisol level as well as a dose-dependent increase in self-rated sedation and plasma growth hormone level. Self-rated anxiety was unaffected in these relatively nonanxious subjects. The diazepam-induced changes in saccadic eye velocity, sedation, and growth hormone and cortisol levels were highly correlated with each other and with increasing plasma diazepam concentration. These results are consistent with a benzodiazepine receptor-mediated action of diazepam. The highly quantifiable and dose-dependent decrease in saccadic eye velocity by benzodiazepines should make this a useful measure of benzodiazepine receptor sensitivity in humans.

Adult↗
PubMed1986

The corticotropin-releasing hormone stimulation test in chronic schizophrenia.

During a drug-free period a group of schizophrenic subjects (N = 9) showed normal mean basal plasma ACTH and cortisol levels in association with normal plasma ACTH and cortisol responses to an infusion of corticotropin-releasing hormone (CRH). Administration of fluphenazine had no effect on basal ACTH and cortisol levels or their responses to CRH (N = 8). These data differ from those previously reported in depressed patients, who showed elevated basal cortisol values in association with a blunted ACTH response to CRH, and add to a growing body of literature which suggests that hypothalamic-pituitary-adrenal regulation is less disturbed in schizophrenia than in depression.

Adrenocorticotropic Hormone↗
PubMed1984

Ocular findings in Turner syndrome. A prospective study.

We performed complete ophthalmological examinations of 30 consecutive patients with Turner syndrome. Twenty-three had 45XO and 7 had 45XO/46XX karyotypes (mosaicism). Non-familial strabismus was the most prominent ocular abnormality and was present in 33% of the patients. Other eye findings included ptosis (16%), hypertelorism (10%), epicanthus (10%), and antimongoloid slants (10%). Red-green color deficiency was found in 10% of the patients. One patient had congenital periodic alternating nystagmus.

Adolescent↗
PubMed1984

Psychiatric implications of basic and clinical studies with corticotropin-releasing factor.

Corticotropin-releasing factor (CRF) is a newly sequenced neuropeptide thought to be a principal stimulus to pituitary corticotropin (ACTH) secretion. Evidence obtained from laboratory animals and primates is reviewed which indicates that CRF not only stimulates the pituitary-adrenal axis but also influences several aspects of CNS function which may be of relevance to psychiatric illness. Clinically, experience in administering ovine CRF to more than 150 individuals shows that CRF can be helpful in resolving differential diagnostic dilemmas in patients with various disorders of the hypothalamic-pituitary-adrenal axis and in furthering an understanding of the pathophysiology of conditions such as Cushing's disease and depression.

Adrenocorticotropic Hormone↗
PubMed1983

Analogies between Cushing's disease and depression: a case report.

A case report is used to illustrate the difficult differential diagnostic dilemma between depression and Cushing's disease that has led to extensive scientific collaboration to test the hypothesis that both diagnoses may fall within a pathophysiological continuum. Unique to the collaborative study underway is the commitment of psychiatric clinical investigators to bring state of the art techniques for studying neurobiology in a disease traditionally viewed as medical, and of endocrinologists to address their expertise in a disease viewed primarily as psychiatric.

Adult↗
PubMed1982

Churg-Strauss syndrome. Development of cardiomyopathy during corticosteroid treatment.

A patient with Churg-Strauss syndrome had pulmonary lesions, vasculitis, gastrointestinal tract involvement, and leukocytosis with hypereosinophilia. A wedge section from the lung showed necrotizing granulomata filled with necrotic eosinophils and fibrinoid, and rimmed by giant cells and eosinophils. Arteries and veins of all sizes were affected with perivascular eosinophilic-rich, palisaded, giant cell granulomata with evidence of partial or complete occlusion. The patient was treated with prednisone, with excellent resolution of his symptoms. Recurrent episodes of pneumonia and wheezing responded to increased levels of prednisone plus bronchodilators and antibiotics. Cardiomyopathy developed after two years while taking prednisone. His condition has been managed with digoxin, diuretics, and increased amount of prednisone. Although our patient has shown clinical improvement in his cardiac status, objective studies show minimal resolution.

Adolescent↗
PubMedDate not supplied

Pre- and post-dexamethasone plasma ACTH levels in depressed patients and normal controls.

Levels of plasma ACTH in relation to dexamethasone administration were evaluated in 16 medication-free patients with a major depressive episode and 39 normal controls. Depressed patients had significantly higher levels of plasma ACTH than controls both at 4:00 p.m. predexamethasone and 4:00 p.m. postdexamethasone. The significance of this finding is discussed.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Birth size and neonatal levels of major components of the IGF system: implications for later risk of cancer.

Pre- and perinatal conditions and processes may affect the risk for some forms of cancer in later life, while the insulin-like growth factor (IGF) system may play a role in both early somatic growth and later carcinogenesis. Birth weight and length, and the variation of major components of the IGF system immediately after birth, were analyzed in relation to selected physiological and pathological variables. The study comprised 331 healthy full-term newborns from whom blood samples were taken during routine phlebotomy no later than the fifth day of life. Measurements of IGF-I, IGF-II and IGF-binding protein-3 concentrations were performed. Birth length and weight were measured and information on socio-economic and medical variables was recorded. The concentrations of all three proteins were lower when blood bilirubin levels were high, possibly as a result of compromised liver function and/or as a component of an activated acute phase reaction. Birth weight was significantly higher by about 46 g among children whose IGF-I was higher by one SD, while the associations of birth weight and length with other components of the IGF system were in the predicted directions, albeit only in trend. We conclude that in early life, growth is related to the IGF system, mostly IGF-I. The latter is lower in children with jaundice, possibly because of hepatic dysfunction and/or as part of an acute phase reaction. We speculate that elevations of IGF-I in early life might explain the increased risk of cancer in individuals born with a higher birth weight.

Adult↗