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Biomedical subjects

M Terzolo

Publications and source records attributed to M Terzolo.

69 records · Page 4Linked to original sources
PubMed1990

Morning to evening changes of human pituitary and adrenal responses to specific stimuli.

We performed a combined stimulation test with the simultaneous application of GnRH (100 micrograms), TRH (200 micrograms) and ACTH (10 micrograms) in 10 healthy adult males at two opposite clock timing, i.e. at 09:00 and 21:00 h. Pituitary (gonadotropins, PRL, TSH) and adrenal (cortisol, aldosterone, progesterone) hormones showed a common trend of enhanced responsiveness to the evening challenge. Differences reached statistical significance in the case of cortisol, aldosterone, PRL and FSH. These findings suggest that the responsiveness of some pituitary and adrenocortical hormones to specific stimuli is physiologically different in humans as a function of the clock timing, being higher in the evening than in the morning. From the clinical standpoint, however, differences in the magnitude of responses were not enough to recommend provocative testing at a particular clock time, at least for routine diagnostic purposes.

Adrenal Glands↗
PubMed1990

Effects of long-term, low-dose, time-specified melatonin administration on endocrine and cardiovascular variables in adult men.

Six healthy adult male volunteers underwent serial blood drawings at 4-hour intervals over 24 hours for the definition of melatonin (MT), prolactin (PRL), cortisol, and testosterone circadian patterns. Serum levels of triiodotironine (T3) and thyroxine (T4) were determined at 0800. Systolic and diastolic blood pressure and heart rate were automatically recorded every 30 minutes for 24 hours. The responses of luteinizing hormone (LH), follicle stimulating hormone (FSH), PRL, thyroid stimulating hormone (TSH), cortisol, and aldosterone to a stimulation test with gonadotrophin-releasing hormone (Gn-RH), thyrotrophin-releasing hormone (TRH), adrenocorticotrophin (ACTH), and testosterone to human chorionic gonadotrophin (HCG) were also evaluated. The same protocol was repeated after a two-month course of treatment with MT, 2 mg per os daily at 1800. After treatment, we recorded a marked elevation of mean serum MT levels with a significant phase-advance of its circadian rhythm. The 24-hour patterns of cortisol and testosterone displayed an anticipation of the morning acrophase of about 1.5 hour (not significant) for cortisol and three hours (P less than 0.05) for testosterone. PRL pattern was unchanged as well as serum levels of thyroid hormones. The circadian organization of the cardiovascular variables did not show any changes after MT supplementation; the pituitary, adrenal, and testicular responses to specific stimuli were comparable before and after treatment. These results are compatible with the view that the MT signal may provide temporal cues to the neuroendocrine network for the organization of testicular circadian periodicity.

Adrenocorticotropic Hormone↗
PubMed1990

Circadian profile of serum melatonin in Cushing's disease and acromegaly.

We evaluated the circadian profiles of serum melatonin (MT) and cortisol in 6 patients with Cushing's disease while those of serum MT and GH were evaluated in 8 patients with acromegaly. The control group consisted of 15 healthy subjects in whom MT, cortisol and GH were determined. The presence of a circadian rhythmicity was validated by the cosinor method, while the diurnal and nocturnal amount of MT secretion were expressed in terms of area under the curve. Gross alterations of MT rhythm were not apparent in Cushing's patients. In acromegalics, we observed a blunted day-night oscillation of MT accounted for by a significant increase of its secretion during the day-time period.

Acromegaly↗
PubMed1990

24-hour profiles of blood pressure and heart rate in Cushing's syndrome: relationship between cortisol and cardiovascular rhythmicities.

We monitored the circadian profiles of cortisol, systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR) in 33 matched normotensive subjects, 32 patients with essential hypertension and 16 patients with Cushing's Syndrome (8 pituitary adenomas, 6 adrenal adenomas and 2 adrenal carcinomas). Each subject underwent serial blood drawings at 4-hr intervals along the 24-hr cycle. BP and HR were automatically recorded every 30 min. Data were analyzed by conventional statistics and by chronobiological procedures (cosinor rhythmometry). Both the control subjects and essential hypertensives showed a circadian profile of BP and HR characterized by a peak in the early afternoon and a clear nocturnal fall (rhythm detection: P less than 0.001). The rhythmicity of BP was disrupted in patients affected by Cushing's Syndrome, whereas the 24-hr oscillation of HR was preserved (P less than 0.001). Our data are compatible with the view that glucocorticoids are involved in the control of BP circadian rhythm, whereas HR is not under their control.

Adult↗
PubMed1988

Ketoconazole treatment in Cushing's disease. Effect on the circadian profile of plasma ACTH and cortisol.

Ketoconazole is an inhibitor of adrenal steroidogenesis used in the treatment of Cushing's disease. Previous data obtained with single blood sampling were controversial as to increased ACTH levels compensatory to the cortisol fall. We have evaluated by chronobiological procedures the circadian profiles of plasma ACTH and cortisol in three patients with Cushing's disease before and after a six-month course of therapy with ketoconazole (600 mg daily). None of the patients complained of any adverse subjective reaction; in particular no sign or symptom of hypoadrenalism and/or hepatotoxicity was recorded. Ketoconazole treatment markedly improved the clinical setting and caused a highly significant (p less than 0.0001) reduction of mean 24-h cortisol values (ciradian MESOR). The expected rise of ACTH did not take place; rather, we detected a slight decrease of the mean circadian MESOR (p less than 0.05). Our data, althought obtained in a very small number of patients, suggest that ketoconazole may have an additional action at central level, at least in some cases of Cushing's disease.

Adrenocorticotropic Hormone↗
PubMed1987

Acute administration of melatonin at two opposite circadian stages does not change responses to gonadotropin releasing hormone, thyrotropin releasing hormone and ACTH in healthy adult males.

We evaluated the effect of a single oral administration of 100 mg melatonin (MT) vs placebo (PL) on the pituitary release of LH, FSH, TSH and prolactin (PRL) after GnRH + TRH and on the adrenocortical release of cortisol, aldosterone and progesterone after ACTH in healthy adult males. We carried out a double blind study in 6 volunteers in winter, at two opposite stages of the circadian cycle: 08:00 and 20:00 h. Injection of GnRH (100 micrograms), TRH (200 micrograms) and ACTH (10 micrograms of the synthetic ACTH 1-17 analogue, Alsactide) was performed one h after MT or PL ingestion. Plasma MT levels were 200-4,000-fold higher after MT than PL thus confirming the effective gastrointestinal absorption of the pineal hormone. The hormonal patterns were superimposable after MT and PL. A higher response of PRL, FSH and cortisol was observed in the evening vs morning protocols independently of previous MT or PL. Our data demonstrate that the acute oral administration of a pharmacological dose of MT at two opposite circadian stages is ineffective to change a variety of pituitary and adrenocortical responses in human male subjects. The circadian chronosusceptibility of pituitary and adrenocortical cells to specific stimuli deserves interest to future investigation.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Plasma steroid responses to circadian-stage-specified injection of different doses of the ACTH analogue alsactide (ACTH 1-17) in healthy adult human males.

Plasma cortisol, progesterone, testosterone and aldosterone levels were measured on serial blood samples drawn in 10 healthy adult human males up to 6h after single administration at about 07 of increasing amounts of the short-chain analogue ACTH-agonist alsactide (Synchrodyn 1-17). The following doses were employed: 2, 4, 8, 10 and 20 micrograms subcutaneously (s.c.), as well as 2, 4 and 8 micrograms intravenously (i.v.). Data were compared with those obtained by placebo (isotonic saline) injections. The s.c. injections of 2 and 4 micrograms resulted to be ineffective in changing the hormonal pattern. A significant rise of cortisol and progesterone, but not of aldosterone and testosterone, followed the s.c. injections of 8 and 10 micrograms. The differential pattern of the glucocorticoid vs. the mineralocorticoid response was also apparent after the s.c. injection of 20 micrograms alsactide; when compared with placebo, this dose was able to elicit a significant increase of all examined hormones except testosterone. All i.v. injections of 2, 4 and 8 micrograms alsactide were effective; the highest dose did cause a sustained rise of plasma cortisol, progesterone and aldosterone, but also the other doses were able to change significantly the mineralocorticoid levels. These results provide evidence that circadian-stage-specified s.c. or i.v. administration of the analogue can be employed in the clinical practice for enhancing selectively and transiently the morning glucocorticoid secretion.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Bilateral adrenalectomy for Cushing's syndrome: a comparison between laparoscopy and open surgery.

We report our experience with bilateral adrenalectomy for treatment of Cushing's syndrome and we compare the outcome of laparoscopy with open surgery in terms of effectiveness and safety. A series of 23 patients underwent bilateral adrenalectomy for treatment of Cushing's syndrome [Cushing's disease in 16, ectopic ACTH syndrome in 2, and ACTH-independent macronodular adrenal hyperplasia (AIMAH) in 5 cases]. From 1993 to 1996, all patients were treated using an open approach (Group A), while from 1997 all patients were treated using a transperitoneal laparoscopic approach (Group B). The comparison between the 2 groups was performed considering patients characteristics, operative times, blood losses, intraoperative and post-operative complications, analgesic consumption, post-operative hospital stay and recovery. Open surgery was performed in 10 patients and laparoscopy in 13 patients. No significant difference was recorded between the two groups as to patients' characteristics and complications. Mean operative time was significantly increased in Group B, while post-operative hospital stay was significantly longer in Group A. Laparoscopic bilateral adrenalectomy can be safely and effectively employed to treat Cushing's syndrome. However, long operatives times may represent a limitation especially in high risk patients.

Adrenalectomy↗
PubMedDate not supplied

[Glucocorticoid-induced osteoporosis: recent findings].

The clinical features, pathogenesis and management of bone involvement in Cushing's syndrome are briefly reviewed. Personal data on bone mineral density and markers of bone turnover in Cushing's syndrome and adrenal incidentalomas are also reported. As long ago as 1932, Harvey Cushing recognized osteoporosis as a serious consequence of endogenous hypercortisolism. The introduction of cortisone in the therapy of autoimmune, rheumatic, allergic or dermatologic disorders was followed by several reports of detrimental effects on bone of patients who had undergone prolonged glucocorticoid treatment. Due to the rarity of Cushing's syndrome, most of the studies in the literature on glucocorticoid-induced osteoporosis refer to exogenous over-exposure to cortisone and its synthetic derivatives. Only a small number of works concern endogenous hypercortisolism, even if the characteristics of bone damage seem qualitatively the same. Finally, very few data are reported on the hypothetical detrimental effect on bone in the condition of the silent hypercortisolism of adrenal incidentalomas. Glucocorticoid-induced osteoporosis in Cushing's syndrome often results in vertebral fractures, and bone loss is more evident in trabecular than in cortical bone. Notwithstanding some distinctive features in osteoporosis induced by endogenous and exogenous glucocorticoid excess, the common eventual picture is notable bone damage that involves mainly the trabecular bone. Prompt and effective therapy is mandatory to reduce the risk of fractures. The present options include calcium and vitamin D supplementation, estrogen replacement therapy, bisphosphonates, either oral or parenteral. A novel approach to the clinical problem of glucocorticoid-induced osteoporosis might, in the future, be based on studies on selective glucocorticoid receptor modulators, a new class of synthetic glucocorticoids that exhibit significant anti-inflammatory and immunosuppressive activities, with reduced side effects on bone.

Adrenal Cortex Neoplasms↗
PubMedDate not supplied

Similarity of the nocturnal profile of serum melatonin at early puberty and early adulthood.

In the present study we determined the nocturnal profile of serum melatonin (MT) concentrations in 10 short normal children at Tanner stage I-II of pubertal development (12.5-14.9 yrs) and in 6 young adults (24-29 yrs). Blood was collected every 30 min from 00(00) to 06(00). We did not find any significant difference in the nocturnal profile of serum MT, as gauged by the comparison of MT concentrations at any time-point tested as well as of the transverse means (84.2 +/- 36.0 pg/ml [M +/- SD] in the children vs 78.7 +/- 10.8 pg/ml in the adults). Mean serum melatonin concentration was not correlated to sex hormone concentration or body surface area. Our findings do not support the view that MT concentrations fall at the beginning of pubertal development and that changes in body size may be the reason for age-dependent changes of serum MT concentrations.

Adolescent↗
PubMedDate not supplied

24-hour profiles of blood pressure and heart rate in Cushing's syndrome. Evidence for differential control of cardiovascular variables by glucocorticoids.

We monitored the circadian profile of cortisol, systolic and diastolic blood pressure (SBP and DBP), heart rate (HR) in 33 normotensive subjects aged 20-40 years, 20 normotensive subjects aged 40-60, 32 patients with essential hypertension and 13 patients with Cushing's syndrome (6 pituitary adenomas, 5 adrenal adenomas and 2 adrenal carcinomas). All controls and patients underwent serial blood drawings at 4-h intervals during the 24-h cycle. BP and HR were recorded every 30 min by an automatic, room-restricted instrument. Data were analyzed by conventional statistics and by chronobiological procedures (cosinor rhythmometry) to quantify rhythm parameters such as the MESOR (rhythm-adjusted average), amplitude (difference between maximum and MESOR) and acrophase (timing of the crest of the rhythm). Both the control and essential hypertensive subjects showed a BP and HR circadian profile characterized by a peak in the early afternoon and a clear nocturnal fall (rhythm detection: p less than 0.001). The chronobiological analysis did not reveal any significant difference between healthy young and aged subjects. BP rhythmicity was disrupted in patients affected by Cushing's syndrome, whereas the 24-h oscillation of HR was preserved (p less than 0.001). Patients with pituitary-dependent Cushing's syndrome had higher BP levels than adrenal-dependent subjects (p less than 0.001). Our data are compatible with the view that glucocorticoids are involved in the control of BP circadian rhythm, whereas HR is not under their control.

Adenoma↗
PubMedDate not supplied

Effects of exogenous melatonin on human pituitary and adrenal secretions. Hormonal responses to specific stimuli after acute administration of different doses at two opposite circadian stages in men.

We evaluated the effect of an acute oral administration of 2 dosages (100 and 1 mg) of melatonin (MT) vs placebo (PL) on pituitary release of LH, FSH, TSH and PRL after GnRH + TRH and on the adrenocortical release of cortisol, aldosterone and progesterone after ACTH in healthy adult males. We carried out a double blind study on 6 volunteers in winter-early spring, at 2 opposite phases of the circadian cycle: 08(00) and 20(00). Injection of GnRH (100 micrograms), TRH (200 micrograms) and ACTH (10 micrograms of the synthetic analogue ACTH 1-17, alsactide) was performed 1 h after MT or PL ingestion. The measurement of plasma MT levels confirmed its effective gastrointestinal absorption after both doses. The hormonal patterns were superimposable after MT and PL. A higher response of FSH, PRL, cortisol and aldosterone was observed in the evening vs morning protocols independently of previous treatment (MT or PL). Our data demonstrate that the acute oral administration of 2 different doses of MT at 2 opposite circadian stages is ineffective as to the modification of a variety of pituitary and adrenocortical responses in human male subjects. The circadian chronosusceptibility of pituitary and adrenocortical cells to specific stimuli deserves interest to future investigation.

Adrenal Cortex Hormones↗
PubMedDate not supplied

High frequency of p53 expression in colo-rectal adenomatous polyps.

Previous studies on p53 protein expression in colonic adenomas showed controversial results. The present study evaluates the p53 expression in colonic adenomas, at different dysplasia degrees, by immunohistochemical analysis, using a newly introduced monoclonal anti-p53 antibody. Paraffin embedded sections of 48 colorectal adenomas, 5 colonic carcinomas and 11 normal colonic biopsies were studied by immunohistochemical analysis using a monoclonal mouse anti-p53 antibody (clone DO-1). Normal colonic mucosa specimens and 5/48 adenomas were found negative for p53 staining. p53-positive nuclei were less than 10% in 22/48 and between 10 and 40% in 15/48 adenomas. In 6/48 adenomas and in 4/5 carcinomas we found a high percentage of p53-positive nuclei (> 40%). Immunohistochemical p53-positivity is a common event in colonic adenomas, not dependent on dysplasia degree. It might be the result of p53 wild-type increase, due to the typical genomic instability of colonic adenomas.

Adenomatous Polyps↗