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Biomedical subjects

M Terzolo

Publications and source records attributed to M Terzolo.

At least 55 records · Page 3Linked to original sources
PubMed1995

Circadian profile of serum melatonin in patients with Cushing's syndrome or acromegaly.

We evaluated the 24-h profile of serum melatonin (MT) in 16 patients with Cushing's syndrome (11 pituitary- and 5 adrenal-dependent) aged 38.1 +/- 13.8 years and in 19 patients with acromegaly due to GH-secreting pituitary adenoma aged 52 +/- 11.9 years. Thirty-three healthy subjects aged 30 +/- 7 years and 26 healthy subjects aged 59 +/- 12 years served as age-matched controls for the two groups of patients, respectively. All the patients had active disease and were off treatment; none had overt hypopituitarism. Blood drawings were collected at 08:00, 12:00, 16:00, 20:00, 22:00, 24:00, 02:00, 04:00 and 06:00 h in controls and patients. Serum MT, cortisol, GH and IGF-I were measured by specific RIA kits and ACTH by IRMA. Cosinor rhythmometry was employed for chronobiological analysis. The acromegalic patients displayed, as a whole group, higher 24-h mean MT levels with respect to age-matched controls (M +/- SD: 52.9 +/- 14.6 vs 32.9 +/- 8.0 pg/ml, p < 0.01) with normally synchronized MT profiles in 11/19 patients. No correlation was apparent between MT and either GH (24-h mean) or IGF-I. In the patients with Cushing's syndrome the circadian profile of serum MT was maintained in 10/16 cases; serum MT levels were comparable to those of controls (48.8 +/- 14.0 vs 50.0 +/- 16.0 pg/ml, NS) without any difference between pituitary- and adrenal-dependent forms. No correlation was found between MT and either ACTH or cortisol levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1995

Doppler echocardiographic patterns in patients with acromegaly.

Cardiovascular problems have long been recognized as responsible for an increased morbidity and mortality in patients with acromegaly. The aim of the present study was to evaluate echocardiographically the prevalence of cardiomyopathy in a cohort of acromegalic patients and to analyze the results in relation to demographic, clinical and hormonal data. This study, a retrospective controlled clinical trial, was performed in 25 acromegalic patients, 12 men and 13 women aged 26-66 years (mean: 52.6). Fifteen patients had an active disease, 10 were cured by previous pituitary surgery. The same echocardiographic parameters were analyzed in 50 healthy subjects aged 30-70 years (mean: 51.4). Serum GH was determined on at least 4 samples drawn over 24 hours and plasma IGF-I on a single point. Standardized parameters of diastolic and systolic function were evaluated by real-time Doppler echocardiography. Twelve patients with active acromegaly underwent also 48-hour ECG registering. Left ventricular (LV) hypertrophy was found in 14/25 patients (56%). No difference was found between patients with active disease (53%) and patients with cured acromegaly (60%). LV mass index was significantly increased in acromegalics in comparison with healthy subjects (137 +/- 43 g/m2 vs 96 +/- 16 g/m2, p < 0.01) and also the indices of LV diastolic function were significantly impaired. Asymmetric septal hypertrophy was found only in one patient. Hypertension was detected in 9/25 patients (36%) without difference between patients with active or cured disease (40% vs 30%, NS). No significant correlation was found between hormonal or clinical data and echocardiographic findings. During Holter monitoring, heart rate of acromegalics was not significantly different from that of controls (78 +/- 12 bpm vs 72 +/- 10 bpm, NS) and only isolated supraventricular or ventricular premature complexes (Lown class 1) were detected. In conclusion, this study provides evidence of subclinical LV dysfunction in acromegaly in the absence of other known causes of heart disease and no significant difference in echocardiographic pattern was apparent between active or cured acromegalics.

Acromegaly↗
PubMed1995

Misdiagnosis of Cushing's syndrome in a patient receiving rifampicin therapy for tuberculosis.

We hereby describe a patient in whom chronic rifampicin treatment led to a misdiagnosis of Cushing's syndrome. He had long-standing insulin-dependent diabetes mellitus and active tuberculosis resistant to conventional treatment. The course was complicated by muscle weakness, lower limb atrophy, unstable glycemic control and hypokalemia. Ectopic Cushing's syndrome was suspected on the basis of high urinary free cortisol excretion (UFC) with a blunted circadian profile of serum cortisol and measurable plasma ACTH concentrations. Dynamic endocrine tests and imaging studies were compatible with occult ectopic ACTH syndrome. After substitution of rifampicin UFC excretion returned to normal within two weeks, as well as the 24-h cortisol profile and dynamic tests. The present case provides a practical example of the possibility to incorrectly suspecting Cushing's syndrome in patients treated with rifampicin, as previously envisaged by pharmacological studies.

Adrenocorticotropic Hormone↗
PubMed1995

Circadian variations of thyrotropin bioactivity in normal subjects and patients with primary hypothyroidism.

Circadian rhythm of TSH secretion is characterized by a pronounced nocturnal increment that is not followed by the expected rise of circulating thyroid hormone levels. These findings suggest that the nocturnal TSH surge may be constituted by molecules with reduced bioactivity. We, therefore, investigated TSH bioactivity (measured as cAMP accumulation in FRTL-5 cells) and its carbohydrate structure (by Concanavalin A affinity chromatography) in different blood pools taken during the day and night from seven normal subjects and from one patient with mild (mPH) and five with severe primary hypothyroidism (sPH). Patients with sPH were also studied during low dose L-T4 treatment. Cosinor analysis showed a significant TSH circadian rhythm in the control group and in L-T4-treated sPH patients. The nocturnal TSH surge was not followed by any increase in free thyroid hormone levels. In normal subjects, the daytime ratio of TSH bioactivity to immunoreactivity (TSH B/I) was higher than the nocturnal one [1.4 +/- 0.6 (+/- SD) vs. 1.1 +/- 0.6; P < 0.02]. The same pattern was observed in the only mPH patient (1.0 +/- 0.2 vs. 0.7 +/- 0.1; P < 0.01), but not in the sPH patients (0.8 +/- 0.3 vs. 0.7 +/- 0.1; P = 0.3). L-T4 administration to sPH patients caused the daytime TSH B/I to increase and restored the day/night difference in the TSH B/I (1.0 +/- 0.3 vs. 0.8 +/- 0.3; P < 0.02). Concanavalin A chromatography showed that a higher percentage of less mature forms of TSH are secreted during the night. These data indicate that TSH molecules secreted during the night are less bioactive and differently glycosylated than those circulating in the same individual during the day, thus explaining why thyroid hormone levels do not rise after the nocturnal TSH surge. In sPH patients, the TSH circadian rhythm is restored during L-T4 administration, and day/night differences in TSH B/I similar to those recorded in normal subjects are observed.

Adult↗
PubMed1995

Adrenal incidentaloma, a five year experience.

Since 1989, 45 patients 26 females and 19 males, aged 19-79 years (median 58) bearing incidentally discovered adrenal masses were studied. Endocrine work-up included determination of urinary catecholamines and their metabolites, measurement of plasma renin activity and aldosterone levels in clino- and orthostatic posture, basal and dynamic (dexamethasone-suppression, o-CRH stimulation) evaluation of hypothalamic-pituitary-adrenal (HPA) axis. The most frequent finding was the reduction of DHEA-S levels below the 3rd percentile of controls in 19 (42%) patients. As a whole group, DHEA-S levels were significantly lower in patients than in controls: 68 (5-1000) micrograms/dL vs 208 (34-326) micrograms/dL; p < 0.001. Three patients (7%) had high 24-h mean serum cortisol levels and 6 (14%) had blunted day-night amplitude of cortisol rhythm. Defective dexamethasone suppressibility was found in 15% of patients vs 8% of controls (p < 0.05). ACTH and cortisol responses after o-CRH did not significantly differ between patients and controls although blunted ACTH responses were found in 22% of cases. The above mentioned endocrine alterations could be accounted for by autonomous cortisol secretion by the adrenal nodule at a rate not sufficient to give clinical expression but able to inhibit to some extent the HPA axis. These results indicate that silent cortisol hypersecretion is frequently observed in patients with adrenal incidentaloma even if progression to overt Cushing's syndrome seems unlikely, at least in a short-term follow-up. From a mere cost-benefit ratio, the evaluation of DHEA-S levels and dex-suppression has sufficient sensitivity to identify the occurrence of silent hypercortisolism.

Adenoma↗
PubMed1994

High prevalence of colonic polyps in patients with acromegaly. Influence of sex and age.

BACKGROUND: An association between acromegaly and colonic polyps has been reported, although risk factors are still uncertain. METHODS: Full colonoscopy was performed with a fiberoptic colonoscopy on 31 acromegalic patients, 11 men and 20 women aged 27 to 85 years (mean, 52.2 years), and on 236 subjects, 127 men and 109 women aged 23 to 84 years (mean, 50.1 years), referred for hemorrhoids, who were considered controls. The colonoscopic findings were evaluated in relation to demographic, clinical, and hormonal data pertaining to the two groups. RESULTS: The prevalence of either adenomatous or hyperplastic polyps was higher in acromegalic patients than in controls (38% vs 14% and 26% vs 10%, respectively; P < .001, respectively). Acromegalics with and without colonic adenomas did not differ significantly in growth hormone and insulinlike growth factor I levels or duration of acromegalic disease and its status (activity or remission); however, patients with adenoma were younger (median age, 50.5 vs 59 years; range, 27 to 85 years vs 39 to 66 years; P < .05). An opposite age pattern was observed in the control group. Indeed, the prevalence of adenoma in acromegalic patients was much higher than that in controls among those less than 50 years of age (46% vs 7%, P < .001); the difference was less remarkable at older ages. Adenomatous polyps were more frequently found in male subjects, in both patients and controls (45% vs 33% [not significant] and 19% vs 9% [P < .05], respectively). CONCLUSIONS: Acromegaly may carry an increased risk of colonic adenoma, especially in younger patients, who usually display more aggressive disease. A smaller increase in risk was observed in elderly patients, in whom disease is reportedly milder. We suggest that acromegalic patients should undergo screening colonoscopy.

Acromegaly↗
PubMed1994

Cyclic Cushing's syndrome due to ectopic ACTH secretion by an adrenal pheochromocytoma.

Pheochromocytoma is a rare cause of ectopic Cushing's syndrome. We report on such a patient in whom ectopic ACTH secretion displayed a cyclic pattern. A 35-year-old woman was referred to us with a diagnosis of ACTH-dependent Cushing's syndrome. A 3.3 cm left-sided adrenal mass was noted at abdominal computerized tomography. At admission, clinical and hormonal data were unrewarding, so it was decided to continue to observe the patient. Four months later, she became symptomatic with hypertensive and psychotic crises and glycemic decompensation. By that time, a full-blown Cushing picture was evident. Severe hypercortisolism was documented with urinary free cortisol ranging 1500-2200 micrograms/24 h, serum cortisol 143-160 micrograms/dl and plasma ACTH 167-218 pg/ml. Neither ACTH nor cortisol values were significantly modified after high-dose dexamethasone, oCRH or metyrapone. Urinary catecholamine and vanilyl mandelic acid excretion were moderately elevated. Chest CT and total body MIBG scan were negative and magnetic resonance of the sella region was inconclusive. No center to periphery ACTH gradient was observed by inferior petrosal sinus catheterization, whereas a significant left to right gradient was found on selective adrenal vein catheterization. A left adrenalectomy was performed and a 4 cm medullary neoplasia was removed. The cells were immunostained for ACTH, neuron-specific enolase and A chromogranin. Signs and symptoms of Cushing's syndrome resolved with normalization of basal and dynamic endocrine evaluations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗
PubMed1994

Biochemical markers of bone and collagen turnover in acromegaly or Cushing's syndrome.

We evaluated serum bone Gla-protein (osteocalcin, BGP), carboxyterminal propeptide of type I procollagen (PICP) and aminoterminal propeptide of type III procollagen (PIIINP) in 15 patients with active acromegaly (6M aged 27-54, 4 PMF aged 39-51, 5MP aged 54-65 years), 12 with active Cushing's syndrome [(CS) 2M of 32 and 42 years; 4PMF aged 25-40; 6MF aged 50-64)] and controls evenly matched for age, sex and menstrual status. Patients with acromegaly were evaluated before and at regular intervals on octreotide treatment (50-150 micrograms t.i.d., s.c.); the duration of the follow-up was 5-49 months (median 28). Endocrine evaluation included measurements of serum GH, IGF-I, BGP, PICP and PIINP. In a case-control analysis, acromegalic patients showed increased BGP (14.3 +/- 2.1 vs 8.3 +/- 2.1 ng/ml p < 0.001) and PIIINP concentrations (4.8 +/- 1.4 vs 3.1 +/- 0.7 micrograms/l, p < 0.02). During octreotide treatment we observed a roughly parallel decline of GH, IGF-I and BGP. BGP and log-transformed 24-h mean GH concentrations were positively correlated (r = 0.48, p < 0.001) as was the case for BGP and IGF-I (r = 0.43, p < 0.001). Also PIIINP correlated with log-transformed GH (r = 0.58, p < 0.001) and IGF-I (r = 0.35, p < 0.05). Serum PICP did not differ in the two groups (152 +/- 55 vs 120 +/- 55 micrograms/l, NS) and did not correlate either with GH or IGF-I. Patients with CS were evaluated measuring serum and urinary cortisol (UFC), ACTH, BGP, PICP, PIIINP.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1994

Endocrine evaluation of incidentally discovered adrenal masses (incidentalomas)

Since 1989, 45 patients [pts; 26 females and 19 males, aged 19-79 yr (median, 58)] bearing incidentally discovered adrenal masses were studied. The aim of the study was to verify the prevalence of hormone activity in clinically silent adrenal masses. Endocrine work-up included determination of urinary catecholamines and their metabolites, measurement of PRA and aldosterone levels in clino- and orthostatic posture, and basal and dynamic [dexamethasone (dex) suppression and ovine CRH stimulation] evaluation of hypothalamic-pituitary-adrenal axis. The most frequent finding was the reduction of dehydroepiandrosterone sulfate (DHEA-S) levels below the third percentile of controls in 19 (42%) pts. DHEA-S levels were significantly lower in pts than in controls [68 (range, 5-1000) vs. 208 (34-326) micrograms/dL; 1.8 (0.1-27.1) vs. 5.6 (0.9-8.8) mumol/L; P < 0.001]. Three pts (7%) had high 24-h mean serum cortisol levels, and 6 (14%) had blunted day-night amplitude of cortisol rhythm. Defective dex suppressibility was found in 15% of pts vs. 8% of controls (P < 0.05). ACTH and cortisol responses to ovine CRH did not significantly differ between pts and controls, although blunted ACTH responses were found in 22% of the cases. The above-mentioned endocrine alterations could be accounted for by autonomous cortisol secretion by the adrenal nodule at a rate not sufficient to give clinical expression, but able to inhibit to some extent the hypothalamic-pituitary-adrenal axis. These results indicate that silent cortisol hypersecretion is frequently observed in pts with adrenal incidentaloma even if progression to overt Cushing's syndrome seems unlikely. Indeed, the size of the mass and the hormone pattern remained substantially unchanged in 9 pts followed up for 12 months. From merely a cost/benefit ratio, the evaluation of DHEA-S levels and dex suppression has sufficient sensitivity to identify the occurrence of silent hypercortisolism.

Adenoma↗
PubMed1993

Serum levels of bone Gla protein (osteocalcin, BGP) and carboxyterminal propeptide of type I procollagen (PICP) in acromegaly: effects of long-term octreotide treatment.

We measured serum concentrations of bone Gla-protein (osteocalcin, BGP) and carboxyterminal propeptide of type I procollagen (PICP) in 14 patients with active acromegaly. Blood was collected at 0800 for measurement of bone Gla-protein (BGP), carboxyterminal propeptide of type I procollagen (PICP), and insulin-like growth factor I (IGF-I); growth hormone (GH) was then determined at 15-minute intervals for 3 hours and the integrated mean was calculated. The same protocol was repeated at regular intervals during treatment with the long-acting somatostatin analog, octreotide, 150-450 micrograms/day for 6-33 months (median 15). In a case-control analysis, serum BGP concentrations recorded in the acromegalic patients were significantly elevated (14.2 +/- 4.2 micrograms/liter versus 8.0 +/- 3.3 micrograms/liter, P < 0.001). Octreotide treatment induced a roughly parallel reduction in serum GH, IGF-I, and BGP. We found a significant positive correlation between BGP levels recorded before and during therapy and the logarithm of corresponding mean GH levels (r = 0.67, P < 0.001). Also IGF-I concentrations were positively correlated with BGP (r = 0.66, P < 0.001). On the other hand, PICP levels recorded in the acromegalics did not differ from control subjects (146 +/- 46 micrograms/liter versus 127 +/- 44 micrograms/liter, NS) and no correlation was found between either GH and PICP or IGF-I and PICP. To conclude, the present data are compatible with the view that GH and IGF-I play an important role in the control of BGP but not PICP production. It could be that BGP and PICP are submitted to different hormonal modulation.

Acromegaly↗
PubMed1993

Evening administration of melatonin enhances the pulsatile secretion of prolactin but not of LH and TSH in normally cycling women.

OBJECTIVE: The aim of the study was to evaluate the effects of exogenous melatonin on the spontaneous pulsatile release of PRL, TSH and LH in normal women. DESIGN: A double blind placebo-controlled protocol was designed to study seven subjects in the mid follicular phase of two non-consecutive cycles. Two mg of exogenous melatonin or placebo were given at 1600 and 2000 h, and blood samples were collected every 10 minutes from 1800 to 2400 h for hormone determination. RESULTS: Melatonin treatment caused a significant upward resetting of the pulsatile pattern of PRL in six out of seven subjects. Average maximal peak height was significantly increased (median 716 mIU/l (range 198-1433) on melatonin vs 324 mIU/l (212-688) on placebo, P < 0.001), nadir value (572 mIU/l (148-1084) vs 216 mIU/l (54-580), P < 0.001) and area under the peak (26352 mIU/l min (5904-93672) vs 12096 mIU/l min (2340-33552), P < 0.001), whereas peak number, amplitude and interpeak interval did not change significantly. TSH pulsatility was unaffected by melatonin administration in four out of six subjects. Distribution of LH patterns after melatonin was inhomogeneous: level of pulsatility was higher in two cases and reduced in three; group analysis did not therefore show significant variation of pulsatility parameters. CONCLUSIONS: Exogenous melatonin has a stimulatory effect on PRL release without affecting the temporal pattern of its pulsatile secretion in normal women. Melatonin has minor, if any, effect on TSH secretion whereas the effect on LH may depend on individual sensitivity.

Adult↗
PubMed1992

Favorable response of metastatic adrenocortical carcinoma to etoposide, adriamycin and cisplatin (EAP) chemotherapy. Report of two cases.

The usefulness of non-specific chemotherapy for advanced adrenocortical carcinoma (ACC) is controversial. We report on 2 young female patients (25 and 19 yr) who presented with a clinical picture of Cushing's syndrome due to histologically confirmed ACC. The first patient underwent radical surgery, but after a disease-free interval of 6 months a local recurrence was apparent. She was reoperated and treated with 6 courses of cisplatin and etoposide chemotherapy. Mitotane (8 g daily) was begun, but 2 months later debulking surgery was again performed. A second-line chemotherapy with the etoposide, adriamycin, cisplatin (EAP) scheme attained a partial remission lasting 7 months, then metastatic spread to the brain led to death of the patient. The survival time was 30 months. The second patient underwent radical surgery and adjuvant mitotane (4 g daily), but multiple lung and mediastinal metastases were diagnosed after an interval of 29 months. Chemotherapy with the EAP regimen (6 courses) without interrupting mitotane attained a partial remission lasting 21+ months. We suggest that the EAP scheme is active in advanced ACC and that its association with mitotane is feasible.

Adrenal Cortex Neoplasms↗
PubMed1991

Hyperthyroidism due to a pituitary adenoma composed of two different cell types, one secreting alpha-subunit alone and another cosecreting alpha-subunit and thyrotropin.

A 37-yr-old female presented with clinical signs and symptoms of mild hyperthyroidism, high serum levels of free T4 (24.2 pmol/L), free T3 (11.7 pmol/L), and sex hormone-binding globulin (157 nmol/L) as well as measurable (by immunofluorometric assay) serum TSH concentrations (1.9 mU/L) in the absence of any known methodological interference. The above finding indicated the presence of hyperthyroidism due to inappropriate secretion of TSH, whose neoplastic origin was documented by computed tomographic scan showing a 1-cm pituitary adenoma. The diagnosis was confirmed by elevated alpha-subunit levels (9.2 micrograms/L) and alpha-subunit/TSH molar ratio (25.2) as well as absent TSH suppression after T3 administration. TRH injection (200 microgram, iv) caused impaired TSH (from 3.0 to 4.8 mU/L) and unexpectedly exaggerated alpha-subunit (from 8.8 to 18.2 micrograms/L) responses. Such a discrepancy was also observed after other dynamic tests. Double gold particle immunostaining of the adenomatous tissue removed at surgery showed that all of the cells contained secretory granules positive for alpha-subunit, while very few cells were positive for TSH beta and alpha-subunit. In conclusion, the present study demonstrates the existence of TSH-induced hyperthyroidism due to a pituitary adenoma composed of two different cell types: one secreting alpha-subunit alone and another cosecreting alpha-subunit and TSH.

Adenoma↗
PubMed1991

Exogenous melatonin enhances the TRH-induced prolactin release in normally cycling women: a sex-specific effect.

The aim of the present study was to analyze the effects of exogenous melatonin (MT) upon pituitary and adrenal responsiveness to releasing hormones in different phases of the menstrual cycle. We evaluated the response of FSH and LH to 100 micrograms gonadotropin releasing hormone, of TSH and prolactin (PRL) to 200 micrograms thyrotropin releasing hormone (TRH), and of cortisol to 10 micrograms ACTH 1-17. We studied eight young women with normal ovulatory cycles in the early follicular (days 5-7) and luteal (days 22-24) phases. Stimulation tests were performed at 18.00 in baseline conditions as well as 1 h after oral intake of exogenous MT (2 mg as a gelatine capsule). We did not observe any significant change in FSH, LH, TSH and cortisol responses to their respective releasing hormones in either phase of the cycle. PRL response to TRH was higher after MT in the follicular phase, when evaluated in terms of net increment and integrated area of response (p less than 0.02 versus baseline conditions for both variables). In the luteal phase, we recorded larger interindividual variability and higher responses after MT were observed in five out of eight subjects. These results suggest that MT may play a facilitatory role in the TRH-induced PRL release in women of reproductive age.

Adrenal Glands↗
PubMed1991

[Drugs and andrological side-effects].

Human sexual behaviour is determined by different regulatory systems. Central and peripheral nervous system, endocrine and vascular systems, all play a pivotal role in the modulation of male sexual activity. Therefore, many steps of possible drug interference can be recognized. In this regard, drugs are usually classified on the basis of their side effects (impairment of libido, erection and/or ejaculation). In the present work we review the sexual-related side effects of drugs of widespread clinical use on the basis of their mechanism and site of action.

Central Nervous System↗
PubMed1990

Melatonin and human cancer.

A number of studies performed in vitro and on experimental animals supported the view that pineal gland inhibits neoplastic growth. Data in humans are scanty and controversial. In the present study we measured serum melatonin (MT), prolactin (PRL) and growth hormone (GH) concentrations, at 08.00 and 24.00, in 132 cancer patients and in 58 healthy control subjects. The patients were stratified according to histology and stage of disease as follows: 30 stage I-II and 45 stage III-IV breast cancer (BC); 39 stage III-IV lung cancer; 18 advanced gastrointestinal (GI) cancer. We also measured MT levels, at the same time-points, in 20 women with primary BC before and after radical mastectomy. Finally, we evaluated the circadian rhythm of serum MT in 18 patients with advanced cancer. On the whole, the patients with advanced tumors showed serum MT levels significantly higher than controls, without any correlation with PRL and GH values. When looking at stage III-IV vs stage I-II BC patients, significantly higher MT levels have been found in the former group. The surgical removal of the primary BC was not associated with any changes in MT values at both time points considered. A highly significant rhythm of serum MT was recorded in advanced cancer patients and the rhythmic parameters were substantially superimposable on those of the control subjects.

Adult↗