Search PubMedSearch

Biomedical subjects

M Terzolo

Publications and source records attributed to M Terzolo.

At least 19 recordsLinked to original sources

Twenty-four hour profile of blood pressure in patients with acromegaly. Correlation with demographic, clinical and hormonal features.

Cardiovascular events are frequently reported in patients with acromegaly and they are usually related to arterial hypertension. Aim of the present study was to assess the 24-hour profile of blood pressure (BP) and heart rate (HR) in patients with active acromegaly and to correlate them with clinical and hormonal data. Sixteen patients and 16 healthy, age and sex matched subjects underwent ambulatory blood pressure monitoring by means of a portable automatic device (SpaceLabs monitor 90207, Kontron) with measurements every 20 minutes for 24 hours. The presence of the nocturnal fall was assessed by the calculation of the night-day systolic and diastolic ratio. The mean 24-hour diastolic BP was significantly higher in acromegalic patients than in controls (79.1+/-11.5 mmHg vs 70.8+/-5.3 mmHg, p<0.05) and the circadian diastolic profile was flatten. In fact, 10/16 patients were defined as nondippers while this figure was 2/16 in the control group (62% vs 12%, p<0.01). Also the mean 24-hour systolic BP was higher in acromegalic patients than in controls (124.8+/-17.2 mmHg vs 114.1+/-8.6 mmHg, p<0.05). The circadian systolic profile paralleled that of diastolic and was flatten, without a significant nocturnal fall. Ten out of 16 patients were nondippers compared to 2/16 controls (62 vs 12%, p<0.01). No significant correlation was found between mean 24-hour BP, either diastolic or systolic, and demographic or hormonal characteristics of the patients. HR patterns did not differ between patients and controls and were characterized by a prominent nocturnal fall.

Acromegaly

Different immunohistochemical patterns of TGF-beta1 expression in benign and malignant adrenocortical tumours.

OBJECTIVE: Transforming growth-factor beta1 (TGF-beta1) influences a number of specific functions of adrenocortical cells in several animal species. The aim of our study was to evaluate by immunohistochemical analysis the presence and distribution of TGF-beta1 in normal adrenal tissue and in different adrenal tumours. PATIENTS: We analysed 8 functioning (5 adenomas and 3 carcinomas) and 15 non functioning (6 adenomas and 9 carcinomas) adrenal tumours and 6 normal adrenal glands. RESULTS: In normal adrenal glands, the glomerulosa and the reticularis zones displayed diffuse cytoplasmic staining, while the fasciculata zone was almost completely negative. Functioning adenomas displayed cytoplasmic staining restricted to compact cells while in nonfunctioning adenomas, prevalently composed by clear cells, no staining was observed. Overall, adrenal carcinomas were characterized by the lack of cytoplasmic positivity and by sporadic positive cells around vessels both in functioning and in nonfunctioning tumours. CONCLUSIONS: TGF-beta1 expression is associated with active steroid secretion in normal adrenal tissue, as well as in benign cortical adenomas, while this relationship is lost in primary adrenal malignancies. These data provide indirect evidence for a regulatory role played by TGF-beta1 on steroid secretory pathways.

Adenoma

Mitotane associated with etoposide, doxorubicin, and cisplatin in the treatment of advanced adrenocortical carcinoma. Italian Group for the Study of Adrenal Cancer.

BACKGROUND: The use of either mitotane or chemotherapy in the treatment of advanced adrenocortical carcinoma (ACC) has led to scanty and controversial results. The recent finding that mitotane is able to reverse in vitro multidrug resistance has provided a rational basis for combining this agent with cytotoxic drugs. The association of mitotane with etoposide, doxorubicin, and cisplatin (EDP) in the treatment of patients with advanced, inoperable ACC was tested in an Italian multicenter Phase II trial. METHODS: Twenty-eight patients (18 women and 10 men; median age, 47 years; range, 27-65 years) with measurable disease were enrolled in the study and evaluated for toxicity and response. There were 18 patients with clinical and/or biochemical evidence of steroid hypersecretion. An EDP schedule (etoposide 100 mg/m2 on Days 5-7, doxorubicin 20 mg/m2 on Days 1 and 8, and cisplatin 40 mg/m2 on Days 1 and 9) was administered intravenously every 4 weeks; concomitantly, patients were given up to 4 g/day of oral mitotane or the maximum tolerated dose, without any interruption between chemotherapy cycles. RESULTS: According to World Health Organization criteria, complete response was achieved in 2 patients and partial response in 13, for an overall response rate of 53.5% (95% CI, 35-72%). Stable disease was observed in 8 patients and progressive disease in 5. Responses occurred in patients with both functioning and nonfunctioning tumors, and more often in those bearing lymph node and lung metastases. Time to progression in responding patients was 24.4 months. Generally, the EDP regimen was well tolerated. Only 4 patients received reduced doses, whereas 3 discontinued early chemotherapy due to toxicity. The addition of mitotane increased neurologic and gastrointestinal side effects. Due to these additional toxicities, only 9 patients regularly took the drug at the planned dose (4 g/day); 11 received the maximum tolerated dose of 3 g/day, 6 received 2 g/day, and 1 received 1 g/day. Mitotane was also responsible for raised serum levels of cholesterol and triglycerides. A complete hormone response (normalization of altered biochemical parameters) was observed in 9 of 16 evaluable patients with functioning tumors. CONCLUSIONS: EDP plus mitotane combination chemotherapy appears to be active and manageable treatment for patients with advanced ACC.

Administration, Oral

Subclinical Cushing's syndrome in adrenal incidentaloma.

OBJECTIVE: Some patients with incidentally discovered adrenal adenomas display autonomous cortisol secretion not fully restrained by pituitary feedback, a condition that may be defined as subclinical Cushing's syndrome. We have evaluated the presence of subclinical Cushing's syndrome and its natural history in a cohort of patients with incidentally discovered adrenal adenomas. PATIENTS: Fifty-three consecutive patients (30 women and 23 men; median age 58 years, range 18-81 years) were studied. Diagnostic procedures were initiated for extra-adrenal complaints. Patients with known extra-adrenal malignancies or patients with hypertension of possible endocrine origin were excluded. MEASUREMENTS: All patients underwent the following endocrine evaluation: (1) measurement of DHEA-S at 0800 h, (2) measurement of serum cortisol at 0800 and 2400 h, (3) measurement of the 24-h excretion of urinary free cortisol (UFC), (4) overnight low-dose dexamethasone suppression test, (5) measurement of plasma ACTH at 0800 h (mean of at least two samples on different days), (6) oCRH stimulation test. Different groups of healthy subjects recruited from the hospital medical staff and their relatives served as controls for the various tests. The same endocrine work-up was repeated after 12 months in 25 patients. All patients were followed up at regular intervals for at least 12 months with clinical examination and abdominal computed tomography. Subclinical hypercortisolism was arbitrarily defined as definitive, probable or possible, according to the degree of endocrine abnormalities. RESULTS: UFC was significantly higher in patients with incidentaloma than in controls (262, 25-690 nmol/24 h versus 165, 25-772 nmol/24 h; P = 0.012). The percentage of subjects who did not suppress on dexamethasone was greater among patients than among healthy subjects (9/53 (17%) versus 5/103 (5%), P = 0.026). Plasma ACTH concentrations were lower in patients with adrenal incidentaloma than in controls (3, 1-9 pmol/l versus 5, 1-14 pmol/l; P = 0.014). These findings consistently point toward a functional autonomy of the adrenal adenomas even if the degree of cortisol excess is mild. Three patients fulfilled the criteria for definitive subclinical hypercortisolism, five for probable and two possible, but none of them experienced clinical and/or biochemical progression to overt hypercortisolism after 12 months. During follow-up, no signs of extra-adrenal malignancy became manifest and the size of the mass did not increase significantly in any patient. CONCLUSIONS: This study provides a clear demonstration of the current opinion that some patients with incidentally discovered adrenal adenomas may be exposed to a subtle, silent hypercortisolism. In some patients, in whom the clustering of more abnormalities in the hypothalamo-pituitary-adrenal axis occurs, subclinical Cushing's syndrome could be assumed. This term should be preferred to that of pre-clinical Cushing's syndrome since the biochemical abnormalities do not become clinically manifest, at least in the short term.

Adenoma

Prevalence of adrenal carcinoma among incidentally discovered adrenal masses. A retrospective study from 1989 to 1994. Gruppo Piemontese Incidentalomi Surrenalici.

BACKGROUND: The incidental discovery of an adrenal mass poses the problem of distinguishing between the frequent benign masses and the infrequent malignant ones that require surgery. Univocal guidelines to approach this problem are unavailable. OBJECTIVE: To perform a survey of the clinical management of incidentally discovered adrenal masses (ie, adrenal incidentalomas). DESIGN: A multicentric retrospective analysis of hospital medical records of adrenal incidentalomas diagnosed during a 5-year period; the medical records were scrutinized for demographic data and clinical details by means of a specifically tailored questionnaire. SETTING: The major surgical and medical centers of Piedmont, a northern Italian region with approximately 4 million inhabitants. The recruitment pattern of these centers was unselected. PATIENTS: The definition of adrenal incidentaloma was limited to patients with a physical examination and a clinical history unindicative of adrenal disease. Exclusion criteria also included hypertension of suspected endocrine origin and a history of neoplasms known to metastasize frequently in the adrenal glands. Two hundred twenty-four medical records were collected, and 210 were analyzed (14 excluded a posteriori). RESULTS: Most patients were in their 50s and 60s, and women were predominantly affected. The frequency of adrenocortical cancer was 13% among patients operated on. The tumor diameter was highly correlated with the risk of cancer; a cutoff at 5 cm had a sensitivity of 93% with a specificity of 64% in discriminating between benign and malignant cortical lesions. CONCLUSIONS: The occurrence of adrenocortical carcinoma among adrenal incidentalomas is not rare. The evaluation of the mass size is a simple and effective method for selecting patients at risk for cancer. The indication for surgery of masses larger than 5 cm, or of masses of any diameter that have suspicious imaging characteristics, limits unnecessary operations and costs.

Adrenal Gland Diseases

Recurrent thromboembolism as a hallmark of Cushing's syndrome.

The present report describes a 54-year-old woman with a history of recurrent thromboembolic events. The clinical and physical examination led to suspect Cushing's syndrome. Screening tests (urinary free cortisol excretion and 1 mg dexamethasone) were inconclusive, but a detailed endocrine work up confirmed the presence of ACTH-dependent hypercortisolism. The patient was cured by the removal of a ACTH-secreting microadenoma by transsphenoidal route. The present case provides a clinical demonstration of a previous experimental evidence that a hypercoagulable state is present in Cushing's syndrome.

Adenoma

Cushing's syndrome due to ACTH-independent bilateral adrenocortical macronodular hyperplasia.

ACTH-independent macronodular adrenocortical hyperplasia (AIMAH) is a rare cause of Cushing's syndrome in which adrenal glands become very enlarged, occupied and distorted by multiple cortical nodules. We report on such two patients, a 44-year-old man and a 40-year-old woman. Physical examination revealed in both cases a classic cushingoid habit. Laboratory studies showed overt hypercortisolism with high urinary free cortisol excretion and elevated serum cortisol with loss of the circadian rhythm. Serum cortisol levels were not modified after high dose dexamethasone. ACTH levels were undetectable both in baseline conditions and following CRH or metyrapone. In both cases, abdominal CT demonstrated bilaterally enlarged adrenal glands which were distorted by multiple bumps. 131I-Norcholesterol scintiscan showed bilateral uptake of the radionuclide. Pituitary region was normal at neuroradiologic imaging. Bilateral adrenalectomy was performed in both cases. In patient I, adrenal glands weighted 77 and 90 g, respectively, while in patient II they were of 90 and 55 g, respectively. At histological examination, the adrenal cortex was occupied by multiple nodular lesions composed mostly of clear cells. In the internodular regions, no evidence of cortical architecture was observed. At the immunohistochemical evaluation, both cases displayed KI-67 staining comparable with that of ACTH-dependent diffuse hyperplasia. Postoperative course was uneventful and signs of Cushing's syndrome resolved in about three months. At the last follow up, the patients are going well on glucocorticoid and mineralocorticoid supplementation. Plasma ACTH levels are 65 and 107 pg/ml, respectively.

Adrenal Cortex

Adrenal incidentaloma: an overview of clinical and epidemiological data from the National Italian Study Group.

BACKGROUND: The incidental discovery of an adrenal mass raises the problem of distinguishing the frequent benign masses from the infrequent malignant ones that require surgery. At present, univocal guidelines to approach this problem are not available. The aim of the present study was to perform a multicentric retrospective analysis of adrenal masses incidentally discovered (adrenal incidentalomas). PATIENTS AND METHODS: Hospital records of adrenal incidentalomas diagnosed over a 15-year period in 29 surgical and medical centers in Italy were scrutinized. Collected cases were 1,013, and 887 were analyzed. RESULTS: The majority of patients were in the 5th and 6th decade and females were predominantly affected. The frequency of adrenocortical cancer was 12% among operated patients (316 cases). The tumor diameter was highly correlated with the risk of malignancy, as well as the CT characteristics such as density, shape and margins. The frequency of pheochromocytoma was 10% among operated patients. CONCLUSIONS: The occurrence of incidentally discovered adrenocortical carcinomas and pheochromocytomas is not rare. Evaluation of the mass size and CT characteristics are simple and effective methods to differentiate malignant lesions. Biochemical screening for pheochromocytoma is mandatory before surgery.

Adolescent

Serum markers of bone and collagen turnover in patients with Cushing's syndrome and in subjects with adrenal incidentalomas.

The aim of this study was to assess serum levels of some markers of bone turnover and collagen synthesis in 22 patients with adrenal incidentalomas (AI), a model of silent glucocorticoid excess, and to compare the results with those obtained in 18 patients with Cushing's syndrome (CS). Osteocalcin (BGP), bone isoenzyme of alkaline phsophatase, carboxy-terminal propeptide of type I procollagen, and carboxy-terminal cross-linked telopeptide of type I collagen were measured as biochemical indexes of bone turnover, and amino-terminal propeptide of type III procollagen was determined as an index of collagen synthesis. Two groups of healthy volunteers evenly matched for sex, age, and menstrual status were used for a case-control analysis of AI and CS groups, respectively. Patients with AI showed a slight, albeit significant, reduction in serum BGP and a mild increase in carboxy-terminal cross-linked telopeptide of type I collagen levels compared with controls [median, 6.6 vs. 7.8 ng/mL (P < 0.05) and 4.2 vs. 3.1 micrograms/L (P < 0.01), respectively]. No significant differences were found when comparing the other markers. Patients with CS had BGP, bone isoenzyme of alkaline phosphatase, and amino-terminal propeptide of type III procollagen levels significantly lower than control values [median, 3.0 vs. 7.3 ng/mL (P < 0.0001); 4.4 vs. 11.5 micrograms/L (P < 0.01); 2.2 vs. 4.3 micrograms/L (P < 0.0001), respectively], but no significant difference in the other markers. These results confirm a clear inhibition of osteoblastic activity in CS and could suggest an enhanced bone metabolism in patients with AI. The degree of impairment of bone turnover in patients with AI does not seem enough to recommend surgery (removal of the adrenal adenoma) in the absence of other indications.

Adrenal Gland Neoplasms

Coexistence of unilateral adrenal macronodule and Cushing's disease. Report of two cases.

The coexistence of an unilateral adrenal macronodule and Cushing's disease is well documented in only few reports. We hereby describe two patients with ACTH-dependent Cushing's syndrome and asymmetric adrenal involvement. In both patients the left-sided adrenal contained a nodule sized 1.5 and 1.4 cm, respectively, while the contralateral gland appeared as normal at abdominal computerized tomography. Adrenal scintiscan revealed a bilateral uptake of the tracer. Dynamic testing of hypothalamic-pituitary-adrenal axis was suggestive of pituitary dependency but neuroradiologic imaging was inconclusive. Inferior petrosal sinus sampling demonstrated a clear center to periphery ACTH gradient and an ACTH-producing pituitary microadenoma was found and removed in both cases. Hypopituitarism ensued postoperatively and Cushing's syndrome resolved but the adrenal nodules regressed only many month after operation. The present cases confirm that the presence of an adrenal mass in a patient with Cushing's syndrome is insufficient to confidently conclude for the adrenal dependency of the syndrome.

Adenoma

Assessment of functional liver mass and plasma flow in acromegaly before and after long-term treatment with octreotide.

Functional liver mass and functional liver plasma flow (FLPF) were assessed in 11 patients with clinical features of acromegaly by determining galactose elimination capacity (GEC) and extrarenal clearance of sorbitol, before and 5 to 7 months after treatment with the long-acting somatostatin analog, octreotide (150 to 600 micrograms/d in three subcutaneous injections). Growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels, as well as liver size by ultrasound, were also recorded. Baseline GEC was increased in every patient but one, for a mean of 0.78 +/- 0.10 g/min (normal, 0.53 +/- 0.07; P < .01). At reevaluation after 5 to 7 months of octreotide treatment, a significant reduction of GEC was observed (0.62 +/- 0.08 g/min, P < .001). Changes of GEC paralleled those of GH (38.6 +/- 34.4 v 11.7 +/- 15.2 micrograms/L, P < .01) and IGF-I (5.0 +/- 1.7 v 2.7 +/- 2.2 U/ml, P < .001). Significant correlations were found between GEC and GH (r = .50, P < .05) and between GEC and IGF-I (r = .55, P < .01). FLPF, assessed by extrarenal clearance of sorbitol, was within the normal limit in all cases (0.98 +/- 0.19 v 0.97 +/- 0.12 L/min, NS) and remained normal after 5 to 7 months of octreotide treatment (0.99 +/- 0.11 L/min). Hepatic structure determined with ultrasonic scanning and conventional liver-function tests were basally normal in all patients, with a slight increase of liver volume in three cases. No change of biochemical and/or morphological features occurred during follow-up evaluation. The results support the hypothesis that GH and especially IGF-I enhance liver metabolic capacity; conversely, functional liver perfusion is largely independent of their actions. Our data also suggest that octreotide is unable to produce well-structured changes of liver circulation when administered long-term.

Acromegaly

Different patterns of steroid secretion in patients with adrenal incidentaloma.

We previously found that a remarkable number of patients with adrenal incidentaloma display partially autonomous cortisol secretion. The amount of hypercortisolism is insufficient to give clinical expression, but enough to inhibit, in some cases, normal adrenal tissue. Other researchers found with high frequency a partial deficiency of 21-hydroxylase. The aim of the present study was to make a combined evaluation of these aspects of adrenal steroidogenesis. Twenty patients (6 men and 14 women, aged 25-74 yr; median, 59 yr) with incidentally discovered adrenal masses were studied. All had an adrenal adenoma histologically proven or diagnosed on the basis of size (< or = 4.0 cm in all but 1) and computed tomography picture (hypodense homogeneous mass with well defined margins). The following parameters were used to evaluate the ACTH-cortisol axis: overnight 1-mg dexamethasone suppression (4 nonsuppressors), ovine CRH stimulation (blunted ACTH-cortisol response in 2 cases), circadian serum cortisol rhythm (blunted night/day ratio in 4 and increased 24-h mean in 1), and 24-h urinary free cortisol excretion (always within the normal range). Three patients had 2 concomitant alterations, and 5 had a single abnormality. Partial deficiency of 21-hydroxylase was assumed in 6 patients who showed an exaggerated 17-hydroxyprogesterone response to ACTH, with a peak value of more than 10 ng/mL (> 30 nmol/L), according to New's nomogram. No abnormalities of the ACTH-cortisol axis were found in these patients, with the exception of low amplitude cortisol rhythm in 1 case. Therefore, 2 distinct patterns, dysregulated and partially autonomous cortisol secretion, on the one hand, and reduced 21-hydroxylase activity, on the other, can be found in a high number of patients bearing an adrenal incidentaloma. They appear mutually exclusive, and the differentiation by endocrine testing is quite clear. Serum dehydroepiandrosterone sulfate was below the third percentile in 13 of 20 patients and could represent a specific marker of cortical adenomas. This finding was evenly distributed among patients with subclinical hypercortisolism or partial enzymatic defect; therefore, low serum dehydroepiandrosterone sulfate is not readily attributable to suppressed ACTH secretion, which actually occurs in only some patients with subclinical hypercortisolism.

Adenoma

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

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

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