Biomedical subjects

A Scillitani

Publications and source records attributed to A Scillitani.

32 records · Page 2Linked to original sources

PubMed1999

Screening of thyrotropin receptor mutations by fine-needle aspiration biopsy in autonomous functioning thyroid nodules in multinodular goiters.

Multinodular goiter (MNG) is characterized by nodules of different size and function. Areas of increased function may emerge, appearing as single, or more frequently, multiple autonomously functioning thyroid nodules (AFTN). The molecular mechanism for the autonomous growth and function of these nodules has been related to mutations in the thyrotropin receptor (TSHR) that constitutively activate the adenylyl cyclase. We searched for mutations in a limited area of the TSHR gene, covering the major mutational hotspot, in 38 AFTNs found in 37 patients with MNGs. We used reverse transcriptase-polymerase chain reaction (RT-PCR) and restriction enzyme analysis of fine-needle aspiration biopsy (FNAB) samples to rapidly identify 4 of the more frequently occurring TSHR mutations: D619G, F631C, T632I and D633E. Mutations were identified in 5 nodules (1 D619G mutation and 4 T632I mutations). Subsequently, the entire transmembrane portion of the TSHR gene was sequenced in a random sample of 12 AFTN samples that were free of mutations by RT-PCR and restriction enzyme analysis. By direct sequencing we identified a new mutation, F666L, in the seventh transmembrane domain in a sample from 1 nodule. Analysis of FMA samples of AFTN is an effective approach to identify TSHR gene mutations because individual mutations may be associated with different growth and function in vitro, our approach might, allow correlation of a given mutation with the clinical behavior in vivo.

Adult↗

PubMed1999

Altered bone mass and turnover in female patients with adrenal incidentaloma: the effect of subclinical hypercortisolism.

The strategy of treatment for patients with adrenal incidentalomas (AI) may depend upon the presence of hormonal hypersecretion. Although alterations of bone turnover have been recently reported, data on bone mineral density (BMD) are not available in AI patients. We evaluated bone turnover and BMD in 32 female AI patients and 64 matched controls. Spinal and femoral BMD were similar in patients and controls. Serum bone GLA protein (6.8+/-3.5 vs. 8.8+/-3.2 ng/mL; P<0.005) and PTH (48.8+/-15.1 vs. 37.2+/-10.9 pg/mL; P<0.0001) were different in patients and controls. Patients were then subdivided into 2 groups: with (n = 8; group A) or without (n = 24; group B) subclinical hypercortisolism. PTH was higher (P<0.05) in group A than in group B and in both groups than in controls (57.1+/-13.6, 46.0+/-14.8, and 37.2+/-10.9 pg/mL, respectively), and bone GLA protein was lower in group A than in group B and controls (3.8+/-2.3, 7.5+/-3.1, and 8.8+/-3.2 ng/mL, respectively; P<0.05). Serum type I cross-linked C telopeptide and fasting urinary deoxypyridinoline/ creatinine were not different in the three groups. BMD at each site was lower (P<0.05) in group A than in group B and controls. Bone mass and metabolism are altered in AI patients with subclinical hypercortisolism and should be taken into account, therefore, when addressing the treatment of choice for these patients.

Adrenal Gland Neoplasms↗

PubMed1998

Global skeletal uptake of technetium-99m methylene diphosphonate in female patients receiving suppressive doses of L-thyroxine for differentiated thyroid cancer.

This study was carried out in order to investigate the possible detrimental effects on bone of levothyroxine (l-T4) suppressive therapy in female patients who had undergone surgery for differentiated thyroid cancer (DTC). Twenty female (14 premenopausal and 6 postmenopausal) patients receiving l-T4 suppressive therapy for DTC were studied. The sample was selected in such a way as to avoid factors influencing bone metabolism other than l-T4. All patients were monitored by sensitive thyroid-stimulating hormone, free triiodothyronine and free thyroxine assays throughout the follow-up. Nineteen healthy (12 premenopausal and 7 postmenopausal) matched women served as controls. In all subjects bone turnover was evaluated by the measurement of global skeletal uptake of technetium-99m methylene diphosphonate (GSU); bone mineral density (BMD) was measured by quantitative computed tomography at the lumbar spine (LS) and by dual-energy X-ray absorptiometry both at the LS and at three femoral sites: the femoral neck, Ward's triangle and the greater trochanter. No significant difference was found in either GSU or BMD between patients (treated for an average period of 68 months) and controls in the whole sample or in any subgroup. Furthermore, no correlations were found between either GSU or BMD and the duration of therapy, daily doses of l-T4 or results of thyroid function tests. Our data show that carefully monitored l-T4 therapy does not influence skeletal turnover (directly reflected by GSU) or the bone density of the spine and femur.

Absorptiometry, Photon↗

PubMed1998

Alterations of bone turnover and bone mass at different skeletal sites due to pure glucocorticoid excess: study in eumenorrheic patients with Cushing's syndrome.

The aim of the present investigation was to study the effect of glucocorticoid excess on bone mass and turnover not influenced by other diseases known to affect skeleton and/or by different gonadal status and sex. We studied several markers of bone turnover and bone mineral density (BMD) by both quantitative computed tomography (at spine and forearm) and dual x-ray absorptiometry (at spine and three femoral sites) in 18 eugonadal female patients affected by Cushing's syndrome (CS) compared to 24 eugonadal healthy female subjects matched for age and body mass index. In CS patients, serum bone Gla protein, a marker of osteoblastic function, was reduced (3.28 +/- 2.3 vs. 6.47 +/- 2.5; P < 0.01), and bone resorption was increased, as indicated by increased urinary hydroxyproline (36.6 +/- 12 vs. 29.0 +/- 9.1, P < 0.05) and urinary deoxypyridinoline (22.1 +/- 8.0 vs. 16.4 +/- 6.3; P < 0.05). BMD was significantly (P < 0.05 or P < 0.01) reduced at all sites, except cortical forearm, in CS patients compared to controls. By comparing z-scores of reduced BMD in CS patients, spinal trabecular BMD was found to be the most severely affected. Furthermore, disease activity, as measured by urinary free cortisol, was significantly correlated with bone Gla protein (r = -0.57; P < 0.02), urinary hydroxyproline (r = 0.57; P < 0.02), urinary deoxypyridinoline (r = 0.48, P < 0.05), and BMD measured at spine and femur. Our results show that compared to matched control subjects, female eumenorrheic CS patients have reduced osteoblastic function, increased bone resorption, and reduced BMD, and that the severity of these abnormalities is statistically related to the severity of disease activity, as indicated by urinary free cortisol. Moreover, our data suggest a site and tissue specificity of the effect of glucocorticoid excess on bone mass.

Absorptiometry, Photon↗

PubMed1998

Assessment of serum total and bone alkaline phosphatase measurement in clinical practice.

The aim of the study was to measure serum levels of the bone-specific isoenzyme of alkaline phosphatase in normal subjects and patients with metabolic bone disease by using an immunoadsorption assay. We studied 140 healthy adults, 122 patients affected by metabolic bone disease and 15 patients with cholestatic liver disease. Mean values of the bone-specific isoenzyme of alkaline phosphatase in healthy men were significantly higher than those found in premenopausal women (17.8 +/- 4.2 U/l vs 15.6 +/- 4.6 U/l, p < 0.02); postmenopausal women had significantly higher levels of bone-specific isoenzyme of alkaline phosphatase (22.6 +/- 6.4 U/l) than premenopausal women (p < 0.0001). After the menopause total alkaline phosphatase increased by 46%, while the increase in bone-specific isoenzyme of alkaline phosphatase was 39%. No significant correlations were found between bone-specific isoenzyme of alkaline phosphatase and either age or years since menopause, in postmenopausal subjects. In patients with bone-specific isoenzyme of alkaline phosphatase above the upper limit of normal, the assay had a sensitivity of 100% only in patients with Paget's disease of bone. In patients with cholestatic liver disease we found no correlation between bone-specific isoenzyme of alkaline phosphatase and either total alkaline phosphatase and gamma-glutamyl transpeptidase, while a positive correlation was found between total alkaline phosphatase and gamma-glutamyl transpeptidase. Our results confirm the role of bone-specific isoenzyme of alkaline phosphatase assay in clinical research; however, its usefulness in clinical practice is unclear once liver involvement has been excluded.

Adult↗

PubMed1997

Pre-Cushing's syndrome not recognized by conventional dexamethasone suppression-tests in an adrenal "incidentaloma" patient.

Pre-Cushing's syndrome has been recently diagnosed in 6-12% of patients affected with incidentally discovered adrenal masses. Some of these patients have been described to show transient hypoadrenalism after surgery, similarly to those affected with overt Cushing's syndrome. We studied a 70-year-old male patient with a large left adrenal mass, incidentally discovered, who displayed 24-h urinary free cortisol levels at the upper limit of the normal range, normal dexamethasone overnight and low-dose suppression tests and not suppressed ACTH levels, increased 17-hydroxyprogesterone response to ACTH stimulation and low upright plasma renin activity with normal serum aldosterone levels; furthermore, DHEAS level was low and 75 Selenium-cholesterol scintigraphy showed unilateral uptake concordant with the side of the mass. Soon after left adrenalectomy, he complained of acute hypoadrenalism requiring cortisol replacement therapy: ten months after surgery he is still hypoadrenal. Moreover, stimulated 17-hydroxyprogesterone and plasma renin activity in clino- and orthostatic posture have become normal. We propose that conventional dexamethasone suppression-tests may be not enough sensitive in this kind of patients and that in selected cases the absence of controlateral uptake at scintigraphy may be more reliable in predicting post-surgical hypoadrenalism.

Adenoma↗

PubMed1997

Skeletal involvement in female acromegalic subjects: the effects of growth hormone excess in amenorrheal and menstruating patients.

Bone involvement is a common clinical feature in acromegalic patients, though previous studies gave divergent results possibly because of the different gonadal status of the patients studied. To study the influence of estrogen milieu in these patients, we evaluated 23 acromegalic patients with active disease, subdivided into two groups: menstruating and amenorrheal patients, comparable for duration and activity of disease. Forty-two matched women served as controls. Skeletal involvement was studied by measuring: (a) the main biomarkers of bone turnover: serum alkaline phosphatase total activity (AP), bone GLA protein (BGP), serum carboxy-terminal propeptide of type I collagen (PICP), serum type I cross-linked N-telopeptide (ICTP), and urinary pyridinoline and deoxypyridinoline corrected for creatinine (Pyr/Cr, D-Pyr/Cr) and urinary calcium/creatinine ratio (Ca/Cr); (b) bone mineral density (BMD), as measured by quantitative computed tomography both at lumbar spine and distal radius, and by dual X-ray absorptiometry both at lumbar spine and at three femoral sites (Ward's triangle, femoral neck, and great trochanter). AP, BGP, ICTP, Pyr/Cr, D-Pyr/Cr were significantly higher in patients than in controls, independent of the menstrual pattern. Higher PICP levels were found in the whole group and in menstruating acromegalics when compared with control women; no difference was found in amenorrheal patients, who in turn showed higher urinary Ca/Cr values. When patients were considered all together, BMD at spine, femoral neck, and trochanter was higher than in controls. In contrast, when the gonadal status was taking into account and, menstruating and amenorrheal subjects were considered separately, BMD at spine, but not in other sites, was significantly higher in menstruating patients than in controls. In contrast, no difference of BMD values at any site was observed between amenorrheal patients and controls. The mean BMD Z scores allowed us to detect an unequal involvement of different skeletal sites. Our results show that bone turnover is increased in acromegalic women and suggest that GH anabolic effect on bone is more evident in the presence of estrogens and that different skeletal sites may be affected differently by hormone excess.

Acromegaly↗

PubMed1996

Age-related changes in the global skeletal uptake of technetium-99m methylene diphosphonate in healthy women.

A short-term evaluation of global skeletal uptake (GSU) of technetium-99m methylene diphosphonate (MDP) was performed in 40 healthy female subjects with a wide age range in order to investigate the clinical performance of the technique and to detect the age-related changes in bone turnover. The results obtained were compared with measurements of the main biochemical markers of skeletal metabolism. We found that GSU increases progressively with age, independently of concomitant changes in renal function; significant correlations with biochemical markers of bone formation were also found. Therefore, the method appears to provide useful information concerning the bone turnover rate, and is also applicable to elderly people owing to its simplicity.

Adult↗

PubMed1995

Characterization of insulin autoantibodies in a patient with autoimmune hypoglycemia.

A 60-year-old man referred because of hypoglycemic bouts was found to have insulin autoantibodies. Total plasma insulin was as high as 1.44 nmol/l. Both plasma free insulin and C-peptide were in the normal range. The indirect immunofluorescence technique showed positivity for antinuclear antibodies. The T-lymphocyte populations in the peripheral blood were normal. When serum binding capacity for pork insulin was measured, antibodies binding pork insulin were not detected. The patient's serum bound 125I-insulin. The binding protein was identified to be an immunoglobulin G. The kinetics of dissociation, studied by the Scatchard analysis of the autoantibody, showed a curvilinear plot, which was analyzed in two components. Cold human insulin was able to compete with 125I-insulin for the antibody binding site (I.C.50 = 1.35 nmol/ml). These antibodies were apparently not associated with antibodies directed against the insulin receptor.

Autoantibodies↗

PubMed1995

Thyroperoxidase microsatellite polymorphism in thyroid diseases.

Autoimmune thyroid diseases (AITD) cluster in families, although the nature of this phenomenon is still poorly understood. One possible approach to the identification of genetic factors contributing to the pathogenesis of AITD is the study of association between polymorphic markers and AITD themselves. In the present study we have analyzed the allelic distribution of sRA-1, a TPO tetranucleotide repeat, among patients with AITD, in comparison with patients with nonautoimmune thyroid diseases and the general population. The polymorphic marker was analyzed by PCR followed by electrophoresis on polyacrylamide denaturant gel. Our data show that no association exists between AITD and any of sRA-1 alleles, despite the important role that TPO plays as a thyroid autoantigen.

Adult↗

PubMed1995

In vivo visualization of pituitary dopaminergic receptors by iodine-123 methoxybenzamide (IBZM) correlates with sensitivity to dopamine agonists in two patients with macroprolactinomas.

We performed in two patients with macroprolactinoma, pituitary scintigraphy with 123 iodine-methoxybenzamide (IBZM), a dopaminergic antagonist that specifically binds to the D2 dopaminergic receptors. In a 34-yr-old woman with basal PRL levels of about 2000 ng/mL, 7.5 mg/day of Bromocriptine (Br) for a month neither reduced PRL levels nor affected tumor size; in this patient single photon emission tomography SPECT failed to show any pituitary accumulation of the tracer. In the other patient, a 27-yr-old man presenting with cerebrospinal fluid rhinorrhea, basal PRL levels were at 5000 ng/mL; magnetic resonance imaging (MRI) demonstrated a huge pituitary tumor, and SPECT showed a very intense concentration of IBZM at the level of the adenoma. PRL levels fell dramatically to 530 ng/mL with only 2.5 mg/day of Br after 4 days; after 6 days with 7.5 mg/day Br, PRL levels were 63 ng/mL, and the patient underwent surgery to correct cerebrospinal fluid leakage. We conclude that, in these two patients, the pituitary scintigraphy with IBZM has given information on the density of dopamine receptors on the adenoma and has correlated with the inhibitory effect of Br on PRL secretion. Whether this tool might be of value in identifying patients with pituitary tumors potentially responsive to Br treatment is still to be investigated.

Adult↗

PubMed1988

Aggregation of human peripheral blood mononuclear cells by calcium ionophore A23187. Comparison with the aggregation of platelets and defective response in Glanzmann's thrombasthenia.

Following exposure to calcium ionophore A23187, washed peripheral blood mononuclear cells (MNC) aggregated and formed thromboxane, like platelets. However, while aspirin strongly inhibited platelet aggregation and thromboxane formation, it had a little effect on the aggregation of MNC. In about 50% of the samples studied, aggregation of MNC was associated with the secretion of ATP. However studies in which exogenous ATP or ADP were used, suggested that the aggregation of MNC is independent of the secretion of nucleotides. MNC from 2 thrombasthenic patients failed to aggregate and bound 9-10 fold less radiolabelled fibrinogen than those from normals when challenged with A23187. However, fibrinogen, which plays a major role in the aggregation of platelets, did not appear to be involved in the aggregation of MNC. A differing behavior of these two types of cells was also found when the effect of plasma was studied on the aggregation response to A23187. Indeed, citrated plasma greatly enhanced the aggregation of platelets while it suppressed the response to MNC. This inhibitory effect of plasma was not detected when heparinized plasma was substituted for citrated plasma. We conclude that the aggregation of MNC in response to A23187 does not involve basic events known to play a major role in the aggregation of platelets. The response to A23187 may be an important probe for understanding basic mechanisms and pathophysiological significance of the aggregation of MNC.

Adult↗

PubMed1985

Cross-over study of muzolimine and hydrochlorothiazide-amiloride in hypertensive patients.

Thiazide therapy is a widely used first line treatment for arterial hypertension. Its useful value, particularly in mild or moderate hypertension, is sometimes reduced by metabolic side-effects, as hypokalaemia and hyperuricaemia. In the present study the antihypertensive efficacy of a new, non-sulphonamide diuretic Bay g 2821 (muzolimine) was evaluated in comparison with the combination of hydrochlorothiazide-amiloride over a period of 4 weeks. A highly significant decrease in systolic and diastolic blood pressures was produced by both treatments. No decrease in serum potassium nor an increase in cholesterol, triglycerides, uric acid or glucose was detected during the 4 week treatment period. Subjective side-effects, such as headache and dizziness, were very rarely observed during Bay g 2821 treatment. The new diuretic appears, therefore, to be effective in the treatment of arterial hypertension without untoward side-effects.

Adult↗

PubMedDate not supplied

[Primary hyperparathyroidism].

Primary hyperparathyroidism (PHPT) is characterized by excessive PTH secretion in respect to calcium homeostasis needs, due to parathyroid adenoma (80% of cases), hyperplasia (15-20%), or carcinoma (1-2%). In familial forms of PHPT, several mutations have an established role: menin gene for MEN type 1, RET for MEN type 2a, calcium-sensing receptor gene for familial hypocalciuric hypercalcemia, parafibromin gene for PHPT-jaw tumour and carcinoma. Etiology of sporadic adenomas (80% of PHPT cases) is less defined, being most commonly found a mutation of menin gene or activation of PRAD1 oncogene. In recent years, the classical features of the disease became less common. Typically, bone involvement is now represented by a reduced bone mass at skeletal sites more rich in cortical tissue. Prominently trabecular skeletal sites are relatively spared, because of the anabolic effects of a slight PTH excess on trabecular tissue. PHPT patients may have increased fracture risk, though it is not clear why bone damage is more severe in a subgroup of patients. Clinical features of hypercalcemia may be fatigue, anorexia, thirst, and polyuria. Vague neurological and psychiatric symptoms, such as weakness, anxiety, depression, paresthesias, and muscular cramps may ameliorate after parathyroidectomy. Recent reports indicate increased cardiovascular mortality in PHPT patients. Diagnosis is based on the detection of hypercalcemia, together with inappropriately high serum PTH levels. Preoperative localization of the diseased glands is mandatory in persistent or recurrent PHPT, as like as when minimally invasive surgery is planned. High resolution ultrasonography and SPECT double-phase 99m Tc-sestamibi scintigraphy are the most commonly employed techniques. Intraoperatory PTH assay may confirm successful surgery when serum concentrations decrease more than 50%. Surgical therapy is indicated in patients with renal or skeletal complications, such as in those with previous parathyrotoxic crisis. Many surgeons in recent years adopted minimally invasive parathyroidectomy. Medical treatment is an option for patients unwilling or unfitted for surgery because of severe concomitant diseases. Employed therapy includes estrogens, SERMs, bisphosphonates and calcimimetics.

Adult↗