PubMed Health⌕ Search

Biomedical subjects

E Martino

Publications and source records attributed to E Martino.

At least 19 recordsLinked to original sources
PubMed2006

Myocardial systolic strain abnormalities in patients with acromegaly: a prospective color Doppler imaging study.

BACKGROUND: Heart abnormalities are frequent findings in patients with acromegaly: systolic abnormalities are considered to be secondary to diastolic changes. AIM: The aim of the study was to evaluate whether early systolic abnormalities might be revealed in acromegalic patients using the high sensitive color Doppler myocardial imaging (CDMI) technique. PATIENTS AND METHODS: Twenty-two consecutive acromegalic patients with active untreated disease (ACROUNTR) were evaluated at baseline and after a 6-month course with SS analogs (SSa) (ACROSSa); 25 healthy subjects served as controls. All subjects underwent conventional 2D-color Doppler echocardiography, pulse wave tissue Doppler imaging (PW-TDI) and CDMI. RESULTS: Mean left ventricular (LV) ejection fraction did not differ in ACROUNTR and in controls; at variance, ACROUNTR patients had reduced mean LV diastolic function (E/A ratio: 0.96+/-0.3 vs controls: 1.6+/-0.3; p<0.002). Impairment of global LV diastolic function was confirmed by PW-TDI in ACROUNTR patients having a normal systolic function. Regional myocardial systolic strain (epsilon) and strain rate (SR) values, indices of regional systolic heart deformation, were lower in ACROUNTR [epsilonsys (S) -19.8+/-2.9 and epsilonsys (L): -17.7+/-2.2] than in controls [epsilonsys (S): -27.9+/-3.8; p<0.001 and epsilonsys (L): -25.3+/-2.6; p<0.001]. In addition, the early phase of diastolic function, evaluated using SR parameters, was impaired in acromegalic patients (p<0.005 vs controls). Strain and SR values were related to serum GH and IGF-I levels (p<0.02) and greatly improved after a 6-month course with SSa [epsilonsys (S) improved to -23.8+/-3.8 (p<0.05) and epsilonsys (L) improved to -24.7+/-2.4 (p<0.03)]. CONCLUSIONS: Our study confirms that ACROUNTR patients have impaired diastolic function. More important, our study clearly shows that ACROUNTR patients have an impairment of regional myocardial systolic function, which is not secondary to diastolic changes. These intramyocardial functional abnormalities improved during medical treatment of acromegaly. It is conceivable that GH-IGF-I excess has detrimental effects either on the diastolic or the systolic phases of heart function.

Acromegaly↗
PubMed2006

Long-term outcome of thyroid function after amiodarone-induced thyrotoxicosis, as compared to subacute thyroiditis.

BACKGROUND: Two main forms of amiodarone- induced thyrotoxicosis (AIT) exist: type 1 AIT is a condition of true hyperthyroidism developing in patients with pre-existing thyroid disorders, and usually requires thyroid ablative treatment. On the other hand, type 2 AIT is a form of destructive thyroiditis occurring in normal thyroids, the management of which usually consists in glucocorticoid treatment. AIM: To assess the long-term outcome of thyroid function in a prospective study of type 2 AIT patients, as compared to patients with De Quervain's subacute thyroiditis (SAT). PATIENTS AND METHODS: Sixty consecutive patients with type 2 AIT were evaluated during oral glucocorticoid treatment (oral prednisone 30 mg/day, gradually tapered and withdrawn over a 3-month period) and followed for 38+/-4 months (range 6-72) thereafter. Sixty consecutive patients with SAT, referred to our Institutes during the same period and treated with the same therapeutic schedule, served as controls. RESULTS: Type 2 AIT patients were older (p<0.0001) and showed a larger male preponderance (M:F 3.6:1 vs 0.5:1, p<0.0001) than SAT patients. Mean serum free T4 (FT4) and free T3 (FT3) concentrations at diagnosis were increased in both conditions, but higher in type 2 AIT than in SAT (FT4 47.6+/-18.8 and 29.6+/-8.3 pmol/l, respectively, p<0.0001; FT3 15.4+/-7.0 and 11.2+/-3.0 pmol/l, respectively, p<0.001). Correction of thyrotoxicosis was obtained in all patients in both groups, but restoration of euthyroidism occurred earlier in SAT than in type 2 AIT (p=0.006). Ten type 2 AIT patients (17%) and 3 SAT patients (5%, p<0.03) became permanently hypothyroid after glucocorticoid withdrawal and required levothyroxine replacement. CONCLUSIONS: A relevant proportion of type 2 AIT patients develop permanent hypothyroidism after correction of thyrotoxicosis. Thus, periodic surveillance of thyroid status is required after type 2 AIT.

Adult↗
PubMed2006

Uptake of amiodarone by thyroidal and non-thyroidal cell lines.

Amiodarone perturbs thyroid function, causing overt hypothyroidism or hyperthyroidism in 15% of patients. Changes in thyroid function are likely due, at least in part, to amiodarone and/or desethylamiodarone (DEA) concentration into the thyroid gland, but mechanisms whereby the drug uptake occurred are not known. Thyroidal (FRTL-5) or non-thyroidal [Chinese hamster ovary wild-type (CHOwt) or CHO stably transfected with NIS (CHO-NIS)] cells were exposed to 10 microM amiodarone or DEA. Cellular content of both drugs was measured by HPLC and normalized by protein concentration. Cellular concentration of the two drugs was higher in FRTL-5 (mean +/- SD 17.2 +/- 1.2 microg/mg protein of amiodarone and 18.9 +/- 0.7 microg/mg protein of DEA) than in CHO-NIS and CHOwt cells (10.8 +/- 0.8 microg/mg protein and 12.8 +/- 0.2 microg/mg protein, respectively, of amiodarone (p < 0.004); 11.9 +/- 0.1 microg/mg protein and 11 +/- 0.2 microg/mg protein, respectively, of DEA (p < 0.0002). DEA concentration was higher than that of amiodarone in all cell lines (p < 0.002). Differences between FRTL-5 and CHO cell lines were not dependent on TSH: in fact, cellular content of either drug did not change in the presence or absence of TSH in the culture medium. NIS did not intervene in amiodarone or DEA entry into thyroid cells, since amiodarone and DEA content was the same in CHOwt and CHO-NIS cells; in addition, KClO4 inhibited NIS function, but had no effect on drug uptake by the cells. At variance, 80 microM DEA reduced 125I uptake by CHO-NIS cells by 40% at 30 min without affecting cell viability. In conclusion, mechanisms whereby amiodarone is taken up by thyroid cells remain largely unknown, but the two main factors involved in thyroid-specific cellular transport, ie, NIS and TSH, seem to be excluded.

Amiodarone↗
PubMed2006

Growth hormone secretion is impaired in amyotrophic lateral sclerosis.

OBJECTIVE: ALS is the most common motor neurone disorder in human adults. Scanty data on endocrine abnormalities have been reported. The aim of the present study was to investigate the GH-IGF-I axis in ALS patients. PATIENTS: Twenty-two ALS patients (12 men, 10 women), mean age 61 years, and 25 normal age- and sex-matched subjects. No patient was under riluzole therapy. MEASUREMENTS: Patients and controls underwent a GHRH plus arginine test. IGF-I was determined at baseline. A complete evaluation of pituitary function was also performed. RESULTS: Mean (+/- SD) basal GH levels were significantly reduced compared with normal controls (0.2 +/- 0.3 vs 1.6 +/- 1.8 ng/ml, P < 0.01), as well as peak GH concentrations after GHRH + arginine administration (12.6 +/- 8.9 vs 39.9 +/- 18.7 ng/ml, P < 0.001). Six (27%) patients showed a normal GH response to stimulus; 7 (32%) patients displayed a moderate GH deficiency; in 9 (40%) patients GH response was markedly deficient. IGF-I levels were normal in the majority of patients (mean +/- SD: 143.6 +/- 63.8 ng/ml). No significant correlation was observed between peak GH concentrations and age, BMI, disease duration, severity or clinical form. A higher incidence of GH deficiency was observed in male compared to female patients (83%vs 60%), with a peak GH response in males significantly lower than in females (8.9 +/- 6.6 vs 17 +/- 9.6 ng/ml, P = 0.03). Eighteen patients repeated the test after 5 months and similar results were obtained. CONCLUSIONS: The present data indicate a reduction of GH secretion in ALS patients.

Aged↗
PubMed2005

Peroxisome proliferator-activated receptor (PPAR)gamma is highly expressed in normal human pituitary gland.

OBJECTIVE: Expression of peroxisome proliferator-activated receptor (PPAR)gamma in normal pituitary seems to be restricted to ACTH-secreting cells. The aim of the study was to evaluate the expression of PPARgamma in normal human pituitary tissue and to study its localization in the pituitary secreting cells. MATERIALS AND METHODS: Normal pituitary tissue samples were obtained form 11 patients with non-secreting adenoma who underwent surgical excision of the tumor. Expression of PPARgamma was evaluated by immunostaining and western blotting; localization of PPARgamma in each pituitary secreting cell lineage was evaluated by double immunofluorescence using confocal microscopy. Pituitary non-functioning adenomas served as Controls. RESULTS: PPARgamma was highly expressed in all pituitary samples with a (mean +/- SD) 81 +/- 6.5% of stained cells; expression of PPARgamma was confirmed by western blotting. Non-functioning pituitary adenomas had 74 +/- 11% PPARgamma positive cells. Expression of PPARy was either in cytoplasm or nuclei. In addition, treatment of GH3 cells, with a PPARgamma ligand was associated with traslocation of the receptor from cytoplasm into the nucleus. Double immunostaining revealed that every pituitary secreting cell (GH, TSH, LH, FSH, PRL and ACTH) had PPARgamma expressed. DISCUSSION: The present study demonstrated that PPARgamma is highly expressed in every normal pituitary secreting cell lineage. It can translocate into the nucleus by ligand binding; however, its role in pituitary hormone regulation remains to be elucidated.

Adrenocorticotropic Hormone↗
PubMed2005

Growth hormone secretion in primary and secondary hyperparathyroidism.

Primary hyperparathyroidism (PHP) is associated with impaired GH secretion. Whether this effect is due to hypercalcemia or to increased serum PTH concentration is unclear. However, patients with familial hypocalciuric hypercalcemia (FHH), who have normal PTH and increased serum calcium concentrations, also have an impaired GH secretion, suggesting that calcium rather than PTH is responsable for this effect on GH secretion. To further investigate this issue, 10 consecutive patients with secondary hyperparathyroidism (SHP) due to vitamin D deficiency were evaluated by the GH response to GHRH+arginine (Arg) test. A group of 60 consecutive untreated PHP patients served as controls. Mean GH response to GHRH+Arg test was 15.8+/-14 microg/l and 37.5+/-16 microg/l (p<0.001) in PHP and in SHP patients, respectively. Forty-two out of 60 (70%) PHP patients had a suppressed or blunted GH response, whereas all SHP patients had normal GH response. The results of the present study confirm and extend our previous observations that PHP is associated with an impaired GH secretion in the majority of cases, and indicate that SHP patients have no abnormality of GH secretion. Thus, hypercalcemia rather than increased serum PTH is responsible for the abnormality of GH secretion.

Adult↗
PubMed2005

Thyroid function differently affects serum cystatin C and creatinine concentrations.

Cystatin C (Cys C) is a cysteine protease inhibitor produced at a constant rate by nucleated cells, filtered through the glomerular membrane and reabsorbed by kidney tubular cells. Aim of this cross-sectional and longitudinal study was to assess serum Cys C and creatinine (Crea) concentrations in thyroid dysfunction. One hundred and eighty-one patients, 26 with untreated non-toxic nodular goiter, 58 with hyperthyroidism, 31 on L-T4 suppressive therapy for non-toxic nodular goiter, 35 with short-term hypothyroidism after L-T4 withdrawal to perform whole body scan for thyroid cancer, 11 with long-term hypothyroidism due to chronic autoimmune thyroiditis and 20 patients with mild hypothyroidism were enrolled in the study. Fifty-seven age- and sex-matched normal subjects served as controls. Serum Cys C, Crea, free T4 (FT4), FT3 and TSH were assessed. Thirty hyperthyroid patients and 35 short-term hypothyroid patients were followed prospectively until euthyroidism was reached by methimazole or L-T4 therapy. The cross-sectional study showed that mean serum Crea concentrations were significantly reduced in overt hyperthyroid or subclinical hyperthyroid patients, while it was increased in overt hypothyroid patients, but not in mild hypothyroidism. Conversely, serum Cys C levels were significantly increased in overt hyperthyroid patients compared to controls (p<0.05), and significantly decreased in short-term, long-term and mild hypothyroids (p<0.05, p<0.05, p<0.01, respectively). However, 36 (62%) hyperthyroid patients and 50 (76%) hypothyroid patients had normal serum Cys C values. In the prospective study, restoration of euthyroidism by either methimazole or L-T4 therapy was associated with normalization of mean serum Cys C concentrations. In conclusion, thyroid dysfunction affects serum Cys C concentration, possibly influencing the production rate of the protein. However, the observation that hyper- or hypothyroid patients have normal serum Cys C levels limits its use as a marker of peripheral thyroid hormone effect.

Adult↗
PubMed2005

Undetectable inferior petrosal sinus levels of PTH-related peptide (PTHrP) in patients with ACTH-dependent Cushing's disease.

PTH-related peptide (PTHrP), a member of the PTH family, is widely expressed in foetal and adult tissues, and it has been found in benign and malignant tumors, including GH and PRL-secreting adenomas. Conflicting data are reported in literature on serum PTHrP concentrations in patients with Cushing's disease. The aim of the present study was to further evaluate peripheral and inferior petrosal sinus (IPS) serum PTHrP concentrations before and after CRH, in a group of consecutive patients with ACTH-dependent Cushing's disease. Nine patients with active ACTH-dependent Cushing's disease (8 women and 1 man, age +/- SD 41 +/- 13 yr) were submitted to peripheral and IPS sampling under fluoroscopic control before and after iv administration of CRH. All patients were subsequently submitted to transsphenoidal surgery and an ACTH-secreting microadenoma was found in all cases. In all patients, serum IPS and peripheral ACTH measurement were in keeping with the diagnosis of ACTH-dependent Cushing's disease. Serum PTHrP concentrations before and after CRH stimulation were below the sensitivity limit of the assay in all samples, and no gradient between IPS and peripheral sampling was observed. Our data, combined with others reported in literature, indicate that PTHrP release by ACTH-secreting tumors is not a common occurrence. Therefore, we conclude that IPS and peripheral PTHrP are of little clinical usefulness.

Adrenocorticotropic Hormone↗
PubMed2005

Androgen receptor polymorphism (CAG repeats) and androgenicity.

Objective Polymorphism of the androgen receptor (AR) has been related to various pathophysiological conditions, such as osteoporosis and infertility. The objectives of this study were to evaluate the frequency of distribution in a normal Italian population and to assess CAG repeats (CAGr) in other conditions, such as hypoandrogenism, potentially influenced by AR polymorphism. Patients and measurements CAGr polymorphism was determined in a group of 91 healthy normoandrogenized subjects, 29 hypoandrogenized patients (hypoplasia of prostate and seminal vesicles, reduced beard or body hair, etc.) and 29 infertile patients by direct sequencing. Results The mean (+/- SD) number of CAG repeats [(CAGr)n] was 21.5 (+/- 1.7) in the control group, 21.4 (+/- 2.0) in the infertile patients and 24.0 (+/- 2.9) in the hypoandrogenic males. The difference was statistically significant between this last group and the other two (P < 0.0001), while there was no difference between normal controls and infertile patients. The frequency distribution showed a shift towards higher CAG length in hypoandrogenized patients compared to controls and infertile patients. If we used a cut-off point of 24.9 (2 SD above the mean), the percentage of patients with 25 or more CAGr repeats was 38% among hypoandrogenized patients, 7% among infertile patients and 5% among the control group. In hypoandrogenized subjects (CAGr)n correlated slightly with testis and prostate volume. The number of CAG repeats was not associated with any of the hormonal parameters, including testosterone, evaluated in the three groups. Conclusions Our normal population, representing subjects from Central Italy, is superimposable on other European populations with regard to (CAGr)n distribution. Hypoandrogenic males have a shift in the frequency distribution towards longer (CAGr)n. Infertile patients are not statistically different from the control group. These findings suggest that, given the same amount of circulating testosterone, as in our hypoandrogenized and control group, the final net androgenic phenotypical effect is due to AR polymorphism.

Adult↗
PubMed2005

Acromegaly: effects on bone metabolism and mass.

GH has a pivotal role in maintaining bone mass and metabolism both during childhood and in adult life. This effect depends on a complex interaction between circulating and peripherically produced GH and IGF-I. In vitro data and the use of genetically modified animals have greatly expanded the understanding of regulatory mechanisms underlying the well known skeletal changes featuring acromegalic disease. The present review focuses on the effects of GH excess on bone metabolism and mass in acromegalic patients with particular attention to the influence on bone metabolism as well as arthropathy of factors such as concomitant hypogonadism, gender, age of patients and therapy.

Acromegaly↗
PubMed2004

Mutations in the SLC26A4 (pendrin) gene in patients with sensorineural deafness and enlarged vestibular aqueduct.

Pendred syndrome and the enlarged vestibular aqueduct (EVA) are considered phenotypic variations of the same entity due to mutations in the SLC26A4 (pendrin) gene. Pendred syndrome consists in sensorineural deafness, goiter and impaired thyroid hormone synthesis while in EVA thyroid function seems to be preserved. The aim of this study was to evaluate thyroid function and morphology and to look for mutations in the SLC26A4 gene in patients presented with EVA. Among 57 consecutive patients with sensorineural deafness 15 with EVA, as assessed by magnetic resonance imaging (MRI), were identified and studied. A complete evaluation of thyroid function including thyroid echography and perchlorate discharge test was carried out in all patients with EVA; all exons of the SLC26A4 gene were amplified from peripheral leukocytes and directly sequenced, using specific intronic primers. Out of 15 patients with EVA, goiter was present in 8 (53%), hypothyroidism in 7 (47%), increased serum thyroglobulin levels in 8 (53%) and a positive perchlorate discharge test in 10 (67%). Nine alleles of the SLC26A4 gene were mutated: 2 novel mutations (L465W and G497R) and 4 already known mutations (T410M, R409H, T505N and IVS1001+1G>A) were found. Four subjects were compound heterozygous and 1 heterozygous (G497R/wt). All patients harbouring mutations in the SLC26A4 gene had goiter and a positive perchlorate discharge test: 3 were slightly hypothyroid and 2 euthyroid. The remaining 10 patients had no mutations in the SLC26A4 gene: 4 of them were hypothyroid, 2 with goiter and positive perchlorate discharge test, 2 without goiter and with negative perchlorate discharge test. Two patients without mutations were euthyroid with positive perchlorate discharge test. Patients with mutations in the SLC26A4 gene had larger thyroid volume (p<0.002), higher serum thyroglobulin (Tg) levels (p<0.002) and greater radioiodine discharge after perchlorate (p=0.09) than patients without mutations. The results of the present study lend support to the concept that all patients with mutated SLC26A4 gene have abnormalities of thyroid function tests.

Adolescent↗
PubMed2004

[Function tests for the Eustachian tube. Current knowledge].

The Eustachian tube regulates the homeostasis of the middle ear. Problems with its function are predominantly found in childhood. As a consequence, otitis and hearing impairment occur. The most important muscle is the tensor tympani muscle. The complexity of the functional anatomy and physiology are reasons why no function test alone is capable of fulfilling all diagnostic needs. The predictive value of the various Eustachian tube function tests for the outcome of a tympanoplasty is not yet clear. An overview of clinically and scientifically relevant tests for the Eustachian tube function is provided.

Eustachian Tube↗
PubMed2004

Molecular mechanisms for pituitary thyrotroph cell growth.

Neuroendocrine, endocrine and autocrine/paracrine signals contribute to the regulation of basal thyrotroph growth. Thyrotropin-releasing hormone (TRH), somatostatin, thyroid hormone (TH), estrogens (Es) and epidermal growth factor, all may play a role both in normal and tumoral thyrotroph proliferation, acting via either plasma membrane receptors and non-genomic steps or nuclear receptors and gene transcription. Signaling features common to all these ligands are involvement of G protein-coupled receptors, mitogen-activated protein kinase cascade and nuclear polyphosphoinositide cycle. In addition, each growth information, independently from the eliciting factor, may be routed intracellularly following a branched pathway, that often links different transduction systems at common check-points, as the Shc-Grb2-SOS complex. Finally, some ligands (e.g. TRH, TH, Es) may display opposite effects on thyrotroph growth, depending on environmental conditions and state of cell differentiation. These ambiguities of response can be interpreted using a "fuzzy" logic-based model of intracellular signaling. Accordingly, check-points common to different transduction cascades may be envisaged as targets for antitumoral therapy selective to the neoplastic thyrotroph cell.

Animals↗
PubMed2003

Microvascular density and vascular endothelial growth factor expression in normal pituitary tissue and pituitary adenomas.

Microvessel density (MVD) represents a measure of angiogenesis and may be used as an indicator of neoplastic aggressiveness. Vascular endothelial growth factor (VEGF) plays a pivotal role as angiogenic promoter by stimulating endothelial cell proliferation and migration and enhancing vascular permeability. The aim of this study was to investigate MVD and VEGF expression in human pituitary adenomas and normal pituitary gland tissues by immunohistochemistry, and to correlate data with clinical characteristics. Fragments from 46 pituitary adenomas (18 non-functioning, 12 ACTH-secreting, 12 GH-secreting, 4 PRL-secreting) and 19 specimens of normal anterior pituitary gland obtained at surgery were evaluated. MVD in normal anterior pituitary was significantly higher than in tumors (69.2 +/- 28.5 vs 29.3 +/- 19.7; p < 0.0001). Within adenomas, no difference was found in MVD when different histotype, size, sex, age, rate of recurrence or medical pre-surgical treatment were considered. The degree of vascularity was somewhat related only to clinical invasiveness, as evaluated by pre-surgical MRI grading (grade 0 p < 0.05 vs grade 1 and vs grade 2). No statistically significant difference in VEGF expression was found between normal tissue and adenomas and among tumors of different histotype (p = 0.3978). Size, sex, age, rate of recurrence and medical pre-surgical treatment did not influence VEGF expression. No correlation was found between MVD and VEGF expression. In conclusion, MVD was reduced in pituitary adenomas with respect to normal gland. VEGF expression is however well preserved in adenomas and this might contribute to adequate tumoral vascular supply with complex mechanisms other than endothelial cells proliferation.

Adenoma↗
PubMed2003

Three-hour spontaneous GH secretion profile is as reliable as oral glucose tolerance test for the diagnosis of acromegaly.

The diagnosis of acromegaly, in an appropriate clinical context, usually relies on lack of GH suppression below 1 microg/l during OGTT coupled with elevated IGF-I levels. On the other hand, in normal subjects glucose-induced inhibition of GH secretory bursts without any further decrease of interpulse GH levels had already been shown. Based on the foregoing, we aimed to compare the diagnostic reliability of OGTT-induced GH nadir with that recorded during 3-h spontaneous GH secretion. In 59 acromegalic patients (17 male and 42 female, age, mean +/- SE 51.5 +/- 1.9, range 21-76 yr) and in 82 normal subjects (43 male and 39 female, age, mean +/- SE 35.7 +/- 1.5, range 15-72 yr) GH secretion was evaluated every 30 min from 0 to 180 min during slow saline infusion or OGTT (75 g at 0 min). A nadir GH concentration below 1 microg/l was recorded in all normal subjects either during OGTT or saline infusion if GH secretion was evaluated over 180 min. In contrast in acromegalic patients a nadir GH concentration below 1 microg/l never occurred in both conditions. This study shows that a 3-h spontaneous GH profile is as reliable as OGTT in the diagnosis of active acromegaly.

Acromegaly↗