Monica Giannetti

Università di Pisa, Pisa, Tuscany, Italy

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Publications (14)49.05 Total impact

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    ABSTRACT: Objective: Sulfate conjugation of thyroid hormones is an alternate metabolic pathway that facilitates the biliary and urinary excretion of iodothyronines and enhances their deiodination rate, leading to the generation of inactive metabolites. A de-sulfating pathway reverses this process and thyromimetic effects have been observed following the parenteral administration of 3,5,3'-triiodothyronine sulfate (T3S) in rats. The present study investigated whether T3S is absorbed after oral administration in humans and if it represents a source of 3,5,3'-triiodothyronine (T3).Methods: Twenty-eight hypothyroid patients (7 men and 21 women, mean age ± SD = 44 ± 11 years) who had a thyroidectomy for thyroid carcinoma were enrolled. Replacement thyroid hormone therapy was withdrawn (42 days for thyroxine, 14 days for T3) prior to radioiodine remnant ablation. A single oral dose of 20, 40, 80 (4 patients/group) or 160 μg (16 patients/group) T3S was administered 3 days before the planned administration of 131I. Blood samples for serum T3S and total T3 (TT3) concentrations were obtained at various times up to 48 hours after T3S administration.Results: At all T3S doses, serum T3S concentrations increased reaching a peak at 2-4 hours and progressively returned to basal levels within 8 to 24 h. The T3S Cmax and area under the curve (AUC0-48h) were directly and significantly related to the administered dose.An increase in serum TT3 concentration levels was observed, significant after 1 hour, further increased at 2 and 4 hours, and then remained steady up to 48 hours after T3S administration. There was a significant direct correlation between the TT3 AUC0-48h and the administered dose of T3S. No changes in serum free thyroxine (FT4) concentrations during the entire study period were observed, while serum TSH levels increased slightly at 48 hours not related to the dose of administered T3S. No adverse events were reported.Conclusions: 1) T3S is absorbed following oral administration in hypothyroid humans; 2) the oral administration of a single dose of T3S is converted to T3 in a dose-dependent manner and results in steady state serum T3 concentrations for 48 hours; 3) T3S may represent a new agent in combination with thyroxine (T4) in the therapy of hypothyroidism, if similar conversion of T3S to T3 can be demonstrated in euthyroid patients who are already taking T4.
    Endocrine Practice 02/2014; · 2.49 Impact Factor
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    ABSTRACT: Obesity is associated with abnormalities of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis. The role of serum IGF-1 measurement for recognition of hypothalamic-pituitary diseases in obesity is still a matter of debate. This study evaluated the serum levels of IGF-1 in a population of severely obese women before and after long-term weight loss obtained by laparoscopic adjustable gastric banding (LAGB). Eighty obese women with body mass index (BMI) of more than 34 kg/m(2) and 80 unrelated age-matched lean controls were enrolled. IGF-1 serum levels were measured together with BMI, liver volume, and intra-abdominal fat thickness assessed by ultrasound. Evaluation was repeated 2 years after LAGB. Our results showed that mean IGF-1 levels in obese subjects before LAGB were significantly lower (p < 0.001) than that observed in age-matched controls. Age and BMI were independent predictors of serum IGF-1 values, overall accounting for 39 % of IGF-1 variability. The mean IGF-1 concentration significantly increased 2 years after LAGB. BMI reduction was independently associated with IGF-1 increase (r = -0.29, p < 0.001). For each point of BMI reduction, the mean increase of serum IGF-1 was 4.39 ng/mL. (1) Severely obese women have low IGF-1 serum levels with respect to normal weight age-matched controls; (2) the extent of IGF-1 deficiency is proportional to increased BMI; (3) after LAGB a spontaneous raise of serum IGF-1 occurs, proportional to the extent of weight reduction; and (4) serum IGF-1 in severely obese subjects may have a limited value for detection of hypothalamic-pituitary diseases.
    Obesity Surgery 05/2012; 22(8):1276-80. · 3.10 Impact Factor
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    ABSTRACT: Nonalcoholic fatty liver disease is a common finding in obese subjects. Increasing evidence has been provided suggesting that it represents the hepatic component of the metabolic syndrome. Aim of this longitudinal study was to evaluate the relationships between several anthropometric measures, including the hepatic left lobe volume (HLLV), and various indicators of the metabolic syndrome in a cohort of severely obese women before and after laparoscopic adjustable gastric banding (LAGB). Seventy-five obese women (mean age 45 ± 10 years and body mass index (BMI) 42.5 ± 4.8 kg m(-2)) underwent LAGB and completed an average (± s.d.) post-surgical follow-up of 24 ± 6 months. Determination of HLLV, subcutaneous and intra-abdominal fat (IAF) was based on ultrasound. The principal component statistical analysis applied to pre-operative measurements, highlighted HLLV as a parameter that clustered with serum insulin, IAF, serum glucose and uric acid, along with triglycerides (TGs), alkaline phosphatase and high-density lipoprotein cholesterol. After LAGB, the average reduction of BMI was 23%, 12% for subcutaneous fat (SCF), 42% for HLLV and 40% for visceral fat. Among body weight, BMI, SCF, IAF and HLLV, reduction of the latter was an independent predictor of reduction of serum transaminases and γ-Glutamyltransferase, glucose, insulin and TGs. In severely obese women: (i) HLLV is a sensitive indicator of ectopic fat deposition, clustering with parameters defining the metabolic syndrome; (ii) weight loss achieved by LAGB is associated with a reduction of liver volume as estimated by HLLV; (iii) among various anthropometric parameters measured, reduction of HLLV that follows LAGB represents the best single predictor of improvement of various cardiometabolic risk factors.
    International journal of obesity (2005) 12/2011; 36(3):336-41. · 5.22 Impact Factor
  • Clinical Chemistry and Laboratory Medicine 05/2011; 49(8):1385-7. · 3.01 Impact Factor
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    ABSTRACT: Bariatric surgery allows stable body weight reduction in morbidly obese patients. In presurgical evaluation, obesity-related co-morbidities must be considered, and a multidisciplinary approach is recommended. Precise guidelines concerning the endocrinological evaluation to be performed before surgery are not available. The aim of this study was to evaluate the prevalence of common endocrine diseases in a series of obese patients scheduled for bariatric surgery. We examined 783 consecutive obese subjects (174 males and 609 females) aged 18-65 years, who turned to the obesity centre of our department from January 2004 to December 2007 for evaluation before bariatric surgery. Thyroid, parathyroid, adrenal and pituitary function was evaluated by measurement of serum hormones. Specific imaging or supplementary diagnostic tests were performed when indicated. The overall prevalence of endocrine diseases, not including type 2 diabetes mellitus, was 47.4%. The prevalence of primary hypothyroidism was 18.1%; pituitary disease was observed in 1.9%, Cushing syndrome in 0.8%, while other diseases were found in less than 1% of subjects. Remarkably, the prevalence of newly diagnosed endocrine disorders was 16.3%. A careful endocrinological evaluation of obese subjects scheduled for bariatric surgery may reveal undiagnosed dysfunctions that require specific therapy and/or contraindicate the surgical treatment in a substantial proportion of patients. These results may help to define the extent of the endocrinological screening to be performed in obese patients undergoing bariatric surgery.
    Obesity Surgery 10/2010; 21(1):54-60. · 3.10 Impact Factor
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    ABSTRACT: TSH-receptor (TSHR) has been found in a variety of cell types, including preadipocytes and adipocytes. In vitro, TSH-mediated preadipocyte and adipocyte responses include proliferation, differentiation, survival, and lipolysis. Objective To measure the response of serum leptin to exogenous administration of recombinant human TSH (rhTSH) in vivo. Patients One hundred patients with differentiated thyroid cancer already treated by total thyroidectomy and (131)I remnant ablation were enrolled. Mean (+/-s.e.m.) body mass index (BMI) was 26.9+/-0.6 kg/m(2). Methods Patients received a standard dose of rhTSH for measurement of thyroglobulin in the follow-up of their disease. Blood samples were taken for the assay of TSH and leptin before the first administration of rhTSH (time 0), and 24 h (time 1), 48 h (time 2), 72 h (time 3), and 96 h (time 4) after the first administration of rhTSH. Results Significant mean serum leptin increments, with respect to basal value, were 16, 13, 18, and 11% at times 1, 2, 3, and 4 respectively. Significant positive correlations of leptin-area under the curve with respect to basal leptin levels (r=0.43; P<0.0001) and BMI (r=0.32; P<0.005) were observed. Conclusions Acute rhTSH administration in hypothyroid subjects under l-thyroxine therapy produces a rise in serum leptin. This increase is proportional to the adipose mass suggesting that a functioning TSHR is expressed on the surface of adipocytes. The role that TSHR activation in adipocytes might play in physiological and pathological conditions remains a matter of investigation.
    European Journal of Endocrinology 07/2010; 163(1):63-7. · 3.14 Impact Factor
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    ABSTRACT: Adiponectin has antisteatosis-anti-inflammatory properties and its circulating levels are reduced in nonalcoholic steatohepatitis (NASH). To assess the role of adiponectin in NASH, we measured expression of adiponectin gene (APM1) and receptors (AdipoR1/AdipoR2) in liver and subcutaneous and visceral fat in subjects with biopsy-proven NASH or pure steatosis (PS). In 103 subjects undergoing gastric bypass or elective abdominal surgery (17 with normal liver histology (C), 52 with PS, and 34 with NASH), RNA was extracted from tissue samples, and quantification of APM1, AdipoR1, and AdipoR2 was carried out by real-time polymerase chain reaction. In NASH vs C, circulating adiponectin levels (3.6[2.4] vs 5.3[4.3] microg/ml, median[interquartile range], p < 0.05) and adiponectin concentrations, APM1, AdipoR1, and AdipoR2 expression in visceral fat were all reduced (p < or = 0.03). These differences disappeared when adjusting for obesity. In contrast, liver AdipoR1 (1.40 [0.46] vs 1.00 [0.32] of controls) and AdipoR2 expression (1.20 [0.41] vs 0.78 [0.43]) were increased in NASH, and group differences were statistically significant (p < 0.0001 for AdipoR1 and p = 0.0001 for AdipoR2). Results for PS were generally intermediate between NASH and C. Liver receptor expression was reciprocally related to circulating adiponectin (rho = -0.42, p < 0.003 for AdipoR1 and rho = -0.26, p < 0.009 for AdipoR2). In multivariate models adjusting for sex, age, fasting plasma glucose, and obesity, liver enzymes levels were directly related to both AdipoR1 and AdipoR2 expression in liver. In obese patients with NASH, adiponectin receptors are underexpressed in visceral fat-as a likely correlate of obesity-but overexpressed in liver, possibly as a compensatory response to hypoadiponectinemia, and positively associated with liver damage.
    Obesity Surgery 11/2008; 19(4):467-74. · 3.10 Impact Factor
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    ABSTRACT: Aim of this study was to investigate the effect of weight loss on structural and functional myocardial alterations in severely obese subjects treated with bariatric surgery. Thirteen severely obese patients (2 males and 11 females) were enrolled in the study. All subjects underwent conventional 2D color Doppler echocardiography. The new ultrasonic techniques used were: (a) integrated backscatter for the analysis of myocardial reflectivity, referred to pericardial interface as expression of myocardial structure (increase in collagen content) and of cyclic variation index as expression of intrinsic myocardial contractility and (b) color Doppler myocardial imaging (CDMI) for the analysis of strain and strain rate (myocardial deformability). All subjects underwent bariatric surgery and were resubmitted to echocardiographic and biochemical examination 6-24 months after surgery. The main finding of the present study was a quite complete normalization of myocardial functional and structural alterations after weight loss. In particular, the cyclic variation index at septum level improved from 14.6 +/- 7.0 before to 25.7 +/- 11.2 (means +/- SD) after surgery (controls: 36.2 +/- 9.1). Mean reflectivity at septum level significantly decreased from 55.8 +/- 9.5 to 46.5 +/- 8.8 (controls: 43.0 +/- 8.0). Also, the strain at septum level significantly improved after surgery (from -11.9 +/- 3.2 to -20.4 +/- 5.3; controls: -23.4 +/- 9). This study establishes: (a) the utility of new ultrasonic techniques to detect very early structural and functional myocardial alterations in severely obese patients, and (b) the regression of these subclinical abnormalities after weight loss achieved by bariatric surgery.
    Cardiology 02/2008; 109(4):241-8. · 1.52 Impact Factor
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    ABSTRACT: Non-alcoholic fatty liver disease is a common finding in obese subjects, and increasing evidence has been provided suggesting that it represents the hepatic component of the metabolic syndrome. The aim of this study was to evaluate whether the extent of liver enlargement is related to the severity of the metabolic syndrome in obese women. The relationship between ultrasound- measured hepatic left lobe volume (HLLV) and various features of the metabolic syndrome was evaluated in 85 obese women. The mean+/-SD value of HLLV in obese women was 431+/-214 ml (range 46-1019 ml) while it was 187+/-31 ml (range 143-258 ml) in lean subjects. In a multiple logistic regression analysis, ultrasound-measured intra-abdominal fat was the only anthropometric measure independently associated with HLLV. A strong positive association was found between HLLV and serum liver enzymes, triglycerides, glucose, insulin, uric acid, C reactive protein, systolic and diastolic blood pressure, while a negative correlation was observed between HLLV and HDL cholesterol. The values of HLLV corresponding to the cut-off values of various risk factors for the diagnosis of the metabolic syndrome were calculated, yielding a mean value of 465 ml. In conclusion, ultrasound measurement of HLLV represents a simple, reliable and low-cost tool for the evaluation of liver involvement in the metabolic syndrome. The strong association between liver enlargement and various cardiovascular risk factors associated with insulin resistance supports the role of liver steatosis as an important link among the many facets of the metabolic syndrome in human obesity.
    Journal of endocrinological investigation 03/2007; 30(2):104-10. · 1.65 Impact Factor
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    ABSTRACT: Obesity is a well-established risk factor for congestive heart failure. Evidence has been provided indicating that insulin resistance could be the mediator between obesity and congestive heart failure, but the pathogenic mechanisms leading to myocardial alterations remain unclear. The aim of this study was to investigate, by ultrasonic integrated backscatter (IBS) analysis, subclinical alterations of left ventricular (LV) structure and function in severe obesity. Sixty consecutive, severely obese people, who were otherwise healthy (15 men, 45 women; mean age +/- SD = 31.8 +/- 7 years), were enrolled. A total of 48 sex- and age-matched nonobese healthy participants were recruited as control subjects. All participants underwent conventional 2-dimensional color Doppler echocardiography, pulsed wave Doppler tissue imaging at mitral annulus level, and IBS. The homeostasis model assessment insulin resistance index was used to assess insulin resistance; the index values in the obese group were significantly higher (mean +/- SD = 4.9 +/- 1.4) than in the control group (0.92 +/- 0.5, P < .0001). Obese patients had a greater LV mass index by height (58.5 +/- 14 g/m(2.7)) than did control subjects (37 +/- 8 g/m(2.7), P < .0001) because of compensation response to volume overload caused by a greater cardiac output (P < .02). Preload reserve was increased in obese patients, as demonstrated by the significant increase in left atrial dimension (P < .0001). This volumetric increase activated the Frank-Starling mechanism, and determined a significantly higher LV ejection fraction (P < .03) in obese patients as compared with control subjects. A slightly reduced LV diastolic function was demonstrated in obese patients (transmitral early to late peak diastolic transmitral flow velocities ratio = 1.1 +/- 0.7) as compared with control subjects (1.5 +/- 0.5, P < .02). Pulsed wave Doppler tissue imaging showed an impairment of diastolic LV longitudinal function and increased LV diastolic filling pressure. The IBS values at septum level, indexed by pericardium interface, were significantly higher for septum in the obese group (57.8 +/- 8%) than in the control group (42.3 +/- 9%, P < .0001). Additional IBS alterations were observed in the obese group, with a significantly lower cyclic variation index both at septum (P < .0001) and at posterior wall (P < .001) levels. A significant association was found between insulin resistance index and both the IBS index of myocardial reflectivity at septum level (expression of increased myocardial collagen content) or LV mass. In conclusion, this study demonstrates that obese patients exhibit myocardial structural and functional alterations related to insulin resistance and to LV volume overload, which could be considered the very early stage of incipient obesity cardiomyopathy.
    Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography 08/2006; 19(8):1063-71. · 2.98 Impact Factor
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    ABSTRACT: BACKGROUND: The aim of this study was to evaluate the relationship between insulin resistance and preclinical abnormalities of the left ventricular structure and function detected in severe obesity by Color Doppler Myocardial Imaging (CDMI). Forty-eight consecutive severely obese patients (Group O) (11 males, 37 females, mean age 32.8+/-7 years) were enrolled. Forty-eight sex- and age-matched non-obese healthy subjects were also recruited as controls (Group C). All subjects underwent conventional 2D-Color Doppler echocardiography and CDMI. The homeostasis model assessment insulin resistance index (HOMA-IR) was used to assess insulin resistance results. Obese subjects had a greater left ventricular mass index (by height) (58.8+/-14 g/m(2.7)) than controls (37+/-8 g/m(2.7)) (P<0.0001), owing to compensation response to volume overload caused by a greater cardiac output (P<0.02). Preload reserve was increased in obese subjects, as demonstrated by a significant increase in left atrial dimension (P<0.0001). Obese patients had a slightly reduced LV diastolic function (transmitral E/A ratio: Group O, 1.1+/-0.8 vs Group C, 1.5 +/-0.5; P<0.002). Cardiac deformation assessed by regional myocardial systolic strain and strain rate (SR) values was significantly lower (abnormal) in obese patients than in controls, both at the septum and lateral wall level. These strain and SR abnormalities were significantly related to body mass index. In addition, the early phase of diastolic function, evaluated using SR, was compromised in obese patients (P<0.001). The HOMA-IR values in obese patients were significantly higher (3.09+/-1.6) than those determined in the control group (0.92+/-0.5) (P<0.0001). The HOMA-IR values, in the obese group, were significantly related to systolic strain and SR values sampled at the septum level (P<0.0001). CONCLUSION: In conclusion, this study has demonstrated that obese patients pointed out systolic structural and functional abnormalities at a preclinical stage, in particular through strain and SR analysis; on the other hand, those altered CDMI parameters well distinguish obese subjects as compared with the control group. Furthermore, another main finding of the study was that myocardial deformation (systolic strain) could have a correlation with insulin resistance level.
    International Journal of Obesity 06/2006; 30(6):948-56. · 5.22 Impact Factor
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    ABSTRACT: In this study, we evaluated the influence of height, weight, body mass index (BMI), body surface area, and body composition [total lean body mass (LBM) and fat body mass] on serum peak TSH levels obtained after recombinant human (rh)TSH. Furthermore, to verify whether the serum peak TSH influenced the efficacy of radioiodine ((131)I), we compared the rate of thyroid remnant ablation according to the patients' BMI. We studied 105 patients with differentiated thyroid carcinoma who underwent rhTSH stimulation test. Serum TSH measurements were performed before and 24, 48, and 72 h after rhTSH administration. We also compared the rate of thyroid remnant ablation among 70 differentiated thyroid carcinoma patients with different BMI. The serum peak TSH after rhTSH was significantly lower in overweight and obese subjects compared with normal-weight subjects (92.1 +/- 41.8, 82.4 +/- 24.2, and 112.7 +/- 46.3 microU/ml, respectively; P = 0.01) and in males compared with females (74.6 +/- 22.3 and 105.0 +/- 43.0 microU/ml, respectively; P = 0.0002). By univariate analysis, serum peak TSH was negatively related to weight, height, body surface area, BMI, LBM, and fat body mass, but only LBM was independently associated with serum peak TSH levels. Although it was confirmed that overweight and obese patients had a lower serum peak TSH, the rate of ablation did not differ among normal-weight, overweight, and obese patients. With this study we demonstrated that LBM is the only parameter independently associated with serum peak TSH after rhTSH administration. However, the serum peak TSH does not influence the rate of (131)I remnant ablation.
    Journal of Clinical Endocrinology &amp Metabolism 08/2005; 90(7):4047-50. · 6.43 Impact Factor
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    ABSTRACT: Total body weight is usually employed to calculate the amount of l-T(4) to be administered in patients with thyroid diseases. The aim of this study was to evaluate the effect of body composition on l-T(4) requirements. Body composition was assessed by dual energy x-ray absorptiometry in 75 patients on TSH-suppressive l-T(4) therapy after conventional thyroid ablation for differentiated cancer. The mean daily dose of l-T(4) was lower in normal-weight (127.5 +/- 21.3 mug/d) vs. overweight (139.4 +/- 24.5) and obese (151.3 +/- 29.1) subjects. There was a much stronger association between the l-T(4) dosage and lean body mass (P < 0.001, r = 0.667) compared with fat mass (P = 0.023, r = 0.26). Measurement of regional tissue composition showed peripheral lean mass as the best correlate with the dose of l-T(4) (r = 0.679, P < 0.001) whereas no correlation was observed with peripheral fat mass. In conclusion, individual l-T(4) requirements are dependent on lean body mass. Age- and gender-related differences in l-T(4) needs reflect different proportions of lean mass over the total body weight. An estimate of lean mass may be helpful to shorten the time required to attain a stable dose of l-T(4), particularly in subjects with high body mass index values that may be due either to increased muscular mass or to obesity.
    Journal of Clinical Endocrinology &amp Metabolism 02/2005; 90(1):124-7. · 6.43 Impact Factor
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    ABSTRACT: Thyroid dysfunction is associated with metabolic changes that affect mass and adipocyte function, as well as lipid and carbohydrate metabolism. Adipose tissue performs complex metabolic and endocrine functions. Leptin and adiponectin are two of the most important adipocytokines, both involved in the regulation of intermediate metabolism. The aim of this study was to evaluate the relationships between thyroid status and circulating levels of the two adipose tissue hormones. We studied 15 patients with hyperthyroidism, 15 patients with hypothyroidism and 15 euthyroid subjects, all matched by sex, age and body mass index (BMI). Serum concentrations of free thyroxine, free tri-iodothyronine, thyrotropin, leptin and adiponectin and anthropometric parameters (weight, height, BMI) were assessed. No significant difference was found among the 3 groups, as assessed by Student's t-test, both for adiponectin and leptin. We conclude that metabolic changes associated with thyroid dysfunction are not related to variations in serum levels of adiponectin or leptin.
    Journal of endocrinological investigation 03/2004; 27(2):RC5-7. · 1.65 Impact Factor