Thyroid Diseases: Lombardi G

Rosato L, Miccoli P, Pinchera A, Lombardi G, Romano M, Avenia N, Bastagli A, Bellantone R, De Palma M, De Toma G, Gasparri G, Lampugnani R, Marini PL, Nasi PG, Pellizzo MR, Pezzullo L, Piccoli M, Testini M. · Dipartimento di Chirurgia - ASL TO/4, Ospedale di Ivrea, Italy. · G Chir. · Pubmed #19351456 No free full text.

Abstract: AIM: To review and to update the management protocols in thyroid surgery proposed two years ago by 1st Consensus Conference called on the topic by the Italian Association of Endocrine Surgery Units (UEC Club). METHOD: The 2nd Consensus Conference took place November 30, 2008 in Pisa within the framework of the 7th National Congress of the UEC Club. A selected board of endocrinologists and endocrine surgeons (chairmans: Paolo Miccoli and Aldo Pinchera; speaker: Lodovico Rosato) examined the individual chapters and submitted the consensus text for the approval of several experts. This plain and concise text provides the rationale of the thyroid patient management and wants to be the most complete possible tool for the physicians and other professionals in the field. CONCLUSIONS: The diagnostic, therapeutic and healthcare management protocols in thyroid surgery approved by the 2nd Consensus Conference are officially those proposed by the Italian Association of Endocrine Surgery Units (UEC Club) and are subject to review by two years.

Pivonello R, De Martino MC, De Leo M, Tauchmanovà L, Faggiano A, Lombardi G, Colao A. · Department of Molecular and Clinical Endocrinology and Oncology, Federico II University of Naples, Italy. · Arq Bras Endocrinol Metabol. · Pubmed #18209877 links to  free full text

Abstract: Cushing's syndrome (CS) is a chronic and systemic disease caused by endogenous or exogenous hypercortisolism, associated with an increase of mortality rate due to the clinical consequences of glucocorticoid excess, especially cardiovascular diseases. After cure, usually obtained by the surgical removal of the tumor responsible for the disease, the normalization of cortisol secretion is not constantly followed by the recovery of the clinical complications developed during the active disease, and it is often followed by the development of novel clinical manifestations induced by the fall of cortisol levels. These evidences were mostly documented in patients with pituitary-dependent CS, after surgical resection of the pituitary tumor. Indeed, despite an improvement of the mortality rate, metabolic syndrome and the consequent cardiovascular risk have been found to partially persist after disease remission, strictly correlated to the insulin resistance. Skeletal diseases, mainly osteoporosis, improve after normalization of cortisol levels but require a long period of time or the use of specific treatment, mainly bisphosphonates, to reach the normalization of bone mass. A relevant improvement or resolution of mental disturbances has been described in patients cured from CS, although in several cases, cognitive decline persisted and psychological or psychiatric improvement was erratic, delayed, or incomplete. On the other hand, development or exacerbation of autoimmune disorders, mainly thyroid autoimmune diseases, was documented in predisposed patients with CS after disease remission. The totality of these complications persisting or occurring after successful treatment contribute to the impairment of quality of life registered in patients with CS after disease cure.

De Bellis A, Bizzarro A, Pivonello R, Lombardi G, Bellastella A. · Department of Clinical and Experimental Medicine and Surgery F. Magrassi, A. Lanzara, Second University of Naples, via Pansini N. 5, 80131, Napoli, Italy. · Pituitary. · Pubmed #16411065 No free full text.

Abstract: The interrelationship between prolactin (PRL) and the immune system have been elucitaded in the last decade, opening new important horizons in the field of the immunoendocrinology. PRL is secreted not only by anterior pituitary gland but also by many extrapituitary sites including the immune cells. The endocrine/paracrine PRL has been shown to stimulate the immune cells by binding to PRL receptors. Increased PRL levels, frequently described in autoimmune diseases, could depend on the enhancement of coordinated bi-directional communications between PRL and the immune system observed in these diseases. Hyperprolactinemia has been described in the active phase of some non organ-specific autoimmune diseases, as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and organ-specific autoimmune diseases, as celiac disease, type 1 diabetes mellitus, Addison's disease, autoimmune thyroid diseases. In these diseases PRL increases the syntesis of IFNgamma and IL-2 by Th1 lymphocytes. Moreover, PRL activates Th2 lymphocytes with autoantibody production. Of particular interest is the association between hyperprolactinemia and levels of anti DNA antibodies, islet cell antibodies (ICA), thyreoglobulin antibodies (TgAb), thyroperoxidase antibodies (TPOAb), adrenocortical antibodies (ACA), transglutaminase antibodies (tTGAb) in SLE, in type 1 diabetes mellitus, in Hashimoto's thyroiditis, in Addison's disease and in celiac disease, respectively. High levels of PRL have been also frequently detected in patients with lymphocytic hypophysitis (LYH). Several mechanisms have been invoked to explain the hyperprolactinemia in LYH. The PRL increase could be secondary to the inflammatory process of the pituitary gland but, on the other hand, this increase could have a role in enhancing the activity of the immune process in LYH. Moreover, the detection of antipituitary antibodies targeting PRL-secreting cells in some patients with idiopathic hyperprolactinemia suggests the occurrence of a possible silent LYH in these patients. Finally, the role of anti-prolactinemic drugs to inactivate the immune process in LYH is still discussed.

Palmieri EA, Fazio S, Lombardi G, Biondi B. · Department of Clinical Medicine, Cardiovascular and Immunological Science, University Federico II School of Medicine, Naples, Italy. · Treat Endocrinol. · Pubmed #16026106 No free full text.

Abstract: Subclinical hypothyroidism (SH), defined by elevated serum levels of thyroid stimulating hormone (TSH) with normal levels of free thyroid hormones, is common in adults, especially in women over 60 years of age. Among individuals with this condition, up to two-thirds have serum TSH levels between 5-10 mU/L and thyroid autoantibodies; almost half of them may progress to overt thyroid failure, the annual percent risk increasing with serum TSH level. There is evidence that elevated TSH levels in patients with SH do not reflect pituitary compensation to maintain euthyroidism, but a mild tissue hypothyroidism sensu strictu. When lasting more than 6-12 months, SH may be associated with an atherogenic lipid profile, a hypercoagulable state, a subtle cardiac defect with mainly diastolic dysfunction, impaired vascular function, and reduced submaximal exercise capacity. The deviation from normality usually increases with serum TSH level ('dosage effect' phenomenon). Restoration of euthyroidism by levothyroxine (LT4) treatment may correct the lipid profile and cardiac abnormalities, especially in patients with an initially higher deviation from normality and higher serum TSH levels. Importantly, a strong association between SH and atherosclerotic cardiovascular disease, independent of the traditional risk factors, has been recently reported in a large cross-sectional survey (the Rotterdam Study). However, whether SH confers a high risk for cardiovascular disease, and whether LT4 therapy has a long-term benefit that clearly outweighs the risks of overzealous treatment in these individuals, remain topics of controversy. Therefore, until randomized, controlled, prospective, and adequately powered trials provide unequivocal answers to these critical questions, it is advisable to prescribe LT4 therapy on a case-by-case basis, taking into account the risk of progressive thyroid failure and the risk of cardiovascular events.

Pagano L, Klain M, Pulcrano M, Angellotti G, Pasano F, Salvatore M, Lombardi G, Biondi B. · Department of Clinical and Molecular Endocrinology and Oncology, Federico II University of Naples, School of Medicine, Naples, Italy. · Minerva Endocrinol. · Pubmed #15765026 links to  free full text

Abstract: Thyroid cancer is the most common endocrine malignancy. More than 90% of primary thyroid cancers are differentiated papillary or follicular types. The treatment of differentiated thyroid carcinoma (DTC) consists of total thyroidectomy and radioactive iodine ablation therapy, followed by L-thyroxine therapy. The extent of initial surgery, the indication for radioiodine ablation therapy and the degree of TSH-suppression are all issues that are still being debated cancers are in relation to the risk of recurrence. Total thyroidectomy reduces the risk of recurrence and facilitates (131)I ablation of thyroid remnants. The aim of radioiodine ablation is to destroy any normal or neoplastic residuals of thyroid tissue. These procedures also improve the sensitivity of thyroglobulin (Tg) as a marker of disease, and increase the sensitivity of (131)I total body scan (TBS) for the detection of persistent or recurrent disease. The aim of TSH-suppressive therapy is to restore euthyroidism and to decrease serum TSH levels, in order to reduce the growth and progression of thyroid cancer. After initial treatment, the objectives of the follow-up of DTC is to maintain adequate thyroxine therapy and to detect persistent or recurrent disease through the combined use of neck ultrasound (US) and serum Tg and (131)I TBS after TSH stimulation. The follow-up protocol should be adapted to the risk of recurrence. Recent advances in the follow-up of DTC are related to the use of recombinant human TSH (rhTSH) in order to stimulate Tg production and the ultrasensitive methods for Tg measurement. Undetectable serum Tg during TSH suppressive therapy with L-T4 does not exclude persistent disease, therefore serum Tg should be measured after TSH stimulation. The results of rhTSH administration and L-thyroxine therapy withdrawal are equivalent in detecting recurrent thyroid cancer, but the use of rhTSH helps to avoid the onset of hypothyroid symptoms and the negative effects of acute hypothyroidism on cardiovascular, hepatic, renal and neurological function. In low-risk DTC patients serum Tg after TSH stimulation, together with ultrasound of the neck, should be used to monitor persistent disease, avoiding diagnostic TBS which has a poor sensitivity. These recommendations do not apply when Tg antibodies are present in the serum, in patients with persistent or recurrent disease or limited thyroid surgery. Low-risk patients may be considered to be in remission when undetectable Tg after TSH stimulation and negative US evaluation of the neck are present. On the contrary, detectable Tg after TSH stimulation is an indicator in selecting patients who are candidates for further diagnostic procedures.

Biondi B, Palmieri EA, Klain M, Schlumberger M, Filetti S, Lombardi G. · Department of Clinical and Molecular Endocrinology and Oncology, University of Naples Federico II, 80131 Naples, Italy. · Eur J Endocrinol. · Pubmed #15762182 links to  free full text

Abstract: Subclinical hyperthyroidism appears to be a common disorder. It may be caused by exogenous or endogenous factors: excessive TSH suppressive therapy with L-thyroxine (L-T4) for benign thyroid nodular disease, differentiated thyroid cancer, or hormone over-replacement in patients with hypothyroidism are the most frequent causes. Consistent evidence indicates that 'subclinical' hyperthyroidism reduces the quality of life, affecting both the psycho and somatic components of well-being, and produces relevant signs and symptoms of excessive thyroid hormone action, often mimicking adrenergic overactivity. Subclinical hyperthyroidism exerts many significant effects on the cardiovascular system; it is usually associated with a higher heart rate and a higher risk of supraventricular arrhythmias, and with an increased left ventricular mass, often accompanied by an impaired diastolic function and sometimes by a reduced systolic performance on effort and decreased exercise tolerance. It is well known that these abnormalities usually precede the onset of a more severe cardiovascular disease, thus potentially contributing to the increased cardiovascular morbidity and mortality observed in these patients. In addition, it is becoming increasingly apparent that subclinical hyperthyroidism may accelerate the development of osteoporosis and hence increased bone vulnerability to trauma, particularly in postmenopausal women with a pre-existing predisposition. Subclinical hyperthyroidism and its related clinical manifestations are reversible and may be prevented by timely treatment.

Fazio S, Palmieri EA, Lombardi G, Biondi B. · Department of Clinical Medicine and Cardiovascular Sciences, University of Naples "Federico II" School of Medicine, 80131, Naples, Italy. · Recent Prog Horm Res. · Pubmed #14749496 links to  free full text

Abstract: Increased or reduced action of thyroid hormone on certain molecular pathways in the heart and vasculature causes relevant cardiovascular derangements. It is well established that overt hyperthyroidism induces a hyperdynamic cardiovascular state (high cardiac output with low systemic vascular resistance), which is associated with a faster heart rate, enhanced left ventricular (LV) systolic and diastolic function, and increased prevalence of supraventricular tachyarrhythmias - namely, atrial fibrillation - whereas overt hypothyroidism is characterized by the opposite changes. However, whether changes in cardiac performance associated with overt thyroid dysfunction are due mainly to alterations of myocardial contractility or to loading conditions remains unclear. Extensive evidence indicates that the cardiovascular system responds to the minimal but persistent changes in circulating thyroid hormone levels, which are typical of individuals with subclinical thyroid dysfunction. Subclinical hyperthyroidism is associated with increased heart rate, atrial arrhythmias, increased LV mass, impaired ventricular relaxation, reduced exercise performance, and increased risk of cardiovascular mortality. Subclinical hypothyroidism is associated with impaired LV diastolic function and subtle systolic dysfunction and an enhanced risk for atherosclerosis and myocardial infarction. Because all cardiovascular abnormalities are reversed by restoration of euthyroidism ("subclinical hypothyroidism") or blunted by beta-blockade and L-thyroxine (L-T4) dose tailoring ("subclinical hyperthyroidism"), timely treatment is advisable in an attempt to avoid adverse cardiovascular effects. Interestingly, some data indicate that patients with acute and chronic cardiovascular disorders and those undergoing cardiac surgery may have altered peripheral thyroid hormone metabolism that, in turn, may contribute to altered cardiac function. Preliminary clinical investigations suggest that administration of thyroid hormone or its analogue 3,5-diiodothyropropionic acid greatly benefits these patients, highlighting the potential role of thyroid hormone treatment in patients with acute and chronic cardiovascular disease.

Biondi B, Palmieri EA, Lombardi G, Fazio S. · Department of Clinical and Molecular Endocrinology and Oncology, University of Naples Federico II School of Medicine, 80131 Naples, Italy. · Ann Intern Med. · Pubmed #12458990 links to  free full text

Abstract: BACKGROUND: Mounting evidence indicates that subclinical thyroid dysfunction has important clinical effects and prognostic implications, supporting the view that it is not a compensated biochemical change sensu strictu. PURPOSE: To review clinical information on the effects of subclinical thyroid dysfunction on the heart. DATA SOURCES: English-language articles identified from files and a MEDLINE search (1970-September 2001), references of relevant articles, textbooks, and meeting abstracts. STUDY SELECTION: Reports on the effects of subclinical hypothyroidism and subclinical hyperthyroidism on the cardiovascular system in humans. DATA EXTRACTION: Data on cardiac structure and performance, arrhythmias, and risk for coronary artery disease were independently assessed by all authors and summarized. DATA SYNTHESIS: Subclinical hypothyroidism is associated with impaired left ventricular diastolic function at rest, systolic dysfunction on effort, and enhanced risk for atherosclerosis and myocardial infarction. Subclinical hyperthyroidism is associated with increased heart rate, atrial arrhythmias, increased left ventricular mass with marginal concentric remodeling, impaired ventricular relaxation, reduced exercise performance, and increased risk for cardiovascular death. All abnormalities were reversed by restoration of euthyroidism (subclinical hypothyroidism) or were blunted by beta-blockade and tailoring of the l -thyroxine dose (subclinical hyperthyroidism). CONCLUSION: The heart responds to the minimal but persistent changes in circulating thyroid hormone levels typical of subclinical thyroid dysfunction. Thus, the condition is not a compensated biochemical change sensu strictu, and timely treatment should be considered in an attempt to avoid adverse cardiovascular effects.

Biondi B, Palmieri EA, Lombardi G, Fazio S. · Department of Clinical and Molecular Endocrinology and Oncology, University of Naples Federico II School of Medicine, Naples, Italy. · Thyroid. · Pubmed #12165114 No free full text.

Abstract: The cardiovascular system is sensitive to the action of thyroid hormone. However, although a wide spectrum of cardiac abnormalities has long been recognized in patients with overt thyroid dysfunction, the question of cardiac involvement in patients with subclinical thyroid dysfunction has been investigated only in the last two to three decades. Most clinical studies have shown that subclinical hypothyroidism or hyperthyroidism is associated with changes in several cardiac parameters. More specifically, the literature on cardiac involvement in subclinical hypothyroidism consistently shows that patients have resting left ventricular diastolic dysfunction evidenced by delayed relaxation, and impaired systolic dysfunction on effort that results in poor exercise capacity. Whether or not subclinical hypothyroidism also affects left ventricular systolic function at rest remains controversial. Studies of subclinical hypothyroid patients before and after euthyroidism was achieved with levothyroxine replacement provided evidence of impaired resting left ventricular systolic function. Indeed, at-rest left ventricular systolic function was substantially normal in most studies of subclinical hypothyroid patients compared to normal control subjects. Drawing on these data, it appears that subclinical hypothyroidism should be considered a mild form of thyroid failure, associated with initial signs of cardiovascular hypothyroidism. Therefore, it would seem appropriate to initiate timely treatment of patients with mild thyroid failure to prevent cardiac involvement.

Biondi B, Palmieri EA, Lombardi G, Fazio S. · Department of Clinical and Molecular Endocrinology and Oncology, University Federico II School of Medicine, 80131 Naples, Italy. · J Clin Endocrinol Metab. · Pubmed #11889145 links to  free full text

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Colao A, Dorato M, Pulcrano M, Rossi FW, Auriemma RS, Lombardi G, Lastoria S. · Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Università degli Studi Federico II, Naples, Italy. · Minerva Endocrinol. · Pubmed #11753242 No free full text.

Abstract: The medical approach to patients with secreting or clinically non-functioning pituitary adenoma as made considerable progress thanks to the use of new somatostatin analogs. They were first used to treat acromegaly in the mid 1980s and numerous studies have shown a reduction in GH concentration in over 90% of acromegalic patients. Good results were obtained using slow-release analog treatment also in TSH-secreting adenomas, whereas the therapeutic efficacy of these peptides in clinically non-functioning adenomas is still controversial. Treatment with somatostatin analogs improves symptoms, normalises hormone secretion and in some cases may induce a reduction in the volume of pituitary adenomas. Scintigraphy with octreotide may help to select patients who respond to this form of treatment.

Colao A, Pivonello R, Lastoria S, Faggiano A, Ferone D, Lombardi G, Fenzi G. · Department of Molecular and Clinical Endocrinology, Federico II University of Naples, Italy. · Eur J Endocrinol. · Pubmed #11068938 links to  free full text

This publication has no abstract.

Spiezia S, Garberoglio R, Milone F, Ramundo V, Caiazzo C, Assanti AP, Deandrea M, Limone PP, Macchia PE, Lombardi G, Colao A, Faggiano A. · Department of Surgery, Ultrasound Guided & Neck Pathologies Surgery Operative Unit, S. Maria del Popolo degli Incurabili ASLNA1 Hospital , Naples, Italy. · Thyroid. · Pubmed #19265492 No free full text.

Abstract: BACKGROUND: Percutaneous radiofrequency thermal ablation (RTA) is a promising new therapeutic approach to manage thyroid nodules (TNs). The aim of this study was to investigate the long-term effectiveness of RTA in inducing shrinkage of TNs as well as in controlling compressive symptoms and thyroid hyperfunction in a large series of elderly subjects with solid or mainly solid benign TNs. METHODS: Ninety-four elderly patients with cytologically benign compressive TNs were prospectively enrolled in the study; 66 of them had nontoxic goiter and 28 had toxic or pretoxic goiter. RTA was performed by using a RITA StarBurst Talon hook-umbrella needle inserted in every single TN under ultrasonographic real-time guidance. TN volume, TN-related compressive symptoms and thyroid function were evaluated at baseline and 12 to 24 months after RTA. RESULTS: All TNs significantly decreased in size after RTA. The mean decrease in TN volume 12 months after RTA was from 24.5 +/- 2.1 to 7.5 +/- 1.2 mL (p < 0.001), with a mean percent decrease of 78.6 +/- 2.0%. Two years after RTA, a 79.4 +/- 2.5% decrease of TNs size was observed. Compressive symptoms improved in all patients and completely disappeared in 83 of 94 (88%) patients. Hyperthyroidism resolved in most patients allowing methimazole therapy to be completely withdrawn in 79% of patients with pretoxic and toxic TNs (100% with pretoxic TNs and 53% with toxic TNs). The treatment was well tolerated by all patients. No patient needed hospitalization after RTA and no major complications were observed. CONCLUSIONS: RTA is an effective and simple procedure for obtaining lasting shrinkage of TNs, controlling compressive symptoms, and treating thyroid hyperfunction. When performed in experienced medical centers, RTA may be a valid alternative to conventional treatments for nontoxic and pretoxic TNs. It is particularly attractive for elderly people for whom surgery and radioiodine therapy are often contraindicated or ineffective.

Brunese L, Romeo A, Iorio S, Napolitano G, Fucili S, Zeppa P, Vallone G, Lombardi G, Bellastella A, Biondi B, Sodano A. · Department of Health Science, Chair of Radiology, University of Molise, Campobasso, Italy. · Eur J Endocrinol. · Pubmed #18644823 No free full text.

Abstract: BACKGROUND: Microcalcifications (aggregated with psammoma bodies), detected by ultrasound (US), are the most specific feature of papillary thyroid cancer (PTC). Using B-flow imaging (BFI), we identified a new sign (the twinkling sign; BFI-TS) in 'suspect' PTC nodules, which appeared to be generated by microcalcifications. OBJECTIVE: To evaluate whether the BFI-TS was predictive of malignancy, we correlated the BFI-TS with the results of fine needle aspiration cytology and histology. DESIGN: Cross-sectional cohort study from September 2006 to April 2008. SETTING: Department of Radiology and Endocrinology, University of Naples Federico II, and Department of Endocrinology, Second University of Naples. PATIENTS: A total of 306 consecutive patients with 539 thyroid nodules >8 mm in diameter. MAIN OUTCOME MEASURE: US and BFI examinations were performed with the Logiq 9 system (General Electric Company, Milan, Italy); all patients underwent cytological examination. RESULTS: Cytology revealed 455 (84.4%) benign nodules and 84 (15.6%) malignant nodules; the latter were confirmed by postsurgical histological examination (76 cases of PTC, 7 follicular carcinoma, and 1 Hürthle cell carcinoma). All suspect nodules, namely, nodules with potential predictors of thyroid malignancy (e.g., microcalcifications and intra-nodal vascularity), were analyzed by cytology or histology (or both). Of 84, 68 (80.9%) of malignant nodules had >or=4 or more BFI-TSs in at least one scan versus only 12 of 455 (2.6%) of benign lesions. CONCLUSIONS: Our results indicate that the BFI-TS could be a reliable diagnostic technique in the management of suspect thyroid nodules.

Palmieri EA, Fazio S, Palmieri V, Lombardi G, Biondi B. · Department of Clinical Medicine and Cardiovascular Sciences, University Federico II School of Medicine, Napoli, Italy. · Eur J Endocrinol. · Pubmed #15191344 links to  free full text

Abstract: OBJECTIVES: To ascertain whether myocardial contractility and total arterial stiffness are significantly altered in human thyrotoxicosis, and to what extent they are affected by acute beta(1)-adrenergic blockade. METHODS: Doppler-echocardiography was used to assess left ventricular (LV) structure and function, hemodynamics and total arterial stiffness in untreated overt hyperthyroid patients before and 2 h after 5 mg bisoprolol given orally compared with age- and sex-matched healthy euthyroid controls. RESULTS: Compared with controls, untreated patients (n=20) had a higher heart rate (HR) and LV stroke index (SI), which were associated with higher pulse pressure (PP), larger LV end-diastolic volume index (EDVI, an index of preload,+11%, P<0.05), marginally increased stress-corrected LV midwall fractional shortening (MWS, an index of myocardial contractility,+5%; P=0.066), and shorter isovolumic relaxation time (IVRT). These changes resulted in a higher cardiac index (CI) and a lower systemic vascular resistance (SVR), which were associated with fairly normal mean blood pressure (BP) but higher PP/stroke volume (an index of total arterial stiffness,+29%; P<0.01). After bisoprolol, compared with controls, the randomly treated patients (n=10) had comparable HR but additionally increased SI; PP remained enhanced, EDVI was further enlarged (+26%, P<0.001), stress-corrected MWS was substantially unchanged, and IVRT remained shorter. Overall, these effects attenuated the high-output state, which was associated with normalization of PP/stroke volume without changes of mean BP. CONCLUSIONS: In human overt hyperthyroidism, myocardial contractility does not play a major role in increasing LV performance, which is instead predominantly sustained by increased preload with enhanced LV diastolic function. In addition, human thyrotoxicosis is associated with increased total arterial stiffness despite fairly normal mean BP. In this scenario, acute beta(1)-adrenergic blockade blunts the cardiovascular hyperkinesia predominantly by slowing HR - a process that is associated with normalization of total arterial stiffness.

Biondi B, Palmieri EA, Fazio S, Cosco C, Nocera M, Saccà L, Filetti S, Lombardi G, Perticone F. · Departments of Endocrinology and Internal Medicine, University of Naples "Federico II" Medical School, 80131 Naples, Italy. · J Clin Endocrinol Metab. · Pubmed #11134131 links to  free full text

Abstract: To determine the clinical impact of endogenous subclinical hyperthyroidism, specific symptoms and signs of thyroid hormone excess and quality of life were assessed in 23 patients (3 males and 20 females; mean age, 43 +/- 9 yr) and 23 age-, sex-, and lifestyle-matched normal subjects by using the Symptoms Rating Scale and the Short Form 36 Health Survey questionnaires. Because the heart is one of the main target organs of the thyroid hormone, cardiac morphology and function were also investigated by means of standard 12-lead electrocardiogram (ECG), 24-h Holter ECG, and complete Doppler echocardiography. Stable endogenous subclinical hyperthyroidism had been diagnosed in all patients at least 6 months before the study (TSH, 0.15 +/- 0.1 mU/L; free T(3), 6.9 +/- 1.1, pmol/L; free T(4), 17.2 +/- 2.3, pmol/L). Fifteen patients were affected by multinodular goiter, and eight patients by autonomously functioning thyroid nodule. The mean Symptoms Rating Scale score (9. 8 +/- 5.5 vs. 4.3 +/- 2.2, P: < 0.001) and both the mental (36.1 +/- 9.5 vs. 50.0 +/- 8.5, P: < 0.001) and physical (42.6 +/- 8.0 vs. 55. 6 +/- 4.1, P: < 0.001) component scores of Short Form 36 Health Survey documented a significant prevalence of specific symptoms and signs of thyroid hormone excess and notable impairment of quality of life in patients. Holter ECG showed a higher prevalence of atrial premature beats in endogenous subclinical hyperthyroid patients than in the controls, but the difference was not statistically significant, although the average heart rate was significantly increased in the patients (P: < 0.001). An increase of left ventricular mass (162 +/- 24 vs. 132 +/- 22 g, P: < 0.001) due to the increase of septal (P: = 0.025) and posterior wall (P: = 0.004) thickness was observed in patients. Systolic function was enhanced in patients as shown by the significant increase of both fractional shortening (P: = 0.005) and mean velocity of heart rate-adjusted circumferential fiber shortening (P: = 0.036). The Doppler parameters of diastolic function were significantly impaired in the patients as documented by the reduced early to late ratio of the transmitral flow velocities (P: < 0.001) and the prolonged isovolumic relaxation time (P: = 0.006). These data indicate that endogenous subclinical hyperthyroidism has a relevant clinical impact and that it affects cardiac morphology and function. Moreover, they suggest that treatment of persistent endogenous subclinical hyperthyroidism should be considered also in young and middle-aged patients to attenuate specific symptoms and signs of thyroid hormone excess, ameliorate the quality of life, and avoid the consequences to the heart of long exposure to a mild excess of thyroid hormone.

Spiezia S, Cerbone G, Assanti AP, Colao A, Siciliani M, Lombardi G. · Surgery Department, Incurabili Hospital, Naples, Italy. · J Ultrasound Med. · Pubmed #10625189 No free full text.

Abstract: The purpose of this study was to explore the potential role of power Doppler sonography in guiding percutaneous ethanol injection of autonomously functioning thyroid nodules. Thirty-two patients with pretoxic adenoma and 15 with toxic adenoma underwent percutaneous ethanol injection under power Doppler sonographic guidance. All patients with pretoxic adenoma and 13 of 15 patients with toxic adenoma were treated successfully (normalization of circulating thyroid hormones and thyroid stimulating hormone levels and disappearance of nodular hyperactivity with complete recovery of extranodular tracer uptake at scintigraphy). Power Doppler sonography showed the progressive reduction of the intranodular blood flow until its extinction after 6 to 12 months. Nodular shrinkage was obtained in all patients (from 10.85 +/-1.04 to 2.9 +/- 0.3 ml in pretoxic adenoma and from 15.4 +/- 1.8 to 4.2 +/- 0.7 ml in toxic adenoma. Power Doppler sonographic guidance seems to improve the outcome of percutaneous ethanol injection, allowing detection of blood flow even in very small vessels, permitting the ethanol to be guided toward the main afferent vessels of the nodules, and making it possible to monitor the diffusion and the effects of ethanol on nodular vascularization.

Cerbone G, Spiezia S, Colao A, Marzullo P, Assanti AP, Lucci R, Zarrilli S, Siciliani M, Fenzi G, Lombardi G. · Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, University Federico II, Napoli, Italy. · J Endocrinol Invest. · Pubmed #10614524 No free full text.

Abstract: Power Doppler (PD) is a recent color-Doppler Ultrasound (US)-technique, which allows to detect the presence of flow even in very small vessels, providing a sort of angiographic micromap. The aim of this study was to evaluate whether percutaneous ethanol injection (PEI) outcome might be improved by injecting the ethanol into the nodule under PD assistance. Thus, 14 patients affected with pretoxic (PTA) and 8 with toxic adenoma (TA) were submitted to this alternative tool. Before PEI, all patients were submitted to a careful endocrinological study, including an US-guided fine-needle biopsy in order to exclude the presence of malignancy. In addition, all the nodules were evaluated at PD-US and their vascular patterns were recorded on videotape and compared with those obtained after treatment. The procedure consisted of slow injection of sterile ethanol under direct PD-US control. The number of PEI sessions was 2.3+/-0.1 in PTA and 3.0+/-0.3 in TA. All patients were also evaluated 3, 6, 12 and 18 months after PEI. Successful therapy was considered when normalization of thyroid hormones and TSH was achieved together with the disappearance of nodular hyperactivity and complete recovery of extra-nodular tracer uptake at scintigraphy. PEI was tolerated very well by all patients. The most common side effect was a transient local or irradiated pain. All patients with PTA and 6 out of 8 patients with TA were successfully treated. In these cases, PD-US showed the progressive reduction of the intranodular blood flow, up to its extinction after 6-12 months, with the presence of little perilesional vascular spots. Nodular shrinkage was obtained in all patients (from 4.7+/-0.7 to 1.1+/-0.4 ml in PTA and from 21.0+/-2.8 to 6.2+/-1.6 ml in TA). In conclusion, PD assistance improves PEI procedure, since it allows to guide the ethanol injection towards the principal afferent vessels of the nodules and to monitor the diffusion and the effects of ethanol on nodular vascularization.

Valentino R, Savastano S, Tommaselli AP, Dorato M, Scarpitta MT, Gigante M, Micillo M, Paparo F, Petrone E, Lombardi G, Troncone R. · CNR, Experimental Endocrinology and Oncology Center (CEOS), Department of Cellular and Molecular Biology and Pathology, University Federico II, Naples, Italy. · Horm Res. · Pubmed #10461017 No free full text.

Abstract: The occurrence of autoimmune thyroid disorders among patients with coeliac disease (CD) is well documented, but the exact prevalence of CD among patients with autoimmune thyroid diseases (ATD) is as yet unclear. We screened 150 newly diagnosed patients with ATD by serum endomysial antibody detection (EmA). In 5 subjects (3.3%) EmA positivity was found; all underwent jejunal biopsy. On gluten-free diet an excellent clinical and histological response was recorded with an improvement of hypothyroidism and reduction of the thyroxine dosage. Our data suggest a significant high prevalence (3.3%) of CD in patients with ATD, in particular with Hashimoto's thyroiditis.

Biondi B, Fazio S, Palmieri EA, Tremalaterra R, Angellotti G, Bonè F, Riccio G, Cittadini A, Lombardi G, Saccà L. · Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Università degli Studi Federico II, Napoli. · Cardiologia. · Pubmed #10389349 No free full text.

Abstract: BACKGROUND: Thyroid hormones greatly affect the cardiovascular system. Although the effects of overt hyperthyroidism on the cardiovascular system have been diffusely studied, only in the last years the effects of subclinical hyperthyroidism on the heart have been investigated. Subclinical hyperthyroidism is a symptomatic or asymptomatic condition with an absent response of thyrotropin (TSH) to thyrotropin-releasing hormone in the presence of normal serum levels of thyroid hormones for the general population, though supraoptimal for the individual. The more frequent causes of endogenous subclinical hyperthyroidism are multinodular goiter, toxic, adenoma and Graves's disease, whereas the exogenous causes are induced by levothyroxine (LT4) therapy used to suppress TSH in patients with nontoxic goiter and differentiated thyroid cancer. This paper reports our experience derived from the study of 60 patients with subclinical hyperthyroidism due to TSH-suppressive therapy with LT4 compared to normal subjects. METHODS: Patients (9 males and 51 females, mean age 39 +/- 10 years) were studied by complete Doppler echocardiography, standard and 24 hour ECG Holter monitoring, exercise test with cycloergometer, and radionuclide ventriculography at rest and during fixed workload (75 W). RESULTS: Holter monitoring showed a significant increase in mean 24 hour heart rate (80 +/- 10 vs 70 +/- 9 b/min, p < 0.001) and supraventricular arrhythmias (42 vs 12 patients, p < 0.003). Echocardiography showed an increase in left ventricular mass index (94 +/- 13 vs 80 +/- 18 g/m2, p < 0.001) due to increased septal and posterior wall thickness. At rest, echocardiographic indices of systolic function (fractional shortening and mean corrected velocity of circumferential fiber shortening) were higher in patients than in controls (fractional shortening 40 +/- 6 vs 34 +/- 4%, p < 0.001; mean corrected velocity of circumferential fiber shortening 1.23 +/- 0.17 vs 1.05 +/- 0.14 circ/s, p < 0.001), while the Doppler indices of diastolic function were significantly impaired as documented by the reduced E/A ratio (1.18 +/- 0.3 vs 1.8 +/- 0.5, p < 0.001) and the prolonged isovolumic relaxation time (94 +/- 13 vs 78 +/- 12 ms, p < 0.001). Exercise tolerance was also significantly impaired in patients with subclinical hyperthyroidism: maximal exercise time (6.4 +/- 0.7 vs 9.4 +/- 1.4 min, p < 0.001) and peak workload (81 +/- 11 vs 121 +/- 17 W, p < 0.001) were significantly reduced and radionuclide ventriculography showed a decrease in ejection fraction during exercise (from 62 +/- 7 to 53 +/- 8%, p < 0.002). CONCLUSIONS: Persistent subclinical hyperthyroidism by TSH-suppressive doses of LT4 significantly affects heart morphology and function. Thus, we suggest that a complete suppression of TSH must be recommended only in patients with differentiated thyroid cancer, while in patients with begin thyroid disease it could be sufficient to maintain subnormal TSH levels.

Biondi B, Fazio S, Palmieri EA, Carella C, Panza N, Cittadini A, Bonè F, Lombardi G, Saccà L. · Department of Endocrinology of the University Federico II, Naples, Italy. · J Clin Endocrinol Metab. · Pubmed #10372711 links to  free full text

Abstract: Although subclinical hypothyroidism is frequently diagnosed, the decision to institute a substitutive therapy with L-T4 remains controversial. Because the cardiovascular system is considered a main target for the action of thyroid hormone, we investigated whether subclinical hypothyroidism induces cardiovascular abnormalities. Twenty-six patients (mean age, 36 +/- 12 yr) were evaluated by Doppler-echocardiography, whereas a subgroup of 10 patients, randomly selected, were reevaluated after 6 months of L-T4 substitutive therapy (mean dose, 68 microg daily). Thirty subjects (matched for age, sex, and body surface area) served as controls. Mean plasma TSH was significantly higher in patients (P < 0.001), whereas mean serum free T4 and free T3 concentrations, although in the normal range, were significantly lower (P < 0.001 and P < 0.005, respectively). Blood pressure and heart rate did not differ from control values. Echocardiogram examination showed no abnormalities of the left ventricular morphology and a slight, but not significant, reduction in the systolic function in the patient group. In contrast, Doppler-derived indices of diastolic function showed significant prolongation of the isovolumic relaxation time (94 +/- 13 vs. 84 +/- 8 msec; P < 0.001), increased A wave (55 +/- 13 vs. 48 +/- 9 cm/sec; P < 0.05), and reduced early diastolic mitral flow velocity/late diastolic mitral flow velocity ratio (1.4 +/- 0.3 vs. 1.7 +/- 0.3; P < 0.001). In the subgroup of 10 patients, thyroid hormone profile was normalized by 6 months of L-T4 substitutive therapy, whereas no changes were observed in the left ventricular morphology. Systolic function was significantly enhanced, as compared with pretreatment values (P < 0.01) but did not differ from control values. Also, systemic vascular resistance was significantly decreased by L-T4 replacement therapy. Assessment of diastolic function showed significant shortening of isovolumic relaxation time (77 +/- 15 vs. 91 +/- 8; P < 0.05), reduction of A wave (51 +/- 13 vs. 60 +/- 12; P < 0.01), and increase of early diastolic mitral flow velocity/late diastolic mitral flow velocity ratio (1.7 +/- 0.4 vs. 1.3 +/- 0.3; P < 0.001). These indices, however, were comparable with those of control subjects. These findings indicate that subclinical hypothyroidism affects diastolic function and that this abnormality may be reversed by L-T4 substitutive therapy.

Faggiano A, Grimaldi F, Pezzullo L, Chiofalo MG, Caracò C, Mozzillo N, Angeletti G, Santeusanio F, Lombardi G, Colao A, Avenia N, Ferolla P. · Department of Molecular and Clinical Endocrinology and Oncology, University of Naples, Via Sergio Pansini 5, 80131 Naples, Italy. · Endocr Relat Cancer. · Pubmed #19004986 No free full text.

Abstract: In patients with postoperative persistent medullary thyroid cancer (MTC), the tumor detection rate is generally low for most of the imaging techniques now available. The aim of this study was to investigate if the clinico-biological profile of the tumor may indicate which imaging technique to perform in order to identify postoperative persistent or relapsing MTC foci. Thirty-five consecutive MTC patients with detectable and progressively increasing postoperative serum concentrations of calcitonin were enrolled in the study. The detection rates of 18F-deoxy-d-glucose (FDG)-positron emission tomography (PET), somatostatin receptor scintigraphy (SRS), and 131I-metaiodobenzylguanidine scintigraphy (MIBG) were compared in relation with calcitonin and carcinoembryonic antigen serum concentrations, Ki-67 score and results of conventional imaging techniques (CIT). FDG-PET positivity was significantly associated with calcitonin serum concentrations >400 pg/ml and Ki-67 score >2.0% (P<0.05), while SRS positivity was associated with calcitonin serum concentrations >800 pg/ml (P<0.05). SRS positivity significantly correlated with tumor appearance at CIT (P<0.01), while FDG-PET was positive in nine CIT-negative patients. The secretive and proliferative tumor profile may guide the choice of the imaging technique to use in the follow-up of patients with MTC. A Ki-67 score >2.0% suggests to perform a FDG-PET in addition to conventional imaging. Calcitonin secretion predicts both FDG-PET and SRS uptake but SRS positivity is generally found only in patients with well defined MTC lesions that are also detectable at the conventional imaging examination. MIBG outcome is not predicted by any clinico-biological factors here investigated.

De Bellis A, Colao A, Savoia A, Coronella C, Pasquali D, Conte M, Pivonello R, Bellastella A, Sinisi AA, Bizzarro A, Lombardi G, Bellastella G. · Department of Clinical and Experimental Medicine and Surgery F. Magrassi, A. Lanzara, Second University of Naples, Italy. · Clin Endocrinol (Oxf). · Pubmed #18221394 No free full text.

Abstract: OBJECTIVE: The occurrence of antipituitary antibodies (APA) in patients with idiopathic hyperprolactinaemia (IH) and the effects of dopamine agonists on these antibodies and long-term pituitary function outcome have been so far not evaluated. This longitudinal study was aimed at investigating, in patients with IH the occurrence of APA and the effect of cabergoline on the pituitary function and behaviour of APA. DESIGN: Sixty-six patients with IH were studied. APA (by indirect immunofluorescence) and pituitary function were investigated every year for 3 years. RESULTS: Seventeen patients resulted APA positive (Group 1) and 49 APA negative (Group 2). Eight patients of Group 1 (Group 1a) and 24 of Group 2 (Group 2a) were asymptomatic and then not treated; instead, nine patients in Group 1 (Group 1b) and 25 in Group 2 (Group 2b), showing symptoms of hyperprolactinaemia, were treated with cabergoline for 2 years. Among the untreated patients, during the follow-up, those with APA positive (Group 1a) showed an increase of APA titres and PRL levels with partial pituitary impairment in some of them; instead those with APA negative (Group 2a) persisted negative with normal pituitary function despite persistent hyperprolactinaemia. Among the treated patients, those with APA positive (Group 1b) showed normalization of PRL levels, APA disappearance and recovery of pituitary function (when initially impaired) during cabergoline treatment, persisting also at last observation (off-therapy). Instead all patients of Group 2b persisted with APA negative during the follow-up with normalization of PRL levels and stable normal pituitary function during cabergoline therapy but showing a further increase of PRL at the last observation. CONCLUSIONS: The presence of APA in some patients with IH suggests a possible occurrence of autoimmune hypophysitis at potential/subclinical stage; an early and prolonged cabergoline therapy could interrupt the progression to an overt clinical stage of the disease. However, the small amount of patients investigated suggests caution against generalization of our assumption and prompts to further controlled studies on a more numerous population to verify these conclusions.

Melis D, Pivonello R, Parenti G, Della Casa R, Salerno M, Lombardi G, Sebastio G, Colao A, Andria G. · Department of Pediatrics, Federico II University, Naples, Italy. · J Pediatr. · Pubmed #17307551 No free full text.

Abstract: OBJECTIVE: To investigate the hypothalamus-pituitary-thyroid axis in patients with glycogen storage disease type 1(GSD1). STUDY DESIGN: Ten patients with GSD1a, 7 patients with GSD1b, and 34 sex- and age-matched healthy control subjects were enrolled in the study. RESULTS: The levels of serum-free thyroxine (FT4) were significantly lower in patients with GSD1a and GSD1b (P < .05), whereas thyrotropin was significantly higher compared with control subjects only in patients with GSD1b (P < .005). Thyroglobulin and thyroperoxidase auto-antibodies were significantly higher in patients with GSD1b than in patients with GSD1a and control subjects (P < .005). After thyrotropin-releasing hormone stimulation, an enhanced thyrotropin response was found in patients with GSD1a and patients with GSD1b (P < .005) compared with control subjects. The presence of a subclinical or overt hypothyroidism was found in 4 of 7 patients with GSD1b and in no patient with GSD1a (chi2 = 7.47, P < .005) or control subject (chi2 = 27.2, P < .0001). CONCLUSIONS: Patients with GSD1b have an increased prevalence of thyroid autoimmunity and hypothyroidism, although patients with GSD1a have little evidence of thyroid abnormalities. Concomitant damage at the level of the hypothalamus or pituitary gland might be hypothesized on the basis of the slightly elevated thyrotropin levels, even in patients with overt hypothyroidism.

Tauchmanovà L, Carrano R, Musella T, Orio F, Sabbatini M, Lombardi G, Fenzi G, Federico S, Colao A. · Department of Molecular and Clinical Endocrinology and Oncology, University Federico II of Naples, 80131 Naples, Italy. · J Endocrinol Invest. · Pubmed #16957411 No free full text.

Abstract: Although thyroid disorders related to the end-stage renal disease (ESRD) are well known, there are discordant data on the function and morphology of the thyroid gland after renal transplantation (RT). The objective of this cross-sectional, case-control study was to investigate the prevalence and risk factors for disorders in the thyroid function and morphology after a successful RT. Fifty consecutive patients (25 females, 25 males) with fully functioning allograft were enrolled. Their age at transplant ranged from 23 to 44 yr (median, 38) and their post-RT follow-up lasted 15-86 months (median, 23). One hundred healthy subjects matched for sex, age and body mass index (BMI) were included as controls. Serum free thyroid hormones, TSH, thyroglobulin, thyroid hormone-binding globulin (TBG) and iodine urinary excretion were determined; ultrasonographic exam of the thyroid gland was performed in all subjects. Age, gender, time elapsed from RT, dialysis duration, kidney function, type of immunosuppression and corticosteroid dose were considered as possible influencing factors for the thyroid function. Hypothyroidism was found in 6% of patients, "low T3 syndrome" in 52%, while another 26% had free T3 (FT3), free T4 (FT4) and TSH in the lowest third of the normal range, suggesting inhibition of the whole hypothalamic-pituitary-thyroid (HPT) axis. Iodine excretion and prevalence of anti-thyroid antibodies were similar in both patients and controls. There was no significant difference in the thyroid function according to different immunosuppressive regimens. In patients, an ultrasonographic exam revealed a very variable thyroid volume ranging from 7.2 to 24.8 ml. Solid nodules were detected in 12 (24%) cases and cystic lesions in another four (8%); they were proven negative at cytological examination. Dialysis duration was longer in patients with thyroid nodules than in those without (p<0.05). Inhomogeneous hypoechoic pattern typical for chronic thyroiditis was more frequent than its biochemical expression. In conclusion, a high prevalence of abnormal thyroid morphology was found in patients after a successful RT, being partly related to a previous uremia. Abnormalities in the thyroid function are likely an expression of the post-transplant general and immunological conditions. Endocrinological follow-up is advisable in patients after RT, in order to discriminate thyroid dysfunctions which need specific treatments from those that can only be followed-up, avoiding inappropriate treatments of biochemical abnormalities.