Giampaolo Papi

Metastases to the thyroid gland: prevalence, clinicopathological aspects and prognosis: a 10-year experience.

Background  Metastases to thyroid (TM) are rarely observed in the clinical practice.

Thyroid hemiagenesis and incidentally discovered papillary thyroid cancer: case report and review of the literature.

Thyroid hemiagenesis (TH) is a rare congenital abnormality in which one thyroid lobe fails to develop. Its prevalence is uncertain, because the absence of one thyroid lobe does not usually cause clinical symptoms. The detection of TH is usually incidental when the evaluation of other thyroid disorders is requested. It is more frequently found in female than in male patients (3:1 ratio) and in the left lobe compared to the right lobe. We report the case of a 54-yr-old man, presenting with a large multinodular right-sided goiter, with mediastinal extension and dysphagia. Thyroid scan and ultrasound study showed the absence of the left lobe. The patient underwent surgery for compressive symptoms, and the operation confirmed the absence of the left lobe. Histological examination demonstrated a multinodular goiter with papillary carcinoma. To our knowledge, this case represents the first reported case of association between TH and papillary thyroid carcinoma in a male patient, and the second in which the tumor arose in the right lobe.

Value of routine measurement of serum calcitonin concentrations in patients with nodular thyroid disease: A multicenter study

Background: The routine measurement of serum calcitonin (CT) has been proposed for patients with nodular thyroid disease (NTD), to detect unsuspected medullary thyroid carcinoma (MTC) before surgery. Objective: To assess the prevalence of hyper-calcitoninemia and MTC in NTD patients; to compare the ability of CT measurement and fine needle aspiration cytology (FNAC) to predict MTC; to identify age groups of NTD patients who should be better candidates than others to undergo routine measurement of CT. Patients and methods: 1425 consecutive patients, referred from April 1, 2003, through March 31, 2004, to four Italian endocrine centers due to NTD, were grouped depending on age, and underwent basal and, in some cases, pentagastrin (Pg)-stimulated CT measurement, FNAC and, when indicated, surgery. Serum CT concentrations were measured by an immunoluminometric assay (ILMA). Results: Hyper-calcitoninemia was found in 23 out of 1425 patients. MTC was discovered in 9 patients, all >40 yr old and showing high CT levels. Sensitivity of basal and Pg-stimulated CT to predict MTC before surgery was 100% for both tests, whereas specificity was 95 and 93%, respectively. CT specificity reached 100% when a cutoff value of 20 pg/ml was taken. FNAC showed an overall 86% sensitivity. When >10 mm MTC nodules were considered, FNAC sensitivity approached 100%. On the contrary, a correct cytological diagnosis was obtained in only one out of five patients with <10 mm MTC nodules (microMTC); in one patient with histologically proved microMTC, FNAC even demonstrated a benign lesion. Hypercalcitoninemia or MTC were associated with chronic thyroiditis in 30 or 33% of cases, respectively. C-cell hyperplasia was found in 57% of hypercalcitoninemic patients without MTC. Conclusions: Basal CT measurement detects elevated CT values in 1.6% of NTD patients. Although CT is not a specific marker of MTC, its routine measurement represents a useful tool in the pre-operative evaluation of NTD patients, particularly those >40 yr old presenting with nodules <10 mm, even when FNAC does not show malignant features. To our knowledge, this is the first trial using ILMA to assess the ability of pre-operative CT measurement to predict MTC in a large series of NTD patients.

Current concepts on Riedel thyroiditis.

Riedel thyroiditis (RT) is an uncommon form of chronic thyroiditis in which the thyroid gland is replaced by fibrous tissue. The etiologic mechanisms underlying RT are unclear: the prevailing view is that it is part of a generalized fibroinflammatory process also involving other organs. The clinical manifestations of RT are protean, often resembling malignancy owing to goiter of remarkably hard consistency. Physical examination, laboratory analysis, cytology, and imaging features are not useful for differentiating between RT and neoplastic diseases or the fibrous variant of Hashimoto thyroiditis in the presurgical evaluation of patients. Histologic examination is necessary to establish the final diagnosis of RT. The present article reviews the most recent concepts about etiologic mechanisms, pathogenesis, diagnosis, and management of RT

Primary paraganglioma of the thyroid gland

We describe the case of a 46-yr-old euthyroid woman, who was submitted to right lobectomy plus isthmusectomy because of a 30 mm large, rapidly growing thyroid nodule. Two cytological examinations of fine needle aspiration biopsy (FNAB) specimens were not diagnostic. Histology showed a neoplasm composed of nests of chief cells, almost completely replacing thyroid parenchyma, infiltrating the capsule and surgical resection margins, and invading perithyroid tissues. Immunohistochemical analysis revealed that the tumor stained positively to chromogranin, synaptophysin, NSE, S-100 protein and tyrosine hydroxylase, whereas no immunoreactivity was detected against cytokeratin, thyroglobulin, TTF-1, calcitonin and CEA. A diagnosis of thyroid paraganglioma (PG) was finally made. No complications developed following operation. Laboratory analysis and imaging study excluded multicentric disease, metastases to neck or extra-cervical organs, and multiple endocrine neoplasia (MEN). We report this unusual case, underscore its clinical and immunohistochemical features and discuss differential diagnosis.

Riedel's thyroiditis and fibrous variant of Hashimoto's thyroiditis: a clinicopathological and immunohistochemical study.

The aim of this study was to analyze and compare clinico pathological aspects of Riedel’s thyroiditis (RT) and the fibrous variant of Hashimoto’s thyroiditis (HTFV), and to show their immunohistochemical features. We reviewed 6 cases of HTFV and 4 cases of RT. Compared to RT, HTFV patients had hypothyroidism, no pressure symptoms, and frequently diagnostic fineneedle aspiration biopsy (FNAB) cytology. At histology, invasion of surrounding tissues and presence of occlusive phlebitis distinguished RT from HTFV. At immunohistochemistry, RT — compared to HTVF — was characterized by: 1) a more abundant fibrous reaction, and granulocytic, monocytic and eosinophil infiltration; 2) few plasmacells, CD8+ T- and B-lymphocytes. The results of our study add further evidence regarding the separation of RT and HTFV in their peculiar clinical, laboratory, cyto-histological and immunohistochemical aspects.

The Association Between Benign Paroxysmal Positional Vertigo and Autoimmune Chronic Thyroiditis Is Not Related to Thyroid Status

Benign paroxysmal positional vertigo (BPPV) is a common form of dizziness that is provoked by changes in head position (1). Some authors (2) have proposed that BPPV may be triggered by the movement of immune-complexes in the inner ear with consequent mechanical stimulation of labyrinthine receptors. Recently, we found a 34% prevalence of Hashimoto’s thyroiditis (HT), a chronic form of thyroiditis, in BPPV patients (3). In our previous letter (3), we compared a group of patients with BPPV with a group of ageand sex-matched healthy subjects without a history of vertigo or thyroid disease. We noted that the mean serum thyrotropin (TSH) was higher in the BPPV group than in the healthy controls and that the titers of anti-thyroid peroxidase antibodies (TPO-Ab) and anti-thyroglobulin antibodies (Tg-Ab) were also higher in the BPPV group than in the controls. Twenty-one percent of the BPPV group had hypothyroidism, whereas only 2% of the control group had it. Moreover, anti-thyroid antibodies were positive in 46 of the BPPV group, whereas they were positive in only 2 subjects of the control group. The association of BPPV with elevated anti-thyroid antibodies (odds ratio [OR] 25.6) was stronger than the association of BPPV with hypothyroidism (OR 12.9). Our previous study (4), therefore, demonstrated an association between thyroid disease and BPPV but did not establish clearly whether this association was between BPPV and decreased thyroid function or between BPPV and thyroid autoimmunity. Therefore, we performed a further study to determine whether BPPV was associated with euthyroid HT. We prospectively recruited 200 patients with euthyroid HT (Group HT-Eu), who were consecutively referred to the Division of Endocrinology, ‘‘A. Gemelli’’ Hospital—Catholic University of Rome and to the Endocrine Outpatient Clinics of ‘‘Ramazzini’’ Hospital— Azienda USL of Modena, Italy, from April 1, 2008 to April 30, 2009. During this period, 818 patients were referred due to HT; however, 618 individuals—326 due to overt hypothyroidism and 292 due to subclinical hypothyroidism—were excluded from the study. Two hundred ageand sex-matched healthy blood donors (Group C) were also included in the study and served as controls. In both study groups, the prevalence of BPPV was determined. The results were statistically analyzed by means of unpaired Student’s t-test (two-tailed) for continuous variables (serum hormones and antibodies) and by means of Chi-square test, df 1, for nominal variables (BPPV and ultrasound HT pattern). Statistical significance was taken as p< 0.05. The diagnosis of BPPV was based on the following criteria: sudden onset of short and temporary (few second-lasting) episodes of rotational vertigo provoked by positioning tests (Dix-Hallpike manoeuvre for posterior semicircular canal or lateral head positionings for lateral semicircular canals) (4,5). The following inclusion and exclusion criteria were used to assign patients to Group HT-Eu. Inclusion criteria were (a) male and female patients older than18 years; (b) normal serum TSH and free thyroxine concentrations; (c) high Tg-Ab and=or TPO-Ab levels. Exclusion criteria were (a) pregnancy; (b) personal history of arterial hypertension, diabetes mellitus, migraines, head trauma, alcohol abuse, psychiatric, inner ear, and cerebrovascular diseases; (c) medications. The inclusion and exclusion criteria for the Group C were as follows: adult male and female healthy patients without personal history of either dizziness or thyroid disease. Patients belonging to Group HT-Eu and Group C were subjected to the following procedures: measurement of serum TSH (normal values: 0.3–4 mIU=L), free thyroxine (0.8– 1.8 pg=mL), Tg-Ab (<100 IU=L), and TPO-Ab (<40 IU=L) antibody concentrations; thyroid ultrasound; and otoneurology visit. Individuals with signs=symptoms of BPPV underwent complete neurological examination; eye movement testing; evaluation of spontaneous nystagmus and dynamic vestibule-ocular reflex function; Dix-Hallpike manoeuvre (4); and lateral head positionings (5). The study protocol was approved by the local ethics committee (register N. 64=2008). All individuals gave informed consent to diagnostic procedures. In Group HT-Eu, 160 out of 200 (80%) patients were female and 40 (20%) were male, aged 49 4 years (median 48 years). In Group C, 160 out of 200 (80%) patients were female, aged 48.2 5.2 years (median 47 years; p1⁄4non significant [NS] vs. Group HT-Eu). The results of this study are summarized in

Clinical Concepts on Thyroid Emergencies

Objective: Thyroid-related emergencies are caused by overt dysfunction of the gland which are so severe that require admission to intensive care units (ICU) frequently. Nonetheless, in the ICU setting, it is crucial to differentiate patients with non-thyroidal illness and alterations in thyroid function tests from those with intrinsic thyroid disease. This review presents and discusses the main etiopathogenetical and clinical aspects of hypothyroid coma (HC) and thyrotoxic storm (TS), including therapeutic strategy flow-charts. Furthermore, a special chapter is dedicated to the approach to massive goiter, which represents a surgical thyroid emergency. Data Source: We searched the electronic MEDLINE database on September 2013. Data Selection and Data Extraction: Reviews, original articles, and case reports on “myxedematous coma,” “HC,” “thyroid storm,” “TS,” “massive goiter,” “huge goiter,” “prevalence,” “etiology,” “diagnosis,” “therapy,” and “prognosis” were selected. Data Synthesis and Conclusion: Severe excess or defect of thyroid hormone is rare conditions, which jeopardize the life of patients in most cases. Both HC and TS are triggered by precipitating factors, which occur in patients with severe hypothyroidism or thyrotoxicosis, respectively. The pillars of HC therapy are high-dose l-thyroxine and/or tri-iodothyroinine; i.v. glucocorticoids; treatment of hydro-electrolyte imbalance (mainly, hyponatraemia); treatment of hypothermia; often, endotracheal intubation and assisted mechanic ventilation are needed. Therapy of TS is based on beta-blockers, thyrostatics, and i.v. glucocorticoids; eventually, high-dose of iodide compounds or lithium carbonate may be of benefit. Surgery represents the gold standard treatment in patients with euthyroid massive nodular goiter, although new techniques – e.g., percutaneous laser ablation – are helpful in subjects at high surgical risk or refusing operation.

A multicenter evaluation of immunoassays for follicle-stimulating hormone, luteinizing hormone and testosterone: Concordance, imprecision and reference values

Background: Numerous laboratories in Italy use radioimmunoassay to determine concentrations of sex hormones (FSH, LH, testosterone). A comparison of assay methods is thus an important starting point for the achievement of universally accepted reference values. Aim: To carry out an external quality assessment for FSH, LH, and testosterone. Materials and methods: Fifteen aliquots from 5 serum pools were assayed in multiple replicates by 16 Italian laboratories with 5 automated immunoassays (Abbott Architect, DiaSorin Liaison, Perkin-Elmer AutoDelfia, Roche Elecsys, Siemens Immulite 2000), and 1 radioimmunoassay (Adaltis). Results: The variance was below 12% for FSH, between 11.61 % and 14.76% for LH, and between 9.57% and 12.48% for testosterone. Assay precision was good, except for Elecsys at low concentrations of FSH and for Immulite at low concentrations of LH and testosterone. ARCHITECT showed a negative bias for FSH and LH and a positive bias for testosterone; Liaison a positive bias for LH; Elecsys a positive bias for FSH and a negative bias for testosterone; Immulite a positive bias for FSH; AutoDelfia a negative bias for FSH and a positive bias for testosterone. Reference ranges at the low end varied widely, even among laboratories using the same assay. Conclusions: The analytical performances of widely used immunoassays for FSH, LH, and testosterone show a fair to strong degree of consistency. A careful evaluation of reference ranges by clinical and laboratory experts needs to be carried out, in order to reach a consensus.

Association between benign paroxysmal positional vertigo and autoimmune chronic thyroiditis

Benign paroxysmal positional vertigo (BPPV) is a peculiar form of dizziness, presenting with attacks of rotational vertigo provoked by changes in head position. 1 Based on the results of noncontrolled studies, some authors have proposed an autoimmune aetiopathogenesis for BPPV, suggesting that it may be triggered by the diffusion of immune-complexes in the inner ear with consequent mechanical stimulation of labyrinthine receptors. 2