Luca Chiovato

Disappearance of humoral thyroid autoimmunity after complete removal of thyroid antigens.

RiassuntoLe malattie autoimmuni della tiroide sono caratterizzate dalla presenza di anticorpi diretti contro la tireoperossidasi (TPO), la tireoglobulina (Tg) e il recettore per l’ormone tireotropo (TSH-R). Questo studio ha valutato se la rimozione completa degli antigeni tiroidei fosse in grado di indurre la scomparsa dei segni di autoimmunità tiroidea circolante. Lo studio è basato su una revisione retrospettiva delle cartelle cliniche di pazienti che erano stati seguiti e trattati secondo un protocollo standard. Sono stati studiati 182 pazienti affetti da tumore differenziato della tiroide i quali, per la coesistenza di una tiroidite cronica autoimmune, di un morbo di Basedow o di una tiroidite focale autoimmune, risultavano positivi per anticorpi anti-TPO (TPOAb), anti-Tg (TgAb) o anti-TSH-R (TRAb). Dei 182 soggetti, 151 erano di sesso femminile e 31 di sesso maschile; l’età media era di 39,7±13,7 anni, con un range da 6 a 81 anni. Tutti i pazienti sono stati sottoposti a tiroidectomia totale e a trattamento con iodio radioattivo allo scopo di ablare il tessuto tiroideo residuo o metastatico. Il follow-up è stato effettuato mediante scintigrafie corporee totali con radioiodio e dosaggio della Tg circolante. La media del follow-up era di 10,1±4,1 anni, con un range di 4–20 anni. A seguito del trattamento con tiroidectomia totale e iodio radioattivo, si è verificata la scomparsa dei TgAb, TPOAb e TRAb. La mediana di scomparsa è stata di 6,3 anni per iTPOAb e di 3,0 anni per i TgAb. La scomparsa del tessuto tiroideo e quella degli anticorpi antitiroide erano correlate in modo statisticamente significativo. La persistenza di TPOAb e TgAb non veniva influenzata dal sesso, dall’età e dalla concomitanza della tiroidite autoimmune o del morbo di Basedow.

IgG4-Related Hypophysitis: A New Addition to the Hypophysitis Spectrum

CONTEXT Hypophysitis is a chronic inflammation of the pituitary gland that comprises an increasingly complex clinicopathological spectrum. Within this spectrum, lymphocytic and granulomatous hypophysitis are the most common forms, but newer variants have recently been reported. OBJECTIVE The aims of the study were to describe a new patient with IgG4-related hypophysitis, review the published literature, and provide diagnostic criteria. SETTING A 75-yr-old man presented with a 1-yr history of frontal headache. Initial studies revealed panhypopituitarism and a mass in both the sella turcica and the sphenoidal sinus. The patient underwent transphenoidal surgery, initiated high-dose prednisone followed by hormone replacement therapy, and was closely monitored for 3 yr. RESULTS Symptoms improved after prednisone, along with shrinkage of the pituitary and sphenoidal masses, but recurred when prednisone dose was lowered. Histopathology showed a marked mononuclear infiltrate in both the pituitary and sphenoidal specimens, mainly characterized by increased numbers of plasma cells. Many of the infiltrating plasma cells (>10 per high-power field) were IgG4-positive. Review of the literature identified 11 cases of IgG4-related hypophysitis (two diagnosed based on pituitary histopathology). CONCLUSIONS We describe the first Caucasian patient with biopsy-proven IgG4-related hypophysitis and provide classification criteria for this disease.

Use of the Italian translation of the Female Sexual Function Index (FSFI) in routine gynecological practice

Aims. To investigate domains of sexual function in healthy women attending a gynecological office for routine annual check-up using the Italian translation of the Female Sexual Function Index (FSFI) according to age, reproductive status and hormonal treatments; and to confirm the usefulness of the FSFI in detecting relevant clinical entities. Methods. Of 720 women (age range 18–65 years), 564 (78%) filled in a short anamnestic questionnaire and the FSFI assessing desire, arousal, lubrication, orgasm, satisfaction and pain. A semi-structured DSM-IV-TR clinical interview was administered to a convenience sample of women selected according to the quartile distribution of the median full scale FSFI score. Analysis of data was performed by frequency tables and non-parametric statistics. Results. The median full scale score of FSFI in our study population was 27.6 (lower quartile: 18.7, upper quartile: 30.9) and the percentage of women under the lower quartile of the distribution was 24.4%. Sexual function decreased progressively with age, being significantly lower after 30 years and after 60 years (χ2 = 52.6; p = 0.0001). Menopausal women had significantly lower median FSFI full scale score compared with fertile women and women who used oral contraception (OC) (p < 0.0001 for both), while users of hormone replacement therapy (HRT) displayed better overall sexual function than untreated postmenopausal women (p < 0.005). A positive diagnosis of female sexual dysfunction (FSD) was evident only in young women scoring under the lower quartile of the distribution (cut-off score: 23.4 for women not taking OC and 20.8 for OC users), while older women were dysfunctional also above the lower quartile of the distribution (cut-off score: 14.1 for menopause, 18.5 for HRT) of the FSFI full scale score. Conclusions. The FSFI is a powerful screening tool for FSD, especially in young fertile women, and may be used effectively in routine gynecological practice.

Thyroid ultrasonography as a tool for detecting thyroid autoimmune diseases and predicting thyroid dysfunction in apparently healthy subjects

In order to establish its usefulness for the diagnosis and follow-up of thyroid autoimmune diseases, thyroid ultrasonography together with free T4 (FT4), free T3 (FT3), TSH, antibodies (Tg Ab) and thyroperoxidase antibodies (TPO Ab) were performed and re-evaluated during a 3-yr follow-up in 482 apparently healthy subjects, living in a borderline iodine-sufficient urban area. Thyroid dysfunction was found in 7 out of 12 (58.3%) subjects with circulating thyroid autoantibodies, who also had thyroid hypoechogenicity (2 had overt and 3 subclinical hypothyroidism at booking; 2 developed subclinical hypothyroidism during the follow-up), and in none of the 12 subjects with normal thyroid echostructure (χ2=7.26, p=0.007). Thyroid dysfunction was found in 4 out of 29 (13.7%) subjects with negative Tg and/or TPO Ab who also had thyroid hypoechogenicity (1 had Graves’ disease at booking, 1 developed Graves’ disease and 2 subclinical hypothyroidism during the follow-up), and in none of the 429 with normal thyroid echostructure (χ2=82.03, p<0.0001). Although positive TPO and/or Tg Ab were more frequent (24/482, 5%) in subjects with thyroid dysfunction (7/11) than in those who remained euthyroid during the study (17/471, χ2=69.66, p<0.0001), thyroid hypoechogenicity had a higher sensitivity than the positivity of thyroid autoantibody tests (100 vs 63.3%) for diagnosing or predicting thyroid dysfunction. In conclusion: 1) thyroid ultrasonography is a useful tool to detect thyroid autoimmune disease in apparently healthy subjects; 2) present and future thyroid dysfunction is more readily predicted by a hypoechogenic pattern at thyroid ultrasound than by the occurrence of serum thyroid autoantibodies.

Raised serum TSH levels in patients with morbid obesity: is it enough to diagnose subclinical hypothyroidism?

OBJECTIVE Morbid obesity (body mass index (BMI)> or =40 kg/m(2)) is associated with thyroid function disturbances, with a high rate of subclinical hypothyroidism (SH) being the most consistently reported. We evaluated the circulating thyroid function parameters in morbid obese patients and related the results to the presence of circulating thyroid antibodies (Thyr-Ab). DESIGN AND METHODS Morbid obese patients were consecutively enrolled (n=350). Two control groups were used: control group (CG)1, healthy normo-weight subjects (n=50); CG2, normo-weight patients with SH (n=56) matched for TSH with the obese patients with SH. Serum levels of free triiodothyronine (FT(3)), free thyroxine (FT(4)), TSH, antithyroglobulin antibodies, and antithyroperoxidase antibodies were measured in all patients. RESULTS i) Compared with CG1, obese patients having thyroid function parameters in the normal range and negative Thyr-Ab showed significantly higher serum TSH and lower free thyroid hormones levels, but a similar FT(4)/FT(3) ratio; ii) SH was recorded in 13.7% obese patients; iii) compared with CG2, obese patients with untreated SH had a significantly lower rate of positive Thyr-Ab (32.1 vs 66.1%; P<0.005); iv) no gender prevalence was observed in SH obese patients with negative Thyr-Ab; and v) the comparison of the untreated SH patients (obese and normo-weight) with CG1 demonstrated that in SH obese subjects, unlike normo-weight SH patients, the FT(3) levels were significantly lower. This resulted in a normal FT(4)/FT(3) ratio in SH obese patients. CONCLUSION Thyroid autoimmunity is not a major cause sustaining the high rate of SH in morbid obese patients. In these patients, the diagnosis of SH itself, as assessed by a raised TSH alone, appears questionable.

Prevalence of psychiatric disorders in thyroid diseased patients.

Several studies have underlined the high prevalence of psychiatric symptoms and disorders in thyroid diseases. The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes, by means of a standardized instrument, i.e., the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised, Upjohn Version (SCID-UP-R). The results showed higher rates of panic disorder, simple phobia, obsessive-compulsive disorder, major depressive disorder, bipolar disorder and cyclothymia in thyroid patients than in the general population. These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities.

Implications of thyroglobulin antibody positivity in patients with differentiated thyroid cancer: a clinical position statement

BACKGROUND Even though the presence of antithyroglobulin antibodies (TgAbs) represents a significant problem in the follow-up of patients with differentiated thyroid cancer (DTC), the current guidelines on the management of DTC that have been published in recent years contain no text concerning the methods to be used for detecting such antibody-related interference in thyroglobulin (Tg) measurement or how to manage TgAb-positive patients in whom Tg cannot be used reliably as a tumor marker. AIM An international group of experts from the European Thyroid Association Cancer Research Network who are involved in the care of DTC patients met twice to form a consensus opinion on how to proceed with treatment and follow-up in TgAb-positive DTC patients based on the available evidence in the literature. Here we will report on the consensus opinions that were reached regarding technical and clinical issues. RESULTS This clinical opinion article provides an overview of the available evidence and the resulting consensus recommendations. The current literature does not provide sufficient data for giving evidence-based answers to many questions arising in the care of TgAb-positive DTC patients. Where insufficient evidence was available, a thorough discussion by a group of physician-scientists, all of whom have a distinguished track record in thyroid cancer care, was held to arrive at a consensus expert opinion. The questions and answers discussed were then summarized into an algorithm for the management of TgAb-positive patients. CONCLUSION We were able to define 26 consensus expert recommendations and a resulting algorithm for the care of TgAb-positive DTC patients.

Prevalence of thyroid autoantibodies in children and adolescents from Belarus exposed to the Chernobyl radioactive fallout

BACKGROUND The long-term effects of ionising radiation, including radioiodine, on thyroid function are not well known. We compared thyroid immunity and function in two groups of children from Belarus, one of whom was exposed to the radioactive fallout of Chernobyl. METHODS We measured serum free thyroxine 4 (free T4), free T3, and thyrotropin hormone (TSH) and the prevalence of thyroid autoantibodies (antithyroglobulin and antithyroperoxidase), in 287 children or adolescents living in Hoiniki (average caesium contamination of 5.4 Ci/km2). We also studied 208 children and adolescents living in Braslav (average contamination <0.1 Ci/km2), who were age 12 years or less at the time of the Chernobyl accident. FINDINGS The prevalence of antithyroglobulin or antithyroperoxidase, or both, was significantly higher (p=0.0001) in individuals living in Hoiniki (56 [19.5%] of 287) than in those living in Braslav (eight [3.8%] of 208). In both villages, no sex differences were found in the antibody prevalence before age 13 years. Thereafter, a significantly higher prevalence of thyroid autoantibodies was found in girls from Hoiniki. The increase in the prevalence of circulating antibodies in the contaminated group was already apparent in individuals who, at the time of the accident, were in utero or newborn (15.7%), and was even more pronounced in children of 9 years or more (35.1%). No major alterations of serum FT-4, FT-3, or TSH were found. INTERPRETATION 6-8 years after the Chernobyl accident, a significant increase in thyroid autoimmunity was found in children exposed to radioactive fallout. Pubertal age in girls is a risk factor for increased prevalence of thyroid autoimmunity. The autoimmune phenomena are limited to an increased prevalence of circulating thyroid autoantibodies without evidence of significant thyroid dysfunction. The future development of clinically relevant thyroid autoimmune diseases, especially hypothyroidism, is a possibility.

TSH-Lowering Effect of Metformin in Type 2 Diabetic Patients: Differences between euthyroid, untreated hypothyroid, and euthyroid on L-T4 therapy patients

OBJECTIVE To assess the interplay between metformin treatment and thyroid function in type 2 diabetic patients. RESEARCH DESIGN AND METHODS The acute and long-term effects of metformin on thyroid axis hormones were assessed in diabetic patients with primary hypothyroidism who were either untreated or treated with levothyroxine (L-T4), as well as in diabetic patients with normal thyroid function. RESULTS No acute changes were found in 11 patients with treated hypothyroidism. After 1 year of metformin administration, a significant thyrotropin (TSH) decrease (P < 0.001) was observed in diabetic subjects with hypothyroidism who were either treated (n = 29; from 2.37 ± 1.17 to 1.41 ± 1.21 mIU/l) or untreated (n = 18; 4.5 ± 0.37 vs. 2.93 ± 1.48) with L-T4, but not in 54 euthyroid subjects. No significant change in free T4 (FT4) was observed in any group. CONCLUSIONS Metformin administration influences TSH without change of FT4 in patients with type 2 diabetes and concomitant hypothyroidism. The need for reevaluation of thyroid function in these patients within 6–12 months after starting metformin is indicated.

Shear wave elastography in the diagnosis of thyroid nodules: feasibility in the case of coexistent chronic autoimmune Hashimoto’s thyroiditis

Objective  ShearWave™ Elastography (SWE) is real‐time, quantitative and user‐independent technique, recently introduced in the diagnostic work‐up of thyroid nodules. Hashimoto’s thyroiditis (HT), characterized by variable degrees of lymphocytic infiltration and fibrosis, might affect shear wave propagation. The aim of this study was to assess the feasibility of SWE in cytologically benign thyroid nodules within both Hashimoto’s and nonautoimmune thyroid glands. The effect of autoimmunity on the gland stiffness was also evaluated.