Publications by authors named "F Bogazzi"

171 Publications

Identification of two different phenotypes of patients with amiodarone-induced thyrotoxicosis and positive thyrotropin receptor antibody tests.

Thyroid 2021 Jul 16. Epub 2021 Jul 16.

Università degli Studi di Pisa Facolta di Medicina e Chirurgia, 9310, Department of Clinical and Experimental Medicine, Pisa, Italy;

Introduction: Serum TSH receptor antibodies (TRAbs) are occasionally found in patients with AIT, and usually orient toward a diagnosis of type 1 AIT (AIT1) due to Graves' disease (GD). However, TRAb role and function in AIT are unsettled.

Methods: Retrospective cohort study of 309 AIT patients followed at a single Academic center over a 30-year period. AIT TRAb-positive patients (n=21, 7% of the whole series) constituted the study group; control groups were type 2 AIT (AIT2) TRAb-negative patients (n=233), and 100 non-AIT patients with GD. Clinical and biochemical data at diagnosis and during the course of disease were compared. Histological samples of patients submitted to total thyroidectomy were retrieved. Stored serum samples were used for a functional assay of TRAb immunoglobulins (IgGs) on Chinese hamster ovary (CHO) cells stably transfected with cDNA encoding for the TSH receptor.

Results: TRAb-positive patients were grouped according to color flow Doppler sonography, thyroidal RAIU, duration of amiodarone therapy before thyrotoxicosis in type 1 (n=9, 43%; TRAb1) or type 2 (n=12, 57%; TRAb2) AIT. TRAb1 patients had clinical and biochemical features indistinguishable from GD controls, and were responsive to methimazole; conversely, TRAb2 patients had clinical features similar to AIT2 controls, and were responsive to glucocorticoids but not to methimazole. The CHO cells functional assay demonstrated that TRAb1 IgGs had a stimulatory effect on cyclic AMP production, which was absent in TRAb2 IgGs. Pathology in TRAb1 showed hyperplastic thyroid follicles and mild lymphocyte infiltration, reflecting thyroid stimulation, whereas TRAb2 samples revealed follicle destruction, macrophage infiltration and sometimes fibrosis, all expression of a destructive process.

Conclusions: Almost 60% of TRAb-positive AIT patients had a destructive thyroiditis. Thus finding TRAb positive tests in AIT patients does not necessarily imply a diagnosis of Graves' disease and type 1 AIT. Rather, it should be evaluated in the clinical and biochemical setting of each AIT patient.
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July 2021

Autoimmune polyendocrine syndrome type 1: an Italian survey on 158 patients.

J Endocrinol Invest 2021 May 18. Epub 2021 May 18.

FIRS Laboratories RSR Ltd, Cardiff, UK.

Background: Autoimmune Polyglandular Syndrome type 1 (APS-1) is a rare recessive inherited disease, caused by AutoImmune Regulator (AIRE) gene mutations and characterized by three major manifestations: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism (CH) and Addison's disease (AD).

Methods: Autoimmune conditions and associated autoantibodies (Abs) were analyzed in 158 Italian patients (103 females and 55 males; F/M 1.9/1) at the onset and during a follow-up of 23.7 ± 15.1 years. AIRE mutations were determined.

Results: The prevalence of APS-1 was 2.6 cases/million (range 0.5-17 in different regions). At the onset 93% of patients presented with one or more components of the classical triad and 7% with other components. At the end of follow-up, 86.1% had CH, 77.2% AD, 74.7% CMC, 49.5% premature menopause, 29.7% autoimmune intestinal dysfunction, 27.8% autoimmune thyroid diseases, 25.9% autoimmune gastritis/pernicious anemia, 25.3% ectodermal dystrophy, 24% alopecia, 21.5% autoimmune hepatitis, 17% vitiligo, 13.3% cholelithiasis, 5.7% connective diseases, 4.4% asplenia, 2.5% celiac disease and 13.9% cancer. Overall, 991 diseases (6.3 diseases/patient) were found. Interferon-ω Abs (IFNωAbs) were positive in 91.1% of patients. Overall mortality was 14.6%. The AIRE mutation R139X was found in 21.3% of tested alleles, R257X in 11.8%, W78R in 11.4%, C322fsX372 in 8.8%, T16M in 6.2%, R203X in 4%, and A21V in 2.9%. Less frequent mutations were present in 12.9%, very rare in 9.6% while no mutations in 11% of the cases.

Conclusions: In Italy, APS-1 is a rare disorder presenting with the three major manifestations and associated with different AIRE gene mutations. IFNωAbs are markers of APS-1 and other organ-specific autoantibodies are markers of clinical, subclinical or potential autoimmune conditions.
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May 2021

PCB153 reduces apoptosis in primary cultures of murine pituitary cells through the activation of NF-κB mediated by PI3K/Akt.

Mol Cell Endocrinol 2021 01 24;520:111090. Epub 2020 Nov 24.

Department of Clinical and Experimental Medicine, University of Pisa, via Savi, 10, 56126, Pisa, Italy. Electronic address:

Polychlorinated biphenyls (PCBs) are persistent pollutants involved in human tumorigenesis. PCB153 is a ubiquitous non-dioxin-like PCB with proliferative and anti-apoptotic effects. To explore the impact of PCB153 in the survival of pituitary cells, we exposed murine pituitary primary cells to PCB153 10 μM for 24 h. Apoptosis was assessed by RT-qPCR, Western-blot, immunoprecipitation, caspase activity, and immunofluorescence. We found that PCB153 decreased pituitary apoptosis through both the extrinsic and intrinsic pathways. PCB153 reduced the level of the pro-apoptotic protein p38-MAPK. Otherwise, PCB153 activated PI3K/Akt and Erk1/2 pathways and enhanced the expression and nuclear translocation of NF-κB. Cotreatments with specific inhibitors revealed that only PI3K/Akt changed the caspase-3 expression and NF-κB activation induced by PCB153. Also, PCB153 decreased the expression of the pro-apoptotic and pro-senescent cyclins p53 and p21. In summary, exposure to PCB153 leads to a downregulation of apoptosis in the pituitary driven by a PI3K/Akt-mediated activation of NF-κB.
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January 2021

Duration of Exposure to Thyrotoxicosis Increases Mortality of Compromised AIT Patients: the Role of Early Thyroidectomy.

J Clin Endocrinol Metab 2020 09;105(9)

Unit of Endocrinology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Context: Patients with amiodarone-induced thyrotoxicosis (AIT) and severely reduced left ventricular ejection fraction (LVEF) have a high mortality rate that may be reduced by total thyroidectomy. Whether in this subset of patients thyroidectomy should be performed early during thyrotoxicosis or later after restoration of euthyroidism has not yet been settled.

Objectives: Mortality rates, including peritreatment mortality and 5-year cardiovascular mortality, and predictors of death, evaluated by Cox regression analysis.

Methods: Retrospective cohort study of 64 consecutive patients with AIT selected for total thyroidectomy from 1997 to 2019. Four groups of patients were identified according to serum thyroid hormone concentrations and LVEF: Group 1 (thyrotoxic, LVEF <40%), Group 2 (thyrotoxic, LVEF ≥40%), Group 3 (euthyroid, LVEF < 40%), Group 4 (euthyroid, LVEF ≥40%).

Results: Among patients with low LVEF (Groups 1 and 3), mortality was higher in patients undergoing thyroidectomy after restoration of euthyroidism (Group 3) than in those submitted to surgery when still thyrotoxic (Group 1): peritreatment mortality rates were 40% versus 0%, respectively (P = .048), whereas 5-year cardiovascular mortality rates were 53.3% versus 12.3%, respectively (P = .081). Exposure to thyrotoxicosis was longer in Group 3 than in Group 1 (112 days, interquartile range [IQR] 82.5-140, vs 76 days, IQR 24.8-88.5, P = .021). Survival did not differ in patients with LVEF ≥40% submitted to thyroidectomy irrespective of being thyrotoxic (Group 2) or euthyroid (Group 4): in this setting, peritreatment mortality rates were 6.3% versus 4% (P = .741) and 5-year cardiovascular mortality rates were 12.5% and 20% (P = .685), respectively. Age (hazard ratio [HR] 1.104, P = .029) and duration of exposure to thyrotoxicosis (HR 1.004, P = .039), but not presurgical serum thyroid hormone concentrations (P = .577 for free thyroxine, P = .217 for free triiodothyronine), were independent predictors of death.

Conclusions: A prolonged exposure to thyrotoxicosis resulted in increased mortality in patients with reduced LVEF, which may be reduced by early thyroidectomy.
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September 2020

Response to the Letter to the Editor: "Comparison Between Total Thyroidectomy and Medical Therapy for Amiodarone-Induced Thyrotoxicosis".

J Clin Endocrinol Metab 2020 08;105(8)

Department of Clinical and Experimental Medicine, Unit of Endocrinology, University of Pisa, Pisa, Italy.

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August 2020