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Article ; Online: COVID-induced thyroid autoimmunity.

Brancatella, Alessandro / Viola, Nicola / Santini, Ferruccio / Latrofa, Francesco

Best practice & research. Clinical endocrinology & metabolism

2023 Volume 37, Issue 2, Page(s) 101742

Abstract: Breakdown of self-tolerance to thyroid antigens (thyroperoxidase, thyroglobulin and the thyrotropin-receptor) is the driver of thyroid autoimmunity. It has been suggested that infectious disease might trigger autoimmune thyroid disease (AITD). ... ...

Abstract	Breakdown of self-tolerance to thyroid antigens (thyroperoxidase, thyroglobulin and the thyrotropin-receptor) is the driver of thyroid autoimmunity. It has been suggested that infectious disease might trigger autoimmune thyroid disease (AITD). Involvement of the thyroid has been reported during severe acute respiratory syndrome virus 2 (SARS-CoV-2) infection, in the form of subacute thyroiditis in subjects with mild coronavirus disease 19 disease (COVID-19) and of painless, destructive thyroiditis in hospitalized patients with severe infection. In addition, cases of AITD, both Graves' disease (GD) and Hashimoto's thyroiditis (HT), have been reported in association with (SARS-CoV-2) infection. In this review, we focus on the relationship between SARS-CoV-2 infection and occurrence of AITD. Nine cases of GD strictly related to SARS-CoV-2 infection and only three cases of HT associated to COVID-19 infection have been reported. No study has demonstrated a role of AITD as a risk factor for a poor prognosis of COVID-19 infection.
MeSH term(s)	Humans ; Autoimmunity ; COVID-19/complications ; SARS-CoV-2 ; Hashimoto Disease/complications ; Autoimmune Diseases/complications ; Graves Disease
Language	English
Publishing date	2023-02-05
Publishing country	Netherlands
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2052339-7
ISSN	1878-1594 ; 1532-1908 ; 1521-690X
ISSN (online)	1878-1594 ; 1532-1908
ISSN	1521-690X
DOI	10.1016/j.beem.2023.101742
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Article: TSH suppressive therapy and bone.

Brancatella, Alessandro / Marcocci, Claudio

Endocrine connections

2020 Volume 9, Issue 7, Page(s) R158–R172

Abstract: Thyroid hormones stimulate bone turnover in adults by increasing osteoclastic bone resorption. TSH suppressive therapy is usually applied in patients with differentiated thyroid cancer (DTC) to improve the disease outcome. Over the last decades several ... ...

Abstract	Thyroid hormones stimulate bone turnover in adults by increasing osteoclastic bone resorption. TSH suppressive therapy is usually applied in patients with differentiated thyroid cancer (DTC) to improve the disease outcome. Over the last decades several authors have closely monitored the potential harm suffered by the skeletal system. Several studies and meta-analyses have shown that chronic TSH suppressive therapy is safe in premenopausal women and men. Conversely, in postmenopausal women TSH suppressive therapy is associated with a decrease of bone mineral density, deterioration of bone architecture (quantitative CT, QCT; trabecular bone score, TBS), and, possibly, an increased risk of fractures. The TSH receptor is expressed in bone cells and the results of experimental studies in TSH receptor knockout mice and humans on whether low TSH levels, as opposed to solely high thyroid hormone levels, might contribute to bone loss in endogenous or exogenous thyrotoxicosis remain controversial. Recent guidelines on the use of TSH suppressive therapy in patients with DTC give value not only to its benefit on the outcome of the disease, but also to the risks associated with exogenous thyrotoxicosis, namely menopause, osteopenia or osteoporosis, age >60 years, and history of atrial fibrillation. Bone health (BMD and/or preferably TBS) should be evaluated in postmenopausal women under chronic TSH suppressive therapy or in those patients planning to be treated for several years. Antiresorptive therapy could also be considered in selected cases (increased risk of fracture or significant decline of BMD/TBS during therapy) to prevent bone loss.
Language	English
Publishing date	2020-06-22
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2668428-7
ISSN	2049-3614
ISSN	2049-3614
DOI	10.1530/EC-20-0167
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Article ; Online: Significance of Thyroglobulin Autoantibodies in Patients With Thyroid Cancer Treated With Lenvatinib.

Sgrò, Daniele / Rossi, Piercarlo / Piaggi, Paolo / Brancatella, Alessandro / Lorusso, Loredana / Bottici, Valeria / Molinaro, Eleonora / Latrofa, Francesco / Elisei, Rossella / Agate, Laura

Journal of the Endocrine Society

2023 Volume 7, Issue 8, Page(s) bvad084

Abstract: Context: Serum thyroglobulin (Tg) is a highly sensitive and specific tumor marker, employed in post-operative management of patients with differentiated thyroid carcinomas. Tumor shrinkage of radioiodine-refractory thyroid cancer (RAIR-DTC) treated with ...

Abstract	Context: Serum thyroglobulin (Tg) is a highly sensitive and specific tumor marker, employed in post-operative management of patients with differentiated thyroid carcinomas. Tumor shrinkage of radioiodine-refractory thyroid cancer (RAIR-DTC) treated with multitarget kinase inhibitors as lenvatinib, expressed according to the Response Evaluation Criteria in Solid Tumors (RECIST), is also associated with a drastic reduction of Tg levels. However, interference caused by circulating thyroglobulin autoantibodies (TgAb) represents the main limitation in the clinical use of Tg. Objective: To evaluate if in RAIR-DTC TgAb could be considered a surrogate marker of Tg in monitoring response to treatment with lenvatinib. Design: We retrospectively evaluated patients who had started lenvatinib and correlated serum Tg and TgAb with the radiological response across visits. Setting: University of Pisa, Italy. Patients: We selected 9/97 RAIR-DTC patients with detectable TgAb. Intervention: None. Main outcome measures: None. Results: Tg values correlated neither with TgAb title nor with radiological response across visits. Greater decreases in TgAb titer correlated with favorable radiological response to lenvatinib after 1 month (Spearman's correlation = 0.74, Conclusion: TgAb evaluation may represent a reliable surrogate marker for Tg trend in evaluating response of RAIR-DTC to treatment with lenvatinib. A multicentric study would be useful to confirm our results.
Language	English
Publishing date	2023-07-10
Publishing country	United States
Document type	Journal Article
ISSN	2472-1972
ISSN (online)	2472-1972
DOI	10.1210/jendso/bvad084
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Article ; Online: Subacute Thyroiditis During the SARS-CoV-2 Pandemic.

Brancatella, Alessandro / Viola, Nicola / Rutigliano, Grazia / Sgrò, Daniele / Santini, Ferruccio / Latrofa, Francesco

Journal of the Endocrine Society

2021 Volume 5, Issue 10, Page(s) bvab130

Abstract: Context: Acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been related to subacute thyroiditis (SAT).: Objective: We compared SAT cases during the SARS-CoV-2 pandemic to those observed in the previous years.: Methods: A cross-sectional, ... ...

Abstract	Context: Acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been related to subacute thyroiditis (SAT). Objective: We compared SAT cases during the SARS-CoV-2 pandemic to those observed in the previous years. Methods: A cross-sectional, retrospective study was conducted at the Endocrinology Unit of University Hospital of Pisa, Italy. We included all patients observed from January 2016 to December 2020 because of an untreated SAT, who had developed the disease within 15 days prior to the visit. SAT cases from 2016 to 2019 (N = 152) are referred to as Results: While during 2016-2019, most SAT cases were observed in the third quarter, in 2020, 2 peaks were seen, superimposable to the SARS-CoV-2 outbreaks in the second and the fourth quarters. In the second and fourth quarters of 2020, we observed higher levels of free thyroxine (FT4), C-reactive protein (CRP), and thyroglobulin (Tg) compared with the same quarters of the years 2016-2019. Pos-SARS-CoV-2 patients had higher FT4 (28.4 vs 24.1 nmol/L), CRP (8.5 vs 3.6 mg/L), and Tg (155 vs 60 µg/L) ( Conclusion: The SARS-CoV-2 pandemic has caused a shift in the annual timing and severity of SAT cases.
Language	English
Publishing date	2021-07-28
Publishing country	United States
Document type	Journal Article
ISSN	2472-1972
ISSN (online)	2472-1972
DOI	10.1210/jendso/bvab130
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Article ; Online: Thyroid autoimmunity, thyroglobulin autoantibodies, and thyroid cancer prognosis.

Viola, Nicola / Agate, Laura / Caprio, Sonia / Lorusso, Loredana / Brancatella, Alessandro / Ricci, Debora / Sgrò, Daniele / Ugolini, Clara / Piaggi, Paolo / Vitti, Paolo / Elisei, Rossella / Santini, Ferruccio / Latrofa, Francesco

Endocrine-related cancer

2023 Volume 30, Issue 7

Abstract: The relevance of thyroid autoimmunity to the prognosis of papillary thyroid carcinoma is still unsettled. We decided to investigate the impact of thyroid autoimmunity on the prognosis of papillary thyroid carcinoma and the handling of TgAbs. We evaluated ...

Abstract	The relevance of thyroid autoimmunity to the prognosis of papillary thyroid carcinoma is still unsettled. We decided to investigate the impact of thyroid autoimmunity on the prognosis of papillary thyroid carcinoma and the handling of TgAbs. We evaluated the clinical course of a large group of patients according to the presence (PTC-LT) or absence (PTC) of lymphocytic thyroiditis at histology. We studied 194 consecutive patients with a diagnosis of PTC and treated them with total thyroidectomy plus ¹³¹I ablation between 2007 and 2009. Median follow-up (with 25th-75th percentiles) was 84.0 (56.4-118.0) months. The remission criteria were: basal Tg < 0.2 ng/mL (or stimulated Tg: < 1), TgAbs < 8 IU/mL (otherwise 'decreasing TgAb trend', a decline of ≥20% in sequential TgAb measurements) and unremarkable imaging. PTC-LT and PTC patients had comparable treatment.TgAbs were detectable in 72.5% of PTC-LT and 16.5% of PTC patients. Time to remission was longer in the detectable than in the undetectable TgAb cohort (28.5 vs· 7.5 months (median); HR: 0.54, CI: 0.35-0.83, P = 0.005). When comparing PTC-LT to PTC patients, the difference was maintained in the detectable TgAb (29.3 vs 13.0 months; HR: 0.38, CI: 0.18-0.80; P = 0.01) but not in the undetectable TgAb cohort (7.7 vs 7.3 months; HR: 0.90, CI: 0.55-1.47; P = 0.68). Using the decreasing TgAb trend, the influence of detectable TgAbs on time to remission was abolished. Thyroid autoimmunity does not influence the prognosis of papillary thyroid carcinoma. A decreasing TgAb trend seems an appropriate criterion to establish the remission of papillary thyroid carcinoma.
MeSH term(s)	Humans ; Thyroglobulin ; Thyroid Cancer, Papillary/surgery ; Iodine Radioisotopes ; Autoantibodies ; Autoimmunity ; Carcinoma, Papillary/surgery ; Carcinoma, Papillary/pathology ; Thyroid Neoplasms/pathology ; Prognosis ; Thyroidectomy ; Retrospective Studies
Chemical Substances	Thyroglobulin (9010-34-8) ; Iodine-131 ; Iodine Radioisotopes ; Autoantibodies
Language	English
Publishing date	2023-06-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1218450-0
ISSN	1479-6821 ; 1351-0088
ISSN (online)	1479-6821
ISSN	1351-0088
DOI	10.1530/ERC-23-0042
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Article ; Online: Cytological and Ultrasound Features of Thyroid Nodules Correlate With Histotypes and Variants of Thyroid Carcinoma.

Sgrò, Daniele / Brancatella, Alessandro / Greco, Giuseppe / Torregrossa, Liborio / Piaggi, Paolo / Viola, Nicola / Rago, Teresa / Basolo, Fulvio / Giannini, Riccardo / Materazzi, Gabriele / Elisei, Rossella / Santini, Ferruccio / Latrofa, Francesco

The Journal of clinical endocrinology and metabolism

2023 Volume 108, Issue 11, Page(s) e1186–e1192

Abstract: Context: Prognosis is excellent for papillary thyroid carcinoma (PTC), noninvasive follicular thyroid neoplasia with papillary-like nuclear features (NIFT-P), and follicular thyroid carcinoma (FTC) but is poor for poorly differentiated thyroid carcinoma ...

Abstract	Context: Prognosis is excellent for papillary thyroid carcinoma (PTC), noninvasive follicular thyroid neoplasia with papillary-like nuclear features (NIFT-P), and follicular thyroid carcinoma (FTC) but is poor for poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC). Among PTCs, the prognosis is more favorable for follicular (FV-PTC) and classic (CV-PTC) than for tall cell (TCV-PTC), and solid (SV-PTC) variants. Objective: To associate histotypes and variants of thyroid carcinoma with ultrasound and cytological features. Methods: Histology of 1018 benign tumors and 514 PTC (249 CV, 167 FV, 49 TC, 34 SV, and 15 other variants), 52 NIFT-P, 50 FTC, 11 PDTC, and 3 ATC was correlated with fine-needle aspiration biopsy categories (Italian classification: TIR1, TIR2, TIR3A, TIR3B, TIR4, and TIR5) and ultrasound features at the Endocrinology Unit, University Hospital of Pisa. In total, 1117 patients with thyroid nodule(s) who underwent thyroidectomy were included. Results: Of PTC, 36.3% had indeterminate cytology (TIR3A or TIR3B), 56.6% were suspicious for malignancy or malignant (TIR4 or TIR5); 84.0% FTC and 69.3% NIFT-P were TIR3A or TIR3B; 72.5% FV-PTC and 73.6% SV-PTC were TIR3A or TIR3B; 79.9% CV-PTC and 95.9% TCV-PTC were TIR4 or TIR5. The association of a hypoechoic pattern, irregular margins, and no microcalcifications was more frequent in TCV-PTC than in CV-PTC (P = .02, positive predictive value = 38.9%; negative predictive value = 85.5%). Conclusion: At cytology, most FTC, NIFT-P, FV-PTC, and SV-PTC were indeterminate, most CV-PTC and TCV-PTC were suspicious for malignancy or malignant. Ultrasound can be helpful in ruling out TCV-PTC.
MeSH term(s)	Humans ; Thyroid Nodule/diagnostic imaging ; Thyroid Nodule/surgery ; Thyroid Nodule/pathology ; Thyroid Neoplasms/diagnostic imaging ; Thyroid Neoplasms/surgery ; Thyroid Neoplasms/pathology ; Thyroid Cancer, Papillary/pathology ; Adenocarcinoma, Follicular/diagnostic imaging ; Adenocarcinoma, Follicular/surgery ; Adenocarcinoma, Follicular/pathology ; Thyroid Carcinoma, Anaplastic ; Retrospective Studies
Chemical Substances	prolinedithiocarbamate (135467-92-4)
Language	English
Publishing date	2023-06-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgad313
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Article ; Online: Activating Antibodies to The Calcium-sensing Receptor in Immunotherapy-induced Hypoparathyroidism.

Lupi, Isabella / Brancatella, Alessandro / Cetani, Filomena / Latrofa, Francesco / Kemp, E Helen / Marcocci, Claudio

The Journal of clinical endocrinology and metabolism

2020 Volume 105, Issue 5

Abstract: Context: Immune checkpoint inhibitors (ICIs), such as programmed cell death protein-1 (PD-1), programmed cell death protein-ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen-4 (CTLA-4) monoclonal antibodies, are approved for the treatment of some ... ...

Abstract	Context: Immune checkpoint inhibitors (ICIs), such as programmed cell death protein-1 (PD-1), programmed cell death protein-ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen-4 (CTLA-4) monoclonal antibodies, are approved for the treatment of some types of advanced cancer. Their main treatment-related side-effects are immune-related adverse events (irAEs), especially thyroid dysfunction and hypophysitis. Hypoparathyroidism, on the contrary, is an extremely rare irAE. Objectives: The aim of the study was to investigate the etiology of autoimmune hypoparathyroidism in a lung cancer patient treated with pembrolizumab, an anti-PD-1. Methods: Calcium-sensing receptor (CaSR) autoantibodies, their functional activity, immunoglobulin (Ig) subclasses and epitopes involved in the pathogenesis of autoimmune hypoparathyroidism were tested. Results: The patient developed hypocalcemia after 15 cycles of pembrolizumab. Calcium levels normalized with oral calcium carbonate and calcitriol and no remission of hypocalcemia was demonstrated during a 9-month follow-up. The patient was found to be positive for CaSR-stimulating antibodies, of IgG1 and IgG3 subclasses, that were able to recognize functional epitopes on the receptor, thus causing hypocalcemia. Conclusion: The finding confirms that ICI therapy can trigger, among other endocrinopathies, hypoparathyroidism, which can be caused by pathogenic autoantibodies.
MeSH term(s)	Adenocarcinoma of Lung/immunology ; Adenocarcinoma of Lung/pathology ; Adenocarcinoma of Lung/therapy ; Antibodies, Monoclonal, Humanized/adverse effects ; Antibodies, Monoclonal, Humanized/therapeutic use ; Autoantibodies/blood ; Humans ; Hypocalcemia/blood ; Hypocalcemia/chemically induced ; Hypoparathyroidism/chemically induced ; Hypoparathyroidism/diagnosis ; Hypoparathyroidism/immunology ; Hypoparathyroidism/metabolism ; Immunotherapy/adverse effects ; Lung Neoplasms/immunology ; Lung Neoplasms/pathology ; Lung Neoplasms/therapy ; Male ; Middle Aged ; Receptors, Calcium-Sensing/immunology ; Receptors, Calcium-Sensing/metabolism ; Withholding Treatment
Chemical Substances	Antibodies, Monoclonal, Humanized ; Autoantibodies ; Receptors, Calcium-Sensing ; pembrolizumab (DPT0O3T46P)
Language	English
Publishing date	2020-02-28
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgaa092
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Article ; Online: Is Subacute Thyroiditis an Underestimated Manifestation of SARS-CoV-2 Infection? Insights From a Case Series.

Brancatella, Alessandro / Ricci, Debora / Cappellani, Daniele / Viola, Nicola / Sgrò, Daniele / Santini, Ferruccio / Latrofa, Francesco

The Journal of clinical endocrinology and metabolism

2020 Volume 105, Issue 10

Abstract: Context: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 18 million people worldwide and the pandemic is still spreading. After the first case we reported, we observed 4 additional cases of subacute thyroiditis (SAT) ... ...

Abstract	Context: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 18 million people worldwide and the pandemic is still spreading. After the first case we reported, we observed 4 additional cases of subacute thyroiditis (SAT) related to SARS-CoV-2 infection. Objectives: The objective of this work is to describe additional cases of SAT associated with SARS-CoV-2 infection to alert physicians that SAT may be a manifestation of SARS-CoV-2 infection. Methods: We describe clinical, biochemical, and imaging features of 4 patients with SAT related to SARS-CoV-2 infection. Results: All patients were female (age, 29-46 years). SAT developed 16 to 36 days after the resolution of coronavirus disease 2019 (COVID-19). Neck pain radiated to the jaw and palpitations were the main presenting symptoms and were associated with fever and asthenia. One patient was hospitalized because of atrial fibrillation. Thyroid function tests (available for 3 individuals) were suggestive of destructive thyroiditis, and inflammatory markers were high. At neck ultrasound the thyroid was enlarged, with diffuse and bilateral hypoechoic areas and (in 3 patients) absent vascularization at color Doppler. Symptoms disappeared a few days after commencement of treatment (prednisone in 3 patients and ibuprofen in 1). Six weeks after the onset of SAT, all patients were asymptomatic and inflammatory markers had returned to normal range. Two patients were euthyroid, whereas 2 were diagnosed with subclinical hypothyroidism. Conclusions: SAT may be an underestimated manifestation of COVID-19. Clinicians should keep in mind the possible occurrence of SAT during and after SARS-CoV-2 infection.
MeSH term(s)	Adult ; Betacoronavirus/isolation & purification ; COVID-19 ; Coronavirus Infections/complications ; Coronavirus Infections/transmission ; Coronavirus Infections/virology ; Female ; Humans ; Middle Aged ; Pandemics ; Pneumonia, Viral/complications ; Pneumonia, Viral/transmission ; Pneumonia, Viral/virology ; Risk Factors ; SARS-CoV-2 ; Thyroiditis, Subacute/etiology ; Thyroiditis, Subacute/pathology
Keywords	covid19
Language	English
Publishing date	2020-08-11
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgaa537
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Article ; Online: Subacute Thyroiditis After Sars-COV-2 Infection.

Brancatella, Alessandro / Ricci, Debora / Viola, Nicola / Sgrò, Daniele / Santini, Ferruccio / Latrofa, Francesco

The Journal of clinical endocrinology and metabolism

2020 Volume 105, Issue 7

Abstract: Context: Subacute thyroiditis (SAT) is a thyroid disease of viral or postviral origin. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that began in Wuhan, China, has spread rapidly worldwide and Italy has been severely affected by this ...

Abstract	Context: Subacute thyroiditis (SAT) is a thyroid disease of viral or postviral origin. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that began in Wuhan, China, has spread rapidly worldwide and Italy has been severely affected by this outbreak. Objectives: The objective of this work is to report the first case of SAT related to SARS-CoV-2 infection. Methods: We describe the clinical, laboratory, and imaging features of an 18-year-old woman who came to our attention for fever, neck pain radiated to the jaw, and palpitations occurring 15 days after a SARS-CoV-2-positive oropharyngeal swab. Coronavirus disease 2019 (COVID-19) had been mild and the patient had completely recovered in a few days. Results: At physical examination the patient presented with a slightly increased heart rate and a painful and enlarged thyroid on palpation. At laboratory exams free thyroxine and free triiodothyronine were high, thyrotropin undetectable, and inflammatory markers and white blood cell count elevated. Bilateral and diffuse hypoechoic areas were detected at neck ultrasound. One month earlier, thyroid function and imaging both were normal. We diagnosed SAT and the patient started prednisone. Neck pain and fever recovered within 2 days and the remaining symptoms within 1 week. Thyroid function and inflammatory markers normalized in 40 days. Conclusions: We report the first case of SAT after a SARS-CoV-2 infection. We alert clinicians to additional and unreported clinical manifestations associated with COVID-19.
MeSH term(s)	Adolescent ; Betacoronavirus/isolation & purification ; Betacoronavirus/pathogenicity ; COVID-19 ; COVID-19 Testing ; Clinical Laboratory Techniques/methods ; Coronavirus Infections/complications ; Coronavirus Infections/diagnosis ; Coronavirus Infections/virology ; Female ; Humans ; Italy ; Leukocyte Count ; Oropharynx/virology ; Pandemics ; Pneumonia, Viral/complications ; Pneumonia, Viral/diagnosis ; Pneumonia, Viral/virology ; Prednisone/therapeutic use ; SARS-CoV-2 ; Thyroid Gland/diagnostic imaging ; Thyroiditis, Subacute/blood ; Thyroiditis, Subacute/diagnosis ; Thyroiditis, Subacute/drug therapy ; Thyroiditis, Subacute/virology ; Thyroxine/blood ; Treatment Outcome ; Triiodothyronine/blood ; Ultrasonography
Chemical Substances	Triiodothyronine (06LU7C9H1V) ; Thyroxine (Q51BO43MG4) ; Prednisone (VB0R961HZT)
Keywords	covid19
Language	English
Publishing date	2020-05-21
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgaa276
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Article ; Online: A severe inactivating PTH/PTHrP signaling disorder type 2 in a patient carrying a novel large deletion of the GNAS gene: a case report and review of the literature.

Brancatella, Alessandro / Mantovani, Giovanna / Elli, Francesca M / Borsari, Simona / Marcocci, Claudio / Cetani, Filomena

Endocrine

2020 Volume 67, Issue 2, Page(s) 466–472

Abstract: Purpose: Pseudohypoparathyroidism (PHP), characterized by multihormone resistance and Albright's hereditary osteodystrophy (AHO), is caused by GNAS mutations. Whole or partial gene deletions are rare. All disorders due to inactivating mutations of the ... ...

Abstract	Purpose: Pseudohypoparathyroidism (PHP), characterized by multihormone resistance and Albright's hereditary osteodystrophy (AHO), is caused by GNAS mutations. Whole or partial gene deletions are rare. All disorders due to inactivating mutations of the GNAS gene are now classified as "inactivating PTH/PTHrP signaling disorder type 2" (iPPSD2). This study reports a family harboring a large GNAS gene deletion in order to improve the knowledge of genotype-phenotype correlation of this disease. Methods: An 18-year-old man with severe diffuse soft ossifications and multihormone resistance underwent to clinical, biochemical, radiological, and genetic studies. A review of the literature of other cases of iPPSD2 due to GNAS large deletions was performed focusing on clinical and biochemical features. Results: The proband presented signs of hypocalcemia and marked AHO features. Laboratory tests revealed hypocalcemia, high levels of serum phosphate, PTH, TSH, and calcitonin despite therapy with calcium carbonate, calcitriol, and levothyroxine. Diffuse soft tissue ossifications and brain calcifications were shown by radiological exams. Family history was remarkable for hypocalcemia, neurocognitive impairment, and cerebral calcifications in his brother and AHO features in the maternal grandfather. The proband's mother showed short stature, whereas physical examination of the father was unremarkable. Genetic analysis of the GNAS gene revealed an unreported large deletion encompassing exons 1-7 in the proband, brother, and mother. By reviewing the literature, only six other cases were described. Conclusions: We report a kindred harboring a large GNAS deletion. A genotype-phenotype correlation was observed in term of severity of tissue ossifications in the siblings but not in the mother.
MeSH term(s)	Adolescent ; Chromogranins/genetics ; GTP-Binding Protein alpha Subunits, Gs/genetics ; GTP-Binding Protein alpha Subunits, Gs/metabolism ; Humans ; Hypocalcemia/genetics ; Male ; Parathyroid Hormone-Related Protein/metabolism ; Pseudohypoparathyroidism/genetics
Chemical Substances	Chromogranins ; Parathyroid Hormone-Related Protein ; GNAS protein, human (EC 3.6.1.-) ; GTP-Binding Protein alpha Subunits, Gs (EC 3.6.5.1)
Language	English
Publishing date	2020-01-14
Publishing country	United States
Document type	Case Reports ; Journal Article ; Review
ZDB-ID	1194484-5
ISSN	1559-0100 ; 1355-008X ; 0969-711X
ISSN (online)	1559-0100
ISSN	1355-008X ; 0969-711X
DOI	10.1007/s12020-020-02195-7
Database	MEDical Literature Analysis and Retrieval System OnLINE

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