nach oben

Journal of Endocrinological Investigation

Erschienen in:

01.12.2019 | Original Article

Low frequency of positive antithyroid antibodies is observed in patients with thyroid dysfunction related to immune check point inhibitors

verfasst von: I. Mazarico, I. Capel, O. Giménez-Palop, L. Albert, I. Berges, F. Luchtenberg, Y. García, L. A. Fernández-Morales, V. J. De Pedro, A. Caixàs, M. Rigla

Erschienen in: Journal of Endocrinological Investigation | Ausgabe 12/2019

Einloggen, um Zugang zu erhalten

Abstract

Introduction

Immune checkpoint inhibitors (ICI), such as programmed death-1 inhibitors (anti-PD1), have become a cornerstone for the treatment of different advanced cancers. These antibodies act as modulators of immune checkpoint proteins. However, ICI can lead to the breaking of immune self-tolerance, inducing autoimmune side effects (irAEs), including endocrinopathies. One of the most frequent endocrine irAE of anti-PD1 is thyroid dysfunction, but the exact mechanism of this disease still remains unknown.

Materials and methods

We conducted a descriptive retrospective study, analyzing 11 patients who received at least one dose of anti-PD1 (nivolumab or pembrolizumab) and presented thyroid irAEs. Data were collected between September 2015 and May 2018 in our hospital. The aim was to analyze the clinically relevant features of thyroid irAEs and the frequency of antithyroid antibodies (ATA) positivity observed on them.

Results and discussion

8 of the 11 patients were treated with nivolumab and the other three patients received pembrolizumab. Six patients presented silent thyroiditis with a thyrotoxicosis phase; three patients developed directly primary/subclinical hypothyroidism and two patients showed primary hyperthyroidism. Thyroid autoantibodies (anti-Thyroglobulin and anti-Thyroid Peroxidase) were assessed in all the 11 patients, and only in two of them (18%) a positive titer was displayed. Anti-TSH receptor antibodies (TRAbs) were examined in five patients, three with painless thyroiditis at the time of thyrotoxicosis and two with primary hyperthyroidism, and they all had undetectable levels.

Conclusions

In our sample of 11 Caucasian patients with thyroid dysfunction related with anti-PD1, we found low frequency of ATA positive titers, comparable to other recent reports in others ethnicities, which could suggest that silent thyroiditis due to pembrolizumab or nivolumab has a different pathogenesis from the classical autoimmune spontaneous thyroiditis. Further investigations are required to completely understand the immune mechanisms involved.

Chalan P, Di Dalmazi G, Pani F, De Remigis A, Corsello A, Caturegli P (2018) Thyroid dysfunctions secondary to cancer immunotherapy. J Endocrinol Invest 41(6):625–638. https://doi.org/10.1007/s40618-017-0778-8 CrossRefPubMed

Cukier P, Santini FC, Scaranti M, Hoff AO (2017) Endocrine side effects of cancer immunotherapy. Endocr Relat Cancer 24(12):T331–T347. https://doi.org/10.1530/ERC-17-0358 CrossRefPubMed

Haanen JBAG, Carbonnel F, Robert C et al (2017) Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann Oncol 28(suppl_4):iv119–iv142. https://doi.org/10.1093/annonc/mdx225 CrossRefPubMed

Ruggeri RM, Campennì A, Giuffrida G et al (2018) Endocrine and metabolic adverse effects of immune checkpoint inhibitors: an overview (what endocrinologists should know). J Endocrinol Invest. https://doi.org/10.1007/s40618-018-0984-z CrossRefPubMed

June CH, Warshauer JT, Bluestone JA (2017) Is autoimmunity the Achilles’ heel of cancer immunotherapy? Nat Med 23(5):540–547. https://doi.org/10.1038/nm.4321 CrossRefPubMed

Corsello SM, Barnabei A, Marchetti P, De Vecchis L, Salvatori R, Torino F (2013) Endocrine side effects induced by immune checkpoint inhibitors. J Clin Endocrinol Metab 98(4):1361–1375. https://doi.org/10.1210/jc.2012-4075 CrossRefPubMed

Kumar V, Chaudhary N, Garg M, Floudas CS, Soni P, Chandra AB (2017) Current diagnosis and management of immune related adverse events (irAEs) Induced by immune checkpoint inhibitor therapy. Front Pharmacol 8:49. https://doi.org/10.3389/fphar.2017.00049 CrossRefPubMedPubMedCentral

Eigentler TK, Hassel JC, Berking C et al (2016) Diagnosis, monitoring and management of immune-related adverse drug reactions of anti-PD-1 antibody therapy. Cancer Treat Rev 45:7–18. https://doi.org/10.1016/j.ctrv.2016.02.003 CrossRefPubMed

Guaraldi F, La Selva R, Samà MT et al (2018) Characterization and implications of thyroid dysfunction induced by immune checkpoint inhibitors in real-life clinical practice: a long-term prospective study from a referral institution. J Endocrinol Invest 41(5):549–556. https://doi.org/10.1007/s40618-017-0772-1 CrossRefPubMed

10.

Delivanis DA, Gustafson MP, Bornschlegl S et al (2017) Pembrolizumab-induced thyroiditis: comprehensive clinical review and insights into underlying involved mechanisms. J Clin Endocrinol Metab 102(8):2770–2780. https://doi.org/10.1210/jc.2017-00448 CrossRefPubMedPubMedCentral

11.

Osorio JC, Ni A, Chaft JE et al (2017) Antibody-mediated thyroid dysfunction during T-cell checkpoint blockade in patients with non-small-cell lung cancer. Ann Oncol Off J Eur Soc Med Oncol. 28(3):583–589. https://doi.org/10.1093/annonc/mdw640 CrossRef

12.

Larkin J, Chiarion-Sileni V, Gonzalez R et al (2015) Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 373(1):23–34. https://doi.org/10.1056/NEJMoa1504030 CrossRefPubMedPubMedCentral

13.

Koh LKH, Greenspan FS, Yeo PPB (2009) Interferon-α induced thyroid dysfunction: three clinical presentations and a review of the literature. Thyroid 7(6):891–896. https://doi.org/10.1089/thy.1997.7.891 CrossRef

14.

Vassilopoulou-Sellin R, Sella A, Dexeus FH, Theriault RL, Pololoff DA (1992) Acute thyroid dysfunction (thyroiditis) after therapy with interleukin-2. Horm Metab Res 24(9):434–438. https://doi.org/10.1055/s-2007-1003353 CrossRefPubMed

15.

Kobayashi T, Iwama S, Yasuda Y et al (2018) Patients with antithyroid antibodies are prone to develop destructive thyroiditis by nivolumab: a prospective study. J Endocr Soc 2(3):241–251. https://doi.org/10.1210/js.2017-00432 CrossRefPubMedPubMedCentral

16.

Yano S, Ashida K, Nagata H et al (2018) Nivolumab-induced thyroid dysfunction lacking antithyroid antibody is frequently evoked in Japanese patients with malignant melanoma. BMC Endocr Disord 18:36. https://doi.org/10.1186/s12902-018-0267-x CrossRefPubMedPubMedCentral

17.

Iadarola C, Croce L, Quaquarini E et al (2019) Nivolumab induced thyroid dysfunction: unusual clinical presentation and challenging diagnosis. Front Endocr (Lausanne). https://doi.org/10.3389/fendo.2018.00813 CrossRef

18.

Alhusseini M, Samantray J (2017) Hypothyroidism in cancer patients on immune checkpoint inhibitors with anti-PD1 agents: insights on underlying mechanisms. Exp Clin Endocrinol Diabetes 125(4):267–269. https://doi.org/10.1055/s-0042-119528 CrossRefPubMed

19.

de Filette J, Jansen Y, Schreuer M et al (2016) Incidence of thyroid-related adverse events in melanoma patients treated with pembrolizumab. J Clin Endocrinol Metab 101(11):4431–4439. https://doi.org/10.1210/jc.2016-2300 CrossRefPubMedPubMedCentral

20.

Orlov S, Salari F, Kashat L, Walfish PG (2015) Induction of painless thyroiditis in patients receiving programmed death 1 receptor immunotherapy for metastatic malignancies. J Clin Endocrinol Metab. https://doi.org/10.1210/jc.2014-4560 CrossRefPubMed

21.

Morganstein DL, Lai Z, Spain L et al (2017) Thyroid abnormalities following the use of cytotoxic T-lymphocyte antigen-4 and programmed death receptor protein-1 inhibitors in the treatment of melanoma. Clin Endocrinol (Oxf) 86(4):614–620. https://doi.org/10.1111/cen.13297 CrossRef

22.

Dulos J, Carven GJ, van Boxtel SJ et al (2012) PD-1 blockade augments Th1 and Th17 and suppresses Th2 responses in peripheral blood from patients with prostate and advanced melanoma cancer. J Immunother 35(2):169–178. https://doi.org/10.1097/CJI.0b013e318247a4e7 CrossRefPubMed

23.

Rotondi M, Coperchini F, Magri F, Chiovato L (2014) Serum-negative autoimmune thyroiditis: what’s in a name? J Endocrinol Invest 37(6):589–591. https://doi.org/10.1007/s40618-014-0083-8 CrossRefPubMed

24.

Angell TE, Min L, Wieczorek TJ, Hodi FS (2018) Unique cytologic features of thyroiditis caused by immune checkpoint inhibitor therapy for malignant melanoma HHS public access. Genes Dis 5(1):46–48. https://doi.org/10.1016/j.gendis.2017.11.002 CrossRefPubMed

Titel: Low frequency of positive antithyroid antibodies is observed in patients with thyroid dysfunction related to immune check point inhibitors
verfasst von: I. Mazarico
I. Capel
O. Giménez-Palop
L. Albert
I. Berges
F. Luchtenberg
Y. García
L. A. Fernández-Morales
V. J. De Pedro
A. Caixàs
M. Rigla
Publikationsdatum: 01.12.2019
Verlag: Springer International Publishing
Erschienen in: Journal of Endocrinological Investigation / Ausgabe 12/2019
Elektronische ISSN: 1720-8386
DOI: https://doi.org/10.1007/s40618-019-01058-x

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Herzinfarkt mit 85 – trotzdem noch intensive Lipidsenkung?

16.05.2024 Hypercholesterinämie Nachrichten

Profitieren nach einem akuten Myokardinfarkt auch Betroffene über 80 Jahre noch von einer intensiven Lipidsenkung zur Sekundärprävention? Um diese Frage zu beantworten, wurden jetzt Registerdaten aus Frankreich ausgewertet.

ADHS-Medikation erhöht das kardiovaskuläre Risiko

16.05.2024 Herzinsuffizienz Nachrichten

Erwachsene, die Medikamente gegen das Aufmerksamkeitsdefizit-Hyperaktivitätssyndrom einnehmen, laufen offenbar erhöhte Gefahr, an Herzschwäche zu erkranken oder einen Schlaganfall zu erleiden. Es scheint eine Dosis-Wirkungs-Beziehung zu bestehen.

Bei Herzinsuffizienz muss „Eisenmangel“ neu definiert werden!

16.05.2024 Herzinsuffizienz Nachrichten

Bei chronischer Herzinsuffizienz macht es einem internationalen Expertenteam zufolge wenig Sinn, die Diagnose „Eisenmangel“ am Serumferritin festzumachen. Das Team schlägt vor, sich lieber an die Transferrinsättigung zu halten.

Erstmanifestation eines Diabetes-Typ-1 bei Kindern: Ein Notfall!

16.05.2024 DDG-Jahrestagung 2024 Kongressbericht

Manifestiert sich ein Typ-1-Diabetes bei Kindern, ist das ein Notfall – ebenso wie eine diabetische Ketoazidose. Die Grundsäulen der Therapie bestehen aus Rehydratation, Insulin und Kaliumgabe. Insulin ist das Medikament der Wahl zur Behandlung der Ketoazidose.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Introduction

Materials and methods

Results and discussion

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 12/2019

A 2019 update on TSH-secreting pituitary adenomas

Prevalence of endocrine disorders and their associated factors in transfusion-dependent thalassemia patients: a historical cohort study in Southern Iran

Overview of results from the Vitamin D Assessment (ViDA) study

Epidemiology, pathogenesis, and diagnosis of Addison’s disease in adults

Transoral thyroidectomy: new method with new complications’ spectrum

“The giant Hans Kraus” (1553): a Renaissance acromegaly by anonymous painter