Management of Thyrotoxicosis Induced by PD1 or PD-L1 Blockade

Brancatella, Alessandro; Lupi, Isabella; Montanelli, Lucia; Ricci, Debora; Viola, Nicola; Daniele, Simona; Antonangeli, L; Sardella, Chiara; Brogioni, Sandra; Piaggi, Paolo; Molinaro, Eleonora; Bianchi, Francesca; Aragona, Michele; Antonuzzo, Andrea; Sbrana, Andrea; Lucchesi, M; Chella, Antonio; Falcone, Alfredo; Prato, Stefano Del; Elisei, Rossella; Marcocci, Claudio; Caturegli, Patrizio; Santini, Ferruccio; Latrofa, Francesco

doi:10.1210/jendso/bvab093

Cited by 6 publications

(12 citation statements)

References 25 publications

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“…We also found that transient thyrotoxicosis is much more common than persistent hyperthyroidism. Similar observations were recently reported among patients with ICI-induced thyroid AEs ( 30 ).…”

Section: Discussionsupporting

confidence: 91%

Immune checkpoint inhibitors, endocrine adverse events, and outcomes of melanoma

Karhapää

Mäkelä

Laurén

et al. 2022

Endocrine Connections

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Objective: Immune checkpoint inhibitors (ICI) can cause endocrine adverse events. However, endocrine AEs could be related to better treatment outcomes. Our aim was to investigate whether this holds true in a real-world setting of metastatic melanoma patients. Design: A retrospective single-institution study. Methods: We included 140 consecutive metastatic melanoma patients treated with ICI between January 2012 and May 2019. We assessed endocrine toxicity and best possible treatment outcomes from electronic patient records, including laboratory parameters, and radiological images. Results: Of the treated patients, 21 patients (15%) were treated with ipilimumab, 46 (33%) with nivolumab, 67 (48%) with pembrolizumab, and six (4%) with combination therapy (ipilimumab + nivolumab). Endocrine AEs appeared in 29% (41/140) patients. Three patients had two different endocrine AEs. Thyroid disorders were the most common: 26% (36/140), followed by hypophysitis: 4% (5/140). Three subjects (2%, 3/140) were diagnosed with autoimmune diabetes. Three patients had to terminate treatment due to endocrine toxicity. Radiological manifestations of endocrine AEs were found in 16 patients (39%, 16/41). Endocrine toxicity was associated with significantly better treatment outcomes. Median progression-free survival (8.1 months, range 5.1 – 11.1 months vs. 2.7 months, range 2.4 – 3.0 months, P < 0.001), and median overall survival (47.5 months, range 15.5 – 79.5 months vs. 23.7 months, range 15.3 – 32.1 months, P = 0.035) were longer for patients experiencing endocrine AEs. Conclusions: The higher number of endocrine AEs suggest regular laboratory monitoring aids in AE detection. Endocrine AEs in metastatic melanoma may correlate with better treatment outcomes.

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Section: Discussionsupporting

confidence: 91%

Immune checkpoint inhibitors, endocrine adverse events, and outcomes of melanoma

Karhapää

Mäkelä

Laurén

et al. 2022

Endocrine Connections

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“…Both hyperthyroidism and destructive thyroiditis have been reported during therapy with PD-1/PD-L1 drugs ( 3 , 18 ). In a recent study, we described two different types of thyrotoxicosis, a type 1 (Graves’ disease like), characterized by persistent hyperthyroidism, and a type 2 (painless destructive thyroiditis) which is more common and usually self-limited ( 6 ). Thyroid scintigraphy at the onset of thyrotoxicosis is the most accurate tool to differentiate the two types of thyrotoxicosis and only type 1 thyrotoxicosis is responsive to anti-thyroid drugs ( 6 ).…”

Section: Discussionmentioning

confidence: 99%

“…From January to June 2021, 34 patients were referred from Oncology and Pneumology units to the Endocrinology unit of University Hospital of Pisa because of destructive thyrotoxicosis due to anti-PD1 and anti-PD-L1 treatment for metastatic solid cancers. Destructive thyrotoxicosis was defined as the finding of high levels of free thyroxine (FT4) and free triiodothyronine (FT3) associated with low to undetectable levels of thyrotropin (TSH) and absent uptake at 99m Technecium (Tc) scintiscan ( 6 ). Of these, 4 subjects were treated with oral prednisone at the dosage of 25 mg/day (tapered to discontinuation in 3 weeks) because of a poor performance status (ECOG score >2) ( 14 ) and an enlarged thyroid volume.…”

Section: Methodsmentioning

confidence: 99%

“…We recently characterized two different types of thyrotoxicosis induced by PD1/PD-L1 blockade, a type 1 characterized by persistent hyperthyroidism responsive to anti-thyroid drugs and a type 2, more common, characterized by a painless destructive thyroiditis that usually has a self-limited course ( 6 ). In addition, we have shown an association between enlarged thyroid volume and severity and duration of thyrotoxicosis ( 6 ). It must be highlighted that in patients with a poorer performance status thyrotoxicosis has been linked to a worst prognosis ( 7 , 8 ).…”

Section: Introductionmentioning

confidence: 99%

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Steroid treatment in the management of destructive thyrotoxicosis induced by PD1 blockade

Brancatella

Pierotti

Viola

et al. 2022

European Thyroid Journal

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Objective. Destructive thyroiditis is the most common endocrine immune related adverse event (iRAEs) in patients treated with anti-PD1/PD-L1 agents. Given its self-limited course, current guidelines recommend no treatment for this iRAE. Nevertheless in patients with enlarged thyroid volume and a poor performance status, thyrotoxicosis may be particularly severe and harmful. Aim of the study is to evaluate if steroid treatment might be useful in improving thyrotoxicosis in subjects with a poor performance status. Methods. We conducted a retrospective study, comparing the course of thyrotoxicosis of 4 patients treated with oral prednisone at the dosage of 25 mg/d (tapered to discontinuation in three weeks) and an enlarged thyroid volume to that of 8 patients with similar thyroid volume who were left untreated. Results. The levels of thyroid hormones were lower in subjects treated compared to those untreated at time 7, 14, 21, 28, 35, 42, 60 and 90 days (P<0.05 at each time). The time to remission of thyrotoxicosis was 24 days in patients treated with steroids and 120 days in untreated patients (P<0.001). At 6 months, the rate of evolution to hypothyroidism was similar in the 2 groups (4/4 in steroid group vs 7/8 in untreated group, P=0.74) and no difference was found in tumor progression (P=0.89). Conclusions. Our preliminary data suggest that in patients with a poor performance status experiencing a severe destructive thyrotoxicosis induced by PD-1 blockade, a short period of administration of oral prednisone is effective in obtaining a quick reduction of the levels of thyroid hormones.

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“…For hyperthyroidism, beta blockers are the mainstay of symptomatic treatment as well as hydration and anti-diarrheals. Agents such as methimazole or propylthiouracil in the case of hyperthyroidism may be less effective in ICI induced hyperthyroidism unless true Graves’ disease is present, and consultation with an endocrinologist is warranted in grade 3 or 4 cases [ 45 ]. Immune-related thyrotoxicosis generally transitions to hypothyroidism and ultimately requires thyroid hormone supplementation [ 46 , 47 , 48 ].…”

Section: Organ-specific Icismentioning

confidence: 99%

The Price of Success: Immune-Related Adverse Events from Immunotherapy in Lung Cancer

Coschi

Juergens

2021

Current Oncology

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Cancer immunotherapy has the goal of enhancing a patient’s intrinsic immune processes in order to mount a successful immune response against tumor cells. Cancer cells actively employ tactics to evade, delay, alter, or attenuate the anti-tumor immune response. Immune checkpoint inhibitors (ICIs) modulate endogenous regulatory immune mechanisms to enhance immune system activation, and have become the mainstay of therapy in many cancer types. This activation occurs broadly and as a result, activation is supraphysiologic and relatively non-specific, which can lead to immune-related adverse events (irAEs), the frequency of which depends on the patient, the cancer type, and the specific ICI antibody. Careful assessment of patients for irAEs through history taking, physical exam, and routine laboratory assessments are key to identifying irAEs at early stages, when they can potentially be managed more easily and before progressing to higher grades or more serious effects. Generally, most patients with low grade irAEs are eligible for re-challenge with ICIs, and the use of corticosteroids to address an irAE is not associated with poorer patient outcomes. This paper reviews immune checkpoint inhibitors (ICIs) including their mechanisms of action, usage, associated irAEs, and their management.

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Management of Thyrotoxicosis Induced by PD1 or PD-L1 Blockade

Cited by 6 publications

References 25 publications

Immune checkpoint inhibitors, endocrine adverse events, and outcomes of melanoma

Immune checkpoint inhibitors, endocrine adverse events, and outcomes of melanoma

Steroid treatment in the management of destructive thyrotoxicosis induced by PD1 blockade

The Price of Success: Immune-Related Adverse Events from Immunotherapy in Lung Cancer

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