Nivolumab-induced hypothyroidism followed by isolated ACTH deficiency

Machado, Catarina; Santos, Lúcia Almeida; Barroso, Ana; Oliveira, Maria João

doi:10.1136/bcr-2019-231236

Cited by 16 publications

(8 citation statements)

References 21 publications

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“…Twelve cases, including the present one, of hypothyroidism with isolated ACTH deficiency as irAEs have been reported (Table II) (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Eight of these patients had isolated ACTH deficiency after having hypothyroidism, whereas the remaining four had both irAEs simultaneously.…”

Section: Discussionmentioning

confidence: 73%

“…Author year these patients had mostly non-specific manifestations except for loss of consciousness caused by hypoglycaemia and hypotension caused by adrenal deficiency (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Patients with hypothyroidism alone tend to be asymptomatic (62.5%) in Table II (8)(9)(10)(11)(12)(13)(14)(15).…”

Section: Table II Reported Cases Of Patients With Primary Hypothyroid...mentioning

confidence: 99%

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Hypothyroidism With ACTH Deficiency During Pembrolizumab Therapy for Lung Cancer: Case Report and Literature Review

Hashinokuchi¹,

Haro²,

Minagawa³

et al. 2023

CDP

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Background/Aim: Immune-checkpoint inhibitors have recently shown great promise in treating various cancers, but often cause immune-related adverse events (irAEs). Simultaneous drug-induced hypothyroidism and isolated adrenocorticotropic hormone (ACTH) deficiency are rare irAEs. This combination of irAEs is associated with paradoxical endocrine dysfunction characterized by large amounts of thyroid-stimulating hormone (TSH) and small amounts of ACTH in the anterior lobe of the pituitary. We herein report a case of hypothyroidism with isolated ACTH deficiency during pembrolizumab therapy for recurrent lung cancer. Case Report: Our patient was a 66-year-old man with recurrence of squamous cell lung carcinoma. Four months after chemotherapy that included pembrolizumab, the patient presented with general fatigue and laboratory tests showed high concentrations of TSH with low concentrations of free-T4. He was diagnosed with hypothyroidism and levothyroxine was prescribed. His ACTH concentration was found to be low 1 week later when he developed an acute adrenal crisis with associated hyponatraemia. We then changed his diagnosis to concurrent hypothyroidism with isolated ACTH deficiency. His condition improved after 3 weeks of administration of cortisol. Conclusion: It is difficult to diagnose a concurrent paradoxical endocrine disorder, such as hypothyroidism with isolated ACTH deficiency, as in the present case. Physicians should pay attention to symptoms and laboratory data to identify various types of endocrine disorders as irAEs.

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Section: Discussionmentioning

confidence: 73%

Section: Table II Reported Cases Of Patients With Primary Hypothyroid...mentioning

confidence: 99%

Hypothyroidism With ACTH Deficiency During Pembrolizumab Therapy for Lung Cancer: Case Report and Literature Review

Hashinokuchi¹,

Haro²,

Minagawa³

et al. 2023

CDP

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“…In cases of mild or moderate hypophysitis, it is advisable to continue anti-PD-L1/PD-L1 mAbs , while the option to suspend or discontinue treatment may be warranted for severe hypophysitis (94). For example, www.ddtjournal.com Drug Discoveries & Therapeutics Advance Publication P7 a NSCLC patient manifested moderate hypophysitis following 33 administrations of nivolumab, while subsequently managing to sustain an additional 50 courses concurrent with hormone replacement (10). Glucocorticoids remain the primary therapy for PD-1/L1-irH until now.…”

Section: Wwwddtjournalcommentioning

confidence: 99%

PD-1/PD-L1 inhibitors associated hypophysitis: An analysis from the FAERS database and case reports

Chen,

Ouyang,

et al. 2024

DD&T

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PD-1/PD-L1 inhibitors, hypophysitis, disproportionality analysis, characteristic, managements To get a thorough understanding of PD-1/L1 inhibitor-related hypophysitis (PD-1/L1-irH), we utilized a combination of disproportionality analysis and case analysis to comprehensively characterize the clinical features of PD-1/L1-irH. Significant signals of hypophysitis were detected for all PD-1/PD-L1 inhibitors in the FAERS (FDA Adverse Event Reporting System). As revealed by both FAERS and the case analysis, PD-1/L1-irH occurred more commonly in males, PD-1 inhibitors users and patients older than 65 years. The median onset time was 101 days in FAERS and 8 cycles in the case analysis. In the case analysis, eight late-onset PD-1/L1-irHs occurred even after a discontinuation of several months (4-15 months). As revealed in FAERS, the outcome of PD-1/L1-irH tended to be poor, generally resulting in 64.66% hospitalization and 12.59% death. Fatigue was the most prominent symptom of PD-1/L1-irH, followed by anorexia, hyponatremia, and hypotension, as revealed by the analysis of 84 cases. Meanwhile isolated adrenocorticotropic (ACTH) deficiency was particularly prevalent for PD-1/L1-irH (85.71%), while gonadal hormones or posterior pituitary hormones deficiencies were rare. Glucocorticoids were administered to almost all cases (81/84), with a physiologic or stress dosage in 61.9% of cases, and a high-dose in 26.2% of cases. Most cases (58.3%) showed a favorable tumor response before diagnosis of PD-1/L1-irH. PD-1/L1-irH may occur throughout the whole therapy period even after discontinuation. Clinicians should pay more attention to PD-1 inhibitor users, males and older patients. Early diagnosis and prompt managements are crucial for PD-1/L1-irH as its potentially life-threatening nature.

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“…In magnetic resonance imaging (MRI), we usually see a picture of small to moderate pituitary enlargement [54], most often with homogeneous enhancement after contrast, along with the thickening of the pituitary gland and subsequent atrophy of the gland and empty saddle syndrome [47,50,55]. During the acute phase of pituitary inflammation, the MRI picture may be normal in 25% of patients [24,[56][57][58].…”

Section: Diagnosticsmentioning

confidence: 99%

“…Regarding lactotropic cell function, both reduced and elevated prolactin (PRL) levels can be found [61]. Isolated cases of ACTH deficiency have also been reported [54,56,57,59,60,62]. Sekizaki et al described a case of nivolumab-induced hypophysitis in which secondary adrenal insufficiency preceded a short phase of a high level of ACTH, with only slightly elevated cortisol levels.…”

Section: Diagnosticsmentioning

confidence: 99%

Endocrine Adverse Events of Nivolumab in Non-Small Cell Lung Cancer Patients—Literature Review

Dudzińska

Szczyrek

Wojas‐Krawczyk

et al. 2020

Cancers

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In recent years, we have observed significant progress in cancer treatment associated with the development of immunotherapy. A programmed cell death 1 molecule (PD-1) on the surface of T lymphocytes may be stimulated via a specific PD-ligand 1 (PD-L1), which inhibits lymphocyte activation and leads to apoptosis. Some malignant cells are characterized by high PD-L1 expression. Nivolumab, an anti-PD-1 antibody, blocks the interaction between PD-1 and its ligands and inhibits the signaling pathway by preventing the tumor-derived PD-L1 from blocking T lymphocytes. In patients with non-small cell lung cancer (NSCLC), it is used either in monotherapy or in combination with other drugs. Immunotherapy is associated with the possibility of immune-related adverse effects (irAE) including endocrinopathies (3–23%). Thyroid disorders are the most common, with severity rarely exceeding grade 2. Hypophysitis, adrenal insufficiency and diabetes are possible complications which require immediate treatment. Individuals with autoimmune diseases diagnosed prior to immunotherapy are at risk of its exacerbation. In the management of patients receiving immunotherapy, evaluation of history of autoimmune diseases, awareness and early diagnosis of irAE are crucial and may affect treatment outcomes.

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Nivolumab-induced hypothyroidism followed by isolated ACTH deficiency

Cited by 16 publications

References 21 publications

Hypothyroidism With ACTH Deficiency During Pembrolizumab Therapy for Lung Cancer: Case Report and Literature Review

Hypothyroidism With ACTH Deficiency During Pembrolizumab Therapy for Lung Cancer: Case Report and Literature Review

PD-1/PD-L1 inhibitors associated hypophysitis: An analysis from the FAERS database and case reports

Endocrine Adverse Events of Nivolumab in Non-Small Cell Lung Cancer Patients—Literature Review

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