Isolated Adrenocorticotropic Hormone Deficiency Caused by Nivolumab in a Patient with Metastatic Lung Cancer

Takaya, Kazuhiko; Sonoda, Miwa; Fuchigami, Ayako; Hiyoshi, Toru

doi:10.2169/internalmedicine.8548-16

Cited by 31 publications

(13 citation statements)

References 37 publications

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“…However, in the present case, the isolated ACTH deficiency appeared to have been caused by nivolumab and occurred without pituitary gland enlargement. Similar cases of nivolumab-induced isolated ACTH deficiency without pituitary gland enlargement have also been reported (22)(23)(24)(25). The nivolumab-induced cases took much longer to diagnose than ipilimumab-induced cases (26).…”

Section: Discussionsupporting

confidence: 63%

Isolated adrenocorticotropic hormone deficiency potentially induced by nivolumab following pseudo‑progression in clear cell renal cell carcinoma: A case report

et al. 2018

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Nivolumab is a monoclonal immunoglobulin G antibody blocking programmed death receptor-1 (PD-1) that promotes the restoration of the natural T-cell-mediated immune response against cancer cells; however, it also causes a number of autoimmune-related adverse events (irAEs) that often involve the endocrine system. The present report describes a 71-year-old man with clear cell renal cell carcinoma metastasis in the lung. Following the 14th course of nivolumab therapy, the patient complained of general malaise, loss of appetite and mild consciousness disturbance. Laboratory tests revealed a severely elevated eosinophil ratio (26.2%) and low sodium value (122 mmol/l). Endocrine system tests revealed that the patient's adrenocorticotropic hormone (ACTH; 4.5 pg/ml) and cortisol (0.1 µg/dl) levels were lower than normal, while those of other pituitary hormones were higher than normal. This case was therefore diagnosed as isolated ACTH deficiency induced by nivolumab. Magnetic resonance imaging (MRI) showed normal pituitary glands. Hydrocortisone replacement therapy improved the clinical symptoms early and enabled the patient to restart nivolumab therapy. Isolated ACTH deficiency due to nivolumab, a PD-1 immune checkpoint inhibitor antibody, is a rare occurrence. This report may be useful for avoiding delays in the diagnosis and treatment of this life-threatening irAE even if no pituitary abnormalities are identified via MRI. NOBUKI FURUBAYASHI, TAKAHITO NEGISHI, TOMOHARU UOZUMI, DAI TAKAMATSU, KOICHI SHIRAISHI

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Section: Discussionsupporting

confidence: 63%

Isolated adrenocorticotropic hormone deficiency potentially induced by nivolumab following pseudo‑progression in clear cell renal cell carcinoma: A case report

et al. 2018

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“…The present case promptly resulted in secondary adrenal insufficiency after transient ACTH elevation. In previous reports, most cases of ICI-induced hypophysitis were diagnosed based on adrenal insufficiency symptoms or hyponatremia with low ACTH and cortisol [5][6][7][8][9][10]. Only one case that resulted in secondary adrenal insufficiency after transient ACTH-dependent Cushing's syndrome was reported [11].…”

Section: Discussionmentioning

confidence: 99%

Nivolumab-induced hypophysitis causing secondary adrenal insufficiency after transient ACTH elevation

et al. 2019

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A 62-year-old man was referred to our department for elevation of plasma ACTH and cortisol levels during nivolumab administration for renal cell carcinoma. Although his ACTH and cortisol levels had been maintained within their reference ranges, they were elevated to 232.7 pg/mL and 21.9 μg/dL, respectively, after eight courses of nivolumab without any subjective symptoms or Cushing's sign. He was hospitalized for endocrinological investigation. ACTH and cortisol returned to their normal ranges (29.18 pg/mL and 11.4 μg/dL, respectively) in the early morning on day 1, but fell down sharply to 3.7 pg/mL and 1.6 μg/dL, respectively, in the early morning on day 2 without subjective symptoms or vital sign changes. Brain magnetic resonance imaging showed no abnormality in his pituitary gland. ACTH response to CRH was apparently normal, but cortisol did not respond to increased ACTH. A rapid ACTH stimulation test showed slightly reduced response of cortisol to exogenous ACTH (1-24). These findings and his clinical course suggested secondary adrenal insufficiency arising from nivolumab-induced hypophysitis. In previous reports, most cases of immune checkpoint inhibitor (ICI)-induced hypophysitis were diagnosed based on adrenal insufficiency symptoms or hyponatremia with low ACTH and cortisol. The ACTH elevation observed in the present case may reflect destruction of the pituitary gland, suggesting that this finding may be important for early detection of ICI-induced hypophysitis. Our case underlines the necessity of close monitoring for subsequent onset of adrenal insufficiency when ACTH elevation is observed during ICI administration.

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“…If hypophysitis is a well-known irAE and involves multiple gland axes, isolated ACTH deficiency is rarely reported, particularly as initial event 5 6. The low level of cortisol associated with an inappropriately low level of ACTH suggested a secondary cortisol insufficiency, which was confirmed by the ACTH stimulation test.…”

Section: Discussionmentioning

confidence: 99%

Isolated adrenocorticotropic hormone (ACTH) deficiency and Guillain-Barré syndrome occurring in a patient treated with nivolumab

et al. 2019

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The increased use of immune checkpoint inhibitors (ICIs) has led to the observation of a variety of immune-related adverse events (irAEs). These irAEs occur usually within the first months after ICIs onset and can involve theorically all organs. We describe two rare irAEs occurring in a 70-year-old caucasian man who was treated with nivolumab for an advanced urothelial cancer of the left kidney. He developed an isolated adrenocorticotropic hormone deficiency that was diagnosed at week 19 and a neurological complication that appeared at week 79 and initially confounded with a lumbar spinal stenosis. Diagnosis of Guillain-Barré syndrome was finally confirmed with the complete resolution of symptoms after 5 days of intravenous immunoglobulin and corticosteroids. We highlight the importance of quickly recognising these potential life-threatening irAEs such as cortisol insufficiency and neurologic adverse events whose initially presentation could be non-specific.

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Isolated Adrenocorticotropic Hormone Deficiency Caused by Nivolumab in a Patient with Metastatic Lung Cancer

Cited by 31 publications

References 37 publications

Isolated adrenocorticotropic hormone deficiency potentially induced by nivolumab following pseudo‑progression in clear cell renal cell carcinoma: A case report

Isolated adrenocorticotropic hormone deficiency potentially induced by nivolumab following pseudo‑progression in clear cell renal cell carcinoma: A case report

Nivolumab-induced hypophysitis causing secondary adrenal insufficiency after transient ACTH elevation

Isolated adrenocorticotropic hormone (ACTH) deficiency and Guillain-Barré syndrome occurring in a patient treated with nivolumab

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