Nivolumab-induced hypothyroidism and selective pituitary insufficiency in a patient with lung adenocarcinoma: a case report and review of the literature

Abstract

Immune checkpoint blockade including programmed cell death 1 pathway inhibition with agents such as nivolumab is gaining ground in a wide array of malignancies, so far demonstrating significantly improved survival rates even in metastatic, often multiply pretreated settings.Although targeted in nature and generally well-tolerated compared with conventional anticancer treatments, these agents are often linked to a newly emerged group of adverse reactions, referred to as immune-related adverse events, which can also affect endocrine organs. This is a case report of a patient who received nivolumab for the treatment of recurrent metastatic non-small cell lung cancer and developed primary hypothyroidism and secondary adrenal insufficiency caused by selective pituitary dysfunction (with preservation of all other endocrine functions). After hormone replacement with daily administration of T4, T3 and hydrocortisone, the patient achieved complete recovery.Adequate characterisation of these rare yet potentially severe entities is essential for prompt diagnostic and therapeutic interventions that will permit us to fully benefit from these new agents’ therapeutic potential.

Anti-PD1 and Anti-PDL1-Induced Hypophysitis: A Cohort Study of 17 Patients with Longitudinal Follow-Up

“…The paucity and non-specificity of symptoms seems to be responsible for delayed diagnosis of PD1/PDL1 inhibitor-induced hypophysitis, or sometimes misdiagnosis both in previous reports [ 9 , 12 , 14 , 15 , 17 ] and herein; this point is illustrated in the present study by fortuitous diagnosis via systematic laboratory monitoring for three of the patients. The correct diagnosis is, however, crucial since pituitary deficiencies can affect quality of life, tolerance to cancer treatment, or even be life-threatening in the case of ACTH deficiency in already fragile patients.…”

“…After this one-year period, laboratory evaluation is recommended in case of clinical signs [ 30 ], but we believe that clinicians should remain vigilant after this period because such signs may be difficult to detect. Furthermore, there is no recommendation regarding follow-up after discontinuation of ICI although some cases have occurred after the discontinuation [ 10 , 12 , 15 ].…”

“…The descriptions of PD1 and PDL1 inhibitor-induced hypophysitis are more recent, probably because these drugs have been approved more recently than the approval of CTLA4 inhibitor. Some case reports described isolated adrenocorticotropic hormone (ACTH) deficiency associated with PD1 and PDL1 inhibitors [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ].…”

Differential diagnosis of autoimmune pituitary failure and pituitary macroadenoma during nivolumab therapy in an NSCLC patient — a case report

“…In the next imaging of the head, no metastatic lesions and enlargement of the pituitary gland were observed, the concentration of all hormones normalised under the influence of substitution treatment, and resolution of previously seen symptoms was observed. The adrenocortical insufficiency induced by hypopituitarism as a complication of anti-PD-1 antibody treatment was hypothesised [16].…”

How I treat cancer special issue

“…These patient-oriented publications were complemented by aspects concerning the oncological profession 4 43. Further, a more profound understanding of challenging side effects was addressed in several articles 44–50. Thus, ESMO Open – Cancer Horizons has established itself as a reliable source of information on the very many aspects of cancer and cancer care published within it.…”