Endocrine Abstracts

Introduction: In the area of Immunotherapy, immunological checkpoints, such as CTLA-4, PD-1 or PD-L1, are membrane proteins involved in the immune response that, when inhibited, cause an increase in T cell activity and a consequent anti-tumor effect. However, this inhibition can also cause adverse effects, including endocrinopathies, such as thyroid dysfunction and hypophysitis.

Clinical case: 59-year-old man, diagnosed with lung cancer, treated with nivolumab (-anti-PD-1), with complaints of fatigue, decreased muscle strength, anorexia, constipation and depressed mood a month after treatment initiation. Laboratory evaluation revealed autoimmune hypothyroidism and secondary adrenal insufficiency (thyroid stimulating hormone: 7.81 µU/ml; free thyroxine: 0.65 ng/dl; anti-thyroid peroxidase antibodies: 185 U/ml; adrenocorticotropin < 0.1 pg/ml; cortisol: 0.5 µg/dl). It was made a magnetic resonance imaging that revealed an enlarged pituitary gland, without associated lesions. Following the diagnosis of primary hypothyroidism and adrenal insufficiency secondary to hypophysitis, the patient received replacement therapy with clear clinical and laboratory improvement.

Discussion: The clinical case describes an uncommon association of hypothyroidism and hypophysitis associated with anti-PD-1 therapy and aims to highlight a recent and often underdiagnosed clinical entity: endocrinopathies related to immune checkpoint inhibition.

In cancer patients receiving anti-PD-1, anti-PD-L1 or anti-CTLA-4 drugs, regular endocrine assessment is recommended to make early diagnosis and treat appropriately. The endocrine laboratory evaluation should be performed before starting to immune checkpoint inhibition therapy as well as during the treatment cycle. The hypothalamic-pituitary-thyroid and hypothalamic-pituitary-adrenal axis are the most frequently affected. The remaining assessment of the pituitary function will depend on the clinic of each patient.

The therapeutic approach consists of hormonal replacement of the deficient endocrine axis.

Conclusion: The early diagnosis of endocrinopathies as well as the timely institution of adequate therapy can have a significant impact on the prognosis and quality of life of these patients.