Endocrine Abstracts

Background: With the increasing use of cancer immunotherapies in advanced solid organ and hematologic malignancies, endocrinologists are beckoned to manage endocrine complications with unique presentations and natural history in the already challenged oncology patient. We describe four patients illustrating the multifarious endocrine adversities of checkpoint inhibitors.

Cases: Patient 1 is a 35-year old male with refractory Hodgkin’s lymphoma, previously euthyroid and euglycemic. He was treated with nivolumab for three months before developing profound antibody-negative hypothyroidism (TSH 71.8 mIU/ml, fT4 <0.3 ng/dl), nephrotic syndrome (20 g proteinuria/d), insulin-requiring anti-GAD positive diabetes mellitus and positive tissue transglutaminase antibodies (pending duodenal biopsy), after six cycles of treatment. He presented a palpable hypoechoic goiter with increased vascularity. Patient 2 is a 76-year old male with metastatic melanoma with rapidly declining to suppressed TSH levels, fT4×3ULN and fT3×2ULN after the second infusion of nivolumab. He had a palpable hypoechoic thyroid gland, with increased vascularity. Thyroid-stimulating immunoglobulins were undetectable while anti-TPO were mildly positive. Within six weeks, he precipitously reverted to hypothyroidism (TSH 85 mIU/ml) and his thyroid gland regressed to marked atrophy. Patient 3 is a 59-year-old male with metastatic melanoma, who was switched to pembrolizumab after developing hypophysitis with ACTH (2 pg/ml) and prolactin (<1.0 ng/ml) deficiencies in addition to diabetes insipidus following four infusions of ipilimumab. He maintained intact thyroid, gonadal and GH axes while continuing pembrolizumab for two years, with stable disease. Patient 4 is a 49-year-old male with relapse of Hodgkin’s lymphoma 4.5 years after autologous stem cell transplantation. He was previously euthyroid, but developed antibody-positive hypothyroidism after 4 cycles of pembrolizumab, demonstrating a hypoechoic ‘honeycomb’ gland. His TSH reached a peak of 37.88 mIU/ml, with corresponding levels of fT4 at 0.36 ng/dl (normal 0.7-2) and fT3 at 1.26 pg/ml (normal 2–4.4), indicating a possible central component to the hypothyroidism. The thyroid gland was barely discernible by ultrasound a year later.

Conclusion: The patterns of thyroid and pituitary dysfunction observed with checkpoint immunotherapy challenge our current understanding of ‘thyroiditis’ and ‘hypophysitis’. Endocrinopathies resulting from these agents are common, mostly permanent and potentially life threatening, calling for regular monitoring, prompt management and coordination of care, so that cancer treatment may be safely continued.