Secondary Adrenal Insufficiency and Primary Hypothyroidism: A Complication of Cancer Immunotherapy

Abstract

Background: Immunotherapy has a fundamental role in cancer treatment. However, there have been found secondary effects in different organs due to its use, such as thyroid gland, pituitary gland, and adrenal glands,. This case report describes a case in relation with nivolumab, an antibody that blocks PD1 protein activity, promoting apoptosis Clinical Case: 67 years-old woman, with history of vulvar melanoma since 2016, complicated by pulmonary metastases. She was started with Nivolumab on 2018, every three weeks. After the her last immunotherapy session, she had less appetite, confusion, and incoherent speaking, and was admitted to the hospital In the Emergency, her blood pressure was 70/40mmHg, heart reate was 120 beats per minute. She was treated with fluid replacement. Her initial lab tests showed sodium 115.0 mmol/l(135.0 - 145.0), Chloride 85.9 mmol/l(98.0 - 109.0), Potassium 4.61 mmol/l (3.5 - 5.1), Hemoglobin 12.0, Leucocytes 6500, Platelets 282000, Total Proteins 7.0 (Albumin 4.0 Globulin 3.1), Alanine aminotransferase 10.0U/L (7-56), Aspartate aminotransferase 33.0 U/L (4-50) Creatinine 0.53. Hormonal Profile: T3 (triiodothyronine) 1.33 ng/ml(0.8 - 2.0), T4 (tetraiodothyronine) 7.27 ug/dl (5.1 - 14.1), TSH (thyroid stimulating hormone) ultrasensitive 12.87 uU/mL(0.27 - 4.2), FSH (Follicle stimulating hormone) 26.6mUI/ml, LH (Hormone)10.86 mIU/ml, Prolactin 60.96 ng/ml (6.0 - 29.9), Cortisol (am)0.22 ug/dl (4.2 - 38.4), ACTH (Corticotrophin-releasing hormone) <1.00, Anti TPO (Anti-Thyroid Peroxidase) negative, Glucose: 145 mg /dl, C Peptide: 0.4 ng/ml (0.9 - 7.1). Her brain MRI did not showcerebral edema or metastases. Conclusion: This case concerns metabolic encephalopathy due to severe hyponatremia caused by a secondary adrenal insufficiency (partial hypopituitarism), subclinical hypothyroidism and hyperprolactinemia, related to Nivolumab immunotherapy. Endocrinologists should be aware PD-1 inhibitor’s side effects, of its immunologic modulation mechanisms as they can cause hypophysitis, pituitary pituitary and thyroid dysfunction