Endocrine Abstracts

Background: Immunotherapy with checkpoint inhibitors (CPI) {CTLA4 and PD-1 inhibitors} have significantly improved outcomes and survival rates in patients with a number of cancers. In the UK, Ipilimumab and Nivolumab are approved for the treatment of advanced malignant melanoma. These are often long term therapies and are associated with immune mediated endocrinopathies.

Case: A 70 year old male presented to the Medical Admissions Unit with a history of lethargy, nausea, postural dizziness and reduced urine output since 4 days. He had a background history of Type 2 Diabetes Mellitus (on Metformin); and Stage IV malignant melanoma of the lower back diagnosed in March 2021 and was initiated on Ipilimumab and Nivolumab combination therapy in July 2022 for progressive disease. He was a non smoker and occasionally consumed alcohol. He had no known drug allergies and denied any significant family history. On examination, he had significant orthostatic hypotension and clinical signs of hypothyroidism. Visual fields were normal on confrontation, he had no peripheral hyperpigmentation and was well virilized. Rest of his systemic examination was unremarkable. Investigations were notable for acute kidney injury with normal electrolytes, a raised TSH (40), low FT4 (< 3) and markedly reduced cortisol (11). An endocrine opinion was sought in view of severe primary hypothyroidism and low cortisol. In light of his background history, a diagnosis of CPI associated endocrine dysfunction was made. He was started on stress dose oral hydrocortisone and further initiated on levothyroxine three days after. Blood tests to screen for other endocrinopathies (LH, FSH, Testosterone, Prolactin) were requested. On follow up in the endocrine clinic, he was detected to have low free testosterone (100) with raised LH (19.3) and FSH (34.7). Prolactin was normal. He responded well to thyroxine and cortisol replacement and is due to start testosterone replacement. Stimulatory testing is planned, but is delayed due to short term tapering Prednisolone course that was initiated for hepatotoxicity associated with CPI. His CT scan 6 months post initiation of immunotherapy showed treatment response and he is planned to continue on treatment for the long term. He is also being closely follow up by the endocrine team.

Conclusion: Clinical manifestations of immune mediated endocrinopathies can be non specific and can overlap with multi-organ involvement in the acute care setting. A clinician must consider endocrine dysfunction as a possibility while managing these patients, thus preventing potential life threatening consequences when recognised early and treated appropriately.