Endocrine Abstracts

A 74-year-old male presented to hospital following an episode of brief loss of consciousness and several hours of post ictal confusion. There was no witnessed seizure activity, tongue biting, or incontinence. His past medical history included SCC right scalp, TIA and primary hypothyroidism. He had been commenced on Cemiplimab (immunotherapy) for metastatic SCC seven months before. On assessment, he appeared well and general examination including neurological examination was normal. However, he was found to have a postural blood pressure drop of 40 mmHg. ECG and Blood tests were unremarkable, except his random cortisol was 163 nmol/l. Repeat 9 am cortisol was 183 nmol/l. Hydrocortisone was commenced as primary adrenal insufficiency could not be ruled out. A differential diagnosis of ictal syncope was also considered but later ruled out after normal MRI and EEG. Subsequently, Synacthen test showed baseline cortisol of 155 nmol/l, rising to 449 nmol/l at 30 minutes and 521 nmol/l at 60 minutes. ACTH was 16 ng/l. He was advised to stop hydrocortisone as primary adrenal insufficiency was ruled out. However, within a few days of stopping hydrocortisone, he felt symptomatic again with dizziness and pre-syncope, and was readmitted to hospital. Oral Hydrocortisone, at a dose of 20 mg daily, was restarted and his symptoms settled. A glucagon stimulation test was performed to investigate possible secondary adrenal insufficiency. Surprising, his morning cortisol came back as <11 nmol/l and remained undetectable (<11 nmol/l) throughout the test, whilst growth hormone levels peaked to 19.6 mg/l confirming severe ACTH deficiency. FSH, LH, testosterone, prolactin and TFTs were all normal. MRI pituitary showed no abnormality. He was treated as isolated ACTH deficiency, secondary to Cemiplimab. He remains well on hydrocortisone replacement. Secondary adrenal insufficiency due to Isolated ACTH deficiency is being increasingly reported to be associated with immune checkpoint inhibitors including Cemiplimab. In our case, clinical presentation was unusual as postural hypotension and syncope are not common with secondary adrenal insufficiency due to preservation of renin-aldosterone axis. Initial investigations were misleading with relatively preserved morning cortisol and good response to Synacthen. However, Cortisol levels became undetectable subsequently with no response to glucagon stimulation confirming diagnosis of severe ACTH deficiency. This case highlights that ACTH deficiency can present with postural syncope and normal morning cortisol levels in the early stages. High index of suspicion and repeated investigations may be required to confirm diagnosis.