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Acute endocrine presentations in general practice

Endocrine immune-related adverse events

VENESSA H. TSANG, Bernard Champion
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What are the endocrine immune-related adverse effects?
Answer: Endocrine irAEs primarily involve the pituitary, thyroid and, rarely, the adrenal glands and pancreas.8  Table 2 details the incidence  of  the most common endocrine irAEs. Pituitary involvement usually manifests as hypophysitis, resulting in the loss of one or more of the pituitary hormones, including adrenocorticotrophic hormone (ACTH), thyroid stimulating hormone (TSH), luteinising hormone (LH) and follicle stimulating hormone (FSH) resulting in hypoadrenalism, hypothyroidism and/or hypogonadism. These patients rarely develop posterior pituitary dysfunction in the form of diabetes insipidus, unless there has been structural damage due to cerebral lesions, surgery or radiotherapy.

The thyroid can become overactive or underactive, and is almost exclusively due to thyroiditis or inflammation of the thyroid gland rather than over-production. However, patients who have previously had Graves’ disease can develop flares, as is common for many other previously diagnosed autoimmune conditions. Thyroiditis can manifest as hyperthyroidism followed by euthyroidism or hypothyroidism, or primary hypothyroidism. Once a patient has commenced on thyroxine they are rarely able to come off the medication, that is, once gland failure has occurred it is usually permanent.

Pancreatic endocrine dysfunction manifesting as diabetes can also occur resulting in ketoacidosis. Patients present in a similar way to patients with type 1 diabetes and often require lifelong insulin therapy. Primary adrenal failure is rare and reported in cases only. 



In what way could Jack’s presentation be a manifestation of endocrine irAEs?
Answer: The symptoms of headache, nausea and vomiting could represent hypophysitis. Further examination to suggest this includes a postural drop in blood pressure. Urgent investigation is important to exclude this irAE. 



What investigations would you perform to clarify the diagnosis?
Answer: The best investigations to perform are a cortisol measurement in the early morning with a matched ACTH. However, given the urgency of the presentation a cortisol measurement taken at any time is helpful. Review of the imaging of the brain is also helpful, and repeat imaging is sometimes required to exclude metastatic disease. Hypophysitis can sometimes be seen on MRI with a swollen pituitary gland and thickened pituitary stalk, but these radiological changes often improve after treatment.

If the cortisol level is abnormal, completion of the pituitary screen including TSH, free T4, electrolytes, prolactin, testosterone, LH and FSH may give clues on the diagnosis and deficiencies of other hormones.



Jack’s blood test results are shown in Table 3, with the main abnormality being the low cortisol level. The T4 level is low with an inappropriately normal TSH level suggesting central or secondary hypothyroidism. Testosterone is also low with inappropriately normal FSH and LH levels suggesting secondary hypogonadism. 


Dr Tsang is Staff Specialist in the Department of Endocrinology at the Royal North Shore Hospital, Sydney; and Senior Lecturer in the Northern Clinical School, Faculty of Medicine and Health at The University of Sydney, Sydney, NSW. Associate Professor Champion is an Endocrinologist and Associate Professor in Medicine at Macquarie University; and Honorary Associate Professor at Nepean Clinical School, The University of Sydney, Sydney, NSW.