Adrenal Insufficiency in Cancer Patients

Introduction to Adrenal Insufficiency

Metastatic destruction of adrenal tissue can occur when bilateral adrenal metastases destroy >90% of adrenal cortex, leading to insufficient cortisol and aldosterone production, as seen in cancer patients 1
Immune checkpoint inhibitors can cause immune-related adrenal insufficiency, requiring similar management but with a different etiology, according to the American College of Clinical Endocrinologists and the European Society for Medical Oncology 1

Morning cortisol levels <140 nmol/L (<5 μg/dL) with elevated ACTH strongly suggest primary adrenal insufficiency, as recommended by the American College of Clinical Endocrinologists 1
Adrenal CT scans are recommended to evaluate for metastases, hemorrhage, or other causes, as suggested by the National Comprehensive Cancer Network and the European Society for Medical Oncology 1
Baseline laboratory values should include morning serum cortisol (8 am) and ACTH, electrolytes (sodium, potassium), and glucose, with interpretation of cortisol <140 nmol/L (<5 μg/dL) with elevated ACTH indicating primary adrenal insufficiency 2
The ACTH stimulation test (Synacthen test) involves administering 0.25 mg of Synacthen intramuscularly or intravenously, measuring serum cortisol after 30 and/or 60 minutes, with a normal value of cortisol >550 nmol/L (>18 μg/dL) at one of the time points, as noted by 2, 3

Immediate administration of IV hydrocortisone 100 mg is recommended for acute management of adrenal crisis, as suggested by the American College of Clinical Endocrinologists and the Endocrine Society 1
Replacement therapy with prednisone (5-10 mg daily) or hydrocortisone (10-20 mg orally in morning, 5-10 mg in early afternoon) is recommended for chronic management, according to the Endocrine Society 1
Patient education on stress dosing instructions, medical alert bracelet, and recognition of symptoms requiring medical attention is crucial, as emphasized by the American Cancer Society 1
In cases of suspected acute adrenal insufficiency, treatment should be started immediately without waiting for test results, with intravenous hydrocortisone (100 mg) and physiological (0.9%) saline solution, as recommended by 2, 1

Hemorrhagic adrenal metastases can cause acute adrenal insufficiency and should be considered in cancer patients with sudden flank/back pain, hypotension, and anemia, although the exact incidence is not well-established 1
Pituitary metastases can cause secondary adrenal insufficiency (low ACTH, low cortisol) and should be considered in patients with appropriate symptoms and brain metastases, as noted by the European Society for Medical Oncology 1
Exogenous steroid intake (oral, inhalative) can make it difficult to interpret low cortisol values, and TSH can be slightly elevated (4-10 IU/L) in adrenal insufficiency due to lack of inhibition by cortisol, as noted by 2
In patients with sepsis, a normal cortisol level may be inappropriately low for the disease state, and in patients with bilateral adrenal tumors, adrenal insufficiency should be ruled out, as recommended by 2, 4
Etiological investigation should be performed after confirming the diagnosis, including determination of 21-hydroxylase autoantibodies (21OH-Ab) to rule out an autoimmune cause, CT of the adrenal glands to rule out tumors, bleeding, or tuberculosis, and measurement of very long-chain fatty acids in male patients to rule out adrenoleukodystrophy, as noted by 2, 4