Year: 2009
Type: article
Abstract: To the Editor: A 78-year-old Chinese man with type 2 diabetes mellitus, hypertension, and hyperlipidemia presented with asthenia and anorexia for more than 1 month. He was not taking any complementary or alternative medication (CAM) and had earlier been prescribed mirtazapine for possible depression, but his symptoms did not improve. Physical examination did not reveal any significant abnormalities, and blood pressure was 130/70 mmHg with no postural hypotension. Chest X-ray was normal, and malignancy screening with tumor markers was unremarkable. Blood investigations showed a high white blood cell count of 12.35 × 109/L with eosinophilic predominance at 5.05 × 109/L. Peripheral blood film revealed no abnormalities except for a slightly high number of white blood cells. Serum sodium level was mildly low at 133 mmol/L. He was not hypothyroid biochemically, but his random cortisol level was low at 7 nmol/L. A high-dose adrenocorticotropic hormone (ACTH) stimulation test revealed inadequate adrenal response, with cortisol levels of 27, 111, and 133 nmol/L at 0, 30, and 60 minutes, respectively. An 8 a.m. sample of ACTH was low at 0.4 pmol/L. The levels of the rest of the pituitary hormones (thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, growth hormone) were normal. Structural magnetic resonance imaging (MRI) of the brain did not reveal any pituitary or hypothalamic abnormality. He was diagnosed with isolated ACTH deficiency (IAD) and started on intravenous hydrocortisone, which was subsequently converted to the oral preparation at 10 mg twice a day. His symptoms improved significantly, and the eosinophilia also resolved with treatment. Asthenia and anorexia are common complaints in elderly people and call for attention to ailments such as occult malignancy, infection, hormonal disorder, adverse drug effects, and depression. These conditions were excluded systematically in this patient through history taking and targeted investigations, and a trial of the antidepressant mirtazapine was also undertaken to no avail. The slightly low sodium level and high eosinophil count raised the possibility of adrenal insufficiency. Inadequate adrenal response with ACTH stimulation confirmed this, and the correspondingly low ACTH level suggested secondary adrenal insufficiency. Use of CAM is common in older Chinese. These products, commonly consumed for pain relief and to improve vitality, may contain glucocorticoids.1 Prolonged administration of exogenous glucocorticoids result in secondary adrenal insufficiency, but a detailed history excluded this possibility in this patient. Because the other pituitary hormones and MRI of the pituitary were normal, the uncommon entity of IAD was confirmed. The commonest cause of secondary adrenal insufficiency is prolonged ingestion of supraphysiological doses of glucocorticoids. Only a small proportion of patients with secondary adrenal insufficiency have IAD.2 Patients with IAD can be asymptomatic during unstressed periods until intervening events trigger an adrenal crisis, resulting in symptoms such as anorexia, asthenia, weight loss, nausea, and vomiting. Unusual presentations of pericardial effusion, recurrent syncope, and severe muscle atrophy have been reported.3 Hyponatremia, hypoglycemia, and a high-normal potassium level are seen biochemically, and anemia, lymphocytosis, and eosinophilia are commonly seen. The most likely etiology of IAD is autoimmune hypophysitis, which can present with other autoimmune endocrinopathies such as primary hypothyroidism, type I diabetes mellitus, and polyglandular autoimmune failure.4–6 In autoimmune hypophysitis, MRI usually shows a symmetrical pituitary mass with bright, homogenous contrast enhancement.7 This was absent in this patient. The definitive diagnosis of autoimmune hypophysitis lies in histology, which typically shows monoclonal lymphocytic infiltration of pituitary tissue, but pituitary biopsy is invasive and not without risk. This emphasizes the need for clinical diagnostic criteria in establishing the condition. Pituitary auto-antibodies have also been identified, but the test for these auto-antibodies is not widely available.8 Genetic mutations have been described in childhood IAD,9 but genetic testing has proven to be of little use in adults. In summary, adrenal insufficiency should be considered as a likely cause for asthenia and anorexia, especially in older people of Asian ethnicities, given that CAM usage is common and widespread. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this letter. Author Contributions: All authors contributed to the writing of the letter. Sponsor's Role: Not applicable.
Institution: Alexandra Hospital
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funder: National Institutes of Health
OpenAlex ID: W1549933705