A case of autoimmune hypoglycemia outside Japan: Rare, but in the era of expanding drug-list, important to suspect
A 72-year-old man of Indian origin had first episode of hypoglycemia 2 months earlier when, 4-5 h after taking lunch, he was found to be disoriented. He was taken to the nearby hospital where level of his plasma blood glucose was found to be 20 mg/dL and intravenous 10% dextrose infusion reversed his symptoms. During hospital stay, he continued to have hypoglycemic episodes in the postabsorptive state. He was not a known diabetic and was not taking any drug known to cause hypoglycemia. There was no family history of diabetes. Result of routine investigations, including hemogram and renal, liver and thyroid function tests, were not significant. During one such episode, plasma blood glucose level was 15 mg/dL and the corresponding serum insulin was 123 mU/L. With provisional diagnosis of insulinoma, imaging studies, including ultrasonography, dual phase computed tomography (CT) and magnetic resonance (MR) imaging of abdomen, MR and CT angiography of the abdomen and contrast-enhanced CT of chest, were done sequentially. All these imaging modalities failed to detect any lesion. At this stage, the patient was referred to us. Review of past history revealed that the patient had ischemic cerebral infarct 8 years back when he was detected to have hypertension. One year back, he suffered from coronary ischemia. The patient never had gastrointestinal surgery. At the time of presentation, he was taking drugs – Pantoprazol, Aspirin, Clopidogrel, Torsemide, Isosorbide dinitrate, Atenolol, Atorvastatin and Amlodipine. General and systemic physical examination did not reveal any abnormality. During his stay in the Endocrine Ward, the patient continued to have hypoglycemia in the postabsorptive state. During one such episode, the plasma blood glucose level was 29 mg/dL, serum insulin was 3162 mU/L and serum C-peptide was 19.05 ng/mL (latter two measured by electrochemiluminescence immunoassay, using a Roche Elecsys 2010 immunoassay analyzer, GmBH, Mannheim, Germany], while serum cortisol and growth hormone responses were adequate. Serum proinsulin level was 420 pmol/L (normal fasting value < 20 pmol/L, measured by radioimmunoassay; Millipore Corporation, Merck Millipore Headquarters, 290 Concord Road, Billerica, MA 01821 USA). Trans-esophageal ultrasonography also failed to locate any lesion. Extended oral glucose tolerance test (OGTT) with 75 g of glucose showed paradoxical hyperglycemia followed by hypoglycemia with very high insulin levels []. These findings were highly suggestive of IAS. Other immunological findings of the patient showed elevated rheumatoid factor titers (>256, normal 0-20) and antinuclear antibody titers on Hep-2 substrate (1:80, normal < 1:20). The serum immunoglobulin G (IgG) level was 2416 mg/dL (normal 960-1968 mg/dL), IgM was 473 mg/dL (normal 125-380 mg/dL) and IgA was 146 mg/dL (normal 90-242 mg/dL), as measured by enzyme-linked immunosorbent assay. Samples for human leukocyte antigen (HLA) studies were collected, which showed HLA-A*02, A * 11, B * 35, B * 51, DRB1 * 0403 and DRB1 * 0404.\nReview of patient's drug intake revealed that he was taking three drugs, viz. Pentoprazol, Clopidogril and Torsemide, which contained sulfur and hydrogen atoms. Under the plan to stop usage of these drugs one by one, to begin with, Pentoprazole was discontinued and the patient was advised to take meals in small quantities frequently. As a follow-up thereof, the patient was observed keenly during the next week for any hypoglycemic symptoms, which were noticed to have subsided gradually. Eventually, the patient was discharged with the said advice. Review after 3 months, with extended OGTT, showed quantum decrease in serum insulin levels along with disappearance of the hyperglycemic phase, which feature was subsisting earlier. In the changed scenario, maximum blood glucose level reached was 183 mg/dL at 1 h []. Subsequent follow-up during the next 6 months revealed that the patient did not have any symptoms of hypoglycemia and was healthy.