A change for good may not be always good! An interesting case of recurrent hypoglycaemia
A 62-year-old man presented with fever, cough, dyspnoea, and unintentional weight loss of 3 kgs within 3 months. Chest X-ray revealed some scattered pulmonary shadows for which a CT scan of chest was planned. During the hospital stay patient developed documented symptomatic and asymptomatic hypoglycaemia almost daily especially in morning hours including two episodes of severe hypoglycaemia for which endocrine opinion was taken.\nOn reviewing the history, the patient was on metformin 500 mg and glimepride 1 mg, each twice a day after meals since 8 yrs. His blood glucose and other metabolic parameters were well controlled on this medication and he was very regular with regards to his diabetic diet and physical exercise. He did regular self blood glucose monitoring with a periodically calibrated glucometer and maintained a good record of his data. He had never been hospitalized for hypoglycaemia or ketoacidosis, so far. The patient had never recorded any severe hypoglycaemic events, so far. However, he noticed that his blood glucose values started to follow a downward trend since last 6 months with an appreciable drop of his fasting capillary blood glucose values by an average of 10-15 mg/dl, despite of regular and relatively liberal diet. Patient also confirmed some of these relatively low values with laboratory plasma glucose values. At this point of time the patient self adjusted his medications by gradually reducing the doses of Oral Hypoglycaemic Agent (OHA) or oral antidiabetic agents. Due to persistent low blood glucose values despite of liberalized diet, he stopped all OHA after 3 months. There was no history suggestive of any renal, hepatic disorder, alcohol consumption, diabetic retinopathy or any other underlying autoimmune disorder. The patient was not on angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) ACEI or ARBs, fluoroquinolones, sulphonamides. He was receiving paracetamol and cefuroxime for his current illness.\nOn examination, patient had a BMI of 23.5 kg/m2. He had no stigmata of chronic kidney disease. However, he had a palpable liver of two finger breadths below the costal margin which was non-tender but there were no other features suggestive of chronic liver disease.\nOn investigation, liver function tests were normal and his serum creatinine was 1.04 mg/dl with a clearance of 88 ml/min. CT scan of the chest performed to diagnose his chest pathology revealed right lower lobe consolidation with multiple pulmonary densities with pleural effusions in both lobes along with a large hypodense mass occupying almost entire right lobe of liver consistent with the provisional diagnosis of hepatocellular carcinoma with pulmonary metastasis, which was confirmed with biopsy [].\nBiochemical tests done during hypoglycaemia (blood glucose 44 mg/dl) showed a serum cortisol level of 36.5 μg/dl, suppressed serum insulin 0.6 IU/ml (3-35 μIU/ml, RIA) and C-peptide level 0.2 ng/ml (0.85-3.3 ng/ml, RIA) with negative serum ketones [], which ruled out endogenous hyperinsulinism. IGF-1 done was normal. In the given clinical scenario, ectopic secretion of big IGF-2 from the tumor mass was suspected but big IGF-2 assay was not available. Hence, a provisional diagnosis of non-islet cell hypoglycaemia as a part of paraneoplastic syndrome due to IGF-2 secreted by hepatocellular carcinoma was made.