Abstract Introduction Hypoglycemia is rare in the non-diabetic population. Based on clinical status, causes can be divided into two groups. In apparently healthy individuals, etiologies include insulinoma, post-bariatric hypoglycemia, autoimmune and factitious hypoglycemia, and hypoglycemia due to insulin or insulin receptor antibodies. In unwell patients, differential diagnoses include malnutrition, IGF-2–secreting non-islet cell tumors, drugs, alcohol, hypopituitarism, and adrenal insufficiency. NICTH is an uncommon paraneoplastic syndrome with an estimated incidence of one per million person-years. It results from IGF-2–mediated insulin receptor activation. Clinical Case A 74-year-old woman was admitted with a 3-month history of fasting and early-morning hypoglycemia characterized by sweating, tremor, palpitations, dizziness, and headache. Capillary glucose during symptomatic episodes ranged 36–40 mg/dL. Her history included intra-abdominal liposarcoma resection two years earlier and laparotomy with adhesiolysis four months prior. She had hypertension but no diabetes or other chronic disease. Similar symptoms had occurred before her initial surgery, improved after debulking, and recurred with tumor regrowth. Current medications included temozolomide, venlafaxine, and benidipine. During hypoglycemia, labs showed plasma glucose 30 mg/dL, insulin 0.4 mIU/L, C-peptide 0.12 µg/L, cortisol 26 µg/dL, GH 3.4 ng/mL, and ketones 2 mmol/L. Anti-insulin antibodies were negative. Insulinoma, non-insulinoma pancreatic cell hyperplasia, post-bariatric hypoglycemia, adrenal insufficiency, GH deficiency, and autoimmune hypoglycemia were excluded. IGF-2 could not be measured, but IGF-1 was markedly low (32 µg/L), suggesting IGF-2 excess. Contrast-enhanced CT revealed a 7 × 5 cm intraabdominal mass consistent with liposarcoma; liver and adrenals were normal. Clinical, biochemical, and imaging findings supported the diagnosis of NICTH. Nutritional support with frequent meals and bedtime cornstarch was initiated, but the patient required continuous IV dextrose. Oral dexamethasone (1 mg) and long-acting octreotide (10 mg IM) were ineffective. IV methylprednisolone (40 mg) resolved hypoglycemia and eliminated dextrose dependence. She was discharged on tapering oral methylprednisolone (32 mg daily) with stable glycemic control. Conclusion NICTH should be considered in patients with hypoglycemia, suppressed insulin and C-peptide, and low ketones. Elevated IGF-2 is not always required; an IGF-2/IGF-1 ratio 10 is diagnostic. Where IGF-2 testing is not feasible, a markedly low IGF-1 in patients with normal pituitary reserve may serve as a surrogate indicator suggestive of NICTH. Our patient had recurrent liposarcoma and compatible biochemical findings confirming NICTH. Surgical resection is the treatment of choice and may be curative. For unresectable disease, glucocorticoids are the mainstay, with recombinant growth hormone and somatostatin analogs as adjuncts.
Bektaş et al. (Thu,) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: