Hypoglycaemia Workup
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Direct answer
Confirm Whipple's triad before ordering a single hormone: symptoms consistent with hypoglycaemia, a laboratory (not meter) glucose below 55 mg/dL during symptoms, and relief after carbohydrate. During a spontaneous or fast-induced episode, draw the critical four-some simultaneously — insulin, C-peptide, beta-hydroxybutyrate — plus a sulfonylurea screen and, when the story fits, cortisol, growth hormone and IGF-2. Inappropriately normal or high insulin with matched C-peptide means endogenous production: insulinoma or sulfonylurea; high insulin with suppressed C-peptide means injected insulin; both low with symptoms points to non-insulin causes — alcohol, adrenal insufficiency, critical illness, or non-islet cell tumour hypoglycaemia. The 72-hour supervised fast remains the diagnostic engine for suspected insulinoma, and over 90 per cent of positives declare themselves within 48 hours.
What you must remember
- Interpretation anchor set: during biochemical hypoglycaemia, insulin of 3 μU/mL or more (18 pmol/L), C-peptide of 0.6 ng/mL or more (200 pmol/L), proinsulin of 5 pmol/L or more, beta-hydroxybutyrate of 2.7 mmol/L or less, and a negative sulfonylurea screen define inappropriately regulated insulin secretion.
- Exogenous insulin: high insulin, low C-peptide, low proinsulin — the single most discriminating pattern in the viva.
- Sulfonylurea: high insulin AND high C-peptide indistinguishable from insulinoma biochemically; only the drug screen (and the prescription history) separates them — in India, over-the-counter combination pills make this screen non-optional.
- Insulinoma epidemiology: 90 per cent benign, solitary, intrapancreatic; roughly 5–10 per cent belong to MEN1 — check calcium and prolactin in every confirmed case; the "rule of tens" is teaching shorthand, not gospel.
- 72-hour fast protocol: no calories, water allowed, hourly capillary glucose, and act on symptoms — endpoint is glucose below 45–55 mg/dL with Whipple's triad; C-peptide suppression at 36 hours is an older equivalent.
- Localisation ladder: CT or MRI first, endoscopic ultrasound next (sensitivity 80–90 per cent for small tumours), then selective arterial calcium stimulation with hepatic venous sampling for the stubborn negative.
- Non-insulin mimics: alcohol (fasting plus impaired gluconeogenesis), severe liver disease, renal failure, adrenal insufficiency, post-bariatric late dumping (GLP-1-driven hyperinsulinaemia), and IGF-2-secreting sarcomas or fibromas with suppressed insulin.
- Treatment bridges: diazoxide or octreotide for unresectable insulinoma, everolimus in metastatic disease, and patient-taught emergency glucagon for all.
The 72-hour fast, step by step
Admit a 44-year-old with early-morning sweats and confusion relieved by juice, not on any diabetes drug. Baseline: weight, IV access, glucose meter calibrated against laboratory values. Hourly capillary glucose; the fast continues while glucose exceeds 60 mg/dL and the patient tolerates it. At 2 a.m. on day two, she becomes diaphoretic and confused: laboratory glucose 41 mg/dL, insulin 14 μU/mL, C-peptide 3.1 ng/mL, proinsulin elevated, beta-hydroxybutyrate 1.1 mmol/L, sulfonylurea screen negative — the full house of endogenous hyperinsulinaemia. End the fast with IV dextrose, then localise: CT shows nothing; endoscopic ultrasound flags a 9 mm hypoechoic nodule in the pancreatic head; intraoperative ultrasound plus surgeon palpation confirms, and enucleation cures. Two exam-worthy side notes: the diagnostic yield of this protocol peaks in the first 48 hours, so a fast abandoned at 48 hours in a symptomatic patient is still complete; and if the same numbers appeared with a positive sulfonylurea screen, the treatment is observation on a medical ward, not a laparotomy.
The marking-scheme trap
Two traps recur. First, working up "hypoglycaemia" on a glucometer reading alone — Whipple's triad demands plasma confirmation, and factitious or artefactual lows (poorly washed hands, site contamination) evaporate on laboratory testing. Second, forgetting the drug screen in the high-C-peptide patient: operating for an insulinoma that is actually glimepiride from a neighbourhood combination pill is the classic medicolegal disaster this topic exists to prevent. A subtler trap is mislabelling post-prandial dumping hypoglycaemia after bariatric surgery as fasting hypoglycaemia — the fast will be normal; the answer lies in a mixed-meal test and the surgical history the candidate never asked about.
Frequently asked questions
What defines Whipple's triad?
Symptoms of hypoglycaemia, a laboratory-confirmed plasma glucose below 55 mg/dL during those symptoms, and prompt relief after glucose ingestion — all three must be documented before investigation proceeds.
How is exogenous insulin misuse detected biochemically?
Elevated insulin with suppressed C-peptide and proinsulin during hypoglycaemia — the injected hormone suppresses the beta cell, so endogenous markers disappear.
What is the endpoint of the 72-hour supervised fast?
Whipple's triad with laboratory glucose below about 45–55 mg/dL, at which point the critical samples are drawn and the fast is terminated with dextrose.
Which localisation test follows negative CT and MRI?
Endoscopic ultrasound; if still negative, selective arterial calcium stimulation with hepatic venous sampling before any reoperation.
Which single additional test is ordered in confirmed insulinoma?
Serum calcium with PTH (and prolactin or genetic testing as indicated) to unmask MEN1 before planning the extent of surgery.