Diagnosis of Hypoglycemia
المؤلف:
Marcello Ciaccio
المصدر:
Clinical and Laboratory Medicine Textbook 2021
الجزء والصفحة:
p418-420
2025-11-12
19
Once the suspicion of hypoglycemia has been confirmed by Whipple’s triad criteria (Fig. 1), it is necessary to make a differential etiological diagnosis to start the most appropriate therapy.
Fig1. Algorithm for the etiological diagnosis of hypoglycemia. (Copyright EDISES 2021. Reproduced with permission)
Patients with diabetes should suspect the possibility of developing hypoglycemia when the self-monitored glucose concentration decreases rapidly or is not >70 mg/dL (3.9 mmol/L). This cutoff allows the patient to intervene preemptively to avoid symptomatic hypoglycemia. In addition, because self-monitoring is usually performed by analytically inaccurate devices, especially at low glucose levels, the 70 mg/dL glucose cutoff provides a margin for their analytical inaccuracy. Hypoglycemiain a diabetic patient must be treated by modifying therapy and then the improvement should be documented. If there is a history of unconscious hypoglycemia (recurrent hypoglycemia without symptoms), a 2–3-week period of scrupulous attention to avoid hypoglycemia is recommended.
Non-diabetes mellitus subjects with hypoglycemia often present with signs and symptoms, such as mental confusion, altered consciousness, epilepsy, or after the casual finding of low plasma glucose concentrations. In a symptomatic subject, the confirmation of hypoglycemia is based on the finding of low plasma glucose levels and the resolution of symptoms after glycemia correction.
The differential diagnosis is based on: (1) accurate anamnesis, which includes a detailed description of the events, the relationship with meal intake (hypoglycemia that occurs 2–3 h after meals is suggestive of hyperinsulinism, whereas if it occurs after prolonged fasting, it suggests an altered mechanism of gluconeogenesis), the presence of comorbidities, and the pharmacological therapy taken by the patient and family members; (2) physical examination; and (3) laboratory data to assess the role of insulin in hypoglycemia genesis (Fig. 2).
Fig2. Algorithm for the etiological diagnosis of hypoglycemia. (Copyright EDISES 2021. Reproduced with permission)
First, drug therapy, especially insulin, and alcohol, should be considered. The presence of diseases, chronic or acute, hormonal deficiencies, non-β-cell tumors, and previous gastric surgery should also be considered.
If all these conditions are absent, and thus the subject is healthy, further laboratory investigations should be per formed. In particular, during an episode of hypoglycemia, blood glucose, insulin, C-peptide, and proinsulin should be measured simultaneously and a toxicological screening for oral hypoglycemic agents should be performed (Table 1). In some cases, patients experience symptoms of hypoglycemia after a short period of fasting; in such cases, continued observation, especially after an overnight fast, could result in an episode of symptomatic hypoglycemia. During the observation period, blood glucose should be measured continuously; if symptoms occur and hypoglycemia is documented (plasma glucose <55 mg/dL), the tests described above should be performed (Table 1). If this approach results in neither symptoms nor hypoglycemia and clinical suspicion remains high, the patient should undergo a stimulus test such as a 72-hour fast. The aim of this test is to induce homeostatic responses allowing the maintenance of plasma glucose concentration not associated with symptoms of hypoglycemia under fasting conditions. Increased release of glucagon, adrenaline, and, to a lesser extent, growth hormone and cortisol are the most critical components of this response. All hormonal responses begin long before the onset of symptomatic hypoglycemia. Normal subjects do not experience symptomatic hypoglycemia after prolonged fasting due to hormone-induced increase in glucose production. Prolonged fasting results in hypoglycemia only if there is a defect in normoglycemia mainteinance due, for example, to an excess of insulin that inhibits endogenous glucose production.
Table1. Differential diagnosis of hypoglycemia
During the 72-hour fast, patients cannot assume food but can only consume sugar-free and caffeine-free drinks. Fasting starts after the last meal. Blood samples should be collected every 6 h until blood glucose is <60 mg/dL; at this point, samples should be collected every 1–2 h. Insulin, C-peptide, and proinsulin should only be assayed in samples with blood glucose <60 mg/dL. Fasting ends when the glucose concentration is <45 mg/dL, the patient exhibits signs and/or symptoms of hypoglycemia, 72 hour have elapsed, or blood glucose is <55 mg/dL if Whipple’s triad has been documented previously. The absence of signs and symptoms of hypoglycemia, as well as a low plasma glucose concentration during a 72-h fast, does not preclude a hypoglycemic disorder that may cause only postprandial symptoms. At the end of the test, 1 mg of intravenous glucagon is administered, and plasma glucose is measured after 10, 20, and 30 min; then, the patient can eat. Insulin is an anti- glycogenolytic, and hyperinsulinemia allows hepatic glycogen storage. Consequently, patients with hypoglycemia secondary to hyperinsulinism (as in the case of insulinoma) respond to glucagon administration (which is a potent glycogenolytic agent) by releasing glucose; in particular, a glycemia increase of at least 25 mg/dL will be observed compared to the glycemia at the end of the test. The healthy subjects, instead, will have released virtually all the hepatic glucose within the 72 hour of fasting and, therefore, will present a reasonable response to the stimulus of glucagon, with a much smaller increase of glycemia.
In case of non-insular tumors suspicion, autoimmune etiology, or hormonal deficiency, the measurement of anti- insulin antibodies, anti-insulin receptor, IGF-1/2, plasma cortisol, glucagon, and growth hormone can be performed.
If symptoms of hypoglycemia occur within 5 h of meals, patients should be assessed in the postprandial state by mixed-meal testing. Specifically, the patient take a nonliquid meal, resulting in the onset of symptoms, and be kept under observation for the next 5 h. Plasma glucose assay will be performed before the mixed meal and after intake every 30 min for the next 5 h. If severe symptoms occur before 5 h, samples should be collected before carbohydrate administration (to assess the correction of symptoms). Insulin, C-peptide, and proinsulin should be tested only in samples of blood glucose <60 mg/dL (Table1).
If an insulinoma is suspected, radiological investigations should confirm the diagnosis. Computed axial tomography (CAT) and nuclear magnetic resonance (NMR) are the most commonly used noninvasive diagnostic procedures to detect the tumor site. However, more invasive techniques, such as endoscopic ultrasonography and venous sampling after arterial stimulation, are more accurate in preoperative localization of insulinoma and superior to standard noninvasive localization techniques. Finally, positron emission tomography (18F-DOPA-PET) is a technique successfully used for the localization of insulinomas, and, in children with hypoglycemia due to congenital hyperinsulinism, it rep resents the gold standard for the lesions localization before surgery.
Autoimmune hypoglycemia is a rare condition characterized by antibodies directed against insulin or the insulin receptor, resulting in hypoglycemia. Detection of anti- insulin and anti-insulin receptor antibodies is necessary to confirm the diagnosis of autoimmune hypoglycemia. Autoimmune hypoglycemia should be suspected when hypoglycemia is associated with high insulin levels (>100 μU/mL) and incompletely suppressed C-peptide levels. Finally, although elevated insulin levels may be observed following exogenous insulin administration, the associated C-peptide levels are usually extremely low.
الاكثر قراءة في التحليلات المرضية
اخر الاخبار
اخبار العتبة العباسية المقدسة
