Sophia L. Wong

Quantitation of Insulin Analogues in Serum Using Immunoaffinity Extraction, Liquid Chromatography, and Tandem Mass Spectrometry.

Insulin analysis is used in combination with glucose, C-peptide, beta-hydroxybutyrate, and proinsulin determination for the investigation of adult hypoglycemia. The most common cause is the administration of too much insulin or insulin secretagogue to a diabetic patient or inadequate caloric intake after administration of either. Occasionally there is a question as to whether hypoglycemia has been caused by an exogenous insulin-whether by accident, intent, or even malicious intent. While traditionally this was confirmed by a low or undetectable C-peptide in a hypoglycemic specimen, this finding is not entirely specific and would also be expected in the context of impaired counter-regulatory response, fatty acid oxidation defects, and liver failure-though beta-hydroxybutyrate levels can lend diagnostic clarity. For this reason, insulin is often requested. However, popular automated chemiluminescent immunoassays for insulin have distinctly heterogeneous performance in detecting analogue synthetic insulins with cross-reactivities ranging from near 0 % to greater than 100 %. The ability to detect synthetic insulins is vendor-specific and varies between insulin products. Liquid Chromatography and Tandem Mass Spectrometry (LC-MS/MS) offers a means to circumvent these analytical issues and both quantify synthetic insulins and identify the specific type. We present an immunoaffinity extraction and LC-MS/MS method capable of independent identification and quantitation of native sequence insulins (endogenous, Insulin Regular, Insulin NPH), and analogues Glargine, Lispro, Detemir, and Aspart with an analytical sensitivity for endogenous insulin of between 1 and 2 μU/mL in patient serum samples.

Macrotroponin Causing Elevation in Cardiac Troponin I

We report a case of macrotroponin causing persistently raised levels of cardiac troponin I (cTnI) in a 57-year-old man with recurrent atypical chest pain. Macrotroponin, a troponin-immunoglobulin complex, should be considered when cTnI values are inconsistent with the clinical picture, and fail to demonstrate a rise and/or fall pattern in suspected cases of acute coronary syndrome. Clear and effective communication between cardiologists and laboratorians is essential in the management of patients with macrotroponin.

Acylcarnitine profile in thyroid disease.

OBJECTIVES To examine acylcarnitine profiles in individuals with hypo- or hyperthyroidism, and determine whether any atypical acylcarnitine species identified would normalize with correction of thyroid status. DESIGN AND METHODS Serum acylcarnitine levels were measured in hypo- and hyperthyroid subjects before and after treatment with thyroxine or thionamide therapy respectively. RESULTS No discernible differences were observed in the serum acylcarnitine profiles between hypo-, hyper- and euthyroid states. CONCLUSIONS Acylcarnitine profiles are relatively unremarkable in thyroid disease.

Nitrous Oxide (N2O)-Induced Acute Psychosis.

Nitrous oxide (N2O), commonly referred to as laughing gas, is a colourless, non-flammable, inorganic volatile with psychedelic effects. It has assorted uses among diverse fields: in medicine and dentistry, N2O provides a source of dissociative anaesthesia and analgesia; in the food and automobile industries, N2O serves as a propellant in whipped cream canisters and as an engine booster, respectively. N2O is inexpensive and readily available at supermarkets as gas cylinders and dispensers for soda streams and whipped cream. It is among the top five most common inhalants abused by adolescents in the United States of America. A questionnaire-based study completed in New Zealand noted that 12% of first-year students at the University of Auckland inhaled N2O recreationally, and 3%used it at least monthly. Even though most people have an unremarkable, or even unpleasant, experience with N2O intoxication, some find the dissociative encounter euphoric, with associated sensations of “floating”, body tingling, warmth and numbness. Various cases of N2O abuse have surfaced in the literature, although isolated psychiatric presentations are uncommon. As cessation from N2O exposure and treatment with vitamin B12 usually lead to complete resolution of psychiatric symptoms, it is important to consider such a precipitant when a patient presents with neuropsychiatric manifestations of an uncertain etiology, especially when N2O use is obtained on history.

Malignant Catatonia Mimicking Pheochromocytoma

Malignant catatonia is an unusual and highly fatal neuropsychiatric condition which can present with clinical and biochemical manifestations similar to those of pheochromocytoma. Differentiating between the two diseases is essential as management options greatly diverge. We describe a case of malignant catatonia in a 20-year-old male who presented with concurrent psychotic symptoms and autonomic instability, with markedly increased 24-hour urinary levels of norepinephrine at 1752 nmol/day (normal, 89–470 nmol/day), epinephrine at 1045 nmol/day (normal, <160 nmol/day), and dopamine at 7.9 μmol/day (normal, 0.4–3.3 μmol/day). The patient was treated with multiple sessions of electroconvulsive therapy, which led to complete clinical resolution. Repeat urine collections within weeks of this presenting event revealed normalization or near normalization of his catecholamine and metanephrine levels. Malignant catatonia should be considered in the differential diagnosis of the hypercatecholamine state, particularly in a patient who also exhibits concurrent catatonic features.

Wine-Colored Plasma and Urine from Hydroxocobalamin Treatment

A 49-year-old male was admitted following a house fire that resulted in burns to 20 % of his total body surface area. Empiric hydroxocobalamin was given for presumed cyanide poisoning secondary to smoke inhalation. Plasma and urine from the patient were noted to have an intense dark red/purple hue (Fig. 1). Approximately 35 % of fire victims experience toxicity from cyanide, generated during pyrolysis of such synthetic materials as plastics, rugs, silks, and furniture. Cyanide inhibits cytochrome oxidase in the electron transport chain and blocks aerobic metabolism, causing a histotoxic hypoxia. Hydroxocobalamin chelates cyanide and forms the nontoxic, renally excreted cyanocobalamin. A common side effect of hydroxocobalamin is a stunning dark red/purple discoloration of the recipient’s skin, mucosal membranes, and body fluids, including plasma and urine. Although the pigmentation is harmless and resolves spontaneously within days, it can cause analytical interference with a number of common chemistry, hematology, and coagulation tests. The clinical significance of these transient alterations remains to be determined. More concerning is the increase in carboxyhemoglobin and methemoglobin and decrease in oxyhemoglobin from hydroxocobalamin interference observed with certain co-oximeters. As smoke inhalation victims often demonstrate concomitant carbon monoxide and cyanide toxicities, initial blood gas measurements should be obtained prior to hydroxocobalamin administration. Our patient had a carboxyhemoglobin level of 20.5 % (normal, < 2.5 %) before hydroxocobalamin treatment, thereby confirming concurrent carbon monoxide poisoning. Figure 1. Wine-colored urine (left) and plasma (right) from hydroxocobalamin treatment for cyanide poisoning.