Amylase as a Diagnostic Tool for Plunging Ranula: Clinical Series and Description of the Technique.

OBJECTIVES: This study describes a technique of measurement for neck cyst amylase content and reviews the experience of a tertiary referral center for cases of suspected plunging ranula. METHODS: A retrospective study was performed at the Manukau Surgical Center in Auckland, New Zealand. Patients with a possible diagnosis of plunging ranula based on clinical presentation and diagnostic aspiration of the cyst contents were included. Demographic data, imaging and laboratory findings were collected, along with findings from surgery and histology. The technique for measuring the amylase of the aspirated cyst contents was also carefully recorded. RESULTS: The 37 cases of confirmed plunging ranula included in this study had a submandibular cystic swelling that was aspirated. Imaging features consistent with a plunging ranula were seen in 89% of the study group. All cases had detectable levels of amylase of ≥3 U/L in the ranula contents. There was large variability (range: 5-560 U/L) in the concentration of amylase, with 70% of the cases demonstrating an amylase concentration below 200 U/L. Aspirates were typically described as viscous (87.5%) and yellow or straw-colored. CONCLUSION: The combination of clinical presentation, imaging and the presence of amylase in the cyst contents is diagnostic for plunging ranula. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:535-538, 2023.

Identification of macrotroponin T: findings from a case report and non-reproducible troponin T results.

OBJECTIVES: Macrotroponin is due to cardiac troponin (cTn) binding to endogenous cTn autoantibodies. While previous studies showed a high incidence of macrotroponin affecting cTnI assays, reports of macrotroponin T, particularly without cTnI reactivity, have been rare. Although the clinical significance of macrotroponin is not fully understood, macroenzymes and complexes are recognised to cause confusion in interpretation of laboratory results. The potential for adverse clinical consequences due to misinterpretation of affected results is very high. METHODS: We describe four cases of macrotroponin T with persistently low high sensitivity cTnT (hs-cTnT) by the 9 min compared to the 18 min variant of the assay. Three cases were serendipitously identified due to the use of a lot number of Roche hs-cTnT affected by non-reproducible results, necessitating measurement of cTnT in duplicate. We identified and characterised these macrotroponin specimens by immunoglobulin depletion (Protein A and PEG precipitation), mixing studies with EDTA and recombinant cTnT. RESULTS: In cases of macro-cTnT, a lower result occurred on the hs-cTnT using the 9 min compared to 18 min variant assay (ratio of 9-18 min hs-cTnT <0.80). Mixing studies with recombinant cTnT or EDTA demonstrated a difference in recovery vs. controls. One of these patients demonstrated a high molecular weight complex for cTnI and cTnT demonstrating a macrocomplex involving both cTn. This patient demonstrated a rise and fall in cTn when measured by several commercial assays consistent with genuine acute cardiac injury. CONCLUSIONS: We identified several cases of macro-cTnT and described associated clinical and biochemical features.

Apparent Hyperthyroidism Caused by Biotin-Like Interference from IgM Anti-Streptavidin Antibodies.

BACKGROUND: Exclusion of analytical interference is important when there is discrepancy between clinical and laboratory findings. However, interferences on immunoassays are often mistaken as isolated laboratory artefacts. The mechanism of a rare cause of interference in two patients that caused erroneous thyroid function tests, and also affects many other biotin dependent immunoassays, was characterized and reported. PATIENT FINDINGS: Patient 1 was a 77-year-old female with worsening fatigue while taking carbimazole over several years. Her thyroid function tests, however, were not suggestive of hypothyroidism. Patient 2 was a 25-year-old female also prescribed carbimazole for apparent primary hyperthyroidism. Despite an elevated free thyroxine, the lowest thyrotropin on record was 0.17 mIU/L. In both cases, thyroid function tests performed by an alternative method were markedly different. Further characterization of both patients' serum demonstrated analytical interference on many immunoassays using the biotin-streptavidin interaction. Sandwich assays (e.g., thyrotropin, follicle-stimulating hormone, troponin T, beta-human chorionic gonadotropin) were falsely low, while competitive assays (e.g., free thyroxine, free triiodothyronine, TSH binding inhibitory immunoglobulin) were falsely high. Pre-incubation of serum with streptavidin microparticles removed the analytical interference, initially suggesting the cause of interference was biotin. However, neither patient had been taking biotin. Instead, a ∼100 kDa immunoglobulin M (IgM) immunoglobulin with high affinity to streptavidin was isolated from each patient's serum. The findings confirm IgM anti-streptavidin antibodies as the cause of analytical interference. SUMMARY: Two patients with apparent hyperthyroidism as a result of analytical interference caused by IgM anti-streptavidin antibodies are described. CONCLUSION: Analytical interference identified on one immunoassay should raise the possibility of other affected results. Characterization of interference may help to identify other potentially affected immunoassays. In the case of anti-streptavidin antibodies, the pattern of interference mimics that due to biotin ingestion. However, the degree of interference varies between individual assays and between patients.

Diagnostic Performance of Pleural Fluid Adenosine Deaminase for Tuberculous Pleural Effusion in a Low-Incidence Setting.

The challenges associated with diagnosing tuberculous pleural effusion have led to the use of pleural fluid adenosine deaminase (pfADA) as a biomarker for Mycobacterium tuberculosis infection. This study retrospectively reviewed the diagnostic performance of pfADA, the pleural fluid lactate dehydrogenase (LD)/ADA ratio, and combinations of these two parameters in 1,637 episodes of pleural effusion in the low-tuberculosis (TB)-incidence setting of Auckland, Aotearoa New Zealand, from between March 2008 and November 2014. The median pfADA in 57 TB pleural effusion episodes (58.1 U/liter) was significantly higher (P < 0.001) than in 1,580 non-TB pleural effusions (11.4 U/liter). The median LD/ADA ratio in TB pleural effusion (8.2) was significantly lower (P < 0.001) than in non-TB pleural effusions (30.5). The pfADA and pleural fluid LD/ADA ratio AUCROC values (that is, receiver operating characteristic [ROC] curve analysis with determination of the ROC area under the curve) were 0.93 and 0.94, respectively. The pfADA thresholds of ≥15 and ≥30 U/liter demonstrated sensitivities of 100% (95% confidence internal = 93.7 to 100) and 93.0% (83.3 to 97.2), specificities of 62.7% (60.3 to 65.0) and 87.3% (85.6 to 88.9), positive predictive values (PPVs) of 8.8% (6.9 to 11.2) and 20.9% (16.4 to 26.4), and negative predictive values (NPVs) of 100% (99.6 to 100) and 99.7% (99.3 to 99.9), respectively. LD/ADA ratio thresholds of <25 and <15 demonstrated sensitivities of 100% (93.5 to 100) and 89.1% (78.2 to 94.9), specificities of 61.6% (59.1 to 64.0) and 84.8% (82.9 to 86.5), PPVs of 8.5% (6.6 to 10.9) and 17.3% (13.3 to 22.0), and NPVs of 100% (99.6 to 100) and 99.5% (99.0 to 99.8), respectively. A combination of pfADA ≥ 30 U/liter and an LD/ADA ratio < 15 increased the specificity and PPV to 97.8% (96.9 to 98.4) and 57.3% (46.5 to 67.5) but decreased the sensitivity to 85.5% (73.8 to 92.4). The primary value of pfADA in a low-TB-incidence setting, such as Auckland, is in utilization of its high NPV.

Falsely raised whole blood chloride caused by systemic absorption of cerium nitrate cream for burns.

Whole blood, serum or plasma chloride is almost exclusively measured by potentiometry with an ion-selective chloride electrode which utilizes membrane selectivity to chloride ions. Other anions such as bromide, iodide and thiosulphate can interfere but usually are not present in high enough concentration to cause significant cross reactivity. A patient from our burns unit had serial chloride measurements on a Radiometer ABL800 blood gas analyser. The results were higher in contrast to plasma measurements on the Abbott Architect Ci8200, which were within reference intervals and in line with the patient's pathophysiological status. This indicated a likely interference with the blood gas analyser chloride estimation. The chloride results on the ABL800 for 3rd, 4th and 5th day after the burn accident were 170, 137 and 119 mmol/L. Corresponding plasma chloride results on the Ci8200 were all around 105 mmol/L. Nitrate was found to be markedly elevated in these samples, and the results were 6.7, 4.9 and 1.1 mmol/L, respectively (reference limit < 0.08 mmol/L). To further demonstrate nitrate was the causative agent, pooled plasma spiked with 7 mmol/L of sodium nitrate caused a rise in the ABL800 chloride from 105 to 202 mmol/L. Later we confirmed that the patient was topically medicated with cerium nitrate cream (Flammacerium®, Sinclair IS Pharma, UK) for his burns. In summary, the results clearly indicated nitrate was the interferent with the ABL800 chloride estimation and the source was the topical burns cerium nitrate cream.

Direct urine ammonium measurement: time to discard urine anion and osmolar gaps.

BACKGROUND: A failure of urine ammonium to increase during acidosis indicates impaired renal acidification, and the urinary ammonium concentration is therefore a useful investigation in determining the cause of a metabolic acidosis. However, urine ammonium measurements are not widely available in routine diagnostic laboratories. This has led to the use of urine anion or osmolar gaps, which are unsatisfactory as surrogates for urine ammonium measurement. METHODS: We evaluated the adaptation of two widely available automated plasma ammonium assays for measurement of urinary ammonium. RESULTS: Both assays showed good recovery and linearity in urine samples spiked with ammonium chloride, and acceptable precision. Urine ammonium concentrations estimated from urinary anion and osmolar gaps showed poor agreement with measured urine ammonium concentrations. CONCLUSIONS: Direct urine ammonium measurements are easily performed with modern autoanalysers by simple adaptation of routine plasma ammonium assays. The use of urine anion and osmolar gaps should be abandoned where direct measurement is available.

Troponins in acute kidney injury.

AIM: To investigate and describe cardiac troponins in subjects with acute kidney injury (AKI). METHODS: A prospective observational study of troponin in subjects presenting with AKI in a tertiary hospital. Creatine kinase-MB (CKMB), troponin I (Abbott Laboratories), and troponin T (Roche 4th generation) were measured. Patients with conditions known to cause elevated troponin levels were excluded. RESULTS: Nineteen subjects were enrolled in the study. Six subjects had troponin I and T concentrations above the 99th percentile of a reference population. There was high concordance of result between troponin I and troponin T. However, the concordance of elevated troponin levels with CKMB was less marked at 45%. Statistically significant factors associated with elevated troponin levels were age over 60 years, abnormal electrocardiogram, and history of previous ischemic heart disease. CONCLUSION: This is the first study able to demonstrate impaired renal function occurring acutely, without known confounders, results in elevated troponin levels. This suggests that impaired renal function disease influences plasma troponin levels in AKI as well as in chronic kidney failure.

Extreme hyperalphalipoproteinaemia in a patient with a solitary paraspinal lipoma.

Increased high-density lipoprotein (HDL)-cholesterol (hyperalphalipoproteinaemia; HALP) is commonly genetic, but may have secondary causes. An association between multiple lipomatosis and HALP has been reported; however, the mechanism for this is unclear. We report the case of a 69-year-old Cook Island woman with extreme HALP who presented with a large paraspinal lipoma. Magnetic resonance imaging showed no other lipomas. She had the metabolic syndrome, a family history suggestive of lipomas and was on lipid-lowering and antihypertensive therapy. Her plasma HDL-cholesterol concentration was 4.9 mmol/L (>95th percentile for age and sex) and was not explained by typical secondary causes. HDL(2) and HDL(3) subfractions were increased, with HDL(2) predominance. The excised lipoma histology demonstrated benign tissue and normal karyotype. Postoperative lipid profiles showed no change in HDL-cholesterol concentrations. In summary, we report a case of extreme HALP that persisted after excision of a solitary paraspinal lipoma.

The effects of seasonal variation of 25-hydroxyvitamin D on diagnosis of vitamin D insufficiency.

AIMS: To explore the effects of seasonal variation on the diagnosis of vitamin D sufficiency and to determine whether age, gender, and ethnicity modify these effects. METHODS: 21,987 adults had a measurement of serum 25-hydroxyvitamin D (25OHD) at Labplus, Auckland City Hospital, between January 2002 and September 2003, and sine curves were fitted for 25OHD versus day of year to predict the 25OHD nadir for each individual. RESULTS: 48% (range: 30-63%) of individuals had 25OHD <50 nmol/L in the month of measurement, but 63% were predicted to have 25OHD <50 nmol/L in late winter or early spring based on expected seasonal variation. The 25OHD levels required to ensure 25OHD levels >50 nmol/L throughout the year varied substantially by season (in summer at least 60-75 nmol/L), and tended to be higher in men than women, decrease with age, and vary with ethnicity. Mean 25OHD levels were very low (<40 nmol/L) in people of Indian, Middle Eastern, and African descent. CONCLUSION: Seasonal variation in 25OHD affects the diagnosis of vitamin D sufficiency. Clinicians should consider the month of sampling when interpreting the results of 25OHD measurements. In New Zealand, a summertime 25OHD <60-75 nmol/L is generally required to ensure year-round 25OHD levels <50 nmol/L.

A case of low cortisol-binding globulin: use of plasma free cortisol in interpretation of hypothalamic-pituitary-adrenal axis tests.

We investigated a patient with suspected hypopituitarism who showed subnormal cortisol responses to stimulation tests with adrenocorticotrophic hormone (ACTH) and hypoglycaemia, but normal ACTH and 11-deoxycortisol responses in the metyrapone test. Cortisol-binding globulin (CBG) was measured by enzyme-linked immunosorbent assay (ELISA), and was used to calculate plasma free cortisol and free cortisol index. The patient had a low plasma CBG concentration. Reinterpreted in terms of free cortisol and free cortisol index, his responses to ACTH were normal. We conclude that despite subnormal total cortisol responses to ACTH and hypoglycaemia, the patient had a normal hypothalamic-pituitary-adrenal (HPA) axis. Measurement of CBG concentration and calculation of free cortisol or free cortisol index can help avoid false interpretations of dynamic tests of the HPA axis based on plasma total cortisol.