Nimalie Perera

Suboptimal Performance of Blood Glucose Meters in an Antenatal Diabetes Clinic

OBJECTIVE The objective of this study was to evaluate the performance of blood glucose meters in diabetes associated with pregnancy (DP). RESEARCH DESIGN AND METHODS Finger-prick blood glucose levels measured using six different glucose meters on 102 patients with DP attending an antenatal clinic were compared with laboratory plasma glucose results. HbA1c and hematocrit were also measured. RESULTS The plasma glucose range was 2.2–9.4 mmol/L with hematocrit 33–37% and mean HbA1c 5.5% ± 0.56 (SD). All meters provided plasma equivalent results except one, which reported whole blood glucose that was adjusted to plasma equivalent values. The absolute glucose difference [meter − plasma glucose] was 0.232 ± 0.69 to 0.725 ± 0.62 mmol/L mean ± SD and bias ranged from 6.1 to 15.8%. Two meters were affected by hematocrit <36% (P < 0.05). CONCLUSIONS Blood glucose meters in current use are not optimally accurate when compared with plasma glucose measurement in DP. Recognition of this deviation is essential to prevent inappropriate treatment of DP.

The danger of using inappropriate point‐of‐care glucose meters in patients on icodextrin dialysis

Diabet. Med. 28, 1272–1276 (2011)

Refsum's Disease—Use of the Intestinal Lipase Inhibitor, Orlistat, as a Novel Therapeutic Approach to a Complex Disorder

Refsums Disease is an inherited metabolic disorder in which a metabolite of branched chain fatty acids accumulates due to lack of appropriate oxidative enzymes. Patients have elevated plasma phytanic acid levels and high concentrations of phytanic acid in a variety of tissues leading to progressive tissue damage. Besides retinal degeneration or retinal dystrophy associated with adult onset retinitis pigmentosa, additional symptoms include chronic polyneuropathy, cerebellar ataxia, sensorineural hearing loss, anosmia, ichthyosis, as well as skeletal, cardiac, hepatic, and renal abnormalities. Current management includes avoidance of dietary sources of branched chain fatty acids and regular plasmapheresis to prevent accumulation of these compounds to ameliorate progressive neurological deficits. Two brothers with Refsums disease who experienced progressive symptoms despite optimal diet and plasmapheresis were commenced on a novel therapy. We report the effect of the intestinal lipase inhibitor, Orlistat, which led to significant reduction (P-value <0.001 on 2-sample unpaired t-test) of mean preplasmapheresis phytanic acid levels with retardation of the progression of most of their dermatological and neurological symptoms.

Hypoadrenalism secondary to topical corticosteroid-containing skin-lightening cream: danger of over-the-counter cosmetic agents.

A 26-year-old Sudanese woman was referred to the endocrinology clinic for investigation of low serum cortisol detected during investigations for fertility difficulties. There were no symptoms or signs to suggest adrenal insufficiency, nor did she have any overt Cushingoid features to suggest exogenous glucocorticoid exposure. Her blood pressure was 120/84 mmHg without postural drop. Although she had a generalised dark complexion, her face was a lighter shade compared with the rest of her body.

The complexity of laboratory testing and diagnosis of steroid excess syndromes associated with herbal remedy use

A middle-aged man presented to an outpatient clinic with features of steroid excess including gradual weight gain, facial/peripheral oedema and truncal adiposity. He had a history of hypercholesterolaemia, hypertension, surgical treatment for left varicocele and infertility with oligospermia. He had symptoms of reduced libido, erectile dysfunction and premature ejaculation for >5 years. This resulted in intermittent use of herbal supplements obtained from his country including ‘Mustika Dewa’ to reduce cholesterol, improve energy levels and ‘Raja Syifa’ for sexual dysfunction (Table 1). Serum electrolytes, creatinine, liver and thyroid function tests, prolactin, fasting plasma glucose and full blood count were normal. The 08Æ00h testosterone level was below the reference interval for his age at 5Æ9 nmol/l (range 6Æ3–26Æ3 nmol/l) with luteinizing hormone 3Æ2 mIU/l ‘low normal’ (range 1Æ0–10Æ0 mIU/l) and high follicle-stimulating hormone 19Æ4 mIU/l (range 1Æ0–8Æ5 mIU/l) in keeping with clinical features of hypogonadism. Fasting total cholesterol was 6Æ4 mmol/l (range 3Æ3–5Æ5 mmol/l), with low-density lipoprotein-cholesterol 4Æ1 mmol/l (Target < 2Æ5 mmol/l, international diabetes federation (IDF) lipid management guidelines). In this patient with physical findings of Cushing’s syndrome and hypogonadism, the plasma cortisol level was surprisingly unmeasurable at <28 nmol/l (range 200–600 nmol/l) and adrenocorticotrophic hormone (ACTH) was completely suppressed to below the limit of detection at <1Æ1 pmol/l (range 2–10 pmol/l). Furthermore, the 24 -h urine free cortisol (UFC) excretion rate was not elevated and was at the lower end of the reference interval at 61 nmol/day (range 50–250 nmol/day). The patient was gradually weaned off the herbal supplements over a few weeks, with close monitoring. A short-synacthen-test performed prior to complete cessation showed an adequate cortisol response 200 nmol/l base line and >550 nmol/l peak, with measurable ACTH 1Æ2 pmol/l, consistent with recovery of the hypothalamic-pituitary-adrenocortical (HPA) axis. This was accompanied by regression of cushingoid features including weight loss, reduction in central adiposity, stabilization of blood pressure and lipids with no change to therapy. Serum and urinary cortisol and ACTH were measured using routine solid-phase competitive chemiluminescent-enzymeimmunoassay on an Immulite2000 automated analyser (Diagnostic Products Corporation, CA,USA) with sensitivity 5Æ5 nmol/l, 1Æ1 pmol/l, 0Æ7 nmol/l respectively, and percentage coefficient of variation for all the assays was less than 10%. This routine cortisol immunoassay is most specific for cortisol with some cross-reactivity to prednisolone (62%), methylprednisone (22%), prednisone (6Æ1%), corticosterone (7Æ5%), cortisone (1Æ0%) and no crossreactivity with other steroids including dexamethasone, beclomethasone, androstenedione or dehydroepiandrosterone sulphate. Serum from the initial sample was then re-analysed by an alternative in-house radioimmunoassay (RIA) method (SEALS, Sydney, NSW, Australia), which is most specific for dexamethasone with insignificant (<0Æ1%) cross-reactivity with other steroids except cortisol 1Æ6%, 11-deoxycortisol 0Æ5%, corticosterone 0Æ5%, 6bhydroxycortisol 0Æ3% and testosterone 0Æ1%. This was positive for a ‘dexamethasone-like-immunoreactive-substance’ (1Æ60 nmol/l), indicating that this exogenous substance was causing endogenous suppression of the HPA axis and his clinical phenotype. UFC is a valuable screening test for endogenous hypercortisolism and false-negative results are unusual, i.e. UFC excretion is reduced with renal impairment, which was not the case in this patient. False-positive UFC results, however, may occur in a few situations such as endogenous depression, poorly controlled DM, high fluid intake, alcoholism, severe obesity, intake of drugs that inhibit 11ß-hydroxysteroid dehydrogenase (liquorice, carbenoxolone) or drugs with variable positive interference with CYP3A4 inducible metabolites of cortisol (rifampicin, phenytoin, phenobarbital and antipyrine). UFC excretion rate has a preliminary extraction of free cortisol before measurement is performed because large number of cortisol metabolites and conjugates in the urine can cross-react with the antibody in the immunoassay. These interfering substances are more soluble than cortisol in urine. Hence, cortisol is first extracted into organic solvents such as dichloromethane (DCM) or ethyl acetate to give a more precise UFC measurement. This patient’s DCM-extracted sample measured for UFC was not increased, while the same urine sample re-tested without the preliminary extraction step revealed the presence of a large molecular weight, soluble nonquantifiable substance possibly representing the exogenous substance and/or its metabolites excreted in this patient’s urine. The herbal preparations were subjected to in vitro analysis on the antibody-based immunoassay platforms after mixing the powders from each sachet individually in Hepes buffer (physiological solution), Table 1. In vivo, however, the ‘possible’ low level of cross-reactivity and significant dilution of these ‘dexamethasone-like-immunoreactive-substances, as well as the extractability of the exogenous substances or its metabolites with DCM in the urine, explains the low serum and urine cortisol levels, respectively, measured on the routine immunoassay platform. Non-antibody-based immunoassays (i.e. structural-based assays) such as tandem mass spectrometry or high-performance liquid chromatography were not available to us at that time for more precise identification of the undisclosed glucocorticoids in each of these samples. Important aspect of this paper is to present the complexities of interpreting ‘routine’ pathology including an unusual situation of false-negative cortisol results with complementary medicine use. Clinical Endocrinology (2011) 74, 276–279

Evaluation of the impact of icodextrin metabolite interference on the accuracy of hospital based glucose meters

Background Accurate glucose measurement is an essential requirement for tight glucose control, especially in critical care environments. 1 Oligomeric forms of maltose that are metabolites of the icodextrin glucose polymer used to maintain the osmotic gradient across the peritoneal membrane in peritoneal-dialysis patients has been shown to result in overestimation of blood glucose values in several point-of-care (POC) glucose analysers with harmful consequences to patients. 2,3 However, the extent of this interference or its impact on intravenous or subcutaneous insulin dosing is not well documented with the current POC glucose measurement methods. Method In this study we compared the analytical interference produced by three Icodextrin metabolites on venous whole blood specimens on five glucometers and in a POC blood-gas analyser. The values obtained were compared with the plasma values, from the same venous whole blood samples, analysed by the hexokinase reference (HK) method. Precision (within run accuracy) and bias were determined for all methods. Results All three metabolites showed clinically significant interference (>10% change) with glucose measurement in three of five glucometers but no significant interference was observed on the blood-gas analyser or the HK methods. The precision was acceptable for most meters (CV Conclusion Interference with the three icodextrin metabolites and correlation to plasma reference method values are the main variables that differentiate the methods. Methods that correlate with the laboratory reference method and have minimal interference with other glucose polymers are preferred for safe glycaemic control in patients using icodextrin for peritoneal dialysis or exposed to metabolites of icodextrin.