Hyperparathyroidism Jaw Tumor Syndrome, an Unforeseen Diagnosis.

Asymptomatic primary hyperparathyroidism (PHPT) is often missed in developing nations due to limited formal healthcare exposure and biochemical screening programs. Many patients are thus only diagnosed once symptomatic. We present a 32-year-old female who developed bony protrusions in her jaw during pregnancy, resulting in a stillbirth. Three months later, during a dental consultation for worsening toothache, jaw abnormalities were detected. Radiological studies revealed bilateral mandibular radiolucent lesions, and bone biopsy confirmed histological features consistent with a brown tumor. These findings raised concerns about underlying PHPT, which was confirmed with a markedly elevated parathyroid hormone level in the presence of significant hypercalcemia. Further examination revealed impaired renal function, normal urine calcium excretion, and bilateral nephrocalcinosis. Low bone mineral density was measured with dual-energy X-ray absorptiometry, and conventional radiology identified additional low-density bony lesions in keeping with brown tumors. A parathyroid MIBI confirmed the presence of a singular parathyroid adenoma. A vague but possible family history, the patient's young age, and the severe renal and skeletal involvement prompted genetic testing. A cell division cycle 73 (CDC73) pathogenic variant, in keeping with primary hyperparathyroidism jaw tumor syndrome, was identified.

A National Laboratory Perspective: The Impact of the Covid-19 Pandemic on the Management of Patients With Non-Communicable Disease in South Africa: Impact of COVID-19 on patients with noncommunicable diseases.

OBJECTIVE: The aim of this study was to determine the impact of the COVID-19 pandemic on test requests for the diagnosis and routine care of patients with various non-communicable diseases (NCD) across South Africa (SA). METHODS: A retrospective audit of laboratory test requests received from hospital outpatient departments and primary healthcare facilities across SA was performed. The following analytes were studied: glycated hemoglobin (HbA1c), lipids profiles, thyroid-stimulating hormone (TSH), and thyroxine (fT4), as well as triiodothyronine (fT3), serum protein electrophoresis (SPE), serum free light chains (SFLC), and prostate specific antigen (PSA); these tests were used as a proxy of NCD detection and follow-up. Requests received during the 3 waves of the pandemic were compared to requests received within the same period during 2017 - 2019. RESULTS: During the first wave, requests for all analytes were reduced, with the biggest reduction observed for SPE (- 37%); TSH (- 29%); fT4 (- 28%); and HbA1c (- 25%). Requests received from urban facilities showed a larger decrease compared to those from rural facilities. During the third wave there was an increase in requests for all analytes; the biggest increase observed was for fT3 (21%) and HbA1c (18%). CONCLUSIONS: The COVID-19 pandemic had a significant impact on the South African population receiving care in the public healthcare sector.

A guide to conducting systematic reviews of clinical laboratory tests.

Clinical laboratory professionals have an instrumental role in supporting clinical decision making with the optimal use of laboratory testing for screening, risk stratification, diagnostic, prognostic, treatment selection and monitoring of different states of health and disease. Delivering evidence-based laboratory medicine relies on review of available data and literature. The information derived, supports many national policies to improve patient care through clinical practice guidelines or best practice recommendations. The quality, validity and bias of this literature is variable. Hence, there is a need to collate similar studies and data and analyse them critically. Systematic review, thus, becomes the most important source of evidence. A systematic review, unlike a scoping or narrative review, involves a thorough understanding of the procedure involved and a stepwise methodology. There are nuances that need some consideration for laboratory medicine systematic reviews. The purpose of this article is to describe the process of performing a systematic review in the field of laboratory medicine, describing the available methodologies, tools and software packages that can be used to facilitate this process.

Serum-free light chain test utilisation at a South African academic laboratory and comparison with serum protein electrophoresis results.

Background: Serum protein electrophoresis (SPE), urine protein electrophoresis and immunofixation electrophoresis were traditionally utilised for the diagnosis of monoclonal gammopathies. The quantitative serum-free light chain (SFLC) assay is reportedly more sensitive and has been introduced to recent clinical guidelines. Objective: This study aimed to investigate SFLC test utilisation and describe SPE findings in patients with abnormal SFLC ratios. Methods: A retrospective audit of SFLC analyses was conducted in Cape Town, South Africa, from May 2018 to April 2020. Agreement between abnormal SFLC ratios and SPE results was determined in a sub-group of patients screened for monoclonal gammopathies. Serum-free light chains were analysed using Freelite® Kappa and Lambda assays. Results: Of the 1425 patients included in the audit, 741 (52%) had abnormal SFLC ratios; 636 (45%) had increased and 105 (7%) had decreased SFLC ratios. In a sub-group analysis of 117 new patients with an abnormal SFLC ratio, 57 had a monoclonal protein (M-protein) on SPE (49%), and 60 (51%) did not. Four out of 60 patients without M-protein had a plasma cell dyscrasia, while renal impairment or inflammatory response accounted for the rest. Of the 57 patients with a M-protein and abnormal SFLC ratio, 41 (72%) had a plasma cell dyscrasia, seven (12%) had lymphomas and nine patients (16%) were unclassifiable. Conclusion: Serum-free light chains should be requested when there is a high index of clinical suspicion. Neither SFLC nor SPE should be performed in isolation when screening patients for monoclonal gammopathy, to ensure that no patient is missed. What this study adds: The study adds to the evidence on SFLC test utilisation. Serum protein electrophoresis alone may miss cases of light chain myeloma, while SFLC performed in isolation may produce false positive results in the setting of inflammatory disorders or renal impairment, leading to unnecessary further investigation.

Survey and situation analysis of personal, employer-related, and environmental factors affecting participation in continuous professional development (CPD) programs of laboratory professionals in Africa.

OBJECTIVES: To determine the level and evaluate factors affecting the participation of laboratory professionals in continuous professional development (CPD) programs in eastern and southern Africa. METHODS: A survey was conducted among laboratory professionals from 14 countries. The CPD participation was defined as low if it was fewer than 2 CPD trainings in the past 2 years. Associations between categorical variables were tested for significance using Fisher exact test. RESULTS: Of the expected 400, 283 (70% response rate) individuals participated in the survey. Of these, 153 (54%) had low CPD participation and 199 (70%) were aware of CPD educational activities in their respective country. Those with diploma certificates attended more CPD programs (P < .001) than those with undergraduate and master's degrees. Awareness of CPD programs was associated with a higher level of CPD participation (P = .0001). Job satisfaction was significantly associated with high levels of CPD participation (P = .02). Other factors associated with high level of participation in CPD programs included affordability (P = .03), funding by employer (P = .0005), and awareness of legal CPD requirements (P = .002). CONCLUSIONS: The CPD programs are considered useful to an individual's professional development, although there was low participation. It is recommended that different formats and platforms be used to expand CPD programs.

Immunologic and vascular biomarkers of mortality in critical COVID-19 in a South African cohort.

Introduction: Biomarkers predicting mortality among critical Coronavirus disease 2019 (COVID-19) patients provide insight into the underlying pathophysiology of fatal disease and assist with triaging of cases in overburdened settings. However, data describing these biomarkers in Sub-Saharan African populations are sparse. Methods: We collected serum samples and corresponding clinical data from 87 patients with critical COVID-19 on day 1 of admission to the intensive care unit (ICU) of a tertiary hospital in Cape Town, South Africa, during the second wave of the COVID-19 pandemic. A second sample from the same patients was collected on day 7 of ICU admission. Patients were followed up until in-hospital death or hospital discharge. A custom-designed 52 biomarker panel was performed on the Luminex® platform. Data were analyzed for any association between biomarkers and mortality based on pre-determined functional groups, and individual analytes. Results: Of 87 patients, 55 (63.2%) died and 32 (36.8%) survived. We found a dysregulated cytokine response in patients who died, with elevated levels of type-1 and type-2 cytokines, chemokines, and acute phase reactants, as well as reduced levels of regulatory T cell cytokines. Interleukin (IL)-15 and IL-18 were elevated in those who died, and levels reduced over time in those who survived. Procalcitonin (PCT), C-reactive protein, Endothelin-1 and vascular cell adhesion molecule-1 were elevated in those who died. Discussion: These results show the pattern of dysregulation in critical COVID-19 in a Sub-Saharan African cohort. They suggest that fatal COVID-19 involved excessive activation of cytotoxic cells and the NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3) inflammasome. Furthermore, superinfection and endothelial dysfunction with thrombosis might have contributed to mortality. HIV infection did not affect the outcome. A clinically relevant biosignature including PCT, pH and lymphocyte percentage on differential count, had an 84.8% sensitivity for mortality, and outperformed the Luminex-derived biosignature.

An investigation of the correlation of vitamin D status and management outcomes in patients with severe COVID-19 at a South African tertiary hospital.

Background: Severe COVID-19 has a poor prognosis, and biomarkers may predict disease severity. This study aimed to assess the effect of baseline Vitamin D (VitD) inadequacy on outcome of patients with severe COVID-19 admitted to intensive care unit (ICU) in a tertiary hospital in South Africa. Methods: Patients with confirmed SARS-CoV-2 were recruited during wave II of the pandemic in Cape Town. Eighty-six patients were included in the study. They were categorized into three groups "VitD deficient, VitD insufficient and VitD sufficient". We combined the VitD deficient with insufficient group to form "VitD inadequate'' group. Cox regression analysis was done to assess the association between VitD status and mortality. Factors with p< 0.05 in adjusted multivariable cox regression were considered statistically significant. Results: The proportion of VitD inadequacy was 64% (55/86), with significantly higher proportion of hypertension (66%; p 0.012). Kaplan Meir curve showed no significant difference in the probability of survival among the COVID-19 patients admitted in the ICU with or without VitD inadequacy. However, patients with elevated serum creatinine were significantly more at risk of dying (Adjusted Hazard Ratio 1.008 (1.002 - 1.030, p<0.017). Conclusion: Our study found a high prevalence of VitD inadequacy (combined deficiency and insufficiency) in COVID-19 patients admitted to the ICU. This may indicate a possible risk of severe disease. Whilst there was no statistically significant relationship between VitD status and mortality in this cohort, baseline VitD may be an important prognostic biomarker in COVID-19 patients admitted to the ICU, particularly in those with comorbidities that predispose to VitD deficiency.

The Association between Plant-Based Diets and Dietary Patterns with Cardiometabolic Risk in a Sample of Commercial Taxi Drivers in South Africa.

The consumption of unhealthy foods and a sedentary lifestyle predispose individuals to non-communicable diseases. This study investigated the distribution and the association of plant-based diets (PBDs) and dietary patterns in relation to the cardiometabolic risks in commercial taxi drivers. A cross-sectional analysis was conducted among males (≥19 years) who consumed street foods sold by vendors in the Cape Metropole. A validated questionnaire was administered, including a quantified 24 h dietary recall, and fasting blood samples were collected for biochemical analyses. Statistical analyses were performed to investigate the association between dietary habits and cardiometabolic risks, while adjusting for confounding variables. The analytic sample consisted of 189 males with a median age of 38 years. The taxi drivers who ranked in the top-third of the healthy plant-based diet index (hPDI) had a 1-4% lower likelihood of having raised triglycerides (TG). Furthermore, consumption patterns including refined grains and meat conferred a 33% lower likelihood of dysglycaemia (p = 0.049), while fish/seafood, potatoes, and vegetables conferred a 43% greater likelihood of low high-density lipoprotein cholesterol (HDL-C) (p = 0.026) and 44% greater probability of raised low-density lipoprotein cholesterol (LDL-C) (p = 0.027). Consumption patterns, including sugar-sweetened beverages and eggs, conferred a 37% greater probability of hypertension (p = 0.047) and 53% greater likelihood of subclinical inflammation (p = 0.017). These preliminary findings require larger and more elaborate studies to explore the associations between PBDs and dietary patterns in at-risk African populations, with or without sedentary lifestyles, and exposure to unhealthy food environments.

Pathology-supported genetic testing for the application of breast cancer pharmacodiagnostics: family counselling, lifestyle adjustments and change of medication.

BACKGROUND: Pathology-supported genetic testing (PSGT) enables transitioning of risk stratification from the study population to the individual. RESEARCH DESIGN AND METHODS: We provide an overview of the translational research performed in postmenopausal breast cancer patients at increased risk of osteoporosis due to aromatase inhibitor therapy, as the indication for referral. Both tumor histopathology and blood biochemistry levels were assessed to identify actionable disease pathways using whole exome sequencing (WES). RESULTS: The causes and consequences of inadequate vitamin D levels as a modifiable risk factor for bone loss were highlighted in 116 patients with hormone receptor-positive breast cancer. Comparison of lifestyle factors and WES data between cases with vitamin D levels at extreme upper and lower ranges identified obesity as a major discriminating factor, with the lowest levels recorded during winter. Functional polymorphisms in the vitamin D receptor gene contributed independently to therapy-related osteoporosis risk. In a patient with invasive lobular carcinoma, genetic counseling facilitated investigation of the potential modifying effect of a rare CDH1 variant co-occurring with BRCA1 c.66dup (p.Glu23ArgfsTer18). CONCLUSION: Validation of PSGT as a three-pronged pharmacodiagnostics tool for generation of adaptive reports and data reinterpretation during follow-up represents a new paradigm in personalized medicine, exposing significant limitations to overcome.

The clinical and epidemiological characteristics of a series of patients living with HIV admitted for COVID-19 in a district hospital.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to evolve. Globally, COVID-19 continues to strain even the most resilient healthcare systems, with Omicron being the latest variant. We made a thorough search for literature describing the effects of the COVID-19 in a high human immunodeficiency virus (HIV)/tuberculosis (TB) burden district-level hospital setting. We found scanty literature. METHODS: A retrospective observational study was conducted at Khayelitsha District Hospital in Cape Town, South Africa (SA) over the period March 2020-December 2021. We included confirmed COVID-19 cases with HIV infection aged from 18 years and above. Analysis was performed to identify predictors of mortality or hospital discharge among people living with HIV (PLWH). Predictors investigated include CD4 count, antiretroviral therapy (ART), TB, non-communicable diseases, haematological, and biochemical parameters. FINDINGS: This cohort of PLWH with SARS-CoV-2 infection had a median (IQR) age of 46 (37-54) years, male sex distribution of 29.1%, and a median (IQR) CD4 count of 267 (141-457) cells/mm3. Of 255 patients, 195 (76%) patients were discharged, 60 (24%) patients died. One hundred and sixty-nine patients (88%) were on ART with 73(28%) patients having acquired immunodeficiency syndrome (AIDS). After multivariable analysis, smoking (risk ratio [RR]: 2.86 (1.75-4.69)), neutrophilia [RR]: 1.024 (1.01-1.03), and glycated haemoglobin A1 (HbA1c) [RR]: 1.01 (1.007-1.01) were associated with mortality. CONCLUSION: The district hospital had a high COVID-19 mortality rate among PLWH. Easy-to-access biomarkers such as CRP, neutrophilia, and HbA1c may play a significant role in informing clinical management to prevent high mortality due to COVID-19 in PLWH at the district-level hospitals.

The association between acid-base status and clinical outcome in critically ill COVID-19 patients admitted to intensive care unit with an emphasis on high anion gap metabolic acidosis.

OBJECTIVE: The aim of this study was to identify arterial blood gas (ABG) abnormalities, with a focus on a high anion gap (AG) metabolic acidosis and evaluate outcomes in coronavirus disease 2019 (COVID-19) patients admitted to the ICU. METHODS: A retrospective, observational study was conducted in a tertiary hospital in Cape Town during the first and second COVID-19 waves. Age, gender, sodium (Na), potassium (K), chloride (Cl), bicarbonate (HCO3std), pH, partial pressure of carbon dioxide (pCO2), creatinine, estimated glomerular filtration rate (eGFR), lactate levels and ABG results were obtained. The Pearson χ2 test or Fisher exact test and the Wilcoxon rank-sum test were used to compare mortality and survival. To identify factors associated with non-survival, a multivariable model was developed. RESULTS: This study included 465 patients, 226 (48%) of whom were female. The sample population's median (IQR) age was 54.2 (46.1-61.3) years, and 63% of the patients died. ABG analyses found that 283 (61%) of the 465 patients had alkalosis (pH ≥ 7.45), 65 (14%) had acidosis (pH ≤ 7.35) and 117 (25%) had normal pH (7.35-7.45). In the group with alkalosis, 199 (70.3%) had a metabolic alkalosis and in the group with acidosis, 42 (64%) had a metabolic acidosis with an increased AG of more than 17. Non-survivors were older than survivors (56.4 years versus 50.3 years, p < .001). CONCLUSION: Most of the COVID-19 patients admitted to the ICU had an alkalosis, and those with acidosis had a much worse prognosis. Higher AG metabolic acidosis was not associated with patients' characteristics.

Clinical characteristics associated with mortality of COVID-19 patients admitted to an intensive care unit of a tertiary hospital in South Africa.

BACKGROUND: Over 130 million people have been diagnosed with Coronavirus disease 2019 (COVID-19), and more than one million fatalities have been reported worldwide. South Africa is unique in having a quadruple disease burden of type 2 diabetes, hypertension, human immunodeficiency virus (HIV) and tuberculosis, making COVID-19-related mortality of particular interest in the country. The aim of this study was to investigate the clinical characteristics and associated mortality of COVID-19 patients admitted to an intensive care unit (ICU) in a South African setting. METHODS AND FINDINGS: We performed a prospective observational study of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection admitted to the ICU of a South African tertiary hospital in Cape Town. The mortality and discharge rates were the primary outcomes. Demographic, clinical and laboratory data were analysed, and multivariable robust Poisson regression model was used to identify risk factors for mortality. Furthermore, Cox proportional hazards regression model was performed to assess the association between time to death and the predictor variables. Factors associated with death (time to death) at p-value < 0.05 were considered statistically significant. Of the 402 patients admitted to the ICU, 250 (62%) died, and another 12 (3%) died in the hospital after being discharged from the ICU. The median age of the study population was 54.1 years (IQR: 46.0-61.6). The mortality rate among those who were intubated was significantly higher at 201/221 (91%). After adjusting for confounding, multivariable robust Poisson regression analysis revealed that age more than 48 years, requiring invasive mechanical ventilation, HIV status, procalcitonin (PCT), Troponin T, Aspartate Aminotransferase (AST), and a low pH on admission all significantly predicted mortality. Three main risk factors predictive of mortality were identified in the analysis using Cox regression Cox proportional hazards regression model. HIV positive status, myalgia, and intubated in the ICU were identified as independent prognostic factors. CONCLUSIONS: In this study, the mortality rate in COVID-19 patients admitted to the ICU was high. Older age, the need for invasive mechanical ventilation, HIV status, and metabolic acidosis were found to be significant predictors of mortality in patients admitted to the ICU.

Haematological predictors of poor outcome among COVID-19 patients admitted to an intensive care unit of a tertiary hospital in South Africa.

BACKGROUND: Studies from Asia, Europe and the USA indicate that widely available haematological parameters could be used to determine the clinical severity of Coronavirus disease 2019 (COVID-19) and predict management outcome. There is limited data from Africa on their usefulness in patients admitted to Intensive Care Units (ICUs). We performed an evaluation of baseline haematological parameters as prognostic biomarkers in ICU COVID-19 patients. METHODS: Demographic, clinical and laboratory data were collected prospectively on patients with confirmed COVID-19, admitted to the adult ICU in a tertiary hospital in Cape Town, South Africa, between March 2020 and February 2021. Robust Poisson regression methods and receiver operating characteristic (ROC) curves were used to explore the association of haematological parameters with COVID-19 severity and mortality. RESULTS: A total of 490 patients (median age 54.1 years) were included, of whom 237 (48%) were female. The median duration of ICU stay was 6 days and 309/490 (63%) patients died. Raised neutrophil count and neutrophil/lymphocyte ratio (NLR) were associated with worse outcome. Independent risk factors associated with mortality were age (ARR 1.01, 95%CI 1.0-1.02; p = 0.002); female sex (ARR 1.23, 95%CI 1.05-1.42; p = 0.008) and D-dimer levels (ARR 1.01, 95%CI 1.002-1.03; p = 0.016). CONCLUSIONS: Our study showed that raised neutrophil count, NLR and D-dimer at the time of ICU admission were associated with higher mortality. Contrary to what has previously been reported, our study revealed females admitted to the ICU had a higher risk of mortality.

Latent class analysis: an innovative approach for identification of clinical and laboratory markers of disease severity among COVID-19 patients admitted to the intensive care unit.

Objective: The aim of this study was to identify clinical and laboratory phenotype distribution patterns and their usefulness as prognostic markers in COVID-19 patients admitted to the intensive care unit (ICU) at Tygerberg Hospital, Cape Town. Methods and results: A latent class analysis (LCA) model was applied in a prospective, observational cohort study. Data from 343 COVID-19 patients were analysed. Two distinct phenotypes (1 and 2) were identified, comprising 68.46% and 31.54% of patients, respectively. The phenotype 2 patients were characterized by increased coagulopathy markers (D-dimer, median value 1.73 ng/L vs 0.94 ng/L; p < 0.001), end-organ dysfunction (creatinine, median value 79 µmol/L vs 69.5 µmol/L; p < 0.003), under-perfusion markers (lactate, median value 1.60 mmol/L vs 1.20 mmol/L; p < 0.001), abnormal cardiac function markers (median N-terminal pro-brain natriuretic peptide (NT-proBNP) 314 pg/ml vs 63.5 pg/ml; p < 0.001 and median high-sensitivity cardiac troponin (Hs-TropT) 39 ng/L vs 12 ng/L; p < 0.001), and acute inflammatory syndrome (median neutrophil-to-lymphocyte ratio 15.08 vs 8.68; p < 0.001 and median monocyte value 0.68 × 109/L vs 0.45 × 109/L; p < 0.001). Conclusion: The identification of COVID-19 phenotypes and sub-phenotypes in ICU patients could help as a prognostic marker in the day-to-day management of COVID-19 patients admitted to the ICU.

Audit of amylase and lipase requests in suspected acute pancreatitis and cost implications, South Africa.

Background: The internationally accepted criteria for the diagnosis of acute pancreatitis (AP) requires two of the three following features to be present: characteristic abdominal pain, elevated serum amylase and/or lipase enzymes, or consistent imaging results. However, sensitivity and specificity can vary depending on the population and cut-off values used. Objective: This study evaluated the suitability of amylase and lipase as first-line diagnostic biomarkers of suspected AP for the local population served by Tygerberg Hospital, South Africa. Methods: This retrospective analysis was conducted in June 2019 using all amylase and/or lipase request data from December 2018. Patient clinical data were included in sensitivity and specificity analyses of amylase, lipase or dual requests for diagnosis of AP. Cost per test data were obtained from the National Health Laboratory Service and used to calculate the total cost of the tests and potential savings. Results: Sensitivity for lipase was 90.0% compared to 50.0% for amylase. Specificity was similar for singular measurements of lipase and amylase. Dual measurement of amylase and lipase showed no improvement in sensitivity (83.3%) and only a minor increase in specificity (97.4%) compared with measurement of lipase alone. The estimated savings was R2522.85 ($174.98 USD), with a potential annual cost saving of R84 423.74 ($5855.69 USD). Conclusion: Lipase was shown to be a more sensitive biomarker compared to amylase for the screening of AP, providing evidence for laboratories to educate local staff and promote improved requesting practices by clinicians. Additionally, preventing unnecessary dual requests may reduce costs.

Consumption of Plant Foods and Its Association with Cardiovascular Disease Risk Profile in South Africans at High-Risk of Type 2 Diabetes Mellitus.

We assessed the distribution and association of cardiovascular disease (CVD) risk factors by plant foods consumption in individuals at high-risk for type 2 diabetes mellitus. This cross-sectional study utilized baseline data of 693 participants in the South African Diabetes Prevention Programme. Participants underwent a physical examination, biochemical analysis, and dietary assessment using a single non-quantified 24-h recall. Group comparisons were conducted to explore the distribution and associations of common CVD risk factors by plant foods consumption. The mean age of the participants was 51 years, with 81% being females. Consumers of yellow-coloured vitamin A-rich vegetables and tubers and maize had significantly lower systolic blood pressure, fasting insulin, low-density lipoprotein cholesterol, triglycerides, and fibrinogen levels. Cereals consumption increased the likelihood of obesity (OR = 1.72 95% CI [1.09, 2.70] p = 0.019) while the consumption of white roots and tubers decreased the likelihood of obesity (AOR = 0.64 95% CI [0.41, 1.00] p = 0.048). This study reported the consumption of some healthy plant foods with lower levels of, and decreased risk for, some CVD risk factors. A further in-depth investigation is needed to understand these associations.

Performance of glucagon stimulation test in diagnosing central adrenal insufficiency in children when utilising the Roche Elecsys® cortisol II assay: a pilot study.

OBJECTIVES: The glucagon stimulation test (GST) is used for the simultaneous assessment of central adrenal insufficiency (CAI) and growth hormone deficiency. The new Roche cortisol II (C II) assay was recently introduced, confounding interpretation of the GST. The performance of the GST in diagnosing central adrenal insufficiency (CAI), utilising the C II assay, was therefore compared with that of the overnight metyrapone test (ONMTPT). METHODS: A diagnostic accuracy study was performed by retrospectively analysing folders and laboratory records of 25 children and adolescents investigated for hypopituitarism with the GST and the ONMTPT between September 2016 and December 2019. The peak serum cortisol (C) of the GST, the post-metyrapone serum 11-deoxycortisol and adrenocorticotropin levels of the ONMTPT were recorded. Diagnostic performance of the GST at a previously suggested cut-off of 374 nmol/L was evaluated. RESULTS: Seventeen boys and 8 girls, aged 1.7-16.3 years (median 7.3 years) were identified. The sensitivity of the post-GST C-level at 374 nmol/L was 0.40 (95% confidence interval [CI] 0.17-0.69), specificity 0.64 (95% CI 0.39-0.84), positive predictive value 0.44 (95% CI 0.19-0.73), negative predictive value 0.60 (95% CI 0.36-0.80), accuracy 0.54 (95% CI 0.35-0.72), positive likelihood ratio (+LR) 0.93 (95% CI 0.49-1.77) and negative LR 1.12 (95% CI 0.40-3.15). The area under the receiver of operating characteristics (ROC) curve was 0.379 (95% CI 0.142-0.615). CONCLUSIONS: This study suggests that the GST at any C II cut-off cannot replace the ONMTPT as a diagnostic test for CAI in children. Findings should be confirmed in a larger study.

Combining HbA1c and glycated albumin improves detection of dysglycaemia in mixed-ancestry South Africans.

Background: Combining HbA1c with glycated albumin (GA) may improve detection of dysglycaemia. As BMI correlates positively with HbA1c and negatively with GA, HbA1c may be more effective in obese and GA in nonobese individuals. Methods: To relate these findings to Africans, we assessed in 1274 South Africans living in CapeTown (male 26%; age 48±16y; BMI 28.7 kg/m2 (range 15.6-73.8); obesity 39.9% and no prior diabetes history) the: (1) correlation of BMI with HbA1c and GA, (2) ability of HbA1c and GA separately and jointly, to detect OGTT-diagnosed dysglycaemia (diabetes plus prediabetes). Data collection took place between 2014 and 2016 in the City of Cape Town. Dysglycaemia was diagnosed by glucose criteria for the OGTT. Youden index was used to optimize diagnostic thresholds for HbA1c and GA. Findings: Normal glucose tolerance, prediabetes and diabetes occurred in 76%, 17% and 7%, respectively. BMI positively correlated with HbA1c [r = 0·34 [95%CI: 0·29,0·39)] and negatively with GA [-0·08 (0·13,0·03)]. For HbA1c the optimal threshold by Youden-index for dysglycaemia diagnosis was: 6·0% (95%CI: 5·8,6·2) and for GA: 13·44% (12·72,14·71). In the nonobese, obese and total cohort, HbA1c-alone detected: 51% (42-60), 72% (65,78), 63% (57,68), respectively; GA-alone detected 55% (52% (46,63), 52% (44, 59) and 53% (47,53), respectively; whereas: HbA1c+GA detected: 69% (60,76), 82% (75,87) and 76% (71, 81). Therefore, for the total cohort detection of dysglycaemia HbA1c-alone vs HbA1c+GA detected 63% (57,68) vs 76% (71,81). Interpretation: The opposite correlations of HbA1c and GA with BMI have now been demonstrated in an African-based population. Improving detection of dysglycaemia by combining HbA1c and GA has important implications for diabetes risk screening. Funding: AES is supported by the intramural programs of the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Minority Health and Health Disparities of the National Institutes of Health (NIH, Bethesda, Maryland, USA). DBS is supported by the intramural program of the Clinical Center of NIH. The South African Medical Research Council (SAMRC) funded the VMH study with funds from the National Treasury under its Economic Competitiveness and Support Package (MRC-RFA-UFSP-01-2013/VMH Study).