The where, who and how of adrenal vein sampling in Australia and New Zealand.

INTRODUCTION: Primary aldosteronism (PA) causes 10-15% of cases of hypertension, and it is increasingly recognised as being under-diagnosed. An interventional radiology procedure, adrenal vein sampling (AVS), is a necessary and important diagnostic procedure for complete workup of PA. There is an anticipated increase in demand for AVS as detection of PA improves. This study aims to describe the current landscape of AVS in Australia and New Zealand (NZ). METHODS: Two surveys exploring AVS methodology and performance were conducted of (i) Endocrinology Unit Heads and (ii) interventional radiologists who perform AVS, at public hospitals with Endocrinology Units across Australia and NZ. RESULTS: Responses were received from 48/53 Endocrinology Unit Heads (91%) and 35 radiologists from 26 sites (87% of AVS sites). AVS was provided at 28/48 Endocrinology sites (58%) across Australia and NZ. In Australia, sites were concentrated in Victoria, New South Wales and Queensland with none in the Northern Territory; in NZ, sites were more evenly distributed across the North and South Islands. AVS was performed by 1-2 dedicated radiologists at 24 sites, 2-3 radiologists at two sites and a rotating roster of radiologists at two sites. Responses to both surveys revealed significant variation in AVS methodology and interpretation of AVS results. CONCLUSION: There is significant heterogeneity in the availability of AVS, the procedural details and the interpretation of results across Australia and NZ, which potentially impacts the quality of patient care and ability to scale up AVS capacity to meet increasing demand.

Predicting Bilateral Subtypes of Primary Aldosteronism Without Adrenal Vein Sampling: A Systematic Review and Meta-analysis.

CONTEXT: Primary aldosteronism (PA) is the most common endocrine cause of hypertension. The final diagnostic step involves subtyping, using adrenal vein sampling (AVS), to determine if PA is unilateral or bilateral. The complete PA diagnostic process is time and resource intensive, which can impact rates of diagnosis and treatment. Previous studies have developed tools to predict bilateral PA before AVS. OBJECTIVE: Evaluate the sensitivity and specificity of published tools that aim to identify bilateral subtypes of PA. METHODS: Medline and Embase databases were searched to identify published models that sought to subtype PA, and algorithms to predict bilateral PA are reported. Meta-analysis and meta-regression were then performed. RESULTS: There were 35 studies included, evaluating 55 unique algorithms to predict bilateral PA. The algorithms were grouped into 6 categories: those combining biochemical, radiological, and demographic characteristics (A); confirmatory testing alone or combined with biochemical, radiological, and demographic characteristics (B); biochemistry results alone (C); adrenocorticotropic hormone stimulation testing (D); anatomical imaging (E); and functional imaging (F). Across the identified algorithms, sensitivity and specificity ranged from 5% to 100% and 36% to 100%, respectively. Meta-analysis of 30 unique predictive tools from 32 studies showed that the group A algorithms had the highest specificity for predicting bilateral PA, while group F had the highest sensitivity. CONCLUSIONS: Despite the variability in published predictive algorithms, they are likely important for decision-making regarding the value of AVS. Prospective validation may enable medical treatment upfront for people with a high likelihood of bilateral PA without the need for an invasive and resource-intensive test.

Aldosterone and renin concentrations and blood pressure in young Indigenous and non-Indigenous adults in the Northern Territory: a cross-sectional study.

OBJECTIVES: To evaluate aldosterone and renin levels and aldosterone-to-renin ratios (ARRs) in young Indigenous and non-Indigenous adults in the Northern Territory, and their association with blood pressure levels. DESIGN: Cross-sectional study; single time point sub-study of two prospective birth cohort studies. SETTING, PARTICIPANTS: Participants in the Aboriginal Birth Cohort (ABC) - born to Indigenous mothers at the Royal Darwin Hospital during 1987-1990 - and the Top End Cohort (TEC) - people born to non-Indigenous mothers in Darwin, recruited during 2007-2009 - aged 32-35 years at the time of this sub-study. MAIN OUTCOME MEASURES: Plasma aldosterone and direct renin concentrations; ARRs (positive screening test result for primary aldosteronism defined as > 70 pmol/mU); systolic and diastolic blood pressure. RESULTS: A total of 255 ABC (205 in remote, 50 in urban locations) and 76 TEC members participated. Median aldosterone concentration was similar for all three groups. The median renin concentration was 7.5 mU/L (interquartile range [IQR], 4.1-12.4 mU/L) in the TEC group, 12.4 mU/L (IQR, 5.1-19 mU/L) in the urban ABC group, and 29.3 mU/L (IQR, 15.0-52.9 mU/L) in the remote ABC group. The median ARR was 10 pmol/mU (IQR, 6-19 pmol/mU) in the remote ABC group, 28 pmol/mU (IQR, 16-70 pmol/mU) in the urban ABC group, and 43 pmol/mU (IQR, 26-74 pmol/mU) in the TEC group. Thirteen urban ABC participants (26%), 21 TEC participants (28%), and six people in the remote ABC group (3%) had ARR values above 70 pmol/mU. Adjusted for age and body mass index (BMI), mean systolic and diastolic blood pressure were lower for women than men in all participant groups; after adjusting for age, sex, and BMI, larger ARR was associated with higher systolic blood pressure in the TEC group but not the two ABC groups. CONCLUSION: Screening test results for primary aldosteronism were positive for about one-quarter of urban Indigenous and non-Indigenous participants. A prospective study that includes confirmatory testing would more accurately assess the prevalence of primary aldosteronism among Indigenous Australians in the Northern Territory.

Mixed insulin can improve control of prednisolone-induced hyperglycaemia.

BACKGROUND: Hyperglycaemia is a common side effect of prednisolone, although there are no widely accepted guidelines for the management of glucocorticoid-induced hyperglycaemia (GIH). Our institution uses mixed insulin in a pre-breakfast or pre-breakfast and pre-lunch regimen, with the rationale that this profile of insulin action matches the physiological effect of prednisolone on blood glucose levels (BGLs). AIM: Evaluate the use of the mixed insulin (NovoMix30) in a pre-breakfast or pre-breakfast and pre-lunch regimen as management for GIH in a tertiary hospital setting. METHOD: We retrospectively evaluated all inpatients coprescribed prednisolone ≥7.5 mg and NovoMix30 for at least 48 hours over a 19-month period. BGLs were evaluated with repeated-measures analysis within four time periods across the day, beginning from the day prior to NovoMix30 administration. RESULTS: A total of 53 patients were identified. NovoMix30 significantly reduced BGLs in the morning (mean 12.7 ± 4.5 vs. 9.2 ± 3.9 mmol/L, P < 0.001), afternoon (mean 13.6 ± 3.8 vs. 11.9 ± 3.8 mmol/L, P = 0.001) and evening (12.1 ± 3.8 vs. 10.8 ± 3.8 mmol/L, P = 0.01). With uptitration of insulin over 3 days, 43% of all BGLs were within the target range, compared with 23% on day 0 (P < 0.001). The final median dose of NovoMix30 was 0.15 (0.10-0.22) units/kg bodyweight, or 0.40 (0.23-0.69) units/mg of prednisolone, which is lower than our hospital guideline recommends. One overnight hypoglycaemic event was observed. CONCLUSION: Mixed insulin as a pre-breakfast or pre-breakfast and pre-lunch regimen can target the hyperglycaemic pattern induced by prednisolone and minimise overnight hypoglycaemia. However, higher doses of insulin than those used in our study are likely required for optimal BGL control.

A low serum alkaline phosphatase may signal hypophosphatasia in osteoporosis clinic patients.

Low serum alkaline phosphatase (ALP) was found in 9% of patients attending an osteoporosis clinic, 0.6% of hospital patients, and 2/22 with an atypical femoral fracture. Hypophosphatasia was diagnosed in 3% of osteoporosis clinic patients with low ALP. Low ALP is a screening tool for hypophosphatasia, a condition potentially aggravated by antiresorptive therapy. INTRODUCTION: Hypophosphatasia (HPP) is an inherited disorder associated with impaired primary mineralisation of osteoid (osteomalacia). HPP may be misdiagnosed as osteoporosis, a reduction in the volume of normally mineralized bone. Both illnesses may result in fragility fractures, although stress and atypical fractures are more common in HPP. Antiresorptive therapy, first-line treatment for osteoporosis, is relatively contraindicated in HPP. Misdiagnosis and mistreatment can be avoided by recognising a low serum alkaline phosphatase (ALP). Our aim was to determine the prevalence of a low ALP (< 30 IU/L) in patients attending an osteoporosis clinic, in a hospital-wide setting, and in a group of patients with atypical femoral fractures (AFF). METHODS: This was a retrospective study of patients attending an osteoporosis clinic at a tertiary hospital during 8 years (2012-2020). Patients were categorised into those with a transiently low ALP, those with low ALP on ≥ 2 occasions but not the majority of measurements, and those with a persistently low ALP. ALP levels were also assessed in hospital-wide records and a group of patients with AFF. RESULTS: Of 1839 patients attending an osteoporosis clinic, 168 (9%) had ≥ 1 low ALP, 50 (2.7%) had low ALP for ≥ 2 months, and seven (0.4%) had persistently low ALP levels. HPP was diagnosed in five patients, four of whom had persistently low ALP levels. The prevalence of HPP was 0.3% in the osteoporosis clinic and 3% in patients with ≥ 1 low ALP. Low ALP occurred in 0.6% of all hospital patients and 2/22 with AFF. CONCLUSION: Persistently low ALP in osteoporosis clinic attendees is easy to identify and signals the possibility of hypophosphatasia, a condition that may be mistaken for osteoporosis and incorrectly treated with antiresorptive therapy.

Aldosterone, Renin, and Aldosterone-to-Renin Ratio Variability in Screening for Primary Aldosteronism.

CONTEXT: The plasma aldosterone concentration (PAC), renin, and aldosterone-to-renin ratio (ARR) are used to screen for primary aldosteronism (PA). Substantial intra-individual variability of PAC and ARR using plasma renin activity in the context of usual antihypertensive therapy has been described, but there is no data on ARR variability calculated using direct renin concentration (DRC). OBJECTIVE: To describe the intra-individual variability of PAC, DRC, and ARR in the absence of interfering medications in patients with and without PA. DESIGN: Retrospective cohort study. PATIENTS: Hypertensive patients referred for investigation of PA, with at least 2 ARR measurements while off interfering medications. SETTING: Endocrine hypertension service of a tertiary center, from May 2017 to July 2021. MAIN OUTCOME MEASURES: PAC, DRC, and ARR variability was calculated as coefficient of variation (CV) and percent difference (PD). RESULTS: Analysis of 223 patients (55% female, median age 52 years), including 162 with confirmed PA, demonstrated high variability with a sample CV of 22-25% in the PAC and sample CV of 41% to 42% in the DRC and ARR in both the PA and non-PA groups. The degree of variability was substantially higher than the assays' analytical CV. Sixty-two patients (38%) with PA had at least one ARR below 70 pmol/L:mU/L (2.4 ng/dL:mU/L), a cut-off for first-line screening of PA. CONCLUSIONS: Significant intra-individual variability in PAC, DRC, and hence ARR occurs in a large proportion of patients being investigated for PA. These findings support the need for at least 2 ARR before PA is excluded or further investigated.

Development and validation of model for sparing adrenal venous sampling in diagnosing unilateral primary aldosteronism.

CONTEXT: Current guidelines recommend adrenal venous sampling (AVS) to identify unilateral primary aldosteronism (UPA) before offering adrenalectomy. However, AVS is costly and technically challenging, limiting its use to expert centres. OBJECTIVE: To establish a model to predict UPA, and therefore, bypass the need for AVS prior to surgery. DESIGN AND SETTING: The model was developed in a Chinese cohort and validated in an Australian cohort. Previously published prediction models of UPA were also tested. PARTICIPANTS: primary aldosteronism patients with a definite subtyping diagnosis based on AVS and/or surgery. MAIN OUTCOME MEASURE: Diagnostic value of the model. RESULTS: In the development cohort (268 UPA and 88 bilateral primary aldosteronism), combinations of different levels of low serum potassium (≤3.0 or 3.5 mmol/l), high PAC (≥15-30 ng/dl), low PRC (≤2.5-10 µIU/ml) and presence of unilateral nodule on adrenal CT (>8-15 mm in diameter) showed specificity of 1.00 and sensitivity of 0.16-0.52. The model of serum potassium 3.5 mmol/l or less, PAC at least 20 ng/dl, PRC 5 µIU/ml or less plus a unilateral nodule at least 10 mm had the highest sensitivity of 0.52 (0.45-0.58) and specificity of 1.00 (0.96-1.00). In the validation cohort (84 UPA and 117 bilateral primary aldosteronism), the sensitivity and specificity of the model were 0.13 (0.07-0.22) and 1.00 (0.97-1.00), respectively. Ten previous models were tested, and only one had a specificity of 1.00 in our cohorts but with a very low sensitivity [0.07 (0.04-0.10) and 0.01 (0.00-0.06) in our development and validation cohorts, respectively]. CONCLUSION: A combination of high PAC, low PRC, low serum potassium and unilateral adrenal nodule could accurately determine primary aldosteronism subtype in 13-52% of patients with UPA and obviate the need for AVS before surgery.

Glucagon-like peptide-1 receptor agonist (GLP1-RA) therapy in type 2 diabetes.

BACKGROUND: Type 2 diabetes (T2D) is a national health priority. Its rising prevalence is accompanied by a high burden of diabetes-related complications, many of which are preventable. Numerous glucose-lowering medications have been developed in recent years with growing evidence relating to their efficacy and safety. These advances have increased the complexity of prescribing decisions in T2D. OBJECTIVE: This review provides clinicians with relevant evidence and practical advice concerning glucagon-like peptide-1 receptor agonists (GLP1-RAs) in T2D. DISCUSSION: The Royal Australian College of General Practitioners recommends GLP1-RAs as an option for second-line therapy in T2D. GLP1-RAs contribute to weight loss and glycated haemoglobin reduction. GLP1-RAs also reduce incidence of cardiovascular events in selected populations, and available evidence suggests renoprotective effects. Common adverse effects include gastrointestinal symptoms, especially in the weeks following treatment initiation. GLP1-RAs should be considered for people with T2D at high cardiovascular risk or where weight loss is a priority.

The Utility of Prophylactic Zoledronic Acid in Patients Undergoing Lung Transplantation.

Osteoporosis is prevalent among lung transplant candidates and is exacerbated post-transplant by immunosuppressive therapy. Low bone mineral density (BMD) is a well-recognized surrogate for fragility fracture risk, which is associated with significant morbidity and mortality. Intravenous zoledronic acid (ZA) effectively reduces BMD loss and prevents fractures in postmenopausal osteoporosis. Many groups, ours included, prophylactically treat lung transplant recipients (LTR) with bisphosphonates, but no documented consensus currently exists. Our protocol comprises ZA every 6-months from transplant wait-listing, with interval reassessment to guide ongoing treatment. We evaluate the impact of a dose of ZA within 6 months of transplantation on BMD and fracture occurrence. A retrospective analysis was performed on all adult LTR from April 2012 to October 2014, of which 60 met our inclusion criteria. LTR who received ZA within 6 months of transplantation (n = 37) were compared to those who did not (n = 23), and followed up for a minimum of three years. Outcome measures were BMD change at the lumbar spine and femur (primary), and fracture occurrence (secondary). LTR treated with ZA within 6 months of transplantation experienced a median BMD change of +8.11% at the lumbar spine and +1.39% at the femur, compared to -1.20% and -3.92%, respectively, in LTR who did not receive a ZA dose within 6 months of transplantation (p = 0.002 & p = 0.008 respectively). Our findings indicate that prophylactic ZA within 6 months of transplantation prevents BMD loss in LTR.

Prevalence of hyperglycaemia without previously recognised diabetes mellitus in the emergency department and subsequent management: a retrospective cross-sectional study.

BACKGROUND: Australian hospital data on hyperglycaemia without previously known diabetes are lacking. AIMS: To determine the prevalence of hyperglycaemia without previously recognised diabetes among all patients screened in the emergency department (ED). Secondary aims are to describe the extent of haemoglobin A1c testing for evaluation of new diabetes, adequate glucose monitoring, treatment of significant hyperglycaemia and documented follow-up plans. METHODS: Patients presenting to ED at the Alfred (tertiary hospital in Melbourne) have undergone screening random plasma glucose (RPG) with their first plasma biochemistry since 2015. Of the 16 268 adults screened from July to December 2015, a retrospective, cross-sectional study was undertaken evaluating those with hyperglycaemia (RPG >7.8 mmol/L) but without previously recognised diabetes as determined from coding data. After patient records were reviewed to correct for coding errors, a nested cohort of 200 such patients were further evaluated. Glucose monitoring was deemed adequate if undertaken for ≥48 h. Significant hyperglycaemia (RPG >11 mmol/L) was considered appropriately treated if insulin/hypoglycaemic agents were prescribed. Documented follow-up plans were acceptable if found in the discharge summary. RESULTS: Among all patients screened, 1178 had hyperglycaemia without coded diabetes. After adjusting for coding errors, the prevalence was 5.2%. Within the nested cohort, only 7.5% had a follow-up haemoglobin A1c ordered, 9.5% underwent adequate glucose monitoring, 6.5% had appropriate treatment of significant hyperglycaemia and 2% had documentation of a follow-up plan. CONCLUSIONS: Hyperglycaemia without previously recognised diabetes is commonly seen and justifies ED screening. However, management of newly detected hyperglycaemia in these patients is suboptimal and requires improvement.

Thrombus risk versus bleeding risk: a clinical conundrum.

A 62-year-old man presented to the Emergency Department with dyspnoea and central pleuritic chest pain radiating posteriorly to between the scapulae. His medical history included hypertension, osteoporosis and chronic kidney disease secondary to focal segmental glomerulosclerosis with relapsing nephrotic syndrome. Significant examination findings included a loud palpable P2 and a displaced apex beat. An ECG revealed sinus tachycardia with a right-bundle branch block and p-pulmonale. A CT pulmonary angiogram and aortogram demonstrated extensive bilateral pulmonary emboli and a descending thoracic aortic dissection. Subsequent ultrasound of the lower limbs confirmed an extensive, non-occlusive deep vein thrombosis in the right calf. Management of this patient involved therapeutic anticoagulation and tight blood pressure control, with plans for surgical repair delayed due to worsening renal impairment and subsequent supratherapeutic anticoagulation. Co-existence of an aortic dissection and PE has been rarely described and optimal management remains unclear.

Recognising the return of nutritional deficiencies: a modern pellagra puzzle.

A 34-year-old previously well woman presented with a 4-week history of diffuse erythema and crusting of skin affecting all four limbs. Examination revealed erythematous skin plaques associated with ulceration and fissuring affecting sun-exposed areas of all four limbs primarily on the dorsal surfaces, and a body mass index of 17 kg/m2 She was admitted under the infectious diseases unit, and an autoimmune and infective screen was performed which returned unremarkable. Dietetic consultation led to the diagnosis of severe protein-energy malnutrition, consequent to a severely restricted, primarily vegan, diet. Analysis of the patient's reported diet with nutritional software revealed grossly suboptimal caloric intake with risk of inadequacy for most micronutrients, vitamins and minerals, including niacin. Oral thiamine, multivitamin, iron supplementation and vitamin B complex were started, and a single intramuscular vitamin B12 dose was administered. Marked improvement was seen after 6 weeks, with near-complete resolution of skin changes. These findings supported a diagnosis of pellagra.

Menstrual cycle characteristics in women with persistent schizophrenia.

OBJECTIVE: Oestradiol has been implicated in the pathogenesis of schizophrenia. Women with schizophrenia often suffer with menstrual dysfunction, usually associated with low oestradiol levels, but whether menstrual dysfunction has an effect on their psychiatric symptoms is not well researched. The aim of this study is to document the menstrual characteristics of women with chronic schizophrenia with focus upon menstrual regularity, menstrual cycle length and menstrual symptoms. To determine which patient characteristics are associated with irregular menses and whether irregular menses are associated with the severity of psychotic symptoms, menstrual symptoms or depressive symptoms. METHOD: Cross-sectional analyses using baseline data of women enrolled in a clinical trial. Inclusion criteria include Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition, Text Revision diagnosis of schizophrenia, schizoaffective or schizophreniform disorder; aged between 18 and 51 years; residual symptoms of psychosis despite treatment with a stable dose of antipsychotic medication for at least 4 weeks. Menstrual cycle characteristics including regularity, cycle length and menstrual associated symptoms were documented. Symptoms of schizophrenia were measured using Positive and Negative Syndrome Scale, cognition was measured using Repeatable Battery for the Assessment of Neuropsychological Status and depression was assessed using the Montgomery-Asberg Depression Rating Scale. Blood samples were collected at baseline for hormone assays. RESULTS: Of the 139 women, 77 (55.4%) had regular menses, 57 (41%) had irregular menses and 5 (3.6%) women had missing data on their menstrual cycle. Use of atypical antipsychotics associated with hyperprolactinaemia was positively associated with irregular menses (odds ratio = 4.4, 95% confidence interval = [1.8, 10.9], p = 0.001), while age more than 30 years was negatively associated (odds ratio = 0.3, 95% confidence interval = [0.1, 0.6], p = 0.004). Women with irregular cycles had significantly lower oestradiol levels than women with regular cycles (213.2 ± 25.0 vs 299.0 ± 27.3, p = 0.03), but there was no difference in Positive and Negative Syndrome Scale, Montgomery-Asberg Depression Rating Scale or Repeatable Battery for the Assessment of Neuropsychological Status between those with regular and irregular cycles. The most common menstrual associated symptoms were decrease in mood with the menstrual cycle (64.8%), bloating (64.8%), cramps (59.7%), back pain (37.6%) and worsening of psychosis symptoms (32.4%). CONCLUSION: Regular menses are associated with higher oestradiol levels and higher rates of cyclical mood symptoms but are not associated with Positive and Negative Syndrome Scale scores. Understanding the effect the menstrual cycle can have on psychiatric illness, such as premenstrual exacerbations, is important for the holistic care of women with schizophrenia.