Elevated glucose promotes MMP13 and ADAMTS5 production by osteoarthritic chondrocytes under oxygenated but not hypoxic conditions.

Type 2 diabetes is linked with increased incidence and severity of osteoarthritis. The purpose of this study was to determine the effect of extracellular glucose within the normal blood glucose and hyperglycemic range on catabolic enzyme production by chondrocytes isolated from osteoarthritic (OA) and macroscopically normal (MN) human cartilage under oxygenated (18.9% oxygen) and hypoxic (1% oxygen) conditions. OA and MN chondrocytes were maintained in 4, 6, 8, or 10 mM glucose for 24 h. Glucose consumption, GLUT1 glucose transporter levels, MMP13 and ADAMTS5 production, and levels of RUNX2, a transcriptional regulator of MMP13, ADAMTS5, and GLUT1, were assessed by enzyme-linked assays, RT-qPCR and/or western blot. Under oxygenated conditions, glucose consumption and GLUT1 protein levels were higher in OA but not MN chondrocytes in 10 mM glucose compared to 4 mM. Both RNA and protein levels of MMP13 and ADAMTS5 were also higher in OA but not MN chondrocytes in 10 mM compared to 4 mM glucose under oxygenated conditions. Expression of RUNX2 was overall lower in MN than OA chondrocytes and there was no consistent effect of extracellular glucose concentration on RUNX2 levels in MN chondrocytes. However, protein (but not RNA) levels of RUNX2 were elevated in OA chondrocytes maintained in 10 mM versus 4 mM glucose under oxygenated conditions. In contrast, neither RUNX2 levels or MMP13 or ADAMTS5 expression were increased in OA chondrocytes maintained in 10 mM compared to 4 mM glucose in hypoxia. Elevated extracellular glucose leads to increased glucose consumption and increased RUNX2 protein levels, promoting production of MMP13 and ADAMTS5 by OA chondrocytes in oxygenated but not hypoxic conditions. These findings suggest that hyperglycaemia may exacerbate chondrocyte-mediated cartilage catabolism in the oxygenated superficial zone of cartilage in vivo in patients with undertreated type 2 diabetes, contributing to increased OA severity.

Examining the impact of COVID-19 on Maori:non-Maori health inequities in Aotearoa, New Zealand: an observational study protocol.

INTRODUCTION: The COVID-19 pandemic has had both direct and indirect impacts on the health of populations worldwide. While racial/ethnic health inequities in COVID-19 infection are now well known (and ongoing), knowledge about the impact of COVID-19 pandemic management on non-COVID-19-related outcomes for Indigenous peoples is less well understood. This article presents the study protocol for the Health Research Council of New Zealand funded project 'Ma te Mohio ka Marama: Impact of COVID-19 on Maori:non-Maori inequities'. The study aims to explore changes in access to healthcare, quality of healthcare and health outcomes for Maori, the Indigenous peoples of Aotearoa New Zealand (NZ) and non-Maori during the COVID-19 outbreak period across NZ. METHODS AND ANALYSIS: This observational study is framed within a Kaupapa Maori research positioning that includes Kaupapa Maori epidemiology. National datasets will be used to report on access to healthcare, quality of healthcare and health outcomes between Maori and non-Maori during the COVID-19 pandemic in NZ. Study periods are defined as (a) prepandemic period (2015-2019), (b) first pandemic year without COVID-19 vaccines (2020) and (c) pandemic period with COVID-19 vaccines (2021 onwards). Regional and national differences between Maori and non-Maori will be explored in two phases focused on identified health priority areas for NZ including (1) mortality, cancer, long-term conditions, first 1000 days, mental health and (2) rheumatic fever. ETHICS AND DISSEMINATION: This study has ethical approval from the Auckland Health Research Ethics Committee (AHREC AH26253). An advisory group will work with the project team to disseminate the findings of this project via project-specific meetings, peer-reviewed publications and a project-specific website. The overall intention of the project is to highlight areas requiring health policy and practice interventions to address Indigenous inequities in health resulting from COVID-19 pandemic management (both historical and in the future).

Audit of antimicrobial stewardship in medical inpatients in Waikato, New Zealand 2021.

AIMS: Given the threat of rising antimicrobial resistance (AMR), 10 audit standards were selected to audit antimicrobial stewardship (AMS) in secondary care to assess guideline adherence and establish quality improvement initiatives in antimicrobial prescribing. METHODS: Patients were included if they received intravenous (IV) antibiotics across seven medical wards in Waikato or Thames hospitals, New Zealand, in November 2021. Audit standards were defined from the regional antimicrobial prescribing policy and adult antimicrobial guidelines. RESULTS: In total, 205 patients were audited. Microbiological sampling standards were met in 87 of 126 occasions (69.0%). Antimicrobial choices adhered to guidelines in 89 of 163 patients (54.6%), where guidelines were available. Documentation of antimicrobial indications in the medical notes and antimicrobial review at 48 to 72 hours met the standards at over 90%. Only 2 of 13 patients (15.4%) receiving piperacillin/tazobactam or a carbapenem were discussed with Infectious Diseases (ID). Documentation of indications and durations on paper-based medication charts was infrequent, around 12%. Evaluating for health equity, similar results were observed for Maori and non-Maori. CONCLUSIONS: Our audit identified specific areas for AMS quality improvement initiatives. Regular audit should become an essential element of the New Zealand AMS strategy. We believe increased AMS resources are required.

Phenotype and energy metabolism differ between osteoarthritic chondrocytes from male compared to female patients: Implications for sexual dimorphism in osteoarthritis development?

OBJECTIVES: The prevalence and severity of knee osteoarthritis (OA) are greater in females than males. The purpose of this study was to determine whether there is an underlying difference in the biology of OA chondrocytes between males and females. METHODS: Chondrocytes were obtained following knee arthroplasty from male and female patients with primary OA. Phenotype marker expression, glucose and fat consumption, and rates of glycolysis and oxidative phosphorylation were compared between females and males. RNAi was used to determine the consequences of differential expression of Sry-box transcription factor 9 (SOX9) and PGC1α between males and females. RESULTS: OA chondrocytes from male donors showed elevated ribonucleic acid (RNA) and protein levels of SOX9, elevated COL2A1 protein synthesis, higher glucose consumption, and higher usage of glycolysis compared to females. OA chondrocytes from females had higher PGC1α protein levels, higher fat consumption, and higher oxidative energy metabolism than males. Knockdown of SOX9 reduced expression of COL2A1 to a greater extent in male OA chondrocytes than females whereas knockdown of PGC1α reduced COL2A1 expression in females but not males. Expression of ACAN and the glycolytic enzyme PGK1 was also reduced in males but not females following SOX9 knockdown. CONCLUSIONS: OA chondrocyte phenotype and energy metabolism differ between males and females. Our results indicate transcriptional control of COL2A1 differs between the two. Differences in chondrocyte biology between males and females imply the underlying mechanisms involved in OA may also differ, highlighting the need to consider sex and gender when investigating pathogenesis and potential treatments for OA.

Using Days Alive and Out of Hospital to measure inequities and possible pathways for them after cardiovascular surgery in Aotearoa New Zealand: study protocol for a secondary data analysis.

INTRODUCTION: In Aotearoa New Zealand (NZ), socioeconomic status and being of Maori ethnicity are often associated with poorer health outcomes, including after surgery. Inequities can be partially explained by differences in health status and health system biases are hypothesised as important factors for remaining inequities. Previous work identified inequities between Maori and non-Maori following cardiovascular surgery, some of which have been identified in studies between 1990 and 2012. Days Alive and Out of Hospital (DAOH) is an emerging surgical outcome metric. DAOH is a composite measure of outcomes, which may reflect patient experience and longer periods of DAOH may also reflect extended interactions with the health system. Recently, a 1.1-day difference in DAOH was observed between Maori and non-Maori at a hospital in NZ across a range of operations. METHODS AND ANALYSIS: We will conduct a secondary data analysis using data from the National Minimum Data Set, maintained by the Ministry of Health. We will report unadjusted and risk-adjusted DAOH values between Maori and non-Maori using direct risk standardisation. We will risk adjust first for age and sex, then for each of deprivation (NZDep18), levels of morbidity (M3 score) and rurality. We will report DAOH values across three time periods, 30, 90 and 365 days and across nine deciles of the DAOH distribution (0.1-0.9 inclusive). We will interpret all results from a Kaupapa Maori research positioning, acknowledging that Maori health outcomes are directly tied to the unequal distribution of the social determinants of health. ETHICS AND DISSEMINATION: Ethics approval for this study was given by the Auckland Health Research Ethics Committee. Outputs from this study are likely to interest a range of audiences. We plan to disseminate our findings through academic channels, presentations to interested groups including Maori-specific hui (meetings), social media and lay press.

Differential Effects of Hypoxia versus Hyperoxia or Physoxia on Phenotype and Energy Metabolism in Human Chondrocytes from Osteoarthritic Compared to Macroscopically Normal Cartilage.

Chondrocyte phenotype and energy metabolism are altered in osteoarthritis (OA). However, most studies characterising the change in human chondrocyte behaviour in OA have been conducted in supraphysiological oxygen concentrations. The purpose of this study was to compare phenotype and energy metabolism in chondrocytes from macroscopically normal (MN) and OA cartilage maintained in 18.9% (standard tissue culture), 6% (equivalent to superficial zone of cartilage in vivo) or 1% oxygen (equivalent to deep zone of cartilage in vivo). MMP13 production was higher in chondrocytes from OA compared to MN cartilage in hyperoxia and physoxia but not hypoxia. Hypoxia promoted SOX9, COL2A1 and ACAN protein expression in chondrocytes from MN but not OA cartilage. OA chondrocytes used higher levels of glycolysis regardless of oxygen availability. These results show that differences in phenotype and energy metabolism between chondrocytes from OA and MN cartilage differ depending on oxygen availability. OA chondrocytes show elevated synthesis of cartilage-catabolising enzymes and chondrocytes from MN cartilage show reduced cartilage anabolism in oxygenated conditions. This is relevant as a recent study has shown that oxygen levels are elevated in OA cartilage in vivo. Our findings may indicate that this elevated cartilage oxygenation may promote cartilage loss in OA.

Ethnic differences in patients undergoing thyroidectomy for non-toxic multinodular goitre.

BACKGROUND: Maori have an increased incidence of thyrotoxicosis when compvared to non-Maori, however there are limited data on benign non-toxic nodular thyroid disease. AIMS: The aims of this study were to determine the rates of non-toxic multinodular goitre (NTMNG) surgery for Maori and non-Maori and to determine if there were differences in thyroid size between Maori and non-Maori undergoing total thyroidectomy for NTMNG. METHODS: Single centre study of patients undergoing thyroidectomy for NTMNG from 1 December 2006 to 30 November 2016. RESULTS: Maori were overrepresented amongst the 427 patients who underwent surgery for NTMNG at 34% compared to the expected ~17% of the background Maori adult population in the region. At the time of surgery, Maori were younger (P = 0.004) and had a larger thyroid gland (P < 0.001) when compared to non-Maori also undergoing total/near total thyroidectomy. Complication rates were low across all ethnic groups. CONCLUSION: Maori have increased rates of surgery for NTMNG compared to non-Maori and thyroid size is larger at the time of surgery. The reasons for this are currently unknown and more research is required.

Midwifery awareness of diabetes in pregnancy screening guidelines in Aotearoa New Zealand.

OBJECTIVE: Effective and timely management of gestational diabetes mellitus (GDM) requires early detection. However, screening rates have been shown to be relatively low in New Zealand, despite the introduction of national screening guidelines in 2014 which indicate that all pregnant women should be screened. Thus, the aim of this study was to explore the awareness of the New Zealand Ministry of Health Diabetes in Pregnancy screening guidelines by New Zealand midwives. DESIGN: A 24-question online survey based upon the New Zealand screening guidelines was distributed via New Zealand midwifery social media groups to explore the awareness of New Zealand midwives with regard to screening for diabetes in pregnancy. Free text comments were also allowed, these were broadly categorized and reviewed. PARTICIPANTS: 174 registered midwives in Aotearoa New Zealand completed the survey. MEASUREMENTS AND FINDINGS: All participants responded that they routinely offer glycated haemoglobin screening for detection of undiagnosed pre-gestational diabetes, and 92.9% identified that this should occur prior to 20 weeks gestation (as per the national guidelines). However, less than two thirds of midwives thought that all women should be screened for GDM, with 18.2% indicating they would only do this if immediate risk factors were present. There also appeared to be some confusion over the time period for screening for GDM with 22.9% indicating that this should occur later than the guideline-recommended timepoint of 24-28 weeks gestation. Participants who identified as Maori and community-based midwives were most likely to screen for GDM 'only if risk factors were present'. Participants practicing for more than 6 years, those aged 45-54 years, and midwives identifying as Maori were most likely to screen for GDM after 28 weeks (though these did not reach statistical significance). KEY CONCLUSIONS: The New Zealand Diabetes in Pregnancy screening guidelines do not appear to be well implemented in our sample group, particularly with regard to screening for GDM. This needs to be evaluated in a larger group of midwives, as education around the timeliness and importance of screening for all women may be required. IMPLICATIONS FOR PRACTICE: A lack of appropriate or timely screening for GDM may mean that women are not being diagnosed or managed appropriately, which in turn may have implications for both mother and child.

He Pikinga Waiora Kimi Ora lifestyle programme: case study of a successful community-based Indigenous diabetes intervention.

AIM: To co-design and implement a whanau-centred, community-based lifestyle programme (Kimi Ora) intended to ensure no worsening of HbA1c and to improve wellbeing for Maori whanau and communities with diabetes or pre-diabetes. METHODS: Maori healthcare providers, community members, research advisors and wider stakeholders used a co-design process underpinned by He Pikinga Waiora to collaboratively develop and implement Kimi Ora Control group comparisons and participants were recruited from Te Kohao Health. Multi-method monitoring and collection captured individual, whanau and community data. RESULTS: Kimi Ora was run in two communities in Aotearoa New Zealand. In total, there were 35 participants who took part in an eight-week programme offered five times alongside a comparison group comprising 21 participants. Kimi Ora resulted in significant improvements on all biomedical measures compared to baseline, and participants had gains relative to the comparison group for variables including weight, BMI, blood pressure and waist measurement. Of particular note was the 100% retention rate and sustained community support for Kimi Ora. CONCLUSIONS: Outcomes from Kimi Ora demonstrate this programme, which was actively tailored for and worked with Maori communities in a responsive and flexible manner, resulted in successful biomedical outcomes, high engagement and high retention.

Letter on an iceberg.

In the public sphere, issues are like icebergs. This somewhat hackneyed metaphor illustrates that, while one facet of an issue is perceived, what is not seen is the hidden substructure of power and culture that form and reinforce it, buoying the issue to prominence above the surface.

Glycaemic control across the lifespan in a cohort of New Zealand patients with type 1 diabetes mellitus.

BACKGROUND: It is well known that tight glycaemic control reduces all-cause mortality and the development of microvascular complications in patients with type 1 diabetes mellitus (T1D), but that effective glycaemic control is difficult to achieve in different age groups. Currently, the state of glycaemic control across the lifespan in patients with T1D in New Zealand is not known. AIM: To determine the differences in glycaemic control with age, gender, rurality and ethnicity in patients with T1D in the Waikato region of New Zealand. METHODS: Retrospective review of clinical records of all patients with T1D on the Waikato Regional Diabetes Database in December 2017 (n = 1303). Glycaemic control was determined by the most recent HbA1c in the past 2 years. RESULTS: Median (25%, 75%) HbA1c was 67 (59, 81) mmol/mol (8.3%) and highest in those aged 15-29 years. Values exceeded clinical recommendations in 85.3% of all patients. Median HbA1c was lower in patients on insulin pump therapy than on multiple daily injections (63 (7.9%) versus 69 mmol/mol (8.5%); P < 0.001), though insulin pumps were significantly less likely to be used by Maori (P = 0.003) and men (P < 0.0001). Worsening glycaemic control was associated with increasing social deprivation (P < 0.001) but was not influenced by rural/urban living. CONCLUSIONS: Poor glycaemic control in Waikato patients with T1D is likely due to inequities in health care, including reduced access to insulin pump therapy, particularly in Maori and socially deprived populations.

Ethnic inequities in screening for diabetes in pregnancy in New Zealand-adherence to national guidelines.

AIM: The aim of this study was to assess adherence to the 2014 Ministry of Health (MoH) screening guidelines for diabetes in pregnancy (DiP) by Maori and non-Maori in the Waikato region. METHODS: Clinical records were reviewed for women without known diabetes before pregnancy who delivered in hospitals or community birth centres in the Waikato region during June-August 2017. Screening rates for DiP were assessed using HbA1c, glucose challenge and/or glucose tolerance tests. RESULTS: Of a total of 807 women, 94% received some form of screening for DiP; 527 (65.3%) underwent HbA1c screening at <20 weeks and 267 (33.1%) underwent testing for gestational diabetes at 24-28 weeks' gestation. However, only 213 (26.4%) received all screening as per the MoH guideline. HbA1c testing was the most common screening performed (83.9% of all pregnancies), and three quarters of women had a glucose load screen at some point during pregnancy. In all measures, screening rates were lower in Maori, with only 17.5% (46 of 263 women) receiving both HbA1c and further glucose load screening in the recommended gestation windows (versus 31.6% (171 of 541) for non-Maori; P<0.0005). CONCLUSIONS: Adherence to screening guidelines for DiP was poor with a marked ethnic inequity. Further work is needed to investigate the barriers to care that drive these differences.

Thyrotoxicosis in an Indigenous New Zealand Population - a Prospective Observational Study.

BACKGROUND: Reported international incidence rates of thyrotoxicosis vary markedly, ranging from 6 to 93 cases per 100 000 per annum. Along with population demographics, exposures, and study design factors, ethnicity is increasingly being recognized as a potential factor influencing incidence. This study aimed to document the epidemiology and clinical presentation of thyrotoxicosis for Maori, the indigenous population in New Zealand. METHODS: A prospective study of adult patients presenting with a first diagnosis of thyrotoxicosis between January 2013 and October 2014 to a single New Zealand center. Demographic data were collected, and detailed clinical assessment performed. RESULTS: With 375 patients, an incidence rate of thyrotoxicosis of 73.0 per 100 000 per annum was identified. Of these, 353 (94.1%) participated in the study. The median age of the cohort was 47 years, 81% were female, and 58% had Graves disease. The overall incidence of thyrotoxicosis for Maori, the indigenous people of New Zealand, was higher than non-Maori (123.9 vs 57.3 per 100 000 per annum). Rates of both Graves disease and toxic multinodular goiter were higher in Maori as compared to non-Maori (incidence rate ratios of 1.9 [1.4, 2.6] and 5.3 [3.4, 8.3], respectively), with this increase being maintained after controlling for age, deprivation, and smoking. CONCLUSIONS: Maori, the indigenous people of New Zealand, have an increased incidence of thyrotoxicosis compared to non-Maori and, in particular, toxic multinodular goiter. A greater understanding of the epidemiology of thyrotoxicosis in other indigenous and marginalized ethnic groups may help to optimize therapeutic pathways, equitable care and outcomes.

Inequitable Long-Term Outcomes for an Indigenous Population After Definitive Treatment of Patients With Graves Disease.

BACKGROUND: Maori, the indigenous people of Aotearoa/New Zealand, have an increased incidence of Graves disease and often require more than one radioiodine (RAI) dose, raising the question as to whether surgery may be preferable in this population. However, there is a lack of outcome data after definitive therapy in an indigenous population. AIM: To assess ethnic differences in thyroid status after definitive therapy for Graves disease. METHODS: Single-center retrospective review of patients treated by RAI or thyroidectomy from 1 December 2001 to 31 March 2013. TSH levels at 1, 2, 5, and 10 years after treatment were recorded. RESULTS: A total of 798 patients were included: 589 received RAI, and 209 underwent surgery. Overall, 48% of patients were euthyroid at 1 year after definitive treatment, and 63.5% were euthyroid by 10 years. Maori were less likely to be euthyroid when compared with Europeans at all time points (e.g., 29.7% vs 57.3% at 1 year and 52.2% vs 70.9% at 10 years, P < 0.0005). Maori were more likely to receive more than one dose of RAI compared with Europeans (30.2% vs 14.2%, P < 0.0005). Persistent thyrotoxicosis at 1 year after RAI was seen in 25.8% of Maori compared with 8.3% of Europeans (P < 0.0005). CONCLUSIONS: Maori have lower rates of optimal thyroid levels than their European counterparts at all time points studied. Early disparity was associated with a higher RAI failure rate. Late differences were due to higher rates of untreated hypothyroidism. Overall, euthyroid rates were low, indicating the need for improvement in care, particularly for indigenous peoples.

Should antenatal corticosteroids be considered in women with gestational diabetes before planned late gestation caesarean section.

Babies born to mothers with gestational diabetes mellitus (GDM) are at a greater risk of developing respiratory complications and hypoglycaemia than those born to mothers without diabetes. However, there is currently insufficient evidence as to whether these risks are altered by antenatal corticosteroids after 37 weeks gestation. This retrospective study suggests that antenatal corticosteroids probably reduce respiratory admissions to the newborn intensive care unit with a mild increase in neonatal hypoglycaemia in women with GDM who deliver via caesarean section after 37 weeks gestation. Consequently, we recommend a randomised, controlled trial is required to determine the efficacy and safety of antenatal corticosteroids specifically in women with GDM.

Increased Admissions Due to Cardiac Complications of Thyrotoxicosis in Maori.

BACKGROUND: As thyrotoxicosis is a risk factor for atrial fibrillation, current guidelines recommend measuring a thyroid-stimulating hormone level in patients with this disorder. Hyperthyroidism may also be associated with other heart diseases including cardiac ischaemia and cardiac failure. Currently, the prevalence of thyrotoxicosis in cardiac admissions in the absence of a rhythm disorder is unknown. AIMS: The aims of this study were: 1) to calculate the prevalence of admissions for thyrotoxicosis-associated cardiac disease, 2) determine the type of cardiac disease i.e. dysrhythmic, ischaemic or cardiac failure, and 3) to assess whether Maori are over-represented amongst patients admitted to hospital with cardiac complications of thyrotoxicosis. METHODS: A retrospective review of admissions with both thyrotoxicosis and cardiac disease from 1 January 2005 to 31 December 2012 inclusive. RESULTS: Seventy-two patients were identified as being admitted for a cardiac complication of thyrotoxicosis, giving a mean of nine admissions per year. Dysrhythmia was the cause for admission in 32 patients, ischaemia in 12, cardiac failure in 11 and mixed cardiac disease in 17. Graves' disease and amiodarone-induced were the most common causes of the thyrotoxicosis (25 and 19 cases, respectively). Of the cohort 26 (36.1%) were Maori (compared to 16.8% of all cardiac admissions over the same period). Maori were more likely to present with cardiac failure than non-Maori (57.7% vs. 26.1%, p=0.008 respectively). CONCLUSIONS: Maori are over-represented amongst patients admitted with cardiac complications of thyrotoxicosis and more often present with cardiac failure than non-Maori. Measurement of thyroid function should be considered in patients presenting not only with atrial fibrillation but also in patients presenting with cardiac failure, particularly if they are Maori.

Treatment choice, satisfaction and quality of life in patients with Graves' disease.

BACKGROUND: Thyrotoxicosis, most often caused by Graves' disease (GD), when treated inadequately may result in premature mortality. There is little consensus as to which of the 3 treatment options available - antithyroid drugs (ATD), radioactive iodine (RAI) and surgery, is better. AIMS: (i) To assess factors involved in treatment choice and treatment satisfaction in patients treated for Graves' disease; (ii) To assess quality of life (QoL) following treatment of Graves' disease. METHOD: Participants were selected from a prospective study cohort assessing thyrotoxicosis incidence and severity. Of the 172 eligible patients with Graves' disease, 123 treated patients participated (64% had received ATD only, 11% RAI and 25% total thyroidectomy, the latter 2 usually after a period of ATD), along with 18 untreated patients with newly diagnosed Graves' disease (overall participation rate, 73%). Consented patients completed a questionnaire detailing factors involved in treatment choice, QoL and satisfaction with treatment. RESULTS: Participants reported that the most important factors in choosing a treatment were the following: the effects on activities of daily living, concern about use of radioiodine, possibility of depression or anxiety, and doctor's recommendations. Satisfaction levels were high across all 3 treatment types. QoL 1-year following treatment was higher than in untreated patients, and comparable with other international studies. CONCLUSIONS: Patient satisfaction with therapy and QoL does not differ by treatment type. Therefore, clinical and social factors, in combination with patient choice and resource availability, should determine which treatment modality patients with Graves' disease should receive.

Rates of unsuspected thyroid cancer in multinodular thyroid disease.

BACKGROUND: Previously the risk of concomitant thyroid cancer in multinodular goitre (MNG) has been reported as approximately 4%. Cancer risk in toxic MNG was often considered lower than for non-toxic MNG, due to a possible protective effect of TSH suppression. However, recent American data suggest an approximately 18% risk of occult malignancy in both toxic and non-toxic MNG. AIMS: To assess malignancy risk in a New Zealand population undergoing thyroidectomy for MNG. METHODS: Single-centre study of patients undergoing thyroidectomy for MNG from 1 December 2006 to 30 November 2016. RESULTS: Six hundred and two patients underwent surgery for MNG (448 non-toxic and 154 toxic). Of these, 95/602 (16%) had thyroid cancer. After excluding patients operated for preoperative suspicion for cancer, 30/401 (8%) patients with non-toxic MNG and 15/151 (10%) with toxic MNG had unsuspected or occult thyroid cancer (p=0.358). Patients with toxic MNG were less likely to undergo preoperative fine needle aspiration than those with non-toxic MNG (34% vs 52%, respectively p=0.0001). Two-thirds of unsuspected thyroid cancers were incidental micropapillary carcinomas and unlikely to alter survival irrespective of therapy. CONCLUSION: Malignancy rates in MNG are higher than historically reported, although most unsuspected cancers are unlikely to alter mortality even if diagnosis is delayed.