Medicine (St Vincent's) - Research Publications
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ItemNo Preview AvailableCytoreductive Surgery of the Primary Tumor in Metastatic Adrenocortical Carcinoma: Impact on Patients' Survival(ENDOCRINE SOC, 2022-03-24)CONTEXT: The role of cytoreduction of adrenocortical carcinoma (ACC) remains poorly understood. OBJECTIVE: To analyze the impact of cytoreductive surgery of the primary tumor in patients with metastatic ACC. DESIGN AND SETTING: We performed a multicentric, retrospective paired cohort study comparing the overall survival (OS) in patients with metastatic ACC who were treated either with cytoreductive surgery (CR group) or without cytoreductive surgery (no-CR group) of the primary tumor. Data were retrieved from 9 referral centers in the American-Australian-Asian Adrenal Alliance collaborative research group. PATIENTS: Patients aged ≥18 years with metastatic ACC at initial presentation who were treated between January 1, 1995, and May 31, 2019. INTERVENTION: Performance (or not) of cytoreductive surgery of the primary tumor. MAIN OUTCOME AND MEASURES: A propensity score match was done using age and the number of organs with metastasis (≤2 or >2). The main outcome was OS, determined from the date of diagnosis until death or until last follow-up for living patients. RESULTS: Of 339 patients pooled, 239 were paired and included: 128 in the CR group and 111 in the no-CR group. The mean follow-up was 67 months. Patients in the no-CR group had greater risk of death than did patients in the CR group (hazard ratio [HR] = 3.18; 95% CI, 2.34-4.32). Independent predictors of survival included age (HR = 1.02; 95% CI, 1.00-1.03), hormone excess (HR = 2.56; 95% CI, 1.66-3.92), and local metastasis therapy (HR = 0.41; 95% CI, 0.47-0.65). CONCLUSION: Cytoreductive surgery of the primary tumor in patients with metastatic ACC is associated with prolonged survival.
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ItemNo Preview AvailableIndependent euglycaemic hyperinsulinaemic clamp studies validate clinically applicable formulae to estimate insulin sensitivity in people with type 1 diabetes(ELSEVIER SCI LTD, 2023-01)BACKGROUND AND AIM: Low insulin sensitivity (IS) increases Type 1 diabetes (T1D) complication risk and can be estimated by simple formulae developed from complex euglycemic hyperinsulinaemic clamp studies. We aimed to validate these formulae using independent clamp data. METHODS: Clamps were performed in 104 T1D adults. Measured glucose disposal rate (GDR) was correlated with eGDR and eLog10 M/I calculated by five IS formulae. RESULTS: Correlations ranged between 0.23-0.40. Two IS formulae (by the authors), using age, sex, HDL-C, HbA1c, pulse pressure, BMI, and waist-hip-ratio had the highest correlation with measured GDR and the best performance in detecting low IS.
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ItemNo Preview AvailableIndependent euglycaemic hyperinsulinaemic clamp studies validate clinically applicable formulae to estimate insulin sensitivity in people with type 1 diabetes (vol 17, 102691, 2023)(ELSEVIER SCI LTD, 2023-01)The authors regret that in the original article, on the second page, in the section with eGDR equations, variables “sex” and “hypertension” were missing categorical values indicators (“F = 0, M = 1”; “Yes = 1, No = 0”, respectively) required to calculate eGDR. It should be corrected by adding “F = 0, M = 1” in two instances and “Yes = 1, No = 0” in one instance. Also, please note that Miller at al. defined “hypertension” as BP ≥140/90mmHg or use of any anti-hypertensive (drug) treatment. The authors apologise for any inconvenience caused.
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ItemImaging for assessment of cancer treatment response to immune checkpoint inhibitors can be complementary in identifying hypophysitis(FRONTIERS MEDIA SA, 2023-11-29)INTRODUCTION: Hypophysitis is reported in 8.5%-14% of patients receiving combination immune checkpoint inhibition (cICI) but can be a diagnostic challenge. This study aimed to assess the role of routine diagnostic imaging performed during therapeutic monitoring of combination anti-CTLA-4/anti-PD-1 treatment in the identification of hypophysitis and the relationship of imaging findings to clinical diagnostic criteria. METHODS: This retrospective cohort study identified patients treated with cICI between January 2016 and January 2019 at a quaternary melanoma service. Medical records were reviewed to identify patients with a documented diagnosis of hypophysitis based on clinical criteria. Available structural brain imaging with magnetic resonance imaging (MRI) or computed tomography (CT) of the brain and 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography with computed tomography (FDG-PET/CT) were assessed retrospectively. The main radiological outcome measures were a relative change in pituitary size or FDG uptake temporally attributed to cICI. RESULTS: There were 162 patients (median age 60 years, 30% female) included. A total of 100 and 134 had serial CT/MRI of the brain and FDG-PET/CT, respectively. There were 31 patients who had a documented diagnosis of hypophysitis and an additional 20 who had isolated pituitary imaging findings. The pituitary gland enlargement was mild, and the largest absolute gland size was 13 mm, with a relative increase of 7 mm from baseline. There were no cases of optic chiasm compression. Pituitary enlargement and increased FDG uptake were universally transient. High-dose glucocorticoid treatment for concurrent irAEs prevented assessment of the pituitary-adrenal axis in 90% of patients with isolated imaging findings. CONCLUSION: Careful review of changes in pituitary characteristics on imaging performed for assessment of therapeutic response to iICI may lead to increased identification and more prompt management of cICI-induced hypophysitis.
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ItemNo Preview AvailableInteractive Calculator to Estimate Insulin Sensitivity (IS) in Type 1 Diabetes(AMER DIABETES ASSOC, 2023-06)Introduction: Euglycemic hyperinsulinemic clamps, although costly, time- and labor-intensive, are “gold standard” in measuring insulin sensitivity (IS). Several formulae to estimate IS in people with Type 1 diabetes (T1D) exist (DOI: 10.1007/978-3-030-81303-1_18-1), using various routine and research assays, and with wide ranging IS results. Aim: To develop a free online tool to estimate IS using different metrics and existent formulae and compare estimated IS with measured glucose disposal rate (GDR) from 104 clamp studies. Methods: We prepared an online tool for calculating IS using 17 formulae. Suitable formula(e) are suggested based on available (clinical and research) data. We also compare calculated IS with measured IS (GDR) from clamp studies in 104 adults with T1D (mean±SD) age 34±7 yrs, T1D duration 10±4 yrs, HbA1c 7.7±1.5%, 33 with microvascular complications). Logistic regression was used to infer probability of calculated IS being below GDR=4.45 mg/kg/min or above GDR=6.5 mg/kg/min, which represent respectively the median and 75th percentile of measured GDR values. Results: A calculator is available at www.bit.ly/estimated-GDR and an example result in the Figure 1. Estimated IS varied widely, but results interpretation is generally consistent. Conclusion: We developed an interactive tool to estimate IS in T1D for clinical and research use. Disclosure A.S.Januszewski: None. P.Niedzwiecki: None. N.Sachithanandan: None. G.M.Ward: None. D.N.O'neal: None. D.Zozulinska-ziolkiewicz: Advisory Panel; Abbott, Lilly, Lilly, Novo Nordisk, Medtronic, Speaker's Bureau; Abbott, Ascensia Diabetes Care, Novo Nordisk, Medtronic, Boehringer-Ingelheim, AstraZeneca. A.Uruska: Other Relationship; Lilly, Boehringer-Ingelheim, AstraZeneca, Ascensia Diabetes Care, Sanofi. A.Jenkins: Advisory Panel; Insulet Corporation, Board Member; Insulin for Life, Research Support; Abbott Diabetes, Medtronic, Hemsley Charitable Trust, Juvenile Diabetes Research Foundation (JDRF), National Institutes of Health.
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ItemInsulinoma: Metastatic Recurrence 38 Years Following Initial Diagnosis in Pregnancy.(The Endocrine Society, 2024-02)A case of recurrent insulinoma spanning 4 decades is described. Following a delayed diagnosis, hyperinsulinemic hypoglycemia was confirmed in a 24-year-old woman during early pregnancy. Initial surgery, culminating in subtotal pancreatectomy, was noncurative. A 1-cm insulinoma was subsequently resected from the head of the pancreas postpartum, with postoperative resolution of hypoglycemia. However, 32 years later, the patient experienced a recurrence of hypoglycemic symptoms. Eventually, a subcentimeter extrapancreatic lesion was identified anterior to the pancreatic head on gallium-68 DOTA-Exendin-4 positron emission tomography/computed tomography. In 2022, a third operation was performed, with excision of a 4 × 3 mm tumor adjacent to the pancreatic head, and histology confirming insulinoma. She was again cured of symptoms.
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ItemIncreased Thyroidal Activity on Routine FDG-PET/CT after Combination Immune Checkpoint Inhibition: Temporal Associations with Clinical and Biochemical Thyroiditis(MDPI, 2023-12)BACKGROUND: FDG-PET/CT used for immune checkpoint inhibitor (ICI) response assessment can incidentally identify immune-related adverse events (irAEs), including thyroiditis. This study aimed to correlate the time course of FDG-PET/CT evidence of thyroiditis with clinical and biochemical evolution of thyroid dysfunction. METHODS: A retrospective review was performed by two independent blinded nuclear medicine physicians (NMPs) of thyroidal FDG uptake in 127 patients who underwent PET/CT between January 2016 and January 2019 at baseline and during treatment monitoring of combination ICI therapy for advanced melanoma. Interobserver agreement was assessed and FDG-PET/CT performance defined by a receiver-operating characteristic (ROC) curve using thyroid function tests (TFTs) as the standard of truth. Thyroid maximum standardized uptake value (SUVmax) and its temporal changes with respect to the longitudinal biochemistry were serially recorded. RESULTS: At a median of 3 weeks after commencing ICI, 43/127 (34%) had a diagnosis of thyroiditis established by abnormal TFTs. FDG-PET/CT was performed at baseline and at a median of 11 weeks (range 3-32) following the start of therapy. ROC analysis showed an area under the curve of 0.87 (95% CI 0.80, 0.94) for FDG-PET/CT for detection of thyroiditis with a positive predictive value of 93%. Among patients with biochemical evidence of thyroiditis, those with a positive FDG-PET/CT were more likely to develop overt hypothyroidism (77% versus 35%, p < 0.01). In the evaluation of the index test, there was an almost perfect interobserver agreement between NMPs of 93.7% (95% CI 89.4-98.0), kappa 0.83. CONCLUSION: Increased metabolic activity of the thyroid on routine FDG-PET/CT performed for tumoral response of patients undergoing ICI therapy is generally detected well after routine biochemical diagnosis. Elevation of FDG uptake in the thyroid is predictive of overt clinical hypothyroidism and suggests that an ongoing robust inflammatory response beyond the initial thyrotoxic phase may be indicative of thyroid destruction.
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ItemSevere Osteoporosis With Pathogenic LRP5 Variant.(The Endocrine Society, 2024-03)A 24-year-old female patient was diagnosed with osteoporosis after presenting with numerous fractures throughout her childhood and adolescence. Risk factors included chronic constipation, severe vitamin D deficiency, and long-term high-dose steroid use for severe eczema. Metabolic bone disorder clinical exome screening (limited panel of metabolic bone disorders and gastrointestinal disorders) was undertaken and revealed a class 4 likely pathogenic variant in the LRP5 gene known to cause osteoporosis. Optimal treatment for patients with this variant is not well defined. A literature review of the condition and potential treatment options is discussed.
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ItemInteractive calculator to estimate insulin sensitivity in type 1 diabetes(WILEY, 2024-05)The gold standard for measuring insulin sensitivity (IS) is the hyperinsulinemic-euglycemic clamp, a time, costly, and labor-intensive research tool. A low insulin sensitivity is associated with a complication-risk in type 1 diabetes. Various formulae using clinical data have been developed and correlated with measured IS in type 1 diabetes. We consolidated multiple formulae into an online calculator (bit.ly/estimated-GDR), enabling comparison of IS and its probability of IS <4.45 mg/kg/min (low) or >6.50 mg/kg/min (high), as measured in a validation set of clamps in 104 adults with type 1 diabetes. Insulin sensitivity calculations using different formulae varied significantly, with correlations (R2) ranging 0.005-0.87 with agreement in detecting low and high glucose disposal rates in the range 49-93% and 89-100%, respectively. We demonstrate that although the calculated IS varies between formulae, their interpretation remains consistent. Our free online calculator offers a user-friendly tool for individual IS calculations and also offers efficient batch processing of data for research.