Use of a dosimetry-based RAI protocol for treatment of benign hyperthyroidism optimises response while minimising exposure to ionising radiation.

BACKGROUND: The optimal treatment strategy for radioiodine (RAI) treatment protocols for benign hyperthyroidism remains elusive. Although individualised activities are recommended in European Law, many centres continue to provide fixed activities. Our institution implemented a dosimetry protocol in 2016 following years of fixed dosing which facilitates the calculation of individualised activities based on thyroid volume and radioiodine uptake. METHODS: This was a retrospective study comparing success rates using a dosimetry protocol targeting an absorbed dose of 150 Gy for Graves' disease (GD) and 125 Gy for Toxic Multinodular Goiter (TMNG) with fixed dosing (200MBq for GD and 400MBq for TMNG) among 204 patients with hyperthyroidism. Success was defined as a non-hyperthyroid state at 1 year for both disease states. Results were analysed for disease specific or patient specific modulators of response. RESULTS: This study included 204 patients; 74% (n = 151) received fixed activities and 26% (n = 53) of activities administered were calculated using dosimetry. A dosimetry-based protocol was successful in 80.5% of patients with GD and 100% of patients with TMNG. Differences in success rates and median activity administered between the fixed (204Mbq) and dosimetry (246MBq) cohort were not statistically significant (p = .64) however 44% of patients with GD and 70% of patients with TMNG received lower activities following treatment with dosimetry as opposed to fixed activities. Use of dosimetry resulted in successful treatment and reduced RAI exposure for 36% of patients with GD, 70% of patients with TMNG, and 44% of patients overall. CONCLUSION: This retrospective clinical study demonstrated that treatment with a dosimetry-based protocol for TMNG and GD achieved comparable success rates to fixed protocols while reducing RAI exposure for over a third of patients with GD and most patients with TMNG. This study also highlighted that RAI can successfully treat hyperthyroidism for some patients with activities lower than commonplace in clinical practise. No patient or disease specific modulators of treatment response were established in this study; however, the data supports a future prospective trial which further scrutinises the individual patient factors governing treatment response to RAI.

Thyroid cancer epidemiology in Ireland from 1994 to 2019 - Rising diagnoses without mortality benefit.

BACKGROUND: The epidemiology and management of thyroid cancer has changed radically in the recent past, with rising international incidence of early-stage papillary thyroid cancer (PTC) in particular. In this paper, we review the epidemiology of thyroid cancer in Ireland. METHODS: A retrospective cohort study of National Cancer Registry of Ireland data, 1994-2019. RESULTS: Records from 4158 patients were analysed. 73 % (n = 3040) were female. The average age was 50.4 years. Patient sex did not change over time (p = 0.662), while age decreased significantly (p < 0.0001). The most common diagnoses were PTC (n = 2,905, 70 %) and follicular thyroid carcinoma (n = 549, 13 %). Incidence rose over threefold (1.8-6.2 cases/100000 person-years). The incidence of T1 PTC rose over twelvefold (0.169-2.1 cases/100000 person-years), while the incidence of stage III and IV disease did not change significantly. Five-year disease-specific survival (DSS) was 85 % and varied significantly by diagnosis - 97 % for PTC versus 5 % for anaplastic thyroid carcinoma. Survival did not change significantly over time. Male sex was a risk factor for more advanced disease (p < 0.0001) but did not independently predict overall survival except in PTC (HR 1.6, p = 0.03). The use of radioactive iodine declined markedly from 49 % to 12.5 %. RAI improved DSS for PTC patients aged over 55 years (p = 0.02) without a notable effect on survival for those under 55 years (p = 0.99). CONCLUSION: The epidemiology and management of thyroid cancer in Ireland has changed dramatically in a manner reflective of international trends.

Blood Micro-sampling: An alternative blood collection method for radioiodine therapy dosimetry.

PURPOSE: Collecting venous blood samples from patients post administration of high therapeutic activities results in radiation exposure to staff collecting the blood. This study investigated the use of finger-tip capillary-blood collection as an alternative to the venous-blood collection method recommended by the European Association of Nuclear Medicine (EANM) dosimetry protocol for quantifying 131I concentration in the critical organ after therapeutic dose of 131I. METHODS: The study included differentiated thyroid cancer patients referred to a thyroid cancer centre at St James's Hospital, Ireland, for therapeutic and diagnostic oral administration of 131I. The 15 patients recruited for this study provided 30 venous and capillary paired-blood samples. The activity concentration of the blood samples was compared between the type of blood (venous vs capillary) and the geometry/volume of the blood (1.0 ml versus 0.03 ml). Other variables were also investigated including administered activities, dose to staff performing the sampling, duration of sampling and time since administration. RESULTS: Blood samples were taken at 2.0-91.9 h post administration using 0.2 ± 0.0 GBq (n = 2) or 4.0 ± 0.1 GBq (n = 28) 131I activities. There was no significant difference found between different blood sampling types (-1.0 ± 4.3 %, p = 0.223), different blood volumes (-3.2 ± 10.0 %, p = 0.070), or between their combination. No significant correlation was found between the percentage differences and investigated parameters. CONCLUSION: A high degree of accuracy was achieved with blood radioactivity quantified using capillary blood collection using the finger-prick method. Further validation of the method would be required prior to implementation, to investigate patient specific factors which may affect accuracy.

Tissue Glucocorticoid Metabolism in Adrenal Insufficiency: A Prospective Study of Dual-release Hydrocortisone Therapy.

BACKGROUND: Patients with adrenal insufficiency (AI) require life-long glucocorticoid (GC) replacement therapy. Within tissues, cortisol (F) availability is under the control of the isozymes of 11ß-hydroxysteroid dehydrogenase (11ß-HSD). We hypothesize that corticosteroid metabolism is altered in patients with AI because of the nonphysiological pattern of current immediate release hydrocortisone (IR-HC) replacement therapy. The use of a once-daily dual-release hydrocortisone (DR-HC) preparation, (Plenadren®), offers a more physiological cortisol profile and may alter corticosteroid metabolism in vivo. STUDY DESIGN AND METHODS: Prospective crossover study assessing the impact of 12 weeks of DR-HC on systemic GC metabolism (urinary steroid metabolome profiling), cortisol activation in the liver (cortisone acetate challenge test), and subcutaneous adipose tissue (microdialysis, biopsy for gene expression analysis) in 51 patients with AI (primary and secondary) in comparison to IR-HC treatment and age- and BMI-matched controls. RESULTS: Patients with AI receiving IR-HC had a higher median 24-hour urinary excretion of cortisol compared with healthy controls (72.1 µg/24 hours [IQR 43.6-124.2] vs 51.9 µg/24 hours [35.5-72.3], P = .02), with lower global activity of 11ß-HSD2 and higher 5-alpha reductase activity. Following the switch from IR-HC to DR-HC therapy, there was a significant reduction in urinary cortisol and total GC metabolite excretion, which was most significant in the evening. There was an increase in 11ß-HSD2 activity. Hepatic 11ß-HSD1 activity was not significantly altered after switching to DR-HC, but there was a significant reduction in the expression and activity of 11ß-HSD1 in subcutaneous adipose tissue. CONCLUSION: Using comprehensive in vivo techniques, we have demonstrated abnormalities in corticosteroid metabolism in patients with primary and secondary AI receiving IR-HC. This dysregulation of pre-receptor glucocorticoid metabolism results in enhanced glucocorticoid activation in adipose tissue, which was ameliorated by treatment with DR-HC.

The growth hormone/insulin-like growth factor-I axis in exercise and sport.

The syndrome of adult GH deficiency and the effects of GH replacement therapy provide a useful model with which to study the effects of the GH/IGF-I axis on exercise physiology. Measures of exercise performance including maximal oxygen uptake and ventilatory threshold are impaired in adult GH deficiency and improved by GH replacement, probably through some combination of increased oxygen delivery to exercising muscle, increased fatty acid availability with glycogen sparing, increased muscle strength, improved body composition, and improved thermoregulation. In normal subjects, in addition to the long-term effects of GH/IGF-I status, there is evidence that the acute GH response to exercise is important in regulating substrate metabolism after exercise. Administration of supraphysiological doses of GH to athletes increases fatty acid availability and reduces oxidative protein loss, particularly during exercise, and increases lean body mass. Despite a lack of evidence that these metabolic effects translate to improved performance, GH abuse by athletes is widespread. Tests to detect GH abuse have been developed based on measurement in serum of 1) indirect markers of GH action, and 2) the relative proportions of the two major naturally occurring isoforms (20 and 22kDa) of GH. There is evidence that exercise performance and strength are improved by administration of GH and testosterone in combination to elderly subjects. The potential benefits of GH in these situations must be weighed against potential adverse effects.

Gender differences in estimating I-131 thyroid uptake from Tc-99m thyroid uptake for benign thyroid disease.

OBJECTIVE: For radioactive Iodine-131 (131I) treatments of thyroid diseases, increased efficacy has been reported for personalized dosimetry treatments. The measurement of Iodine-131 thyroid uptake (131IU) is required in these cases. This study aims to investigate whether 99mTc thyroid uptake (99mTcU) may be used in place of 131IU for implementing personalised treatments. METHODS: A retrospective study of 152 benign thyroid disease 131I treatments was carried out during 2012-2020; 117 treatments were for female patients while 35 were for male patients diagnosed with either Graves' disease, multinodular goitre or toxic nodules. RESULTS: A statistically significant correlation was found between 131IU and 99mTcU data, with the data more correlated for male than female patients (r = 0.71 vs 0.38, p-value < 0.001). Patient age and time difference between the two respective uptake measurements significantly influenced the uptake correlation in females but not for the male cohort, although there was no significant difference between the parameters across gender. Thyroid diagnosis and hormone levels showed a significant correlation with uptakes in both genders. Estimating 131IU based on 99mTcU was shown to be predictive for male but not in female patients (R2 = 91% vs 16%). CONCLUSION: Estimating 131IU based on 99mTcU is not recommended for females at our centre. Males reported good correlation, but a larger sample would be needed for validation. ADVANCES IN KNOWLEDGE: The initial findings showed a significant gender difference in benign thyroid uptake parameters at our centre, highlighting the potential need for gender consideration when planning 131IU patient management and when reporting studies results.

A Pilot Study of Gut-Brain Signaling After Octreotide Therapy for Unintentional Weight Loss After Esophagectomy.

BACKGROUND: Recurrence-free patients after esophageal cancer surgery face long-term nutritional consequences, occurring in the context of an exaggerated postprandial gut hormone response. Acute gut hormone suppression influences brain reward signaling and eating behavior. This study aimed to suppress gut hormone secretion and characterize reward responses and eating behavior among postesophagectomy patients with unintentional weight loss. METHODS: This pilot study prospectively studied postoperative patients with 10% or greater body weight loss (BWL) beyond 1 year who were candidates for clinical treatment with long-acting octreotide (LAR). Before and after 4 weeks of treatment, gut hormone secretion, food cue reactivity (functional magnetic resonance imaging), eating motivation (progressive ratio task), ad libitum food intake, body composition, and symptom burden were assessed. RESULTS: Eight patients (7 male, age: mean ±â€…SD 62.8 ±â€…9.4 years, postoperative BWL: 15.5 ±â€…5.8%) participated. Octreotide LAR did not significantly suppress total postprandial plasma glucagon-like peptide-1 response at 4 weeks (P = .08). Postprandial symptom burden improved after treatment (Sigstad score median [range]: 12 [2-28] vs 8 [3-18], P = .04) but weight remained stable (pre: 68.6 ±â€…12.8 kg vs post: 69.2 ±â€…13.4 kg, P = .13). There was no significant change in brain reward system responses, during evaluation of high-energy or low-energy food pictures, nor their appeal rating. Moreover, treatment did not alter motivation to eat (P = .41) nor ad libitum food intake(P = .46). CONCLUSION: The protocol used made it feasible to characterize the gut-brain axis and eating behavior in this cohort. Inadequate suppression of gut hormone responses 4 weeks after octreotide LAR administration may explain the lack of gut-brain pathway alterations. A higher dose or shorter interdose interval may be required to optimize the intervention.

Cardiometabolic and psychological effects of dual-release hydrocortisone: a cross-over study.

BACKGROUND: Adrenal insufficiency (AI) is associated with increased cardiovascular morbidity and mortality and reduced quality of life (QoL). Optimum glucocorticoid (GC) dosing and timing are crucial in the treatment of AI, yet the natural circadian secretion of cortisol is difficult to mimic. The once-daily dual-release hydrocortisone (DR-HC) preparation (Plenadren®), offers a more physiological cortisol profile and may address unmet needs. METHODS: An investigator-initiated, prospective, cross-over study in patients with AI. Following baseline assessment of cardiometabolic risk factors and QoL, patients switched from their usual hydrocortisone regimen to a once-daily dose equivalent of DR-HC and were reassessed after 12 weeks of treatment. RESULTS: Fifty-one patients (21 PAI/30 SAI) completed the study. Mean age was 41.6 years (s.d. 13), and 58% (n = 30) were male. The median daily HC dose before study entry was 20 mg (IQR 15-20 mg). After 3 months on DR-HC, the mean SBP decreased by 5.7 mmHg, P = 0.0019 and DBP decreased by 4.5 mmHg, P = 0.0011. There was also a significant reduction in mean body weight (-1.23 kg, P = 0.006) and BMI (-0.3 kg/m2, P = 0.003). In a sub-analysis, there was a greater reduction in SBP observed in patients with SAI when compared to PAI post-DR-HC. Patients reported significant improvements in QoL using three validated QoL questionnaires, with a greater improvement in PAI. CONCLUSION: Dual-release hydrocortisone decreases BP, weight and BMI compared with conventional HC treatment, even at physiological GC replacement doses. Additionally, DR-HC confers significant improvements in QoL compared to immediate-release HC, particularly in patients with PAI, which is also reflected in the patient preference for DR-HC.

Comparative Microbiological and Whole-Genome Analysis of Staphylococcus aureus Populations in the Oro-Nasal Cavities, Skin and Diabetic Foot Ulcers of Patients With Type 2 Diabetes Reveals a Possible Oro-Nasal Reservoir for Ulcer Infection.

Patients with type 2 diabetes are at higher risk for periodontal disease and diabetic foot ulcer infections (DFUIs), the latter of which are predominantly caused by staphylococcal bacteria. Staphylococci have also been detected in the mouth, nose and gums (the oro-nasal cavity) of patients with periodontal disease and can move between the mouth and nose. The present study investigated if the oro-nasal cavity and/or periodontal pockets (PPs) in diseased gum tissue can provide a microbial reservoir for DFUIs. Eighteen patients with type 2 diabetes and at least three natural teeth (13 patients with ulcers and 5 patients without ulcers) underwent non-invasive microbiological sampling of PP, oro-nasal, skin and ulcer sites. Staphylococci were recovered using selective chromogenic agar, definitively identified and subjected to DNA microarray profiling, whole-genome sequencing and core-genome multilocus sequence typing (cgMLST). Staphylococcus aureus and Staphylococcus epidermidis were recovered from both the oro-nasal and ulcer sites of 6/13 and 5/13 patients with ulcers, respectively. Molecular typing based on the staphylococcal protein A (spa) gene and DNA microarray profiling indicated that for each patient investigated, S. aureus strains from oro-nasal and ulcer sites were identical. Comparative cgMLST confirmed that isolates from multiple anatomical sites of each individual investigated grouped into closely related, patient-distinct clusters (Clusters 1-7). Isolates belonging to the same cluster exhibited an average of 2.9 allelic differences (range 0-11). In contrast, reference genomes downloaded from GenBank selected as representatives of each sequence type identified in the present study exhibited an average of 227 allelic differences from the most closely related isolate within each cluster.

A Surviving Case of Acanthamoeba Granulomatous Amebic Encephalitis in a Hematopoietic Stem Cell Transplant Recipient.

BACKGROUND Acanthamoeba are free-living amoebae with potential to infect immunocompromised hosts. The mortality rate of granulomatous amebic encephalitis (GAE) due to Acanthamoeba exceeds 90% and there are currently no reports of survival of this infection in recipients of hematopoietic stem cell transplant. CASE REPORT We report herein the case of a 32-year-old man presenting to our service with abrupt neurological deterioration and seizures 5 months after allogeneic stem cell transplantation for Hodgkin lymphoma. Clinical and imaging findings were non-specific at presentation. Multiple circumscribed, heterogenous, mass-like lesions were identified on MRI. Brain biopsy was performed and revealed multiple cysts and trophozoites suggesting a diagnosis of granulomatous amebic encephalitis. PCR testing confirmed Acanthamoeba. Treatment with miltefosine, metronidazole, azithromycin, fluconazole, pentamidine isethionate, and co-trimoxazole was instituted and the patient survived and shows continued improvement with intensive rehabilitation. CONCLUSIONS We report the first successful outcome in this setting. The diagnosis would have been missed on cerebrospinal fluid analysis alone, but was rapidly made by histological analysis of brain biopsy. This diagnostically challenging infection is likely under-recognized. Early brain biopsy and commencement of a prolonged miltefosine-containing anti-ameba regimen can be curative.

Spurious HbA1c results in patients with diabetes treated with dapsone.

SUMMARY: Measurement of glycated haemoglobin (HbA1c) has been utilised in assessing long-term control of blood glucose in patients with diabetes, as well as diagnosing diabetes and identifying patients at increased risk of developing diabetes in the future. HbA1c reflects the level of blood glucose to which the erythrocyte has been exposed during its lifespan, and there are a number of clinical situations affecting the erythrocyte life span in which HbA1c values may be spuriously high or low and therefore not reflective of the true level of glucose control. In the present case series, we describe the particulars of three patients with diabetes who had spuriously low HbA1c levels as a result of dapsone usage. Furthermore, we discuss the limitations of HbA1c testing and the mechanisms by which it may be affected by dapsone in particular. LEARNING POINTS: Various conditions and medications can result in falsely low HbA1c. Dapsone can lead to falsely low HbA1c by inducing haemolysis and by forming methaemoglobin. Capillary glucose measurement, urine glucose measurements and fructosamine levels should be used as alternatives to HbA1c for monitoring glycaemic control if it was falsely low or high.

A simple and cost-effective approach to assessment of pituitary adrenocorticotropin and growth hormone reserve: combined use of the overnight metyrapone test and insulin-like growth factor-I standard deviation scores.

CONTEXT: The insulin tolerance test (ITT) is the gold standard for assessment of ACTH and GH reserve in patients with suspected hypopituitarism. It is labor intensive and costly. OBJECTIVE: The objective of the study was to determine whether use of the overnight metyrapone test (OMT) and plasma IGF-I sd scores (SDS) could provide a cost-effective alternative to the ITT. DESIGN: This was a retrospective chart review. SETTING: The study was conducted at a teaching hospital. PARTICIPANTS AND INTERVENTION: Charts from 100 patients with organic pituitary disorders were reviewed. All underwent the OMT unless 0900 h plasma cortisol was less than 80 or greater than 450 nmol/liter when ACTH deficiency or ACTH sufficiency, respectively, was diagnosed. Patients were considered GH deficient if the age-related IGF-I SDS was less than -3 or if they had three or more other pituitary hormone deficiencies. Patients were considered GH sufficient if age-related IGF-I SDS was greater than the 95th centile established from patients with known GH deficiency. Thirty-three underwent an ITT. MAIN OUTCOME MEASURES: The proportion of patients in whom ACTH and GH reserve could be assessed using OMT/IGF-I SDS was measured. The concordance with results was obtained from ITT. RESULTS: Fifty-five patients were ACTH sufficient and 45 were ACTH deficient. Twenty-one were GH sufficient and 33 were GH deficient based on IGF-I SDS and other pituitary hormone deficiencies, whereas 46 could not be classified. There was near-uniform concordance between OMT/IGF-I SDS and ITT. Initial investigation using OMT/IGF-I SDS resulted in a significant cost saving. CONCLUSIONS: ACTH and GH reserve can be accurately and cost-effectively investigated using OMT/IGF-I SDS in approximately 50% of patients with organic pituitary disorders.

Personalized Cardio-Metabolic Responses to an Anti-Inflammatory Nutrition Intervention in Obese Adolescents: A Randomized Controlled Crossover Trial.

SCOPE: Chronic inflammation and hypoadiponectinemia are characteristics of obesity-induced insulin resistance (IR). The effect of an anti-inflammatory nutrition supplement (AINS) on IR and adiponectin biology in overweight adolescents was investigated. The secondary objective was to examine the extent to which individuals' biomarker profiles, derived from baseline phenotypes, predicted response or not to the AINS. Additionally, the impact of DNA methylation on intervention efficacy was assessed. METHODS AND RESULTS: Seventy overweight adolescents (13-18 years) were recruited to this randomized controlled crossover trial. Participants received an AINS (long chain n-3 PUFA, vitamin C, α-tocopherol, green tea extract, and lycopene) and placebo for 8 weeks each. Homeostatic model assessment (HOMA)-IR, adiponectin, inflammatory profiles, and DNA methylation were assessed. HOMA-IR was unchanged in the total cohort. High-molecular-weight (HMW) adiponectin was maintained following the AINS while it decreased over time following the placebo intervention. HOMA-IR decreased in 40% of subjects (responders) following the AINS. Responders' pretreatment phenotype was characterized by higher HOMA-IR, total and LDL cholesterol, but similar BMI in comparison to nonresponders. HMW adiponectin response to the AINS was associated with bidirectional modulation of adipogenic gene methylation. CONCLUSION: The AINS modulated adiponectin biology, an early predictor of type 2 diabetes risk, was associated with bidirectional modulation of adipogenic gene methylation in weight-stable overweight adolescents. HOMA-IR decreased in a sub-cohort of adolescents with an adverse metabolic phenotype. Thus, suggesting that more stratified or personalized nutrition approaches may enhance efficacy of dietary interventions.

Toward the development of a test for growth hormone (GH) abuse: a study of extreme physiological ranges of GH-dependent markers in 813 elite athletes in the postcompetition setting.

There is a need to develop a test to detect GH abuse by elite athletes. Measured levels of GH in blood or urine, however, provide little information on the GH-IGF-I axis. Previous studies have identified a series of indirect markers of GH action that are markedly altered by the administration of GH, but to a lesser degree by acute exercise. This study was undertaken to determine the physiological range of these GH-dependent variables in elite athletes after a competitive event to determine whether such values differ from resting values in normal and athletic subjects and to establish whether any adjustments to this range are required on the basis of age, gender, demographic characteristics, or the nature of the exercise performed. Serum samples were collected from 813 elite athletes (537 males and 276 females; age range, 17-64 yr) from 15 sporting disciplines within 2 h of completion of a major competitive event. IGF-I, IGF-binding protein 2 (IGFBP-2), IGFBP-3, acid-labile subunit, and the bone and soft tissue markers, osteocalcin, carboxyl-terminal propeptide of type I procollagen, carboxyl-terminal cross-linked telopeptide of type I collagen, and procollagen type III were measured. Sporting category, gender, age, height, weight, body mass index (BMI), and racial group of the athlete were documented, and results were compared both to normative data and to values obtained from elite athletes under resting conditions. Forty-one percent of IGF-I values in male athletes and 41% of values in female athletes were above the upper limits of 99% reference ranges derived from resting values in a normal population. Postcompetition levels of all variables except carboxyl-terminal propeptide of type I procollagen and carboxyl-terminal cross-linked telopeptide of type I collagen differed from resting values. There was a consistent age-dependent fall in measured levels of all variables (P < 0.0001) with the exception of IGFBP-2, which increased with age (P < 0.0001). BMI, but not height, exerted a small, but significant, influence on several variables. After adjustment for age, there were no significant differences in the levels of any of the measured variables between sporting categories. IGFBP-2 and IGFBP-3 were lower in 35 black athletes compared with those in 35 white athletes matched for age, gender, height, BMI, and sporting category. We have demonstrated that there are predictable age-dependent levels of GH-dependent markers in elite athletes that are consistent even at the extremes of physical exertion and that these are independent of sporting category. Normative data applicable to white athletes are provided. This provides important groundwork for the development of a test for GH abuse, although these values may be specific for the reagents and assays used.

Glucose as a risk predictor in acute medical emergency admissions.

AIMS: The aims of this study were to examine the relationship between admission blood glucose and mortality in a large, unselected cohort of acutely ill medical patients and to assess the impact of diabetes on this relationship. METHODS: We studied the broad pattern of acute medical admissions over an eight year period and the impact of admission serum glucose on in-hospital mortality. Significant predictors of outcome, including acute illness severity and co-morbidity, were entered into a multivariate regression model, adjusting the univariate estimates of the glycaemic status on mortality. RESULTS: There were 45,068 consecutive acute medical emergency admissions between 2005 and 2012. The normoglycaemic (>4.0 ≤7.0 mmol/l) cohort (86%) had a 3.9% in-hospital mortality. Both hypoglycaemia (OR: 3.23: 95% CI: 2.59-4.04; p<0.001) and hyperglycaemia (OR: 2.1; 95% CI: 1.9-2.4; p<0.001) predicted an increased risk of an in-hospital death. Neither of these increased risks were fully adjusted nor explained by a highly predictive outcome model, using multiple acute illness parameters. Hyperglycaemia did not carry similar adverse prognostic implications for patients with diabetes. CONCLUSION: In patients without diabetes, an abnormal serum glucose is independently predictive of an increased mortality among the broad cohort of acute emergency medical patients. Similar disturbances of glucose homeostasis for patients with diabetes do not confer equivalent adverse prognostic implications.

Management of squamous cell cancer of the oesophagus in a patient with a polyglandular endocrinopathy (APECED) and achalasia.

INTRODUCTION: We report a case of a 37-year-old man, with a background of a rare polyglandular autoimmune syndrome and achalasia, who developed an oesophageal tumour. Both autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) or type I polyglandular syndrome and achalasia confer increased risk of development of oesophageal squamous cell carcinoma. METHODS: Despite having had multiple endoscopic examinations and dilatations in the recent past, this patient presented with dysphagia, and on endoscopy, he was found to have a mid-oesophageal tumour. A multidisciplinary team approach was vital in his management as careful monitoring of underlying disorders including Addison's disease and hypoparathyroidism were challenging during neoadjuvant chemoradiotherapy and in the perioperative period. RESULTS: He made an uneventful recovery after a three-stage oesophagectomy, and histologically, he had a complete pathological response. CONCLUSION: To our knowledge, this is the first successful outcome of a patient with APECED and oesophageal carcinoma in the literature.

Metastatic insulinoma in a patient with type 2 diabetes mellitus: case report and review of the literature.

Pancreatic neuroendocrine tumors (NETs) are extremely rare, and although insulinomas are the commonest, less than 10% of insulinomas are malignant. Most patients with insulinomas present with neuroglycopenic symptoms and weight gain attributable to insulin excess. Here, we report a case where a 67-year-old lady with a background history of type 2 diabetes mellitus and breakthrough hyperinsulinism who presented with coma. The biochemical profile revealed features typical of insulinoma, and CT and endosonography confirmed a pancreatic tumor with large volume right-sided liver metastases (biopsy confirming a neuroendocrine tumor). The patient underwent successful one-step RO surgical resection, distal pancreatectomy, splenectomy, and right hepatectomy, and 9 months postoperatively, she remains free of recurrent disease. She remains a diabetic.

The physiology of growth hormone and sport.

The growth hormone (GH)/ insulin-like growth factor-I (IGF-I) axis exerts short-and long-term metabolic effects that are potentially important during exercise. Exercise is a potent stimulus to GH release and there is some evidence that the acute increase in GH is important in regulating substrate metabolism post-exercise. Regular exercise also increases 24-hour GH secretion rates, which potentially contributes to the physiologic changes induced by training. The effects of GH replacement in GH-deficient adults provide a useful model with which to study the effects of the more long-term effects of the GH/ IGF-I axis. There is convincing evidence that GH replacement increases exercise capacity. Measures of exercise performance including maximal oxygen uptake (VO2max) and ventilatory threshold (VeT) are impaired in GH deficiency and improved by GH replacement, probably through some combination of increased oxygen delivery to exercising muscle, increased fatty acid availability with glycogen sparing, increased muscle strength, improved body composition and improved thermoregulation. Administration of supraphysiologic doses of GH to athletes increases fatty acid availability and reduces oxidative protein loss particularly during exercise, and increases lean body mass. It is not known whether these effects translate to improved athletic performance, although recombinant human GH is known to be widely abused in sport. The model of acromegaly provides evidence that long-term GH excess does not result in improved performance but it is possible that a "window" exists in which the protein anabolic effects of supraphysiologic GH might be advantageous.

Technology insight: measuring prolactin in clinical samples.

Measurement of prolactin is one of the most commonly undertaken hormonal investigations in evaluating patients with reproductive disorders. Hyperprolactinemia is found in up to 17% of such cases. Diagnostic evaluation of hyperprolactinemia is difficult but is facilitated by a logical approach where a thorough patient history is obtained, secondary causes of hyperprolactinemia are excluded, and the limitations of current prolactin assays are appreciated. Once hyperprolactinemia has been confirmed, attempts to establish the underlying cause can start. Given current workloads, laboratories rely on automated platforms to measure prolactin, most of which employ two-site immunoassay sandwich methods. Although generally robust and reliable, such immunoassays are susceptible to interference, and good collaboration between clinicians and the laboratory helps to minimize problems. A major challenge facing laboratories is correct differentiation of patients with true hyperprolactinemia from those with macroprolactinemia. Macroprolactin is a high-molecular-mass, biologically inactive form of prolactin that is detected to varying degrees by all prolactin immunoassays. Conservative estimates suggest that the presence of macroprolactin leads to misdiagnosis in as many as 10% of all reported instances of biochemical hyperprolactinemia. In the absence of specific testing, macroprolactin represents a diagnostic pitfall that results in the misdiagnosis and mismanagement of large numbers of patients.

Diagnosis, misdiagnosis and management of hyperprolactinemia.

Hyperprolactinemia is a commonly encountered disorder that suppresses both male and female gonadal function. The etiology includes pituitary tumors, hypothalamic or pituitary stalk lesions, drugs and hypothyroidism. In women, the hyperprolactinemic syndrome is characterized by menstrual disorders with or without galactorrhea, while men present with hypogonadism and related symptoms. Occasionally, a pituitary macroadenoma may be associated with pressure symptoms and/or hypopituitarism. Clinically, the most important cause of hyperprolactinemia is a prolactin-secreting pituitary adenoma. The majority of patients with prolactinomas are successfully managed medically with dopamine agonists such as cabergoline or bromocriptine. Misdiagnosis of hyperprolactinemia owing to immunoassay interference by a biologically minimally active form of prolactin termed macroprolactin is common in laboratory medicine . Alhough the etiology of macroprolactinemia is unclear, the condition is commonly associated with the presence of circulating antiprolactin antibodies. In the absence of specific testing, macroprolactin represents a diagnostic pitfall resulting in misdiagnosis and mismanagement of patients. This review examines the investigation and treatment of hyperprolactinemia in the broadened context of screening for macroprolactin and the consequences of failure to identify its presence.