Cognitive performance in midlife type 2 diabetes: results from the ENBIND study.

AIMS: To establish the impact of uncomplicated type 2 diabetes on cognitive and neuropsychological performance in midlife. METHODS: We performed a cross-sectional study of middle-aged adults with uncomplicated type 2 diabetes and a cohort of healthy control participants. General cognition was assessed using the Montreal Cognitive Assessment test and neuropsychological assessment was undertaken using a detailed neuropsychological assessment battery. RESULTS: A total of 152 participants (102 with type 2 diabetes and 50 controls) were recruited (mean age 52 ± 8 years, 51% women). Participants with midlife type 2 diabetes were more than twice as likely to make an error on the Montreal Cognitive Assessment test [incidence rate ratio 2.44 (95% CI 1.54 to 3.87); P < 0.001]. Further, type 2 diabetes was also associated with significantly lower memory composite score [ß: -0.20 (95% CI -0.39 to -0.01); P = 0.04] and paired associates learning score [ß: = -1.97 (95% CI -3.51, -0.43); P = 0.01] on the neuropsychological assessment battery following adjustment for age, sex, BMI, educational attainment and hypercholesterolaemia. CONCLUSIONS: Even in midlife, type 2 diabetes was associated with small but statistically significant cognitive decrements. These statistically significant decrements, whilst not clinically significant in terms of objective cognitive impairment, may have important implications in selecting out individuals most at risk of later cognitive decline for potential preventative interventions in midlife.

Measurement of selected androgens using liquid chromatography-tandem mass spectrometry in reproductive-age women with Type 1 diabetes.

STUDY QUESTION: What information does androgen profiling using liquid chromatography tandem mass spectrometry (LC-MS/MS) provide in reproductive-age women with Type 1 diabetes (T1D)? SUMMARY ANSWER: In T1D women, androstenedione proved most useful of the measured androgens in differentiating subgroups based on clinical phenotypes of hyperandrogenism (HA) and polycystic ovary syndrome (PCOS). WHAT IS KNOWN ALREADY: The prevalence of HA and PCOS are increased in women with T1D. These observations are based on measurement of serum androgens using immunoassays, to-date no studies using LC-MS/MS have been reported in reproductive-age women with T1D. STUDY DESIGN, SIZE, DURATION: This was a cross-sectional study with recruitment of three groups of reproductive-age women: women with T1D (n = 87), non-diabetic women with (N = 97) and without PCOS (N = 101). PARTICIPANTS/MATERIALS, SETTING, METHODS: Using LC-MS/MS, we aimed to characterize androgen profiles and PCOS status in women with T1D, and interpret findings in relation to cohorts of non-diabetic women with and without PCOS. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to non-diabetic women, dehydroepiandrosterone/dehydroepiandrosterone sulphate (DHEA/DHEAS) ratio was lower (P < 0.05) in women with T1D. Testosterone levels were greater in T1D women with clinical HA and anovulation compared to those without clinical HA and with regular cycles, while androstenedione levels were greater in T1D women with HA and anovulation compared to those with HA and regular cycles and also those without HA and with regular cycles (P < 0.05 for all). Compared to T1D women without PCOS, the 18% of T1D women who had PCOS were younger with lower BMI, an older age of menarche, and were more likely to have a positive family history of PCOS (P < 0.05 for all). Androgen levels did not differ between women with T1D and PCOS compared to BMI-matched non-diabetic women with PCOS, but androstenedione levels were greater in T1D women with PCOS compared to obese women with PCOS (P < 0.05). LIMITATIONS, REASONS FOR CAUTION: Relatively small subgroups of patients were studied, reducing the power to detect small differences. Free testosterone levels were not measured using equilibrium dialysis, and were not calculated - commonly used formulae have not been validated in T1D. WIDER IMPLICATIONS OF THE FINDINGS: Androstenedione is a sensitive biochemical marker of clinical hyperandrogenism and PCOS in T1D. T1D women with PCOS are leaner than those without PCOS but are more likely to have a family history of PCOS. Women with T1D and PCOS have a similar biochemical phenotype to lean non-diabetic women with PCOS but differ from obese women with PCOS. The mechanisms underlying PCOS in T1D and its clinical significance require further investigation. STUDY FUNDING/COMPETING INTEREST(S): The study was part-funded by the Meath Foundation. The authors have no competing interests.

Endocrine profiles in 693 elite athletes in the postcompetition setting.

OBJECTIVE: To measure a profile of hormones in a group of elite athletes. Increasing awareness of the widespread use of hormones as performance-enhancing agents focusses attention on what may be considered as normal in this unusual group. DESIGN: Blood samples were obtained from 813 volunteer elite athletes from a cross-section of 15 sporting categories. An endocrine profile was measured on a subset of 693. PARTICIPANTS: Volunteer elite athletes. Samples were drawn within two hours of an event at a major national or international competition. MEASUREMENTS: Demographics and hormone profiles were obtained on 454 male and 239 female elite athletes. RESULTS: Hormone profiles showed significant differences in 19 of the 24 measured variables between sexes and between all of the 15 sporting disciplines in men and 11 out of 24 in women. 16.5% of men had low testosterone levels, whereas 13.7% of women had high levels with complete overlap between the sexes. Women had a lean body mass 85% that of men - sufficient to account for sex differences in performance. There were highly significant correlations between many of the measured hormones. CONCLUSIONS: Hormone profiles from elite athletes differ from usual reference ranges. Individual results are dependent on a number of factors including age, gender and physique. Differences in profiles between sports suggest that an individual's profile may contribute to his/her proficiency in a particular sport. The IOC definition of a woman as one who has a 'normal' testosterone level is untenable.

Polycystic ovary syndrome influences the level of serum amyloid A and activity of phospholipid transfer protein in HDL2 and HDL3.

STUDY QUESTION: Is polycystic ovary syndrome (PCOS) associated with altered levels of pro-inflammatory high-density lipoproteins (HDL) and activity of HDL-associated enzymes? SUMMARY ANSWER: In PCOS, HDL contained increased levels of the inflammatory marker serum amyloid A (SAA) and altered functioning of HDL-associated phospholipid transfer protein (PLTP), with these changes being independent of BMI, body fat and insulin resistance (IR). WHAT IS KNOWN ALREADY: PCOS is associated with adipocyte-derived inflammation, which potentially increases the risk of cardiovascular disease and diabetes. SAA is an inflammatory marker that is released from hypertrophic adipocytes and interacts with HDL, reducing their anti-atherogenic properties. No studies have previously investigated if SAA-associated HDL influences the HDL-associated enzymes namely, PLTP and cholesterol ester transfer protein (CETP) in women with PCOS. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Obese women with PCOS were matched with controls for BMI and percentage body fat (n = 100/group; cohort-1); a subset of these women (n = 64/group; cohort-2) were further matched for IR. HDL in blood samples was subfractionated into HDL2 and HDL3 by rapid ultracentrifugation. SAA was measured in serum, HDL2 and HDL3 by an enzyme-linked immunosorbent assay and the activities of PLTP and CETP were measured in HDL2 and HDL3 by fluorimetric assays. MAIN RESULTS AND THE ROLE OF CHANCE: In the PCOS women from cohort-1, SAA was increased in serum, HDL2 and HDL3 (P = 0.038, 0.008 and 0.001 versus control, respectively), as was the activity of PLTP in HDL2 and HDL3 (P = 0.006 and 0.009 versus controls, respectively). In the PCOS women from cohort-2, SAA was increased in serum, HDL2 and HDL3, although only significantly in HDL3 (P = 0.083, 0.120 and 0.034 versus controls, respectively), as was the activity of PLTP in HDL2 and HDL3, although this was only significant in HDL2 (P = 0.045 and 0.070 versus controls, respectively). LIMITATIONS, REASONS FOR CAUTION: First, insulin sensitivity was not determined by the euglycaemic-hyperinsulinaemic clamp. Secondly, the method used to estimate body fat was not able to discriminate between visceral and peripheral fat. Thirdly, larger study groups would be required to confirm if PCOS independently contributed to SAA-related HDL and functional changes to this lipoprotein, independent of BMI, percentage body fat and IR. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to highlight the usefulness of HDL-associated SAA as a marker to identify increased inflammation in women with PCOS. This study also identified that the functioning of HDL was altered in women with PCOS. These findings illustrate a mechanism through which cardiovascular disease may increase in PCOS. STUDY FUNDING/COMPETING INTERESTS: Funded by the Irish Endocrinology Society. No competing interests. CLINICAL TRIAL REGISTRATION NUMBER: NCT001195168.

Factors influencing elevated serum apolipoprotein B48 in diabetic and control participants.

Factors influencing the concentration of apolipoprotein B48 (apo B48) at fasting and post-prandial time frames are still being elucidated. This study assesses some possible contributing factors including the presence of type 2 diabetes and gender using an established enzyme-linked immunosorbent assay (ELISA) method. Apo B48 and triglyceride (TG) levels were measured before and for two, four and six hours post-prandially in 49 poorly controlled participants with type 2 diabetes and in 60 apparently healthy participants (controls). Apo B48 levels in the control participants increased post-prandially, peaking at four hours (14.81 ± 7.72 µg/mL) with similar responses demonstrated in TG concentrations. Post-prandial apo B48 levels were significantly higher in male control participants as demonstrated by apo B48 area under the curve (AUC); similar responses were also confirmed in triglyceride AUC. Post-prandial apo B48 concentrations in control participants correlated with HOMA-IR (P < 0.05). Apo B48 continued to increase throughout the six hours in participants with type 2 diabetes (17.73 ± 13.46 µg/mL), when levels were significantly greater than in the control participants (13.04 ± 7.67 µg/mL) (P < 0.05) despite a decrease in accompanying TG levels in participants with type 2 diabetes. Using an ELISA method, this study demonstrated that gender, insulin resistance (as evidenced by HOMA-IR) and diabetes status influence serum apo B48 levels. These effects were only apparent post-prandially.

Screening for undiagnosed pancreatic exocrine insufficiency (PEI) in a cohort of diabetic patients using faecal elastase testing and PEI scoring system.

INTRODUCTION: Type 1 and type 2 diabetes mellitus (DM) are often accompanied by mild forms of pancreatic exocrine insufficiency (PEI). The prevalence rates of PEI in diabetic patients are unclear and variable depending on the testing modality and the studies published. The clinical consequences of PEI in diabetics are also not well defined. AIM: We aimed to determine the prevalence of PEI in a diabetic cohort using the faecal elastase-1 (FE-1) assay as a screening test and to validate a patient-reported symptom-based scoring system, the (PEI-S) for diagnosing PEI within this patient population. METHODS: Two hundred and three diabetic patients attending diabetic and gastroenterology outpatients of a university hospital without previously known PEI were recruited for the study. Demographic parameters, PEI score (PEI-S), and glycated hemoglobin (HBA1c) were documented in standardized data sheets, and a stool sample was obtained. A FE-1 value < 200 µg/g and or a PEIS of > 0.6 was used as the screening cut-off for PEI. RESULTS: One hundred sixty-six patients returned faecal samples. The prevalence of PEI, as measured by low FE-1, was 12%. Smoking was associated with an increased risk of developing PEI in this diabetic population. No other independent risk factors were identified. The PEI-S system did not differentiate between people with diabetes having a normal and low FE1. CONCLUSION: 12% of this mixed, real-life cohort of type 1 and 2 DM patients had undiagnosed PEI, as defined by an FE-1 score of less than 200 µg/g. While this may appear low, given the rising prevalence of type 2 DM worldwide, there is likely an unrecognized burden of PEI, which has long-term health consequences for those affected. The PEI-S, a symptom-scoring system for patients with PEI, did not perform well in this patient group.

Leucocytosis in women with polycystic ovary syndrome (PCOS) is incompletely explained by obesity and insulin resistance.

OBJECTIVES: Low-grade chronic inflammation predicts cardiovascular outcomes and is observed in women with polycystic ovary syndrome (PCOS). Whether this is entirely a cause or consequence of insulin resistance (IR) is unknown. METHODS: Seventy pairs of women with and without PCOS, matched for age, body mass index (BMI) and IR (HOMA, QUICKI and Avignon index), were generated from a larger cohort of 103 women with and 104 BMI-matched women without PCOS. Women with PCOS were studied in the follicular phase of the menstrual cycle. White cell count (WCC), high-sensitivity CRP (hsCRP) and a series of 12 cytokines and growth factors were measured. These inflammatory markers were also compared between women with PCOS and 10 normal women studied in the follicular, peri-ovulatory and luteal stages. RESULTS: When all subjects were compared, WCC (6.75 × 10(9) vs 5.60 × 10(9 ) g/l, P < 0.005), hsCRP (4.04 vs 2.90 mg/l, P < 0.05) and IL-6 (1.11 vs 0.72 pg/ml, P < 0.05) were greater in women with PCOS. Pair-matching for IR eliminated between-group differences in hsCRP and cytokines but did not alter the difference in WCC (6.60 × 10(9) vs 5.60 × 10(9 ) g/l, P < 0.005). WCC was greater in PCOS compared to normal women at all stages of the menstrual cycle. CONCLUSIONS: Low-grade inflammation occurs in PCOS. Increased hsCRP and cytokines are associated with IR, but increased WCC is observed even when IR is accounted for. The explanation for this and its clinical significance is unknown.

Neurosarcoidosis-related intracranial haemorrhage: three new cases and a systematic review of the literature.

BACKGROUND AND PURPOSE: Intracranial haemorrhage in neurosarcoidosis (NS-ICH) is rare, poorly understood and the diagnosis of NS may not be immediately apparent. METHODS: The clinical features of three new NS-ICH cases are described including new neuropathological findings and collated with cases from a systematic literature review. CASES: (i) A 41-year-old man with headaches, hypoandrogenism and encephalopathy developed a cerebellar haemorrhage. He had neuropathological confirmation of NS with biopsy-proven angiocentric granulomata and venous disruption. He responded to immunosuppressive therapy. (ii) A 41-year-old man with no history of hypertension was found unconscious. A subsequently fatal pontine haemorrhage was diagnosed. Liver biopsy revealed sarcoid granulomas. (iii) A 36-year-old man with raised intracranial pressure headaches presented with a seizure and a frontal haemorrhage. Hilar lymph node biopsy confirmed sarcoidosis, and he was treated successfully. Systematic review: Twelve other published cases were identified and collated with our cases. Average age was 36 years and M:F = 2.3:1; 46% presented with neurological symptoms and 31% had CNS-isolated disease. Immediate symptoms of ICH were acute/worsening headache or seizures (60%). ICH was supratentorial (62%), infratentorial (31%) or subarachnoid (7%). Forty percent had definite NS, 53% probable NS and 7% possible NS (Zajicek criteria). Antigranulomatous/immunosuppressive therapy regimens varied and 31% died. CONCLUSIONS: This series expands our knowledge of the pathology of NS-ICH, which may be of arterial or venous origin. One-third have isolated NS. Clinicians should consider NS in young-onset ICH because early aggressive antigranulomatous therapy may improve outcome.

The Effect of Time-Restricted Eating on Insulin Levels and Insulin Sensitivity in Patients with Polycystic Ovarian Syndrome: A Systematic Review.

Results: 2662 papers were identified with 37 selected for full-text review and one paper meeting criteria for inclusion. Ramadan fasting was the only time-restricted eating regimen trialled in this population with no strong evidence of a significant effect on insulin levels. Conclusion: As the systematic review retrieved only one study investigating time-restricted eating to reduce insulin in patients with PCOS, there is no evidence to suggest that this intervention is effective. From the narrative review, based on studies in other patient groups, time-restricted eating could improve insulin resistance in those with PCOS; however, well-designed studies are required before this intervention can be recommended.

Non-pharmacological interventions for cognition in patients with Type 2 diabetes mellitus: a systematic review.

Midlife Type II diabetes mellitus (T2DM) is an important yet often unrecognized risk factor for the later development of dementia. We conducted a systematic review to assess the efficacy of non-pharmacological interventions (namely diet, exercise and cognitive training) for T2DM on cognition. A search strategy was constructed and applied to four databases: EMBASE, Medline, CINAHL and Web of Science. Peer-reviewed journal articles in English were considered assessing the effect of exercise, dietary or cognitive training/stimulation-based interventions (or any combination of these) in patients with T2DM on cognition. Results were dual-screened and extracted by two independent reviewers. Of 4820 results, 3782 remained after de-duplication. Forty full-texts were screened and two studies were included in the final review. The first assessed the impact of a 10-year intensive lifestyle intervention on T2DM-related complications (Look-AHEAD study) and the second was a post hoc analysis of T2DM patients from a trial of a physical activity intervention in older non-demented adult with functional limitations (LIFE study). Whilst the Look-AHEAD study found no impact on diagnosis of mild cognitive impairment or dementia, the LIFE study demonstrated beneficial effects on global cognitive function and delayed memory specifically in older adults with T2DM. There is insufficient evidence to fully assess the effect of non-pharmacological interventions on cognition in T2DM. Well-constructed trials must be designed to specifically assess the effect of non-pharmacological and multi-domain interventions for cognition in patients with T2DM in midlife. All trials examining interventions in T2DM should consider cognition as at least a secondary outcome.

Findings in cattle consigned to Victorian knackeries between 2009 and 2018.

OBJECTIVE: To describe the causes of death or culling in cattle in Victoria, Australia, through surveillance at knackeries. METHODS: Data were collected from 2797 adult cattle consigned to four Victorian knackeries over a 10-year period (2009-2018, inclusive). Cattle were sampled either at the point of collection or at a knackery. A single best-fit diagnosis was assigned to each case to describe the cause of loss. RESULTS: Sampled cattle were predominantly female dairy cattle originating from the three main dairying regions in Victoria. The most commonly diagnosed conditions were calving paralysis (6.8%), followed by mastitis (6.4%), hypocalcaemia (6.4%) and dystocia (5.9%). "Unknown" accounted for 24.2% of the cattle examined. CONCLUSION: This study provides a unique insight into the causes of death and culling in cattle consigned to Victorian knackeries. The periparturient period was identified as a high risk period for knackery consignment in adult female cattle.

Effects of 18 months of L-T4 replacement in women with subclinical hypothyroidism.

CONTEXT: Some of the cardiovascular and renal abnormalities seen in overt hypothyroidism have also been reported in subclinical hypothyroidism (SCH). Short-term L-T4 replacement in SCH improves cardiovascular risk markers and reduces carotid intima-media thickness (CIMT), a surrogate marker of atherosclerosis. The haemodynamic and renal effects of L-T4 replacement in SCH are poorly understood. OBJECTIVES: To compare cardiovascular risk factors and renal variables in women with SCH and normal women. To study the effects of L-T4 replacement in SCH subjects on these variables and on structural and functional changes in common carotid and brachial arteries. DESIGN: Fifty-six women with SCH before and after L-T4 replacement for 18 months and 56 normal women of similar age distribution were studied. Blood Pressure (BP), plasma lipids and homocysteine were measured and renal function evaluated [estimation of glomerular filtration rate (eGFR) using standard equations and measurement of serum Cystatin-C] in women with SCH before and after 18 months of l-T4, and in healthy women. CIMT and endothelial function (using brachial artery ultrasound) were studied before and after L-T4 in a subgroup of women with SCH. RESULTS: Systolic and diastolic BP, total cholesterol, triglyceride, LDL-cholesterol, lipoprotein(a) and homocysteine were greater in SCH (P < 0.05), and following L-T4 replacement decreased (P < 0.05) to levels that no longer differed from normal subjects. Estimated GFR was reduced and serum Cystatin-C increased (P < 0.05) in SCH. These variables also normalized following L-T4. Following L-T4 replacement the carotid artery baseline diameter increased by 7.1% and CIMT decreased by a mean value of 13%, while brachial artery diameter increased basally by 12.5% and following endothelium-dependent vasodilatation by 17.5% (P < 0.05). However, the increment following reactive hyperaemia did not differ before or following L-T4 replacement. CONCLUSION: Normalization of cardiovascular risk factors following L-T4 replacement in SCH potentially explains reduced CIMT. Increased carotid and brachial artery diameters and normalized eGFR indicates a haemodynamic effect of L-T4 replacement, the importance of which requires further investigation.

Does thyrotoxic periodic paralysis have a genetic predisposition? A case report.

Thyrotoxic periodic paralysis is a rare complication of hyperthyroidism where increased influx of potassium into skeletal muscle cells leads to profound hypokalaemia and paralysis. Most cases arise sporadically in Asians; however, it is being increasingly reported in Caucasians. It is regarded as a channelopathy where a genetic and/or acquired defect in the sodium-potassium (Na/K-ATPase) pump renders it more sensitive to excess thyroid hormone in susceptible individuals. Because the clinical presentation is similar to familial hypokalaemic periodic paralysis, genes implicated in this autosomal-dominant condition became candidates for thyrotoxic periodic paralysis, particularly if they were known to have thyroid hormone-responsive elements. These include the voltage-gated calcium (CACNA1S) and sodium (SCN4A) channel genes, KCNJ18 which encodes the inwardly rectifying potassium channel Kir2.6, and subunits of the Na/K-ATPase genes. Although no single pathogenetic mutation has been identified in thyrotoxic periodic paralysis, several single-nucleotide polymorphisms in these genes have been associated with it. We describe a 27-year-old Caucasian Irish male who presented with acute onset limb paralysis and severe hypokalaemia. He was diagnosed as having thyrotoxic periodic paralysis secondary to Graves' disease based on clinical presentation, biochemical findings and rapid response to intravenous potassium. Genetic analysis identified heterozygous variants in three candidate genes: KCNJ18 (c.576G>C), SCN4A (c.2341G>A) and CACNA1S (c.1817G>A). Since these variants are not disease causing and occur at high prevalences of 50%, 2-3% and 1%, respectively, in the normal population, they do not explain the clinical phenotype in our patient suggesting that acquired environmental triggers or as-yet unidentified gene mutations remain as leading pathogenetic co-factors in thyrotoxic periodic paralysis.

Evidence for marsh mallow (Malva parviflora) toxicosis causing myocardial disease and myopathy in four horses.

REASON FOR PERFORMING THE STUDY: Investigation of toxicosis caused by Malva parviflora was required after 4 horses from the same farm developed severe muscle fasciculations, tachycardia, sweating and periods of recumbency leading to death or euthanasia after ingesting the plant. OBJECTIVES: To describe historical, clinical, clinicopathological and pathological findings of 4 horses with suspected M. parviflora toxicosis. The role of cyclopropene fatty acids (found in M. parviflora) and mechanism for toxicosis are proposed. STUDY DESIGN: Case series. METHODS: Historical, physical examination, clinicopathological and pathological findings are reported. Due to similarities with atypical myopathy or seasonal pasture myopathy acyl carnitine profiles were performed on sera from 2 cases and equine controls. Presence of cyclopropene fatty acids was also examined in sera of 2 cases. RESULTS: M. parviflora had been heavily grazed by the horses with little other feed available. Horse 1 deteriorated rapidly and was subjected to euthanasia. Horse 2 was referred to hospital where severe myocardial disease and generalised myopathy was determined; this horse was subjected to euthanasia 36 h after admission. Horse 3 died rapidly and Horse 4 was subjected to euthanasia at onset of clinical signs. Post-mortem examinations performed on 3 horses revealed acute, multifocal cardiac and skeletal myonecrosis. Myocyte glycogen accumulation was absent when examined in Horse 2. Acyl carnitine profiles revealed increased C14-C18 acyl carnitine concentrations in cases relative to controls. Cyclopropene fatty acids were detected in sera of cases but not controls. CONCLUSION: These findings suggest aetiology different to that of atypical myopathy or seasonal pasture myopathy. We hypothesise that cyclopropene fatty acids in M. parviflora interfere with fatty acid ß-oxidation in horses in negative energy balance, causing the clinical signs and abnormal acyl carnitine profiles. These equine cases suggest a pathophysiological course that closely mimics the human genetic condition very long chain acyl CoA dehydrogenase deficiency.

The nutritional management of type 3c (pancreatogenic) diabetes in chronic pancreatitis.

Type 3c diabetes mellitus (T3cDM), also known as pancreatogenic diabetes, refers to diabetes caused by disease of the exocrine pancreas. T3cDM is not commonly recognised by clinicians and frequently it is misclassified as T1DM, or more commonly, T2DM. T3cDM can be difficult to distinguish from T1DM and T2DM, and it often co-exists with the latter. The aim of this review is to describe T3cDM, along with its complications, diagnosis and management. We focus on the nutritional implications of T3cDM for those with chronic pancreatitis, and provide a practical guide to the nutritional management of this condition.

Endocrinopathies and renal outcomes in lithium therapy: impact of lithium toxicity.

BACKGROUND: Lithium is the mainstay of treatment for bipolar disorder, mania and an augmentation therapy in patients with treatment resistant depression. It has a narrow therapeutic index, with recognized adverse multi-system and endocrine side effects. AIM: To assess the impact of lithium therapy, in particular lithium toxicity, on the development of endocrine and renal disorders in a cohort of patients in a single tertiary referral centre in Ireland. STUDY DESIGN: A retrospective analysis was performed of the prevalence of lithium toxicity and renal, thyroid and parathyroid dysfunction in our study population. METHODS: We collected laboratory data from the Clinical Chemistry department of the Adelaide and Meath Hospital incorporating the National Children's Hospital (AMNCH), Dublin, Ireland. Our study population included all patients who had at least one serum lithium measurement from January 1st 2000 to December 31st 2014 inclusive. RESULTS: A total of 580 patients were included in the study. Among our study group, 70 patients (12.1%) had 1 toxic lithium measurement (lithium level >1.2 mmol/l). 27.8% (n > 161) of patients developed stage 3 Chronic kidney Disease (CKD) or higher, which was commoner in those patients who developed toxic lithium levels (P < 0.0001) and in those who developed hypernatraemia (P > 0.0001). 16.2% of patients (n > 94) had one serum sodium >145 mmol/l during follow up. 60 patients(10.3%) had a TSH >10 mU/l, while complete suppression of TSH (<0.05 mU/l) was observed in 22 patients (3.8%) during follow-up. 4% (n > 37) of the study population had ≥1 serum corrected calcium level > 2.55 mmol/l, and 4 patients had biochemical confirmation of primary hyperparathyroidism but PTH levels were only performed in 2.8% (n > 16) of the studypopulation. CONCLUSION: Stage 3 CKD is common in patients receiving lithium therapy. Lithium toxicity is associated with CKD and hypernatraemia. Thyroid dysfunction and hypercalcaemia are common in patients receiving lithium therapy. Patients receiving lithium therapy require surveillance of renal, thyroid and bone biochemistry.

Effects of high-dose growth hormone on glucose and glycerol metabolism at rest and during exercise in endurance-trained athletes.

CONTEXT: Recombinant human-GH (r-hGH), in supraphysiological doses, is self-administered by athletes in the belief that it is performance enhancing. OBJECTIVE: The objective of this study was to determine whether r-hGH alters whole-body glucose and glycerol metabolism in endurance-trained athletes at rest and during and after exercise. DESIGN: This was a 4-wk double-blind placebo-controlled trial. SETTING: This study was conducted at St. Thomas Hospital (London, UK). PARTICIPANTS: Twelve endurance-trained male athletes were recruited and randomized to r-hGH (0.2 U/kg.d) (n = 6) or identical placebo (n = 6) for 4 wk. One (placebo group) withdrew after randomization. INTERVENTION: Intervention was conducted by randomization to r-hGH (0.2 U/kg x d) or identical placebo for 4 wk. MAIN OUTCOME MEASURES: Whole-body rates of appearance (Ra) of glucose and glycerol (an index of lipolysis) and rate of disappearance of glucose were measured using infusions of d-[6-6-2H2]glucose and 2H5-glycerol. RESULTS: Plasma levels of glycerol and free fatty acids and glycerol Ra at rest and during and after exercise increased during r-hGH treatment (P < 0.05 vs. placebo). Glucose Ra and glucose rate of disappearance were greater after exercise during r-hGH treatment (P < 0.05 vs. placebo). Resting energy expenditure and fat oxidation were greater under resting conditions during r-hGH treatment (P < 0.05 vs. placebo). CONCLUSIONS: r-hGH in endurance-trained athletes increased lipolysis and fatty acid availability at rest and during and after exercise. r-hGH increased glucose production and uptake rates after exercise. The relevance of these effects for athletic performance is not known.

Cystic fibrosis-related diabetes in adults.

We aimed to examine the differences between patients with cystic fibrosis-related diabetes (CFRD), and those with normal glucose handling in adults with cystic fibrosis (CF) in Ireland. We conducted a retrospective analysis of patients who attend the national referral centre for adult CF. Patients were diagnosed as having CFRD by the American Cystic Fibrosis Foundation criteria for diagnosis of CFRD. Of 259 patients, 150 were classifiable and 81 (54%) were classified as having CFRD. The groups with and without CFRD were not significantly different with regard to age (median 28.4 vs 26.0 years), sex (males 56% vs 55%) or BMI (median 20.9 vs 21.3 kg/m2). The group with CFRD had poorer lung function (mean % predicted FEV1 49.9 vs 66.4, P < 0.001), poorer bone mineral density (T-scores at the lumbar spine -1.95 vs -1.44, P < 0.05 and femur -1.19 vs -0.57, P < 0.01) and a greater proportion of PSEUDOMONAS AERUGINOSA positive sputum cultures (82.5% vs 64.2%, P < 0.05). No patients with CFRD carried the R1 17H mutation whilst 19% of the group without CFRD were heterozygous for this defect (P < 0.001). In conclusion, CFRD was highly prevalent in adults. The presence of CFRD was associated with poorer lung function, poorer bone mineral density and an increased prevalence of PSEUDOMONAS AERUGINOSA in sputum. The R1 17H mutation may be protective for CFRD.

Spontaneous resolution of avascular necrosis of femoral heads following cure of Cushing's syndrome.

UNLABELLED: Avascular necrosis (AVN) is a rare presenting feature of endogenous hypercortisolism. If left untreated, complete collapse of the femoral head may ensue, necessitating hip replacement in up to 70% of patients. The majority of the described patients with AVN due to endogenous hypercortisolaemia required surgical intervention. A 36-year-old female, investigated for right leg pain, reported rapid weight gain, bruising and secondary amenorrhoea. She had abdominal adiposity with violaceous striae, facial plethora and hirsutism, atrophic skin, ecchymosis and proximal myopathy. Investigations confirmed cortisol excess (cortisol following low-dose 48h dexamethasone suppression test 807nmol/L; 24h urinary free cortisol 1443nmol (normal<290nmol)). Adrenocorticotrophic hormone (ACTH) was <5.0pg/mL. CT demonstrated subtle left adrenal gland hypertrophy. Hypercortisolaemia persisted after left adrenalectomy. Histology revealed primary pigmented micronodular adrenal disease. Post-operatively, right leg pain worsened and left leg pain developed, affecting mobility. MRI showed bilateral femoral head AVN. She underwent right adrenalectomy and steroid replacement was commenced. Four months after surgery, leg pain had resolved and mobility was normal. Repeat MRI showed marked improvement of radiological abnormalities in both femoral heads, consistent with spontaneous healing of AVN. We report a case of Cushing's syndrome due to primary pigmented nodular adrenocortical disease, presenting with symptomatic AVN of both hips. This was managed conservatively from an orthopaedic perspective. Following cure of hypercortisolaemia, the patient experienced excellent recovery and remains symptom free 4 years after adrenalectomy. This is the first report of a favourable outcome over long-term follow-up of a patient with bilateral AVN of the hip, which reversed with treatment of endogenous hypercortisolaemia. LEARNING POINTS: AVN of femoral head can be a presenting feature of hypercortisolism, both endogenous and exogenous.Rarely, treatment of hypercortisolaemia can reverse AVN without the need for orthopaedic intervention.Primary pigmented nodular adrenal disease is a rare cause of ACTH-independent Cushing's syndrome.