Insulin Autoimmune Syndrome: a rare case of hypoglycaemia resolving with immunosuppression.

We report a case of a 58-year-old male presenting with confusion and hypoglycaemia. There had been no prior exposure to oral hypoglycaemic agents or insulin. He was found to have inappropriate endogenous hyperinsulinaemia. Insulinoma was excluded by detailed endocrine assessment. Insulin antibodies were positive in keeping with a diagnosis of insulin autoimmune syndrome (IAS). He was treated with prednisolone 5mg once daily and nutritional supplements leading to resolution of acute confusion and hypoglycaemic episodes. The patient also had severe psoriasis and following discharge was treated with a variety of immunosuppressant therapies. This was associated with disappearance of insulin antibodies after twelve months of follow up. While it is possible that there was spontaneous resolution of insulin antibodies, we speculate that his prednisolone and immunosuppressant therapy may have suppressed insulin antibody production. There are several well recognised associations with IAS and autoimmune conditions, including Grave's disease, systemic lupus erythematous and rheumatoid arthritis. To our knowledge this is the first reported case of insulin autoimmune syndrome, resolving with immunosuppressant treatment of psoriasis.

Risk of pre-eclampsia in women taking metformin: a systematic review and meta-analysis.

AIMS: To perform meta-analyses of studies evaluating the risk of pre-eclampsia in high-risk insulin-resistant women taking metformin prior to, or during pregnancy. METHODS: A search was conducted of the Medline, EMBASE, Web of Science and Scopus databases. Both randomized controlled trials and prospective observational cohort studies of metformin treatment vs. placebo/control or insulin either prior to or during pregnancy were selected. The main outcome measure was the incidence of pre-eclampsia in each treatment group. RESULTS: Overall, in five randomized controlled trials comparing metformin treatment (n = 611) with placebo/control (n = 609), no difference in the risk of pre-eclampsia was found [combined/pooled risk ratio (RR), 0.86 (95% CI 0.33-2.26); P = 0.76; I2  = 66%]. Meta-analysis of four cohort studies again showed no significant effect [RR, 1.21 (95% CI 0.56-2.61); P = 0.62; I2  = 30%]. A meta-analysis of eight randomized controlled trials comparing metformin (n = 838) with insulin (n = 836), however, showed a reduced risk of pre-eclampsia with metformin [RR, 0.68 (95% CI 0.48-0.95); P = 0.02; I2  = 0%]. No heterogeneity was present in the metformin vs. insulin analysis of randomized controlled trials, whereas high levels of heterogeneity were present in studies comparing metformin with placebo/control. Pre-eclampsia was a secondary outcome in most of the studies. The mean weight gain from time of enrolment to delivery was lower in the metformin group (P = 0.05, metformin vs. placebo; P = 0.004, metformin vs. insulin). CONCLUSIONS: In studies randomizing pregnant women to glucose-lowering therapy, metformin was associated with lower gestational weight gain and a lower risk of pre-eclampsia compared with insulin.

A randomised controlled trial evaluating the effect of potassium supplementation on vascular function and the renin-angiotensin-aldosterone system.

There is limited evidence on the effect of potassium supplementation on the vasculature in patients at increased cardiovascular risk. Potassium increases aldosterone and there is a strong association of hyperaldosteronism with poor cardiac outcomes. We aimed to determine whether potassium supplementation has a significant medium-term effect on aldosterone levels and, if so, what the overall effect of this is on vascular function in patients at moderate cardiovascular disease risk. Forty patients at moderate cardiovascular disease risk were included in a randomised placebo-controlled crossover study. Patients were assigned to 64 mmol potassium chloride or placebo for 6 weeks. Vascular function was assessed using pulse-wave analysis including the detection of a change in augmentation index to salbutamol and nitroglycerine-induced vasodilation. There was no change in augmentation index with potassium vs placebo (25.2±1.4 vs. 26.0±1.3%, respectively). Potassium improved brachial systolic blood pressure (131.8±2.2 vs. 137.1±2.4 mm Hg; P=0.013), central systolic blood pressure (123.2±2.3 vs. 128.4±2.3 mm Hg; P=0.011) and central diastolic blood pressure (80.3±1.3 vs. 83.7±1.4 mm Hg; P=0.019). Plasma renin activity and serum aldosterone both increased with potassium (P=0.001 and P=0.048 respectively). We found that potassium supplementation had no effect on endothelial function or pulse-wave analysis. It lowered brachial systolic and central blood pressure. It was associated with increased plasma renin activity and serum aldosterone.

A case of euglyacemic diabetic ketoacidosis in a patient with gestational diabetes mellitus.

A 30-year old woman at 30 weeks gestation with insulin-controlled gestational diabetes was admitted with nausea and vomiting. Plasma glucose was 3.3 mmol/l with pH 7.23 and raised capillary ketones at 6.1 mmol/l. She was diagnosed with euglycaemic diabetic ketoacidosis. Cardiotocography showed good fetal movement and accelerations. She was given intramuscular betamethasone and started on intravenous dextrose, insulin and 0.9% saline with potassium chloride with resolution of ketosis. Euglycaemic diabetic ketoacidosis has been reported during pregnancy in patients with type 1 and type 2 diabetes. We believe that this is a report of such an occurrence in a patient with gestational diabetes.

A comparison of the use of urinary cortisol to creatinine ratios and nocturnal salivary cortisol in the evaluation of cyclicity in patients with Cushing's syndrome.

CONTEXT: Cyclical Cushing's syndrome is detected in our center by collecting sequential early morning urine (EMU) samples for cortisol to creatinine ratio over 28 d. The Endocrine Society suggests that nocturnal salivary cortisol (NSC) may be used to assess patients for cyclical Cushing's. However, there is only very limited evidence that it correlates with EMU testing or that it demonstrates cycling over 28 d. OBJECTIVE: We sought to correlate NSC with EMU results collected the following morning and to determine whether NSC could be used to detect cyclical Cushing's. DESIGN AND SETTING: An observation study of 28-d collections for NSC and EMU was performed in a tertiary referral center over 1 yr. PATIENTS: A 28-d collection of NSC and EMU was performed in 10 patients with confirmed or suspected Cushing's syndrome. MAIN OUTCOME MEASURE: The main outcome of the study was the correlation of salivary and urinary cortisol with graphical assessment of results for cycling. RESULTS: Eleven collections were performed. One patient with cyclical Cushing's completed the collection before and after cabergoline therapy. Two hundred seventy matched salivary and urinary results were correlated (r = 0.79; P < 0.001). In two patients with cyclical Cushing's, EMU and NSC followed a similar cyclical pattern. In one patient with recurrent cyclical Cushing's, cortisol was elevated in both saliva and urine but with more prominent cycles in saliva. CONCLUSION: NSC correlated well with EMU. NSC detected all cases of cyclical Cushing's. Therefore, NSC may prove to be an additional option or replacement for EMU in detecting cyclical Cushing's syndrome.

100 cases of primary aldosteronism: careful choice of patients for surgery using adrenal venous sampling and CT imaging results in excellent blood pressure and potassium outcomes.

OBJECTIVE: Patients with primary aldosteronism (PA) who are suitable for surgery should undergo adrenal computerised tomography (CT) and adrenal venous sampling (AVS). A retrospective study was performed of 100 patients with PA. We determined the optimal AVS lateralisation ratio for unilateral disease and reviewed adrenalectomy outcomes evaluating which characteristics predicted hypertension cure. METHODS: AVS was performed in 93 patients. Lateralisation criteria were assessed using ROC curve analysis. The outcome of adrenalectomy was reviewed in 39 patients and predictive factors for cure determined using univariate and multivariate analysis. RESULTS: Of previously published criteria, ROC curve analysis found a cortisol corrected aldosterone affected to unaffected (Aldo/Cort A:U) cut-off of 2·0 was the best predictor of adenoma identifying 80·4% of patients. A novel ratio calculated by dividing the affected to unaffected ratio by the unaffected to peripheral ratio [(Aldo/Cort A:U)/(Aldo/Cort U:IVC)] was successful in identifying 87·0% of patients. Cure rate for blood pressure after adrenalectomy was 38·5% with improvement in 59·0%. On univariate analysis, predictors of post-operative hypertension were increased weight, raised creatinine, left ventricular hypertrophy (LVH) and male sex. On multivariate analysis, male sex and higher pre-operative systolic blood pressure were predictive. CONCLUSIONS: Patients with PA should have CT scanning and AVS. Aldo/Cort A:U >2·0 is the most accurate of previously published ratios in predicting unilateral disease. When patients were carefully selected for surgery, 97% had cure or improvement in blood pressure control. Further confirmatory work is required on a novel ratio which was even more predictive in our series.

Does iodine gas released from seaweed contribute to dietary iodine intake?

Thyroid hormone levels sufficient for brain development and normal metabolism require a minimal supply of iodine, mainly dietary. Living near the sea may confer advantages for iodine intake. Iodine (I(2)) gas released from seaweeds may, through respiration, supply a significant fraction of daily iodine requirements. Gaseous iodine released over seaweed beds was measured by a new gas chromatography-mass spectrometry (GC-MS)-based method and iodine intake assessed by measuring urinary iodine (UI) excretion. Urine samples were obtained from female schoolchildren living in coastal seaweed rich and low seaweed abundance and inland areas of Ireland. Median I(2) ranged 154-905 pg/L (daytime downwind), with higher values (~1,287 pg/L) on still nights, 1,145-3,132 pg/L (over seaweed). A rough estimate of daily gaseous iodine intake in coastal areas, based upon an arbitrary respiration of 10,000L, ranged from 1 to 20 µg/day. Despite this relatively low potential I(2) intake, UI in populations living near a seaweed hotspot were much higher than in lower abundance seaweed coastal or inland areas (158, 71 and 58 µg/L, respectively). Higher values >150 µg/L were observed in 45.6% of (seaweed rich), 3.6% (lower seaweed), 2.3% (inland)) supporting the hypothesis that iodine intake in coastal regions may be dependent on seaweed abundance rather than proximity to the sea. The findings do not exclude the possibility of a significant role for iodine inhalation in influencing iodine status. Despite lacking iodized salt, coastal communities in seaweed-rich areas can maintain an adequate iodine supply. This observation brings new meaning to the expression "Sea air is good for you!"

Diabetic nephropathy and chronic kidney disease at a busy diabetes clinic: a study of outpatient care and suggestions for improved care pathways at a subspecialty specialist diabetic renal clinic.

Prior to establishing a specialist diabetic renal clinic in our unit, we studied across 12 months all 1845 patients attending one of our diabetes clinics with a serum creatinine >150 µmol/l. Diabetic control was examined along with renal function and cardiovascular risk using current audit standards. 74 such patients were identified (male:female 54:20 mean HbA1c 7.8% (sd ± 1.45) and age 64.2 years (± 12.8). 30 patients had creatinine >200 µmol/l and 15 >250 µmol/l. Using the chronic kidney disease classification, 33, 28 and 6 patients were in groups III, IV and V with 7 patients undergoing renal replacement therapy. 65% of patients met JBS2 audit standards of blood pressure using a mean of 2.93 agents (sd ± 1.43). Ace-inhibitors or angiotensin receptor blockers were used in 81% and 81% were on regular antiplatelet or anticoagulant therapy. Audit standard for total cholesterol and LDL were met in 89% and 97% of patients respectively. All patients identified in our study were in CKD class III-V and therefore we considered also alternative inclusion criteria. 136 patients had a urinary ACR ≥ 30 mg/mmol. Using this and/or the serum creatinine level above identified 197 patients from the clinic. This study shows that measurement of serum creatinine alone is not sufficiently sensitive but extended criteria identified a 10% subgroup who will now be offered detailed assessments and intensified therapies at a subspecialty in-house renal clinic. eGFR has recently been added to our computerised proforma and will enable us to further refine inclusion criteria.