11C-Metomidate PET-CT versus adrenal vein sampling to subtype primary aldosteronism: a prospective clinical trial.

OBJECTIVE: Adrenal vein sampling (AVS) is recommended to subtype primary aldosteronism, but it is technically challenging. We compared 11C-Metomidate-PET-computed tomography (PET-CT) and AVS for subtyping of primary aldosteronism. METHODS: Patients with confirmed primary aldosteronism underwent both AVS and 11C-Metomidate PET-CT (post-dexamethasone). All results were reviewed at a multidisciplinary meeting to decide on final subtype diagnosis. Primary outcome was accuracy of PET versus AVS to diagnosis of unilateral primary aldosteronism based on post-surgical biochemical cure. Secondary outcome was accuracy of both tests to final subtype diagnosis. RESULTS: All 25 patients recruited underwent PET and successful AVS (100%). Final diagnosis was unilateral in 22 patients, bilateral in two and indeterminate in one due to discordant lateralization. Twenty patients with unilateral primary aldosteronism underwent surgery, with 100% complete biochemical success, and 75% complete/partial clinical success. For the primary outcome, sensitivity of PET was 80% [95% confidence interval (95% CI): 56.3-94.3] and AVS was 75% (95% CI: 50.9-91.3). For the secondary outcome, sensitivity and specificity of PET was 81.9% (95% CI: 59.7-94.8) and 100% (95% CI: 15.8-100), and AVS was 68.2% (95% CI: 45.1-86.1) and 100% (95% CI: 15.8-100), respectively. Twelve out of 20 (60%) patients had both PET and AVS lateralization, four (20%) PET-only, three (15%) AVS-only, while one patient did not lateralize on PET or AVS. Post-surgery outcomes did not differ between patients identified by either test. CONCLUSION: In our pilot study, 11C-Metomidate PET-CT performed comparably to AVS, and this should be validated in larger studies. PET identified patients with unilateral primary aldosteronism missed on AVS, and these tests could be used together to identify more patients with unilateral primary aldosteronism. VIDEO ABSTRACT: http://links.lww.com/HJH/B918.

Psychometric properties of the thyroid-specific quality of life questionnaire ThyPRO in Singaporean patients with Graves' disease.

BACKGROUND: Graves' disease is the most common cause of hyperthyroidism. It results in accelerated tissue metabolism with multi-organ involvement ranging from cardiovascular to neuropsychological function. This results in a negative impact on the quality of life (QOL) of the individual patient. We aim to evaluate the psychometric properties of ThyPRO, a Thyroid-related Patient Reported Outcome questionnaire, and validate its use in our multi-ethnic Asian patients with Graves' hyperthyroidism. METHODS: Forty-seven consecutive Graves' hyperthyroidism patients answered the ThyPRO questionnaire at baseline and at 4 months after treatment initiation. Data were recorded for thyroid related symptoms and signs, thyroid function tests and thyroid volume. We analyzed the internal consistency using Cronbach's alpha, construct validity by evaluating relationship between clinical variables and ThyPRO scales, ceiling and floor effects, and responsiveness of ThyPRO to treatment based on Cohen's effect size. RESULTS: Correlations between individual scale scores and free thyroxine concentrations were moderate and statistically significant: 0.21-0.64 (p <  0.05). There was high internal consistency between the items in this instrument, Cronbach's alpha > 0.7 for all scales. ThyPRO was responsive to the changes in QOL after treatment (Effect Size: 0.20-0.77) in 9 of the 14 scales including the hyperthyroid symptoms and psychosocial scales (Tiredness, Cognitive complaints, Anxiety, Emotional susceptibility, Impact on Social, Daily and Sex life). CONCLUSION: This study provides evidence that ThyPRO has satisfactory measurement properties in hyperthyroid Graves' disease patients in Singapore population with the potential to complement clinical care.

Therapeutic plasma exchange for control of thyroid storm.

Therapeutic plasma exchange (TPE) for thyroid storm has recently been upgraded to a category II indication after decades though its recommendation level still remains at Grade 2C according to the American Society for Apheresis (ASFA). In the absence of prospective randomized controlled trials due to the rarity of thyroid storm, retrospective data from case series continue to elevate the clinical evidence supporting TPE as a life-saving modality for complicated thyroid storm patients. We report three cases of life-threatening thyroid storm from Graves' disease rescued by TPE via rapid reduction in circulating thyroid hormones. Each patient underwent TPE when it was judged that other thyroid storm treatment options were futile or unsafe. The first patient received 4 cycles of TPE while the second patient received 9 cycles of TPE, and the third patient received 2 cycles of TPE with satisfactory clinical improvement. Plasma FT4 and TSH receptor antibody levels of the first case declined by 41.3% and >50% respectively right after the first round of TPE; plasma FT4 of the second patient dropped by up to 31.6% during the course of TPE; plasma FT4 and TSH receptor antibody of the third patient declined by 66% and 56.2% respectively after the first cycle of TPE. This demonstrates the safety, efficacy, and feasibility of TPE in thyroid storm especially when other therapeutic interventions are contraindicated. TPE operates via the elimination of serum proteins-bound thyroid hormones, thyroid autoantibodies, cytokines, and catecholamines in addition to increasing unsaturated binding sites for thyroid hormones.

Vasodilatory Actions of Glucagon-Like Peptide 1 Are Preserved in Skeletal and Cardiac Muscle Microvasculature but Not in Conduit Artery in Obese Humans With Vascular Insulin Resistance.

OBJECTIVE: Obesity is associated with microvascular insulin resistance, which is characterized by impaired insulin-mediated microvascular recruitment. Glucagon-like peptide 1 (GLP-1) recruits skeletal and cardiac muscle microvasculature, and this action is preserved in insulin-resistant rodents. We aimed to examine whether GLP-1 recruits microvasculature and improves the action of insulin in obese humans. RESEARCH DESIGN AND METHODS: Fifteen obese adults received intravenous infusion of either saline or GLP-1 (1.2 pmol/kg/min) for 150 min with or without a euglycemic insulin clamp (1 mU/kg/min) superimposed over the last 120 min. Skeletal and cardiac muscle microvascular blood volume (MBV), flow velocity and blood flow, brachial artery diameter and blood flow, and pulse wave velocity (PWV) were determined. RESULTS: Insulin failed to change MBV or flow in either skeletal or cardiac muscle, confirming the presence of microvascular insulin resistance. GLP-1 infusion alone increased MBV by ∼30% and ∼40% in skeletal and cardiac muscle, respectively, with no change in flow velocity, leading to a significant increase in microvascular blood flow in both skeletal and cardiac muscle. Superimposition of insulin to GLP-1 infusion did not further increase MBV or flow in either skeletal or cardiac muscle but raised the steady-state glucose infusion rate by ∼20%. Insulin, GLP-1, and GLP-1 + insulin infusion did not alter brachial artery diameter and blood flow or PWV. The vasodilatory actions of GLP-1 are preserved in both skeletal and cardiac muscle microvasculature, which may contribute to improving metabolic insulin responses and cardiovascular outcomes. CONCLUSIONS: In obese humans with microvascular insulin resistance, GLP-1's vasodilatory actions are preserved in both skeletal and cardiac muscle microvasculature, which may contribute to improving metabolic insulin responses and cardiovascular outcomes.

GLP-1 and Insulin Recruit Muscle Microvasculature and Dilate Conduit Artery Individually But Not Additively in Healthy Humans.

CONTEXT: Glucagon-like peptide-1 (GLP-1) and insulin increase muscle microvascular perfusion, thereby increasing tissue endothelial surface area and nutrient delivery. OBJECTIVE: To examine whether GLP-1 and insulin act additively on skeletal and cardiac microvasculature and conduit artery. DESIGN: Healthy adults underwent three study protocols in random order. SETTING: Clinical Research Unit at the University of Virginia. METHODS: Overnight-fasted participants received an intravenous infusion of GLP-1 (1.2 pmol/kg/min) or normal saline for 150 minutes with or without a 2-hour euglycemic insulin clamp (1 mU/kg/min) superimposed from 30 minutes onward. Skeletal and cardiac muscle microvascular blood volume (MBV), flow velocity, and flow; brachial artery diameter, flow velocity, and blood flow; and pulse wave velocity (PWV) were measured. RESULTS: GLP-1 significantly increased skeletal and cardiac muscle MBV and microvascular blood flow (MBF) after 30 minutes; these remained elevated at 150 minutes. Insulin also increased skeletal and cardiac muscle MBV and MBF. Addition of insulin to GLP-1 did not further increase skeletal and cardiac muscle MBV and MBF. GLP-1 and insulin increased brachial artery diameter and blood flow, but this effect was not additive. Neither GLP-1, insulin, nor GLP-1 and insulin altered PWV. Combined GLP-1 and insulin infusion did not result in higher whole-body glucose disposal. CONCLUSION: GLP-1 and insulin at physiological concentrations acutely increase skeletal and cardiac muscle microvascular perfusion and dilate conduit artery in healthy adults; these effects are not additive. Thus, GLP-1 and insulin may regulate skeletal and cardiac muscle endothelial surface area and nutrient delivery under physiological conditions.

Severe hypoglycemia associated with an illegal sexual enhancement product adulterated with glibenclamide: MR imaging findings.

PURPOSE: To describe the magnetic resonance (MR) imaging findings associated with severe hypoglycemia after consumption of an illegal sexual enhancement product (Power 1 Walnut) adulterated with glibenclamide, an oral hypoglycemic agent used to treat diabetes mellitus. MATERIALS AND METHODS: Institutional review board approval was obtained for this retrospective study. Records in eight male patients with severe hypoglycemia of unknown cause, without prior treatment for diabetes, and with positive blood toxicology results for glibenclamide were reviewed. MR imaging included diffusion-weighted imaging and, in some patients, MR angiography, dynamic contrast material-enhanced perfusion MR imaging, and MR spectroscopy. RESULTS: In seven patients, there were hyperintense abnormalities on diffusion-weighted and T2-weighted images in the hippocampus and cerebral cortex, sparing the subcortical white matter and cerebellum. Three patients had abnormalities of the splenium of the corpus callosum, and one had widespread involvement, including the caudate nucleus, basal ganglia, and internal capsule bilaterally. In three patients, unilateral cortical involvement, which did not conform to the typical cerebral arterial territories, was noted. In one patient, perfusion MR imaging showed slightly increased relative cerebral blood volume, and MR spectroscopy revealed no evidence of abnormal lactate in the affected cerebral cortex. CONCLUSION: Diffusion-weighted MR imaging findings in patients with severe hypoglycemia showed typical lesions in the hippocampus and cerebral cortex, but the caudate nucleus and basal ganglia were involved in only the most severely affected patient. The splenium of the corpus callosum and internal capsule were also abnormal in three patients, and unilateral cortical lesions could be distinguished from acute ischemic stroke by the pattern of involvement and MR angiographic, perfusion, and spectroscopic findings.