Clinical performance of multiplatform mutation panel and microRNA risk classifier in indeterminate thyroid nodules.

INTRODUCTION: We evaluated the clinical performance of an expanded mutation panel in combination with microRNA classification (MPTX) for the management of indeterminate thyroid nodules. MATERIALS AND METHODS: MPTX included testing of fine-needle aspirates from multiple centers with a combination of ThyGeNEXT mutation panel for strong and weak driver oncogenic changes and ThyraMIR microRNA risk classifier (both from Interpace Diagnostics; Pittsburgh, PA). MPTX test status (positive or negative) and MPTX clinical risk classifications (low, moderate, or high risk) were determined blind to patient outcomes. Surgical pathology and clinical follow-up records of patients from multiple centers were used to determine patient outcomes. MPTX performance was assessed by Kaplan Meier analysis for cancer-free survival of patients, with risk of malignancy determined by hazard ratio (HR). RESULTS: Our study included 140 patients with AUS/FLUS or FN/SFN nodules, of which 13% had malignancy. MPTX negative test status and MPTX low risk results conferred a high probability (94%) that patients would remain cancer-free. MPTX positive test status (HR 11.2, P < 0.001) and MPTX moderate-risk results (HR 8.5, P = 0.001) were significant risk factors for malignancy, each conferring a 53% probability of malignancy. MPTX high-risk results elevated risk of malignancy even more so, conferring a 70% probability of malignancy (HR 38.5, P < 0.001). CONCLUSIONS: MPTX test status accurately stratifies patients for risk of malignancy. Further classification using MPTX clinical risk categories enhances utility by accurately identifying patients at low, moderate, or high risk of malignancy at the low rate of malignancy encountered when clinically managing patients with indeterminate thyroid nodules.

Clinical impact of testing for mutations and microRNAs in thyroid nodules.

BACKGROUND: We report results of a multicenter clinical experience study examining the likelihood of patients with indeterminate thyroid nodules to undergo surgery or have malignant outcome based on multiplatform combination mutation and microRNA testing (MPT). METHODS: MPT assessed mutations in BRAF, HRAS, KRAS, NRAS, and PIK3CA genes, PAX8/PPARγ, RET/PTC1, and RET/PTC3 gene rearrangements, and the expression of 10 microRNAs. Baseline clinical information at the time of MPT and clinical follow-up records were reviewed for 337 patients, of which 80% had negative MPT results. Kaplan Meier analysis for cumulative probability of survival without having a surgical procedure or malignant diagnosis over the course of patient follow-up was determined for MPT results of 180 patients, among which only 14% had malignancy. RESULTS: A negative MPT result in nodules with Bethesda III or IV cytology (2009) conferred a high probability of non-surgical treatment, with only 11% expected to undergo surgery and a high probability of survival without malignancy (92%) for up to 2 years follow up. A positive MPT result conferred a 57% probability of malignancy and was an independent risk factor for undergoing surgical treatment (Hazard Ratio [HR] 9.2, 95% confidence intervals 5.4-15.9, P < .0001) and for malignancy (HR 13.4, 95% confidence intervals 4.8-37.2, P < .0001). For nodules with weak driver mutations, positive microRNA test results supported high risk of cancer while negative results downgraded cancer risk. CONCLUSION: MPT results are predictive of real-world decisions to surgically treat indeterminate thyroid nodules, with those decisions being appropriately aligned with a patient's risk of malignancy over time.

Comprehensive management of post-transplant diabetes mellitus: from intensive care to home care.

Post-transplant diabetes mellitus (PTDM) is a common complication of solid organ and hematopoietic transplantation. This clinically oriented review article briefly summarizes the pathophysiology of PTDM, then presents a comprehensive clinical approach to diagnosis and therapy. Topics include the key clinical aspects of PTDM screening, diagnosis, and management during all phases following transplantation from the intensive care unit, to the inpatient ward, to the outpatient arena.

Unusual case of amiodarone-induced thyrotoxicosis: "illicit" use of a technetium scan to diagnose a transiently toxic thyroid nodule.

OBJECTIVE: To present an unusual case of amiodarone-induced thyrotoxicosis (AIT) associated with an autonomously functioning thyroid nodule, which was detected by means of a technetium scan; review the existing literature regarding the association of AIT with autonomous thyroid nodules; and explore the use of radioisotope imaging studies in patients with AIT. METHODS: We describe a 62-year-old man with paroxysmal atrial fibrillation, receiving long-term amiodarone therapy, who was referred by his cardiologist for evaluation of abnormal thyroid function tests. He was found to have an unusual case of AIT, associated with an autonomously functioning thyroid nodule. RESULTS: Thyroid function studies obtained by the patient's cardiologist had shown a completely suppressed thyrotropin level and a free thyroxine level of 3.5 ng/dL. A 24-hour thyroid iodine 123 uptake and technetium Tc 99m pertechnetate scan revealed a "single, strong focus in the right thyroid lobe, with the rest of the thyroid gland...not well visualized." Thyroid ultrasonography disclosed a single, well-defined 1.5-cm solid nodule. Repeated thyroid function studies revealed a normal thyrotropin level of 2.87 micro IU/mL and a normal free thyroxine level of 2.4 ng/dL. The patient was managed conservatively with follow-up surveillance. CONCLUSION: Prospective studies should be performed to better ascertain the value of Tc 99m thyroid scanning in determining the cause of AIT. Until such studies have been completed, we suggest that nuclear studies are unlikely to be cost-effective for assessing all patients with AIT. One logical strategy would be to gain experience with scans in only those patients with known thyroid nodules, which have been detected during physical examination or by ultrasonography. The potential clinical utility of such an approach would be of considerable interest.

"Waste not, want not": determining the optimal priming volume for intravenous insulin infusions.

BACKGROUND: Insulin adsorbs to plastics used for intravenous (IV) tubing. As a result, clinical IV insulin infusion procotols advise an initial priming volume of up to 50 mL, which may be wasteful-especially since most institutions use 100-mL IV solution bags. In this brief report, we sought to determine the optimal priming volume required for clinical IV insulin infusions. METHODS: One hundred units of regular human insulin was dissolved into 100 mL of 0.9% NaCl. Employing a standard polypropylene infusion set, a priming infusion was started. At 10- mL intervals, from 0 to 50 mL, effluent was collected directly into glass vials. After dilution (1:10,000) using a proprietary buffer, insulin concentrations were then measured using a double antibody radioimmunoassay. Twenty individually prepared insulin bags were tested in this manner. RESULTS: Insulin levels without prime were 15.8% [95% confidence interval (CI), 9.1-22.6%] lower than insulin levels following 50 mL of prime (designated as "maximal values"). After a priming volume of 10 mL, insulin adsorption losses fell to a marginally significant 6.6% (95% CI, 0.1-13.1%). Following 20 mL of prime, insulin concentrations were indistinguishable from maximal values (3.4% loss, 95% CI, -0.2% to 7.1%). CONCLUSIONS: For standard IV insulin infusions, a priming volume of 20 mL is sufficient to minimize the effect of insulin adsorption losses to IV lines. Priming volumes exceeding 20 mL are wasteful, increase costs, and generate unnecessary work for nurses and pharmacists.

Hemorrhagic pheochromocytoma associated with systemic corticosteroid therapy and presenting as myocardial infarction with severe hypertension.

Pheochromocytomas classically present with paroxysms of hypertension and adrenergic symptoms including headaches, palpitations, tremor, and anxiety. However, these tumors can be clinically silent and occasionally present only when catecholamine release is up-regulated by exogenous stimuli. In addition, the clinical presentation of pheochromocytoma can mimic a number of more common medical conditions, including migraine headaches, cardiac arrhythmias, and myocardial infarction, making diagnosis difficult. In this report, we present the case of a young woman who, while receiving oral corticosteroid therapy for presumed migraine headaches, suffered a myocardial infarction and ultimately hemorrhaged into a previously undiagnosed pheochromocytoma. Our patient exhibited severe, labile hypertension after the administration of iv beta-blockade for presumed myocardial ischemia, raising our initial clinical suspicion for pheochromocytoma. In this paper we review some of the key clinical issues related to this complex case, including steroid-induced stimulation of catecholamine synthesis and release, the role of pheochromocytoma in myocardial ischemia and electrocardiographic changes, and the rare complication of tumor hemorrhage. We then briefly review the essential diagnostic and management strategies for this rare but potentially lethal tumor, with specific emphasis on pheochromocytoma-related cardiovascular emergencies and the surgical management of tumor hemorrhage.

Improving glycemic control in the cardiothoracic intensive care unit: clinical experience in two hospital settings.

OBJECTIVE: Recent studies suggest that strict perioperative glycemic control improves clinical outcomes after cardiothoracic surgery. However, optimal methods and targets for controlling blood glucose (BG) levels in this setting have not been established. Currently published intensive insulin infusion protocols (IIPs) have important practical limitations, which may affect their utility. In this article, the authors present their experience with a safe, effective, nurse-driven IIP, which was implemented simultaneously in 2 cardiothoracic intensive care units (CTICUs). DESIGN: Prospective cohort study. SETTING: Tertiary referral hospital and community teaching hospital. PARTICIPANTS: CTICU patients. INTERVENTIONS: A standardized, intensive IIP was used for all patients admitted to both CTICUs. Hourly BG levels, relevant baseline variables, and clinical interventions were collected prospectively from the active hospital chart and CTICU nursing records. MEASUREMENTS AND MAIN RESULTS: The IIP was used 137 times in 118 patients. The median time required to reach target BG levels (100-139 mg/dL) was 5 hours. Once BG levels decreased below 140 mg/dL, 58% of 2,242 subsequent hourly BG values fell within the narrow target range, 73% within a "clinically desirable" range of 80 to 139 mg/dL, and 94% within a "clinically acceptable" range of 80 to 199 mg/dL. Only 5 (0.2%) BG values were less than 60 mg/dL, with no associated adverse clinical events. CONCLUSIONS: The IIP safely and effectively improved glycemic control in 2 CTICUs, with minimal hypoglycemia. Based on prior studies showing the benefits of strict glycemic control, the implementation of this IIP should help to reduce morbidity and mortality in CTICU patients.

Critical issues in endocrinology.

Endocrine emergencies are commonly encountered in the ICU. This article focuses on several important endocrine emergencies, including diabetic hyperglycemic states, adrenal insufficiency, myxedema coma, thyroid storm, and pituitary apoplexy. Other endocrine issues that are related to intensive care, such as intensive insulin therapy, relative adrenal insufficiency, and thyroid function test abnormalities are also covered in detail.