Amiodarone-induced thyrotoxicosis in adults with congenital heart disease--clinical presentation and response to therapy.

OBJECTIVE: The development of amiodarone-induced thyrotoxicosis (AIT) can threaten the hemodynamic stability of adult patients with congenital heart disease (CHD). Here, we describe the natural history and treatment response of AIT in this at-risk population. METHODS: We studied retrospectively all cases of AIT that occurred in CHD patients at our institution after a minimum of 3 months on amiodarone. Subjects were identified from the cohort of adults with CHD who were treated at the Mayo Clinic Adult CHD clinic between 1987 and 2009. RESULTS: We identified 23 cases of AIT: 7 were type 1, 13 were type 2, and 3 were undefined due to insufficient data. Most patients were symptomatic (17 of 23, 74%), with arrhythmia and weight loss as the most common symptoms. The majority (12 of 23, 52%) were initially observed; 10 patients (43%) were treated medically and 1 patient (5%) underwent thyroidectomy. Four patients from the observation group eventually required active treatment and 3 patients from the medical group required surgery. Asymptomatic patients tended to resolve under observation (5 of 7, 71.4%) rather than progress to active treatment (0 of 4) (P = .06). Discontinuation of amiodarone, AIT type, or use of perchlorate did not impact AIT duration. CONCLUSION: AIT in CHD patients exhibits a wide range of severity and sensitivity to medical therapy. Asymptomatic patients display a trend toward AIT resolution with observation alone. Amiodarone continuation does not appear to impact management outcome or disease duration. Additional studies in this high-risk population could identify elements of pathophysiology that would point toward better disease prevention and treatment.

Contemporary issues in medical professionalism challenges and opportunities.

Physician organizations, academic institutions and accrediting bodies agree that professionalism is important to medicine. A number of them have created codes of conduct and competencies related to professionalism. Yet studies have shown that physicians face challenges as they seek to put the principles of professionalism into practice. This article examines four realities of medicine today-the potential for conflicts of interest, the advent of social media, the lack of professionalism education beyond medical school and residency, and the lack of support from organizations for which physicians work-that challenge medical professionalism.

Whose best interest?

In the summer of 1910, William James Mayo, M.D., delivered the commencement address at Rush Medical College in Chicago. In his speech, he uttered words that have become the cornerstone of Mayo Clinic's model of care: "The best interest of the patient is the only interest to be considered, and in order that the sick may have the benefit of advancing knowledge, a union of forces is necessary." In this article, we reflect on issues raised by Mayo's speech that strike at the very heart of our professional identity and ask two questions: Is medicine's foremost concern the best interest of the patient? And has medicine really united over the last century in the service of patients?

An innovative model for tuberculosis control: an academic medical center-public health department partnership.

Between 1996 and 1999, the incidence rate of active tuberculosis (TB) in Olmsted County, Minnesota, increased by 365%--from 3.4 cases per 100,000 population to 15.8 per 100,000 people. The need for early detection and treatment of TB, efficient care delivery, and cost containment led to the establishment in 2001 of an innovative centralized TB clinic. The clinic was established through a collaboration between Mayo Clinic and the Olmsted County Public Health Department. Following its inception, conversion rates for sputum-positive culture increased from 69.2% to 92%, and the percentage of patients taking part in directly observed therapy increased from 20.8% to 94.6%. Because of successful medical outcomes and acceptance by patients, providers, and the community, the clinic model lends itself to replication elsewhere in the United States.

Development and application of magnetic resonance elastography of the normal and pathological thyroid gland in vivo.

PURPOSE: To noninvasively assess the shear stiffness of the thyroid gland in vivo in order to determine whether magnetic resonance elastography (MRE) might hold clinical utility in the diagnosis of thyroid disease. MATERIALS AND METHODS: Quantitative parametric images of thyroid stiffness in normal volunteers and patients were produced and quantitative stiffness values measured. Average gland stiffness was determined by region of interest analysis of the parametric images. This technique was used to assess stiffness of the thyroid in normal individuals (n = 12), patients with Hashimoto's thyroiditis (HT; n = 5), and patients with a solitary benign (n = 8) or malignant (n = 2) thyroid nodule. RESULTS: Mean shear modulus of normal thyroid glands was 1.9 +/- 0.6 kPa at 100 Hz and 1.3 +/- 0.5 kPa at 80 Hz, while that of HT glands was 2.8 +/- 0.6 kPa and 1.8 +/- 0.6 kPa at 80 Hz, respectively (P = 0.004 at 100 Hz). Elastographic parameters could not differentiate benign from malignant thyroid nodules in these small sample sizes. CONCLUSION: We developed a method for the application of MRE to the study of thyroid gland pathology. The results show that the HT gland can be differentiated from normal thyroid. The clinical utility of this imaging modality in the diagnosis and management of thyroid disease awaits further study.

Standardized care processes to improve quality and safety of patient care in a large academic practice: the Plummer Project of the Department of Medicine, Mayo Clinic.

There are opportunities to improve quality and safety of care provided to adult patients. The Plummer Project of the Department of Medicine at the Mayo Clinic (Rochester, MN, USA) is an initiative to redesign outpatient practice. We used multidisciplinary teams to standardize the tasks essential to improve patient care. With the initiative to standardize the rooming process, patient care and safety improved with greater accuracy of the medication list. The standardization also improved physician efficiency because trained clinical assistants helped address the needs of the patient. Physicians were satisfied by the new process and the technology enhancements. Clinical assistants were also highly satisfied by the training process. The quality and safety of patient care can be significantly improved by practice redesign. This practice redesign was satisfying for all, especially the patients, physicians and support team in our practice.

Endocrinopathy in POEMS syndrome: the Mayo Clinic experience.

OBJECTIVE: To determine the prevalence and characteristics of endocrinopathies at diagnosis of POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome. PATIENTS AND METHODS: From January 1, 1960, through June 30, 2006, we identified 170 patients with POEMS syndrome in the Mayo Clinic dysproteinemia database. We abstracted information about endocrine abnormalities from their medical records. RESULTS: Of the 170 patients with POEMS syndrome during the entire study period, the 64 patients seen after 2000 had more complete endocrine evaluations; of these 64 patients, 54 (84%) had a recognized endocrinopathy (38 men; median age, 50 years; interquartile range, 43-59 years). Hypogonadism was the most common endocrine abnormality; 26 (79%) of 33 men had subnormal total testosterone levels, and 10 men had gynecomastia. Among the 35 patients with measured prolactin levels, 7 men and 3 women had elevated levels. Hypothyroidism was noted in 17 men and 11 women. Abnormalities in glucose metabolism were present in 24 (48%) of 50 patients; 16 patients had impaired fasting glucose levels, and 8 were diagnosed as having diabetes. Adrenal insufficiency (defined by an abnormal response of cortisol to stimulation with standard high-dose [250 microg] synthetic adrenocorticotropic hormone) was noted in 6 of 9 patients tested. Fourteen (27%) of 51 patients tested had hypocalcemia. Twenty-nine (54%) of 54 patients had evidence of multiple endocrinopathies in the 4 major endocrine axes (gonadal, thyroid, glucose, and adrenal). CONCLUSION: The high prevalence of endocrinopathy in our study, to our knowledge the largest published series of POEMS cases, calls for a thorough endocrine investigation in patients presenting with this syndrome.

The effect of computerized physician-order entry on outpatient prescription errors.

Little information is available regarding the use of computerized physician-order entry (CPOE) in the outpatient setting or the role of pharmacists in preventing prescription errors with CPOE. This study evaluated the effect of CPOE on pharmacist-intercepted prescription errors in the outpatient setting by using data collected from a retrospective survey of 4527 prescriptions ordered in the outpatient clinics of a tertiary academic center between 1996 and 2002. The use of CPOE increased from 1% in 1996 to 59% in 2002 (P < .001); during the same period, intercepted prescription errors with computerized prescriptions decreased when compared with handwritten prescriptions (4.9% vs. 7.4%; P = .0048). The most common intercepted prescription error involved the dosage form, followed by quantity dispensed, medication dosage, and drug allergy. These conclusions suggest a decrease in outpatient intercepted prescription errors associated with CPOE. The pharmacist plays a critical role in the prevention of prescription errors, as the errors discovered in the study would have reached the patients if not for their interception by these health care professionals.

Changes in skeletal muscle protein metabolism and myosin heavy chain isoform messenger ribonucleic acid abundance after treatment of hyperthyroidism.

BACKGROUND: Hyperthyroidism causes a hypermetabolic state and skeletal muscle dysfunction, but the underlying mechanism remains incompletely defined. OBJECTIVE: The objective of the study was to determine whether treatment of hyperthyroidism causes changes in amino acid fluxes, synthesis rates of muscle proteins, and expression of muscle myosin heavy chain (MHC) that may impact skeletal muscle function and metabolic rate. METHODS: Eight hyperthyroid patients were studied (TSH 0.008 +/- 0.001 mU/liter) before treatment and at least 9 months after correction of hyperthyroidism (TSH 2.3 +/- 0.4) (P < 0.03). Fluxes of leucine and phenylalanine as well as muscle protein synthesis rates were measured using L[1,2 13C] leucine and L(15N) phenylalanine as tracers. mRNA levels of selected genes were measured in muscle biopsy samples. RESULTS: Treatment decreased resting metabolic rate that paralleled changes in fluxes of leucine and phenylalanine accompanied by improved muscle strength and mass. Synthesis rates of mixed muscle proteins (P = 0.01), sarcoplasmic (P = 0.04), and mitochondrial (P = 0.08) proteins decreased, whereas MHC synthesis was unchanged. Selective increases in mRNA abundance of muscle MHC1 isoform (P = 0.04) and decrease of MHCIIA (P = 0.007) and MHCIIx (P = 024) were observed. Muscle mitochondrial oxidative enzymes and mRNA levels of mitochondrial proteins were unchanged, but uncoupling protein2 and uncoupling protein3 mRNA levels (P = 0.02) decreased. CONCLUSION: Increased amino acid flux, mixed muscle protein synthesis, and synthesis of sarcoplasmic proteins are consistent with the hypermetabolic state in hyperthyroidism. After treatment, MHC synthesis rates were unchanged, but mRNA levels of isoforms of MHC found in slow-twitch and fast-twitch fibers increased and decreased, respectively. These results offer a mechanistic explanation for posttreatment improvement in muscle functions in hyperthyroidism.

Randomized, double-blind, placebo-controlled trial of long-acting release octreotide for treatment of Graves' ophthalmopathy.

CONTEXT: Despite a strong rationale for trials of somatostatin analogs in the treatment of Graves' ophthalmopathy (GO), recent studies have provided conflicting results. OBJECTIVE: The objective of the study was to determine whether octreotide long-acting release (LAR) is effective treatment for active GO. DESIGN: This was a prospective, randomized, double-blind, placebo-controlled study. SETTING: The setting was a single tertiary referral center. PATIENTS: Twenty-nine consecutive euthyroid patients with active GO [clinical activity score (CAS) >or= 3] were enrolled; 25 completed the study. INTERVENTION: Patients received four monthly doses of either octreotide LAR (20 mg) or saline by im injections. MAIN OUTCOME MEASURES: Primary measure was a change in CAS; the secondary measure was changes in retrobulbar tissue volume, proptosis, lid fissure width, range of motion, and diplopia fields. RESULTS: Median (range) CAS change was 2.5 (1, 5) in the treatment and 1.0 (0, 7) in the placebo group (P = 0.02). Median lid fissure width improved in the treatment group, (decreased 1 mm on the right and 0.5 mm on the left), compared with the placebo group (no change on the right, P < 0.01; increased 1 mm on the left, P < 0.01). No other significant differences between groups were identified. CONCLUSIONS: CAS improved to a greater extent in octreotide-LAR-treated patients than the control group. However, this finding may not represent clinical benefit because patients with higher baseline CAS were overrepresented in the treatment group, and the control group was small. In contrast, treatment-related improvement in eyelid fissure width was noted, suggesting that octreotide LAR may be useful in the treatment of a subgroup of active GO patients with significant lid retraction.

The impact of overt and subclinical hyperthyroidism on skeletal muscle.

OBJECTIVE: Patients with overt hyperthyroidism (OH) commonly have proximal limb muscle weakness that improves after correction of hyperthyroidism. It is unclear, however, if patients with milder degrees of hyperthyroidism (referred to as subclinical hyperthyroidism or SCH) may also have a degree of muscle weakness. This may have clinical relevance as SCH patients are often elderly and may therefore have concurrent sarcopenia of aging and would represent a previously unrecognized complication of SCH. DESIGN: We measured both thigh strength and cross-sectional area in patients with OH (n = 30) or SCH (n = 24), both prior to treatment of hyperthyroidism and again at 6-9 months after the restoration of a euthyroid state. Euthyroid controls (n = 48) were studied at similar time intervals. MAIN OUTCOME: Prior to treatment, both knee flexor and extensor muscle strength was reduced in both patients with OH and SCH compared to controls (p < 0.05). After treatment all strength measurements improved in the OH group (p < 0.01) while in the SCH group the majority of muscle strength measurements improved (p < 0.05). Midthigh muscle cross-sectional area was reduced in both the OH and SCH group at baseline (p < 0.05) compared to controls and increased significantly following treatment (p < 0.05). There were no significant changes in any parameter in the euthyroid control (EC) group during the study period. CONCLUSIONS: The finding that muscle strength and cross-sectional area are reduced in SCH and improved after treatment lends support for the clinical decision to treat rather than observe this condition. This may have particular relevance to certain SCH patient groups including the elderly who are prone to falls and athletically active younger patients who require optimal skeletal muscle function.

Symptomatic hyperthyroidism in a patient taking the dietary supplement tiratricol.

An 87-year-old woman was referred for evaluation of nervousness, tremor, insomnia, and fatigue of 2 months' duration. Initial laboratory evaluation revealed a suppressed thyrotropin level and an elevated triiodothyronine level. A review of her medications revealed that she had started taking several dietary supplements at the recommendation of her chiropractor before the onset of symptoms. One of these was tiratricol (3,5,3'-triiodothyroacetic acid or Triac), a substance sold as a dietary supplement despite classification as a drug by the Food and Drug Administration. Tiratricol has weak thyromimetic effects, can inhibit pituitary thyrotropin secretion, and in higher doses can significantly stimulate metabolism. Such was the case with this patient who presented with signs, symptoms, and biochemical evidence of hyperthyroidism that promptly resolved after discontinuation of tiratricol therapy. To our knowledge, this is the first reported case of documented thyrotoxicosis secondary to tiratricol use. Because tiratricol is still available for sale on several Internet sites, this case emphasizes the importance of inquiring about the use of dietary supplements in all patients. The availability of such products on the Internet increases the already complex task of monitoring patients' use of dietary supplements.

Professionalism: good for patients and health care organizations.

Professionalism is an indispensable element in the compact between the medical profession and society that is based on trust and putting the needs of patients above all other considerations. The resurgence of interest in professionalism dates back to the 1980s when health maintenance organizations were formed and proprietary influences in health care increased. Since then, a rich and comprehensive literature has emerged in defining professionalism, including desirable individual attributes and behaviors and how they may be taught, promoted, and assessed. More recently, scholarship has shifted from individual to organizational professionalism. This literature addresses the role that health care organizations can play to establish environments that are conducive to the consistent expression of professionalism by individuals and health care teams. We reviewed interdisciplinary empirical studies from health care effectiveness and outcomes, organizational sciences, positive psychology, and social psychology, finding evidence that organizational and individual professionalism is associated with a wide range of benefits to patients and the organization. We identify actionable organizational strategies and approaches that, if adopted, can foster and promote combined organizational and individual professionalism. In doing so, trust in the medical profession and its institutions can be enhanced, which in turn will reconfirm a commitment to the social compact.

Body mass index and the development of amiodarone-induced thyrotoxicosis in adults with congenital heart disease--a cohort study.

INTRODUCTION: Amiodarone-induced thyrotoxicosis (AIT) is a recognized complication of amiodarone treatment with limited management options. Its predisposing factors are incompletely defined yet a higher prevalence was reported in adults with congenital heart disease (CHD). Therefore we sought to determine the incidence and risk factors for AIT in adults with CHD. METHODS: At a tertiary care center we followed a historical cohort of amiodarone-treated CHD patients for the period 1987-2009. Follow-up concluded at AIT diagnosis or with last thyroid assessment on amiodarone. Cumulative incidence of AIT was calculated. AIT association with nutritional status was hypothesized a priori. RESULTS: AIT developed in 23/169 patients or 13.6%. The AIT incidence peaked in the 3rd year at 7.7%. AIT patients had a lower body mass index (BMI) at AMIO initiation compared with the rest of the cohort (mean ± standard deviation: 21.9 ± 2.9 vs. 25.1 ± 5.0; p<0.001). Patients with BMI<21 were more likely to develop thyrotoxicosis (RR=6.1) compared to those with BMI>25 (p<0.001). Presence of goiter was strongly associated with AIT (RR 3.6, p=0.002). Affected patients had a trend for higher cyanotic heart disease prevalence (34.8% vs. 17.8%, p=0.059). On multivariate analysis body mass index and goiter remained independent predictors of outcome. CONCLUSIONS: BMI<21 at initiation of amiodarone therapy and presence of goiter are strong predictors of AIT in this population. Its incidence is time dependent. These predictors can be used clinically in assessing overall impact of amiodarone therapy in congenital heart disease patients.

A risk prediction index for amiodarone-induced thyrotoxicosis in adults with congenital heart disease.

Amiodarone therapy in adults with congenital heart disease (CHD) is associated with a significant risk of amiodarone-induced thyrotoxicosis (AIT). We developed a risk index to identify those patients being considered for amiodarone treatment who are at high risk for AIT. We reviewed the health records of adults with CHD and assessed the association between potential clinical predictors and AIT. Significant predictors were included in multivariate analyses. The parameter estimates from multivariate analysis were subsequently used to develop a risk index. 169 adults met eligibility criteria and 23 developed AIT. The final model included age, cyanotic heart disease and BMI. The risk index developed identified 3 categories of risk. Their AIT likelihood ratios were: 0.37 for low risk (95% CI 0.15-0.92); 1.12 for medium risk (95% CI 0.65-1.91); and 3.47 for high risk (95% CI 1.7-7.11). The AIT predicted risk in our population was 5% for the low risk group, 15% for the medium risk group and 47% for the high risk group. Conclusions. We derived the first model to quantify the risk for developing AIT among adults with CHD. Before using it clinically to help selecting among alternative antiarrhythmic options, it needs validation in an independent population.

The application of design principles to innovate clinical care delivery.

Clinical research centers that support hypothesis-driven investigation have long been a feature of academic medical centers but facilities in which clinical care delivery can be systematically assessed and evaluated have heretofore been nonexistent. The Institute of Medicine report "Crossing the Quality Chasm" identified six core attributes of an ideal care delivery system that in turn relied heavily on system redesign. Although manufacturing and service industries have leveraged modern design principles in new product development, healthcare has lagged behind. In this article, we describe a methodology utilized by our facility to study the clinical care delivery system that incorporates modern design principles.

Changes in body composition in women following treatment of overt and subclinical hyperthyroidism.

OBJECTIVE: To determine changes in weight, body composition, and bone density after treatment of overt hyperthyroidism (OH) and subclinical hyperthyroidism (SCH) in women. METHODS: Women with OH and SCH referred to the Mayo Clinic Thyroid Clinic were recruited. Hyperthyroid patients and euthyroid control women were matched for age (within decade) and body mass index. Patients with OH and SCH were treated to normalize thyroid function test results and were restudied after 6 months of normal thyroid function. Baseline and posttreatment studies included measurement of height, weight, bone density, lean mass, fat mass, and thigh muscle cross-sectional area. All participants had normal thyroid function test results for at least 6 months before completion of the posttreatment studies. RESULTS: Twenty-four patients with OH, 21 patients with SCH, and 36 control patients were studied. In the OH group, fat-free mass increased from a mean of 36.8 kg (95% confidence interval [CI], 34.8-38.8) to 40.4 kg (95% CI, 38.5-42.3); in the SCH group, fat-free mass increased from a mean of 40.3 kg (95% CI, 38.1-42.5) to 42.2 kg (95% CI, 39.7-44.7). In both groups, fat mass increased to approximately the same extent, and both groups experienced significant weight gain with no change in percent body fat. Thigh muscle cross-sectional area increased in both groups -- from 100.6 cm(2) (95% CI, 92.7-108.5) to 113.3 cm(2) (95% CI, 105.5-121.1) in the OH group and from 106.1 cm(2) (95% CI, 96.7-115.5) to 112.2 cm(2) (95% CI, 102.0-122.4) in the SCH group. Bone density increased in patients with OH (P<.01) and in patients with SCH (P<.05). CONCLUSIONS: Treatment of OH and SCH leads to increases in muscle area and bone density. Weight gain reflects increases in both fat and fat-free mass. While these results provide some support for actively treating SCH in women, further prospective studies are needed to determine whether the changes documented translate into real patient benefit.