Myxedema Heart and Pseudotamponade.

CONTEXT: Thyroid hormone plays a critical role in cardiovascular function. Severe hypothyroidism can be associated with "myxedema heart" characterized by relative bradycardia and pericardial effusion. Effusions associated with severe hypothyroidism can be large. Despite the large volume of effusions, tamponade is not a common consequence. However, with the incorporation of echocardiography into routine practice for evaluation of effusion, echocardiographic findings suggestive of clinical tamponade occur frequently. CASE DESCRIPTION: We report a series of 3 patients with large pericardial effusions secondary to severe hypothyroidism. These cases serve to demonstrate the discordance between echocardiographic signs consistent with tamponade with a patient's stable clinical hemodynamics. We also report the development of bronchial obstruction, a rare complication of a large effusion due to severe hypothyroidism. CONCLUSIONS: While pericardial effusion associated with severe hypothyroidism has been described for decades, the echocardiographic findings may be less well known and may lead to unnecessary downstream testing or invasive management. We use our case series to facilitate a summary of what is known about the epidemiology, mechanism and physiology, and expected outcomes of myxedema associated pericardial effusion. Finally, in the setting of current paucity of clinical guidelines, we aim to familiarize clinicians with the phenomenon of pseudotamponade and suggest management strategies for myxedema associated pericardial effusion to guide clinicians to use conservative medical management in majority of cases.

Detection of Atypical Femur Fractures.

The 2019 International Society for Clinical Densitometry (ISCD) Position Development Conference Task Force for monitoring with dual-energy X-ray absorptiometry (DXA) identified detection of atypical femur fractures (AFFs) as an important topic and established this working group to answer key questions in this area. The authors conducted a systematic review of the literature and deliberated on proposed ISCD positions, which were then reviewed by an external expert panel and vetted at the 2019 ISCD Position Development Conference in Kuala Lumpur on March 23, 2019. This paper summarizes the final ISCD positions and the rationale for supporting these positions. Default-length femur imaging or extended-length femur imaging as well as full-length femur imaging (FFI), both single-energy and dual-energy scans, by DXA can detect abnormalities in the spectrum of AFF. It is important to visually inspect all DXA scans of the hip and femur, and report on findings of focal periosteal and endosteal thickening at the lateral cortex (grade: Good, A, W). FFI is the preferred DXA scan mode for detecting abnormalities in the spectrum of AFF. The FFI report should state the absence or presence of abnormalities in the spectrum of AFF. If focal thickening is present on the lateral cortex, the report should state whether a lucent line is seen (grade: Fair, C, W). The ISCD recommends considering the use of bilateral FFI in patients who are currently or have been in the past year on potent antiresorptive therapy (ie, oral or intravenous bisphosphonate or subcutaneous denosumab therapy) for a cumulative period of 3 or more years, especially those on long-term glucocorticoid therapy (grade: Fair, B, W). More research is needed to determine the role of repeat testing and the optimal time interval for follow-up DXA scans, whether an automated measuring tool would perform better than visual inspection, whether FFI would change patient management and outcomes, and the cost-effectiveness of FFI.

Are race and sex associated with the occurrence of atypical femoral fractures?

BACKGROUND: Prior studies have suggested that Asian patients and women may be more likely to sustain atypical femoral fractures in association with bisphosphonate use. However, they do not account for confounders such as asymptomatic patients who are long-term bisphosphonate users or patients sustaining osteoporotic fractures. QUESTIONS/PURPOSES: The purpose of this study was to determine the differences in sex and racial association with atypical femoral fractures by comparing demographic characteristics of patients who sustained an atypical bisphosphonate-associated fracture with patients on long-term bisphosphonates without fractures and with patients who sustained osteoporotic fractures. METHODS: Three groups from prospective registries were identified: (1) patients with atypical femur fractures associated with long-term bisphosphonate use (BFF) (n = 54); (2) patients on long-term bisphosphonates but with no associated fractures (BNF) (n = 119); and (3) patients with osteoporotic proximal femur fractures not associated with bisphosphonates (PFF) (n = 216). Age, sex, and self-reported race/ethnicity were documented and compared. Multivariate and univariate analyses were done as well as age- and sex-stratified analyses. RESULTS: Age and sex distributions of the BFF and BNF patients were similar. There was a higher percentage of Asian patients in the BFF group (17%) than in the BNF group (3%; p = 0.004) as well as Hispanics (13% versus 3% in BNF; p = 0.011). Patients in the BFF group were younger than those in the PFF group (67.5 versus 78.4 years; p < 0.001) and had fewer males (7% versus 14%; p < 0.001). CONCLUSIONS: These data suggest that Asians are at higher risk for atypical bisphosphonate-associated fractures. We recommend closer followup in Asian patients who are taking bisphosphonates. LEVEL OF EVIDENCE: Level III, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Healing delayed but generally reliable after bisphosphonate-associated complete femur fractures treated with IM nails.

BACKGROUND: Bisphosphonate therapy for osteoporosis has been associated with atypical femoral fractures. To date, there have been few reports in the literature regarding the preoperative and postoperative courses of patients who have sustained bisphosphonate-associated complete atypical femur fractures. OBJECTIVES/PURPOSES: The purposes of this study were to (1) characterize the preoperative course of patients who eventually presented with bisphosphonate-associated complete atypical femur fractures (duration of bisphosphonate treatment, pain history, risk of converting a nondisplaced fracture to a complete fracture); (2) evaluate the percentage of patients who achieved radiographic union of those fractures after treatment; and (3) determine the patients' recovery of function using the Short Musculoskeletal Functional Assessment. METHODS: Thirty-three patients with 41 atypical, low-energy femur fractures associated with ≥ 5 years of bisphosphonate use were treated with intramedullary nailing between 2004 and 2011 at one center. The main outcome measurements were Short Musculoskeletal Functional Assessment for function and radiographic evaluation for fracture healing. Patients had been treated with bisphosphonates for an average of 8.8 years (range, 5-20 years) before presentation. RESULTS: Patients reported a mean of 6 months of pain before presentation (range, 1-8 months). Sixty-six percent of patients with surgically treated complete fractures became pain-free and 98% were radiographically healed by 12 months. Sixty-four percent of patients who underwent intramedullary nailing reported a functional return to baseline within 1 year. Patients who reported major functional limitations at latest followup listed pain and apprehension as the major causes of their limitation. CONCLUSIONS: Patients with surgically treated bisphosphonate-associated complete femur fractures achieved generally reliable although delayed fracture healing if malaligned, and nearly two-thirds of patients returned to self-reported baseline function within 1 year. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

A retrospective review of patients with atypical femoral fractures while on long-term bisphosphonates: including pertinent biochemical and imaging studies.

OBJECTIVE: To elucidate the effects of prolonged bisphosphonate (BP) exposure on the development of atypical fragility fractures, and to define the associated risk factors. METHODS: Approval was obtained from the institutional review board, and a retrospective chart analysis was performed on 51 patients who had been on BPs for at least 3 years and had complete subtrochanteric or diaphyseal femoral fracture(s) between January 2005 and April 2011. All relevant data were available for 25 patients (mean age, 67.52 years). All fractures included in the study were low- or no-energy. Relevant clinical and demographic data were collected regarding age, gender, ethnicity, height, weight, and comorbid medical conditions. Imaging and laboratory data collected on all patients included: calcium, alkaline phosphatase, 25-hydroxyvitamin D (25-OHD), intact parathyroid hormone, serum c-telopeptide, and urine n-telopeptide levels, bone mineral density, radiography, and magnetic resonance imaging. RESULTS: Most of the patients in this study were Caucasian, were on alendronate, had bilateral findings, and almost half had prodromal symptoms. The 25-OHD level was suboptimal (<30 ng/mL) in 45.8% of the patients. Mean BP duration was 9.84 years, and mean bone density was in the osteopenic, not osteoporotic, range. CONCLUSION: Characteristics of patients with atypical BP-related fracture include relatively young age, long duration of BP use, suboptimal 25-OHD level, and bone density in the nonosteoporotic range. All of these may be significant risk factors for insufficiency fracture development.

Surgical treatment improves clinical and functional outcomes for patients who sustain incomplete bisphosphonate-related femur fractures.

OBJECTIVE: To describe the outcomes for patients treated at a single institution, who sustained incomplete bisphosphonate-induced femoral fractures. DESIGN: Retrospective review. SETTING: University-based academic medical center. PATIENTS: Thirty-one patients with 43 incomplete fractures met the inclusion criteria. INTERVENTION: Nonoperative management or surgical intervention for fractures with refractory symptoms or progression of fracture lucency on radiographs. MAIN OUTCOME MEASUREMENTS: Radiographic assessments and the Short Musculoskeletal Functional Assessment to gauge functional status. RESULTS: The cohort was all women with an average age of 69.2 (range: 46-92) years and had been treated with bisphosphonate therapy for an average of 9.1 (range: 5-20) years. The average healing time for all incomplete fractures was 9.4 (range: 1.5-36) months. Forty-nine percent of the fractures (21 of 43 fractures) were ultimately treated with surgery for impending complete fracture or failure of nonsurgical management. Of the incomplete fractures treated with surgery, 81% became pain free and 100% were radiographically healed at a mean of 7.1 (range: 1.5-12) months. In contrast, of the nonoperatively treated incomplete fractures, only 64% were pain free at latest follow-up, with only 18% of fractures demonstrating radiographic evidence of healing at an average of 11 (range: 6-24) months. Standardized dysfunction index from the Short Musculoskeletal Functional Assessment was better (19.7) in the surgical group than in the nonsurgical group (19.7 vs. 25.7, P = 0.0017). CONCLUSIONS: A higher percentage of patients treated surgically became asymptomatic and demonstrated radiographic evidence of healing earlier than those treated nonsurgically. Surgical intervention is effective for relief of symptoms when treating incomplete bisphosphonate-related femur fractures, and patients should be counseled to the potential benefits of prophylactic surgery. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Frequency of incomplete atypical femoral fractures in asymptomatic patients on long-term bisphosphonate therapy.

OBJECTIVE: The purpose of our study was to determine the frequency and imaging features of atypical femoral fractures in a consecutive asymptomatic patient population on long-term bisphosphonate treatment and search for distinguishing clinical and laboratory parameters in the subset of patients with fractures. SUBJECTS AND METHODS: Two hundred femoral radiographs in 100 asymptomatic patients (93 women and seven men; age range, 47-94 years; mean age, 69.3 years) were prospectively reviewed by two radiologists. All patients had received bisphosphonate treatment for at least 3 years and had no history of pain or recent trauma. MRI studies were performed when a fracture was suspected on radiographs. Bone mineral density, serum calcium, albumin, 25-hydroxy vitamin D, intact parathyroid hormone (iPTH), serum C-telopeptide, and urine N-telopeptide values were obtained. RESULTS: Two of 100 patients (2%) had three insufficiency fractures. Both patients, 50 and 57 years old, were white, active, and had been receiving bisphosphonate therapy for 8 years. The patient with bilateral atypical femoral fractures showed typical features of bisphosphonate-related incomplete atypical femoral fractures. MRI confirmed the radiographic findings in both patients. The two patients with incomplete atypical femoral fractures were significantly younger than those without atypical femoral fractures. There were no significant differences among the fracture and nonfracture groups in terms of clinical or laboratory results, except for mean iPTH, which was significantly decreased in the fracture group. CONCLUSION: The 2% frequency of incomplete atypical femoral fractures in asymptomatic patients on long-term bisphosphonate therapy is higher than suggested in the literature. Aside from age and mean iPTH, there were no significant differences in clinical or laboratory data between the two groups.

Bisphosphonate-related complete atypical subtrochanteric femoral fractures: diagnostic utility of radiography.

OBJECTIVE: The objective of our study was to evaluate the diagnostic utility of conventional radiography for diagnosing bisphosphonate-related atypical subtrochanteric femoral fractures. MATERIALS AND METHODS: Retrospective interpretation of 38 radiographs of complete subtrochanteric and diaphyseal femoral fractures in two patient groups-one group being treated with bisphosphonates (19 fractures in 17 patients) and a second group not being treated with bisphosphonates (19 fractures in 19 patients)-was performed by three radiologists. The readers assessed four imaging criteria: focal lateral cortical thickening, transverse fracture, medial femoral spike, and fracture comminution. The odds ratios and the sensitivity, specificity, and accuracy of each imaging criterion as a predictor of bisphosphonate-related fractures were calculated. Similarly, the interobserver agreement and the sensitivity, specificity, and accuracy of diagnosing bisphosphonate-related fractures (i.e., atypical femoral fractures) were determined for the three readers. RESULTS: Among the candidate predictors of bisphosphonate-related fractures, focal lateral cortical thickening and transverse fracture had the highest odds ratios (76.4 and 10.1, respectively). Medial spike and comminution had odd ratios of 3.8 and 0.63, respectively. Focal lateral cortical thickening and transverse fracture were also the most accurate factors for detecting bisphosphonate-related fractures for all readers. The sensitivity, specificity, and overall accuracy for diagnosing bisphosphonate-related fractures were 94.7%, 100%, and 97.4% for reader 1; 94.7%, 68.4%, and 81.6% for reader 2; and 89.5%, 89.5%, and 89.5% for reader 3, respectively. The interobserver agreement was substantial (κ > 0.61). CONCLUSION: Radiographs are reliable for distinguishing between complete femoral fractures related to bisphosphonate use and those not related to bisphosphonate use. Focal lateral cortical thickening and transverse fracture are the most dependable signs, showing high odds ratios and the highest accuracy for diagnosing these fractures.

Papillary thyroid carcinoma metastatic to skin may herald aggressive disease.

OBJECTIVE: To describe an unusual case of papillary thyroid carcinoma presenting as a skin lesion on the nose. METHODS: We describe the clinical, pathologic, and immunohistochemistry findings of the patient and briefly review the relevant literature. RESULTS: An asymptomatic 73-year-old man noted a skin lesion on his nose, which when biopsied, revealed histopathologic characteristics consistent with papillary thyroid cancer and was immunohistochemistry positive for thyroid transcription factor-1 and thyroglobulin, also consistent with a neoplasm of thyroid origin. Subsequent physical examination showed a large left thyroid mass, and further workup demonstrated invasion of the trachea and surrounding musculature. In addition, metastases to the sternum, spine, lungs, and liver were noted. Fine-needle aspiration biopsy performed on the thyroid mass confirmed papillary thyroid carcinoma. Although there was evidence of systemic metastases, total thyroidectomy was suggested to the patient to allow optimal treatment by radioactive iodine. At operation, the cancer demonstrated fixation to the trachea and musculature, as well as infiltration of the surrounding soft tissues. Only the portion of the left thyroid mass that could be mobilized was removed. Final pathologic examination confirmed papillary thyroid carcinoma. Cutaneous metastases of thyroid carcinoma are infrequent, and, as the presenting feature of thyroid carcinoma, are even more rare. This case is noteworthy because a skin lesion was the presenting feature of thyroid carcinoma and histopathologic findings together with immunophenotyping provided the initial diagnosis. CONCLUSIONS: In this patient, as in most published cases, the cutaneous metastasis was shown to occur in the setting of extensive metastases. This case also demonstrates that papillary thyroid carcinoma in men older than age 50 years can behave very aggressively.

Laparoscopic adjustable gastric banding for morbidly obese adolescents affects android fat loss, resolution of comorbidities, and improved metabolic status.

BACKGROUND: The distribution of weight loss and its impact on metabolic health has not been documented for laparoscopic adjustable gastric banding (LAGB) in the adolescent population. We hypothesized that LAGB in obese adolescents would result in loss of android fat mass, resolution of comorbidities, and improvement in metabolic status. STUDY DESIGN: Adolescents ages 14 to 17 who met criteria for bariatric surgery were enrolled in our FDA-approved LAGB trial. Demographic data, body mass index, body composition and bone density, laboratory evaluations, and comorbid conditions were assessed pre- and postoperatively. RESULTS: Forty-five patients had complete 1-year followup and 41 patients had complete 2-year followup. Mean preoperative weight was 299 + or - 57 lb and body mass index was 48 + or - 6.4 kg/m(2). The percent excess weight losses at 6 months, 1 year, and 2 years were 31 + or - 16, 46 + or - 21, and 47 + or - 22, respectively. At 1-year followup, patients after LAGB had a significant decrease in their total and android fat mass. In addition, 47 of 85 identified comorbidities (55%) were completely resolved and 25 (29%) were improved in comparison with baseline. Improvements in alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, hemoglobin A1c, fasting insulin, triglycerides, and high density lipoprotein, were also seen. CONCLUSIONS: The percent excess weight loss after LAGB in morbidly obese adolescents is approximately 45% at 1- and 2-year followup, with the majority of weight loss consisting of android fat mass. Resolution or improvement of comorbidities is seen, and improved metabolic status, as demonstrated by liver function tests, lipid levels, and measures of glucose homeostasis, may be expected. These data support LAGB as an appropriate surgical option for morbidly obese adolescents.