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Introduction: Dual energy X-ray absorptiometry (DXA) is a clinically proven method for measuring bone mineral density (BMD) in the lumbar spine, hip, femoral neck, and forearm. It is used for manag...

OBJECTIVE Orthotopic liver transplant recipients are at high risk of fragility fractures both in pre-liver transplant (pre-LT) and in the immediate posttransplant (post-LT) period. The aims of this study were to identify risk factors associated with post-LT fracture and identify factors that contribute to changes in bone mineral density (BMD) in post-LT as they relate to the risk of fracture in the immediate post-LT period. METHODS We conducted a retrospective cohort study of first-time LT recipients who had BMD testing within 2-year pre-LT and 1-year post-LT. We assessed factors associated with immediate post-LT fracture using logistic regression models and linear regression models. RESULTS New fractures occurred in 41/286 (14.3%) of LT recipients during the first year following LT. In multivariate analysis, we noted an increased odds of fracture for patients with prior history of fracture (P < .001), patients who were older (P = .03), patients with higher end-stage liver disease score (P = .03), and patients with lower BMD. After adjustment for multiple testing, only a history of prior fracture was statistically significant. CONCLUSION Our study demonstrated that prior fracture at any site was associated with developing a new fracture in the first year post-LT.

The liver plays an important role in bone and mineral metabolism of patients with end-stage liver disease. These patients are known to have an increased risk of osteoporosis and fractures before liver transplant (LT) with reported fracture incidence of 10-56%. The cause is multifactorial, which includes their underlying liver disease, chronic illness, vitamin D deficiency, and hyponatremia. The impact of hyperglycemia and diabetes mellitus on bone health in liver transplant recipients is not known. Hypothesis: Hyperglycemia increases risk of fracture and osteoporosis in pre- LT patients undergoing LT. Methods: To answer this question, we did a retrospective chart review of consecutive first time, single organ LT recipients at our institution from 2011-2014, who had BMD performed prior to transplantation. We identified 393 patients but included only 209 patients who carried a diagnosis of hyperglycemia or diabetes (type 2 DM, type 1 DM, steroid induced DM and hyperglycemia). BMD was defined based on WHO criteria as Normal, osteopenia and osteoporosis. Hemoglobin A1C was divided into 4 quartiles (A1C ≤5.6%, 5.7-6.4%, 6.5-7.9%, and ≥8%); fasting blood glucose was defined as any venous glucose checked before 9am and labeled as a fasting lab in the chart. Fasting blood glucose was divided into those with BG200 mg/dL. We chose labs closest to the transplant date. Pre LT fracture was compared with hemoglobin A1C and BMD as well as fasting glucose. STATA statistical program was used to calculate Fisher T-test. Results: Baseline characteristics of our cohort were as follows. Median BMI was 27.9 (16.2, 45.6). Majority had hepatitis C (33%), NASH 12%, and alcoholic liver disease 23%. Average MELD score was 15 (6-40). Average wait time to transplant was 90 days. 29% of patients had normal BMD, 46% osteopenia and 25% osteoporosis. From the total 209 patients reviewed, 17 had a fracture prior to transplant of which 14/17 had vertebral fractures. The only variable that correlated with risk of fracture was hemoglobin A1C. Higher level of Hemoglobin A1C correlated with the presence of fracture p= 0.04. BMD did not correlate with fracture p= 0.28. There was no association between BMD and Fasting glucose level p=0.55. There was no correlation between fasting glucose and risk of fracture p=0.44. Discussion: This study suggests that a correlation between the presence of pre LT fracture and HgA1C exists. Other factors such as BMD and fasting BG did not correlate with fracture. Those with higher hemoglobin A1C prior to liver transplant might be at risk for fracture compared to those without diabetes or hyperglycemia (A1C

Context: Tumor induced osteomalacia related to anaplastic thyroid cancer has never been reported. Objective: We describe a case of tumor induced osteomalacia (TIO) in a patient with a fibroblast growth factor 23 (FGF-23) secreting anaplastic thyroid carcinoma. The current imaging modalities are reviewed. Design and intervention: Clinical, biochemical, and radiological assessments were done, including computer tomography (CT) of the neck and skull to thigh positron emission tomography (PET)/CT. The patient underwent surgical tumor debulking three days after presentation due to airway compromise. Molecular studies of the resected tissue were performed using reverse transcriptase–polymerase chain reaction (RT-PCR) and gel electrophoresis for the phosphaturic mesenchymal tumor FGF-23. Results: Resected tissue demonstrated features of anaplastic thyroid cancer with positive markers for FGF-23 protein, consistent with a FGF-23 secreting paraneoplastic tumor. The patient's metastatic burden rapidly progressed as demonstrated by a dramatic rise in serum FGF-23 levels and worsening hypophosphatemia in concert with progression of the metastatic lesions on PET/CT. Conclusion: We believe that our patient's rapidly progressive anaplastic thyroid cancer was responsible for persistent hypophosphatemia and osteomalacia, substantiated by the finding of FGF-23 protein within the thyroid tumor cells. Our case indicates that anaplastic thyroid cancer can cause TIO. Keywords: Anaplastic thyroid cancer, Tumor induced osteomalacia, FGF 23, Hypophosphatemia, Osteomalacia

Background Thyroid cancer often recurs in the neck. Well-differentiated thyroid cancer metastasizes to the neck in about 40%, and recurs after surgery in about 20%-30%. Surgery is the treatment of choice, with biochemical remission in 21-66%, but some patients are poor surgical candidates or refuse surgery, and permanent nerve injury and hypoparathyroidism are substantial complications. The 2018 National Comprehensive Cancer Network (NCCN) guidelines state that in select patients with unresectable, non-radioiodine-avid, and progressive disease, local therapies such as ultrasound guided ethanol ablation (EA) can be considered. Recent systematic reviews have confirmed the efficacy and safety of EA, and show that this minimally invasive therapy compares favorably to surgical resection in non-randomized studies. Objectives To determine the rate, type, and outcomes of nerve injury after EA for neck metastases from thyroid cancer. Methods IRB approval was obtained. Retrospective review of medical records of all EA performed from March 2004 through August 2018. Data collected included sex, age, histologic type of thyroid cancer, date of all EA sessions, and number of tumor sites injected per EA session. Nerve injury was defined as a neurologic deficit with immediate onset after ethanol injection that lasted beyond the effect of local anesthetic. Diagnosis was made based on symptoms and functional deficit as described during follow up phone calls or visits. Confirmatory laryngoscopy was not performed. Results During the 14 year period 104 patients received EA; 64 females with mean age 60 (range 23-90) and 40 males with mean age 54 (range 24-85). A total of 298 sites were treated (lymph nodes and local extra-nodal recurrence) in 169 ethanol injection sessions (mean 1.8, range 1-7). Histologic diagnosis was papillary in 89.4% (classic 87, follicular variant 4, tall cell variant 2), medullary 6 (5.8%), and follicular 4.8% (follicular 1, Hurthle cell variant 4). Recurrent laryngeal nerve (RLN) deficit occurred in 2, superior laryngeal nerve (SLN) deficit in 1 and sympathetic deficit in 1. Nerve injury occurred in 4/104 patients (3.8%), 4/169 EA sessions (2.4%), and 4/298 EA sites (1.3%). All EA with nerve injury were in level VI, including a very deep injection associated with the sympathetic chain injury. The dysphonia from two RLN injuries recovered fully at 1 week and at 3 months. One SLN injury had no hoarseness but could not project a loud voice while singing with his church choir and recovered in 1 month. The one patient with ptosis recovered almost completely, did not notice any residual problems, but physical examination demonstrated a subtle difference in palpebral elevation 1 year after EA. Conclusion Nerve injuries after EA are infrequent and most resolve completely within 3 months.

Anaplastic thyroid cancer is one of the most lethal malignancies, with dismal prognosis, resistance to multimodal treatments and a median survival of only 5-6 months. Advances in the discovery of genetic pathway aberrations involved in this aggressive disease have been made, and multiple novel therapies targeting these pathways are undergoing clinical trials. So far, there is no single effective treatment for this disease; however, multimodal therapies with a combination of surgery, radiation and chemotherapy hold some promise. We conducted a PubMed search using the words thyroid neoplasm, anaplastic thyroid carcinoma, anaplastic thyroid cancer and anaplastic thyroid neoplasm, revealing 1673 publications. We review the pathophysiology, current treatments and advances made in identifying the alterations in genetic pathways, as well as novel therapies targeting these pathways.

To review literature and present a schematic approach to hypophosphatasia (HPP) evaluation and management applicable to practicing physicians to ease its recognition and diagnosis.Studies were obtained from online databases PubMed and MEDLINE using keyword 'hypophosphatasia.'HPP is a rare disease characterized by low serum alkaline phosphatase along with diverse musculoskeletal symptoms that mimic different disorders. To date, the prevalence of HPP and its impact on adults has been unrecognized. There is lack of evidence from larger and long-term studies examining the adult type of this condition.It is essential to increase awareness on the complexity of the pathophysiology and clinical features of HPP, which causes debilitating physical conditions that severely affects quality of life. A better comprehension of adult forms of HPP is essential to reduce a delay in diagnosis as well as ensure suitable management.ALP = alkaline phosphatase; HPP = hypophosphatasia; PEA = phosphorethanolamine; PLP = pyridoxal-5-phosphate; PPi = inorganic pyrophosphate; TNSALP/TNAP = tissue-nonspecific alkaline phosphatase.

Anaplastic thyroid cancer (ATC) is rare and associated with a short life expectancy. The majority of patients have coexisting differentiated thyroid carcinoma or long standing history of goiter. Al...

Hypoparathyroidism is a rare endocrine disorder in which parathyroid hormone (PTH) production is abnormally low or absent, resulting in low serum calcium and increased serum phosphorus. The most common cause of hypoparathyroidism is parathyroid gland injury or inadvertent removal during thyroid surgery. Current treatments include supplementation with calcium and active vitamin D, with goal albumin-corrected serum calcium level in the low-normal range of 8-9mg/dl. Complications of the disease include renal dysfunction, nephrocalcinosis, kidney stones, extracellular calcifications of the basal ganglia, and posterior subcapsular cataracts, as well as low bone turnover and increased bone density. Until January 2015, hypoparathyroidism was the only classic endocrine disease without an available hormone replacement. Recombinant human PTH 1-84, full length parathyroid hormone, is now available for a selected group of patients with the disease who are not well controlled on the current standard therapy of calcium and active vitamin D. In addition, the role of PTH replacement on quality of life, intracerebral calcifications, cataracts, improving bone turnover, and reduction of renal complications of the disease remains to be further investigated.

Anaplastic thyroid carcinoma (ATC) is more common in women than in men, with a ratio of 1.9:1. The tumor occurs in older individuals and has a median (mean) age of 69 (66.5) years. ATC often exists coincidentally with, or in patients with a history of, differentiated thyroid cancer, suggesting a dedifferentiated process. ATC comprises only 3.8 % of thyroid cancers worldwide and is seen more frequently in regions of iodine deficiency. Iodine supplementation has reduced the frequency by 40–80 %. ATC usually presents with the sudden onset of a neck mass. The tumor produces both airway and esophageal obstructive symptoms including dyspnea, dysphagia, hoarseness (due to recurrent laryngeal nerve involvement), pain, cough, and hemoptysis, and death occurs shortly thereafter. The median tumor size at onset is 6.8 cm but may be as large as 25 cm. Initial imaging is required to assess the extent of disease, and FDG-PET is particularly helpful in locating disease locations. Metastatic disease at presentation occurs commonly, with lung and mediastinal lesions being identified most frequently. Other sites include the bone, liver, brain, heart, adrenal glands, and kidney, many of these being sites rarely affected by differentiated thyroid cancers. Initial evaluation should include not only anatomic staging but an assessment of the patient’s performance status, after which, a realistic discussion of the patient’s therapeutic options and desire for aggressive versus palliative management should be held. Restaging and goals of care should be reassessed after initial therapy and periodically thereafter. Causes of death are both from local obstructive complications and distant metastases.

Anaplastic thyroid cancer (ATC) has a dismal prognosis, with a median overall survival of only 4.9 months and 1-year survival of 20 %. Stage IVA (intrathyroidal) tumors have the best prognosis, while IVC patients (distant metastases) have the worst. The most favorable prognosis is seen in patients with an incidental focus of ATC, but even these uncommon patients do not all survive, indicating that microscopic metastases are present early and aggressive therapy is required. Unfortunately, the median frequency of stage IVA lesions is only 10 %, compared to 40.1 % and 45.8 % for stages IVB and IVC, respectively. Predictors of survival in many but not all studies include completeness of surgical resection, delivery of higher doses of external radiation, smaller tumor size, and locoregionally confined disease. Younger age is more favorable in some studies, while gender does not affect survival. Historically, most studies using combination therapy have not prolonged survival, although several recent reports using multimodal therapy have shown some promise. In a few studies, elevated white blood cell counts, dyspnea, dysphagia, and higher intensity of uptake on FDG-PET imaging have been associated with a worse prognosis. What remains unexplained is why some patients present with stage IVA disease, while most are more advanced. A better understanding of the critical genetic abnormalities present in each stage is needed in order to design better therapies to improve survival.

It is unknown whether allowing patients to have BMD (bone mineral density) studies acquired while wearing radiolucent clothing adlib contributes appreciably to the measurement error seen. To examine this question, a spine phantom was scanned 30 times without any clothing, while draped with a gown, and while draped with heavy winter clothing. The effect on mean BMD and on SD (standard deviation) was assessed. The effect of clothing on mean or SD of the area was not significant. The effect of clothing on mean and SD for BMD was small but significant and was around 1.6% for the mean. However, the effect on BMD precision was much more clinically important. Without clothing the spine phantom had an least significant change of 0.0077 gm/cm(2), while when introducing variability of clothing the least significant change rose as high as 0.0305 gm/cm(2). We conclude that, adding clothing to the spine phantom had a small but statistically significant effect on the mean BMD and on variance of the measurement. It is unlikely that the effect on mean BMD has any clinical significance, but the effect on the reproducibility (precision) of the result is likely clinically significant.

We quantitated how often review of recent radiology studies provides information useful to the densitometrist. While preparing bone mineral density (BMD) reports on 1012 consecutive patients, radiology reports in electronic medical records (EMRs) for the previous 5 years at potentially relevant sites (lumbar spine X-rays, abdominal computed tomography (CT) scans, and so forth) were reviewed. When a study was found, it received a grade according to how relevant findings were to the BMD report: "1" for studies that were irrelevant, "2" for those that confirmed the impression formed from review of the BMD images, "3" for those that clarified the impression that was unclear after reviewing the BMD images, and "4" for those that revealed new relevant data when no abnormality was noted on review of the BMD images. A total of 562 patients (55.5%) had a radiologic study at a site of potential interest within the past 5 years. Fifty-three patients (5.2% of all patients) had a grade 4 study, 88 patients (8.7% of all patients) had a grade 3 study, and 185 patients (18.3% of all patients) had a grade 2 study. Two hundred sixty-four patients (25.8%) had a grade 2 or 3 study, and 299 (29.5%) had a grade 2–4 study. The radiographic study that was most likely to be found in patients' EMR was chest X-ray (34.7% of all patients), but it was also the one that was least likely to have any relevance to the reader; only 10.5% of the total chest X-rays were graded 2–4. The next most likely studies to be found in patients' EMR were abdominal CT scans (18.0% of all patients) and lumbar spine X-rays (14.4% of all patients), but these studies were much more likely to be useful to the reader, as 62.6% of abdominal CT scans and 78.1% of lumbar spine X-rays were graded 2–4. The likelihood of a patient having radiologic examinations in the EMR at sites potentially relevant to the BMD reader is high, but the likelihood that these clarify abnormalities noted on BMD is only moderate. Review of the EMR is unlikely to be relevant when the dual-energy X-ray absorptiometry images are normal.

Since the initial development of the implantable defibrillator in the 1970s by Michel Mirowski, and commercial introduction in 1985, national surveys and industry analysts have estimated that more than 160,000 implants have been performed in the United States (1). Multicenter randomized trials have demonstrated the effectiveness of the implantable cardioverter-defibrillator (ICD) for reducing mortality in high-risk patient groups (2,3). It has been estimated that more than 700,000 patients are eligible for an ICD in the United States. The newest generation of ICDs are capable of defibrillation of ventricular fibrillation, pace termination of ventricular tachycardia, single or dual chamber pacing, and cardiac resynchronization therapy (CRT) depending on the model. In addition, ICDs now have multiple additional features including extensive programming options, detailed event histories, and real-time telemetry. Unfortunately, even with the most recent generation of ICDs, adverse clinical events such as inappropriate detection (providing tachycardia therapy when no ventricular arrhythmia was present) and lead failures remain relatively common, approaching 50% in the first 2 years (4,5). In addition, a multicenter study that analyzed terminal events in patients with first-generation ICDs, found that approximately 15% of patients who had sudden death presumed secondary to arrhythmias had ICDs that indicated battery depletion (5,6). Finally during 2005 a number of well publicized recalls for potentially fatal device malfunction caused both the public and physicians to question the reliability of ICD therapy. This chapter reviews the basic follow-up of ICDs, and how to troubleshoot an ICD suspected of malfunction.

Asymptomatic hyperparathyroidism developed in a 65-yr-old man with a history of metastatic papillary thyroid carcinoma. Pertinent laboratory values were: calcium, 10.8 mg/dl (2.70 mmol/liter) [reference range, 8.9– 10.1 mg/dl (2.22–2.52 mmol/liter)]; intact PTH, 135.1 pg/ml (14.3 pmol/liter) [15–50 pg/ml (1.6–5.3 pmol/liter)]; and albumin, 4.5 g/dl (45 g/liter) [3.5–5.0 g/dl (35–50 g/liter)]. Phosphorus, creatinine, and 25-hydroxyvitamin D levels were within normal limits. Thyroid ultrasound for follow-up of his thyroid cancer revealed a 3.0 1.3 0.7-cm cystic mass in the left thyroid bed (Fig. 1A). Twenty-five milliliters of clear fluid were removed from the cyst, revealing an intact PTH of 821 pg/ml (87.1 pmol/liter). Serum calcium was 9.0 mg/dl (2.25 mmol/liter) at 6 months and 9.1 mg/dl (2.27 mmol/liter) at 24 months, with intact PTH 56.5 pg/ml (6 ng/liter) and reduction of the cyst to 0.7 0.6 0.7 cm (Fig. 1B). Parathyroid cysts are rare. An uncommon cause of primary hyperparathyroidism is a functional parathyroid cyst (1). Few parathyroid cysts (10–15%) are functional (presenting with hyperparathyroidism) (2). Functional cysts are treated with surgical excision (3, 4), although successful treatment with aspiration has been described in one case report (3). They mimic thyroid and thymic cysts, thus presenting a diagnostic challenge (4). The presence of elevated intact PTH in aspirated fluid is diagnostic. Parathyroid cysts have absent uptake on radioiodine thyroid scans and rarely are positive on sestamibi parathyroid scans (5). Ultrasound, computed tomography, and magnetic resonance imaging show a cystic cervical or mediastinal mass (5). Aspiration of a functioning parathyroid cyst can be both diagnostic and therapeutic. Acknowledgments