ISSN Online Research Articles

Headache Medicine: updates and bibliometric analysis

Introduction
 Headache Medicine is the official scientific journal of the Brazilian Headache Society that has been publishing clinical and experimental, qualitative, and quantitative research on headaches and orofacial pain for 28 years, as well as aspects related to pain that may have implications for headaches. In constant updating, Headache Medicine demonstrates commitment and scientific ethics following the international criteria for publication in the medical field.
 Objective
 Describe updates made in 2020 to the management and editorial process and bibliometric data from Headache Medicine publications and accesses to demonstrate their impact on headache science.
 Methods
 Data on the quantity and location of accesses until September 2022 were obtained from Google Analytics. The most accessed and read articles (originals, reviews, or case reports) were identified through the statistical reports of the Open Journal Systems (OJS). The journal's H5 index and the citations of each published paper were consulted in Publish or Perish and Google Scholar, respectively.
 Results
 In 2020, Headache Medicine obtained ISSN online, migrated its management to OJS, registered a Digital Object Identifier (DOI) on all articles published, linked the authors' ORCiD to the publication, and updated the publication of the numbers of each issue. Google Analytics has been monitoring Headache Medicine for just 2 years and has already accounted for more than 38,000 accesses from 150 countries. Brazil (29,282 accesses), the United States (2,186 accesses), Portugal (1,434 accesses) and China (377 accesses) are the 4 countries with the most access. Headache Medicine has published 202 original articles, reviews or case reports since 2010. The three most accessed articles with abstract and full article are literature review: Topiramate and cognitive function: review (Santos et al., 2005) with 1,152 accesses, Pizotifen for the treatment of migraine.
 (To see the complet abstract, please, check out the PDF.)

Pendampingan Model Pembelajaran Inovatif di Sekolah Dasar Kecamatan Simeulue Timur Kabupaten Simeulue

This mentoring program aims to improve the ability of teachers in integrating innovative learning models in learning in elementary school (SD) 1 Kecamatan Simeulue Timeur Aceh. The ability to integrate innovative learning models in learning requires specific skills in their application. Responding to that, done by the teachers to be able to integrate innovative learning model effectively according to the demand of learning in elementary school. Methods of assistance are conducted through several stages of activity, including: preparation, implementation, evaluation and reflection, and follow-up. Outcomes generated through the mentoring program include: an innovative learning model guidebook in elementary school, teacher model of integrating innovative learning model, and scientific article published in ISSN online journal. The results of the devotion program indicate that the increasing ability of teachers in integrating innovative learning models in learning in SD1 Simeulue Timur Sub-district Simeulue. Thus, the assistance performed has been run effectively and in accordance with the expected results.

WASTED OF YOUNG COCONUT SHELL AND SKINS AS AN ALTERNATIVE POLYBAG AND CHARCOAL BRICKET

The community service activities carried out by the team on this occasion aim to provide several alternative side incomes for young coconut entrepreneurs. Some of the problems partners face in this regard are specifically in: a). Waste of young coconut shells and young coconut shells that are just thrown away and piled up beside/behind the young coconut business; b) the bookkeeping system is still traditional; there are even partners who did not record the books beforehand. Specific targets or solutions expected in this community service area). Partners can process young coconut waste into a new source of income, namely by making used coconut shells into natural and environmentally friendly pots/polybags by planting aglaonema flowers, and b). The scraps of peel and fragments of young coconut shell waste can be used as a fuel substitute for charcoal or briquettes. The service team handed over TTG in the form of closed burning barrels from used barrels for optimal combustion and simple financial training to determine the income from selling young coconuts to partners. Method of Implementation This service is carried out by carrying out the initial approach method, training, and mentoring on how to manufacture the finished product so that the alternative side income can be achieved maximally. The outputs produced in this activity are as follows: a) print and online mass media publications; (b) activity videos uploaded on youtube, and (c) articles in national journals with ISSN online and in print (d) trademarks (billboards/banners) creative designs, social media and also business location points on google maps.

The Urgency of Granting Authority of Judiciary Institutions in Dispute) Effectiveness of Duties and Functions of Civil Service Police as Law Enforcers of Regional Regulations in Ternate City

Ternate City Government in its efforts to make Ternate City a cultured, religious, harmonious, independent, just and environmentally friendly city in accordance with the vision of its government, of course, requires regional apparatus that work effectively and optimally in order to realize the vision of the government. One of the regional apparatus is the Civil Service Police Unit (Satpol PP), which according to the mandate of the laws and regulations has the function and duty of maintaining and carrying out public order and order, including its function of enforcing regional laws in Ternate City. A number of Ternate City regional regulations that are enforced with the aim of creating peace and public order, such as controlling street vendors, squatters, street children and others, of course, must be supported by the effectiveness of the duties and functions of the Satpol PP of the Ternate City Government.In previous studies on the topic of the existence of Satpol PP duties and functions, there has not been a single research study that has questioned the effectiveness of Satpol PP's duties and functions as law enforcer of local regulations, so it can be said that the study to be investigated by this researcher is still a relatively problem. has never been studied by previous researchers. Therefore, it can be said that this research has a novelty and originality side.The general objective of this research is to examine in depth the form of effectiveness of Satpol PP's duties and functions as law enforcer of regional regulations in Ternate City. Meanwhile, the specific objectives of research on this topic are expected to become material for recommendations for local governments and / or stakeholders in fixing and establishing policies (policies) related to the existence of Satpol PP as law enforcers of regional regulations.The method in this study uses a socio-juridical research type with a qualitative research type. Research with the socio-juridical type was used with the reason to identify the form of effectiveness of the Satpol PP's duties and functions as law enforcers of regional regulations in Ternate City. The nature of this research is exploratory in nature which aims to test whether there is a cause and effect relationship between the various problem variables under study. While the approach in this research is to use a conceptual approach (conceptual approach) and a legal instrument approach (statute approach). Data collection techniques in this study were carried out by collecting primary and secondary legal materials in the form of legal policy regulations that regulate the duties and functions of Satpol PP and interviews with informants who are considered relevant to the problems being studied.The research stages in the form of data tracing, data processing, and data completion of research results will be carried out for 6 (six) months in 1 (one) year running period. The mandatory output from the results of this research is in the form of publications in national journals that are ISSN online. Meanwhile, the tentative additional output is in the form of enrichment of teaching materials

ReviewISSN Print 0719-2460 - ISSN Online 0719-2479. Attribution 4.0 International (CC BY 4.0). www.joralres.com/20211Periodontitis como factor desencadenante de enfermedades sistémicas crónicas. Revisión bibliográfica

ReviewISSN Print 0719-2460 - ISSN Online 0719-2479. Attribution 4.0 International (CC BY 4.0). www.joralres.com/20211Periodontitis como factor desencadenante de enfermedades sistémicas crónicas. Revisión bibliográfica

Pengembangan Pengelolaan Dana Desa Terhadap Kesejahtraan Masyarakat Desa Di Kabupaten Konawe Selatan Provinsi Sulawesi Tenggara

Development of village fund management is very much needed by the community so that it can be enjoyed by all levels of society in the villages. The seriousness of the government in developing villages is evidenced by the start of allocation of the Village Fund budget for 2015. The allocation of the Village Fund is mandated by Law (Law) Number 6 of 2014 concerning Villages and Government Regulation (PP) Number 6 of 2014 concerning Village Funds Sourced from STATE BUDGET. The regulation explained that the administration of the village government adheres to the principle of decentralization and the task of assistance. The principle of decentralization raises village internal funding (Desa APBD), while the principle of co-administration provides an opportunity for Villages to obtain funding sources from the government above it (APBN, Provincial APBD, Regency / City APBD). This study aims to observe what the development of village funds looks like, how they are implemented and the impact of the use of village funds in supporting development activities and community empowerment. The research method used is a qualitative research method that relies on observing places, actors and activities in Konawe Selatan Regency, Southeast Sulawesi Province, which was chosen as a case study. Initial observations show that the Village Fund does not have significant results in improving the welfare of the community. These indications are evident in the welfare of the community which has not improved with the existence of the village fund. Therefore it is necessary to develop a good management of village funds to improve the welfare of rural communities, especially in Konawe Selatan District. The output to be achieved is the scientific publication with ISSN Online and the level of technological Readiness that will be achieved 1-3.

PKM Pemberdayaan Masyarakat dalam Pengembangan Produk Olahan Pisang Sale Sidodadi Ramunia

This community service program generally aims to increase the income of housewives in processing banana sale products in Sidodadi Village, Beringin District, Deli Serdang Regency. This service has specific targets and outcomes. Specific targets and outputs that will be produced include: One article published through ISSN online journals, Publications in mass print / online / university repository, Increasing competitiveness (increasing quality, quantity, and value added of goods, services, trademarks ), Increasing the application of science and technology in society, Improving community values (arts, culture, social, peace, education, health). The method of approach in the implementation of community service activities, through the method of exposure and discussion, training, assistance, simulation, observation, interviews, field notes, and cooperation with the main objective to improve the economy of the village of Sidodadi Romania through processing banana sale.

PERSEPSI MAHASISWA PGSD TERHADAP IMPLEMENTASI KKNI DI UNIVERSITAS NEGERI MEDAN

This study aims to describe the perception of PGSD students on the implementation of KKNIbased curriculum at Medan State University (Unimed). The research study focused on the implementation of 6 KKNI tasks, namely: routine task, Critical Book Report (CBR), Critical Journal Review (CJR), idea engineering, project, and mini research. This research is a descriptive quantitative research, by taking sample of research from Unimed student of PGSD as much as 240 people. Data were collected by using observation and questionnaire, then analyzed by using descriptive statistic. Outcomes resulting from the results of this study include: (1) research reports that contribute to the direction of policy courses and faculty in running KKNI in the future, (2) national journals with ISSN online that contribute to the development of science, especially related with the implementation of KKNI in Higher Education, and (3) recommendation of institutional policy toward the implementation of KKNI in the future. The result of the research shows that the perception of PGSD students on the implementation of KKNI is 3.33 (83.25%) with Good category. That is, PGSD students have a good perception on the implementation of KKNI in Universitas Negeri Medan. Keywords : perception, PGSD, curriculum, KKNI

1 Copyright © by Indiana State University Clinical Practice in Athletic Training All rights reserved. ISSN Online 2577-8188 Volume 1 – Issue 1 – June 2018 Welcome to Clinical Practice in Athletic Training: Letter from the Editor-in-Chief

1 Copyright © by Indiana State University Clinical Practice in Athletic Training All rights reserved. ISSN Online 2577-8188 Volume 1 – Issue 1 – June 2018 Welcome to Clinical Practice in Athletic Training: Letter from the Editor-in-Chief

Engasjement i undervisningen

The notion «enthusiasm» is commonly used to describe excellent teaching, among students as well as university teachers. The word may contain many connotations, but when applied as a criterion for teaching, enthusiasm is commonly categorized as a personality trait. Researchers have often studied operationalized instructional behaviors associated with enthusiastic teaching, whereas research on teachers’ own subjective views on enthusiasm are rarer. This article presents some findings from an online questionnaire administered at the University of Oslo in 2015, which was answered by 1 229 staff members holding different teaching positions. Degrees of enthusiasm in teaching are matched with data about different teaching obligations. Many university teachers regard enthusiasm as a personal trait, but interest in subject matter is considered even more important for their enthusiasm. Teachers’ descriptions of Uniped, volume 39 no 2-2016 p. 102–117 ISSN online: 1893-8981

Security Issues in Contemporary European Integration Process, Book review of Europolity, Continuity and Change in European Governance, vol.8, no.2 (New Series), Centre for European Studies, 2014, ISSN print 2344-2247, ISSN online 2344-2255, ISSN-L2344-2247

Security Issues in Contemporary European Integration Process, Book review of Europolity, Continuity and Change in European Governance, vol.8, no.2 (New Series), Centre for European Studies, 2014, ISSN print 2344-2247, ISSN online 2344-2255, ISSN-L2344-2247

Long-Acting Growth Hormone for Replacement Therapy

GH replacement therapy has shown important beneficial effects on body composition, bone metabolism, lipid metabolism, and quality of life in adults with GH deficiency with a good safety profile (1, 2). Current management is based on daily sc injections before bedtime that are often experienced as cumbersome by the patient and may therefore affect adherence to treatment. Sustainedrelease GH formulations or long-acting GH for less frequent injections have therefore been developed. The paper by Biller et al. (3) published in this issue of the JCEM reports the results from a large 6-month study of adults with GH deficiency demonstrating efficacy and safety of a sustained-release formulation of GH with once weekly sc administration. The study concluded that the treatment was well tolerated and all clinical beneficial end-points were met, such as reduction in fat mass. GH is a powerful metabolic hormone with lipolytic actions, protein anabolic effects, and insulin antagonistic effects (4). The plasma pattern of GH, including pulse frequency, basal levels, and total integrated levels is influenced by several factors, including gender, age, and adiposity (5). Therefore, pattern of GH delivery and GH exposure may have an impact on the effects obtained by treatment. The importance of the mode of GH administration is supported by a number of animal studies demonstrating that a changed pattern of GH exposure has different effects on growth and metabolism (6). The GH secretion is suppressed by food and augmented by fasting. It is therefore a fasting hormone mobilizing energy from fat stores by lipolysis, inducing gluconeogenesis in the liver, and preserving protein mass during fasting through its protein anabolic action, i.e. in many aspects the reverse action to insulin in the postprandial state (7). Moreover, the gene expression and activity of some important regulatory enzymes in the liver are dependent on the pattern of GH exposure (8, 9). The clinical importance for safety and efficacy of not delivering GH in a physiological pulsatile manner is therefore something to consider in the pharmaceutical development of GH products for treatment. Current practice of GH treatment both in children and in adults is to administer GH as a bedtime sc injection. The basis for this practice comes from early observations that daily sc injections gave a better growth response in GHdeficient children than three injections per week (10). Moreover, the closest similarity to a normal diurnal metabolite pattern was achieved with evening sc injections of GH to GH-deficient adults (11). The diurnal plasma GH profile following daily sc evening injections is, however, an intermediate between a pulsatile and a continuous GH exposure time profile (12) and is therefore not physiological. The bedtime administration of GH means that most of the GH action occurs during the night in the fasting state. This is, however, the regime that has proved its safety and efficacy of modern GH therapy in children and in adults (1). Having a more continuous exposure, such as during treatment with long-acting GH, means that GH exerts its action both in fasting and in the fed state during the day, meaning that the normal interaction and balance with insulin is further set aside. The clinical importance of this is not clear. Whether the same efficacy and safety can be obtained by moving the GH exposure toward a more continuous pattern has been studied mainly in adults. In one small pediatric study, however, GH delivered either as daily sc injections or as a continuous GH administration using a sc pump demonstrated the same growth rate by the two treatment modes, but the serum IGF-I response was higher in the group receiving continuous GH (13). Studies in adults comparing the same dose of GH administered as a daily sc injection or as a continuous infusion have, in agreement with the pediatric experience, shown that the IGF-I and ISSN Print 0021-972X ISSN Online 1945-7197 Printed in U.S.A. Copyright © 2011 by The Endocrine Society doi: 10.1210/jc.2011-0689 Received April 20, 2011. Accepted April 22, 2011.

The Academic and Clinical Endocrinology Physician Workforce in the U.S.

In this era of U.S. health care reform, it would be optimal for planning purposes to have a clear picture of the supply/demand balance of the U.S. physician workforce. This is particularly important in endocrinology because of the associated care for chronic and costly medical conditions, such as diabetes and osteoporosis. However, there is no central, reliable, complete, and up-to-date physician database in the United States. In the absence of such data, how can we intelligently plan for a cost-effective and prevention-focused health care system? How can those with a stake in the health care system optimize the future clinical, scientific, and academic workforce? These are questions that prompted the report by Desjardins et al. (1) in this issue of the JCEM. But first, a little background. Can we reasonably estimate the size of the current and future deficit in the endocrinology workforce? We have reviewed this question in the past (2). On the “demand side,” there are 26 million people with diabetes in the United States (3, 4), 10 million have osteoporosis (5), and about 12 million have a thyroid nodule requiring evaluation (6). Nearly 34% of adults have the metabolic syndrome, and one third of the U.S. population is obese ( 100 million). Therefore, the total number of Americans with endocrine disorders comprises a substantial fraction of the population (nearly 150 million), and this figure does not even include other common disorders such as hyperand hypothyroidism, polycystic ovarian syndrome, or less common diseases of the pituitary, parathyroid, and adrenal glands. In hospitals, the caseload is certainly high because approximately 30% of inpatients have diabetes. Obviously, the 2000–2500 practicing clinical endocrinologists in the United States (see below) cannot handle this burden, nor should they in an ideal world. Most patients can be managed by primary care providers and ancillary personnel. But even 10% of those patients (i.e. 15 million) could not be handled by the current pool of endocrinologists; this would yield a panel of approximately 6000 patients per endocrine physician. If a normal physician workload or panel would include 3000–4000 patients, this would predict approximately a 30–50% shortfall for the current demand. One could even argue that this is an underestimation because the population is aging and the diabetes epidemic progresses. Why can’t primary care providers manage patients with diabetes, osteoporosis, thyroid nodules, etc.? Is endocrine care really that complicated? The answer is yes; endocrine diagnosis and management are becoming increasingly complex. For example, there has been an explosion in the number of diabetes and osteoporosis drugs, often used in combination. There are now seven types of insulin and analogs, each with particular characteristics, and that figure does not even include the different premix preparations. It is difficult to maintain expertise on every one of these drugs. And then there are devices and technology: insulin pumps, glucometers, and continuous glucose monitoring systems. Who should get these devices, and more importantly, who will ensure that their use translates into meaningful clinical improvements? Who should be evaluated for islet or pancreas transplantation and how does one make that happen? In the controversial field of thyroid cancer and nodules, endocrinologists are needed to interpret results of aspiration cytology and make cost-effective decisions on utilization of imaging and treatment options. Contemporary treatment of osteoporosis now involves expensive biologicals (e.g., recombinant human PTH and denosumab) that also demand special expertise. Furthermore, there are also multiple complex and sometimes conflicting practice guidelines, and economic incentives, malpractice concerns, and quality assessment measures are all driving outpatients to, not away from, endocrinologists. On the quality improvement side, primary care providers and hospitals are under financial pressure to ISSN Print 0021-972X ISSN Online 1945-7197 Printed in U.S.A. Copyright © 2011 by The Endocrine Society doi: 10.1210/jc.2011-0516 Received February 25, 2011. Accepted February 28, 2011.

Nesidioblastosis No Longer! It's All about Genetics

The past two decades have witnessed rapid advances in elucidating genetic forms of hyperinsulinemic hypoglycemia that have dramatically eclipsed our previous concepts about congenital hyperinsulinism in infants and children. Before this time, persistent hypoglycemia in infants, a disorder first described as “idiopathic hypoglycemia of infancy” in the mid-1950s (1), was attributed to nesidioblastosis, a supposed disturbance in embryonic morphogenesis in which insulin cells continued to bud off pancreatic ducts beyond the time of birth (2). This increase in -cell mass was presumed to explain hypoglycemia in infants affected with nesidioblastosis. By the mid1980s, however, studies by Rahier et al. (3) and other pathologists had convincingly proven that nesidioblastosis is merely a normal feature of the pancreas in early infancy. In pediatrics, use of the term has fortunately been abandoned. Interestingly, nesidioblastosis continues to be mentioned in adults as if it were still a specific entity. For example, patients with hypoglycemia post gastric bypass surgery have recently been labeled as having nesidioblastosis (4). The recognition of a genetic, as opposed to an embryological, basis for congenital hyperinsulinism evolved from the recognition of familial cases with either dominant or recessive patterns of inheritance (5). Currently, thanks to work by many investigators, eight different loci have been associated with hyperinsulinism: ABCC8, KCNJ11, HADH1, GCK, GLUD1, SLC16A1, UCP2, and HNF4a (Table 1). Mutations of these loci have significant differences in phenotype and inheritance pattern that can be helpful in differentiation and management. The first defects to be discovered, and still the most common genes associated with hyperinsulinism, involve the ABCC8 and KCNJ11 genes that are located together on the short arm of chromosome 11 and encode the two subunits of the -cell ATP-dependent potassium channel: SUR1 and Kir6.2. Recessive mutations of these genes cause a severe form of neonatal hypoglycemia that frequently requires near-total pancreatectomy. In addition, these mutations are responsible for the focal form of congenital hyperinsulinism, caused by isodisomy for a paternally transmitted ABCC8 or KCNJ11 mutation. Dominant missense mutations of these genes have also been discovered that can be associated with either medically controllable or medically unresponsive hyperinsulinism (6, 7). Mutations in HADH1, which encodes SCHAD, a fatty acid oxidation enzyme, cause the only other recessive form of hyperinsulinism (8). Dominant, activating mutations of GCK, which encodes glucokinase, can cause hyperinsulinism that responds poorly to medical therapy. Other dominant forms of hyperinsulinism include activating mutations of GLUD1, which encodes glutamate dehydrogenase, a key step in amino acidstimulated insulin secretion; inactivating mutations of UCP2, a mitochondrial uncoupling protein; activating mutations of SLC16A1 (encodes MCT1), a plasma membrane pyruvate transporter; and inactivating mutations of HNF4a, a nuclear transcription factor also associated with maturity-onset diabetes of the young 1, a form of monogenic diabetes of youth. Phenotypic features that distinguish some of these disorders can be helpful in suggesting the likely gene involved. Large birth weight is common in ABCC8, KCNJ11, GCK, and HNF4a defects. Hyperammonemia is a distinctive feature of GLUD1 mutations [“hyperinsulinism/hyperammonemia (HI/HA) syndrome”]. Protein-sensitive hypoglycemia occurs in HI/HA and SCHAD hyperinsulinism, due to hypersensitivity to leucine stimulation of insulin release. Protein sensitivity also occurs with mutations of ABCC8 and KCNJ11, but it is not due to leucine sensitivity. Hypoglycemia after ISSN Print 0021-972X ISSN Online 1945-7197 Printed in U.S.A. Copyright © 2011 by The Endocrine Society doi: 10.1210/jc.2011-0164 Received January 19, 2011. Accepted January 28, 2011.

IGF-I: Panacea or Poison?

In the area of aging research, the “holy grail” has been to discover the genetic or circulating factors that could predict longevity, with the aim of understanding causation and thus developing strategies that can enable individuals to enjoy a long and healthy life. One of the systems that has received much attention recently has been the GH/IGF-I/insulin system of ligands and receptors. In more primitive organisms such as Caenorhabditis elegans and Drosophila melanogaster, there is solid evidence that decreasing signaling through the insulin/IGF-I receptors leads to longevity (1). In mice, caloric restriction resulting in a similar reduction in insulin/IGF-I receptor signaling has also been associated with longevity. The exact causality remains to be determined, although reductions in reactive oxygen species and other noxious factors have been proposed as possible mediators (2). More specifically, in mammalian species, the role of the IGF system has been studied in the cardiovascular system (CVS) and cancer to determine causality, as in the study by Van Bunderen et al. (3) in this issue of JCEM. The association of the IGF-I system, namely IGF-I and the IGF binding proteins (IGFBPs), and cardiovascular disorders has been studied in older populations. In a large group of Danish men and women, low IGF-I and IGFBP-3 levels were associated with an increased risk of ischemic strokes (4). In a German cohort, higher IGF-I levels in men but lower IGF-I levels in women showed increased odds ratios for coronary artery disease (5). In a separate nested case-control study from Denmark, individuals without ischemic heart disease (IHD) were followed for 15 yr; those with low IGF-I levels and higher IGFBP-3 levels had an increased risk for developing IHD (6). On the other hand, other studies have shown that whereas there is an increased risk of fatal IHD with low IGF-I levels, all-cause mortality was not increased. As described in this issue of JCEM, Van Bunderen et al. (3) studied over 1200 Dutch subjects from Amsterdam that were participating in a Longitudinal Aging Study. All subjects had serum IGF-I measurements, and the endpoints were all-cause mortality, cardiovascular disease (CVD), and nonfatal CVD and cancer. Their results demonstrated a “U-shaped” relationship between IGF-I levels and CVD mortality, i.e. low and high levels were related to the increased CVD mortality. In contrast, there was no relationship between serum IGF-I levels and the other outcomes including cancer. The study therefore supports some previous studies, but not others. Questions remain, however. First, how can we explain the “U-shaped” relationship between IGF-I levels and CVD mortality; and second, because epidemiological studies are purely associations, is there a causal relationship between IGF-I levels and the outcomes? Mouse models have provided insights into the effects of IGF-I and the CVS. Reductions in circulating IGF-I levels were associated with impaired cardiac tissue development, and mice with specific IGF-IR-KO in cardiac muscle fail to demonstrate exercise-induced cardiac hypertrophy (7). Transgenic overexpression of IGF-I in cardiomyocytes leads to cardiomegaly mediated by an increased number of cells in the heart (8) and prevents activation of cell death in the viable myocardium after infarction, limiting ventricular dilation, myocardial loading, and cardiac hypertrophy (9). IGF-I can enhance proliferation of vascular smooth muscle cells (10), and transgenic IGF-I expression in vascular smooth muscle cells affected regeneration after aortic balloon denuvation of the endothelium. Thus, it was concluded that lack of IGF-I is detrimental to cardiovascular homeostasis. However, in mice with reduced circulating IGF-I levels (created by liver-specific IGF-I gene deletion), aging-induced cardiomyocyte mechanical dysfunction was prevented (11). Interestingly, persistent local IGF-I expression is sufficient to initially induce physiological cardiac hypertrophy in which peak aortic outflow velocity is increased relative to controls in the absence of any ISSN Print 0021-972X ISSN Online 1945-7197 Printed in U.S.A. Copyright © 2010 by The Endocrine Society doi: 10.1210/jc.2010-1737 Received July 28, 2010. Accepted August 9, 2010.

Graves’ Disease after Unilateral Riedel’s Thyroiditis

Riedel’s thyroiditis, also termed “invasive fibrous thyroiditis,” is the rarest form of autoimmune thyroiditis and can be associated with systemic fibrotic processes, Hashimoto thyroiditis (1, 2), and Graves’ disease (3). A case of hyperthyroidism followed by spontaneous hypothyroidism and Riedel’s thyroiditis has been reported (4). Two previously reported patients from our institution had invasive fibrous thyroiditis that evolved from antecedent Graves’ disease, as indicated by thyroid dysfunction, bilateral ophthalmopathy, and positive TSH receptor-stimulating autoantibodies (5). We present a new case. In 2004, a 26-yr-old woman presented with a mass in the left thyroid lobe, pain, and respiratory distress. Thyroid function was normal. A tracheostomy and biopsy showed Riedel’s thyroiditis. Therapy with corticosteroids and tamoxifen stabilized the disease. After 1 yr, the tracheostomy was closed. In 2008, her TSH level was less than 0.01 mIU/liter, her free T4 was 4.5 ng/dl (58 pmol/liter; normal, 0.8 –1.8 ng/dl or 10 –23 pmol/ liter), and her serum was strongly positive for TSH receptor antibodies (52%; normal, 16%). The diagnosis of Graves’ hyperthyroidism was made. Her 24-h iodine131 uptake was 33% (upper limit of normal, 29%). She was treated with 19.7 mCi iodine-131. Computed tomography of the neck, performed in 2004 and 2008, showed left lobe thyroid enlargement and compression of the trachea (Fig. 1). Ultrasonography of the thyroid in 2008 (Fig. 2) showed hypervascularity in the areas not affected by Riedel’s thyroiditis; the absence of vascularity in the hypoechoic areas of the left lobe corresponded to Riedel’s involvement, as shown by computed tomography. The present case is of interest because Graves’ disease developed after 3 yr of stability of Riedel’s thyroiditis. In this case, the fibrotic process with extra thyroidal extension was unilateral. Graves’ hyperthyroidism developed in the uninvolved areas of the thyroid. This case and similar reported cases support the notion of autoimmune ISSN Print 0021-972X ISSN Online 1945-7197 Printed in U.S.A. Copyright © 2010 by The Endocrine Society doi: 10.1210/jc.2009-2609 Received December 8, 2009. Accepted April 16, 2010. FIG. 1. Computed tomographic images of the neck. A, Image taken with contrast (2004). Note partial involvement of the left lobe with fibrosis (F), extrathyroidal extension, and significant tracheal narrowing (black arrow) and engulfment of the common carotid artery (white arrow). Also note the uninvolved part of left lobe (L). The right lobe of the thyroid (R) is completely uninvolved. B, Image taken without contrast (2008). Note the stability and partial resolution of the process in the left lobe. (F denotes partially resolved left lobe fibrosis; L, uninvolved part of the left thyroid lobe; R, right lobe. The black arrow shows improved tracheal narrowing.) S P E C I A L F E A T U R E

Hypophosphatemic Osteomalacia after Low-Dose Adefovir Dipivoxil Therapy for Hepatitis B

A 40-yr-old male presented with a 5-month history of bone pain involving both knees, ankles, and several ribs with no antecedent trauma. He had an antalgic gait, tenderness involving the bony margins of both knees, but no synovitis. He had a history of chronic hepatitis B infection, receiving lamivudine at a daily dose of 100 mg for 43 months and adefovir dipivoxil (adefovir) at a daily dose of 10 mg for the past 29 months. He had been receiving tramadol hydrochloride intermittently for pain relief. Investigations revealed a reduced serum phosphate level of 2.0 mg/dl (0.64 mmol/liter), normal serum corrected calcium of 8.8 mg/dl (2.20 mmol/liter), PTH of 39 pg/ml (4.1 pmol/liter), 25-hydroxyvitamin D3 level of 24.4 ng/ml (61 nmol/liter), and 1,25-hydroxyvitamin D level of 57 pmol/liter. Bone-specific alkaline phosphatase was elevated at 85.4 g/liter (normal, 3.7–20 g/liter). The urine deoxypyridinoline/creatinine ratio was elevated at 11 nmol/mmol (normal, 2.3–5.4 nmol/ mmol) with an estimated glomerular filtration rate of 60.1 ml/min. A 24-h urinalysis demonstrated hyperphosphaturia at 1.054 g/d (34 mmol/d) [normal, 0.465– 0.93 g/d (15–30 mmol/d)], hypercalciuria at 580 mg/d (14.5 mmol/d) [normal, 100 –300 mg/d (2.5–7.5 mmol/d)], glycosuria, and massive aminoaciduria. The 24-h creatinine excretion was normal at 1.41 g/d (12.5 mmol/d) [normal, 1.02–2.03 g/d (9 –18 mmol/d)]. Calculated maximal tubular phosphate reabsorption was reduced at 0.3% (normal, 0.8 –1.3%). Magnetic resonance imaging of both knees revealed microfractures across the femoral and tibial metaphyses (Fig. 1). A whole body bone scan showed intense uptake at the subchondral bone of both knees and several bilateral ribs (Fig. 2A). The diagnosis of hypophosphatemic osteomalacia in the context of Fanconi’s syndrome secondary to adefovir therapy was made. Fanconi’s syndrome is a recognized complication of high-dose adefovir therapy when used in the treatment of HIV (1). However, at the time of writing, there were only two other published reports of hypophosphatemic osteomalacia after low-dose adefovir therapy (2, 3). Fifteen weeks after cessation of adefovir and after regular phosphate supplementation, the patient reported significant improvement in his knee and other bony pain. ISSN Print 0021-972X ISSN Online 1945-7197 Printed in U.S.A. Copyright © 2010 by The Endocrine Society doi: 10.1210/jc.2009-2051 Received September 23, 2009. Accepted October 27, 2009. * T.W. and C.M.G. are joint first authors. FIG. 1. Left knee coronal proton-density weighted magnetic resonance image. There are incomplete undisplaced fractures across the femoral and tibial metaphyses, consistent with recent insufficiency fractures. S P E C I A L F E A T U R E