Therapy with Zoledronic Acid, 5 Mg,for a Patient with Paget Disease of Bone

ObjectiveTo describe the effects of an infusion of zoledronic acid in a patient with Paget disease of bone (PD) who had been treated unsuccessfully with several other bisphosphonates.MethodsThe patient’s treatment history is described, and his response to various bisphosphonates, including zoledronic acid, is discussed.ResultsThe patient was a 61-year-old man when a diagnosis of PD was made on the basis of an elevated serum alkaline phosphatase (ALP) level of 391 U/L (reference range, 45 to 135). Pagetic bone changes were noted on bone scan and x-ray examinations. Treatment with etidronate had no effect on ALP levels. This intervention was followed by 2 courses of intravenous therapy with pamidronate, which decreased ALP levels by 57% and 55% without inducing a remission. Subsequent oral treatment with alendronate and then risedronate yielded unsustained biochemical remissions of 6 months each. Most recently, therapy with an infusion of 5 mg of zoledronic acid induced a remission that is thus far 20 months in duration. With this therapy, the patient has experienced no side effects, and he has noted a decrease in bone pain.ConclusionThis case study shows that a patient with PD who received successive treatments with several bisphosphonates with inadequate responses or only brief remissions was more effectively treated with a single 5-mg infusion of zoledronic acid. This patient’s therapeutic responses illustrate the relative efficacy of available bisphosphonates and the potential for longer-lasting remissions with zoledronic acid in patients with PD. (Endocr Pract. 2008;14:607-610)     

A Case of Hypercalcemia Associated with Castleman Disease

ObjectiveTo present a case of hypercalcemia associated with Castleman disease.MethodsThe details of case presentation, evaluation, diagnosis, and treatment are reviewed in a 25-year-old woman with severe hypercalcemia, joint pain, conjunctival injection, and lymphadenopathy.ResultsEndocrinopathies such as primary hyperparathyroidism were ruled out. Infectious and rheumatologic laboratory evaluations revealed normal results. On a whole-body scan, the patient was noted to have diffusely increased osseous uptake in conjunction with increased periarticular uptake, consistent with a metabolic superscan. After extensive evaluation, the patient underwent a right axillary lymph node biopsy and was found to have multicentric Castleman disease. She was treated with high-dose corticosteroids and eventually immunomodulators to help control her disease.ConclusionTo the best of our knowledge, this is the first published case report demonstrating hypercalcemia in association with Castleman disease. The pathologic mechanism is likely bone turnover mediated by cytokines such as interleukin-6. (Endocr Pract. 2010;16:1007-1011)     

Neurologic Complications of Paget Disease of Bone

ObjectiveTo review the epidemiology, evaluation, and management of the neurologic complications associated with Paget disease of bone (PDB).MethodsWe reviewed the English-language medical literature using MEDLINE data sources from 1950 to August 2008 and manually searched cross-references from original articles and reviews. Search terms included “Paget* disease of bone” and “neurologic* complications,” “cranial nerve,” “spinal cord,” or “peripheral nerve.”ResultsSeveral neurologic problems in the central and peripheral nervous systems may complicate PDB. Up to 76% of patients may have some form of neurologic involvement. Neurologic complications can occur in patients with a long history of PDB as well as in patients with previously unrecognized disease. The primary mechanisms of nerve damage in PDB involving the spine are ischemic myelitis and compression due to bone hypertrophy. Evaluation includes determining the serum alkaline phosphatase level and imaging by radiography, bone scintigraphy, computed tomographic scanning, and, for lesions of the central nervous system, magnetic resonance imaging. If a soft-tissue mass is found, biopsy should be considered to exclude the presence of sarcoma. Treatment strategies include calcium, vitamin D, bisphosphonates, and possibly surgical intervention for refractory cases.ConclusionNeurologic sequelae of PDB may be underappreciated. Despite the paucity of data guiding treatment, zoledronic acid is a reasonable first-line therapy. Lack of response to treatment or relapse should prompt diagnostic reevaluation with a heightened suspicion for tumor. (Endocr Pract. 2009;15:158-166)     

Celiac Disease Manifesting as Isolated Hypocalcemia

ObjectiveTo describe a patient who presented with hypocalcemia and hypocalciuria as the initial manifestations of celiac disease, despite a normal vitamin D status.MethodsWe review the diagnostic evaluation, treatment, and biochemical and bone mineral density responses of a patient with asymptomatic celiac disease, which was initially suggested because of a low serum calcium level that became attributable to isolated malabsorption of calcium.ResultsA 36-year-old woman presented with hypocalcemia in the presence of normal serum 25- hydroxyvitamin D and high serum 1,25-dihydroxyvitamin D levels. She had hypocalciuria and secondary hyperparathyroidism that were refractory to pharmacologic calcium and cholecalciferol supplementation. Fecal calcium excretion indicated malabsorption of calcium, and biopsy of the small intestine demonstrated pathologic changes characteristic of celiac disease. Bone mineral density, determined by dual-energy x-ray absorptiometry, was in the osteopenic range at the femoral neck. The initiation of a gluten-free diet resulted in correction of all biochemical abnormalities and a substantial increase in bone mineral density.ConclusionPrimary intestinal malabsorption of calcium without concomitant vitamin D deficiency is possible in celiac disease because of the preferential involvement of the proximal small intestine early in the disease process. Our patient had hypocalcemia caused by celiac disease and values for serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D that were normal and elevated, respectively. Correction was demonstrated after dietary gluten withdrawal. (Endocr Pract. 2004;10:203-207)     

Papillary Carcinoma of a Thyroglossal Duct Cyst in a Patient with Thyroid Hemiagenesis: Effectiveness of Conservative Surgical Treatment

ObjectiveTo describe a case of thyroglossal duct cyst carcinoma that arose in a patient with right thyroid lobe hemiagenesis.MethodsWe present the imaging, physical examination findings, treatment, and clinical course of the study patient.ResultsA 35-year-old woman was evaluated for a neck mass that had been present for 6 months and was slowly growing. She reported a previous diagnosis of right hemithyroid agenesis. The patient’s preoperative workup included ultrasonography of the neck and head and neck T1- and T2-weighted magnetic resonance imaging, which showed right hemithyroid agenesis and a cystic lesion in the median region of the neck below the hyoid bone. Findings from chest x-rays and thyroid function tests were normal. The patient underwent a modified Sistrunk procedure that included removal of the median portion of the hyoid bone. Histologic findings showed a 2.5-cm thyroglossal duct cyst with a 0.6-cm focus of follicular variant of papillary carcinoma with invasion of the cyst wall. Total thyroidectomy was not performed because of the absence of tumoral invasion of the parenchyma around the thyroglossal duct cyst and because the patient was at low risk for aggressive disease. Cervical ultrasonography examinations were performed 6, 12, and 24 months after treatment, and all findings were normal. Presently, the patient is symptom-free after 4 years of follow-up and has no evidence of disease.ConclusionIncidentally discovered, well-differentiated thyroid cancer that is confined to a thyroglossal duct cyst in a patient at low risk for aggressive disease can be adequately treated by a modified Sistrunk procedure that includes the median portion of the hyoid bone. (Endocr Pract. 2008;14:465-469)     

Thymic Hyperplasia and Graves Disease: Management of Anterior Mediastinal Masses in Patients with Graves Disease

ObjectiveTo describe a case of an anterior mediastinal mass (AMM) in a patient with Graves disease.MethodsWe report the clinical presentation, diagnosis, management, and outcome of a 34-year-old man with dyspnea on exertion.ResultsInitial evaluation of the patient’s complaints revealed a large AMM on chest radiography and then chest computed tomography. After occurrence of additional symptoms, the patient was diagnosed as having Graves disease and treated with antithyroid medications. Despite an appropriate biochemical response, he continued to experience severe dyspnea on exertion. A repeated computed tomographic scan 8 weeks after initiation of therapy showed no appreciable decrease in size of the AMM. He elected to undergo thymectomy. An intraoperative phrenic nerve injury resulted in a paralyzed left hemidiaphragm, leaving the patient with considerable difficulties in his career and profoundly decreased exercise tolerance.ConclusionThe differential diagnosis of an AMM includes several malignant lesions with a risk often warranting early surgical excision. In light of the association of benign thymic hyperplasia with Graves disease, thymectomy may be delayed in expectation of thymic regression with medical therapy. The timing of regression is variable, and very few reports exist in the literature. In our current case, the patient opted for thymectomy relatively early and had an unfortunate complication. The lack of clinical evidence regarding management of an enlarged thymus in patients with Graves disease, however, makes management decisions more difficult. (Endocr Pract. 2009;15: 534-539)     

Bisphosphonates and Osteonecrosis of the Jaw: A Retrospective Study

ObjectiveTo assess the prevalence of osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonate therapy and in those who were bisphosphonate naïve.MethodsWe undertook a retrospective review of medical records of patients at the New York Harbor Health Care System from 1999 through 2004. Charts were selected for review if patients had a Current Procedural Terminology (CPT) code suggestive of ONJ or if they had ever received bisphosphonate therapy.ResultsAmong 1,951 medical records reviewed, we identified 2 patients with ONJ who had received bisphos-phonates and 2 patients with ONJ who were bisphospho-nate naïve. Both patients treated with bisphosphonates had multiple myeloma and were receiving monthly infusions. They had initially received pamidronate before treatment was changed to zoledronic acid. In each case, ONJ was precipitated by a routine dental extraction. The prevalence of ONJ in our patient population receiving intravenously administered bisphosphonates was 1 in 71.5. Of the 2 cases of ONJ in bisphosphonate-naïve patients, osteora-dionecrosis was clearly incriminated in 1 patient and potentially the causative factor in the other patient as well. No patients receiving orally administered bisphosphonates had ONJ, nor did this complication occur in any patients receiving parenteral bisphosphonate therapy for disorders such as osteoporosis or Paget’s disease of bone.ConclusionBisphosphonates remain an important option for management of metabolic bone disease and complications of malignant disease. The overall prevalence of ONJ in patients receiving bisphosphonates seems to be very low; however, patients receiving intense parenteral therapy for an underlying malignant condition appear to have a uniquely elevated risk for the development of this complication. A causal relationship between bisphosphonates and ONJ remains to be proved and merits further investigation. (Endocr Pract. 2007;13:232-238)     

Diagnostic Challenge of Pheochromocytoma in a Patient Receiving Levodopa for Parkinson's Disease

ObjectiveThe diagnosis of pheochromocytoma in patients receiving levodopa is challenging because the standard diagnostic biochemical tests may be confounded by dopaminergic therapy. We aim to showcase our experience with the diagnosis of pheochromocytoma in a patient with a known case of Parkinson’s disease who was receiving levodopa.MethodsWe present the case of an elderly male who was diagnosed as having pheochromocytoma while receiving dopaminergic therapy for Parkinson’s disease.ResultsA 75-year-old man presented with vague abdominal symptoms. Computed tomography revealed a 3.5 × 3.2 cm right adrenal mass with a well-defined margin. As revealed by magnetic resonance imaging, the mass was hypointense on T1-weighted and hyperintense on T2-weighted images. Biochemical tests revealed elevated levels of urinary dopamine, which was considered to be caused by levodopa therapy. However, concurrent elevation in urinary adrenaline and his metanephrine and vanillylmandelic acid levels suggested an underlying case of pheochromocytoma. An ¹²³I-metaiodobenzylguanidine (¹²³I-MIBG) scintigraphy scan performed under levodopa therapy showed positive tracer uptake in the right adrenal gland. Histopathology of the adrenalectomy specimen confirmed the diagnosis of pheochromocytoma.ConclusionOur experience with the present case indicates that although the standard diagnostic biochemical tests for pheochromocytoma may be confounded by dopaminergic therapy, ¹²³I-MIBG scintigraphy has diagnostic value for confirming pheochromocytoma even in patients receiving dopaminergic therapy. (Endocr Pract. 2014;20:e112-e115)     

Segmentation of organs-at-risk in cervical cancer CT images with a convolutional neural network

PurposeWe introduced and evaluated an end-to-end organs-at-risk (OARs) segmentation model that can provide accurate and consistent OARs segmentation results in much less time.MethodsWe collected 105 patients’ Computed Tomography (CT) scans that diagnosed locally advanced cervical cancer and treated with radiotherapy in one hospital. Seven organs, including the bladder, bone marrow, left femoral head, right femoral head, rectum, small intestine and spinal cord were defined as OARs. The annotated contours of the OARs previously delineated manually by the patient’s radiotherapy oncologist and confirmed by the professional committee consisted of eight experienced oncologists before the radiotherapy were used as the ground truth masks. A multi-class segmentation model based on U-Net was designed to fulfil the OARs segmentation task. The Dice Similarity Coefficient (DSC) and 95th Hausdorff Distance (HD) are used as quantitative evaluation metrics to evaluate the proposed method.ResultsThe mean DSC values of the proposed method are 0.924, 0.854, 0.906, 0.900, 0.791, 0.833 and 0.827 for the bladder, bone marrow, femoral head left, femoral head right, rectum, small intestine, and spinal cord, respectively. The mean HD values are 5.098, 1.993, 1.390, 1.435, 5.949, 5.281 and 3.269 for the above OARs respectively.ConclusionsOur proposed method can help reduce the inter-observer and intra-observer variability of manual OARs delineation and lessen oncologists’ efforts. The experimental results demonstrate that our model outperforms the benchmark U-Net model and the oncologists’ evaluations show that the segmentation results are highly acceptable to be used in radiation therapy planning.     

Multiple Disease Associations in Autoimmune Polyglandular Syndrome Type II

ObjectiveAutoimmune polyglandular syndrome type II (APS II) is characterized by adrenal insufficiency (Addison’s disease), autoimmune thyroid disease, and/or type 1 diabetes mellitus (DM1). Multiple other autoimmune diseases have been associated with APS II. Here we report a case of a patient with APS II who over the course of 10 years developed Addison’s disease, hypothyroidism, DM1, Hashimoto’s encephalopathy, vitiligo, celiac disease, seronegative arthritis, and ulcerative colitis. This is a particularly aggressive course of APS II, and this combination of autoimmune diseases has not been previously reported.MethodsA 25-year-old female with a history of ulcerative colitis (UC), celiac disease, and DM1 presented to our institution with mental status changes. She was diagnosed with Hashimoto’s encephalopathy and treated with high-dose steroids and intravenous immunoglobulin (IVIG). She recovered well from her encephalopathy but her posthospitalization course was complicated due to the development of Addison’s disease, vitiligo, seronegative arthritis, and hypothyroidism.ResultsThe current understanding of APS II and its autoimmune disease associations are briefly summarized.Submitted for publication April 10, 2014 Accepted for publication July 10, 2014 The association of UC and Hashimoto’s encephalopathy with APS II is novel and discussed in detail.ConclusionA case of a patient with APS II with a dramatic development of 8 autoimmune diseases over 10 years is described. The novel APS II developments of Hashimoto’s encephalopathy and UC are discussed. This case highlights the potential complexity and severity of the clinical course of APS II. (Endocr Pract. 2014;20:e250-e255)     

Nonischemic Cardiomyopathy Associated with Autoimmune Polyglandular Syndrome Type II

ObjectiveTo report a case of nonischemic cardiomyopathy associated with autoimmune polyglandular syndrome type II (APS-II).MethodsWe describe our patient’s clinical features, evaluation, and outcome. In addition, a literature review of cardiomyopathy associated with polyendocrinopathy syndromes is presented.ResultsThe component disorders of APS-II are Addison’s disease in combination with either autoimmune thyroid disease or type 1 (insulin-dependent) diabetes. Although numerous other autoimmune conditions have been reported in conjunction with APS-II, cardiomyopathy has not been previously described as part of this syndrome. The current patient was a 32-year-old man who, during a 5-year period, was diagnosed as having type 1 diabetes mellitus, Crohn’s disease, and Addison’s disease. In 2001, he presented with severe heart failure that progressed rapidly and eventually necessitated cardiac transplantation.ConclusionAlthough autoimmune cardiomyopathy has been associated with other autoimmune disorders, to our knowledge this is the first reported case of cardiomyopathy in association with an autoimmune polyglandular syndrome. Patients with this syndrome should undergo clinical evaluation for heart failure. (Endocr Pract. 2007;13:59-62)     

Atypical Femoral Fracture in an Osteogenesis Imperfecta Patient Successfully Treated with Teriparatide

ObjectiveWe report a case of a successfully healed atypical femoral fracture (AFF) following treatment with teriparatide in a patient with osteogenesis imperfecta (OI). To our knowledge, no successful treatment of AFFs with teriparatide in this subpopulation has ever been described.MethodsThis is a case report of an AFF treated with teriparatide.ResultsThe patient was treated with hormone replacement therapy for 18 years and bisphosphonates for 9 years before suffering a spontaneous AFF in the form of a dislocated noncomminute transverse fracture of the right femoral shaft, and an open reduction and internal fixation (ORIF) with a T2 Femoral Nail was done. Due to nonunion and another fracture distal to the nail, the patient was reoperated on with exchange ORIF and off-label treatment with teriparatide 20 μg/day was started. An X-ray 1 month later showed early signs of fracture healing. A subsequent X-ray 6 months after the last operation showed a solid healing of both right femoral fractures.ConclusionThis is a rare case that highly suggests a potential fracture healing effect of teriparatide treatment and highlights a potential significant practical therapeutic consideration in relation to the management of AFF with delayed healing. (Endocr Pract. 2014;20:e187-e190)     

Pituitary Macroadenoma in a Patient with Poems Syndrome in Conjunction with Castleman Disease: First Report of a Case and Review of Related Literature

ObjectiveTo describe the first reported case of a patient with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) in conjunction with the endocrinologic manifestation of panhypopituitarism due to a large clinically nonfunctioning pituitary adenoma.MethodsWe present the clinical, laboratory, and radiologic details of the case and review the relevant updated literature.ResultsA 48-year-old man with hypopituitarism and progressive polyneuropathy presented to an outside hospital with confusion and diaphoresis. He also had diffuse lymphadenopathy, monoclonal gammopathy, and skin lesions consistent with a diagnosis of POEMS syndrome. Cytopathologic study of a lymph node showed findings consistent with Castleman disease. A large suprasellar mass was found to be the cause of the hypopituitarism.ConclusionPOEMS syndrome is a rare paraneoplastic condition, commonly associated with Castleman disease, that manifests with progressive distal polyneuropathy and a monoclonal plasma cell disorder, often accompanied by endocrinopathy, organomegaly, skin changes, sclerotic bone lesions, ascites, erythrocytosis, and thrombocytosis. Our current patient had all 5 classic features of POEMS syndrome along with some diagnostic elements of Castleman disease, sclerotic bone lesions, and thrombocytosis. To our knowledge, this is the first known reported case of a patient whose endocrinologic manifestation of POEMS syndrome was panhypopituitarism attributable to a large clinically nonfunctioning pituitary adenoma. (Endocr Pract. 2010;16:97-101)     

Tall-Cell Variant Papillary Thyroid Carcinoma Arising from Struma Ovarll

ObjectiveTo present a case of tall-cell variant (TCV) papillary thyroid carcinoma (PTC) arising from Struma ovarii (SO) and to discuss special considerations in the management of this patient.MethodsThe clinical presentation and relevant pathologic features of a patient with PTC-TCV developing from SO are described, and a concise review of literature regarding this topic is also presented.ResultsA 36-year-old woman with a history of stable right ovarian dermoid cyst presented with amenorrhea and was found to have a significantly enlarged right ovary with multiple cysts. Following laparoscopic cystectomy, pathology revealed mature cystic teratoma (SO) with associated PTC-TCV. Based on this finding, she underwent right salpingo-oophorectomy, right pelvic lymph node dissection, and partial omentectomy. Pathology was negative for extra-ovarian disease, and her tumor was staged as pT1pN0M0. Total thyroidectomy was performed in preparation for radioactive iodine (RAI) therapy. A diagnostic iodine-131 (I-131) scan showed residual uptake in the neck with faint uptake in the lower left quadrant of the abdomen and was followed by therapy with 90 mCi of I-131. The patient had an unremarkable course with no clinical or biochemical evidence of disease recurrence to date.ConclusionsThis is to our knowledge the first reported case of TCV-PTC arising from SO. The presence of this aggressive variant of PTC factored into our decision to proceed with thyroidectomy and I-131 ablation, despite the lack of conclusive evidence in the literature. Recent discoveries on the natural history of thyroid-derived TCV-PTC were critical in choosing the appropriate management for this patient’s disease. (Endocr Pract. 2014;20:e24-e27)     

Spurious Case of XX Maleness in A Patient With A History of Wiskott-Aldrich Syndrome

ObjectiveTo alert endocrinologists about the potential for karyotype confusion in patients who have undergone bone marrow transplantation.MethodsClinical, laboratory, and imaging data are reported on a young adult male patient who initially presented because of concerns about short stature.ResultsAn 18-year-old fully virilized male patient with a history of Wiskott-Aldrich syndrome had undergone successful bone marrow transplantation in infancy. The donor was his older sister. Many years later, he underwent evaluation because of short stature and was found to have a 46, XX karyotype. This unexpected finding led to several costly laboratory and imaging studies, as well as a new diagnosis of a disorder of sex development. The patient was referred to our medical center for further evaluation of XX sex reversal. A skin biopsy was eventually performed, which revealed a 46, XY karyotype. This unusual case highlights the fact that a peripheral blood specimen from bone marrow transplant recipients reflects the genetic makeup of the bone marrow donor.ConclusionAlthough the cytogenetic changes that occur in recipients of bone marrow transplants are well known to hematologists and oncologists, they are not commonly recognized by other health care providers. Increased awareness of this potential situation in long-term survivors of bone marrow transplantation is needed. (Endocr Pract. 2011;17:e1-e3)     

Cushing’s Disease and Pregnancy: Case Report and Literature Review

ObjectiveTo describe a patient with untreated Cushing’s disease who had 2 spontaneous pregnancies that resulted in healthy babies on both occasions.MethodsWe present a case report with clinical, laboratory, and imaging data and discuss the literature pertaining to pregnancy in patients with Cushing’s syndrome.ResultsA 28-year-old woman came to our endocrinology clinic with a 1-year history of symptoms and signs of Cushing’s syndrome. An elevated 24-hour urinary cortisol excretion and an unsuppressed 1-mg overnight dexamethasone test confirmed the diagnosis. On her next visit, she reported a confirmed pregnancy, which ultimately resulted in the birth of a normal child. Further work-up subsequently showed 2 elevated 24-hour urinary cortisol values, loss of diurnal variation, and an elevated corticotropin level. There was lack of suppression on low-dose and high-dose overnight dexamethasone suppression tests. Magnetic resonance imaging of the pituitary showed normal findings. Inferior petrosal sinus sampling was recommended, but she declined the procedure. The patient returned 3 years later for reevaluation, at which time she reported the birth of another healthy child by cesarean delivery 10 months previously. There were no reported maternal or fetal complications. Examination at this visit revealed buccal pigmentation and proximal myopathy. Investigations showed increased 24-hour urinary cortisol excretion and serum corticotropin levels. Repeated magnetic resonance imaging disclosed a microadenoma on the right side of the pituitary. Unstimulated inferior petrosal sinus sampling showed a gradient to the right; thus, the presence of pituitary-dependent Cushing’s disease was confirmed.ConclusionOur case demonstrates that patients with pituitary-dependent Cushing’s disease are more likely to have spontaneous pregnancies with favorable outcomes than are patients with Cushing’s syndrome due to other causes. Our patient, despite having Cushing’s disease for more than 7 years, had 2 uneventful pregnancies that produced normal healthy children, without exacerbation of her disease during pregnancy. (Endocr Pract. 2007;13: 296-299)     

Ascending aorta to common femoral artery bypass: An unusual but successful method for revascularization of the lower extremity: Report of case

A 61-year-old woman presented with symptoms and signs of severe ischemia in the left leg. Rest pain was present, and the leg was pulseless. The patient reported a complicated history of repeated strokes. Complete evaluation revealed mitral valve disease, atrial fibrillation, and occlusion of the distal aorta and left iliac and femoral arteries. Corrective surgery consisted of mitral valve replacement and concomitant ascending aorta to left common femoral and femoral graft to right femoral artery bypass. Recovery was uneventful. The cardiac and vascular prostheses functioned well and provided complete relief of ischemia.     

Macromelia Masquerading as an Acromegaloid Syndrome in an Adult with Klippel-Trénaunay Syndrome

ObjectiveTo describe a case of Klippel-Trénaunay syndrome in an adult patient with symmetric macromelia suggestive of an acromegaloid syndrome.MethodsWe report clinical and laboratory data that were extracted from the medical records of the study patient. We also survey the relevant reports identified through a MEDLINE search of the English-language literature published between January 1, 1996, and June 2, 2007, using the phrase, Klippel-Trénaunay syndrome.ResultsA 28-year-old man was admitted to the hospital for weeping lymphedema of the left lower extremity. He had pronounced symmetric hypertrophy of all distal extremities, port-wine stains on his right neck, and varicosities on his left groin. The patient’s insulinlike growth factor 1 concentration was 92 ng/mL (reference range, 117-329 ng/mL), which did not support the diagnosis of acromegaly. Klippel-Trénaunay syndrome is a rare congenital condition that belongs to a family of disorders characterized by tissue overgrowth. Classically, the syndrome presents as a triad of vascular malformations, cutaneous hemangiomas, and bone or soft-tissue hypertrophy usually affecting one extremity. The tissue hypertrophy in this syndrome is typically localized and asymmetric.ConclusionThe recognition that the tissue hypertrophy in Klippel-Trénaunay syndrome can occur symmetrically will help avoid unnecessary and extensive workup for acromegaly. (Endocr Pract. 2008;14:109-111)     

Iatrogenic Osteoporosis,Bilateral Hip Osteonecrosis,and Secondary Adrenal Suppression in an Hiv-Infected Man Receiving Inhaled Corticosteroids and Ritonavir-Boosted Highly Active Antiretroviral Therapy

ObjectiveTo report the first case of severe osteoporosis associated with a vertebral pathologic fracture and osteonecrosis of femoral heads in an HIV-infected man receiving inhaled corticosteroids and ritonavir-boosted antiretroviral therapy.MethodsWe describe an HIV-infected man with severe osteoporosis, bilateral hip osteonecrosis, and secondary adrenal suppression, including detailed clinical, laboratory, and radiographic data, and review the related literature.ResultsA 60-year-old man with a 15-year history of HIV infection and a medical history of long-standing bronchiectasis treated with inhaled corticosteroids and hypogonadism treated with testosterone was referred to the endocrinology clinic after experiencing an osteoporotic vertebral fracture. He was taking ritonavir-boosted antiretroviral therapy. Osteonecrosis of both hips was also diagnosed, which required total hip replacement therapy.Laboratory evaluation revealed adrenal insufficiency due to increased effect of exogenous inhaled steroids and no other secondary causes of osteoporosis. A bone densitometry study showed osteoporosis of both hips and the lumbar spine. He was treated with intravenous pamidronate. During treatment, he developed bilateral femoral fractures after minor trauma.ConclusionsGiven the potential for increased serum levels of inhaled corticosteroids in patients taking ritonavirboosted highly active antiretroviral therapy, attention must be paid to the risk of bone loss in HIV-infected patients taking inhaled corticosteroids. Prescribing calcium and vitamin D supplementation and considering early osteoporosis screening are reasonable measures for this patient population. Interaction between inhaled corticosteroids and ritonavir may increase risk of hypothalamus-pituitary-adrenal axis suppression. (Endocr Pract. 2011;17:74-78)     

Valosin-containing protein (VCP): structure,functions, and implications in neurodegenerative diseases

Valosin-containing protein (VCP) is a hexameric protein belonging to the type II AAA+ (ATPases Associated with diverse cellular Activities) protein family. VCP governs multiple cellular processes and its diverse functions are determined by its interaction with a wide variety of partners and cofactors. Recently, mutations in VCP were suggested to cause inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia, amyotrophic lateral sclerosis, and Huntington’s disease. However, the pathogenic mechanisms of VCP mutations in these diseases are still largely unknown. In this review, we summarize the structure and cellular functions of VCP, especially focusing on apoptosis and two major cellular degradation pathways, the ubiquitin–proteasome system and autophagy. We also list the representative VCP mutations and discuss their potential association with neurodegenerative diseases.