Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Utility of rituximab treatment for exophthalmos, myxedema, and osteoarthropathy syndrome resistant to corticosteroids due to Graves’ disease: a case report

Abstract Background Exophthalmos, myxedema, and osteoarthropathy syndrome is a very rare condition that is associated with Graves’ disease. The presence of dermopathy and the involvement of joint/bone tissues indicate that it seems to be related with the severity of the autoimmune process. Owing to its low incidence, there is a lack of information regarding its treatment and clinical follow-up. Some cases improved after use of high doses of steroids; however, some patients do not respond to this treatment. Recently, the effectiveness of rituximab for treatment of Graves’ ophthalmopathy resistant to corticosteroids has been demonstrated. However, it has never been used for the treatment of exophthalmos, myxedema, and osteoarthropathy syndrome (particularly for the treatment of osteoarticular manifestations). Case presentation We present the case of a 54-year-old Mexican woman previously treated for Graves’ disease who developed post-iodine hypothyroidism and exophthalmos, myxedema, and osteoarthropathy that did not improve after high doses of steroids (intravenous and oral). Her exophthalmos, myxedema, and osteoarthropathy syndrome symptoms improved as early as 6 months after treatment with rituximab. Conclusion Exophthalmos, myxedema, and osteoarthropathy syndrome is a non-classical presentation of Graves’ disease, whose clinical manifestations could improve after treatment with rituximab, particularly in those patients with lack of response to high doses of corticosteroids

Hiperparatiroidismo terciario como presentación de enfermedad ósea metabólica en trasplante renal: un reto diagnóstico-terapéutico. Presentación de un caso clínico

Tertiary hyperparathyroidism (THPT) is characterized by hypercalcemia and autonomous hyperparathyroidism in the context of persistent secondary hyperparathyroidism (SHPT). THPT is related with extraskeletal calcifications, calciphylaxis, fractures, bone pain, progressive loss of bone mineral density, nephrocalcinosis, lithiasis, kidney allograft dysfunction and rejection, neuropsychiatric alterations, cardiovascular disease, and high morbimortality. Subtotal parathyroidectomy is the gold standard for treatment, with high cure rates. We described a case of THPT as a manifestation of Bone Mineral Metabolism Disease after a successful kidney transplant, with an insidious evolution and severe bone damage, with an adequate response to subtotal parathyroidectomy. We evidenced that early diagnosis and treatment of THPT in kidney transplant recipients is essential to the diminution of comorbidities, the improvement of prognosis and the optimization of health resources.El hiperparatiroidismo terciario se caracteriza por hipercalcemia e hiperparatiroidismo autónomo en el contexto de hiperparatiroidismo secundario persistente. El HPT3 se relaciona con calcificaciones extraesqueléticas o calcifilaxis, fracturas, dolor óseo, pérdida progresiva de la densidad mineral ósea, nefrocalcinosis, litiasis, disfunción o rechazo del aloinjerto, alteraciones neuropsiquiátricas, enfermedad cardiovascular y aumento de la morbimortalidad. La paratiroidectomía subtotal es el tratamiento de elección, con altas tasas de curación. Presentamos el caso de una paciente con hiperparatiroidismo terciario como enfermedad ósea metabólica después de un trasplante renal exitoso, con evolución insidiosa y daño óseo severo, con adecuada respuesta al tratamiento oportuno con paratiroidectomía subtotal. El diagnóstico y tratamiento oportuno del hiperparatiroidismo terciario en el paciente con trasplante renal es fundamental para disminuir la incidencia de comorbilidades, mejorar el pronóstico del paciente y optimizar recursos de salud

Cardiovascular Risk and Metabolic Syndrome Characteristics in Patients with Nonfunctional Pituitary Macroadenoma

Context. An elevated incidence of type 2 diabetes and cardiovascular disease (CVD) has been reported in patients with nonfunctional pituitary macroadenoma (NFPMA). There is no information about metabolic syndrome and cardiovascular risk in patients with NFPMA in our population. Objective. Analyze the metabolic syndrome (MetS) components and estimate cardiovascular risk in patients with NFPMA. Design and Setting. Retrospective study, at the tertiary care center. Patients and Methods. 71 patients with NFPMA treated according to a preestablished multimodal protocol. Main Outcome Measures. Prevalence of diabetes, hypertension, high cholesterol, obesity, and cardiovascular risk and its relationship with the clinical and biochemical characteristics. Results. The prevalence of diabetes, hypertension, high cholesterol, and obesity at diagnosis was 30%, 27%, 48%, and 85% and did not change upon the last visit. The prevalence of MetS changes from 54 to 48% (p=0.001). NFPMA patients showed a significant increase risk for high total cholesterol (SMR 1.68, 95% CI 1.28–2.17, p=0.001) and diabetes (SMR 3.19, 95% CI 2.19–4.49, p=0.01). According to Globorisk, the male gender was an evidence of high CVD before (81% versus 18%, p=0.01) and after (72% versus 28%, p=0.01) multimodal treatment. Conclusion. A high prevalence of cardiovascular and metabolic disease and a high cardiovascular risk were evidenced in patients with NFPMA, especially in men. Risk factors such as the personal history of hypertension and dyslipidemia could explain the foregoing, so the control and treatment of metabolic parameters and cardiovascular risk should be an integral part of the follow-up of these patients

Symptomatic Primary Hyperparathyroidism as a Risk Factor for Differentiated Thyroid Cancer

Background. The primary hyperparathyroidism (PHPT) is a common disease for the endocrinologist. The concomitant thyroid disease and differentiated thyroid cancer (DTC) appear to be more frequent in patients with PHPT than in the general population. The aim of this study was to characterize patients with symptomatic PHPT with and without DTC and analyze frequency and risk factors. Methods. We consecutively studied patients with symptomatic PHPT diagnosed and treated at our center between 2013 and 2015. Patients with subclinical and syndromic forms of PHPT were excluded. Clinical and biochemical characteristics of patients with and without DTC were compared and risk factors were determined. All patients were studied with thyroid ultrasound and thyroid gammagraphy with TC-MIBI. Two expert surgeons performed all the surgical procedures. Results. In 59 patients included, we found 12 cases of PTC (20.3%). The final histopathological report of the PTC was 7 cases of follicular variant, 2 cases of oncocytic variant, 2 cases of classic variant, and 1 case of columnar cells variant of PTC. Patients with thyroid cancer were older than patients without thyroid cancer (62 ± 9.5 versus 52 ± 15.8, p = 0.03). Higher preoperative levels of iPTH were associated with PTC (p=0.03) [OR 5.16 (95% CI: 1.08-24.7)]. Conclusion. PTC is frequent in patients with symptomatic PHPT. Thyroid nodules in patients with symptomatic PHPT must be studied before parathyroidectomy. In symptomatic PHPT, higher level concentration of parathormone (PTH) was associated with higher risk of DTC

Quality of life evaluation in Mexican patients with severe obesity before and after bariatric surgery

Introduction: In Mexico, neither the 36-item Short Form Health Survey (SF-36) nor the Bariatric Analysis and Reporting Outcome System (BAROS) instruments have been used to assess quality of life (QoL) before and after bariatric surgery (BS). Objective: To describe changes in QoL using the SF-36 and BAROS questionnaires in patients with severe obesity before and after BS. Methods: Clinical and anthropometric data of patients undergoing bariatric surgery between 2015 and 2016 were collected. Statistical significance was considered with a p-value < 0.05. Results: 230 patients were analyzed, 98 before and 132 and after BS; most were females (81 %). Initial body mass index was 48 kg/m2 (44-53). SF-36-measured QoL showed an increase in the physical component score from 43 to 54.2 points (p < 0.001), and in the mental component, from 53.3 to 56.6 points after BS. With BAROS, 98.5 % showed good to excellent QoL results within the first three months after BS. Conclusion: When measured with the SF-36 and BAROS questionnaires, QoL of Mexican patients with severe obesity was found to improve after BS

Biochemical Characteristics of Bone Mineral Metabolism before and throughout the First Year after Kidney Transplantation, Persistent Hyperparathyroidism, and Risk Factors in a Latin Population

Bone mineral metabolism disease, which included persistent hyperparathyroidism, is common after successful kidney transplantation (KT) and is related with negative outcomes in kidney transplant recipients. There is a lack of information about bone mineral metabolism, persistent hyperparathyroidism, and its risk factors in Latin kidney transplant recipients (KTRs). Material and Methods: A retrospective study was conducted in 74 patients aged 18–50 years with evolution of 12 months after KT and estimated glomerular filtration rate (eGFR) >60 ml/min; biochemical data of bone mineral metabolism before and at 1, 3, 6, and 12 months of KT were registered. Results. Age was 33 (IQR 27–37) years; 54% (n = 40) were men. Before KT, all patients had hyperparathyroidism, 40% (n = 30) hypocalcemia, 86% (n = 64) hyperphosphatemia, and 42% (n = 31) hyperphosphatasemia. After KT, an increase of calcium and a diminution of PTH, phosphorus, and alkaline phosphatase were corroborated (p=0.001). All patients had hypovitaminosis D (deficiency: 91% (n = 67); insufficiency: 9% (n = 7)); 40% (n = 30) had persistent hyperparathyroidism at 12 months. Hyperphosphatasemia before KT (OR = 4.17 (95% CI: 1.21–14.44); p=0.04), hyperparathyroidism at 6 months (OR = 1.84 (95% CI; 1.67–2.06); p=0.02), hypovitaminosis D at 6 months (OR = 3.94 (95% CI: 1.86–17.9); p=0.01), and hyperphosphatasemia at 6 months (OR = 1.47 (95% CI: 1.07–2.86); p=0.03) were risk factors for persistent hyperparathyroidism at 12 months after KT. Conclusion. Persistent hyperparathyroidism at 6 months, hypovitaminosis D, and hyperphosphatasemia are risk factors for persistent hyperparathyroidism at 1 year of KT in Latin population

Persistent Primary Hyperparathyroidism, Severe Vitamin D Deficiency, and Multiple Pathological Fractures

Persistent primary hyperparathyroidism (PHPT) refers to the sustained hypercalcemia state detected within the first six months following parathyroidectomy. When it coexists with severe vitamin D deficiency, the effects on bone can be devastating. We report the case of a 56-year-old woman who was sent to this center because of persistent hyperparathyroidism. Her disease had over 3 years of evolution with nephrolithiasis and hip fracture. Parathyroidectomy was performed in her local unit; however, she continued with hypercalcemia, bone pain, and pathological fractures. On admission, the patient was bedridden with multiple deformations by fractures in thoracic and pelvic members. Blood pressure was 100/80, heart rate was 86 per minute, and body mass index was 19 kg/m2. Calcium was 14 mg/dL, parathormone 1648 pg/mL, phosphorus 2.3 mg/dL, creatinine 2.4 mg/dL, urea 59 mg/dL, alkaline phosphatase 1580 U/L, and vitamin D 4 ng/mL. She received parenteral treatment of hypercalcemia and replenishment of vitamin D. The second surgical exploration was radioguided by gamma probe. A retroesophageal adenoma of 4 cm was resected. Conclusion. Persistent hyperparathyroidism with severe vitamin D deficiency can cause catastrophic skeletal bone softening and fractures