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1.
J Pediatr Endocrinol Metab ; 33(1): 139-145, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31811804

RESUMO

Background The objective of this study was to evaluate the age at onset and frequency of individual pituitary hormone deficiencies (PHDs) in optic nerve hypoplasia (ONH). Methods We performed a retrospective chart review of patients ≤21 years of age evaluated between 1996 and 2014. Patients were included if they had: (1) ONH diagnosed by an ophthalmologist and/or magnetic resonance imaging (MRI), (2) documentation of pituitary hormone function on at least two separate occasions and (3) at least one PHD documented or a midline abnormality of the brain on MRI. Results Thirty-two patients (18 females, 14 males) were included (median age, 8 years [range, 1.1-21.0 years]). All patients had ONH (bilateral, n = 31; unilateral, n = 1) and at least one midline abnormality of the brain. At least one PHD was present in 75% of patients (n = 24). The remaining 25% of patients (n = 8) did not develop any PHD at least until the last follow-up (<2-8.6 years of follow-up), despite the presence of ONH and a midline abnormality of the brain. The median age (years) at diagnosis of antidiuretic hormone (ADH), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH) and growth hormone (GH) deficiencies was 0.5, 0.6, 0.7 and 1.6, respectively. Twenty-three percent of all PHDs were identified during the neonatal period, 56% by 12 months and 72% by 36 months of age. The latest age at diagnosis of GH, ACTH and TSH deficiencies was 9.6, 9.9 and 12.6 years, respectively. Conclusions The majority of the PHDs in ONH develop within the first 3 years of life. We propose evaluation for endocrinopathies at the time of diagnosis of ONH, with repeat assessment for new deficiencies every 3-4 months until age 3 years and at least semi-annually until growth and puberty are complete.

2.
Bone ; 122: 76-81, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30772600

RESUMO

The Rickets Severity Score (RSS) was used to evaluate X-linked hypophosphatemic rickets (XLH), a genetic disorder mediated by increased circulating FGF23. The reliability of the RSS was assessed using data from a randomized, phase 2 clinical trial that evaluated the effects of burosumab, a fully human anti-FGF23 monoclonal antibody, in 52 children with XLH ages 5 to 12 years. Bilateral knee and wrist radiographs were obtained at baseline, week 40, and week 64. We evaluated the relationships of the RSS to the Radiographic Global Impression of Change (RGI-C), serum alkaline phosphatase (ALP), height Z-score, 6-minute walk test (6MWT) percent predicted, and the Pediatric Orthopedic Society of North America Pediatric Outcomes Data Collection Instrument (POSNA-PODCI). The RSS showed moderate-to-substantial inter-rater reliability (weighted kappa, 0.45-0.65; Pearson correlation coefficient (r), 0.83-0.89) and substantial intra-rater reliability (weighted Kappa, 0.66; r = 0.91). Baseline RSS correlated with serum ALP (r = 0.47). Baseline RSS identified two subgroups (higher [RSS ≥1.5] and lower RSS [RSS <1.5]) that discriminated between subjects with greater and lesser rachitic disease. Higher RSS was associated with more severe clinical features, including impaired growth (Z-score, -2.12 vs -1.44) and walking ability (6MWT percent predicted, 77% vs 86%), more severe self-reported pain (29.9 [more severe] vs 45.3 [less severe]) and less physical function (29.6 [more severe] vs 40.9 [less severe]). During burosumab treatment, greater reductions in RSS corresponded to higher RGI-C global scores (r = -0.65). Improvements in RSS correlated with decreased serum ALP (r = 0.47). These results show the reliability of the RSS in XLH, and demonstrate that higher RSS values are associated with greater biochemical, clinical, and functional impairments in children with XLH.

3.
J Eval Clin Pract ; 25(2): 300-305, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30378218

RESUMO

RATIONALE, AIMS, AND OBJECTIVES: Waist circumference (WC) and waist-to-height ratio (WHtR) are superior surrogate markers of central obesity than body mass index. However, WC is not measured routinely in paediatric clinics. The objective of this study was to implement measurement of WC during routine assessment of children in an ambulatory outpatient clinic setting and subsequent dissemination of cardiometabolic risk counselling in children with central obesity (defined as WHtR ≥0.5). METHOD: Prospective cohort of patients aged 6 to 20 years. Study period was divided into three phases: baseline (3 months), process improvement (2 months), and implementation (6 months). Define-Measure-Analyse-Improve-Control (DMAIC) strategy was applied. Measurement of WC was implemented as a component of the physical examination in patients. Outcome measures were (1) improvement in frequency of WC measurement and (2) utilization of WHtR in cardiometabolic risk counselling. RESULTS: Waist circumference was not measured in any patient during baseline phase (n = 551). During process improvement phase, of the total 347 patients, WC was measured in 35% vs target of 30%. In the implementation phase, WC was measured in 37% patients (365 out of 964). Of these 365 patients, 175 (48%) had elevated WHtR, and 73% of them (n = 128) were counselled about their increased cardiometabolic risk. CONCLUSIONS: Application of an evidence-based DMAIC protocol led to significant improvement in assessment for central obesity in an ambulatory clinic practice and appropriate counselling regarding cardiometabolic risk reduction in children and adolescents with central obesity over an 8-month period. Meticulous planning and execution, frequent reinforcement, and integrating feedback from the involved multi-disciplinary team were important factors in successful implementation of this quality improvement project.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Aconselhamento , Razão Cintura-Estatura , Adolescente , Criança , Estudos Transversais , Humanos , Síndrome Metabólica , Pediatria , Medicina Preventiva , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Adulto Jovem
4.
Horm Res Paediatr ; 90(5): 291-298, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30497080

RESUMO

BACKGROUND: Previous studies suggest normal mineral status in children receiving elemental formula. However, a recent multicenter survey described 51 children who developed hypophosphatemia and bone disease while receiving elemental formula. Our aim is to determine the prevalence of metabolic bone disease in children receiving extensively hydrolyzed or amino acid-based formula. METHODS: We established a retrospective cohort using an institutional database of tube-fed children. We defined a "confirmed case" as a child with biochemical and radiographic evidence of bone disease (rickets and/or low-trauma fractures). We defined a "suspected case" as a child who had biochemical evidence and/or radiographic evidence of bone disease but with incomplete data during the review period. RESULTS: A total of 102 tube-fed children receiving elemental or semi-elemental formula were identified. The four elemental and semi-elemental formulas evaluated were Neocate®, EleCare®, Pregestimil®, and Alimentum®. Not all children had complete monitoring data performed during the review period. Of the children receiving Neocate who had monitoring data (46%), 23% developed hypophosphatemia and radiographic abnormalities (fractures or rickets), which resolved with phosphorus supplementation and/or change in the formula brand. CONCLUSIONS: We estimate that at least 11% and up to 23% of all tube-fed children receiving Neocate develop metabolic bone disease. Based upon the estimated prevalence, we recommend cautious use of this formula with monitoring for evolving bone disease in this population.


Assuntos
Doenças Ósseas Metabólicas/epidemiologia , Fórmulas Infantis , Fenômenos Fisiológicos da Nutrição do Lactente , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Prevalência , Estudos Retrospectivos
5.
Clin Endocrinol (Oxf) ; 89(3): 330-335, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29846957

RESUMO

BACKGROUND: There is a lack of consensus on the cardiometabolic consequences of mild subclinical hypothyroidism (SCH) among children. The objective of the current study was to compare lipid profiles in children with mild SCH with those of euthyroid children. STUDY DESIGN: Retrospective medical record review. PATIENTS: Children (ages 2-18 years) who had undergone simultaneous measurement of TSH, free thyroxine (T4) and lipids. Lipids in children with mild SCH (TSH 5-<10 mIU/L and normal free T4, n = 228) were compared with those in euthyroid children (n = 1215). RESULTS: TSH level was positively associated with total cholesterol and nonhigh density lipoprotein (non-HDL) cholesterol [ß 0.05(0.03-0.08), P < .0001 and ß 0.05(0.03-0.08), P < .0001, respectively]. Total cholesterol was significantly higher in children and adolescents with mild SCH compared with euthyroid children (4.43 ± 1.14 mmol/L vs 4.2 ± 0.85 mmol/L, P = .0005). Similarly, non-HDL cholesterol level was also higher in children with mild SCH relative to euthyroid children (3.08 ± 1.14 mmol/L vs 2.91 ± 0.8 mmol/L, P = .001). The adjusted odds ratio of having elevated total cholesterol and elevated non-HDL cholesterol was greater in children with mild SCH compared with euthyroid children (OR 1.88, 95% CI; 1.28-2.73; P = .001 and 1.72, 95% CI 1.2-2.5; P = .003, respectively). The presence of thyroid autoimmunity was not associated with higher rates of dyslipidaemia. CONCLUSIONS: Mild SCH in children and adolescents was associated with higher rates of elevated total cholesterol and elevated non-HDL cholesterol. Randomized placebo controlled studies are warranted to determine if treatment of mild SCH in children leads to improvement in lipid profile.


Assuntos
Dislipidemias/sangue , Dislipidemias/complicações , Hipotireoidismo/sangue , Hipotireoidismo/etiologia , Adolescente , Criança , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Masculino , Estudos Retrospectivos , Testes de Função Tireóidea , Tireotropina/sangue
7.
Endocr Rev ; 37(5): 521-547, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27588937

RESUMO

Hypercalcemia occurs in up to 4% of the population in association with malignancy, primary hyperparathyroidism, ingestion of excessive calcium and/or vitamin D, ectopic production of 1,25-dihydroxyvitamin D [1,25(OH)2D], and impaired degradation of 1,25(OH)2D. The ingestion of excessive amounts of vitamin D3 (or vitamin D2) results in hypercalcemia and hypercalciuria due to the formation of supraphysiological amounts of 25-hydroxyvitamin D [25(OH)D] that bind to the vitamin D receptor, albeit with lower affinity than the active form of the vitamin, 1,25(OH)2D, and the formation of 5,6-trans 25(OH)D, which binds to the vitamin D receptor more tightly than 25(OH)D. In patients with granulomatous disease such as sarcoidosis or tuberculosis and tumors such as lymphomas, hypercalcemia occurs as a result of the activity of ectopic 25(OH)D-1-hydroxylase (CYP27B1) expressed in macrophages or tumor cells and the formation of excessive amounts of 1,25(OH)2D. Recent work has identified a novel cause of non-PTH-mediated hypercalcemia that occurs when the degradation of 1,25(OH)2D is impaired as a result of mutations of the 1,25(OH)2D-24-hydroxylase cytochrome P450 (CYP24A1). Patients with biallelic and, in some instances, monoallelic mutations of the CYP24A1 gene have elevated serum calcium concentrations associated with elevated serum 1,25(OH)2D, suppressed PTH concentrations, hypercalciuria, nephrocalcinosis, nephrolithiasis, and on occasion, reduced bone density. Of interest, first-time calcium renal stone formers have elevated 1,25(OH)2D and evidence of impaired 24-hydroxylase-mediated 1,25(OH)2D degradation. We will describe the biochemical processes associated with the synthesis and degradation of various vitamin D metabolites, the clinical features of the vitamin D-mediated hypercalcemia, their biochemical diagnosis, and treatment.


Assuntos
Hipercalcemia/diagnóstico , Hipercalcemia/terapia , Vitamina D/efeitos adversos , Animais , Cálcio/sangue , Humanos , Hipercalcemia/etiologia , Hipercalciúria/etiologia , Mutação/fisiologia , Nefrocalcinose/etiologia , Nefrolitíase/etiologia , Vitamina D3 24-Hidroxilase/genética
10.
Mayo Clin Proc ; 88(9): 996-1009, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24001492

RESUMO

As female athletic participation has increased, the positive effects of exercise on health have become evident. However, with this growth in sports activity, a set of health problems unique to the female athlete has emerged. The female athlete triad as first described in 1992 by the American College of Sports Medicine consisted of disordered eating, amenorrhea, and osteoporosis; the definition was updated in 2007 to include a spectrum of dysfunction related to energy availability, menstrual function, and bone mineral density. For this review, a comprehensive search of databases-MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Scopus, from earliest inclusive dates to January 2013-was conducted by an experienced librarian with input from the authors. Controlled vocabulary supplemented with keywords such as female athlete triad, amenorrhea, oligomenorrhea, fracture, osteopenia, osteoporosis, bone disease, anorexia, bulimia, disordered eating, low energy availability was used to search for articles on female athlete triad. Articles addressing the prevalence, screening, and management of the female athlete triad were selected for inclusion in the review. This article reviews the current definitions of the triad components, epidemiology, pathophysiology, and recommended screening and management guidelines. The lack of efficacy of current screening of athletes is highlighted. Low energy availablity, from either dietary restriction or increased expenditure, plays a pivotal role in development of the triad. Athletes involved in "lean sports" (those that emphasize weight categories or aesthetics, such as ballet, gymnastics, or endurance running) are at highest risk. Treatment is centered on restoring energy availability to reverse adverse changes in the metabolic milieu. Prevention and early recognition of triad disorders are crucial to ensure timely intervention. Caregivers and physicians of female athletes must remain vigilant in education, recognition, and treatment of athletes at risk.


Assuntos
Síndrome da Tríade da Mulher Atleta/diagnóstico , Amenorreia/diagnóstico , Amenorreia/etiologia , Atletas , Densidade Óssea , Feminino , Síndrome da Tríade da Mulher Atleta/terapia , Humanos , Anamnese , Fatores de Risco
12.
Mayo Clin Proc ; 88(2): 176-83, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23374621

RESUMO

OBJECTIVE: To determine temporal trends in incidence and risk factors of nutritional rickets in a community-based population. PATIENTS AND METHODS: Rochester Epidemiology Project data were used to identify all children (aged <18 years) residing in Olmsted County, Minnesota, between January 1, 1970, and December 31, 2009, with diagnostic codes corresponding to rickets, vitamin D deficiency, hypovitaminosis D, rachitis, osteomalacia, genu varum, genu valgum, craniotabes, hypocalcemia, hypocalcemic seizure, and tetany. Record abstraction was performed to select individuals with radiographic confirmation of rickets. Age- and sex-matched controls were identified for the evaluation of risk factors. The main outcome measure was radiographic evidence of rickets without identifiable inherited, genetic, or nonnutritional causes. Incidence rates were calculated using Rochester Epidemiology Project census data. RESULTS: Of 768 children with eligible diagnostic codes, 23 had radiographic evidence of rickets; of these, 17 children had nutritional rickets. All 17 children were younger than 3 years, and 13 (76%) were of nonwhite race/ethnicity. Clinical presentation included poor growth (n=12), leg deformity (n=8), motor delay (n=5), leg pain (n=3), weakness (n=3), and hypocalcemia or tetany (n=2). The incidence of nutritional rickets in children younger than 3 years was 0, 2.2, 3.7, and 24.1 per 100,000 for the decades beginning in 1970, 1980, 1990, and 2000, respectively (P=.003 for incidence trend). Nutritional rickets was associated with black race, breast-feeding, low birth weight, and stunted growth (P<.05 for all). Four of 13 patients (31%) who underwent 25-hydroxyvitamin D testing had values less than 10 ng/mL. CONCLUSION: Nutritional rickets remains rare, but its incidence has dramatically increased since 2000. Not all cases of rickets can be attributed to vitamin D deficiency.


Assuntos
Hipocalcemia/epidemiologia , Osteomalacia/epidemiologia , Raquitismo/epidemiologia , Deficiência de Vitamina D/epidemiologia , Causalidade , Pré-Escolar , Comorbidade , Demografia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Minnesota/epidemiologia , Fatores de Risco
13.
Bone ; 54(1): 21-7, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23352924

RESUMO

The presentation of hypophosphatasia (HPP) diagnosed in adults demonstrates a wide range of clinical manifestations, many of which are nonspecific. We sought to assess clinical characteristics of adult HPP by evaluation of Mayo Clinic Rochester adults diagnosed with HPP from 1976 through 2008. Subjects were identified by diagnostic code or medical records. Inclusion criteria were age ≥18 years at diagnosis; low serum alkaline phosphatase (AP) without bisphosphonate therapy; and one additional element: elevated pyridoxal 5'-phosphate (PLP) or urine phosphoethanolamine (PEA), evidence of osteomalacia, or family history. We were unable to distinguish manifesting carriers from silent unaffected carriers due to lack of a prospective standardized clinical evaluation and the absence of genetic testing. HPP was diagnosed in 22 unrelated adults (median age 49 years; 68% women). Most patients (68%) were symptomatic at presentation with features including musculoskeletal pain (41%) or incident fracture (18%). A history of fracture was present in 54%: hip/femoral neck (23%), feet (23%, all women), wrist (18%), and spine (9%, all men). Nine patients (36%) had multiple fractures while 4 (all women) had subtrochanteric femur fractures. Radiographic chondrocalcinosis (27%) and documented pyrophosphate arthropathy (14%) were only observed in women. Median minimum serum AP was 43% below the lower normal limit. Urine PEA was elevated in 15/16 patients (94%). PLP median was 68 µg/L (normal, 5-50 µg/L) and all (n=8) were above normal. Symptomatic subjects had more fractures and chondrocalcinosis, lower median minimum AP and PLP and higher median PEA levels. Clinical features more common in fracture patients included symptoms at presentation, history of childhood rickets, dental abnormalities, lower median minimum AP and PLP, and higher median urine PEA. Four subjects had iliac crest bone biopsies, with 2/4 specimens consistent with osteomalacia. These results suggest that adult HPP demonstrates a wide spectrum of clinical manifestations including musculoskeletal pain, fractures, chondrocalcinosis and dental anomalies with some overlap in laboratory characteristics in relationship to disease severity. In addition to genetic and environmental factors, gender may influence the clinical expression of HPP.


Assuntos
Hipofosfatasia/diagnóstico , Hipofosfatasia/patologia , Adulto , Idoso , Feminino , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/etiologia , Fraturas Ósseas/patologia , Humanos , Hipofosfatasia/complicações , Hipofosfatasia/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Radiografia
14.
Arch Biochem Biophys ; 523(1): 77-86, 2012 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-22426203

RESUMO

The kidney is essential for the maintenance of normal calcium and phosphorus homeostasis. Calcium and inorganic phosphorus are filtered at the glomerulus, and are reabsorbed from tubular segments by transporters and channels which are regulated by 1α,25-dihydroxyvitamin (1α,25(OH)(2)D) and parathyroid hormone (PTH). The kidney is the major site of the synthesis of 1α,25(OH)(2)D under physiologic conditions, and is one of the sites of 24,25-dihydroxyvitamin D (24,25(OH)(2)D) synthesis. The activity of the 25(OH)D-1α-hydroxylase, the mixed function oxidase responsible for the synthesis of 1α,25(OH)(2)D, is regulated by PTH, 1α,25(OH)(2)D, fibroblast growth factor 23 (FGF23), inorganic phosphorus and other growth factors. Additionally, the vitamin D receptor which binds to, and mediates the activity of 1α,25(OH)(2)D, is widely distributed in the kidney. Thus, the kidney, by regulating multiple transport and synthetic processes is indispensible in the maintenance of mineral homeostasis in physiological states.


Assuntos
Rim/metabolismo , Vitamina D/metabolismo , Absorção , Animais , Cálcio/metabolismo , Humanos , Rim/enzimologia , Fósforo/metabolismo
15.
J Clin Endocrinol Metab ; 97(3): E423-7, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22337913

RESUMO

BACKGROUND: Mutations of the CYP24A1 gene, which encodes the 1,25-dihydroxyvitamin D-24-hydroxylase cytochrome P450, Cyp24A1, are predicted to result in elevated 1,25-dihydroxyvitamin D concentrations, hypercalcemia, hypercalciuria, nephrolithiasis, and bone disease. Treatment of hypercalcemia associated with CYP24A1 gene mutations has not been described. METHODS: The genetic basis of a syndrome in a 44-yr-old Caucasian male characterized by intermittent hypercalcemia, hypercalciuria, elevated serum 1,25-dihydroxyvitamin D, undetectable serum 24,25-dihydroxyvitamin D, metabolically active nephrolithiasis, and reduced bone mineral density of the lumbar spine was examined. Sequencing of the CYP24A1 gene and biochemical and genetic analysis of seven family members in three generations was carried out. Because of hypercalcemia, hypercalciuria, and metabolically active nephrolithiasis, the patient was treated with a cytochrome 3A inhibitor, ketoconazole, 200 mg orally every 8 h, for 2 months. RESULTS: The sequence of the CYP24A1 gene showed two canonical splice junction mutations in the proband. Analysis of family members showed a phenotype associated one or both mutations, suggesting autosomal dominant transmission with partial penetrance of the trait. After therapy with ketoconazole, statistically significant reductions in previously elevated urinary calcium into the normal range were noted. Previously elevated serum 1,25-dihydroxyvitamin D and calcium concentrations decreased, and previously decreased PTH concentrations increased into the normal range, but the differences were not statistically significant. CONCLUSIONS: In a syndrome characterized by intermittent hypercalcemia, hypercalciuria, elevated 1,25-dihydroxyvitamin D, undetectable 24,25-dihydroxyvitamin D concentrations, splice junction mutations of the CYP24A1 gene, and autosomal dominant transmission of the trait, treatment with ketoconazole is useful in reducing urinary calcium.


Assuntos
Inibidores de 14-alfa Desmetilase/uso terapêutico , Calcitriol/sangue , Hipercalcemia/tratamento farmacológico , Hipercalciúria/tratamento farmacológico , Cetoconazol/uso terapêutico , Esteroide Hidroxilases/genética , Adulto , Genótipo , Humanos , Hipercalcemia/sangue , Hipercalcemia/genética , Hipercalciúria/sangue , Hipercalciúria/genética , Masculino , Mutação , Síndrome , Resultado do Tratamento , Vitamina D3 24-Hidroxilase
16.
Am J Med Genet A ; 152A(4): 1016-9, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20358619

RESUMO

Loeys-Dietz syndrome (LDS, OMIM # 609192) caused by heterozygous mutations in TGFBR1 and TGFBR2 has recently been described as an important cause of familial aortic aneurysms. These patients have craniofacial and skeletal features that overlap with the Marfan syndrome (MFS), and more importantly, have significant vascular fragility as is seen in MFS and Ehlers-Danlos syndrome Type IV (EDS-IV). The skeletal phenotype with respect to low bone mineral density and skeletal fragility is not clear. We present two patients with LDS with significant skeletal fragility. The first is a 17-year-old male who had talipes equinovarus, diaphragmatic and inguinal and herniae, aortic root dilatation necessitating surgical repair, craniofacial and skeletal dysmorphism consistent with LDS, and a history of numerous fragility fractures leading to significant skeletal deformity. He was found to be heterozygous for a c.923T > C transition in exon 4 of TGFBR2. The second is a 26-year-old male with submucous cleft palate, talipes equinovarus, pectus excavatum requiring surgery, inguinal hernia, and aneurysms in the ascending aorta, abdominal aorta, carotid, subclavian, vertebral and brachial arteries requiring surgical repairs. He also had craniofacial and skeletal dysmorphism consistent with LDS, multiple fractures in childhood, low bone mineral density, and was found to be heterozygous for a c.1561 T > C transition in exon 7 of TGFBR2. These case studies highlight the importance of paying close attention to fractures and bone density in patients with LDS. Osteopenia or osteoporosis may become increasingly important issues as earlier detection and treatment of the vascular complications of LDS improves life expectancy in these patients.


Assuntos
Osso e Ossos/patologia , Mutação em Linhagem Germinativa/genética , Síndrome de Loeys-Dietz/genética , Receptores de Fatores de Crescimento Transformadores beta/genética , Adolescente , Adulto , Biópsia , Criança , Pré-Escolar , Humanos , Recém-Nascido , Masculino
17.
Endocr Pract ; 13(2): 169-75, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17490932

RESUMO

OBJECTIVE: To describe a case of granulomatous hypophysitis occurring after treatment with interferon alfa-2b and ribavirin for hepatitis C. METHODS: Clinical, radiologic, laboratory, and pathologic assessments of a woman with granulomatous hypophysitis and interferon-induced thyroiditis are presented. RESULTS: A 42-year-old woman with hepatitis C was treated with interferon alfa-2b and ribavirin for 5 months. She was referred after symptoms of thyrotoxicosis developed, in conjunction with laboratory and radiographic evidence of thyroiditis. During the initial evaluation, she was weak and hypotensive; biochemical evaluation showed undetectable plasma cortisol and corticotropin concentrations. Magnetic resonance imaging revealed diffuse enlargement of the pituitary gland, which encroached on but did not compress the optic chiasm. Treatment with supraphysiologic doses of prednisone resulted in clinical and radiographic improvement. Once physiologic doses of glucocorticoids were instituted, however, follow-up magnetic resonance imaging showed substantial progression of the diffuse pituitary enlargement and mild compression of the optic chiasm. Surgical debulking of the mass and histologic evaluation showed chronic, noncaseating granulomatous hypophysitis. An extensive evaluation for secondary causes of granulomatous inflammation of the pituitary revealed only an elevated angiotensin-converting enzyme level; no organisms were identified. After 2 courses of high-dose glucocorticoids, she had radiographic evidence of decreased size of the pituitary lesion but continued to have multiple anterior pituitary hormone deficiencies. CONCLUSION: Granulomatous hypophysitis and sarcoidosis of the pituitary are rare disorders. Hypophysitis should be considered in patients receiving interferon and ribavirin therapy who have symptoms consistent with pituitary dysfunction.


Assuntos
Granuloma/patologia , Interferon-alfa/efeitos adversos , Doenças da Hipófise/patologia , Ribavirina/efeitos adversos , Adulto , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Feminino , Granuloma/induzido quimicamente , Hepatite C/tratamento farmacológico , Humanos , Hipopituitarismo/induzido quimicamente , Hipopituitarismo/tratamento farmacológico , Hipopituitarismo/patologia , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Doenças da Hipófise/induzido quimicamente , Proteínas Recombinantes , Ribavirina/uso terapêutico , Tireoidite/induzido quimicamente , Tireoidite/patologia , Tireotoxicose/induzido quimicamente , Tireotoxicose/patologia
18.
Endocr Pract ; 12(1): 35-42, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16524861

RESUMO

OBJECTIVE: To highlight a strategy for potential detection of mesenchymal tumors in oncogenic malacia, as illustrated by 3 cases. METHODS: Three case reports are presented in which successful localization of the offending neoplasm was accomplished by using whole-body Tc 99m sestamibi scanning. Alternative localization techniques are also reviewed. RESULTS: Oncogenic osteomalacia occurs infrequently and is caused by neoplasms that secrete phosphatonins, substances that interfere with proximal tubular resorption of phosphorus and can result in phosphaturia, hypophosphatemia, reduced 1,25-dihydroxyvitamin D concentration, and osteomalacia. Removal of the underlying neoplasm results in complete resolution of all biochemical, pathologic, and physical manifestations of this disorder, as shown in our 3 patients. Because the neoplasms are small and can occur in any tissue compartment, they are difficult to localize, a feature that often results in therapeutic failure. CONCLUSION: We conclude that use of whole-body Tc 99m sestamibi scanning may be an appropriate and cost-effective initial strategy for the localization of peripheral phosphatonin-secreting tumors.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Lipomatosas/diagnóstico por imagem , Neoplasias de Tecido Conjuntivo/diagnóstico por imagem , Osteomalacia/diagnóstico por imagem , Tecnécio Tc 99m Sestamibi , Idoso , Neoplasias Ósseas/complicações , Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Mesoderma/patologia , Pessoa de Meia-Idade , Neoplasias Lipomatosas/complicações , Neoplasias Lipomatosas/patologia , Neoplasias Lipomatosas/cirurgia , Neoplasias de Tecido Conjuntivo/complicações , Neoplasias de Tecido Conjuntivo/patologia , Neoplasias de Tecido Conjuntivo/cirurgia , Osteomalacia/etiologia , Osteomalacia/patologia , Cintilografia , Medição de Risco , Amostragem , Sensibilidade e Especificidade , Índice de Gravidade de Doença
19.
Pflugers Arch ; 451(4): 579-87, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16151791

RESUMO

The phosphatonin, secreted frizzled-related protein-4 (sFRP-4), induces phosphaturia and inhibits 25-hydroxyvitamin D 1alpha-hydroxylase activity normally induced in response to hypophosphatemia. To determine the mechanism by which sFRP-4 alters renal phosphate (P(i)) transport, we examined the effect of sFRP-4 on renal brush border membrane (BBMV) Na(+)-dependent P(i) uptake, and the abundance and localization of the major Na(+)-P(i)-IIa co-transporter in proximal tubules and opossum kidney (OK) cells. Infusion of sFRP-4 increased renal fractional excretion of P(i) and decreased renal beta-catenin concentrations. The increase in renal P(i) excretion with sFRP-4 infusion was associated with a 21.9 +/- 3.4% decrease in BBMV Na(+)-dependent P(i) uptake (P < 0.001) compared with a 39.5 +/- 2.1% inhibition of Na(+)-dependent P(i) transport in renal BBMV induced by PTH (P < 0.001). sFRP-4 infusion was associated with a 30.7 +/- 4.8% decrease in Na(+)-P(i)-IIa co-transporter protein abundance (P < 0.01) assessed by immunoblotting methods compared to a 45.4 +/- 8.8% decrease induced by PTH (P < 0.001). In OK cells, sFRP-4 reduced surface expression of a heterologous Na(+)-P(i)-IIa co-transporter. We conclude that sFRP-4 increases renal P(i) excretion by reducing Na(+)-P(i)-IIa transporter abundance in the brush border of the proximal tubule through enhanced internalization of the protein.


Assuntos
Túbulos Renais Proximais/efeitos dos fármacos , Túbulos Renais Proximais/metabolismo , Proteínas Proto-Oncogênicas/farmacologia , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIa/metabolismo , Animais , Células Cultivadas , Humanos , Túbulos Renais Proximais/citologia , Masculino , Gambás , Ratos , Ratos Sprague-Dawley
20.
Mayo Clin Proc ; 80(6): 745-51, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15948297

RESUMO

OBJECTIVE: To determine whether fibroblast growth factor 23 (FGF23) concentrations are altered in women with ovarian cancers in which FGF physiology is known to be abnormal. PATIENTS AND METHODS: Between May 2002 and September 2003 at the Mayo Clinic in Rochester, Minn, plasma or serum FGF23 concentrations were measured in 39 healthy women and in 14 with benign ovarian tumors, 14 with early-stage ovarian cancer, and 13 with advanced-stage ovarian cancer. Immunohistochemistry using anti-human FGF23 antibodies was performed on tissue from benign masses and advanced-stage tumors. RESULTS: Serum or plasma FGF23 concentrations were significantly higher in women with advanced-stage ovarian cancer compared with concentrations in women with early-stage ovarian cancer or benign disease or in healthy women. A significant positive correlation was seen between serum iFGF23 and cFGF23 concentrations and stage of disease. Serum iFGF23 and cFGF23 concentrations were positively correlated with serum phosphorus among women with ovarian cancer. No patients with elevated iFGF23 or cFGF23 concentrations had hypophosphatemia. Immunohistochemistry detected FGF23 tissue staining in malignant ovarian cancer cells. CONCLUSION: Serum or plasma FGF23 concentrations are elevated in patients with advanced-stage epithellal ovarian cancer without reductions in serum phosphate concentrations. The presence of elevated FGF23 concentrations in patients with an ovarian mass should suggest advanced-stage disease.


Assuntos
Cistadenocarcinoma Seroso/sangue , Fatores de Crescimento de Fibroblastos/sangue , Neoplasias Ovarianas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Cistadenocarcinoma Seroso/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Neoplasias Ovarianas/patologia , Estudos Retrospectivos
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