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PURPOSE: The aim of this study is to review the clinical and laboratory characteristics, diagnostic and treatment modalities of tumor-induced osteomalacia (TIO) cases managed in a single center. MATERIAL METHODS: Demographic and clinical features, biochemical findings, diagnostic procedures, treatment modalities, and outcomes of nine patients who had the diagnosis of TIO were reviewed retrospectively. RESULTS: Mean age of the study group (F/M: 4/5) was 45.8 ± 10.8 years, and mean time from the onset of symptoms to diagnosis was 4.7 ± 2.8 years. The clinical manifestations were muscle weakness and difficulty in walking (8/9), hip pain (3/9), multiple fractures (2/9), stress fracture (2/9). Mean plasma phosphorus concentration was 1.28 ± 0.4 mg/dl at presentation. We performed radionuclide imaging modalities (18F-FDG PET/CT, Ga68-DOTATATE PET/CT, octreotide scintigraphy) in seven of nine patients, and tumor was detected in all. Lower extremity (n = 6; %67), head region (n = 2; %22) and thorax (n = 1; %11) were the tumor locations of our cases. Eight patients underwent surgery and remission was achieved postoperatively in all of the operated patients and plasma phosphorus level normalized in 4 ± 2 days. Pathological examination revealed mesenchymal tumors with different subtypes. Recurrence occurred in three patients at 13 ± 10.5 months after the first surgery. Two patients were reoperated and radiotherapy was also performed in one of them. CONCLUSION: Hypophosphatemia necessitates careful evaluation for the etiology. TIO is one of the important causes of adult-onset hypophosphatemic osteomalacia. Diagnosis of TIO is essential because the laboratory and clinical findings resolve after appropriate treatment.
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Hipofosfatemia , Neoplasias de Tecido Conjuntivo , Osteomalacia , Síndromes Paraneoplásicas , Adulto , Humanos , Pessoa de Meia-Idade , Neoplasias de Tecido Conjuntivo/diagnóstico por imagem , Neoplasias de Tecido Conjuntivo/etiologia , Osteomalacia/etiologia , Osteomalacia/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Retrospectivos , Síndromes Paraneoplásicas/diagnóstico , Síndromes Paraneoplásicas/etiologia , Síndromes Paraneoplásicas/terapia , Hipofosfatemia/etiologia , Hipofosfatemia/terapia , FósforoRESUMO
PURPOSE: Transglutaminase 2 (TG2) is associated with mobilization, invasion, and chemoresistance of tumor cells. We aimed to determine whether the immunohistochemical staining with TG2 antibody differs between metastatic and non-metastatic papillary thyroid cancer patients. METHODS: We included 76 patients with papillary thyroid cancer (72% female, median age 52 (24-81) years, follow-up time 107 (60-216) months). Thirty of them with no metastasis, 30 of them with only lymph node metastasis and 16 patients with distant ± lymph node metastasis. Immunohistochemical staining of TG2 antibody was evaluated in the primary tumor and extra-tumoral tissue. We also divided subjects into two groups according to their primary tumor TG2 staining score (group A, high risk group: ≥3, n = 43; group B, low risk group: <3, n = 33). RESULTS: Vascular invasion (p < 0.001), thyroid capsule invasion (p < 0.001), extrathyroidal extension (p < 0.001), intrathyroidal dissemination (p = 0.001), lymph node metastasis (p < 0.001), presence of aggressive histology (p < 0.001) were significantly higher in group A. No significant difference was found between the groups in terms of distant metastasis. Based on ATA risk classification 95.5% of patients with low risk were in group B but 86.8% of intermediate risk and 56.3% of high risk were in group A. In regression analysis, lymph node metastasis increased by 1.9 times with each one point increase in TG2 staining score. CONCLUSION: TG2 staining score of the primary tumor may be a predictive factor for lymph node metastasis. High or low TG2 scores may effect the frequency of follow-up and decision of treatment regimens.
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Neoplasias da Glândula Tireoide , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Metástase Linfática/patologia , Proteína 2 Glutamina gama-Glutamiltransferase , Tireoidectomia , Linfonodos/patologia , Fatores de Risco , Estudos RetrospectivosRESUMO
CONTEXT: The aims of the study are to compare characteristics of subacute thyroiditis (SAT) related to different etiologies, and to identify predictors of recurrence of SAT and incident hypothyroidism. METHODS: This nationwide, multicenter, retrospective cohort study included 53 endocrinology centers in Turkey. The study participants were divided into either COVID-19-related SAT (Cov-SAT), SARS-CoV-2 vaccine-related SAT (Vac-SAT), or control SAT (Cont-SAT) groups. RESULTS: Of the 811 patients, 258 (31.8%) were included in the Vac-SAT group, 98 (12.1%) in the Cov-SAT group, and 455 (56.1%) in the Cont-SAT group. No difference was found between the groups with regard to laboratory and imaging findings. SAT etiology was not an independent predictor of recurrence or hypothyroidism. In the entire cohort, steroid therapy requirement and younger age were statistically significant predictors for SAT recurrence. C-reactive protein measured during SAT onset, female sex, absence of antithyroid peroxidase (TPO) positivity, and absence of steroid therapy were statistically significant predictors of incident (early) hypothyroidism, irrespective of SAT etiology. On the other hand, probable predictors of established hypothyroidism differed from that of incident hypothyroidism. CONCLUSION: Since there is no difference in terms of follow-up parameters and outcomes, COVID-19- and SARS-CoV-2 vaccine-related SAT can be treated and followed up like classic SATs. Recurrence was determined by younger age and steroid therapy requirement. Steroid therapy independently predicts incident hypothyroidism that may sometimes be transient in overall SAT and is also associated with a lower risk of established hypothyroidism.
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COVID-19 , Hipotireoidismo , Tireoidite Subaguda , Humanos , Feminino , Tireoidite Subaguda/epidemiologia , Tireoidite Subaguda/etiologia , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Estudos Retrospectivos , SARS-CoV-2 , Hipotireoidismo/etiologia , Hipotireoidismo/complicações , EsteroidesRESUMO
The aim of this study was to evaluate the efficacy of cabergoline in normalizing plasma IGF-I levels in acromegaly patients with elevated IGF-I levels after surgery and/or SRL therapy. Acromegaly patients (n: 143) were evaluated retrospectively. Patients with elevated IGF-I levels after surgery and/or SRLs therapy and a fixed dose of SRLs treatment for the last six months with no history of radiotherapy in the last three years were included in the study (n: 12). Previous treatment regimens, baseline PRL and IGF-I levels (ULNR), sella MRI, and immunohistochemical findings were evaluated. Cabergoline was used as an add on (n: 11) or single medical treatment (n: 1). The median duration of treatment with SRL alone was 12 months (range 6-48 months). The mean IGF-I value before cabergoline therapy was 1.45±0.4 ULNR. The mean cabergoline dose and duration of treatment were 1.55±0.75 mg/week and 9±6.3 months, respectively. IGF-I normalization was only achieved in patients with serum IGF-I concentration<1.5×ULNR before the onset of cabergoline treatment (n: 9). In some of the patients with IGF-I normalization, baseline prolactin levels were normal (n: 3). Immunopositivity for prolactin in adenoma tissue was found in three patients with IGF-I normalization. Cabergoline therapy is effective in the normalization of IGF-I levels even in normoprolactinemic acromegaly patients when IGF-I levels are mildly or moderately elevated during SRL therapy.
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Acromegalia , Hormônio do Crescimento Humano , Acromegalia/tratamento farmacológico , Cabergolina/uso terapêutico , Ergolinas/efeitos adversos , Ergolinas/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I , Prolactina , Estudos RetrospectivosRESUMO
SUMMARY Dilated cardiomyopathy (DCM) is characterized by systolic dysfunction and is usually idiopathic. A rare cause of reversible DCM is hypocalcemia. Calcium plays a key role in myocardial contraction. Hypocalcemia can lead to a decrease in contraction, left ventricular systolic dysfunction, and heart failure with reduced ejection fraction (EF). Hypocalcemia-related reversible DCM reports are rare. Herein, we present two cases with heart failure caused by hypocalcemia developed due to hypoparathyroidism. The first case presented with severe heart failure and an extremely low serum calcium level (4.4 mg/dL) due to idiopathic hypoparathyroidism. The second case, which was also admitted with heart failure due to hypocalcemia, had iatrogenic hypoparathyroidism due to a subtotal thyroidectomy. In both cases, patients had reduced left ventricular systolic functions (EF was 33% and 42%, respectively). After calcium replacement and heart failure treatment, calcium levels were normalized. A significant and rapid improvement in heart failure was achieved in both cases (EF 60% and 50%, respectively). Serum calcium levels should always be measured in patients with heart failure, and the etiology of hypocalcemia should be sought. In addition to the standard pharmacotherapy of heart failure with reduced EF, calcium supplementation is essential for treating these patients.
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Patients with primary aldosteronism induced hypertension are more likely to experience cardiovascular events compared to patients with essential hypertension. Primary aldosteronism may therefore have distinct adverse effects on cardiovascular structure and function, independent of hypertension. However, current data on such effects of primary aldosteronism are conflicting. The aim of the present study was to investigate the influence of primary aldosteronism on vascular structure and endothelial function, using intima-media thickness as a vascular remodeling index and flow-mediated dilation as a functional parameter. In total, 70 participants were recruited from patients with resistant hypertension. Twenty-nine patients diagnosed with primary aldosteronism and 41 patients with essential hypertension were prospectively enrolled. Primary aldosteronism was due to aldosterone-producing adenoma in 10 cases and due to idiopathic adrenal hyperplasia in 19 cases. All patients underwent ultrasound of the common carotid intima-media thickness and flow-mediated dilation of the brachial artery. Primary aldosteronism patients had significantly lower flow-mediated dilation (3.3 [2.4-7.4] % vs 14.7 [10.3-19.9] %, P < 0.01) and significantly higher carotid intima-media thickness (0.9 [0.7-1.0] mm vs 0.8 [0.6-0.9] mm, P = 0.02) compared to patients with essential hypertension. These differences remained significant after adjusting for age, sex, diabetes mellitus, 24-hours systolic blood pressure, and smoking (P < 0.01). No differences in either outcome were observed between the adenoma and adrenal hyperplasia groups (both P > 0.05). Hypertensive patients with hyperaldosteronism appear to exhibit deteriorative effects on both vascular structure and function, independent of hypertension.
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Artéria Braquial , Artérias Carótidas , Espessura Intima-Media Carotídea , Endotélio Vascular/fisiopatologia , Hiperaldosteronismo , Hipertensão , Aldosterona/sangue , Anti-Hipertensivos/uso terapêutico , Artéria Braquial/diagnóstico por imagem , Artéria Braquial/fisiopatologia , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/fisiopatologia , Correlação de Dados , Feminino , Humanos , Hiperaldosteronismo/complicações , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/metabolismo , Hiperaldosteronismo/fisiopatologia , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Masculino , Pessoa de Meia-IdadeRESUMO
Background The association of subacute thyroiditis (SAT) and papillary thyroid carcinoma is a rare finding. In this study, we aimed to investigate the prevalence of differentiated thyroid cancer in a cohort of patients followed with the diagnosis of SAT. Patients and methods We retrospectively screened medical records of Endocrinology and Metabolism outpatient clinic in the past 20 years for patients with SAT. Patients with nodules and suspicious ultrasonography findings who underwent fine needle aspiration biopsy (FNAB) and operated due to malignancy risk were identified. Results We identified 137 (100 females, 37 males) patients with reliable records to confirm the diagnosis of SAT. The mean age of female patients was 41.1 ± 9.1 (range, 20-64) and of male patients was 43.0 ± 9.3 (range, 20-65). One or more FNAB was performed in 23 of the patients (16.8%) at the beginning and/or during the follow-up period when needed. Seven patients with suspicious FNAB findings were operated, and histopathological examination of the nodules confirmed the diagnosis of papillary thyroid carcinoma in 6 patients (4.4%). Conclusions Our observations suggesting a relatively higher prevalence of thyroid cancer in a small series of SAT patients warrant further studies to identify the real frequency of differentiated thyroid cancer and its association with inflammatory pathogenesis of SAT. This finding is compatible with the trend of increased thyroid cancer incidence all over the world. A repeat ultrasonography after resolution of clinical and inflammatory findings, and FNAB should be recommended to all patients with suspicious nodules.
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Câncer Papilífero da Tireoide/epidemiologia , Tireoidite Subaguda/epidemiologia , Adulto , Idoso , Biomarcadores Tumorais/sangue , Biópsia por Agulha Fina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Câncer Papilífero da Tireoide/patologia , Testes de Função Tireóidea , Tireoidite Subaguda/patologiaRESUMO
OBJECTIVE: Osteoporosis, osteosclerosis, and lytic bone lesions have been observed in patients with systemic mastocytosis (SM). We examined bone mineral density (BMD) biochemical turnover markers and serum tryptase levels in SM, which is considered a rare disease. MATERIALS AND METHODS: Seventeen adult patients (5 females, 12 males; median age: 33 years, range: 20-64) with mastocytosis were included in this study. We investigated the value of quantitative ultrasound (QUS) of the calcaneus in the assessment of BMD in SM patients, as well as BMD of the lumbar spine (L1-L4), femoral neck, and distal radius using dual energy x-ray absorptiometry (DXA) and plasma tryptase levels, biochemical markers of bone turnover. RESULTS: At lumbar spine L1-L4, the femoral neck, and the distal radius or as calcaneus stiffness, 12 of 17 patients had T-scores of less than -1 at least at 1 site, reflecting osteopenia. Three of 17 patients had T-scores showing osteoporosis (T-score <-2.5). There was no relationship between DXA and bone lesion severity. We also found a significant positive correlation between tryptase levels and disease severity, as well as between disease severity and pyridinoline (p<0.01 by Spearman's test). CONCLUSION: DXA and calcaneal QUS may not be appropriate techniques to assess bone involvement in SM patients because of the effects of osteosclerosis. This study further shows that the osteoclastic marker pyridinoline is helpful in patients with severe disease activity and sclerotic bone lesions to show bone demineralization.
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Langerhans cell histiocytosis (LCH) is a rare disease in which the most common endocrine manifestation is diabetes insipidus (DI). Data on anterior pituitary function in patients with LCH are limited. Thus, the present study investigated anterior pituitary function in LCH patients with DI via the evaluation of clinical and radiological findings at disease onset and during follow-up. The present study retrospectively evaluated nine patients with LCH (five males and four females). All diagnoses of LCH were made following histological and/or immunophenotypic analyses of tissue biopsies, bronchoalveolar lavage, or cerebrospinal fluid (CSF). Basal and, if necessary, dynamic pituitary function tests were used to assess anterior pituitary function, and magnetic resonance imaging (MRI) scans were used to image the pituitary. The LCH treatment modality was based on organ involvement. The mean age at onset of DI was 27.6 years (range 15-60 years). One patient (11%) exhibited single organ involvement, while eight patients (89%) displayed multisystem organ involvement. On admittance, one patient had hypogonadotropic hypogonadism, one patient exhibited panhypopituitarism [hypogonadotropic hypogonadism, central hypothyroidism, hypocortisolism, and growth hormone (GH) deficiency], and four patients (44%) displayed hyperprolactinemia. The MRI data revealed infundibular enlargement in seven patients (78%), a thalamic mass in one patient (11%), and the absence of the bright spot in all patients. A single patient (11%) showed a mass in the pons that had a partially empty sella. The patients were treated with radiation therapy (RT), chemotherapy (CT), or a combination of both (RT+CT) and were followed up for a median of 91.8 months (range 2-318 months). Seven patients were assessed during the follow-up period, of whom four patients (57.1%) developed anterior pituitary hormone deficiency, three (43%) were diagnosed with GH deficiency, and one (14%) exhibited gonadotropin deficiency. The gonadotropin deficiency in the patient, which was diagnosed on admittance, was resolved during the follow-up period. DI persisted in all patients, and the conditions of the seven patients who have remained on follow-up are stable. In the present study, patients with LCH exhibited altered function in the anterior pituitary as well as the posterior pituitary, which may be due to the natural course of the disease or the effects of treatment. The present findings indicate that anterior pituitary function should be assessed in LCH patients on admittance and during follow-up, especially in LCH patients with multisystem organ involvement.
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Histiocitose de Células de Langerhans/patologia , Hipófise/patologia , Adolescente , Adulto , Terapia Combinada , Feminino , Histiocitose de Células de Langerhans/tratamento farmacológico , Histiocitose de Células de Langerhans/radioterapia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Hipófise/metabolismo , Estudos Retrospectivos , Resultado do TratamentoRESUMO
INTRODUCTION: The mesurement of midnight salivary cortisol provides the most sensitive method for screening of Cushing's sendrome. However the clinical significance of spectral error is the requirement for determination of normal reference values in each population for each test, which will be used as the diagnostic method. Salivary cortisol levels may be affected by individual factors such as nutrition, sleep, medication, activity, and gender. Being a non-invasive method, midnight salivary cortisol (MSC) has been used as a valuable indicator of free plasma cortisol. MATERIAL AND METHODS: Midnight salivary cortisol was assessed in randomly selected 100 Turkish patents who underwent to a detailed physical examination. Saliva samples were collected at 00:00 to plastic tubes with the help of plastic pipettes, without brushing their teeth, but after rinsing their mouth. Salivary cortisol was measured with luminescense immunoassay kit. Differences and correlations were analysed. RESULTS: The mean midnight salivary cortisol of the healthy population was 0.21 ±0.03 µg/dl. Body mass index, age, sex, smoking, exercise, educational status alcohol, had no effect on the MSC. CONCLUSIONS: Consequently, normal salivary cortisol reference ranges must be used for different assays and different populations in order to evaluate more accurately pituitary-adrenal axis pathology in clinical practice.
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One form of prolactin (PRL) is macroprolactin with high molecular mass. Many macroprolactinemic patients have no pituitary adenomas and no clinical symptoms of hyperprolactinemia, it is controversial whether macroprolactinemia is a benign condition that does not need further investigation and treatment. In this study, we aimed to compare macroprolactinemic patients (group I) with the true hyperprolactinemic patients (group II) for the presence of pituitary adenoma. We investigated 161 patients with hyperprolactinemia, whose magnetic resonance imaging records of the pituitary were taken. All patients were questioned for irregular menses, infertility and examined for galactorrhea. Patients were screened for macroprolactinemia by polyethylene glycol precipitation, and a recovery of ≤40% and normal monomeric PRL level was taken as an indication of significant macroprolactinemia. Of 161 patients with hyperprolactinemia, 60 (37.26%) had macroprolactinemia. PRL levels of group II were lower than those of group I (P = 0.011), although monomeric PRL levels of group II were higher than those of group I (P = 0.0005). Of 60 macroprolactinemic patients, 16 (26.7%) had pituitary adenomas. The prevalence of pituitary adenomas was lower in group I, compared with group II (P = 0.0005). No significant differences were found between the prevalences of irregular menses and infertility of group I and II (P = 0.084, P = 0.361). Prevalence of galactorrhea in group I was lower than that in group II (P = 0.048). Prevalence of pituitary adenomas in macroprolactinemic patients is lower compared with the true hyperprolactinemic patients, but may be higher than that found in other recent studies and in the general population.
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Adenoma/epidemiologia , Hiperprolactinemia/complicações , Neoplasias Hipofisárias/epidemiologia , Prolactinoma/complicações , Adenoma/sangue , Adulto , Feminino , Humanos , Hiperprolactinemia/sangue , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Hipófise/patologia , Neoplasias Hipofisárias/sangue , Prevalência , Prolactina/sangue , Prolactinoma/sangue , Estudos RetrospectivosAssuntos
Neoplasias das Glândulas Suprarrenais/complicações , Febre de Causa Desconhecida/etiologia , Interleucina-6/metabolismo , Proteínas de Neoplasias/metabolismo , Feocromocitoma/complicações , Adolescente , Neoplasias das Glândulas Suprarrenais/metabolismo , Feminino , Humanos , Feocromocitoma/metabolismo , Fatores de TempoAssuntos
Adolescente , Feminino , Humanos , Neoplasias das Glândulas Suprarrenais/complicações , Febre de Causa Desconhecida/etiologia , /metabolismo , Proteínas de Neoplasias/metabolismo , Feocromocitoma/complicações , Neoplasias das Glândulas Suprarrenais/metabolismo , Feocromocitoma/metabolismo , Fatores de TempoAssuntos
Agranulocitose/patologia , Anticorpos Anticitoplasma de Neutrófilos/metabolismo , Doenças da Medula Óssea/patologia , Plasmócitos/patologia , Propiltiouracila/efeitos adversos , Vasculite/induzido quimicamente , Vasculite/imunologia , Adulto , Agranulocitose/induzido quimicamente , Agranulocitose/metabolismo , Doenças da Medula Óssea/induzido quimicamente , Doenças da Medula Óssea/metabolismo , Feminino , Doença de Graves/tratamento farmacológico , Humanos , Propiltiouracila/uso terapêutico , Vasculite/patologiaRESUMO
OBJECTIVE: The study aimed to investigate the effect of high dose radioactive iodine (RAI) on parathyroid function in patients with differentiated thyroid cancer. METHODS: Nineteen patients (8 men/11 women, age 46.5 +/- 13.2 years) undergoing RAI for thyroid remnant ablation were enrolled in the study. The biochemical parameters related to parathyroid function [serum calcium (Ca), phosphate (P), creatinine (Cr), alkaline phosphatase (ALP), intact parathyroid hormone (iPTH), urinary Ca, cAMP concentrations and the maximum tubular capacity for phosphate per unit volume of glomerular filtrate (TmP/GFR)] were evaluated at baseline and at the 1st, 3rd, 6th and 12th months of RAI administration. SPSS 15.0 was used for statistical analysis. RESULTS: For all patients, thyroid-stimulating hormone levels were >30 U/ml at baseline and <0.1 U/ml at the following visits. Serum iPTH levels were decreased significantly at the 6th month and reached basal levels at the 12th month (baseline vs. 6th p = 0.027, 1st vs. 6th p = 0.011, 3rd vs. 6th p = 0.047, 3rd vs. 12th p = 0.014, 6th vs. 12th p = 0.001). At the 6th month, P and TmP/GFR levels were higher (p = 0.036, 0.017, respectively), and urinary cAMP measurements were lower (p = 0.020) compared to those of the 1st month. No difference was detected concerning the other parameters. Serum Ca levels decreased below 2.1 mmol/l in several patients (n = 5 at 1st month, n = 4 at 3rd month, n = 8 at 6th month and n = 3 at 12th month) without clinical symptoms. CONCLUSIONS: The study indicated a transient decline in PTH levels at the 6th month following RAI therapy. Although this decrease did not cause symptoms in any of the present cases, this pattern might be important especially in individuals with diminished parathyroid background.
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Radioisótopos do Iodo/administração & dosagem , Radioisótopos do Iodo/efeitos adversos , Glândulas Paratireoides/fisiopatologia , Glândulas Paratireoides/efeitos da radiação , Doses de Radiação , Radioterapia/efeitos adversos , Neoplasias da Glândula Tireoide/radioterapia , Cálcio/sangue , Feminino , Humanos , Radioisótopos do Iodo/uso terapêutico , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/metabolismo , Hormônio Paratireóideo/sangue , Dosagem Radioterapêutica , Neoplasias da Glândula Tireoide/sangue , Fatores de TempoRESUMO
Familial tumoral calcinosis (TC) is characterized by elevated serum phosphate concentrations, normal or elevated 1,25(OH)2 vitamin D, as well as periarticular and vascular calcifications. Recessive mutations in the mucin-like glycosyltransferase GalNAc transferase-3 (GALNT3) and the phosphaturic hormone fibroblast growth factor-23 (FGF23) have been shown to result in TC. In the present study, mutational analyses were performed on two patients with TC to determine the molecular basis of their diseases. Analysis of the first patient revealed a novel, homozygous base insertion (1102_1103insT) in GALNT3 exon 5 that results in a frameshift and premature stop codon (E375X). The second patient had a novel homozygous transition (1460 g>a) in GALNT3 exon 7, which caused a nonsense mutation (W487X). Both mutations are predicted to markedly truncate the mature GALNT3 protein product. Although the patients carry GALNT3 mutations, these individuals presented with low-normal serum concentrations of intact biologically active FGF23 and high levels of C-terminal FGF23. In order to discern a possible relationship between GALNT3 and FGF23 in TC, a comprehensive assessment of the reported TC mutations was also performed. In summary, we have detected novel GALNT3 mutations that result in familial TC, and show that disturbed serum FGF23 concentrations are present in our TC cases as well as in previously reported cases. These studies expand our current genetic understanding of familial TC, and support a pathophysiological association between GALNT3 and FGF23.
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Calcinose/genética , Mutação , N-Acetilgalactosaminiltransferases/genética , Sequência de Aminoácidos , Sequência de Bases , Calcinose/patologia , Análise Mutacional de DNA , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/sangue , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Humanos , Dados de Sequência Molecular , N-Acetilgalactosaminiltransferases/sangue , N-Acetilgalactosaminiltransferases/metabolismo , Polipeptídeo N-AcetilgalactosaminiltransferaseRESUMO
BACKGROUND: Clodronic acid, a first-generation bisphosphonate, has been successfully used in the treatment of high bone turnover states, Paget's disease and osteolytic bone metastases. However, controversies remain over its optimal dosage and method of administration in the treatment of postmenopausal osteoporosis. In this study we aimed to evaluate the effect of clodronic acid treatment for 3 years on bone mineral density (BMD) in women with postmenopausal osteoporosis. METHODS: This was a prospective, open-label, randomised, controlled study that was conducted in an outpatient clinic at the Bone Metabolism Unit of a tertiary referral centre university hospital. Thirty postmenopausal women (age range 48-73 years) with osteoporosis and a control group of 49 osteoporotic women (age range 47-74 years) received randomised therapy. The clodronic acid group of participants received oral doses of clodronic acid 800 mg plus elemental calcium 500 mg and 400 IU of vitamin D daily, while the control group was treated with calcium and vitamin D only. BMD was measured by dual energy x-ray absorptiometry at yearly intervals. Biochemical markers of bone turnover were also measured. RESULTS: In this clinical study of postmenopausal women with osteoporosis, 36 months of clodronic acid treatment significantly increased average femoral neck BMD by 3.2 +/- 2.9%, trochanter BMD by 2.2 +/- 2.9% and lumbar spine BMD by 3.1 +/- 3%. In the control group, femoral neck, trochanter and lumbar spine BMD decreased by -6 +/- 2.7%, -7.3 +/- 2.5% and -5.4 +/- 2%, respectively (p<0.01, p<0.05 and p<0.05 for clodronic acid vs control, respectively). There was a significant decrease in urinary hydroxyproline (-38.3%) over 3 years in the clodronic acid group compared with baseline (p<0.05), while no significant change occurred in the control group. Clodronic acid was well tolerated and compliance was good. There were no clinically meaningful differences in the incidence of individual adverse events between the groups. CONCLUSION: These results indicate that daily oral administration of clodronic acid 800 mg provides benefits to skeletal bone density in osteoporotic postmenopausal women. Calcium and vitamin D supplementation alone did not prevent further bone loss.
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Conservadores da Densidade Óssea/uso terapêutico , Ácido Clodrônico/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Idoso , Densidade Óssea/efeitos dos fármacos , Cálcio/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Vitamina D/uso terapêutico , Vitaminas/uso terapêuticoRESUMO
Lymphocytic hypophysitis is an unusual inflammatory lesion that is caused by autoimmune destruction of the pituitary gland. We report a case of 42-year-old man who presented with a 6-month history of severe headache, blurred vision in the right eye, hearing loss, polyuria, polydipsia, and impotence. Medical history showed that he and his mother had osteopetrosis. The results of the physical examination and laboratory tests showed that secondary hypothyroidism, hypogonadism, and hypocortisolism had developed. Central diabetes insipidus was diagnosed by water deprivation test. MRI of the sella showed pituitary enlargement with symmetrical suprasellar expansion, compression of the chiasma, thickened infundibulum, and involvement of both bilateral cavernous sinuses and clivus. Hormonal substitution with hydrocortisone, levothyroxine, and DDAVP resulted in rapid improvement of all symptoms and signs. Transsphenoidal biopsy was diagnostic of lymphocytic hypophysitis. In spite of extensive literature reviewing, we have not been aware of any case of lymphocytic hypophysitis with clivus involvement. The present case represents a variant of lymphocytic hypophysitis which has progressed to involve bilateral cavernous sinuses and the clivus.
Assuntos
Doenças Autoimunes , Hipopituitarismo , Linfocitose , Adulto , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/patologia , Seio Cavernoso/patologia , Fossa Craniana Posterior/patologia , Desamino Arginina Vasopressina/uso terapêutico , Diabetes Insípido Neurogênico/etiologia , Terapia de Reposição Hormonal , Humanos , Hidrocortisona/uso terapêutico , Hipopituitarismo/diagnóstico , Hipopituitarismo/tratamento farmacológico , Hipopituitarismo/patologia , Linfocitose/diagnóstico , Linfocitose/dietoterapia , Linfocitose/patologia , Masculino , Tiroxina/uso terapêuticoRESUMO
The syndrome of McCune-Albright syndrome (MAS) is clasically defined as a triad presentation with the findings of polyostotic fibrous dysplasia, café-au-lait spots, and sexual precocity. However, not all patients present with complete symptoms. A 52-year-old man was diagnosed as having a variant of McCune-Albright syndrome with the following findings: polyostotic fibrous dysplasia, acromegaly due to pituitary tumor and subclinical hyperthyroidism due to toxic multinodular goiter. Sexual precocity and café-au-lait spots were not noted. Acromegaly was confirmed by laboratory examination (IGF-1, glucose suppression test and TRH stimulation test). Long acting somatostatin analogue was used as treatment. Although the pituitary tumor could not be removed due to technical problems, mass lesions on the cranium were removed subtotally. Histopathological evaluation demonstrated that the lesion complied with fibrous dysplasia. Genomic DNAs were isolated from the craniofacial bones and peripheral leucocytes of the patient. After amplifying the related regions, Gs alpha (Gs alpha) gene was analysed by automatic DNA sequence analysis. An activating mutation of the Gs alpha gene (Arg 201 Cys) was found in the genomic DNA isolated from the bone tissue of the patient, but not in the genomic DNA isolated from the blood. We described a case of MAS associated with Gs alpha mutation in the bone tissue, presenting with polyostotic fibrous dysplasia, subclinical hyperthyroidism and acromegaly.