RESUMO
Three euthyroid patients with Hashimoto's thyroiditis developed hypothyroidism after the administration of rifampin. We studied 67 patients with tuberculosis. All of them were treated with rifampin. Of the 67 patients, 42 had negative tests for anti-thyroid antibodies (ATA) and 25 had positive tests for ATA. The diagnosis of Hashimoto's thyroiditis was made on the basis of positive tests for ATA. After the administration of rifampin, TSH levels were not significantly altered in all of the former 42 ATA-negative patients and in 22 of the latter 25 ATA-positives, but TSH levels increased in the other three (Patients 1, 2 and 3) of the latter 25 ATA-positives. Three euthyroid Hashimoto's patients (Patients 1, 2 and 3) developed hypothyroidism after the administration of rifampin. This rifampin-induced hypothyroidism resolved in each, once rifampin was discontinued. A) Patient 1: a 62-yr-old man with lymphoma had pulmonary tuberculosis. After the administration of rifampin, serum TSH increased to 170 mU/l; B) Patient 2: a peritoneal-biopsy specimen containing Langhans' giant cells led to a diagnosis of tuberculous peritonitis in a 66-yr-old woman with ascites. After the administration of rifampin, TSH increased to 12.4 mU/l; C) Patient 3: a 56-yr-old woman with a liver abscess and lymphadenopathy underwent lymph-node biopsy that showed Mycobacterium tuberculosis with caseating granulomas. After the administration of rifampin, TSH increased to 21.3 mU/l. After its administration, Patients 1, 2 and 3 developed hypothyroidism, and received T4. When rifampin was discontinued, the hypothyroidism resolved. After the course of rifampin-therapy had been completed, T4 was discontinued. At-risk patients who receive rifampin may become hypothyroid.
Assuntos
Antibióticos Antituberculose/efeitos adversos , Hipotireoidismo/induzido quimicamente , Rifampina/efeitos adversos , Idoso , Feminino , Doença de Hashimoto/complicações , Humanos , Hipotireoidismo/complicações , Linfoma/complicações , Masculino , Pessoa de Meia-Idade , Peritonite/complicações , Peritonite/tratamento farmacológico , Rifampina/uso terapêutico , Tireotropina/sangue , Tiroxina/administração & dosagem , Tuberculose/tratamento farmacológicoRESUMO
AIM/HYPOTHESIS: We analysed Japanese MODY patients for mutations in the HNF-1 alpha gene. METHODS: Fifty unrelated Japanese patients with early-onset diabetes (diagnosed at 25 years of age or younger) or with a strong family history of diabetes were screened for mutations in the HNF-1 alpha gene. Functional studies of the mutant HNF-1alpha were carried out. RESULTS: We identified three new mutations in the HNF-1 alpha gene in the families with a strong family history for diabetes. One mutation (L518P519fsTCC --> A) was identified in three unrelated families, while the other two mutations (T521I and V617I) were identified in one family. We also identified the A site of the promoter (+102G-to-C), which was reported previously. We examined the functional properties of the mutant HNF-1alpha. By increasing the amount of L518P519fsTCC-->A-HNF-1alpha, increasing inhibition of the transcription of human transthyretin (TTR) was observed (up to 61% of the control). Increasing amounts of T521I-HNF-1alpha or V617I-HNF-1alpha mutant proteins increased TTR promoter transcription up to 4.3-fold and 2.4-fold, respectively, whereas both increased transcription up to 12.4-fold of the control. CONCLUSION/INTERPRETATION: The L518P519fsTCC --> A was identified for the first time and this mutation might be a common cause of Japanese MODY3 in Okinawa area. In addition, both the T521I and V617I mutations were present in two patients in the same family. Since the prevalence of these mutations is relatively high (10%, 5/50), the HNF-1 alpha gene needs to be screened for mutations in patients either with early-onset diabetes or with a strong family history for diabetes.
Assuntos
Proteínas de Ligação a DNA , Diabetes Mellitus Tipo 2/genética , Proteínas Nucleares , Fatores de Transcrição/genética , Adulto , Substituição de Aminoácidos , Animais , Células COS , Cisteína , Feminino , Mutação da Fase de Leitura , Deleção de Genes , Glicina , Fator 1 Nuclear de Hepatócito , Fator 1-alfa Nuclear de Hepatócito , Fator 1-beta Nuclear de Hepatócito , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Mutação de Sentido Incorreto , Linhagem , Ativação TranscricionalRESUMO
In hyperthyroid Graves' disease, short-term methimazole is sufficient to induce lasting remission in some patients, but even long-term treatment fails to do so in others. We have evaluated the role of autoimmune abnormalities in the helper T cell type 2 (TH2)-interleukin-13 (IL-13)-TSH receptor system in maintaining hyperthyroidism by comparing IgE levels in patients with various thyroid diseases. One hundred and ninety-three patients with hyperthyroid Graves' disease were treated with methimazole, and blood samples were obtained to measure serum levels of T4, T3, TSH, thyroglobulin, antimicrosomal antibody, TSH binding inhibitory Ig (TBII), thyroid-stimulating antibody, thyroid stimulation-blocking antibody, IgE, interferon-gamma, IL-4, and IL-13. Elevation of serum IgE (> or = 170 U/mL) was found in 35.5% of patients with hyperthyroid Graves' disease, and serum levels of T4, T:1, antimicrosomal antibody, and TBII were significantly greater in patients with IgE elevation than in those with normal serum IgE. During methimazole treatment, there was a parallel decrease in the serum T4 concentration in the presence or absence of an IgE elevation. However, there was a significantly smaller decrease in TBII in patients with elevated IgE than in those with normal IgE. As a result, the remission rate was significantly greater in patients with normal IgE than in those with IgE elevation. Serum levels of IL-13 were elevated in 64.7% of patients with IgE elevation in the absence of detectable TH1 marker, interferon-gamma. These findings suggest that in one third of patients with hyperthyroid Graves' disease, TH2 cells are stimulated and secrete excess amounts of IL-13, which subsequently stimulates B cells to synthesize more TSH receptor antibody and IgE, so that during methimazole treatment TBII decreases less in patients with IgE elevation, producing a lower remission rate.
Assuntos
Doença de Graves/imunologia , Imunoglobulina E/sangue , Metimazol/uso terapêutico , Células Th2/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antitireóideos/uso terapêutico , Biomarcadores/sangue , Feminino , Bócio/sangue , Bócio/imunologia , Bócio Nodular/sangue , Bócio Nodular/imunologia , Doença de Graves/sangue , Doença de Graves/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Tireoidite Autoimune/sangue , Tireoidite Autoimune/imunologia , Tiroxina/sangue , Fatores de Tempo , Tri-Iodotironina/sangueRESUMO
OBJECTIVE: We studied the association between type 1 diabetes with autoimmune thyroid disease (AITD) and A/G allele polymorphism in exon 1 of the CTLA-4 gene in a Japanese population. RESEARCH DESIGN AND METHODS: We studied 74 Japanese type 1 diabetic patients with or without AITD and 107 normal subjects to identify the association between CTLA-4 polymorphism and type 1 diabetes using polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The frequency of the CTLA-4 G allele differed significantly between the type 1 diabetic patients (61%) and the normal control subjects (48%) (P = 0.016). The difference in the CTLA-4 G allele became greater between patients with a younger age of onset of type 1 diabetes (age at onset <30 years) and the normal control subjects (64% and 48%, respectively). However, the frequency of the CTLA-4 G allele did not differ between type 1 diabetic patients with younger and older age of onset (64% vs. 57%). The G allele frequencies in the patients with younger-onset type 1 diabetes and AITD increased more than in the control patients (P = 0.025). These differences reflected a significant increase in the frequency of G/G genotype--that is, 54% in those with younger-onset type 1 diabetes and AITD, 39% in those without AITD, and 28% in control subjects. CONCLUSIONS: An association was detected between the CTLA-4 gene polymorphism and younger-onset type 1 diabetes with AITD. The G variant was suggested to be genetically linked to AITD-associated type 1 diabetes of younger onset in this apanese population. The defect in these patients presumably lies in a T-cell-mediated autoimmune mechanism.
Assuntos
Antígenos de Diferenciação/genética , Povo Asiático/genética , Diabetes Mellitus Tipo 1/genética , Imunoconjugados , Polimorfismo Genético , Tireoidite Autoimune/genética , Abatacepte , Adolescente , Adulto , Idade de Início , Idoso , Alanina , Antígenos CD , Autoanticorpos/sangue , Antígeno CTLA-4 , Criança , Diabetes Mellitus Tipo 1/imunologia , Feminino , Glutamato Descarboxilase/imunologia , Humanos , Ilhotas Pancreáticas/imunologia , Isoenzimas/imunologia , Japão , Masculino , Pessoa de Meia-Idade , Treonina , Tireoidite Autoimune/imunologiaRESUMO
Diabetic muscle infarction (DMI) is a rare complication of diabetes mellitus. We report the first recorded case in Japan. A 45-year-old Japanese woman presented with severe pain in the left antero-medial thigh. She had a 14-year history of Type 2 diabetes mellitus (DM). She had first noticed pain in her left thigh after a walk 2 weeks prior to presentation. The pain worsened progressively. She noticed a firm mass in her left thigh. T2-weighted magnetic resonance imaging (MRI) demonstrated a high-intensity signal in the muscle bulk of the anterior component of the left thigh. A needle biopsy of the mass showed necrosis. She was treated with bedrest and an antiplatelet agent. The mass disappeared 8 weeks after admission. DMI is a rare complication of poorly controlled diabetes mellitus. Twenty-seven cases with DMI have been reported in the English literature but we believe this is the first Japanese case with DMI.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Infarto/diagnóstico , Músculo Esquelético/irrigação sanguínea , Repouso em Cama , Biópsia , Feminino , Humanos , Infarto/fisiopatologia , Infarto/terapia , Japão , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Dor , Inibidores da Agregação Plaquetária/uso terapêuticoRESUMO
A 71-year-old woman was admitted to our hospital because of severe hypertriglyceridemia. The patient had a 26-year history of non-insulin-dependent diabetes mellitus and hyperlipidemia (T-chol 300 mg/dl, TG 300 mg/dl). She was treated with sulfonylurea and clofibrate. Seven years before admission, she had undergone a radical mastectomy for cancer of the left breast. After the operation, she had received tamoxifen and fluorouracil. One month before admission, she had marked hypertriglyceridemia (triglyceride 2,106 mg/dl). After discontinuation of tamoxifen and fluorouracil, her serum triglyceride level decreased to 372 mg/dl; when tamoxifen was given again, it increased to 581 mg/dl, and her hepatic triglyceride lipase activity decreased from 0.228 to 0.164 mumol FFA/ml/min. Apolipoprotein E phenotype was wild type E3/3. The concentration of sex-hormone-binding globulin increased from 110 to 130 nmol/l. These changes associated with tamoxifen treatment were similar to those seen after administration of estrogen. Tamoxifen, an anti-estrogen, has been used as adjuvant therapy in cases of estrogen-receptor-positive breast cancer. Tamoxifen has some weak estrogenic activity. The tamoxifen-induced hypertriglyceridemia seen in this case was an effect of its estrogenic action.
Assuntos
Antagonistas de Estrogênios/efeitos adversos , Hipertrigliceridemia/induzido quimicamente , Tamoxifeno/efeitos adversos , Idoso , Neoplasias da Mama/tratamento farmacológico , Feminino , HumanosRESUMO
Marked differences have been reported in the prevalence of glutamic acid decarboxylase (GAD) antibodies between Caucasian (63-84%) and Japanese (30-50%) or Asian (5-50%) IDDM patients. Using a new immunoprecipitation assay based on 125I-labelled recombinant human GAD65 we have reassessed prevalence of GAD65 antibodies in Japanese patients. We also assessed prevalence of IA-2 antibodies. GAD65 antibodies were detected in 83.3% of sera taken within 1 year of onset, comparable to the prevalence reported in Caucasian patients. Positivity decreased to 66.7% after 2 to 3 years and to 54.3% after 3 years from onset, still higher than previously reported Asian prevalence. Except in one patient, high antibody levels persisted chronically, up to 12 years. There was no difference in the prevalence of GAD65 antibodies between Japanese IDDM patients with and without autoimmune thyroid disease (AITD). IA-2 antibodies were detected in 64.7% of sera taken within 1 year of onset. Prevalence of IA-2 antibodies was lower than that of GAD65 antibodies. The difference in positivity in Asian IDDM patients between present and previous reports arose from the sensitivity of our assay for GAD65 antibodies. Additionally, the patients we studied had classic IDDM with a well-defined onset. We conclude that prevalence of GAD65 antibodies in Japanese IDDM patients is comparable to that in Western studies. There was no relationship of GAD65 antibody positivity to coexistence of AITD. Our results suggest that autoimmunity is the most significant cause of Japanese IDDM.
Assuntos
Autoanticorpos/sangue , Diabetes Mellitus Tipo 1/imunologia , Glutamato Descarboxilase/imunologia , Glândula Tireoide/imunologia , Adolescente , Adulto , Autoanticorpos/imunologia , Autoanticorpos/metabolismo , Criança , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/imunologia , Feminino , Seguimentos , Glutamato Descarboxilase/análise , Humanos , Radioisótopos do Iodo , Japão , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Testes de Precipitina , Proteínas Recombinantes/análise , Valores de Referência , Tireoidite Autoimune/sangue , Tireoidite Autoimune/imunologia , Fatores de TempoRESUMO
OBJECTIVE: The role of the renin-aldosterone system and the ability of renal sodium reabsorption to facilitate pressure natriuresis were analyzed by using a sufficient number of Japanese patients with essential hypertension. METHODS: We studied 3222 normal Japanese subjects (610 in Kashiwa City Hospital and 2612 in Shinshu University Hospital), 741 Japanese patients with essential hypertension (256 in Kashiwa City Hospital and 485 in Shinshu University Hospital), 20 patients with aldosterone-producing adenomas and 11 patients with idiopathic hyperaldosteronism to determine the possible roles of sodium, renal function, and plasma aldosterone concentration (PAC) on blood pressure elevation. Inappropriate elevation of aldosterone levels [elevation of the aldosterone:plasma renin activity (PRA) ratio] was used to assess aldosterone action. RESULTS: The peak of the serum sodium distribution curve was approximately 2 mmol/l higher in the patients with essential hypertension than it was in controls. The prevalence of higher serum sodium concentrations (> or = 147 mmol/l) also was increased significantly hypertensive patients. Age-related deterioration of renal function did not explain the hypertension and abnormal sodium metabolism in the hypertensive patients. In stepwise regression analysis, the serum sodium concentration was related inversely to the PRA and positively to the PAC:PRA ratio. Although there was an inverse relationship between urinary sodium excretion (representing sodium intake) and the PRA, urinary sodium excretion proved not to be significant as a source of variation in the PAC or in the PAC:PRA ratio in the hypertensive patients. Although the PAC was within the normal range in patients with serum sodium concentrations of 147 mmol/l or more and an elevated PAC:PRA ratio, it was inappropriately high for the stimulus applied, as indicated by the PRA; this is similar to the situation with aldosterone-producing adenomas or idiopathic hyperaldosteronism. CONCLUSION: Serum sodium distribution patterns differed between normal subjects and patients with essential hypertension in this Japanese population. The deterioration of renal function and increased sodium intake did not explain this abnormal sodium metabolism. A higher serum sodium concentration is related to an elevated blood pressure, and, in some patients, an inappropriate elevation of plasma aldosterone levels. Of the Japanese hypertensive patients, 10-14% exhibited serum sodium concentrations of 147 mmol/l or more and inappropriate elevations of aldosterone level (suppressed PRA and normal aldosterone level). The defect in these patients presumably lies in the inappropriately high secretion of aldosterone.
Assuntos
Hipertensão/metabolismo , Rim/fisiopatologia , Sistema Renina-Angiotensina/fisiologia , Sódio/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/sangue , Aldosterona/sangue , Pressão Sanguínea/fisiologia , Feminino , Humanos , Hipertensão/sangue , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Sódio/sangue , Sódio/urinaRESUMO
OBJECTIVE: Human T-lymphotrophic virus type I (HTLV-I) is a retrovirus that causes adult T-cell leukaemia (ATL). This virus is associated with a variety of autoimmune disorders. The possible association between HTLV-I Infection and autoimmune thyroiditis has not been fully studied. We therefore evaluated anti-thyroid peroxidase antibodies (TPOAb) and anti-thyroglobulin antibodies (TGAb) in the sera of patients with ATL, carriers of HTLV-I, and in healthy control subjects to investigate the possible association between such infection and auto-immune thyroiditis. PATIENTS AND METHODS: Fifty-two ATL patients (21 males, 31 females; mean age 56.4 years) and 50 HTLV-I carriers (18 males, 32 females; mean age 56.7 years) were studied. The control subjects were 877 healthy adults (271 males, 606 females; mean age 54.8 years) who were negative for HTLV-I antibody. TPOAb, TGAb, thyroxine (T4) and thyrotrophin (TSH) were measured in serum using a radioimmunoassay kit. RESULTS: Positivity for thyroid autoantibodies (TPOAb and/or TGAb) was found in 21 of 52 ATL patients (40.4%), 15 of 50 HTLV-I carriers (30.0%), and 120 of 877 control subjects (13.7%). The difference between the HTLV-I-Infected and the control subjects was statistically significant (P < 0.005). Female control subjects had a significantly higher prevalence of positivity for thyroid autoantibodies than the males (17.3 vs 5.5%, P < 0.001). Carriers of HTLV-I and patients with ATL of each sex showed an equally high prevalence of positivity for thyroid autoantibodies. Of the subjects who were positive for thyroid autoantibody, 7.5% of control subjects, 19.0% of ATL patients, and 40.0% of HTLV-I carriers had hypothyroidism. A significant difference in this respect was noted between the HTLV-I infected subjects and the control subjects (P < 0.005). CONCLUSIONS: This study demonstrates a high prevalence of positivity for thyroid autoantibodies (TPOAb and/ or TGAb) in the adult T-cell leukaemia patients and the HTLV-I carriers. The adult T-cell leukaemia patients and the HTLV-I carriers each had a high prevalence of hypothyroidism. There was an association between HTLV-I infection and autoimmune thyroiditis.
Assuntos
Portador Sadio/imunologia , Infecções por Deltaretrovirus/imunologia , Vírus Linfotrópico T Tipo 1 Humano , Leucemia de Células T/imunologia , Tireoidite Autoimune/virologia , Autoanticorpos/sangue , Feminino , Humanos , Hipotireoidismo/imunologia , Hipotireoidismo/virologia , Iodeto Peroxidase/imunologia , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Tireoglobulina/imunologia , Tireoidite Autoimune/imunologiaRESUMO
Mutation of the cytochrome P450c17 (CYP17) gene causes 17 alpha-hydroxylase deficiency (17OHD). Recently, several researchers have elucidated the molecular basis of 17OHD by gene analysis. We experienced a case of 17OHD and intended to reveal the abnormality of the CYP17 gene in this Japanese female with 17OHD. Leukocytes were obtained from the patient, her mother and sister, and normal control subjects. We amplified the CYP17 gene using polymerase chain reaction and performed the sequence analysis using the dideoxy terminator method and restriction enzyme analysis. We found that the patient had one base-pair deletion at the position of amino acid 438. An identical result was obtained with restriction enzyme analysis. This G deletion altered the reading frame and resulted in a premature stop codon at position 443; the ligand of heme iron (Cys: cystine 442) was absent. This small mutation may account for the patient's clinical manifestations of 17OHD. This is the first case of 17OHD with only one base pair deletion of the CYP17 gene.
Assuntos
Hiperplasia Suprarrenal Congênita , Deleção de Sequência , Esteroide 17-alfa-Hidroxilase/genética , Adulto , Sequência de Bases , Éxons , Feminino , Humanos , Masculino , Dados de Sequência Molecular , Núcleo Familiar , Reação em Cadeia da Polimerase , Valores de Referência , Mapeamento por RestriçãoRESUMO
In order to investigate the extrapituitary action of TRH on the thyroid, serum T3, T4, and TSH levels after im administration of TRH were analyzed in 63 patients with untreated hyperthyroid Graves' disease, in 60 euthyroid patients with treated Graves' disease, in 8 patients with subacute thyroiditis, and in 140 healthy subjects. TRH administration in the healthy subjects resulted in a significant increase in serum T3 and T4 levels after 2 h. However, in the patients with untreated hyperthyroid Graves' disease, a significant decrease in serum T3 and T4 levels with undetectable TSH was found 2 h after TRH administration. In the patients with subacute thyroiditis, serum T3 levels also significantly decreased after TRH administration. When a decrease in serum T3 and T4 levels after TRH administration in the patients with hyperthyroid Graves' disease was analyzed in terms of thyroid microsomal antibody and thyroglobulin antibody, a decrease in serum T3 and T4 levels was largest in patients with thyroid microsomal antibody and thyroglobulin antibody. In contrast, an increase in serum T3 and T4 levels in response to TRH in the euthyroid patients with Graves' disease was largest in patients without thyroid autoantibodies. It is concluded that TRH acts directly on the thyroid to suppress the thyroid hormone secreting activity in the absence of circulating TSH and that thyroid autoantibodies affect thyroidal response after TRH administration.
Assuntos
Doença de Graves/sangue , Metimazol/uso terapêutico , Tireoidite Subaguda/sangue , Hormônio Liberador de Tireotropina/farmacologia , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Adolescente , Adulto , Idoso , Autoanticorpos/sangue , Criança , Feminino , Doença de Graves/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Glândula Tireoide/imunologiaRESUMO
In an attempt to study the natural course of Hashimoto's thyroiditis and simple goiter, 74 euthryroid patients with Hashimoto's thyroiditis and 212 patients with simple goiter were followed for 10 years. In 204 patients with simple goiter (96.2%) it remained as a simple goiter throughout the observation period, whereas 8 patients (3.8%) later had Hashimoto's thyroiditis as evidenced by the appearance of circulating thyroid autoantibodies. These 8 patients had HLA typing significantly different from that of control subjects. None of the patients with simple goiter had hyperthyroid Graves' disease despite the fact that 17.5% of those patients had mild to moderate exophthalmos with either Moebius' sign or von Graefe's sign. In contrast, 12 patients with Hashimoto's thyroiditis (16.2%) had exophthalmos with Moebius' sign and/or von Graefe's sign, and 4 of 12 such patients later had hyperthyroid Graves' disease. TSH binding inhibitory immunoglobulin was detected in 3 of 4 such patients with hyperthyroid Graves' disease. Forty-nine patients with Hashimoto's thyroiditis (66.2%) still remained euthyroid but 20 of those (27.0%) turned into hypothyroidism during the 10-year follow-up.
Assuntos
Bócio Nodular/fisiopatologia , Doença de Graves/fisiopatologia , Glândula Tireoide/fisiopatologia , Tireoidite Autoimune/fisiopatologia , Adolescente , Adulto , Idoso , Autoanticorpos/sangue , Criança , Exoftalmia/etiologia , Feminino , Seguimentos , Bócio Nodular/sangue , Doença de Graves/sangue , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Glândula Tireoide/imunologia , Hormônios Tireóideos/sangue , Tireoidite Autoimune/sangueRESUMO
Although the factors that cause developments or exacerbations of autoimmune thyroid dysfunction are not known, the changes of glucocorticoids might modulate the autoimmune responses. We compared the postoperative changes in thyroid function in one patient with Carney's complex with primary adrenocortical nodular dysplasia (PAND) and 19 patients with Cushing's disease due to ACTH-producing pituitary adenoma. Thyroid dysfunction developed after surgery for glucocorticoid excess in two patients; one with Carney's complex had transient hypothyroidism after bilateral adrenalectomy for PAND, and the other had transient hyperthyroidism due to thyroiditis after removal of ACTH-producing pituitary adenoma for Cushing's disease. Both patients had no thyroid autoantibodies at the time of surgery. None of the remaining 18 patients had clinically evident thyroid disease or increased antithyroidantibody titers. Development of autoimmune thyroid dysfunction may be observed after surgery for glucocorticoid excess in the patients with any forms of Cushing's syndrome, even who do not have thyroid antibodies.
Assuntos
Adenoma/cirurgia , Doenças do Córtex Suprarrenal/cirurgia , Adrenalectomia , Doenças Autoimunes/etiologia , Síndrome de Cushing/cirurgia , Hipertireoidismo/etiologia , Hipotireoidismo/etiologia , Neoplasias Hipofisárias/cirurgia , Complicações Pós-Operatórias , Adenoma/metabolismo , Hormônio Adrenocorticotrópico/metabolismo , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/metabolismoRESUMO
Carney's complex is composed of myxoma, spotty pigmentation and endocrine overactivity. A 27-year-old male was diagnosed to have Carney's complex on the basis of intense spotty pigmentations on his face, soles and palms, and bilateral adrenal nodular hyperplasia on computed tomography scanning (CT) and magnetic resonance imaging (MRI). Total bilateral adrenectomy was done; histological findings were compatible with primary pigmented adrenocortical disease (PPNAD). Recently, his sister and one of his brothers were suspected to have Carney's complex with PPNAD. We report the first familial case of Carney's complex with PPNAD and spotty pigmentations in Japan.
Assuntos
Doenças do Córtex Suprarrenal/complicações , Mixoma/complicações , Transtornos da Pigmentação/complicações , Doenças do Córtex Suprarrenal/cirurgia , Glândulas Suprarrenais/patologia , Adrenalectomia , Adulto , Síndrome de Cushing/complicações , Síndrome de Cushing/cirurgia , Humanos , Hiperplasia , MasculinoRESUMO
We experienced 41 cases of Cushing's syndrome (12 males and 29 females, 15 years old - 65 years old) during the last 20 years. These included 20 patients with unilateral adrenal adenoma (Cushing's syndrome), 19 patients with bilateral adrenal hyperplasia (Cushing's disease), one patient with adrenal carcinoma and one patient with primary adrenocortical nodular dysplasia (PAND). Moreover, these cases included some special ones, i.e. 5 cases with destructive thyroiditis after treatment, 2 cases with aggravation of arthritis after treatment, a case of Carney's complex with PAND, one case with paradoxical response to dexamethasone, and one case combined with empty sella syndrome. The most specific clinical signs were moon face (95% occurrence), hypertension (95%) and subcutaneous bruising (80%). Other significant signs were eye edema (66%), buffalo hump (68%), subcutaneous purpura (63%) and osteoporosis (49%). Skin striae was not a common sign in our cases (41%). Renal stone was observed in only 20% of our patients but was a significant sign in this syndrome. There was no difference in the occurrence of each clinical sign between Cushing's syndrome and Cushing's disease. The elevation of white blood cell count (WBC) and serum sodium, a decrease of serum potassium, and a decrease of reabsorption of phosphate (%TRP) were observed. Thyroid-stimulating hormone (TSH) and human growth hormone (HGH) were suppressed in patients with Cushing's syndrome and patients with Cushing's disease. These results were consistent with those of previous reports. However, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (PRL) were high in those patients with Cushing's syndrome and those with Cushing's disease. Oral glucose tolerance test was carried out in 34 patients before and after treatment. Thirty-one percent of those had diabetes mellitus and 26% had impaired glucose tolerance (IGT). The response of IRI in this test was high in patients with Cushing's syndrome and patients with Cushing's disease, and decreased 4 weeks after treatment in those with Cushing's syndrome but remained high in those with Cushing's disease. Plasma ACTH level and urinary 17-OHCS excretion were significantly higher in Cushing's disease than in Cushing's syndrome. During an 8mg-high-dose dexamethasone suppression test, urinary 17-OHCS excretion in 13 of 14 patients with Cushing's disease (93%) was suppressed by more than 50% of baseline on the second day of testing. However, all of 18 patients with Cushing's syndrome, who had an 8mg-dexamethasone suppression test, failed to suppress urinary 17-OHCS by 50% of baseline.(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Adenoma/metabolismo , Neoplasias das Glândulas Suprarrenais/metabolismo , Síndrome de Cushing/metabolismo , Adenoma/diagnóstico , Adolescente , Corticosteroides/metabolismo , Neoplasias das Glândulas Suprarrenais/diagnóstico , Glândulas Suprarrenais/diagnóstico por imagem , Glândulas Suprarrenais/metabolismo , Glândulas Suprarrenais/patologia , Adulto , Idoso , Síndrome de Cushing/diagnóstico , Feminino , Teste de Tolerância a Glucose , Humanos , Hiperplasia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Hormônios Adeno-Hipofisários/metabolismo , Tomografia Computadorizada por Raios XRESUMO
We investigated the in vitro and in vivo effects of MDP-Lys(L18), a derivative of muramyl dipeptide (MDP), on megakaryocyte progenitor cells (megakaryocyte colony-forming units, CFU-Meg) in the mouse bone marrow and spleen. When CFU-Meg culture was performed with a suboptimum concentration (2%) of pokeweed mitogen-stimulated mouse spleen-conditioned medium (PWM-SCM), addition of 0.1-20 micrograms/ml of MDP-Lys(L18) increased the number of megakaryocyte colonies. The size of the megakaryocyte colonies (the number of megakaryocytes per colony) was also significantly increased by the addition of MDP-Lys(L18) under the same culture conditions in comparison with cultures without MDP-Lys(L18). MDP-Lys(L18) itself did not stimulate megakaryocyte colony formation without PWM-SCM, and it failed to enhance megakaryocyte colony formation in cultures with an optimum PWM-SCM concentration (10%). Furthermore, no effect of MDP-Lys(L18) was observed in cultures of phagocytic cell-depleted bone marrow cells. However, MDP-Lys(L18) enhanced megakaryocyte colony formation in cultures of T-lymphocyte-depleted bone marrow cells. The culture supernatant from a macrophage cell line, J774.1, plus MDP-Lys(L18) enhanced in vitro megakaryocyte colony formation in cultures with a suboptimum PWM-SCM concentration. Although interleukin 1 (IL-1)beta in the culture supernatant of J774.1 plus MDP-Lys(L18) was increased in a dose-dependent manner in response to MDP-Lys(L18), the effect of the culture supernatant was not blocked by an anti-IL-1 antibody, and IL-1 beta failed to enhance megakaryocyte colony formation in the presence of suboptimum PWM-SCM levels. The enhancement of megakaryocyte colony formation by MDP-Lys(L18) could be neutralized, however, by an anti-interleukin 6 (IL-6) antibody. Intraperitoneal administration of MDP-Lys(L18) (100 micrograms daily for 3 days) significantly increased the number of bone marrow and spleen megakaryocyte colonies at 24 to 72 h after the final injection. These in vitro and in vivo observations strongly suggest that MDP-Lys(L18) indirectly enhances the proliferation and differentiation of mouse CFU-Meg via colony-stimulating factor(s) other than IL-1, probably as a result of the stimulation of macrophages to produce IL-6.
Assuntos
Acetilmuramil-Alanil-Isoglutamina/análogos & derivados , Hematopoese/efeitos dos fármacos , Megacariócitos/citologia , Acetilmuramil-Alanil-Isoglutamina/farmacologia , Animais , Células da Medula Óssea , Ensaio de Unidades Formadoras de Colônias , Interleucina-1/farmacologia , Interleucina-6/fisiologia , Macrófagos/fisiologia , Masculino , Camundongos , Baço/citologiaRESUMO
A patient with hypogonadotropic hypogonadism and anosmia (Kallmann's syndrome) is described. Anosmia has been believed to be due to hypoplasia of the rhinencephalon. This anatomical defect was demonstrated in vivo in a patient with Kallmann's syndrome by magnetic resonance imaging (MRI).
Assuntos
Hipogonadismo/patologia , Sistema Límbico/anormalidades , Transtornos do Olfato/patologia , Adolescente , Hormônio Foliculoestimulante/sangue , Hormônio Liberador de Gonadotropina/administração & dosagem , Humanos , Hipogonadismo/sangue , Hipogonadismo/complicações , Hormônio Luteinizante/sangue , Imageamento por Ressonância Magnética , Masculino , Transtornos do Olfato/sangue , Transtornos do Olfato/complicações , Síndrome , Testosterona/sangueRESUMO
BACKGROUND: Hypothyroidism may result from the production of antibodies that block the actions of thyrotropin. How often these thyrotropin-blocking antibodies are a cause of hypothyroidism and whether their production may cease, causing hypothyroidism to disappear, have not been extensively studied. METHODS: We determined the frequency with which thyrotropin-blocking antibodies were present in 172 hypothyroid patients with goitrous autoimmune thyroiditis (Hashimoto's disease) and 64 hypothyroid patients with atrophic autoimmune thyroiditis (idiopathic primary hypothyroidism). For 6 to 11 years we then followed 21 of these patients who were found to have thyrotropin-blocking antibodies. They received levothyroxine therapy for 3.5 to 8 years, after which it was discontinued. At frequent intervals during this time we measured the patients' serum concentrations of thyroxine, triiodothyronine, thyrotropin, and thyrotropin-blocking antibodies (measured as immunoglobulins that inhibit thyrotropin binding and immunoglobulins that inhibit thyrotropin bioactivity). RESULTS: Thyrotropin-blocking antibodies were detected in 9 percent of the patients with goitrous autoimmune thyroiditis and in 25 percent of those with atrophic autoimmune thyroiditis. Among the 21 patients studied serially while receiving levothyroxine, thyrotropin-blocking antibodies disappeared in 15 (group 1), 7 of whom had goiter initially, and persisted in 6 (group 2), none of whom had goiter initially. Levothyroxine therapy was subsequently discontinued in these 21 patients. Six of those in group 1 (four with goiter) remained euthyroid (mean follow-up after discontinuation of therapy, 2.1 years), and nine became hypothyroid again within 3 months. All six patients in group 2 remained hypothyroid. CONCLUSIONS: Hypothyroidism in some patients with autoimmune thyroiditis may be due to thyrotropin-blocking antibodies. The production of thyrotropin-blocking antibodies may subside, producing remissions of hypothyroidism. Chronic autoimmune thyroiditis may therefore cause transient as well as permanent hypothyroidism.
Assuntos
Autoanticorpos/análise , Hipotireoidismo/etiologia , Tireoidite Autoimune/complicações , Tireotropina/imunologia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Hipotireoidismo/imunologia , Masculino , Pessoa de Meia-Idade , Remissão Espontânea , Tireoidite Autoimune/tratamento farmacológico , Tireoidite Autoimune/imunologia , Tireotropina/sangue , Tiroxina/sangue , Tiroxina/uso terapêutico , Tri-Iodotironina/sangueRESUMO
A 72-year-old woman complaining of somnolence and thirst was diagnosed to have a hypercalcemic crisis (corrected serum calcium level, 17.4 mg/dl) associated with encephalopathy and nephropathy. Imaging diagnostic techniques demonstrated a retroperitoneal tumor at the median site of right renal pelvis. Hormonal studies revealed that plasma levels of thromboxane B2, prostaglandin (PG) E2, 6-keto prostaglandin F1 alpha (PGF1 alpha) and prostaglandin F2 alpha (PGF2 alpha) were markedly elevated. The tumor was successfully removed by operation; her serum calcium level and PG levels normalized without any treatment indicating that this case belongs to the category of humoral hypercalcemia of malignancy (HHM). Pathologically, this tumor was diagnosed to be a benign neurilemoma. Parathyroid hormone-related protein (PTHrP) radioimmunoassay and Northern blot hybridization for PTHrP mRNA were negative. The current case demonstrates that hypercalcemic crisis could be induced by a curable benign neurilemoma, and suggests that this HHM-like morbidity was associated with markedly elevated plasma PG levels.