RESUMO
Survival rates have been excellent in patients treated for Hodgkin lymphoma (HL) during childhood and adolescence. Unfortunately, severe treatment related late effects have been observed. It was therefore an important aim of the cooperative pediatric HL therapy studies in Germany to reduce the number of late effects without jeopardizing the excellent treatment results. Progress and relapses of HL were analyzed to obtain important information for the future salvage therapy. All late effects were documented and their etiologies analyzed. Information obtained from bacterial infections and late deaths following splenectomy were used to inform patients at risk and their local physicians about necessary preventive measurements. Procarbazine was recognized as major gonadotoxic agent in boys and eliminated successively from the treatment regimens. Parenthood was normal in female patients when compared to the German female population documenting normal ovarian function except in patients with pelvic radiation. Radiation was the most important risk factor for thyroid diseases, cardiac late effects and subsequent malignant neoplasms, especially thyroid and breast cancer. A special screening program was initiated for women with chest radiotherapy, since they had a high risk of breast cancer already at a young age. The results of the HL Late Effects Research Project are important for the aftercare of patients and for the design of future HL treatment regimens.
Assuntos
Terapia Combinada/efeitos adversos , Doença de Hodgkin/terapia , Adolescente , Criança , Detecção Precoce de Câncer , Coração/efeitos da radiação , Doença de Hodgkin/mortalidade , Humanos , Neoplasias Induzidas por Radiação/etiologia , Neoplasias Induzidas por Radiação/prevenção & controle , Infecções Oportunistas/etiologia , Procarbazina/efeitos adversos , Procarbazina/uso terapêutico , Lesões por Radiação/etiologia , Lesões por Radiação/prevenção & controle , Fatores de Risco , Terapia de Salvação/efeitos adversos , Esplenectomia/efeitos adversos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
CONTEXT: In 21-hydroxylase (CYP21A2) deficiency (21OHD), the level of in vitro enzymatic function allows for classification of mutation groups (null, A, B, C) and prediction of disease severity. However, genital virilization in affected females correlates only weakly with CYP21A2 mutation groups, suggesting the influence of genetic modifiers. OBJECTIVE: The objective of the study was to investigate the influence of the polymorphic CAG and GGn repeats of the androgen receptor (AR) gene on the degree of genital virilization in 21OHD females. DESIGN AND PATIENTS: Design of the study was the determination of CYP21A2 genotype, degree of genital virilization (Prader stage), and X-weighted biallelic mean of AR CAG and GGn repeat length in 205 females with 21OHD. OUTCOME MEASUREMENTS: Correlation of AR CAG and GGn repeat lengths with Prader stages using nested stepwise logistic regression analysis was measured. RESULTS: CYP21A2 mutation groups null and A showed significantly higher levels of genital virilization than groups B and C (P < 0.01). However, Prader stages varied considerably within mutation groups: null, Prader I-V (median IV); A, Prader I-V (median IV); B, Prader I-V (median III); C, 0-III (median I). Mean GGn repeat length of patients was not significantly associated with Prader stages, classified as low (0-I), intermediate (II-III), or severe (IV-V) (odds ratio per repeat: 0.98, 95% confidence interval 0.71-1.35). In contrast, patients with Prader 0-I showed a trend toward longer CAG repeats without reaching statistical significance (P = 0.07, odds ratio per repeat: 0.82, 95% confidence interval 0.65-1.02). CONCLUSION: Neither CAG nor GGn repeat lengths are statistically significant modifiers of genital virilization in females with 21OHD.
Assuntos
Hiperplasia Suprarrenal Congênita/genética , Receptores Androgênicos/genética , Esteroide 21-Hidroxilase/genética , Repetições de Trinucleotídeos/genética , Virilismo/genética , Hiperplasia Suprarrenal Congênita/classificação , Hiperplasia Suprarrenal Congênita/patologia , Alelos , Primers do DNA , Feminino , Amplificação de Genes , Genótipo , Humanos , Reação em Cadeia da Polimerase , Deleção de Sequência , Virilismo/classificação , Virilismo/patologiaRESUMO
Congenital adrenal hyperplasia (CAH) [OMIM 201 910] is a group of autosomal recessive disorders most commonly due to 21-hydroxylase deficiency and presenting with a wide range of clinical manifestations. A limited number of inactivating pseudogene-derived mutations account for the majority of 21-hydroxylase gene ( CYP21) mutations, additional rare mutations can be found in single families and small populations. We found three novel CYP21 mutations in CAH patients suffering from the classical form of the disease, of which one is a frameshift mutation (1353-1354insA) leading to a premature termination codon (K277K, Q228A...E294X), one results in a premature stop codon (2551C>T, R444X), and one is a missense mutation (2609T>C; P463L). The frameshift and premature stop mutations can be predicted to result in a CYP21 protein without any residual enzyme activity. To determine the functional consequences of the P463L mutation, the IN VITRO enzyme activity was studied in COS-7 cells and revealed a reduced 21-hydroxylase activity of 2.6+/-0.8 (SD)% for the conversion of 17-hydroxyprogesterone (17OHP) to 11-deoxycortisol and of 3.0+/-0.5 % for the conversion of progesterone to 11-deoxycorticosterone (DOC). We conclude that functional analyses of unknown mutations provide information on the disease severity and should be always performed when novel CYP21 mutations are detected. Knowledge of the residual 21-hydroxylase function improves both genetic counselling and individual clinical management in CAH patients.
Assuntos
Hiperplasia Suprarrenal Congênita/genética , Mutação Puntual , Esteroide 21-Hidroxilase/genética , Animais , Células COS , Chlorocebus aethiops , Análise Mutacional de DNA , Feminino , Humanos , Recém-Nascido , Masculino , Análise de Sequência de DNA , Esteroide 21-Hidroxilase/metabolismo , TransfecçãoAssuntos
Diagnóstico de Enfermagem , Síndrome de Turner/enfermagem , Adolescente , Adulto , Criança , Pré-Escolar , Terapia Combinada/enfermagem , Associações de Consumidores , Análise Citogenética , Feminino , Seguimentos , Alemanha , Humanos , Lactente , Recém-Nascido , Equipe de Assistência ao Paciente , Gravidez , Síndrome de Turner/diagnóstico , Síndrome de Turner/genética , Síndrome de Turner/terapia , Ultrassonografia Pré-Natal/enfermagemRESUMO
We describe the successful treatment of a neonate with Kasabach-Merritt syndrome who received local irradiation and interferon alpha therapy after failure of corticosteroid treatment. A male neonate, born after an uneventful pregnancy, had a huge haemangioma involving the upper right cervical region as well as severe thrombocytopenia. He was treated with corticosteroids, interferon alpha and radiotherapy. Prednisolone therapy (5 mg kg(-1) day(-1)) was started at 41 days of age. No therapeutic effect was observed after 2 weeks. At this time the tumour size had increased dramatically, platelet counts had decreased progressively and coagulation abnormalities had developed. Because corticosteroid therapy had been ineffective and the child was in a life-threatening condition, irradiation was delivered up to a total dose of 9.5 Gy in five fractions. Simultaneously, prednisolone therapy was slowly decreased and interferon alpha therapy (3 million U m(-2) day(-1)) was started and continued for 6 weeks. After irradiation with 9.5 Gy and beginning interferon alpha therapy, the tumour decreased in size and coagulation parameters normalized within 4 weeks. 6 months later, platelet counts and coagulation parameters were still normal. The tumour had further decreased in size. No acute severe side effects were observed. Radiation therapy combined with interferon alpha treatment is an alternative treatment modality when high dose corticoid steroid therapy has been ineffective in patients with Kasabach-Merritt syndrome, despite the risks of growth delay and secondary malignancy. In children showing no response to corticosteroids, radiotherapy and/or interferon alpha should be considered in Kasabach-Merritt syndrome.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Hemangioma/tratamento farmacológico , Hemangioma/radioterapia , Interferon-alfa/uso terapêutico , Terapia Combinada , Coagulação Intravascular Disseminada/tratamento farmacológico , Coagulação Intravascular Disseminada/radioterapia , Humanos , Recém-Nascido , Masculino , Síndrome , Trombocitopenia/tratamento farmacológico , Trombocitopenia/radioterapiaRESUMO
OBJECTIVE: In girls with congenital adrenal hyperplasia (CAH), genital ambiguity usually leads to a rapid neonatal diagnosis. Rarely, CAH causes complete virilization and male sex assignment with a delayed diagnosis. After being confronted with very specific problems in two of such patients, we collected data of patients with CAH and complete virilization in a nationwide study to delineate specific problems of these rare patients in order to improve their management. DESIGN AND PATIENTS: Through the German Working Group of Paediatric Endocrinology (Arbeitsgemeinschaft Pädiatrische Endokrinologie, APE), questionnaires were sent to all members caring for patients with CAH and complete virilization in their endocrine clinics. Data from 16 patients from 10 paediatric endocrine centres were assessed by questionnaire. RESULTS: The following problems have been encountered. (1) Sex assignment/gender identity: initially all patients had a male sex assignment. Six patients were diagnosed during the first month of life. Five were reassigned to female sex immediately, one at the age of 19 months. Except in one girl demonstrating some tomboyish behaviour, gender role behaviour in these patients did not differ from unaffected girls. Ten patients were diagnosed late at 3.4--7 years of age. In seven patients with a late diagnosis, male sex assignment was maintained; one of them expressed some concerns about living as a male. In three patients late sex reversal was performed, gender identity is very poor in one and new sex assignment is currently under consideration. (2) SURGERY: irrespective of the sex assigned, all patients had between one and three surgical procedures, including clitoris reduction and (repeated) vaginoplasties in patients with female sex assignment. Hysterectomy and ovarectomy were performed in patients with male sex assignment. (3) Short stature: patients with a late diagnosis of CAH had extremely advanced bone ages of +6.3 to +9.5 years, leading to severely reduced final height of 137 to 150 cm in adult patients. Patients tended to follow height percentiles of genetic females. One pubertal patient was suicidal due to short stature. (4) Central precocious puberty (CPP): prolonged exposition to adrenal androgens led to CPP in one patient. He was treated with GnRH analogues until gonadectomy. CONCLUSIONS: Patients with CAH and complete virilization have a high risk of being diagnosed late. There are major problems and uncertainties of the patients' families and the treating physicians concerning gender assignment. Gender identity is disturbed in some patients. In addition, multiple surgical procedures are necessary and short stature as well as central precocious puberty might be important to avoid late sequelae. While some surgical interventions are probably unavoidable, most of these issues could be resolved with an early diagnosis. Thus, especially for these patients, a neonatal screening programme for CAH would be of paramount importance.
Assuntos
Hiperplasia Suprarrenal Congênita/complicações , Virilismo/etiologia , Adolescente , Hiperplasia Suprarrenal Congênita/psicologia , Hiperplasia Suprarrenal Congênita/cirurgia , Estatura , Feminino , Identidade de Gênero , Genitália/cirurgia , Humanos , Histerectomia , Ovariectomia , Puberdade Precoce/etiologia , Virilismo/psicologia , Virilismo/cirurgiaRESUMO
Short stature is one of the main features of Turner syndrome. Today, most patients are treated with growth hormone (GH) to improve adult height. We have reviewed the literature reporting adult height in patients with Turner syndrome treated with GH alone or in combination with oxandrolone. The reported adult heights as well as the height gain over projected or predicted height are still preliminary and vary considerably among studies. There is some evidence that the age of onset of therapy, dose of GH, duration of GH therapy, target height, time of estrogen substitution, or concurrent treatment with oxandrolone affect adult height. The reported height gains over projected height range from -0.20 to +16.0 cm (median: 5.1 cm) in patients treated with GH and from +0.68 cm to +10.3 (median: 6.40 cm) in patients treated with GH and oxandrolone. Thus, the presently available data are extremely varied and need further detailed analysis after all ongoing clinical trials have published the final results of all patients included in the study.
Assuntos
Hormônio do Crescimento Humano/uso terapêutico , Síndrome de Turner/tratamento farmacológico , Adolescente , Estatura , Criança , Estrogênios/administração & dosagem , Feminino , Hormônio do Crescimento Humano/administração & dosagem , Humanos , Oxandrolona/administração & dosagem , Oxandrolona/uso terapêuticoRESUMO
OBJECTIVE: To identify parameters which predict individual growth response to recombinant human GH (rhGH) therapy and to combine these parameters in a prediction model. DESIGN: Fifty-eight prepubertal patients with GH deficiency (17 females) participated in this prospective multicenter trial with 1 year of follow-up. METHODS: Auxological measurements, parameters of GH status and markers of bone metabolism were measured at baseline and at 1, 3 and 6 months after the start of rhGH treatment. Correlations with height velocity during the first 12 months of treatment (HV+12) were calculated. Prediction models were derived by multiple regression analysis. RESULTS: The model which best predicted HV+12 combined the following parameters: pretreatment bone age retardation as a fraction of chronological age, pretreatment serum levels of IGF-I, urinary levels of deoxypyridinoline (a marker of bone resorption) after 1 month of treatment and height velocity after 3 months of treatment. This model explained 89% of the variation in HV+12 with a standard deviation of the residuals of 0.93 cm/year. Defining successful rhGH therapy as a doubling of pretreatment height velocity, the model had a specificity of 90% and a sensitivity of 100% in predicting therapeutic success. CONCLUSIONS: This model is an accurate and practicable tool to predict growth response in GH-deficient children. It may help to optimize rhGH therapy by individual dose adjustment and contribute to improved overall outcomes.
Assuntos
Crescimento , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Modelos Biológicos , Adolescente , Aminoácidos/urina , Estatura , Desenvolvimento Ósseo , Reabsorção Óssea , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Estudos Longitudinais , Masculino , Estudos Prospectivos , Análise de Regressão , Fatores de TempoAssuntos
Varicela/prevenção & controle , Herpesvirus Humano 3/imunologia , Imunoglobulina G/análise , Recém-Nascido Prematuro/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Sangue Fetal/imunologia , Humanos , Imunoglobulina M/análise , Lactente , Recém-Nascido , Transmissão Vertical de Doenças InfecciosasRESUMO
Several multiple regression models have been developed to predict the first-year growth response to human growth hormone (hGH) in children with growth hormone deficiency (GHD). It was the aim of this study to analyse the significance of various growth parameters for a height prediction model. Data from 148 prepubertal children with idiopathic GHD were evaluated. The prediction model was developed by means of univariate and stepwise linear regression analysis and an "all possible" regression approach using Mallow's C(p) statistics. Six out of eight selected variables had a significant influence on the first-year growth rate. The most important parameter was the difference between target height SDS and height SDS at the start of therapy (THSDS-HSDSCO), accounting for 23.95% and 25.74% of the variability. No other single variable or combination of variables was more informative than the variable THSDS-HSDSCO alone. From these data, growth velocity for the first year of hGH treatment was estimated as 1.106 (THSDS-HSDSCO) + 6.8 cm/y +/- 2.2 cm (SE), allowing a prediction for different intervals between THSDS and HSDSCO. This equation was validated in a small group of 18 GHD patients demonstrating a predicted vs. observed first-year growth rate of 9.4 +/- 1.1 vs. 9.5 +/- 2.6 cm/y. We conclude that the difference between THSDS and height SDS at the start of therapy is an important predictor of the first-year growth response in children treated with hGH for idiopathic GHD. Unlike in previous studies, additional parameters did not increase predictability.
Assuntos
Transtornos do Crescimento/tratamento farmacológico , Crescimento/efeitos dos fármacos , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Fatores Etários , Peso ao Nascer , Criança , Pré-Escolar , Interpretação Estatística de Dados , Feminino , Hormônio do Crescimento Humano/farmacologia , Humanos , Modelos Lineares , Masculino , Modelos Teóricos , Fatores Sexuais , Fatores de TempoRESUMO
PURPOSE: To further reduce therapy-related late effects in patients with pediatric Hodgkin's disease (HD) while maintaining the high cure rates achieved with vincristine, prednisone, procarbazine, and doxorubicin (OPPA) or OPPA/cyclophosphamide, vincristine, prednisone, and procarbazine (COPP) chemotherapy and involved-field radiotherapy. The risk of testicular dysfunction was addressed by substituting etoposide for procarbazine (OEPA) in the induction therapy for boys. Radiation doses and fields were further reduced. PATIENTS AND METHODS: Three hundred nineteen boys and 259 girls younger than 18 years with previously untreated HD, enrolled onto the study between 1990 and 1995, were allocated to treatment group (TG)1 (early stages), TG2 (intermediate stages), or TG3 (advanced stages). All groups underwent two cycles of OEPA (boys) or OPPA (girls) for induction chemotherapy. TG2 and TG3 continued on additional two or four cycles, respectively, of COPP. Low-dose radiotherapy was given to the initially involved sites, ie, reduced involved fields. RESULTS: Initial response to OPPA or OEPA induction was virtually identical. Eight of 578 patients experienced early progression of HD. Thirty-seven relapses, three secondary tumors, and no secondary leukemias have been recorded, with a median follow-up duration of 5.1 years (maximum, 8.1 years). Thirteen of 578 patients died. The probability of 5-year event-free survival/overall survival is 91%/98% in the total group, 94%/97% with OPPA, and 89%/98% with OEPA induction therapy. Risk factor analysis showed two significant prognostic factors: histologic subtype NS2 and "B" symptoms. OEPA induction therapy, large mediastinal tumor, and age were not significant. Preliminary studies of testicular function indicate a lower risk of germ cell damage than previously documented with OPPA. CONCLUSION: OEPA is a satisfactory alternative to OPPA. Radiotherapy can be confined to involved sites when combined with appropriate chemotherapy. The DAL-HD-90 regimen represents a comprehensive treatment program for all stages of pediatric HD and offers a favorable benefit/risk ratio, combining excellent disease control, moderate acute toxicity, and reduced long-term toxicity.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Adolescente , Áustria , Criança , Pré-Escolar , Terapia Combinada , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Alemanha , Doença de Hodgkin/radioterapia , Humanos , Masculino , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Doses de Radiação , Fatores de Risco , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
Two cases of infantile liver cirrhosis of unknown origin occurred in a circumscribed rural area of Northern Germany. Both children had increased dietary copper exposure. The search for additional cases of what appeared to be idiopathic copper toxicosis (ICT) revealed a cluster of affected infants in this region, raising questions about the relative importance of genetic and environmental factors that are considered to be etiologic. We gathered clinical and pathologic data concerning the patients, analyzed the pedigrees of affected families, and searched for possible environmental factors contributing to the pathologic process. We encountered 8 cases of infantile liver cirrhosis in 5 families in Emsland, a circumscribed and predominantly rural area of Northern Germany; ICT was definitely proven in 2 cases. Clinical presentation and liver pathology in 6 additional cases were consistent with the diagnosis of ICT. Pedigrees of affected families revealed complex relationships with occasional consanguinity of parents, suggesting autosomal recessive inheritance. The households were served by private wells with water of low pH flowing through copper pipes, suggesting the possibility of increased alimentary copper exposure. These findings support earlier conclusions that ICT develops when an infant with a genetic predisposition is exposed to a copper-enriched diet.
Assuntos
Cobre/intoxicação , Predisposição Genética para Doença , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/genética , Idade de Início , Dieta , Feminino , Alemanha/epidemiologia , Humanos , Lactente , Cirrose Hepática/epidemiologia , Cirrose Hepática/patologia , Masculino , Linhagem , Água/químicaRESUMO
BACKGROUND: Testicular dysfunction with elevated follicle-stimulating hormone (FSH) levels (indicating oligospermia and/or azoospermia) is a major late sequelae after treatment for Hodgkin's disease (HD) with high cumulative doses of procarbazine, cyclophosphamide, or chlorambucil. Etoposide is a newer antineoplastic agent that is effective in the treatment of HD. However, little is known regarding its testicular toxicity, especially in the pediatric age group. METHODS: The authors evaluated testicular function in 46 young adults in first continuous complete remission after stage-dependent treatment for HD with the vincristine, etoposide, prednisone, and doxorubicin (OEPA) or OEPA/cyclophosphamide, vincristine, procarbazine, and prednisone [COPP] chemotherapy regimens and involved field irradiation, excluding patients with ilioinguinal radiotherapy. Pubertal development was documented and a standardized intravenous gonadotropin-releasing hormone test was performed measuring testosterone and basal and stimulated levels of FSH and luteinizing hormone (LH). RESULTS: Testicular volumes, Tanner stages of pubic hair, and genital development were found to be appropriate or slightly delayed for the patients' chronologic age. All 27 patients had normal basal levels of FSH and LH after treatment of Ann Arbor Stage I-IIA HD with 2 courses of OEPA. Stimulated FSH and LH levels were found to be elevated only in rare patients, thus indicating normal endocrine function and spermatogenesis. However, basal and stimulated FSH levels were outside the +2 standard deviation range in 37.5% and 83.3% of patients receiving 2 cycles of OEPA and 2 cycles of COPP chemotherapy, and in 36.4% and 66.7% of patients receiving 2 cycles of OEPA and 4 cycles of COPP chemotherapy, demonstrating a high risk of oligospermia or azoospermia with these regimens. Basal LH levels essentially were normal, whereas stimulated LH levels frequently were elevated. CONCLUSIONS: Testicular function was found to be normal in patients with Stage I-IIA HD when etoposide was used in combination with vincristine, prednisone, and doxorubicin (2 cycles of OEPA). Additional chemotherapy with cyclophosphamide and procarbazine (2 cycles of OEPA and 2 or 4 cycles of COPP) negatively affected spermatogenesis and possibly Leydig cell function in a considerable number of patients. This major gonadotoxic effect most likely is due to procarbazine, although an additional effect of etoposide and cyclophosphamide cannot be excluded.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Etoposídeo/farmacologia , Hormônio Foliculoestimulante/sangue , Doença de Hodgkin/tratamento farmacológico , Hormônio Luteinizante/sangue , Testículo/efeitos dos fármacos , Adolescente , Adulto , Fatores Etários , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/farmacologia , Doxorrubicina/administração & dosagem , Doença de Hodgkin/fisiopatologia , Humanos , Masculino , Metotrexato/administração & dosagem , Metotrexato/farmacologia , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Procarbazina/farmacologia , Puberdade/efeitos dos fármacos , Puberdade/fisiologia , Indução de Remissão , Testículo/patologia , Testículo/fisiopatologia , Testosterona/sangue , Vincristina/administração & dosagem , Vincristina/farmacologiaAssuntos
Hormônio do Crescimento Humano/uso terapêutico , Síndrome de Turner/tratamento farmacológico , Determinação da Idade pelo Esqueleto , Estatura/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Relação Dose-Resposta a Droga , Hormônio do Crescimento Humano/administração & dosagem , HumanosRESUMO
While autoantibodies against thyroid peroxidase (TPO) are known to produce cytotoxicity in vitro, their in vivo effects are still obscure. In addition, the mechanism of TPO autoantibody creation needs to be disclosed because the localization of TPO on thyrocytes is considered to be restricted to the apical membrane, which is not in contact with immunocompetent cells. In order to study these crucial processes in the pathogenesis of thyroid autoimmunity, the ultrastructural localization of TPO and IgG was determined and quantified in thyrocytes of normal thyroid gland and thyroid tissue of patients suffering from Graves' disease. This was done by using ultrathin frozen sections and the immunogold method. IgGs were detected in the follicular lumen, close to the apical membrane, in transport vesicles, the endoplasmic reticulum, and the Golgi apparatus of thyrocytes from patients with Graves' disease. The labeling of TPO in the basolateral membrane was distinctly lower than that of the apical membrane, but was significant in comparison to the plasma membrane labeling of fibroblasts present in the same sections. These data indicate that thyroid autoantibodies may perform their cytotoxic function in intracellular compartments besides the plasma membrane. TPO molecules on the basolateral membrane of HLA class II antigen-positive thyrocytes may initiate antigen presentation of TPO as well as the formation and uptake of TPO autoantibodies.