Recent recommendations from ATA guidelines to define the upper reference range for serum TSH in the first trimester match reference ranges for pregnant women in Rio de Janeiro

ABSTRACT Objectives: American Thyroid Association (ATA)'s new guidelines recommend use of population-based trimester-specific reference range (RR) for thyrotropin (TSH) in pregnancy. The aim of this study was to determine first trimester TSH RR for a population of pregnant women in Rio de Janeiro State. Subjects and methods: Two hundred and seventy pregnant women without thyroid illness, defined by National Academy of Clinical Biochemistry, and normal iodine status were included in this sectional study. This reference group (RG) had normal median urinary iodine concentration (UIC = 219 μg/L) and negative anti-thyroperoxidase antibodies (TPOAb). Twin pregnancy, trophoblastic disease and use of drugs or supplements that influence thyroid function were excluded. In a second step, we defined a more selective reference group (SRG, n = 170) by excluding patients with thyroiditis pattern on thyroid ultrasound and positive anti-thyroglobulin antibodies. This group also had normal median UIC. At a final step, a more selective reference group (MSRG, n = 130) was defined by excluding any pregnant women with UIC < 150 μg/L. Results: In the RG, median, 2.5th and 97.5th percentiles of TSH were 1.3, 0.1, and 4.4 mIU/L, respectively. The mean age was 270 ± 5.0 and the mean body mass index was 25.6 ± 5.2 kg/m2. In the SRG and MSRG, 2.5th and 975th percentiles were 0.06 and 4.0 (SRG) and 0.1 and 3.6 mIU/L (MSRG), respectively. Conclusions: In the population studied,TSH upper limit in the first trimester of pregnancy was above 2.5 mIU/L. The value of 3.6 mIU/L, found when iodine deficiency and thyroiditis (defined by antibodies and ultrasound characteristics) were excluded, matches recent ATA guidelines.

Bullous pemphigoid associated with milia, increased serum IgE, autoantibodies against desmogleins, and refractory treatment in a young patient

Abstract: Bullous pemphigoid is a blistering autoimmune disease characterized by two hemidesmosomal proteins (anti-BP180 and 230). Pemphigus, by contrast, is characterized by two autoantibodies (anti-desmoglein 1 and 3). Coexistence of autoantibodies of bullous pemphigoid and pemphigus in a patient is rare. A 25-year-old male patient was admitted to our hospital, reporting a 3-month history of multiple papules, vesicles, and erosions over an extensive erythema on the entire body. Laboratory tests showed high levels of serum IgE, anti-BP180 antibodies, and anti-desmoglein 1 and 3. Histopathologic and immunopathologic features were characterized by bullous pemphigoid. No improvement was seen with systemic corticosteroid therapy, however, pulse corticosteriod therapy combined with methylprednisolone, immunosuppressants, immunomodulators, and plasmapheresis led to the recovery of his condition with numerous milia.

Thyroid autoimmunity in patients with hyperprolactinemia: an observational study / Autoimunidade tireoidiana em pacientes com hiperprolactinemia: um estudo observacional

Objective : To establish whether there is a relationship between hyperprolactinemia and primary thyroid disorders, focusing on patients with autoimmune features. Materials and methods : The medical records of 100 patients with hyperprolactinemia (HPRL) were retrospectively examined. Records of thyroid ultrasonography (USG), basal serum levels of thyroid stimulating hormone, circulating free thyroxine, free triiodothyronine, antithyroglobulin (anti-Tg), and antithyroperoxidase (anti-TPO) antibodies were analyzed. In 100 control subjects, matched by age and gender with HPRL patients, thyroid USG, thyroid function tests (TFTs), and autoantibody panel were obtained. Results : The median PRL in patients was 93 ng/mL (range: 37-470). Twenty-five patients (25%) and 22 controls (22%) had positive anti-Tg and/or anti-TPO titers (P = 0.739). The median serum PRL was 98 (37-470) ng/mL in patients with positive thyroid autoantibodies, and 92 (40-470) ng/mL in patients who were negative (P = 0.975). Among the individuals with autoantibody positivity TFTs abnormalities were more frequent in HPRL patients (60%, out of 25 patients, 14 with subclinical hypothyroidism and one with hyperthyroidism) than in controls (9.1%, out of 22 patients, 2 with subclinical hyperthyroidism) (P < 0.001). Twenty-seven patients with HPRL and 31 controls had goiter (27 vs. 31%, P = 0.437). Forty-six patients (46%) and 50 (50%) controls had one or more of the features of thyroid disorder, which were goiter, positive thyroid autoantibody, and thyroid function abnormality (P = 0.888). Conclusion : HPRL may be associated with more severe thyroid dysfunction in patients with thyroid autoimmunity. .

Objetivo : Verificar se existe uma relação entre a hiperprolactinemia e distúrbios primários da tireoide, focando em pacientes com características autoimunes. Materiais e métodos : Os prontuários de 100 pacientes com hiperprolactinemia (HPRL) foram examinados retrospectivamente. Foram analisados registros de ultrassonografia da tireoide (USG), níveis séricos basais de hormônio tireoestimulante, tiroxina livre, triiodotironina livre e anticorpos antitireoglobulina (anti-Tg) e antitireoperoxidase (anti-TPO). Foram obtidos de 100 controles, pareados por idade e sexo com pacientes com HPRL, USG, testes de função da tireoide (TFTs) e painel de autoanticorpos. Resultados : A média de PRL em pacientes foi de 93 ng/mL (variação: 37-470). Vinte e cinco pacientes (25%) e 22 controles (22%) foram positivos para títulos de anti-Tg e/ou anti-TPO (P = 0,739). A mediana de PRL sérica foi de 98 (37-470) ng/mL em pacientes positivos para autoanticorpos tiroidianos e 92 (40-470) ng/mL em pacientes negativos (P = 0,975). Entre os indivíduos positivos para autoanticorpos, as anormalidades da TFTs foram mais frequentes em pacientes HPRL (60%; de 25 pacientes, 14 com hipotireoidismo subclínico e um com hipertireoidismo) do que nos controles (9,1%; de 22 pacientes, 2 com hipertireoidismo subclínico) (P < 0,001). Vinte e sete pacientes com HPRL e 31 controles apresentavam bócio (27 contra 31%; P = 0,437). Quarenta e seis pacientes (46%) e 50 (50%) controles tiveram uma ou mais das características de problemas de tireoide, como bócio, autoanticorpos antitireoide e anormalidades da função tiroidiana (P = 0,888). Conclusão : A HPRL pode estar associada à disfunção da tireoide mais grave em pacientes com autoimunidade contra a tireoide. .

Desempenho diagnóstico e associações clínicas dos anticorpos contra componentes da cromatina no lúpus eritematoso sistêmico juvenil / Diagnostic performance and clinical associations of antibodies to the chromatin antigenic system in juvenile systemic lupus erythematosus

OBJETIVOS: Determinar a frequência de anticorpos contra componentes da cromatina no lúpus eritematoso sistêmico juvenil (LESJ) e correlacionar a presença desses autoanticorpos com manifestações clínicas e atividade da doença. MÉTODOS: Os anticorpos anticromatina (anti-CHR), antinucleossomo (anti-NCS) e anti-dsDNA foram medidos em 175 indivíduos, incluindo 37 pacientes com LESJ ativo e 41 com doença inativa, 47 com doenças autoimunes não lúpicas, e 50 crianças saudáveis. Um teste ELISA in house foi desenvolvido com nucleossomos purificados a partir de timo de bezerro para determinar os anticorpos IgG e IgG3 anti-NCS. Anti-CHR e anti-dsDNA foram detectados por kits comerciais de ELISA (INOVA). RESULTADOS: Anticorpos anti-NCS e anti-CHR exibiram não só uma alta especificidade para LESJ, mas também uma frequência semelhante em LESJ ativo e inativo. Os níveis séricos de anti-CHR e IgG/IgG3 anti-NCS não diferiram entre LESJ ativo e inativo. Houve correlação entre o SLEDAI e os anticorpos anti-dsDNA, mas não com os anticorpos contra outros componentes da cromatina. Houve associação de anticorpos anti-dsDNA, anti-CHR e IgG/IgG3 anti-NCS com proteinúria e baixos níveis séricos de C4. Foram observados anticorpos anti-NCS em 14% dos pacientes com LESJ na ausência de anticorpos anti-dsDNA. CONCLUSÕES: Nossos dados indicam que os anticorpos anti-NCS e anti-CHR são marcadores diagnósticos relevantes para LESJ e parecem estar correlacionados com a atividade da nefrite lúpica no LESJ. O anticorpo IgG3 anti-NCS não parece ser mais relevante como marcador de atividade da doença ou nefrite ativa no LESJ em comparação ao anticorpo IgG anti-NCS.

OBJECTIVES: To determine the frequency of antibodies to chromatin components in juvenile systemic lupus erythematosus (JSLE), and to correlate the presence of these autoantibodies with clinical manifestations and disease activity. METHODS: Anti-chromatin (anti-CHR), anti-nucleosome core particle (anti-NCS) and anti-dsDNA antibodies were measured in 175 individuals, including 37 patients with active JSLE and 41 with inactive disease, 47 non-lupus autoimmune disease patients (non-lupus AD), and 50 healthy children. An in-house ELISA was developed with purified nucleosome core particles from calf thymus to determine IgG and IgG3 anti-NCS antibodies. Anti-CHR and anti-dsDNA antibodies were detected by commercial ELISA kits (INOVA). RESULTS: Anti-NCS and anti-CHR antibodies exhibited high specificity for JSLE and similar frequency in active and inactive JSLE. Anti-CHR and IgG/IgG3 anti-NCS serum levels did not differ between active and inactive JSLE. SLEDAI correlated with anti-dsDNA antibodies but not with antibodies to other chromatin components. There was association of anti-dsDNA, anti-CHR and IgG/IgG3 anti-NCS antibodies with proteinuria and low C4 serum levels. Anti-NCS antibodies in the absence of anti-dsDNA were observed in 14% of the JSLE patients. CONCLUSIONS: Our data indicate that anti-NCS and anti-CHR antibodies are relevant diagnostic markers for JSLE and appear to be correlated with JSLE lupus nephritis activity. IgG3 isotype anti-NCS antibodies do not seem to be more relevant than IgG anti-NCS antibodies as markers of disease activity or active nephritis in JSLE.

Autoanticuerpos anti-galectina-8 en pacientes con lupus eritematoso sistémico / Antibodies against galectin-8 in patients with systemic lupus erythematosus

Background: The family of lectins known as galectins (galectins 1-14) are involved in the regulation of the immune system and in oncogenesis. During a search for antigens recognized by antibodies produced by a patient with systemic lupus erythematosus (SLE) we found reactivity against galectin-8, for which autoantibodies have not been previously described. Aim: To determine the frequency of autoantibodies against galectin-8 in lupus patients compared with healthy controls. Patients and Methods: Galectin-8 was purified from a bacterial expression system and used in immunoblot assays as antigen to screen the sera of 55 SLE patients and matched controls. Disease activity was evaluated using the Mexican Modification of the Systemic Lupus Erythematosus Disease Activity Index (MEX-SLEDAI). Results: Reactivity against galectin-8 was detected in 30% of SLE patients, compared to 7% of controls (p=0.003). We could not detect any particular SLE manifestation associated to the presence of these autoantibodies. Conclusions: This is the first description of autoantibodies against galectin-8. Its higher frequency in patients with SLE suggests a pathogenic role. Further studies are needed to determine their clinical relevance.

Estudo longitudinal do eixo hipófise-tireóide durante a gravidez / Longitudinal study of pituitary-thyroid axis in pregnancy

A tireóide sofre importantes modificações durante a gravidez. Visando mostrar as modificações no eixo hipófise-tireóide ao longo deste período, estudamos a função tireoidiana de 587 mulheres, com dosagens de TSH, T4 livre, anti-TPO, betahCG no 1°. trimestre e TSH, T4 livre e anti-TPO no 2°. e 3°. trimestres. Observamos aumento progressivo do TSH no 2°. (média: 2,14mU/L) e 3°. (média: 2,76mU/L) trimestres, em relação ao 1°. (média: 1,39mU/L). No grupo com TSH abaixo do valor de referência (0,4mU/L) no 1°. trimestre, a média de bhCG foi de 129.200UI/L, enquanto no grupo que apresentou níveis normais de TSH, a média foi de 34.200UI/L. Observamos, também, uma ligeira diminuição do T4 livre no 2°. e 3°. trimestres em relação ao 1°. (médias: 1°: 1,15; 2°: 0,99; 3°: 0,94ng/dl). A presença de anti-TPO positivo ocorreu em 13,9 por cento das mulheres. Não foram observadas alterações significativas nos valores médios de TSH e T4 livres naquelas com ou sem auto-imunidade. Entretanto, proporções significativamente maiores de gestantes apresentaram valores hormonais fora da faixa da normalidade em todos os trimestres da gestação. Concluímos que a função tireoidiana é afetada pela gravidez, com tendência ao declínio durante seu progresso, sendo este fenômeno mais marcante no grupo de gestantes anti-TPO positivas.

Antibodies to Ro/SS-A and La/SS-B in systemic lupus erythematosus and other autoimmune disorders.

AIM: 1. To study the presence of anti-Ro/SS-A, anti-La/SS-B, anti-Sm and anti-nRNP in diagnosed antinuclear factor (ANF) positive systemic lupus erythematosus (SLE) cases and their association with various organ involvement. 2. To study autoantibodies in other autoimmune disorders. MATERIAL AND METHODS: A total of 4050 suspected cases of autoimmune disorders referred for serological work up were evaluated for ANF by indirect immunofluorescence technique, anti-dsDNA by PHA, autoantibodies to Ro-SS-A and La/SS-B by ELISA and rheumatoid factor was tested by latex agglutination using commercial kits. RESULTS: Out of 4050 patients 19.5% were ANF positive and 5% were anti-dsDNA positive. Out of these 50 diagnosed ANF positive cases of SLE, an incidence of anti-dsDNA 54%, anti-Sm 25.9%, anti-nRNP 29.6%, anti-Ro/SS-A 10% and anti-La/SS-B was 22% was observed. In rheumatoid arthritis, 17.4% positivity of anti-Ro/SS-A and 39.1% positivity for anti-La/SS-B was observed. In SLE with renal involvement, joint complaints and skin or malar rash were seen in 66%, 56% and 46%, respectively. CONCLUSION: Determining anti-Ro/SS-A and anti-La/SS-B antibody could be important in evaluating patients with suspected connective tissue disorders, who usually show diverse clinical presentations like skin, kidney and joint manifestations. The most prominent feature in anti-Ro/SS-A and anti-La/SS-B positive patients was skin involvement and sicca complex in 60% of SLE patients.

Study on serum sperm agglutination in cases of unexplained infertility.

In our study we investigated 100 couples of unexplained infertility in order to detect the presence of anti-spermatozoal antibodies. Both auto-immunity and Iso-immunity have been found responsible in 12.5% of couples of primary infertility & 10% of couples of secondary infertility. As many as, 21% of cases of unexplained infertility were attributed to presence of antibodies in sera of infertile couples. Here, we highlight the importance of anti-spermatozoal antibodies testing in the first instance itself in cases of unexplained infertility.