2023 UPDATE: Luso-Brazilian evidence-based guideline for the management of antidiabetic therapy in type 2 diabetes.

BACKGROUND: The management of antidiabetic therapy in people with type 2 diabetes (T2D) has evolved beyond glycemic control. In this context, Brazil and Portugal defined a joint panel of four leading diabetes societies to update the guideline published in 2020. METHODS: The panelists searched MEDLINE (via PubMed) for the best evidence from clinical studies on treating T2D and its cardiorenal complications. The panel searched for evidence on antidiabetic therapy in people with T2D without cardiorenal disease and in patients with T2D and atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), or diabetic kidney disease (DKD). The degree of recommendation and the level of evidence were determined using predefined criteria. RESULTS AND CONCLUSIONS: All people with T2D need to have their cardiovascular (CV) risk status stratified and HbA1c, BMI, and eGFR assessed before defining therapy. An HbA1c target of less than 7% is adequate for most adults, and a more flexible target (up to 8%) should be considered in frail older people. Non-pharmacological approaches are recommended during all phases of treatment. In treatment naïve T2D individuals without cardiorenal complications, metformin is the agent of choice when HbA1c is 7.5% or below. When HbA1c is above 7.5% to 9%, starting with dual therapy is recommended, and triple therapy may be considered. When HbA1c is above 9%, starting with dual therapyt is recommended, and triple therapy should be considered. Antidiabetic drugs with proven CV benefit (AD1) are recommended to reduce CV events if the patient is at high or very high CV risk, and antidiabetic agents with proven efficacy in weight reduction should be considered when obesity is present. If HbA1c remains above target, intensification is recommended with triple, quadruple therapy, or even insulin-based therapy. In people with T2D and established ASCVD, AD1 agents (SGLT2 inhibitors or GLP-1 RA with proven CV benefit) are initially recommended to reduce CV outcomes, and metformin or a second AD1 may be necessary to improve glycemic control if HbA1c is above the target. In T2D with HF, SGLT2 inhibitors are recommended to reduce HF hospitalizations and mortality and to improve HbA1c. In patients with DKD, SGLT2 inhibitors in combination with metformin are recommended when eGFR is above 30 mL/min/1.73 m2. SGLT2 inhibitors can be continued until end-stage kidney disease.

Pitfalls in the Diagnostic Evaluation of Hyperprolactinemia.

An appropriate diagnostic evaluation is essential for the most appropriate treatment to be performed. Currently, macroprolactinemia is the third most frequent cause of nonphysiological hyperprolactinemia after drugs and prolactinomas. Up to 40% of macroprolactinemic patients may present with hypogonadism symptoms, infertility, and/or galactorrhea. Thus, the screening for macroprolactin is indicated not only for asymptomatic subjects but also for those without an obvious cause for their prolactin (PRL) elevation. Before submitting patients to macroprolactin screening and pituitary magnetic resonance imaging, one should rule out pregnancy, drug-induced hyperprolactinemia, primary hypothyroidism, and renal failure. The magnitude of PRL elevation can be useful in determining the etiology of hyperprolactinemia. PRL values >250 ng/mL are highly suggestive of prolactinomas and virtually exclude nonfunctioning pituitary adenomas (NFPAs) and other sellar masses as the etiology of hyperprolactinemia. However, they can also be found in subjects with macroprolactinemia, drug-induced hyper-prolactinemia or chronic renal failure. By contrast, most patients with NFPAs, drug-induced hyperprolactinemia, macroprolactinemia, or systemic diseases present with PRL levels <100 ng/mL. However, exceptions to these rules are not rare. Indeed, up to 25% of patients harboring a microprolactinoma or a cystic macroprolactinoma may also have PRL <100 ng/mL. Falsely low PRL levels may result from the so-called "hook effect," which should be considered in all cases of large (≥3 cm) pituitary adenomas associated with normal or mildly elevated PRL levels (≤250 ng/mL). The hook effect may be unmasked by repeating PRL measurement after a 1:100 serum sample dilution.

Acromegaly: clinical features at diagnosis.

BACKGROUND: Acromegaly is a rare and underdiagnosed disorder caused, in more than 95% of cases, by a growth hormone (GH)-secreting pituitary adenoma. The GH hypersecretion leads to overproduction of insulin-like growth factor 1 (IGF-1) which results in a multisystem disease characterized by somatic overgrowth, multiple comorbidities, physical disfigurement, and increased mortality. OBJECTIVE: This article aims to review the clinical features of acromegaly at diagnosis. DISCUSSION/CONCLUSION: Acromegaly affects both males and females equally and the average age at diagnosis ranges from 40 to 50 years (up to 5% of cases < the age 20). Due to insidious onset and slow progression, acromegaly is often diagnosed five to more than ten years after its onset. The typical coarsening of facial features include furrowing of fronthead, pronounced brow protrusion, enlargement of the nose and the ears, thickening of the lips, skin wrinkles and nasolabial folds, as well as mandibular prognathism that leads to dental malocclusion and increased interdental spacing. Excessive growth of hands and feet (predominantly due to soft tissue swelling) is present in the vast majority of acromegalic patients. Gigantism accounts for up to 5% of cases and occurs when the excess of GH becomes manifest in the young, before the epiphyseal fusion. The disease also has rheumatologic, cardiovascular, respiratory, neoplastic, neurological, and metabolic manifestations which negatively impact its prognosis and patients quality of life. Less than 15% of acromegalic patients actively seek medical attention for change in appearance or enlargement of the extremities. The presentation of acromegaly is more often related to its systemic comorbidities or to local tumor effects.

The Role of Isotretinoin Therapy for Cushing's Disease: Results of a Prospective Study.

Objective. This prospective open trial aimed to evaluate the efficacy and safety of isotretinoin (13-cis-retinoic acid) in patients with Cushing's disease (CD). Methods. Sixteen patients with CD and persistent or recurrent hypercortisolism after transsphenoidal surgery were given isotretinoin orally for 6-12 months. The drug was started on 20 mg daily and the dosage was increased up to 80 mg daily if needed and tolerated. Clinical, biochemical, and hormonal parameters were evaluated at baseline and monthly for 6-12 months. Results. Of the 16 subjects, 4% (25%) persisted with normal urinary free cortisol (UFC) levels at the end of the study. UFC reductions of up to 52.1% were found in the rest. Only patients with UFC levels below 2.5-fold of the upper limit of normal achieved sustained UFC normalization. Improvements of clinical and biochemical parameters were also noted mostly in responsive patients. Typical isotretinoin side-effects were experienced by 7 patients (43.7%), though they were mild and mostly transient. We also observed that the combination of isotretinoin with cabergoline, in relatively low doses, may occasionally be more effective than either drug alone. Conclusions. Isotretinoin may be an effective and safe therapy for some CD patients, particularly those with mild hypercortisolism.

Second Attempt of Cabergoline Withdrawal in Patients with Prolactinomas after a Failed First Attempt: Is it Worthwhile?

Successful discontinuation of cabergoline (CAB) treatment has been reported in 31-75% of prolactinomas patients treated for at least 2 years. In contrast, it is not well established whether CAB therapy can be successfully withdrawn after a failed first attempt. This prospective open trial was designed to address this topic and to try to identify possible predictor factors. Among 180 patients with prolactinomas on CAB therapy, the authors selected those who fulfilled very strict criteria, particularly additional CAB therapy for at least 2 years, normalization of serum prolactin (PRL) levels following CAB restart, no tumor remnant >10 mm, no previous pituitary radiotherapy or surgery; and current CAB dose ≤1.0 mg/week. Recurrence was defined as an increase of PRL levels above the upper limit of normal. A total of 34 patients (70.6% female) treated with CAB for 24-30 months were recruited. Ten patients (29.4%) remained without evidence of recurrence after 24-26 months of follow-up. Twenty-four patients (70.6%) recurred within 15 months (75% within 12 months) after drug withdrawal and ~80% were restarted CAB. Median time to recurrence was 10.5 months (range, 3-15). Despite overlapping values, non-recurring patients had significantly lower mean PRL levels before withdrawal. Moreover, the recurrence rate was lower in subjects without visible tumor on pituitary magnetic resonance imaging (MRI) than in those with small remnant tumor (60 vs. 79%), though the difference was not statistically significant (P = 0.20). No other characteristic could be identified as a predictor of successful CAB discontinuation. In conclusion, a second attempt of CAB withdrawal after two additional years of therapy may be successful, particularly in patients with lower PRL levels and no visible tumor on pituitary MRI. Close monitoring of PRL level is mandatory, especially within the first year after withdrawal, where most recurrences are detected.

High prevalence of arterial hypertension in a Brazilian Northeast population of low education and income level, and its association with obesity and metabolic syndrome.

OBJECTIVE: The objectives of this study are to estimate the prevalence of arterial hypertension (AH) in an adult population with a predominance of families with low education and income levels, in the hinterlands of Pernambuco, Brazil, and to analyze its association with other factors related to cardiovascular diseases (CVD). METHODS: A cross-sectional study in 2008/2009 was conducted with a sample of 198 subjects stratified by age, and representative of the urban adult population of the Canaã district of city of Triunfo, in the hinterlands of Pernambuco, Brazil. RESULTS: One hundred ninety eight individuals with average age of 57.7 years old (31 to 90 years-old), mainly women (65.6%), and with low income and education levels (81.3% with a monthly income of less than one minimum wage) were evaluated. Among these, 127 (64.1%) were identified as having AH, 54 (42.5%) of whom had no prior diagnosis. From those who were previously diagnosed, only 31.3% had good blood pressure control. Higher prevalence was observed in those individuals with lower incomes, higher body mass indexes (BMI), and those with metabolic syndrome (MS). CONCLUSION: These data demonstrated that there was a high prevalence of AH in the urban, low education and income levels adult population of Triunfo, strongly associated with lower income levels, elevated BMI, and the presence of MS; and a high prevalence of bad blood pressure control among the previously diagnosed cases. These results indicate that more effective interventions for early detection and adequate control of this disease and its comorbidities are necessary.

High prevalence of arterial hypertension in a Brazilian Northeast population of low education and income level, and its association with obesity and metabolic syndrome

OBJECTIVE: The objectives of this study are to estimate the prevalence of arterial hypertension (AH) in an adult population with a predominance of families with low education and income levels, in the hinterlands of Pernambuco, Brazil, and to analyze its association with other factors related to cardiovascular diseases (CVD). METHODS: A cross-sectional study in 2008/2009 was conducted with a sample of 198 subjects stratified by age, and representative of the urban adult population of the Canaã district of city of Triunfo, in the hinterlands of Pernambuco, Brazil. RESULTS: One hundred ninety eight individuals with average age of 57.7 years old (31 to 90 years-old), mainly women (65.6%), and with low income and education levels (81.3% with a monthly income of less than one minimum wage) were evaluated. Among these, 127 (64.1%) were identified as having AH, 54 (42.5%) of whom had no prior diagnosis. From those who were previously diagnosed, only 31.3% had good blood pressure control. Higher prevalence was observed in those individuals with lower incomes, higher body mass indexes (BMI), and those with metabolic syndrome (MS). CONCLUSION: These data demonstrated that there was a high prevalence of AH in the urban, low education and income levels adult population of Triunfo, strongly associated with lower income levels, elevated BMI, and the presence of MS; and a high prevalence of bad blood pressure control among the previously diagnosed cases. These results indicate that more effective interventions for early detection and adequate control of this disease and its comorbidities are necessary.

Treatment of type 2 diabetes in Latin America: a consensus statement by the medical associations of 17 Latin American countries / Tratamiento de la diabetes tipo 2 en América Latina: declaración de consenso de las asociaciones médicas de 17 países latinoamericanos

Latin America faces unique challenges in the treatment of type 2 diabetes mellitus. The Asociación Latinoamericana de Diabetes (Latin American Diabetes Association, ALAD) brought together medical associations in 17 countries in Latin America to produce a consensus statement regarding the treatment of type 2 diabetes. The goal of the document is to provide practical recommendations that will guide clinicians through a simple decision-making process for managing patients. The cornerstone elements for therapeutic decision making are: severity of hyperglycemia, clinical condition of the patient (stable or with metabolic decompensation), and body mass index. The consensus includes a section devoted specifically to patients with obesity. Information is presented as highly-relevant clinical questions. The algorithm is based on the scientific recommendations of the 2006 ALAD guidelines (a document prepared using an evidence-based approach) and data from recent randomized controlled studies.

América Latina se enfrenta a algunos retos excepcionales en el tratamiento de la diabetes mellitus tipo 2. La Asociación Latinoamericana de Diabetes (ALAD) reunió a las asociaciones médicas de 17 países latinoamericanos con el fin de producir una declaración de consenso sobre el tratamiento de la diabetes tipo 2. El objetivo de ese documento es brindar recomendaciones prácticas que guíen a los médicos a lo largo de un sencillo proceso decisorio para el tratamiento de los pacientes. Los elementos fundamentales para la toma de decisiones terapéuticas son la gravedad de la hiperglucemia, el estado clínico del paciente (estable o con descompensación metabólica) y el índice de masa corporal. El documento contiene un apartado dedicado específicamente a los pacientes obesos y la información se presenta en forma de preguntas clínicas sumamente pertinentes. El algoritmo se basa en las recomendaciones científicas de las directrices de la ALAD del año 2006 (documento preparado con un método basado en datos probatorios) y en datos obtenidos de estudios controlados aleatorizados recientes.

[Prevalence of diabetes and associated factors in an urban adult population of low educational level and income from the Brazilian Northeast wilderness]. / Prevalência de diabetes melito e fatores associados em população urbana adulta de baixa escolaridade e renda do sertão nordestino brasileiro.

BACKGROUND: Diabetes mellitus (DM) is a public health problem in Brazil. The objective of this study was to investigate the prevalence of DM and its relation with socio-demographic features and other cardiovascular risk factors in a adult population from the wilderness of Pernambuco, Brazil. SUBJECTS AND METHODS: In 2008/2009 a cross-sectional study in the adult urban population of Canãa district, city of Triunfo, in the wilderness of Pernambuco/Brazil was conducted. A representative sample of 198 individuals, with average age of 57.7 years, 80% with primary education and 81.3% with a monthly income of less than 1 minimum wage was randomly selected. RESULTS: A prevalence of diabetes of 13.6% and 7.6% of disglycemia (6.6% of impaired fasting glycemia, and 1.0% of impaired glucose tolerance) was found. Among those with diabetes, 24% had no prior diagnosis. Among diabetics, metabolic syndrome (MS) and arterial hypertension (AH) were diagnosed in 87.5% and 68%, respectively. Besides these, there was a positive and significant association between DM and BMI, and between DM and MS. CONCLUSION: These data demonstrate a high prevalence of DM in the adult urban population from the wilderness of Pernambuco/Brazil. These results as well as their association with obesity and MS, indicate that more effective interventions are necessary for the prevention of these diseases also outside principal urban centers.

Prevalência de diabetes melito e fatores associados em população urbana adulta de baixa escolaridade e renda do sertão nordestino brasileiro / Prevalence of diabetes and associated factors in an urban adult population of low educational level and income from the Brazilian Northeast wilderness

INTRODUÇÃO: O diabetes melito (DM) constitui problema de saúde pública no Brasil. Este estudo teve por objetivo investigar a prevalência de DM, sua relação com características sociodemográficas e outros fatores de risco cardiovascular em uma população adulta do sertão de Pernambuco/Brasil. SUJEITOS E MÉTODOS: Foi conduzido em 2008/2009 estudo transversal na população adulta e urbana do Distrito de Canaã, município de Triunfo, sertão de Pernambuco/Brasil. Amostra representativa constituída por 198 indivíduos com idade média de 57,7 anos foi aleatoriamente selecionada, em que 80,0 por cento tinham apenas o ensino fundamental, e 81,3 por cento tinham renda mensal inferior a um salário-mínimo. RESULTADOS: Foi encontrada prevalência de 13,6 por cento de DM e de 7,6 por cento de disglicemia (6,6 por cento de glicemia de jejum alterada e 1,0 por cento de tolerância diminuída à glicose). Dos diabéticos, 24,0 por cento não tinham diagnóstico. Nos diabéticos, 87,5 por cento apresentavam síndrome metabólica (SM) e 68,0 por cento eram hipertensos. Houve associação positiva e significativa entre DM e IMC e entre DM e SM. CONCLUSÃO: Foi encontrada elevada prevalência de DM nessa população adulta urbana do sertão nordestino. Esses resultados assim como a sua associação com obesidade e síndrome metabólica indicam a necessidade de ações mais efetivas na prevenção dessas enfermidades.

BACKGROUND: Diabetes mellitus (DM) is a public health problem in Brazil. The objective of this study was to investigate the prevalence of DM and its relation with socio-demographic features and other cardiovascular risk factors in a adult population from the wilderness of Pernambuco, Brazil. SUBJECTS AND METHODS: In 2008/2009 a cross-sectional study in the adult urban population of Canãa district, city of Triunfo, in the wilderness of Pernambuco/Brazil was conducted. A representative sample of 198 individuals, with average age of 57.7 years, 80 percent with primary education and 81.3 percent with a monthly income of less than 1 minimum wage was randomly selected. RESULTS: A prevalence of diabetes of 13.6 percent and 7.6 percent of disglycemia (6.6 percent of impaired fasting glycemia, and 1.0 percent of impaired glucose tolerance) was found. Among those with diabetes, 24 percent had no prior diagnosis. Among diabetics, metabolic syndrome (MS) and arterial hypertension (AH) were diagnosed in 87.5 percent and 68 percent, respectively. Besides these, there was a positive and significant association between DM and BMI, and between DM and MS. CONCLUSION: These data demonstrate a high prevalence of DM in the adult urban population from the wilderness of Pernambuco/Brazil. These results as well as their association with obesity and MS, indicate that more effective interventions are necessary for the prevention of these diseases also outside principal urban centers.

Treatment of type 2 diabetes in Latin America: a consensus statement by the medical associations of 17 Latin American countries. Latin American Diabetes Association.

Latin America faces unique challenges in the treatment of type 2 diabetes mellitus. The Asociación Latinoamericana de Diabetes (Latin American Diabetes Association, ALAD) brought together medical associations in 17 countries in Latin America to produce a consensus statement regarding the treatment of type 2 diabetes. The goal of the document is to provide practical recommendations that will guide clinicians through a simple decision-making process for managing patients. The cornerstone elements for therapeutic decision making are: severity of hyperglycemia, clinical condition of the patient (stable or with metabolic decompensation), and body mass index. The consensus includes a section devoted specifically to patients with obesity. Information is presented as highly-relevant clinical questions. The algorithm is based on the scientific recommendations of the 2006 ALAD guidelines (a document prepared using an evidence-based approach) and data from recent randomized controlled studies.

Association of lipoprotein lipase D9N polymorphism with myocardial infarction in type 2 diabetes: the genetics, outcomes, and lipids in type 2 diabetes (GOLD) study.

The association of polymorphisms affecting lipid metabolism with the risk of myocardial infarction (MI) in type 2 diabetes mellitus was investigated. The Genetics, Outcomes and Lipids in type 2 Diabetes (GOLD) Study is a prospective, multicenter study, conducted on 990 patients presenting diabetes and MI (n=386), or diabetes without previous manifestation of stroke, peripheral or coronary arterial disease (n=604), recruited from 27 institutions in Brazil. APO A1 (A/G -75 and C/T +83) and APO C3 (C/G 3'UTR) non-coding sequences, CETP (Taq 1B), LPL (D9N), APO E (epsilon2, epsilon3, epsilon4,), PON-1 (Q192R), and two LCAT variants Arg(147)-->Trp and Tyr(171)-->Stop were tested by PCR-RFLP. There was a higher prevalence of LPL DN genotype (19% vs.12%, p=0.03) and a higher frequency of the N allele (11% vs. 7%) among subjects with MI when compared to controls, with an odds ratio of MI for carriers of 9N allele of 2.46 (95% CI=1.79-3.39, p<0.0001). This association was present in men and women, in non-smokers and in hypertensive patients. A logistic regression model including gender, duration of diabetes, systolic blood pressure, HDL-C, left ventricle hypertrophy and D9N polymorphism showed that the latter still remained significantly associated with MI (OR=1.50, 95% CI=1.02-2.25, p=0.049). These findings suggest that D9N polymorphism can be a useful risk marker for myocardial infarction and that further potential candidate genes should be screened for exploratory analysis and for future therapeutic intervention in diabetes.

[Brazilian Consensus on second-generation antipsychotics and metabolic disorders]. / Consenso Brasileiro sobre antipsicóticos de segunda geração e distúrbios metabólicos.

OBJECTIVE: To discuss current aspects of use of antipsychotics considering their metabolic side effects profile, which includes weight gain, dyslipidemias, diabetes and metabolic syndrome. Such metabolic effects increase the risk of mortality by cardiovascular disease, which is the leading cause of death among schizophrenic patients. METHOD: A consensus meeting was held, with participation of endocrinologists and psychiatrists specialists in schizophrenia and, based on a literature review, an article was elaborated emphasizing practical and helpful recommendations to clinicians. RESULTS AND CONCLUSIONS: Monitoring metabolic side effects is essential to patients taking antipsychotics, particularly in the case of second generation antipsychotics. Efficacy and tolerability should be carefully balanced in all phases of treatment.

Consenso Brasileiro sobre antipsicóticos de segunda geração e distúrbios metabólicos: [revisão] / Brazilian Consensus on second-generation antipsychotics and metabolic disorders: [review]

OBJETIVO: Discutir os aspectos atuais do tratamento com os antipsicóticos, levando-se em consideração o perfil de efeitos metabólicos, tais como ganho de peso, diabetes, dislipidemias e síndrome metabólica. Tais fatores aumentam o risco de doença cardiovascular, que é a principal causa de morte nos portadores de esquizofrenia. MÉTODO: Foi realizada uma reunião de consenso com psiquiatras especialistas em esquizofrenia e endocrinologistas, os quais, com base nas evidências provenientes de ampla revisão da literatura, elaboraram um documento com recomendações que auxiliam a prática clínica. RESULTADOS E CONCLUSÕES: A avaliação periódica dos efeitos adversos metabólicos em pacientes que fazem uso de antipsicóticos é fundamental para a prática clínica, especialmente nos caso de antipsicóticos de segunda geração. O equilíbrio entre eficácia e tolerabilidade deve ser cuidadosamente considerado em todas as etapas do tratamento.

OBJECTIVE: To discuss current aspects of use of antipsychotics considering their metabolic side effects profile, which includes weight gain, dyslipidemias, diabetes and metabolic syndrome. Such metabolic effects increase the risk of mortality by cardiovascular disease, which is the leading cause of death among schizophrenic patients. METHOD: A consensus meeting was held, with participation of endocrinologists and psychiatrists specialists in schizophrenia and, based on a literature review, an article was elaborated emphasizing practical and helpful recommendations to clinicians. RESULTS AND CONCLUSIONS: Monitoring metabolic side effects is essential to patients taking antipsychotics, particularly in the case of second generation antipsychotics. Efficacy and tolerability should be carefully balanced in all phases of treatment.

Cushing's syndrome in pregnancy: an overview: [review]

Cushing's syndrome (CS) during pregnancy is a rare condition with fewer than 150 cases reported in the literature. Adrenal adenomas were found to be the commonest cause, followed by Cushing's disease. The gestation dramatically affects the maternal hypothalamic-pituitary-adrenal axis, resulting in increased hepatic production of corticosteroid-binding globulin (CBG), increased levels of serum, salivary and urinary free cortisol, lack of suppression of cortisol levels after dexamethasone administration and placental production of CRH and ACTH. Moreover, a blunted response of ACTH and cortisol to exogenous CRH may also occur. Therefore, the diagnosis of CS during pregnancy is much more difficult. Misdiagnosis of CS is also common, as the syndrome may be easily confused with preeclampsia or gestational diabetes. Because CS during pregnancy is usually associated with severe maternal and fetal complications, its early diagnosis and treatment are critical. Surgery is the treatment of choice for CS in pregnancy, except perhaps in the late third trimester, with medical therapy being a second choice. There does not seem to be a rationale for supportive treatment alone.

A ocorrência de síndrome de Cushing (SC) durante a gravidez é rara, com menos de 150 casos reportados na literatura. Os adenomas adrenais parecem ser a causa mais comum seguidos da doença de Cushing. A gestação afeta de maneira dramática o eixo hipotálamo-hipófise-adrenal materno resultando em aumento da produção hepática da globulina ligadora de corticosteróides (CBG), aumento dos níveis séricos, salivares e livres urinários de cortisol, falta de supressão do cortisol após administração de dexametasona e produção placentária de CRH e ACTH. Além disso, pode também ocorrer bloqueio da resposta do ACTH e do cortisol ao CRH exógeno. Assim, o diagnóstico de SC durante a gravidez torna-se muito mais difícil. A falha em diagnosticar SC é também comum, já que a síndrome pode ser facilmente confundida com pré-eclampsia ou diabetes gestacional. Uma vez que a SC de ocorrência na gravidez é usualmente associada com graves complicações materno-fetais, seu diagnóstico e tratamento precoces tornam-se críticos. A cirurgia é o tratamento de escolha para a SC na gravidez, exceto, talvez, no final do 3º trimestre, sendo o tratamento medicamentoso a segunda escolha. Não parece haver nenhum arrazoado para o tratamento de suporte isoladamente.

[Endogenous Cushing's syndrome: clinical and laboratorial features in 73 cases]. / Síndrome de Cushing endógena: características clínico-laboratoriais em 73 casos.

We studied clinical and laboratorial features of 73 patients with endogenous Cushing's syndrome, subdivided as follows: 46 (63%) with Cushing's disease (CD), 21 (28.7%) with an adrenal tumor and 6 (8.2%) with ectopic ACTH secretion (EAS). The rate of typical manifestations of hypercortisolism was similar regardless its etiology. In 100% of cases of Cushing's syndrome we observed serum cortisol levels greater than 1.8 microg/dL in low-dose dexamethasone (DMS) suppression tests, as well as elevation of serum or salivary midnight cortisol. However, urinary free cortisol was normal in 11.5% of patients. ACTH levels were suppressed in patients with adrenal tumors, normal or high in CD and always high in EAS. In the 8-mg overnight DMS suppression test, serum cortisol suppression > 50% was observed in 78.2% of cases of CD and in 33.3% of subjects with EAS, while an 80% suppression was only seen in CD. After stimulation with CRH or DDAVP an ACTH increase > 35% occurred in 81% of individuals with CD and 16.6% of those with EAS, while an ACTH increase > 50 achieved 100% specificity. Moreover, the combination of serum cortisol suppression > 50% and an ACTH increase > 35% in both tests only occurred in Cushing's disease. Pituitary magnetic resonance imaging identified 100% of macroadenomas and 59.4% of microadenomas in patients with CD. Among 10 patients that underwent bilateral inferior petrosal sinus sampling, a central-to-peripheral ACTH gradient > 3 after CRH or DDAVP had 90% sensitivity and 100% specificity for Cushing's disease.

Síndrome de cushing endógena: características clínico-laboratoriais em 73 casos / Endogenous cushings syndrome: clinical and laboratorial features in 73 cases

Avaliamos as características clínico-laboratoriais de 73 pacientes com síndrome de Cushing (SC) endógena, assim distribuídos: 46 (63 por cento) com doença de Cushing (DC), 21 (28,7 por cento) com tumores adrenais (TA) e 6 (8,2 por cento) com a síndrome do ACTH ectópico (SAE). A freqüência de manifestações clássicas do hipercortisolismo foi similar, independentemente da etiologia da SC. Em 100 por cento dos casos de SC, observaram-se níveis do cortisol sérico (CS) > 1,8 µg/dL após supressão com doses baixas de dexametasona (DMS), além de elevação do cortisol à meia-noite (sérico ou salivar). Contudo, o cortisol livre urinário foi normal em 11,5 por cento dos pacientes. Os níveis de ACTH mostraram-se suprimidos nos pacientes com TA, normais ou elevados na DC e sempre elevados na SAE. No teste de supressão noturna com 8 mg de DMS, supressão do CS > 50 por cento foi observada em 78,2 por cento dos casos de DC e 33,3 por cento dos casos de SAE, enquanto uma supressão > 80 por cento foi exclusiva da DC. Após estímulo com CRH ou DDAVP, um incremento do ACTH > 35 por cento aconteceu em 81 por cento dos indivíduos com DC e em 16,6 por cento daqueles com SAE, ao passo que um incremento do ACTH > 50 por cento restringiu-se à DC. A combinação de incremento do ACTH > 35 e supressão do CS > 50 por cento foi também exclusiva da DC. A ressonância magnética visualizou 100 por cento dos macroadenomas e 59,4 por cento dos microadenomas hipofisários nos casos de DC. Em 10 pacientes submetidos ao cateterismo bilateral do seio petroso inferior, um gradiente centro-periferia de ACTH > 3 pós-CRH ou DDAVP teve sensibilidade de 90 por cento e especificidade de 100 por cento para a doença de Cushing.

We studied clinical and laboratorial features of 73 patients with endogenous Cushings syndrome, subdivided as follows: 46 (63 percent) with Cushings disease (CD), 21 (28.7 percent) with an adrenal tumor and 6 (8.2 percent) with ectopic ACTH secretion (EAS). The rate of typical manifestations of hypercortisolism was similar regardless its etiology. In 100 percent of cases of Cushings syndrome we observed serum cortisol levels greater than 1.8 µg/dL in low-dose dexamethasone (DMS) suppression tests, as well as elevation of serum or salivary midnight cortisol. However, urinary free cortisol was normal in 11.5 percent of patients. ACTH levels were suppressed in patients with adrenal tumors, normal or high in CD and always high in EAS. In the 8-mg overnight DMS suppression test, serum cortisol suppression > 50 percent was observed in 78.2 percent of cases of CD and in 33.3 percent of subjects with EAS, while an 80 percent suppression was only seen in CD. After stimulation with CRH or DDAVP an ACTH increase > 35 percent occurred in 81 percent of individuals with CD and 16.6 percent of those with EAS, while an ACTH increase > 50 achieved 100 percent specificity. Moreover, the combination of serum cortisol suppression > 50 percent and an ACTH increase > 35 percent in both tests only occurred in Cushings disease. Pituitary magnetic resonance imaging identified 100 percent of macroadenomas and 59.4 percent of microadenomas in patients with CD. Among 10 patients that underwent bilateral inferior petrosal sinus sampling, a central-to-peripheral ACTH gradient > 3 after CRH or DDAVP had 90 percent sensitivity and 100 percent specificity for Cushings disease.