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ABSTRACT Hyperprolactinemia is a frequent cause of menstrual irregularity, galactorrhea, hypogonadism, and infertility. The most common etiologies of hyperprolactinemia can be classified as physiological, pharmacological, and pathological. Among pathological conditions, it is essential to distinguish prolactinomas from other tumors and pituitary lesions presenting with hyperprolactinemia due to pituitary stalk disconnection. Proper investigation considering clinical data, laboratory tests, and, if necessary, imaging evaluation, is important to identify the correct cause of hyperprolactinemia and manage the patient properly. This position statement by the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and Brazilian Society of Endocrinology and Metabolism (SBEM) addresses the recommendations for measurement of serum prolactin levels and the investigations of symptomatic and asymptomatic hyperprolactinemia and medication-induced hyperprolactinemia in women.

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ABSTRACT Dopamine agonists are the first line of treatment for patients with symptomatic hyperprolactinemia due to prolactinomas and in those with idiopathic hyperprolactinemia. Treatment with these agents is effective in 80%-90% of the cases. Infertility treatment of patients with hyperprolactinemia is also carried out with dopamine agonists, aiming for the normalization of prolactin levels. The risk of symptomatic growth of prolactinomas during pregnancy is dependent on the tumor's size, duration of previous treatments, and prolactin levels. Notably, the corresponding risk is relatively low in cases of microprolactinomas (<5%). Remission of hyperprolactinemia occurs in about 30% of the patients after drug treatment and may also occur after pregnancy and menopause. The use of some drugs, such as antidepressants and antipsychotics, is a frequent cause of hyperprolactinemia, and managing this occurrence involves unique considerations. This position statement by the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and Brazilian Society of Endocrinology and Metabolism (SBEM) addresses the recommendations for measurement of serum prolactin levels and the investigations of symptomatic and asymptomatic hyperprolactinemia and drug-induced hyperprolactinemia in women.

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OBJECTIVE: To investigate the effect of therapeutic listening on state anxiety and surgical fears in preoperative colorectal cancer patients. METHOD: A randomized controlled trial with 50 patients randomly allocated in the intervention group (therapeutic listening) (n = 25) or in the control group (n = 25). The study evaluated the changes in the variables state anxiety, surgical fears and physiological variables (salivary alpha-amylase, salivary cortisol, heart rate, respiratory rate and blood pressure). RESULTS: In the comparison of the variables in the control and intervention groups in pre- and post-intervention, differences between the two periods for the variables cortisol (p=0.043), heart rate (p=0.034) and surgical fears (p=0.030) were found in the control group, which presented reduction in the values ​​of these variables. CONCLUSION: There was no reduction in the levels of the variables state anxiety and surgical fears resulting from the therapeutic listening intervention, either through the physiological or psychological indicators. However, the contact with the researcher during data collection, without stimulus to reflect on the situation, may have generated the results of the control group. Clinical Trial Registration: NCT02455128.

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ABSTRACT Objective: To investigate the effect of therapeutic listening on state anxiety and surgical fears in preoperative colorectal cancer patients. Method: A randomized controlled trial with 50 patients randomly allocated in the intervention group (therapeutic listening) (n = 25) or in the control group (n = 25). The study evaluated the changes in the variables state anxiety, surgical fears and physiological variables (salivary alpha-amylase, salivary cortisol, heart rate, respiratory rate and blood pressure). Results: In the comparison of the variables in the control and intervention groups in pre- and post-intervention, differences between the two periods for the variables cortisol (p=0.043), heart rate (p=0.034) and surgical fears (p=0.030) were found in the control group, which presented reduction in the values ​​of these variables. Conclusion: There was no reduction in the levels of the variables state anxiety and surgical fears resulting from the therapeutic listening intervention, either through the physiological or psychological indicators. However, the contact with the researcher during data collection, without stimulus to reflect on the situation, may have generated the results of the control group. Clinical Trial Registration: NCT02455128.

RESUMO Objetivo: Investigar o efeito da escuta terapêutica sobre a ansiedade estado e os medos relacionados à cirurgia em pacientes no pré-operatório de cirurgia de câncer colorretal. Método: Ensaio clínico, aleatorizado e controlado, realizado com 50 pacientes que foram aleatoriamente designados para o grupo intervenção (escuta terapêutica) (n=25) ou para o grupo controle (n=25). O estudo avaliou as mudanças nos níveis de ansiedade das variáveis ansiedade estado, medos relacionados à cirurgia e variáveis fisiológicas (alfa-amilase salivar, cortisol salivar, frequência de pulso, frequência respiratória e pressão arterial). Resultados: Na comparação das variáveis nos grupos controle e intervenção nos momentos pré e pós-intervenção, constataram-se diferenças entre os momentos no grupo controle para as variáveis cortisol (p=0,043), frequência de pulso (p=0,034) e medos relacionados à cirurgia (p=0,030), com redução dos valores dessas variáveis. Conclusão: Não houve redução nos níveis das variáveis ansiedade estado e medos relacionados à cirurgia decorrente da realização da escuta terapêutica, seja por meio dos indicadores fisiológicos ou psicológicos. Contudo, o acolhimento dado pela pesquisadora na coleta de dados, sem estímulo reflexivo à situação, pode ter gerado os resultados do grupo controle. Registro de Ensaio Clínico: NCT02455128.

RESUMEN Objetivo: Investigar el efecto de la escucha terapéutica sobre la ansiedad-estado y los miedos de pacientes relativos a la cirugía de cáncer colorrectal en el preoperatorio. Método: Se trata de un ensayo clínico, aleatorizado y controlado, realizado entre 50 pacientes designados aleatoriamente para el grupo intervención (escucha terapéutica) (n=25) o para el grupo control (n=25). El estudio evaluó los cambios en los niveles de ansiedad de las variables ansiedad-estado, miedos relativos a la cirugía y variables fisiológicas (alfa-amilasa salival, cortisol salival, frecuencia cardiaca, frecuencia respiratoria y presión arterial). Resultados: Al comparar las variables entre los grupos control e intervención en los momentos pre y post-intervención, se constataron diferencias en el grupo control para las variables cortisol (p=0,043), frecuencia cardiaca (p=0,034) y miedos relacionados a la cirugía (p=0,030), con reducción de los valores de esas variables. Conclusión: No hubo reducción en los niveles de las variables ansiedad-estado y miedos relacionados a la cirugía derivado de la realización de la escucha terapéutica, ya sea mediante indicadores fisiológicos o psicológicos. Sin embargo, la acogida propiciada por la investigadora en la colecta de datos, sin estímulo reflexivo a la situación, podría haber generado los resultados del grupo control. Registro de Ensayo Clínico: NCT02455128.

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Abstract Objective: To assess the feasibility and reliability of apparent diffusion coefficient (ADC) measurements of normal adrenal glands. Materials and methods: This was a retrospective study involving 32 healthy subjects, divided into two groups: prepubertal (PreP, n = 12), aged from 2 months to 12.5 years (4 males; 8 females); and postpubertal (PostP, n = 20), aged from 11.9 to 61 years (5 males; 15 females). Diffusion-weighted magnetic resonance imaging (DW-MRI) sequences were acquired at a 1.5 T scanner using b values of 0, 20, 500, and 1000 s/mm2. Two radiologists evaluated the images. ADC values were measured pixel-by-pixel on DW-MRI scans, and automatic co-registration with the ADC map was obtained. Results: Mean ADC values for the right adrenal glands were 1.44 × 10-3 mm2/s for the PreP group and 1.23 × 10-3 mm2/s for the PostP group, whereas they were 1.58 × 10-3 mm2/s and 1.32 × 10-3 mm2/s, respectively, for the left glands. ADC values were higher in the PreP group than in the PostP group (p < 0.05). Agreement between readers was almost perfect (intraclass correlation coefficient, 0.84-0.94; p < 0.05). Conclusion: Our results demonstrate the feasibility and reliability of performing DW-MRI measurements of normal adrenal glands. They could also support the feasibility of ADC measurements of small structures.

Resumo Objetivo: Avaliar se a medida do coeficiente de difusão aparente (CDA) das glândulas suprarrenais é factível e reprodutível. Materiais e métodos: Neste estudo foram incluídos, retrospectivamente, 32 indivíduos saudáveis divididos em dois grupos: pré-púbere (PreP) (n = 12; 2 meses a 12,5 anos; 4 masculinos e 8 femininos) e pós-púbere (PostP) (n = 20; 11,9-61 anos; 5 masculinos e 15 femininos). Imagens de difusão por ressonância magnética (DWI) das glândulas suprarrenais foram realizadas em aparelho de 1,5 T utilizando-se b valores de 0, 20, 500 e 1000 s/mm2. As medidas do CDA das glândulas suprarrenais foram obtidas pixel-a-pixel por dois radiologistas após co-registro automático do mapa de CDA com DWI. Resultados: A média dos valores do CDA da glândula suprarrenal direita foi 1,44 × 10-3 mm2/s no grupo PreP e 1,23 × 10-3 mm2/s no grupo PostP, e da glândula esquerda foi 1,58 × 10-3 mm2/s e 1,32 × 10-3 mm2/s, respectivamente. Os valores de CDA foram mais altos no grupo PreP comparados aos do PostP (p < 0,05). A concordância interobservador foi quase perfeita (coeficiente de correlação intraclasse: 0,84-0,94; p < 0,05). Conclusão: Estes resultados mostram que medir o CDA das glândulas suprarrenais é factível e reprodutível. Esta técnica poderia ser utilizada para medir o CDA de estruturas pequenas.

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OBJECTIVE: To assess the feasibility and reliability of apparent diffusion coefficient (ADC) measurements of normal adrenal glands. MATERIALS AND METHODS: This was a retrospective study involving 32 healthy subjects, divided into two groups: prepubertal (PreP, n = 12), aged from 2 months to 12.5 years (4 males; 8 females); and postpubertal (PostP, n = 20), aged from 11.9 to 61 years (5 males; 15 females). Diffusion-weighted magnetic resonance imaging (DW-MRI) sequences were acquired at a 1.5 T scanner using b values of 0, 20, 500, and 1000 s/mm2. Two radiologists evaluated the images. ADC values were measured pixel-by-pixel on DW-MRI scans, and automatic co-registration with the ADC map was obtained. RESULTS: Mean ADC values for the right adrenal glands were 1.44 × 10-3 mm2/s for the PreP group and 1.23 × 10-3 mm2/s for the PostP group, whereas they were 1.58 × 10-3 mm2/s and 1.32 × 10-3 mm2/s, respectively, for the left glands. ADC values were higher in the PreP group than in the PostP group (p < 0.05). Agreement between readers was almost perfect (intraclass correlation coefficient, 0.84-0.94; p < 0.05). CONCLUSION: Our results demonstrate the feasibility and reliability of performing DW-MRI measurements of normal adrenal glands. They could also support the feasibility of ADC measurements of small structures.

OBJETIVO: Avaliar se a medida do coeficiente de difusão aparente (CDA) das glândulas suprarrenais é factível e reprodutível. MATERIAIS E MÉTODOS: Neste estudo foram incluídos, retrospectivamente, 32 indivíduos saudáveis divididos em dois grupos: pré-púbere (PreP) (n = 12; 2 meses a 12,5 anos; 4 masculinos e 8 femininos) e pós-púbere (PostP) (n = 20; 11,9-61 anos; 5 masculinos e 15 femininos). Imagens de difusão por ressonância magnética (DWI) das glândulas suprarrenais foram realizadas em aparelho de 1,5 T utilizando-se b valores de 0, 20, 500 e 1000 s/mm2. As medidas do CDA das glândulas suprarrenais foram obtidas pixel-a-pixel por dois radiologistas após co-registro automático do mapa de CDA com DWI. RESULTADOS: A média dos valores do CDA da glândula suprarrenal direita foi 1,44 × 10-3 mm2/s no grupo PreP e 1,23 × 10-3 mm2/s no grupo PostP, e da glândula esquerda foi 1,58 × 10-3 mm2/s e 1,32 × 10-3 mm2/s, respectivamente. Os valores de CDA foram mais altos no grupo PreP comparados aos do PostP (p < 0,05). A concordância interobservador foi quase perfeita (coeficiente de correlação intraclasse: 0,84-0,94; p < 0,05). CONCLUSÃO: Estes resultados mostram que medir o CDA das glândulas suprarrenais é factível e reprodutível. Esta técnica poderia ser utilizada para medir o CDA de estruturas pequenas.

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Congenital adrenal hyperplasia (CAH) is an autossomic recessive disorder caused by impaired steroidogenesis. Patients with CAH may present adrenal insufficiency with or without salt-wasting, as well as various degrees of virilization and fertility impairment, carrying a high incidence of testicular adrenal rest tumors and increased incidence of adrenal tumors. The diagnosis of CAH is made based on the adrenocortical profile hormonal evaluation and genotyping, in selected cases. Follow-up is mainly based on hormonal and clinical evaluation. Utility of imaging in this clinical setting may be helpful for the diagnosis, management, and follow-up of the patients, although recommendations according to most guidelines are weak when present. Thus, the authors aimed to conduct a narrative synthesis of how imaging can help in the management of patients with CAH, especially focused on genitography, ultrasonography, computed tomography, and magnetic resonance imaging.

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Congenital adrenal hyperplasia (CAH) is an autossomic recessive disorder caused by impaired steroidogenesis. Patients with CAH may present adrenal insufficiency with or without salt-wasting, as well as various degrees of virilization and fertility impairment, carrying a high incidence of testicular adrenal rest tumors and increased incidence of adrenal tumors. The diagnosis of CAH is made based on the adrenocortical profile hormonal evaluation and genotyping, in selected cases. Follow-up is mainly based on hormonal and clinical evaluation. Utility of imaging in this clinical setting may be helpful for the diagnosis, management, and follow-up of the patients, although recommendations according to most guidelines are weak when present. Thus, the authors aimed to conduct a narrative synthesis of how imaging can help in the management of patients with CAH, especially focused on genitography, ultrasonography, computed tomography, and magnetic resonance imaging.

Hiperplasia congênita de suprarrenal (CAH) é uma doença autossômica recessiva causada por deficiências enzimáticas na esteroidogênese. Clinicamente, os pacientes com CAH podem apresentar insuficiência adrenal com ou sem perda de sal, vários graus de virilização e diminuição na fertilidade, alta incidência de restos adrenais testiculares e de tumores adrenais. O diagnóstico de CAH é feito baseado nos resultados da avaliação hormonal e genotípica, em casos selecionados. O seguimento dos pacientes é principalmente feito com avaliação clínica e hormonal. Métodos de diagnóstico por imagem podem ser muito úteis não só no diagnóstico como no manejo e seguimento dos pacientes com CAH. Porém, as recomendações, de acordo com a maioria dos consensos, quando existem, são escassas. Nesse contexto, com base em uma revisão sistemática, o objetivo deste artigo foi sintetizar a literatura em relação a como os métodos de diagnóstico por imagem podem ser úteis no manejo dos pacientes com CAH, com foco em genitografia, ultrassonografia, tomografia computadorizada e ressonância magnética.

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CONTEXT: Molecular diagnosis of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) has not been straightforward. OBJECTIVE: To conduct a comprehensive genetic analysis by Multiplex Ligation dependent Probe Amplification (MLPA) and evaluate its reliability for the molecular CAH-21OHD diagnosis. PATIENTS AND METHODS: We studied 99 patients from 90 families with salt-wasting (SW; n=32), simple-virilizing (SV; n=29), and non-classical (NC; n=29) CAH-21OHD. Molecular analysis was sequentially performed by detecting the most frequent point mutations by allele-specific oligonucleotide polymerase chain reaction (ASO-PCR), large rearrangements by MLPA, and rare mutations by direct sequencing. Parental segregation was evaluated. RESULTS: ASO-PCR detected microconversions in 164 alleles (91.1%). MLPA identified CYP21A1P large conversions to CYP21A2 in 7 of the remaining 16 (43.7%), 30-kb deletions including the 3'-end of CYP21A1P, C4B, and the 5'-end of CYP21A2 in 3 of the 16 (18.7%), and a complete CYP21A2 deletion in one (6.3%). Five alleles (2.7%) required direct sequencing; three mutations located in the CYP21A2 gene and two derived from CYP21A1P were found. No parental segregation was observed in patients with the c.329_336del and/or the CL6 cluster mutations. These cases were not diagnosed by ASO-PCR, but MLPA detected deletions in the promoter region of the CYP21A2 gene, explaining the genotype/phenotype dissociation. CONCLUSION: Using the proposed algorithm, all alleles were elucidated. False-positive results in MLPA occurred when mutations or polymorphisms were located close to the probe-binding regions. These difficulties were overcome by the association of MLPA with ASO-PCR and paternal segregation. Using these approaches, we can successfully use MLPA in a cost-effective laboratory routine for the molecular diagnosis of CAH-21OHD.

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INTRODUCTION: Cortisol awakening response (CAR) is a rapid increase of cortisol levels within 30-45 min after awakening. OBJECTIVE: This study evaluates CAR compared with cortisol circadian rhythm in active and in remission Cushing's disease (CD). MATERIALS AND METHODS: We evaluated healthy controls (HC, n=19), obese (OB, n=10), in remission (n=08), and active CD patients (n=10). Salivary free cortisol (SF) was determined at 0800, 1100, 1700, 2000, and 2300 h on the first day. CAR was obtained the next morning immediately upon awakening and at 15, 30, 45, and 60-min post-wake up. RESULTS: We observed differences in SF levels throughout the day in HC, OB, and in remission CD (ANOVA P=0.0001) but not in active CD (P=0.2). We demonstrated SF increment after awakening in HC, OB, and in remission CD (ANOVA P=0.007), with no effect of time on SF in active CD. The relative increment of SF obtained at the peak after awakening (CARi%) in the active CD (67±57%) was lower than in HC (154±107%), OB (240±188%), and in remission CD (186±184%) patients (P=0.009). There was a negative correlation between the SF at awakening and the CARi% in HC (r=-0.8), OB (r=-0.78), and in remission CD (r=-0.74) but not in active CD (r=-0.35; P=0.31). CONCLUSION: This study originally described a blunted CAR in active CD in contrast to its presence in HC, OB, and in remission CD. This subtle dysfunction of the hypothalamus-pituitary-adrenal axis may represent a distinct and additional physiopathological phenomenon superimposing the dysregulated cortisol circadian rhythm in this disease.

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