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Our results support the possibility that altered miRNA expression profile might be involved in corticotrophic tumorigenesis. However, the lack of knowledge about miRNA target genes postpones full understanding of the biological functions of down-regulated or up-regulated miRNAs in corticotropinomas.

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CTNNB1 mutations are not common in childhood ACT but appear to associate with poor prognosis. Nevertheless, most ACT exhibit increased expression of β-catenin and WISP2 and reduced expression of Wnt inhibitor genes (DKK3, SFRP1, and AXIN1). Thus, in addition to CTNNB1 mutations, other genetic events affecting the Wnt/β-catenin pathway may be involved in childhood adrenocortical tumorigenesis.

Our data show that despite similar variability between both methods, LNSF has a superior diagnostic performance than UFC and should be used as the primary biochemical diagnostic test for CS diagnosis.

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course.

Salivary cortisol is an index of plasma free cortisol and is obtained by a noninvasive procedure. We have been using salivary cortisol as a tool for physiological and diagnostic studies, among them the emergence of circadian rhythm in preterm and term infants. The salivary cortisol circadian rhythm in term and premature infants was established between 8 and 12 postnatal weeks. In the preterm infants the emergence of circadian rhythm was parallel to the onset of sleep rhythm. We also studied the use of salivary cortisol for screening for Cushings syndrome (CS) in control and obese outpatients based on circadian rhythm and the overnight 1 mg dexamethasone (DEX) suppression test. Salivary cortisol was suppressed to less than 100 ng/ dl after 1 mg DEX in control and obese patients. A single salivary cortisol measurement at 23:00 h and again after 1 mg DEX above the 90th percentile of the obese group values had sensitivity and specificity of 93 and 93% (23:00 h), and 91 and 94% (after DEX), respectively. The sensitivity improved to 100% when we combined both parameters. We also studied 11 CS children and 21 age-matched primary obese children for whom salivary cortisol sensitivity and specificity were 100/95% (23:00 h), and 100/95% (1 mg DEX), respectively. Similar to adults, sensitivity and specificity of 100% were obtained by combining 23:00 h and 1 mg DEX. The measurement of salivary cortisol is a useful tool for physiological studies and for the diagnosis of CS in children and adults on an outpatient basis. Correspondence

A dosagem do cortisol salivar, que avalia a fração livre do hormônio, tem se tornado cada vez mais popular, com vários ensaios comerciais disponíveis. Neste artigo avaliamos criticamente os diferentes ensaios disponíveis para dosagem de cortisol salivar e suas aplicações em situações fisiológicas e patológicas. Esta técnica tem se mostrado útil para o estudo do ritmo circadiano do cortisol e para a avaliação de insuficiência adrenal, nos primeiros dias de vida de recém-nascidos a termo e pré-termo. Adicionalmente, tem sido utilizada para avaliar o eixo hipotálamo-hipófise-adrenal (HHA) em alterações da função cognitiva, em situações de estresse, ansiedade, depressão, síndrome do pânico, na avaliação da privação de sono em pacientes trabalhadores noturnos e naqueles com fadiga crônica. Recentemente, a dosagem de cortisol salivar têm sido empregada no diagnóstico da síndrome de Cushing (SC), inclusive em crianças: sua dosagem às 24:00h apresenta sensibilidade diagnóstica superior a todos os outros parâmetros para detectar pacientes com a condição, mesmo naqueles com hipercortisolismo intermitente ou leve. Utilizando a dosagem do cortisol salivar, avaliamos a acurácia diagnóstica do teste de supressão com dexametasona (DEX, 8mg e 24mg) no diagnóstico diferencial da SC. Nossos dados sugerem que a medida do cortisol salivar, quando comparada ao cortisol plasmático, melhora a acurácia diagnóstica do teste de supressão com altas doses de DEX, mesmo utilizando critérios mais rigorosos. É importante que o pesquisador e o clínico estejam cientes das possíveis diferenças geradas pelos diferentes ensaios, para interpretarem adequadamente os intervalos de referências. Os ensaios para cortisol salivar devem ser padronizados e interpretados com base em valores de corte, obtidos em cada laboratório, utilizando amostras de controles normais da população, de obesos e de pacientes com pseudo-Cushing e SC comprovada. Os laboratórios de pesquisa ou laboratórios comerciais devem, desta forma, realizar a validação de seus ensaios para dosagem de cortisol salivar, tornando-os mais disponíveis à prática clínica.