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INTRODUCCIÓN: La Enfermedad de Cushing es una de las causas menos prevalentes de hipertensión arterial secundaria (HTA) (0,7 a 2,4 casos por millón de personas), sin embargo conlleva un aumento de la morbi-mortalidad que se relaciona con el tiempo de exposición al exceso de corticoides 6, lo cual representa un problema debido a que la inespecificidad de los síntomas y su baja prevalencia, llevan a un retraso diagnóstico de 2 a 4 años 6, generando un incremento del riesgo cardiovascular pese a una resolución completa de la enfermedad 6-9. Este artículo tiene como objetivo describir la presentación clínica de la Enfermedad de Cushing como causa de HTA secundaria. CASO CLÍNICO: Paciente femenina de 36 años con HTA de 7 años de evolución, a quien se identificó adenoma hipofisario productor de ACTH, con posterior exéresis transesfenoidal parcial, presentando enfermedad persistente, en quien se optó manejo farmacológico a base de inhibidor de la esteroidogénesis para control de la enfermedad. DISCUSIÓN: La HTA es un problema de salud pública considerado el principal factor de riesgo para discapacidad y muerte prematura 2, con las causas secundarias como responsables de gran afectación en la calidad de vida, tomando en cuenta que estas son potencialmente curables. El manejo de la enfermedad de Cushing (EC) es principalmente quirúrgico 6,13-14, pero en caso de enfermedad persistente existen alternativas para control de la enfermedad 6,15-16, siendo los fármacos inhibidores de la esteroidogénesis los más usados. CONCLUSIONES: La EC es una causa poco frecuente hipertensión arterial secundaria, pero implica un importante compromiso de la calidad de vida, al igual que otras etiologías secundarias, por lo que es fundamental tener en cuenta las características clínicas y bioquímicas que sugieran una etiología secundaria que lleven a un diagnóstico y tratamiento oportunos.

INTRODUCTION: Cushing's Disease is one of the least prevalent causes of secondary hypertension (0.7 to 2.4 cases per million people), however it entails an increase in morbidity and mortality that is related to the chronic exposure of corticosteroids 6, which represents a problem because the no specificity of the symptoms and their low prevalence lead to a diagnostic delay of 2 to 4 years 6, increasing the cardiovascular risk despite complete resolution of the disease 6 -9. The purpose of this article aims to describe the clinical presentation of Cushing Disease (CD) as a cause of secondary hypertension. CLINICAL CASE: 36-year-old female patient with hypertension of 7 years of evolution, in whom an ACTH-producing pituitary adenoma was identified, with subsequent partial transsphenoidal excision, presenting persistent disease, in whom pharmacological management based on a steroidogenesis inhibitor was chosen. for disease control. DISCUSSION: Hypertension is a public health problem, considered the main risk factor for disability and premature death 2, with secondary causes responsible for great impact on quality of life, considering that these are potentially curative. The management of CD is mainly surgical 6,13-14, but in cases of persistent disease there are alternatives to control the disease 6,15-16, with steroidogenesis inhibitor drugs being the most used. CONCLUSIONS: CD is a rare cause of secondary hypertension, but it implies a significant compromise in quality of life, like other secondary etiologies, so it is essential to consider the clinical and biochemical characteristics that suggest a secondary etiology, which can lead to timely diagnosis and treatment.

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OBJECTIVE: To explore pituitary tumors by methylome and transcriptome signatures in a heterogeneous ethnic population. METHODS: In this retrospective cross-sectional study, clinicopathological features, methylome, and transcriptome were evaluated in pituitary tumors from 77 patients (61% women, age 12-72 years) followed due to functioning (FPT: GH-secreting n = 18, ACTH-secreting n = 14) and nonfunctioning pituitary tumors (NFPT, n = 45) at Ribeirao Preto Medical School, University of São Paulo. RESULTS: Unsupervised hierarchical clustering analysis (UHCA) of methylome (n = 77) and transcriptome (n = 65 out of 77) revealed 3 clusters each: one enriched by FPT, one by NFPT, and a third by ACTH-secreting and NFPT. Comparison between each omics-derived clusters identified 3568 and 5994 differentially methylated and expressed genes, respectively, which were associated with each other, with tumor clinical presentation, and with 2017 and 2022 WHO classifications. UHCA considering 11 transcripts related to pituitary development/differentiation also supported 3 clusters: POU1F1-driven somatotroph, TBX19-driven corticotroph, and NR5A1-driven gonadotroph adenomas, with rare exceptions (NR5A1 expressed in few GH-secreting and corticotroph silent adenomas; POU1F1 in few ACTH-secreting adenomas; and TBX19 in few NFPTs). CONCLUSION: This large heterogenic ethnic Brazilian cohort confirms that integrated methylome and transcriptome signatures classify FPT and NFPT, which are associated with clinical presentation and tumor invasiveness. Moreover, the cluster NFPT/ACTH-secreting adenomas raises interest regarding tumor heterogeneity, supporting the challenge raised by the 2017 and 2022 WHO definition regarding the discrepancy, in rare cases, between clinical presentation and pituitary lineage markers. Finally, making our data publicly available enables further studies to validate genes/pathways involved in pituitary tumor pathogenesis and prognosis.

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Corticotroph cells give rise to aggressive and rare pituitary neoplasms comprising ACTH-producing adenomas resulting in Cushing disease (CD), clinically silent ACTH adenomas (SCA), Crooke cell adenomas (CCA) and ACTH-producing carcinomas (CA). The molecular pathogenesis of these tumors is still poorly understood. To better understand the genomic landscape of all the lesions of the corticotroph lineage, we sequenced the whole exome of three SCA, one CCA, four ACTH-secreting PA causing CD, one corticotrophinoma occurring in a CD patient who developed Nelson syndrome after adrenalectomy and one patient with an ACTH-producing CA. The ACTH-producing CA was the lesion with the highest number of single nucleotide variants (SNV) in genes such as USP8, TP53, AURKA, EGFR, HSD3B1 and CDKN1A. The USP8 variant was found only in the ACTH-CA and in the corticotrophinoma occurring in a patient with Nelson syndrome. In CCA, SNV in TP53, EGFR, HSD3B1 and CDKN1A SNV were present. HSD3B1 and CDKN1A SNVs were present in all three SCA, whereas in two of these tumors SNV in TP53, AURKA and EGFR were found. None of the analyzed tumors showed SNV in USP48, BRAF, BRG1 or CABLES1. The amplification of 17q12 was found in all tumors, except for the ACTH-producing carcinoma. The four clinically functioning ACTH adenomas and the ACTH-CA shared the amplification of 10q11.22 and showed more copy-number variation (CNV) gains and single-nucleotide variations than the nonfunctioning tumors.

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Abstract Objectives: to analyze, evaluate and describe the usefulness of petrosal sinus sampling for diagnosing central Cushing's syndrome. Materials and methods: the technical aspects and results of bilateral venous sampling of the petrosal sinuses at the Hospital Universitario San Vicente de Paul in Medellín, Colombia, from January 1, 2012 to December 31, 2018, were analyzed. Results: the average age was 43.3 years, with a range from 19 to 69 years. Laterality could be shown in 68.2% of cases, with a tendency to be located on the left in 53.3%. The central source of ACTH production could be shown in 95.4% of cases, with a basal average central/peripheral ratio of 21.7, and 70.8 after stimulation. All samples at 3, 5 and 10 minutes were confirmatory following stimulation. Conclusion: in our retrospective study, petrosal sinus catheterization provided laboratory confirmation of the central source of ACTH production in a high percentage of patients, with no immediate complications.

Resumen Objetivos: analizar, evaluar y describir la utilidad del muestreo de senos petrosos para diagnóstico del síndrome de Cushing de origen central. Material y métodos: se analizaron los aspectos técnicos y resultados del muestreo bilateral venoso de senos petrosos, desde el 1° de enero de 2012 a 31 de diciembre de 2018 en el Hospital Universitario San Vicente de Paúl en Medellín, Colombia. Resultados: el promedio de edad fue 43.3 años con un rango de edad desde los 19 hasta los 69 años. La lateralidad pudo ser demostrada en 68.2% de los casos con una tendencia a la localización en el lado izquierdo en 53.3%. El origen central de producción de ACTH logró ser demostrado en 95.4% de los casos, con una relación central/periferia basal promedio de 21.7 y postestimulación de 70.8. Todas las muestras a los 3, 5 y 10 minutos fueron confirmatorias tras la estimulación. Conclusión: en nuestro estudio retrospectivo el cateterismo de senos petrosos confirmó la fuente central de producción de ACTH por laboratorio en un alto porcentaje de pacientes sin ninguna complicación inmediata.

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INTRODUCTION: Individuals with pituitary adenomas may have organic consequences of their disease or therapy, and psychological changes can compromise their quality of life (QoL). This study aimed to determine the anthropometric profile and health indicators of patients with pituitary adenoma before and after pituitary surgery. METHODS: Forty-four patients were included in this study. Out of these, 22 patients had nonfunctioning adenomas (50%), 17 acromegaly (38.6%), and 5 patients with Cushing's disease (11.4%). Anthropometric measurements included body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR). Health indicators included body fat percentage (BF%), basal metabolic rate (BMR), maximal oxygen uptake (VO2 max), and hand grip strength. Physical activity level (the International Physical Activity Questionnaire [IPAQ]), subjective perception of health, body image (Body Shape Questionnaire), body satisfaction (Stunkard Figure Rating Scale) were used. RESULTS: The mean patient age was 47.2 ± 14.6 years; of which 25 were women (56.8%). Before surgery, 75.0% were overweight or obese, 84.1% had WC with risk of metabolic complications, and 90.0% had WHR with cardiovascular risk. There was a high BF% in 56.4% of cases, low BMR in 65.1%, lower VO2 max in 16.2%, and below-average grip strength in 88.6%. Hypopituitary patients had poorer cardiorespiratory fitness. The IPAQ showed reduction in physical activity, and 79.5% of patients were dissatisfied with their body image. Patients with nonfunctioning adenomas had better perception of their health while those with Cushing's disease had more distorted body image. Postoperatively, patients with acromegaly showed improvement in WHR and physical activity level, and patients with Cushing's disease showed improvement in anthropometric variables. CONCLUSIONS: These findings emphasize the need for continuous monitoring of this population for anthropometric indicators associated with metabolic and cardiovascular comorbidities as well as body satisfaction.

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Los adenomas de hipófisis son tumores benignos originados en uno de los cinco tipos celulares de la hipófisis anterior. La insuficiencia suprarrenal secundaria ocurre cuando las glándulas adrenales no producen hormonas por la falta de hormona adenocorticotrópica hipofisaria o del factor liberador de corticotropina hipotalámico. Se presenta el caso de una paciente de 37 años de edad, que un año atrás comenzó con fasciculaciones musculares de piernas y brazos, debilidad muscular, cansancio fácil, dolores musculares, cefalea hemicránea derecha, intensa y pulsátil, entre otros síntomas. Se le realizaron varios estudios (dosificación de cortisol en sangre, hormona adenocorticotrópica, calcio y fósforo en sangre y orina, resonancia magnética de cráneo) que permitieron el diagnóstico de adenoma de hipófisis con déficit aislado de hormona adenocorticotrópica e insuficiencia suprarrenal secundaria. El tratamiento con esteroides y suplementos de calcio garantizaron la evolución favorable.

Pituitary adenomas are benign tumors arising from one of the five cell types in the anterior pituitary. Secondary adrenal insufficiency occurs when the adrenal glands do not produce hormones due to the lack of pituary adrenocorticotropic hormone or hypothalamic corticotropin-releasing factor. The case of a 37-year-old female patient who started developing muscle twitching in legs and arms, muscular weakness, fatigue, muscle aches, severe and throbbing hemicrania on the right side, among other symptoms, a year ago is presented. Several tests were performed (cortisol level, adrenocorticotropic hormone, calcium and phosphorus in blood and urine, magnetic resonance imaging of the skull), leading to the diagnosis of pituitary adenoma with isolated adrenocorticotropic hormone deficiency and secondary adrenal insufficiency. Treatment with steroids and calcium supplements ensured a satisfactory recovery.