RESUMEN
PURPOSE: Endocrinopathies constitute ~ 10% of secondary hypertension (SH) etiologies. Primary aldosteronism, pheochromocytoma (PHEO), and Cushing's syndrome are common causes. Early identification and treatment result in resolution/improvement of SH. The aim of this study was to characterize the clinical course, outcomes, and remission-associated prognostic factors of SH related to adrenal tumors. METHODS: Retrospective cohort study including patients with SH who underwent adrenalectomy from 2000 to 2019. Postoperative outcomes were analyzed. Remission was defined as normalization of blood pressure without drug use. RESULTS: Eighty-three patients with SH were included. Mean ± SD age was 38.8 ± 14.2 years and 75.9% were women. Diagnosis was PHEO in 35 patients (42.2%), aldosteronoma (APA) in 28 (33.7%), cortisol producing adenoma (CPA) in 16 (19.3%), and ACTH-dependent Cushing's in 4 (4.8%). Laparoscopic adrenalectomy was performed in 81 (97.6%) patients. Mean ± SD follow-up was 57.4 ± 49.6 months (range 1-232). Surgical morbidity occurred in 7.2% of patients and there was no mortality. Remission of SH occurred in 61(73.5%): 100% of ACTH-dependent Cushing's, 85.7% of PHEO, 68.8% of CPA, and 57.1% of APA. Biochemical phenotype and the combination of larger tumor size, number of antihypertensive drugs, male gender, older age, obesity, and preoperative SH for more than 5 years were associated with less likely clinical remission in patients with APA (p = 0.004), CPA (p < 0.0001), and PHEO (p < 0.0001). CONCLUSION: SH remission rates are 57-100% after adrenalectomy. Several prognostic factors could be used to predict SH control. Adrenalectomy provides good clinical outcome and must be considered a treatment option in all surgical candidates.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Síndrome de Cushing , Hipertensión , Neoplasias de las Glándulas Suprarrenales/complicaciones , Neoplasias de las Glándulas Suprarrenales/cirugía , Adrenalectomía , Adulto , Anciano , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/etiología , Síndrome de Cushing/cirugía , Femenino , Humanos , Hipertensión/epidemiología , Hipertensión/etiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
The islet amyloid polypeptide (IAPP) or amylin maintains a key role in metabolism. This 37-residues-peptide could form pancreatic amyloids, which are a characteristic feature of diabetes mellitus type 2. However, some species do not form amyloid fibril structures. By employing a biomimetic approach, we generated an extensive panel of optimized sequences of IAPP, which could drastically reduce aggregation propensity. A structural and cellular characterization analysis was performed on the C-terminal domain with the highest aggregation propensity. This allowed the observation of an aggregative phenomenon dependent of the lipid environment. Evaluation of the new F23R variant demonstrated inhibition of ß-sheet structure and, therefore, amyloid formation on the native C-terminal, phenomenon that was associated with functional optimization in calcium and cholesterol management coupled with the optimization of insulin secretion by beta cells. When F23R variant was evaluated in microglia cells, a model of amyloidosis, cytotoxic conditions were not registered. In addition, it was found that C-terminal sequences of IAPP could modulate cholesterol metabolism in hepatocytes through regulation of SREBP-2, apoA-1, ABCA1, and LDLR, mechanism that may represent a new function of IAPP on the metabolism of cholesterol, increasing the LDL endocytosis in hepatocytes. Optimized sequences with only one residue modification in the C-terminal core aggregation could diminish ß-sheet formation and represent a novel strategy adaptable to other pharmacological targets. Our data suggest a new IAPP function associated with rearrangements on metabolism of cholesterol in hepatocytes.