Caracterización clínica de pacientes chilenos con displasia fibrosa/síndrome de McCune-Albright / Clinical features of Chilean patients with Fibrous Dysplasia/McCune-Albright Syndrome

BACKGROUND: Fibrous Dysplasia/McCune-Albright Syndrome (FD/MAS) is characterized by a spectrum of manifestations that may include fibrous dysplasia of bone and multiple endocrinopathies. AIM: To describe the clinical spectrum, the study and follow-up of patients with FD/MAS cared at our institution. MATERIAL AND METHODS: Review of medical records of 12 pediatric and adult patients (11 women) who met the clinical and genetic diagnostic criteria for FD/ MAS. RESULTS: The patients' mean age at diagnosis was 4.9 ± 5.5 years. The most common initial clinical manifestation was peripheral precocious puberty (PPP) in 67% of patients and 75% had café-au-lait spots. Fibrous dysplasia was present in 75% of patients and the mean age at diagnosis was 7.9 ± 4.7 years. Ten patients had a bone scintigraphy, with an age at the first examination that varied between 2 and 38 years of age. The most frequent location of dysplasia was craniofacial and appendicular. No patient had a recorded history of cholestasis, hepatitis, or pancreatitis. In four patients, a genetic study was performed that was positive for the pathogenic variant of guanine nucleotide binding protein, alpha stimulating (GNAS). CONCLUSIONS: These patients demonstrate the variable nature of the clinical presentation and study of FD/MAS. It is essential to increase the index of diagnostic suspicion and adherence to international recommendations.

Reporte de caso de feocromocitoma bilateral asociado a mutación del gen TMEM127. Primer caso chileno / Bilateral pheochromocytoma associates with TMEM127 gene mutation. Report of one case

Up to 40% of Pheochromocytoma/paraganglioma syndromes are associated with germline mutations. Therefore, they are considered familial and heritable. We report a 65 year old woman with hypertension, bilateral adrenal nodules found in the CT scan and elevated urinary metanephrines. Her genetic testing showed a c.117_120delGTCT TMEM127 gene mutation. She was subjected to a laparoscopic bilateral adrenal excision. After five years of follow up, no recurrence of the disease has been recorded.

Actualización en el manejo clínico de la hipertensión hiporreninémica / Update in the clinical management of low renin hypertension

The renin-angiotensin-aldosterone system modulates volume, sodium and potassium homeostasis. In the setting of a high sodium diet, up to 30% of patients with hypertension have a low or suppressed renin and increased volume. This phenotype of low renin hypertension (LRH) is multifactorial and includes infrequent inherited genetic syndromes, milder phenotypes of classic diseases and environmental exposures. All these conditions have in common a higher cardiovascular risk mediated by the over activation of the mineralocorticoid receptor (MR), present not only in the kidney, but also in vasculature, myocardium and adipocytes. Consequently, the aim of LRH treatment goes beyond the control of blood pressure and requires antagonizing MR with specific pharmacologic agents, pursuing normalization of renin as a clinical objective. Due to the unusual evaluation of renin status by non-endocrinologists and lack of disease awareness, only a minority of hypertensive patients receive this pathophysiologically-driven treatment that should reduce cardiovascular outcomes.

¿Como optimizar el diagnóstico funcional de los incidentalomas suprrarenales? Importancia de un estudio protocolizado / How to optimize the functional diagnosis of suprarenal incidenta- lomas? Importance of a protocolized study

Adrenal incidentalomas are an increasingly common pathology. Although historically they have been considered largely non-functioning, recent evidence suggests that the usually performed study is incomplete and/or not sensitive enough. In the last decade the clinical spectrum of adrenal hypercortisolism has expanded considerably, including milder cases which are also associated with cardiovascular morbidity and even mortality. Furthermore, primary aldosteronism has also expanded beyond the classic phenotype with advanced vascular damage, resistant hypertension and hypokalemia, currently including asymptomatic, normotensive and normokalemic patients. For this reason, a correct protocolized study is essential in all adrenal incidentalomas, including a precise radiological characterization, as well as a systematic hormonal evaluation using more sensitive cut points. The findings of this workup are relevant, because they allow a more individualized approach to the medical and surgical management of these patients.

Los incidentalomas suprarrenales son una patología cada vez más frecuente. Si bien históricamente han sido considerados no funcionantes en su gran mayoría, evidencia reciente sugiere que el estudio habitual es incompleto y/o poco sensible. En la última década el espectro clínico del hipercortisolismo de origen adrenal se ha ampliado de forma considerable, incluyendo casos leves que también se asocian a morbilidad cardiovascular e incluso mortalidad. Por otro lado, el hiperaldosteronismo primario también ha expandido su fenotipo más allá del clásicamente descrito con daño vascular avanzado, hipertensión resistente e hipokalemia, abarcando en la actualidad a pacientes asintomáticos, normotensos y normokalemicos. Por esta razón es imprescindible un correcto estudio protocolizado en todo incidentaloma suprarrenal, incluyendo una precisa caracterización radiológica, así como una evaluación hormonal sistemática utilizando puntos de corte más sensibles. Los hallazgos de este estudio son relevantes, pues permiten guiar de forma más individualizada el manejo médico y quirúrgico de estos pacientes.

Estudio e identificación de microRNA en exosomas urinarios en hipertensión arterial mineralocorticoide / Study and identification of microRNA in urinary exosomes in mineralocorticoid arterial hypertension

About 15% of the essential hypertensive patients would have a low activity of the 11ßHSD2 enzyme, which inactivates cortisol (F) to cortisone (E). Gene expression can be negatively regulated by miRNA. Urinary exosomes and their specific content (miRNA/proteins) represent a valuable tool as a biomarker for the diagnosis and prognosis of the disease. Aim: To evaluate the expression of miRNA specific for 11ßHSD2 in samples of urinary exosomes and to determine its association with biochemical variables associated with mineralocorticoid metabolism. Subjects and Methods: Cross-sectional study in subjects between 10-60 years. They were classified into subjects with high F/E (> p75) and low cortisone (< p25) and control subjects. The urinary exosomes were isolated with the Invitrogen kit. Bioinformatic analysis was performed with Mir Walk to identify specific miRNAs of HSD11B2. The expression of miRNA was evaluated by qRT PCR. The comparisons were made with the Mann-Whitney test. Results: 7.1% of the subjects are suggestive of a partial deficiency of 11ßHSD2 (NC-AME). The expression of miR-488 was higher in NC-AME than in controls (5839 ± 1719 vs 3,437 ± 2,581; p = 0.01). We found positive associations between mir-615 and ARP; miR-488 and the sodium/potassium ratio; miR-1205 with age and urinary sodium excretion; miR-494 with age, activity MMP9 and NGAL. Conclusion: We identified high expression of miR488 in NC-AME subjects and associations of miRNAs with biochemical variables associated with mineralocorticoid metabolism. Thus, exosomes and their miRNA content could be potential regulators and biomarkers of 11ßHSD2 activity.

Hiperaldosteronismo primario y otras formas de hipertensión arterial endocrina / Primary hyperaldosteronism and other forms of endocrine arterial hypertension

La hipertensión arterial (HTA) dependiente de mineralocorticoides representa actualmente una de las formas secundarias de hipertensión de mayor prevalencia. Entre las causas más prevalentes está el hiperaldosteronismo primario (HAP) cuya prevalencia es cercana al 10 por ciento de la población de hipertensos. El HAP se detecta principalmente por una elevación de la razón aldosterona a actividad renina plasmática (ARR), ya que la hipokalemia es infrecuente de encontrar. La fisiopatología del HAP se presenta como un desequilibrio en el control electrolítico a nivel renal, por mayor actividad del receptor mineralocorticoides (MR), lo cual aumenta el volumen intravascular y la presión arterial. Recientemente se ha demostrado también que el exceso de aldosterona afecta también el endotelio vascular, el tejido cardiaco entre otros. Este exceso puede ser por una alteración a nivel de la glándula suprarrenal (generalmente hiperplasia o adenoma) o formas genéticas (familiares). Por otra parte, alteraciones parciales o totales de la enzima 11ß-Hidroxiesteroide deshidrogenasa tipo 2 (11ß-HSD2) resulta en una metabolización total o parcial de cortisol, imitando los efectos de aldosterona sobre MR. La actividad de esta enzima se evalúa midiendo la razón cortisol a cortisona en suero por HPLC-MS/MS. La prevalencia de alteraciones parciales de la actividad de la enzima 11ß-HSD2 en estudios de cohorte alcanza en alrededor del 15 por ciento en población hipertensa. El diagnóstico del HAP o deficiencias de 11BHSD2, permitiría un tratamiento específico del cuadro hipertensivo mediantes el uso de bloqueadores del receptor mineralocorticoideo y/o uso de corticoides de acción prolongada sin actividad mineralocorticoidea como dexametasona o betametasona.(AU)

Mineralocorticoid arterial Hypertension represents currently one of the secondary forms of hypertension most prevalent. Among the most prevalent causes is the primary aldosteronism (PA) whose prevalence is close to 10 percect of the hypertensive population. PA is detected by elevated aldosterone to plasma renin activity ratio (ARR) and the hypokalemia is rare to find. The pathophysiology of PA is presented as a renal electrolyte imbalance, increasing mineralocorticoid receptor (MR) activity, intravascular volume and blood pressure. Recently it has also shown that excessive aldosterone also affects vascular endothelium, heart tissue among others. This excess can be associated to an adrenal gland (usually hyperplasia or adenoma) or genetic (familiar) alteration. Similarly, partial or total impairment in 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2) enzyme affects the cortisol metabolism, mimicking the effects of aldosterone on MR. The activity of this enzyme is evaluated by measuring the serum cortisol to cortisone ratio by HPLC-MS/MS. The prevalence of partial alterations of the activity of 11ß-HSD2 enzyme in cohort studies reached at around 15 percent in hypertensive population. The diagnosis of PA or an impairment in 11ß-HSD2 activity allows specific treatments of hypertensive patients using mineralocorticoid receptor blockers and/or use of long-acting corticosteroids without mineralocorticoid activity as dexamethasone or betamethasone.(AU)

Diseño de una escala ecográfica predictora de malignidad en nódulos tiroideos: Comunicación preliminar / An ultrasound score to predict the presence of papillary thyroid carcinoma: Preliminary report

Background: Thyroid nodules are common and associated to a low risk of malignancy. Their clinical assessment usually includes a fine neddle aspiration biopsy (FNAB). Aim To identify ultrasonographic characteristics associated to papillary thyroid carcinoma (PTC) and generate a score that predicts the risk of PTC. Material and methods: Retrospective review of all fine needle aspiration biopsies of the thyroid performed in a lapse of two years. Biopsies that were conclusive for PTC were selected and compared with an equal amount of randomly selected biopsies that disclosed a benign diagnosis. Results: One hundred twenty two biopsies of a total of 1,498 were conclusive for PTC. Univariate analysis showed associations with PTC for the presence of micro-calcifications (Odds ratio (OR) 49.2: 95 percent confidence intervals (CI) 18.7-140.9), solid predominance (OR 25.1; 95 percent CI 6-220), hypoechogenicity (OR 23.5, 95 percent CI 6.5-122.6), irregular borders (OR 17, 95 percent CI 7.2-42.9), lymph node involvement (OR 12.3, 95 percent CI2.7-112), central vascularization (OR 12.2, 95 percent CI 4.8-33.3), local invasion and hyperechogenicity (OR 0.2; CI95 percent CI 0.03-0.6). Multivariate analysis disclosed microcalcifications (OR 28.1; CI 95 percent 8.9-89), hypoechogenicity (OR 9.4; 95 percent CI 1.5-59.5) and irregular borders (OR 4.7; CI 95 percent 1.5-15) as the variables independently associated with the presence of PTC. The prevalence of PTC in the presence of the three variables was 97.6 percent (Likelihood ratio (LR) 45) and 5.4 percent in their absence (LR 0.06). Conclusions: This scale predicts the presence or absence of PTC using simple ultrasound characteristics.