ABSTRACT
Resumen Introducción: Los tumores de las células de la granulosa de tipo juvenil (TCGJ) son muy poco fre cuentes, especialmente en menores de 1 año. Los signos de pubertad precoz constituyen la presenta ción clínica más importante. Objetivo: Presentar una lactante con pubertad precoz periférica, con diagnóstico de TCGJ, discutiendo las claves de su tratamiento y seguimiento. Caso Clínico: Lactante de 10 meses que presentó telarquia, vello púbico y tumor abdominal palpable acompañado de niveles plasmáticos de Estradiol aumentados, gonadotrofinas muy bajas e imágenes que mostraban masa ovárica gigante. Se realizó salpingooforectomía, obteniéndose regresión absoluta de signos y síntomas. La biopsia demostró TCGJ por lo que se tomó inhibina B (InB) como marcador después de la cirugía. Esta hormona estaba alta inicialmente, pero descendió rápidamente. El seguimiento se basó en InB, Hormona antimulleriana (AMH) y estradiol como se describe en este tipo de tumores. Conclusiones: Los TCGJ son muy infrecuentes en pediatría; deben sospecharse en niñas con puber tad precoz periférica. El tratamiento quirúrgico en la gran mayoría es curativo, pero debe mantenerse un estricto control con marcadores tumorales, siendo los más específicos la InB y la AMH y en menor escala los niveles de Estradiol.
Abstract Introduction: Juvenile granulosa cell tumors (JGCT) are very rare, especially in infants under the age of one. The most frequent presentation is with signs of precocious puberty. Objective: Present an in fant with peripheral precocious puberty, diagnosis of JGCT and follow up. Clinical case: 10-month-old female infant with thelarche, pubic hair and palpable abdominal mass accompanied with eleva ted levels of estradiol, very low gonadotrophins and images that show a very large ovarian mass. A sapingooforectomy was carried out with full regression of symptoms and signs and improvement of laboratory exams. The biopsy showed TCGJ so inhibin B (InB) was taken as tumoral marker after surgery. This hormone was high initially, but rapidly declined. Follow-up was based on InB, antimu-llerian Hormone (AMH) and estradiol as described in this type of tumors. Conclusions: Juvenil gra nulosa cell tumors are very infrequent in pediatric age, but should be suspected in girl with peripheral precocious puberty. The majority of cases improve with surgery, but strict surveillance of tumoral markers is needed. The most specific markers are inhibin B and anti mullerian hormone (AMH), followed by estradiol levels.
Subject(s)
Humans , Female , Infant , Ovarian Neoplasms/diagnosis , Puberty, Precocious/etiology , Granulosa Cell Tumor/diagnosis , Ovarian Neoplasms/complications , Granulosa Cell Tumor/complicationsABSTRACT
Background: Type I familial hyperaldosteronism is caused by the presence of a chimaetic gene CYPl 1B1/CYP11BZ which encodes an enzyme with aldosterone synthetase activityregulated by adrenocorticotrophic hormone (ACTH). Therefore, in patients with FH I is possible to normalize the aldosterone levels with glucocorticoid treatment. Recently it has been shown that aldosterone plays a role in the production of endothelial oxidative stress and subclinical inflammation. Aim: To evaluate subclinical endothelial inflammation markers, Me Metalloproteinase 9 (MMP-9) and ultrasensitive C reactive protein (usPCR), before and after glucocorticoid treatment in family members with FH-I caused by a de novo mutation. Patients and methods: We report three subjects with FH-I in a single family (proband, father and sister). We confirmed the presence of a chimaeric CYPl 1B1/CYP11B2 gene by ¡ong-PCR in all of them. Paternal grandparents were unaffected by the mutation. The proband was a 13year-old boy with hypertension stage 2 (in agree to The JointNational Committee VII, JNC-vIl), with an aldosterone/plasma rennin activity ratio equal to 161. A DNA paternity test confirmed the parental relationship between the grandparents and father with the index case. MMP-9 and usPCR levels were determined by gelatin zymography and nephelometry, respectively. Results: All affected subjects had approximately a 50 percent increase in MMP-9 levels. Only the father had an elevated usPCR. The endothelial inflammation markers returned to normal range after glucocorticoid treatment. Conclusions: We report a family canying a FH-I caused by a de novo mutation. The elevation of endothelial inflammation markers in these patients and its normalization after glucocorticoid treatment provides new insight about the possible deleterious effect of aldosterone on the endothelium.
Subject(s)
Adolescent , Female , Humans , Male , C-Reactive Protein/analysis , Endothelium, Vascular , Hyperaldosteronism/genetics , Matrix Metalloproteinase 9/blood , Mutation/genetics , Vasculitis/blood , Cytochrome P-450 CYP11B2/genetics , Aldosterone/blood , Biomarkers/blood , Hyperaldosteronism/blood , Oxidative Stress/physiology , Paternity , Polymerase Chain Reaction/methods , /genetics , Vasculitis/geneticsABSTRACT
Type I familial hyperaldosteronism (HAF-I) is caused by the presence of a chimeric gene CYP11B1/CYP11B2 which encodes an enzyme with aldosterone synthetase activity regulated by ACTH. HAF-I patients present with severe hypertension at young ages and a greater risk of stroke. AIM: To characterize clinical and biochemical presentation of family members with HAF-I. To evaluate endothelial oxidative stress markers before and after glucocorticoid treatment. PATIENTS AND METHODS: We evaluated three family members with HAF-I confirmed with a genetic test (XL-PCR) for chimeric gene CYP11B1/CYP11B2. The index case was a 13 years old boy with stage 2 hypertension (Joint National Committee VIIth report), plasma aldosterone/ plasma renin activity (AP/ARP) ratio of161 and normal plasma potassium. His father had primary hyperaldosteronism diagnosed at 25 years of age with hypertension and hypokalemia. His sister was 15 years old, with a normal blood pressure and an AP/ARP ratio of 37.6. RESULTS: All subjects had plasma xanthine-oxidase levels in the upperlimit of normal. Malondialdehyde was above normal in the index case and his father. These markers returned to normal with glucocorticoid treatment. CONCLUSIONS: We report a HAF-I carrying family with a wide phenotypical variability between affected members. Elevation of endothelial oxidativestress markers and its normalization after glucocorticoid treatment, may indicate that aldosterone produces endothelial damage and increases cardiovascular risk.