Un caso de hipercalcemia hipocalciúrica de causa genética en niño prepúber / Genetic hypercalcemic hypocalciuria in a prepubertal boy

Un paciente de 12 años consultó por vómitos recurrentes asociados con cefaleas, con varios episodios durante 7 meses, y retraso ponderal secundario a esa sintomatología. Había recibido previamente un tratamiento con antibióticos e inhibidores de la bomba de protones, por diagnóstico de gastritis a Helicobacter pylori, después de biopsia gástrica realizada durante una videoendoscopía digestiva alta. Se desconoce su historia familiar porque es hijo adoptivo. Al examen físico el paciente estaba adelgazado, sin tumoración a nivel de cuello; presentaba genitales prepuberales. Como el paciente continuó con vómitos cíclicos recurrentes, siguieron exámenes complementarios donde se constató en 2 oportunidades hipercalcemia (13,2-13,6 mg/dl), acompañada de hipofosfatemia (2,7 mg/dl). Con un diagnóstico presuntivo de hiperparatiroidismo primario se realizaron dosajes de laboratorio: calcemia total e iónica elevada (12,1 y 5,6mg/dl respectivamente), fosfatemia baja (2,8 mg/dl), fosfatasa alcalina sérica normal (151 mU/ml), PTH sérica normal (47,1 pg/ml), 25(OH)vitamina D sérica adecuada (22 ng/ml). La ecografía de glándulas tiroides y paratiroides mostró una imagen redondeada hipoecoica, avascular, de 4 mm axial por 4 mm cefalocaudal, por 3 mm ánteroposterior en topografía paratiroidea derecha, planteándose la posibilidad de hipertrofia paratiroidea versus adenopatía. Se realizó estudio de paratiroides por imágenes: centellograma con 99mTc-MIBI y PET-CT con 18F-colina, pero no se constató captación anormal. Se realizaron nuevos estudios de laboratorio: en orina de 24 horas el calcio era de 19 mg, el cociente calcio/creatinina urinaria 0,03 mg/mg, la reabsorción tubular de fósforo normal (82%) y el cociente de las tasas de depuración de calcio y creatinina muy bajo (0,00046). El CTX sérico era bajo. El diagnóstico clínico fue de hipercalcemia hipocalciúrica; ante la falta de antecedentes familiares, se realizó un estudio de posibles mutaciones puntuales en el gen del receptor de calcio (CaSR), hallándose la presencia en heterocigosis de la mutación p.Arg185Gln (p.R185Q) en la posición 554 (c.554G>A) del exón 4 del gene CaSR. Esto implica el cambio de una arginina por glutamina en el codón 185 de la proteína, y confirma el origen genético de la hipercalcemia hipocalciúrica en nuestro paciente. La edad ósea era de 12 años, y se indicó un tratamiento con testosterona i.m. a bajas dosis para acelerar el desarrollo puberal; luego de 4 aplicaciones mensuales su talla se ha incrementado en 4 cm y su peso en 3 kg. Una aplicación subcutánea de denosumab (60 mg) no controló la hipercalcemia. Continuó por un año con hipoorexia y un episodio de vómitos por semana, pero actualmente tiene buen apetito y excelente tolerancia digestiva. Se le ha prescripto cinacalcet oral (AU)

A 12-year-old patient who consulted for recurrent vomiting associated with headaches, with several episodes for 7 months, and low body weight. The patient had previously received treatment with antibiotics and proton pump inhibitors, due to gastritis with Helicobacter pylori, after gastric biopsy performed during videoendoscopy. His family history is unknown because he is an adopted son. At physical examination the patient was thin, without neck tumor; he had prepubertal genitalia. As he patient continued with recurrent vomiting, he was admitted for further evaluation. Laboratory studies revealed hypercalcemia (13.2-13.6 mg/dl), accompanied by hypophosphatemia (2.7 mg/dl). With a presumptive diagnosis of primary hyperparathyroidism, complementary determinations were performed: total and high total and ionized serum calcium (12.1 and 5.6 mg/dl, respectively), normal serum alkaline phosphatase (151 mU/ml), and PTH (47.1 pg/ml), and normal serum 25(OH) vitamin D (32 ng/ml). The ultrasonography of thyroid and parathyroid glands showed a rounded hypoechoic, avascular image, 4 mm in diameter in the lower right parathyroid topography. A parathyroid imaging studies were performed: scintigraphy with 99mTc-MIBI and PET-CT with 18F-choline, but no abnormal uptake was observed. New laboratory studies were carried out: in 24-hour urine the calcium was 19 mg, the urinary calcium/creatinine ratio was 0.03 mg/mg, the tubular reabsorption of phosphorus was normal (82%) and the ratio of clearances rates of calcium and creatinine very low (0.00046). Serum CTX was low. The clinical diagnosis was hypocalciuric hypercalcemia; in the absence of a family history, a study of possible point mutations in the calcium receptor gene (CaSR) was carried out; there was a heterozygous mutation: p.Arg185Gln (p.R185Q) at position 554 (c.554G)>A) of exon 4 of the CaSR gene. This involves the exchange of an arginine for glutamine at codon 185 of the protein, and confirms the genetic origin of the hypocalciuric hypercalcemia in our patient. Bone age was 12 years, and a treatment with testosterone i.m. at low doses to accelerate pubertal development was started; after 4 monthly applications height has increased by 4 cm and weight by 3 kg. Loss of appetite and a weekly episode of postprandial vomiting continued during one yeas, but now his appetite is normal and vomiting has subsided. A subcutaneous application of denosumab (60 mg) did not control hypercalcemia. He has been prescribed oral cinacalcet (AU)

Efectos óseos de la cirugía bariátrica / Effects of bariatric surgery on bone

La cirugía bariátrica es un recurso terapéutico cuyo uso para el manejo de la obesidad mórbida crece rápidamente. La intervención induce varios cambios en el perfil hormono-metabólico de los pacientes: disminuye la absorción de calcio, caen los niveles de vitamina D, se produce un hiperparatiroidismo secundario que acelera el recambio óseo, aumentan algunas citoquinas como la adiponectina, el GLP-1 y la esclerostina, y disminuyen otras como la leptina, la ghrelina, el GIP y la amilina. El estradiol cae por disminución de la aromatización periférica de la testosterona. Hay disminución de la carga mecánica en el esqueleto, especialmente en los miembros inferiores. Todo esto lleva a pérdida de la masa ósea, que es variable y más marcada en el fémur proximal que en la columna. El riesgo de fractura aumenta, aunque no todas las series lo han demostrado. Los pacientes con marcada disminución del peso corporal poscirugía deberían ser controlados, procurandoun buen aporte de calcio y otros nutrientes, la suplementación con vitamina D y el monitoreo de la densitometría ósea. (AU)

Bariatric surgery is a therapeutic resource for the management of morbid obesity; its use is growing rapidly. The intervention induces several changes in the hormonal and metabolic profile of patients: decreased calcium absorption, falling levels of vitamin D, secondary hyperparathyroidism which accelerates bone turnover; increased level of some cytokines such as adiponectin, GLP-1 and sclerostin, and decreased levels of others such as leptin, ghrelin, GIP and amylin. Estradiol falls due to decreased peripheral aromatization of testosterone. There is a decrease in the mechanical load on the skeleton, especially in the lower limbs. All this leads to loss of bone mass, which is variable and more marked in the proximal femur than in the spine. The risk of fracture increases, although it has not been shown in all series. Patients with marked decrease in body weight after bariatric surgery should be controlled carefully to insure a good supply of calcium and other nutrients, vitamin D supplementation, and the monitoring of bone mineral density. (AU)

Vulnerability of healthy vertebrae in patients with and without previous vertebral fracture.

Vertebral deformities are associated with a marked increase in morbidity, mortality, and burden in terms of sanitary expenditures. Patients with vertebral fractures have a negative impact in their health, less quality of life, and loss of functional capacity and independence. The purpose of this study was to explore the vulnerability of healthy vertebrae in patients who have sustained already a compression fracture and in patients who do not have prevalent fractures in the thoracic spine; and to explore the association of the deformity in healthy vertebrae with different variables, such as bone mineral density (BMD), body mass index, age, loss of height, presence of clinical kyphosis, history of other osteoporotic fractures, and falls occurring during the last year. Clinical data and complementary studies from 175 postmenopausal outpatients were analyzed. These women (age: 69.7±11.1 years) had not received any treatment for osteoporosis. Anteroposterior and lateral radiographs of the thoracic spine and bone densitometry of the hip were obtained; morphometry was performed in 1575 thoracic vertebrae from T4 to T12. The angle of wedging of each vertebral body was calculated using a trigonometric formula. Then, the sum of wedge angles of vertebral bodies (SWA) was determined, and Cobb angle was measured. In patients with vertebral fractures, after excluding the angles of fractured vertebral bodies, the mean wedge angle of the remaining vertebrae (MWAhealthy) was calculated. The same procedure was followed in patients without vertebral fractures. MWAhealthy was considered as an indicator of the structural vulnerability of non-fractured vertebrae. Patients with prevalent fractures had lower BMD, wider Cobb angle, and higher sum of wedge angles than patients without vertebral fractures. The proportion of patients with accentuation of clinical kyphosis was higher in the group with prevalent vertebral fractures. A highly significant difference was found in the MWAhealthy, which was higher in patients with prevalent fractures (4.1±1.3° vs. 3.0±1.1°; p<0.001). Patients showing vertebral fractures had 7.1±4.2 cm height loss in average, significantly superior than that found among non-fractured women (3.6±3.2 cm; p<0.01). In multivariate analysis, the increase of MWAhealthy was associated with advancing age (p<0.02), lower femoral neck BMD (p<0.005), presence of clinical kyphosis (p<0.01) and vertebral fractures (p<0.02). This study presents evidence that a series of factors independently influence the increase in wedging deformity of vertebral bodies that are not fractured yet. These factors could contribute to an increased vulnerability of the vertebrae, making them more susceptible to fracture.

Aprendizaje en hipnosis profunda: potenciación de capacidades mentales?

En esta investigación los autores se propusieron enfrentar la solución de las dificultades académicas individuales de los estudiantes en la asignatura de Histología, empleando la hipnosis durante parte de su estudio individual, y luego comparar los resultados anteriores en la disciplina con los obtenidos en el examen aplicado después de la intervención. En el período de evaluaciones finales del primer semestre del curso 1997, siete estudiantes en riesgo académico fueron sometidos a inducción hipnótica, para que estudiaran la materia en dos sesiones de hipnosis muy profunda, durante las cuales se les dieron sugerencias de seguridad, concentración máxima, reforzamiento de capacidades intelectuales, aumento de la afectividad positiva hacia el estudio, potenciación de las capacidades de memoria, análisis, síntesis, resumen y generalización. El proceso transcurrió con sordera selectiva y visión selectiva. Los resultados en el examen final fueron comparados mediante la prueba de los signos, con los resultados anteriores obtenidos en la asignatura, comprobándose un aumento significativo del rendimiento(AU)