Recomendaciones para el manejo de la lisis tumoral / Recommendations for tumor lysis syndrome management

El síndrome de lisis tumoral representa una complicación potencialmente letal provocada por la liberación masiva de ácidos nucleicos, potasio y fosfato hacia la circulación como resultado de la lisis de células neoplásicas, las cuales se caracterizan por una rápida capacidad de proliferación y alta sensibilidad a fármacos. Esto puede ocurrir de forma espontánea antes del inicio del tratamiento y agravarse luego de haberse iniciado la quimioterapia. Presenta una alta mortalidad. Su prevención continúa siendo la medida terapéutica más importante. El cuadro clínico se caracteriza por la existencia de trastornos del metabolismo hidroelectrolítico, en particular, hipercalemia, hiperfosfatemia e hiperuricemia y por la aparición de una lesión renal aguda. Una adecuada intervención terapéutica implica hidratación intravenosa y medidas para prevenir o corregir las alteraciones metabólicas. En este artículo, se proponen lineamientos para seguir tanto en la etapa diagnóstica como en el tratamiento de esta complicación.

The tumor lysis syndrome represents a potentially lethal complication caused by the massive release of nucleic acids, potassium and phosphate into the circulation as a result of the lysis of neoplastic cells, which are characterized by a rapid proliferation capacity and high sensitivity to drugs. This may occur spontaneously prior to the start of treatment, becoming worse after the initiation of chemotherapy. It presents a high mortality; its prevention continues being the most important therapeutic measure. The clinical picture is characterized by the existence of hydroelectrolytic metabolism disorders, in particular hyperkalemia, hyperphosphatemia and hyperuricemia and by the appearance of an acute renal lesion. Adequate therapeutic intervention involves intravenous hydration and measures to prevent or correct metabolic alterations. This article proposes guidelines to follow both in the diagnostic stage and in the treatment of this complication.

Hipomagnesemia en recién nacidos con encefalopatía hipóxico isquémica en hipotermia corporal total / Hypomagnesemia in newborns with hypoxic ischemic encephalopathy and whole-body hypothermia

Resumen: Introducción: En recién nacidos (RN) con encefalopatía hipóxico isquémica (EHI) en hipotermia se describen alte raciones metabólicas que se asocian a pronóstico neurológico. La hipomagnesemia ha sido reportada en la literatura, pero no es medida ni corregida en todos los centros de atención neonatal. Objeti vo: Evaluar la frecuencia de hipomagnesemia e hipocalcemia en RN con EHI en tratamiento con hipotermia corporal total y evaluar la respuesta al aporte de sulfato de magnesio. Pacientes y Méto do: Estudio prospectivo, observational y descriptivo en RN con EHI sometidos a hipotermia corporal total, hospitalizados entre los años 2016-2017. Se realizó medición seriada en sangre de magnesemia (Mg) y calcemia (Ca). Con Mg menor o igual de 1,8 mg/dl se administró suplemento como sulfato de Mg para mantener niveles entre 1,9 y 2,8 mg/dl. Se describió la frecuencia de hipomagnesemia e hipocalcemia y su presentación en el tiempo. Se realizó registro prospectivo de evolución clínica. Se hizo un análisis estadístico descriptivo, con medidas de tendencia central. Resultados: Se incluyeron 16 pacientes. Presentaron hipomagnesemia 13/16 (81,3%), la que fue precoz (6-36 h de vida), nor malizándose con aporte de sulfato de magnesio, requiriendo 2a dosis 4 de ellos. Presentaron hipo- calcemia 6/16 (37,5%). Conclusiones: La hipomagnesemia es frecuente (80%), similar a lo descrito en la literatura. Dado su importancia fisiológica debe controlarse y corregirse, de igual manera que el calcio.

Abstract: Introduction: In newborns with the diagnosis of hypoxic-ischemic encephalopathy (HIE) treated with hypother mia, metabolic alterations are observed, which are associated with neurological prognosis. Hypo magnesemia has been reported frequently in the literature in these patients, but it is not measured or corrected in all neonatal healthcare centers. Objective: To evaluate the frequency of hypomag nesemia and hypocalcemia in newborns with HIE treated with whole-body hypothermia and to evaluate the response to the magnesium sulfate administration. Patients and Method: Prospective, observational and descriptive study in hospitalized newborns with the diagnosis of HIE and trea ted with whole-body hypothermia between the years 2016 and 2017. Serial blood measurement of magnesemia (Mg) and calcemia (Ca) was performed. When presenting an Mg level < 1.8 mg/dl, supplementation with magnesium sulfate was administered to maintain levels between 1.9 and 2.8 mg/dl. The frecuency of hypomagnesemia, hypocalcemia and clinical evolution was registered. A descriptive statistical analysis was performed, with central tendency measures. Results: Sixteen ca ses were included, 13 of them presented hypomagnesemia (81.3%), with early-onset (6-36 hours of life), which was normalized with magnesium sulfate treatment, receiving a second dose 4 patients. Six of 16 patients presented hypocalcemia (37.5 %). Conclusions: Hypomagnesemia is frequent (80%), similar to that described in the literature, and should be controlled and corrected early, given its physiological role, in the same way that calcium is controlled.

Uremic lion face syndrome / Face Leonina na Síndrome Urêmica

Abstract Mineral bone disorder is a common feature of chronic kidney disease. Lion face syndrome is rare complication of severe hyperparathyroidism in end-stage renal disease patients, which has been less commonly reported due to dialysis and medical treatment advances in the last decade. The early recognition of the characteristic facial deformity is crucial to prompt management and prevent severe disfigurement. The authors present a rare case of severe hyperparathyroidism presenting with lion face syndrome and bone fractures.

Resumo O distúrbio mineral e ósseo é uma característica comum da doença renal crônica. A síndrome da face leonina é uma complicação rara do hiperparatireoidismo grave em pacientes com doença renal terminal, que tem sido menos relatada devido aos avanços na diálise e tratamento médico na última década. O reconhecimento precoce da deformidade facial característica é crucial para estimular o tratamento precoce e prevenir a desfiguração severa. Os autores apresentam um caso raro de hiperparatireoidismo grave, apresentando síndrome da face leonina e fraturas ósseas.

Diagnóstico diferencial del raquitismo hipocalcémico. caso clínico / Differential diagnosis in hypocalcemic rickets: a clinical case

Introducción: La hipocalcemia es un hallazgo infrecuente en los pacientes atendidos en los servicios de urgencia pediátricos. El raquitismo se puede presentar como una hipocalcemia crónica la mayoría de las veces asintomática, sin embargo, algunos pacientes presentan tetanias hipocalcémica. Objetivo: Presentar el caso clínico de una niña con raquitismo hipocalcémico, cuyo diagnóstico fue tardío. Caso clínico: Prescolar de 2 años 5 meses con alteración en la marcha, mal incremento ponderal, espasmos musculares y signos de raquitismo activo. Los exámenes revelaron hipocalcemia severa, normofosfemia, fosfatasa alcalina y PTH elevada y niveles normales de 25 hidroxivitamina D. Se manejó con calcio y calcitriol, y se diagnosticó raquitismo vitamina D dependiente tipo I. Conclusión: Los síntomas y signos clásicos de raquitismo, así como la hipocalcemia, deben hacernos plantear hoy en día el diagnóstico de raquitismo. Un mejor conocimiento de esta patología permitirá evitar el retraso en el diagnóstico y un tratamiento más oportuno.

Introduction: Hypocalcemia is rare in patients attending pediatric emergency services. Rickets can present as a chronic hypocalcemia often asymptomatic, poor growth rate, psychomotor delay and bone abnormalities, but some patients may present tetanic seizures. Although its incidence has decreased, a resurgence of rickets has been described. Objective: To present a case of a child with hypocalcemic rickets, whose diagnosis was delayed. Case report: Preschool of 2,4 years old with gait disturbance, poor growth rate, muscle spams and signs of active rickets. Laboratory results showed hypocalcemia, normophosphemia, alkaline phosphatase, high PTH and normal 25-hydroxyvitamin D levels. She received treatment with calcium and calcitriol and had a good response; Vitamin D dependent rickets type I was diagnosed. Conclusion: Classics signs and symptoms of rickets, as hypocalcemic manifestations, should lead us today to diagnose rickets. Better knowledge of this disease will avoid retarded diagnosis and give a suitable treatment.

Miocardiopatía por hipocalcemia / Hypocalcemic cardiomyopathy

Se presenta el caso de un varón de 56 años, portador de Miocardiopatía dilatada, considerada, en algún momento, como terminal. Se comprobó que presentaba de base una hipocalcemia crónica secundaria a hipoparatiroidismo. Se discute su notable respuesta a administración de calcio e infusión de levosimendan IV fármaco inotropo positivo que actúa sensibilizando al calcio.

Miocardiopatía hipoclacémica secundaria a hipoparatiroidismo postiroidectomía: Caso clínico / Hypocalcemic cardiomyopathy secondary to hypoparathyroidism after a thyroidectomy: Report of one case

Calcium plays a central role in ventricular function. We report a 37 year-old woman with chronic hypoparathyroidism and hypocalcemia secondary to a thyroidectomy performed when she was 18 years old, as treatment for a Graves Basedow's disease. She did not have previous cardiac symptoms and rapid progressive congestive heart failure developed after the beginning of levothyroxin supplementation for post operative hypothyroidism. Echocardiography revealed severe systolic and diastolic left ventricular dysfunction, mitral and tricuspid valve insufficiency, systolic pulmonary hypertension, left atrial enlargement and pericardial effusion. Calcium supplementation in addition to diuretics, captopril and digoxin were followed by rapid clinical improvement. Follow up until 18 months showed persistent left ventricular dilatation and systolic dysfunction, with improvement of all the other ecocardiographic findings.

Incidencia de hipocalcemia pos tiroidectomía total / Incidence of hypocalcemia after total thyroidectomy

Background: Postoperative hypocalcemia is one of the most common complications of thyroid surgery. It is related to the type of disease (malignant or benign), the number of identified parathyroid glands during the surgical procedure, and the surgeon's experience. Total thyroidectomy is the procedure of choice in our hospital for benign and malignant thyroid disease, but it can increase the incidence of complications. Aim: To evaluate the incidence of postoperative hypocalcemia in patients subjected to a total thyroidectomy. Material and methods: Two studies were performed. A retrospective review of medical records of 448 patients subjected to total thyroidectomy, looking for serum calcium levels of less than 8 mg/dl and clinical signs of hypocalcemia. In a second study, 45 patients were followed with measurements of preoperative and postoperative serum calcium levels. Results: In the retrospective study, only 136 records had reliable information. Clinical signs of hypocalcemia were registered in 14 percent of patients and a low serum calcium level was detected in 50 percent. In the prospective study, 42 percent of patients had a postoperative low serum calcium level and seven patients (15 percent) had symptoms. Patients were handled with oral calcium and calcitriol in some cases. Ninety nine percent of patients had normal serum calcium levels two moths after surgery. Conclusions: In this series, the rate of postoperative hypocalcemia after total thyroidectomy is similar to internaitonal reports.

Hypocalcemia due to vitamin D deficiency in exclusively breastfed infants.

This report is based on observations during the conduct of a study of hypocalcemia in infants and children. In a study of 50 cases, 13 exclusively breast fed infants manifesting with hypocalcemic seizures were confirmed to have vitamin D deficiency. None of the 13 infants had received vitamin D supplementation. All of them had biochemical evidence of hyperparathyroidism and low levels of 25 (OH) Vit D3 and promptly responded to therapy with vitamin D and calcium. All the mothers of these 13 infants had low levels of 25 (OH) Vit D3. Mothers of 5 infants had reported reduced exposure to sunlight due to religious reasons. This report emphasizes the need to supplement Vitamin D in exclusively breast fed infants and also to encourage exposure to sunlight in them and their mothers.

Neonatal pseudohypoparathyroidism.

The case of a neonate is presented who had early onset seizure associated with hypocalcemia, hyperphosphatemia, and raised parathyroid hormone. The infant did not have any stigmata of pseudohypoparathyroidism. The hypocalcemia was initially resistant to calcium therapy, but responded to vitamin D analog therapy. The diagnosis of 'neonatal pseudohypoparathyroidism' was entertained; the infant remained stable and seizure-free with normal serum biochemistry during 3 months of follow-up.

Completa recuperación de grave síndrome de hueso hambriento usando infusión crónica ambulatoria de calcio intravenoso. Caso clínico / Complete recovery of hungry bone syndrome using intravenous calcium infusion. Report of one case

We report a 29 years old woman with a highly symptomatic primary hyperparathyroidism. After parathyroid adenoma excision, she presented a prolonged and life threatening hypocalcemia, due to a severe hungry bone syndrome. Conventional treatment with oral and intravenous calcium and calcitriol supplementation failed to raise serum and urinary calcium or to relief symptoms. After one month, we indicated a continuous intravenous calcium infusion allowing, during 6 months, an adequate outpatient management. Initial T scores for bone density were markedly low (L2-L4: -3.14; femoral neck: -3.07) and they increased 17 per cent after 18 days of calcium infusion. After 147 days of treatment bone density was normal, increasing by 61 per cent. The present case shows that the hungry bone syndrome can be a real risk for patients and a complex therapeutic challenge. With an appropriate calcium supply an early, fast and complete recovery of bone mass can be achieved.

Extracellular calcium-sensing receptor: structural and functional features and association with diseases

The recently cloned extracellular calcium-sensing receptor (CaR) is a G protein-coupled receptor that plays an essential role in the regulation of extracellular calcium homeostasis. This receptor is expressed in all tissues related to this control (parathyroid glands, thyroid C-cells, kidneys, intestine and bones) and also in tissues with apparently no role in the maintenance of extracellular calcium levels, such as brain, skin and pancreas. The CaR amino acid sequence is compatible with three major domains: a long and hydrophilic aminoterminal extracellular domain, where most of the activating and inactivating mutations described to date are located and where the dimerization process occurs, and the agonist-binding site is located, a hydrophobic transmembrane domain involved in the signal transduction mechanism from the extracellular domain to its respective G protein, and a carboxyterminal intracellular tail, with a well-established role for cell surface CaR expression and for signal transduction. CaR cloning was immediately followed by the association of genetic human diseases with inactivating and activating CaR mutations: familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism are caused by CaR-inactivating mutations, whereas autosomal dominant hypoparathyroidism is secondary to CaR-activating mutations. Finally, we will comment on the development of drugs that modulate CaR function by either activating (calcimimetic drugs) or antagonizing it (calcilytic drugs), and on their potential therapeutic implications, such as medical control of specific cases of primary and uremic hyperparathyroidism with calcimimetic drugs and a potential treatment for osteoporosis with a calcilytic drug

Hipocalcemia / Hypocalcemia

A hipocalcemia está sendo diagnosticada mais freqüentemente pelos clínicos, e a conduta depende do conhecimento da sua fisiopatologia. A manutenção da calcemia dentro da normalidade é o resultado da interação do PTH e da vitamina D sobre o osso, rim e o intestino. O receptor de sensor de cálcio deve ser incluído na sua análise. O diagnóstico é realizado pela dosagem de cálcio, ou melhor, do cálcio ionizado. O diagnóstico diferencial entre várias causas de hipocalcemia pode ser realizado, permitindo um tratamento direcionado. Nesta revisão, veremos os mecanismos responsáveis no diagnóstico diferencial e a terapêutica apropriada.

Efecto de bajas dosis del pamidronato (APD) oral sobre la calcemia de pacientes osteopénicas u osteoporóticas / Effect of low doses of oral pamidronate (APD) on the calcemia of osteopenic or osteoporotic patients

El pamidronato (APD) oral se indica para tratar la osteítis de Paget en un rango de dosis altas, 400-900 mg/día. Con estas dosis ocasionalmente se presenta hipocalcemia, la que es interpretada como una sobredosis. Para prevenir este efecto se recomienda el uso concomitante de sales de calcio. En el tratamiento de los síndromes osteoporótipos el APD es utilizado en dosis menores, 200 mg/dia, y a estas dosis el efecto antirresortivo es sólo parcial y transitorio. Sin embargo también estos casos son suplementados sistemáticamente con sales de calcio o vitamina D. Para definir si estas asociaciones afectan la calcemia se estudarion a 129 mujeres postemonopáusicas, con el diagnóstico de osteopenia u osteoporosis, tratadas durante 6-10 meses con 200 mg/día de APD. Un grupo (n:13) recibió APD solamente, otras recibieron además 1g/día de sales de calcio (n:61), o 0,015-0,025 mg/día de vitamina D (n:10) o ambos suplementos a la vez (n:45). En todos los grupos se comprobó una tendencia hacia el aumento de la calcemia dentro del rango normal. Este aumento fue significativo (p<0,05) salvo en quienes sólo recibieron APD. Los marcadores de resorción ósea (HOP/Cr) no disminuyeron en el 27 por ciento de las pacientes tratadas con APD + Ca y en el 33 por ciento de las tratadas con APD + Ca + vit D, significando una menor respuesta al APD en esas pacientes. Se concluye que al utilizar dosis bajas de APD, la administración de suplementos de calcio no debiera ser sistemática, la calcemia no tiende a disminuir, reservándose para los casos con dietas muy deficitarias y no indicándose para prevenir supuestos efectos hipocalcemiantes del APD. Además las sales de calcio puedem interaccionar disminuyendo la eficacia del bisfosfonato, hecho que es sugerido pero no demonstrado en este trabajo.

Phototherapy induced hypocalcemia.

Sixty neonates with hyperbilirubinemia were included in the study. There were 20 preterm (Group A) and 20 full term (Group B) neonates. Ten neonates from each group formed the control group. The study group neonates were managed with phototherapy while the control group neonates were not subjected to phototherapy. Serum calcium levels of the two groups were studied. Ninety per cent preterm neonates and seventy-five per cent full term neonates developed hypocalcemia after being subjected to phototherapy. There was a highly significant fall in the total as well as ionized calcium levels in the study group in contrast to the control group. It is recommended that neonates under phototherapy should be given supplemental calcium to prevent hypocalcemia.

Calcium imbalance in hypoparathyroidism.

Extracellular fluid calcium is a tightly controlled variable. Hypoparathyroid state may result in profound calcium imbalance and moderate to severe hypocalcaemia. During 1974-89, 108 cases of hypoparathyroidism (97 post-surgical and 11 idiopathic) were seen. In the post-thyroidectomy group, 83 cases (85%) presented with acute transient hypocalcaemia with spontaneous recovery within 7-10 days. Chronic hypoparathyroidism was seen in 25 cases (14 post-surgical and 11 idiopathic). Convulsions resembling epileptic fits were seen in 9 cases (36%). Pseudopapilloedema was seen in three cases presenting with fits. The administration of phenobarbitone and dilantin aggravated convulsions in 9 patients. The other manifestations were psychiatric illness, cataract and calcification of basal ganglion. Biochemical findings included persistent hypocalcaemia with normal or raised serum phosphorus and lowered daily urinary excretion of calcium. Twenty three of 25 chronic hypoparathyroid cases were treated with vitamin D3 (1-3 mg/day) and calcium supplements (600-1000 mg/day)while 1 alfa-calcidol or calcitriol was used in two patients. Four patients receiving treatment with vitamin D3 developed transient hypercalcaemia with raised plasma levels of 25 hydroxy-vitamin D3. They responded to a reduction in dosage of vitamin D3. One patient was later changed over to 1-alfa-calcidol and another to calcitriol.

Hipocalcemia neonatal / Neonatal hypocalcemia

La hipocalcemia neonatal es una alteración frecuente especialemente en el prematuro; entre las causas propuestas para explicar su aparición se incluyen: hipoparatiroidismo funcional, resistencia periférica a la hormona paratiroidea, hipercalcitonienemia, anormalidades en el metabolismo de la vitamina D, hipomagnesemia, hiperfosfatemia y disminución de la absorción intestinal de calcio. Se recomienda iniciar tratamiento cuando los niveles séricos de calcio iónico sean inferiores a 3 mg/dL (0.75 mmol/L) independientemente de que existan manifestaciones clínicas o no. La infusión contínua de sales de calcio con cuidado constante es el tratamiento más seguro y eficaz