Hiperparatiroidismo primario / Primary hyperparathyroidism

Resumen El hiperparatiroidismo primario (HPP) se define como un trastorno endocrinológico caracterizado por hipercalcemia y niveles de hormona paratiroidea (PTH) elevados o inadecuadamente normales resultado de la secreción excesiva de PTH de una o más glándulas paratiroides. Con respecto a la causa, en un 85% se debe a un adenoma paratiroideo único y un 95% de los casos son esporádicos, sin un factor etiológico identificable. La presentación clásica en la mayoría de los casos es de forma asintomática, sin embargo, sus síntomas o signos clásicos incluyen los derivados de la afectación renal, donde la nefrolitiasis es la manifestación clínica más frecuente de la afectación ósea y de la hipercalcemia. El diagnóstico es bioquímico, sin necesidad de estudio imagenológico, el cual se realiza únicamente como pruebas localizadoras prequirúrgicas. El tratamiento definitivo es quirúrgico, siendo la paratiroidectomía con abordaje cervical el procedimiento de elección.

Primary hyperparathyroidism (PHP) is defined as an endocrine disorder characterized by hypercalcemia and elevated or inadequately normal parathyroid hormone (PTH) levels resulting from the excessive secretion of PTH from one or more parathyroid glands. The cause of this disorder is due, in 85%, to a single parathyroid adenoma and most cases (95%) are sporadic, without an identifiable etiologic factor. PHP is asymptomatic in most patients, however, classic symptoms or signs include those derived from renal involvement, where nephrolithiasis is the most frequent clinical manifestation, and those derived from bone affectation and hypercalcemia. The diagnosis is biochemical, without the need for an imaging study, which is performed only as pre-surgical locator tests. The definitive treatment is surgical, being the parathyroidectomy with cervical approach the procedure of choice.

Therapy for persistent hypercalcemic hyperparathyroidism post-renal transplant: cinacalcet versus parathyroidectomy / Tratamento do hiperparatireoidismo hipercalcêmico persistente pós-transplante renal: cinacalcete versus paratireoidectomia

ABSTRACT Background: Persistent hyperparathyroidism post-transplant is associated with increases in the incidence of cardiovascular events, fractures, and deaths. The aim of this study was to compare both therapeutic options available: parathyroidectomy (PTX) and the calcimimetic agent cinacalcet. Methods: A single center retrospective study including adult renal transplant recipients who developed hypercalcemia due to persistent hyperparathyroidism. Inclusion criteria: PTH > 65 pg/mL with serum calcium > 11.5 mg/dL at any time after transplant or serum calcium persistently higher than 10.2 mg/dL one year after transplant. Patients treated with cinacalcet (n=46) were compared to patients treated with parathyroidectomy (n=30). Follow-up period was one year. Clinical and laboratory data were analyzed to compare efficacy and safety of both therapeutic modalities. Results: PTX controlled calcemia faster (month 1 x month 6) and reached significantly lower levels at month 12 (9.1±1.2 vs 9.7±0.8 mg/dL, p < 0.05); PTX patients showed significantly higher levels of serum phosphate (3.8±1.0 vs 2.9±0.5 mg/dL, p < 0.05) and returned PTH to normal levels (45±51 pg/mL). Cinacalcet, despite controlling calcium and phosphate in the long term, decreased but did not correct PTH (197±97 pg/mL). The proportion of patients that remained with PTH above normal range was 95% in the cinacalcet group and 22% in the PTX group. Patients treated with cinacalcet had better renal function (creatinine 1.2±0.3 vs 1.7±0.7 mg/dL, p < 0.05). Conclusions: Surgical treatment was superior to cinacalcet to correct the metabolic disorders of hyperparathyroidism despite being associated with worse renal function in the long term. Cinacalcet proved to be a safe and well tolerated drug.

RESUMO Introdução: O hiperparatireoidismo persistente pós-transplante está associado a aumento na incidência de eventos cardiovasculares, fraturas e óbitos. O objetivo deste estudo foi comparar as opções terapêuticas disponíveis: paratireoidectomia (PTX) e o agente calcimimético cinacalcete. Métodos: Estudo retrospectivo de um único centro incluiu pacientes transplantados renais adultos que desenvolveram hipercalcemia devido a hiperparatireoidismo persistente. Critérios de inclusão: PTH > 65 pg/mL com cálcio sérico > 11,5 mg/dL a qualquer momento após o transplante, ou cálcio sérico persistentemente superior a 10,2 mg/dL um ano após o transplante. Os pacientes tratados com cinacalcete (n = 46) foram comparados aos pacientes tratados com paratireoidectomia (n = 30). O período de acompanhamento foi de um ano. Dados clínicos e laboratoriais foram analisados para comparar a eficácia e a segurança de ambas as modalidades terapêuticas. Resultados: a PTX controlou a calcemia mais rapidamente (mês 1 x mês 6) e atingiu níveis significativamente mais baixos no mês 12 (9,1 ± 1,2 v.s. 9,7 ± 0,8 mg/dL, p < 0,05); pacientes submetidos à PTX apresentaram níveis significativamente mais altos de fósforo sérico (3,8 ± 1,0 v.s. 2,9 ± 0,5 mg/dL, p < 0,05) e retornaram aos níveis normais de PTH (45 ± 51 pg/mL). O cinacalcete, apesar de controlar o cálcio e o fósforo no longo prazo, diminuiu, mas não corrigiu o PTH (197 ± 97 pg/mL). A proporção de pacientes que permaneceram com PTH acima da faixa normal foi de 95% no grupo cinacalcete e 22% no grupo PTX. Os pacientes tratados com cinacalcete apresentaram melhor função renal (creatinina 1,2 ± 0,3 v.s. 1,7 ± 0,7 mg/dL, p < 0,05). Conclusões: O tratamento cirúrgico foi superior ao cinacalcete para corrigir os distúrbios metabólicos do hiperparatireoidismo, apesar de estar associado a pior função renal no longo prazo. Cinacalcete provou ser um medicamento seguro e bem tolerado.

Tratamiento de hipoparatiroidismo con parathormona recombinante humana [rhPTH(1-84)] / Hypoparathyroidism treated with recombinant human parathyroid hormone [rhPTH(1-84)]

El hipoparatiroidismo (hipoPTH) es una enfermedad infrecuente caracterizada por hipocalcemia y niveles inapropiadamente bajos o ausentes de parathormona. Presentamos el caso de un hombre de 25 años, deportista de alto rendimiento, con antecedente de hipoPTH secundario a tiroidectomía total dos años antes por cáncer papilar multifocal bilateral tiroideo, estadificado como T3 N1b M0, derivado por hipocalcemia sintomática. Presentaba calcemias promedio de 7mg%, síntomas de hipocalcemia en reposo y múltiples internaciones. Inicialmente, se optimizó tratamiento convencional con aporte de calcio vía oral hasta 12g/día, vitamina D y calcitriol, sin mejoría clínica ni bioquímica. Se descartaron malabsorción y complicaciones crónicas de hipoPTH. Se evidenció a través de cuestionario de salud SF-36 disminución de la calidad de vida. Se indicó sustitución con parathormona recombinante humana [rhPTH(1-84)] 50μg/día subcutánea con posterior ascenso a 75μg y reducción progresiva de la medicación por vía oral. Actualmente se encuentra asintomático, sin requerimiento de calcio ni vitamina D, mantiene calcemias de 9mg%, realiza actividad deportiva y demuestra marcada mejoría en la calidad de vida según cuestionario SF-36 (36-Item Short Form Health Survey).

Hypoparathyroidism (HypoPT) is a rare disease characterized by low calcium and inappropriately low circulating parathormone levels. We present the case of a 25-year-old high-performance athlete male, with history of HypoPT after total thyroidectomy for papillary thyroid carcinoma (T3 N1b M0) two years before, who was referred to our clinic for symptomatic hypocalcemia. The patient reported serum calcium average levels of 7mg%, presented symptoms of hypocalcemia at rest and had multiple hospital admissions. First, standard treatment was optimized by calcium supplementation up to 12g/d and active vitamin D, not showing clinical or biochemical improvement. Malabsorption and complications of chronic HypoPT were ruled out. The 36-Item Short Form Health Survey (SF-36) demonstrated an impaired quality of life (QoL). Full-length recombinant human parathyroid hormone [rhPTH(1-84)] therapy was started with 50μg/d subcutaneous, and later adjusted to 75μg/d and the oral treatment gradually decreased. Currently, he is asymptomatic, with serum calcium levels above 9mg%, without receiving oral medication. He performs sports activity and shows marked improvement in quality of life according to SF-36 questionnaire.

The effectiveness and safety of parathyroid hormone in fracture healing: A meta-analysis

The very large economic and social burdens of fracture-related complications make rapid fracture healing a major public health goal. The role of parathyroid hormone (PTH) in treating osteoporosis is generally accepted, but the effect of PTH on fracture healing is controversial. This meta-analysis was designed to investigate the efficacy and safety of PTH in fracture healing. The EMBASE, PubMed, and Cochrane Library databases were systematically searched from the inception dates to April 26, 2018. The primary randomized clinical trials comparing PTH treatment for fracture healing with placebo or no treatment were identified. We did not gain additional information by contacting the authors of the primary studies. Two reviewers independently extracted the data and evaluated study quality. This meta-analysis was executed to determine the odds ratio, mean difference, standardized mean difference, and 95% confidence intervals with random-effects models. In total, 8 randomized trials including 524 patients met the inclusion criteria. There were significant differences in fracture healing time, pain relief and function improvement. There were no significant differences in the fracture healing rate or adverse events, including light-headedness, hypercalcemia, nausea, sweating and headache, except for slight bruising at the injection site. We determined that the effectiveness and safety of PTH in fracture healing is reasonably well established and credible.