Pegvisomant in acromegaly: a multicenter real-life study in Argentina

ABSTRACT Objective To describe the long term safety and efficacy of pegvisomant (PEGV), and the predictors of treatment response in patients with acromegaly in the real life setting. Subjects and methods We retrospectively reviewed the clinical, hormonal and radiological data of acromegalic patients treated with PEGV in 17 Argentine centers. Results Seventy-five patients (age range 22-77, 51 females) with acromegaly have been treated with PEGV for up to 118 months (median 27 months). Before PEGV, 97.3% of patients had been treated with medical therapy, surgery and/or radiotherapy, two patients had no previous treatment. At that time, all patients had an IGF-1 above the upper normal limit (ULN) (mean 2.4 x ULN ± 0.98, range 1.25-7). At diagnosis of acromegaly 84% presented macroadenomas, prior to PEGV only 23,5% of patients remained with tumor remnant > 1 cm, the remaining showed normal or less than 1 cm images. Disease control (IGF-1 ≤ 1.2 x ULN) was achieved in 62.9% of patients with a mean dose of 11.8 mg/day. Thirty-four patients (45%) received PEGV monotherapy, while 41 (55%) received combined therapy with either somatostatin analogues and/or cabergoline. Adverse events related to PEGV were: local injection site reaction in 5.3%, elevated liver enzymes in 9.3%, and tumor size growth in 9.8%. Pre-PEGV IGF-I level was the only predictor of treatment response: 2.1 x ULN vs 2.8 x ULN in controlled and uncontrolled patients respectively (p < 0.001). Conclusion this long term experience indicates PEGV treatment was highly effective and safe in our series of Argentine patients with acromegaly refractory to standard therapies. Arch Endocrinol Metab. 2019;63(4):320-7

Efecto de una sola dosis de ácido zoledrónico en un caso de enfermedad de Paget ósea / Effect of a single dose of zoledronic acid in a case of Paget bone disease

La enfermedad de Paget es un trastorno crónico del remodelado óseo, caracterizado por un aumento de la resorción ósea producido por osteoclastos atípicos, seguido por un incremento acelerado de la formación ósea, lo que resulta en la formación de hueso en mosaico desorganizado. Un excelente marcador bioquímico para orientar el diagnóstico y seguimiento es la fosfatasa alcalina (FAL). Se presenta el caso de un paciente de 90 años, de sexo masculino, con diagnóstico de enfermedad de Paget. Se inicia tratamiento con pamidronato vía oral con respuesta parcial, por lo que se rota a pamidronato endovenoso. Disminuyen el dolor y la concentración plasmática de FAL, persistiendo con centellograma óseo patológico. Luego de varios años de tratamiento, con adecuado aporte de calcio y vitamina D, comienza nuevamente con dolor y valores elevados de FAL. Se decide iniciar tratamiento con ácido zoledrónico endovenoso 4 mg, única aplicación, obteniéndose remisión clínica y bioquímica desde hace cuatro años y mejoría de la imagen centellográfica. Este informe refiere la buena respuesta, sostenida en el tiempo, al tratamiento con única dosis de ácido zoledrónico en un paciente que presentó resistencia al pamidronato.

Paget's disease is a chronic disorder of bone remodeling characterized by increase of bone resorption by atypical osteoclasts, followed by rapid increase in bone formation resulting in a disorganized mosaic bone. The biochemical marker for early diagnosis and monitoring is serum alkaline phosphatase (ALP). We report the case of a 90 year old male, with diagnose of Paget's disease. Pamidronate treatment was started orally with partial response, so it was switched to intravenous pamidronate. Pain intensity and FAL levels diminished. The scyntigraphic scan, however, though improved, persisted abnormal. After several years of treatment, with adequate calcium and vitamin D support, the patient presents pain and increase of FAL. We administered intravenous zoledronic acid (4 mg) in a single dose. After this treatment we observed clinical and biochemical remission during four years and a significantly improvement in the scintigraphy. We report a case of Paget´s disease, resistant to pamidronate treatment in whom a single dose of zoledronic acid produced clinical and biochemical remission during 4 years and a significant improvement in the scintigraphic scan.