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

Riesgo aumentado de lesiones colónicas preneoplásicas en acromegalia: estudio multicéntrico caso control. Resultados preliminares / Increased risk of pre-cancerous bowel lesions in acromegaly: Multicentre case-control study. Preliminary results

Introducción: El riesgo de desarrollar neoplasias colónicas en pacientes acromegálicos y su relación directa con los niveles elevados de GH/IGF-1 no están bien establecidos y continúan siendo motivo de controversia en la literatura mundial. El objetivo de este trabajo fue evaluar el riesgo de desarrollar lesiones neoplásicas avanzadas (LNA) (adenomas mayores a 1 cm, componente velloso mayor del 75% y/o displasia de alto grado), en pacientes con acromegalia, comparado con un grupo control. Materiales y métodos: Estudio multicéntrico caso-control retrospectivo. Ciento treinta y siete pacientes con acromegalia que realizaron videocolonoscopia (VCC) fueron incluidos inicialmente, aunque solo 69 cumplieron criterios de inclusión. Sesenta y dos controles fueron obtenidos: por cada caso (paciente con acromegalia) 2 «controles¼ fueron seleccionados aleatorizadamente e igualados por edad y sexo. El riesgo se expresó en odds ratio (OR) y su correspondiente intervalo de confianza (IC) del 95%. La significación estadística fue considerada una p < 0,05. Resultados: De los 69 pacientes con VCC completa y datos adecuados para su análisis, 28 presentaron VCC positiva con hallazgos de pólipos (40%) y 41 VCC negativa o normal (60%). Dentro del grupo con VCC positiva, 14 presentaron LNA (20%) y solo un paciente presentó diagnóstico de cáncer colorrectal. Para el análisis caso-control se incluyó a 31 pacientes frente al grupo control (n = 62) que cumplieron con los criterios de inclusión. La presencia de pólipos colónicos, adenomas y LNA en los pacientes con acromegalia fue de 19/31 (61,9%), 14/31 (45,16%) y 10/31 (32,25%), y en el grupo control de 18/62 (29,03%), 11/62 (17,74%) y 4/62 (6,45%), respectivamente. El riesgo de adenomas y LNA fue mayor en el grupo de acromegalia en comparación con el grupo control, siendo ambos resultados estadísticamente significativos: adenomas OR 2,54 (IC 1,22-5,25) p = 0,005, LNA OR: 7,3 (2,4-25), p = 0,00. Conclusión: La acromegalia se asocia a un mayor riesgo de lesiones colónicas preneoplásicas. Este hallazgo justifica el cribado con VCC al diagnóstico en pacientes con acromegalia.

Background: The risk of developing cancerous lesions in the colon of acromegaly patients and their direct relationship with elevated growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels is not well established, and is still controversial in the international literature. The objective of this study was to evaluate the risk of developing advanced neoplastic lesions (ALN: greater than 1 cm adenomas, villous component greater than 75% and/or high grade dysplasia) in patients with acromegaly compared to a control group. Materials and methods: A multicentre, retrospective case-control study was conducted initially on 137 patients with acromegaly (cases) who underwent videocolonoscopy (VCC), although only 69 met inclusion criteria. Sixty-two controls were obtained, and for each case two "controls" were randomly selected and matched by age and gender. Risk was expressed as odds ratio (OR) and its corresponding 95% con"dence interval (CI). P values < .05 were considered statistical significantly. Results: Of the 69 acromegaly patients with a completed VCC and adequate data for their analysis, 28 had a positive VCC with findings of polyps (40%), and 41 VCC negative with no lesions (60%). Within the group with positive VCC, 14 were ALN (20%) and one a colorectal cancer. In the case-control analysis, 31 cases were to be analysed against the control group (n = 62). The presence of colonic polyps, adenomas, and ALN in patients with acromegaly was 19/31 (61.9%), 14/31 (45.16%), and 10/31 (32.25%), respectively, and in the control group, it was 18/62 (29.03%), 11/62 (17.74%), and 4/62 (6.45%), respectively. The risk of adenomas and ALN was higher in the acromegaly group compared to the control group: adenomas OR: 2.54 (95% CI 1.22-5.25) P=.005, ALN OR: 7.3 (2.4-25) P=.00. Conclusion: This preliminary case control study showed an increased risk of pre-cancerous colprectal lesions in patients with acromegaly, supporting the VCC screening at diagnosis.

Análisis de un registro de adenomas pituitarios / Analysis of a pituitary adenoma registry

Dada la complejidad que reviste el enfoque diagnóstico y terapéutico de los tumores pituitarios, el registro y análisis de la experiencia clínica acumulada es de gran ayuda en la toma de decisiones. En este trabajo se informan datos clínico-terapéuticos, extraídos de un registro computarizado, sobre 519 de un total de 670 pacientes con adenomas pituitarios. Trescientos cuarenta y cinco fueron mujeres (66%) y 174 varones (34%), de 14 a 80 años de edad. El diagnóstico final fue: acromegalia en 176, enfermedad de Cushing en 153, prolactinoma en 101 y adenoma clínicamente no-funcionante (ANF) en 89. La edad media al momento del diagnóstico de acromegalia fue 43.9 ± 13.5 (16-80), para enfermedad de Cushing 35.7 ± 12.9 (14-72), para prolactinomas 30.0 ± 13.4 (15-79) y para ANF 52.1 ± 15.2 (17-79) años. La creación de un registro institucional de tumores de hipófisis es un instrumento de gran utilidad para el análisis de la experiencia adquirida y constituye una herramienta valiosa para mejorar la estrategia terapéutica, optimizar la relación costo/beneficio y mejorar el cuidado del paciente. Contribuye a la docencia médica, tanto en el pre como en el posgrado y da base a la realización de trabajos de investigación clínica, aportando a la difusión y transferencia de conocimientos.

Collection and analysis of data obtained during the clinical treatment of pituitary tumours are of great utility in the decision making process, when facing clinical situations. We report here data on 519 from 670 patients with pituitary adenomas obtained from a computerized registry. Three hundred and forty five were females (66%) and 174 males (34%), aged 14-80. Final diagnosis was acromegaly in 176, Cushing's disease in 153, prolactinoma in 101 and clinically non-functioning adenoma in 89. Mean age at diagnosis was 43.9 ± 13.5 (16-80) for acromegalics, 35.7 ± 12.9 (14-72) for Cushing's, 30.0 ± 13.4 (15-79) for prolactinoma and 52.1 ± 15.2 (17-79), for non-functioning tumours. The setup of an institutional registry on pituitary tumours constitutes a useful tool to analyze clinical experience, optimize the cost/benefit ratio of procedures used for diagnosis and to ameliorate therapeutic strategies, improving patient's care. It greatly contributes to teaching medical students as well as to post-graduate physicians and provides a basis for developing clinical research.

La corrección de la sustitución excesiva de cortisol mejora la morbilidad en pacientes con hipopituitarismo: un estudio piloto / Correction of Cortisol Overreplacement Ameliorates Morbidities in Patients with Hypopituitarism: A pilot study

Context: Hyporituitarism in adults is known to be associated with deleterious effects on body composition, lipid profile and quality of life (QoL). This was attributed to GH deficiency. The potential role of glucocorticoid overreplacement had never been investigated. Objective: To investigate whether reduction in glucocorticoid replacement dose to more physiological one could ameliorate the "AO-GHD"-attributed symptomatology in patients with hypopituitarism. Design: Eleven patients with panhypopituitarism taking 20-30 mg/day of hydrocortisone, but on no GH replacement were switched to 10 to 15 mg of hydrocortisone daily. Both basally and 6-12 months later, their body mass index, body composition by dual-energy x-ray absorptiometry, lipid profile, and the score of quality of life, QOL-AGHDA were measured. Results: Within 6-12 months of lower hydrocortisone dose, subjects lost an average of 7.1 kg of total body fat and 4.1 kg of abdominal fat. No changes were seen in lean body mass, bone mineral content and HOMA-IR Plasma total cholesterol and triglyceride concentrations decreased significantly (<0.05) and the QoL improved (p=0.018). Conclusions: Our pilot study suggests that decreasing the glucocorticoid replacement dose to ~ 15 mg/ day is beneficial in terms of patients' body composition, lipid profile and quality of life.