Glucose metabolism outcomes after pituitary surgery in patients with acromegaly.

AIM: To investigate the impact of pituitary surgery on glucose metabolism and to identify predictors of remission of diabetes after pituitary surgery in patients with acromegaly. METHODS: A national multicenter retrospective study of patients with acromegaly undergoing transsphenoidal surgery for the first time at 33 tertiary Spanish hospitals (ACRO-SPAIN study) was performed. Surgical remission of acromegaly was evaluated according to the 2000 and 2010 criteria. RESULTS: A total of 604 acromegaly patients were included in the study with a total median follow up of 91 months (interquartile range [IQR] 45-163). At the acromegaly diagnosis, 23.8% of the patients had diabetes mellitus (DM) with a median glycated hemoglobin (HbA1c) of 6.9% (IQR 6.4-7.9) [51.9 mmol/mol (IQR 46.4-62.8)]. In the multivariate analysis, older age (odds ratio [OR] 1.02, 95% CI 1.00-1.05), dyslipidemia (OR 5.25, 95% CI 2.81 to 9.79), arthropathy (OR 1.39, 95% CI 2.82 to 9.79), and higher IGF-I levels (OR 1.30, 95% CI 1.05 to 1.60) were associated with a greater prevalence of DM. At the last follow-up visit after surgery, 21.1% of the DM patients (56.7% of them with surgical remission of acromegaly) experienced diabetes remission. The cure rate of DM was more common in older patients (hazard ratio [HR] 1.77, 95% CI 1.31 to 2.43), when surgical cure was achieved (HR 2.10, 95% CI 1.01 to 4.37) and when anterior pituitary function was not affected after surgery (HR 3.38, 95% CI 1.17 to 9.75). CONCLUSION: Glucose metabolism improved in patients with acromegaly after surgery and 21% of the diabetic patients experienced diabetes remission; being more frequent in patients of older age, and those who experienced surgical cure and those with preserved anterior pituitary function after surgery.

Pegvisomant and pasireotide in PRL and GH co-secreting vs GH-secreting Pit-NETs.

The objective of the study was to evaluate the efficacy of second-line therapies in patients with acromegaly caused by a growth hormone (GH) and prolactin (PRL) co-secreting pituitary neuroendocrine tumor (GH&PRL-Pit-NET) compared to their efficacy in patients with acromegaly caused by a GH-secreting pituitary neuroendocrine tumor (GH-Pit-NET). This is a multicenter retrospective study of patients with acromegaly on treatment with pasireotide and/or pegvisomant. Patients were classified in two groups: GH&PRL-Pit-NETs when evidence of hyperprolactinemia and immunohistochemistry (IHC) for GH and PRL was positive or if PRL were >200 ng/dL regardless of the PRL-IHC and GH-Pit-NETs when the previously mentioned criteria were not met. A total of 28 cases with GH&PRL-Pit-NETs and 122 with GH-Pit-NETs met the inclusion criteria. GH&PRL-Pit-NETs presented at a younger age, caused hypopituitarism, and were invasive more frequently than GH-Pit-NETs. There were 124 patients treated with pegvisomant and 49 with pasireotide at any time. The efficacy of pegvisomant for IGF-1 normalization was of 81.5% and of pasireotide of 71.4%. No differences in IGF-1 control with pasireotide and with pegvisomant were observed between GH&PRL-Pit-NETs and GH-Pit-NETs. All GH&PRL-Pit-NET cases treated with pasireotide (n = 6) and 82.6% (n = 19/23) of the cases treated with pegvisomant normalized PRL levels. No differences in the rate of IGF-1 control between pegvisomant and pasireotide were detected in patients with GH&PRL-Pit-NETs (84.9% vs 66.7%, P = 0.178). We conclude that despite the more aggressive behavior of GH&PRL-Pit-NETs than GH-Pit-NETs, no differences in the rate of IGF-1 control with pegvisomant and pasireotide were observed between both groups, and both drugs have shown to be effective treatments to control IGF-1 and PRL hypersecretion in these tumors.

Effectiveness of combined first-line medical treatment in acromegaly with prolactin cosecretion.

OBJECTIVE: The aim of this study is to compare the response to first-line medical treatment in treatment-naive acromegaly patients with pure growth hormone (GH)-secreting pituitary adenoma (GH-PA) and those with GH and prolactin cosecreting PA (GH&PRL-PA). DESIGN: This is a retrospective multicentric study of acromegaly patients followed from 2003 to 2023 in 33 tertiary Spanish hospitals with at least 6 months of first-line medical treatment. METHODS: Baseline characteristics, first-line medical treatment strategies, and outcomes were analyzed. We employed a multiple logistic regression full model to estimate the impact of some baseline characteristics on disease control after each treatment modality. RESULTS: Of the 144 patients included, 72.9% had a GH-PA, and 27.1% had a GH&PRL-PA. Patients with GH&PRL-PA were younger (43.9 ± 15.0 vs 51.9 ± 12.7 years, P < .01) and harboring more frequently macroadenomas (89.7% vs 72.1%, P = .03). First-generation somatostatin receptor ligand (fgSRL) as monotherapy was given to 106 (73.6%) and a combination treatment with fgSRL and cabergoline in the remaining 38 (26.4%). Patients with GH&PRL-PA received more frequently a combination therapy (56.4% vs 15.2%, P < .01). After 6 months of treatment, in the group of patients under fgSRL as monotherapy, those patients with GH&PRL-PA had worse control compared to GH-PAs (29.4% vs 55.1%, P = .04). However, these differences in the rate of disease control between both groups disappeared when both received combination treatment with fgSRL and cabergoline. CONCLUSION: In GH&PRL-PA, the biochemical control achieved with fgSRL as monotherapy is substantially worse than in patients harboring GH-PA, supporting the inclusion of cabergoline as first-line medical treatment in combination with fgSRLs in these subgroups of patients.

Considering belimumab during pregnancy: A more viable option over time.

OBJECTIVE: To share our experience with belimumab in lupus pregnant women and to review the relevant published literature on its use in this scenario. METHODS: A prospective observational study of pregnant patients with lupus was conducted. Additionally, MEDLINE and EMBASE databases were searched, and a secondary hand search of the literature was performed. Studies were evaluated and visualised descriptively. RESULTS: Sixteen pregnancies of 12 lupus women were included, six (involving eight pregnancies) received belimumab throughout their illness, five of them during some period of gestation. In this group, there was one miscarriage, one elective termination and seven live foetuses (including two live twins). There was one type I intrauterine growth retardation, and a preterm pregnancy due to premature rupture of membranes (PPROM). One mild lupus flare was detected. There were no cases of pre-eclampsia, gestational diabetes mellitus or hypertension. All neonates had normal Apgar scores at birth, none needed critical care. There were no congenital anomalies. After the search, we identified 10 case reports and case series, and five registries. Among the 39 reported cases (41 pregnancies), there were 5 PPROM, 4 pre-eclampsia, and 1 eclampsia. All women made full recoveries. Nineteen new-borns had low birth weight. There were no malformations. While registries did not indicate an increased risk of birth defects or pregnancy loss, there was a higher risk of neonatal infections. CONCLUSIONS: Belimumab may be an option for pregnant women with difficult-to-control lupus. Further research is needed to confirm the absence of association between belimumab and foetal harm.

Differences between GH and PRL co-secreting and GH-secreting pituitary adenomas. A series of 604 cases.

PURPOSE: To evaluate differences in clinical presentation and in surgical outcomes between growth hormone-secreting pituitary adenomas (GH-PAs) and GH and prolactin co-secreting pituitary adenomas (GH&PRL-PAs). METHODS: Multicenter retrospective study of 604 patients with acromegaly submitted to pituitary surgery. Patients were classified into two groups according to serum PRL levels at diagnosis and immunohistochemistry (IHC) for PRL: a) GH&PRL-PAs when PRL levels were above the upper limit of normal and IHC for GH and PRL was positive or PRL levels were >100ng/and PRL IHC was not available (n=130) and b) GH-PAs who did not meet the previously mentioned criteria (n=474). RESULTS: GH&PRL-PAs represented 21.5% (n=130) of patients with acromegaly. The mean age at diagnosis was lower in GH&PRL-PAs than in GH-PAs (P<0.001). GH&PRL-PAs were more frequently macroadenomas (90.6% vs. 77.4%, P=0.001) and tended to be more invasive (33.6% vs. 24.7%, P=0.057) than GH-PAs. Furthermore, they had presurgical hypopituitarism more frequently (OR 2.8, 95% CI 1.83-4.38). IGF-1 upper limit of normality (ULN) levels at diagnosis were lower in patients with GH&PRL-PAs (median 2.4 [IQR 1.73-3.29] vs. 2.7 [IQR 1.91-3.67], P=0.023). There were no differences in the immediate (41.1% vs 43.3%, P=0.659) or long-term post-surgical acromegaly biochemical cure rate (53.5% vs. 53.1%, P=0.936) between groups. However, there was a higher incidence of permanent arginine-vasopressin deficiency (AVP-D) (7.3% vs. 2.4%, P=0.011) in GH&PRL-PAs patients. CONCLUSIONS: GH&PRL-PAs are responsible for 20% of acromegaly cases. These tumors are more invasive, larger and cause hypopituitarism more frequently than GH-PAs and are diagnosed at an earlier age. The biochemical cure rate is similar between both groups, but patients with GH&PRL-PAs tend to develop permanent postsurgical AVP-D more frequently.

Resultados del seguimiento de pacientes con carcinoma diferenciado de tiroides en Castilla-La Mancha (2001-2015). Estudio CADIT-CAM / Follow-up and results in patients with differentiated thyroid carcinoma in Castilla-La Mancha (2001-2015). The CADIT-CAM study

Objetivo: El estudio CADIT-CAM es un estudio retrospectivo diseñado para analizar las características clínicas, el tratamiento y los resultados finales de los pacientes con cáncer diferenciado de tiroides (CDT) en Castilla-La Mancha. Pacientes y métodos: Se ha incluido a 1.434 pacientes diagnosticados en 7 hospitales castellano-manchegos, entre 2001 y 2015. Resultados: El 77% eran mujeres, con una edad media al diagnóstico de 48 años, y el tipo histológico principal fue carcinoma papilar en el 93%. El tamaño el tumor fue descendiendo de forma significativa a lo largo de los 15 años (p <0,05). El tratamiento con radioyodo se ha utilizado en el 84% de la serie, habiendo disminuido su utilización a lo largo del estudio, sobre todo en los de bajo riesgo de recurrencia. Existió recurrencia en el 22% de los pacientes, siendo los factores relacionados con la misma: sexo masculino, mayor tamaño tumoral, multifocalidad, presencia de metástasis linfáticas o a distancia o de afectación extratiroidea así como la presencia de anticuerpos antitiroglobulina con evolución desfavorable. Al final del seguimiento, el 76,2% de los casos estaban libres de enfermedad y el 2,4% de los pacientes habían fallecido por CDT, siendo la supervivencia global de la cohorte del 95,1% a los 15 años de seguimiento. Conclusiones: Las características del CDT de la cohorte de Castilla-La Mancha son similares a las de otras series españolas. Los resultados finales son excelentes y las tendencias del tratamiento se han ido adaptando al riesgo de recurrencia de los pacientes

Objective: The CADIT-CAM study was designed to retrospectively analyze the clinical characteristics, treatments, and outcomes of patients with differentiated thyroid carcinoma (DTC) in Castilla La Mancha. Patients and methods: A total of 1434 patients from 7 hospitals in Castilla La Mancha were enrolled into the study from 2001 to 2015. Results: Seventy-seven percent of patients were female, with a mean age at diagnosis of 48 years. Papillary thyroid carcinoma accounted for 93% of cases. Mean tumor size was significantly smaller at final follow-up (P<.05). Radioiodine ablation (RA) was performed in 84% of patients, and its use decreased during the study, especially in tumors with low recurrence risk. Recurrence occurred in 22% of patients and was associated to male gender, greater tumor size, multifocality, lymph node metastases, extrathyroid involvement, distant metastases and increasing thyroglobulin antibody titers. At the end of follow-up 76.2% of patients were alive and free of disease, 2.4% had died from DTC. Overall survival of the cohort was 95.1% at 15 years of follow-up. Conclusions: Characteristics of DTC in this Spanish cohort are similar to those reported in other studies in our country. Final results were excellent and use of treatment (RA) was consistent with risk-stratified recommendations

Follow-up and results in patients with differentiated thyroid carcinoma in Castilla-La Mancha (2001-2015). The CADIT-CAM study. / Resultados del seguimiento de pacientes con carcinoma diferenciado de tiroides en Castilla-La Mancha (2001-2015). Estudio CADIT-CAM.

OBJECTIVE: The CADIT-CAM study was designed to retrospectively analyze the clinical characteristics, treatments, and outcomes of patients with differentiated thyroid carcinoma (DTC) in Castilla La Mancha. PATIENTS AND METHODS: A total of 1434 patients from 7 hospitals in Castilla La Mancha were enrolled into the study from 2001 to 2015. RESULTS: Seventy-seven percent of patients were female, with a mean age at diagnosis of 48 years. Papillary thyroid carcinoma accounted for 93% of cases. Mean tumor size was significantly smaller at final follow-up (P<.05). Radioiodine ablation (RA) was performed in 84% of patients, and its use decreased during the study, especially in tumors with low recurrence risk. Recurrence occurred in 22% of patients and was associated to male gender, greater tumor size, multifocality, lymph node metastases, extrathyroid involvement, distant metastases and increasing thyroglobulin antibody titers. At the end of follow-up 76.2% of patients were alive and free of disease, 2.4% had died from DTC. Overall survival of the cohort was 95.1% at 15 years of follow-up. CONCLUSIONS: Characteristics of DTC in this Spanish cohort are similar to those reported in other studies in our country. Final results were excellent and use of treatment (RA) was consistent with risk-stratified recommendations.

Rhabdomyolysis due to primary hyperaldosteronism

La rabdomiólisis puede ser secundaria a traumatismos, excesiva actividad muscular, enfermedades musculares hereditarias y otras causas médicas. El hiperaldosteronismo primario se caracteriza por hipertensión, hipopotasemia, actividad de renina plasmática suprimida y secreción aumentada de aldosterona. La rabdomiólisis no es frecuente en el hiperaldosteronismo primario. Presentamos el caso de una mujer de 42 años que sufrió una rabdomiólisis como manifestación inicial de un hiperaldosteronismo primario. También realizamos una búsqueda bibliográfica para identificar casos de rabdomiólisis como primera manifestación de hiperaldosteronismo primario; 16 casos cumplieron criterios de inclusión. Cuando aparece rabdomiólisis en un paciente con hipopotasemia y alcalosis metabólica debe sospecharse un hiperaldosteronismo primario: si se confirma, la causa más probable será un adenoma productor de aldosterona (AU)

Rhabdomyolysis may be secondary to trauma, excessive muscle activity, hereditary muscle enzyme defects and other medical causes. Primary hyperaldosteronism is characterised by hypertension, hypokalemia, suppressed plasma renin activity, and increased aldosterone excretion. Rhabdomyolysis is not common in primary hyperaldosteronism. We report here a 42-year-old woman presenting with rhabdomyolysis as heralding symptom of primary hyperaldosteronism. We also carried out a search of the literature to identify all cases of rhabdomyolysis as the first-recognized expression of a primary hyperaldosteronism. Sixteen cases met the criteria for inclusion. When rhabdomyolysis occurs in a patient with hypokalemia and metabolic alkalosis, primary hyperaldosteronism has to be suspected: if confirmed, an aldosterone-producing adenoma is the most probable cause (AU)

Growth hormone therapy and the heart.

The growth hormone (GH)-insulin-like growth factor-1 axis has great relevance for the regulation of cardiac growth, structure, and function. GH deficiency may result in impaired cardiac performance, manifest by a reduction in left ventricular mass and ejection fraction, but data are inconsistent. GH therapy is recommended treatment in adult patients with GH deficiency, but in acromegaly, in which there is excess GH, the main cause of mortality is cardiovascular disease. The purposes of this study were to perform (1) a case-controlled study comparing cardiac morphology and function in 53 GH-deficient patients (34 men, mean age 38.1 +/- 15.2 years, 22 with childhood-onset GH deficiency) and 46 healthy controls (29 men, mean age 37.8 +/- 12.4 years) and (2) a longitudinal study to assess the effect of introducing GH therapy in 37 subjects for a mean period of 26 +/- 22 months. At study entry, all subjects underwent electrocardiography and 24-hour ambulatory electrocardiographic monitoring, systolic and diastolic blood pressure assessment, detailed echocardiography, and exercise tolerance tests. There were no significant differences in left ventricular mass, left ventricular dimensions, systolic or diastolic function indexes, or blood pressure at rest in patients compared with controls. Exercise duration was significantly shorter and peak heart rate during exercise (chronotropic response) lower in the GH-deficiency group than in controls (p <0.05). After GH treatment, there were no significant changes in echocardiographic parameters or blood pressure, but an improvement in exercise duration (p = 0.019) was found, particularly in the subgroup with childhood-onset GH deficiency (n = 16). In conclusion, patients with GH deficiency did not show cardiac structural or functional differences compared with healthy controls, with no significant changes after GH treatment. However, these patients exhibited improved exercise capacity, especially those with childhood-onset GH deficiency.