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.

Revisiting the usefulness of the short acute octreotide test to predict treatment outcomes in acromegaly.

Introduction: We previously described that a short version of the acute octreotide test (sAOT) can predict the response to first-generation somatostatin receptor ligands (SRLs) in patients with acromegaly. We have prospectively reassessed the sAOT in patients from the ACROFAST study using current ultra-sensitive GH assays. We also studied the correlation of sAOT with tumor expression of E-cadherin and somatostatin receptor 2 (SSTR2) . Methods: A total of 47 patients treated with SRLs for 6 months were evaluated with the sAOT at diagnosis and correlated with SRLs' response. Those patients whose IGF1 decreased to <3SDS from normal value were considered responders and those whose IGF1 was ≥3SDS, were considered non-responders. The 2 hours GH value (GH2h) after s.c. administration of 100 mcg of octreotide was used to define predictive cutoffs. E-cadherin and SSTR2 immunostaining in somatotropinoma tissue were investigated in 24/47 and 18/47 patients, respectively. Results: In all, 30 patients were responders and 17 were non-responders. GH2h was 0.68 (0.25-1.98) ng/mL in responders vs 2.35 (1.59-9.37) ng/mL in non-responders (p<0.001). GH2h = 1.4ng/mL showed the highest ability to identify responders (accuracy of 81%, sensitivity of 73.3%, and specificity of 94.1%). GH2h = 4.3ng/mL was the best cutoff for non-response prediction (accuracy of 74%, sensitivity of 35.3%, and specificity of 96.7%). Patients with E-cadherin-positive tumors showed a lower GH2h than those with E-cadherin-negative tumors [0.9 (0.3-2.1) vs 3.3 (1.5-12.1) ng/mL; p<0.01], and patients with positive E-cadherin presented a higher score of SSTR2 (7.5 ± 4.2 vs 3.3 ± 2.1; p=0.01). Conclusion: The sAOT is a good predictor tool for assessing response to SRLs and correlates with tumor E-cadherin and SSTR2 expression. Thus, it can be useful in clinical practice for therapeutic decision-making in patients with acromegaly.

Acromegaly disease activity according to ACRODAT®, a cross-sectional study in Spain: ACROVAL study.

OBJECTIVES: To evaluate disease activity status using the Acromegaly Disease Activity Tool (ACRODAT®) in a cohort of Spanish acromegaly patients, to assess the relationship between the level of disease activity according to both ACRODAT® and the physicians' clinical evaluation, and to study the potential discrepancies in the perception of symptoms between physicians and patients. DESIGN: Multicenter, observational, descriptive and cross-sectional study. METHODS: Disease activity was assessed in adult patients with acromegaly under pharmacological treatment during at least 6 months using ACRODAT®. RESULTS: According to ACRODAT®, 48.2%, 31.8% and 20.0% of a total of 111 patients were classified as having a stable disease (S), mild disease activity (M-DA) and significant disease activity (S-DA) respectively. ACRODAT® classification of disease activity significantly correlated with physicians' opinion, with a moderate inter-rater agreement and a specificity of 92.45% (PPV = 86.21%). No correlation was found between IGF-I levels and severity of symptoms or quality of life (QoL). A decision to take clinical action was significantly more frequent in S-DA and M-DA patients than S patients but no action was taken on 5 (22.7%) and 27 (77.1%) S-DA and M-DA patients, respectively CONCLUSIONS: ACRODAT® detected disease activity in 51.8% of patients. Interestingly, although M-DA and S-DA patients were likely to be in the process of being controlled, action was not always taken on these patients. ACRODAT® is a validated and highly specific tool that may be useful to routinely monitor acromegaly and to identify patients with non-obvious disease activity by incorporating "patient-centred" parameters like symptoms and QoL to the clinical evaluation of acromegaly.

Craniopharyngioma in the Elderly: A Multicenter and Nationwide Study in Spain.

BACKGROUND: Craniopharyngioma (CP) is a rare tumor in the elderly whose clinical features and prognosis are not well known in this population. AIM: To evaluate the clinicopathological features and therapeutic outcomes of CP diagnosed in the elderly. PATIENTS AND METHODS: This was a retrospective, multicenter, national study of CP patients diagnosed over the age of 65 years and surgically treated. RESULTS: From a total of 384 adult CP patients, we selected 53 (13.8%) patients (27 women [50.9%], mean age 72.3 ± 5.1 years [range 65-83 years]) diagnosed after the age of 65 years. The most common clinical symptoms were visual field defects (71.2%) followed by headache (45.3%). The maximum tumor diameter was 2.9 ± 1.1 cm. In most patients, the tumor was suprasellar (96.2%) and mixed (solid-cystic) (58.5%). The surgical approach most commonly used was transcranial surgery (52.8%), and more than half of the patients (54.7%) underwent subtotal resection (STR). Adamantinomatous CP and papillary CP were present in 51 and 45.1%, respectively, with mixed forms in the remaining. Surgery was accompanied by an improvement in visual field defects and in headaches; however, pituitary hormonal hypofunction increased, mainly at the expense of an increase in the prevalence of diabetes insipidus (DI) (from 3.9 to 69.2%). Near-total resection (NTR) was associated with a higher prevalence of DI compared with subtotal resection (87.5 vs. 53.6%, p = 0.008). Patients were followed for 46.7 ± 40.8 months. The mortality rate was 39.6% with a median survival time of 88 (95% CI: 57-118) months. DI at last visit was associated with a lower survival. CONCLUSION: CP diagnosed in the elderly shows a similar distribution by sex and histologic forms than that diagnosed at younger ages. At presentation, visual field alterations and headaches are the main clinical symptoms which improve substantially with surgery. However, surgery, mainly NTR, is accompanied by worsening of pituitary function, especially DI, which seems to be a predictor of mortality in this population.

Posterior pituitary tumours: the spectrum of a unique entity. A clinical and histological study of a large case series.

PURPOSE: In 2017, the WHO established that pituicytoma, granular cell tumour (GCT) and spindle cell oncocytoma (SCO) are posterior pituitary tumours (PPT). Recent data suggests that these tumours probably arise from the pituicytes and may constitute a spectrum of a unique histopathological entity. Our aim is to report the clinical findings and surgical outcomes of 16 patients with PPT. We also evaluated the tissue specimens available in light of current knowledge. METHOD: Cross-sectional study with retrospective data. RESULTS: PPT were 7 pituicytomas, 3 GCT and 6 SCO. Patients mean age was 55 years old and 75% were female. Basal hormonal study showed hyperprolactinemia (43.7%) and hypopituitarism (37.5%). There was no case of diabetes insipidus (DI). MRI showed sellar/suprasellar masses with mean size of 19.7mm. PPT was not suspected in any patient. Fifteen patients underwent surgery and complications were common: 20% had perioperative bleeding (one patient died because of a massive haemorrhage), 57.1% hypopituitarism, 35.7% permanent DI and 21.4% underwent a second surgery. Pathological findings shown positivity for thyroid transcription factor 1, vimentin and negativity for cytokeratin and chromogranin A in all specimens evaluated. S100 protein was positive in 88.8% of tumours. Ki67 was ≥ 3% in 66.6% and ranged from 4-7% in SCO. CONCLUSION: PPT have similar histology, clinical features and are frequently misdiagnosed as nonfunctioning pituitary tumours. However, post-surgical complications including haemorrhage are common. A high clinical suspicion is needed to presume the diagnosis prior surgery and diminish the high morbidity of these tumours.

Asociación de obesidad general y abdominal con hipertensión, dislipemia y presencia de prediabetes en el estudio PREDAPS / Association of general and abdominal obesity with hypertension, dyslipidemia and prediabetes in the PREDAPS study

Introducción y objetivos: Algunas medidas antropométricas muestran mayor capacidad que otras para discriminar la presencia de factores de riesgo cardiovascular. Este trabajo estima la magnitud de la asociación de diversos indicadores antropométricos de obesidad con hipertensión, dislipemia y prediabetes (glucemia basal o glucohemoglobina alteradas). Métodos: Análisis transversal de la información recogida en 2.022 sujetos del estudio PREDAPS (etapa basal). Se definió obesidad general como índice de masa corporal ≥ 30 kg/m2 y obesidad abdominal con 2 criterios: a) perímetro de cintura (PC) ≥ 102 cm en varones/PC ≥ 88 cm en mujeres, y b) índice cintura/estatura (ICE) ≥ 0,55. La magnitud de la asociación se estimó mediante regresión logística. Resultados: La hipertensión arterial mostró la asociación más alta con la obesidad general en mujeres (OR = 3,01; IC95%, 2,24-4,04) y con la obesidad abdominal según el criterio del ICE en varones (OR = 3,65; IC95%, 2,66-5,01). La hipertrigliceridemia y los valores bajos de colesterol unido a lipoproteínas de alta densidad mostraron la asociación más alta con obesidad abdominal según el criterio del ICE en mujeres (OR = 2,49; IC95%, 1,68-3,67 y OR = 2,70; IC95%, 1,89-3,86) y la obesidad general en varones (OR = 2,06; IC95%, 1,56-2,73 y OR = 1,68; IC95%, 1,21-2,33). La prediabetes mostró la asociación más alta con obesidad abdominal según el criterio del ICE en mujeres (OR = 2,48; IC95%, 1,85-3,33) y con obesidad abdominal según el criterio del PC en varones (OR = 2,33; IC95%, 1,75-3,08). Conclusiones: Los indicadores de obesidad abdominal mostraron la mayor asociación con la presencia de prediabetes. La relación de los indicadores antropométricos con hipertensión y con dislipemia mostró resultados heterogéneos (AU)

Introduction and objectives: Some anthropometric measurements show a greater capacity than others to identify the presence of cardiovascular risk factors. This study estimated the magnitude of the association of different anthropometric indicators of obesity with hypertension, dyslipidemia, and prediabetes (altered fasting plasma glucose and/or glycosylated hemoglobin). Methods: Cross-sectional analysis of information collected from 2022 participants in the PREDAPS study (baseline phase). General obesity was defined as body mass index ≥ 30 kg/m2 and abdominal obesity was defined with 2 criteria: a) waist circumference (WC) ≥ 102 cm in men/WC ≥ 88 cm in women, and b) waist-height ratio (WHtR) ≥ 0.55. The magnitude of the association was estimated by logistic regression. Results: Hypertension showed the strongest association with general obesity in women (OR, 3.01; 95%CI, 2.24-4.04) and with abdominal obesity based on the WHtR criterion in men (OR, 3.65; 95%CI, 2.66-5.01). Hypertriglyceridemia and low levels of high-density lipoprotein cholesterol showed the strongest association with abdominal obesity based on the WHtR criterion in women (OR, 2.49; 95%CI, 1.68-3.67 and OR, 2.70; 95%CI, 1.89-3.86) and with general obesity in men (OR, 2.06; 95%CI, 1.56-2.73 and OR, 1.68; 95%CI, 1.21-2.33). Prediabetes showed the strongest association with abdominal obesity based on the WHtR criterion in women (OR, 2.48; 95%CI, 1.85-3.33) and with abdominal obesity based on the WC criterion in men (OR, 2.33; 95%CI, 1.75-3.08). Conclusions: Abdominal obesity indicators showed the strongest association with the presence of prediabetes. The association of anthropometric indicators with hypertension and dyslipidemia showed heterogeneous results (AU)

Prevalence of acromegaly in patients with symptoms of sleep apnea.

Acromegaly is a rare disease with nonspecific symptoms with acral enlargement being almost universally present at diagnosis. The estimated prevalence is 40-125 cases/million but targeted universal screening studies have found a higher prevalence (about 10 fold). The aim of the ACROSAHS study was to investigate the prevalence of acromegaly and acromegaly comorbidities in patients with sleep apnea symptoms and acral enlargement. ACROSAHS was a Spanish prospective non-interventional epidemiological study in 13 Hospital sleep referral units. Facial and acral enlargement symptoms including: ring size and shoe size increase, tongue, lips and jaws enlargement, paresthesia or carpal tunnel syndrome and widening of tooth spaces, as well as other typical acromegaly comorbidities were recorded with a self-administered questionnaire of patients who attended a first visit for sleep apnea symptoms between 09/2013 and 07/2014. Serum insulin-like growth factor type 1 (IGF1) was measured in patients with ≥1 acral symptom to determine the prevalence of acromegaly. Of the 1557 patients enrolled, 1477 with complete data (72% male) were analyzed. 530 patients (36%) reported at least 1 acral enlargement symptom and were tested for IGF-1, 41 were above range, persisted in 7, and among those, 2 cases of acromegaly were diagnosed (prevalence of at least 1.35 cases/1000). Overall, 1019 patients (69%) had ≥2 acromegaly symptoms and should have been screened according to guidelines; moreover 373 patients (25%) had ≥1 symptom of acral enlargement plus ≥3 other acromegaly symptoms. In conclusion, in patients with sleep apnea symptoms and acral enlargement, we found an acromegaly prevalence of at least 1.35 cases per 1000 and a high prevalence of typical acromegaly symptoms. It is important that sleep specialists are aware of acromegaly symptoms to aid with acromegaly diagnosis.

Use of lanreotide in combination with cabergoline or pegvisomant in patients with acromegaly in the clinical practice: the ACROCOMB study / Uso de lanreotida en combinación con cabergolina o pegvisomant en la práctica clínica en pacientes con acromegalia: el estudio ACROCOMB

PURPOSE: To describe real-world use of lanreotide combination therapy for acromegaly. PATIENTS AND METHODS: ACROCOMB is a retrospective observational Spanish study of patients with active acromegaly treated with lanreotide combination therapy between 2006 and 2011. 108 patients treated at 44 Spanish Endocrinology Departments were analyzed separately: 61 patients received lanreotide/cabergoline (cabergoline cohort) and 47 lanreotide/pegvisomant (pegvisomant cohort). RESULTS: Patient median age was 50.8 years in the cabergoline cohort and 42.7 years in the pegvisomant cohort. Prior medical treatments were somatostatin analogue (SSA) monotherapy (40 [66%] patients) or dopamine agonists (7 [11%] patients) in the cabergoline cohort and SSA (29 [62%] patients) or pegvisomant monotherapy (16 [34%] patients) in the pegvisomant cohort. Across both cohorts 12 patients were previously untreated, and prior therapy was unknown/missing in 4 patients. Median duration of combined treatment was 1.6 years (0.1–6) and 2.1 years (0.4–6.3) in the cabergoline and pegvisomant cohorts, respectively. At baseline, median insulin growth factor (IGF)-I values were 149% upper limit of normal (ULN) (15–505%) in the cabergoline cohort and 156% ULN (15–534%) in the pegvisomant cohort, and decreased to 104% ULN (13–557%) p<0.001 and 86% ULN (23–345%) p<0.0001, respectively, at end of study (EOS). Normal age-adjusted values of IGF-I were obtained in 48% of lanreotide/cabergoline-treated patients and 70% of lanreotide/pegvisomant-treated patients at EOS. There were no significant changes in hepatic, cardiac or glycaemic parameters in either cohort. CONCLUSION: In clinical practice lanreotide treatment combinations are useful options for patients with acromegaly when monotherapy is insufficient; particularly, the combination of lanreotide and pegvisomant in patients not controlled with either SSA or pegvisomant alone has high efficacy and is well-tolerated

PROPÓSITO: Describir el uso de lanreotida en combinación terapéutica en acromegalia en la práctica clínica. PACIENTES Y MÉTODOS: ACROCOMB es un estudio observacional, retrospectivo, de pacientes con acromegalia activa tratados en centros hospitalarios españoles con lanreotida en combinación con cabergolina o pegvisomant entre 2006 y 2011. Se revisaron los datos clínicos de 108 pacientes tratados en 44 departamentos de endocrinología: 61 pacientes recibieron lanreótido/cabergolina (cohorte cabergolina) y 47 lanreotida/pegvisomant (cohorte pegvisomant). RESULTADOS: La edad mediana de los pacientes fue de 50,8 años en la cohorte de cabergolina y 42,7 años en la de pegvisomant. Los tratamientos médicos previos a la combinación con lanreótido fueron análogos de somatostatina (SSA) en monoterapia (40 [66%] pacientes) o agonistas de la dopamina (7 [11%] pacientes) en la cohorte de cabergolina y SSA (29 [62%] pacientes) y pegvisomant en monoterapia (16 [34%] pacientes) en la de pegvisomant. Doce pacientes no habían recibido tratamiento previo y en 4 pacientes se desconocía la terapia previa. La mediana de duración del tratamiento fue de 1,6 años (0,1-6) y 2,1 años (rango 0,4 a 6,3) en las cohortes de cabergolina y pegvisomant, respectivamente. Al inicio del estudio el valor mediano del factor de crecimiento de insulina-I era 149% el límite superior normal (LSN) (15-505%) en la cohorte de cabergolina y 156% LSN (15-534%) en la de pegvisomant. Al final del estudio se redujeron a 104% LSN (13-557%) p < 0,001 y 86% LSN (23-345%) p < 0,0001, respectivamente. Al final del estudio, se reportaron valores normales de factor de crecimiento de insulina-I ajustados por edad en el 48% de los pacientes tratados con lanreotida/cabergolina y 70% de los tratados con lanreotida/pegvisomant. No hubo cambios significativos en los parámetros hepáticos, cardíacos o glucémicos. CONCLUSIÓN: En la práctica clínica las combinaciones con lanreotida son una opción útil en el tratamiento de pacientes con acromegalia que no está bien controlada en monoterapia, ya sea con SSA carbegolina o pegvisomant; particularmente, la combinación de lanreotida y pegvisomant tiene una alta eficacia y se tolera bien

Use of lanreotide in combination with cabergoline or pegvisomant in patients with acromegaly in the clinical practice: The ACROCOMB study.

PURPOSE: To describe real-world use of lanreotide combination therapy for acromegaly. PATIENTS AND METHODS: ACROCOMB is a retrospective observational Spanish study of patients with active acromegaly treated with lanreotide combination therapy between 2006 and 2011. 108 patients treated at 44 Spanish Endocrinology Departments were analyzed separately: 61 patients received lanreotide/cabergoline (cabergoline cohort) and 47 lanreotide/pegvisomant (pegvisomant cohort). RESULTS: Patient median age was 50.8 years in the cabergoline cohort and 42.7 years in the pegvisomant cohort. Prior medical treatments were somatostatin analogue (SSA) monotherapy (40 [66%] patients) or dopamine agonists (7 [11%] patients) in the cabergoline cohort and SSA (29 [62%] patients) or pegvisomant monotherapy (16 [34%] patients) in the pegvisomant cohort. Across both cohorts 12 patients were previously untreated, and prior therapy was unknown/missing in 4 patients. Median duration of combined treatment was 1.6 years (0.1-6) and 2.1 years (0.4-6.3) in the cabergoline and pegvisomant cohorts, respectively. At baseline, median insulin growth factor (IGF)-I values were 149% upper limit of normal (ULN) (15-505%) in the cabergoline cohort and 156% ULN (15-534%) in the pegvisomant cohort, and decreased to 104% ULN (13-557%) p<0.001 and 86% ULN (23-345%) p<0.0001, respectively, at end of study (EOS). Normal age-adjusted values of IGF-I were obtained in 48% of lanreotide/cabergoline-treated patients and 70% of lanreotide/pegvisomant-treated patients at EOS. There were no significant changes in hepatic, cardiac or glycaemic parameters in either cohort. CONCLUSION: In clinical practice lanreotide treatment combinations are useful options for patients with acromegaly when monotherapy is insufficient; particularly, the combination of lanreotide and pegvisomant in patients not controlled with either SSA or pegvisomant alone has high efficacy and is well-tolerated.

Intrasellar chordoma associated with a primitive persistent trigeminal artery.

Chordomas located primarily in the sellar region are uncommon, and may be misdiagnosed non-functioning pituitary adenoma. Furthermore, the association of a persistent primitive trigeminal artery (PPTA) with an intrasellar chordoma is extremely rare, and no similar cases have been reported in the literature to date. The coexistence of intrasellar chordoma (ISC) and PPTA makes safe and complete tumor resection challenging, and preoperative endovascular occlusion of this artery may be helpful. We report a case of a 32-year-old man who developed right hemifacial paresthesias and a cranial nerve six palsy. MRI study demonstrated the presence of a primary ISC associated with a PPTA. Angiographic balloon test occlusion of the PPTA revealed no neurological changes, so this vessel was endovascularly occluded by coiling. The lesion was subtotally removed through a sublabial transsphenoidal approach, without intraoperative bleeding complications. Histological examination of the lesion was consistent with the diagnosis of chordoma. Detailed preoperative neurovascular evaluation may be useful to detect vascular anomalies associated with intracranial chordomas, such as PPTA. In this report we emphasize the importance of appropriate treatment of vascular anomalies prior intrasellar lesions resection that may facilitate surgery and avoid potential hazardous intraoperative bleeding complications.

Analysis of IGF(CA)19 and IGFBP3-202A/C gene polymorphisms in patients with acromegaly: association with clinical presentation and response to treatments.

OBJECTIVE: IGF1 and IGFBP3 gene polymorphisms have been recently described. However, their potential role in the setting of acromegaly and its outcome is unknown. In this study, we analyze these polymorphisms in patients with acromegaly and investigate their association with clinical presentation and response to treatments. DESIGN: A retrospective observational study was conducted in patients with acromegaly to analyze IGF1 and IGFBP3 gene polymorphisms. METHODS: A total of 124 patients with acromegaly (57.3% women, mean age 44.9±13.1 years old) were followed up for a period of 11.4±8.0 years in eight tertiary referral hospitals in Spain. Clinical and analytical data were evaluated at baseline and after treatment. IGF1 and IGFBP3 gene polymorphisms were analyzed using PCR and specific primers. RESULTS: Baseline laboratory test results were GH 19.3 (8.0-39.6) ng/ml, nadir GH 11.8 (4.1-21.5) ng/ml, and index IGF1 2.65±1.25 upper limit of normal. Regarding the IGF1 gene polymorphism, we did not find any association between the number of cyto-adenosine (CA) repeats and patients' baseline characteristics. Nevertheless, a trend for higher nadir GH values was observed in patients with <19 CA repeats. Regarding the IGFBP3 polymorphism, the absence of an A allele at the -202 position was associated with a higher baseline IGF1 and a higher prevalence of cancer and polyps. There were no differences in response to therapies according to the specific genotypes. CONCLUSIONS: Polymorphisms in the IGF1 and IGFBP3 genes may not be invariably determinant of treatment outcome in acromegalic patients, but they may be associated with higher nadir GH levels or baseline IGF1, and determine a higher rate of colorectal polyps and cancer.

Escape and lipodystrophy in acromegaly during pegvisomant therapy, a retrospective multicentre Spanish study.

BACKGROUND: Pegvisomant is an effective treatment for acromegaly. OBJECTIVE: To investigate escape (loss of biochemical control in patients previously controlled) and lipodystrophy in acromegalic patients treated with pegvisomant and to evaluate possible associations with clinical features. PATIENTS AND METHODS: Multicentre retrospective study involving 19 Spanish centres. RESULTS: Ninety-seven patients were included (59% women, mean age at diagnosis 42 ± 13 years, 80% macroadenomas); mean follow-up on pegvisomant was 5 ± 2·5 years, and 89 (92%) achieved normal IGF-1. Escape was reported in 30/89 (34%) of responders, after a mean treatment duration of 25 ± 21 months. The mean initial dose of pegvisomant was 11 ± 5 mg/day, and mean dose at escape was 14 ± 7 mg/day. Most patients (26/30, 87%) achieved control with dose increase (57%), additional medical treatment (3%) or both (27%). Mean new dose that controlled IGF-1 after escape was 20 ± 7 mg/day. Treatments associated were somatostatin analogues (SSA in 47%), cabergoline (CAB in 47%) and both (6%). Lipodystrophy was observed in 15 patients (13 females), mild in six, moderate in six, severe in three and persistent in four. Among patients with lipodystrophy, three escaped and three were nonresponders to pegvisomant. Four patients discontinued the drug, and four had dose reductions because of lipodystrophy. It tended to be more frequent in females (P = 0·06) and in patients treated with triple association SSA+CAB+PEG (P = 0·018). No relationship between escape and clinical variables was found, except prior CAB (P = 0·04) and metformin treatment (0·02) and grade of lipodystrophy (P = 0·02). CONCLUSIONS: A significant proportion of patients treated with pegvisomant escaped (34%); however, the majority (87%) was easily controlled with either dose increase, further medical treatment or both. Lipodystrophy developed in 15%, mostly females, and influenced the response to treatment.

Changes in acromegaly treatment over four decades in Spain: analysis of the Spanish Acromegaly Registry (REA).

Since 1997 there is an online National Registry of acromegalic patients in Spain (REA). We aimed to study changes in acromegaly treatment and outcomes over the last four decades in Spain. In REA clinical and biochemical data are collected at diagnosis and updated every one to 2 years. We analyzed the first treatment received and the different treatments administered according to decade of diagnosis of acromegaly: prior to 1980, 1980-1989, 1990-1999 and 2000-2009. Surgical cure rates according to pretreatment with long-acting somatostatin receptor ligands (SRLs) were also analyzed. 1,658 patients were included of which 698 had accurate follow-up data. Treatment of acromegaly changed over time. Surgery was the main treatment option (83.8 %) and medical treatment was widely used (74.7 %) both maintained over decades, while radiation therapy declined (62.8, 61.6, 42.2 and 11.9 % over decades, p < 0.001). First treatment type also changed: surgery was the first line option up until the last decade in which medical treatment was preferred (p < 0.001). Radiotherapy was barely used as first treatment. Treatment combinations changed over time (p < 0.001). The most common treatment combination (surgery plus medical therapy), was received by 24.4, 16.4, 25.3 and 56.5 % of patients over decades. Medical treatment alone was performed in 7.3, 6, 7.2 and 14.7 % over decades. Type of medical treatment also changed, SRLs becoming the first medical treatment modality in the last decades, whereas dopamine agonist use declined (p < 0.001). Surgical cure rates improved over decades (21, 21, 36 and 38 %, p = 0.002) and were not influenced by SRL pre-surgical use. Acromegaly treatment has changed in Spain in the last four decades. Surgery has been the main treatment option for decades; however, medical therapy has replaced surgery as first line in the last decade and radiotherapy rates have clearly declined. SRLs are the most used medical treatment.

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