Endocrine and metabolic aspects of the COVID-19 pandemic.

COVID-19 infection has tremendously impacted our daily clinical practice as well as our social living organization. Virtually all organs and biological systems suffer from this new coronavirus infection, either because the virus targets directly specific tissues or because of indirect effects. Endocrine diseases are not an exception and some of endocrine organs are at risk of direct or indirect lesion by COVID-19. Although there is still no evidence of higher predisposition to contract the infection in patients with diabetes and/or obesity, the coexistence of these conditions contributes to a worse prognosis because both conditions confer an impaired immunologic system. Cytokines storm can be amplified by these two latter conditions thereby leading to multisystemic failure and death. Glycaemic control has been demonstrated to be crucial to avoiding long hospital stays, ICU requirement and also prevention of excessive mortality. Endocrine treatment modifications as a consequence of COVID-19 infection are required in a proactive manner, in order to avoid decompensation and eventual hospital admission. This is the case of diabetes and adrenal insufficiency in which prompt increase of insulin dosage and substitutive adrenal steroids through adoption of the sick day's rules should be warranted, as well as easy contact with the health care provider through telematic different modalities. New possible endocrinological targets of COVID-19 have been recently described and warrant a full study in the next future.

Multidisciplinary management of acromegaly: A consensus.

The 13th Acromegaly Consensus Conference was held in November 2019 in Fort Lauderdale, Florida, and comprised acromegaly experts including endocrinologists and neurosurgeons who considered optimal approaches for multidisciplinary acromegaly management. Focused discussions reviewed techniques, results, and side effects of surgery, radiotherapy, and medical therapy, and how advances in technology and novel techniques have changed the way these modalities are used alone or in combination. Effects of treatment on patient outcomes were considered, along with strategies for optimizing and personalizing therapeutic approaches. Expert consensus recommendations emphasize how best to implement available treatment options as part of a multidisciplinary approach at Pituitary Tumor Centers of Excellence.

Diagnostic Performance Evaluation of a Computer-Assisted Imaging Analysis System for Ultrasound Risk Stratification of Thyroid Nodules.

OBJECTIVE. Ultrasound-based stratification of the malignancy risk of thyroid nodules has potential variability. The purpose of this study is to evaluate the diagnostic effectiveness of the first commercially available system for computer-aided diagnosis (CADx) imaging analysis. MATERIALS AND METHODS. Ultrasound images of 300 thyroid nodules (135 of which were malignant) acquired before surgical treatment were retrospectively reviewed by a thyroid expert, and his classification of each image was then compared with the classification rendered by an image analysis program (AmCAD-UT, AmCAD Biomed). The American Thyroid Association (ATA) classification system, the European Thyroid Imaging Reporting and Data System (EU-TIRADS), and the classification system jointly proposed by American and Italian associations of clinical endocrinologists (the American Association of Clinical Endocrinologists [AACE], the American College of Endocrinology [ACE], and Associazione Medici Endocrinologi [AME]) were used for risk stratification. RESULTS. The diagnostic performance of the thyroid expert when the ATA system was used was as follows: sensitivity, 87.0%; specificity, 91.2%; positive predictive value, 90.5%; and negative predictive value, 90.9%. Compared with the expert, the CADx program, when used with the three classification systems, had a similar sensitivity but a lower specificity and positive predictive value. Regarding the negative predictive value, the results of the expert did not differ from those of the CADx program when it applied the ATA classification system (90.9% vs 86.3%; p = 0.07). The ROC AUC value was 0.88 for the expert clinician and 0.72 for the CADx program when the ATA classification system was used. CONCLUSION. The CADx ultrasound image analysis program described in the present study is useful for risk stratification of thyroid nodules, but it does not perform better than a sonography expert.

More patients reach glycaemic control with a fixed-ratio combination of insulin glargine and lixisenatide (iGlarLixi) than with basal insulin at 12 weeks of treatment: A post hoc time-to-control analysis of LixiLan-O and LixiLan-L.

The present post hoc analysis of two 30-week clinical trials compared efficacy and hypoglycaemia outcomes at early study visits with iGlarLixi (insulin glargine U100 [iGlar] and lixisenatide) vs iGlar alone in patients with type 2 diabetes (T2D) uncontrolled on oral antidiabetic drugs (OADs; LixiLan-O trial) or basal insulin (LixiLan-L trial). Time to control, defined as days to achieve glycated haemoglobin (HbA1c) <53 mmol/mol (<7%) or fasting plasma glucose (FPG) ≤7.2 mmol/L, was estimated using the Kaplan-Meier method. In the LixiLan-O and LixiLan-L trials, 60% and 46% of patients, respectively, reached HbA1c <53 mmol/mol (<7%) with iGlarLixi at 12 weeks, vs 45% and 24%, respectively, with iGlar. In the LixiLan-O trial, the median time to target HbA1c was approximately half with iGlarLixi vs iGlar (85.0 vs 166.0 days; P < .0001). In the LixiLan-L trial, the median time to target HbA1c was 153.0 days with iGlarLixi, while target HbA1c was never reached by 50% of patients with iGlar (P < .0001). Time-to-target FPG and hypoglycaemia outcomes were similar between treatments. In T2D uncontrolled on OADs or basal insulin, iGlarLixi resulted in glycaemic control in more patients than did iGlar at early treatment time points.

Consistent findings in glycaemic control, body weight and hypoglycaemia with iGlarLixi (insulin glargine/lixisenatide titratable fixed-ratio combination) vs insulin glargine across baseline HbA1c, BMI and diabetes duration categories in the LixiLan-L trial.

AIMS: To assess the impact of baseline characteristics on clinical outcomes in the LixiLan-L trial, a randomized open-label trial designed to evaluate the efficacy and safety of iGlarLixi, a novel fixed-ratio combination of insulin glargine 100 U (iGlar) plus lixisenatide, in comparison with iGlar over 30 weeks in a population of patients with type 2 diabetes mellitus (T2DM) inadequately controlled on a previous regimen of basal insulin alone or in combination with 1 or 2 oral glucose-lowering drugs. MATERIALS AND METHODS: In this exploratory analysis of LixiLan-L (N = 736), efficacy outcomes were assessed within population subgroups derived from the following baseline characteristics: glycated haemoglobin [HbA1c; <8%, ≥8% (<64, ≥64 mmol/mol)]; duration of T2DM (<10, ≥10 years); body mass index (<30, ≥30 kg/m2 ). Furthermore, the incidence of symptomatic hypoglycaemia with plasma glucose ≤3.9 mmol/L (≤70 mg/dL) was also analysed according to the same subgroups. RESULTS: Compared with the iGlar treatment group, patients treated with iGlarLixi showed consistently greater reductions in HbA1c during the treatment period, with higher percentages of patients achieving the HbA1c target level of <7% (<53 mmol/mol) in all of the subpopulations tested (P < .0001 for all), having consistent mitigation of body weight gain and with no major differences in the incidence of hypoglycaemia. CONCLUSIONS: iGlarLixi consistently improved glycaemic control compared with iGlar in all baseline characteristic subgroups of patients with T2DM inadequately controlled with insulin, including difficult-to-treat subgroups of patients with long duration of diabetes, obesity and high HbA1c. Clinical trial number: NCT02058160 (clinicaltrials.gov).

Long-term treatment with pegvisomant for acromegaly: a 10-year experience.

BACKGROUND: Efficacy of the GH-receptor antagonist pegvisomant (PEG) has differed between preclinical and observational studies mainly due to dose adjustment and IGF-I normalization criteria. An escape phenomenon has also been described, but its definition and underlying causes have not been fully established. OBJECTIVE: To re-evaluate the outcomes of long-term PEG in a series of previously published patients and analyse the escape phenomenon. METHODS: We reviewed all patients with acromegaly resistant to SSA in whom PEG was started as monotherapy, who had been included in a previous publication. We prospectively evaluated 64 (56·3% women) from six tertiary care referral hospitals in Spain, for whom data as of June 2014 were available. Escape to PEG was defined as confirmed loss of biochemical control (IGF-I >1·2xULN), after at least 6 months of previous control with a stable dose of PEG. RESULTS: Patients were followed up for 13·0 (5·9-34·8) years since diagnosis, and 9·0 (4·1-10·4) years since the first administration of PEG. Fifty-one (89·5%) patients had an adequate IGF-I control at the last follow-up visit, 9 of them without treatment. Tumour growth was reported in 6 of 64 cases (9·4%), none of whom had received prior radiotherapy (P = 0·011). Seven patients died during follow-up. We found 16 escapes in 10 patients (15·6%). We identified potential underlying causes in 9 cases (tumour regrowth, previous treatment modifications, concomitant menopause and change in testosterone administration). The reason was unknown in 7 escapes, which occurred in 6 patients (9·4%). All patients, except one, achieved subsequent biochemical control after treatment adjustment. CONCLUSIONS: We reassure the efficacy and safety of long-term PEG. An escape phenomenon may occur, but it can be overcome by adjusting therapy.

Treatment of acromegaly in the era of personalized and predictive medicine.

Acromegaly is a chronic disorder usually diagnosed late in the disease evolution. Such delayed diagnosis, together with the inability to achieve the treatment goals of normalizing biochemical disease markers and controlling tumour mass may result in substantial morbidity and mortality. Somatostatin analogues (SSA) are accepted as first-line medical therapy or as second-line therapy in patients undergoing unsuccessful surgery and are considered a cornerstone in the treatment of acromegaly. However, because a high percentage of patients experience SSA medical treatment failure, the identification of biomarkers associated with a successful or unsuccessful response to all classes of medical therapy would help in the choice of treatment and potentially allow for a quicker normalization of biochemical parameters. The current treatment algorithms for acromegaly are based upon a "trial-and-error" approach with additional treatment options provided when disease is not controlled. In many other diseases, therapeutic algorithms have been evolving towards personalized treatment with the medication that best matches individual disease characteristics, using biomarkers that identify therapeutic response. Additionally, a personalized approach to complementary treatment of comorbidities present in the acromegalic patient is also required. This review will discuss the development of a potential treatment algorithm for acromegaly addressing the biochemical control of the disease as well of its associated comorbidities, under a personalized approach based upon markers of prognostic and predictive significance, such as tumour size, MRI adenoma signal, GH value after acute octreotide test, granular adenoma pattern, Ki-67, somatostatin receptor phenotype, aryl hydrocarbon-interacting protein expression, gsp mutations, RAF kinase activity, E-cadherin and beta-arrestin-1.

Register-based information on thyroid diseases in Europe: lessons and results from the EUthyroid collaboration.

Objective: Registers of diagnoses and treatments exist in different forms in the European countries and are potential sources to answer important research questions. Prevalence and incidence of thyroid diseases are highly dependent on iodine intake and, thus, iodine deficiency disease prevention programs. We aimed to collect European register data on thyroid outcomes to compare the rates between countries/regions with different iodine status and prevention programs. Design: Register-based cross-sectional study. Methods: National register data on thyroid diagnoses and treatments were requested from 23 European countries/regions. The provided data were critically assessed for suitability for comparison between countries/regions. Sex- and age-standardized rates were calculated. Results: Register data on ≥1 thyroid diagnoses or treatments were available from 22 countries/regions. After critical assessment, data on medication, surgery, and cancer were found suitable for comparison between 9, 10, and 13 countries/regions, respectively. Higher rates of antithyroid medication and thyroid surgery for benign disease and lower rates of thyroid hormone therapy were found for countries with iodine insufficiency before approx. 2001, and no relationship was observed with recent iodine intake or prevention programs. Conclusions: The collation of register data on thyroid outcomes from European countries is impeded by a high degree of heterogeneity in the availability and quality of data between countries. Nevertheless, a relationship between historic iodine intake and rates of treatments for hyper- and hypothyroid disorders is indicated. This study illustrates both the challenges and the potential for the application of register data of thyroid outcomes across Europe.

Long-term efficacy evaluation of a protocol for the management of symptomatic thyroid cysts with ultrasound-guided percutaneous ethanol injection.

AIM: To evaluate the long-term efficacy of percutaneous ethanol injection treatment (PEIT) as an alternative to thyroid surgery in symptomatic thyroid cysts. PATIENTS AND METHODS: 100 subjects (48±12 years; 58% women) with symptomatic thyroid cysts relapsing after drainage were prospectively included. PEIT was conducted using an established procedure, and the initial cyst volume, symptoms and pain perceived by the patient were assessed. The volume of instilled alcohol was ≤2ml without re-extraction in all cases. Patients were followed-up for more than 3 years and final cyst volume and symptom improvement were assessed. RESULTS: Mean maximum cyst diameter before drainage was 3.1±1.2cm. In 71% of patients ≤2 PEIT sessions were required. Median maximum cyst volume was 12.7 (5.4-21.7)ml before the first drainage and median total volume extracted from the cysts was 13.0 (6.2-37.0)ml. After a mean follow-up period of 52±10 months, 98% of patients reported a complete absence of symptoms. The final median volume for the whole group was 0.8 (0.1-2.0)ml with a median volume reduction of 94 (81-99)%. A final volume reduction greater than 65% was observed in 90% of cases. Reported pain during the procedure was absent or mild in 76.4% of cases. CONCLUSIONS: PEIT is a safe and well-tolerated first-line treatment for symptomatic thyroid cysts with long-term effectiveness.

Long-term efficacy evaluation of a protocol for the management of symptomatic thyroid cysts with ultrasound-guided percutaneous ethanol injection.

AIM: To evaluate the long-term efficacy of percutaneous ethanol injection treatment (PEIT) as an alternative to thyroid surgery in symptomatic thyroid cysts. PATIENTS AND METHODS: 100 subjects (48±12 years; 58% women) with symptomatic thyroid cysts relapsing after drainage were prospectively included. PEIT was conducted using an established procedure, and the initial cyst volume, symptoms and pain perceived by the patient were assessed. The volume of instilled alcohol was ≤2ml without re-extraction in all cases. Patients were followed-up for more than 3 years and final cyst volume and symptom improvement were assessed. RESULTS: Mean maximum cyst diameter before drainage was 3.1±1.2cm. In 71% of patients ≤2 PEIT sessions were required. Median maximum cyst volume was 12.7 (5.4-21.7)ml before the first drainage and median total volume extracted from the cysts was 13.0 (6.2-37.0)ml. After a mean follow-up period of 52±10 months, 98% of patients reported a complete absence of symptoms. The final median volume for the whole group was 0.8 (0.1-2.0)ml with a median volume reduction of 94 (81-99)%. A final volume reduction greater than 65% was observed in 90% of cases. Reported pain during the procedure was absent or mild in 76.4% of cases. CONCLUSIONS: PEIT is a safe and well-tolerated first-line treatment for symptomatic thyroid cysts with long-term effectiveness.

Relationship between ghrelin and the metabolic syndrome in the elderly: a longitudinal population-based study.

CONTEXT: Ghrelin regulates energy homeostasis and may contribute to the development of the metabolic syndrome (MS) in the elderly. OBJECTIVE: To study the relationship between ghrelin and the MS, IGF-I and life style factors over a 2-year follow-up. DESIGN: Longitudinal population-based study, starting from 2002; 2 years follow-up. PARTICIPANTS: Three hundred and thirteen (153 men/160 women) individuals living independently older than 70 years. RESULTS: MS was found in 54.9% of men and 61% of women. In the 229 subjects available at follow-up, ghrelin was higher in men than in women at basal (P = 0.002) and 2-year follow-up (P = 0.004). Ghrelin decreased over time in both genders (P < 0.01). Ghrelin was lower in individuals showing MS compared to non-MS (P = 0.08), but this difference was more evident at 2-year follow-up (P = 0.016), mostly due to men with MS (P = 0.002) and even after adjustment for BMI, gender and age. Individuals with MS had an OR of 1.67 (95% CI: 1.0-2.78) for low ghrelin (< first tertile); when adjusting by BMI, gender and age, only high triglycerides with OR 1.8 (1.0-3.3), remained statistically significant among the MS components. IGF-I showed a positive correlation with ghrelin only in individuals without MS (r(s) 0.403, P < 0.001) with no gender differences; this relationship was not found in MS (r(s) 0.120, P = 0.129). A positive association of ghrelin was found with academic level, alcohol consumption and smoking. CONCLUSIONS: Ghrelin is higher in old men in comparison to women and decreases over time with a steeper decline in subjects with MS; moreover, in these subjects ghrelin/IGF-I correlation is lost.

Precision medicine in the treatment of acromegaly.

Acromegaly is a chronic disorder usually diagnosed late in the disease evolution, leading to substantial morbidity and mortality related to this long period of undiagnosed state as well as the difficulty in achieving normalization of GH hypersecretion and controlling tumor mass. First generation somatostatin analogues (SSA) are accepted as the first-line medical therapy or as second-line therapy in patients undergoing unsuccessful surgery. However, because a high percentage of patients experience SSA treatment failure, the inclusion of biomarkers associated with a successful or non-successful response to these drug (as well as to all classes of medical therapy) is necessary to better guide the choice of treatment, potentially allowing for a quicker achievement of disease control. The current treatment algorithms for acromegaly are based upon a "trial and error" approach with additional treatment options provided when disease is not controlled. In many other diseases, their therapeutic algorithms have been evolving towards personalizing treatment with medication that best matches individual disease characteristics, using biomarkers that identify therapeutic response, thus allowing the personalization of the therapy. It is time to introduce this approach to acromegaly treatment algorithms. This paper reviews the potential tools for doing so.

Distinct pattern of peripheral lymphocyte subsets in Graves' disease with persistency of anti-TSHR autoantibodies.

Background: Graves' disease (GD) is characterized by the production of autoantibodies against the TSHR (TRAbs). With long-term treatment, serum concentrations of TRAbs decline but in some patients, despite being clinically stable, TRAbs persist for many years.Objective: To investigate whether GD patients with persistence of TRAbs constitute a subset of patients that could be identified by phenotypic analysis of circulating lymphocytes, suggesting disease heterogeneity.Materials and methods: Peripheral blood lymphocytes (including naïve, memory and effector T and B cells, Th17, regulatory T cells (Treg), recent thymic emigrants (RTEs) and double positive CD4+CD8+ (DP) cells) were analysed by flow cytometry in a cross-sectional study in 25 clinically stable GD patients, five patients at onset of GD disease and 40 healthy donors (HDs).Results: GD patients with persistence of TRAbs showed a lower percentage of Treg and lower absolute numbers of central and effector memory CD8+ T cells than HD. No differences in RTEs were found in peripheral blood from GD patients compared to HD. Stable GD patients had higher percentage of DP cells of effector phenotype than HD.Conclusions: Using extensive phenotypic analysis of lymphocyte subpopulations, it is possible to detect changes that help to identify patients with persistent TSHR antibodies and may contribute to understand why the autoimmune response is maintained.

Strategic reflections of the Spanish Society of Endocrinology and Nutrition on the future of the speciality in the period 2018-2022. / Reflexión estratégica de la Sociedad Española de Endocrinología y Nutrición sobre el futuro de la especialidad en el periodo 2018-2022.

Endocrine diseases are experiencing an important increase in their prevalence, due to causes of various kinds, including the epidemic of obesity and malnutrition, the aging of the population, but also the effect of endocrine disruptors, among others. On the other hand, new technologies, both in terms of molecular and genetic analysis, image and new therapeutic devices, require that the endocrine professional community in Spain must be in constant training. The connection with patients through their associations, increasingly active, and with the civil society in general, the professional commitment and demand of various social groups for a modern and equitable care, and to carry out research that facilitates the achievement of advances for patients, forces the specialist in endocrinology and nutrition and the Spanish Society of Endocrinology and Nutrition (SEEN) to position themselves and respond to all these challenges. In this document, the SEEN presents its proposals and its strategy until 2022.

[Metabolic syndrome and cardiovascular disease in elders: results of the Mataró Ageing study]. / Síndrome metabólico y enfermedad cardiovascular en ancianos: resultados del Estudio de Envejecimiento de Mataró

BACKGROUND AND OBJECTIVE: The metabolic syndrome (MS) is a constellation of factors apparently associated to an increased cardiovascular risk, and with a reported increasing prevalence in parallel with aging process. The aim of this study was to assess the prevalence of MS in elder subjects according to the criteria of the National Education Program (ATP-III) and the International Diabetes Federation (IDF). SUBJECTS AND METHOD: Population-based cross-sectional study including 313 individuals (153 men and 160 women) older than 70 years. The prevalence of MS was evaluated according to both definitions and its association with cardiovascular disease (CD) was investigated. RESULTS: MS was observed in 50.2% of subjects according to ATP-III (41.5% of men and 58.6% of women; p = 0.004) and in 57.9% when using IDF criteria (54.9% of men and 61% of women; p = 0.29). Prevalence differences were observed between ATP-III and IDF only in men. No differences were found in the frequencies of the different components of the MS for the 2 definitions, neither for tobacco consumption, ethanol intake and educational level. There was no differences in the coexistence of CD in relation the presence or absence of MS, no matter the definition used; also, no special association with CD was found for any of the individual components of the MS. CONCLUSIONS: Among a representative population sample of old people living in a Mediterranean community, despite a very high frequency of MS, there was no excess prevalence of CD in those identified as having MS.

Hormonal determinants of depression and cognitive function in independently-living elders.

OBJECTIVE: To study the potential associations among circulating insulinlike growth factor 1 (IGF-1) and adrenal and gonadal steroids with cognitive status and depression in a group of independently-living elders. DESIGN: Population-based cross sectional study. METHODS: A total of 313 individuals (160 women and 153 men, with a mean age of 76.7±7 years) participated in this study. A physical examination, assessment of functional capacity, cognitive function, depression, educational level and measurement of plasma cortisol, dehydroepiandrosterone (DHEA) and its sulphate (DHEAs), testosterone, estradiol, and IGF-1 were performed. RESULTS: In women, adrenal steroids showed a negative correlation with global cognition (ß=-0.79; p=0.03 for DHEA and ß=-0.27; p=0.002 for cortisol). A positive correlation with IGF-1 (ß=0.026; p=0.04) was found for cognition in women after adjustment for depression. For memory function, DHEA correlated negatively but no relationship with IGF-1 and cortisol was observed. No relationships with cognition were observed in men for any of the steroids or other hormones studied. Educational level showed the highest protective effect (odds ratio [OR] = 6.25) for preserved cognition for both sexes; in women, OR for deteriorated cognition with age, DHEA and cortisol were 1.14, 1.57 and 1.09, respectively. No associations between depression and hormonal profile were found in either sex. CONCLUSIONS: Educational level was positively associated with cognitive function in independently-living elderly men and women, while adrenal steroids were associated with impaired cognition in elderly women but not in men. The hormonal milieu seemed to have little or no influence on depression in the men and women studied.

Increased Burden of Cerebral Small Vessel Disease in Patients With Type 2 Diabetes and Retinopathy.

OBJECTIVE: We sought to examine the presence and severity of brain small vessel disease (SVD) in patients with type 2 diabetes and diabetic retinopathy (DR) compared with those without DR. RESEARCH DESIGN AND METHODS: We evaluated 312 patients with type 2 diabetes without previous cardiovascular disease (men 51%; mean age 57 years; age range 40-75 years); 153 patients (49%) had DR. MRI was performed to evaluate the presence and severity (age-related white matter changes scale) of white matter lesions (WMLs) and lacunes, and transcranial Doppler ultrasound was used to measure the Gosling pulsatility index (PI) of the middle cerebral artery (MCA). RESULTS: The prevalence of lesions of cerebral SVD (WML and/or lacunes) was higher in patients with DR (40.2% vs. 30.1% without DR, P = 0.04). Age (P < 0.01) and systolic blood pressure (P = 0.02) were associated with the presence of SVD. The severity of SVD was associated with age and the presence of DR (P < 0.01 and P = 0.01, respectively). Patients with DR showed a higher MCA PI compared with those without DR (P < 0.01). Age, systolic and diastolic blood pressure, and retinopathy and its severity were associated with an increased MCA PI (P < 0.01 for all variables). A positive correlation was found between MCA PI values and the presence and severity of SVD (P < 0.01 for both variables). CONCLUSIONS: Patients with type 2 diabetes who have DR have an increased burden of cerebral SVD compared with those without DR. Our findings suggest that the brain is a target organ for microangiopathy, similar to other classic target organs, like the retina.

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.