Molecular determinants of enhanced response to somatostatin receptor ligands after debulking in large GH-producing adenomas.

OBJECTIVE: Large somatotrophic adenomas depict poor response to somatostatin receptor ligands (SRLs). Debulking has shown to enhance SRLs effect in some but not all cases and tumour volume reduction has been proposed as the main predictor of response. No biological studies have been performed so far in this matter. We aimed to identify molecular markers of response to SRLs after surgical debulking in GH-secreting adenomas. DESIGN: We performed a multicenter retrospective study. PATIENTS: 24 patients bearing large GH-producing tumours. MEASUREMENTS: Clinical data and SRLs response both before and after surgical debulking were collected, and 21 molecular biomarkers of SRLs response were studied in tumour samples by gene expression. RESULTS: From the 21 molecular markers studied, only two of them predicted enhanced SRLs response after surgery. Tumours with improved response to SRLs after surgical debulking showed lower levels of Ki-67 (MKI67, FC = 0.17 and P = .008) and higher levels of RAR-related orphan receptor C (RORC) (FC = 3.1 and P Ë‚ .001). When a cut-off of no detectable expression was used for Ki-67, the model provided a sensitivity of 100% and a specificity of 52.6% with an area under the curve of 65.8%. Using a cut-off of 2 units of relative expression of RORC, the prediction model showed 100% of sensitivity and specificity. CONCLUSIONS: High levels of RORC and low levels of Ki-67 identify improved SRLs response after surgical debulking in large somatotropic adenomas. To determine their expression would facilitate medical treatment decision-making after surgery.

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.

Executive summary of the position statement of the Spanish Societies SEQCML/SEEN/SEEP. Recommendations for the measurement of sex steroids in clinical practice.

Accurate measurement of sex steroids, particularly testosterone and estradiol, is relevant for the diagnosis and treatment of a wide range of conditions. Unfortunately, current chemiluminescent immunoassays have analytical limitations with important clinical consequences. This document reviews the current state of clinical assays for estradiol and testosterone measurements and their potential impact in different clinical situations. It also includes a series of recommendations and necessary steps to introduce steroid analysis by mass spectrometry into national health systems, a methodology recommended for more than a decade by international societies.

Recommendations for the measurement of sexual steroids in clinical practice. A position statement of SEQCML/SEEN/SEEP.

The proper clinical approach to a wide range of disorders relies on the availability of accurate, reproducible laboratory results for sexual steroids measured using methods with a high specificity and sensitivity. The chemiluminescent immunoassays currently available have analytical limitations with significant clinical implications. This position statement reviews the current limitations of laboratory techniques for the measurement of estradiol and testosterone and their impact on diverse clinical scenarios. A set of recommendations are provided to incorporate steroid hormone analysis by mass spectrometry in national health systems. International societies have recommended this methodology for a decade.

Molecular characterization of epithelial-mesenchymal transition and medical treatment related-genes in non-functioning pituitary neuroendocrine tumors.

Introduction: Different medical therapies have been developed for pituitary adenomas. However, Non-Functioning Pituitary Neuroendocrine Tumors (NF-PitNET) have shown little response to them. Furthermore, epithelial-mesenchymal transition (EMT) has been linked to resistance to medical treatment in a significant number of tumors, including pituitary adenomas. Methods: We aimed to evaluate the expression of EMT-related markers in 72 NF-PitNET and 16 non-tumoral pituitaries. To further explore the potential usefulness of medical treatment for NF-PitNET we assessed the expression of somatostatin receptors and dopamine-associated genes. Results: We found that SNAI1, SNAI2, Vimentin, KLK10, PEBP1, Ki-67 and SSTR2 were associated with invasive NF-PitNET. Furthermore, we found that the EMT phenomenon was more common in NF-PitNET than in GH-secreting pituitary tumors. Interestingly, PEBP1 was overexpressed in recurrent NF-PitNET, and could predict growth recurrence with 100% sensitivity but only 43% specificity. In parallel with previously reported studies, SSTR3 is highly expressed in our NF-PitNET cohort. However, SSTR3 expression is highly heterogeneous among the different histological variants of NF-PitNET with very low levels in silent corticotroph adenomas. Conclusion: NF-PitNET showed an enhanced EMT phenomenon. SSTR3 targeting could be a good therapeutic candidate in NF-PitNET except for silent corticotroph adenomas, which express very low levels of this receptor. In addition, PEBP1 could be an informative biomarker of tumor regrowth, useful for predictive medicine in NF-PitNET.

Gestational diabetes prevalence and outcomes in women undergoing assisted reproductive techniques (ART).

Infertility affects millions worldwide and use of assisted reproductive techniques (ART) is in high demand. AIMS: To investigate whether women that underwent ART at our hospital had a higher incidence of GDM than women who conceived spontaneously, if the ART subtype affects the GDM rate and to study obstetrical outcomes in women with GDM in both groups. METHODS: This was a retrospective analysis of prospectively collected data of singleton pregnancies attended at Hospital Universitari Dexeus between 2008 and 2019. Age<18 years, pregestational diabetes, metformin prior to pregnancy and multiple pregnancies were excluded. RESULTS: A total of 29,529 patients were included. Pregnancy was achieved by ART in 2596 (8.8%): in vitro fertilisation (IVF/ICSI) 32.8%, frozen embryo transfer (FET) 37.7%, oocyte donor receptors (ODR) 17.2% and insemination 12.2%. The GDM rate was 8.9% (12.7% in ART vs 8.5% in non-ART, p<0.001). The GDM was 11.2% in IVF/ICSI, 17.7% in ODR, 13% in FET and 9.1% in the insemination group (p=0.001). In a multivariable analysis adjusting for age, parity and BMI, ART was not associated with GDM [OR 1.03 (0.90-1.19)], nor was type of ART. Pregnancy outcomes in GDM patients were similar in both groups except for C-section rates (30.0% in ART vs 15.9% in non-ART (p<0.001). CONCLUSIONS: Despite a higher prevalence of GDM in ART pregnancies, ART was not associated with an increased risk of GDM when adjusting for age, parity and BMI. The prognosis of GDM in ART and non-ART was similar except for C-section rates.

Recommendations on the pathological report of pituitary tumors. A consensus of experts of the Spanish Society of Endocrinology and Nutrition and the Spanish Society of Pathology.

Pituitary neuroendocrine tumors (PitNETs) constitute, together with other tumors of the sellar region, 15-25% of intracranial neoplasms. In 2017, the World Health Organization proposed a new classification of PitNETs. The main innovation with respect to the 2004 classification was the recommendation to include in the immunohistochemical evaluation of PitNETs the determination of the transcription factors of the 3 pituitary cell lineages: Pit-1, Tpit and SF-1. Additionally, other clinicopathological classifications with a predictive capacity of tumor behavior during follow-up were proposed. Given these changes, it is appropriate to adapt the knowledge generated during the last 15 years to the daily practice of the treatment and monitoring of PitNETs at the Centers of Excellence in Pituitary Pathology. This document includes the positioning of the Spanish Society of Endocrinology and Nutrition (SEEN) and the Spanish Society of Pathology (SEAP) on the classification and denomination of the PitNETs and the information that the pathologist should provide to the clinician to facilitate the treatment and monitoring of these tumors.

[Recommendations on the pathological report of pituitary tumors. A consensus of experts of the Spanish Society of Endocrinology and Nutrition and the Spanish Society of Pathology]. / Recomendaciones sobre el diagnóstico e informe anatomopatológico de los tumores neuroendocrinos hipofisarios. Consenso de expertos de la Sociedad Española de Endocrinologia y Nutrición y de la Sociedad Española de Anatomía Patológica.

Pituitary neuroendocrine tumors (PitNETs) constitute, together with other tumors of the sellar region, 15-25% of intracranial neoplasms. In 2017, the World Health Organization proposed a new classification of PitNETs. The main innovation with respect to the 2004 classification was the recommendation to include in the immunohistochemical evaluation of PitNETs the determination of the transcription factors of the 3 pituitary cell lineages: Pit-1, Tpit and SF-1. Additionally, other clinicopathological classifications with a predictive capacity of tumor behavior during follow-up were proposed. Given these changes, it is appropriate to adapt the knowledge generated during the last 15 years to the daily practice of the treatment and monitoring of PitNETs at the Centers of Excellence in Pituitary Pathology. This document includes the positioning of the Spanish Society of Endocrinology and Nutrition (SEEN) and the Spanish Society of Pathology (SEAP) on the classification and denomination of the PitNETs and the information that the pathologist should provide to the clinician to facilitate the treatment and monitoring of these tumors.

Recommendations on the pathological report of pituitary tumors. A consensus of experts of the Spanish Society of Endocrinology and Nutrition and the Spanish Society of Pathology. / Recomendaciones sobre el diagnóstico e informe anatomopatológico de los tumores neuroendocrinos hipofisarios. Consenso de expertos de la Sociedad Española de Endocrinologia y Nutrición y de la Sociedad Española de Anatomía Patológica.

Pituitary neuroendocrine tumors (PitNETs) constitute, together with other tumors of the sellar region, 15-25% of intracranial neoplasms. In 2017, the World Health Organization proposed a new classification of PitNETs. The main innovation with respect to the 2004 classification was the recommendation to include in the immunohistochemical evaluation of PitNETs the determination of the transcription factors of the 3 pituitary cell lineages: Pit-1, Tpit and SF-1. Additionally, other clinicopathological classifications with a predictive capacity of tumor behavior during follow-up were proposed. Given these changes, it is appropriate to adapt the knowledge generated during the last 15 years to the daily practice of the treatment and monitoring of PitNETs at the Centers of Excellence in Pituitary Pathology. This document includes the positioning of the Spanish Society of Endocrinology and Nutrition (SEEN) and the Spanish Society of Pathology (SEAP) on the classification and denomination of the PitNETs and the information that the pathologist should provide to the clinician to facilitate the treatment and monitoring of these tumors.

Criteria for diagnosis and postoperative control of acromegaly, and screening and management of its comorbidities: Expert consensus. / Criterios para el diagnóstico y el control poscirugía de la acromegalia, y el cribado y el manejo de sus comorbilidades: recomendaciones de expertos.

Acromegaly is a rare disease with many comorbidities that impair quality of life and limit survival. There are discrepancies in various clinical guidelines regarding diagnosis and postoperative control criteria, as well as screening and optimal management of comorbidities. This expert consensus was aimed at establishing specific recommendations for the Spanish healthcare system. The existing recommendations, the scientific evidence on which they are based, and the main controversies are reviewed. Unfortunately, the low prevalence and high clinical variability of acromegaly do not provide strong scientific evidences. To mitigate this disadvantage, a modified Delphi questionnaire, combining the best available scientific evidence with the collective judgment of experts, was used. The questionnaire, generated after a face-to-face debate, was completed by 17 Spanish endocrinologists expert in acromegaly. A high degree of consensus was reached (79.3%), as 65 of the total 82 statements raised were accepted. Some criteria for diagnosis and postoperative control were identified by this procedure. Regarding comorbidities, recommendations have been established or suggested for screening and management of oncological, cardiovascular, respiratory (sleep apnea), metabolic (dyslipidemia and diabetes), musculoskeletal, and hypopituitarism-related disorders. Consensus recommendations may facilitate and homogenize clinical care to patients with acromegaly in the Spanish health system.

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.

Laparoscopic surgery in patients with sporadic and multiple insulinomas associated with multiple endocrine neoplasia type 1.

There have recently been reports of a limited number of laparoscopic procedures in patients with clinically manifest hyperinsulinism. However, the precise role of laparoscopy remains unknown. Between January 1998 and September 2003, 11 consecutive patients (10 women and 1 man; mean age, 40 years; age range, 22-66 years) with sporadic insulinoma and two female patients (25 and 40 years old) with multiple insulinomas associated with multiple endocrine neoplasia type 1 (MEN-1) were operated on using the laparoscopic approach. Endoscopic ultrasonography was used to localize the tumor preoperatively in 90% of patients with sporadic insulinoma. In patients with MEN-1, computed tomography and octreoscan-(111)In demonstrated multiple tumors. Laparoscopic ultrasonography (LapUS) was performed in all patients for operative decision-making. Of 11 patients with sporadic insulinoma, laparoscopic enucleation (LapEn) was planned in 8 patients, but in 1 patient, the use of LapUS missed the tumor and the patient was converted to open surgery. Mean operating time after LapEn (seven patients) was 180 minutes, and the mean blood loss was 200 ml. The mean hospital stay was 5 days. In three of the 11 patients, laparoscopic spleen-preserving distal pancreatectomy (LapSPDP) was performed; the mean operative time was 240 minutes, and the mean blood loss was 360 ml. Postoperative complications occurred in three of seven patients after LapEn (three pancreatic fistulas managed conservatively, and one case of bleeding requiring reoperation). LapSPDP was performed in both patients with MEN-1; in one patient with splenic vessel preservation (SVP), the operating time was 210 minutes and blood loss was 650 ml, with a hospital stay of 6 days. In another patient without SVP, the operating time was 150 minutes and blood loss was 300 ml. The latter patient developed a 4-cm splenic infarct managed conservatively, and the hospital stay was 14 days. LapEn and LapSPDP are feasible and safe and achieved cure in patients with sporadic insulinoma and multiple insulinomas associated with MEN-1. However, the risk of pancreatic leakage after LapEn remains high, and LapSPDP without SVP may be associated with splenic infarct.

Cardiovascular risk factors in acromegaly before and after normalization of serum IGF-I levels with the GH antagonist pegvisomant.

Acromegaly is associated with premature cardiovascular mortality. GH replacement therapy decreases inflammatory markers of cardiovascular risk, but little is known about these markers in patients with acromegaly. The GH receptor antagonist, pegvisomant, reduces IGF-I levels in 98% of patients treated. We investigated the effects of GH receptor blockade on inflammatory and other cardiovascular risk markers in active acromegaly. Forty-eight patients with acromegaly and 47 age- and body mass index-matched controls were included. The study consisted of 3 parts: a cross-sectional study, a prospective randomized 12-wk placebo-controlled study, and a longitudinal open-label study of up to 18 months of pegvisomant treatment. After baseline evaluation, patients with acromegaly were randomized to placebo (n = 14), 10 mg (n = 12), 15 mg (n = 10), or 20 mg (n = 12) daily pegvisomant for 12 wk. Subsequently, all patients received at least 10 mg pegvisomant daily for up to 18 months, with dose adjustments to achieve a normal IGF-I level. Anthropometry, GH, IGF-I, and pegvisomant levels were measured monthly. C-reactive protein (CRP), IL-6, homocysteine, lipoprotein(a), glucose, insulin, triglycerides, total cholesterol, and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol were determined at baseline, 4 and 12 wk in the placebo-controlled study and at 3-month intervals (during which IGF-I levels were normal) in the longitudinal study. In the cross-sectional study, patients had lower CRP than did controls [median, 0.3 (range, 0.2-0.8) vs. 2.0 (0.6-3.7) mg/liter; P < 0.0001] and had higher insulin [78.6 (55.8-130.2) vs. 54.5 (36.6-77.5) pM, P = 0.0051]. IL-6, homocysteine, triglycerides, lipoprotein(a), LDL cholesterol and HDL cholesterol were not different between groups. In the placebo-controlled study, CRP increased in patients treated with 20 mg pegvisomant, compared with placebo (mean +/- SEM, 13.7 +/- 3.6 vs. 0.5 +/- 3.3 mg/liter; P = 0.010). There were no significant differences in IL-6, homocysteine, glucose, insulin, triglyceride, total cholesterol, LDL cholesterol and HDL cholesterol levels. In the longitudinal open-label study (median duration, 15.6 months), CRP increased by 2.0 +/- 0.5 mg/liter (P = 0.0002). Total cholesterol and triglycerides increased (0.22 +/- 0.11 mM, P = 0.050; and 0.25 +/- 0.09 mM, P = 0.007, respectively), whereas lipoprotein(a) decreased (-70 +/- 33 mg/liter, P = 0.039). Glucose, insulin, homocysteine, HDL cholesterol, and IL-6 did not change. We conclude that patients with active acromegaly have lower CRP and higher insulin levels than healthy controls. Administration of pegvisomant increases CRP levels. We propose that GH secretory status is an important determinant of serum CRP levels, although additional studies are needed to determine the mechanism and significance of this finding.

Measurement of free testosterone in normal women and women with androgen deficiency: comparison of methods.

Androgen deficiency in women is increasingly recognized as a new clinical syndrome and has raised our awareness of the importance of accurate and well-validated measurements of serum free testosterone (T) concentrations in women. Therefore, we compared serum free T levels measured by equilibrium dialysis to those measured by a direct RIA (analog method) and to those calculated from the law of mass action (requires the measurement of total T and SHBG). We also calculated the free androgen index, 100 x T/SHBG, as a simple index known to correlate with free T. Subjects were 147 women with variable androgen and estrogen statuses. All were studied three times in 1 month and included women 1) with regular menses (estrogen positive, T positive), 2) more than 50 yr old and not receiving estrogen (estrogen negative, T positive), 3) receiving estrogen (estrogen positive, T negative), and 4) with severe androgen deficiency secondary to hypopituitarism (estrogen negative, T negative). Calculated values for free T using the laws of mass action correlated well with those obtained from equilibrium dialysis (r = 0.99; P < 0.0001). However, the agreement depended strongly on the specific assays used for total T and SHBG. In contrast, the direct RIA method had unacceptably high systematic bias and random variability and did not correlate as well with equilibrium dialysis values (r = 0.81; P < 0.0001). In addition, the lower limit of detection was higher for the direct RIA than for equilibrium dialysis or calculated free T. Free androgen index correlates well with free T by equilibrium dialysis (r = 0.93; P < 0.0001), but is a unitless number without reference to the physical reality of free T. We conclude that the mass action equation and equilibrium dialysis are the preferred methods for use in diagnosing androgen deficiency in women.

Benign and malignant nodular thyroid disease in acromegaly. Is a routine thyroid ultrasound evaluation advisable?

Data on the prevalence of benign and malignant nodular thyroid disease in patients with acromegaly is a matter of debate. In the last decade an increasing incidence of thyroid cancer has been reported. The aim of this study was to evaluate the prevalence of goiter, thyroid nodules and thyroid cancer in a large series of patients with acromegaly with a cross-sectional study with a control group. Six Spanish university hospitals participated. One hundred and twenty three patients (50% men; mean age 59±13 years; disease duration 6.7±7.2 years) and 50 controls (51% males, mean age 58±15 years) were studied. All participants underwent thyroid ultrasound and fine needle aspiration. Cytological analysis was performed in suspicious nodules between 0.5 and 1.0 cm and in all nodules greater than 1.0 cm. Goiter was more frequently found in patients than in controls (24.9 vs. 8.3%, respectively; p<0.001). Nodular thyroid disease as well as nodules greater than 1 cm were also more prevalent in acromegalic patients (64.6%, vs. 28.6%, p<0.05 and 53.3 vs. 28.6%, respectively; p<0.05), and all underwent fine needle aspiration. Suspicious cytology was detected in 4 patients and in none of the controls. After thyroidectomy, papillary thyroid carcinoma was confirmed in two cases (3.3% of patients with thyroid nodules), representing 1.6% of the entire group of patients with acromegaly (2.4% including a case with previously diagnosed papillary thyroid carcinoma). These data indicated that thyroid nodular disease and cancer are increased in acromegaly, thus justifying its routine ultrasound screening.

[Epidemiology of acromegaly in Spain]. / Epidemiología de la acromegalia en España.

Epidemiology of acromegaly in Spain does not differ from that reported in other published series. Prevalence rate is approximately 60 cases per million, peak incidence occurs in middle age, more women are affected (61%), and there is a substantial delay between occurrence of the first symptoms and diagnosis. Studies REA (Spanish Acromegaly Registry) and OASIS analyzed the epidemiology, clinical characteristics, and management of the disease in Spain. Surgery, performed in more than 80% of patients, has been (and continues to be) the main treatment for the past four decades. In the past decade, however, more patients have received somatostatin analogs (SSAs) as first-line treatment. Use of radiation therapy has significantly decreased in recent decades. Somatostatin analogs (SSAs) are the most commonly used drugs, administered to 85% of patients; however, only 12%-15% continue on drug treatment alone. The surgical remission rate was 38.4% in the last decade, with a significant improvement over decades. Preoperative treatment with SSAs has no influence on surgical cure rates. Second-line therapies used after surgical failure in the past decade included SSAs in 49% of patients, repeat surgery in 27%, radiotherapy in 11%, pegvisomant in 15%, and dopamine agonists in 5%. Mean cost of acromegaly treatment was 9.668€ (data estimated in 2009 and adjusted in 2010), of which 71% was due to the cost of SSAs. Patients treated with pegvisomant have a more aggressive form of the disease and higher comorbidity rates.

Criterios para el diagnóstico y el control poscirugía de la acromegalia, y el cribado y el manejo de sus comorbilidades: recomendaciones de expertos / Criteria for diagnosis and postoperative control of acromegaly, and screening and management of its comorbidities: Expert consensus

La acromegalia es una enfermedad rara, con abundantes comorbilidades que deterioran la calidad de vida y limitan la supervivencia. Existen discrepancias en diversas guías clínicas respecto al diagnóstico y los criterios de control poscirugía, así como para el cribado y el manejo óptimo de las comorbilidades. El objetivo de este consenso de expertos ha sido establecer recomendaciones específicas para nuestro ámbito asistencial español. Hemos revisado las recomendaciones existentes, la evidencia científica que las sustentan y las principales controversias. Desafortunadamente, la baja prevalencia y la elevada variabilidad clínica de la acromegalia no permiten disponer de evidencias científicas sólidas. Para atenuar este inconveniente hemos utilizado un cuestionario Delphi modificado, que combina la mejor evidencia científica disponible con el juicio colectivo de expertos. Tras un debate presencial se generó el cuestionario que fue respondido por un grupo de 17 endocrinólogos españoles expertos en acromegalia. Se consiguió un alto grado de consenso (79,3%), aceptando 65 de un total de 82 aseveraciones planteadas. De esta manera, se han perfilado algunos criterios diagnósticos y de control poscirugía. Respecto a las comorbilidades, se han establecido o precisado recomendaciones para el cribado y el manejo de las enfermedades oncológica, cardiovascular, respiratoria (apnea del sueño), metabólica (dislipidemia y diabetes), osteoarticular e hipopituitarismo. Las recomendaciones consensuadas pueden facilitar y homogeneizar la asistencia clínica a los pacientes con acromegalia de nuestro sistema sanitario español

Acromegaly is a rare disease with many comorbidities that impair quality of life and limit survival. There are discrepancies in various clinical guidelines regarding diagnosis and postoperative control criteria, as well as screening and optimal management of comorbidities. This expert consensus was aimed at establishing specific recommendations for the Spanish healthcare system. The existing recommendations, the scientific evidence on which they are based, and the main controversies are reviewed. Unfortunately, the low prevalence and high clinical variability of acromegaly do not provide strong scientific evidences. To mitigate this disadvantage, a modified Delphi questionnaire, combining the best available scientific evidence with the collective judgment of experts, was used. The questionnaire, generated after a face-to-face debate, was completed by 17 Spanish endocrinologists expert in acromegaly. A high degree of consensus was reached (79.3%), as 65 of the total 82 statements raised were accepted. Some criteria for diagnosis and postoperative control were identified by this procedure. Regarding comorbidities, recommendations have been established or suggested for screening and management of oncological, cardiovascular, respiratory (sleep apnea), metabolic (dyslipidemia and diabetes), musculoskeletal, and hypopituitarism-related disorders. Consensus recommendations may facilitate and homogenize clinical care to patients with acromegaly in the Spanish health system