Cholecalciferol Use Is Associated With a Decreased Risk of Incident Morphometric Vertebral Fractures in Acromegaly.

CONTEXT: Skeletal fragility is observed in 30% to 60% of acromegaly patients, representing an emerging complication of the disease that increases disability. Despite several studies having investigated the clinical and hormonal prognostic factors for the occurrence of vertebral fractures (VFs) in acromegaly, very few data are available on their prevention/treatment including the effect of vitamin D (VD) supplementation, which has been reported to have a fracture-protective effect in several studies in patients with osteoporosis. OBJECTIVE: We aimed to investigate the role of cholecalciferol (D3) supplementation in the prevention of incident VFs (i-VFs) in acromegaly. METHODS: A longitudinal, retrospective and multicenter study was performed on 61 acromegaly patients treated and untreated with D3 supplementation. RESULTS: Twenty-six patients were treated with D3 supplementation according to clinical guidelines. The median D3 weekly dosage was 8500 IU (interquartile range [IQR]: 3900). The median duration of D3 supplementation was 94 months (IQR: 38). At last follow-up, i-VFs were diagnosed in 14 patients (23%). I-VFs were less prevalent in patients on D3 supplementation (14.3% of cases) compared to patients not treated with D3 (85.7%; P = .02). The final level of serum V25OH-D was significantly lower in patients who developed i-VFs (28.6 ng/mL, IQR: 4.1) compared to patients who did not develop i-VFs (34.2 ng/mL, IQR: 9.6; P = .05). The logistic regression confirmed the protective role of D3 supplementation on the occurrence of i-VFs (odds ratio: 0.16; 95% CI, 0.03-0.79; P = .01). CONCLUSION: It is likely that D3 supplementation could lead to a reduction in i-VFs in acromegaly.

A pharmacophore screening approach of homeopathic phenols for a renovated design of fragment-optimized Bauhiniastatin-1 as a drug against acromegaly.

OBJECTIVE: Acromegaly is a fatal and chronic disease that is caused by the abnormal secretion of growth hormone (GH) by the pituitary adenoma or pituitary tumor, resulting in an increased circulated concentration of insulin-like growth factors 1 (IGF-1), where in most of the cases it is secreted by a pituitary tumor. Higher levels of GH cause an increase in IGF-1 in the liver leading to multiple conditions such as cardiovascular diseases, glucose imbalance, cancer, and sleep apnea. Medical treatments such as surgery and radiotherapy can be used as the first choice of patients; however, specified human growth hormone control should be an essential treatment strategy due to an incidence rate of 0.2-1.1 yearly. Therefore, the main focus of this study is to develop a novel drug for treating acromegaly by exploiting medicinal plants that have been screened using phenol as a pharmacophore model to identify target therapeutic medicinal plant phenols. MATERIALS AND METHODS: The screening identified thirty-four pharmacophore matches of medicinal plant phenols. These were selected as suitable ligands and were docked against the growth hormone receptor to calculate their binding affinity. The candidate with the highest screened score was fragment-optimized and subjected to absorption, distribution, metabolism, and excretion (ADME) analysis, in-depth toxicity predictions, interpretation of Lipinski's rule, and molecular dynamic simulations to check the behavior of the growth hormone with the fragment-optimized candidate. RESULTS: The highest docking energy was calculated as -6.5 K/mol for Bauhiniastatin-1. Enhancing the performance of Bauhiniastatin-1 against the growth hormone receptor with fragment optimization portrayed that human growth hormone inhibition can be executed in a more efficient and better way. Fragment-optimized Bauhiniastatin-1 (FOB) was predicted with high gastrointestinal absorption, a water solubility of -2.61 as soluble, and synthetic accessibility of 4.50, achieving Lipinski's rule of 5, with low organ toxicity prediction and interpreting a positive behavior against the targeted protein. The discovery of a de novo drug candidate was confirmed by the docking of fragment-optimized Bauhiniastatin-1 (FOB), which had an energy of -4,070 Kcal/mol. CONCLUSIONS: Although successful and completely harmless, present healthcare treatment does not always eradicate the disease in some individuals. Therefore, novel formulas or combinations of currently marketed medications and emergent phytochemicals will provide new possibilities for these instances.

Looking at the spine in controlled Acromegaly.

Skeletal fragility with high risk of vertebral fractures (VFs) is an emerging complication of growth hormone (GH) hypersecretion. VFs often coexist with spine arthropathy and both clinical conditions negatively impact on quality of life of acromegalic subjects. Management of spine osteopathy and arthropathy in acromegaly could be challenging since both complications can persist or even progress after biochemical control of disease. This article analyzes the latest evidence about possible pathophysiological links between VFs and spine arthropathy in active and controlled acromegaly, as well as the diagnostic and therapeutic aspects concerning the holistic management of acromegalic osteo-arthropathy.

The effect of mindfulness therapy in acromegaly, a pilot study.

BACKGROUND: Patients with acromegaly have often several comorbidities, including decreased quality of life, mood alterations and chronic pain. Mindfulness is effective at improving mood, quality of life and pain management; however, there is no data available on its effect in patients with acromegaly. OBJECTIVE: We aimed at evaluating changes in quality of life, mood, pain, sleep, self-compassion, life satisfaction, blood pressure and heart rate after a mindfulness program. DESIGN AND PATIENTS: This was a randomized, multicentre, international clinical trial (Barcelona-BCN and Bergamo-BG) of 60 patients, 30 per centre. MEASUREMENTS: The intervention group participated in an 8-week face-to-face group program; the control group followed normal clinical routine. In BG, patients performed a classic Mindfulness Based Stress Reduction program; in BCN they performed an adapted program including elements of mindfulness and compassion with a greater focus on daily life. RESULTS: In the BCN intervention group there was an increase in night-time hours in bed (p = 0.05) after the program. In both centres there was a trend to a reduction of the time to start sleeping (p = 0.06 BCN, p = 0.07 BG). In BCN, the intervention group reduced the pain score compared to the control group (p = .02), and an improvement in self-compassion was found (p = .04). In both centres, heart rate decreased significantly in the intervention group during a single 2-hour session. This was evidenced at the first and the last program session (BCN p = .013 and p = .009; BG < 0.001 and p = .04). A training effect was found in BG, where heart rate fell more in the last session than in the first (p = 002). CONCLUSIONS: We have demonstrated for the first time the value of a mindfulness program in patients with acromegaly, analysing possible effects and advantages, and clarifying the usefulness of a specific protocol for the disease.

Characterization of vitamin D metabolism in active acromegaly in the setting of bolus (150,000 IU) cholecalciferol treatment.

PURPOSE: To reveal distinctive features of vitamin D metabolism in patients with active acromegaly compared to healthy individuals, particularly in the setting of cholecalciferol treatment. METHODS: The study group included 34 adults with active acromegaly, and the control group included 30 apparently healthy adults with similar age, sex, and BMI. All participants received a single dose (150,000 IU) of cholecalciferol aqueous solution orally. Laboratory assessments including serum vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3 and 24,25(OH)2D3), free 25(OH)D, vitamin D-binding protein (DBP) and parathyroid hormone (PTH) as well as serum and urine biochemical parameters were performed before the intake and on Days 1, 3, and 7 after the administration. All data were analyzed with nonparametric statistics. RESULTS: Patients with acromegaly had tendency to lower baseline 25(OH)D3 levels (p = 0.05) and lower 25(OH)D3 levels (p < 0.05) during the follow-up. They were also characterized by PTH suppression (lower baseline PTH levels and lower prevalence of secondary hyperparathyroidism), altered production of main vitamin D metabolites (higher 1,25(OH)2D3 and lower 24,25(OH)2D3 levels with corresponding lower 25(ОН)D3/1,25(ОН)2D3 and higher 25(ОН)D3/24,25(ОН)2D3 ratios) as well as concordant biochemical features (higher levels of serum phosphorus and albumin-adjusted calcium levels) throughout the study (p < 0.05). The acromegaly group showed an increase in DBP levels after cholecalciferol intake as opposed to the control group (p < 0.05) and had lower increase in free 25(OH)D levels (p < 0.05). Δ25(OH)D3 was similar between the groups (p > 0.05), showed a negative correlation with the disease activity markers-both IGF-1 levels (r = -0.44, p < 0.05) and fasting GH levels (r = -0.56, p < 0.05)-and lacked correlation with BMI in the acromegaly group (p > 0.05). CONCLUSION: Patients with active acromegaly have dysregulated vitamin D metabolism characterized by higher 1,25(ОН)2D3, lower 24,25(ОН)2D3 and altered DBP production. The response to vitamin D supplementation in acromegaly patients might be influenced by hormonal excess. Obtained results require reproducibility check and further study to develop specific clinical recommendations. TRIAL REGISTRATION: NCT04844164 (release date: April 9, 2021; retrospectively registered).

Illness-related burden, personal resources and need for support in patients with acromegaly: Results of a focus group analysis.

OBJECTIVE: It was the aim of this study to evaluate illness-related burdens and support needs of patients with acromegaly to identify hitherto unadressed research questions and to open up avenues for improvements in patient care. This was done by using the focus group approach as a qualitative research method. DESIGN: Seven patients with acromegaly took part in a focus group moderated by an external medical communication specialist. The discourse focused on topics such as impact of the illness on everyday life, support needs and personal resources. The discussion was recorded and transcribed and analyzed by qualitative content analysis. RESULTS: Participants reported a huge impact of acromegaly on daily life, ranging from time expenditure for managing their illness, to bodily and mental sequelae and strain caused by physical disfigurement. Patients' coping strategies included family support, physical activities and humor. The participants wished for a sound patient-doctor relationship, more interdisciplinary and holistic treatment, medical rehabilitation services with special knowledge on acromegaly-related morbidity, a stable contact person in the medical process and reliable information material for themselves and their relatives. CONCLUSIONS: The results provide multi-facetted impressions of the overwhelming impact of acromegaly and unmet support needs of the afflicted patients. Further quantitative research is necessary to examine the generalisibility of the present results in order to implement tailored support measures. We suggest to develop standardized questionnaires to explore the prevalence and severity of the addressed problems in a large patient sample and to establish screening instruments to monitor disease burden in clinical practice.

Prevalence of vertebral fractures and serum sclerostin levels in acromegaly.

OBJECTIVE: An increased prevalence of vertebral fractures (VFs) has been reported in previous studies. The aim of this study was to evaluate the association between bone mineral density (BMD), bone turnover markers, serum sclerostin levels, and vertebral fractures (VFs) in acromegaly patients. We also evaluated the effects of gonadal status, disease activity, treatment modality, age, sex, and body mass index (BMI) on skeletal endpoints. DESIGN: Case-control study. PATIENTS AND MEASUREMENTS: Seventy acromegaly patients (M/F:36/34, mean age 45.5 ± 11.9 years) and 70 controls (M/F:31/39; mean age 45.66 ± 11.9 years) were included. VFs, BMD, calcium metabolism, markers of bone turnover, and sclerostin levels were evaluated. BMD was measured by dual-energy X-ray absorptiometry (Hologic QDR 4500). Conventional lateral radiography of the spine was performed and the Genant method was used for the assessment of fractures of T4-L5 vertebrae. RESULTS: The prevalence of vertebral fractures was higher in acromegalic patients as compared with the control group (72.9 vs. 20%; p < 0.001). Serum phosphate (P) levels (3.46 ± 0.59 mg/dl vs. 3.11 ± 0.44 mg/dl; p < 0.001) and b-cross laps (CTx) levels (0.47 µg/l, range 0.04-2.38 vs. 0.28 µg/l, range 0.11-0.80; p < 0.001) were significantly higher in acromegaly patients than control subjects. Serum sclerostin levels were similar between either acromegaly patients and control subjects or acromegaly patients with VF and without VF. In the means of treatment modality, VFs were more frequent in patients treated with adjuvant gamma knife radiosurgery (GKS) (p = 0.07). In the binary logistic regression analysis, the age of the acromegaly patients, the presence of hypogonadism, and GKS treatment were the factors significantly correlated with the occurrence of spinal fractures. CONCLUSIONS: The prevalence of VFs in patients with acromegaly is higher than in control subjects. Since advanced age, the presence of hypogonadism and GKS treatment were the factors predicting VFs in acromegaly; radiological evaluations should be considered as an emerging tool especially in those patients. Although markers of bone turnover elevated in acromegaly, they were not useful for the prediction of fractures. Serum sclerostin levels showed no discrepancy between the two groups and further studies are required for assessment of sclerostin role in this form of secondary osteoporosis.

Effects of anodyne treatment on local blood flow and cutaneous sensation of the foot in a patient with peripheral neuropathy secondary to acromegaly.

Acromegaly is an excessive amount of serum growth hormone, which may present with sensorimotor polyneuropathy, affecting sensation and/or blood flow in the limbs. Symptoms include numbness, tingling or pain with impaired sensation including kinesthesia and proprioception. We report here of a 48-year-old male with a defined diagnosis of acromegaly and surgical excision of a pituitary adenoma 20 years ago. Recently he reports feet stepping on, and not feeling, objects under foot and balance problems starting 10 years ago. This study used a single-subject A-B-A design to show that behavioral changes are evident only in the presence of an intervention. Intervention consisted of Monochromatic Infrared Light Energy (MIRE), delivered by the Anodyne Therapy System (ATS). The DRT-4 laser Doppler measured red blood cell flux (flow), concentration and velocity. Levels of significance utilized the two standard deviation band method. Peripheral sensation of eight sites on each foot assessed using Semmes-Weinstein monofilaments (SWM) revealed a lack of sensation in the feet. A treatment effect as exhibited by blood flow velocity and red blood cell concentration was detected after the third week of treatment indicating peripheral dilation of the microvasculature. MIRE was an effective intervention for the treatment of acromegaly - induced polyneuropathy in this patient.

Pharmacological Acromegaly Treatment: Cost-Utility and Value of Information Analysis.

OBJECTIVES: To conduct a cost-utility analysis comparing drug strategies involving octreotide, lanreotide, pasireotide, and pegvisomant for the treatment of patients with acromegaly who have failed surgery, from a Brazilian public payer perspective. METHODS: A probabilistic cohort Markov model was developed. One-year cycles were employed. The patients started at 45 years of age and were followed lifelong. Costs, efficacy, and quality of life parameters were retrieved from the literature. A discount rate (5%) was applied to both costs and efficacy. The results were reported as costs per quality-adjusted life year (QALY), and incremental cost-effectiveness ratios (ICERs) were calculated when applicable. Scenario analyses considered alternative dosages, discount rate, tax exemption, and continued use of treatment despite lack of response. Value of information (VOI) analysis was conducted to explore uncertainty and to estimate the costs to be spent in future research. RESULTS: Only lanreotide showed an ICER reasonable for having its use considered in clinical practice (R$ 112,138/US$ 28,389 per QALY compared to no treatment). Scenario analyses corroborated the base-case result. VOI analysis showed that much uncertainty surrounds the parameters, and future clinical research should cost less than R$ 43,230,000/US$ 10,944,304 per year. VOI also showed that almost all uncertainty that precludes an optimal strategy choice involves quality of life. CONCLUSIONS: With current information, the only strategy that can be considered cost-effective in Brazil is lanreotide treatment. No second-line treatment is recommended. Significant uncertainty of parameters impairs optimal decision-making, and this conclusion can be generalized to other countries. Future research should focus on acquiring utility data.

The X-linked acrogigantism-associated gene gpr101 is a regulator of early embryonic development and growth in zebrafish.

We recently described X-linked acrogigantism (X-LAG), a condition of early childhood-onset pituitary gigantism associated with microduplications of the GPR101 receptor. The expression of GPR101 in hyperplastic pituitary regions and tumors in X-LAG patients, and GPR101's normally transient pituitary expression during fetal development, suggest a role in the regulation of growth. Nevertheless, little is still known about GPR101's physiological functions, especially during development. By using zebrafish models, we investigated the role of gpr101 during embryonic development and somatic growth. Transient ectopic gpr101 expression perturbed the embryonic body plan but did not affect growth. Loss of gpr101 led to a significant reduction in body size that was even more pronounced in the absence of maternal transcripts, as well as subfertility. These changes were accompanied by gastrulation and hypothalamic defects. In conclusion, both gpr101 loss- and gain-of-function affect, in different ways, fertility, embryonic patterning, growth and brain development.

Cost-effectiveness analysis of second-line pharmacological treatment of acromegaly in Spain.

Objective: To estimate the cost-effectiveness of second-line pharmacological treatments in patients with acromegaly resistant to first-generation somatostatin analogues (FG SSA) from the Spanish National Health System (NHS) perspective.Methods: A Markov model was developed to analyze the cost-effectiveness of pegvisomant and pasireotide in FG SSA-resistant acromegaly, simulating a cohort of patients from the treatment beginning to death. Treatment with pegvisomant or pasireotide was compared to FG SSA retreatment. Efficacy data were obtained from clinical trials and utilities from the literature. Direct health costs were obtained from Spanish sources (€2018).Results: The Incremental Cost Effectiveness Ratio (ICER) of pegvisomant vs. FG SSA was €85,869/Quality-adjusted life years (QALY). The ICER of pasireotide vs. FG SSA was €551,405/QALY. The ICER was mainly driven by the incremental efficacy (4.41 QALY for pegvisomant vs. FG SSA and 0.71 QALY for pasireotide vs. FG SSA), with a slightly lower increase in costs with pegvisomant (€378,597 vs. FG SSA) than with pasireotide (€393,151 vs. FG SSA).Conclusion: The ICER of pasireotide compared to FG SSA was six times higher than the ICER of pegvisomant vs. FG SSA. Pegvisomant is a more cost-effective alternative for the treatment of acromegaly in FG SSA-resistant patients in the Spanish NHS.

Natural History of Acromegaly: Incidences, Re-operations, Cancers, and Mortality Rates in a National Cohort.

BACKGROUND: Acromegaly is so rare that its natural history, including incidence, risk of cancers, and mortality rates, remains elusive. This natural study utilized a nationwide database to provide a better understanding of acromegaly's disease course. METHODS: A cohort of 1,195 acromegaly patients were identified and followed-up from 1997 to 2013. Incidence, operation, and re-operation rates were calculated. Excessive mortality and cancer risk related to acromegaly were estimated by standardized mortality ratio (SMR) and standardized incidence ratio (SIR). RESULTS: The incidence was 2.78 per million-person-years, with little gender predominance (female vs. male, 49.5 vs. 50.5%, respectively). There was female predominance only among 50 and 60 year-olds (incidence rate ratio: 1.37 and 1.43, p < 0.001 and p = 0.002). Among them, 673 (56.3%) had hypophysectomy surgery, and the young-onset (<40 years) patients had more re-operations (15.5%, p = 0.01). The overall mortality rate was 22.3 per 1,000 person-years, with a median survival of 4.67 years (with no gender differences, p = 0.38). The overall SMR of acromegaly patients was 1.41, and the onset-age-specific SMRs of the early- and middle-onset patients were higher than for those with late-onset. There were 87 newly diagnosed cancers in the cohort, with an incidence rate of 10.6 per 1,000 person-years (median 5.4 years). The overall SIR of cancers was 1.91, and there were no differences among gender, onset-age, and disease duration (all SIR >1, approximately 2). CONCLUSION: Acromegaly is associated with an excessive risk of mortality and two-fold higher risk of cancers. Patients with acromegaly should be managed appropriately after the diagnosis.

Acromégalie : améliorer la prise en charge: Acromegaly: improving care.

Acromegaly is characterized by increased release of growth hormone (GH) and, consequently, Insulin-Like Growth Factor I (IGF-I), most often by a pituitary adenoma. Prolonged exposure to excess hormone leads to progressive somatic disfigurement and a wide range of systemic manifestations that are associated with increased mortality. Transsphenoidal adenomectomy is the treatment of choice of GH-secreting pituitary tumors but surgical cure is not achieved in around 50% of patients, then adjuvant treatment is necessary. Mortality in acromegaly is normalized with biochemical control and has decreased in the last decade with the increased use of adjuvant therapy. Both GH and IGF-I are currently biomarkers for assessing disease activity in patients with acromegaly. However, discordance between GH and IGF-I results is encountered in a quarter of treated patients. The impacts of such a discrepancy over mortality and morbidity and the risk of biochemical and/or clinical recurrence are unclear. Moreover, despite a good biochemical control, some symptoms persist, leading to a decreased quality of life. Back pain due to vertebral fractures seem to be frequent in these patients and underdiagnosed. In patients with acromegaly, bone mineral density is not a reliable predictor of fracture risk. A more accurate evaluation of bone microstructural alterations associated with GH hypersecretion and vertebral fractures may be provided by new radiological devices analyzing alteration of trabecular microarchitecture, leading to a better prevention. © 2019 Published by Elsevier Masson SAS. All rights reserved. Cet article fait partie du numéro supplément Les Must de l'Endocrinologie 2019 réalisé avec le soutien institutionnel de Ipsen-Pharma.

Surgical-pharmacological interactions in the treatment of acromegaly.

INTRODUCTION: Acromegaly requires a multimodal treatment approach that includes surgery by an expert pituitary neurosurgeon, pharmacological treatment with one or more of the available drugs and radiation therapy. These treatment alternatives are not mutually exclusive but rather complement each other when properly indicated in the individual patient. In this review, we summarize and analyze the available data concerning the choice of the surgical approach (microscopy vs. endoscopy) and the interactions between medical treatment with somatostatin analogs and pituitary surgery. AREAS COVERED: Technical aspects, complications and outcome of transsphenoidal surgery (TSS); Advantages and disadvantages of the microscopic and endoscopic approaches; Safety and efficacy of somatostatin analogs (SSA); Primary pharmacological therapy versus primary TSS; Benefits of the preoperative treatment with SSA; and the effect of surgical tumor debulking in the therapeutic response to SSA. EXPERT COMMENTARY: Continuing efforts at improving surgical techniques and at generating more efficacious pharmacological therapies for acromegaly are likely to improve the outcome of these patients. However, an integral approach of the patient aimed not only at achieving biochemical criteria of cure but also at treating the individual comorbidities is mandatory to improve the quality of life of these patients and to reduce their mortality rate.

AcroVoice: eliciting the patients' perspective on acromegaly disease activity.

PURPOSE: To determine how patients define acromegaly disease activity and treatment success and to quantify from the patients' perspective the relative importance of each disease parameter included in the ACRODAT®. METHODS: One hundred acromegaly patients on medical therapy (mean age = 47.1 years; SD = 11.96) completed an online preference study evaluating hypothetical patient profiles described in terms of insulin-like growth factor-I (IGF-I) levels, tumor size, comorbid conditions, signs/symptoms, and quality of life (QoL). Participants first completed a single-profile task experiment by rating 20 single patient profiles as exhibiting stable, mild, or significant disease activity based on treatment success. Next, participants completed a double-profile discrete choice experiment (DCE) by selecting the patient that was doing "better" from 15 profile pairs. Results were analyzed using logistic and conditional logistic models. RESULTS: When choosing between stable vs. mild or significant disease activity, signs/symptoms, tumor size, and IGF-I levels were weighted equally; IGF-I and signs and symptoms were valued equally when selecting mild vs. significant disease activity. The DCE showed that, statistically, all disease parameters, except comorbid conditions, predicted health status equally. Tumor size and IGF-I levels each accounted for 23% of the decision-making process; QoL, signs/symptoms, and comorbid conditions accounted for 21%, 19%, and 14%, respectively. CONCLUSION: All five ACRODAT® parameters had some influence on disease activity from the patients' perspective. To account for patients' preferences and optimize treatment and outcomes, a holistic disease management approach should be employed.

Guía de recomendaciones para el diagnóstico clínico, bioquímico y por imágenes de la acromegalia. Federación Argentina de Sociedades de Endocrinología (FASEN) - 2017 / Guidelines for the clinical, biochemical and imaging diagnosis of acromegaly. Federación Argentina de Sociedades de Endocrinología (FASEN) - 2017

RESUMEN Objetivo El objetivo de esta guía es formular pautas para el diagnóstico de acromegalia adecuadas a los parámetros internacionales y a los recursos disponibles en Argentina. Participantes El grupo de trabajo propuesto por la Federación Argentina de Sociedades de Endocrinología (FASEN) incluyó un equipo multidisciplinario compuesto por 5 médicos endocrinólogos (4 especialistas y una profesional joven), un neurocirujano y una bioquímica, expertos en el tema. Evidencia Esta guía basada en la evidencia se desarrolló utilizando la metodología AGREE para describir tanto las recomendaciones como la calidad de las pruebas. Los borradores de esta guía fueron revisados por un grupo multidisciplinario de especialistas reconocidos en acromegalia. Conclusiones Utilizando un enfoque basado en la evidencia, esta guía aborda la evaluación diagnóstica de la acromegalia en Argentina.

ABSTRACT Objective The aim is to formulate guidelines for the clinical, biochemical and imaging diagnosis of acromegaly in accordance with international criteria and resources available in Argentina. Participants The task force selected by FASEN included a multidisciplinary team of 5 endocrinologists (4 senior and 1 junior), a neurosurgeon and a biochemist, experts in the field. Evidence This evidence-based guidelines were developed using the AGREE methodology to describe both the recommendations and the quality of evidence. The draft of these guidelines was reviewed by endocrinologists, biochemists and neurosurgeons experts in the field. Conclusions Using an approach based on evidence, these guidelines address the diagnosis of acromegaly in Argentina.

Development of ACRODAT®, a new software medical device to assess disease activity in patients with acromegaly.

PURPOSE: Despite availability of multimodal treatment options for acromegaly, achievement of long-term disease control is suboptimal in a significant number of patients. Furthermore, disease control as defined by biochemical normalization may not always show concordance with disease-related symptoms or patient's perceived quality of life. We developed and validated a tool to measure disease activity in acromegaly to support decision-making in clinical practice. METHODS: An international expert panel (n = 10) convened to define the most critical indicators of disease activity. Patient scenarios were constructed based on these chosen parameters. Subsequently, a panel of 21 renowned endocrinologists at pituitary centers (Europe and Canada) categorized each scenario as stable, mild, or significant disease activity in an online validation study. RESULTS: From expert opinion, five parameters emerged as the best overall indicators to evaluate disease activity: insulin-like growth factor I (IGF-I) level, tumor status, presence of comorbidities (cardiovascular disease, diabetes, sleep apnea), symptoms, and health-related quality of life. In the validation study, IGF-I and tumor status became the predominant parameters selected for classification of patients with moderate or severe disease activity. If IGF-I level was ≤1.2x upper limit of normal and tumor size not significantly increased, the remaining three parameters contributed to the decision in a compensatory manner. CONCLUSION: The validation study underlined IGF-I and tumor status for routine clinical decision-making, whereas patient-oriented outcome measures received less medical attention. An Acromegaly Disease Activity Tool (ACRODAT) is in development that might assist clinicians towards a more holistic approach to patient management in acromegaly.

Utility of baseline serum phosphorus levels for predicting remission in acromegaly patients.

PURPOSE: High GH and IGF I levels increase tubular phosphate reabsorption in patients with acromegaly. We aimed to investigate the utility of serum phosphorus levels as an indicator for predicting chance of remission in acromegaly patients. DESIGN: Fifty-one patients (n: 51; F: 24, M: 27) with diagnosis of acromegaly were included in the study. Plasma IGF-1, Phosphorus (P) and nadir GH levels on oral glucose tolerance test (OGTT) at the time of diagnosis were analysed retrospectively. Patients were classified into two groups according to their plasma P levels; P ≤ 4.5 mg/dl (Group-1, n: 23, 45.1%), P > 4.5 mg/dl (Group-2, n: 28, 54.9%). Two groups were compared according to remission status; remission (n: 27) and non-remission (n: 24). Remission was defined with absence of clinical symptoms, normal plasma IGF-1 (adjusted for age and gender) and GH levels (<1 mcg/dl) at least 3 months after initial treatment. RESULTS: Serum P levels decreased significantly after treatment in both groups (p < 0.001). There was a significant correlation between baseline phosphorus levels and remission rates, nadir GH in OGTT, pituitary adenoma size and Ki-67 scores (p = 0.001, r: -0.51; p = 0.01, r: 0.44; p = 0.001, r: 0.52; p = 0.02, r: 0.71, respectively). Mean baseline P levels were significantly higher in patients with non-remission (4.8 vs 4.2, P < 0.001). Logistic regression analysis did not reveal an independent effect on remission with any of these risk factors. CONCLUSION: High serum P levels may be an indicator for a low likelihood of onset of remission in acromegaly patients. Further studies with wider spectrum are needed to make specific suggestions.

Anatomy, Physiology, and Laboratory Evaluation of the Pituitary Gland.

The pituitary gland functions prominently in the control of most endocrine systems in the body. Diverse processes such as metabolism, growth, reproduction, and water balance are tightly regulated by the pituitary in conjunction with the hypothalamus and various downstream endocrine organs. Benign tumors of the pituitary gland are the primary cause of pituitary pathology and can result in inappropriate secretion of pituitary hormones or loss of pituitary function. First-line management of clinically significant tumors often involves surgical resection. Understanding of normal pituitary physiology and basic testing strategies to assess for pituitary dysfunction should be familiar to any skull base surgeon.

Octreotide LAR treatment of acromegaly in "real life": long-term outcome at a tertiary care center.

OBJECTIVE: To report our day-to day experience with the long-term use of octreotide LAR in the treatment of acromegaly. PATIENTS AND METHODS: Patients with acromegaly managed between 2003 and 2012 with octreotide LAR for a median of 27 months (interquartile ranges 12-60) and who had not received radiation therapy or concomitant treatment with cabergoline were retrospectively evaluated. Both primarily treated patients (n = 33) and patients who received octreotide after failed pituitary surgery (adjunctive treatment, n = 124) were included. Full biochemical response was defined as the achievement of a GH <2.5 ng/mL and an IGF-1 <1.2 times the upper limit of normal (× ULN); we also evaluated efficacy using a GH cut off of <1 ng/mL. RESULTS: Over 60% of the patients achieved a GH of <2.5 ng/mL. The combined GH (<2.5 ng/mL) and IGF-1 (<1.2 × ULN) target was achieved by 35.5 and 33.6% of the patients treated primarily and adjunctively, respectively; these figures dropped to 22.6 and 23% when using a GH target of <1 ng/mL. All patients reported a significant improvement in acromegalic symptoms. Lower pretreatment GH and IGF-1 levels were both associated with a higher probability of achieving the composite biochemical target. CONCLUSION: Currently recommended GH and IGF-1 targets are reached by <36% of patients treated with octreotide LAR in a day-to day practice context. Nevertheless, in most instances a clinical benefit and an improvement in biochemical markers can be clearly documented.