Body Composition, Sarcopenia, and Serum Myokines in Acromegaly: A Narrative Review.

Patients with active acromegaly have a higher percentage of lean body mass, a lower percentage of fat body mass, and an increase in their extracellular water compartment compared to healthy individuals. However, muscle function appears to be compromised in patients with acromegaly, with some experiencing worsened physical performance and sarcopenia. Myokine alterations, insulin resistance, dysregulation of protein metabolism, muscle oxidative stress, neuromuscular junction impairment, and increased ectopic intramuscular fat deposits may play roles in muscle dysfunction in patients with acromegaly.

Intraocular Pressure (IOP) in Patients with Acromegaly versus Healthy Controls: A Systematic Review and Meta-Analysis.

PURPOSE: Acromegaly is an uncommon condition but affects numerous organ systems. It has been found that patients with acromegaly can experience ocular changes, such as raised intraocular pressure (IOP). Numerous studies have since been carried out to determine whether there is a significant difference between IOP in patients with acromegaly and healthy controls and there is much disagreement in the literature. This study aims to perform a systematic review and meta-analysis to establish whether there is a significant difference in IOP between the two groups in a larger population. METHODS: A systematic literature search was performed using PubMed, Scopus, and Web of Science to access relevant databases and to locate outcome studies. Eligibility criteria included type of publication, participant characteristics, and report of outcomes. Data analysis was conducted with a fixed-effects model. RESULTS: Three articles were included in the final analysis. The mean value of IOP corrected for central corneal thickness (IOPcc) for the group of 102 patients with acromegaly was 15.33 with confidence levels of 13.05-17.62 [mmHg]. The mean difference between the control and acromegaly group was 1.17 with confidence levels of 0.64 to 1.70 [mmHg], which was found to be statistically significant (p < 0.001). CONCLUSION: The results of the meta-analysis indicate that acromegaly is associated with increased IOP. As raised IOP is a risk factor for the development of glaucoma, detailed IOPcc evaluation should be an important procedure in the follow-up visits of patients with acromegaly.

Correlation between insulin-like growth factor and complexity of glucose time series index in patients with newly diagnosed acromegaly: a PILOT study.

BACKGROUND: Acromegaly has a high risk of abnormal glucose metabolism. The complexity of the glucose time series index (CGI) is calculated from refined composite multi-scale entropy analysis of the continuous glucose monitoring (CGM) data. CGI is a new indicator of glucose imbalance based on ambulatory glucose monitoring technology, which allows for earlier response to glucose metabolism imbalance and correlates with patient prognosis. OBJECTIVE: To compare the differences in glucose metabolic profile and CGI between acromegaly with normal glucose tolerance (NGT) and healthy subjects. METHODS: Eight newly diagnosed patients with acromegaly (GH group) and eight age- and gender-matched healthy subjects (Control group) were included in this study. All participants underwent oral glucose tolerance test (OGTT) and 72-h CGM. A refined composite multi-scale entropy analysis was performed on the CGM data to calculate the CGI and we compare the differences in glycemic profiles and CGI between the two groups. RESULTS: After OGTT, compared with the control group, patients in the GH group had higher 2 h blood glucose (BG) (mmol/L) [GH vs control, 6.7 (6.1, 7.0) vs 5.2 (3.8, 6.3), P = 0.012], 3 h BG [5.1 (3.8, 6.5) vs 4.0 (3.4, 4.2), P = 0.046], mean BG [6.3 (6.1, 6.5) vs 5.5 (5.1, 5.9), P = 0.002], 2 h insulin (mU/L) [112.9 (46.8, 175.5) vs 34.1 (17.1, 55.6), P = 0.009], and 3 h insulin [26.8 (17.1, 55.4) vs 10.4 (4.2, 17.8), P = 0.016]. CGI was lower in the GH group [2.77 (1.92, 3.15) vs 4.2 (3.3, 4.8), P = 0.008]. Spearman's correlation analysis showed insulin-like growth factor (IGF) (r = -0.897, P < 0.001) and mean glucose (r = -0.717, P = 0.003) were significantly negatively correlated with CGI. Multiple linear stepwise regression showed that IGF-1 (r = -0.652, P = 0.028) was independent factor associated with CGI in acromegaly. CONCLUSION: IGF-1 was significantly associated with CGI, and CGI may serve as a novel marker to evaluate glucose homeostasis in acromegaly with normal glucose tolerance.

Shared decision-making and detection of comorbidities in an online acromegaly consultation with and without the Acromegaly Disease Activity Tool ACRODAT® using the simulated person approach.

OBJECTIVE: A patient-centered approach to the management of acromegaly includes disease activity control, shared decision-making and identification of comorbidities. The Acromegaly Disease Activity Tool (ACRODAT®) is intended to assist physicians in providing such holistic management. The present study investigated this claim using the simulated person (SP) approach. METHODS: We studied patient-doctor interaction via online video consultation in a randomized prospective study design with SPs trained to simulate a specific acromegaly profile. We analyzed the proportion of conversation time devoted to health content and the specific acromegaly and comorbidity relevant categories mentioned in the conversation. We collected physicians' feedback on the usefulness of ACRODAT®, SPs subjective perception of the quality of the conversation and compared consultations with and without ACRODAT® using a qualitative approach. RESULTS: The sample (N = 30) consisted of endocrinologists treating patients with acromegaly in Germany. For SP-physician interactions (N = 60), the proportion of time spent on conversation content (e.g. IGF-I, quality of life) was distributed according to the focus of the patient profile. Comorbidities were less well identified than the need for a change in therapy. Only 18.3% of the SPs were actively asked to participate in the decision-making process. ACRODAT® did not lead to any significant differences in the course of the discussion. CONCLUSIONS: Shared decision-making was underrepresented in this SP-physician interaction in acromegaly management. Physicians adapted the content of the discussion to the SP's needs, but did not adequately address comorbidities. According to the analysis criteria used, ACRODAT® did not contribute to a more holistic patient management in the present study.

Acromegaly: Incidence, Patient Characteristics And Treatment Patterns In A 10-Year Nationwide Retrospective Hospital Cohort Study.

INTRODUCTION: Acromegaly is a multisystemic disease associated with numerous comorbidities, notably cardiovascular disease and cancer. The objective of our study was to estimate the contemporary prevalence and incidence of acromegaly and its complications in a nationwide French retrospective cohort. METHODS: First, the positive predictive value of the ICD-10 acromegaly code E22.0 was checked by individually reviewing 132 medical records from one teaching hospital. Second, to estimate the prevalence of acromegaly, data of patients hospitalized between 2012 and 2021 were extracted from the PMSI French hospital database, using the dedicated ICD-10 code. Third, in a 2015-2020 subset cohort, we estimated the incidence of acromegaly, prevalence of complications and risk ratios of associated comorbidities or complications in subgroups of interest. RESULTS: A total of 7,943 adult patients were identified, with a positive predictive value of 87%, resulting in a prevalence of 10.4/100,000 in France. Annual incidence was 0.76/100,000. The most frequent complications were hypertension (43%), sleep apnea (34.3%) and diabetes (31.3%), mostly with onset before diagnosis. Patients with diabetes were at higher risk for most comorbidities: myocardial infarction (odds ratio (OR) 3.14 [1.92-5.13]), ischemic stroke (1.64 [1.18-2.28]) and cancer of any type (1.53 [1.27-1.84]). These risks were partially attenuated after adjustment for other cardiovascular risk factors, becoming respectively 1.52 [0.89-2.59], 0.92 [0.64-1.33] and 1.09 [0.88-1.34]. Treatment involved pituitary surgery in 43% and radiotherapy in 4.6% of patients. CONCLUSION: This study was the first, in a large population, to estimate the contemporary incidence and prevalence of acromegaly in non-selected patients at nationwide level in France. We found higher prevalences of complications than previously reported in tertiary specialized expert centers, probably reflecting suboptimal management in non-selected hospitals, whether specialized or not.

Clinico-radio-pathological predictors of outcomes in patients with acromegaly undergoing endoscopic transsphenoidal surgery.

Background: Acromegaly is a rare chronic endocrine disorder with variable biochemical remission rates from 40% to 85%. Hence, understanding the factors predicting biochemical cures helps in planning targeted and personalized treatment. We aimed to study the various clinico-radio-pathological predictors of outcomes in patients with pituitary neuroendocrine tumor (PitNET) who underwent transsphenoidal surgery (TSS) at 3 months follow-up. Methods: Our cohort included 61 consecutive patients with acromegaly treated at an institute in northwest India between January 2019 and June 2021. The outcomes of TSS were assessed at the end of 3 months postoperatively as defined by Endocrine Society Guidelines 2014. Results: The mean age at diagnosis was 38 ± 12 years, with the majority being females (67.2%). The median tumor volume was 2376 mm3 with high insulin-like growth factor-1 levels (3.12 ± 1.76 times the upper reference limit). Forty-two patients (68.8%) had radiological evidence of cavernous sinus invasion. Overall, the biochemical remission rate at 3 months was 34.4%. Unlike preoperative Knosp grading, T2-hypointensity was not predictive of biochemical remission. The granularity of PitNET, as well as immunohistochemical (IHC) markers such as Ki-67 index somatostatin receptor subtype (SSTR2/5) and low-molecular-weight cytokeratin (CAM5.2) expression, failed to show any significant correlation with remission. Conclusion: Overall, bulky tumors, higher hormone burden, and advanced Knosp grades translated to lower rates of biochemical remission in the present study cohort. Contrary to earlier studies, conventional IHC markers such as Ki-67, SSTR2/5, and CAM5.2 were not useful for predicting biochemical remission at 3 months.

AB031. Endoscopic transsphenoidal surgery for functional pituitary adenoma: shifting paradigms towards pseudocapsule-based resection.

BACKGROUND: Functional pituitary adenomas (PAs) manifest as intricate clinical syndromes, and surgery emerges as the principal intervention to mitigate associated morbidity and mortality. The endoscopic transsphenoidal surgery (ETS) approach stands as the preferred method for addressing PAs, with postoperative remission acting as a pivotal prognostic factor. METHODS: This study seeks to evaluate the influence of different surgical techniques and complications of ETS on functional PAs, focusing on both Acromegaly and Cushing's disease (CD). Patient records, including characteristics, perioperative assessments, postoperative complications, and follow-up data, were systematically gathered. Tumor resection methods were categorized into: (I) complete pseudocapsule resection; and (II) complete piecemeal resection. Post-surgery, daily monitoring of serum cortisol levels continued for a consecutive 3-day period until values of 2 µg/dL or less were achieved. Growth hormone levels were reassessed 12 weeks later, targeting a level of <0.14 g/L. A follow-up enhanced magnetic resonance imaging examination was conducted 3 months post-surgery to confirm the absence of residual tumors. RESULTS: The study identified 46 patients (23 with acromegaly and 13 with CD) who underwent endoscopic surgery between 2020 and 2023. Twenty-six patients underwent piecemeal resection (January 2020 to December 2022), while 10 patients underwent complete pseudocapsule removal (January to December 2023). No significant changes in surgical complications were observed between the two techniques. No instances of carotid artery injury, epistaxis, intracranial infection, or loss of olfaction were reported. In the pseudocapsule group, one patient experienced transient vision loss. Notably, 80% of patients in the pseudocapsule group achieved remission as compared to 57.7% in the piecemeal group. CONCLUSIONS: Pseudocapsule-based resection exhibited a remarkable remission rate, a low complication rate, and an absence of recurrence in functional adenoma patients. Despite the limited number of cases and our early experience, further studies are warranted to validate its effectiveness and safety.

AB092. Imaging the histopathology subtypes of the growth hormone-secreting pituitary neuroendocrine tumor.

BACKGROUND: Sparsely granulated (SG) growth hormone-secreting pituitary neuroendocrine tumors (GH-PitNETs) often present with a more aggressive clinical course compared to densely granulated (DG) tumors. These subtypes exhibit distinct biological and imaging characteristics. Thus, this study aims to differentiate between the histopathological subtypes of GH-PitNETs using pre-operative magnetic resonance imaging (MRI). METHODS: A retrospective analysis was conducted on 83 acromegalic patients treated at our institution between 2000 and 2010. Tumor volumes were segmented from preoperative MRIs, including T1-weighted, T2-weighted, T1 with contrast, and T2 fluid attenuated inversion recovery (FLAIR) sequences. Reference regions of interest (ROIs) were delineated using gray and white matter from the same sequences. Two pathologists reviewed pathology specimens for anti-cytokeratin (CAM 5.2) and Pit-1 expression. Clinical and radiological biomarkers were compared between SG and DG patients. RESULTS: A total of 83 patients with complete histopathology and 51 patients with complete MRIs were included in the analysis. SG PitNETs exhibited higher rates of supra-sellar invasion (61.5%, P<0.001), larger tumor sizes, lower pre-operative GH levels, and increased post-operative residual tumor (65.4%, P<0.001) compared to DG PitNETs. Additionally, SG PitNETs showed greater hyperintensity on T2-weighted images and enhanced contrast, whereas DG PitNETs exhibited less contrast enhancement. Utilization of these imaging biomarkers demonstrated an 94.1% accuracy in T2 FLAIR and overall of 78.7% predicting the histopathological subtypes of GH-PitNETs. CONCLUSIONS: Distinct histopathological subtypes of GH-PitNETs represent crucial prognostic factors. Utilizing multimodal pre-operative MRIs, clinicians can accurately identify sparsely granulated GH-PitNETs, facilitating improved treatment planning strategies.

Manifestations of Endocrine Disease in the Lower Extremities: Beyond the Diabetic Foot.

The aim of this narrative review was to discuss manifestations of endocrine disease other than diabetic foot in the lower extremities. Acromegaly, Addison's disease, Cushing's syndrome, hypo- and hyperthyroidism, hypo- and hyperparathyroidism, autoimmune polyglandular syndrome, hypopituitarism, and glucagonoma are among the endocrine diseases that may present with clinical manifestations in the lower extremities. Clinical signs vary depending on the underlying condition. Clinical suspicion is necessary for early diagnosis. Treatment of the underlying endocrine disease usually results in improvement of lower-extremity manifestations.

GH receptor polymorphisms guide second-line therapies to prevent acromegaly skeletal fragility: preliminary results of a pilot study.

Background: Skeletal fragility is characterized by increased frequency of vertebral fractures (VFs) in acromegaly. Several trials were conducted to identify modifiable risk factors and predictors of VFs, with limited data on the prognostic role of GH receptor (GHR) isoforms. In this study, we investigated the potential role of GHR polymorphism on the occurrence of incidental VFs (i-VFs), in patients treated with second-line medical therapies. Methods: A longitudinal, retrospective, observational study was conducted on a cohort of 45 acromegalic patients not-responsive to first-generation somatostatin receptor ligands (fg-SRLs) and treated with GHR antagonist (Pegvisomant) or with the second-generation SRLs (Pasireotide long-acting release). Results: Second line treatments were Pegvisomant plus fg-SRLs in 26 patients and Pasireotide LAR in 19 patients. From the group treated with fg-SRLs+Peg-V, the fl-GHR isoform was identified in 18 patients (69.2%) and the d3-GHR isoform in 8 patients (30.8%). I-VFs arose exclusively in fl-GHR isoform carriers (p=0.039). From the group treated with Pasireotide LAR, the fl-GHR isoform was identified in 11 patients (57.9%), and the d3-GHR isoform in 8 patients (42.1%). I-VFs arose exclusively in d3-GHR isoform carriers (p=0.018). Patients with fl-GHR isoform had a higher risk for i-VFs if treated with fg-SRL+Peg-V (OR: 1.6 95%IC: 1.1-2.3, p=0.04), and a lower risk if treated with Pasi-LAR (OR: 0.26 IC95%: 0.11-0.66, p=0.038). Conclusions: Our data support a predictive role of the GHR isoforms for the occurrence of i-VFs in acromegalic patients treated with second-line drugs, tailored to the individual patient. The knowledge of the GHR polymorphism may facilitate the choice of second-line therapies, improving the therapeutic approach, in the context of personalized medicine.

Myocardial Mechanics in Acromegaly: A Meta-Analysis of Echocardiographic Studies.

INTRODUCTION: Evidence on myocardial deformation, detected by speckle tracking echocardiography (STE), in patients with acromegaly is scanty. AIM: The aim of the present meta-analysis was to provide an updated information on left ventricular (LV) systolic function assessed by global longitudinal strain (GLS) in patients with acromegaly and preserved LVEF. METHODS: Following the PRISMA guidelines, systematic searches were conducted across bibliographic databases (Pub-Med, OVID, EMBASE and Cochrane library) to identify eligible studies from inception up to June 30-2024. Clinical studies published in English reporting data on LV mechanics in patients with acromegaly and controls were included. The statistical difference of the echocardiographic variables of interest between groups such as LVEF and global longitudinal strain (GLS) was calculated by standardized mean difference (SMD) with 95% confidence interval (CI) by using random-effects models. RESULTS: Seven studies including 288 patients with acromegaly and 294 healthy individuals were considered for the analysis. Pooled average LVEF values were 64.6 ± 1.5% in the healthy control group and 64.0 ± 1.3% in the acromegaly group (SMD: - 0.21 ± 0.22, CI -0.62/0.22, p = 0.34); the corresponding values of GLS were - 19.1.1 ± 1.2% and - 17.5 ± 1.2% (SMD: -0.52 ± 0.27, CI - 1.05/0.01, p = 0.05). No difference was found between the two groups for both global circumferential strain (GCS) and global radial strain (GRS). CONCLUSIONS: Our findings suggest that patients with acromegaly in which LVEF is completely comparable to healthy controls show an impairment in GLS of borderline statistical significance. Whether GLS assessment can actually unmask early alterations of systolic function in patients with acromegaly better than LVEF will need to be investigated by future studies.

Skeletal fragility in pituitary disease: how can we predict fracture risk?

Pituitary hormones play a crucial role in regulating skeletal physiology, and skeletal fragility is a frequent complication of pituitary diseases. The ability to predict the risk of fracture events is crucial for guiding therapeutic decisions; however, in patients with pituitary diseases, fracture risk estimation is particularly challenging. Compared to primary osteoporosis, the evaluation of bone mineral density by dual X-ray absorptiometry is much less informative about fracture risk. Moreover, the reliability of standard fracture risk calculators does not have strong validations in this setting. Morphometric vertebral assessment is currently the cornerstone in the assessment of skeletal fragility in patients with pituitary diseases, as prevalent fractures remain the strongest predictor of future fracture events. In recent years, new tools for evaluating bone quality have shown promising results in assessing bone impairment in patients with pituitary diseases, but most available data are cross-sectional, and evidence regarding the prediction of incident fractures is still scarce. Of note, apart from measures of bone density and bone quality, the estimation of fracture risk in the context of pituitary hyperfunction or hypofunction cannot ignore the evaluation of factors related to the underlying disease, such as its severity and duration, as well as the specific therapies implemented for its treatment. Aim of this review is to provide an up-to-date overview of all major evidence regarding fracture risk prediction in patients with pituitary disease, highlighting the need for a tailored approach that critically integrates all clinical, biochemical, and instrumental data according to the specificities of each disease.

Transsphenoidal Surgery for Pituitary Tumors.

Transsphenoidal surgery for the treatment of pituitary masses in cats and dogs has become a more established treatment over the last 2 decades. Although expert centers and surgeons that provide this service remain limited, the patient population presented for pituitary surgery increases with wider availability of advanced imaging, together with more challenging cases. In this review, the current state of hypophysectomy is described with future challenges and opportunities.

Growth Hormone-Secreting Pituitary Adenoma and Difficult Airway: Awake Oral Fiberoptic Intubation Approach.

Acromegaly is a rare endocrine disorder characterized by excessive growth hormone (GH) secretion, usually due to a pituitary adenoma. This condition leads to progressive somatic disfigurement, including enlarged hands, feet, and facial features, and is often associated with systemic complications such as cardiovascular disease, diabetes mellitus, and sleep apnea. Anesthesia for patients with acromegaly presents unique challenges due to the characteristic anatomical and physiological changes associated with the condition. Acromegaly, resulting from excessive GH secretion, often leads to difficult airway management, cardiovascular complications, and metabolic abnormalities. Transnasal transsphenoidal excision of pituitary adenoma is a minimally invasive surgical technique employed to remove pituitary tumors. This approach, which utilizes the nasal passages and sphenoid sinus to access the pituitary gland, offers several advantages, including reduced recovery time, minimal scarring, and lower risk of complications compared to traditional craniotomy. Awake fiberoptic intubation is one of the recommended strategies to secure an expected difficult airway such as in acromegaly. This case highlights the importance of preoperative planning and the role of an oral fiberoptic technique in managing the airway in surgeries like the transnasal approach.

Incidence of bronchiectasis in patients with acromegaly: a cohort study.

Objective: Associations between acromegaly and several respiratory diseases, such as obstructive lung disease or sleep apnea, have been suggested, but the relationship between bronchiectasis and acromegaly is unclear. We investigated whether acromegaly is related to the development of bronchiectasis. Materials and methods: Using the Korean National Health Insurance System database between 2006 and 2016, we studied the relationship between acromegaly and bronchiectasis in patients with acromegaly (n=2593) and controls (1:5 age- and sex-matched subjects without acromegaly, n=12965) with a mean follow-up period of 8.9 years. Cox proportional hazards regression analysis was used to assess the risk of bronchiectasis in patients with acromegaly compared with controls after adjusting for age, sex, household income, place, type 2 diabetes, hypertension, and dyslipidemia. Results: The mean age of the participants was 47.65 years, and male subjects comprised 45.62% of the cohort. The incidence rate of bronchiectasis in patients with acromegaly was 3.64 per 1,000 person-years and was significantly higher than that in controls (2.47 per 1,000 person-years) (log-rank test p = 0.002). In multivariable Cox proportional hazards regression modeling, the risk of bronchiectasis was significantly higher in patients with acromegaly than that in controls (HR: 1.49; 95% CI: 1.15-1.94, p = 0.0025) after adjusting for age, sex, household income, place, type 2 diabetes, hypertension, and dyslipidemia. Conclusions: Our results suggest that acromegaly may be associated with bronchiectasis.

An Overview of Cardiovascular Risk in Pituitary Disorders.

Cardiovascular comorbidities owing to hormonal excess or deficiency are the main cause of mortality in patients with pituitary disorders. In patients with Cushing's Disease, there is an increased prevalence of cardiovascular diseases and/or risk factors including visceral obesity, insulin resistance, atherosclerosis, arterial hypertension, dyslipidaemia, hypercoagulability as well as structural and functional changes in the heart, like cardiac hypertrophy and left ventricle (LV) dysfunction. Notably, these demonstrate limited reversibility even after remission. Furthermore, patients with acromegaly may manifest insulin resistance but also structural and functional heart changes, also known as "acromegalic cardiomyopathy". Patients with prolactinomas demonstrate an aggravation of metabolic parameters, obesity, dysregulation of glucose and lipid metabolism as well as endothelial dysfunction. Hypopituitarism and conventional hormonal replacement therapy may also contribute to an unhealthy metabolic status, which promotes atherosclerosis and may lead to premature mortality. This review discusses the literature on cardiovascular risk in patients with pituitary disorders to increase physician awareness regarding this aspect of management in patients with pituitary disorders.

Outcome of endoscopic transsphenoidal surgery for acromegaly: Comparison of using and not using the floor standing pneumatic powered endoscope-holder system.

Introduction: Endoscopic transsphenoidal surgery can be performed by two surgeons, including an endoscopist (PE/2S), and by a single surgeon with an endoscope-holder system (PE/1S + H). We analyzed the surgical outcome, and outcome predictors in acromegaly patients in endoscopic transsphenoidal surgery using floor standing pneumatic endoscope-holder system. Methods: Endoscopic transsphenoidal surgery was performed with PE/1S+H (n = 51) and PE/2S (n = 20). Postoperative remission was evaluated by the 2010 consensus criteria for acromegaly. We compared the surgical results of PE/2S style and PE/1S+H style, and investigated the factors associated with favorable surgical outcomes. Results: There was no difference in clinical background between the PE/2S and the PE/1S + H groups. The remission rates for PE/2S and PE/1S+H were 65.0% and 82.4%, respectively, with no significant difference (p = 0.128). In consecutive 71 cases, statistically useful predictors of remission were low preoperative growth hormone (GH) level (<12 ng/mL), low Knosp grade (0-2), and low revised Knosp grade (0-3A). In the conventional Knosp grade 0-2 and 3/4, the sensitivity was 0.76 and the specificity was 0.81. In the revised Knosp grade 0-3A and 3B/4, the sensitivity was 0.96 and the specificity was 0.44. Conclusion: The outcome of GH-producing pituitary neuroendocrine tumors surgically removed by PE/1S+H could be almost equivalent to that by PE/2S. Preoperative low GH level and Knosp grades, including revised Knosp grades, are useful preoperative predictors for surgical remission of acromegaly.

GIP receptor antagonism eliminates paradoxical growth hormone secretion in some patients with acromegaly.

CONTEXT: About 30% of patients with active acromegaly experience paradoxically increased growth hormone (GH) secretion during the diagnostic oral glucose tolerance test (OGTT). Endogenous glucose-dependent insulinotropic polypeptide (GIP) is implicated in this paradoxical secretion. OBJECTIVE: We used the GIP receptor (GIPR) antagonist GIP(3-30)NH2 to test the hypothesis that GIP mediates this paradoxical response when GIPR is abundantly expressed in somatotropinomas. DESIGN, PATIENTS, SETTING, INTERVENTIONS: 25 treatment-naïve patients with acromegaly were enrolled. Each patient underwent one OGTT during simultaneous placebo infusion and one OGTT during a GIP(3-30)NH2 infusion. Blood samples were drawn at baseline and regularly after infusions to measure GH. We assessed pituitary adenoma size by magnetic resonance imaging and GIPR expression by immunohistochemistry on resected somatotropinomas. For mechanistic confirmation, we applied in vitro and ex vivo approaches. MAIN OUTCOME MEASURE: The effect of GIP(3-30)NH2 on paradoxical GH secretion during OGTT as a measure of GIP involvement. RESULTS: In four of seven patients with paradoxical GH secretion, GIP(3-30)NH2 infusion completely abolished the paradoxical response (P = 0.0003). Somatotrophs were available from three of four of these patients, all showing abundant GIPR expression. Adenoma size did not differ between patients with and without paradoxical GH secretion. CONCLUSIONS: Of 25 patients with acromegaly, seven had paradoxical GH secretion during OGTT, and pharmaceutical GIPR blockade abolished this secretion in four. Corresponding somatotroph adenomas abundantly expressed GIPR, suggesting a therapeutic target in this subpopulation of patients. In vitro and ex vivo analyses confirmed the role of GIP and the effects of the antagonist.

Characteristics and treatment of a silent somatotroph tumor that had transformed to a functional type: a case report and literature review.

Background: "Functionalization" of silent pituitary neuroendocrine tumors (PitNETs) is a pretty rare clinical phenomenon that reportedly occurs most often with silent corticotroph tumors (SCTs). We report the case of silent somatotroph tumor (SST) that had transformed to functional type. We also review similar cases of SST with functionalization. Case Description: A 43-year-old man without suggestive symptoms of a pituitary tumor was referred with a lesion in the sellar region detected incidentally. Serum insulin-like growth factor 1 (IGF-1) (348 ng/mL) was high, whereas growth hormone (GH) was within the normal range. A glucose GH inhibition test showed inhibition of GH to 0.4 ng/mL. Subtotal tumorectomy was performed via a transnasal-sphenoidal approach. Histopathological examination of the operative specimen showed weak expression of GH and diffuse staining of pituitary-specific transcription factor-1 (Pit-1). The final pathological diagnosis was SST. Five years after the first surgery without follow-up, the patient presented again because of headache, impaired vision, bone pain, and high blood glucose concentrations for 2 months. Physical examination showed early acromegalic features. Of interest, greatly increased concentrations of GH (7.2 ng/mL) and IGF-1 (533 ng/mL) were found. Magnetic resonance imaging showed the recurrence of tumor. A diagnosis of acromegaly was considered. The patient underwent a second transsphenoidal pituitary tumor resection, after which his serum GH and IGF-1 concentrations decreased. Unlike the original surgical specimen, immunohistochemical examination of the tissue resected during the second surgery showed strong GH positivity, with similarly strong Pit-1 positivity. The patient was followed up for 6 months without octreotide treatment. At the last follow-up, he was found to have high serum concentrations of GH and IGF-1, which demonstrated another progression of the remnant PitNET. After two courses of octreotide acetate microspheres (20 mg/month), the acromegaly was under control. Conclusions: In addition to SCTs, other silent PitNETs could also functionalize. Medical teams of PitNETs should recognize this rare phenomenon and conduct long-term follow-up. After functionalization, these tumors have a high recurrence rate, requiring multiple therapies and long-term follow-up. Further research is essential to determine the mechanism of regulation of secretion of GH by such tumors.

Medical treatment of acromegaly - When the tumor size matters: A narrative review.

Medical treatment of acromegaly is generally positioned as a second line of treatment after pituitary adenoma surgery. With the rising availability and variety of medications for acromegaly increases our understanding of their effectiveness and safety. Volume of the published data on the impact of medical therapy on biochemical control of acromegaly, contrasts a relative lack of publications which comprehensively address pituitary tumor alterations under different drug modalities. Assessment of changes in GH-secreting adenoma volume is often overshadowed by clinicians' focus on GH and IGF-I levels during acromegaly treatment. Close analysis of studies published in the last two decades, reveals that both an increase and decrease in somatotropinoma volume are possible during treatment with any of available drugs for acromegaly. Changes in pituitary tumor size may arise from the biological nature of adenoma itself, independently of the administered medications. Therefore, an individual approach is necessary in the treatment of patients with acromegaly, based on repeated insight to their clinical, biochemical, pathological and imaging characteristics. In this review, we summarize and comment how pituitary tumor size is affected by the treatment with all currently available drugs in acromegaly: long-acting somatostatin receptor ligands of the first generation (octreotide LAR and lanreotide autogel) and the second generation (pasireotide-LAR), as well as pegvisomant (PEG) and cabergoline (CAB).