bluuebunny/crossref_metadata_2025_split huggingface dataset:
Giant Prolactinomas: An Experience From South India
Authors: S Vishwanath , George Belinda , Ayyar Vageesh , Bantwal Ganapathi , Appaiah Sonali 
Published: May 2021

Abstract
Giant prolactinomas are large lactotroph adenomas, defined as those with maximum dimension of &gt;4cm. They constitute &lt;5% of all prolactin secreting tumors, and are more frequently seen in men. They present with features of hyperprolactinemia and hypopitutarism and are responsive to dopamine agonist therapies. In the current study we have shared our experience on management of giant prolactinomas over the last 15 years. We collected clinical data retrospectively from medical records of patients with giant prolactinoma managed at our institute over the last 15 years. This study describes the symptomatology, tumor characteristics and response to therapy. Our study included 21 patients with 15 males and 6 females. The mean age of presentation was 32 ± 10.3 years, ranging between 10 to 53 years. Vision defect was the predominant complaint (57%, 12 patients), followed by headache (52%, 11 patients). Erectile dysfunction was a presenting feature in 13% of men (2 patients) and amenorrhea/galactorrhea in 33% of women (2 patients). Seizure was seen in 10% of the patients (2 patients) and 10% (2 patients) were diagnosed with giant prolactinoma on evaluation for primary infertility. Tumor associated pituitary dysfunction manifested as hypogonadism in 67%, 14 patients, central hypothyroidism in 38%, 8 patients, and hypocortisolism in 1 patient. The median maximum tumor dimension was 4.4 cm with median basal PRL of 7168 ng/ml. Five patients underwent debulking surgery (24% of the patients) prior to endocrinology referral for indications such as apoplexy/raised intracranial tension. All patients received cabergoline and a mean dose of 2.1 ± 1.7 mg/week (range, 1-7 mg/week) was prescribed to attain a median nadir prolactin level of 48 ng/ml over a median period of 4 months (range, 1-40 months). The follow-up MRI data was analysed for 13 patients. Tumor shrinkage of &gt;50% from the baseline was seen in all but 1 patient (92%) and 2 patients had disappearance of radiologically detectable tumor. Although giant prolactinomas have a greater tumor burden than the more common macroprolactinomas, the responsiveness to dopamine agonist therapy is excellent and surgical therapy is reserved for any exceedingly large tumors to relieve compression on vital structures.
Increased Serum High-Sensitivity C-Reactive Protein in Growth Hormone-Deficient Patients With Non-Functioning Pituitary Tumors
Authors: Seki Yasufumi , Ichihara Atsuhiro 
Published: May 2021

Abstract
Introduction: Growth hormone (GH) deficiency, the most common hormone deficit complicated with pituitary tumors, is associated with higher mortality and cardiovascular events. Inflammation, as measured by high-sensitivity C-reactive protein (hs-CRP), has been reported to be associated with cardiovascular events. However, the association between hs-CRP and GH deficiency is still unknown. We retrospectively evaluated the association between serum hs-CRP levels and GH secretion in patients with non-functioning pituitary tumors (NFPTs). Methods: In this retrospective study, adult patients with non-functioning pituitary adenoma (NFPA) and Rathke’s cyst who received a GH-releasing pepitide-2 (GHRP-2) test from 2013 until 2016 were included. Patients with a history of pituitary surgery or radiation, or estimated GFR lower than 30 mL/min/1.73m2 were excluded. Results: Of 81 patients (70 NFPA and 11 Rathke’s cyst), 44% were diagnosed as severe GH deficiency by GHRP-2 test. Serum hs-CRP level was significantly higher in the male patients (P = 0.001) and the patients with regularly alcohol intake (P = 0.011) and was significantly correlated with BMI (r = 0.35, P = 0.002), creatinine (r = 0.41, P &lt; 0.001), eGFR (r = -0.29, P = 0.009), peak GH response to GHRP-2 (r = -0.48, P &lt; 0.001), AST (r = 0.32, P = 0.004), ALT (r = 0.34, P = 0.002), γGTP (r = 0.41, P &lt; 0.001), HDL-cholesterol (r = -0.33, P = 0.003) and triglyceride (r = 0.25, P = 0.02). Smoking habit (P = 0.084), age (r = 0.18, P = 0.10), LDL-cholesterol (r = 0.16, P = 0.15), IGF-1 (r = -0.14, P = 0.23) and IGF-1 SD score (r = -0.11, P = 0.32) were not significantly correlated with serum hs-CRP level. Peak GH response to GHRP-2 (β = -0.24, P = 0.024) was a significant variable to determine serum hs-CRP level after adjustment for age, sex, BMI, regularly alcohol intake and serum creatinine, γGTP and HDL-cholesterol levels. Conclusion: Increased serum hs-CRP levels in the GH-deficient patients with NFPTs suggested the contribution of GH deficiency to pathogenesis of inflammation associated with cardiovascular diseases.
One Fourth of Adult Patients With Acromegaly Have Tall Stature With Similar Frequency in Males And Females
Authors: Bogusławska Anna , Gilis-Januszewska Aleksandra , Magdid Kesson , Godlewska Magdalena , Olszewska Marta , Nowak Andrzej Jerzy , Starzyk Jerzy , Korbonits Marta , Hubalewska-Dydejczyk Alicja 
Published: May 2021

Abstract
Introduction: Tall stature (TS) is a manifestation of growth hormone (GH) excess, with higher prevalence reported for males. The aim of this study was (i) to evaluate the relationship between height of patients with GH excess related to midparental height (MPH) and population mean height; (ii) to test whether TS patients with acromegaly come from tall families. Methods: Single-centre, observational study on 101 consecutive adult patients with acromegaly and no family history of pituitary adenoma. Patients were analysed in two subgroups depending on height using country-specific data: 1) normal stature and 2) TS group, defined as either height above gender-specific 97 percentile or as &gt;1.5 country-specific standard deviation (SD) from MPH. Results: Twenty-four percent of acromegaly patients (13 females/11 males) met one or both of the TS criteria. TS patients were significantly younger at the diagnosis (mean±SD, 33.6±13.4 vs 50.6±12.3 years) and at first symptoms (median 27.5, range 23-42 vs 41 (33-54) years) with greater tumour size and higher basal GH concentration than normal stature patients (p&lt;0.01). The TS criteria based on the 1.5 SD above MPH identified more TS patients than the above 97 percentile height (92% vs 38%) and especially increased the diagnosis of TS in women (92% vs 31%). There was no difference in height of family members of acromegaly patients with or without TS. Height of family members were not taller than the population mean. Conclusion: One fourth of adult patients with acromegaly have TS with similar frequency in males and females. Based on our data TS patients with acromegaly do not come from tall families.
Prevalence of Abnormal Glucose Metabolism in Acromegaly & Impact of Treatment Modalities on Glucose Metabolism
Authors: Khan Sajjad Ali , Ram Nanik , Masood Muhammad Qamar 
Published: May 2021

Abstract
Objective: To determine the frequency of diabetes mellitus impaired glucose tolerance and impaired fasting glucose in Pakistani patients with acromegaly and to establish the impact of the intervention (surgery/ medical) on glucose metabolism.
Methods: Eighty-nine patients fulfilling the endocrine society criteria for acromegaly diagnosis were included. A data of baseline, growth hormone (GH), Insulin-like growth factor-1 (IGF-1) level, Hemoglobin A1C (HbA1C), fasting blood glucose (FBG), and random blood glucose (RBS) levels were reviewed before and after the intervention (surgery/medical therapy). Normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes mellitus (DM) were defined based on the 2003 ADA criteria. Patients were grouped into normoglycemic (NGT) and dysglycemic (IFG, IGT, and DM) based on FBS, RBS, and HbA1C.
Results: Major risk factors for dysglycemia included age (15-45 years), male sex (33.70%), obesity (45.7%), and macroadenoma (76%). Both mean GH levels (58.29 vs. 54.36 ng/dl) and IGF-1 levels (862.98 vs. 824.32 ng/dl) were higher among the normoglycemic than dysglycemia. Pre-surgery, NGT, IFG, IGT, IFG, and IGT combined and DM were found in 48.31, 5.61, 1.1, 5.61, and 39.32 % of the subjects, respectively. Post-surgery, HbA1C improved in 79.5%, deteriorated in 6.8%, and remained the same in 13.6%. Similarly, it improved in 67.4.7% post-medical therapy. Both FBS and RBS improved post-surgery and medical therapy. Further, the number of anti-diabetic drugs used also decreased post-surgery.
Conclusion: Dysglycemia is more common among patients with acromegaly as compared to the general population and tends to be poorly controlled in untreated acromegaly. Glycemic control improves significantly after the surgery and medical therapy.
Keywords: Acromegaly, Diabetes Mellitus, Transsphenoidal surgery
Safety and Efficacy of Pegvisomant in Pediatric Growth Hormone Excess
Authors: Tatsi Christina , Wajnrajch Michael Paul , Camacho-Hubner Cecilia , Stratakis Constantine A 
Published: May 2021

Abstract
Objective: Pediatric growth hormone excess (GHE) and gigantism are mainly managed by pituitary surgery. However, a large percentage of patients require further medical management. Data for the pediatric population are scares and decisions are usually based on adult published data. We have initiated a study to investigate the efficacy and safety of pegvisomant in children and adolescents with GHE. MethodsThe study is registered in ClinicalTrials.gov (Identifier: NCT03882034, An open-label phase 3 study of the safety and efficacy of pegvisomant in children with growth hormone excess). Eligible patients must be children or adolescents (age: 24 months -18 years) with GHE with persistent disease after surgical or radiation therapy. The patients will receive pegvisomant via subcutaneous daily injection for one year and outcomes will be measured at baseline and at the end of the study. The main measure of efficacy is the change of IGF-1 from baseline to the end of the study. The main measure of safety is the description of side effects over the duration of the study. ConclusionsWe will collect data on the safety and efficacy of medical treatment for pediatric patients with GHE.
Somatotroph Adenomas have a Predilection to Invade the Cavernous Sinus and Resection of the Medial Wall of the Cavernous Sinus Offers the Highest Potential for Biochemical Remission in Acromegaly
Authors: Mohyeldin Ahmed , Katznelson Laurence , Fernandez-Miranda Juan 
Published: May 2021

Abstract
Recurrence and remission rates vary widely among different histological subtypes of pituitary adenoma. Invasion of the medial wall of the cavernous sinus is a known mechanism that may account for such failed clinical outcomes as its removal has long been considered unattainable. The use of modern endoscopic techniques allows for direct intraoperative evaluation of invasion and resection of the medial wall of the cavernous sinus with low morbidity when performed by highly experienced surgeons. In this retrospective study we evaluated 105 consecutive primary pituitary adenomas operated by a single surgeon including 28 corticotroph, 27 gonadotroph, 24 somatotroph, 15 lactotroph, 5 null-cell, 5 plurihormonal, and 1 dual adenoma; 53 caused hypersecretory syndromes, specifically acromegaly (30), hyperprolactinemia (15) and Cushing’s disease (8). In each case, we performed meticulous intraoperative inspection of the medial wall with its surgical removal when invasion was suspected, regardless of functional status. Medial wall resection was performed in 46% of pituitary adenomas, and 38/48 walls confirmed pathologic evidence of invasion rendering a positive predictive value of intraoperative evaluation of medial wall invasion of 79%. Furthermore, we show for the first time that the rate of medial wall invasion among pathological subtypes is dramatically different. Somatotroph tumors invaded the medial wall much more often than other adenoma subtypes, 83% intraoperatively and 71% histologically, followed by plurihormonal tumors (40%) and gonadotrophs (33%), both with intraoperative positive predictive value of 100%. The least likely to invade were corticotroph, at a rate of 32% intraoperatively and 21% histologically, and null-cell adenomas at 0%. Removal of the medial wall caused no permanent morbidity with no carotid artery injuries and 2 patients with transient diplopia. We report that resecting the medial wall of the cavernous sinus in acromegaly offers the highest potential for biochemical remission with average postoperative day 1 GH levels at 0.96 ug/l and early surgical remission rates at 90% (100% with adjuvant therapy) based on normalization of IGF-1 levels 3 to 6 months after surgery; these results are significantly better than previously reported but longer follow-up is required for definitive conclusions. Our findings may explain the failed biochemical remission rates seen in acromegaly and illustrate the relevance of advanced surgical techniques for successful outcomes in pituitary surgery.
The Pharmacological Burden of Comorbidities in Acromegaly
Authors: Fleseriu Maria , Barkan Ariel , Schneider Maria del Pilar , Darhi Yannis , de Pierrefeu Amicie , Munoz Kathryn , Ribeiro-Oliveira Antonio , Melmed Shlomo 
Published: May 2021

Abstract
Background: Acromegaly is characterized by excess GH and elevated IGF-I often treated by surgery, pharmacotherapy (somatostatin analogs, GH receptor antagonists, dopamine agonists) and/or radiotherapy.1 Common associated comorbidities include cardiovascular disorders and hypopituitarism, often requiring additional pharmacotherapy.2 We therefore assessed the most common comorbidities and related pharmacological burden in patients with acromegaly in a real-world clinical setting.
Methods: The MarketScan database was examined for medical claims from Jan 2010 to Jan 2020. We defined 2 groups: Group 1 - patients with acromegaly (2 diagnoses [ICD-9-CM/ICD-10-CM] on dates within &gt;30 days) who had ≥1 medication for acromegaly since diagnosis, with ≥3 months coverage prior to index date (diagnosis date or first treatment available); Group 2 - a matched cohort (MC) with no acromegaly-related medical claims; direct matching (1:5 based on age, sex and follow-up duration) was performed. Group proportions and quantitative differences were compared by chi-squared tests and t-tests, respectively (unpaired due to different cohort sizes).
Results: 1,175 patients with and 5,875 without acromegaly were analyzed. Across both groups, median (95% CI) age was 50 (49, 51) years, 50% were female, median (95% CI) follow-up was 751 (702, 805) days. Comorbidities reported in ≥20% patients with acromegaly vs the MC were cardiovascular system disorders (68% vs 48%), hypopituitarism/hypothalamic disorders (26% vs 0%), sleep apnea (25% vs 8%), malignant neoplasms (23% vs 9%), arthritis and muscular skeletal disorders (20% vs 13%); frequencies were significantly higher in patients with acromegaly vs the MC (all p&lt;0.0001). Thyroid replacement, lipid modifying and renin-angiotensin system agents were the most common treatments related to these comorbidities, all used more frequently in acromegaly (35%, 34% and 34%, respectively) vs the MC (9%, 26% and 25%, respectively; all p&lt;0.0001). Overall in patients with acromegaly vs the MC, mean (SD) number of different oral medications used was 12.01 (10.49) vs 7.21 (7.99); 5% vs 20% and 79% vs 58% took 0 and ≥3 oral medications, respectively (all comparisons p&lt;0.0001). Significantly more patients with acromegaly vs the MC took medications typically taken while fasting e.g. levothyroxine (34% vs 9%) and omeprazole (14% vs 9%), both p&lt;0.01.
Conclusions: In this real-world analysis, patients with acromegaly had more comorbidities, compared with a matched population and required many concomitant medications. Oral medication use with or without fasting was higher in patients with acromegaly. These findings elucidate further physician understanding of the pharmacological burden of acromegaly comorbidities.
Funding: This ongoing study is sponsored by Ipsen.
1.Katznelson L J Clin Endocrinol Metab 2014:99:3933-51
2.Gadelha M Endocr Rev 2019:40:268-332
The Musashi1 RNA-Binding Protein Functions as a Leptin-Regulated Enforcer of Pituitary Cell Fate and Hormone Production
Authors: Banik* Jewel , Lim* Juchan , Linda Hardy L , Odle Angela Katherine , Childs Gwen V , MacNicol Melanie C , MacNicol Angus M 
Published: May 2021

Abstract
The pituitary gland is the major endocrine organ that produces and secretes hormones in response to hypothalamic signals to regulate important processes like growth, reproduction, and stress. The anterior pituitary adapts to metabolic and reproductive needs by exhibiting cellular plasticity, resulting in altered hormone production and secretion. The adipokine, leptin, serves a critical role to couple energy status to pituitary function. We have recently reported that the cell fate determinant, Musashi, functions as a post-transcriptional regulator of target mRNA translation in the mouse pituitary and have speculated that Musashi may modulate pituitary cell plasticity. However, the underlying mechanisms governing such pituitary plasticity are not fully understood. Musashi is an mRNA binding protein that is required for self-renewal, proliferation, and to control the differentiation of stem and progenitor cells. We have recently shown that Musashi is expressed in Sox2+ pituitary stem cells and surprisingly, we also found Musashi expression in all differentiated hormone expressing cell lineages in the adult anterior pituitary. The role of Musashi in these mature differentiated cells is unknown. We have observed that a range of critical pituitary mRNAs, including the lineage specification transcription factors Prop1 and Pou1f1, as well as hormone mRNAs including Tshb, Prl, and Gnrhr, all contain consensus Musashi binding elements (MBEs) in their 3’ untranslated regions (3’ UTRs). Using RNA electrophoretic mobility shift assays (EMSAs) and luciferase mRNA translation reporter assays we show that Musashi binds to these mRNAs and exerts inhibitory control of mRNA translation. Moreover, we determined that leptin stimulation opposes the ability of Musashi to exert translational repression of the Pou1f1 and Gnrhr 3’ UTRs. This de-repression does not require regulatory phosphorylation of Musashi on two conserved C-terminal serine residues. Interestingly in the same cell assay system, Musashi exerts translational activation of the Prop1 3’ UTR. We observed that this translational activation requires Musashi phosphorylation on the two regulatory C-terminal serine residues, consistent with the requirement for regulatory phosphorylation to drive translational activation of Musashi target mRNAs during Xenopus oocyte cell maturation. The distinction between MBEs in 3’ UTRs that exert repression (Pou1f1, Prl, Tshb, and Gnrhr) and the Prop1 3’ UTR that directs translational activation is under investigation. We propose that Musashi acts as a bifunctional regulator of pituitary hormone production and lineage specification and may function to maintain pituitary hormone plasticity in response to changing organismal needs.
Features of Slowly Progressive Type 1 Diabetes Mellitus in Overweight Adolescents
Authors: Romanenkova Elizaveta , Eremina Irina , Zilberman Lubov , Laptev Dmitry , Kuraeva Tamara , Bezlepkina Olga , Peterkova Valentina 
Published: May 2021

Abstract
Background: he obesity epidemic has led to an increase in the incidence of type 1 diabetes mellitus (T1DM) on the background of overweight. The combination of T1DM and obesity can lead to an erroneous diagnosis of type 2 diabetes (T2DM). Methods: The study included 35 adolescents with T1DM. Inclusion criteria were obesity at onset, high titer of diabetes-associated autoantibodies, and insulin requirement less than 0.5 U/kg with a diabetes duration of more than 6 months. We assessed the level of HbA1c, fasting level of insulin and c-peptide, and level during the Mixed-Meal Tolerance Test, the immunological status of GADA, IA-2, ZnT8, ICA. Results: The age of onset was 12.7 years [10.6; 14.5], the tanner stage of puberty was 4 [3; 5]. Sex distribution: boys (n = 25) - 71.5%, girls (n = 10) - 28.5%. HbA1c at the time of onset equaled 8,9% [7.4; 10.45]. Ketosis/diabetic ketoacidosis was registered in 47.8%. The duration of the diabetes was 1.7 years at the moment of examination [0.7; 2.9]. The fasting level of C-peptide - 1.37 mμg/ml [1.0.9; 2.19], insulin level (n = 26) - 13.93 uU/ml [9.57; 19.77]. The maximum level of stimulated secretion of C-peptide (n = 21) - 5.13 mμg/ml [3.05; 6.07], of insulin secretion (n = 21) - 58.59 uU/ml [31.02; 79.74]. Higher HOMA of insulin resistance (n = 25) was detected in 72% of the examined patients. In the study of pancreatic autoantibodies, an increase in ICA was detected in 57% (median of titer 1.68 [0.28;11.7]), IA-2 - 67% (192.8 ME/ml [65; 310.1]), GAD - 59% (90.25 ME/ml [32.27; 214.6]), ZnT8 - 82% (350.5 [90.4; 506.05]). The presence of 2 or more autoantibodies is found in 94% of cases. Dyslipidemia was observed in 34.8%, arterial hypertension was identified in 23% of patients. Received therapy: insulin 82%; metformin 0.02%; metformin + insulin 5.7%. Median daily dose per patient was 0.3 U/kg [0.2; 0.5]. Conclusion: T1DM in adolescents with obesity and overweight has a similar clinical picture both with T1DM (insulin dependence, high titer of autoantibodies, ketosis) and T2DM (slow progression of the disease, low insulin requirement, preserved secretion of c-peptide, and insulin for more than 1.5 years). We hypothesize that obesity and insulin resistance may contribute to DM onset at an earlier date, even if a satisfactory function of pancreatic beta-cells is still preserved. Given that the onset of the disease in our group falls on adolescence it seems that pubertal insulin resistance also contributes to the features of the course of the disease. Understanding the role of obesity in the progression of disorders of carbohydrate metabolism will allow postponing the acute manifestation of the disease and initiation of insulin therapy through lifestyle modifications in patients at risk. A long period of preserved insulin secretion opens up the possibility of new personalized therapies.