bluuebunny/crossref_metadata_2025_split huggingface dataset:
What Does SGLT2 Inhibition Add in Managing Hyponatremia Secondary to Syndrome of Inappropriate Antidiuresis (SIAD)?
Authors: Jalal Fadzliana Hanum , Ibrahim Luqman , Lim Quan Hziung , Chooi Kheng Chiew , Rajendran Santhanaruben , Ratnasingam Jeyakantha , Paramasivam Sharmila Sunita , Vethakkan Shireene Ratna , Lim Lee-Ling 
Published: May 2021

Abstract
Background: Apart from treating the underlying causes, other treatment options for SIAD are of limited success. Drug repurposing of SGLT2 inhibitors for use in SIAD has been suggested. Clinical Case: A 72 years old gentleman with type 2 diabetes mellitus, hypertension, ischemic cardiomyopathy (ejection fraction 40%) and paranoid personality disorder presented with 3-day history of confusion, vomiting and reduced appetite. On examination, he was fully alert, afebrile, blood pressure 173/81 mmHg, heart rate 83 beats per minute and euvolemic. There were fine crackles in the lung bases bilaterally. Random capillary blood glucose level was 5.6 mmol/L (100 mg/dL) and there was no hypoxia. Laboratory results were suggestive of SIAD (serum sodium [Na] 115 mmol/L, serum osmolality 241 mmol/kg, urine osmolarity 458 mmol/kg, spot urine Na 56.7 mmol/L) with normal fT4 (17.6 pmol/L [1.37 ng/dL]), TSH (1.6 mIU/L) and cortisol (821 nmol/L [29.7 mcg/dL]) levels. Medications at admission were daily dosing of olanzapine 7.5 mg, sitagliptin/metformin 50/850 mg, losartan 50 mg, rosuvastatin 10 mg and aspirin 100 mg. Further investigations for causes of SIAD including magnetic resonance imaging of the brain and contrast-enhanced computed tomography of thorax, abdomen and pelvis were normal. He was treated with fluid restriction (1 liter/day) and furosemide (oral 20 mg daily for 2 doses, followed by intravenous 20 mg twice daily for 3 doses) on day 1-4, leading to negative fluid balance (total 3300 ml) with an increment in serum Na to 124 mmol/L on day 5. However, this was accompanied by a reduction in systolic blood pressure (148 to 118 mmHg) and serum potassium level (4.7 to 3.7 mmol/L), along with marked increases in urea (2.7 to 8.8 mmol/L) and creatinine levels (51 to 75 µmol/L) (eGFR from &gt;90 to 87 mL/min/1.73m2). Hence, furosemide was stopped and empagliflozin 12.5 mg daily was initiated on day 5 with continuation of fluid restriction. Serum Na level increased by 2 mmol/L to 126 mmol/L after 12 hours and by 3 mmol/L (to 129 mmol/L) on subsequent day with negative fluid balance (950 ml per 24 hours). Urea and eGFR levels improved and losartan was reintroduced for blood pressure control. There was no euglycemic diabetic ketoacidosis episode. Patient was discharged on day 10 with a serum Na level of 131 mmol/L. Outpatient follow up 5 days after discharge showed further improvement in serum Na level to 134 mmol/L with serum osmolality 286 mmol/kg and urine osmolarity 672 mmol/kg. Clinical Lesson: SGLT2 inhibition can be considered as one of the treatment options of hyponatremia secondary to SIAD with good tolerability
Drug Induced Hyperprolactinemia
Authors: Venkatanarasu Ashok , Boddula Raman , Basavaraju Santosh , Chinte Chimutai , Tickoo Vidya 
Published: May 2021

Abstract
Introduction: Drugs are a common cause of hyperprolactinemia. It is essential to differentiate this cause from other pathological causes which avoids unnecessary investigations. Detailed history will help us in identifying the responsible drug and withdrawing the same will be rewarding. Here we are reporting a case series of drug induced hyperprolactinemia. Methods: It was a cross-sectional observational study. Subjects were recruited from our outpatient department. Hyperprolactinemia was defined as blood prolactin levels &gt;30 ng/mL in females and &gt;24 ng/mL in males, regardless of the presence of symptoms. Serum prolactin was repeated one week after holding the suspected drug(s). Drug induced hyperprolactinemia is defined as normalisation of serum prolactin on discontinuation of the offending drug. Demographics, clinical presentation and offending drug name were entered in pre designed proforma.
Results: Total of 32 subjects were studied in this study with age of 35.5±10.8years. Predominantly female subjects were present with female to male ratio 5.4. Basal prolactin was 132±68.7ng/mL and after holding the drug prolactin value was 16.9±8.2. Proton pump inhibitors in combination with prokinetics were the leading cause (71.8%) and followed by multiple drug combinations (15.6%), anti-psychiatric drugs(9.3%) and oral contraceptives(3.1%). Overall 86.75% of subjects were having symptomatic presentation. Commonest clinical presentation among the women was galactorrhea (88.9% of female subjects) followed by irregular menstrual cycles (59% of female subjects) and breast heaviness in 29.6%. Among the men erectile dysfunction was common presentation, noted among 80% of them. Asymptomatic presentation was there in 6.25% of subjects. All subjects were improved clinically after withdrawal of the the offending drug(s).
Conclusions: Most of the subjects were clinically symptomatic. Most common symptom in female was galactorrhea followed by irregular menses and breast heaviness, and erectile dysfunction in males. All subjects were improved clinically after withdrawal of the offending drug(s). A detailed drug history is rewarding and avoids unnecessary investigations for hyperprolactinemia
Pituitary Stalk Lesions - Single Center Long Term Observation
Authors: Kluczynski Lukasz , Godlewska Magdalena , Rogozinski Damian , Nowak Andrzej Jerzy , Zygmunt-Gorska Agata , Wojcik Malgorzata , Starzyk Jerzy , Hubalewska-Dydejczyk Alicja , Gilis-Januszewska Aleksandra 
Published: May 2021

Abstract
Background & Methods: Pituitary stalk lesions (PSL) are various changes located in the pituitary infundibulum. The underlying pathology and exact diagnosis are difficult to establish due to their unique anatomical locus. A retrospective observational analysis of 60 adult patients (34W/26M) with pituitary lesions was performed. The mean age of diagnosis was 33.8 years (SD 23.7). The etiologies were divided into 3 groups (congenital, inflammatory, neoplastic), classified as exact, probable or unknown and characterized hormonally. Aim: To present the etiological spectrum of pituitary stalk lesions and their clinical and hormonal characteristics on the basis of long term observation in the pediatric/adult endocrinology departments of our university. Results: The most common causes of PSL were neoplasms (20/60, 33.3%, 14W/6M); congenital malformations were detected in 17/60 (28.3%, 6W/11M), while inflammatory etiology was found in 15/60 (25.0%, 9W/6M) of patients. The exact diagnosis was established in 26/60 (43.3%) cases (16 congenital malformations, 6 adenomas, 1 pituitary cancer, 1 craniopharyngioma, 1 germinoma and 1 lymphocytic hypophysitis [LH]). The probable cause was suggested in 26/60 patients (43.3%) - 10 with the suspicion of LH, 4 with histiocytosis, 3 with a metastatic tumor from a disseminated cancer, 3 craniopharyngiomas, 1 posterior pituitary lobe ectopy, 1 prolactinoma, 1 granular cell tumor, 2 adenomas and 1 pituicytoma. The origin of 8/60 PSL (13.3%) remains unknown. During hormonal assessment the most common insufficiency concerned the gonadal axis found in 29/60 (48.3%) of patients, followed by thyroid (26/60, 43.4%), somatotropic (21/60, 35.0%) and adrenal axis (20/60, 33.3%) insufficiencies. Hyperprolactinemia was detected in 20/60 (33.3%) of patients, while diabetes insipidus was confirmed in 15/60 (25%) of cases. 45 patients presented at least 1 hormonal deficit, some of them were transient. In clinical aspect, symptoms associated with hormonal deficits led to the initiation of diagnostic work-up in 29 patients (48.3%; including 15 patients (25.0%) with growth retardation). Neurological symptoms such as headaches, visual disturbances and seizures were seen in 13 patients (21.7%). Polydipsia and polyuria were the primary presentation in 11 cases (18.3%), while 5 cases (8.3%) had a clinical manifestation of hormone overproduction. Incidental diagnosis was seen in 2 female patients (3.3%). Conclusions: The diagnosis, management and treatment of the pituitary stalk lesions remains challenging. Difficulties in establishing the exact diagnosis might also be related to the non-specific, transient characteristics of the symptoms and hormonal insufficiencies. Long term observations might help better the understanding of the disease and result in improvement of management.
Relationship Between 24-Hour Serum LH and Testosterone Concentrations and Their Interrelationships With Other Pituitary Hormones in Healthy Older Men
Authors: van der Spoel Evie , Roelfsema Ferdinand , van Heemst Diana 
Published: May 2021

Abstract
Background: With ageing, LH levels rise while T levels decline in men, although this decline in T levels could also be caused by a change in health status, including body composition, inflammation, and comorbidities. Not only levels of LH and T change with age, but levels of other pituitary hormones also change concomitantly with age. It could be hypothesized that these hormonal changes are synchronized with each other.
Objective: In this study, we aimed to determine the relationship between 24-h serum LH and T concentrations in healthy older men. Besides, we aimed to determine which health factors, including body composition, metabolic and inflammatory markers, and LH-T related markers are associated with the strength of this LH-T relationship. Furthermore, we explored the interrelationships between LH and T with 24-h serum concentrations of GH, TSH, cortisol, and ACTH.
Design: Hormones were measured in serum samples collected every 10 min during 24 h from 20 healthy men, comprising 10 offspring of long-lived families and 10 control subjects, with a mean (SD) age of 65.6 (5.3) years. We performed cross-correlation analyses to assess the relative strength between two 24-h hormone concentration series for all possible time shifts.
Results: A mean (95% confidence interval) maximal correlation coefficient of 0.21 (0.10 – 0.31) at lag time 60 min was found between LH and total T concentrations. Results were comparable for calculated free, bioavailable, or secretion rates of T. Men with strong LH-T cross-correlations had, compared to men with no LH-T relationship, lower fat mass (18.5 (14.9 – 19.7) vs. 22.3 (18.4 – 29.4) kg), waist circumference (93.6 (5.7) vs. 103.1 (12.0) cm), hsCRP levels (0.7 (0.4 – 1.3) vs. 1.8 (0.8 – 12.3) mg/L), IL-6 levels (0.8 (0.6 – 1.0) vs. 1.2 (0.9 – 3.0) pg/mL), and 24-h mean LH levels (4.3 (2.0) vs. 6.1 (1.5) U/L), and stronger LH-T feedforward synchrony (1.5 (0.3) vs. 1.9 (0.2)). Furthermore, T was positively cross-correlated with TSH (0.32 (0.21 – 0.43)), cortisol (0.26 (0.19 – 0.33)), and ACTH concentrations (0.26 (0.19 – 0.32)).
Conclusions: LH concentrations were followed by T concentrations/secretion with a delay of 60 min in healthy older men, which is in line with literature. Men with a strong LH-T relationship had more favorable body composition, inflammatory markers, 24-h mean LH levels, and LH-T feedforward synchrony. In contrast, chronological age and 24-h mean T levels were not associated with the strength of the LH-T relationship. This observation could indicate that LH and health markers play a bigger role in determining the strength of LH-T cross-correlations than T and chronological age. Furthermore, we observed positive correlations between T and TSH, cortisol, and ACTH concentrations. These exploratory analyses could indicate that T and other hormones are driven by a common regulator or that there is crosstalk between these hormones.
Testing of Adrenal Axis Function in Patients With Combined Pituitary Hormone Deficiency Caused by PROP1 Mutation
Authors: Gilis-Januszewska Aleksandra , Rogoziński Damian , Nowak Andrzej Jerzy , Piwońska-Solska Beata , Zygmunt-Górska Agata , Wójcik Małgorzata , Starzyk Jerzy , Hubalewska-Dydejczyk Alicja 
Published: May 2021

Abstract
Background: The mechanism of adrenal axis deterioration in PROP1 mutation remains uncertain and challenging. Aim: The aim of the project was to investigate the adrenal axis function in patients with combined pituitary function deficiency and PROP1 mutation. Methods: We performed the corticotrophin (CRH) stimulation test in 15 patients ((8W/7M) with confirmed CPHD due to the PROP1 mutation. 9/15 were familial cases from four families. Time of observation (ToO) was calculated since the first pituitary axis/ACTH insufficiency has occurred. The results were reported in the group with confirmed Adrenal Insufficiency (AI) and without AI defined as cortisol &gt;18 ug/dl at any point during CRH test. ACTH is reported in pg/ml and cortisol in ug/dl, time of test is given in minutes (0‘, 15’,30’,45’,60’,120’). Results: The mean age of the group was 40,6 ± 12,1 years with mean 34,7 ± 10,3 years of CPHD observation (range 18 – 54 years). The In 5/15 the cortisol response met the criteria excluding AI. Among siblings there were patients both with/without AI. Both subgroups had similar ToO (without AI 35,6 ± 10,0 years vs 34,2 ± 10,3 years with AI). Mean time of AI duration was 15,0 ± 9,3 years. In the group of 5 patients without AI the mean morning cortisol was 12,48 ± 4,31 and ACTH was 31,26 ± 5,43. The mean maximal concentration of cortisol and ACTH were 24,94 ± 3,6 and 123,6 ± 39,9 respectively; Mean increase of cortisol was 12,46 ±4,04 and 92,34±34,48 for ACTH. In 10 patients with AI the mean morning cortisol was 3,33±1,39 and ACTH 22,71±6,75. The mean maximal concentration of cortisol and ACTH were 10,15±4,47 and 97,05 ± 59,15 respectively; Mean increase of cortisol was 6,83 ± 3,41 and 74,35 ± 53,72 for ACTH. For two patients high ACTH increase from 36,7 to 260 and from 28,65 to 112,0 was observed. Analysis of cortisol and ACTH response in both groups revealed that in group without AI the time of peak of ACTH was observed in 15’ (2/5) and 30’ (3/5) vs. in 15’(3/10), 30’(6/10) and 45’ in group with AI. The peak cortisol was observed in 30’, 45’ and 60’ (3/5) in group without AI vs 60’(6/10) or 120’ (4/10) in AI group. The mean maximal increase of ACTH was by 4,09±1,46 and 4,12±1,58 in AI group vs no AI group respectively. Conclusions: In patients with PROP1 mutation the adrenal axis can deteriorate long after other axis insufficiencies, however there are patients with no adrenal insufficiency even during lifelong observation. There is no specific order of deterioration even among affected siblings. In the vast majority of patients independently of cortisol increase there is ACTH response after CRH. Further studies on the pituitary function deterioration in patients with PROP1 mutation should be carried out to understand better the underlying mechanism and to set up the diagnostic timing and procedures.
Vertebral Fractures Occur Regardless of Acromegaly Activity and Are Best Predicted by Proximal Femur Cortical Volumetric Bone Mineral Density
Authors: Kuzma Martin , Vanuga Peter , Sagova Ivana , Pavai Dusan , Jackuliak Peter , Killinger Zdenko , Binkley Neil , Winzenrieth Renaud , Genant Harry K , Payer Juraj 
Published: May 2021

Abstract
Introduction: Vertebral fractures (VFs) in patients with acromegaly are not associated with bone mineral density (BMD) decrease. Previous studies showed impaired trabecular bone parameters among acromegaly patients. However, recent studies suggest that cortical bone could also play a role in VF development. Objective: Evaluate the utility of dual energy x-ray absorptiometry (DXA) BMD and bone structural parameters to determine VF risk among acromegaly patients. Patients and Methods: A single-center two years prospective follow up of acromegaly patients regardless of age, gender, disease activity or associated treatments was conducted. Pituitary hormones, glucose metabolism and bone turnover markers in all subjects were assessed. Each subject had L1-4 spine, femoral neck (FN) and total hip (TH) BMD measured using DXA, and TBS measurement performed ± 7 days from blood sampling. 3D Shaper was used to assess proximal femur trabecular and cortical volumetric (v) BMD, cortical surface (s) BMD and cortical thickness (Cth). VF assessment was performed using the lateral spine imaging IVA™ mode with a Hologic Horizon® densitometer using semi-quantitative approach. Study outcomes were assessed at two time points - baseline and month 24. Results: Seventy subjects (34 M/36F), mean age 55.1 years, including 26 with active disease were studied. After two years a significant decrease in IGF-1 (-30%), osteocalcin (-18%) and TH cortical vBMD (-3%; all p≤0.05) was observed. During follow-up, 13 patients nine of them with controlled disease, developed VF; these patients had greater increase in CTx and decrease in TBS, sBMD, cortical and trabecular vBMD at TH and neck. Multivariate analysis of fracture prediction showed cortical vBMD at TH and neck as best parameters for fracture prediction with AUC 0.766 and 0.774; respectively. TBS was negatively associated with fasting plasma glucose (FPG), HBA1c at each time period. Conclusions: Decrease in cortical vBMD was the most sensitive and specific predictor of incident VF suggesting that cortical bone is involved in fracture development among acromegaly patients. In addition, TBS was strongly negatively associated with glucose metabolism, suggesting glucose intolerance could lead to trabecular bone impairment.
GH Receptor Exon 3 Genotype and Echocardiographic Abnormalities in Patients With Active Acromegaly
Authors: Serrano Karla , Espinosa Etual , Marrero-Rodríguez Daniel , Almeida Eduardo , Silva-Roman Gloria , Peña-Martinez Eduardo , Sosa Ernesto , Mercado Moises 
Published: May 2021

Abstract
Background: The GH receptor (GHR) exon 3 polymorphism occurs at a genomic level. Approximately 50-60% of the population is homozygous for the exon-3 containing genotype (+3/+3), 30-40% are heterozygous (+3/-3) and 10-20% are homozygous for the exon-3 lacking genotype (-3/-3). Some studies suggest that children homo- and heterozygous for the GHR exon 3 lacking genotype (-more efficient 3/-3 and +3/-3, respectively) respond better to treatment with exogenous rhGH and there is also in vitro evidence showing a more efficient signal transduction through this exon 3 deleted isoform. Some studies have found that patients with acromegaly harboring the exon 3-deleted genotype may have a higher prevalence of diabetes and hypertension. Hypothesis and Objective: Patients with active acromegaly harboring the exon 3-lacking GHR genotype may have more echocardiographic abnormalities than those who are homozygous for the exon 3 containing genotype. Patients and Methods: This is a cross-sectional study of patients with active acromegaly, defined by an IGF-1 level &gt; 1.3 times the upper limit of normal (x ULN), who underwent transthoracic echocardiography. Exon-3 GHR genotype was determined by PCR using previously described sense and antisense primers. Results: The cohort consisted of 28 patients, 54% female, with a mean age of 51 ± 12 years. Mean disease duration at the time of echocardiographic examination was 4.48 ± 4.7 years; median basal GH and IGF-1 were 12 ± 26 ng/mL and 2.4 ± 1.04 x ULN. The prevalence of hypertension and diabetes were 43% and 36%, respectively. Fifty three percent of the patients were homozygous for the exon 3-containaing genotype (+3/+3), 18% were homozygous for the exon 3-lacking genotype (-3/-3) and 29% were heterozygous (+3/-3). Clinical and biochemical features did not differ between patients with the different GHR genotypes, except for hypertension that was more prevalent in the +3/+3 genotype group (60% vs 23%, p= 0.04). The frequency of the different echocardiographic parameters was similar among groups (left ventricular hypertrophy 33% vs 15%, p= 0.27; diastolic dysfunction 47% vs 31%, p= 0.39; subclinical systolic dysfunction 42% vs 54%, p= 0.54; left ventricular ejection fraction 59±10% vs 60±16%, p= 0.83); aortic valve abnormalities 19% vs 15%, p=0.63; mitral valve abnormalities 46% vs 15%, p=0.07). Conclusions: Echocardiographic abnormalities in patients with active acromegaly do not differ among patients with the different GHR exon 3 genotypes. The clinical spectrum of acromegaly varies considerably. Although such variability is usually related to the severity of the hypersomatotropinemia, in many patients this is not the case.
USP8 Somatic Mutations in Cushing’s Disease and Silent Corticotropinomas
Authors: Lamback Elisa Baranski , Lima Carlos Henrique de Azeredo , Miranda Renan Lyra , Guterres Alexandro , Andreiuolo Felipe , Wildemberg Luiz Eduardo Armondi , Gadelha Monica Roberto 
Published: May 2021

Abstract
Background: Somatic mutations in the ubiquitin-specific peptidase 8 (USP8) gene have been described in Cushing’s disease (CD). These mutations increase proopiomelanocortin transcription resulting in ACTH production and seem to correlate with somatostatin receptor type 5 (SST5) expression. Aims: Screen USP8 in patients with corticotropinomas and correlate USP8 mutational status with SST5 expression in CD. Methods: Tumor DNA was extracted and then exon 14 amplified by PCR. SST5 was assessed by immunohistochemistry (clone UMB4) and quantified multiplying the percentage of positive cells (0,0%; &lt;10%,1;10-50%, 2; 51-80%, 3; &gt;80%, 4) and intensity (mild, 1; moderate, 2; intense, 3), giving a score (IRS) from 0-12 with ≥ 6 considered high. Results: Among 59 patients, 38 had CD and 21 silent corticotropinomas. In CD, 13 (34.2%) patients had pathogenic mutations (6 had p.Ser719del; 5 had p.Pro720Arg and 2 had p.Pro720Gln). In the mutated CD group, all were women and had median age of 34.5 years (20-46). Median ACTH was 64.7pg/mL [(34.8-330.0), normal &lt;46], urinary free cortisol (UFC) 435.0μg/24h [(87.0-1386.0), normal &lt;100], cortisol after overnight 1mg dexamethasone suppression test (ODST) 17.4μg/dL [(5.0-48.7), normal &lt;1.8], salivary cortisol (SC) 8.1μg/dL [(1.0-15.5), normal &lt;0.35]. Median largest tumor size was 0.9 cm (0-1.9), ki-67 1.7 (0.2-10.0) and IRS 12 (1-12). In wild-type CD group, 19 (76.0%) were women and had median age was 35.0 years old (14-62). Median ACTH was 59.7 (39.0-137.0), UFC 305.8 (77.0-1302.0), cortisol after ODST 23.6 (10.0-33.3), SC 0.67 (0.27-1.28). Median largest tumor diameter 0.7cm (0-3.3), ki-67 1.8 (0.2-10) and IRS 4 (0-12). SC was higher in mutated group compared to wild-type (p=0.001) as well as IRS (p=0.009). In silent corticotropinomas, 2 (9.5%) had pathogenic mutations (1 p.Ser718Pro and 1 p.Pro720Arg): male, 36 years old, 3.2 cm tumor, Ki-67 4%, IRS 6; and female, 52 years old, 3.4 cm tumor, Ki-67 2.5%, IRS 12, respectively. One tumor had a variant not reported as pathogenic (p.Thr739Ala): male, 46 years old, 3.7 cm tumor, Ki-67 0.5%, IRS 0. USP8-wild-type silent corticotropinomas had IRS 0-2. Conclusion: One third of CD patients presented with somatic USP8 mutation. Similar to another study, about 10% of silent corticotropinomas also presented somatic USP8 mutation. Expression of SST5 was high in USP8-mutated CD and higher than wild-type group.