Purpose
The aim of this study was to review therapeutic outcomes of the medical treatment of patients with acromegaly based on real-world data from the Croatian Acromegaly Registry.
Methods
In this ...retrospective study we investigated 163 patients (101 female, 62 male, age at diagnosis 47.2 ± 13.4 years) treated between 1990 and 2020, of which 53 were treated medically (32.5%). The duration of follow-up was 115.8 ± 304.4 months. The remission rate after the pituitary surgery was achieved in 66.5% (
n
= 105/158; 5 patients refused surgery). Patients who did not achieve disease remission or had a relapse during follow-up (
n
= 2), underwent reoperation (
n
= 18/60, 30%) and/or radiotherapy (
n
= 33/60, 55%) and/or medical treatment (
n
= 53/60, 88.3%). One patient refused further treatment after the failure of the first pituitary surgery.
Results
Out of 53 patients treated with medical therapy, monotherapy was used in 34 (64.2%) and combination therapy in 19 (35.8%) patients. Remission (IGF-I < 1.2 upper limit of normal, ULN) was achieved in 51 patients (96.2%). Out of 53 patients, 21 (39.6%) were treated with first-generation somatostatin receptor ligand (SRL-1) monotherapy, 10 (18.9%) with dopamine agonist (DA) monotherapy, one (1.9%) with pegvisomant monotherapy, 13 (24.4%) with a combination of SRL-1 and DA, three (5.7%) with a combination of SRL-1, DA and pegvisomant, two (3.8%) with a combination of second-generation somatostatin receptor ligand (SRL-2), DA and pegvisomant and in one (1.9%) temozolomide was added on top of SRL-1 and DA. Two patients currently have active disease, both on SRL-1 monotherapy, of whom one is non-adherent to the treatment. Radiotherapy was applied to 27 (50.9%) patients on medical therapy.
Conclusion
Our results indicate that almost all patients with active acromegaly after pituitary surgery can achieve biochemical control with medical treatment.
The aim is to present our case series documenting indications, laparoscopic technique, surgical and endocrinologic outcomes of laparoscopic partial adrenalectomy. In the period from April 2011 until ...October 2021, we performed 39 procedures. The patients were divided into three groups: unilateral adrenal gland tumor with a normal contralateral gland (group 1), tumor of the solitary adrenal gland (group 2), and adrenal cysts (group 3). There were 20 patients in group 1, 6 patients in group 2, and 13 patients in group 3. The most common histology in group 1 was adenoma (40%), all tumors in group 2 were renal cell carcinoma metastases, and all cysts in group 3 were benign. There were no major complications (Clavien Dindo grade ≥2) in the whole cohort. All patients in groups 1 and 3 had favorable endocrinologic outcomes, and 50% of group 2 patients required lifelong hydrocortisone replacement therapy. The procedure is safe and feasible with favorable outcomes in the hands of a high volume adrenal surgeon.The aim is to present our case series documenting indications, laparoscopic technique, surgical and endocrinologic outcomes of laparoscopic partial adrenalectomy. In the period from April 2011 until October 2021, we performed 39 procedures. The patients were divided into three groups: unilateral adrenal gland tumor with a normal contralateral gland (group 1), tumor of the solitary adrenal gland (group 2), and adrenal cysts (group 3). There were 20 patients in group 1, 6 patients in group 2, and 13 patients in group 3. The most common histology in group 1 was adenoma (40%), all tumors in group 2 were renal cell carcinoma metastases, and all cysts in group 3 were benign. There were no major complications (Clavien Dindo grade ≥2) in the whole cohort. All patients in groups 1 and 3 had favorable endocrinologic outcomes, and 50% of group 2 patients required lifelong hydrocortisone replacement therapy. The procedure is safe and feasible with favorable outcomes in the hands of a high volume adrenal surgeon.
The purpose of the present study was to analyze the impact of the neutrophil-lymphocyte ratio (NLR) on the long-term outcomes of patients with adrenocortical carcinoma (ACC).
This retrospective, ...single-institution study included 48 patients with the diagnosis of ACC. The primary outcomes of the study were differences in overall survival (OS) and disease-specific survival (DSS) with respect to the NLR level.
Patients with ENSAT stage IV had higher levels of NLR compared to those with ENSAT stage I-III (5.7 (1.6-12.5) vs 3.3 (1.3-11); p = .01). A higher NLR was also observed among patients with cortisol-secreting tumors (4.6 (1.7-12.5) vs 2.8 (1.3-10.3); p = .003) and those with Ki-67 index >10% (4.3 (1.3-12.5) vs 2.6 (1.6-11.0); p = .005). With respect to survival, the univariate analysis revealed worse ACC-related survival (p = .02) and OS (p = .004) in patients with NLR >3.9 than in those with NLR ≤3.9. In addition, patients with NLR >3.9 had a higher Weiss score (p = .046), a higher Ki-67 index (p = .006) and a higher disease stage (p = .01) compared to patients with NLR ≤3.9. No differences between the groups were observed regarding excess glucocorticoid secretion.
The study demonstrated that a higher NLR level in ACC patients was associated with unfavorable outcomes in terms of DSS and OS. These results indicate that NLR might be used as an additional marker in ACC risk stratification and identification of patients with the most adverse prognosis.
Abstract
Context
Pathogenesis of autonomous steroid secretion and adrenocortical tumorigenesis remains partially obscure.
Objective
To investigate the relationship between transcriptome profile and ...genetic background in a large series of adrenocortical tumors and identify new potential pathogenetic mechanisms.
Design
Cross-sectional study.
Setting
University Hospitals of the European Network for the Study of Adrenal Tumors (ENSAT).
Patients
We collected snap-frozen tissue from patients with adrenocortical tumors (n = 59) with known genetic background: 26 adenomas with Cushing syndrome (CS- cortisol-producing adenoma CPA), 17 adenomas with mild autonomous cortisol secretion (MACS-CPAs), 9 endocrine-inactive adenomas (EIAs), and 7 adrenocortical carcinomas (ACCs).
Intervention
Ribonucleic acid (RNA) sequencing.
Main Outcome Measures
Gene expression, long noncoding RNA (lncRNA) expression, and gene fusions. Correlation with genetic background defined by targeted Sanger sequencing, targeted panel- or whole-exome sequencing.
Results
Transcriptome analysis identified 2 major clusters for adenomas: Cluster 1 (n = 32) mainly consisting of MACS-CPAs with CTNNB1 or without identified driver mutations (46.9% of cases) and 8/9 EIAs; Cluster 2 (n = 18) that comprised CP-CPAs with or without identified driver mutation in 83.3% of cases (including all CS-CPAs with PRKACA mutation). Two CS-CPAs, 1 with CTNNB1 and 1 with GNAS mutation, clustered separately and relatively close to ACC. lncRNA analysis well differentiate adenomas from ACCs. Novel gene fusions were found, including AKAP13-PDE8A in one CS-CPA sample with no driver mutation.
Conclusions
MACS-CPAs and EIAs showed a similar transcriptome profile, independently of the genetic background, whereas most CS-CPAs clustered together. Still unrevealed molecular alterations in the cAMP/PKA or Wnt/beta catenin pathways might be involved in the pathogenesis of adrenocortical tumors.
Abstract
Context
Urine steroid metabolomics, combining mass spectrometry-based steroid profiling and machine learning, has been described as a novel diagnostic tool for detection of adrenocortical ...carcinoma (ACC).
Objective, Design, Setting
This proof-of-concept study evaluated the performance of urine steroid metabolomics as a tool for postoperative recurrence detection after microscopically complete (R0) resection of ACC.
Patients and Methods
135 patients from 14 clinical centers provided postoperative urine samples, which were analyzed by gas chromatography–mass spectrometry. We assessed the utility of these urine steroid profiles in detecting ACC recurrence, either when interpreted by expert clinicians or when analyzed by random forest, a machine learning-based classifier. Radiological recurrence detection served as the reference standard.
Results
Imaging detected recurrent disease in 42 of 135 patients; 32 had provided pre- and post-recurrence urine samples. 39 patients remained disease-free for ≥3 years. The urine “steroid fingerprint” at recurrence resembled that observed before R0 resection in the majority of cases. Review of longitudinally collected urine steroid profiles by 3 blinded experts detected recurrence by the time of radiological diagnosis in 50% to 72% of cases, improving to 69% to 92%, if a preoperative urine steroid result was available. Recurrence detection by steroid profiling preceded detection by imaging by more than 2 months in 22% to 39% of patients. Specificities varied considerably, ranging from 61% to 97%. The computational classifier detected ACC recurrence with superior accuracy (sensitivity = specificity = 81%).
Conclusion
Urine steroid metabolomics is a promising tool for postoperative recurrence detection in ACC; availability of a preoperative urine considerably improves the ability to detect ACC recurrence.
Summary
Objective
Hypercoagulability is a commonly described complication in patients with Cushing's syndrome (CS). The aim of this study was to assess the long‐term effects of surgical remission ...from CS on serum levels of coagulation and fibrinolytic markers.
Design and methods
Eighteen patients with active CS (16 women, 2 men; age: 38·6 ± 13·7 years) were enrolled in the study. We measured serum levels of coagulation and fibrinolytic markers during active CS and 6 months after remission. The control group comprised 18 age‐ and sex‐matched healthy individuals.
Results
Six months after remission from CS, patients had lower levels of factors II (P < 0·001), V (P = 0·02), XI (P = 0·04) and XII (P < 0·001), protein C (P < 0·001), protein S (P = 0·002), antithrombin (P = 0·03), antithrombin Ag (P = 0·008), plasminogen (P = 0·03) and C1 inhibitor (P = 0·001), and aPTT was longer than at enrolment (P = 0·001). Levels of PAI‐1 and factors VII, VIII and IX tended to normalize, but there were no significant differences in these parameters before and after surgery, nor were differences found in haemostatic and fibrinolytic markers between the patients in remission and control individuals, except for factor XII (P = 0·02) and protein C (P = 0·004), which were lower among patients in remission.
Conclusion
Six months after remission from CS, patients' risk of thromboembolism is comparable to that of healthy individuals.
The aim of our study was to evaluate the efficacy and safety of Leksell gamma-knife radiosurgery in the treatment of residual growth hormone-secreting pituitary adenomas after the surgery.
We ...conducted a retrospective analysis of 23 acromegaly patients treated with gamma-knife radiosurgery between 1996 and 2019. The therapeutic success of radiosurgery was defined as IGF-1 normalization without suppressive medication (complete response) or as IGF-1 normalization with medication (partial response).
The median follow-up was 57 (10-198) months. Complete response was achieved in 11 patients (47.8%) with actuarial remission rates of 17.4%, 26.1%, 39.1% and 47.8% at 1, 2, 4, and 7 years, respectively. The median time to complete the response was 21 (6-85) months. Partial response was achieved in another nine patients (39.1%) after a median time of 48 (6-144) months from radiosurgery. Patients who achieved complete remission had significantly lower IGF-1 levels before radiosurgery (p = 0.016) as well as smaller tumour volume (p = 0.016) and radiologically less invasive tumours (p = 0.022) in comparison to patients who did not achieve IGF-1 normalization. Tumour growth control after radiosurgery was established in all patients. During the follow-up, new hormone deficiencies were found in seven patients (30.4%) which corresponds to the incidence of one new case of hypopituitarism per 7.1 patient years.
Gamma-knife radiosurgery offers endocrine remission and tumour growth control in a substantial proportion of patients with GH-secreting adenomas. Given the high cost of life-long medical treatment and a moderate risk of radiation-induced side effects, radiosurgery for growth hormone-secreting pituitary adenomas should be considered in all patients with residual tumours.
Context:
Adrenocortical adenomas (ACAs) are among the most frequent human neoplasias. Genetic alterations affecting the cAMP/protein kinase A signaling pathway are common in cortisol-producing ACAs, ...whereas activating mutations in the gene encoding β-catenin (CTNNB1) have been reported in a subset of both benign and malignant adrenocortical tumors. However, the molecular pathogenesis of most ACAs is still largely unclear.
Objective:
The aim of the study was to define the genetic landscape of sporadic unilateral ACAs.
Design and Setting:
Next-generation whole-exome sequencing was performed on fresh-frozen tumor samples and corresponding normal tissue samples.
Patients:
Ninety-nine patients with ACAs (74 cortisol-producing and 25 endocrine inactive) negative for p.Leu206Arg PRKACA mutation.
Main Outcome Measures:
Identification of known and/or new genetic alterations potentially involved in adrenocortical tumorigenesis and autonomous hormone secretion, genotype-phenotype correlation.
Results:
A total of 706 somatic protein-altering mutations were detected in 88 of 99 tumors (median, six per tumor). We identified several mutations in genes of the cAMP/protein kinase A pathway, including three novel mutations in PRKACA, associated with female sex and Cushing's syndrome. We also found genetic alterations in different genes involved in the Wnt/β-catenin pathway, associated with larger tumors and endocrine inactivity, and notably, in many genes of the Ca2+-signaling pathway. Finally, by comparison of our genetic data with those available in the literature, we describe a comprehensive genetic landscape of unilateral ACAs.
Conclusions:
This study provides the largest sequencing effort on ACAs to date. We thereby identified somatic alterations affecting known and novel pathways potentially involved in adrenal tumorigenesis.
This study provides the largest DNA sequencing effort in adrenocortical adenomas up to now. Somatic alterations in known and novel pathways potentially involved in adrenal tumorigenesis are reported.
Ginekomastijom nazivamo povećanje dojke u muškaraca uzrokovano proliferacijom žljezdanog tkiva. Posljedica je poremećenog omjera estrogena i androgena u plazmi ili lokalno u žljezdanom tkivu dojke. ...Uzroci ginekomastije uglavnom su benigni. Fiziološka ginekomastija česta je pojava i nalazimo ju u novorođenčadi, u pubertetu i u starijoj dobi. Nefiziološka ginekomastija može nastati kao posljedica raznih kroničnih bolesti (npr. hipogonadizam, ciroza jetre, zatajenje bubrega), upotrebe lijekova ili drugih tvari i, rijetko, tumora. Obradu započinjemo pažljivim uzimanjem anamneze i fizikalnim pregledom, nakon čega, prema potrebi, obradu proširujemo ciljanim radiološkim i laboratorijskim pretragama. Terapija ginekomastije temelji se na liječenju bolesti koja ju je uzrokovala, odnosno prekidu primjene lijekova/tvari koji su je potencijalno izazvali.
Risk factors for increased mortality in hip fracture patients include older age, male sex, fracture type, bone mineral density, and pre-existing co-morbidities. The role of biochemical and other ...anthropometric parameters on hip fracture mortality remains unclear. The aim of this study was to identify the risk factors for one-year mortality in patients with hip fractures. A total of 236 consecutive patients (59 males) with hip fractures were followed over a one-year period. Patient age, gender, type of fracture, type of treatment, time from admission to surgery, type of anesthesia, body mass index, and electrocardiograms were recorded. Complete blood counts, serum electrolytes, urea, creatinine, d-dimers, calcium, phosphate, osteocalcin, and beta-isomerised C-terminal telopeptide of collagen type I (β-CTX) were measured at admission and estimated glomerular filtration rate (eGFR) was calculated. Multivariate Cox regression models were used to analyze the association of these parameters with survival. One-year mortality rate was 28.4 %. Age was independently associated with mortality (HR 1.117, 95 % CI 1.062–1.174,
P
< 0.001). In a multivariable model, mortality was increased in patients with higher β-CTX (HR 4.63 95 % CI 1.87–11.45,
P
= 0.001) and lower eGFR (HR 0.972, 95 % CI 0.956–0.987,
P
< 0.001). Patients younger than 84 years, with eGFR < 55.4 ml/min had ten times higher mortality rates (3.2 vs. 24.5 %, HR 9.73, 95 % CI 2.06–45.93) as well as those with β-CTX > 0.276 g/L (3.5 vs. 25.7 %, HR 9.5, 95 % CI 2.11–42.76). Advanced age, high β-CTX levels, and impaired renal function are independent risk factors of mortality in patients with hip fractures.
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