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.
Farmakološko liječenje osteoporoze indicirano je kod pacijenata visokog rizika za prijelom kosti kod kojih su isključeni sekundarni uzroci osteoporoze i koji nemaju kontraindikacije za primjenu ...terapije. Danas su nam na raspolaganju: četiri bisfosfonata (alendronat, risedronat, ibandronat i zoledronatna kiselina), humano monoklonalno antitijelo na RANK ligand (denosumab; engl. receptor activator of nuclear factor kappa-B), analog paratiroidnog hormona (PTH, teriparatid) i selektivni modulatori estrogenskih receptora (SERM, raloksifen i bazedoksifen), te dva nova anabolika: analog PTH-sličnog proteina (abaloparatid) i humanizirano monoklonalno antitijelo na sklerostin (romosozumab). Abaloparatid i romosozumab još nisu dostupni u Hrvatskoj, a zoledronatna kiselina nije registrirana za liječenje osteoporoze, no koristi se u svakodnevnoj kliničkoj praksi za ovu indikaciju. Placebo-kontrolirana istraživanja pokazala su kako se farmakološkim liječenjem rizik za vertebralni prijelom može smanjiti za 30 – 70 %, za prijelom kuka do 50 %, a za ne-vertebralni za 15 – 35 %. U pacijenata visokog rizika za prijelom kao inicijalna farmakoterapija savjetuje se antiresorptivna terapija, dok se u onih s teškom osteoporozom i vrlo visokim rizikom za prijelom kao inicijalna terapija savjetuju anabolici. Hormonska terapija (estrogen i kombinacija estrogen/progestin) može se koristiti kod žena s postmenopauzalnom osteoporozom koje imaju perzistentne menopauzalne simptome i ne toleriraju drugu dostupnu terapiju za osteoporozu, uzevši u obzir potencijalne kontraindikacije i rizike. U odabiru optimalne terapije potrebno je u obzir uzeti individualni rizik za prijelom kod svakog pacijenta, te učinkovitost, cijenu, jednostavnost primjene i potencijalne nuspojave pojedinog lijeka.
Complete surgical removal of adrenocortical carcinoma (ACC) represents the only chance of long-term cure. In this study, we compared the long-term outcomes of ACC patients depending on whether they ...had adrenal surgery performed in a high-volume (HVC) or in a low-volume (LVC) center. This retrospective study included 49 patients from the Croatian ACC Registry with the European Network for the Study of Adrenal Tumors (ENSAT) stage I-III ACC, of which 35 underwent surgery in a HVC whereas 14 of them were operated in one of the LVCs. Patients operated in the LVCs had a significantly higher rate of ACC recurrence (57.1% vs. 22.9%;
= 0.02). Accordingly, RFS was significantly longer in patients operated on in HVC (
= 0.04). The difference in RFS remained significant after controlling for age, gender, tumor size, Ki-67 index, Weiss score, and type of surgery (HR 4.55; 95% CI 1.16-17.88;
= 0.03). In addition, there is a tendency towards longer DSS in patients in the HVC group compared to those in the LVC group (
= 0.05). These results point to the centralization of adrenal surgery as a key prerequisite for improving the outcomes of ACC patients.
Objective
Hypercoagulability is a commonly described complication in patients with Cushing’s syndrome. Recent clinical studies have indicated various abnormalities of coagulation and fibrinolysis ...parameters which may be related to that phenomenon. The aim of this study was to investigate the mechanisms underlying the hypercoagulable state in patients with Cushing’s syndrome.
Research methods and procedures
A wide range of serum markers involved in the processes of blood coagulation and fibrinolysis was measured in a group of 33 patients with Cushing’s syndrome and 31 healthy controls. No participant was taking medication which could influence the result or had known diseases, except hypertension and diabetes, which could affect blood coagulation or fibrinolysis parameters.
Results
Patients with Cushing’s syndrome had higher levels of clotting factors II (
P
= 0.003), V (
P
< 0.001), VIII (
P
< 0.001), IX (
P
< 0.001), XI (
P
< 0.001) and XII (
P
= 0.019), protein C (
P
< 0.001), protein S (
P
< 0.001), C1-inhibitor (
P
< 0.001) and plasminogen activator inhibitor-1 (PAI-1) (
P
= 0.004). The activity of fibrinolytic markers, plasminogen (
P
<
0.001), antithrombin (
P
< 0.001) and antithrombin antigen (
P
=
0.001) was also increased in the patient group.
Conclusion
The study has demonstrated hypercoagulability in patients with Cushing’s syndrome manifest as increased prothrombotic activity and compensatory activation of the fibrinolytic system. We propose the introduction of thromboprophylaxis in the preoperative and early postoperative periods, combined with a close follow-up in order to prevent possible thromboembolic events in patients with Cushing’s syndrome.
Background and Importance. In the last eight years temozolomide (TMZ) has been used as the last-line treatment modality for aggressive pituitary tumors to be applied after the failure of surgery, ...medical therapy, and radiotherapy. The objective was to achieve a rapid control of tumor growth and hormone normalization with concurrent chemoradiotherapy in a patient with very aggressive ACTH pituitary adenoma. Clinical Presentation. We describe a patient with an aggressive ACTH-producing adenoma treated with concurrent temozolomide and radiotherapy. The patient suffered from an aggressive ACTH adenoma resistant to surgical and medical treatment. After two months of concurrent temozolomide and radiotherapy, cortisol normalization and significant tumor shrinkage were observed. After 22 months of follow-up, there is still no evidence of tumor recurrence. Conclusion. Concurrent treatment with temozolomide and irradiation appears to be highly effective in the achievement of the tumor volume control as well as in the control of ACTH secretion in aggressive ACTH adenoma.
This study aimed to assess the diagnostic performance of
Tc-sestamibi SPECT/CT and
F-choline PET/CT in detecting hyperfunctioning parathyroid glands in patients undergoing surgery for primary ...hyperparathyroidism (PHPT).
A retrospective analysis was conducted on patients who underwent PHPT-related surgery between April 2019 and May 2022. The study focused on patients undergoing either
Tc-sestamibi SPECT/CT (81 patients) or
F-choline PET/CT (33 patients) scans before surgery to pinpoint hyperfunctioning parathyroid gland(s). In the majority of patients,
F-choline PET/CT was performed after negative or inconclusive findings on
Tc-sestamibi SPECT/CT. Pathohistological reports were utilized as the reference standard for evaluating the accuracy of the imaging findings.
The study encompassed 83 patients (70 females, 84.3%) with an average age of 57.2 years (24-80 years). The pathohistological analysis identified a total of 98 glands. In a per-lesion analysis, the detection rate of
Tc-sestamibi SPECT/CT was 57% (95% CI 45.3-68.1), while the detection rate of
F-choline PET/CT was 90.3% (95% CI 74.3-98.0).
The results of our study showed the significant usefulness of
F-choline PET/CT in patients with negative or inconclusive results of
Tc-sestamibi SPECT/CT in accurately locating hyperfunctioning parathyroid glands in PHPT patients.
Diabetes mellitus (DM) can lead to the development of macro- and microvascular complications. Homocysteine (Hcy) may play a role in the development of cardiovascular (CV) diseases (CVDs). The role of ...Hcy in the development of the vascular complications associated with DM is not clearly defined. Despite a strong initial assumption regarding the importance of Hcy in DM and its complications, over time “enthusiasm has waned” because several studies showed unconvincing and occasionally contradictory results. A universal conclusion is not easy to draw given the diversity of studies (e.g. number of patients, design, folic acid and vitamin B status, ethnic differences, genetic background). For some complications, most results encourages further investigation. Impaired renal function is a major independent determinant of high total Hcy (tHcy) levels. However, the role of hyperhomocysteinaemia (HHcy) in the development of diabetic kidney disease (DKD) has yet to be determined. Hcy-lowering therapies can significantly decrease Hcy levels but their effects on CVD risk reduction are conflicting. Further studies are needed to determine the influence of Hcy-lowering therapy on CVD risk reduction, especially in patients with DM.
•Homocysteine metabolism may be modulated by insulin and glucose.•The regulation of enzymes involved in homocysteine metabolism in diabetes is complex.•Homocysteine as a risk factor in diabetes requires reassessment.
Objective
Indices based on aldosterone/cortisol (A/C) concentration in the successfully cannulated adrenal vein (AV) and in the inferior vena cava (IVC) (AV/IVC) appear to be possible markers to ...verify the subtype of primary aldosteronism (PA) in the case of inconclusive results of adrenal vein sampling (AVS). The variability of results in previous studies encouraged us to calculate AV/IVC and adrenal A/C cutoff values that could predict the aetiology of PA.
Methods
This retrospective study included 96 patients who underwent AVS due to PA between 2015 and 2020. The derivation cohort ultimately consisted of 60 patients with bilaterally successful AVS and a clear diagnosis of unilateral or bilateral disease. Receiver operating characteristic analysis was used to find the optimal A/C and AV/IVC cutoff values predicting the subtype of PA. The validation cohort consisted of 11 patients with either unsuccessful cannulation or a borderline lateralization index (LI), those patients underwent adrenalectomy because their indices were suggestive of unilateral disease based on the derivation cohort data.
Results
The cutoff values of A/C ≤ 0.63 or AV/IVC ≤ 0.37 identified unaffected glands with a sensitivity of 91.2% and 97.1%, respectively, and a specificity of 90.7% and 88.4%, respectively. Unilateral ipsilateral gland involvement was characterized by A/C ≥ 3.5 or AV/IVC ≥ 3.4 with a corresponding specificity of 100%. All patients in the validation cohort achieved biochemical remission postoperatively.
Conclusions
A/C and AV/IVC cutoff values could be a useful tool to determine the subtype of PA in patients with unilateral successful AVS as well as in patients with a borderline LI.
Objective
The purpose of the study was to compare the long‐term outcomes of patients with localized adrenocortical carcinoma (ACC) subjected to open vs laparoscopic surgery.
Design
Retrospective ...study.
Patients
This retrospective study included 46 patients with the ACC ENSAT stage I‐stage III of whom 23 underwent open surgery (OA group), whereas 23 were subjected to laparoscopic adrenalectomy (LA group). The main outcomes analysed in the study were differences between the OA and LA groups in recurrence‐free survival (RFS) and overall survival (OS).
Results
Patients in OA group had larger tumours (120 70‐250 mm vs 75 26‐110 mm; P < .001), higher Ki‐67 index (16 1‐65 % vs 10 1‐25 %; P = .04) and higher disease stage (P = .01) compared with the patients in the LA group. The median duration of follow‐up for patients underwent OA and LA was 51 (12‐174) and 53 (5‐127) months, respectively. Eight patients (5 OA and 3 LA) experienced recurrent disease, whereas six patients (3 OA and 3 LA) died during follow‐up. No differences in RFS and OS were found between patients who underwent open or laparoscopic surgery.
Conclusion
The study demonstrated that in patients with localized ACC and without invasion of extra‐adrenal tissues, LA is a plausible treatment option in terms of RFS and OS. However, our results are limited to referral centres with large experience in the management of patients with ACC and may not necessarily apply to nonspecialized centres.
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