Subtyping primary aldosteronism by inconclusive adrenal vein sampling: A derivation and validation study in a tertiary centre.

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.

Gamma-knife radiosurgery in acromegaly: the results from the Croatian acromegaly registry.

PURPOSE: 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. MATERIALS AND METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Open vs laparoscopic adrenalectomy for localized adrenocortical carcinoma.

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.

Diagnostic Performance of 99mTc-Sestamibi SPECT/CT and 18F-Choline PET/CT in Locating Hyperfunctioning Parathyroid Glands in Patients with Primary Hyperparathyroidism.

OBJECTIVE: This study aimed to assess the diagnostic performance of 99mTc-sestamibi SPECT/CT and 18F-choline PET/CT in detecting hyperfunctioning parathyroid glands in patients undergoing surgery for primary hyperparathyroidism (PHPT). METHODS: 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 99mTc-sestamibi SPECT/CT (81 patients) or 18F-choline PET/CT (33 patients) scans before surgery to pinpoint hyperfunctioning parathyroid gland(s). In the majority of patients, 18F-choline PET/CT was performed after negative or inconclusive findings on 99mTc-sestamibi SPECT/CT. Pathohistological reports were utilized as the reference standard for evaluating the accuracy of the imaging findings. RESULTS: 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 99mTc-sestamibi SPECT/CT was 57% (95% CI 45.3-68.1), while the detection rate of 18F-choline PET/CT was 90.3% (95% CI 74.3-98.0). CONCLUSION: The results of our study showed the significant usefulness of 18F-choline PET/CT in patients with negative or inconclusive results of 99mTc-sestamibi SPECT/CT in accurately locating hyperfunctioning parathyroid glands in PHPT patients.

The Effect of Surgeon Expertise on the Outcome of Patients with Adrenocortical Carcinoma.

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%; p = 0.02). Accordingly, RFS was significantly longer in patients operated on in HVC (p = 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; p = 0.03). In addition, there is a tendency towards longer DSS in patients in the HVC group compared to those in the LVC group (p = 0.05). These results point to the centralization of adrenal surgery as a key prerequisite for improving the outcomes of ACC patients.

The clinical course of patients with adrenal incidentaloma: is it time to reconsider the current recommendations?

OBJECTIVE: The current guidelines for the management of adrenal incidentaloma advise hormonal and radiological follow-up of patients for 2-5 years after the initial diagnosis. However, the vast majority of adrenal incidentaloma are non-functional benign cortical adenomas that require no treatment, so the routine application of the current strategies often results in a number of unnecessary biochemical and radiological investigations. The aim of this study was to analyse the clinical course of patients with adrenal incidentaloma and to provide a critical review of the current management strategy of the disease. DESIGN AND METHODS: This was a retrospective study performed in the Croatian Referral Center for adrenal gland disorders. The study included 319 consecutive patients with adrenal incidentaloma, 174 of which were followed for at least 24 months. RESULTS: The vast majority of patients were diagnosed with benign adrenal masses, whereas in about 5% of them adrenal tumor corresponded to adrenal carcinoma or metastasis. Tumor density was found to be superior to tumor size in distinguishing benign adrenal masses from malignant tumors and pheochromocytomas. During the follow-up, no patient demonstrated a clinically significant increase in tumor size. In addition, no changes, either in metanephrines and normetanephrines or in the activity of renin-aldosterone axis, were observed during the follow-up. Six patients developed subclinical Cushing's syndrome (SCS) whereas eight patients with SCS showed biochemical remission during follow-up. CONCLUSION: The study suggests that the risk of an adrenal mass initially diagnosed as benign and non-functional becoming malignant or hormonally active is extremely low. Therefore, the clinical management of those patients should be tailored on an individual basis in order to avoid unnecessary procedures.