Connshing syndrome (CoSh) (adrenal-related synchronous aldosterone (A) and cortisol (C) excess) represents a distinct entity among PA (primary hyperaldosteronisms) named by W. Arlt et al. in 2017, but the condition has been studied for more than 4 decades. Within the last few years, this is one of the most dynamic topics in hormonally active adrenal lesions due to massive advances in steroids metabolomics, molecular genetics from CYP11B1/B2 immunostaining to genes constellations, as well as newly designated pathological categories according to the 2022 WHO classification. In gross, PA causes 4–10% of all high blood pressure (HBP) cases, and 20% of resistant HBP; subclinical Cushing syndrome (SCS) is identified in one-third of adrenal incidentalomas (AI), while CoSh accounts for 20–30% to 77% of PA subjects, depending on the tests used to confirm autonomous C secretion (ACS). The clinical picture overlaps with PA, hypercortisolemia being mild. ACS is suspected in PA if a more severe glucose and cardiovascular profile is identified, or there are larger tumours, ACS being an independent factor risk for kidney damage, and probably also for depression/anxiety and osteoporotic fractures. It seems that one-third of the PA-ACS group harbours mutations of C-related lines like PRKACA and GNAS. A novel approach means we should perform CYP11B2/CYP11B1 immunostaining; sometimes negative aldosteronoma for CYP11B1 is surrounded by micronodules or cell clusters with positive CYP11B1 to sustain the C excess. Pitfalls of hormonal assessments in CoSh include the index of suspicion (check for ACS in PA patients) and the interpretation of A/C ratio during adrenal venous sample. Laparoscopic adrenalectomy is the treatment of choice. Post-operative clinical remission rate is lower in CoSh than PA. The risk of clinically manifested adrenal insufficiency is low, but a synthetic ACTH stimulating testing might help to avoid unnecessary exposure to glucocorticoids therapy. Finally, postponing the choice of surgery may impair the outcome, having noted that long-term therapy with mineralocorticoids receptors antagonists might not act against excessive amounts of C. Awareness of CoSh improves management and overall prognosis.

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The Entity of Connshing Syndrome: Primary Aldosteronism with Autonomous Cortisol Secretion

Macro-PTH, a rare cause of unexplained elevated serum PTH levels

Objective To compare the efficacy and safety between conservative treatment and surgery for the patients with small (1-3cm) nonfunctional adrenal incidentaloma (NFAI). Methods The patients with small (1-3cm) NFAI who received conservative treatment or surgery in our hospital from November 2018 to December 2019 were retrospectively collected. A total of 83 patients were included in this study. They were divided into two groups according to the treatment methods: the surgery group (n=51) and the conservative treatment group (n=32).Then patients’ demographics, tumor characteristics, functional indicators and complications were compared. Statistical analysis was performed using t-test for continuous variables and Pearson chi-square test or Fisher’s exact test for categorical variables. Results At the time of diagnosis, after 3 months, after 6 months, after 12 months, and after 24 months, we found that there was no significant difference between the two groups in systolic blood pressure, diastolic blood pressure, serum potassium levels, and hormone levels. 51 patients chose to have surgery, of which 41 patients chose RLA and 10 patients chose RARLA. RARLA group patients had the highest total cost and conservative treatment group patients had the lowest cost, and the difference was significant (P < 0.001). There was no significant difference in tumor size in the conservative treatment group between at the time of diagnosis and after 24 months (P = 0.305). Conclusion Surgical treatment is more effective for 1-3cm NFAI, but conservative treatment is safer and more economical. Follow-up after conservative or surgical treatment is necessary.

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For small (1-3cm) nonfunctional adrenal incidentaloma (NFAI), which option is more appropriate for conservative treatment or surgery?

Adrenal incidentalomas are a common occurrence. Most of them are adrenocortical adenomas that do not cause harm and do not require surgery, but a non-negligible proportion of incidentalomas is represented by functionally active masses, including cortisol-secreting adenomas (12%), pheochromocytomas (3–6%), aldosterone-secreting adenomas (2–3%), as well as malignant nodules, such as adrenocortical carcinomas (2–5%), which can be either functioning or non-functioning. All patients with an adrenal incidentaloma should undergo a few biochemical screening and confirmatory tests to exclude the presence of a functionally active mass. In this approach-to-the-patient-based review, we will summarize current recommendations on biochemical evaluation and management of functionally active adrenal incidentalomas. For this purpose, we will present four case vignettes, whereby we will describe how patients were managed, then we will review and discuss additional considerations tied to the diagnostic approach, and conclude with practical aspects of patient perioperative management. To improve the perioperative management of patients with functional adrenal incidentalomas, multidisciplinary meetings are advocated.

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S. Lovriha

Papers

Is the Adrenal Incidentaloma Functionally Active? An Approach-To-The-Patient-Based Review

A case report of PTH elevation due to immunoassay interference