Publications

Autonomous cortisol secretion (ACS) has a relatively high prevalence in patients with primary aldosteronism (PA). There is still a lack of relevant studies to analyze the influence of ACS on diagnosing and managing PA. The objective of the study was to evaluate the influence of ACS on image–adrenal venous sampling (AVS) correlation and the postoperative results. This was a retrospective study using the Taiwan Primary Aldosteronism Investigation database from July 2017 to April 2020, with 327 PA patients enrolled. A total of 246 patients were included in the image–AVS analysis. Patients who had undergone unilateral adrenalectomy and a 12-month follow-up were included in the postoperative analysis. Sixty-five patients (26.4%) had ACS. The image–AVS discordance rate was higher in the ACS group compared to the non-ACS group (75.4% (n = 49) vs 56.4% (n = 102); odds ratio (OR) = 2.37 (CI: 1.26–4.48); P = 0.007). The complete biochemical success rate was higher in the non-ACS group than that in the ACS group (98.1% (n = 51) vs 64.3% (n = 9); OR = 28.333 (CI: 2.954–271.779); P = 0.001). In logistic regression analysis, ACS was the only factor associated with lower biochemical success (OR = 0.035 (CI: 0.004–0.339), P = 0.004). PA patients with ACS have higher image–AVS discordance rate and worse biochemical outcomes after surgery. ACS was the only negative predictor of postoperative biochemical outcomes. Further studies and novel biomarkers for AVS are crucial for obtaining better postoperative outcomes in PA patients with ACS.

Connshing syndrome is a rare disease characterized by mixed overproduction of mineralocorticoids and glucocorticoids from adrenal adenoma. We will describe a clinical case that illustrates a rare combination of aldosterone-cortisol co-secreting formation of the left adrenal gland against a background of bilateral macronodular adrenal hyperplasia, and the role of diagnostic methods in determining appropriate tactics for patient treatment. In January 2022, 49-year-old male was admitted to the Endocrinology Research Centre with complaints of increased blood pressure of 220/110 mm Hg, despite multicomponent antihypertensive therapy. According to the hormonal profile, primary hyperaldosteronism was confirmed (aldosterone 2770 pmol/l was increased, renin 0.5 mU/l, and hypokalemia was 2.71 mmol/l against a background of discontinuation of drugs that affect the renin-angiotensin system). ACTH-independent hypercortisolism was confirmed (cortisol in saliva in the evening was 60.33 nmol/l, dexamethasone suppression test was negative (cortisol was 238.8 nmol/l in the morning), ACTH in the morning was 4.88 pg/ml). Once spironolactone (250 mg per day) was introduced in addition to moxonidine (0.6 mg per day), nifedipine (90 mg per day), doxazosin (6 mg per day), the patient’s blood pressure and potassium was stabilized. As a result of MSCT of the abdominal cavity, the formation 30×35×41 mm in the left adrenal gland and the formation is 32×18×17 mm in the right adrenal gland were observed. The density was 17 HU in the native phase in the left adrenal gland, the absolute washout coefficient was 93%, the density was 9 HU in the native phase in the right adrenal gland, the absolute washout coefficient was 72%. To lateralize the side of aldosterone hyperproduction, adrenal vein sampling was performed. Unilateral hyperproduction of aldosterone on the left was confirmed (selectivity coefficient on the left was 27.5, on the right was 4.2 (both more than 3.0). The lateralizing gradient on the left was 2.8 (more than 2.0). Taking into account hypercortisolemia, a calculation was carried out on plasma normetanephrine levels. Laparoscopic left-sided adrenalectomy was performed in August of 2022. After surgical treatment, spironolactone was discontinued, but the patient was forced to take multicomponent antihypertensive therapy due to nephropathy (C3bA3) and a long history of arterial hypertension due to untimely treatment. Primary hyperaldosteronism is associated with increased cardiovascular risk, and hypercortisolism increases the risk of developing diabetes mellitus and osteoporosis. This case demonstrates the consequences of a late diagnosis of the mixed overproduction of mineralocorticoids and glucocorticoids caused by adrenal adenoma.

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.