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

Abstract

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.

Multiple pathological fractures and muscle atrophy caused by a parathyroid carcinoma with postoperative hungry bone syndrome: A case report

“…HBS is a rare postoperative complication in some patients with PHPT, and the mechanism is the action of osteoclasts after radical resection of PC. 5,14 After radical resection of PC, the sudden decrease of PTH, which acts on bone resorption of osteoclasts does not affect the process of osteogenesis of osteoblasts; osteoclasts activity is replaced by osteoblasts activity, resulting in a rapid increase of calcium uptake, which leads to a large amount of serum calcium into the bone and deposit in the bone tissues, inducing severe symptomatic hypocalcemia such as numbness of perioral sites and fingertips, tetany, and even dyspnea. Studies have been reported currently that risk factors of occurrence of HBS include high PTH with a previous long-term elevated concentration, high calcium levels, and excessive ATP elevation, and so forth.…”

“…Studies have been reported currently that risk factors of occurrence of HBS include high PTH with a previous long-term elevated concentration, high calcium levels, and excessive ATP elevation, and so forth. 5,15,16 Active preoperative measures may reduce the incidence of postoperative HBS, Davenport and Stearns reported that preoperative pamidronate in combination with high doses of oral alfacalcidol and calcium supplements can prevent postoperative symptomatic hypocalcemia and help to prevent the occurrence of HBS. 17 In our case, the patient was given intravenous zoledronic acid combined with oral calcitriol before the operation in order to prevent the occurrence of HBS after parathyroid surgery since he had the above high-risk factors of postoperative HBS.…”

“…3 Hungry bone syndrome (HBS), a serious complication after parathyroid surgery, characterized by severe hypocalcemia following parathyroidectomy due to rapid drop of PTH after a previous long-term elevated concentration and associated bone remineralization, usually accompanied by hypophosphatemia and hypomagnesemia. 4,5 So far, few cases of PC with muscle atrophy as the main symptom have been reported. Here, we present a PC patient with multiple pathological fractures and muscle atrophy as main symptoms and preoperative HBS complicated by parathyroidectomy.…”

Editorial: Case reports in hypertension: 2022

“…The disease has been studied for more than 40 years. Recently, this has become one of the most dynamic topics in hormonally active adrenal lesions due to significant progress in steroid metabolomics, molecular genetics of the immune CYP11B1/B2 gene constellation, and newly developed pathological types in the 2022 WHO classification ( 6 ). Lihua Hu et al described the management of a 49-year-old woman with coexisting primary aldosteronism (PA) and subclinical Cushing's syndrome due to a right adrenal adenoma.…”

Endocrine Hypertension: The Urgent Need for Greater Global Awareness

“…Co-secretion of aldosterone and cortisol from an adrenal tumour can lead to the development of Connshing (CoSh) syndrome. 60 ACTH dependent and independent CS can rarely co-exist. 61 Though the common components of Multiple Endocrine Neoplasia 2 (MEN2) are primary hyperparathyroidism, PCC, and medullary thyroid cancer, it can rarely cause ACTH dependent CS (both Cushing' disease and ectopic ACTH or CRH secretion).…”