Bankstown Hospital - Grand Rounds - Further Reading

Welcome to the Grand Rounds Further Reading List, Endocrinology edition, brought to you by the Clinical Library, on Level 4, next to the Auditorium.

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Gadelha, M., et al. (2023). "Cushing's syndrome." The Lancet 402(10418): 2237-2252  https://doi.org/10.1016/S0140-6736(23)01961-X doi: 10.1016/S0140-6736(23)01961-X.  REQUEST ARTICLE

                Endogenous Cushing's syndrome results from excess glucocorticoid secretion, which leads to a myriad of clinical manifestations, comorbidities, and increased mortality despite treatment. Molecular mechanisms and genetic alterations associated with different causes of Cushing's syndrome have been described in the last decade. Imaging modalities and biochemical testing have evolved; however, both the diagnosis and management of Cushing's syndrome remain challenging. Surgery is the preferred treatment for all causes, but medical therapy has markedly advanced, with new drug options becoming available. Nevertheless, several comorbidities remain even after patient remission, which can affect quality of life. Accurate and timely diagnosis and treatment are essential for mitigating chronic complications of excess glucocorticoids and improving patient quality of life. In this Seminar, we aim to update several important aspects of diagnosis, complications, and treatment of endogenous Cushing's syndrome of all causes.

Isand, K., et al. (2025). "Delphi panel consensus on recommendations for thromboprophylaxis of venous thromboembolism in endogenous Cushing's syndrome: a position statement." European Journal of Endocrinology 192(3): R17-R27  https://doi.org/10.1093/ejendo/lvaf017 REQUEST ARTICLE

The objective of this study was to establish recommendations for thromboprophylaxis in patients with endogenous Cushing's syndrome (CS), addressing the elevated risk of venous thromboembolism (VTE) associated with hypercortisolism. A Delphi method was used, consisting of 4 rounds of voting and subsequent discussions. The panel included 18 international experts from 11 countries and 4 continents. Consensus was defined as ≥75% agreement among participants. Recommendations were structured into the following categories: thromboprophylaxis, perioperative management, and VTE treatment. Consensus was reached on several critical areas, resulting in 14 recommendations. Key recommendations include: thromboprophylaxis should be considered at time of CS diagnosis and continued for 3 months after biochemical remission, provided there are no obvious contraindications. The standard weight-based prophylactic dose of low molecular–weight heparin is the preferred agent for thromboprophylaxis in patients with CS. Additionally, perioperatively and around inferior petrosal sinus sampling, thromboprophylaxis should be reconsidered if not already initiated at diagnosis. For VTE treatment, extended thromboprophylaxis is advised continuing for 3 months after Cushing is resolved. These Delphi consensus-based recommendations aim to standardize care practices and enhance patient outcomes in CS by providing guidance on thromboprophylaxis, including its initiation and continuation across various disease states, as well as the preferred agents to use. The panel also highlighted key areas for further research, particularly regarding the use of direct oral anticoagulants in CS and the management of mild CS and mild autonomous cortisol secretion. Additionally, the optimal duration of anticoagulant prophylaxis following curative treatment remains uncertain.

Nieman, L. K., et al. (2025). "Cushing syndrome." Nature Reviews Disease Primers 11(1): 4  https://doi.org/10.1038/s41572-024-00588-w REQUEST ARTICLE

Cushing syndrome (CS) is a constellation of signs and symptoms caused by excessive exposure to exogenous or endogenous glucocorticoid hormones. Endogenous CS is caused by increased cortisol production by one or both adrenal glands (adrenal CS) or by elevated adrenocorticotropic hormone (ACTH) secretion from a pituitary tumour (Cushing disease (CD)) or non-pituitary tumour (ectopic ACTH secretion), which stimulates excessive cortisol production. CS is associated with severe multisystem morbidity, including impaired cardiovascular and metabolic function, infections and neuropsychiatric disorders, which notably reduce quality of life. Mortality is increased owing to pulmonary emboli, infection, myocardial infarction and cerebrovascular accidents. The clinical presentation is variable and because some CS signs and symptoms are common in the general population, the diagnosis might not be considered until many features have accumulated. Guidelines recommend screening patients with suspected CS with 24-h urine cortisol, bedtime salivary cortisol and/or 1 mg dexamethasone suppression test. Subsequently, determining the aetiology of CS is important as it affects management. The first-line therapy for all aetiologies of endogenous CS is surgical resection of the causal tissue, including corticotroph adenoma or ectopic tumour for ACTH-dependent CS or unilateral or bilateral adrenalectomy for adrenal CS. Second-line therapies include steroidogenesis inhibitors for any cause of CS, pituitary radiation (with or without steroidogenesis inhibitors) for CD, and bilateral adrenalectomy for ACTH-dependent causes of CS.

Ragnarsson, O., et al. (2024). "A clinical perspective on ectopic Cushing’s syndrome." Trends in Endocrinology & Metabolism 35(4): 347-360  https://doi.org/10.1016/j.tem.2023.12.003 doi: 10.1016/j.tem.2023.12.003 REQUEST ARTICLE

About 10?20% of individuals with Cushing?s syndrome (CS) have ectopic CS (ECS), that is, an adrenocorticotropin (ACTH)-producing tumour outside the pituitary gland.ACTH-secreting neuroendocrine neoplasia (NENs) can arise from many organs, although bronchial NEN, small cell lung cancer (SCLC), thymic NEN, pheochromocytoma, and pancreatic NEN are the most common.Patients with ECS frequently present with severe hypercortisolism. The risk of life-threatening complications is high in these cases, and associated with poor prognosis unless the hypercortisolism is prompt relieved.A good outcome in patients with ECS requires a methodical approach, incorporating diagnosis of ECS, tumour localization and resection where possible, and control of the cortisol excess using steroidogenesis inhibitors and/or adrenalectomy as required.

Young, J., et al. (2020). "MANAGEMENT OF ENDOCRINE DISEASE: Cushing’s syndrome due to ectopic ACTH secretion: an expert operational opinion." European Journal of Endocrinology 182(4): R29-R58  https://doi.org/10.1530/EJE-19-0877  REQUEST ARTICLE

Ectopic ACTH syndrome (EAS) is rare but is frequently a severe condition because of the intensity of the hypercortisolism that may be dissociated from the tumoral condition. EAS should often be considered as an endocrine emergency requiring an emergency response both in terms of diagnostic procedures and therapeutic interventions. Patient management is complex and necessitates dual skills, in the diagnosis and treatment of CS and in the specific management of neuroendocrine tumors (NET). Therefore, initial management should be performed ideally by experienced endocrinology teams in collaboration with specialized hormonal laboratory, modern imaging platforms and intensive care units. Diagnostic procedures vary according to the endocrine and tumoral contexts but should be reduced to a minimum in intense hypercortisolism. Preventive and curative treatments of cortisol-induced comorbidities, non-specific management of hypercortisolism and etiological treatments should be considered simultaneously. Therapeutic strategies vary according to (1.) the intensity of hypercortisolism, the general condition of the patient and associated comorbidities and (2.) the tumoral status, ranging from resectable ACTH secreting tumors to non-resectable metastatic endocrine tumors or occult tumors. The ideal treatment is complete excision of the ACTH-secreting tumor that can be performed rapidly or after preoperative preparation using cortisol-lowering drugs. When this is not possible, the therapeutic strategy should be discussed by a multidisciplinary experienced team in a personalized perspective and include variable combinations of pharmacological agents, bilateral adrenalectomy and non-specific tumoral interventions. Here we discuss the diagnosis and therapeutic strategies including the modern, currently available tools and emphasize on the operational effectiveness of care.

. Available via CIAP

• UptoDate: Endocrinology and Diabetes. Available via CIAP (including mobile access).
• Therapeutic Guidelines: Diabetes. Available via CIAP (including mobile access)