Among the adrenal causes of Cushing’s syndrome, unilateral diseases like adenoma and carcinoma account for most cases. Other causes include bilateral diseases like primary pigmented nodular adrenal dysplasia (PPNAD), MAS and ACTH-independent adrenal hyperplasia (AIMAH). PPNAD is usually associated Carney complex with an inactivating mutation of the PRKAR1A gene. AIMAH occurs as a result of the expression of legitimate and illegitimate receptors on the adrenal gland which respond to their respective ligands causing excessive cortisol secretion. Recently, an inactivating mutation in the ARMC5 tumour suppressor gene has been identified in a subset of patients with AIMAH.
Ectopic ACTH secretion causing Cushing’s syndrome is a para-neoplastic manifestation, commonly occurring with small-cell lung cancer, bronchial and thymic NET among other tumours. Ectopic Corticotropin-releasing hormone (CRH) secretion is very rare which can also lead to Cushing’s syndrome.
The clinical manifestations of Cushing’s syndrome can range from mild to severe involvement of multiple tissues and can be non-specific. Common features include truncal obesity, moon facies, increased fat in the dorsocervical area, ecchymoses, plethora, striae, proximal muscle weakness, thin skin, pigmentation of the skin, osteopenia/ osteoporosis with fractures, avascular necrosis of bone, mood changes, hypertension, impairment of glucose tolerance or worsening of glycemic control, susceptibility to infections, edema, deep vein thrombosis/ pulmonary thromboembolism. Women can present with irregular menstrual cycles and features of hyper- androgenism.
Author(s) Details:
Santosh B
Department of Endocrinology, Yashoda Hospital, Secunderabad, Telangana, India.
Raman Boddula
Department of Endocrinology, Yashoda Hospital, Secunderabad, Telangana, India.
Ashok Venkatanarasu
Department of Endocrinology, Yashoda Hospital, Secunderabad, Telangana, India.
Aditya Hegde
Department of Endocrinology, Yashoda Hospital, Secunderabad, Telangana, India.
Chimutai Chinte
Department of Endocrinology, Yashoda Hospital, Secunderabad, Telangana, India.
Vidya Tickoo
Department of Endocrinology, Yashoda Hospital, Secunderabad, Telangana, India.
Recent Global Research Developments in Adrenal and Ectopic Causes of Cushing’s Syndrome: Clinical Features and Insights
Global Epidemiology of Cushing’s Disease:
A systematic review and meta-analysis highlighted the global epidemiology of Cushing’s disease, which is primarily caused by ACTH-secreting pituitary adenomas. The study found a pooled prevalence of 2.2 per 100,000 and an incidence rate of 0.24 per 100,000 person-years [1] .
ESE Clinical Update on Cushing’s Syndrome 2021:
This report from the European Society of Endocrinology covers various aspects of Cushing’s Syndrome, including diagnostic dilemmas, management strategies, and future challenges. It emphasizes the importance of accurate diagnosis and the management of both adrenal and ectopic causes [2] .
Latest Insights into Cushing’s Syndrome:
This research topic explores the diverse causes of adrenal Cushing’s Syndrome, including adrenal carcinoma and hyperplastic syndromes. It discusses the broad clinical spectrum of the disease, which can affect multiple systems such as diabetes, hypertension, and psychiatric disorders [3] .
Ectopic Corticotropin Secretion:
A study on ectopic ACTH secretion from non-pituitary tumors, which accounts for about 10% of Cushing’s Syndrome cases. This research provides insights into the clinical features and challenges in diagnosing ectopic Cushing’s Syndrome [4] .
Management of Ectopic ACTH Syndrome:
This article discusses the management of ectopic ACTH syndrome, including medical and surgical options. It highlights the importance of a multidisciplinary approach to effectively manage this condition [2] .
References
- Giuffrida, G., Crisafulli, S., Ferraù, F. et al. Global Cushing’s disease epidemiology: a systematic review and meta-analysis of observational studies. J Endocrinol Invest 45, 1235–1246 (2022). https://doi.org/10.1007/s40618-022-01754-1
- ESE Clinical Update on Cushing’s Syndrome 2021
https://www.ese-hormones.org/media/z1el5vx4/ese-cu-cushings-webinar-report_v13-web.pdf - Latest Insights into Cushing’s Syndrome
- https://www.frontiersin.org/research-topics/47164/latest-insights-into-cushings-syndrome/magazine
- Ioannis Ilias, David J. Torpy, Karel Pacak, Nancy Mullen, Robert A. Wesley, Lynnette K. Nieman, Cushing’s Syndrome Due to Ectopic Corticotropin Secretion: Twenty Years’ Experience at the National Institutes of Health, The Journal of Clinical Endocrinology & Metabolism, Volume 90, Issue 8, 1 August 2005, Pages 4955–4962, https://doi.org/10.1210/jc.2004-2527
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