An update on adrenal endocrinology: significant discoveries in the last 10 years and where the field is heading in the next decade
Open accessAbstract
The last 10 years have produced an amazing number of significant discoveries in the field of adrenal endocrinology. The development of the adrenal gland was linked to specific molecules. Cortisol-producing lesions were associated mostly with defects of the cyclic AMP (cAMP) signaling pathway, whereas aldosterone-producing lesions were found to be the result of defects in aldosterone biosynthesis or the potassium channel KCNJ5 and related molecules. Macronodular adrenal hyperplasia was linked to ARMC5 defects and new genes were found to be involved in adrenocortical cancer (ACC). The succinate dehydrogenase (SDH) enzyme was proven to be the most important molecular pathway involved in pheochromocytomas, along with several other genes. Adrenomedullary tumors are now largely molecularly elucidated. Unfortunately, most of these important discoveries have yet to produce new therapeutic tools for our patients with adrenal diseases: ACC in its advanced stages remains largely an untreatable disorder and malignant pheochromocytomas are equally hard to treat. Thus, the challenge for the next 10 years is to translate the important discoveries of the previous decade into substantial advances in the treatment of adrenal disorders and tumors.
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KCNJ5 mutations lead to increased sodium conductance and cellular depolarization, leading to calcium influx, increased intracellular calcium signaling, and increased CYP11B2 mRNA expression with increased aldosterone production and glomerulosa cell proliferation.
“These mutations lead to increased sodium conductance and cellular depolarization leading to calcium influx, increased intracellular calcium signaling, and increased CYP11B2 mRNA expression with increased aldosterone production and glomerulosa cell proliferation (123).”
From Adrenal incidentaloma (2020) · cites this paper as [123]
Mutations in VHL, RET, NF1, SDHB, and SDHD account for 90% of all pheochromocytomas and paragangliomas.
“Mutations in VHL, RET, NF1, SDHB, and SDHD account for 90% of all pheochromocytomas and paragangliomas (123).”
From Adrenal incidentaloma (2020) · cites this paper as [123]
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References 105 · Cited by 7
Research works printed but not linked: 1
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- Authors
- Kamilaris, C. D. C., & Stratakis, C. A.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Stratakis, Constantine A.
- Venue
- HORMONES
- Published
- 2018-11-19
- Volume
- 17
- Issue
- 4
- Pages
- 479-490
- ISSN
- 1109-3099 (ISSN-L)
- 2520-8721
- PMC
- PMC6294814
- OpenAlex
- W2900899666
- Cited by
- 7
- References
- 105
- Citations by year
- 2025: 1 · 2021: 3 · 2020: 2 · 2019: 1
- FWCI
- 0.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- HORMONES (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Child Health and Human Development
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (ZIAHD008920, Z01-HD008920, HD008920)
- Topics
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- adrenal development, cAMP signaling, KCNJ5, macronodular adrenal hyperplasia, ARMC5, adrenocortical carcinoma, succinate dehydrogenase, pheochromocytoma, molecular pathogenesis
- MeSH terms
- Adrenal Gland Neoplasms, Cushing Syndrome, Endocrinology, Humans, Pheochromocytoma, History, 21st Century
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