Grand Challenge in Adrenal Endocrinology: Is the Legacy of the Past a Challenge for the Future of Precision Medicine?

Chiodini, Iacopo; Gennari, Luigi

doi:10.3389/fendo.2021.747006

Cited by 3 publications

(3 citation statements)

References 73 publications

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“…These data could represent, in the future, a milestone to start from for personalizing the diagnostic procedures and therapeutic management of these patients. Given the significant prevalence of mHC in the general population, developing precision medicine in this field could lead to reducing the economic and social costs caused by the deleterious effects of the complications of mHC [ 128 ].…”

Section: Discussionmentioning

confidence: 99%

Pathophysiology of Mild Hypercortisolism: From the Bench to the Bedside

Favero

Cremaschi

Parazzoli

et al. 2022

IJMS

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Mild hypercortisolism is defined as biochemical evidence of abnormal cortisol secretion without the classical detectable manifestations of overt Cushing’s syndrome and, above all, lacking catabolic characteristics such as central muscle weakness, adipose tissue redistribution, skin fragility and unusual infections. Mild hypercortisolism is frequently discovered in patients with adrenal incidentalomas, with a prevalence ranging between 5 and 50%. This high variability is mainly due to the different criteria used for defining this condition. This subtle cortisol excess has also been described in patients with incidentally discovered pituitary tumors with an estimated prevalence of 5%. To date, the mechanisms responsible for the pathogenesis of mild hypercortisolism of pituitary origin are still not well clarified. At variance, recent advances have been made in understanding the genetic background of bilateral and unilateral adrenal adenomas causing mild hypercortisolism. Some recent data suggest that the clinical effects of glucocorticoid (GC) exposure on peripheral tissues are determined not only by the amount of the adrenal GC production but also by the peripheral GC metabolism and by the GC sensitivity. Indeed, in subjects with normal cortisol secretion, the combined estimate of cortisol secretion, cortisone-to-cortisol peripheral activation by the 11 beta-hydroxysteroid dehydrogenase enzyme and GC receptor sensitizing variants have been suggested to be associated with the presence of hypertension, diabetes and bone fragility, which are three well-known consequences of hypercortisolism. This review focuses on the pathophysiologic mechanism underlying both the different sources of mild hypercortisolism and their clinical consequences (bone fragility, arterial hypertension, subclinical atherosclerosis, cardiovascular remodeling, dyslipidemia, glucose metabolism impairment, visceral adiposity, infections, muscle damage, mood disorders and coagulation).

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Section: Discussionmentioning

confidence: 99%

Pathophysiology of Mild Hypercortisolism: From the Bench to the Bedside

Favero

Cremaschi

Parazzoli

et al. 2022

IJMS

Self Cite

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“…Besides levoKTZ and osilodrostat, which could be of interest in future studies, and relacorilant, which is now on trial, in the future, other molecular targets could be considered. Indeed, the 11BHSD1 enzyme is among the determinants of the GC exposure at the peripheral target tissues and its modulation has been already advocated as a possible drug target for treating hypercortisolemic states, both functional and tumor induced [ 35 ]. Indeed, selective inhibitors of the hepatic 11BHSD1 have been suggested to be potentially useful for patients with mHC and insulin resistance and/or diabetes [ 41 , 110 ], but also in eucortisolemic patients with diabetes [ 111 ].…”

Section: Discussionmentioning

confidence: 99%

“…Nowadays, more and more authors also agree on the fact that the intention of searching for HidHyCo in patients with increased probability of having mHC, such as those with insulin-treated and/or complicated diabetes, scarcely controlled hypertension and unexplainable bone fragility, highly depends on the sensitivity of the physician rather than on the specificity of the available tests [ 1 , 34 , 35 ]. Therefore, increasing our awareness in suspecting HidHyCo and our skills in diagnosing mHC will increase the number of patients diagnosed with hypercortisolism, thus requiring appropriate management.…”

Section: Diagnosis Of Mild Hypercortisolismmentioning

confidence: 99%

Management and Medical Therapy of Mild Hypercortisolism

Favero

Cremaschi

Falchetti

et al. 2021

IJMS

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Mild hypercortisolism (mHC) is defined as an excessive cortisol secretion, without the classical manifestations of clinically overt Cushing’s syndrome. This condition increases the risk of bone fragility, neuropsychological alterations, hypertension, diabetes, cardiovascular events and mortality. At variance with Cushing’s syndrome, mHC is not rare, with it estimated to be present in up to 2% of individuals older than 60 years, with higher prevalence (up to 10%) in individuals with uncontrolled hypertension and/or diabetes or with unexplainable bone fragility. Measuring cortisol after a 1 mg overnight dexamethasone suppression test is the first-line test for searching for mHC, and the degree of cortisol suppression is associated with the presence of cortisol-related consequences and mortality. Among the additional tests used for diagnosing mHC in doubtful cases, the basal morning plasma adrenocorticotroph hormone, 24-h urinary free cortisol and/or late-night salivary cortisol could be measured, particularly in patients with possible cortisol-related complications, such as hypertension and diabetes. Surgery is considered as a possible therapeutic option in patients with munilateral adrenal incidentalomas and mHC since it improves diabetes and hypertension and reduces the fracture risk. In patients with mHC and bilateral adrenal adenomas, in whom surgery would lead to persistent hypocortisolism, and in patients refusing surgery or in whom surgery is not feasible, medical therapy is needed. Currently, promising though scarce data have been provided on the possible use of pituitary-directed agents, such as the multi-ligand somatostatin analog pasireotide or the dopamine agonist cabergoline for the—nowadays—rare patients with pituitary mHC. In the more frequently adrenal mHC, encouraging data are available for metyrapone, a steroidogenesis inhibitor acting mainly against the adrenal 11-βhydroxylase, while data on osilodrostat and levoketoconazole, other new steroidogenesis inhibitors, are still needed in patients with mHC. Finally, on the basis of promising data with mifepristone, a non-selective glucocorticoid receptor antagonist, in patients with mild cortisol hypersecretion, a randomized placebo-controlled study is ongoing for assessing the efficacy and safety of relacorilant, a selective glucocorticoid receptor antagonist, for patients with mild adrenal hypercortisolism and diabetes mellitus/impaired glucose tolerance and/or uncontrolled systolic hypertension.

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PURsuit of Endocrinology (PURE): A National Survey among First-Year Endocrinology Residents Across India

Nagendra,

Mondal,

Bhat

et al. 2023

Indian Journal of Endocrinology and Metabolism

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Background: Endocrinology has been a popular choice of super-specialisation in India in recent years. The PURsuit of Endocrinology (PURE) survey aims to determine the factors that facilitated the selection of endocrinology as the area of super-specialisation among first-year residents across India. Methods: We conducted an electronic questionnaire-based survey among first-year residents across India. The questionnaire evaluated the respondents’ demographics, feeder speciality, challenges during preparation, factors influencing endocrinology as a career preference, unappealing aspects of the subject and future career plans. Results: A total of 81 (43 males and 38 females) responses were recorded. The mean age was 31.3 ± 3.3 years, with 63% married. Internal medicine was the feeder speciality in 92.5% of cases. Work–life balance was the critical consideration for pursuing endocrinology in 91.4%, followed by professional satisfaction (64.2%) and the scope of having a solo practice (43.2%). Interestingly, there was less emphasis on monetary satisfaction (12.3%). Almost half of the respondents intended to practice in a government academic institution (46.9%) or in an independent set-up (45.7%). Conclusions: The PURE survey suggests that work–life balance and professional satisfaction are the key driving factors behind the choice of endocrinology. An increasing interest among the residents to join as faculty in academic institutions, apart from having self-owned private clinics, is a welcome finding.

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Grand Challenge in Adrenal Endocrinology: Is the Legacy of the Past a Challenge for the Future of Precision Medicine?

Cited by 3 publications

References 73 publications

Pathophysiology of Mild Hypercortisolism: From the Bench to the Bedside

Pathophysiology of Mild Hypercortisolism: From the Bench to the Bedside

Management and Medical Therapy of Mild Hypercortisolism

PURsuit of Endocrinology (PURE): A National Survey among First-Year Endocrinology Residents Across India

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