<h2><span class="orange-text">READ, LISTEN, OR WATCH TO LEARN MORE ABOUT HYPERCORTISOLISM</span></h2>

<h2>Information about type 2 diabetes (T2D) and hypercortisolism</h2>

<h3>PREVALENCE OF HYPERCORTISOLISM IN DIFFICULT-TO-CONTROL TYPE 2 DIABETES</h3><p>Buse JB, Kahn SE, Aroda VR, et al. <em>Diabetes Care</em>. 2025;48(12):2012-2020. doi:10.2337/dc24-2841</p>

<h2>Information about the clinical consequences of hypercortisolism</h2>

<h3>Increased risk of cardiometabolic comorbidities in patients with adrenal incidentalomas with and without autonomous cortisol secretion</h3><p>Elhassan YS, Alahdab F, Prete A, et al. Natural history of adrenal incidentalomas with and without mild autonomous cortisol excess: a systemic review and meta-analysis. <em>Ann Intern Med</em>. 2019;171(2):107-116. doi:10.7326/M18-3630</p>

<h2>Information about assessing and diagnosing hypercortisolism</h2>

<h3>Clinical approach to evaluating incidentally discovered adrenal adenomas</h3><p>Vaidya A, Hamrahian A, Bancos I, Fleseriu M, Ghayee HK. The evaluation of incidentally discovered adrenal masses. <em>Endocr Pract</em>. 2019;25(2):178-192. doi:10.4158/DSCR-2018-0565</p>

<h3><strong>CORTISOLINCONTROL.COM</strong></h3><p>Patients can learn how excess cortisol can keep blood sugar high and cause health issues such as high blood pressure and unexplained weight gain.</p>

<h2><span class="navy-text"></span>PODCASTS<span class="navy-text"></span></h2>

<p class="align-center"><strong><span class="navy-text">Cushing</span>’<span class="navy-text">s disease and syndrome: The evolving story of hypercortisolism</span></strong></p><p class="align-center"><span class="navy-text">In a podcast from Pituitary World News, experts discuss how the understanding of Cushing syndrome has expanded to include a variety of symptoms, disease causes, and laboratory test result ranges.</span></p>

<div><p>Learn how cortisol is controlled by the HPA axis</p></div>

<p>Cortisol is an abundant hormone secreted by the adrenal glands.</p><p>It plays an integral role in the body's response to stress and regulates essential physiological functions.</p><p>Cortisol production is controlled by the hypothalamic-pituitary-adrenal (HPA) axis.</p><p>This axis is regulated by a negative feedback loop and is crucial for overall health and well-being.</p><p>In a normal diurnal rhythm, cortisol levels rise and fall, with the lowest levels at night and highest levels in the morning.</p><p>Diurnal rhythm is necessary to maintain homeostasis.</p><p>The hypothalamus releases corticotropin releasing hormone (CRH) to stimulate the synthesis, and release of adrenocorticotropic hormone (ACTH) by the pituitary gland.</p><p>ACTH activates the adrenal glands to synthesize and release cortisol into the bloodstream.</p><p>The negative feedback loop occurs when circulating cortisol stimulates the glucocorticoid receptors activity, inhibiting hypothalamus activity.</p><p>Hypercortisolism or Cushing syndrome occurs when there is prolonged exposure to high levels of cortisol, disrupting the diurnal rhythm, resulting in various health complications.</p><p>Endogenous hypercortisolism is caused by a disruption of the HPA axis, and is classified as ACTH-dependent, or ACTH-independent.</p><p>ACTH-dependent hypercortisolism is caused by excess ACTH secreted from a pituitary nodule, or an ectopic nodule outside of the HPA axis.</p><p>In both cases, ACTH stimulates the adrenal glands to secrete excess cortisol, disrupting the HPA-axis negative feedback loop.</p><p>ACTH-independent hypercortisolism is caused by an adrenal source, this results in autonomous cortisol secretion disrupting the HPA axis.</p><p>Hypercortisolism due to an adrenal nodule often does not cause the same physical manifestations, and it is more common than previously thought.</p><p>Hypercortisolism manifests in many ways, and its evaluation and management requires an individualized approach.</p>

Hypothalamus-­pituitary­-adrenal (HPA) axis video thumbnail.

Hypothalamus-Pituitary-Adrenal (HPA) Axis

<p>Learn about different treatments available to patients with hypercortisolism</p>

<p>Hypercortisolism may be due to a pituitary source, ectopic source, or an adrenal source.</p><p>Ectopic nodules can occur anywhere in the body, not just the lungs.</p><p>Early detection of hypercortisolism and treatment are essential for preventing or reversing disease symptoms associated with the risk of patient deaths.</p><p>Treatment options include surgery, radiotherapy, and medical therapy.</p><p>Transsphenoidal surgery (TSS) is the first line of treatment for Cushing disease patients.</p><p>TSS removes the pituitary nodule that is secreting excess ACTH to treat hypercortisolism.</p><p>Initial remission rates after TSS are variable depending on a surgeon's experience, as well as the nodule size, and its location—and may lead to complications such as hypopituitarism.</p><p>Repeat surgery may be considered in patients when the initial surgery was not successful or for recurrent Cushing disease.</p><p>In patients with persistent or recurrent pituitary nodules radiotherapy may be used.</p><p>Radiotherapy is used to shrink the nodule and may help prevent regrowth.</p><p>However, there is significant delay in response to treatment and after radiotherapy hypopituitarism may develop.</p><p>If an adrenal gland nodule is the source of hypercortisolism, another surgical option is an adrenalectomy, which removes one or both of the adrenal glands.</p><p>This treatment may offer immediate resolution of hypercortisolism.</p><p>However, bilateral adrenalectomy will result in adrenal insufficiency and require lifelong hormone replacement therapy.</p><p>Medical therapy is an option in cases where surgery has failed, the patient is awaiting surgery, or the patient is not a candidate for surgery or radiotherapy.</p><p>Medical therapy may have different mechanisms of action—including reducing the amount of ACTH produced, acting on the adrenal gland limiting the amount of cortisol produced, or by modulating cortisol activity on the glucocorticoid receptors.</p><p>Medical therapies are non-invasive and help control and reduce the symptoms associated with hypercortisolism.</p><p>However, this treatment may be associated with side effects, thus frequent monitoring is required.</p>

 Treatments for people with hypercortisolism video thumbnail.

Treatments for patients with hypercortisolism

<p>Learn about the different tests used to screen hypercortisolism</p>

<p>Cortisol is essential throughout the body, thus its management is crucial for overall health and well-being.</p><p>Hypercortisolism, also known as Cushing syndrome, occurs when there is prolonged exposure to overproduced cortisol.</p><p>There are several screening tests that have been used to diagnose hypercortisolism, however, we will focus on the three most often used in practice.</p><p>The overnight dexamethasone suppression test, or DST, assesses responsiveness of the HPA axis.</p><p>A 1-milligram dexamethasone tablet is taken between 11 PM and midnight, followed by a blood sample collection in the morning to measure serum cortisol levels.</p><p>DST detects autonomous cortisol secretion and is the preferred test for patients with adrenal adenoma.</p><p>However, certain drugs can influence test results, leading to false positives and false negatives, and there are special recommendations for certain patient populations.</p><p>Late-Night Salivary Cortisol test, or LNSC, measures the concentration of cortisol in the saliva, when cortisol should be at its lowest level.</p><p>The LNSC test is simple to perform.</p><p>Patients are instructed to collect their saliva between 11 PM and midnight.</p><p>The LNSC detects the loss of diurnal rhythm, and is the most sensitive for detecting Cushing disease reoccurrence.</p><p>However, this test requires multiple sample collections, and many factors may influence the result.</p><ul><li><p>The urinary free cortisol test, or UFC, measures unbound cortisol in the urine</p></li><li><p>A patient collects urine over a 24-hour period</p></li><li><p>The UFC detects the gross overproduction of cortisol</p></li><li><p>A UFC value that exceeds the upper limit of normal may indicate hypercortisolism</p></li><li><p>Up to three UFC tests should be performed to confirm results</p></li></ul><p>Patients with renal dysfunction could produce false negative results, and high fluid intake may result in false positive results.</p><p>An individualized approach is recommended when determining the various appropriate tests, the number of times to repeat, and results need to be analyzed properly.</p><p>Early recognition and screening of hypercortisolism can prevent the long-term consequences of Cushing syndrome and reduce mortality rates.</p>

Tests for hypercortisolism video thumbnail.

Screening tests for hypercortisolism

<h3>CATALYST Study Results: Phase 1</h3><p>Take a look at the latest data regarding the prevalence of hypercortisolism in patients with difficult-to-control T2D</p>

<h3>Increased risk of comorbidities and CARDIOVASCULAR (CV) events with hypercortisolism</h3><p>Take a look at a review of the Petramala et al. 2020 study</p>

Increased risk of comorbidities and cardiovascular events with hypercortisolism PDF.

<h3>Difficult-to-control diabetes: is cortisol at play?</h3><p>This review captures highlights from a roundtable discussion from experts</p>

Difficult­-to-­control diabetes: is cortisol at play? PDF.

<h3>DEXAMETHASONE SUPPRESSION TEST (DST) patient tool</h3><p>Help patients understand how to take a 1-mg DST test and how it works</p>

Dexamethasone Suppression Test (DST) Patient Tool PDF.

<h3>COULD IT BE HYPERCORTISOLISM?</h3><div><div><p>Patients can review this checklist with their doctor to determine if testing for hypercortisolism is appropriate for them</p></div></div>

Resources

Difficult&#173;-to-&#173;control diabetes: is cortisol at play? PDF.

Hypothalamus-&#173;pituitary&#173;-adrenal (HPA) axis video thumbnail.

Resources

READ, LISTEN, OR WATCH TO LEARN MORE ABOUT HYPERCORTISOLISM

Information about type 2 diabetes (T2D) and hypercortisolism

PREVALENCE OF HYPERCORTISOLISM IN DIFFICULT-TO-CONTROL TYPE 2 DIABETES

Information about the clinical consequences of hypercortisolism

Increased risk of cardiometabolic comorbidities in patients with adrenal incidentalomas with and without autonomous cortisol secretion

Information about assessing and diagnosing hypercortisolism

Clinical approach to evaluating incidentally discovered adrenal adenomas

Information for your patients

CORTISOLINCONTROL.COM

PODCASTS

VIDEOS

EDUCATIONAL BROCHURES

CATALYST Study Results: Phase 1

Increased risk of comorbidities and CARDIOVASCULAR (CV) events with hypercortisolism

Difficult-to-control diabetes: is cortisol at play?

DEXAMETHASONE SUPPRESSION TEST (DST) patient tool

COULD IT BE HYPERCORTISOLISM?