Types of Hypercortisolism

THERE ARE 2 TYPES OF HYPERCORTISOLISM: ACTH-INDEPENDENT AND ACTH-DEPENDENT1

Both types of hypercortisolism are characterized by a loss of the normal diurnal rhythm of cortisol.2

Adrenocorticotropic hormone (ACTH)-independent hypercortisolism (cortisol-secreting adrenal adenoma or hyperplasia)

Cortisol fluctuations in a patient with an adrenal adenoma2

Twenty-four hour cortisol levels in a normal subject versus a patient with unilateral adrenal adenoma, showing elevated levels and loss of normal diurnal variation in the adenoma group.
ACTH-INDEPENDENT HYPERCORTISOLISM IS Characterized by a gradual onset, progression, and worsening of signs and symptoms
Cortisol productionAutonomous secretion of excess cortisol1
Cortisol levelsNormal to slightly elevated1
ACTH levelsSuppressed or lower limit of normal3
DHEAS levelsLow-normal or suppressed4
Signs and featuresPatients typically do not display phenotypic features specific to the disorder5
Associated conditionsType 2 diabetes (T2D), bone fragility, hypertension, obesity, dyslipidemia, and mood disorders6

Hear from patients who have ACTH-independent hypercortisolism

Nicole, a real patient.

Nicole, age 26

Diagnosed with multiple syndromes/disorders prior to hypercortisolism diagnosis

Read her story
Pat, a real patient.

Pat, age 69

Weight gain, mood swings, and multiple comorbidities lead to a hypercortisolism diagnosis

Read his story

ACTH-dependent hypercortisolism (pituitary or ectopic tumor)

CORTISOL FLUCTUATIONS IN A PATIENT WITH a PITUITARY ADENOMA7

Twenty-four hour cortisol levels in a normal subject versus a patient with pituitary adenoma, showing elevated levels and loss of normal diurnal variation in the adenoma group.
ACTH-DEPENDENT HYPERCORTISOLISM IS CHARACTERIZED BY A MORE RAPID ONSET, PROGRESSION, AND WORSENING OF SIGNS AND SYMPTOMS
Cortisol productionSignificantly elevated secretion of cortisol1
Cortisol levelsUpper limit of normal or high1
ACTH levelsUpper limit of normal to high3
DHEAS levelsOften elevated, since DHEAS is stimulated by ACTH4
Signs and featuresPatients typically display phenotypic features that are disorder-specific1
• Proximal myopathy
• Easy bruising
• Facial fullness
• Buffalo hump
• Striae
• Truncal obesity
Associated conditionsT2D, bone fragility, hypertension, obesity, dyslipidemia, and mood disorders6

Consider The Suspected Source Of Excess Cortisol

A significant proportion of patients with hypercortisolism presenting initially with T2D will have an adrenal source8-11—it is important to select an initial screening test with sensitivity to detect all etiologies of hypercortisolism.

Among patients with TYPE 2 DIABETES (T2D) who were found to have hypercortisolism, the most common source was an adrenal abnormality8-11

Adrenal source of hypercortisolism

Percentage of people with adrenal source of hypercortisolism across four study populations with type 2 diabetes: seventy-three percent in people with T2D and hemoglobin A1c greater than eight percent, seventy-eight percent in hospitalized patients with T2D, fifty-two percent in patients with T2D, and eighty-eight percent in people with T2D with or without hypertension.

Hear from patients who have ACTH-dependent hypercortisolism

Jenny, a real patient.

Jenny, age 33

Being treated for the symptoms of hypercortisolism and considering transsphenoidal surgery

Read her story
Charsetta, a real patient.

Charsetta, age 47

Overt Cushingoid symptoms and multiple pituitary adenomas led to a hypercortisolism diagnosis

Read her story
Twenty-four percent.

Nearly 1 in 4 patients with difficult-to-control T2D had endogenous hypercortisolism12

UNCOVER PREVALENCE

The 1-mg dexamethasone suppression test detects all etiologies of hypercortisolism13

VIEW SCREENING

Learn more about hypercortisolism

VIEW RESOURCES

References

1. Guaraldi F, Salvatori R. J Am Board Fam Med. 2012;25(2):199-208. doi:10.3122/jabfm.2012.02.110227 2. van Aken MO, Pereira AM, van Thiel SW, et al. J Clin Endocrinol Metab. 2005;90(3):1570-1577. doi:10.1210/jc.2004-1281 3. Debono M, Newell-Price JD. Front Horm Res. 2016;46:15-27. doi:10.1159/000443861 4. Chiodini I, Ramos-Rivera A, Marcus AO, Yau H. J Endocr Soc. 2019;3(5):1097-1109. doi:10.1210/js.2018-00382 5. Di Dalmazi G, Vicennati V, Garelli S, Casadio E, et al. Lancet Diabetes Endocrinol. 2014;2(5):396-405. doi:10.1016/S2213-8587(13)70211-0 6. Favero V, Cremaschi A, Parazzoli C, et al. P Int J Mol Sci. 2022;23(2):673. doi:10.3390/ijms23020673 7. Oster H, Challet E, Ott V, et al. Endocr Rev. 2017;38(1):3-45. doi:10.1210/er.2015-1080 8. Chiodini I, Torlontano M, Scillitani A, et al. Eur J Endocrinol. 2005;153(6):837-844. doi:10.1530/eje.1.02045 9. Catargi B, Rigalleau V, Poussin A, et al. J Clin Endocrinol Metab. 2003;88(12):5808-5813. doi:10.1210/jc.2003-030254 10. Steffensen C, Pereira AM, Dekkers OM, Jørgensen JO. Eur J Endocrinol. 2016;175(6):R247-R253. doi:10.1530/EJE-16-0434 11. Giovanelli L, Aresta C, Favero V, et al. J Endocrinol Invest. 2021;44(8):1581-1596. doi:10.1007/s40618-020-01484-2 12. Buse JB, Kahn SE, Aroda VR, et al. Diabetes Care. 2025;48(00):1-9. doi:10.2337/dc24-2841 13. DeFronzo RA, Auchus RJ, Bancos I, et al. BMJ Open. 2024;14(7):e081121. doi:10.1136/bmjopen-2023-081121