Cushing Disease Flashcards
Who described Cushing’s Disease in 1912, and what percentage of endogenous hypercortisolism does it account for?
Harvey Cushing described Cushing’s Disease in 1912. It accounts for 60–80% of endogenous hypercortisolism.
What is the most common cause of Cushing’s Syndrome, and what does it include?
The most common cause is Cushing’s Disease (CD), and Cushing’s Syndrome includes all forms of endogenous hypercortisolism, such as CD, adrenal, and ectopic forms.
What does ACTH stand for, and what is its role in Cushing’s Disease?
ACTH stands for Adrenocorticotropic Hormone. In Cushing’s Disease, excessive secretion of ACTH is caused by pituitary corticotroph adenomas.
What are corticotropinomas, and what size do they typically have in Cushing’s Disease?
Corticotropinomas are tumors causing CD. They are usually microadenomas that do not cause symptoms by local mass effect. Macroadenomas cause mass effect when their size exceeds 15 mm in diameter.
Explain the pathophysiology of Cushing’s Disease.
Excessive ACTH leads to overproduction of cortisol from the adrenal cortex. This hypersecretion creates a vicious cycle of sustained cortisol oversecretion.
What are the epidemiological characteristics of Cushing’s Disease?
CD has an estimated prevalence of nearly 40 per million, with an incidence ranging from 1.2 to 2.4 per million per year. It affects women three times more frequently than men, and common symptoms appear between the third and sixth decades of life.
What is Iatrogenic Cushing’s Syndrome, and what causes it?
Iatrogenic Cushing’s Syndrome is caused by the exogenous administration of glucocorticoids, often for immunosuppressive or oncological purposes.
What somatic mutations are commonly found in patients with CD?
Somatic mutations in the USP8 gene are common in corticotroph adenomas in CD, found in 31–63% of cases.
What is a common effect of elevated ACTH levels in Cushing’s Disease?
Elevated ACTH levels commonly result in bilateral adrenocortical hyperplasia, which may be diffuse or nodular.
How does the prevalence of Cushing’s Disease differ between men and women, and at what age do symptoms commonly appear?
CD affects women three times more frequently than men, and common symptoms typically appear between the third and sixth decades of life. No reported difference in prevalence between older men and women.
Describe the case presentation of the patient. What were her initial complaints and observed physical characteristics? (according to case presentaion in the chapter)
The patient, a 26-year-old woman, initially experienced irregular menstruation and episodes of amenorrhea. Over the next few years, she gained weight, noticed increased bruising, and observed heightened facial hair growth. Physical examination revealed centripetal obesity, a moon face, facial hirsutism, thin fragile skin with wide purple striae, proximal myopathy, and high blood pressure (150/100 mm Hg).
What initial laboratory tests were performed, and what were the findings for this patient?
Initial laboratory tests showed dyslipidemia and impaired fasting glucose. Subsequent biochemical confirmation of hypercortisolism included urinary free cortisol (UFC) of 450.4 nmol/24h (normal range: 38–275 nmol/24h), late-night serum cortisol of 1291.9 nmol/L, and serum cortisol after 1 mg overnight dexamethasone suppression test (DST) of 276.2 nmol/L.
What are the first-line biochemical tests recommended for a patient with suspected hypercortisolism, according to the guidelines?
The recommended initial tests are:
Urinary free cortisol (UFC)
Late-night cortisol (salivary or serum)
1 mg overnight dexamethasone suppression test (DST) with administration between 23:00 h and midnight and cortisol measurement between 08:00 and 09:00 h the next morning.
What diagnostic criteria suggest Cushing’s Syndrome based on biochemical tests?
Diagnostic criteria suggesting CS are:
UFC greater than the normal range
Late-night salivary cortisol above the normal range
“Awake” late-night serum cortisol level >7.5 μg/dL (207 nmol/L)
Serum cortisol >1.8 μg/dL (50 nmol/L) after 1 mg overnight DST.
What is the term for conditions associated with unspecific overactivity of the hypothalamic–pituitary–adrenal (HPA) axis, and what conditions are typically associated with it?
The terms are “functional hypercortisolic state,” “hypercortisolism in the absence of Cushing’s syndrome,” and “pseudo-Cushing.” Conditions associated with it include pregnancy, chronic exercise, major psychiatric disorders, chronic alcoholism, poorly controlled diabetes, morbid obesity, malnutrition, and anorexia nervosa.
What test is recommended to distinguish between true Cushing’s Syndrome and pseudo-Cushing in patients with conditions associated with a functional hypercortisolic state?
The 2 mg 48 h (low-dose) dexamethasone suppression test (DST), combined with a corticotropin-releasing hormone (CRH) test, is recommended for distinguishing between CS and pseudo-Cushing.
Did the patient in the case present with conditions associated with pseudo-Cushing, and what further steps were taken?
The patient did not present with conditions associated with pseudo-Cushing. Therefore, the possibility was considered unlikely, and the focus shifted to establishing the cause of CS.
What is cyclical Cushing’s syndrome, and in which form of endogenous CS does it most often occur?
Cyclical Cushing’s syndrome is a rare condition where periods with active CS and eucortisolemia alternate. It most often occurs in Cushing’s Disease (CD), but it can occur in all forms of endogenous CS.
