Cushing syndrome and Cushing disease: Clinical sciences

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Introduction0:00–0:46

Cushings syndrome refers to a combination of clinical features and symptoms that arise as a result of long term exposure to high glucocorticoid levels in the blood.
Based on the underlying cause. Cushing syndrome can be iatrogenic which occurs from exogenous administration of glucocorticoids act independent, which is specific to adrenal cortisol hypersecretion and act dependent, which can be due to either ectopic ACTH secretion by nonpituitary tumors or excessive pituitary ACTH secretion.
Moreover Cushing syndrome caused by excessive secretion of a by pituitary adenoma is called Cushing disease. Now, if your patient presents with a chief concern, suggesting Cushing syndrome.

H&P0:46–3:04

The first step is to obtain a focused history and physical examination as well as labs including a basic metabolic panel or BMP high glucocorticoid levels in the blood affect almost every system in the body.
So your patient will have various clinical manifestations. For example, history will often reveal central nervous system symptoms such as irritability and depressed mood as well as metabolic conditions like glucose intolerance or diabetes, mellitus.
Next, high glucocorticoid levels can suppress gonadotropin secretion. So your patients might report symptoms involving the reproductive system like decreased libido and amenorrhea.
The physical exam reveals the glucocorticoid effects on fat redistribution and findings like central obesity, moon facies or round face and Buffalo hump, which refers to fat accumulation on the back of the neck.
Additionally, you might notice skin changes such as thin skin, acne, hirsutism and purple and broad abdominal striae. Next, let's take a look at cardiovascular findings.
Normally, the kidneys inactivate cortisol by converting it into cortisone which cannot bind mineralocorticoid receptors and exert cardiovascular effects.
But in Cushing's syndrome, there's too much cortisol. So the kidneys are unable to inactivate everything from the blood.
As a result, cortisol remains active and begins binding mineralocorticoid receptors in the kidneys, subsequently causing sodium reuptake and increasing potassium excretion.
Ultimately, this leads to findings such as elevated BP and peripheral edema. Next, let's take a look at muscles.
Since glucocorticoids stimulate protein degradation, you might notice muscular atrophy, especially of gluteal and upper leg muscles.
Finally, as far as labs go, keep in mind that your patient is losing potassium through the kidneys. So you will often notice hypokalemia.
Additionally, your patient might present with hyperglycemia due to glucose intolerance or uncontrolled diabetes mellitus.
Now, with these findings, you should suspect Cushing Syndrome. So your next step is to determine the underlying cause.

Suspect Cushing syndrome3:04–3:32

First check if there's a long term use of exogenous glucocorticoids, exogenous glucocorticoids come in many forms. So be sure to specifically ask about all delivery methods of glucocorticoids, including oral injection inhaler or topical, which are typically used to treat various inflammatory conditions.
Now, if your patient has been prescribed exogenous glucocorticoids to treat a specific inflammatory condition, you can clinically diagnose iatrogenic Cushing syndrome.

Exogenous Glucocorticoid use3:32–3:52

In this case, the management consists of lowering the dosage or if possible, gradually tapering off the medication. On the flip side.
If there is no exogenous glucocorticoid use, you need to assess if your patients blood cortisol levels are truly elevated before going any further to do this.

No Exogenous Glucocorticoid use3:52–4:24

You can obtain either a late night salivary cortisol, a 24 hour urinary free cortisol level or a low dose overnight dexamethasone suppression test.
Now, if Cortisol levels are below or within the reference range, then your patient does not have Cushing's Syndrome. So you should consider alternative diagnoses.
However, if cortisol levels exceed the reference range, you can confirm the diagnosis of Cushing Syndrome. Your next step is to assess the underlying cause by obtaining a plasma adrenocorticotropic hormone or a level test.

Cushing syndrome4:24–4:41

If the plasma ACTH level is below the reference range. Diagnose act independent Cushing syndrome, which typically occurs due to excessive cortisol secretion by the adrenal glands.

ACTH-independent Cushing syndrome4:41–4:41

ACTH-independent Cushing syndrome4:41–5:56

Next, obtain an adrenal gland imaging like CT or MRI imaging will typically reveal either an adrenal tumor or adrenal gland hyperplasia with these findings diagnose adrenal cortisol hypersecretion as the cause of Cushing Syndrome.
Now, here's a clinical pearl to keep in mind, important conditions associated with adrenal cortisol hypersecretion include adrenocortical adenoma and adrenocortical carcinoma, as well as macronodular adrenal hyperplasia once you determine the cause of ACTH independent Cushing syndrome, consult your surgery team for tumor resection or bilateral adrenalectomy.
In case of adrenal hyperplasia. Following adrenalectomy, your patient will require a lifelong glucocorticoid and mineralocorticoid replacement.
Other treatment options include medical therapy with adrenal steroidogenesis inhibitors like mitotan, which can help manage symptoms of excess cortisol.
All right. Now let's go back and take a look at individuals who are presenting with act plasma levels that are normal or above the reference range.
In this case, diagnose ACTH Dependent Cushing syndrome, which occurs when excess ACTH overstimulates adrenal glands which eventually release too much cortisol.

ACTH-dependent Cushing syndrome5:56–6:27

Once you diagnose ACTH dependent Cushing syndrome. The next step is to determine the source of the excess act by obtaining a pituitary MRI.
Now, let's say the MRI shows no pituitary adenoma or reveals a micro adenoma thats smaller than 10. In such cases, the pituitary gland may or may not be the source of excess act.
So you should proceed with an invasive procedure called inferior petrosal sinus sampling. It involves sampling act from the veins, draining the pituitary gland and determining the central to peripheral ACTH pituitary gradient, which is the difference in act concentration between pituitary venous blood and peripheral tissue venous blood if the gradient is absent, meaning that there is no excessive act secretion from the pituitary gland.

Central-to-peripheral ACTH pituitary gradient6:27–7:03

This confirms an ectopic source of act as the cause of Cushing Syndrome. These cases are frequently observed in individuals with occult ACTH secreting tumors such as small cell lung cancer management includes further workup to find the underlying cause and treat it, which typically includes tumor resection.

Ectopic ACTH source7:03–7:32

However, if the pituitary gradient is present, it indicates that the source of excess ACTH is the pituitary gland. So you can diagnose cushing disease.
Again, consult your surgery team for tumor resection which may involve procedures like transphenoidal adenomectomy. This might be followed by hormone replacement therapy like thyroid hormone and glucocorticoids.

Cushing disease7:32–8:18

Alternatively, if surgery is too risky or unsuitable, for some reason, you may consider radiotherapy. Other treatment options include medical therapy with adrenal steroidogenesis inhibitors like ketoconazole and metyraPONE or somatostatin receptor ligans like passo.
Finally, let's go back to the pituitary MRI results. If the MRI findings reveal a pituitary adenoma, that's 10 millimeters or larger, you can go ahead and diagnose Cushing's disease.
Again, treatment involves surgical consultation for tumor resection with hormone and glucocorticoid replacement. Other treatment options include radiotherapy as well as medical therapy with adrenal steroidogenesis inhibitors.

Pituitary Adenoma > 10 mm8:18–9:07

Heres one last clinical pearl to keep in mind. Since Cushings syndrome can affect multiple organs, it's important to screen for and treat any associated complications including heart conditions, osteoporosis, insulin resistance, diabetes, mellitus and venous thromboembolism.
All right. As a quick recap Cushing syndrome refers to a combination of clinical features and symptoms that arise as a result of long term exposure to high glucocorticoid levels.
Identifying the cause starts by assessing whether the patient uses exogenous glucocorticoids, which leads to a clinical diagnosis of iatrogenic Cushing syndrome.

Review9:07–10:01

If you rule out exogenous corticosteroids, you need to check your patients cortisol levels. If elevated, obtain a plasma act level to differentiate between act independent and ACTH dependent Cushing syndrome.
Act independent cases are usually due to adrenal tumors or hyperplasia which result in cortisol hypersecretion. On the other hand, ACTH Dependent Cushing syndrome is caused by an ectopic source of act like small cell lung cancer or it might be due to pituitary adenoma.
Treatment of Cushing syndrome focuses on addressing the underlying cause, which may involve tumor resection, radiotherapy and medications like adrenal steroidogenesis inhibitors.
Cushing syndrome and Cushing disease: Clinical Sciences | Osmosis