Approach to adrenal masses: Clinical sciences

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Introduction 0:00–0:47

Adrenal masses are abnormal growths that develop in one or both adrenal glands, which are triangular shaped glands located on top of each kidney.
The majority of adrenal masses are benign adenomas which can be either nonfunctional, meaning they don't secrete hormones, or functional, meaning they secrete hormones like normal adrenal tissue would, which can cause specific symptoms depending on which hormone they secrete.
When an adrenal mass is discovered, the two main questions that arise are if the mass is malignant or benign and if it's functional.
Now when a patient presents with a chief concern suggesting an adrenal mass, your first step is to obtain a focused history and physical examination.

Focused H&P 0:47–0:56

Next, you must determine if the patient is asymptomatic or symptomatic. If your patient is asymptomatic, then you should ask about any recent imaging that has been done.

Adrenal Incidentaloma 0:56–1:44

Typically, these patients present after an incidental finding of an adrenal mass on CT or MRI usually performed for an unrelated issue such as trauma or other intraabdominal problem.
They might also have a history of malignancy so make sure to ask. The physical exam is often normal in these patients, leading you to consider an adrenal incidentalloma.
Your next step is to obtain a CT scan or an MRI of the abdomen. If imaging reveals a mass less than 4 centimeters with regular shape, smooth borders, and a low density of less than 10 Hounsfield units on CT, it's most likely a benign adrenal adenoma.

Benign Adrenal Adenoma 1:44–2:31

These tumors have a very low malignant potential and usually remain stable in size. Small benign asymptomatic adenomas do not require any surgical intervention.
Here's a clinical pearl. Most adrenal incidentalomas are non-functional, but those that are at least 1 centimeter should be investigated further with imaging and biochemical testing to identify adrenal hyperfunction.
Now, let's go back and look at malignant masses. The patient will present with a mass 4 centimeters or larger with an irregular shape and irregular borders and a density of 10 Hounsfield units or more.

Malignant Adrenal Mass 2:31–3:52

Other findings consistent with malignancy include hypervascularity, necrosis, and calcifications. These findings should make you suspicious for malignancy and you should consider a malignant mass.
Keep in mind that adrenal malignancy can be primary, but sometimes it can be metastatic, most often from the lungs, kidney, colon, lymphomas, or skin melanomas.
So, if you suspect a malignant mass, your next step is to stage the mass using the TNM system, which might require additional imaging like a PET CT scan.
Once the tumor has been staged, your patient needs to be referred for a surgical consultation for resection. Often the diagnosis of adrenal malignancy is confirmed after surgical resection on postoperative pathology of the mass.
All right, now that we've covered asymptomatic adrenal masses, let's discuss symptomatic or hormonally functional ones. Here's a high yield fact.

Symptomatic 3:52–5:09

The adrenal gland is made up of the adrenal cortex that surrounds the inner adrenal medulla. The cortex is divided into three zones that secrete different hormones starting from the outermost layer and working inward.
The zona glomerulosa secretes mineralo corticoids, namely aldosterone. The zona fasciculata produces glucocorticoids like cortisol, and the zona reticularis secretes weak sex hormones, particularly dehydroepiandrosterone sulfate, also known as DHEAS.
The adrenal medulla, on the other hand, secretes catecholamines, including norepinephrine and epinephrine. Because each hormone produces a different effect, a thorough history and physical examination can provide clues about which hormone is being produced by the tumor.
All right, let's discuss a patient with a cortisol hyper-secreting adrenal adenoma. These patients may present with a history of fatigue, irritability, or lethargy, and they may report symptoms of depression or memory deficits and possibly even weight gain.

Cortisol Hypersecreting Adrenal Adenoma 5:09–8:28

Your physical exam might find evidence of Cushing's syndrome depending on the duration and severity of hypercortisolism.
This can include truncal obesity, purplish red abdominal stria, bruising, acne, hirsutism, or muscle weakness. With these findings, consider hypercortisolism.
And obtain labs to test for cortisol hypersecretion. Here's a clinical pearl.
Most patients with cortisol hypersecreting adrenal adenomas have subclinical Cushing's syndrome and don't present with the classic clinical features of overt Cushing's syndrome.
Instead, they often present with diabetes, hypertension, or dyslipidemia. Now, remember that adrenocorticotropic hormone or ACTH normally stimulates cortisol production, and there's a negative feedback mechanism in place where high levels of cortisol inhibit ACTH secretion.
Based on this principle, evaluation of cortisol hypersecretion begins with a low dose overnight dexamethasone suppression test.
Which involves giving your patient a low dose of dexamethasone in the evening and measuring serum cortisol the next morning.
Other studies that can be done include measuring 24 hour urinary cortisol, late night salivary cortisol, and serum ACTH.
Findings that support cortisol hypersecretion include an overnight dexamethasone suppression test showing an increased morning cortisol level, meaning cortisol secretion was not suppressed, along with an elevated 24 hour urinary cortisol, an elevated late night salivary cortisol, and a low serum ACTH.
Now, to confirm the presence of an adrenal mass, order a CT or MRI of the abdomen. If it shows a solitary unilateral adrenal mass, you're dealing with a cortisol producing adrenal adenoma.
And here's another clinical pearl. Cushing's syndrome and Cushing disease both present with signs and symptoms of hypercortisolism.
Cushing's syndrome refers to the hypercortisol state either by endogenous or exogenous. Excess of cortisol from any cause.
Cushing disease is a specific type of Cushing's syndrome, where a pituitary adenoma overproduces ACTH, which then stimulates the adrenal gland to secrete excess cortisol.
OK, now let's move on and discuss aldosterone hypersecreting adenoma. Your patient might report a history of fatigue, muscle weakness, or cramping, headaches, or palpitations.

Aldosterone Hypersecreting Adenoma 8:28–10:29

They may also have a history of hypertension that requires multiple medications to control. The physical exam might reveal hypertension and no peripheral edema.
With this clinical presentation, consider hyperaldosteronism. Your next step is to order labs to test for aldosterone hypersecretion.
Now, since aldosterone inhibits renin, you should measure the plasma aldosterone concentration or PAC and the plasmin renin activity or PRA and calculate the PAC to PRA ratio.
Also perform either an oral sodium loading test or a saline infusion test where the patient is either given a high sodium diet for 3 days or a saline infusion over 4 hours after which serum aldosterone is measured.
Normally high sodium levels will suppress aldosterone. So, if your laboratory results include increased plasma aldosterone, decreased renin activity, a PAC to PRA ratio greater than 30, and an increased urine or serum aldosterone after sodium loading, this points towards a diagnosis of hyperaldosteronism.
Next, obtain a CT scan or MRI of the abdomen to assess for a discrete adrenal mass. If it shows a solitary unilateral adrenal mass, diagnose an adrenal aldosterinoma.
Finally, let's talk about pheochromocytoma. Patients typically present with episodic headaches, palpitations, and sweating, and sometimes blurred vision or weight loss.

Pheochromocytoma 10:29–12:02

Physical exam findings include hypertension, tachycardia, and possibly pallor. With these findings, consider pheochromocytoma and obtain labs.
Labs include 24 hour urine fractionated metanephrines or plasma-free metanephrines, which are compounds formed from the degradation of catecholamines.
Elevated urine or serum metanephrines support a diagnosis of pheochromocytoma. Next, obtain a CT scan or MRI of the abdomen to evaluate for a discrete adrenal mass.
If you see an adrenal mass, your diagnosis of pheochromocytoma is confirmed. Here's one last clinical pearl.
Pheochromocytoma can be associated with genetic syndromes like multiple endocrine neoplasia or men type 2, neurofibromatosis type 1, and von Hippel-Lau disease.
So genetic testing is recommended for all patients with a pheochromocytoma. All right, as a quick recap, adrenal incidentalloma refers to a mass discovered incidentally on an abdominal CT scan or MRI performed for another reason.

Review 12:02–12:21

Adrenal masses can be benign or malignant as well as nonfunctional or functional. Functional tumors include cortisol-producing masses, adrenal aldosteronoma, and pheochromocytoma.