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Adrenal Cortical Adenoma: Causes, Symptoms, and Treatment

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An adrenal cortical adenoma is a neoplasm of adrenal glands. Read the article for more information.

Medically reviewed by

Dr. Shaikh Sadaf

Published At October 13, 2023
Reviewed AtFebruary 28, 2024

Introduction:

Unlike their germ cell character, endocrine tumors of MEN (multiple endocrine neoplasia) syndromes have distinct features. Cortical nonfunction leads to mass lesions in adrenal glands. Hypercortisolism leads to conditions like Cushing syndrome, hyperaldosteronism, and adrenogenital syndromes. Adrenal insufficiency or hypocortisolism leads to conditions such as Addison's disease and acute adrenocortical lack.

What Leads to Adrenal Adenoma?

Adrenal adenomas are a result of adrenal hyperfunction or hyperadrenalism. They can be classified into functional and non-functional adrenocortical neoplasms. Hyperaldosteronism-initiated conditions like Cushing syndrome, a potential carcinoma. The difference between active and non-functional adrenal insufficiency is measured based on steroid hormones' morphological features.

They are mainly caused due to gene mutations—mutation of the CTNNB1 gene responsible for inducing non-secreting adrenocortical adenomas. In addition, the mutation of PRKACA (cortisol-producing adenoma), GNAS1(McCune Albright syndrome), MENIN (multiple endocrine neoplasm type 1), and ARMC5 (hereditary bilateral adrenal adenoma) are all associated with adrenal adenomas.

What Causes Adrenal Insufficiency?

It is seen in both hyper and hypo-adrenal functions. Causes of adrenal insufficiency are:

  • In Acute Conditions: Waterhouse-Friderichsen syndrome, the sudden withdrawal of long-term corticosteroid therapy and stress in patients with chronic conditions.

  • In Chronic Conditions: Autoimmune adrenalitis and tuberculosis are major contributors. Systemic amyloidosis, sarcoidosis, and fungal infections are minor contributors.

What Are the Symptoms Associated With Adrenocortical Adenomas?

Mostly, they are asymptomatic. They are associated with adrenal hormones, and glucocorticoid-associated adrenal tumors may show symptoms like:

  • Obesity.

  • Hypertension.

  • Hyperglycemia.

  • Fatigue.

  • Depression.

  • Menstrual irregularities.

  • Proximal muscle weakness.

  • Acne.

  • Fracture.

  • Osteopenia.

  • Stretch marks on the abdomen.

  • Low potassium, calcium, and magnesium levels in the body.

What Are the Morphological Features of Adrenocortical Adenomas?

  • Adrenocortical adenomas demonstrate a well-circumscribed, nodular lesion that invades an adrenal gland or lies outside the adrenal capsule.

  • On cut sections, they exhibit a yellowish-brown layer between the neoplastic cells. These are lipid cells arranged within them.

  • Adrenocortical adenomas are small, measuring around one to two centimeters in diameter. This minimal size makes them undetectable from foci or nodular hyperplasia.

  • Microscopically, they are seen as small cells with varying shapes and sizes (pleomorphism).

  • The cytoplasm of these cells shows eosinophilic to vascular activity depending on the lipid content.

  • Mitotic activity within the cell is not observed.

What Factors Increase the Risk of Developing Adrenal Adenoma?

Certain individuals might inherit predispositions that elevate their susceptibility to adrenal adenoma. Including:

  • Hereditary bilateral adrenal adenoma (ARMC5 genetic mutation).

  • PRKACA genetic mutation.

  • McCune Albright syndrome (GNAS1 genetic mutation).

  • CTNNB1 genetic mutation.

  • Multiple endocrine neoplasm type 1 (MENIN genetic mutation).

  • KCNJ5 genetic mutation.

  • ATP2B3 genetic mutation.

  • CTNNB1 genetic mutation.

  • CACNA1D genetic mutation.

  • ATP1A1 genetic mutation.

How Does Adrenocortical Cancer Show Up?

  • The lesion caused by adrenocortical carcinomas is large and invasive, making them malignant.

  • However, small lesions confined to the adrenal glands are also observed.

  • During the cut sections, the tumor shows irregular patterns and poorly demarcated borders containing necrotized lesions, bleeding, and cystic changes.

  • The invasion of the tumor extends to the adrenal vein and inferior vena cava.

  • Microscopically, they exhibit well-differentiated cells.

  • The cells of adrenocortical adenoma and carcinoma show a similar pattern. Both of the conditions exhibit pleomorphism in their cellular practice.

  • Adrenocortical carcinomas show metastatic properties. They invade locally and metastasize through the blood.

  • The survival rate of patients suffering from adrenocortical carcinoma is about two years.

  • Childhood adrenocortical carcinomas are associated with virilism. It is characterized by secondary sex features like the growth of facial hair in females. Such tumors are less aggressive.

  • In adults, it produces mixed functional cancers known as Cushing-virilizing syndrome. They are more aggressive than childhood carcinomas.

How Are Adrenocortical Adenomas Identified?

  • Adrenocortical adenomas are primarily encountered in autopsy studies. Their discovery is accidental most of the time and is found during abdominal imaging.

  • They are often known as incidentally discovered tumors.

  • Not all adenomas of adrenal glands exhibit hyperadrenalism. Most of the incidentally discovered tumors have been known to show non-hyperfunctioning hyperplastic nodules.

Is It Possible for an Adrenal Adenoma to Develop Into Cancer?

Cancerous adrenal adenomas can develop, however this is uncommon. Adrenocortical carcinoma is the most typical malignant tumor that develops in the adrenal glands. Adrenocortical carcinoma tumors that are functional produce too many hormones, similar to adrenal adenomas. They might exhibit signs and symptoms like functional adrenal adenomas.

Adrenocortical carcinoma affects approximately 1 in 1 million persons. Adrenal tumors are often benign (noncancerous).

What Are the Differential Diagnosis for Adrenocortical Adenomas?

The differential diagnosis for adrenocortical adenomas includes:

  • Nodular Hyperplasia.

  • Cysts.

  • Myelolipoma.

  • Hemangioma.

  • Hamartoma.

  • Metastasis.

  • Granulomatosis.

  • Pheochromocytoma.

  • Angiomyolipoma.

  • Carcinoma.

What Are the Diagnostic Tests to Evaluate Adrenocortical Adenomas?

Various tests are done to evaluate adrenocortical adenomas from benign to malignant conditions.

  • Computed Tomography (CT): This is done to evaluate the presence of a tumor.

  • Fine Needle Aspiration Biopsy: This is done to check for metastatic conditions.

  • Plasma ACTH (Adrenocorticotropic Hormone) Level: It is used as a diagnostic agent to check for hyper and hypo values of hormones.

  • Urine Test: The presence of metanephrines is checked in urine for pheochromocytoma.

  • Plasma Aldosterone Test: This is done to evaluate the sodium and potassium levels in the bloodstream.

What Are the Treatments for Adrenal Adenoma?

The treatment for adrenocortical adenomas depends on functioning and non-functioning tumors. Some of the surgical procedures are:

  • Adrenalectomy (Removal of Adrenal Glands): Adrenal glands are removed with the help of laparoscopy. Single or both glands are removed depending on the spread of the lesion. A single gland is also capable of producing sufficient hormones.

  • Supplements: Hormonal replacement therapy produces hormones to carry out normal functions of the body.

  • Medications: This is taken in case of imbalanced hormones, where surgery is not required.

Can Cancers of the Adrenal Gland Be Avoided?

Adrenal adenoma and other adrenal gland tumors cannot be avoided. Numerous adrenal adenoma risk factors are genetically predisposed. Even if there is no family history of adrenal gland tumors, individuals risk developing an adrenal adenoma.

What Is the Prognosis for Individuals Diagnosed With Adrenal Adenoma?

Most individuals with adrenal adenoma remain asymptomatic, with no impact on health. Non-functional adenomas are monitored biannually for the first year, then annually for a couple of years, and subsequently every five years. Treatment, including surgery or medication, is initiated if the tumor enlarges or becomes symptomatic. Functional adenomas, when treated, typically don't lead to long-term health complications.

Conclusion:

Adrenal adenomas cause the overproduction of hormones. If non-functional adrenal glands cause adrenocortical adenomas, they can be treated with hormonal therapy. If over-functional hormones cause them, they can turn malignant, and surgery can remove the tumor.

Dr. Shaikh Sadaf
Dr. Shaikh Sadaf

Endocrinology

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adrenal cortical adenoma
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