Adrenal adenoma

Adrenal adenoma

The increased use and technical advancement of abdominal imaging technologies in recent years has resulted in the detection of previously undetected adrenal tumors on a more frequent basis.

Adrenal adenomas are benign neoplasms of the adrenal cortex. Adrenal adenomas are the most prevalent source of accidentally discovered adrenal tumors, often known as adrenal incidentalomas. Adrenal adenomas can be hormonally active or dormant. These tumors are often discovered by chance during unrelated imaging, and only in a few cases do patients report with symptoms and/or characteristics of hormonal disorders, most commonly overproduction of an adrenal hormone.

Adrenocortical adenomas are ACTH-independent illnesses that are frequently associated with hyperadrenal syndromes such as Cushing's syndrome (hypercortisolism) or Conn's syndrome (hyperaldosteronism), which is also known as primary aldosteronism. Furthermore, new case reports lend support to the association of adrenocortical adenomas with hyperandrogenism or florid hyperandrogenism, which can result in hyperandrogenic hirsutism in females.


Physiology of the Adrenal glands

Physiology of the Adrenal glands

The adrenal glands' purpose in human body is to release specific hormones directly into the bloodstream. Many of these hormones have to do with how the body reacts to stress, and others are essential for survival. Both the adrenal cortex and the adrenal medulla perform different and independent activities in the adrenal glands. A different hormone is secreted by each zone of the adrenal cortex. The adrenal gland is responsible for the production of several important hormones, including:


Cortisol is a glucocorticoid hormone generated by the zona fasciculata that serves a number of functions in the body. It aids in the regulation of the body's usage of lipids, proteins, and carbs; suppresses inflammation; controls blood pressure; raises blood sugar; and can reduce bone growth. This hormone is also responsible of the sleep/wake cycle. It is secreted at times of stress to provide a burst of energy and assist it deal with an emergency scenario.


This mineralocorticoid hormone released by the zona glomerulosa is essential in the regulation of blood pressure and electrolytes (sodium and potassium). Aldosterone signals the kidneys, causing them to take more salt into the circulation and release potassium into the urine. This means that aldosterone also serves to maintain blood pH by managing electrolyte levels in the blood.

DHEA and Androgenic Steroids

These zona reticularis-produced hormones are weak male hormones. They are precursor hormones that are transformed into female hormones (estrogens) in the ovaries and male hormones in the testes (androgens). The ovaries and testes, on the other hand, generate far more estrogens and androgens.

Epinephrine (Adrenaline) and Norepinephrine (Noradrenaline)

The adrenal medulla, the innermost region of the adrenal gland, regulates hormones that trigger the fight or flight response. The adrenal medulla secretes many hormones, the most important of which are epinephrine (adrenaline) and norepinephrine (noradrenaline), which have comparable activities.

These hormones can, among other things, increase the heart rate and power of cardiac contractions, increase blood supply to the muscles and brain, relax airway smooth muscles, and aid in glucose (sugar) metabolism. They also govern the constriction of blood vessels (vasoconstriction), which helps to maintain blood pressure and raises it in reaction to stress.

Epinephrine and norepinephrine, like numerous other hormones generated by the adrenal glands, are frequently triggered in physically and emotionally stressful situations when your body need more resources and energy to withstand unusual pressure.


Pathophysiology of Adrenal Adenoma

Pathophysiology of Adrenal Adenoma

Adrenocortical adenomas, if functioning, can interfere with the normal functions of the adrenal cortex. The three zones responsible for the production of the three primary classes of adrenal steroids are located within the adrenal glands. As a result, functional adrenocortical adenomas can cause adrenal steroid oversecretion in patients with pure or mixed endocrine disorders, a disease known as hyperadrenalism.


Histopathology of Adrenal Adenoma

Histopathology of Adrenal Adenoma

The microscopic histopathological examination of tissue samples taken from the adrenal cortex of people who have adenoma-related symptoms like primary aldestronism (PA) shows that adenoma cells are bigger, have distinct cytoplasm, and have more variance in nuclear size. This result is based on a study of adrenal cortex tissue samples from healthy (normal) and afflicted (adenoma-associated) patients. 


Epidemiology of Adrenal Adenoma

Epidemiology of Adrenal Adenoma

Depending on the parameters utilized, the reported prevalence of adrenal incidentaloma varies. According to CT scan data, the prevalence of adrenal incidentalomas ranges from 0.35 % to 1.9 %. An autopsy series, on the other hand, revealed a frequency of 2 %. Adrenal adenomas account for around 54% of adrenal incidentalomas. Adrenal adenomas are more prevalent in women (55 %) than in males (45 %).

The average age upon diagnosis is 57 years (range 16 to 83 years). Hormone hypersecretion is seen in 15% of adrenal incidentalomas. The reported prevalence of hypercortisolism ranges from 1% to 29% (average 9%), hyperaldosteronism ranges from 1.5 % to 3.3 %, and pheochromocytoma ranges from 1.5 % to 11 %. 

In rare cases, a patient may have bilateral adenomas, in which case alternative causes of bilateral adrenal masses, such as metastatic illness, congenital adrenal hyperplasia, lymphoma, infections, bleeding, and infiltrative diseases of the adrenal glands, should be investigated.


Causes of Adrenal Adenoma

Causes of Adrenal Adenoma

According to the published reports, the majority of adrenocortical adenomas are caused by neoplastic growth of adrenal cortical cells within the three different layers of the adrenal cortex. In humans, the adrenal cortex is divided into three concentric zones: the zona glomerulosa, zona fasciculata, and zona reticularis, which react to the body's physiological needs for steroid hormones under normal conditions. The adrenal cortex is thought to be a dynamic organ, with senescent cells being replaced by freshly differentiated cells.

This continual renewal promotes organ remodeling, which adds to the adrenal cortex's dynamic properties. Similarly, the developmental physiology of the adrenal cortex is thought to play a critical role in the creation of adrenocortical malignancies. As a result, the molecular pathways involved in normal adrenal gland growth are like two-edged swords that can lead to the creation of malignancies inside the adrenal cortex.

Furthermore, new research suggests that mutations altering the adrenocortical region's molecular pathways might induce aberrant proliferation and tumor growth. The cyclic AMP-dependent protein kinase was discovered through these investigations. A signaling has been identified as a critical modulator of cortisol production, and mutations related with cyclic AMP - protein kinase dysregulation A pathways have been implicated in the pathophysiology of the adrenocortical system.


Can Adrenal Adenoma be inherited?

hereditary adrenal adenomas

The majority of adrenal adenomas are not hereditary. They frequently appear on their own in patients who have no family history of malignancies. They can, however, form in rare situations in patients with particular genetic diseases such as multiple endocrine neoplasia type 1 (MEN1) and familial adenomatous polyposis (FAP). Both of these diseases are inherited in an autosomal dominant pattern.


Adrenal Adenoma Signs and Symptoms

Adrenal Adenoma Signs

Non-secreting adrenal adenomas, or those that release modest quantities of hormones, are typically asymptomatic and are detected by accident on abdominal imaging. Obesity, hypertension, hyperglycemia, fatigue, depression, menstruation abnormalities, proximal muscle weakness, acne, facial plethora, striae, fractures, and osteopenia can all be indications of glucocorticoid generating adrenal tumors. 

Aldosterone-secreting tumors can cause resistant hypertension, which is defined as uncontrolled blood pressure despite the administration of three or more antihypertensive drugs from various classes. Muscle weakness, hypokalemia, hypomagnesemia, and hypernatremia are some of the other symptoms.


How can Adrenal Adenoma be Diagnosed?

Adrenal Adenoma Diagnoses

In evaluating adrenal tumors, there are two basic objectives. The first purpose is to distinguish between benign and malignant masses, and the second is to determine if the tumors are overproducing hormones.

For the diagnosis of adrenal tumors, a CT scan is the preferred imaging method. Adrenal cancer detection is highly sensitive when the tumor size is more than 4.0 cm. On a non-contrast CT scan, adrenal lesions with fewer than 10 HU (Hounsfield units) strongly imply a benign adenoma. Some benign adenomas may have a HU value of more than ten. A delayed contrast-enhanced CT scan might help distinguish them from cancerous tumors. For the examination of adrenal tumors, an MRI is a better option than a CT scan, although it is costlier.

Fine-needle aspiration biopsy of adrenal tumors is seldom required in individuals with a solitary adrenal lesion who have a history of non-adrenal malignancy and no additional metastases. Before any invasive operation is performed in these situations, a pheochromocytoma must be ruled out.

All patients with adrenal adenoma should be evaluated for Cushing syndrome, and those with pheochromocytoma and hypertension should be evaluated for hyperaldosteronism.

A low dose dexamethasone suppression test is used to identify Cushing syndrome. The greatest negative predictive value for Cushing syndrome is a plasma cortisol level of less than 1.8 mcg/dL following an overnight injection of 1mg dexamethasone. An abnormal test is validated by collecting 24-hour urine free cortisol and measuring plasma ACTH levels. Cushing syndrome is defined by a fourfold increase in 24-hour urine cortisol levels.

Pheochromocytoma is diagnosed by measuring 24-hour urine fractionated metanephrines or plasma fractionated metanephrines.

Measurements of plasma aldosterone and plasma renin activity are recommended in hypertensive individuals with adrenal adenoma. The diagnosis is verified in individuals with plasma aldosterone concentrations more than 15ng/dL and aldosterone to plasma renin activity greater than 20, by establishing a lack of aldosterone suppressibility with sodium loading. Before surgery, individuals over the age of 40 should have a selective adrenal vein sample for localisation reasons.


Treatment of Adrenal Adenoma

Treatment of Adrenal Adenoma

Adrenal tumors larger than 4 cm in diameter, hormonally indeterminate, or suspected of being malignant are treated by adrenalectomy. Adrenalectomy is also used to treat benign adrenal adenomas that are smaller than 4 cm in size and are hormonally active on biochemical tests (Cushing syndrome, hyperaldosteronism, and pheochromocytoma). The treatment of an adrenal adenoma is determined by whether the tumor is malignant or benign, the size of the adrenal gland and the afflicted adrenal, as well as the hormone released:

Cushing's syndrome

Cushing's syndrome induced by an adrenal adenoma is generally treated via laparoscopic unilateral adrenalectomy. It is important to note that the contralateral adrenal gland is frequently atrophied, and patients may require post-operative hydrocortisone treatment until the hypothalamic-pituitary-adrenal axis recovers, which might take 6-18 months. Failure to provide glucocorticoids after surgery might result in acute adrenal insufficiency.

Response monitoring focuses on the resolution of the original findings and symptoms. Many individuals will see considerable improvements in glycemic management and/or hypertension. Weight loss is also frequent following a successful surgical procedure. Cushing's syndrome bodily changes are normally reversible, but they may take months or more to resolve fully, and some patients may not have complete remission.


Primary hyperaldosteronism (Conn's syndrome)

There are medical and surgical therapy options for people with primary hyperaldosteronism. In general, surgical interventions are more effective, while medical therapy is reserved for individuals who are unfit for surgery.

Laparoscopic total adrenalectomy is the recommended surgical option for primary hyperaldosteronism caused by an adenoma. Patients should consume a high salt diet for the first few weeks following surgery to compensate for moderate hypoaldosteronism caused by continuous suppression of the renin-angiotensin system. The majority of patients will not need mineralocorticoid supplements.

Patients with hyperaldosteronism who are unable to undergo surgery owing to old age or comorbidities, or who refuse surgery, are treated with aldosterone antagonists such as spironolactone or eplerenone. However, side effects such as unpleasant gynecomastia, nausea, and headache might contribute to poor compliance. While eplerenone may be more pleasant for many people, but it may be less effective.

Hormonally inactive adenomas are initially maintained by reimaging every 3 to 6 months for the first year, then yearly for the next 1 to 2 years, and they should also have a repeat hormonal evaluation every year for the next 5 years. Adrenalectomy is advised if the mass expands to be more than 1 cm in diameter or becomes hormonally active.



The main curative therapy for pheochromocytoma is surgical resection. A successful excision requires a collaborative effort from the endocrinologist and the patient prior to surgery, as well as the surgical team and anaesthesiologist during surgery. A beneficial conclusion is significantly more difficult to achieve if all of the above-mentioned teams do not communicate often and adequately.

The 2014 Clinical Practice Guideline for Pheochromocytoma from the United States Endocrine Society recommends a laparoscopic adrenalectomy (minimally invasive procedure) for most adrenal tumors, unless they are invasive or greater than 6.0 cm.

It is vital to emphasize that bigger tumors can be treated using a minimally invasive technique, but the team must be prepared to switch to an open operation if necessary.Unless the tumor is small, non-invasive, and in an easy-to-manipulate position, an open approach (conventional surgical technique) is currently chosen for extra-adrenal disease.

While previous data indicated the need for a minimally invasive approach with malignant and/or metastatic disease, current research indicates a successful operation is feasible and results in a shorter hospital stay. Literature within the last decade has also demonstrated that the robotic technique may be successfully utilized for adrenal tumors.

A complete or total adrenalectomy is often conducted; however, a procedure known as "cortical-sparing" might leave a remnant of the adrenal gland in the hopes of avoiding life-long steroid replacement if both the left and right adrenal glands must be removed. This is especially relevant in individuals with MEN and VHL-related disease, since they are more likely to develop bilateral pheochromocytomas. The risk of leaving adrenal tissue is recurrent disease.

According to a recent cohort research, despite a 13% recurrence risk in patients who received cortical-sparing adrenalectomy for pheochromocytoma, there was no difference in survival compared to their whole adrenalectomy counterparts.


Prognosis of Adrenal Adenoma

Prognosis of Adrenal Adenoma

Patients with adrenal adenomas have a great long-term prognosis. Adrenal adenomas that do not function are seldom treated. Adrenal incidentalomas with no abnormal hormone production had a 17 percent, 29 percent, and 47 percent probability of becoming hormonally active in 1, 2, and 5 years, respectively. Adrenal adenoma converting into adrenocortical cancer is highly uncommon.



Adrenal adenoma

The increased use and technical advancement of abdominal imaging technologies in recent years has resulted in the detection of previously undetected adrenal tumors on a more frequent basis.

Adrenal cortical adenoma is a frequent benign tumor that develops from the adrenal gland's cortex. It is more frequent in adults, but it can occur in any age. Non-secreting adrenal adenomas produce minimal quantities of hormones, are normally asymptomatic, and are frequently detected by accident on abdominal imaging. Adrenal tumors that produce glucocorticoids can mimic the symptoms and signs of Cushing syndrome. Adrenal cortical adenomas are not considered to have the potential for malignancy.

Adrenal adenomas are frequently classified as endocrine-inactive tumors due to the fact that the majority of them are non-functioning and asymptomatic. Symptoms of functional adrenocortical adenomas are consistent with mixed endocrine disorders. Functional adrenocortical adenomas demonstrate symptoms consistent with mixed endocrine syndromes.

In most reported cases of adrenocortical adenoma, patients have presented with one or multiple endocrine syndromes such as hyperaldosteronism/Conn's Syndrome, hypercortisolism/Cushing's syndrome, hyperandrogenism/feminization, virilization, or hirsutism.

Due to their asymptomatic nature, most recorded cases of adrenal adenomas were discovered by accident after autopsy or during medical imaging, namely CT scan and magnetic resonance imaging. Although adrenocortical adenomas are difficult to distinguish from normal adrenal cortex, once separated, they appear as well-circumscribed lesions.

Many primary, metastatic, benign, and malignant entities are included in the differential diagnosis of adrenal adenoma. Because adrenal metastases can be identified in up to 25% of patients with known source lesions, radiologists must regularly determine whether an adrenal tumor is benign or malignant. The question has the potential to have a direct impact on the clinical care of the patient. For example, a workup for otherwise respectable lung cancer may reveal the existence of an adrenal tumor, implying the likelihood of metastatic tumor.

Surgery is used to treat a hormonally active (functional) adrenal tumor. The therapy for a malignancy is determined by the underlying tumor's cell type, dissemination, and location. Non-functional adrenal cortical adenomas are not precancerous, and surgical removal is not recommended.