What is Adrenal Cortical Nodular Hyperplasia?
The adrenal glands are two structures situated above the kidneys. Each gland is divided into two main parts with different functions: the outer part (cortex) and the inner part (medulla). The cortex is further split into three layers, each responsible for secreting a certain hormone. The outer layer secretes aldosterone, the middle one secretes cortisol, and the inner one secretes androgens, or male sex hormones. The medulla, on the other hand, secretes hormones called epinephrine and norepinephrine when we’re stressed.
Sometimes, the adrenal glands can grow larger than normal due to the presence of nodules, which are usually non-functioning. Adrenal gland tumors are quite common and are usually found by accident when a person has a scan for a different health issue. They have been found in up to 4% of people, and the chances increase with age, diabetes, hypertension, and obesity. The detection of these nodules has also increased due to advances in imaging technology and more frequent use of scans, such as MRIs and CT scans.
These unintentionally discovered nodules, often dubbed “incidentalomas,” are usually not harmful. However, there are exceptions. Some adrenal gland tumors, which make up less than 10% of all cases, secrete cortisol. A more serious but quite rare type of adrenal cancer makes up less than 2% of all cases. This type can spread to other parts of the body. Because the adrenal gland has many blood vessels despite its small size, it can be prone to cancer spreading from other parts of the body. The most common cancers to spread to the adrenal gland are lung, gastrointestinal, kidney, and breast. If nodules are found in both adrenal glands simultaneously, it might indicate cancer spread, and this should raise concern.
What Causes Adrenal Cortical Nodular Hyperplasia?
Adrenal cortical hyperplasia comes from various causes, including hormone-related factors and non-hormone-related factors. Other conditions may also show similar symptoms to this illness.
Dr. Harvey Cushing discovered Cushing Disease, where certain cells in the pituitary gland become overactive. For the most part, this disease is the cause of Cushing Syndrome. If a person has a pituitary gland tumor larger than 6 millimeters, it’s likely they have Cushing disease.
Another cause for adrenal gland enlargement is an excess of ACTH, a hormone, usually linked to certain cancers like lung, bronchial carcinoid and small cell lung cancer. Sometimes, conditions like pigmented nodular adrenal disease or macro nodular adrenal hyperplasia may cause Cushing Syndrome with no connection to ACTH. The latter is mostly found in men in their late 40s and causes the adrenal glands to grow enormous, up to 20-25 times their normal size.
The Carney complex (CNC) is a rare genetic mutation. Most cases are inherited, but up to 30% of them are new mutations. Many names have been used to describe this condition, including NAME and LAMB syndrome.
The symptoms vary and diagnosis might be delayed because the condition is rare. Less than 750 cases are currently known. The characteristic symptoms include skin spots, tumors in the glands, tumorous growths called myxomas and non-gland tumors. The Carney complex can be confirmed if two or more of these symptoms are found. Or, it can be identified if there is only symptom, but a family member has CNC or the genetic mutation. Cardiac myxomas and certain types of tumors are the leading causes of death in these patients.
Risk Factors and Frequency for Adrenal Cortical Nodular Hyperplasia
Research shows that up to 10% of elderly people might develop adrenal nodules. These are rarely found in people under 30, so if they are, more tests are needed. Lesions, another type of nodule, that are smaller than 1 cm and rated less than 10 Hounsefield units on a CT scan are usually harmless and might not need extra investigation.
Macronodular adrenal hyperplasia (MAH) is a very rare condition, affecting less than 1% of patients with a condition called endogenous Cushing syndrome. This syndrome is itself relatively uncommon, occurring in about 1 in every 26,000 people. MAH most frequently affects people in their 40s to 50s and seems to affect both genders equally.
Patients with a condition called PPNAD typically show signs before age 30 and in half of the cases, symptoms start before age 15. Gender and puberty status can affect the development of Cushing syndrome in PPNAD: after puberty, it impacts females more than males. By the age of 40, more than 70% of females with a particular mutation (PRKAR1A) develop PPNAD, compared with 45% of males.
Signs and Symptoms of Adrenal Cortical Nodular Hyperplasia
Doctors usually perform a thorough physical examination looking for telltale signs to diagnose Cushing’s disease. These signs can include obesity, especially in the stomach or trunk of the body, high blood pressure, purple stretch marks on the skin, muscle wasting, and changes in skin color. They will also look for symptoms linked to an increase in cortisol, a hormone produced by the body, such as:
- Significant weight gain
- Irregular menstrual cycles
- Excessive hair growth
Additional signs, like bone thinning, fat buildup in the back of the neck, and fertility issues, can also be a clue for a condition known as adrenal hyperplasia. If these signs are present and the patient has a history of taking corticosteroid medications, further diagnostic tests might not be needed. But, if the reason for these symptoms is unclear, more tests, such as a brain MRI, and chest, and abdominal pelvic CT scans may be ordered to find out the cause of the disease.
Testing for Adrenal Cortical Nodular Hyperplasia
On rare occasions, individuals with adrenal cortical hyperplasia can have increased levels of a hormone called aldosterone. This can result in symptoms like high blood pressure, diminished potassium levels, and a condition called metabolic alkalosis which affects the pH level of your blood. These people might also exhibit higher cortisol levels, identified by several specific lab tests.
The 24-hour urine cortisol test measures how much cortisol is present in your urine over a day. If an adult has levels higher than 50 to 100 micrograms per day, it might indicate Cushing syndrome. Although, some people with milder cases of Cushing syndrome might still have normal cortisol levels.
The low-dose dexamethasone suppression test assesses the response of the adrenal glands to ACTH, a hormone that controls cortisol production. This entails taking a small dose of dexamethasone, a medication that mimics cortisol, and then checking for cortisol in your blood the next morning. In normal people, the morning cortisol level should be very low. But in individuals with Cushing’s syndrome, it will be elevated.
The late-night salivary cortisol test checks the cortisol level in your saliva between 11 p.m. and midnight. Individuals with Cushing syndrome will usually have elevated cortisol levels at this time. This test is straightforward and can be done multiple times at home using special saliva collection kits.
Once increased cortisol levels have been established, doctors will first rule out causes for its excess that might be external, like certain medications. Further laboratory tests, along with brain MRI for ACTH-dependent or abdomen CT scans for ACTH-independent scenarios, may also be needed based on the patient’s circumstances. In children, the overgrowth of the adrenal gland can often be due to congenital adrenal hyperplasia.
Imaging techniques like computed tomography (CT) scan and magnetic resonance imaging (MRI) play a vital role in diagnosing and treating adrenal conditions. The CT scan is the primary choice for adrenal imaging due to its wide accessibility and reliable outcomes. The MRI method can provide additional information if CT findings are inconclusive, or can be used if avoiding radiation exposure is preferred. Various features of the adrenal masses discovered during the scans can provide essential insights about their nature, be it benign or malign.
Treatment Options for Adrenal Cortical Nodular Hyperplasia
Cushing disease, a type of pituitary gland tumor, is the most common cause of Cushing syndrome. Though it’s hard to draw a clear line between normal and abnormal pituitary glands, a pituitary tumor larger than 6 millimeters often signals Cushing disease.
The primary treatment for this type of tumor involves surgery achieved through the nasal cavity, known as a transsphenoidal microsurgical approach. This surgery has a high success rate, leading to complete resolution in up to 90% of smaller tumors and less than 70% in larger ones. There’s another less common surgical method called endoscopic tumor resection, which has seen improved patient outcomes recently.
The second most frequent cause of Cushing syndrome is an abnormal release of ACTH, a hormone, usually due to certain cancers like lung cancer, bronchial carcinoid tumors, and small cell lung cancer.
The treatment approach for this can differ based on the patient’s overall health condition. If the patient has an active Cushing syndrome and is in good health, removing the tumor causing the hormone release is the best option. However, if the patient’s health is poor, medication is the preferred route. Sometimes, medical treatment may take precedence for urgently controlling high cortisol levels or in cases where the tumor cannot be precisely located. If the patient has persistent high cortisol levels and cannot undergo surgery due to the uncontrolled hormone release, bilateral surgical removal of the adrenal glands and life-long hormone replacement therapy are recommended.
Another reason for Cushing syndrome can be ACTH-independent hypercortisolism. This could arise from certain conditions like primary pigmented nodular adrenal disease (PPNAD) or ACTH-independent macronodular adrenal hyperplasia (AIMAH). Both conditions are managed by surgically removing the adrenal glands on both sides and prescribing life-long glucocorticoid replacement.
What else can Adrenal Cortical Nodular Hyperplasia be?
Adrenal cortical adenoma is a type of adrenal tumor, typically found on one side and in a singular form. However, there have been reports of cases where it appears on both sides too. These tumors are not usually encapsulated and their surfaces appear yellow, sometimes having brown spots.
Pheochromocytoma is another type of adrenal tumor, which despite being rare, is the second most common tumor found in samples removed from the adrenal gland. Further, it makes up about 7% of all primary adrenal tumors. Its classic symptoms are recurrent headaches, sweating, and rapid heart rate, but they only manifest in roughly 30% of the cases. Under the microscope, this tumor looks pretty similar to the normal adrenal medulla i.e., the inner part of the adrenal gland.
There is another type of adrenal tumor, adrenocortical carcinoma, which is even rarer and aggressive as well. The prevalence of adrenocortical carcinoma ranges between 0.5 and 12 cases per one million people. Their cells are less organized than in adenomas and they often show signs of tissue death, increased cell division, invasion into neighboring tissues and spread to distant organs.
Other conditions that can affect the adrenal glands and need to be considered when making a diagnosis include congenital adrenal hyperplasia (a genetic disorder affecting the adrenal glands), metastases (spread of cancer from other organs), lymphoma (a type of blood cancer), myelolipoma (benign tumor), amyloidosis (an abnormal protein build-up), and infections like tuberculosis, histoplasmosis, and blastomycosis.
What to expect with Adrenal Cortical Nodular Hyperplasia
The success of the usual surgery for adrenal cortical hyperplasia can vary based on many factors. However, a positive response to specific types of water pills that help keep potassium in the body, such as spironolactone, could indicate a good outlook. On the other hand, constant high blood pressure and failure of multiple organs often point to a poor outcome. Multiple organ failure means that several important organs are showing signs of damage.
The general survival rate for Cushing syndrome, regardless of the cause, has changed significantly over the last 70 years. In the early 1950s, it was just over 4.5 years. Problems with blood vessels in the heart and brain, as well as complications from infections, were found to negatively affect general outcomes and increase the standard death rate.
Possible Complications When Diagnosed with Adrenal Cortical Nodular Hyperplasia
Traditional adrenal cortical hyperplasia surgery is associated with a variety of complications. The most common issue is bleeding, which can happen during or after the surgery, affecting more than one out of five patients. Additionally, complications related to the surgical incision such as hernia and wound problems can occur.
Medical complications linked to surgical removal of the adrenal gland, or adrenalectomy, include effects caused by the systemic removal of cortisol, a hormone produced by the adrenal gland.
When it comes to laparoscopic surgery, or “keyhole” surgery — where operations are performed through small incisions — the most common severe complications are infections and blood clots.
Finally, depending on the organ systems affected, surgical complications can be categorized into renal (kidney-related), cardiac (heart-related), and pulmonary (lung-related) issues.
Common Complications:
- Bleeding during or after surgery
- Hernia from surgical incision
- Wound complications
- Effects from the systemic removal of cortisol
- Infections from laparoscopic “keyhole” surgery
- Blood clots from laparoscopic surgery
- Kidney-related complications
- Heart-related complications
- Lung-related complications
Preventing Adrenal Cortical Nodular Hyperplasia
If you discover a growth in your adrenal gland that was detected accidentally, one possible cause could be adrenal cortical hyperplasia. This condition requires various lab tests and imaging studies to be diagnosed, especially after ruling out the use of corticosteroid medications. Adrenal cortical hyperplasia has different types, like PPNAD or AIMAH, both characterized by low ACTH levels and high cortisol levels.
Abdominal scans, such as CT scans or MRIs, can be helpful in identifying important findings related to the diagnosis. The most effective treatment, if diagnosed, is a surgical procedure to remove both affected glands. This operation, however, would require the patient to take hormone replacement therapy for life.
