Adrenal Metastasis - Causes, Diagnosis, and Treatment

Introduction

Adrenal glands are capped on both kidneys. Anatomically, the adrenal gland is divided into the outer cortex and inner medulla region. The cortex produces cortisone and aldosterone hormones. At the same time, the medulla produces adrenaline and noradrenaline hormones. Together they regulate metabolic function, stress regulation, blood pressure, and immune response and help fight emergency situations. Most of the time, tumors of adrenal glands are spread from other organs of origin. Adrenal cancers show a high metastatic rate.

How Does an Adrenal Tumor Cell Vary From a Normal Adrenal Tissue?

The difference between an adrenal cell tumor and a normal adrenal tissue are as follows:

• Normal Adrenal Physiology: The normal adrenal tissue has three layers of the mucosa lining it. They are zona glomerulosa having spherical cells; zona fasciculata having cells in columnar arrangement; and zona reticularis, having cells randomly arranged in a network. These layers together are called GFR cells. All the cells have blood capillaries in between them and are nucleated cells. The cells in the GFR layer are the cells of the adrenal cortex region. The innermost or basement membrane is the adrenal medulla. The adrenal medulla consists of chromaffin cells. These chromium cells have a high affinity for chromium salt, hence, the name.

• Secretion: The zona glomerulosa secretes a mineralocorticoid hormone known as aldosterone. The zona fasciculata secretes glucocorticoid and the zona reticularis produces sex corticoid hormones respectively. The adrenal medulla cells, the chromaffin cells, produce androgen hormones called epinephrine (75 to 80 percent) and norepinephrine (25 to 30 percent).

• Adrenal Tumor Pathophysiology: The cut section on microscopy shows an adrenal tumor devoid of any adrenal cells making the observation difficult. The mass contains cystic focal space. It is homogenous and fleshy. Areas of chromaffin are filled with hemorrhage. These cells have a Zellballen arrangement which means nests of cells. This is due to the delicate blood vessels which run in between them. The cells are polygonal in shape and uniform, and nuclei are round and filled with chromatin. The metastatic tumor cells appear very blended. The risk of malignancy is higher in paragangliomas or extra-adrenal tumors, with ten to twenty percent of tumor cells showing germ cell mutations. It is observed more in the young population.

What Are the Functions of Adrenal Glands?

Adrenal glands are responsible for the following mechanism of the body:

• It prevents muscle wasting.

• It helps in the bone resorption process or increases calcium intake.

• It increases insulin output by beta cell exhaustion.

• Increases glomerular filtration rate (GFR). The sodium is retained from bodily fluid, and potassium is expelled.

• Increases neural excitability.

• Maintains normal blood pressure with the help of norepinephrine.

• It has anti-allergic action on cells. It produces an anti-inflammatory response in cells.

What Is Adrenal Metastasis?

Adrenal tumors are highly metastatic and can spread from the adrenal gland to distant organs or primary tumors traveling the body to grow in other distant organs. Metastasis damages multiple organs. Most of the time, the cells die by passing through the blood vessels. The migrated cells then divide into abnormal masses, giving rise to a tumor mass. The metastatic tumor exhibits the same character at the site of origin, irrespective of where the cancer spreads. For example, colon cancer cells formed in the liver show the characteristics of colon cancer and not liver cancer. The lymph node is the most common site of metastasis in the adrenal gland. Previously spread to the bone marrow cells was noted.

What Causes Dysfunction of Adrenal Glands?

Many factors are associated with adrenal gland dysfunction, such as:

• Leukemia Inhibitory Factor: This helps suppress the abnormal proliferation of cancer cells. It regulates the stem cells of the embryo. However, overexpression of leukemia inhibitory factors can lead to the promotion of cancer cells and yield metastasis.

• Gene Mutations: Mutation of gene MEN 2A and 2B seen in familial syndromes like pheochromocytoma (a type of neuroendocrine tumor).

• Hormonal Insufficiency: The glucocorticoid hormones cortisol and aldosterone are responsible for creating responses during illness and stress. Lack of aldosterone production disrupts the salt balance in the body and causes low blood pressure.

• Medications: Prolonged use of steroids or surgical removal of adrenal glands can lead to adrenal insufficiency. Prednisone, a glucocorticoid hormone, can lead to conditions such as asthma, rheumatoid arthritis, and ulcerative colitis. This happens because glucocorticoid blocks the release of ACTH.

• Tumors: Seen in conditions like pheochromocytomas which are familial syndromes, adrenocortical adenomas caused due to hyperfunction of adrenal glands, and adrenocortical carcinomas of the adrenal glands.

• Infections: Attacking the body's immune system leads to various diseases. Seventy percent of infections are caused due to autoimmune disorders.

The most common adrenal gland tumor seen in pediatric patients is neuroblastoma. Neuroblastoma is caused due to mutation of the NF-1 gene. In adults, the most common adrenal tumor is pheochromocytoma. They arise from the chromaffin cell of the adrenal medulla. If they arise from extra-adrenal glands, they are called paraganglioma. They are associated with succinate dehydrogenase mutations. Clinically, patients may present abdominal mass.

What Are the Signs and Symptoms of Adrenal Insufficiency?

Some of the presenting symptoms are:

• Low blood pressure and shock.

• Salt craving.

• Darkening of the skin.

• Mouth ulcers.

• Muscle pain.

• Irritability.

• Irregular menstrual period.

• Fever.

• Dehydration.

• Nausea, vomiting, and loss of appetite.

• Weakness.

• Apathy.

• Feeling depressed.

• Low blood sugar level.

How to Diagnose Adrenal Metastasis?

The physician will ask for detailed medical history followed by further tests to confirm the diagnosis. Some of the tests performed are:

• Blood Tests: This is done to measure the volume of potassium, cortisol, and adrenocorticotropic hormone (ACTH) levels in the blood. Antibodies in association with autoimmune diseases can also be evaluated.

• Urine Test: There will be increased catecholamine metabolites, vanillin mandelic acid, metanephrine, and epinephrine.

• Serum Biochemistry: The presence of serum ferritin and serum lactate dehydrogenase (LDH) gives a poor prognosis for the condition.

• Biopsy: The cells show neuroendocrine tumor (NET) markers such as bombesin, synaptophysin, and chromogranin cells. A small round blue tumor cell is observed. In the case of neuroblastoma Homer Wright - pseudorosettes are also seen.

• Insulin-Induced Hypoglycemia Test: This is done to determine the hypothalamus, pituitary gland, and brain response to stress. This is done to evaluate for secondary adrenal insufficiency.

• Immunophenotyping: It shows positive for CD 56, 57, CD 68, and CD 10.

• Computed Tomography (CT): An imaging scan of the abdomen is done. This is done to check the size of the adrenal glands, any tumor present, bleeding, or other abnormality about the adrenal glands.

• Magnetic Resonance Imaging (MRI): An MRI scan of the pituitary is recommended for secondary adrenal insufficiency.

What Are the Treatment Options Available to Treat Adrenal Metastasis?

The prognosis of overall adrenal metastasis is poor for the absence of intra-tumoral calcification. Treatments depend upon the patient's immune response and the extent of the spread of the tumor to the body parts. Some treatments are:

• Hormone Replacement Therapy: This includes substituting steroid hormones that the body is incapable of producing, such as hydrocortisone replacing cortisol and Fludrocortisone acetate replacing aldosterone.

• Intravenous Injection: This is practiced, especially in Addison's disease. This includes Hydrocortisone, salt water, and sugar.

• Surgery: Surgically removing the adrenal glands is done. However, this procedure is not completely curable, and the disease can reoccur.

• Immunotherapy: Certain drugs help in inhibiting cancer cells.

Conclusion

Adrenal metastasis is one of the most malignant conditions. The rule of ten percent governs most adrenal cancers. It occurs ten percent in malignant cases, ten percent bilaterally, ten percent familial, ten percent extra-adrenal, and ten percent in pediatric patients.