Anatomy, Abdomen and Pelvis, Adrenal Glands (Suprarenal Glands)

The adrenal glands, also called the suprarenal glands, are a significant part of the endocrine system. The paired adrenal glands are triangular shaped organs that measure approximately 5 cm by 2 cm, are located on the superior aspect of each kidney, and weigh 4 to 5 grams each.

The adrenal glands secrete several vital hormones that play a significant role in the regulation of the immune system, body metabolism, salt and water balance, and aid the body during periods of stress.

The adrenal glands lie close to very important vessels and organs. The right adrenal gland is close to the right hemidiaphragm, liver, and inferior vena cava. The left adrenal gland lies proximal to the aorta, spleen, and tail of the pancreas. 

The adrenal gland is composed of two distinct tissues, the outer layer or cortex and the inner layer or medulla. The adrenal cortex tends to be fattier and thus has a more yellow hue. The adrenal medulla is more of a reddish-brown color. A thick capsule consisting of connective tissue surrounds the entire adrenal gland. 

The adrenal cortex is much larger than the smaller medulla which only accounts for approximately 15% of the gland. It is composed of three distinct zones:

Zona glomerulosa (outer layer)

• The zona glomerulosa is responsible for the synthesis of mineralocorticoids, of which the most important is aldosterone. This hormone plays an important role in electrolyte balance and regulation of blood pressure.

Zona fasciculata (middle layer)

• The zona fasciculata produces glucocorticoids of which the predominant hormone is cortisol. This hormone plays a role in the regulation of blood sugar via gluconeogenesis. Cortisol also modulates the immune system and modulates metabolism of fat, protein, and carbohydrates. The secretion of cortisol is regulated by adrenocorticotropic hormone which is released from the pituitary gland.

Zona reticularis (inner zone)

• The zona reticularis produces androgens and plays a role in the development of secondary sexual characteristics. The primary androgen produced in the zona reticularis is dehydroepiandrosterone (DHEA), which is the most abundant hormone in the body. It serves as a precursor for the synthesis of many other hormones produced by the adrenal gland such as progesterone, estrogen, cortisol, and testosterone.

The function of these three zones can be remembered by the mnemonic "Salt, Sugar, Sex," as they correlate to the function of the hormones produced in each layer of the adrenal cortex.  The names of these zones can also be recalled by remembering "GFR" for Glomerulosa, Fasciculata and Reticularis

The adrenal medulla synthesizes catecholamines. Catecholamines are made from the precursor of dopamine and combined with tyrosine, thus resulting in Norepinephrine. Once norepinephrine has been created, it is then methylated via Phenylethanolamine N-methyltransferase (PNMT) which is only found in the adrenal medulla. [3]

Since the adrenal glands make a significant amount of important hormones, the glands require a large blood supply and are extremely well vascularized.

The three chief sources of blood to the adrenal glands include:

1. The superior adrenal arteries, which are small branches coming off the inferior phrenic artery
2. The middle adrenal artery comes directly off the abdominal aorta
3. The inferior adrenal artery originates from the renal artery bilaterally

The venous drainage from the adrenal glands is dependent on the side of the gland. The left adrenal gland is anatomically further away from the inferior vena cava, and therefore the left adrenal vein drains into the left renal vein. The right adrenal vein is much closer to the inferior vena cava and drains directly into this large vessel.[2]

When removing a pheochromocytoma, a neuroendocrine tumor based on the chromaffin cells of the adrenal medulla that produces large amounts of catecholamines, it is crucial to ligate the adrenal vein before manipulation of the organ. If the adrenal vein is not ligated before manipulation of the organ, large amounts of catecholamines could enter the systemic circulation. This causes a catecholamine rush, resulting in an overtly exacerbated "flight or fight," response. Interestingly, these tumors tend to occur most frequently in 40 to 50-year-old Americans.

For standardized test purposes, remember that MEN-II is associated with pheochromocytoma and medullary thyroid cancer.[1]

The adrenal cortex is noteworthy in its use of cholesterol as a significant precursor for its hormones.

Pathological events of the cortex zones result in the following:

• Zona Glomerulosa: Conn syndrome is manifested by hyperaldosteronism, which excites the response of the renin-aldosterone-angiotensin system (RAA). This results in a patient who is typically on three anti-hypertensives with persistent hypertension.  Laboratory chemistry would typically indicate hypokalemia and mild hypernatremia.
• Zona Fasiculata: Cushing disease is manifested by elevated levels of cortisol resulting in abdominal striae with significant central obesity, buffalo hump of the nape of the neck, and hyperglycemia. Other attributes include poor wound healing.
• Zona Reticularis: Precocious puberty is manifested by early puberty in males or virtualization of young females with androgenic characteristics.

The adrenal medulla is made of specialized cells known as chromaffin cells. These cells aggregate in small clusters around blood vessels. The chromaffin cells in the medulla synthesize epinephrine and norepinephrine. These sympathetic hormones have many physiological activities including playing a role in the "fight or flight" response, increasing heart rate, force of contraction of the heart, metabolic rate, and cognitive awareness.

Adrenal Incidentaloma

• These happen more frequently than expected, and can approach up to 4% of CT scans.
• If a patient has a history of prior cancer, this may be an indication for biopsy.
• If the patient is known to have no primary cancer, it is then imperative to rule out a functional adrenal overgrowth.

An algorithm for adrenal incidentaloma includes addressing if the tumor is functional.

Perform appropriate adrenal functional tests such as the low dose-dexamethasone suppression test, plasma metanephrines, and plasma aldosterone. If these are positive, the patient will likely need an adrenalectomy. [3]

If the tests are negative, consider possible metastasis. Is there a history of a primary cancer? If the answer is yes, can a biopsy confirm metastatic disease? Do not biopsy an adrenal incidentaloma unless there is a known history of cancer. This can lead to seeding a primary adrenal cancer from the biopsy into the surrounding tissues. Breast and lung cancer are the most common primary cancers metastasizing to the adrenal. 

If there is no history of cancer and the adrenal incidentaloma is less than 4 cm, repeat CT in 4 to 6 months. If it is larger than 4 to 6 cm, perform a functional workup and consider a possible adrenalectomy.

Non-functional masses are identified by the biochemical work-up.

Typically, these masses are less than 4 cm.

A functional mass that produces functional hormones requires intervention, whether medical or surgical. These include:

• (G) Elevated aldosterone: Conn syndrome
• (F) Elevated cortisol: Cushing syndrome
• (R) Elevated androgens: Precocious Puberty [3]