Adrenal Insufficiency Panel- Basic

What is Adrenal Insufficiency and What are the Symptoms?

Adrenal insufficiency (AI) is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones, primarily cortisol; but may also include impaired production of aldosterone (a mineralocorticoid), which regulates sodium conservation, potassium secretion, and water retention. Craving for salt or salty foods due to the urinary losses of sodium is common.

Addison's disease, , the auto-immune type of primary adrenal insufficiency, and congenital adrenal hyperplasia can manifest as adrenal insufficiency. If not treated, adrenal insufficiency may result in abdominal pains, vomiting, muscle weakness and fatigue, depression, low blood pressure, weight loss, kidney failure, changes in mood and personality, and shock (adrenal crisis).

Whatever the cause, adrenal insufficiency was invariably fatal until 1949, when cortisone was first synthesized, and glucocorticoid- replacement treatment became available. However, despite this breakthrough, the diagnosis and treatment of patients with the disorder remain challenging.

Adrenal Insufficiency (AI) Caused by Medications

A study conducted by the researchers at the University of Bologna analyzed over 8,000 cases of AI to identify the common causes of drug-associated AI and the changes that have occurred in the field over the past two decades. The researchers found that 97.5% of the cases were serious, and 41.1% required hospitalization.

The number of AI cases has increased over the years, with most of them being caused by steroids. The prevalence of these drugs has also increased over the years. In 2015, the number of cases involving monoclonal antibodies had reached 33%. Although the majority of these cases were caused by non-steroidal anti-inflammatory drugs, the researchers noted that over 70% of them were also on steroids.

What Lab Tests are Used to Initiate Diagnosis of Adrenal Insufficiency?

 Discounted Labs’ basic adrenal insufficiency panel includes cortisol, ACTH, and DHEA as a starting point. Depending on lab test results, physicians may choose to do an ACTH stimulation test, renin test, aldosterone test, potassium, sodium, and a CT scan of the adrenal glands. In order to check for Addison's Disease, the auto-immune type of primary adrenal insufficiency, labs should be drawn to check 21-hydroxylase autoantibodies.

Cortisol Blood Test

What is Cortisol?

Cortisol (hydrocortisone) is the most prominent glucocorticosteroid, and it is essential for the maintenance of several body functions. Like other glucocorticosteroids, cortisol is synthesized from the common precursor cholesterol in the zona fasciculata of the cortex of the adrenal gland. For the transport of cortisol in blood, about 90% of cortisol is bound to corticosteroid-binding globulin (CBG) and to albumin. Only a small amount of cortisol circulates unbound in blood and is free to interact with its receptors.

Functions of Cortisol

The most important physiological effects of cortisol are the increase in blood glucose levels (enhancement of gluconeogenesis, catabolic action) and its anti-inflammatory and immunosuppressive action.

Production of Cortisol in the Body

Synthesis and secretion of cortisol by the adrenal gland are controlled by a negative feedback mechanism within the hypothalamus-pituitary-adrenal cortex-axis. If the cortisol level is low, corticotropin-releasing hormone (CRH) is secreted by the hypothalamus, which causes the pituitary to release adrenocorticotropic hormone (ACTH). This stimulates the synthesis and secretion of cortisol by the adrenal gland. Cortisol itself acts in a negative feedback mechanism on the pituitary gland and the hypothalamus. In addition, stress is followed by increased cortisol secretion.

Cortisol Blood Levels During the Day

Serum cortisol concentrations normally show a diurnal variation. Maximum concentrations are usually reached early in the morning and then concentrations decline throughout the day to an evening level that is about half of the morning concentration; therefore, for interpretation of results, it is important to know the collection time of the serum sample.

What the Cortisol Test Can Help to Diagnose

The cortisol status of a patient is used to diagnose the function or malfunction of the adrenal gland, the pituitary, and the hypothalamus. Thereby, cortisol serum concentrations are used for monitoring several diseases with an overproduction (eg, Cushing syndrome) or underproduction (eg, Addison disease) of cortisol and for monitoring several therapeutic approaches (eg, dexamethasone suppression therapy in Cushing syndrome and hormone replacement therapy in Addison disease).

Factors that Affect Cortisol Blood Levels

Pregnancy, contraceptives, and estrogen therapy give rise to elevated cortisol concentrations. In samples from patients who have been treated with prednisolone, methylprednisolone, or prednisone, falsely elevated concentrations of cortisol may be determined. During metyrapone tests, 11-deoxycortisol levels are elevated. Falsely-elevated cortisol values may be determined due to cross-reactions. Patients suffering from 21-hydroxylase-deficiency exhibit elevated 21-deoxycortisol levels and this can also give rise to elevated cortisol levels.

The time of sample collection must be taken into account when interpreting results due to the cortisol secretion circadian rhythm. Severe stress can also give rise to elevated cortisol levels.

As with all tests containing monoclonal mouse antibodies, erroneous findings may be obtained from samples taken from patients who have been treated with monoclonal mouse antibodies or who have received them for diagnostic purposes. In rare cases, interference due to extremely high titers of antibodies to streptavidin and ruthenium can occur. The test contains additives, which minimize these effects.

The determination of cortisol in 24-hour urine is the method of choice for the detection of Cushing syndrome since cortisol excretion in urine is not subject to the diurnal rhythm of cortisol secretion.

Potential Interference for the Cortisol Test

This test may exhibit interference when the sample is collected from a person who is consuming a supplement with a high dose of biotin (also termed as vitamin B7 or B8, vitamin H, or coenzyme R). It is recommended to ask all patients who may be indicated for this test about biotin supplementation. Patients should be cautioned to stop biotin consumption at least 72 hours prior to the collection of a sample.

ACTH Test

What is Adrenal Corticotropic Hormone (ACTH)?

Adrenocorticotropic hormone is a hormone secreted in the anterior (front) pituitary gland in your brain.

The role of ACTH is to maintain appropriate levels of the stress hormone cortisol, which is released by the adrenal glands. Cortisol is our body’s natural alarm system. As our body’s primary stress hormone, it works with different parts of the brain to influence our fear, mood, and motivation.

Cortisol is best known for fueling the body’s “fight-or-flight” response in a crisis. But, cortisol also has a critical role in a variety of things the body does, like:

• Controlling the sleeping and waking cycle
• Boosting energy levels to better handle stress (and restore normal levels afterward)
• Influences how the body uses carbs, proteins, and fats
• Reducing inflammation
• Regulating blood pressure
• Increasing blood sugar

What Are the Symptoms of High or Low ACTH Induced Cortisol?

Symptoms of high cortisol can include; high blood pressure, obesity, high blood sugar levels, and edema. Low cortisol levels can cause weight loss, fatigue, low blood pressure, and muscle weakness.

What is the ACTH Test?

If you’re experiencing the symptoms of a cortisol imbalance, your doctor may order an ACTH test to measure the levels of both ACTH and cortisol in the blood . The ACTH test will help your doctor detect the diseases that are associated with too much or too little cortisol in the body. Your doctor might also perform a physical examination before making a firm diagnosis.

DHEA Test

Dehydroepiandrosterone (DHEA) is a hormone produced by the adrenal gland. It is also made in the brain. DHEA leads to the production of androgens and estrogens (male and female sex hormones). As almost all DHEA is derived from the adrenal glands, blood measurements of DHEA-S are useful to detect excess adrenal activity as seen in adrenal cancer or hyperplasia, including certain forms of congenital adrenal hyperplasia.

Although serum DHEA-S levels are low in patients with primary or central adrenal insufficiency, a low level of this steroid is not sufficient by itself for establishing the diagnosis. A normal age- and sex-adjusted serum DHEA-S level, however, practically rules out the diagnosis of adrenal insufficiency.