Glucocorticoid Therapy - An overview

Introduction

The adrenal cortex's zona fasciculata produces steroid hormones known as glucocorticoids. These molecules are released into the peripheral circulation in a circadian, ultradian, and stress-related manner, all under the direction of the hypothalamic-pituitary-adrenal (HPA) axis. The preservation of resting and stress-related homeostasis is significantly aided by the action of glucocorticoids on a wide range of physiological processes. At the cellular level, glucocorticoids control the growth, differentiation, and programmed cell death (apoptosis) of different types of cells. They may also alter the methylation status of cytosine-guanine dinucleotides (CpG) found in the regulatory regions of many genes, resulting in significant epigenetic changes.

When glucocorticoids are administered at supraphysiologic levels, the hypothalamic-pituitary-adrenal (HPA) axis is suppressed, which prevents the adrenal glands from producing enough cortisol when glucocorticoid therapy is abruptly discontinued. The therapeutic use of glucocorticoids is now also constrained by glucocorticoid resistance.

What Are the Effects of Glucocorticoid Therapy?

Immune:

The immunological and metabolic effects of glucocorticoids can be generally divided into two groups. Additionally, glucocorticoids are crucial for embryonic growth and maintaining body fluid balance.

Glucocorticoids interact with the glucocorticoid receptor to exert their effects:

• The expression of anti-inflammatory proteins should be increased.

• Reduce the expression of inflammatory-promoting proteins.

It has been demonstrated that glucocorticoids are important for the growth and homeostasis of T lymphocytes. This has been demonstrated in transgenic mice with altered T cell lineage sensitivity to glucocorticoids, either enhanced or diminished.

Metabolic:

These hormones were involved in glucose metabolism and gave rise to the term "glucocorticoid." In the fasting state, cortisol promotes a number of processes that work together to raise and maintain appropriate blood glucose concentrations.

• Stimulation of gluconeogenesis, specifically in the liver: This process, which is significant in carnivores and some herbivores, leads to the synthesis of glucose from non-hexose substrates like amino acids and glycerol from triglyceride breakdown. The metabolic activity of glucocorticoids that is probably best known is their ability to increase the expression of enzymes involved in gluconeogenesis.

• The mobilization of amino acids from extrahepatic tissues acts as gluconeogenic substrates.

• A mechanism to conserve glucose is the inhibition of glucose absorption in muscle and adipose tissue.

• Induction of fat oxidation in adipose tissue: The fatty acids liberated during lipolysis are used to produce energy in tissues like muscle, and the glycerol liberated during this process serves as an additional substrate for gluconeogenesis.

• Hypernatremia and hypokalemia are caused by an increase in salt retention and potassium excretion.

• An increase in hemoglobin concentration may result from a macrophage or other phagocyte being unable to consume red blood cells.

• A rise in uric acid in the urine.

• Elevated calcium levels in the urine and hypocalcemia.

• Alkalosis.

• Leukocytosis.

Excessive glucocorticoid levels brought on by medication administration or hyperadrenocorticism have an impact on a variety of systems. Examples include the reduction of bone growth, the suppression of calcium absorption (both of which can result in osteoporosis), the slow healing of wounds, the deterioration of muscles, and the increased risk of infection. These findings point to several glucocorticoid involvements in less dramatic physiological processes.

What Are the Uses of Glucocorticoid Therapy?

Adrenal insufficiency may be treated with low doses of glucocorticoids. Oral or inhaled glucocorticoids are used to reduce a variety of autoimmune, inflammatory, and allergy illnesses in significantly larger doses. The secondary treatment for asthma is inhaled glucocorticoids. In order to avoid acute transplant rejection and graft-versus-host disease, they are also given as post-transplant immunosuppressants. They impede later reparative processes as well as do not stop an infection, though. Historically, glucocorticoids have been used to treat inflammation-related pain. Corticosteroids have a limited ability to relieve pain, and they may have unfavorable side effects when used to treat tendinopathies.

What Are the Side Effects of Glucocorticoid Therapy?

Following all the side effects of glucocorticoid therapy:

• Immune dysfunction.

• Steroid diabetes is characterized by hyperglycemia, increased gluconeogenesis, insulin resistance, and decreased glucose tolerance. Patients are more susceptible to bruising and skin fragility.

• Low intestinal calcium absorption results in a negative calcium balance.

• Reduced bone density caused by steroids-induced osteoporosis (osteoporosis, osteonecrosis, higher fracture risk, slower fracture repair).

• Weight gain brought on by hunger stimulation and increased visceral and truncal fat deposition (central obesity); corticosteroid-induced lipodystrophy.

• Exogenous Cushing's syndrome, or chronic or severe usage of hydrocortisone.

• Memory and concentration problems.

• A lack of adrenal function (if used for a long time and stopped suddenly without a taper).

• Weakness decreased muscle mass and tendon and muscle breakdown (proteolysis).

• Expansion of the malar fat pads and enlargement of the skin's tiny blood vessels.

• The epidural space has lipomatosis (that is the presence of numerous lipomas in the body).

• Stimulation of the central nervous system (euphoria, psychosis).

• Menstrual irregularities and anovulation.

• Delayed puberty and inadequate growth.

• Increased urea production increased plasma amino acids.

• Nitrogen balance is negative.

• Increasing ocular pressure-related glaucoma.

• Cataract.

• Withholding of topical steroids.

Why Is It Necessary to Gradually Reduce the Dosage of Steroid Medications Like Prednisone Before Stopping Them?

The following withdrawal symptoms could occur if you stop taking prednisone abruptly or taper off too quickly:

• Extreme tiredness.

• Weakness.

• Body pain.

• Aching joints.

• Nausea.

• Reduced appetite.

• Lightheadedness.

• Angry or moody behavior.

In addition to causing withdrawal symptoms, improper Prednisone tapering may exacerbate the patient's current symptoms. Additionally, improper tapering could worsen recurring symptoms if the patient uses prednisone for a chronic condition, inflammatory bowel disease, or rheumatoid arthritis.

Prednisone is similar to the hormone cortisol, which adrenal glands naturally produce. The synthesis of cortisol is decreased by adrenal glands if the patient takes Prednisone for a prolonged period of time. Adrenal glands have time to regain their regular function after a Prednisone dose reduction. The length of time it takes to stop taking Prednisone depends on the condition being treated, the dosage and duration of the course, and other medical conditions. To fully recover, it could take anywhere from a week to several months.

Conclusion

Glucocorticoids are a component of the immune system's feedback loop, which lowers some elements of immunological activity like inflammation. As a result, they are employed in medical practice to treat conditions including allergies, asthma, autoimmune illnesses, and sepsis that are brought on by an overactive immune system. Glucocorticoids have a wide range of (pleiotropic) actions, some of which may be adverse. They are used in high doses to treat cancer because they disrupt some of the aberrant pathways in cancer cells. This involves reducing the negative effects of anticancer medications and inhibiting lymphocyte growth, as in the treatment of lymphomas and leukemias.

The most significant human glucocorticoid is cortisol (also known as hydrocortisone). It is necessary for life and regulates or supports a number of critical metabolic, immune, and homeostatic processes. Synthetic glucocorticoids come in a variety of forms, and they are frequently used in general medicine and a wide range of medical specialties to treat glucocorticoid deficiencies or weaken the immune system.