Adrenalism

The symptoms related to hyperadrenalism are known as Cushing's syndrome, and are caused by overproduction of corticosteroids, aldosterone, and androgenic steroids. Symptoms related to hypoadrenalism, such as Addison's disease, are caused by the underproductions of the hormones listed above. Furthermore, adrenalism may be caused by other external factors, which will be further discussed in the article.

Etiology

The adrenal glands produce important hormones that have specific roles in the homeostasis of the body, which are regulated by other glands. These hormones include aldosterone, a mineralocorticoid that regulates the amount of salt in tissue and body fluids, cortisol, a glucocorticoid that regulates metabolism and usage of macronutrients in the body, and sex hormones, such as androgens and estrogen that promote the development of secondary sex characteristics. The adrenal glands also produce epinephrine (adrenaline) and norepinephrine (noradrenaline).

The production of cortisol is regulated by the hypothalamic–pituitary–adrenal axis and the hormones that are produced in the axis, namely corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH). The CRH produced by the hypothalamus stimulates the pituitary gland to produce ACTH, which stimulates the adrenal gland to produce cortisol. A negative feedback loop is formed as high levels of cortisol inhibit the hormones produced in the axis.

The production of aldosterone is regulated via the renin-angiotensin II-aldosterone system, a system composed of baroreceptors and juxtaglomerular cells. Changes in the homeostasis of the human body, such as osmolality are detected by the system, which causes a chain reaction that ends with the adrenal gland either increasing or suppressing the production of aldosterone.

Hyperadrenalism

Hyperadrenalism refers to the overactivity of the adrenal glands. This is usually indicated by the excessive production of the hormones produced by the adrenal glands. As the hormones produced are regulated by a range of systems in the body, overactivity of the adrenal glands can be caused by different systemic dysfunctions, leading to the overproduction of specific hormones.

Overproduction of Cortisol/ Hypercortisolism (HCM)

When the body is exposed to an excess level of cortisol, generalized symptoms that are referred to as Cushing's syndrome appear. However, the condition may only be temporary, known as pseudo-Cushing's syndrome (PCS). Therefore, it is important to understand the cause of the syndrome to differentiate between PCS and HCM. HCM itself also has many causes, such as adrenal adenomas and carcinomas causing the adrenal gland to be unresponsive to the negative feedback loop. An increase in ACTH production could be due to a pituitary adenoma, or ectopic ACTH production, where tumors growing outside the hypothalamic-pituitary-adrenal axis also secrete ACTH.

Overproduction of aldosterone/ Hyperaldosteronism

The difference between primary hyperaldosteronism and secondary hyperaldosteronism lies in the causation of excess aldosterone, where primary hyperaldosteronism refers to the overproduction of aldosterone from the adrenal glands, and secondary hyperaldosteronism refers to the overactivation of the RAAS system. Primary hyperaldosteronism presents as a tumor in the gland, known as Conn Syndrome. Secondary hyperaldosteronism may occur from a renin-producing tumor, or other edematous disorders that affect the baroreceptors and juxtaglomerular cells.

Hypoadrenalism

Hypoadrenalism, or adrenal insufficiency, is a condition indicated by the underproduction of hormones that are related to the adrenal glands. Underactivity of the adrenal gland is also caused by the adrenal glands, or by other systemic dysfunctions, leading to insufficient production of hormones. This can be further classified into Primary Adrenal Insufficiency, where the damaged adrenal glands cannot produce hormones, or Secondary Adrenal Insufficiency, where the pituitary gland does not produce enough ACTH to stimulate the adrenal gland to produce hormones. The type of adrenal insufficiency will affect which hormones can or cannot be produced.

Underproduction of cortisol/ Hypocortisolism

Hypocortisolism can be caused by autoimmune disorders, cancer, fungal infections, tuberculosis infection of the adrenal glands and inherited disorders of the endocrine gland. In primary adrenal insufficiency, the damaged glands are unable to produce cortisol. The lack of cortisol will not initiate the negative feedback loop, which will cause the pituitary gland to continue producing ACTH and CRH, leading to symptoms that are related to Addison's disease. In secondary adrenal insufficiency, the pituitary gland does not produce enough ACTH to stimulate the production of cortisol. Hypocortisolism will lead to hypoglycemia and hypotension.

Underproduction of aldosterone/ Hypoaldosteronism

Hypoaldosteronism occurs in primary adrenal insufficiency, but not secondary adrenal insufficiency. This is because secondary adrenal insufficiency is related to the pituitary gland and its ability to produce ACTH, which is not a hormone that regulates the production of Aldosterone from the adrenal gland. However, primary adrenal insufficiency is caused by damage to the adrenal glands, which leads to underproduction of the hormones. Primary adrenal insufficiency causes hypoaldosteronism along with hypocortisolism.