Adrenalism

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Diagram of the kidney and the adrenal gland. The adrenal gland is directly superior to the kidney. Illu adrenal gland.jpg
Diagram of the kidney and the adrenal gland. The adrenal gland is directly superior to the kidney.

Adrenalism describes the condition of an excessive or substandard secretion of hormones related to the adrenal glands, which are found directly superior to the kidneys. [1] [2] Adrenalism can be further distinguished as hyperadrenalism, referring to the excessive secretion of hormones, and hypoadrenalism, referring to the insufficient secretion of hormones. [3] [4]

Contents

The symptoms related to hyperadrenalism are known as Cushing's syndrome, and are caused by overproduction of corticosteroids, aldosterone, and androgenic steroids. [3] 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. [4]

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. [5] The adrenal glands also produce epinephrine (adrenaline) and norepinephrine (noradrenaline). [5]

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. [6]

The production of aldosterone is regulated via the renin-angiotensin II-aldosterone system, a system composed of baroreceptors and juxtaglomerular cells. [7] [8] 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. [8]

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)

A detailed list of symptoms related to Cushing's Syndrome, which is caused by hypercortisolism. Cushing's syndrome (vector image).svg
A detailed list of symptoms related to Cushing's Syndrome, which is caused by hypercortisolism.

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. [6] 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. [9]

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. [10]

Legs of a Caucasian Woman with Addison's Disease. Hypocortisolism causes a chain reaction that leads to hyperpigmentation. Addison'sLegs.jpg
Legs of a Caucasian Woman with Addison's Disease. Hypocortisolism causes a chain reaction that leads to hyperpigmentation.

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. [4] It is important to note that the type of adrenal insufficiency will affect which hormones can or cannot be produced. [11]

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. [11] 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. [11]

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. [12]

Symptoms

Hyperaldrenalism, also known as Cushing's Syndrome, [13] often causes remarkable symptoms in patients, including obesity in the upper body, thin limbs, weak skeleton, and hypertension. Besides the changes in physical health, patients' mental health will also be affected. They are generally more prone to anxiety and fatigue. [14] [11] On the other hand, hypoadrenalism, often referred to as Addison's disease, will cause stronger fatigue in patients with a reduction in body weight and appetite. Hypotension, hypoglycemia, and nausea will also be observed. [15]

Treatments

Treatment of adrenalism varies from surgery to radiotherapy, and medications. The choices of therapy depend on the cause of adrenalism and are listed in descending order of invasiveness of the treatment to the patient. The general idea of the treatment is to replenish the lowered cortisol level by direct supplement or increasing the production level of cortisol in the human body in case of hypoadrenalism, and to reduce the cortisol level by killing or suppressing the adrenal gland in case of hyperadrenalism.

Surgery

Medical practitioners usually recommend surgical treatment for adrenalism caused by tumors since it is one of the most direct ways to cure the disease permanently. With a solid tumor overstimulating or suppressing the normal function of the adrenal glands, surgeons can locate the tumor and remove it using the traditional surgical method. If the tumor is found at the pituitary gland, neurosurgeons would perform the surgery either by craniotomy where the skull is opened and the whole pituitary gland is exposed for tumor cleaning, or by microsurgery where all surgical tools are placed into the brain through the nasal cavity. Microscopes are used to locate the tumor which is then removed with precision. [16] The positive aspect of undergoing adrenal surgery is that it is still currently the fastest solution to adrenalism that can permanently cure the disease. The disadvantage side of removing the adrenal gland is that patients would need to undergo cortisol replacement medication for months, if not life-long, to restore the body's normal hormone level, as well as the risk of invasive surgery itself. [17]

Radiotherapy

Radiotherapy can be an option to treat adrenalism, as it is effective in killing cancer cells across a large surface area. Radiation therapy for cancer.jpg
Radiotherapy can be an option to treat adrenalism, as it is effective in killing cancer cells across a large surface area.

Radiotherapy is also a prompt option for treating adrenalism. It is employed when standard surgery does not work against tumors, or if the patient is not suitable for surgery. Such therapy is useful in treating early-stage adrenalism caused by cancer. It can effectively penetrate small cancer cells across a large area. As a result, it is still effective in situations where cancers have spread out. Normal adrenal levels are usually restored within weeks. There are 2 common ways to treat adrenalism with radiation, namely conventional external beam or stereotactic radiosurgery. The former administers a high dose of radiation around the gland aiming to destroy or reduce the size of the tumor or kill the cell directly by inhibiting cellular proliferation of the cells through exposure to radiation quickly. [12] On the other hand, stereotactic radiosurgery utilizes a series of gamma radiation precisely on the adrenal gland to induce cell death, greatly lowering the side effect of the therapy on surrounding organs such as damaging neighboring cells with normal functions and leading to hormonal dysregulation. However, in post-surgical follow-ups, neurological impact and a high risk of cell mutations are recorded since ionizing radiation is employed in stereotactic radiotherapy.

Medications

Physicians usually recommend medications to patients whose adrenalism is not caused by cancer, since chemotherapy has been proven to be ineffective. [19] Common use of medications include drugs that suppress cortisol production in the adrenal gland by inhibiting 11-beta hydroxylase. Ketoconazole and metyrapone fall under this drug category. [20] Besides mediating the function of adrenal glands, medications may also be given to destroy the gland internally for hyperadrenalism to lower hormone levels. Mitotane is administered to promote apoptosis at the adrenal gland with the downregulation of P450 enzymes and accumulation of free cholesterol which direct cell oxidation rapidly, causing permanent cell death in the glands. [21] Moreover, doctors may prescribe hydrocortisone or prednisolone to patients as a hormone replacement therapy to replenish the depleted adrenal level in patients with Addison's disease. [22] The benefits of medications are that it is non-invasive and the risk of treatment is greatly lowered. On the other hand, the downsides of medications are their low therapeutic effectiveness and a relatively longer time required to illustrate the therapeutic effect. Moreover, past experiences observe side effects of the medication including vomiting, muscle pain, hypertension, and hypokalemia.

Related Research Articles

<span class="mw-page-title-main">Adrenal gland</span> Endocrine gland

The adrenal glands are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex which produces steroid hormones and an inner medulla. The adrenal cortex itself is divided into three main zones: the zona glomerulosa, the zona fasciculata and the zona reticularis.

<span class="mw-page-title-main">Adrenocorticotropic hormone</span> Pituitary hormone

Adrenocorticotropic hormone is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological stress. Its principal effects are increased production and release of cortisol and androgens by the cortex and medulla of the adrenal gland, respectively. ACTH is also related to the circadian rhythm in many organisms.

<span class="mw-page-title-main">Cushing's syndrome</span> Symptoms from excessive exposure to glucocorticoids such as cortisol

Cushing's syndrome is a collection of signs and symptoms due to prolonged exposure to glucocorticoids such as cortisol. Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, a round red face due to facial plethora, a fat lump between the shoulders, weak muscles, weak bones, acne, and fragile skin that heals poorly. Women may have more hair and irregular menstruation. Occasionally there may be changes in mood, headaches, and a chronic feeling of tiredness.

<span class="mw-page-title-main">Adrenal cortex</span> Cortex of the adrenal gland

The adrenal cortex is the outer region and also the largest part of the adrenal gland. It is divided into three separate zones: zona glomerulosa, zona fasciculata and zona reticularis. Each zone is responsible for producing specific hormones. It is also a secondary site of androgen synthesis.

<span class="mw-page-title-main">Addison's disease</span> Endocrine disorder

Addison's disease, also known as primary adrenal insufficiency, is a rare long-term endocrine disorder characterized by inadequate production of the steroid hormones cortisol and aldosterone by the two outer layers of the cells of the adrenal glands, causing adrenal insufficiency. Symptoms generally come on slowly and insidiously and may include abdominal pain and gastrointestinal abnormalities, weakness, and weight loss. Darkening of the skin in certain areas may also occur. Under certain circumstances, an adrenal crisis may occur with low blood pressure, vomiting, lower back pain, and loss of consciousness. Mood changes may also occur. Rapid onset of symptoms indicates acute adrenal failure, which is a clinical emergency. An adrenal crisis can be triggered by stress, such as from an injury, surgery, or infection.

Cushing's disease is one cause of Cushing's syndrome characterised by increased secretion of adrenocorticotropic hormone (ACTH) from the anterior pituitary. This is most often as a result of a pituitary adenoma or due to excess production of hypothalamus CRH that stimulates the synthesis of cortisol by the adrenal glands. Pituitary adenomas are responsible for 80% of endogenous Cushing's syndrome, when excluding Cushing's syndrome from exogenously administered corticosteroids. The equine version of this disease is Pituitary pars intermedia dysfunction.

<span class="mw-page-title-main">Primary aldosteronism</span> Medical condition

Primary aldosteronism (PA), also known as primary hyperaldosteronism or Conn's syndrome, refers to the excess production of the hormone aldosterone from the adrenal glands, resulting in low renin levels and high blood pressure. This abnormality is caused by hyperplasia or tumors. Many experience fatigue, potassium deficiency and high blood pressure which may cause poor vision, confusion or headaches. Symptoms may also include: muscular aches and weakness, muscle spasms, low back and flank pain from the kidneys, trembling, tingling sensations, dizziness/vertigo, nocturia and excessive urination. Complications include cardiovascular disease such as stroke, myocardial infarction, kidney failure and abnormal heart rhythms.

<span class="mw-page-title-main">Adrenal insufficiency</span> Medical condition

Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones. The adrenal glands, also referred to as adrenal cortex normally secretes glucocorticoids, mineralocorticoids, and androgens. These hormones are important in regulating blood pressure, electrolytes, and metabolism as a whole. Deficiency of these hormones leads to symptoms ranging from abdominal pain, vomiting, muscle weakness and fatigue, low blood pressure, depression, mood and personality changes to organ failure and shock. Adrenal crisis may occur if a person having adrenal insufficiency experiences stresses, such as an accident, injury, surgery, or severe infection; this is a life-threatening medical condition resulting from severe deficiency of cortisol in the body. Death may quickly follow.

Corticotropes are basophilic cells in the anterior pituitary that produce pro-opiomelanocortin (POMC) which undergoes cleavage to adrenocorticotropin (ACTH), β-lipotropin (β-LPH), and melanocyte-stimulating hormone (MSH). These cells are stimulated by corticotropin releasing hormone (CRH) and make up 15–20% of the cells in the anterior pituitary. The release of ACTH from the corticotropic cells is controlled by CRH, which is formed in the cell bodies of parvocellular neurosecretory cells within the paraventricular nucleus of the hypothalamus and passes to the corticotropes in the anterior pituitary via the hypophyseal portal system. Adrenocorticotropin hormone stimulates the adrenal cortex to release glucocorticoids and plays an important role in the stress response.

<span class="mw-page-title-main">Hypopituitarism</span> Medical condition

Hypopituitarism is the decreased (hypo) secretion of one or more of the eight hormones normally produced by the pituitary gland at the base of the brain. If there is decreased secretion of one specific pituitary hormone, the condition is known as selective hypopituitarism. If there is decreased secretion of most or all pituitary hormones, the term panhypopituitarism is used.

<span class="mw-page-title-main">Metyrapone</span> Chemical compound

Metyrapone, sold under the brand name Metopirone, is a medication which is used in the diagnosis of adrenal insufficiency and occasionally in the treatment of Cushing's syndrome (hypercortisolism). It is part of the steroidogenesis inhibitor class of drugs.

<span class="mw-page-title-main">Hypoaldosteronism</span> Medical condition

Hypoaldosteronism is an endocrinological disorder characterized by decreased levels of the hormone aldosterone. Similarly, isolated hypoaldosteronism is the condition of having lowered aldosterone without corresponding changes in cortisol.

Secondary hypertension is a type of hypertension which by definition is caused by an identifiable underlying primary cause. It is much less common than the other type, called essential hypertension, affecting only 5-10% of hypertensive patients. It has many different causes including endocrine diseases, kidney diseases, and tumors. It also can be a side effect of many medications.

Nelson's syndrome is a disorder that occurs in about one in four patients who have had both adrenal glands removed to treat Cushing's disease. In patients with pre-existing adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas, loss of adrenal feedback following bilateral adrenalectomy can trigger the rapid growth of the tumor, leading to visual symptoms and hyperpigmentation. The severity of the disease is dependent upon the effect of ACTH release on the skin, pituitary hormone loss from mass compression, as well as invasion into surrounding structures around the pituitary gland.

In humans and other animals, the adrenocortical hormones are hormones produced by the adrenal cortex, the outer region of the adrenal gland. These polycyclic steroid hormones have a variety of roles that are crucial for the body’s response to stress, and they also regulate other functions in the body. Threats to homeostasis, such as injury, chemical imbalances, infection, or psychological stress, can initiate a stress response. Examples of adrenocortical hormones that are involved in the stress response are aldosterone and cortisol. These hormones also function in regulating the conservation of water by the kidneys and glucose metabolism, respectively.

Pseudohyperaldosteronism is a medical condition which mimics the effects of elevated aldosterone (hyperaldosteronism) by presenting with high blood pressure (hypertension), low blood potassium levels (hypokalemia), metabolic alkalosis, and low levels of plasma renin activity (PRA). However, unlike hyperaldosteronism, this conditions exhibits low or normal levels of aldosterone in the blood. Causes include genetic disorders, acquired conditions, metabolic disorders, and dietary imbalances including excessive consumption of licorice. Confirmatory diagnosis depends on the specific root cause and may involve blood tests, urine tests, or genetic testing; however, all forms of this condition exhibit abnormally low concentrations of both plasma renin activity (PRA) and plasma aldosterone concentration (PAC) which differentiates this group of conditions from other forms of secondary hypertension. Treatment is tailored to the specific cause and focuses on symptom control, blood pressure management, and avoidance of triggers.

The ACTH test is a medical test usually requested and interpreted by endocrinologists to assess the functioning of the adrenal glands' stress response by measuring the adrenal response to adrenocorticotropic hormone or another corticotropic agent such as tetracosactide or alsactide (Synchrodyn). ACTH is a hormone produced in the anterior pituitary gland that stimulates the adrenal glands to release cortisol, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and aldosterone.

<span class="mw-page-title-main">Adrenal crisis</span> Medical condition

Adrenal crisis is a potentially life-threatening medical condition requiring immediate emergency treatment. It is a constellation of symptoms that indicate severe adrenal insufficiency. This may be the result of either previously undiagnosed or untreated Addison's disease, a disease process suddenly affecting adrenal function, suddenly stopping intake of glucocorticoids or an intercurrent problem in someone known to have Addison's disease, congenital adrenal hyperplasia (CAH), or other form of primary adrenal insufficiency.

Hypoadrenocorticism in dogs, or, as it is known in people, Addison's disease, is an endocrine system disorder that occurs when the adrenal glands fail to produce enough hormones for normal function. The adrenal glands secrete glucocorticoids such as cortisol and mineralocorticoids such as aldosterone; when proper amounts of these are not produced, the metabolic and electrolyte balance is upset. Mineralocorticoids control the amount of potassium, sodium, and water in the body. Hypoadrenocorticism is fatal if left untreated.

Adrenal gland disorders are conditions that interfere with the normal functioning of the adrenal glands. Adrenal disorders may cause hyperfunction or hypofunction, and may be congenital or acquired.

References

  1. ↑ "Gray's Anatomy" (42nd ed.). Elsevier. Retrieved 2023-03-28.
  2. ↑ "Adrenalism", The Free Dictionary, retrieved 2023-03-26
  3. 1 2 "Overactive Adrenal Glands/Cushing's Syndrome". www.hopkinsmedicine.org. 2022-06-08. Retrieved 2023-03-27.
  4. 1 2 3 "Adrenal Insufficiency (Addison's Disease)". www.hopkinsmedicine.org. 2020-07-20. Retrieved 2023-03-27.
  5. 1 2 "Adrenal Glands". www.hopkinsmedicine.org. 2021-08-08. Retrieved 2023-03-27.
  6. 1 2 Uwaifo GI, Hura DE (2023). "Hypercortisolism". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID   31855370 . Retrieved 2023-03-27.
  7. ↑ Scott JH, Menouar MA, Dunn RJ (2023). "Physiology, Aldosterone". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID   29261963 . Retrieved 2023-03-27.
  8. 1 2 Fountain JH, Kaur J, Lappin SL (2023). "Physiology, Renin Angiotensin System". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID   29261862 . Retrieved 2023-03-27.
  9. ↑ Cushing's Syndrome Archived 2011-04-10 at the Wayback Machine at The National Endocrine and Metabolic Diseases Information Service. July 2008. Citing: * Nieman LK, Ilias I (December 2005). "Evaluation and treatment of Cushing's syndrome". The American Journal of Medicine. 118
  10. ↑ Dominguez A, Muppidi V, Gupta S (2023). "Hyperaldosteronism". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID   29763159 . Retrieved 2023-03-28.
  11. 1 2 3 4 "What are the symptoms of adrenal gland disorders?". National Institute of Child Health and Development. Retrieved 2023-03-28.
  12. 1 2 "External Beam Radiation Therapy for Cancer - NCI". www.cancer.gov. 2018-05-01. Retrieved 2023-03-28.
  13. ↑ [ "Cushing's syndrome"], Wikipedia, 2022-11-28, retrieved 2023-03-28{{citation}}: Check |url= value (help)
  14. ↑ "Primary Hyperadrenalism: Cushing's Syndrome - LabCE.com, Laboratory Continuing Education". www.labce.com. Retrieved 2023-03-28.
  15. ↑ "Addison's disease". nhs.uk. 2018-06-22. Retrieved 2023-03-28.
  16. ↑ "Cushing syndrome - Diagnosis and treatment - Mayo Clinic". www.mayoclinic.org. Retrieved 2023-03-28.
  17. ↑ "Are people with Cushing's disease refractory to surgery and radiotherapy better served with long-term pharmacotherapy or bilateral adrenalectomy?". www.healio.com. Retrieved 2023-03-28.
  18. ↑ Chen HH, Kuo MT (September 2017). "Improving radiotherapy in cancer treatment: Promises and challenges". Oncotarget. 8 (37): 62742–62758. doi:10.18632/oncotarget.18409. PMC   5617545 . PMID   28977985.
  19. ↑ "Chemotherapy for Adrenal Cancer". www.cancer.org. Retrieved 2023-03-28.
  20. ↑ Loli P, Berselli ME, Tagliaferri M (December 1986). "Use of ketoconazole in the treatment of Cushing's syndrome". The Journal of Clinical Endocrinology and Metabolism. 63 (6): 1365–1371. doi:10.1210/jcem-63-6-1365. PMID   3023421.
  21. ↑ Lo Iacono M, Puglisi S, Perotti P, Saba L, Petiti J, Giachino C, et al. (October 2021). "Molecular Mechanisms of Mitotane Action in Adrenocortical Cancer Based on In Vitro Studies". Cancers. 13 (21): 5255. doi:10.3390/cancers13215255. PMC   8582505 . PMID   34771418.
  22. ↑ "Addison's disease - Treatment". nhs.uk. 2017-10-20. Retrieved 2023-03-28.
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