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.
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 zona fasiculata and zona reticularis, respectively. ACTH is also related to the circadian rhythm in many organisms.
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders characterized by impaired cortisol synthesis. It results from the deficiency of one of the five enzymes required for the synthesis of cortisol in the adrenal cortex. Most of these disorders involve excessive or deficient production of hormones such as glucocorticoids, mineralocorticoids, or sex steroids, and can alter development of primary or secondary sex characteristics in some affected infants, children, or adults. It is one of the most common autosomal recessive disorders in humans.
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 the adrenal cortex—normally secrete 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.
Corticotropic cells, 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.
Lipoid congenital adrenal hyperplasia is an endocrine disorder that is an uncommon and potentially lethal form of congenital adrenal hyperplasia (CAH). It arises from defects in the earliest stages of steroid hormone synthesis: the transport of cholesterol into the mitochondria and the conversion of cholesterol to pregnenolone—the first step in the synthesis of all steroid hormones. Lipoid CAH causes mineralocorticoid deficiency in affected infants and children. Male infants are severely undervirilized causing their external genitalia to look feminine. The adrenals are large and filled with lipid globules derived from cholesterol.
Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is a form of congenital adrenal hyperplasia (CAH) which produces a higher than normal amount of androgen, resulting from a defect in the gene encoding the enzyme steroid 11β-hydroxylase (11β-OH) which mediates the final step of cortisol synthesis in the adrenal. 11β-OH CAH results in hypertension due to excessive mineralocorticoid effects. It also causes excessive androgen production both before and after birth and can virilize a genetically female fetus or a child of either sex.
Congenital adrenal hyperplasia due to 17α-hydroxylase deficiency is an uncommon form of congenital adrenal hyperplasia (CAH) resulting from a mutation in the gene CYP17A1, which produces the enzyme 17α-hydroxylase. It causes decreased synthesis of cortisol and sex hormones, with resulting increase in mineralocorticoid production. Thus, common symptoms include mild cortisol deficiency, ambiguous genitalia in men or amenorrhea at puberty in women, and hypokalemic hypertension. However, partial (incomplete) deficiency often has inconsistent symptoms between patients, and affected women may be asymptomatic except for infertility.
Adrenocorticotropic hormone deficiency is a rare disorder characterized by secondary adrenal insufficiency with minimal or no cortisol production and normal pituitary hormone secretion apart from ACTH. ACTH deficiency may be congenital or acquired, and its symptoms are clinically similar to those of glucocorticoid deficiency. Symptoms consist of weight loss, diminished appetite, muscle weakness, nausea, vomiting, and hypotension. Low blood sugar and hyponatremia are possible; however, blood potassium levels typically remain normal because affected patients are deficient in glucocorticoids rather than mineralocorticoids because of their intact renin-angiotensin-aldosterone system. ACTH may be undetectable in blood tests, and cortisol is abnormally low. Glucocorticoid replacement therapy is required. With the exception of stressful situations, some patients with mild or nearly asymptomatic disease may not require glucocorticoid replacement therapy. As of 2008 about two hundred cases have been described in the literature.
Triple-A syndrome or AAA syndrome is a rare autosomal recessive congenital disorder. In most cases, there is no family history of AAA syndrome. The syndrome was first identified by Jeremy Allgrove and colleagues in 1978; since then just over 100 cases have been reported. The syndrome is called Triple-A due to the manifestation of the illness which includes achalasia, addisonianism, and alacrima. Alacrima is usually the earliest manifestation. Neurodegeneration or atrophy of the nerve cells and autonomic dysfunction may be seen in the disorder; therefore, some have suggested the disorder be called 4A syndrome. It is a progressive disorder that can take years to develop the full-blown clinical picture. The disorder also has variability and heterogeneity in presentation.
The steroidogenic acute regulatory protein, commonly referred to as StAR (STARD1), is a transport protein that regulates cholesterol transfer within the mitochondria, which is the rate-limiting step in the production of steroid hormones. It is primarily present in steroid-producing cells, including theca cells and luteal cells in the ovary, Leydig cells in the testis and cell types in the adrenal cortex.
Pseudohyperaldosteronism is a medical condition which mimics the effects of elevated aldosterone (hyperaldosteronism) by presenting with high blood pressure, 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 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.
Cholesterol side-chain cleavage enzyme is commonly referred to as P450scc, where "scc" is an abbreviation for side-chain cleavage. P450scc is a mitochondrial enzyme that catalyzes conversion of cholesterol to pregnenolone. This is the first reaction in the process of steroidogenesis in all mammalian tissues that specialize in the production of various steroid hormones.
The adrenocorticotropic hormone receptor or ACTH receptor also known as the melanocortin receptor 2 or MC2 receptor is a type of melanocortin receptor (type 2) which is specific for ACTH. A G protein–coupled receptor located on the external cell plasma membrane, it is coupled to Gαs and upregulates levels of cAMP by activating adenylyl cyclase. The ACTH receptor plays a role in immune function and glucose metabolism.
Melanocortin 2 receptor accessory protein 2 is a protein that in humans is encoded by the MRAP2 gene. MRAP2 is a transmembrane accessory protein to a family of five receptors called the melanocortin receptors (MC1-5). Human genome sequencing analysis led to the discovery of MRAP2, Human MRAP2 gene is located in chromosome 6q14.3, a different chromosomal location from that of human MRAP which is a paralogy to MRAP2. MRAP2 is thought to be involved in regulating the expression of the melanocortin (MC1-5) and some non-melanocortin receptors such as ghrelin receptor (GHSR-1a), orexin (OX1R) receptor and prokineticin receptor (PKR-1).
Walter L. Miller is an American endocrinologist and professor emeritus of pediatrics at the University of California, San Francisco (UCSF). Miller is expert in the field of human steroid biosynthesis and disorders of steroid metabolism. Over the past 40 years Miller's group at UCSF has described molecular basis of several metabolic disorders including, congenital adrenal hyperplasia, pseudo vitamin D dependent rickets, severe, recessive form of Ehlers-Danlos syndrome, 17,20 lyase deficiency caused by CYP17A1 defects, P450scc deficiency caused by CYP11A1 defects, P450 oxidoreductase deficiency.
Glucocorticoid deficiency is a condition where the body doesn’t produce enough glucocorticoid hormones.
Late onset congenital adrenal hyperplasia (LOCAH), also known as nonclassic congenital adrenal hyperplasia, is a milder form of congenital adrenal hyperplasia (CAH), a group of autosomal recessive disorders characterized by impaired cortisol synthesis that leads to variable degrees of postnatal androgen excess.
Melanocortin 2 receptor accessory protein is a transmembrane accessory protein that in humans is encoded by the MRAP gene located in chromosome 21q22.11. Alternate splicing of the MRAP mRNA generates two functionally isoforms MRAP-α and MRAP-β.
Generalized glucocorticoid resistance or Chrousos syndrome is a rare genetic disorder that can run in families or be sporadic. It is characterized by partial or generalized target-tissue insensitivity to glucocorticoids.
