Glucocorticoids: restoring balance during stress

While we often associate the term ‘stress’ with anxiety, the term really encompasses any challenge that has potential to disrupt homeostasis. This includes physical stressors like infection or injury. The physiological requirements in response to these diverse challenges are all mediated – at least in part – by the glucocorticoid cortisol.

PHYSIOLOGICAL EFFECTS

Glucocorticoids are cholesterol-derived steroid hormones synthesised and secreted by the adrenal gland. They are anti-inflammatory in all tissues, and control metabolism in muscle, fat, liver and bone. Glucocorticoids also affect vascular tone, and in the brain influence mood, behaviour and sleep‒wakefulness cycles.

Glucocorticoid excess (due to pathology such as Cushing’s syndrome or prescribed synthetic glucocorticoids) can cause immunosuppression, muscle atrophy, central adiposity, hepatosteatosis, osteoporosis, insulin resistance, hypertension, depression and insomnia.

Elevated glucocorticoids can therefore be damaging, and so their production is under the strict control of the hypothalamic-pituitary-adrenal (HPA) axis (Figure 1). Activation of the hypothalamus initiates the release of corticotrophin-releasing hormone (CRH), which in turn signals to the anterior pituitary to release adrenocorticotrophin (ACTH). This then signals to the cortical layer of the adrenal gland to release glucocorticoids, which can act on peripheral tissues.

Over time, elevated circulating glucocorticoids feed back to the hypothalamus and pituitary to block further release of CRH and ACTH respectively, which inhibits glucocorticoid release. As a consequence, glucocorticoids are secreted in a pulsatile manner, and display a diurnal rhythm where circulating hormone levels peak at the onset of waking.

MAINTAINING BALANCE

In the context of maintaining normal homeostasis, the daily peak of glucocorticoid is very important. The transient peak increases vascular tone and alertness, mobilises energy and has a priming effect on the immune system. Essentially, your morning dose of cortisol prepares you to face the potential challenges in your day.

Stresses encountered through the day can drive additional pulses of glucocorticoids from the adrenal which drive sustained, elevated glucocorticoid levels. This produces the same physiological response but with a greater magnitude. In a ‘fight or flight’ context for example, glucocorticoids increase vascular tone and alertness, mobilise energy (prepare you to run) and prime the immune system (prepare you for injury). These preparatory effects increase the likelihood that the stressor can be overcome, so that normal homeostasis can be quickly restored.

It seems paradoxical that a potent immunosuppressive hormone would prime the immune system, but facilitating activation of immune cells is beneficial. It increases the ability of the immune system to detect pathogens/injury and respond accordingly, and it facilitates resolution and repair, to restore balance. In the context of chronic infection or disease, however, the role of glucocorticoids changes, in order to prevent escalation and limit damage.

Glucocorticoids act directly on cells within the damaged tissue to block production of inflammatory signals (cytokines, chemokines) that attract immune cells. They act directly on the immune cells to inhibit their ability to infiltrate the tissue, and in some cell types induce their death. Glucocorticoids also promote activation of scavenger immune cells that help remove cell debris, promote repair and prevent lasting damage (such as fibrosis). At the cellular level, glucocorticoids are able to control metabolism, inflammation, adhesion, migration and survival, in a cell-specific and context-specific manner.

MECHANISM OF ACTION

Glucocorticoids mediate their cellular effects through binding and activating the glucocorticoid receptor (GR), which is expressed in almost every tissue. Glucocorticoids diff use into the cell, and bind and activate the GR, which then moves into the nucleus.

The GR can bind DNA directly at specific glucocorticoid response elements (GREs), and then recruit coactivator or corepressor proteins to increase or decrease expression of target genes. The GR can also bind or tether itself to other DNA-bound transcription factors and modulate their ability to change gene expression (Figure 2).

The specific genes that the GR can control ‒ and therefore the cellular processes that glucocorticoids can regulate ‒ are critically determined by the ability of the GR to bind. This adds an additional layer of control, because gene accessibility and transcription factor expression and activity are cell-specific and dynamically regulated.

For example, liver-specific transcription factors such as HNF4 (hepatocyte nuclear factor 4) facilitate GR binding to (and regulation of) metabolic genes, whereas macrophage-specific transcription factors such as PU.1 recruit GR to genes important in immunity.

Glucocorticoid responses are therefore fine-tuned to consider context. This is how glucocorticoids can control metabolism in liver, activation of macrophages, and promote death of T-cells.

The GR is also recruited by the proinflammatory transcription factor NFκB (nuclear factor-κB). In contrast to HNF4 and PU.1, NFκB is expressed in every cell, but only binds DNA when activated in response to a pathogen or tissue damage. Consequently, the GR is only recruited to (and inhibits) proinflammatory genes if NFκB is activated. This explains why the GR (and glucocorticoids) is a potent inhibitor of inflammation only when required: i.e. when inflammation is already present.

Glucocorticoids (through the GR) are therefore perfectly adapted to integrate incoming signals from other pathways in order to respond appropriately to each specific challenge. We still have a long way to go in order to fully understand the whole spectrum of glucocorticoid action. However, we now have some insight into how, by adding a few additional points of control, glucocorticoids can co-ordinate diverse cellular effects to reach a common goal: the restoration of balance following stress.

Giorgio Caratti, Postdoctoral Fellow, University of Ulm, Germany

Pauline Pfänder, PhD Student, German Cancer Research Center (DKFZ), Germany

Laura Matthews, University Academic Fellow, University of Leeds

Cortisol Test: MedlinePlus Medical Test

What happens during a cortisol test?

A cortisol test is usually in the form of a blood test. During a blood test, a health care professional will take a blood sample from a vein in your arm, using a small needle. After the needle is inserted, a small amount of blood will be collected into a test tube or vial. You may feel a little sting when the needle goes in or out. This usually takes less than five minutes.

Because cortisol levels change throughout the day, the timing of a cortisol test is important. A cortisol blood test is usually done twice a day–once in the morning when cortisol levels are at their highest, and again around 4 p.m., when levels are much lower.

Cortisol may also be measured in a urine or saliva test. For a cortisol urine test, your health care provider may ask you to collect all urine during a 24-hour period. This is called a “24-hour urine sample test.” It is used because cortisol levels vary throughout the day. For this test, your health care provider or a laboratory professional will give you a container to collect your urine and instructions on how to collect and store your samples. A 24-hour urine sample test usually includes the following steps:

• Empty your bladder in the morning and flush that urine away. Record the time.
• For the next 24 hours, save all your urine passed in the container provided.
• Store your urine container in the refrigerator or a cooler with ice.
• Return the sample container to your health provider’s office or the laboratory as instructed.

A cortisol saliva test is usually done at home, late at night, when cortisol levels are lower. Your health care provider will recommend or provide you with a kit for this test. The kit will likely include a swab to collect your sample and a container to store it. Steps usually include the following:

• Do not eat, drink, or brush your teeth for 15-30 minutes before the test.
• Collect the sample between 11 p.m. and midnight, or as instructed by your provider.
• Put the swab into your mouth.
• Roll the swab in your mouth for about 2 minutes so it can get covered in saliva.
• Don’t touch the tip of the swab with your fingers.
• Put the swab into the container within the kit and return it to your provider as instructed.

Glucocorticoids

Glucocorticoids

In contrast to loss of mineralocorticoids, failure to produce glucocorticoids is not acutely life-threatening. Nevertheless, loss or profound diminishment of glucocorticoid secretion leads to a state of deranged metabolism and an inability to deal with stressors which, if untreated, is fatal.

In addition to their physiologic importance, glucocorticoids are also among the most frequently used drugs, and often prescribed for their anti-inflammatory and immunosuppressive properties.

Cortisol and Glucocorticoid Receptors

The vast majority of glucocorticoid activity in most mammals is from cortisol, also known as hydrocortisone. Corticosterone, the major glucocorticoid in rodents, is another glucocorticoid.

Cortisol binds to the glucocorticoid receptor in the cytoplasm and the hormone-receptor complex is then translocated into the nucleus, where it binds to its DNA response element and modulates transcription from a large battery of genes, leading to changes in the cell’s phenotype. Genomics analysis indicates that 29% of human genes have a glucocorticoid response element, which explains the huge number of effects glucocorticoids have on physiology.

Only about 10% of circulating cortisol is free. The remaining majority circulates bound to plasma proteins, particularly corticosteroid-binding globulin (transcortin). This protein binding likely decreases the metabolic clearance rate of glucocorticoids and, because the bound steroid is not biologically active, tends to act as a buffer and blunt wild fluctuations in cortisol concentration.

Physiologic Effects of Glucocorticoids

There seem to be no cells that lack glucocorticoid receptors and as a consequence, these steroid hormones have a huge number of effects on physiologic systems. That having been said, it can be stated that the best known and studied effects of glucocorticoids are on carbohydrate metabolism and immune function.

Effects on Metabolism

The name glucocorticoid derives from early observations that these hormones were involved in glucose metabolism. In the fasted state, cortisol stimulates several processes that collectively serve to increase and maintain normal concentrations of glucose in blood. These effects include:

• Stimulation of gluconeogenesis, particularly in the liver: This pathway results in the synthesis of glucose from non-hexose substrates such as amino acids and lipids and is particularly important in carnivores and certain herbivores. Enhancing the expression of enzymes involved in gluconeogenesis is probably the best known metabolic function of glucocorticoids.
• Mobilization of amino acids from extrahepatic tissues: These serve as substrates for gluconeogenesis.
• Inhibition of glucose uptake in muscle and adipose tissue: A mechanism to conserve glucose.
• Stimulation of fat breakdown in adipose tissue: The fatty acids released by lipolysis are used for production of energy in tissues like muscle, and the released glycerol provide another substrate for gluconeogenesis.

Effects on Inflammation and Immune Function

Glucocorticoids have potent anti-inflammatory and immunosuppressive properties. This is particularly evident when they administered at pharmacologic doses, but also is important in normal immune responses. As a consequence, glucocorticoids are widely used as drugs to treat inflammatory conditions such as arthritis or dermatitis, and as adjunction therapy for conditions such as autoimmune diseases.

The early manifestations of glucocorticoid deficiency, which can be severe, include excessive secretion of a number of inflammatory cytokines. This reflects the normal role of cortisol in suppressing cytokine responses.

Other Effects of Glucocorticoids

Glucocorticoids have multiple effects on fetal development. An important example is their role in promoting maturation of the lung and production of the surfactant necessary for extrauterine lung function. Mice with homozygous disruptions in the corticotropin-releasing hormone gene (see below) die at birth due to pulmonary immaturity.

Several aspects of cognitive function are known to both stimulate glucocorticoid secretion and be influenced by glucocorticoids. Fear provides an interesting example of this. Fear-inducing stimuli lead to secretion of glucocorticoids from the adrenal gland, and treatment of phobic individuals with glucocorticoids prior to a fear-inducing stimulus can blunt the fear response.

Excessive glucocorticoid levels resulting from administration as a drug or hyperadrenocorticism have effects on many systems. Some examples include inhibition of bone formation, suppression of calcium absorption and delayed wound healing. These observations suggest a multitide of less dramatic physiologic roles for glucocorticoids.

Control of Cortisol Secretion

Cortisol and other glucocorticoids are secreted in response to a single stimulator: adrenocorticotropic hormone (ACTH) from the anterior pituitary. ACTH is itself secreted under control of the hypothalamic peptide corticotropin-releasing hormone (CRH). The central nervous system is thus the commander and chief of glucocorticoid responses, providing an excellent example of close integration between the nervous and endocrine systems.

Virtually any type of physical or mental stress results in elevation of cortisol concentrations in blood due to enhanced secretion of CRH in the hypothalamus. This fact sometimes makes it very difficult to assess glucocorticoid levels, particularly in animals. Observing the approach of a phlebotomist, and especially being restrained for blood sampling, is enough stress to artificially elevate cortisol levels several fold!

Cortisol secretion is suppressed by classical negative feedback loops. When blood concentrations rise above a certain theshold, cortisol inhibits CRH secretion from the hypothalamus, which turns off ACTH secretion, which leads to a turning off of cortisol secretion from the adrenal. The combination of positive and negative control on CRH secretion results in pulsatile secretion of cortisol. Typically, pulse amplitude and frequency are highest in the morning and lowest at night.

ACTH binds to receptors in the plasma membrane of cells in the zona fasiculata and reticularis of the adrenal. Hormone-receptor engagement activates adenyl cyclase, leading to elevated intracellular levels of cyclic AMP which leads ultimately to activation of the enzyme systems involved in biosynthesis of cortisol from cholesterol.

Disease States

The most prevalent disorder involving glucocorticoids in man and animals is hyperadrenocorticism or Cushings disease. Excessive levels of glucocorticoids are seen in two situations:

• Excessive endogenous production of cortisol, which can result from a primary adrenal defect (ACTH-independent) or from excessive secretion of ACTH (ACTH-dependent).
• Administration of glucocorticoids for theraputic purposes. This is a common side-effect of these widely-used drugs.

Cushing’s disease has widespread effects on metabolism and organ function, which is not surprising considering the ubiquitous distribution of glucocorticoid receptors. A diverse set of clinical manifestations accompany this disorder, including hypertension, apparent obesity, muscle wasting, thin skin, and metabolic aberrations such as diabetes.

Insufficient production of cortisol, often accompanied by an aldosterone deficiency, is called hypoadrenocorticism or Addison’s disease. Most commonly, this disease is a result of infectious disease (e.g. tuberculosis in humans) or autoimmune destruction of the adrenal cortex. As with Cushing’s disease, numerous and diverse clincial signs accompany Addison’s disease, including cardiovascular disease, lethargy, diarrhea, and weakness. Aldosterone deficiency can be acutely life threatening due to disorders of electrolyte balance and cardiac function.

Updated October 2019. Send comments to [email protected]

Glucocorticoids – an overview | ScienceDirect Topics

4.2.2 Hypothalamic-Pituitary-Adrenal Axis

Stress challenges physiological stability (Pariante & Lightman, 2008). These demands result in brief increases in heart rate and mild elevations in cortisol returning to normal levels quickly. During a stress response, changes in physiological functioning occur. The release of glucocorticoids (i.e., cortisol) and the catecholamine neurotransmitters, epinephrine, and norepinephrine from the adrenal glands leads these. The hypothalamic-pituitary-adrenal (HPA) axis mediates this process. Oxytocin, opioids, and dopamine also play significant parts in stress modulation.

Stress results from the perception of a threat. This harm-eliciting stimulus triggers the brain’s amygdala. Corticotropin-releasing hormone or factor (CRH or CRF) in the hypothalamus is released, which releases adrenocorticotropic hormone in the pituitary. The pituitary sends messages to the adrenal cortex to release epinephrine and cortisol. Epinephrine provides short-term adaptive modulation. Cortisol has longer-term effects. Cortisol has several functions: to modulate blood sugar, to regularly suppress the immune response reducing inflammation, and to modulate the stress reaction, but only briefly.

The stress-signaling molecule, CRF, provokes serotonin in the dorsal raphe nucleus (DRN). Dysfunctional serotonergic inhibitory projections from the dorsal raphe nuclei lead to excessive responses to threat and fear. Periaqueductal gray matter (PAG or central gray) transmits these responses. The DRN projects to the bed nucleus of the stria terminalis. When this form of serotonin activates this system, anxiety and fear arise. Drugs to block CRF are being investigated to treat anxiety, depression, and addiction (Newman et al., 2018). This “science” attests to the biomental realities of human emotion embedded in the body.

The stress hormone, cortisol, from the adrenals is crucial to health and disease when unregulated. Prolonged, elevated cortisol levels interfere with learning and memory, lower immune function, negatively affect bone density, and increase weight gain, blood pressure, cholesterol, and heart disease. Emotional dysregulation—anxiety, irritability, and mood malaise—accompanies these changes. Relaxation and laughter lower cortisol levels and the stress response.

The adrenal glands are part of an adaptive system involved in the maintenance of a homeostatic balance in response to stress. Physical or emotional stressors and inflammatory processes activate adrenal functions. In normal states of anticipatory anxiety or good stress (i.e., eustress), the adrenals release cortisol, epinephrine, and norepinephrine to preserve a healthy equilibrium. The adrenals release epinephrine and norepinephrine into the circulation and start the “fight-or-flight” response. They increase respiration and heart rate; glucose also rises. Healthy cortisol levels contribute to carbohydrate, protein, and fat metabolism, regulate blood glucose, and suppress the immune system. This change in moderation is healthy; it increases alertness and ensures survival.

However, excess release of neurotransmitters and glucocorticoids from the adrenals, if left unchecked, advances several pathological responses. Cortisol’s more damaging effect lasts if high cortisol levels persist. The stress reaction can become a response lasting several hours. If not modulated, balanced, and stabilized by stress reduction, damaging chronic stress sets in. A network of CNS neurons with peripheral nervous system effects and the HPA axis mediate the control and release of these molecules from the adrenal glands. It has a central role, along with the amygdala, in modulating positive and negative emotionality.

Gender differences in managing stress show that males use rapid “fight-flight” reactions in contrast to women, who use “tend and befriend” responses. While this generalization may be valid, an individual’s context, different physiologies, and coping capacities influence the ways she or he will manage exposure and response to stressful life events.

Cortisol | Lab Tests Online

Sources Used in Current Review

Griffing, G. (Updated 2014 March 11). Serum Cortisol. Medscape Drugs & Diseases [On-line information]. Available online at http://emedicine.medscape.com/article/2088826-overview. Accessed February 2015.

Straseski, J. (Updated 2015 January). Adrenal Hyperfunction – Cushing Syndrome. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/CushingSyndrome.html?client_ID=LTD#tabs=0. Accessed February 2015.

Wisse, B. (Updated 2013 November 7). Cortisol blood test. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003693.htm. Accessed February 2015.

(© 1995–2015). Cortisol, Serum. Mayo Clinic Mayo Medical Laboratories [On-line information]. Available online at http://www.mayomedicallaboratories.com/test-catalog/Overview/8545. Accessed February 2015.

Straseski, J. (Updated 2014 November). Adrenal Insufficiency. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/AdrenalInsufficiency. html?client_ID=LTD. Accessed February 2015.

Morley, J. (Revised 2013 February). Overview of the Endocrine System. The Merck Manual Professional Edition [On-line information]. Available online through http://www.merckmanuals.com. Accessed February 2015.

Pagana, K. D., Pagana, T. J., and Pagana, T. N. (© 2015). Mosby’s Diagnostic & Laboratory Test Reference 12th Edition: Mosby, Inc., Saint Louis, MO. Pp 301-303.

Sources Used in Previous Reviews

MayoClinic.com. Cushings Syndrome (online information). Available online through http://www.mayoclinic.com. Accessed March 2008.

Restituto P, et.al. Advantage of salivary cortisol measurements in the diagnosis of glucocorticoid related disorders. Clin Biochem. 2008 Feb 5 [Epub ahead of print]. Available online through http://www.ncbi.nlm.nih.gov/pubmed. Accessed March 2008.

De Castro M, Moreira A. Screening and Diagnosis of Cushings Syndrome. Arq Bras Endocrinol Metab 2007;51/8.

Henry’s Clinical Diagnosis and Management by Laboratory Methods. 21st ed. McPherson R, Pincus M, eds. Philadelphia, PA: Saunders Elsevier: 2007.

Pituitary Network Association. Adrenal Insufficiency (Secondary Addison’s or Addison’s Disease). Available online through  http://www.pituitary.org/. Accessed March 2008.

Thomas, Clayton L., Editor (1997). Taber’s Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition].

Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosby’s Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO.

Jain, T. (2004 February 2, Updated). Cortisol level. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003693.htm.

(2002 June). Cushing’s syndrome. NIDDK, NIH Publication No. 02-3007 [On-line information]. Available online through http://www.niddk.nih.gov.

(© 2005). Cortisol, Serum or Plasma. ARUP’s Guide to Clinical Laboratory Testing [On-line information]. Available online through http://www.arup-lab.com.

(© 1995-2004). Cushing’s Syndrome. The Merck Manual Second Home Edition [On-line information]. Available online through http://www.merck.com.

Raff, H. and Findling, J. (2003). A Physiologic Approach to Diagnosis of the Cushing Syndrome. Ann Intern Med. 2003;138:980-991 [on-line journal]. Available online through http://www.annals.org.

Pagana K, Pagana T. (2006). Mosby’s Manual of Diagnostic and Laboratory Tests. 3rd edition. St. Louis: Mosby Elsevier.

(© 1995-2011). Unit Code 8545: Cortisol, Serum. Mayo Clinic Mayo Medical Laboratories [On-line information]. Available online at http://www.mayomedicallaboratories.com/test-catalog/Overview/8545. Accessed September 2011.

Meikle, W. and Roberts, W. (Updated 2011 January). Adrenal Insufficiency. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/AdrenalInsufficiency.html?client_ID=LTD#tabs=0. Accessed September 2011.

Adler, G. (Updated 2011 July 25). Cushing Syndrome. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/117365-overview. Accessed September 2011.

(2009 May). Adrenal Insufficiency and Addison’s Disease. National Endocrine and Metabolic Diseases Information Service [On-line information]. Available online at http://endocrine.niddk.nih.gov/pubs/addison/addison.aspx. Accessed September 2011.

Eckman, A. (2009 November 23). Cortisol. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003693.htm. Accessed September 2011.

Eckman, A. (2009 November 23). Cortisol-urine. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003703.htm. Accessed September 2011.

Meikle, A. W. and Roberts, W. (Updated 2011 January). Adrenal Hyperfunction – Cushing Syndrome. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/CushingSyndrome.html. Accessed September 2011.

Pagana, K. D. & Pagana, T. J. (© 2011). Mosby’s Diagnostic and Laboratory Test Reference 10th Edition: Mosby, Inc., Saint Louis, MO. Pp 311-313.

Adrenocorticotropic hormone | You and Your Hormones from the Society for Endocrinology

Alternative names for adrenocorticotropic hormone

Adrenocorticotrophin; Corticotropin

What is adrenocorticotropic hormone? 

Corticotrophin-releasing hormone from the hypothalamus acts on the pituitary (inset), which secretes ACTH. ACTH travels to the adrenal glands via the bloodstream (arrow). Cortisol from the adrenal then feeds back to the hypothalamus to shut down the cycle.

Adrenocorticotropic hormone is made in the corticotroph cells of the anterior pituitary gland. It is secreted in several intermittent pulses during the day into the bloodstream and transported around the body. Like cortisol, levels of adrenocorticotropic hormone are generally high in the morning when we wake up and fall throughout the day and lowest during sleep. This is called a diurnal (circadian) rhythm. Once adrenocorticotropic hormone reaches the adrenal glands, it binds on to receptors causing the adrenal glands to secrete more cortisol, resulting in higher levels of cortisol in the blood. It also increases production of the chemical compounds that trigger an increase in other hormones such as adrenaline and noradrenaline.

How is adrenocorticotropic hormone controlled?

Secretion of adrenocorticotropic hormone is controlled by three inter-communicating regions of the body, the hypothalamus, the pituitary gland and the adrenal glands. This is called the hypothalamic–pituitary–adrenal (HPA) axis. When cortisol levels in the blood are low, a group of cells in the hypothalamus release a hormone called corticotrophin-releasing hormone (CRH) which stimulates the pituitary gland to secrete adrenocorticotropic hormone into the bloodstream. High levels of adrenocorticotropic hormone are detected by the adrenal gland receptors which stimulate the secretion of cortisol, causing blood levels of cortisol to rise. As the cortisol levels rise, they start to slow down the release of corticotrophin-releasing hormone from the hypothalamus (long loop inhibition) and adrenocorticotropic hormone from the pituitary gland (short loop inhibition). As a result, the adrenocorticotropic hormone levels start to fall and consequently cortisol. This is called a negative feedback loop.

Stress, both physical and psychological, also stimulates adrenocorticotropic hormone production and hence increases cortisol levels.

What happens if I have too much adrenocorticotropic hormone?

The effects of too much adrenocorticotropic hormone are mainly due to the increase in cortisol levels. Higher than normal levels of adrenocorticotropic hormone may be due to:

• Cushing’s disease – this is the most common cause of increased adrenocorticotropic hormone. It is caused by a non-cancerous tumour called an adenoma located in the pituitary gland, which produces excess amounts of adrenocorticotropic hormone. (Please note, Cushing’s disease is just one of the numerous causes of Cushing’s syndrome).
   
• Rarely, a tumour outside the pituitary gland, producing adrenocorticotropic hormone (also called ectopic adrenocorticotropic hormone tumour).
   
• Adrenal insufficiency including addison’s disease (although cortisol levels are low, adrenocorticotropic hormone levels are raised).
   
• Congenital adrenal hyperplasia (a genetic disorder with inadequate production of cortisol, aldosterone or both).

What happens if I have too little adrenocorticotropic hormone?

Lower than normal levels of adrenocorticotropic hormone may be due to:

• Cushing’s syndrome related to an adrenal tumour (endogenous) or due to long term use of steroid medication for other diseases (exogenous). Although adrenocorticotropic hormone levels are low, cortisol levels are raised.
   
• Conditions affecting the pituitary gland, e.g. hypopituitarism.
   
• Side-effect of pituitary surgery or radiation therapy.

Too little adrenocorticotropic hormone could lead to a poorly functioning adrenal gland due to insufficient production of cortisol.

Last reviewed: Dec 2020

Cushing Syndrome in Children | Cedars-Sinai

Not what you’re looking for?

What is Cushing syndrome in children?

Cushing syndrome is a hormone disorder. It’s caused by having high levels of the hormone cortisol over a long time. Cushing syndrome is fairly rare. It most often affects adults who are 20 to 50 years old. But it can also occur in children. It is sometimes called hypercortisolism.

What causes Cushing syndrome in a child?

Cushing syndrome happens when there is too much cortisol in the body. The disorder often starts with the pituitary gland. A tumor in the gland makes too much adrenocorticotropin hormone (ACTH). That causes the adrenal glands to make too many corticosteroids.

Another main cause is taking glucocorticoids medicine like prednisone for a long time. These are sometimes used to treat chronic diseases such as asthma. Other causes include:

• Certain kinds of cancer
• Tumor on an adrenal gland
• An inherited endocrine disorder
• Certain chronic conditions such as inflammatory bowel disease, lupus, or rheumatoid arthritis

What are the symptoms of Cushing syndrome in a child?

Cushing syndrome may cause:

• Excess weight gain, especially in the upper body, face, and neck
• Fat pad on the back of the neck
• Red streaks (striae) on the belly (abdomen)
• Thin arms and legs
• Slow growth rate
• High blood pressure
• Fragile and thin skin
• Darkened color of the skin
• Acne
• Bruising
• Stretch marks on abdomen, thighs, buttocks, arms, and chest
• Bone and muscle weakness
• Severe fatigue
• High blood sugar
• Irritability and anxiety
• In girls: Excessive hair growth and irregular or no menstrual period
• In boys: Low sex drive and infertility

The symptoms of Cushing syndrome may be like other health conditions. Make sure your child sees his or her healthcare provider for a diagnosis.

How is Cushing syndrome diagnosed in a child?

The healthcare provider will ask about your child’s health history, and give him or her a physical exam. Your child may also need tests such as:

• Blood tests. These are done to measure levels of cortisol.
• Urine tests. These are also done to measure levels of cortisol.
• X-ray. This test uses small amounts of radiation to make images of the inside of the body.
• 24-hour urinary test. Urine is collected over a 24-hour period to test for cortisol.
• CT scan. This test uses a series of X-rays and a computer to make detailed images of the inside of the body. A CT scan shows images of any part of the body, including the bones, muscles, fat, and organs.
• MRI. This test uses large magnets, radio waves, and a computer to make detailed images of the inside of the body.
• Dexamethasone suppression test. This test shows if the excess cortisol are from the pituitary gland or from tumors in other places.
• Corticotropin-releasing hormone (CRH) stimulation test. This test shows if the cause is a pituitary tumor or an adrenal tumor.

How is Cushing syndrome treated in a child?

Treatment will depend on your child’s symptoms, age, and general health. It will also depend on how severe the condition is.

Treatment may include:

• Changing the dose of glucocorticoid hormone medicine, or switching to a different medicine
• Surgery to remove a tumor on an adrenal gland or the pituitary gland
• Surgery to remove the adrenal glands
• Medicines that block the excess production of cortisol
• Radiation treatment of the pituitary gland
• Chemotherapy or immunotherapy medicines

What are possible complications of Cushing syndrome in a child?

Untreated Cushing syndrome may cause:

• Abnormal growth and development, especially sexual development
• High blood pressure
• An impaired immune system
• Diabetes
• Infertility

How can I help my child live with Cushing syndrome?

Cushing syndrome can affect a child’s growth, development, and self-esteem. Getting treatment as soon as possible can help lessen problems. Make sure to work with your child’s healthcare providers on a care plan that works for your child.

When should I call my child’s healthcare provider?

Call your child’s healthcare provider if your child has any symptoms of Cushing syndrome.

Key points about Cushing syndrome in children

• Cushing syndrome is a rare disorder caused by having high levels of cortisol over a long time.
• It’s caused by a tumor on the pituitary gland or adrenal gland, or taking some kinds of medicine.
• Cushing syndrome may cause excess weight, slow growth, and problems with sexual development.
• Treatment may include medicines or surgery.
• Cushing syndrome can affect a child’s growth, development, and self-esteem. Getting treatment as soon as possible can help lessen problems.

Next steps

Tips to help you get the most from a visit to your child’s healthcare provider:

• Know the reason for the visit and what you want to happen.
• Before your visit, write down questions you want answered.
• At the visit, write down the name of a new diagnosis, and any new medicines, treatments, or tests. Also write down any new instructions your provider gives you for your child.
• Know why a new medicine or treatment is prescribed and how it will help your child. Also know what the side effects are.
• Ask if your child’s condition can be treated in other ways.
• Know why a test or procedure is recommended and what the results could mean.
• Know what to expect if your child does not take the medicine or have the test or procedure.
• If your child has a follow-up appointment, write down the date, time, and purpose for that visit.
• Know how you can contact your child’s provider after office hours. This is important if your child becomes ill and you have questions or need advice.

Not what you’re looking for?

90,000 Adrenal gland diseases: description of the disease, causes, symptoms, cost of treatment in Moscow

The adrenal glands are an important part of the body’s endocrine system. These paired organs are located in the lumbar region in the immediate vicinity of the kidneys. Despite their small size, the adrenal glands can affect the work of all organs, without exception. The main tool in this case is the production of hormones. A small amount of these chemicals is enough to force the internal organs to comply with the needs of the body.

As part of the adrenal glands, the cortical and medullary portions are isolated. The first produces massive complex chemical compounds – steroid hormones. There are several types of them:

• controls the balance of fluids and basic salts in the body, aldosterone. This hormone is produced by cells of the glomerular cortex;

• glucocorticoid hormones help the body cope with stress, are produced by the bundle zone of the cortex.They contribute to an increase in blood sugar levels as well as blood pressure;

• sex hormones: testosterone in men, estrogens in women. These chemicals control puberty, the appearance of secondary sex characteristics, and make it possible to conceive and carry offspring. These hormones are produced by the cells of the reticular cortex.

The brain substance produces two main hormones responsible for the body’s response to stress – adrenaline and norepinephrine.Their typical effect is to improve muscle nutrition and provide additional energy. This goal is achieved by two main means – an increase in heart rate and an increase in blood pressure. In addition, adrenaline and norepinephrine promote the release of glucose into the blood from the depot cells of the liver and skeletal muscles.

The work of the adrenal glands is directly controlled by the pituitary gland – the central endocrine gland located in the cranial cavity in the vicinity of the hypothalamus – one of the most important parts of the brain.The rate of steroid production is influenced by adrenocorticotropic hormone (ACTH). With its help, the pituitary gland can both increase and decrease the rate of formation of aldosterone and glucocorticoid hormones.

Since adrenal hormones, as a rule, have several effects on the body’s work at once, their lack or excess will inevitably lead to negative consequences. Moreover, adrenal diseases will always be extremely diverse. There may be several reasons for this behavior of organs.

Excess hormones often provoke swelling. She releases too many of them into the blood. An excess of aldosterone causes the appearance of a picture of the disease, which is called Conn’s syndrome. In this case, a disorder of the exchange of fluid and salts in the body occurs. An excess of aldosterone provokes fluid and sodium retention, while potassium levels, on the contrary, decrease. This imbalance causes dysregulation of blood pressure, heart rate, and skeletal muscle weakness.

The active production of glucocorticoids leads to the appearance of Itsenko-Cushing’s syndrome. Excess glucocorticoids have several consequences: excess fat deposition, discoloration of the skin, decreased immunity, and increased blood pressure and blood sugar levels.

A tumor of the adrenal medulla of the pheochromocytoma periodically releases a huge amount of adrenaline and norepinephrine into the bloodstream. The result is an increase in blood pressure and heart rate.Since arenaline and norepinephrine do not live long in the body and are quickly destroyed, the symptoms are paroxysmal.

Lack of hormones, as well as excess, will certainly cause negative symptoms. Aldosterone deficiency is called hypoaldosteronism. This disease is similar to Connes syndrome, only exactly the opposite. Excess fluid is excreted from the body along with sodium. Retention of potassium negatively affects skeletal muscle and heart function.

Steroid hormone deficiency is a major contributor to Addison’s disease. Lack of glucocorticoids causes skin discoloration, persistently low blood pressure, and muscle weakness. The blood sugar level is lowered in relation to the norm.

In addition to tumors, genetic diseases can affect the function of the adrenal glands. Proteins-enzymes are in charge of the formation of hormones. Their spatial structure depends on the structure of the gene’s DNA molecule. The wrong structure of the enzyme excludes its participation in chemical reactions.As a result, hormones will not be produced, and their precursors will not be able to affect the functioning of the body. This situation underlies the adrenogenital syndrome. Due to a defect in enzymes, the adrenal cortex does not produce active glucocorticoids. The child develops signs of chronic adrenal insufficiency from birth.

Organ function and hormone production can be compromised by inflammation caused by pathogens or the aggressive behavior of the body’s own immune system.It is especially difficult for these small endocrine organs in infectious diseases. Influenza viruses, meningococcal infections, and other pathogens can damage the adrenal glands. There is an acute lack of hormones due to the destruction of the adrenal glands, for which there is a special term – Waterhouse-Friedrichsen syndrome. In addition, a specific infection such as tuberculosis affects the adrenal glands.

In addition to tumors and genetic diseases, the adrenal glands are often affected by cysts and benign growths that do not produce hormones.Such diseases include vascular tumor angioma, formation of lipoma from adipose tissue, as well as fluid cysts.

The pathologies of these endocrine glands affect children, as well as adult men and women. In some cases, symptoms of adrenal gland disease appear from birth, in others they develop gradually over time.

Diagnosis of the causes and symptoms of adrenal diseases is based on a variety of examination methods. An endocrinologist will first of all examine the complaints and establish how long ago the symptoms of distress appeared.At the initial appointment, the doctor will necessarily assess the patient’s appearance, reveal changes in skin color, excessive development of subcutaneous tissue on the abdomen. Measuring blood pressure is an important step in diagnosing adrenal disease. High blood pressure indicates excess, low blood pressure indicates a lack of hormones.

Routine laboratory blood tests are performed if any adrenal disease is suspected. With Itsenko-Cushing’s disease, a reduced number of leukocytes (leukopenia) is found.Biochemical analysis in this case fixes a high level of blood glucose. If an excess or deficiency of aldosterone is suspected, the determination of the amount of sodium and potassium in the blood is critical.

A blood test for hormone levels is one of the main diagnostic methods. An excess of hormones allows one to suspect Itsenko-Cushing’s or Conn’s syndrome. Inadequate steroid levels indicate chronic adrenal insufficiency (Addison’s disease). It is advisable to donate blood in the morning on an empty stomach.The day before, a specialist endocrinologist usually advises to refrain from smoking, intense physical activity. It is necessary to consult a doctor about the possibility of taking prescribed medications the day before.

To diagnose diseases of the adrenal glands, several indicators are examined in the blood:

• the content of dehydroepiandrosterone sulfate (DEA-s). The indicator is increased in tumors of the adrenal cortex, as well as adrenogenital syndrome – a hereditary disease of the exchange of steroid hormones.The norm for women is from 810 to 8991 nmol / l, for men – 3591-11907 nmol / l;

• total cortisol content. The indicator is informative for the diagnosis of Itsenko-Cushing’s syndrome and Addison’s disease. The norm for children and adolescents under 16 years old is from 83 to 580 nmol / l. For people over 16 years old, the normative indicator is 138-635 nmol \ l;

• aldosterone content. This test is used to detect Connes syndrome and hypoaldosteronism.The norm for people of all ages is 35-350 pg / ml;

• adrenocorticotropic hormone (ACTH) content. This analysis is performed to exclude hormonal disruptions due to a disorder in the functioning of the pituitary gland. The norm is 8.3-57.8 pg / ml.

In urine, hormone metabolites are detected in the laboratory – the result of their chemical transformations in the body. Excessive or insufficient level makes it necessary to continue the examination to find out the exact cause of the disease.This method is used to diagnose pheochromocytoma. The amount of metanephrine and normetanephrine is determined in the urine.

Modern diagnostic methods allow you to look inside the body and see a picture of the anatomical structure of the adrenal glands. For this purpose, an ultrasound examination is mandatory. Its results help to suspect a specific cause of the disease – tumor, inflammation, genetic pathology.

Computed tomography or magnetic resonance imaging will help to clarify the results of ultrasound.The diagnostic value of these two methods is due to the fact that it is possible to assess not only the anatomy of the adrenal glands themselves, but also of neighboring organs. In the first case, X-ray radiation is used to obtain images and radiation exposure is present. In the second, the phenomenon of nuclear magnetic resonance is used to construct an image. In this case, there is no radiation exposure.

CT and MRI performed with the preliminary administration of a contrasting pharmacological preparation make it possible to assess the vascular system of the kidney and adrenal gland, which is especially important in the diagnosis of tumor formations.If the tumor is malignant, a separate stage of diagnosis is the search for its secondary foci of growth in other organs and lymph nodes (metastases).

Radioisotope research – scintigraphy – is an effective method for diagnosing adrenal diseases. For diagnostics, a preliminary introduction of a radioisotope pharmaceutical preparation is used. Then, using a gamma camera, the specialist takes an image of the organ in the form of a combination of colors. Areas colored in shades of red indicate an intense accumulation of the drug in the adrenal gland tissue.Areas of weak drug accumulation are marked with shades of blue. Scintigraphy is especially effective in diagnosing hormone-producing tumors – aldosteromas, corticosteromas, pheochromocytomas.

If you suspect Itsenko-Cushing’s syndrome, densitometry is performed – a study of bone density. An excess of steroids causes the phenomenon of osteoporosis – a rarefaction of the bone substance.

Forecast

The prognosis for the treatment of adrenal gland diseases is individual, depending on the specific type of disease.Lack of aldosterone and glucocorticoids is now successfully treated with hormonal drugs. An excess of hormones provoked by a tumor is eliminated after its removal. Early detection of a malignant neoplasm allows for a timely start of treatment. In the late stages of the disease with the presence of metastases, the prognosis is poor.

Glucocorticoids reduce the risk of death and the need for mechanical ventilation in patients with COVID-19 and high levels of C-reactive protein

Until now, experts do not have a clear position regarding the use of glucocorticosteroids (GCS) in the treatment of patients with COVID-19.The experience of managing patients with other viral pneumonias (against the background of influenza, for example) shows that the administration of glucocorticoids can increase mortality and the need for mechanical ventilation, slow down the clearance of viral particles, and increase the risk of secondary infections. On the other hand, a retrospective analysis of a series of patients with COVID-19 and ARDS was recently published, showing a reduction in mortality with the use of glucocorticoids. Preliminary results from the RECOVERY study showed a reduction in mortality in patients with COVID-19 randomized to use dexamethasone (so far only a preprint of the corresponding article is available https: // www.medrxiv.org/).

Keller et al. published the results of an observational study that assessed the effect of GCS prescribed in the first 48 hours on the need for ventilation and mortality in hospitalized patients with COVID-19. The study included 1806 patients, 140 of whom were prescribed GCS. Patients on GCS and without them were similar in basic characteristics, with the exception of such parameters as the presence of concomitant pathology requiring GCS prescription (asthma, systemic inflammatory diseases).In the general cohort, early GCS administration was not associated with an increase in the incidence of the primary endpoint (need for mechanical ventilation + hospital mortality). In subgroup analysis, heterogeneity in the incidence of the endpoint was found only for patients with different values ​​of C-reactive protein (CRP). Thus, for patients with high CRP values ​​(more than 20 mg / dL), GCS administration led to a significant decrease in mortality and the need for mechanical ventilation (OR 0.23; 95% CI 0.08-0.70, within the framework of multivariate analysis taking into account clinical parameters – 0.twenty; 95% CI 0.06-0.67). On the contrary, in patients with a low CRP value (less than 10 mg / dL), mortality and the need for mechanical ventilation were significantly higher (OR 2.64; 95% CI 1.39-5.03, with multivariate analysis – OR 3.14; 95% CI 1.52-6.50).

The results of this study allow for a clear selection of patients with COVID-19 who may benefit from the appointment of affordable and cheap GCS. Of course, the type of study (retrospective observational) does not exclude the possibility of an erroneous result, which requires appropriate prospective randomized trials.

Based on materials:

Marla J Keller, et al. Effect of Systemic Glucocorticoids on Mortality or Mechanical Ventilation in Patients With COVID-19. J. Hosp. Med 2020; 8; 489-493. Published Online First July 22, 2020.doi: 10.12788 / jhm.3497

https://www.journalofhospitalmedicine.com/

Text: Shakhmatova O.O.

Cushing’s disease in cats

Cushing’s disease in cats. Treatment. (812) 607-68-62

Cushing’s disease is a metabolic disorder resulting from an imbalance in hormone levels in the body.Cushing is the name of the neurosurgeon who discovered this disease. In Cushing’s disease, there is an overproduction of glucocorticoids (important hormones in the body) produced by the adrenal glands. Cortisol is an important hormone produced by the adrenal glands. Cortisol plays a key role in the proper functioning of the body. However, too much cortisol should not be present. When the adrenal glands are not working properly, the level of cortisol in the blood rises dramatically. High levels of cortisol are highly debilitating.The adrenal glands are located above the kidneys and their proper functioning is vital to overall well-being.

Hair loss is the most common symptom of Cushing’s disease. The cat becomes lethargic and physical activity decreases markedly. There are also dermatological changes in the form of skin thinning and increased skin pigmentation. When the cat is lifted, tears may form in the skin. In many cases, by the time the disease is detected, the condition of the cat is critical.Some cats may show hard bumps on the skin. Diabetes is common with Cushing’s disease in cats. Other symptoms include:
increased appetite;
increased thirst;
Frequent urination;
protruding belly;
inability to endure physical activity;
muscle weakness;
enlarged liver;
heavy breathing.

Types of Cushing’s diseases.
Cushing’s disease is divided into three types: pituitary, adrenal, and iatrogenic.
Tumor growth in a specific gland often leads to pituitary and adrenal Cushing’s disease. As a result, both glands (pituitary and adrenal glands) produce excess cortisol. Pituitary tumors form in the brain, while adrenal tumors form in the kidneys. Cushing’s disease often develops due to pituitary tumors. Iatrogenic Cushing’s disease develops when too many corticosteroids are taken to treat a medical condition. In this case, the cat is treated with a gradual reduction in the dosage of the drug.Taking corticosteroids should not be stopped abruptly, as this can lead to bad consequences.

Treatment is aimed at stopping or reducing excess cortisol production. Cats suffering from Cushing’s disease are often prescribed medications that can be given by injection or by mouth. Depending on your cat’s health, the veterinarian will select the appropriate medication that will give the best results. The following drugs are usually prescribed:
lysodren;
nizoral;
anipril;
trilostane.
If drugs are ineffective in treating the disease, surgery may be used to remove the affected gland in which the tumor has formed.

CONSULT THE VETERINARY (812) 607-68-62

Page not found |

Page not found |

404.Page not found

Monthly archive

MonTueWedWedFtFtSaSun

1

23242526272829

3031

12

12

1

3031

12

15161718192021

25262728293031

123

45678910

12

17181920212223

31

2728293031

1

1234

567891011

12

891011121314

11121314151617

28293031

1234

12

12345

6789101112

567891011

12131415161718

19202122232425

3456789

17181920212223

24252627282930

12345

13141516171819

20212223242526

2728293031

15161718192021

22232425262728

2930

Archives

Tags

Settings
for visually impaired

The level of GDF15 increases in conditions of glucocorticoid deficiency and is modulated by their replacement

Growth differentiation factor 15 (GDF15) is a stress-induced hormone acting in the hindbrain that activates the nervous system, which is involved in negative reactions and a decrease in food intake and body weight.Anorexia, weight loss, nausea and vomiting are common manifestations of glucocorticoid (GC) deficiency. It has been suggested that HA deficiency may be associated with elevated GDF15 levels. The aim of this study was to determine the effect of primary adrenal insufficiency (PNI) and HA replacement on circulating GDF15 levels.

Methods. Circulating concentrations of GDF15 were measured in patients with Addison’s disease after HA withdrawal and in healthy volunteers. Significantly higher levels of GDF15 (mean ± standard deviation) were observed in the Addison’s disease group compared with the healthy group: 739.1 ± 225.8 and 497.9 ± 167.7 pg / ml, respectively (p = 0.01) …The effect of replacing hydrocortisone with GDF15 was evaluated in 3 independent groups of PNI with classic congenital adrenal hyperplasia or Addison’s disease.

Results. Intravenous hydrocortisone replacement reduced GDF15 in all groups. The response of GDF15 to an increase in HA replacement in healthy volunteers with pharmacologically mediated cortisol deficiency was investigated. A dose-dependent difference in GDF15 levels was observed between groups with values ​​of 491.0 ± 157.7; 427.0 ± 152.1 and 360 ± 143.1 pg / ml with low, medium, and high HA substitution, respectively (p <0.0001).

Conclusions. GDF15 is elevated in states of HA deficiency and is restored by HA replacement. Given the localization of GDF15 action in the hindbrain and its effect on appetite, further research is needed to determine the effect of GDF15 on the occurrence of anorexia and nausea, which are common symptoms of HA deficiency.

Melvin A. et al. GDF15 is elevated in conditions of glucocorticoid deficiency and is modulated by glucocorticoid replacement. J.Clin.Endocrinol. Metab. 2019.

Medicna newspaper “Zdorovya Ukrainy 21 storichchya” No. 2 (471), since 2020 p.

NEWS ON THE TOPIC Endocrinology

90,000 Hormones: what you need to know about cortisol and how this hormone affects aging

You can disappear for hours in the gym, eat right and use only natural cosmetics – but this is not a guarantee that you will be healthy from your fingertips to the core.Sarah Gottfried, author of Tame Your Hormones: Simple Ways to Be Healthy, recently published by AST, insists that in order to be healthy, you need to know everything about your hormonal balance. And we agree with her. While you wait for the complete tutorial on hormone domestication to be delivered, here’s an excerpt on cortisol. How it affects stress and the rate of aging – read below.

Cortisol 101

Cortisol is a hormone that controls hunger, digestion, blood pressure, how you sleep and wake up, physical activity and the ability to deal with stress.It belongs to the glucocorticoid family – a funny name for a substance that can raise your glucose levels. This is the main job of cortisol: to raise glucose and store excess glucose in the liver through a process called glycogen storage. Glucose gives you energy. If your cells don’t get enough of it, you wither. And in case you do a lot of physical exercise, you “run out of breath”. Suddenly you begin to feel that something is wrong with your head, you are irritated, you have obvious hypoglycemia, which means: the main energy reserves have been spent.As the most powerful glucocorticoid, cortisol gives us life and strength through three key properties. He:

• increases blood sugar;

• raises blood pressure;

• regulates inflammation.

How women respond to stress: men fight and women talk

When men are stressed, they tend to react in a classic way, that is, fight or run. Men are more likely than women to hit or run away.Most often, men use “avoidance” methods such as alcohol abuse. The stress response of men is thought to underlie their poorer health than women and their shorter life expectancy.

The first data on men’s reaction to stress was obtained by Walter Cannon – the same doctor who formulated the concept of “fight or flight”. It has been suggested that this principle applies to women as well. But new evidence suggests that stress triggers a different response in women, dubbed by UCLA professor Shelley Taylor as “caring and being friends.”Women under stress seek companionship and companionship, which is uncommon for men.

This is exactly what I do as part of the de-stress program. When I talk to other mothers and we discuss our life or the problems of the ugly behavior of our children and husbands, we form a kind of stress-reducing network that protects women and increases oxytocin – the hormone “love”, which in turn acts as a neurotransmitter, or neurotransmitter (chemical the substance of the brain). According to the famous remark of Aristotle, the total is stronger than the sum of the parts, and oxytocin in the blood and brain lowers cortisol.

We used to think that men and women produce different amounts of cortisol in response to stress, and this has led to all sorts of theories about women, high cortisol and emotionality. What’s really true is that women don’t just produce more cortisol than men, they produce a lot more oxytocin to protect themselves from stress. The level of this powerful hormone increases when we kiss or hug, have sex, give birth or breastfeed.Because female neurocirculation relies more on oxytocin than male neurocirculation and estrogen enhances the effect of oxytocin, women are more likely than men to have a “care and befriend” response. Of course, in case of a serious threat, women also run and try to escape, but this is not their primary and not their most important instinct, unlike men.

Cortisol and Aging

Women in their twenties have the hormonal gold standard and normally produce tiny amounts of cortisol – 15 to 25 milligrams a day.(Men at the same age produce 25–35 milligrams a day.) Until recently, we had little understanding of how cortisol changes with age; it turned out that cortisol levels tend to rise as a person gets older. In fact, between the ages of 50 and 89, cortisol levels rise by 20 percent in both women and men. There is a theory that higher cortisol is associated with a decrease in sleep quality, which usually begins in middle age.

It is likely that the aging process (more than stress) is the primary factor in high cortisol after fifty years, especially if we take into account the studies that were carried out at the time the subjects reached fifty years, which means that they are dealing with people in generally happy with their lives and experiencing little stress.When you are between the ages of eighteen and fifty, the opposite is true. As, for example, in a study of more than 300,000 Americans, whose worst mental health was at 35-50 years.

Another subtle age shift is that your cells become more resistant to cortisol. High cortisol leads to a whole list of disorders associated with an excess of this hormone. However, as we age, we do not absorb cortisol into our cells as we did at the age of 20-30 (not to mention that high cortisol itself accelerates aging).This means that the more cortisol in the blood we have with age, the less it is in our cells. These two imbalances – in the blood and in the cells – give us a sense of fatigue (low cortisol) and anxiety, tension (high cortisol).

How High Cortisol Accelerates the Aging Process

Remember that cortisol’s main job is to normalize blood sugar levels. When you produce too much cortisol, your blood sugar goes off the charts. This is the path to pre-diabetes or diabetes.Both are common causes of accelerated aging. To slow down the aging process, you need to avoid overworking the adrenal glands and constantly elevated cortisol. New data suggests you keep your fasting glucose level below 87 milligrams. A tricky question: Who is aging faster – a marathon runner or a Tibetan monk? You know the answer. The marathon runner has higher cortisol levels because he runs, gets injured, and therefore ages faster. Not only that, prolonged increases in cortisol lead to a domino effect: when your adrenal glands manicly produce cortisol, the rest of the hormone cascade cascades downward.And this is by no means a happy picture. The skin sags. Muscles become weak. Your confidence and resilience is undermined. Mind and body are no longer as alert as they once were. But something particularly worries me: Extensive research shows that prolonged exposure to high cortisol restricts blood flow to the brain. It has a negative effect on brain function, lowers emotional intelligence, and enhances aging cognitive function. To summarize, your memory starts to deteriorate, and then dementia hits you.Yes, Alzheimer’s disease begins to develop more than thirty years before symptoms appear. Uncontrolled stress is bad for the brain, and wayward cortisol is a warning sign.

Daily cycle: don’t waste energy when you doze

Our bodies are programmed to produce cortisol in different quantities depending on the time of day. Ideally, we produce a lot in the morning, less during the day, very little in the evening, and a minimal amount when we sleep. This is precisely what is called the diurnal variation or diurnal cycle.Just like a flower opens and closes within 24 hours. This process reflects the measurement of “daily cortisol” at four points between 6 am and 10 pm: when we wake up, before lunch, before dinner, and when we are going to bed. This chart should look like a smooth curve with a slight downward slope as the day progresses.

The release of cortisol in the morning, usually between six and eight hours, is called the cortisol wake-up response (CAR1). Under normal circumstances, your CAR allows you to get out of bed feeling like you have recovered your strength.It also sets one of the most important circadian (circadian) rhythms – another significant aspect of hormonal control. Based on a 24-hour cycle, circadian rhythms define your biochemical and physiological peaks and valleys – almost like the tide, but only inside your body. When the cortisol drops, around midnight, the hormone is at its lowest, and your cells do the most repair and treatment. If cortisol is still high at night, your body is unable to carry out the recovery work it needs.

Sometimes, when you need to relax, you suddenly find a second wind. And this is not good: at the moment when rest is most needed, high cortisol gives you the wrong signal that you do not need rest. And this leads to further depletion of the adrenal glands, because they had to heal overnight. What’s more, the depletion of the adrenal glands will lead to a depletion of important neurotransmitters for wellness, including serotonin, dopamine, norepinephine, and epinerfin.

In addition, it is during the night that your hormones have a chance to harmonize and synchronize with each other.For example, melatonin and growth hormone, which help you fall asleep and sleep, are produced primarily at night. If you are missing one or both of these, your cortisol can rise significantly at night. Over time, the lack of sleep can worsen: you will not be able to fall asleep due to high cortisol. An endless loop will start.

Once upon a time, within the framework of traditional culture, people began to relax when the sun went down and it got dark. Artificial light allows us to write emails, listen to webinars, sign school permits for children, order birthday gifts, and have a late family dinner.Unsurprisingly, when your evening cortisol is high, you can’t fall asleep, stay awake for extended periods, and have good, deep sleep. Hundreds of women have told me that they do not understand why, after sleeping for eight hours, they feel tired in the morning. I ask them what they do before going to bed. Most often, they respond by checking emails, making a to-do list for the next day, or watching a detective story. You don’t need to have a Harvard gynecology degree to figure out why these women can’t sleep a wink.

Most people with overwhelming stress symptoms have low cortisol in the morning and high in the evening, and it should be the other way around. You don’t need this inversion. You need a daily variation: lower cortisol levels towards evening.

A drug for the treatment of age-related memory loss has been developed – Gazeta.Ru

Researchers from the University of Edinburgh (UK) have developed an experimental drug that was able to reverse age-related decline in cognitive functions in mice.The drug’s base compound is designed to reduce the production of glucocorticoids, stress hormones thought to damage the brain’s learning and memory centers over time. The results of study are published in the Journal of Neuroscience .

“Most surprisingly, even short-term inhibition was able to restore memory to old mice,” says Jonathan Seckl, professor of molecular medicine. “I don’t think anyone would have thought about the possibility of returning youth.”

Human testing is scheduled to begin within a year.

It has long been known that glucocorticoids (a class of steroid hormones that mediate the body’s response to stressful situations) play a role in age-related memory loss. Although short-term exposure to glucocorticoids increases memory formation during stressful situations, chronically high hormone levels cause cognitive decline in humans and animals. The exact mechanism behind this process has yet to be established, but researchers speculate that excessive exposure to hormones makes certain parts of the brain more vulnerable.

Jonathan Seckl and his collaborators focused on the type 1 11β-hydroxysteroid dehydrogenase enzyme (11β-HSD1). It generates an active version of a key glucocorticoid hormone in brain cells and several other tissues, providing a target for fine-tuning the system without blocking the overall stress response. Treatment with this enzyme appears to have little effect on blood glucocorticoids produced in the adrenal glands. Instead, the enzyme acts as an enhancer for intracellular glucocorticoids.“If you remove the amplifier, you will still have stress hormones, but now they will no longer scream so loudly and provoke wear and tear”, – quotes Compulent as saying Sekla.

Edinburgh scientists have shown that knocking out one or both copies of the gene for this enzyme can preserve memory in elderly mice. The researchers then developed a compound that penetrates the brain and inhibits the enzyme. Just ten days of treatment in two-year-old mice (the maximum lifespan of an average laboratory rodent) was sufficient to improve spatial memory.Later, the animals managed to restore the cognitive abilities of the young organism. “It is important to emphasize that we are focused on fighting pathology, not just improving memory,” notes one of the authors of the work, Brian Walker.

Researchers do not know how an experimental compound will affect humans, but some evidence suggests that drugs with a similar mechanism may be effective. For example, carbenoxolone, which suppresses 11β-HSD1 (among others) and is prescribed for stomach ulcers, improves certain types of memory in both healthy older men and patients with type 2 diabetes (type 2 diabetes is considered a risk factor for Alzheimer’s disease and is also associated with an increased content of glucocorticoids in the body).Carbenoxolone, however, is not suitable for treating memory loss, says Seckl, due to serious side effects (high blood pressure, etc.).

The authors estimate that approximately 20 to 30 percent of people aged 75 and over have elevated glucocorticoid levels (more precise numbers are not available). Most of the victims lose, first of all, the so-called declarative memory, that is, the ability to learn new facts and memorize, for example, lists. People with age-related memory loss are at a higher risk of developing Alzheimer’s and other forms of dementia, although the condition itself is not considered a type of dementia.Testing of an experimental drug in mice with Alzheimer’s disease has just begun.

Previous attempts to reduce the effects of glucocorticoids on memory have met with limited success. Blocking the hormone in the blood interferes with the body’s normal response to stress, and the benefits of blocking hormone receptors appear to diminish over time, even with continued medication. Therefore, most drugs aimed at improving cognitive functions (memantine, donepezil, etc.)), act directly on neurotransmitters in the brain.