[Music] [Applause] [Music] hi this is Tom from zerof finals.com in this video I'm going to be going through cortisol and the adrenal axis and you can find written notes on this topic at serto finals.com cortisol or in the Endocrinology section of the second edition of the zero to finals medicine book and you can find flash cards and questions to train your knowledge on this content and help you remember the information for longer at members. zerof finals.com so let's jump straight in cortisol is a glucocorticoid steroid hormone secreted by the two adrenal glands an adrenal gland sits above both kidneys in the abdomen cortisol is a stress hormone released in response to stress and it helps the body to cope with the stress it has several actions within the body it increases alertness it inhibits the immune system and reduces inflammation it inhibits bone formation it raises the blood glucose level it increases metabol ISM and it supports cardiovascular function increasing the heart rate blood pressure and cardiac output cortisol is released in pulses throughout the day and in response to stressful stimuli it has dial variation meaning that it's high and low at different times of the day cortisol typically peaks in the early morning triggering the person to wake up and get going and it's at its lowest late in the evening helping the person to relax and fall asleep there might be additional spikes throughout the day in response to stressful stimuli let's talk about glucocorticoids and mineralocorticoids there are two types of steroid hormone produced by the ad Ral glands cortisol which is a type of glucocorticoid and aldosterone which is a type of mineralocorticoid glucocorticoids for example cortisol help the body to cope with stress they regulate the immune system and they reduce inflammation medications that act as glucocorticoids include pricone Hydrocortisone and dexamethasone mineralocorticoids for example aldosterone help regulate the balance of electrolytes and the blood pressure they act on the nephrons in the kidneys to increase sodium reabsorption from the urine back into the body from the distal tubule increase potassium secretion from the body into the urine from the distal tubu and increase hydrogen secretion from the body into the urine from the collecting ducts they cause more sodium retention and more potassium and hydrogen secretion when sodium is reabsorbed in the kidneys water will follow it by osmosis this means that more fluid is contained within the body this leads to an increased intravascular volume or the volume of fluid within the blood vessels which increases the blood pressure therefore aldosterone and mineralocorticoids work to increase the blood pressure fludrocortisone is a mineralocorticoid medication used to replace aldosterone in patients with adrenal insufficiency where aldosterone is low it's also used to treat postural hypotension which is a low blood pressure on standing up as it helps to increase and maintain the blood pressure in these patients let's go through the hypothalamic pituitary adrenal axis cortisol is controlled by two structures in the brain called the hypothalamus and the pituitary gland specifically the anterior part of the pituitary this is called the hypothalamic pituitary adrenal Axis or the HPA axis the hypothalamus releases corticotropin releasing hormone or crh crh stimulates the anterior pituitary to release adrenocorticotropic hormone or act AC stimulates the adrenal glands to release cortisol cortisol travels off to the body tissues to carry out its effects it also travels back to the brain and has a suppressing effect on the hypothalamus and the pituitary this is called negative feedback cortisol suppresses the release of crh and act helping to keep the cortisol levels within normal limits when the cortisol level gets too high it suppresses the secretion of crh and act lower crh and lower ACT results in less adrenal gland stim imulation and less cortisol secretion returning the cortisol levels back to normal an example of negative feedback in action is when we give patients glucocorticoid steroid medications such as pricone for an extended period the pricone acts on the hypothalamus and pituitary like cortisol suppressing the release of crh and AC there are very low levels of crh and act with very little stimulation of the adrenal glands and the adrenals stop producing cortisol in this way extended use of exogenous steroids meaning steroids originating outside the body such as pedicone shuts down the production of endogenous steroids meaning steroids origin ating inside the body the body cannot function without glucocorticoids since the body is not producing steroids naturally the patient becomes entirely dependent on the steroids that they're taking every day suddenly stopping the steroids can be dangerous leading to life-threatening adrenal crisis with insufficient glucocorticoids in the body this means that steroid medications need to be slowly reduced to give the body time to restart the natural production of glucocorticoids when the cortisol levels get too low there is less suppression of crh and act resulting in more crh and act secre more adrenal stimulation and more cortisol secretion bringing the levels back up next let's talk about Cushing's syndrome excessive glucocorticoids or cortisol leads to Cushing's syndrome you can remember the causes of Cushings syndrome with the cape pneumonic C is for Cushing's Disease with which is a Petry adenoma or hormone secreting tumor of the pure Tre releasing excessive act which in turn stimulates the adrenals to release excessive cortisol A is for an adrenal adenoma which is an adrenal tumor secreting excessive cortisol P is for Paran neoplastic syndrome for example ectopic AC secreted by a small cell lung cancer tumor this ectopic act stimulates the adrenal glands to release excessive cortisol e is for exogenous steroids meaning patients that are taking long-term corticosteroids at a higher dose a ttip for you Cushing's Disease refers to a specific scenario where a pituitary releases excessive act the ACT stimulates the release of excessive cortisol by the adrenal glands causing Cushing syndrome therefore Cushing's disease causes Cushing's syndrome however Cushing syndrome has other causes as well as Cushing's Disease the distinction between Cushing's Disease and Cushing's syndrome is worth remembering Cushing syndrome results in typical symptoms and signs of a round face sometimes called a moon face central obesity abdominal strier or stretch marks on the abdomen an enlarged fat pad on the upper back which is sometimes called a buffalo hump proximal limb muscle wasting which causes thin arms and legs legs and difficulty standing from a sitting position without using their arms to help male pattern facial hair in women which is called [Music] huismans somnia or difficulty sleeping and anxiety and depression metabolic effects of too much cortisol and Cushing syndrome include hypertension or blood pressure cardiac hypertrophy or growth of the heart muscle type 2 diabetes dyslipidemia with a raised cholesterol and raised triglycerides and osteoporosis with reduced bone mineral density next let's talk about adrenal insufficiency inadequate cortisol is referred to as adrenal insufficiency adrenal insufficiency is potentially life-threatening adrenal insufficiency presents with potential symptoms of fatigue muscle weakness muscle cramps dizziness and fainting due to low blood pressure thirst and craving salt weight loss abdominal pain depression and reduced libido signs of adrenal insufficiency on examination include bronze hyperpigmentation of the skin particularly in the skin creases on the palms of the hands in scars on the lips and the Buckle mucosa inside the cheek and hypotension or low blood pressure particularly postural hypotension with a drop in blood pressure of more than 20 mm of mercury on standing a Tom tip for you a high level of act causes skin pigmentation by stimulating melanocytes in the skin to produce melanin similar to the action of melany stimulating hormone increased skin pigmentation is a sign of Cushing's disease where excessive act comes from a pituitary adenoma and of primary adrenal insufficiency where there is inadequate cortisol from the adrenals with a lack of negative feedback on the pituitary leading to high act Addison's disease refers specifically to when the adrenal glands have been damaged resulting in reduced cortisol and aldosterone secretion this is called primary adrenal insufficiency it's primary as the problem is with the direct source of cortisol the adrenal glands the most common cause of Addison's disease is autoimmune where the immune system gets confused and inappropriately attacks and damages the adrenal glands low cortisol means reduced negative feedback on the hypothalamus and Petry leading to increased crh and act secondary adrenal insufficiency occurs where inadequate Act is produced by the pituitary gland for example after surgical removal of the pituitary or damage to the pituitary inadequate act means low adrenal stimulation and insufficient cortisol release it is secondary as the problem is one step back from the adrenal glands tertiary adrenal insufficiency occurs when the hypothalamus produces inadequate crh usually due to suppression by exogenous glucocorticoids for example long-term treatment with pedicone inadequate crh and act mean low adrenal stimulation and reduced cortisol secretion it is tertiary as the problem is two steps back from the adrenal glands adrenal crisis also known as addisonian crisis describes an acute presentation of severe adrenal insufficiency where the absence of steroid hormones leads to a lifethreatening emergency it presents with reduced Consciousness hypotension or a low blood pressure hypoglycemia or a low blood glucose level and hyponatremia or a low sodium and hyperemia or H potassium treatment of adrenal Cris is includes emergency administration of intramuscular or intravenous hydrocortisone next let's talk about testing cortisol and act can be tested on a blood sample a single cortisol result is unreliable as the levels fluctuate significantly throughout the day there should be a relatively reliable increase in cortisol in the morning therefore taking an early morning cortisol at 8 or 9 a.m. may be used as an initial test for adrenal insufficiency in adrenal insufficiency the early morning cortisol may be lower than expected Dynamic tests involve giving a hormone and seeing how the body responds the short Sy actin test is used for adrenal insufficiency and the dexamethazone suppression test is used for Cushing syndrome let's talk in more detail about the short s actin test the short s actin test also known as the ACT stimulation test is used to diagnose primary adrenal insufficiency it involves giving a dose of synan which is synthetic act and monitoring the blood cortisol before and at 30 and 60 minutes after the dose the synthetic act stimulates healthy adrenal glands to produce cortisol the cortisol level should at least double in primary adrenal insufficiency the damaged and dysfunctional adrenal glands fail to respond to act so the cortisol levels will not double finally let's talk about the dexamethasone suppression test the dexamethazone suppression test is used to diagnose Cushings syndrome it involves giving a dose of dexamethasone which is a synthetic glucocorticoid and monitoring what happens to the cortisol levels using blood tests dexamethasone causes negative feedback on the hypothalamus and pituitary reducing the crh and act output lower crh and act means less stimulation of the adrenal glands and less production of cortisol a normal response to dexamethasone is suppressed cortisol in patients with an adrenal adenoma dexamethasone will have no effect on the amount of cortisol released the tumor is secreting large amounts of cortisol without requiring stimulation by act dexamethasone will suppress the ACT but this will have no effect on the cortisol release in fact Act will already be suppressed by the high cortisol level before dexamethasone is even given in patients with ectopic act for example small cell lung cancer secreting act dexamethasone will have no effect on how much cortisol is released it will suppress act released by the pure tree but there will still be lots of act from Elsewhere for examp example the lung cancer tumor stimulating the adrenal glands to continue releasing lots of cortisol the initial test in suspected Cushing syndrome is the lowd dose dexamethazone suppression test a low dose of dexamethazone is given in patients with a pituitary adenoma a low dose of dexamethasone will not be able topr supress the ACT release therefore cortisol will not be suppressed further testing involves the high do dexamethasone suppression test in patients with a pituitary adenoma a high dose of dexamethasone is enough to suppress the ACT resulting in lower cortisol so to summarize the Baseline act cortisol results in the low dose test and cortisol results in the high dose test a normal response is a normal act at Baseline a low cortisol after the low dose test and a low cortisol after the high dose test in an adrenal adenoma there's a low Baseline act as it's suppressed by all the cortisol and the cortisol is not suppressed on the low dose test and not suppressed on the high dose test in a pituitary adenoma there's a high Baseline act from the pituitary adenoma the cortisol is not suppressed on the lowd dose test but it is suppressed and is low on the high dose test and when there's a topic act for example in small C lung cancer the Baseline Act is high cortisol is not suppressed on the low dose test and not suppressed on the high dose test researchers consistently shown that testing yourself after learning a topic has a powerful effect on how long you retain that information this is known as the testing effect studying and then testing yourself results in longer-lasting and stronger recall on that information when tested at a later date even when compared with additional study sessions if you're preparing for a medical exam and you're not regularly testing your knowledge and practicing your recall you're failing to maximize your potential the zero to finals member site contains flashcards short answer questions multiple choice questions and extended matching questions that are purpose built to supplement the zero finals content helping you build your internal database of knowledge and take advantage of the powerful testing effect if you like the Zer to finals notes books videos and podcasts then you'll love the memb site