[Music] [Applause] [Music] hi this is Tom from zerof finals.com in this video I'm going to be going through Cushings syndrome and you can find written notes on this topic at zerof finals.com Cushings or in the Endocrinology section of the second edition of the zero to finals medicine book and you can find flash card and questions to train your knowledge and help you remember the information for longer at members. zof finals.com so let's jump straight in Cushing syndrome refers to the features of prolonged high levels of glucocorticoids such as cortisol in the body to understand Cushing syndrome we need to start by talking about cortisol 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 metabolism 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 to stressful stimuli let's go through the hypothalamic petur 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 act stimulates the adrenal glands to release cortisol cortisol travels off to the body tissues to car car out its effects it also travels back to the brain and has a suppressing effect on the hypothalamus and the pure Tre 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 suppressing is the secretion of crh and act lower crh and lower ACT results in less adrenal gland stimulation 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 so such as pedicone for an extended period the pedicone acts on the hypothalamus and pituitary like cortisol suppressing the release of crh and act 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 EX extended use of exogenous steroids meaning steroids originating outside the body such as pedicone shuts down the production of endogenous steroids meaning steroids originating inside the body next let's talk about the causes of Cushing syndrome you can remember the causes of Cushing's syndrome with the cape pneumonic C is for Cushing's disease which is a Petry adenoma or hormone secreting tumor of the P 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 act 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 Aon tip for you Cushing's Disease refers to a specific scenario where a p adenoma 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 next let's talk about the features 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 and difficulty standing from a sitting position without using their arms to help male pattern facial hair in women which is called hutis easy bruising and poor skin healing insomnia or difficulty sleeping and anxiety and depression metabolic effects of Cushing syndrome include hypertension or high blood pressure cardiac hypertrophy or growth of the heart muscle type 2 diabetes dyslipidemia which involves a raised cholesterol and triglycerides in the blood and osteoporosis with thinning of the bones a Tom tip for you a high level of act causes skin pigmentation by stimulating melanocytes in the skin to produce melanin similar to melanocytes stimulating hormone this is an important sign of Cushing's disease where excessive act comes from a pituitary adenoma skin pigmentation can also be caused by primary adrenal insufficiency where the adrenal glands fail to produce enough cortisol there is a lack of negative feedback and the pituitary gland responds by releasing lots of act trying very hard to stimulate the adrenal glands to release more cortisol patients with Cushing syndrome caused by an adrenal adenoma or exogenous steroids do not have skin hyperpigmentation next 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 requ re iring 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 T dexamethasone will have no effect on how much cortisol is released it will suppress act released by the pure Tre but there will still be lots of act from Elsewhere for 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 do Dex thone suppression test a low dose of dexamethasone is given in patients with a pituitary adenoma a low dose of dexamethasone will not be able to suppress the ACT release therefore cortisol will not be suppressed further testing involves the high do dexamethasone suppression test in patients with 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 lowd dose test and not suppressed on the high dose test in a pituitary adenoma there's a high Baseline act from the pitri 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 ectopic act for example in small cell lung cancer the Baseline Act is high cortisol is not suppressed on the low dose test and not suppressed on the high dose test there are several other invest investigations for Cushings syndrome a 24-hour urinary free cortisol is an alternative to the dexamethasone suppression test this involves collecting 24 hours worth of urine to see how much cortisol is excreted over that period however this is a cumbersome test to carry out and does not indicate the underlying cause so the dexamethazone suppression test is preferred other investigations include blood tests and scans a full blood count may show a high white cell count a renal profile or us an May Show Low pottassium if an adrenal adenoma is also secreting aldosterone an MRI scan of the brain can be used to look for a pituitary adenoma a CT scan of the chest can be used to look for small cell lung cancer and a CT scan of the abdomen can be used to look for adrenal tumors finally let's talk about treatment the primary treatment is to remove the underlying cause of the Cushing syndrome transphenoidal surgery through the nose can be used to remove a pituitary adenoma surgery can be used to remove an adrenal tumor and surgery may be possible to remove the tumor that's producing ectopic act for example small cell lung cancer although this is not always possible where surgical removal of the underlying cause is not possible another option is to surgically remove both adrenal glands which is called an adrenalectomy and give the patient lifelong steroid replacement therapy metone is a medication that reduces the production of cortisol in the adrenals and is occasionally used to treat Cushings research has 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 final's member site contains flashcards short answer questions multiple choice questions and extended matching questions that are purpose built to supplement the zero to finals content helping you build your internal database of knowledge and take advantage of the powerful testing effect if you like the zero to finals notes books videos and podcasts then you'll love the memb site