Cushing's Syndrome

[Music] Hello and welcome to the Zero Definals podcast. My name is Tom and in this episode I'm going to be talking to you about Cushing's Syndrome. And if you want to follow along with written notes on this topic, you can follow along at zerodefinals.com/cushings or in the endocrinology section of the Zero Definals medicine book. So let's get straight into it. Cushing's Syndrome is used to refer to the signs and symptoms that develop after prolonged abnormal elevation of cortisol. Cushing's disease is used to refer to the specific condition where a pituitary adenoma or a tumor in the pituitary gland secrete excessive ACTH or adrenal corticotrophic hormone. Cushing's disease causes Cushing's syndrome, but Cushing's syndrome is not always caused by Cushing's disease. So what are the features of Cushing's syndrome? There's a large number of features of Cushing's syndrome and they don't easily fit into a handy pneumonic. I find it easier to picture the patient as very round in the middle with thin weak limbs and then imagine the effects of high levels of stress hormone on the body. When we talk about them being round in the middle with thin limbs, patients are described as having a round moon-like face, central obesity, abdominal striay, where the central obesity has stretched the skin and caused stretch marks on the skin, a buffalo hump which is a fat pad on the upper back and proximal limb muscle wasting which causes the thin limbs. High levels of stress hormone causes hypertension, cardiac hypertrophy, hyperglycemia and type 2 diabetes, depression and insomnia, difficulty sleeping. There's some added important effects of high levels of steroid on the body which is osteoporosis or thinning of the bones and easy bruising and poor skin healing. Let's talk about the causes of Cushing's syndrome. It could be caused by exogenous steroids, so this is where doctors give steroids to patients to treat long-term conditions and this could be due to polymageurumatica or poorly controlled asthma or other inflammatory conditions. It could be caused by Cushing's disease, which we've already talked about being a pituitary adenoma that releases excessive acthe and stimulates the adrenal glands to produce excessive amounts of steroid hormone. It may be caused by an adrenal adenoma which is a hormone secreting tumor of the adrenal glands and you can also get perineoplastic cushing's and this is where excessive acthe is being released from a cancer that's not in the pituitary gland and it stimulates excessive cortisol release. Acthe that's released from somewhere other than the pituitary gland is called ectopic acthe. The most common cause of perineoplastic cushing syndrome is small cell lung cancer that's releasing the acthe. The dexamethasone suppression test is the test of choice for diagnosing Cushing's syndrome and it's worth understanding how the dexamethasone suppression test works. The test involves initially giving the patient the low-dose test and if the low-dose test is normal, Cushing's can be excluded. If the low-dose test is abnormal then a high-dose test is performed to differentiate between the causes of Cushing's syndrome. To perform the test the patient takes a dose of dexamethasone which is a synthetic glucocorticoid steroid at night time for example at 10 pm and then their cortisol and acthe level is measured in the morning at 9 am. The intention is to find out whether the dexamethasone suppresses their normal morning spike of cortisol. The low-dose dexamethasone suppression test involves giving 1 milligram of dexamethasone. A normal response to this is for the dexamethasone to suppress the release of cortisol by affecting negative feedback on the hypothalamus and pituitary gland. The hypothalamus responds by reducing the CRH output and the pituitary response by reducing the acthe output. The lower CRH and acthe levels result in a lower cortisol level. When the cortisol level is not suppressed in the low-dose test this is the abnormal result seen in Cushing's syndrome. The high-dose dexamethasone suppression test involves giving 8 milligrams of dexamethasone and this is performed after an abnormal result on the low-dose test. In Cushing's disease which remembers a pituitary adenoma the pituitary still shows some response to the negative feedback and the 8 milligrams of dexamethasone is enough to suppress the cortisol. Whether it's an adrenal adenoma the cortisol production is independent of the pituitary gland. Therefore cortisol is not suppressed however the acthe level is suppressed due to the negative feedback on the hypothalamus. Whether it's ectopic acthe, for example from a small cell lung cancer, neither the cortisol or the acthe level will be suppressed because the acthe level production is independent of the hypothalamus and pituitary gland. So to summarize in the high-dose dexamethasone suppression test a pituitary adenoma results in suppressed cortisol and suppressed acthe. And adrenal adenoma results in not suppressed cortisol so still a raised cortisol however a suppressed acthe. And in ectopic acthe in a paranoia plastic syndrome this results in both the cortisol and the acthe. H remaining high so they're not suppressed by the higher dose of dexamethasone. There are a few other investigations that you can use in Cushing's syndrome. Performing a 24 hour collection of urinary free cortisol can be used as an alternative to the dexamethasone suppression test to diagnose Cushing's syndrome but it does not indicate that underlying cause and it's also cumbersome to carry out collecting urine for 24 hours. Other investigations include a full blood count which may show a raised white cell count and electrolytes which may show a low potassium if the aldosterone is being secreted by an adrenal adenoma. An MI brain can be used to look for a pituitary adenoma, a chest CT scan can be used to look for a small cell lung cancer and an abdominal CT scan can be used to look for adrenal tumors. Let's talk about the treatment of Cushing's syndrome. The main treatment is to remove the underlying cause to surgically remove the tumor that's producing excessive hormones. Transphenoidal operations, which involve going through the nose can be used to remove a pituitary adenoma. Surgery can also be used to remove an adrenal tumor or surgery to remove the tumor that's producing ectopic ACTH in a paraneoplastic syndrome. If the surgical removal of the cause is not possible, another option is to remove both the adrenal glands and give the patient replacement steroid hormones for life. Thanks for listening to this episode on Cushing's syndrome. A big thank you to Harry Watchman for perfectly addressing this podcast. If you found the podcast helpful and you want written notes on this topic and all the other topics head over to Amazon and pick up a copy of the Zero to Finals Medicine book. You can also find the Zero to Finals Pediatrics book on Amazon, which covers all the key topics you need for your Pediatrics exams. You can also find a full audio book version of the Zero to Finals Medicine book on Audible, which is available to download so that you can take all the topics with you wherever you go. You can also find notes as well as videos, illustrations and questions completely free on the Zero to Finals website at zerotofinals.com. And I hope you tune in for the next episode, which will be on adrenal insufficiency.