Cushing's syndrome: Why is it difficult to diagnose?

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Cushing's syndrome: Why is it difficult to diagnose?

20 Oct, 2:30 PM

welcome good evening doctors it's so lovely to see you all once again here tuned in for another amazing live session Happening Here on Netflix a little bit on the session happening tonight the topic is Cushing syndrome and why is it difficult to diagnose now we all know Cushing syndrome is uh marked by significant glucocorticoid excess and the features associated with that are features that we commonly see such as obesity hypertension uh obesity high potential then we also see menstrual irregularity uh depression diabetes so there is an awesome step in the clinical presentation of individuals with and without the disorder and that's where the confusion sets in and I think we can all agree that we could do with an expert guidance in that matter and for that we have a faculty and Mentor tonight Dr ganpati Ben 12 he is a proficient and expert endocrinologist practicing in Bangalore he completed his mbbs and MD in Internal Medicine from myso Medical College further did a DNB and DM in endocrinology from PGI Chandigarh Dr ganpati has published many papers as well in National and international prayer forums he is the immediate past president of endocrine Society of India and currently professor and head of Endocrinology at St John's Medical College at Bangalore thank you so much for joining us tonight and we look forward to learning from you sir yeah thank you Dr Fatima uh I'm uh glad I'm on this platform and if you ask an endocrinologist uh which is a most toughest disease to make a diagnosis all will invariably say Cushings because it's very difficult uh whom to screen when to screen what to screen that's the thing we don't have any clear diagnostic criteria though we have a uh what do you call a protocol but still many times we may not be able to make find where is the lesion you find okay this patient has excess cortisol you did overnight dexamethasone suppression test uh it's not surprisable you do acths high you do that I mean MRI of the pituitary gland it doesn't show anywhere what do you do then we start checking the chest abdomen you don't find anywhere we are stuck then we do an ipss it doesn't give any conclusion reserves so this is one of the most toughest uh I would say this is a stove Magnus and to treat it's a Cushing syndrome comprises the symptoms and signs associated with prolonged exposure to inappropriately elevated levels of free gluco fatty bites when we say Cushing syndrome it is used to describe all causes of glucocorticate access and when we say Cushing's Disease it's predominantly is good for pituitary dependent Cushing syndrome now coming to the classification so whenever you have excess cortisol hypocortisolic State we will classify them into acts dependent and ACTH independent now acts dependent Cushing's Disease pretty dependent that's the most common it could be ectopic ACTH ectopic CRS very there one or two case reports macro nodular adrenal hyperplasia then you have hydrogenic some people treat with 124 ACTH and that could be a cost acid is independent coming predominantly from the Eternal glands adrenal adenoma or carcinoma then you have primary pigmented nodular adrenal hyperplasia we call it a Carnage syndrome and then incidentally we found that she came with the weight gain fractures of the back of the vertebrae especially the T10 to L2 and then had Cushings we didn't 2D Eco and it showed uh mixomas in the cardia in the atrium so she's going to get operated in one setting we are trying to remove the mixoma Plus in the same setting we are also trying to remove the bilateral glands so making all bad syndrome is another one which is associated with fibrous dysplasia GH excess and cortisol axis and sometimes it can be because of aberrant receptor expression that is a gastric inhibitory polypeptide interleukin-1 beta hydrogenic this is the most commonest cause patients will be taking prednisolone dexamethasone for so many other reasons and this is and there are some other causes of hypercortisolism like alcoholism pseudo uh cushions we call it as alcoholism depression obesity and pregnancy coming to the physical symptoms and signs so coming to discriminatory future so if you have lay a facial plethora this is a major manifestation proximal myopathy another major manifestation or publish or violations try more than one centimeter wide and non-tapering ends easy bruisability spontaneous bruisability that's another one and in children weight gain with reduced height percentile is cushions and will proved otherwise so these are major manifestation other symptoms include hypertension in a young age osteoporosis and vertical facts is less important thing diabetes nowadays you get in the 20s and the 30s so that's not a major manifestation hypertension in a child osteoporosis invertebral facts is less than 35 years that's also a major manifestation less discriminatory includes central obesity buffalo hump supraclavicular fullness facial fullness this is important see because of the patientfulness what happens you're not able to see the tragus so if you see that start suspecting hypercortisol with the state acne and hirsutism skin thinning we call it as a little sign poor wound healing peripheral edema and some other symptoms and complications like fatigue weight gain depression mood appetite change impairment of concentration and memory back pain olitarian area so it's a cause of secondary polycystic ovaries recurrent infections especially when you have very high levels of cortisol say you can actually get a uh you can get a fungal infections and you can also get uh a duodenal ulceration can also happen in these type of patients kidney stones so this is how they look like you can see the stretch marks the easy breathability and x-ray wise you can see that in the chest x-ray you find that there are fractures and so the crack the the characteristics include exuberant calcific uh uh your calcification you can say so in these type of patients exuberant not getting the term so callus formation rather so exuberant callous formation pulling a fracture is a sine equivalent noun you can say of cushions or hypercortisolic state periodic Cushing how do you suspect so as I told you children weight gain and no increase in height is Cushing's Antelope otherwise so here they can have facial plethora acne acanthosis easy breathability Supra temporal and supraclavicular Pad of fat moon phases fungal infection same thing headaches hypertension coagulability growth deceleration with concavity and weight gain central obesity so normally what happens uh in children because they are active you may get a generalized obesity nephrolithiasis bone fractures IGT type 2 diabetes depression anxiety mood swings irritability and fatigue this is how the growth chart looks like you can see you can see that the weight percentile is more than 97 centile and the height is dropping sentiles so this patient was in the 50th Center you can see in the third third year fourth year 50th 60th 70 or 8th year and then in the ninth year it dropped percentile so this is so dropping in height percentile whereas increase in weight percentiles is a classical feature of cushions etiology wise Cushing's Disease at 14 years of age less than seven is more of adrenal more commonly it's the tumors are the ACC that's more common in the younger age group a little bit about genetics there are some gene mutations like the men one the cdk1 the cdk and B1 AIP sth dicer one abnormal protein expressions like the brg one hdac2 uh pttg egfr so then you have the bhima that is bilateral macro nodal adrenal hyperplasia we had a patient like this huge masses of adrenals in the both the adrenal gland we we did a little ectomy of one side and then periods secondary for the genetic analysis and it came as arnc5 mutations we had a patient and for which we did this foreign [Music] so in the modern era there are five major challenges associated with the diagnosis of cushions as you know there is an epidemic of obesity and diabetes now these signs of Cushings which are rarely caused by the glucocorticoid axis and this is the question of whether to scream for the syndrome furthermore there is an increased use of exogenous glucocorticoids either for the treatment of disease say ra all these things will be using this mixed connected tissue disorders or saruptively so they this leads to their Cushing syndrome phenotype without an endogenous cause and there is also confusion caused by non-pathological hypercortisolism not associated with Cushings which may present with symptoms consisted with Cushing syndrome we call this as pseudo cushions this is what I told you like alcoholism depression morbid obesity they all come into this category um so there is uncertainty which is the best screening test for cushions and how to individualize the choice of test to prevent false positive interpretation of the results and then there are certain conditions where it is very difficult because you have a condition known as mind cushions or cyclical cushions two three months hypercordialism then they don't have a renal failure incidental adrenal Mass pregnancy so it's very difficult to diagnose so a little bit about the signs and symptoms this is a busy slide I'll just talk about certain things growth normally what happens when you have obesity you tend to gain in height whereas in this what happens you decrease height so decreasing weights and time is a indication then uh very important in the adipose tissue distribution if we get increased temporal supraclavicular dorsal cervical adipose mainly to moon phases or central obesity as I told you more than one centimeter okay there are certain things like this see now decreased memory short-term memory is particularly affected may be assist at the bedside by a recall of three cities or objects they can also have a decreased cognitive ability may be assess at the bedside by another one uh so I told you about English infection especially mycotic infections hypertension and another thing is may result in deep vein thrombosis and Pulmonary embolism it's quite common in severe hypercortisolism infertility you can have secondary infertility you can have hypogonadism because of excess cortisol having a suppressive effect and then another important thing is Central serious Courier written uh retinopathy it's an uncommon feature but then you'll have to keep in mind glucocorticults are responsible for this okay insomnia especially following difficult falling asleep frequent Awakening or early Awakening obstructive sleep apnea is seen in up to 23 50 prevalence in questions compared to 23 percent in the general population so how should you approach the clinician approach to these patients so what signs and symptoms of Cushing's are currently present what is the duration of the signs and symptoms have the number of signs and symptoms increased are they progressing in severity do all of the signs and symptoms fall into a single systemic category example reproductive or are many systems affected are there cognitive memories psychiatric features not usually associated with other signs or symptoms other signs and symptoms common at this age are in this population cohort uh are we dealing with physiological hypercortisolism or pseudo cushions in children is if appropriate for ages what is the state of libertal development did it occur at the normal age and in the usual tempo of probation how does a growth curve show is it Crossing syntiles downwards so when a Cushing syndrome's phenotype is present exogenous exposure to glucocorticus should be excluded that's the reason one of the first test what we do is get an ATM cortisol suppose you had taken exogenous safety steroids your cortisol will be very low so that we come to know that we are dealing with a case of exogenous cushions so what are the recommended tests one is urine free cortisol so what you have to do you have to collect this 24 hour urinary free card it's all morning eight o'clock to the next day morning eight o'clock you will collect the urine sample the problems is one is it could be incomplete many times people don't I mean take it properly collect it properly uh suppose you take uh so that is one renal failure this is not much of use if it is a mild or a cyclic hypercortisolism or you take an excess fluid more than five liters then it comes you get a falsely negative results salivary cortisol is another one bedtime or late night celebrity cortisol confounders include older age hypertension diabetes smoking variable bedtime suppose night shift workers in oil is not useful and once again maybe mild or cyclic hypercordialism in some cases it's useful some it may not be what we do is the overnight dexamethasone separation test we give one milligram of dexona at 11 PM and the next day morning at eight o'clock we checked the serum cortisol and if it is less than 1.8 micrograms per deciliter that means it does not have hypercortisolism if it is more than that probably we are dealing with the a hypercortical state like because tbz abnormality abnormal dexamethrow suppose the patient is on refurbation it can metabolize dexamethasone so you may get a falsely high value so you have to be caused which is about these things other things or another test one cortisol is highest in the morning and least in the night in a patient with Cushings what happens is the cortisol is higher in the night so that there is an inverse pattern so the so we call it as loss of circadian rhythm and this is one of the important tests even in pregnancy where you have because of the hyper esogenic State there is a increase CBJ your cortisol numbers may be more but then off uh the Circadian pattern you start suspecting probably we are dealing with the cushions the other thing include Lotus dexa 0.5 milligrams sixth hourly for two days six o'clock twelve o'clock six o'clock twelve o'clock next say the same and then Thursday morning at eight o'clock we checked the uh serum cortisone if it is less than 1.8 we say it's something we have found that whether the patient I see whenever you have Cushings what do you do are there evidences of hyper cortisolism what are the evidence of symptoms or signs probability hypertension osteoporosis in a young if these things Etc are there we know there is evidence of hypercortisolism now once we have evidence of hypercortisolum so in endocrinology we teach like this anyhow on an excess you suppress it so what we do is we do this suppression test now first test is we do an AM cortisol why because we want to roll out exogenous cos then we do a 11 pm cortisol why do you do this to see what has happened to the Circadian rhythm so is it maintained or not so in the night it should be lesser but if it is high indirectly we say it's more and then we do overnight dexamethasone separation test and if it is low that means we don't have any cortisol axis so you can get false positive tests in obesity psychiatric disorder alcohol abuse especially with a one milligram dexamethasone acute illness in the shift workers it can be normal so that's what you have to do when they become normal so two to three week two weeks you'll have to give them rest I'll come back to the original and then do the test patients on medications like the cyp3a4 which are enzyme inducers yeah you'll get a falsely high value cyclical cushions during that falsely negative in cyclical cushions or abnormal dexamethasone clearance test so these are the drugs which can come in the way drugs that decrease dexamethasone metabolism like etoconazole return aware Fluoxetine deltasm atidine Etc and the drugs increase like pheny time phenobarbital carbonzepine Etc drugs that increase CBJ estrogens might attain and drugs that increase urinary free cortisol phenofibrate carbamazepine hydrocortisone licorice so for one milligram dexamethasone the cutoff is 1.8 micrograms per deciliter sensitivity 98 percent specificity 81 percent urine free cortisol 91 sensitivity 81.5 specificity late night ceremony costumes cortisol very good sensitivity specifically approximately 97 percent so late night uh monitoring for recurrence late night cortisol 0.27 micrograms per distillate anything more than that 75 to 90 sensitivity 93 to 95 percent specificity urinary record is all hundred percent specificity with 68 percent sensitivity desperation test is not recommended because it's just it's experimental and one milligram overnight extra suppression 1.8 sensitive specificity we don't know during pregnancy low dose dexa if you do falsely positive because CBG induced estrogen excess is there 24 hour free cortisol if it is more than three-fourths elevated in the second and third trimester yes then it is important and the late night celebrity record isolated is more than two to three fold upper limit of normal once again we say it's because of that I told you before difficult to identify pathological hypercordialism so mild or cyclical cushions a renal failure incidental adrenal mass and pregnancy then you have non-pathological hypercortisolism but they are not associated with Cushings obligate exercise pregnancy uncontrolled diabetes sleep apnea pain alcoholism especially withdrawal psychiatric disorders stress extreme obesity glucocard resistance syndrome so now what is screen how do you screen I told you no you can either do a one milligram overnight dexa separation and if the serum cortisol is more than 1.8 microgram per deciliter or you can do a 24 hour urinary free cortisol if it is more than 50 microgram for 24 hours with the best asses that you will come in human sense essay or a midnight salary cortisol more than 0.13 microgram per deciliter or due to a serum cortisol in the midnight and if it is more than 7.5 micrograms for this later we are dealing with a case of hypercortisolism without any doubt is it ACTH dependent or is it is independent when you say ACTH independent when the Acres level is less than 5 I program per ml now when you get 5 piagram per ml we say it's ACTH independent then how do you proceed do an adrenal CT so if I find normal or micro nodules that means we are dealing with probably a little you will have to do uh the low-dose dexamethasone suppression test and if you find there is a paradoxical increase in cortisol probably we are dealing with PP energy that is primary pigmented nodular retinal hyperplasia if you get a single mass or macro nodules if it is unilateral large one we are probably dealing with adrenal carcinoma or an adenoma bigger one if it is bilateral then we are dealing with the macro nodular adrenal disease or bilateral hyperplasis or we also call it as uh bhima that's what you call it bilateral macronodial adrenal disease if the acetate is more than 29 then we call we are dealing with ACTH dependent Cushing syndrome so we have to do an MRI of the pituitary so if the MRI shows tumor yeah we are dealing with pituitary cushions if it is negative MRI then what do you do you may have to do an inferior petrasal sinus sampling and when you do the inferior pattern design is sampling if the central to peripheral ratio is more than 3 or crh we are dealing with Cushings if there is no gradient probably we are dealing with an ectopic ACTH you may have to do a chest CT abdominal MRI octoor Edge scan yeah now coming to ectopic acts syndrome the age of onset so the age of onset is normally higher in ectopic ACTH syndrome compared with the Cushings more common in males 0.621 is to one mining the neuroendocrine tumors comprise four percent it's in the fifth to sixth decade small cell lung carcinoma and aggressive tumors associated with much higher ACTH and cortisol level so here the characteristic feature is the present with rapid onset of clinical signs and symptoms hyperpigmentation weight loss is characteristic normally we say cushions you get weight gain here you get weight loss and mineral corticoid effects in the sense you find that hypertension with hypokalemia as opposed to the classical Cushing syndrome others include carcinoid syndromes they behave like cushions only because they're slowly growing they are indolent so they may mimic like a pituitary dependent only lung another common source 45 percent of cases are there in the lung timing it's around 11 percent pancreatic neuroendocrine tumors it's around eight percent middle and thyroid carcinoma six percent fear from a cytomas five percent so the sources uh biomarkers so if you have a neuroendocrine or carciner tumor or a gastonoma what do you do Phi hia chromogranin a for a gastonoma gas in Middle thyroid carcinoma cytoma catecholamines and metanephrines carcinoma hypercalcemia pancreatic cancer ghrh coming to the diagnostic imaging it's an important tool in the location and characterization of Cushings it's very important bitter MRI when you tell you ask them for a thin section one to two mm with high resolution and with gadolinium they can also use 18 floor fdg pet for detection of small functioning product of adenomas and for the adrenals adrenal city is the best distinction between Cushing's Disease and other causes people have tried CT or MRI of the neck chest abdomen and pelvis for ectopic source they have also tried labeled octet scanning pet gallium uh dodeca Tetra acetic acid tyrosine three oxide Pet City this may help in the localization of an ectopic cardio tropin source and then inferior petrol sinus sampling can be done when the tumor is not visible in an MRI so this is a DOTA take gallium dotted pet MRI in a 45 year old woman a presenter with slow onset of cushions and the scan demonstrates uh Avid pancreatic tail neuroendocrine tumor and extensive bilobar liver myths with Central photopenia likely secondary to tumor necrosis so liver biopsy showed a well-differentiated neuroinophen tumor of intermediate grade with a Ki of 67.5 which is quite significant another one borderline enlarged hilar lymph node with intense dotted ability in a 46 year old woman with the recurrence of ectopic acid syndrome 19 years after right middle and upper lobectomy for a typical pulmonary carcinoid tumor a patient remains in complete remission three years after repeat the academy and rejection of the right Highland node which is con which confirm metastatic typical pulmonary carcinoid ok so the what is the treatment of Cushings you have to remove that suppose you have a tumor in the pituitary gland remove it because that is Curative you have an adrenal tumor remove it but then sometimes you will not find it or the patient is not fit for surgery then what do you do then we actually start them on medical lineup management so you have a lot of medical lineup therapy so you can divide them into pituitary directed therapies adrenal directed therapies which could be adenostatic or adenolytic or it can make glucocortical receptor antagonist so what are the drugs available you have at the level of the pituitary might retinoic acid roscovitin Jeff Tina Bay at the level of the adrenals so you have imidazoles method upon might retain oscillator stat ear Ketoconazole uh so these are the drugs which are available I will talk to them in detail so ketocorosal is a drug which we commonly use we started 200 milligram can go up to 1200 milligrams this requires gastric acid for absorption uh the problem with this is it can produce serious hepatic toxicity so liver enzyme monitoring is important can produce hypogonadism in men okay so you have to be very cash so liver monitoring very very important method upon inhibits the last step the 7 beta hydroxylase and aldosterone synthase quite rapid acting rapid answer of action but because you're blocking the last step that is 11 day off Squad is all the cortisol what happens the precursors above that will increase and that's the reason if I can find that cortisol is low but you find that the mineral corticoid uh products can increase so you can get hypertension with hypokalemia and the adrenal androgens can increase also oscillator stat is a newer one one to 30 milligram orally rapid onset of action the same side effects as methiropound method of an inside drug which we can use it in pregnancy also might attain it is a lytic it can adrenolytic we can say slower onset but then very powerful agent especially for adrenal cortical carcinomas we use this suppose somebody is morbidly sick because of the hypercortisolic state and you want to control it is planned for surgery and is very sick give him automated infusions so what are the rational for the use of this theology Genesis inhibitors for the treatment of ACTH dependent Cushings I told you surgery is the first choice but then if it is not possible or it's unsuccessful or it recurs then we require second line treatments and that's the reason we want to use this medical line of management if sterothy Genesis Inhibitors are the only treatment they must be continued until more definitive therapy is given alternatively Inhibitors can be used in conjunction with radiotherapy with intermittent withdrawal either yearly or when signs are better insufficiency appear to assess if the radiation has been effective none of these have any tumor direct effect which is potential limitation of the action in Cushing's disease you can add not only one drug you can even add second drug especially when one drug does not control you can add a second does or when a dose dependent side effect is observed then also you can add what are the additional treatment consideration comorbidities should be treated specifically preventive cash should continue on receive age appropriate routinely recommended recombinated or inactivated vaccines avoiding live itinerated vaccine influence the prophylaxis covid-19 vaccine drugs should be taken into account for long-term treatment redirected therapies neuromodulated drugs directly influence the HPA axis then you have the nuclear receptor ligands indirectly influenced the HPS axis like the P par gamma pilot Zone prosecutorzone rhetoric acid receptors Agonist has been used is very expensive it comes to around three and a half lakhs per month somebody like nambani types can only afford that or you have an insurance for that so the side effect of that is speciatite can actually lead to hyperglycemia it's quite common and the mechanism of hyperglycemuse they say is because of glp deficiency and that's why drugs like a glp-1 is a paragonist or giving an uh dpb4 Inhibitors are supposed to help against this drug serotonin cyproheptide answer in written they inhibit the hypothalamic factors that from or may exert a direct inhibitory effect on crh in the AVP secretion from the hypothalamus response rate is over timosolamide so this one is in fact for pituitary carcinomas actually we use this type of a drug so the cell apoptosis by methylating DNA specifically at the guanine o6 position thus interfering with the next DNA replication cycle will not go into the detail about that other roscovitin which is a cyclin dependent cdk and cyclinic inhibitor then you have so this is where it acts not go into the detail retinoic acid receptor Agonist so you they can antagonize the effect of transcription factors such as activator protein 1 or Nur 77 or nur1 then you have Jeff tiny bit which is the epidermal growth factor which is expressed in both the normal picture and the cortical adenomas uh say the E this receptor controls Palm C expression and inhibition has been studied as a possible Target for the treatment of Cushing's which is a c terminal heat shock protein 90 inhibitor extracted from the milk thistle seeds so it can be used in these type of patients and then peripheral glucocortic identical is mifa Preston which we used as an apotrophicient is actually used here uh the problem with this is it is acting at the level of the receptor so what happens is we don't know how to monitor so one way of monitoring is patients with diabetes in fact we use this drug methodistone so here what happens is the sugar level comes down that's how we come to know the drug is effective or not if your measure cortisol they'll be very high because it's a receptor blocker so that's why we don't measure that another way is actually you can look at the ears in a fill count in normally what happens in Cushings the eosinophils are lesser and if a eosinophil starts increasing that's the way you know that probably we are dealing with uh the patient is improving or the patient starts losing weight is another indicator that probably the drug is working yeah these are the drugs available and before I finish I want to talk a little bit about subclinical hypercortisolism and pregnancy three four slides about that so up to 30 of adrenalines in Dental of mass are associated with subclinical hypercordialism you are subclinical hypothyroidism similarly subclinical hypo hypercortisolism so you have a biochemical evidence of hypercortisolism in patients without typical signs or symptoms of Cushing syndrome what are the diagnostic tests one milligram overnight dexa and if the cortisol is less than 1.8 microgram per deciliter it indicates a normal response values more than five definite subclinical hypercortisolism values between 1.82 5 microgram per deciliter additional test include late night salad cortisol and dhes whereas ACTH and urinary free cortisol seems less helpful they can also have reduced level of adrenal androgens measured by lcms can be used as a markers radiologically we say incident Lomas larger than one centimeter in them you'll have to look for this city is the best amazing technique and normally what happens when they are benign you find that in a non-contrast the hounsfield unit is less than 10 and then you find that absolute washout is more than 60 percent and relative washout more than 40 percent that suggests we are dealing with a benign adrenal Mass if the Baseline hit you itself is around 30 40 we are probably dealing with a more serious lesion the European Society guideline says adult activity should be performed in patients with urilateral adenomas with a lack of Separation to dexamethasone separation test that is cortisol more than 5 microgram per deciliter and at least two comma mid it is potential related hypochondria say patient has osteoporosis the patient has developed nuanced diabetes so then probably we should probably remove this tumor little bit about pregnancy and Cushings etiology of Cushing's differs in pregnant and non-pregnant women pregnancy prevalence of adrenal disorders particularly adenomous 60 percent than Cushing's disease is the central one which is around 30th non-pregnant 70 percent is cushion reference is probably related to the higher impact on fertility so you can have three categories patient categories can be encount pregnancy in the context of known Cushings denova development of cushions development of clinical features and complications similar with Cushing's during pregnancy like stria arterial hypertension diabetes hirsutism is rare indeed over questions during pregnancy because most cases are due to benign adrenal adenomas without hyperandrogenism so the diagnosis should be supported by lab and imaging procedures because the serum cortisol increases due to estrogen induced production of CBG it can produce false positive results on Lotus dexa separation urinary cortisol more than three-fold elevation in the second and third trimester probably we are dealing with that I told you loss of circadian rhythm is another way by which you can find out nocturnal salivary cortisol in the third trimester if it is more than Point say 0.25.26 and 0.33 microgram per deciliter we are measuring the record is a three cortisol levels so that also we can do it so to conclude a clear understanding of the pathophysiology of cortisol axis States helps to inform the choice of screening test for patients with a high pre-test clinical probability of having Cushing syndrome when the results of these tests are consistently abnormal patients likely have the syndrome and should process to test for the differential diagnosis when patients have discordant results reasons for inconsistency should be sought was a test chosen that carries a high likelihood of falsely abnormal result in that specific patient when the patient have normal results but the clinical suspicion is quite High the repeat testing should be done to evaluate for cyclic disease unfortunately it's still often difficult to be certain about the diagnosis in such cases then what we do watchful waiting for the clinical and biochemical progression may be the safest approach for patients although frustrating for both patients and clinicians thank you for patient hearing thank you so much just giving a moment for all the doctors to put in their queries in the comment box dear doctors um I'm sure you all would have some queries to ask Dr banwalza post the sessions which is giving you a moment here you have a question from Dr venkatesh as a pseudo Cushing's definition and how can we differentiate between that and actually clinical questions the pseudo cushion is like suppose the patient is obese patient is having depression uh alcoholism especially withdrawal so these are the times when you can get a false positive result say if you do an overnight dexamethasone separation test there is one milligram of dexamethasone at 11 PM and the data clock when you check the serum cortisol it should be less than 1.8 micrograms if it is more than that probably in in this type of patients it can be positive then how will it differentiate you can do what is known as load as prolonged one point five milligrams six thousand for two days that is six o'clock 12 O'Clock six o'clock twelve o'clock the next day also repeat at six o'clock twelve o'clock six o'clock 12 o'clock and the Third Day morning you measure the second cortisol in majority of the pseudo Cushings they'll all become less than 1.8 so telling that we are dealing with the pseudo cushions in this type of patients I hope that answers your question so uh could you just please reiterate on the medical management of cushions like a gist of it one more time please yeah sure so one is drugs acting at the level of the pituitary to steroidogenesis inhibitor acting at the level of the adrenals and finally acting at the level of the uh uh receptor level I'll come from below upwards at the level of the receptor we have actually what we have right now is Method upon sorry mifa peristone so mephuprystone is actually an artificiant so what it does is it will block the glucocortical receptor now because of that the cortisol levels in the blood is more but then they are not acting it's like a resistance syndrome like cortisol resistance you don't have any features how will you monitor if you measure chord is a little bit High but then what can happen is if you have diabetes in addition the sugar starts coming down there was a trial known as a zodiac trial where they actually use this drug and after that the drug of choice for Cushing's with the medical line of management with diabetes is actually mephuprystal uh then what happens because this cortisol it can act on the mineral cortical receptors so sometimes you can get worsening of hypertension with hypokalemia because the cortisol is not acting sometimes you can also get an additions like features so what happens the patient starts losing weight is blood pressure starts dropping down because it's now developed the analytical insufficiency how will you manage that so for that what we do is we stop the drug and put them on dexamethasol hydrocortisone is good but then it you require to give 16 for higher doses compared to dexamethasone where you have to give just four folds so dexamethasone is a way of it and at the level of the adrenal gland we use mainly Ketoconazole so Ketoconazole 200 milligram once or twice daily after two they measure the code you will see whether it has come down and you find if it is not come down you can go up but the very important thing is you must monitor for the liver enzymes and to counter that side effect you have what is liver Ketoconazole not yet available in India okay so then you have which can destroy the ideal gland also like you have magnitude and that's also available very expensive it's an adrenal lighting we'll use 8 grams 9 grams 10 grams and all whereas here we can use 3-4 grams and we can maintain that at the level of the pituitary we have pacilitate very expensive drug I told you three and a half lakhs per month so that one or you can use chemical in a simpler drug what you use for prolactinoma Center so that you can actually use it so that is fairly okay 10 15 percent decrease you can do people have tried using glitter zones also Cipro heptagonism right so This Is How We Do It okay um doctors please continue putting in your queries if you have any uh so from my end from your years of experience as an endocrinologist what are the few uh clinical pictures that you get immediately get an inkling that okay this could be Cushing syndrome your tips and your uh major manifestation one is proximal muscle weakness yeah facial plethora and then easy blues ability spontaneous bruisability okay and um what is that violations try and that should be more than one centimeter non-tapering that is how the characteristic future is okay so these are four manager manifestation and suppose we find osteoporosis I told you we have now having a patient yeah osteoporosis with vertebral fractures which is just around 26 years okay so that's another way and hypertension say 20 year old somebody's having hypertension and another way is high potential with hypokalemia then also you start suspecting though we suspect cons but then you should think about this also and then also one more thing is uh I obesity is seen But if if I told you no Supra temporal dorsal survival and uh temporal when super temporal and the temporal fat will mask your tragus so you're not able to see that that's a clue for you that's an interesting one I hope you've noted it down doctors so these are the signs from your uh end right so five to six interesting okay with that this is a tough topic so it becomes difficult for them I hope I have simplified it yes and we need to revisit uh the lecture and also like make our own note that would really help us I think for a topic like this I'm sure our doctors will do that I hope you'll know doctors that you can watch a recording of this session in the replay section we'll be back with another amazing session with Dr vanquel of course and sir thank you so much yet again for coming in with making time for us in your busy schedule really grateful for how you always manage to give us your time thank you so much uh one question is it okay okay fine how do you support the patient yes after adelectomy though it's very important see when you're doing a bilateral ectomy it's mandatory that the patient Beyond hydrocortisone and also on plutocortisone because both of them have been lost you must give them a steroid alert card telling that this patient requires steroids for survival okay that is number one and you in that it will be written you had to give hydrocortisone if it's found lying on the road or something is happening you give Hydrocortisone and just because he's taking steroid doesn't mean that you stop the steroids so in that it will be written so we give a 3. we have it with us and we give it them to all of them how do you monitor suppose if the patient starts putting a lot of weight that means we are giving an excess dose that is a dose of uh the hydrocortisone suppose you find that uh the blood pressure is increasing you can downtight it the dose of protocol so that is how and also you can measure the sodium potassium so if the potassium is low that means we are giving a higher dose the potassium is high that means we are not treated properly if new stretch marks are happening that means we are treating overdosing and slightly reduce the dose so clinical judgment and one or two tests especially for mineral corticult effect that is a protocol I hope that answers your question Dr rajat Dr bontrol thank you yet again and hope to see you soon good night sir bye


Cushing's syndrome remains an extremely complex endocrine condition. It comprises a large group of signs and symptoms that reflect prolonged and inappropriately high exposure of tissue to glucocorticoids. More often patients have a number of features that are caused by cortisol excess but that are also common in the general population, such as obesity, depression, diabetes, hypertension, or menstrual irregularity. As a result, there is an overlap in the clinical presentation of individuals with and without the disorder. The choice of tests, the integrity of the specimens and the quality of endocrine assays are key factors for optimal patient care. On Medflix, Dr. Ganapathi Bantwal joins us LIVE to provide us with extensive guidance on how to overcome these diagnostic challenges.


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