Hello everyone. Today inshallah we are going to have a simple clinical approach to management of a case of heretism. When I say heretism I don't mean hypertriosis. Hypertriosis is the non-androgenic distribution of hair which may be excessive than normal because of medical reasons or endocrininal reasons. But hair shooters mainly is androgenic distribution of hair in a female. And this is typically a tool to predict hyper androgenism plus or minus acne, male pattern hair loss and uh oily skin, changes in body shape. But the main sign that is going to be associated with heretism is menstrual irregularities. And we are talking today about terminal hair. Terminal hair is long hair, pigmented hair make up the hair of the eyebrows, the scalp, the auxilary and pubic areas, not the lenovo or valless hair. So heretism here can be divided into androgenic causes, non-androgenic causes and idiopathic causes. In our practice guys, we mainly focus on excluding the most dangerous causes and then it could be anything else. So bear with me until we talk about the causes. I need to have a quick evaluation for my case. through the history I'm going to know if this patient is having history of any drug intake that could be the reason changes in her weight or facial contour the presence of other factors that could be a late for hyper androgenism like the acne the hair loss the balding and definitely the menstrual and reproductive history. Not to mention that we need to do physical examination mainly to have a score. This score is called fermentin galway scoring. This score is going to depend on the presence of hair in different body areas. And as you can see we are going to consider a diagnosis of heretism when we have a score of eight or more. Okay. Not also to forget that the onset, course and duration of uh this appearance of hair is very very important guys because if we are talking about new onset worsening hyperandrogenism which is heretism also this could need the exclusion of androgen secretreting tumors and if the patient is post-menopausal I'm going to think about ovarian hyperstyosis. But if it's something like gradual, it's taking forever, it's increasing by time, it's progressive but not acute. Okay, I'm going to think about mainly the ovarian causes and I'm after excluding it, I'm going to think about the androgenic causes but of course non-malignant. Okay. the hormonal profile is going to be my tool to diagnose the hyperandroenism. So I'm I'm looking for total testun. I'm looking for sex hormone binding globulin and I have a test that combine both of them which is the recommended test in uh our college in the RC. We are going to do what's called free androgen index. The free androgen index is going to calculate both of them. The total test divided by the sex hormone binding globulin. If this is high and let's be very specific, if it's more than five nanom per liter, I'm going to complete my road to exclude androgen secretreting tumors and non-classical c. Of course, I'm we are talking here about an adult lady. I'm not talking about a small lady. So if I'm talking about someone who is having irregular menes and now she's having heretism, she's having other size of signs of hyper androgenism and she is having a high preandroen index and going on with uh let's say excluding androgen causes like androgen hormone reducing pathologies. Okay. and of course androgen secretreting tumors. We could think about doing the uh deoxycortisol for example if from the physical examination you are suspecting that this is has something to do with crushing syndrome. So yeah okay I'm going to do the uh deoxycortisol and we can do the uh cortic cortisol in the morning and in the evening. Okay. To diagnose cushing syndrome. Of course, we can also use 17 hydroxy progesterone to diagnose. Yes. Exactly. The non-classical CA. Yes. So 17 hydroxy progesterone is our key to diagnose what's called the adult onset or late onset congenital adrenal hyperplasia which looks the same as PCO. PCO could give us some signs and symptoms. Late onset C is going to give us the same signs and symptoms. But in PCO the free androgen index is going to be five or less and mainly less than five. In case of androgen secretreting tumors and late onset C the free androgen index is going to be more than five. The is telling us that the DHA levels are not in a great value because sometimes they are not reflecting the real adrenal state in this woman. Why so? Because they are not very specific and they are really um influenced by the age. So the greater the age the more the decrease in the level of DHEA. So I I don't really recommend that this could be a routine test and also they do not recommend doing the serum and dione or DHEA levels in patient with herism because it's not going to be of a great value. Okay. Next would be if I have excluded all those if everything else is normal I could think of something that is not androgenic like prolactin like thyroid dysfunction plus or minus cortisol of course I'm going to do adjuvent ultrasound evaluation to solidify my diagnosis okay so ultrasound is going to be helpful but it's not a routine tool also in the management of heretism unless you need to know whether this is uh ovarian mass or or ovarian cyst or what's going wrong with the patient ovary. Okay. Otherwise, if you have a clear diagnosis from the uh investigations and from physical examination, you don't know need to go through the ultrasound evaluation. However, you still need to know the features of the iota group, the international ovarian tumor analysis group. This is very helpful in your practice. This is very sensitive up to 95% sensitivity and 91% specificity. We have features for benign ovarian cysts and features of malignant cancerous ovarian cysts and we have a score. Okay, you might have heard about the iota score. Uh and we applied to know if the cyst the patient is having is predicting for a malignant tumor or it is predicting for a benign tumor or or even a simple cyst. Okay. And you have here what we mean about uniocular, solid, multilocular and so on. I got you the iota terms to make it simpler for you. Now let's go back to go in depths with the causes and do you know mainly in the exam they are going to bring you a scenario and ask you about the best next step and the most important differential diagnosis in heretism in our practice would be yes exactly the PCO versus delayed onset congenital adrenal hyperlasia especially if I'm talking about a permenopausal or pre-menopausal lady. She's not postoposal yet. So having a ovarian tumor is not really common. Having ovarian hypertosis is not common and more commonly she's going to have a problem with her ovary or her adrenal in a benign way. So the PCO we know for sure that we have a criteria to diagnose PCO. This criteria or the roter dam criteria is really useful in diagnosing PCO and yet we cannot diagnose PCO depending on a single feature. We have to do the combination of features. Okay. So according to the Rotterdam criteria and I'm going to stress over some points here okay so please make your notes take your notes first of all I need a woman with oligo ovulation or anovvulation clinical hyperandroenism or and biochemical hyper androgenism you unilateral or bilateral polycystic ovary on pelvic scan and we have a cutff. The ovarian volume should be 10 cm cube or more or elevated antimarian hormone in adults and of course after exclusion of less common hormonal pathology. Those are the main four criterias in the Rotterdam criteria. I need to have at least two of those four. The the first one is a must. So between those three, we need to have two. And take care guys, I can depend only on clinical hyperandrogenism. Having biochemical evidence of hyperandrogenism is of course an important addition in my diagnosis but it's not a must if I'm having a clear clinical hyperandrogenism. Okay. If I'm having oligoation or an ovulation plus clinical hyperandrogenism, I don't need to have the ultrasound criteria. And this is very important according to the Ashri 2023 guideline. Ultrasound is not required to confirm the diagnosis in women presenting with irregular cycles and clinical or biochemical hyperandrogenism. Moreover, the AMH levels are not recommended in adolescence. So if we are having a case of adolescent and this lady is having now irregularities in demands and she's having heretism already am is not useful in her case the polycystic ovarian morphology should not be used for diagnosis of PCO in adolescence also why so because guys ovary is yet to reach its peak maturity. So maybe she's going to have the small cyst, the primordial cysts, okay, all over her ovaries. And you might think that this is PCO. It's not PCO. So within eight years of minors if you find a patient coming to you and her first monarch was just 7 years 6 years 5 years ago you shouldn't have the polycystic ovarian morphology within your diagnosis and I have seen this too much okay this is going to lead to overdiagnosis of PCO in adolescence. So please depend on the Rotterdam criteria. Please think that you don't need both clinical and biochemical this and this or this. And don't use the PCO morphology on the pelvic for adolescence. Don't use the AMH for adolescence. And if you are having clear clinical diagnosis plus clinical hyperandrogenism or irregularities and or biochemical hyperandrogenism you don't need the ultrasound. This is for the PCO so far and if you have excluded everything else now you can finalize the diagnosis of PCO. We have next the androgen secretreting tumors which we need to exclude specifically in cases of recent onset very progressive very rapid presence of hyperandrogenism. Not only this, if she is having verilizing symptoms, this patient is not only having a small rise in testosterone, we are talking about huge number of testosterone levels. The realizing symptoms are totally different from hyperandrogenism symptoms. The realizing symptoms mean voice horseness or voice change male muscle distribution breast involution. So I'm talking about something really big. This is mostly androgen secretreting tumor whether it was adrenal or ovarian. So again age don't forget about age. Am I dealing with adolescent or a patient in her uh pre reproductive age or I'm talking about someone who is permenopausal or monoposal. It's totally going to change your route for differential diagnosis. You can go for MRI or CT for the adrenals or the ovaries if needed. Okay. If other uh investigations like the ultrasound or uh the total testosterone levels are not really conclusive. Take care that sometimes ovarian tumors are very tricky. hydrogen secretreting ovarian tumors. They are really small in the ultrasound sometimes and they don't really appear this easy and they are not giving huge number of testosterone in some cases. Okay. Some cases they are not going to give huge number of cestosterones like certuli tumor for example. Sometimes it give uh slightly rise of testosterone levels. So it's not going to be easy to diagnose. You have to put everything on the table and search for the cause. So when you have persistent substantial increase in total testosterone, this is not normal. This prompt investigation for adrenal or ovarian tumors. Even if it's not really high, only having total testosterone level more than twice the normal level should prompt investigation for tumors. The most important differential diagnosis in our practice also which mimic the PCO is delayed onset C A. This is going to happen because of the enzyme defect and this enzyme defect which is the 21 hydroxilase deficiency. It's not like the early onset or the typical CE. The typical C is going to appear after the baby female has been born. But this late onset or atypical uh C is going to appear mainly after puberty. The result is going to be elevated levels of 17 hydroxy progesterone. 17 hydroxy progesterone is androgenic and this is why this patient is going to have heretism and signs and symptoms of hyperandroenism. more common of course in young women. I just told you just after puberty and she's now in the peak of her reproductive age. Ovarian hypertosis is something to look for during postmenopausal years. It can happen in premenopausal year but it's not that common. This patient is going to have rapid onsided heretism worsening badly fertilization, obesity and insulin resistance. Also the reason why she's having ovarian hyperyosis is the over production of gonadotropines like LH. And this is by far the most accepted theory. But this elevated LH is going to do what? It's going to stimulate the ovarian stroal cell to differentiate into the cell. The cell are the main ovarian source of androgen. So again this lady is going to have heretism virilization. Moreover, they are not only linked to vilization and heretism, but also to metabolic abnormalities like obesity and insulin resistance and the risk of endometrial hyperlasia. You would say how indometrial hyperplasia because please always remember that when you have a large amount of androgens in in the system of any of us this could lead to peripheral conversion of testosterone to estrogen in peripheral sets. Okay. So this woman is not only at risk for having complications like verilization or heritis. No, I'm talking about metabolic complications. I'm talking about risk of endometrial hyperplasia. So, diagnosing it and the treatment of ovarian hypercyosis is also very important for her health in general, not only cosmetically. Other causes is going to be treated as well if it was prolactin or drug induced or whatever. But we have something that is not really common. It's only 3% of women with androgen excess which is called hyperandrogenic insulin resistant aansis negrians syndrome. This is going to happen with people who are having extremely high levels of insulin severe state of insulin resistance. So those ladies are going to have a state of hyper androgenism, insulin resistance of course and moreover they are going to have a canthtosis negus uh as uh dermatology symptom. So those who are severely hyper androgenic and sometime it could be up to the level of signs of vilization they are really difficult to treat. their problem is really complex and of course they are going to have multiple uh comorbidities and also metabolic syndrome. So in for those ladies we are going to offer some drugs we can uh offer of course changing of her sty uh lifestyle and healthy lifestyle and so on but take care please that some drugs that they could be taking could be the cause also that increase the state of herism. uh in those ladies. For non-androgenic factors, we mainly talked about the eatrogenic or drug induced, we have also idiopathic causes. Idiopathic causes could be up to 50%. So if I have excluded everything and specifically in someone who is having only heretism there is no irregularities in manses the ovary is looking normal no evidence of adrenal or ovarian tumor this is idiopathic heretism but you are not going to exclude this unless you have excluded or ruled out all other dangerous differential diagnosis. If we focus on the androgen secretreting tumors, I just need you to remember that those cause of heretism and virilization are going to have some clues in the exam. The first one is the clinical history of rapid regression of symptoms presence of vilization. Some of them can be having cushionid features also. Best way to diagnose androgen secretreting tumor is clinical presentation. Remember when I told you that sometimes some ovarian tumors androgens secretreting ovarian tumors are going to be very tricky to diagnose because they don't give us high levels of androgens and also some biochemical markers like suppression or stimulation test could be misleading with those types of tumors. So think about it when you think about diagnosing those types of tumor in the exam. Just having the word of rapid rapid excessive heretism or signs of baralization is enough for you to exclude androgen secretreting tumor. This could be ovarian or adrenal. The realizing tumors which is famous in the ovary are the ceruli leic cell tumors. Those tumors guys are not common. They are rare sex cord gonad stumal tumors. Those viralizing tumors mostly are going to be leic or granulosa cells or leoas or they could be certuli le cell tumor. So leic cell tumors are two parts. They are not only one kind. They could be leic cell tumor only or certi cells only or a combination of both of them. And this is why they are having different signs and symptoms among literatures. You have to be uh alert for what type of tumor exactly the paper or uh the website or the book is talking about. Some books and some literatures are speaking in general. So this is why I'm I'm telling you in the exam we are not going to depend mainly on the uh biochemical investigations. We are going to depend on the clinical examination. Sex cord ovarian cancers usually happen in young women but again they can happen at any age. While if the tumor is composed only of leic cells, those are more commonly to be seen in post monoposal women. So this is why I'm telling you it's it's not really specific in some literature'ses and this is why there are so many conflicts about the type or the nature uh of the certiex cell tumor. how it appears, how it looks like, how it's going to be presented uh in the woman. You are going to find some papers talking about this rare tumor uh as a case study, okay, in post-menopausal women. We are saying here that it is mostly observed in postmenopausal women. Yes. When when it's combined like certuli le cell tumor, this is rare to be seen in a postmenopausal woman. Okay. So just take care of the uh hestopathology of the cancer. They are by far going to cause viralization and heretism in 75% of cases. If it happens in a young patient, this could lead to precautious sudo puberty. Okay. So this is also an important differential diagnosis. Mainly they are going to appear as a unilateral solid tumor. But they can be bilateral. Yes, they can. And we have some case studies talking about bilateral. Excel tumor which is very very rare. Okay, those tumors almost benign. They are not malignant. So just removing that tumor or the ovary is going to be a cure. You don't need an extensive pelvic clearance or anything. Okay. So, so far we have talked about all the causes that we have for hyperandroenism and heretism. At the very end, we are going to talk about the management. Management is going to depend on what the patient want. Does the patient want something to treat the hair cosmology or she's seeking something related to fertility? She needs something to do with the irregularities of her menes. This is very very important to know before determining a plan for the treatment. So of course after the lifestyle modification and cosmetic procedure with whether it was going to be laser or creams or whatever if she is seeking fertility we can delay the drug treatment because mostly they are going to be treatgen if she's not seeking fertility and um she is okay with taking the COC's we can give her COC's that contain anti-androgens, right? Or we can give her anti-androgens plus COC's or any kind of contraceptions. Okay. If she is uh okay to take the Cuc we are going to give her something that contain separatone or drosperinone or neutral progesterine. We can also in case of severe heretism add finest or spyronolone. Again in our exam they don't mainly ask about cosmology of course or the cosmotic procedures. They mainly want you to know how to treat the TCO. They want you to know what types of COC are containing anti-androgens. If she cannot take COC's as a formulation of COC's like for example she is contraindicated to take estrogen we can give her the anti-androgens alone and of course we are going to give her any other type of contraception because those are tatoggenic and they are they are very dangerous if she is having a male boy also at the end of This file you are going to uh find some algorithm and flowcharts to summarize all what we have told according to the onset according to the cause and uh finally according to the clinical history and physical examination it's really helpful to sum up everything and here this This is the flow chart not not not uh mine this is from the uh RC and the Ashri. So uh again guys I'm going to consider in my diagnosis onset duration the course of heretism the patient age very important to know if there is any verily symptom or not she's monoposal or not there any signs or symptoms for abdominal or pelvic mass that is going to make me think that yeah I'm dealing with adrenal or ovarian tumor. And of course, if they told me in this scenario anything about ultrasound features, not to forget that when you are having elevated 17 hydroxy progesterone more than 200, this is mostly late onset adrenal hyperlasia. Don't think about ordering and dione or dha. However, if you are having in the scenario high and d while the DHEA is normal, this is mainly PCO. I hope we have gone through a simple approach. I needed to go through also the approach for diagnosing a case of hyperandrogenism. Let me show it to you. which depend mainly on the RC guideline in how to diagnose a case with hyperandrogenism according to the physical signs of course and recommending the pre-androgen index and according to the result of pre-androgen index we are going either or we are talking here mainly about someone that we have excluded other causes from the clinical exam examination like she's not having a prolactin issue, she's not having thyroid issue or she's not having cotenoid features. I'm thinking only of a pure case of hyper androenism. If you are having signs of virilization or uh the free androgen index is greater than five, you have to exclude androgen secretreting tumors and the late onset CH. How to do this? by doing the 17 hydroxy progress theorem measured in the follicular phase if it's greater than 200 this is by far non-classical if it's borderline and I not really sure and the signs and symptoms are not really suggestive for adrenal secretreting tumors I can confirm this by act stimulation test stimulation test is totally diagnostic for congenital adrenal hyperplasia. That's all. Thank you so much for paying attention. See you next time. Take care everyone.