to the cases and then talk about management. But really who hasn t had a patient come into the

Transcription

1 JODIE REIDER, MD 1 So I m going to begin with just presenting a few cases and then at the end of the talk we ll go back to the cases and then talk about management. But really who hasn t had a patient come into the office and complain of concerns that they might have low T, especially since the marketing for testosterone lately has I think really skyrocketed. If you watch television and watch any of the commercials there is a lot of commercials for low T, and sometimes they don t even mention testosterone therapy but they are sort of warning their patients that they might have it because of some vague symptoms of maybe lack of wellbeing or decreased energy or fatigue, but typically those are associated, are put out by drug companies to encourage patients to inquire about their testosterone. So the first case I m going to present is a 40 year old obese male referred for fatigue and low testosterone. He reports low libido but normal erectile function, wakes up tired, he mentions he snores at night, naps during the day, just feels like he has no motivation whatsoever. But he does have a several year history of obesity with weight gain and he has a body mass index of about 40. His other past medical history is significant for prediabetes and dyslipidemia, he reports normal pubertal development, no prior medications and is not taking any drugs or denies taking any drugs. And aside from obesity and prehypertension there is nothing significant on exam. And then usual fatigue laboratories were normal including in my area we often will check a morning cortisol though clinically he looks more like cortisol excess. And so his primary care physician checked his testosterone in the clinic and this was done at 2:00 pm. His total testosterone I ll talk about assays in a minute but his total testosterone by tandem mass spec was 223, so just below normal with a free testosterone in the low normal range. And then follow-up labs obtained at 7:00 a.m. showed a total

2 JODIE REIDER, MD 2 testosterone by a different assay, radio amino assay of 250, which is just in the low normal range with normal gonadotropins, prolactin and a PSA. So case 2, I just wanted to in case 2 is a 54 year old male with a history of obesity and chronic pain secondary to a motor vehicle accident who is on chronic opioids with an intrathecal hydromorphone pump and he presented himself with because he had recently noticed loss of axillary hair, chest and public hair, loss of libido, absent spontaneous and stimulated erection, hot flashes, sweating, breast enlargement. He also reported a remote history of head trauma related to the motor vehicle accident, which was complicated by transient seizures. He denies a history of nontraumatic fractures, his exam basically shows an obese man with supraclavicular fat pad fullness, gynecomastia, absent chest and axillary hair, scant pubic hair, slightly small testes although not dramatically so, 15 ml is just slightly small, and a normal digital rectal examination and his labs were dramatically low, his testosterone was only 20 with undetectable FSH and LH. And then the third case is a 68 year old overweight man presenting with low libido, erectile dysfunction and recently detected low testosterone. Just has a history of hypertension, hyperlipidemia, treated with a few antihypertensives and a statin. No other pertinent medications. He doesn t smoke, he doesn t drink alcohol, he doesn t report any drug use aside from being overweight his exam was normal and his total testosterone at 8:00 a.m. was 240, so just below normal. So does this patient have hypogonadism or low testosterone and what further tests would you perform? Would you treat with testosterone and what are your treatment options?

3 JODIE REIDER, MD 3 So male hypogonadism is defined as either low testosterone or a decrease in sperm production, but for the purposes of this talk I m really going to be focusing on the low testosterone. In a younger male we worry as well about decreased sperm production but a lot of the men I see are no longer concerned about reproduction. So testosterone circulates mostly bound to protein and it s mostly bound to sex hormone binding globulin and also albumin. There is a very small portion that is the free or active form of testosterone about 2%, and then bio available testosterone refers to the testosterone that is completely free and that which is weakly bound to albumin and the term comes from or the term bio available just refers to the fact that that which is bound to albumin is weakly bound and considered to be pretty much bio available in addition to their free testosterone. So which testosterone to check? If you use EpiCare and you try to order a testosterone it s overwhelming the list of possibilities. There is testosterone by LC-MS/MS which is tandem mass spectrometry. There is testosterone by radio amino assay. There is a testosterone battery which you don t know if that s going to be done by radio amino assay or tandem mass spec. And then there is a bio available testosterone assay. So total testosterone, the lower limit of normal is usually around 300 for most assays but you really do have to look at the reference range of whatever lab it s drawn and it s usually an accurate reflection of someone s testosterone status unless you are me, in which case you have a population of patients who typically has a binding protein abnormality. But factors that you need to consider when assessing a total testosterone value that could lead to inaccurate or unreliable results are first the assay. So tandem mass spec is recommended if you are going to order

4 JODIE REIDER, MD 4 testosterone because it is the most accurate, again it should be a morning sample. Radio amino assay is not terrible but it becomes less accurate when the testosterone is in the indeterminate range which I ll talk about in a second. Age is a factor. You know testosterone when they report it doesn t say there is no age separation for this is normal for this age and etc. But testosterone levels do change with age and I have a slide that will review that as well, but basically testosterone levels do decline with age. And it s unclear if that s, if that s a natural phenomenon or if that s unnatural. Concomitant illness so acute illness, chronic illness can lower testosterone, medications there can be day to day variation in testosterone, so you wouldn t want to make a diagnosis of low testosterone based on just one value, and then time of day and sex hormone binding globulin levels. So regarding time of day, so this slide is I think is a really nice slide. On the X axis you can see time of day and on the Y axis serum testosterone, and red is young males and in blue is old, many may argue or beg to differ with the old, but older men. And for young men you can see that there is a variation in testosterone throughout the day so that testosterone levels peak in the morning and then start to decline by the afternoon and evening hours and then rise back up in the morning. So if you check an afternoon testosterone you may very well get a low value but they may have a very normal morning value. You can see that in older men first their total testosterone values are about half to two-third that of younger males, and they start to lose a bit of that variation in testosterone throughout the day.

5 JODIE REIDER, MD 5 So conditions associated with alterations in sex hormone binding globulin I just highlighted here I think two of the most common. So decreased SHBG can be seen most significantly in obese patients and in Pittsburgh it s what was in my clinic, most patients tend to be overweight or obese. Also it can be decreased with nephrotic syndrome, hypothyroidism, glucocorticoids, progestins and androgenic steroids. So if a patient is not obese and you perform a laboratory evaluation sometimes they ll come in asking for testosterone, they re buff you know and you get a very low SHBG level you should be a little suspicious that they may be abusing anabolic steroids. Increased levels are seen predominantly with aging but another population I see a lot with is patients with cirrhosis and then I mean most men are not taking estrogen, but that s something that can increase it, HIV, hypothyroidism and anticonvulsants. This slide nicely illustrates how important this SHBG becomes when interpreting total testosterone levels in individuals who are obese. So on the left what you can see is that (I think I have a pointer) total testosterone levels do tend to be lower in obese patients and higher in patients who are not. But the free testosterone levels are relatively similar and that is largely in part because of altered sex hormone binding globulin levels. So if you suspect an SHBG abnormality it s recommended that you check SHBG and consider a calculation of free or bioavailable testosterone. Both can be measured directly or calculated from the total testosterone SHBG and albumin measurements. Most available labs are not available to perform accurate direct measurements so if you order a bioavailable panel it may not be accurate. If you order a free T level with a lab they re often either calculating it from the total or performing a direct measurement by radio, I mean or by analog method and it s just not very accurate at all. So what we recommend and what many recommend is

6 JODIE REIDER, MD 6 to use a testosterone bioavailable calculator, this I think is in your slides that you have available to you, but it s if anybody wants to write it down because I think it doesn t project very well, it s but if you just Google testosterone calculator to be honest this comes up, and it s the Issam, ISSAM calculator. And basically you just enter in their albumin, SHBG, and testosterone from a morning tandem aspect sample and if they re calculated bioavailable testosterone is less than 70 you can feel very confident or pretty confident that they have low testosterone. If it s above 100 or sorry, yeah, if it s below 70 you can be fairly confident they have hypogonadism, if it s above 100 you can be fairly confident they don t. But if it s in the range it s not clear and that s sort of a grey area. So typically we diagnose androgen deficiency if the testosterone in 8:00 a.m. serum total is less than 200 on at least 2 occasions with normal SHBG levels, or the calculated bioavailable is less than 70. They may have low testosterone however if the total testosterone is in the range, or if they calculated bioavailable is In 2006 the Endocrine Society published guidelines on testosterone therapy in adult men with androgen deficiency syndrome and this slide I don t want it to be misleading to suggest that the blood work is not important and that you really can t rely on the testosterone values but what this slide highlights is that the threshold level below which, the threshold level for testosterone below which androgen deficiency occurs, below which symptoms may improve with therapy with testosterone is not really known. And when these guidelines were published, what s not really clear when you just look at the guidelines, is there s a lot of you know argument about what the lower threshold should be and who should be treated. So there s good evidence that truly hypogonadal men with a total testosterone below 200 benefit from therapy but when the level is between 200 and 300 it s just really not clear.

7 JODIE REIDER, MD 7 So once you determine that your patient has low testosterone, then you have to decide is it primary or secondary, primary being testicular failure and secondary being pituitary or hypothalamic disease. And just a very quick review which I m sure you re all familiar with is from medical school but maybe it s not as fresh in your memory, but basically testosterone is produced in the testes, it s produced by the leydig cells of the testes, understimulation by LH from the anterior pituitary, and then sperm is produced by their Sertoli cells in the seminiferous tubules, understimulation by FSH. So testosterone then feeds back to the hypothalamus and pituitary to decrease FSH and LH secretion. And then there s further inhibition on FSH by inhibin. So primary hypogonadism is diagnosed when a patient has low testosterone and high gonadotropins. Sometimes it gets a little tricky because you ll get the lab results and just FSH will be high, not LH and that really indicates seminiferous tubule failure and decrease in sperm production, but it s really often just early primary. So the testosterone deficiency may not be as prominent yet. And then secondary hypogonadism occurs when you have low testosterone and low inappropriately normal gonadotropins. Okay so I don t want to spend too much time with the medical student review because I want to go back and revisit therapy and talk about that. I think that will be a more interesting discussion and leave time for questions. But just to quickly review the causes of primary hypogonadism, you know if you get a patient like this, the most common cause of that is going to be Klinefelter s syndrome for which you would want to get a karyotype. There are some other things that present typically in infancy like vanishing testes, that s usually due to a thrombotic event or testicular torsion in utero, anorchia. And then other secondary causes of testicular failure that can happen, it can be seen in obesity, certainly malnutrition illnesses, I think most commonly I see chemotherapy, a history of

8 JODIE REIDER, MD 8 chemotherapy, orchitis as a young child-mumps, certainly neurodegenerative illnesses, and trauma are all common. And then secondary hypogonadism if you have a patient who has a history of anosmia or lack of smell we think of Kallmann s which is failure, lack of GNRH stimulation of the pituitary to produce FSH and LH so you end up with a hypogonadotropic hypogonadism, Prader Willi patients have a lot of secondary hypogonadism and then other acquired causes so obviously pituitary tumors, pituitary disease, infiltrated diseases such as hemochromatosis, inflammatory diseases, COPD, I mean a lot of chronic illness basically can cause secondary hypogonadism and certainly if it s acute you would want to treat the acute illness and then reassess testosterone levels later but some of these patients are chronically ill and then run the risk for being hypogonadal. Patients with other endocrine disorders, hypoprolactinemia most specifically, certainly anabolic steroid use and then multiple medications. The meds I just want to highlight are glucocorticoids, so patients obviously if they re on long term steroids they re at risk, and then patients on opioids, we see that very commonly. Aldactone can cause impaired testosterone action at the receptor, it s not going to lower your actual testosterone level. So signs and symptoms, so if you watch the commercials you would think that the symptoms on the right here are the most specific symptoms of hypogonadism, but these include sort of lack of energy, motivation, depression, poor concentration and memory, sleep disturbances. And then on laboratories you might see mild anemia, the patient may have increased body fat, decreased lean body mass and diminished physical or work performance. But the more specific features of course are basically low libido, sexual dysfunction, breast discomfort, gynecomastia, if they have eunuchoid body habitus that s what you see with Klinefelter s where your lower segment is longer than your

9 JODIE REIDER, MD 9 upper segment or your arm span is greater than your height and so that could suggest, obviously patients who have aspermia, if they lose their body hair, notice their tsetse are getting smaller or have small testes, if they have a history of infertility, height loss or low trauma fractures, hot flashes or sweating. And conditions associated with a high prevalence, I sort of eluded to this earlier, but basically obviously anybody with a pituitary tumor or sellar mass or a history of pituitary radiation, patients on medications which I just reviewed that can cause low testosterone, HIV patients there s some data that treating them with testosterone if it s low may help with weight maintenance and improvement in muscle strength, so that s a high risk population, patients with end stage renal disease, moderate to severe COPD obviously infertility, diabetes, and osteoporosis. But screening of the general population is not recommended, so this a high risk population you could consider screening, but you don t want to just screen the general population, like I feel the ads are advocating, you know go to your doctor and complain tell them that they should check your T. So sort of a separate issue is hypogonadism in the aging male, so I think that it s a completely different situation when you have a patient who s sort of in their twenties to fifty age. But once you re above the age of 65 then the diagnosis and treatment is highly controversial. So testosterone levels do decline with normal aging and there s no consensus on what normal is. Testosterone therapy there have been several studies looking at whether or not it would benefit older men and so there are potential benefits on libido, erectile function, mood, body composition, muscle strength and bone density, but there are concerns for adverse events. And so this study, so on the bottom of the

10 JODIE REIDER, MD 10 slide on the second study I m going to, or rather third study I m going to discuss is the one I feel people are most familiar with. It was published in the New England Journal of Medicine a few years ago that showed an increased risk of cardiovascular events in older men treated with testosterone. But there have been several studies that have not shown that increased risk and so the population of patients that was studied with the high risk population, they were averaging around the age of 75, they were overweight, many of them had hypertension, hyperlipidemia, and other cardiovascular risk factors, they were relatively immobile, and they achieved very high testosterone levels. They used AndroGel in doses of 5-15 milligrams which most of us don t use 15 milligrams too often, and the T levels achieved were between the range of , some even over 1000 and that s a pretty robust level of testosterone. So the cardiac events too were, first of all the study was small and the events were highly variable. I mean some patients had increased atrial fibrillation, and some patients had an increased incidence of heart failure but it wasn t sort of one cardiovascular event that a lot of them had, it was multiple different events. So, well let me go back. And so based on this there s really no, there s very little consensus, some would treat if the testosterone is below 300, some would treat if the testosterone is below 200 and of course this is a patient population you want to check sex hormone binding globulin levels and assess the bioavailable testosterone to guide you as well. I can tell you some of my colleagues feel very strongly about not treating this patient population unless they have very compelling reasons to treat them. So this is according to the endocrine society guidelines, how to approach a patient when you suspect they may have low testosterone. So you do a history and physical, you look for signs and symptoms, you check a morning total testosterone and I would recommend (20:02) if you can and

11 JODIE REIDER, MD 11 then if it s normal you can feel confident they don t have hypogonadism. Unless of course you suspect they have very low sex hormone binding globulin levels in which case you would want to check those to calculate a bioavailable. So if the morning total testosterone is low, then you want to exclude reversible causes; like a medical illness, drugs, nutritional deficiency, and then repeat the testosterone and as I mentioned if you suspect a sex hormone binding globulin abnormality you would want to calculate, you would want to check that with an albumin and calculated bioavailable level. You also, a lot of people forget this, want to check a semen analysis in anybody who s relatively young or in anybody who you re not sure about the diagnosis, or when fertility is an issue. So once you confirm the testosterone is low, then you determine if they have primary or secondary hypogonadism. If it s primary we typically recommend getting a karyotype if it s clinically relevant for that patient, if they re beyond reproductive years then that s probably not very helpful. And then in patients who have secondary hypogonadism we basically recommend screening for any other pituitary hormone deficiencies particularly checking prolactin because hemochromatosis can cause this, we check iron indices and then an MRI in circumstances. So you know the guidelines say basically the testosterones below 150 or they have panhypopituitarism, a high prolactin or other signs or symptoms of mass affects like headaches, vision changes, visual field defects. I can tell you, I personally if it s below 200, it s kind of my threshold, or certainly if they have any other pituitary hormone deficiencies, not just panhypopituitarism. I tend to check a pituitary MRI. Okay. So the guidelines recommend that when testosterone therapy is initiate that you give testosterone to achieve a therapeutic target in the mid normal range for young men which is about Then for older men you aim for a total testosterone in the range. I can tell you in

12 JODIE REIDER, MD 12 my personal preference is if the, depending on their age and other comorbidities, I might even just aim for you know in someone who s older. It is important in older men to also discuss with them that at some point you re probably going to taper them off of it because you know it s probably not physiologic to be continuing on testosterone therapy into your eighties. So there are, I m going to just quickly review the testosterone preparations so that we can get to the, back to the cases. But basically there are so many preparations out there these days and you know just since 5 years ago. I mean there s 3 different gels, there s a patch, there s injectable testosterone, and then there s buckle testosterone which I ve never used but basically the injectable testosterone is injected usually weekly or every other week and the key thing I just want to point out is it s important to check the levels mid way between injections. If you check it right before or right after you re going to get highly discrepant results. For so there s, this is the only patch actually, Androderm, it s typically applied at night over the skin on the back, thigh or upper arm, and the thing again I just want to skip over these very quickly because they are available to you. But Androderm, basically for Androderm and the gel, it s very important to read the product information and find out when the best time is to check their levels because depending on the formulation it varies. So for instance for Androderm you re going to assess the morning testosterone level, 3-12 hours post application. So for most men they re going to apply it at night, you re going to check their level the next morning and then you ll adjust the dose based on the results. We mostly wait 4-6 weeks to kind of assess levels after starting on therapy but you could check sooner if desired. For AndroGel there are now 2 different formulations that s also important to recognize, there s a 1% and a 1.62%. the 1.62% is more concentrated so you don t have to apply so much gel. And so it comes

13 JODIE REIDER, MD 13 in both a pump and packets both of them do, the 1% and the 1.62%. I prefer often the pump I just think it s easier for patients, the packets can be messy. But patients who travel a lot, they prefer to have packets so they can take them with them. And then this is just basically from the drug website showing how to apply the AndroGel, the different, you can see that for the 1% you can apply to the shoulders or abdomen, but for the 1.62% it s just the shoulders and then the dosing you can t just, it s not directly convertible. So for AndroGel 1% it s 5, 7.5 or 10 grams which equates to 50, 75 or 100 milligrams of testosterone, but then when you move to the more concentrated the doses are milligrams, 40.5 milligrams etc., so you really just have to look at the product information. For additional transdermal gels there s Testim, this comes in a little tube. It s applied in the morning to the shoulders and/or upper arms and you adjust the dose based on the pre-morning testosterone level, so for most of the gels that s the case, and yeah for most on including Fortesta. So for most of the gels you check it in the morning basically before the application. Oh you know what that s wrong, sorry. For Testim and for AndroGel you check it in the morning before application and then for Fortesta it s applied to the medial thighs and you check the 2 hours after application the morning. This has led to a lot of confusion for my patients because a lot of times what happens is insurance will only cover one or another, it gets changed by a nurse over the phone, they get the other formulation, they don t know to change the location of where they apply it and they also don t know that they need to have their blood work drawn at a different time, so you really have to be on a high radar for this. I mean I have to look it up every time for these formulations just to make sure that I m checking it at the proper time. So there s also a transdermal solution, Axiron. You know I sort of thought it was like stick of testosterone or some sort of something like that where it came on sort

14 JODIE REIDER, MD 14 of a deodorant style formulation but really what it is, it s a topical solution that then is applied into this applicator that s been applied under the arm. And I have a handful of patients on this. And then there s Straint which is buckle tablets. I ve never used these, these are an option for patients who can t tolerate any of the other formulations, I do believe it s rather expensive. And so which to choose? I can tell you that for me cost is a number one priority and I think for most of my patients cost is probably the number one issue. So injectable testosterone tends to be the cheapest, but it s not always the case. For many patients the gels are then going to be the next option or the patch. Some insurances you have to try the patch first before you can get the gels, some insurances will only cover Axiron and Fortesta, or Testim but they won t cover AndroGel, etc. So it is difficult you kind of go over with the patient what you re going to start them on then you find out that it s not covered which is, it s difficult but eventually you ll get something that works for the patient. One other thing I wanted to mention with injectable testosterone, it s highly viscus. So if you start a patient on injectable testosterone we usually recommend that you give them obviously an intramuscular injection it s going to take a ¾ to 1 inch needle, but you want a smaller needle for the injection maybe a 23 gauge but for actually drawing it up out of the testosterone vial, a larger needle. So I usually give them both, a larger needle to draw it up out of the vial, like 18 gauge, and then a smaller needle to do the injection.

15 JODIE REIDER, MD 15 Okay so compliance is another thing. So patients you don t think are going to be compliant, often the injections will work better for patients who have an adverse reaction like a patch, you can move to a gel. Injections sometimes cause mood changes for some patients, it s better if you dose it weekly or every other week but if you choose to dose it, if you do it that way it s better. But some people will dose it once a month which I don t advise, that can lead to high peaks and valleys and may exacerbate the mood changes, you can obviously have pain at the injection sight. Then there s transference concerns so patients who use gels, you know once you apply it you have to be sure to wash your hands and not touch anything for a period of time after, so men who have young children are particularly sensitive to this issue. And then there s abuse concerns, so I obviously don t like to give injectable testosterone to anybody who I m suspecting an abuse concern. Some patients will come into the office for their testosterone but it s that little bit inconvenient if you dose it properly every 1-2 weeks. So potential adverse effects, the more common ones you have to worry about erythrocytosis, or an increase in hematocrit, acne and oily skin, detection of a sub clinical prostate cancer, growth of a metastatic prostate cancer, and don t forget that testosterone reduces sperm count, you know I don t want to, I try not to say to patients it s an adequate contraceptive but I mean it really, it lowers their sperm count so if one of their concerns is fertility you don t want to put them on testosterone. Depending on the type of hypogonadism they need they may be a candidate for other therapies and I usually refer them to a reproductive endocrinologist. So less common, testosterone is aromatized to estrogen they can get worsening gynecomastia, or they can develop gynecomastia, it can worsen male patterned balding, worsen BPH, cause growth of a breast cancer or induce or worsen

16 JODIE REIDER, MD 16 obstructive sleep apnea. Actually I meant to point this out earlier. Obstructive sleep apnea is a very common cause of secondary hypogonadism and when you identify and treat it the testosterone levels improved so I have a very low threshold for screening for that before diagnosing somebody with hypogonadism. Contraindications and precautions; prostate cancer, breast cancer, palpable prostate nodule, unexplained rise in PSA, high hematocrit, hyperviscosity, untreated sleep apnea, it can get worse with therapy, basically severe BPH symptoms and congestive heart failure, because testosterone therapy can cause fluid accumulation. So when monitoring testosterone you want to evaluate the patient every 3 months after initiation and then at least annually. Monitor their levels 2-3 months after initiation, check a hematocrit at baseline and then at 3 months and annually if their hematocrit rises above 54% or above the normal range we usually stop the prescription until the hematocrit declines and then restart at a lower dose. Monitoring their bone marrow density is recommended if it they have a you know you can sort of do a screening bone density in the beginning, which is sort of controversial in someone who has borderline low levels. But if they have truly low levels then that is important. Then monitoring as you wold anybody with osteoporosis every 1-2 years and then you re supposed to, you should check a digital rectal examination and a PSA prior to therapy at 3 months and then in accordance with prostate cancer guidelines which is typically about once a year.

17 JODIE REIDER, MD 17 Then for patients who are on therapy you would refer to urology basically if they have an abnormal urologic exam, if they have sever BPH symptoms and then if there s a significant rise in PSA and I have to look it up every time. But basically if their PSA rise above 4 there s an increase in greater than 1.4 ng/ml in any 12 month period or an increase in the PSA velocity. The urologists actually have their own sort of threshold for what they consider high, this is what the Endocrine Society recommends, but and this is when I would refer. Okay so back to the cases, is this time right, do I still have about 10 minutes, I think, okay. So back to case one, so just to summarize it s a 40 year old, obese man, with pre diabetes, pre hypertension, fatigue, low libido, and low to low normal testosterone. So it s kind of metabolic syndrome looking and because of his, so basically because of his obesity and concerns for low SHBG I feel in this patient it d be important to assess his total testosterone SHBG and albumins so that you can calculate a bioavailable testosterone. Because of his fatigue and snoring there s a concern for sleep apnea, so that would be important to evaluate and treat prior to testosterone therapy. If low testosterone therapy is detected in this patient his FSH and LH remember were normal, so it appears secondary and so I would want to rule out other causes of secondary hypogonadism such as hemochromatosis, Cushing s syndrome or glucocorticoid excess, pituitary disease which by checking other pituitary hormones and consider checking an MRI. So in his case a sleep study did reveal severe sleep apnea. I can tell you I have such a difficult time getting my patients to get this done, you know I order it, they re like oh I just don t think I have it, now this guy had a lot of very classic sleep apnea symptoms but some of them just have daytime

18 JODIE REIDER, MD 18 fatigue. And they re often reluctant but I think it s very important. He couldn t tolerate the CPAP mask because he had a goatee and was unwilling to shave it for the therapy and so it was a struggle to really get the sleep apnea adequately treated. But his repeat labs fortunately showed that he did not have low testosterone. So his total testosterone by tandem mass spec was 298 which is you know definitely raises some concern but his SHBG was only 11 which is low and when you calculate his bioavailable testosterone it was well over 100 so it s difficult because there s not a lab test when I make this calculation that I can show the patient that says you do not have low testosterone, it s just my medical opinion and sometimes they seek another opinion if they don t agree with me, but you know in this patient and I did of course, repeat the results to confirm that this was accurate, and encouraged him to have his sleep apnea treated. So I would no treat him with testosterone. For case 2 it s a 50 year old, this guy is just classically hypogonadal, he has all the symptoms, he has all the signs and he has risk factors that I see this most commonly in the patients that have an intrathecal pump either of morphine or hydromorphone and he also is obese and has a history of head trauma. So his testosterone was severely low with undetectable FSH and LH levels. His repeat, I repeated his ADM labs just for confirmation given they were so low, you know you worry about lab error of course although clinically with his clinical presentation I was fairly confident. So in his repeat labs his testosterone levels were extremely low. You know he is someone who I would worry about a sex hormone binding globulin abnormality and he did have on the low side his SHBG levels, but when the testosterone level is that low it s never going to correct to normal. And so I did work him up for other secondary causes just because of the severity of his low testosterone and so

19 JODIE REIDER, MD 19 his prolactin and other pituitary hormones were normal. I even did an ACTH stimulation test because chronic opioids can be associated with secondary adrenal insufficiency and his morning cortisol was kind of on the low-ish side. His pituitary MRI was normal, his iron indices were normal and his Cushing s screen was negative. His DEXA did show osteopenia and in fact it did improve with therapy. His breast imaging showed severe gynecomastia. He fortunately wasn t bothered by it and you know you can offer these patients aromatase inhibitors if it gets worse or surgical removal. So he was secondary hypogonadism, secondary to chronic opioids. I first gave him the patch, he had a skin reaction. I then gave him AndroGel and he s done fairly well, I mean he, I think compliance is always a factor with these patients but he had both improvement in his symptoms and his bone density. And finally the third case a 68 year old basically aging male, not that old but older than 65 with erectile dysfunction and low testosterone, relatively healthy, but he does have history of hypertension, hyperlipidemia and he s overweight. So I repeated his 8:00 a.m. labs with SHBG and albumin since he s older and there s a concern for higher SHBG levels and his 8:00 am repeat total testosterone levels one was low, one was low normal and his calculated bioavailable levels were in kind of the grey area. So one was low, one was in the grey area. So and his FSH, LH and Prolactin were normal. This patient, I don t know, I think if you asked my colleagues if this patient is hypogonadal, 50% may say yes and 50% may say no. I think he doesn t really have overwhelming symptoms of hypogonadism, but you know he might benefit from treatment. If you were to consider treatment I think it s important to consider the financial issues, it s a large cost to the healthcare market treating patients with testosterone so I would never treat anybody whose bioavailable was

20 JODIE REIDER, MD 20 less than 70 in this situation and I wouldn t treat anybody whose total testosterone-i m sorry did I say that wrong? I would never treat anybody in this situation whose bioavailable was above 100, excuse me, and I wouldn t treat them if their total testosterone was above 300. But in the grey area, I think it s an individual basis. If he had a lot of cardiovascular risk factors, I would not treat him. And so in this situation you would want to screen for other causes of low T. You could consider a DEXA scan but if his testosterone levels are in that range it s probably not going to have a significant impact on his bones either his current testosterone level or therapy. You can discuss the potential risks and benefits and then aim for a testosterone in the low normal range. Okay and that s it, so if I have time for questions I ll take questions. Thank you.