All right, so I think we'll get started. Welcome everyone to our first in the series of two ITE Live 2024 sessions. And today, we'll be reviewing reproduction, pituitary, and bone. I'm the moderator, Salil Akura, and I practice at Columbia University Medical Center in New York. And thank you to our panel for joining us. So if we can move on to the next slide. And this is a list of our faculty, all of whom were wonderful and really great contributors to the ITE exam and wonderful collaborators. So thank you all so much for dedicating your time to this endeavor. And then the next slide, please. And these are just our disclosures, which are also available online. So we can move forward from this one as well. And just some important points about ITE. It really should be treated as a learning exercise by programs rather than a formal high stakes knowledge assessment. And really, it's to give fellows and programs a general picture of areas to focus on when studying for the boards. And for programs, really to focus where they should focus their curricular efforts on, as there may be areas where all the fellows would benefit from learning more about. So that's just how we really see the ITE as an exam that's used to develop your curriculum as opposed to being a high stakes exam. So the fellows as well, they can focus their studying once they've reviewed their own individual answers. Next slide, please. And this is just a list of the fellows' performance. As you can see, we had 769 fellows who participated in the course. And the scores improved with the fellows' training years, which makes sense as a lot of our knowledge is based on access to patient care. So this was also provided in your score report. So we can move on to the next slide as well. And this just goes into a little bit more detail by topic area, which had some slight changes from years past. But most of the percentage correct were similar to years past. And we'll go over questions now that either gave fellows some trouble when they were taking it or important teaching points and knowledge points. Go on to the next slide, please. So we'll start with Dr. Shin, who'll go over male and female reproduction. So thank you for joining us today. And I'll turn the mic over to you. Yeah. Aloha. Good morning, everyone. This is Terry Shin. I'm calling in from Honolulu here in Hawaii. The weather is nice and breezy and perfect. So, I think we'll just go ahead and get started, but glad to be on today. So, we have a 33-year-old man with Kalman syndrome that was referred for fertility management for the past nine months. He has been treated with ACG 1000 international units by subcutaneous injection every other day. On this regimen, his testes increased in size from two to four milliliters in the first six months and have now reached a plateau. So, his hormone profile, with a sample drawn on the day of his injection when it was due, his testosterone came back at 350 nanograms per deciliter. His estradiol is at 40 micrograms per milliliter. His LH is at 0.6 and his FSH is at 1.0. So, again, testosterone is normal, estradiol is right at the upper limit of normal, and then LH and FSH are on the low end with the scene analysis that shows azoospermia. So, which of the following would be most helpful in improving this patient's fertility in this case? So, A is add FSH 75 international units daily, B, increase the ACG dosage to 1500 international units every other day, C, switch from ACG to recombinant LH injections, or D, switch to clomiphene citrate 50 milligrams daily. And so, in this case, the answer was to add FSH 75 international units daily. So, in this case, with secondary hypogonadism with infertility, spermatogenesis can be induced with hormonal therapy in the form of either exogenous gonadotropins. So, generally, you can use a combination of ACG with FSH. GnRH can also be used. So, why was add FSH 75 international units daily the correct answer? So, patients who have congenital hypogonadotrophic hypogonadism and prepubertal testes with size less than 4 milliliters, generally, the combination of both ACG and FSH to stimulate the growth of the seminiferous tubules. Men who are generally hypogonadal after normal puberty, however, has been completed and have normal testicular size treatment with ACG alone is generally sufficient. Again, in this case, this patient had a very longstanding hypogonadism requiring a combination of both. The other three and why they weren't the correct answer. So, increase the ACG dosage to 1500 units every other day would be of no benefit. So, if you look at the patient's trough testosterone, it was in the normal range and estradiol was already at the upper limit of normal at 40. So, if we were to increase ACG dosage at that point, it would lead to a higher estradiol level. The recombinant LH is generally not used as a very short half-life, estimated at 1 to 5 hours. So, if you were to stimulate spermatogenesis, you'd have to give repeated injections. So, the long half-life of ACG means fewer injections for the patient and more convenience overall. And it's cheaper with ACG than recombinant LH. And then finally, treatment with clomiphene. This requires an intact hypothalamus. Again, this patient has Kalman syndrome. So, the fact that the HPA axis is not intact would not lead to sufficient increase in LH production in this case. Okay, moving on. So, next question. So, a 32-year-old male presents for evaluation of a three-month history of tender gynecomastia, reports fatigue and decreased libido. Although he can still get and sustain an erection, he has been taking finasteride for male pattern balding or baldness. Physical exam, his BMI is 22 kilograms per meter squared. He has normal facial, axillary, and pubic hair. His thyroid gland is normal in size with no palpable nodules. He has bilateral gynecomastia that's tender to palpation. His phalluses is normal, and testes are 15 milliliters bilaterally with no palpable masses. So, laboratory test results, total testosterone is 100, so low. Estradiol is 140, which is high. FSH is at 1, so we're at the lower limit of normal. LH is low at 0.5, and prolactin, slightly elevated at 25. So, which of the following most likely explains this patient's hormonal profile? A, would be decreased 5-alpha reductase activity due to finasteride. B, estrogen-secreting testicular tumor. C, hyperprolactinemia, or D, hyperthyroidism. So, the correct answer in this case was estrogen-secreting tumor, number or letter B. So, in this case, you have to really look at the lab. So, with finasteride, right, there is a modestly finasteride can modestly increase your serum testosterone concentrations by blocking the conversion of testosterone to dihydrotestosterone, but it would not explain this patient's hormonal profile since the patient's testosterone was low in this case. For B, is the correct answer as it best explains the significantly elevated estradiol level with the suppressed gonadotropins due to the estrogen-mediated negative feedback and given the low testosterone levels. The estradiol levels were greater than threefold than normal, which may reflect an increase in testicular secretion of estradiol, increased extraclanular aromatization of estrogen precursors secreted by the adrenal glands, increased extraclanular aromatase activity or exposure to exogenous estrogens. Specifically, leading cell tumors can secrete estradiol directly in about 50% of cases, and generally, gynecomastia precedes the development of a palpable testicular mass. So, it can be detected, tumor can be detected by ultrasonography in those cases. So, C, hyperprolactinemia, this can suppress gonadotropin-releasing hormone secretion resulting in low total testosterone concentration in gynecomastia. However, if you look at the prolactin, it was just minimally elevated, which won't be sufficient to lower testosterone to the degree in this case. It also wouldn't explain the high estradiol level. So, in this case, elevated prolactin is most likely due to result of stimulation of lactotroph by the estrogen-secreting tumor itself. Finally, D, hyperthyroidism is not consistent with this presentation, especially since its testosterone value is low rather than high normal as would be expected in hyperthyroidism where you'll generally have high SHBG levels. Okay. So, those are two questions for male reproduction. We'll move on to female reproduction at this point, unless there are any specific questions. It doesn't look like there are so far. Okay, great. All right. So, moving on. So, question 84, a 32-year-old woman is referred for an ovulatory infertility. She has a history of irregular periods, acne, polycystic ovarian syndrome was diagnosed at age 16 years. Her blood pressure is 130 over 80. She continues to have irregular cycles of around 25 to 50 days and has been unable to conceive for the past six months. Metformin was started three months ago to induce ovulation, and she has had two periods since then but has not conceived. Serum ACG is negative. On physical exam, her BMI is 32. So, in this patient's case, which of the following treatments would most effectively induce ovulation and result in a live birth? So, A, clomiphene citrate, B, continuation of metformin, C, ganatropin therapy with recombinant FSH, D, letrozole, E, progesterone suppositories. So, the correct answer in this case is D, letrozole. So, again, the question was which treatment is most effective in inducing ovulation and resulting in live birth in a patient with PCOS? So, letrozole is the correct answer based on the reproductive network trial comparing second-generation erythematase inhibitors with clomiphene citrate. It demonstrated a higher rate of ovulation induction and live birth with letrozole compared to clomiphene, specifically women with obesity and polycystic ovarian syndrome. Clomiphene citrate was historically prescribed to induce ovulation but is found to be less effective. So, generally, it would be second-line at this point. Metformin may increase ovulatory pregnancy rates but specifically is not shown to improve live birth rates. Ganatropin therapy with recombinant FSH is generally not used as first-line therapy for ovulation induction in women with polycystic ovarian syndrome as a greater risk of multiple gestation and ovarian hyperstimulation syndrome. So, it's generally used in women who have not responded to letrozole and clomiphene. Progesterone suppositories are prescribed for women with hypothalamic amenorrhea, not for women with polycystic ovarian syndrome. They do improve menstrual cycles but they are not shown to increase rates of ovulation induction specifically. Okay, so, moving on. A 32-year-old woman presents with a six-month history of amenorrhea, hot flashes, and night sweats. She previously had regular monthly menses and has normal secondary sexual characteristics. She has a history of well-controlled type 1 diabetes mellitus diagnosed at age 28 years but is otherwise in good health. Both her mother and maternal aunt had early menopause at age 39 years and 40 years, respectively. The patient has a 19-year-old brother with intellectual disability. So, laboratory tests shows an FSH at 90, which is high. Estradiol levels are less than 20. TSH is 3, normal. Prolactin at 7, which is normal. And A1c is 6.5% elevated. So, which of the following tests is most likely to identify this patient's diagnosis? So, A, 21-hydroxylase antibody measurement. B, anti-malarian hormone measurement. C, FMR1 genetic testing. D, karyotype analysis or E, TPO antibody measurement. And the correct answer in this case is C, FMR1 genetic testing. So, this question is specifically asking about fragile X mutation screening. So, this should be performed in any woman with primary ovarian insufficiency, so menopause before age 40 years, and in women who have a family history of primary ovarian insufficiency, male relatives with learning disorders, autism or intellectual disability, which was the key in this case, or family members with ataxia and or dementia, just suggestive of fragile X-related ataxia. So, to come to that correct diagnosis, you would choose FMR1 genetic testing, which would most likely identify the diagnosis of fragile X syndrome pre-mutation carriers. The answer A, the positive 21-hydroxylase antibodies are seen in women with autoimmune oophoritis, and they may predict risk of adrenal insufficiency. However, given her family history specifically with a male relative with a learning disorder, fragile X syndrome is more likely in this case. Anti-malarian hormone, which is an indicator of follicle number and would be low in premature ovarian insufficiency and high in polycystic ovarian syndrome, may be helpful, but does not identify the patient's diagnosis in this case. So, care type analysis is not performing in women with primary ovarian insufficiency to rule out mosaic Turner syndrome. There are a small percentage of girls with Turner syndrome with mosaicism that have normal puberal development and regular menses for a few years after menarche. However, this patient has had normal puberty and regular menses until about six months ago. Just to recap, she's about 30 years or so. So, this would make Turner syndrome less likely. Thyroid antibodies may be positive in patients with autoimmune thyroid disease and concomitant autoimmune premature ovarian insufficiency, but the autoimmune condition would not explain the family history of learning disorder and early menopause in the relatives. Great. Thank you, Dr. Shin. There is one question in the question and answer, and is letrozole for assigned therapy, or do we need to try metformin and other meds for PCOS for infertility before we start it? Yeah. So, going back specifically, it was a combination of improving ovulation and live births. So, in this case, if metformin is not shown to improve live births specifically, and this patient has been attempting to have children and has been unsuccessful despite some restoration of menses, so you would, at that point, go to letrozole. So, this would be an add-on therapy. It wouldn't necessarily be first-line specifically for infertility treatment, if that makes sense. And then, the last question before we move on is, would letrozole be a first option for people without PCOS also? I have to double check on that, but letrozole, I believe, is also first-line in these cases of Great. Thank you so much. And then, we'll move on to the pituitary section, and Dr. Tritos and Dr. Don-Angelo will be presenting this section. Yeah. So, hello, everyone. I'm Ines Don-Angelo. I'll be presenting today's session. So, I'm going to start with the pituitary section, and then we'll move on to the next slide. Yeah. So, hello, everyone. I'm Ines Don-Angelo. I'll be presenting cases along with Dr. Nicholas Tritos. So, we can move on to the next slide. So, this first case of a 19-year-old man who presents with pubertal delay and frontal headaches. In retrospect, he has had poor energy, frequent urination, increased thirst, and a 46-pound weight gain over the past two years. Testing documents a prolactin concentration slightly elevated at 42.7, conformal dilution, and hypopituitarism, including AVP deficiency, formerly known as central diabetes insipidus. On imaging, he's found to have a 2.3-centimeter cystic cellar mass with supercellar extension, abutting the optic chiasm, and ophthalmology has been devised by lateral homonymous hemianopsia. Next slide. So, the question is, which of the following is this patient's most likely diagnosis? So, the options are A, chronic pharyngioma, B, gonadotropadenoma, C, like in her cell histocytosis, D, prolactinoma, or E, saline corticotropadenoma. And the answer is chronic pharyngioma. The key features in this vignette that suggest a diagnosis of chronic pharyngioma are the presence of AVP deficiency in the cystic cellar-supercellar mass. So, this patient has AVP deficiency, which indicates a primarily hypothalamic origin of this tumor, such as seen in chronic pharyngiomas. These tumors occur in children and teenagers, as seen in this case, but there is also a distinct second peak in older adults between ages 50 and 74. Next slide. So, again, the presence of the cystic tumor and the presence of AVP deficiency are pretty typical presentation for chronic pharyngioma. AVP deficiency does not occur at a time of diagnosis of pituitary adenomas. So, the options of gonadotropadenoma, prolactinoma, and saline corticotropadenoma are incorrect. So, AVP deficiency can happen as a complication of pituitary surgery for adenomas, but not as a presenting clinical finding. And also, this patient does not have laryngeal cell hisocytosis. This condition usually presents with a filtrative disease of the hypothalamus and stalk, and there is stalk thickening on MRI rather than the noted cystic mass lesion in this case. And also, this patient does not have prolactinoma. The patient's prolactin elevation is mild and most consistent with hypothalamic damage or stalk effect rather than prolactinoma. In prolactinoma of the size 2.3 millimeters, the prolactin would be expected to be much higher. Dr. Tritos? Yes, thank you. Good afternoon. Nick Tritos, Pituitary Endocrinology at Mass General, and this is a second pituitary case for today. A 41-year-old woman is referred for evaluation of possible Cushing syndrome. Hypertension was diagnosed two years ago and diabetes mellitus was diagnosed last year. She has gained 25 pounds over two years, mostly in her midsection. Early tests were ordered by the PCP and showed a 24-hour urinary free cortisol of 45 micrograms per 24 hours, normal being up to 50, so this is normal. Serum cortisol after an overnight 1 milligram dexamethasone suppression test was 3.2 micrograms per deciliter, which is abnormal. Normal is conventionally taken up to 1.8 micrograms per deciliter. With a dexamethasone level that was adequate, as you can see, 234 nanograms per deciliter indicating adequate exposure to dexamethasone. Current medications include Losartan 100 milligrams daily, metformin 500 milligrams twice daily, an oral contraceptive pill, cetirizine 10 milligrams daily. On physical exam, blood pressure is 140 over 90 with a pulse of 76. Her BMI is 32.2 kilograms per meter square. She has some facial rounding and an obese abdomen with no striae. Which of the following is the best next step in the patient's management? A. Measure 24-hour urinary free cortisol after stopping the oral contraceptive. B. Measure plasma ACTH. C. Obtain two bedtime salivary cortisol measurements. D. Perform another dexamethasone suppression test with 2 milligrams this time, and E. Perform pituitary directed MRI. And the correct answer is C. Obtain two bedtime salivary cortisol measurements, and as you can see, the majority of test participants chose the correct answer. So let's discuss why this is the correct answer. So the three tests that can be used primarily to diagnose Cushing's are 24-hour urinary free cortisol, 1 milligram dexamethasone suppression test, and late night salivary cortisol measurements. This patient has technically an abnormal result on a one screening test, serum cortisol above 1.8 micrograms per deciliter on the overnight dexamethasone suppression test, and a urinary free cortisol that was high normally, but still normal. So the key issue here is that she takes a combined oral contraceptive pills and oral estrogen increases cortisol binding globulin, which will raise the measurement of total serum cortisol, which is what we measure in the assay. So in this case, the dexamethasone suppression test is not reliable and should not be done actually in a patient on a combined OCP. Late night salivary cortisol correlates very well with free serum cortisol levels and is therefore reliable in women and oral estrogen. Another possibility would be to stop the oral contraceptive for about six weeks and perform another dexamethasone suppression test, but this was not offered as an option. Performing an MRI of the pituitary would not be indicated at this point since we have not established the diagnosis of Cushing's and of course could unveil an incidental microadenoma, which is present in about 10% of the general population. Similarly, measuring plasma ACTH would be indicated after Cushing's syndrome is established in order to distinguish between ACTH dependent and ACTH independent Cushing's syndrome. But at this point, it's not, it doesn't have a place. Repeating the dexamethasone suppression test with two milligrams is not needed because serum dexamethasone already reached an adequate level with a one milligram dose and this patient's serum cortisol may have not suppressed even with a high dose dexamethasone for the reasons we discussed. So finally, measuring 24-hour urine free cortisol after stopping the oral contraceptive pill is not necessary because urinary free cortisol is not affected by changes in cortisol binding globulin. Thank you. And Dr. Donangelo will present the last question. Hello. Yeah. So for the third case, we have a case of a 36-year-old man who seeks evaluation for a two-month history of increasing tiredness, excessive thirst, and polyuria. He also noticed intermittent back pain and shortness of breath when exercising. He has no relevant medical history and he has a 25-year cigarette smoking history. On examination, his blood pressure is 125 over 80, pulse rate 68 and regular. His height is 74 inches, weight 190 pounds for a BMI of 24. He has no clinical stigma of endocrine dysfunction and he does have mild tenderness over the mytholastic vertebrae, but the rest of the examination findings are normal. Laboratory testing shows a fasting blood sugar of 75, normal calcium 8.8, normal sodium 142, potassium 3.9, creatinine 1.2. He does have a normal thyroid axis with a TSH of 0.9 and PT4 of 1.2, 8 a.m. cortisol is reassuring at 13.5. He has mild elevated prolactin of 34 and gonadal axis shows normal LH, FSH, and a testosterone of 330 on the low end of the reference range. Due to his polyuria polydipsia, he was asked to do a water deprivation test, and on this investigation, the baseline urine osmolality is very low at 123. After eight hours of water restriction, the urine osmolality did not change much. It's 137. And after he was given the small paracet injection, the urine osmolality appropriately went up to 885, again, supporting the diagnosis of APD deficiency or a central genomic deficiency. Next slide. On imaging, he had an MRI of the cellar, and this is a satchel view. In this view, we can see that the anterior pituitary gland appears normal. The posterior pituitary bright spot is not seen, and there is a thickening of the pituitary stalk above. The CT of the chest shows bilateral upper and middle zone micronodular cystic infiltrates, and the retinoploid bone scan showed increased focal tracer uptake in several vertebrae. So the question is, which of the following in this patient is this patient's most likely unifying diagnosis? So option A is germ cell tumor, B, Hodgkin's lymphoma, C, Langerhans cell cytosis, and D, lymphangitis carcinomatosis, E, tuberculosis. And the correct answer is Langerhans cell histocytosis. So the key factors in diagnosis of Langerhans cell histocytosis in this case are its multisystemic disorder presentation with pituitary, pulmonary, and skeletal involvement. So Langerhans cell histocytosis is a rare hematologic disease characterized by accumulation of mononuclear phagocytes in various tissues and organs. So the multisystem disorder presentation is a pretty typical presentation. So regarding pituitary, patient had polyuria, polydipsia, and the result of the water deprivation test is consistent with APD deficiency. And the MRI does show the typical focal thickening of the epithelium. He did have a reassuring anterior pituitary function, at least on baseline testing, and his mild hyperprolactinemia is most consistent with stock effect. Langerhans cell histocytosis can appear at any age and should be always considered in patients with isolated APD deficiency. An estimated 10% to 15% of patients with idiopathic APD deficiency actually do have Langerhans cell histocytosis. Pulmonary involvement is seen in about 10% of cases, mostly in adults. And the high-resolution CT of the chest does show, like in this case, a combination of multiple cyst and nodules in the mid-to-upper zone and also interstitial thickening. And as in this case, cigarette smoking is a key etiologic factor. Bone involvement is also common, affecting most cases, and can be associated with localized vein. Rheumatologic studies demonstrate lesions that are typically hard on bone scan. As for the other options offered, germ cell tumors can present with APD deficiency and stalk or hypothalamic mass, but they typically present at a younger age, in childhood or adolescence. And pulmonary infiltrates and also the bone lesions would not be anticipated. And regarding tuberculosis option, pituitary gland involvement and skeletal involvement are recognized manifestations of mycobacterial infection, but the patient did not have a medical history of disseminated tuberculosis. And moreover, the imaging findings of pulmonary tuberculosis are different. In this case, CT imaging would show patchy or poor differentiated consolidation in the upper loads that can progress with cavitation and is often associated with lymphadenopathy. Lymphagitis carcinomatosis denotes a diffuse infiltration and obstruction of parenchymal lymphatic system by tumor cells, usually the adenocarcinoma, or an imaging of the chest that could be interlobal or cephalothickening and reticular nodule changes. And although disseminated malignancy can present with vertebral and pulmonary metastasis, the patient's young age, relative duration of symptoms, no notable medical history would make this a very typical presentation of disseminated malignancy. And similarly, for Hodgkin's lymphoma, the clinical pictures and radiologic findings are not typical for this condition. Great. Thank you both. I don't see any questions here yet, so maybe we can move on to the bone section. And Dr. Malabanon and Dr. Annapattawi will be presenting the bone section, so I'll turn it over to you both. Maybe next, yeah, good evening, good afternoon, everyone. I'm glad to be on today. I'll be presenting more questions with Dr. Malabanon. So the first case here is a 65-year-old man who presents for follow-up of normal calcimic primary hyperparathyroidism. He has had elevated PTH concentrations for the past two years with consistently normal serum calcium. He has a kidney stone, recent bone density testing documents osteoporosis with a T-score of negative 2.7 at the lumbar spine. Ultrasound and system EB imaging have not localized a parathyroid adenoma. Next. Lab studies showed normal serum calcium of 9.3, normal vitamin D, magnesium, phosphate, kidney function, as well as normal 24-hour urine calcium. However, he had elevated PTH of 100. Next. Which of the following is the best next step in this patient's management? A. Selective venous sampling, B. Refer to a parathyroid surgeon for bilateral neck exploration, C. Repeat ultrasound and system EB imaging in one year, D. Hydrochlorothiazide 25 milligram daily, E. Alendronate 70 milligram weekly. The correct answer is B. Refer to a parathyroid surgeon for bilateral neck exploration and parathyroidectomy. So this patient has normal calcimic primary hyperparathyroidism, which is diagnosed by elevated PTH concentrations with consistently normal serum calcium on at least two occasions during a three to six months period after excluding secondary causes. Patients with this condition are less likely to have a positive localization study due to a higher risk for multiglandular disease and a smaller parathyroid adenoma size. So these are the indications for parathyroid surgery in asymptomatic patients with primary hyperparathyroidism and hypercalcemia. The indications are age less than 50, serum calcium more than one above the upper limit of normal, skeletal complications manifesting by osteoporosis either by dexa or fragility fractures, renal complications manifesting by decreased renal function, elevated 24-hour urine calcium, or presence of kidney stones or nephrocalcinosis clinically or on imaging. So patients with normal calcimic primary hyperparathyroidism should have a parathyroidectomy if they have the criteria for surgery similar to patients with hypercalcemia. The reason is to prevent disease complications as these patients may develop osteoporosis, fractures and renal complications, even if preoperative imaging studies are negative. So looking at the other options, selective VNS sampling is an invasive test that has yet to be studied, especially in normal calcimic patients. Repeat ultrasound and system EBS in one year is not appropriate because this patient has complications including osteoporosis and kidney stones, and studies may still remain non-localizing even after one year. Hydrochlorothiazide is not indicated after a single episode of nephrolithiasis and urinary calcium is not elevated in this patient. The last option is alendronate to treat osteoporosis, which may improve bone density in normal calcimic patients similar to patients with hypercalcemia. However, it would not reduce risk of future nephrolithiasis or renal complications. Thank you, and next to Dr. Milibannon. I don't know if anyone has questions. Yes, thank you, Abir. It looks like there's a question. I don't know how to get it. I'm muted, sorry. I can read the question. It says, would you advise starting a bisphosphonate after parathyroidectomy for this patient, or how would you treat the osteoporosis in this case? Yes, I would, because, yes, I would start bisphosphonate to decrease risk of fractures. And I don't know what Dr. Malavanian would, if you would do anything different. Well, we do know that after parathyroidectomy for normal calciumic primary parathyroidism, there is some increase in bone density. But the amount of bone density increase is kind of directly proportional to the elevation of calcium. So there may not be much. But we do know within the first one to two years, there may be some increase. So if they're at high risk for fracture, if they fractured, I would probably agree with Dr. Adnatawi. But if not, you might be able to wait and bide your time. But there is a little controversy. I don't think there's any clear guidelines regarding that. Correct, yes. Great, thank you. And then the next question is, has the 24-hour urine calcium level criteria now changed? You mentioned greater than 400. I think this question is referring specifically to the primary hyperparathyroidism surgical guidelines. So she's asking? I think the question is, what is the cutoff for the 24-hour urine for referral for parathyroidectomy, if I'm understanding it correctly? Yeah, for 400. 400 milligrams per 24 hours. So I don't know if she, like, that's, these are the cutoffs. Yeah, exactly. Oh, sorry. Yeah. It said. Yeah, I remember one year, it actually had dropped away. They didn't have it available. But then it came back. So it's still 400 milligrams. Yeah, I think the confusion may have been, it said, isn't it greater than 250 for women and greater than 300 for men? But I think the consensus is 400. Yes, yes. So I think we've answered the three questions related to that, so thank you. Yeah, thank you. So question two. We have a 56-year-old woman with end-stage kidney disease due to hypertension and has been on hemodialysis for eight years. She is referred because of a pelvic fracture and a femoral NAC-T score of minus 2.2. Medications for the past six years include calcetriol, 0.5 micrograms twice daily, and sinicalcet, 90 milligrams twice daily. Lab results show a serum calcium that's a little bit low at 8.1, phosphate that's a little bit high at 5.2, 25-hydroxy-D at 24, slightly below the optimal range, PTH slightly high at 78, and a total alkaline phosphatase that's overtly low at 48. An ILEA crest biopsy is performed after double tetracycline labeling to look at bone histomorphometry. Next slide, please. So the question is, which of the following is most likely to be found on bone biopsy? A, adynamic bone disease, B, mixed renal osteodystrophy, C, osteitis fibrosis cystica, D, osteomalacia, and E, osteoporosis. And the correct answer is adynamic bone disease. So the situation with chronic kidney disease in the bone is quite complex. And this chart, this figure shows the interaction between the kidneys, the bone, the parathyroid glands, and the gut, as well as the vitamin D system. And overall, when you have, actually, if you can click on the next, yes, thank you. So the first change that occurs in chronic kidney disease is this decrease in phosphate clearance. And the serum phosphate will start to rise. Often, PTH will go up a little bit, but also FGF23 will rise as well. FGF23 is the primary phosphatoric factor within the body. What that does is it increases the amount of phosphate in the body. What that does is it increases phosphatoria by decreasing reabsorption of phosphate at the kidney. It also decreases phosphate absorption at the gut by decreasing production of 125 vitamin D. As a result, no, go back. As a result, the PTH levels will increase because of the drop in 125 and decrease the PTH has action on the osteoblast, which will increase alkaline phosphatase, increasing bone formation and osteoid production. But at the same time, you have decreased clearance of 784 PTH, which is one of the metabolites that is cleared by the kidneys. That does cause some PTH resistance and ultimately decreases the alkaline phosphatase. So you can see this is very, very complex. Next slide. So the reason adynamic bone disease is the correct answer, the most appropriate answer, is that it's fairly common in dialysis. It's also associated with a relatively low PTH, low alkaline phosphatase, and it's exacerbated by acinetocalcin and calcitriol. So in this patient, the kicker is really the low alkaline phosphatase. I know the PTH is slightly high, but probably lower than you would normally expect in somebody on dialysis. With this, you have a reduction in the number of osteoblasts and osteoclasts. There's a markedly reduced bone turnover and no accumulation of osteoids. So you're really not forming any bone and not repairing any bone. As a result, the bone is much more fragile and subject to fracture. These patients are at high risk. If you give them bisphosphonates or other potent antiresorptives, they have a higher risk for fracture. Now, mixed renal osteodystrophy typically has both hyperparathyroidism and osteomalasic features. They may have a high PTH and a high alkaline phosphatase. And it's usually not quite as high as we typically see with osteitis fibrosis cystica. In those patients, the PTH is very, very high. Alkaline phosphatase is very, very high. And they do have some elevation in calcium. Or the calcium may be normal in secondary hyperparathyroidism. So again, the alkaline phosphatase is really key in that setting. Osteomalacia, very similar. They have an overtly low 25-hydroxy-D, not just suboptimal, and a high alkaline phosphatase as a result. And then finally, osteoporosis may be present. But it's not the correct answer, because this patient has abnormal alkaline phosphatase and more consistent with adynamic bone. I would also mention that alkaline phosphatase sometimes can run low normal. And you may be better off checking a bone-specific alkaline phosphatase, given that alkaline phosphatase can also come from the liver and that can muddy the water. But in this question, the alkaline phosphatase is overtly low. Next slide. OK, if there's no questions, we can move on to the last question. OK, so we have a 48-year-old man referred for evaluation and management of muscle pain, fatigue, and weakness on physical exam. He has proximal muscle weakness. His lumbar spine T-score is minus 3.3. His labs show a normal chemistry panel. 25-hydroxy-D is slightly low at 28, slightly suboptimal. 125-D level is low at 12. PTH is slightly high at 98. SPEP and UPEP are both normal, as well as free Kappa and Lambda light chains. Serum phosphate is very low at 1.1 to 1.3. And FGF23 is 350, overtly elevated. Next slide. So the question is, which of the following treatments should be recommended now? Choice A is alendronate. Choice B is cholecalciferol and calcitriol. Choice C is potassium phosphate. Choice D is potassium phosphate and calcitriol. And choice E is zoligarnic acid. Next slide. Thank you. So the correct answer is choice D, potassium phosphate and calcitriol. And the majority of the respondents had chosen that. Next slide. So again, just to review, in terms of phosphate homeostasis, if the serum phosphate levels drop, FGF23 levels should decrease. 125 levels should markedly increase as a result to help increase the reabsorption of phosphate and the increased absorption of phosphate at the gut. PTH also may slightly decrease as well as a result. So in this patient, they have an inappropriate elevation of FGF23 and an inappropriately low 125 level. Next slide. So in this case, the diagnosis is tumor-induced osteomalacia. There is typically a mesenchymal tumor that produces excess FGF23, which leads to decreased serum phosphate reabsorption and excessive phosphaturia, as well as a decrease in 125 levels. The treatment of choice in these patients ultimately is to remove the tumor, but can be treated in the meantime with both calcitriol and potassium phosphate. There is now also an FGF23 monoclonal antibody, which is another option, but that was not included as a choice. Potassium phosphate alone is incorrect because it will be inadequate as PTH will rise further in response to the phosphate load. Cholecalciferol and calcitriol is also incorrect because they will be inadequate by themselves to correct the hypophosphatemia. You need a source of phosphate to allow the calcitriol to enhance phosphate absorption. And then finally, we do not use alendronate or zologenic acid in patients with osteomalacia because it can worsen the osteomalacia, causing some pain and increased fracture risk. Great, thank you. There are actually two questions related to this. I'll start with the second question first because it relates to this last question that you presented, and it is, where is the tumor in tumor-induced osteomalacia usually located? It can be located in a variety of areas. It's typically in the appendicular skeleton, although there have been reports of tumors being found in the skull, in the sinuses, or in the mouth. So it's really quite a search for that needle in the haystack. Often, we'll consider using a gallium deodoratate scan to help locate it, but by no means is that a guarantee you'll find it. So I had a recent patient who actually had it located in the thoracic spine, which opted for some very, very difficult treatment. And then I guess there's another question. What are the treatment options for adynamic bone disease? So ultimately, you may need to think about an anabolic therapy. Again, these patients may have PTH resistance, and there are some case reports in which PTH may be used to help stimulate bone formation in those patients. I don't believe we have very much data on rhomozoosomab, the sclerostin antibody in those patients. Great, thank you. I don't know if there are any other questions. All right, it looks like there aren't. So thank you very much to our panelists. We really appreciate you taking the time to come and clarify these important points. And then our next session will be Monday, this coming Monday, April 29 from 5 to 6 PM Eastern time. And that session will focus on diabetes, lipids, and obesity, adrenal, and thyroid. And thank you again to our participants for joining us today. And thank you again to our participants for joining us and for our panelists.

ITE Live 2024

reproduction

pituitary

bone

Salil Akura

fertility management

bone disorders

calcimic primary hyperparathyroidism

tumor-induced osteomalacia