The JCEM Case Reports Clinical Pearls session at ENDO 2025 featured three presentations of rare challenging endocrine cases that could answer questions for endocrinologists who could be treating patients with similar symptoms, possibly triggering further investigations that might lead to optimal outcomes.
The audience for the third-annual JCEM Case Reports Clinical Pearls session at ENDO 2025 in San Francisco was much bigger than the first session convened for ENDO 2023 in Chicago. That first session in Chicago took place soon after the journal JCEM Case Reports launched in late 2022, so it sort of made sense that it was relegated to one of those small rooms on an upper floor. This time in San Francisco, the JCEM Case Reports Clinical Pearls session commanded a full theater, and the theater was filled: a testament to the interest of endocrinologists wanting to learn about challenging cases and the the eureka moments that led to optimal care.
When the open-access journal JCEM Case Reports (JCEMCR) was announced, editor-in-chief William F. Young, Jr., Tyson Family Endocrinology Clinical Professor and professor of medicine, Mayo Clinic College of Medicine and Science, Mayo Clinic, Rochester, Minn. told Endocrine News that the editors are looking for case reports on common endocrine disorders with unique — diagnostic, ethical, management — challenges; on rare endocrine disorders that present in a different way; recognition of a new association with an endocrine tumor; or other endocrine diagnosis.
These sessions at ENDO aim to highlight those challenges. Young has spoken before about how case reports can lead to a link between two unusual findings that could lead to further investigation. “In the third annual Clinical Pearls from JCEM Case Reports the attendees heard presentations from early-career aspiring endocrinologists on the management of Cushing disease in pregnancy, the presentation and management of metastatic choriocarcinoma-related paraneoplastic thyroid storm, and the management of hypophosphatemic osteomalacia,” Young says. “Each case presentation was followed by a content expert who put the topic into a broader context and expounded on the key pearls that clinicians should take away from the session.”
Successful Medical Management of Cushing Disease in Pregnancy
Angeliki Theodorou, MD, of the Division of Endocrinology in the Department of Medicine in the Memorial Sloan Kettering Cancer Center in New York, presented two case studies she and her mentor Eliza B. Geer, MD, wrote for JCEMCR, two cases of pregnant women with recurrent Cushing disease (CD), a rare disorder that carries many diagnostic and therapeutic challenges.
No drug to date has been approved to treat CD in pregnancy, and surgery is usually the first option for treating Cushing syndrome, but many pregnant women are not candidates for surgery. How serious CD is in pregnancy can even be tricky to detect. “Cushing syndrome in pregnancy itself presents high risk for both mother and the fetus, including fetal loss, gestational diabetes, preeclampsia, and fetal growth restriction,” Theodorou says. “Cortisol normally rises during pregnancy making it difficult to use the standard non-pregnant reference ranges to assess disease severity.”
In the two cases Theodorou and Geer write for JCEMCR, they describe using metyrapone, a drug that has not been approved by the U.S. Food and Drug Administration for pregnancy. Theodorou says that this choice wasn’t made without careful consideration. “In these cases, metyrapone was chosen, but it introduces concerns such as potential increases in blood pressure and hypokalemia, which require careful monitoring,” she says. “Metyrapone also raises theoretical concerns for fetal virilization by increasing androgen levels, and also neonates must be monitored for adrenal insufficiency and stress-dose glucocorticoids should be considered during labor.”
Theodorou goes on to explain that metyrapone at the time was the most commonly used agent in other similar case reports without any significant adverse events. Other agents used in pregnancy were cabergoline and ketoconazole. “However, cabergoline was mainly administered in patients with prolactinomas, and it’s not as effective in lowering cortisol levels,” she says. “And ketoconazole has known teratogenic and anti-androgenic effects. Other treatment options were not available or not used at the time, so metyrapone was the most reasonable choice.”
So to the two cases: The first case is that of a 31-year-old woman with recurrent CD who gave birth to twins while on metyrapone. Uneventful pregnancy, healthy twins at 37 weeks. Postpartum she developed hypertension which resolved spontaneously and she remained on metyrapone. The second case involves a 29-year-old woman with recurrent CD since adolescence, who conceived naturally on metyrapone. But Postpartum she developed preeclampsia which required temporary antihypertensive therapy.
“Although we had in mind that cortisol levels naturally increased during pregnancy, the clinical well-being of both mother and fetus were taken into account for these decisions. This example show that each case should be evaluated separately, always having in mind the clinical well-being of the mother and the fetus.” – Angeliki Theodorou, MD, Division of Endocrinology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, N.Y.
The two cases, while similar, also speak to the importance of tailored medicine. In the first case, the woman required a lower dose of metyrapone, while in the second case, metyrapone dose was kept unchanged during pregnancy. Theodorou says that in the first case, metyrapone doses were decreased when urinary cortisol were repeatedly in normal range — the non-pregnant normal range. But in the second case, doses remain unchanged with cortisol values above the upper limit. “Although we had in mind that cortisol levels naturally increased during pregnancy, the clinical well-being of both mother and fetus were taken into account for these decisions,” she says. “This example show that each case should be evaluated separately, always having in mind the clinical well-being of the mother and the fetus.”
Current guidelines for women with persistent or recurrent CD who want to conceive suggest bilateral adrenalectomy before conception, and again, some pregnant women might not be candidates for or decline surgery, so Theodorou and Geer agree that it’s essential to have comprehensive discussions with each patient about the potential risks and benefits of all treatment options. “And if surgery is not an option, metyrapone is a viable option for managing Cushing,” Theodorou says. “However, it requires careful monitoring and those adjustments, and of course, management should be individualized.”
A Case of Metastatic Choriocarcinoma-Related Paraneoplastic Thyroid Storm
Nidhi Gupta, MD, a second-year internal medicine resident at Baylor Scott and White in Temple, Texas, presented a case she and her co-authors wrote on thyroid storm due to gestational trophoblastic disease (GTD) with metastatic choriocarcinoma — a rare but potentially life-threatening endocrine emergency. A woman with molar pregnancy and metastatic choriocarcinoma presented with thyroid storm (Burch-Wartofsky point scale of 45) a few weeks after the evacuation of GTD.
The patient, a 38-year-old woman, had recently undergone evacuation of a molar pregnancy when she returned weeks later with signs of thyroid storm, scoring 45 on the Burch–Wartofsky Point Scale. Laboratory testing revealed profoundly elevated thyroid hormones (T3 and T4) and suppressed TSH, while her human chorionic gonadotropin (hCG) level exceeded 900,000 mIU/mL. “In a normal nonpregnant woman, it should be less than five,” Gupta explained. “She was in a very severe range, and this was all because of the cancer—metastatic choriocarcinoma that had already spread to her lungs and brain.”
Gupta’s team moved quickly to stabilize the patient with propylthiouracil, esmolol infusion, and intravenous fluids, later transitioning to methimazole for safer long-term control. Only after the thyroid storm was under control could the oncology team beginchemotherapy for the choriocarcinoma.
“It was an intensive chemotherapy regimen started in the ICU itself after we did the stabilization and anti-thyroid medications were given,” Gupta says. “Combining these two diseases—the cancer and the thyroid storm—and timing the medications was intricate,” Gupta said. “It required experts from endocrinology, oncology, OB/GYN, intensive care, and even international consultants to coordinate care.” They went out of the way to reach out to more international experts so that the things are managed appropriately and in a timely manner.”
Despite the aggressive chemotherapy regimen, the cancer showed signs of low-grade resistance, prompting a hysterectomy 113 days after the initial presentation. The surgery was successful, and the patient received three additional cycles of chemotherapy. Six months later, the outcome was nothing short of extraordinary:
- Thyroid function normalized,
- hCG levels returned to the normal nonpregnant range, and
- All metastatic lesions resolved.
“She is now asymptomatic with no evidence of recurrence,” Gupta reported. “Her functional status is absolutely normal, and she continues regular follow-up with OB/GYN, oncology, and endocrinology.”
“It’s like solving a puzzle. “You need a high index of suspicion— because the pregnant patient comes in at six weeks of gestation, and then you end up managing a thyroid storm, giving her chemotherapy and removing her uterus. It’s a lot. You learn from every expert around you, and that’s how you grow as a physician.”- Nidhi Gupta, MD, internal medicine resident at Baylor Scott and White in Temple, Texas.
The case was not without its bittersweet elements. The patient lost her uterus, ending future fertility, but she survived a life-threatening condition and continues to care for her existing child. “We could save her life, and she is doing well,” Gupta reflected. “This was truly a team effort, overcoming financial and insurance barriers and bringing together specialists from around the world.”
For Gupta, the experience reaffirmed her passion for endocrinology and the intellectual challenge of complex endocrine emergencies. “It’s like solving a puzzle,” she said. “You need a high index of suspicion— because the pregnant patient comes in at six weeks of gestation, and then you end up managing a thyroid storm, giving her chemotherapy and removing her uterus. It’s a lot. You learn from every expert around you, and that’s how you grow as a physician.”
Two Cases of Improved Bone Mineral Density
Lara McHan, MD, previously of the University of Rochester Strong Memorial Hospital in Rochester, N.Y. now a combined Med-Peds Endocrine fellow at the University of Washington/Seattle Children’s Hospital, presented two cases of patients with fibroblast growth factor-23 (FGF23)-mediated hypophosphatemia who had low bone mineral density (BMD) at diagnosis and remarkable improvements in BMD with treatment. The first patient is a 43-year-old man who suffered years of progressive pain and multiple fractures. He was diagnosed with tumor-induced osteomalacia (TIO), a rare cause of FGF23-mediated hypophosphatemia, after imaging identified a subcutaneous left flank mass.
McHan says that one of the main challenges for this case is how rare a TIO diagnosis is. She says there are only about 1,000 cases documented in the literature, and it’s not something that is taught in medical school. “If people aren’t familiar with TIO, they may not connect the dots and think of that diagnosis,” McHan says. “There was a retrospective review of cases that showed that the average time from symptom onset to diagnosis of TIO was about three years. For patients, that’s three years of medical uncertainty, poor quality of life, seeing several different specialists, being misdiagnosed, and often receiving unnecessary or ineffective treatment.”
This patient took longer to finally get a diagnosis of TIO. He had seen multiple specialists, had joint injections to manage the pain. The specialists weren’t able to figure out what was going on, and the patient had multiple fractures and surgery on both sides of his hip. “If we’re able to diagnose this earlier, we can potentially prevent some of these irreversible skeletal complications of TIO,” McHan says.
“If people aren’t familiar with [tumor-induced osteomalacia], they may not connect the dots and think of that diagnosis. There was a retrospective review of cases that showed that the average time of diagnosis was about three years. For patients, that’s three years of this medical uncertainty, poor quality of life, seeing several different specialists, being misdiagnosed, and often receiving unnecessary or ineffective treatment.” – Lara McHan, MD, University of Rochester Strong Memorial Hospital, Rochester, N.Y.
Once the TIO diagnosis was made, surgeons excised the tumor, which resulted in rapid symptom improvement. McHan and her co-author and mentor Marilyn Augustine, MD, also of the University of Rochester, write that the patient experienced a 96% increase in lumbar spine (LS) BMD after surgery.
The funny thing is that the patient had noticed the mass in his left flank years ago, but he just thought it was a little nodule. “It wasn’t painful, never bothered him, and he didn’t think anything of it. But then to realize that was the cause of these symptoms I think was interesting. Now he’s doing really well, and his quality of life is much better after treatment. By removing the tumor, he was essentially cured of TIO and now just has routine follow-up.”
The second patient is a 48-year-old nonverbal man with autism and intellectual disability who had months of progressively declining mobility, presumed pain, and multiple fractures. McHan is trained in adult and pediatric medicine, so she has experience with patients who can’t always voice what’s wrong with them. She explains that when you have a patient who has intellectual disability and is non-verbal, you really can’t rely on them to be your historian. “The history and physical exam are such important components when thinking through a differential diagnosis and work-up and eventually getting to what the problem is,” she says. “It’s really necessary to rely on caregivers in these cases to recognize new symptoms.”
This patient lives in a group home and had been really active, but the staff started to notice he was sitting around more than usual and seemed to be in pain. He was admitted to the hospital and had to have surgery, but McHan says that expedited his workup when endocrine was consulted for his fracture history. He was found to have low phosphorous – something that endocrinologists are trained to test for. “We know that phosphorus is important in bone health and routine laboratory testing doesn’t include phosphorus,” McHan says. “If you have a patient coming in to a general provider for evaluation of nonspecific symptoms such as fatigue, weakness, and pain, they are probably not thinking to check a phosphorus. But when they are evaluated by an endocrinologist, phosphorous is part of the work-up for low BMD.”
The patient was diagnosed with FGF23-mediated hypophosphatemia. McHan and Augustine write that the patient has had multiple scans over several years, but no FGF23-secreting tumor has been identified.
He has been maintained on medical treatment with phosphorous and calcitriol with improvement in functioning and 48% increase in LS BMD. “He got better pretty quickly with medical management,” McHan says. “But I do wonder how long before that insult of not being able to ambulate — was he maybe having pain, weakness, fatigue that just went unrecognized because he couldn’t voice those concerns? So it is a challenge in these patients, and I am grateful that he had good caregivers who were able to notice that there was a change in his activity and demeanor.”
“This is the third time we have hosted Clinical Pearls from JCEM-CR and the number of attendees is increasing each year,” Young says. “The concise and intriguing case presentations are outstanding and the astute clinical pearls from our content experts are a real treat. We are already planning for the fourth edition at ENDO2026 in Chicago in June, 2026!”
Bagley is the senior editor of Endocrine News. He wrote about the relationship between type 2 diabetes and liver disease, and how endocrinologists can take the lead in treatment in the August issue.
Loading ...