Three case studies from JCEM Case Reports highlight the work by early-career Hispanic and Latino researchers from around the country. Maria Daniela Hurtado Andrade, MD, PhD, Carlos S. Botero Suarez, MD, and Nicolas Villarraga discuss these highly unusual cases that put their problem-solving skills to the test.

When JCEM Case Reports was launched at the end of 2022, its goal was to “impart valuable insights and clinical nuances that cannot be found in large case series, clinical trials, or practice guidelines,” according to the journal’s editor-in-chief, William F. Young, Jr., MD, a professor of medicine at the Mayo Clinic College of Medicine and Science in Rochester, Minn., who added that many of his best teaching and learning opportunities have been based on the care of single patients with “challenging clinical scenarios.”

Three such challenging clinical scenarios are presented here that also highlight the research of the Endocrine Society’s early-career members from the Hispanic and Latino communities: Maria Daniela Hurtado Andrade, MD, PhD, discusses “A False Pituitary Tumor” from the May 2023 issue; Carlos S. Botero Suarez, MD, talks about the article, “Diabetic Muscle Infarction: An Uncommon Diabetic Complication with a Lack of Standardized Treatment” from the March 2023 issue; and Nicolas Villarraga gives his team’s perspective on “Unique Presentation and Perioperative Management of a Giant Pheochromocytoma” also from the May 2023 issue.

“Each of these case reports highlight important clinical pearls,” Young tells Endocrine News. “For example, Hurtado Andrade and colleagues caution us that when evaluating a patient for a pituitary mass, it is important to recognize the possibility of intracranial hypotension (due to a cerebrospinal fluid leak) in patients who have the constellation of a diffusely enhancing pituitary gland on MRI, postural headaches, and intact pituitary function. Villarraga and colleagues enlighten us on many of the unique challenges in managing large and highly functioning pheochromocytomas. And Botero Suarez and colleagues share a case of diabetic myonecrosis and the clinical intuition and diagnostic tests needed to make this diagnosis and provide guidance on treatment.”

A False Pituitary Tumor

Study coauthor Maria Daniela Hurtado Andrade was still an endocrinology fellow at the Mayo Clinic in Rochester, Minn., when she encountered the case of a 24-year-old male patient who was referred to endocrinology for evaluation of pituitary enlargement without a hypo-enhancing lesion on magnetic resonance imaging (MRI). The mass was discovered during prior evaluation of progressively worsening headaches over five years. Hurtado Andrade reviewed the details of the case with study coauthor Alice Chang (also at the Mayo Clinic), who is an expert in the pituitary gland and was surprised by the absence of hypo-enhancement, given that most pituitary masses take up less gadolinium than a normal pituitary does.

Hurtado Andrade and Chang then got a message from neurosurgeon John L. D. Atkinson (also a study coauthor and also at the Mayo Clinic), who was reviewing the patient’s medical records in preparation for his consultation, saying that he did not believe the patient had a pituitary mass, despite the MRI findings. Instead, Atkinson believed that the patient had a cerebrospinal fluid (CSF) leak that may make the pituitary gland appear enlarged when it is really not. “From the endocrinology perspective,” says Hurtado Andrade, “this is something that we do not see commonly in clinical practice. However, from the neurosurgery perspective, these are not rare.” The Mayo Clinic is a referral center for CSF leaks, so Atkinson is familiar with this condition and an expert at treating it, although it is still relatively rare. But a neurosurgeon might be more aware of the possibility than an endocrinologist, and he knew CSF leak should be considered, explains Hurtado Andrade.

This surprising development that came the day before Hurtado Andrade was to see the patient prompted her to read any related literature. Although there was not all that much, it was enough to educate her on what questions to ask the patient.

What confirmed Atkinson’s suspicion was backing up to the patient’s history and physical examination. “What was very particular in this case was that the patient was having headaches located behind his eyes, that were worse at the end of the day as well as worse with more time spent upright,” Hurtado Andrade says. “He also became progressively debilitated by the headaches over the course of several years and began projectile vomiting.”

The orthostatic headache and projectile vomiting together narrowed the differential considerably and led the team to consider intracranial hypotension. The patient’s history was also remarkable for two spinal surgeries related to a nerve schwannoma — one to resect the schwannoma and fuse the vertebrae, the second to correct what went wrong during the first.

“We see pituitary masses in clinical practice very commonly, especially at the Mayo Clinic because we are a referral center. As such, we see these ‘zebra’ or rare cases that are not classic pituitary masses, but that you need to be aware of. This is not something that non-referral centers are likely to see, but endocrinology providers must be aware because it will change management. These unusual cases allow us to think outside of the box.”

Maria Daniela Hurtado Andrade, MD, PhD, endocrinologist and obesity medicine specialist, Mayo Clinic, Jacksonville, Fla.

“Spinal instrumentation is among the most frequent causes of CSF leak,” says Hurtado Andrade, “so that clue combined with his classic presentation pointed to CSF leak. Generally, we use imaging to confirm something that we were already thinking about based on the history and physical exam.” In this case, however, that confirmation may not have been so straightforward to an endocrinologist, but Atkinson was able to compare images from over the years and saw that the low pressure inside the skull had existed for some time. Hurtado Andrade says that learning how to spot these findings was invaluable, even though she has not seen another case of CSF leak with apparent pituitary enlargement to date.

For this patient, the story has a happy ending: He underwent testing to localize the CSF leak, which was then fixed. His headaches cleared up within days.

As a fellow, Hurtado Andrade presented cases on a quarterly basis to her co-fellows and feels this one was an important one to understand. “We see pituitary masses in clinical practice very commonly, especially at the Mayo Clinic because we are a referral center. As such, we see these ‘zebra’ or rare cases that are not classic pituitary masses, but that you need to be aware of. This is not something that non-referral centers are likely to see, but endocrinology providers must be aware because it will change management. These unusual cases allow us to think outside of the box.”

JCEM Case Reports now fills that role for Hurtado Andrade, now with an MD and PhD to her name and practicing at the Mayo Clinic in Jacksonville, Fla. “[William F. Young, Jr., M.D] is passionate about education. In his role as the editor-in-chief, he is committed to sharing educational clinical pearls from these rare cases that you may not see on a daily basis, but at some point in your career, they may come to you and you need to be aware of,” she says. “This journal is a very good resource, and I highly recommend it.”

Diabetic Muscle Infarction: An Uncommon Diabetic Complication

“This case was written to contribute to the medical literature and share information about a rare complication of diabetes mellitus known as diabetic myonecrosis (DMI),” explains lead author Carlos S. Botero Suarez, MD, a fellow at the University of Central Florida HCA Healthcare GME, Greater Orlando, in Kissimmee, Fla. “This case report aimed to increase awareness among medical professionals about the condition, its presentation, diagnostic challenges, and potential management approaches.”

DMI was first described in 1965, and only 126 cases had been reported by 2015. To date, management guidelines have yet to be standardized, and DMI had not so far been clearly described in African Americans, despite that diabetes mellitus disproportionally affects this population.

The patient in Botero Suarez and team’s case was a 42-year-old African American man who presented at the Orlando VA Medical Center, where he was admitted for the evaluation of new-onset right lower extremity swelling and associated intense pain, progressively worsening over the course of two weeks. The patient’s history was significant for hypertension, poorly controlled type 2 diabetes mellitus complicated by end-stage-renal-disease, retinopathy, and progressive bilateral peripheral neuropathy. Although he had been on insulin therapy for more than 10 years, adherence to an appropriate regimen was a challenge. He had been on semaglutide and aspart insulin twice daily prior to admission and had recently stopped taking glargine because of hypoglycemic episodes.

His laboratory results and presentation raised suspicion for deep vein thrombosis and cellulitis, which were later ruled out with further testing. Magnetic resonance imaging (MRI) revealed right rectus femoris muscle and adductor muscle edema, subcutaneous edema, and fascial fluid, all findings consistent with DMI. Management comprised low-dose aspirin, acetaminophen, and tighter glycemic control with a continuous glucose monitor.

“JCEM Case Reports has been a great medium for doctors and trainees to submit their interesting cases and share them with the rest of the medical community. Its open-access nature, as well as its engaged peer-review process and streamlined submission process, makes it a highly recommended journal for clinicians.”

Carlos S. Botero Suarez, MD, fellow, University of Central Florida HCA Healthcare GME, Greater Orlando, Kissimmee, Fla.

Says Botero Suarez: “He was later seen in follow-up visits at the endocrinology outpatient clinic, during which a recurrent episode of DMI was noted, this time on the left lower extremity. The episode persisted for several months before subsiding with NSAIDs and rest.” This recurrence came as a surprise, given the patient’s improved glycemic control. He later died from kidney failure.

The pathogenesis of DMI is not clear, although it is known to occur slightly more commonly in females (54%) and has a mean age of presentation of 44.6 years. Hypothesized mechanisms do exist, however. “Diabetic microangiopathy could lead to impaired blood flow to muscles, contributing to muscle infarction,” explains Botero Suarez. “Atherosclerosis could also contribute to reduced blood flow and tissue damage. Vasculitis with thrombosis could obstruct blood flow to muscles. Ischemia-reperfusion injury occurs when blood flow is restored after a period of reduced circulation, leading to tissue damage due to oxidative stress and inflammation. These mechanisms could individually or collectively contribute to the development of DMI in individuals with uncontrolled diabetes.”

Thus, this case is important to demonstrate to clinicians that DMI is a potential complication in patients with poorly controlled diabetes mellitus. Further, Botero Suarez and team suggest some potential management approaches: “It’s important to differentiate DMI from other conditions that present similarly, such as cellulitis or thrombosis. MRI of the lower extremities is the modality of choice in diagnosis. Biopsies should be avoided, but they are generally reserved to rule out other etiologies such as infectious causes. Conservative management with pain control, tight glycemic control, and potentially low-dose aspirin could be considered. Recurrences can occur, so ongoing monitoring is important.”

This case clearly fills a void in the existing literature, which is precisely what JCEM Case Reports aims for. “JCEM Case Reports has been a great medium for doctors and trainees to submit their interesting cases and share them with the rest of the medical community,” agrees Botero Suarez. “Its open-access nature, as well as its engaged peer-review process and streamlined submission process, makes it a highly recommended journal for clinicians.”

Unique Presentation and Perioperative Management of a Giant Pheochromocytoma

Nicolas Villarraga, from the University of Minnesota School of Medicine in Minneapolis, and Shalamar Sibley, MD, MPH, associate professor of medicine at the University of Minnesota, staff physician at the Minneapolis VA Health Care System, and their team presented the case of a 62-year-old female with a giant 15.9-cm cystic pheochromocytoma and symptoms including nausea and vomiting that necessitated preoperative medication delivery via a nasojejunal (NJ) tube. This patient also required high-dose alpha-blockade; she was treated preoperatively with an oral phenoxybenzamine solution at a dose quadruple the typical dose.

“This is an interesting case,” explains Villarraga. “The diagnosis of pheochromocytoma is rare, and having a pheochromocytoma of that size is even more rare. Furthermore, the treatment strategy of preparing a larger dose of phenoxybenzamine than is typically given and delivering it as an oral solution via NJ tube is unique. To our knowledge this is the first report of such. Our goal was to highlight the rarity of a pheochromocytoma of that size and highlight the alternative approach for preoperative blood pressure control we utilized given the clinical circumstances.”

Indeed, the rarity of giant (>7–10 cm) pheochromocytoma in addition to the broad spectrum of presentations make this an ideal case to advance preoperative management guidelines. Prior to admission, the patient had lost 80 pounds. Says Villarraga: “The significant weight loss our patient had experienced was probably due to a combination of factors, including mass-related compression with decreased appetite, and the potential for changes in metabolism and significant dehydration. She was experiencing significant nausea and vomiting.”

“The diagnosis of pheochromocytoma is rare, and having a pheochromocytoma of that size is even more rare. Furthermore, the treatment strategy of preparing a larger dose of phenoxybenzamine than is typically given and delivering it as an oral solution via NJ tube is unique. To our knowledge this is the first report of such.”

Nicolas Villarraga, medical student, University of Minnesota School of Medicine, Minneapolis, Minn.

A radical left nephrectomy and adrenalectomy were done. Post-surgery, the endocrine team did not see her again for some time. “This patient’s overall health was poor,” Villarraga says. “She needed a prolonged period of outpatient recovery. She had a stay in the interim at a different facility for a period of time.”

More recently, the patient has established outpatient follow-up endocrine care. She had repeat plasma metanephrine screening, which returned within normal range. “It took time for her to recover, but over time she dramatically improved and was glad to feel so much better,” Villarraga says. “In retrospect, she noted she had not been aware of how ill she had become preoperatively. She is grateful for her recovery.”

Some key takeaways from this case include that medical management of giant pheochromocytomas may need to be aggressive. “Teamwork is key,” Villarraga says. “The level of alpha-blockade needed may exceed the typically reported dosage. In our case, 240 mg per day of phenoxybenzamine was required. In addition, an alternative delivery method of phenoxybenzamine may be required for the period of preoperative preparation if the patient is not reliably able to have good oral intake. We collaborated with our pharmacists to utilize a solution administered via NJ tube.”

Another takeaway is that masses appearing to arise from the upper pole of the kidney should be considered for pheochromocytoma screening. This patient’s tumor was originally thought to be of renal origin. Nephrectomy was necessary because a safe dissection plane between the tumor and kidney without the risk of rupturing the tumor could not be established.

Combined, this report contributes to an important area of endocrine management, preoperative management of giant pheochromocytomas; JCEM Case Reports provided the platform. “We are glad that JCEM now has a journal dedicated to case reports. This journal is an important new addition and a good resource for the medical community,” says Villarraga.

According to Young, one of the missions of JCEMCR is to provide a peer reviewed venue to share unique cases and the complexities of clinical presentation, diagnosis, and management. “These three case reports are excellent examples of why the Endocrine Society founded this new journal,” he explains, adding “I am especially delighted to see early-career endocrinologists view the journal to as a forum to not only share their interesting cases, but to also learn from others!”

Horvath is a freelance journalist based in Baltimore, Md. In the June issue, she profiled Cherie L. Butts, PhD, who discussed her ENDO 2023 meet the Scientist session, “A research career in government and industry, making sure drugs are safe and meaningful” in “A Call to Action.”