Utility of Intraoperative Ultrasound in Identifying Pituitary Adenoma Hidden Behind a Cystic Lesion in Cushing’s Disease

Posted on May 29, 2025 by MaryO

Highlights

  • •
    Intraoperative ultrasound enhances tumor localization during endoscopic pituitary surgery for MRI-negative Cushing’s disease.
  • •
    Our findings support intraoperative US as a valuable adjunct in cases where preoperative imaging fails to reveal a lesion.
  • •
    Further studies are expected to validate the efficacy of intraoperative ultrasound as a useful tool for MRI-negative Cushing’s disease.

Abstract

Cushing’s disease with inconclusive MRI findings presents a significant diagnostic and surgical challenge due to the difficulty in localizing the causative pituitary adenoma. This case report highlights the use of intraoperative ultrasound as an adjunct for tumor detection and successful resection in a Cushing disease patient with hidden adenoma. A 55-year-old female with a history of hypertension, diabetes, and a recent cerebral infarction presented with clinical and biochemical features of Cushing’s disease. Brain MRI revealed a 10 mm non-enhancing cystic lesion in the sella, making it difficult to confirm the underlying pathology. Inferior petrosal sinus sampling suggested a right-sided lesion, leading to an endoscopic endonasal transsphenoidal surgery. Intraoperatively, ultrasound was employed to assess the sellar region, initially identifying a cystic structure consistent with a Rathke’s cleft cyst. Following fluid drainage, ultrasound revealed an iso-echoic lesion with a distinct margin, which was subsequently resected and confirmed as a pituitary adenoma on histopathological examination.
The patient experienced postoperative biochemical remission, with normalization of ACTH levels and resolution of hypertension and diabetes. This case demonstrates that intraoperative ultrasound can be a valuable tool for tumor localization in suspicious MRI-negative Cushing’s disease. By aiding in the identification of adenomas obscured by cystic lesions or surrounding structures, intraoperative ultrasound may improve surgical outcomes. Further studies are warranted to validate its efficacy in routine clinical practice.

Introduction

Cushing’s disease is caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma, leading to hypercortisolism and significant metabolic disturbances. Magnetic resonance imaging (MRI) is the primary imaging modality for detecting pituitary adenomas; however, in approximately 30–40 % of cases, no visible adenoma is detected, a condition known as MRI-negative Cushing’s disease [1,2]. The absence of a discernible lesion on MRI poses a diagnostic and therapeutic challenge, often necessitating additional testing such as bilateral inferior petrosal sinus sampling (IPSS) to confirm pituitary-dependent Cushing’s syndrome [3]. Given the limitations of imaging, treatment strategies for MRI-negative Cushing’s disease require a multimodal approach.
The first-line treatment for Cushing’s disease, regardless of MRI findings, is transsphenoidal surgery. However, MRI-negative cases are associated with lower remission rates due to the difficulty in localizing the microadenoma intraoperatively [4]. When surgery fails or is not feasible, alternative treatments such as repeat surgery, radiotherapy, bilateral adrenalectomy, or medical therapy are considered [5]. Despite these therapeutic options, long-term disease control remains challenging, highlighting the need for improved diagnostic tools and targeted treatment strategies.
The authors aim to report the use of intraoperative ultrasound in a Cushing disease patient with hidden adenoma, demonstrating its possibility to detect tumors that were not visible on MRI and facilitate successful tumor resection, ultimately leading to remission.

Section snippets

Case report

A 55-year-old female patient was referred from the endocrinology department for evaluation of Cushing’s disease. She had been on medication for hypertension and diabetes for the past seven years. Two months prior, she suffered an acute cerebral infarction, resulting in left-sided hemiparesis.
The endocrinology department diagnosed her with Cushing’s disease based on a dexamethasone suppression test. Brain MRI revealed a 10 mm non-enhancing cystic mass in the right side of the sella. (Fig. 1) Due…

Diagnostic approach for MRI-negative cushing’s disease

Diagnosing MRI-negative Cushing’s disease is particularly challenging due to the absence of a visible pituitary adenoma on standard imaging. A stepwise diagnostic approach is necessary to confirm the presence of ACTH-dependent hypercortisolism, differentiate between pituitary and ectopic sources, and localize the tumor. The initial step involves biochemical confirmation of endogenous hypercortisolism through tests such as the 24-hour urinary free cortisol, and the low-dose dexamethasone…

Conclusion

MRI-negative Cushing’s disease presents significant challenges not only for neurosurgeons but also for endocrinologists. The conventional hypophysectomy is invasive and has a high risk of causing other complications. The present case report showed that intraoperative ultrasound can be used effectively in a Cushing disease patient with hidden adenoma. We hope to derive more definitive conclusions through future case studies.

CRediT authorship contribution statement

Min Ho Lee: Writing – review & editing, Writing – original draft, Data curation, Conceptualization. Tae-Kyu Lee: Writing – review & editing, Conceptualization.

Ethics approval

The study was approved by the appropriate institutional research ethics committee and certify that the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
Informed consent was obtained from the patient included in this study.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

References (28)

More at https://www.sciencedirect.com/science/article/abs/pii/S0967586825002516

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Ivory Tower: New PET Scan Molecule Offers Breakthrough in Detecting Cushing’s Syndrome

Posted on April 7, 2025 by MaryO

Asignificant advancement in medical imaging has been achieved by experts at the Postgraduate Institute of Medical Education and Research. Researchers from endocrinology and nuclear medicine departments have introduced a new PET scan molecule that enhances the detection of adenoma/small tumour causing Cushing’s syndrome. This development promises to improve surgical interventions and patient outcomes.

A collaborative effort between Dr Rama Walia from the endocrinology department and Dr Jaya Shukla from nuclear medicine department has resulted in the development of GA-68 MDEsMO, a specialised PET scan molecule. This innovative compound is designed to pinpoint tumors in the pituitary gland, which are often responsible for the excessive cortisol production characteristic of Cushing’s syndrome.

By providing a more precise visualisation of these tumours, the new technique enables neurosurgeons to operate with greater accuracy, preserving the normal functions of the pituitary gland and enhancing patients’ quality of life.

Recognising its potential, this pioneering technology was honoured at the institution’s recent Research Day.

Affects entire body

Cushing’s syndrome is a complex endocrine disorder that occurs due to an overproduction of cortisol, a hormone that influences multiple physiological processes. When cortisol levels surge beyond normal, it disrupts the body’s balance, leading to widespread health complications. The primary cause of this condition is a minuscule tumor within the pituitary gland, making diagnosis particularly challenging.

Currently, only 60 to 70 per cent of patients receive an accurate diagnosis due to the minuscule size of these tumors — often measuring less than a millimeter. The introduction of GA-68 MDEsMO is expected to bridge this diagnostic gap by facilitating early detection, thus enabling timely surgical intervention.

Hormonal disruptions

The pituitary gland, often referred to as the “master gland”, plays a crucial role in regulating hormone production. However, when affected by a tumor, it triggers an excessive release of hormones, leading to systemic damage.

Typical symptoms include unexplained weight gain, obesity and noticeable changes in skin texture. Many patients develop distinctive pink or purplish stretch marks on the abdomen, thighs and arms. Women may experience excessive hair growth, while men could suffer from reduced fertility and erectile dysfunction. Additionally, skin thinning, severe acne and heightened susceptibility to bruising are common indicators of the disease.

Understanding cortisol

Cortisol, a steroid hormone, is essential for stress regulation and overall metabolic balance. Produced by the adrenal glands, it influences numerous bodily functions through interactions with cortisol receptors present in most cells. The secretion of cortisol is managed by a complex system involving the hypothalamus, pituitary gland, and adrenal glands. Given its widespread presence, cortisol plays a vital role in multiple physiological processes, including immune response, metabolism, and blood pressure regulation.

However, any disruption in cortisol levels—whether an excess or deficiency—can lead to significant health challenges. This underscores the importance of precise diagnosis and timely treatment for disorders like Cushing’s syndrome. The introduction of GA-68 MDEsMO marks a crucial step in advancing medical science’s ability to manage and treat this condition effectively. —

https://www.tribuneindia.com/news/punjab/ivory-tower-new-pet-scan-molecule-offers-breakthrough-in-detecting-cushings-syndrome/

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From Weight Gain To Diabetes

Posted on March 10, 2025 by MaryO
Cushing’s syndrome happens when the body has too much cortisol, the stress hormone. It can cause weight gain, high blood pressure, and diabetes. So how to keep your health in check and what are the treatment options available? In an exclusive interview with Times Now, an Endocrinologist explains its symptoms, causes, and treatments.
We often blame stress for everything—from sleepless nights to stubborn weight gain. But did you know your body’s stress hormone, cortisol, could be at the root of more serious health issues like high blood pressure and diabetes? Yes, you read that right! But how? We got in touch with Dr Pranav A Ghody, Endocrinologist at Wockhardt Hospital, Mumbai Central, who explains how excessive cortisol levels can lead to a condition known as Cushing’s Syndrome.
What Exactly is Cortisol, and Why is it Important?
Hormones are the body’s chemical messengers, travelling through the bloodstream to regulate essential functions. Among them, cortisol, produced by the adrenal glands (tiny glands sitting above the kidneys), plays a crucial role in controlling blood pressure, blood sugar, energy metabolism, and inflammation. The pituitary gland, located at the base of the brain, regulates cortisol through another hormone called Adrenocorticotropic Hormone (ACTH).
Often referred to as the “stress hormone,” cortisol spikes when we’re under stress. However, when levels remain high for too long, it can lead to Cushing’s Syndrome, a disorder first identified in 1912 by Dr Harvey Cushing.

What Causes Cushing’s Syndrome?

Dr Ghody explains that Cushing’s Syndrome occurs when the body is exposed to excessive cortisol, which can happen in two ways:

1. Exogenous (External) Cushing’s Syndrome
This is the most common form and results from prolonged use of steroid medications (such as prednisone) to treat conditions like asthma, rheumatoid arthritis, and lupus, or to prevent transplant rejection. Since steroids mimic cortisol, long-term use can disrupt the body’s hormone balance.
2. Endogenous (Internal) Cushing’s Syndrome
This occurs when the body produces too much cortisol due to a tumour in the pituitary gland, adrenal glands, or other organs (lungs, pancreas, thymus). While rare—affecting about 10 to 15 people per million annually—it’s more common in women between 20 and 50 years old. When caused by a pituitary tumour, it’s specifically called Cushing’s Disease.

Symptoms: How To Recognize Signs Of Cushing’s Syndrome

Excess cortisol affects multiple organs, leading to a variety of symptoms. This includes:

– Weight gain around the belly (central obesity)
– Rounded, puffy face (moon face)
– Excess facial and body hair (hirsutism)
– Fat accumulation on the upper back (buffalo hump)
– Thin arms and legs
– Dark red-purple stretch marks on the chest and abdomen
– Extreme fatigue and muscle weakness
– Depression or anxiety
– Easily bruising with minimal trauma
– Irregular menstrual cycles in women
– Reduced fertility or low sex drive
– Difficulty sleeping
High blood pressure and newly diagnosed or worsening diabetes are also common red flags.

Why is Cushing’s Syndrome Often Misdiagnosed?

Dr Ghody explains that while severe cases of Cushing’s Syndrome are easier to identify, milder forms can often be missed or mistaken for conditions like obesity, diabetes, or polycystic ovary syndrome (PCOS).

Diagnosing Cushing’s Syndrome involves:
1. Measuring cortisol levels in the blood, urine, or saliva.
2. Identifying the source through ACTH hormone testing, MRI/CT scans, and advanced techniques like Inferior Petrosal Sinus Sampling (IPSS) or nuclear medicine scans
Treatment Options: How is Cushing’s Syndrome Managed?
Once diagnosed, the treatment depends on the cause:
– If due to steroid medication, the dosage is gradually reduced under medical supervision.
– If caused by a tumour, surgery is the primary treatment. Some patients, especially those with pituitary tumours, may require repeat surgery, gamma knife radiosurgery, or medications to control cortisol levels.

Can You Prevent Cushing’s Syndrome?

While complete prevention isn’t always possible, Dr Ghody shares some key strategies to reduce risk:

– Use steroids cautiously – If prescribed, take the lowest effective dose for the shortest time. Never stop abruptly without consulting a doctor.
– Genetic screening for people at risk – If you have a family history of pituitary or adrenal tumours, regular monitoring can help with early detection.
– Maintain a healthy lifestyle – A diet rich in fresh vegetables, and fruits, low sodium intake, adequate calcium, and vitamin D can help manage the metabolic effects of excess cortisol.
– Avoid alcohol and tobacco – These can further disrupt hormone balance and overall health.
“Cushing’s Syndrome can be life-threatening if left untreated, but early diagnosis and proper management can significantly improve quality of life. So if you experience unexplained weight gain, blood pressure spikes, or other symptoms, consult an endocrinologist to manage hormonal imbalances,” he said.

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Personalized Noninvasive Diagnostic Algorithms Based on Urinary Free Cortisol in ACTH-dependant Cushing’s Syndrome

Posted on November 9, 2024 by MaryO

Julie Lavoillotte, Kamel Mohammedi, Sylvie Salenave, Raluca Maria Furnica, Dominique Maiter, Philippe Chanson, Jacques Young, Antoine Tabarin
The Journal of Clinical Endocrinology & Metabolism, Volume 109, Issue 11, November 2024, Pages 2882–2891
https://doi.org/10.1210/clinem/dgae258

Abstract

Context

Current guidelines for distinguishing Cushing’s disease (CD) from ectopic ACTH secretion (EAS) are questionable, as they use pituitary magnetic resonance imaging (MRI) as first-line investigation for all patients. CRH testing is no longer available, and they suggest performing inferior petrosal sinus sampling (BIPPS), an invasive and rarely available investigation, in many patients.

Objective

To establish noninvasive personalized diagnostic strategies based on the probability of EAS estimated from simple baseline parameters.

Design

Retrospective study.

Setting

University hospitals.

Patients

Two hundred forty-seven CD and 36 EAS patients evaluated between 2001 and 2023 in 2 French hospitals. A single-center cohort of 105 Belgian patients served as external validation.

Results

Twenty-four-hour urinary free cortisol (UFC) had the highest area under the receiver operating characteristic curve for discrimination of CD from EAS (.96 [95% confidence interval (CI), .92–.99] in the primary study and .99 [95% CI, .98–1.00] in the validation cohort). The addition of clinical, imaging, and biochemical parameters did not improve EAS prediction over UFC alone, with only BIPPS showing a modest improvement (C-statistic index .99 [95% CI, .97–1.00]). Three groups were defined based on baseline UFC: < 3 (group 1), 3–10 (group 2), and > 10 × the upper limit of normal (group 3), and they were associated with 0%, 6.1%, and 66.7% prevalence of EAS, respectively. Diagnostic approaches performed in our cohort support the use of pituitary MRI alone in group 1, MRI first followed by neck-to-pelvis computed tomography scan (npCT) when negative in group 2, and npCT first followed by pituitary MRI when negative in group 3. When not combined with the CRH test, the desmopressin test has limited diagnostic value.

Conclusion

UFC accurately predicts EAS and can serve to define personalized and noninvasive diagnostic algorithms.

Read the article here: https://academic.oup.com/jcem/article/109/11/2882/7645065

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Insights on Diagnosing and Managing Cushing’s Syndrome

Posted on August 18, 2024 by MaryO

Cushing’s syndrome, or endogenous hypercortisolemia, is a rare condition that both general practice clinicians and endocrinologists should be prepared to diagnose and treat. Including both the pituitary and adrenal forms of the disease, the Endocrine Society estimates that the disorder affects 10 to 15 people per million every year in the United States. It is more common in women and occurs most often in people between the ages of 20 and 50.

Even though Cushing’s remains a rare disease, cortisol recently made waves at the American Diabetes Association 84th Scientific Session. A highlight of the meeting was the initial presentation of data from the CATALYST trial, which assessed the prevalence of hypercortisolism in patients with difficult-to-control type 2 diabetes (A1c 7.5+).

CATALYST is a prospective, Phase 4 study with two parts. In the prevalence phase, 24% of 1,055 enrolled patients had hypercortisolism, defined as an overnight dexamethasone suppression test (ODST) value greater than 1.8 µg/dL and dexamethasone levels greater than 140 µg/dL. Results of CATALYST’s randomized treatment phase are expected in late 2024.

Elena Christofides, MD, FACE, founder of Endocrinology Associates, Inc., in Columbus, OH, believes the CATALYST results will be a wake-up call for both physicians and patients seeking to advocate for their own health. “This means that nearly 1 in 4 patients with type 2 diabetes have some other underlying hormonal/endocrine dysfunction as the reason for their diabetes, or significant contribution to their diabetes, and they should all be screened,” she said. “All providers need to get comfortable with diagnosing and treating hypercortisolemia, and you need to do it quickly because patients are going to pay attention as well.”

In Dr. Christofides’ experience, patients who suspect they have a hormonal issue may start with their primary care provider or they may self-refer to an endocrinologist. “A lot of Cushing’s patients are getting diagnosed and treated in primary care, which is completely appropriate. But I’ve also met endocrinologists who are uncomfortable diagnosing and managing Cushing’s because it is so rare,” she said. “The important thing is that the physician is comfortable with Cushing’s or is willing to put in the work get comfortable with it.”

According to Dr. Christofides, the widespread popular belief that “adrenal fatigue” is causing millions of Americans to feel sick, tired, and debilitated may be creating barriers to care for people who may actually have Cushing’s. “As physicians, we know that adrenal fatigue doesn’t exist, but we should still be receptive to seeing patients who raise that as a concern,” said Dr. Christofides. “We need to acknowledsalige their lived experience as being very real and it can be any number of diseases causing very real symptoms. If we don’t see these patients, real cases of hypercortisolemia could be left undiagnosed and untreated.”

Dr. Christofides, who also serves as a MedCentral Editor-at-Large, said she reminds colleagues that overnight dexamethasone suppression test (ODST) should always be the first test when you suspect Cushing’s. “While technically a screening test, the ODST can almost be considered diagnostic, depending on how abnormal the result is,” she noted. “But I always recommend that you do the ODST, the ACTH, a.m. cortisol, and the DHEAS levels at the same time because it allows you to differentiate more quickly between pituitary and adrenal problems.”

Dr. Christofides does see a place for 24-hour urine collection and salivary cortisol testing at times when diagnosing and monitoring patients with Cushing’s. “The 24-hour urine is only positive in ACTH-driven Cushing’s, so an abnormal result can help you identify the source, but too many physicians erroneously believe you can’t have Cushing’s if the 24-hour urine is normal,” she explained. “Surgeons tend to want this test before they operate and it’s a good benchmark for resolution of pituitary disease.” She reserves salivary cortisol testing for cases when the patient’s ODST is negative, but she suspects Cushing’s may be either nascent or cyclical.

Surgical resection has long been considered first-line treatment in both the pituitary and adrenal forms of Cushing’s. For example, data shared from Massachusetts General Hospital showed that nearly 90% of patients with microadenomas did not relapse within a 30-year period. A recent study found an overall recurrence rate of about 25% within a 10-year period. When reoperation is necessary, remission is achieved in up to 80% of patients.

As new medications for Cushing’s syndrome have become available, Dr. Christofides said she favors medical intervention prior to surgery. “The best part about medical therapy is you can easily stop it if you’re wrong,” she noted. “I would argue that every patient with confirmed Cushing’s deserves nonsurgical medical management prior to a consideration of surgery to improve their comorbidities and surgical risk management, and give time to have a proper informed consent discussion.”

In general, medications to treat Cushing’s disease rely on either cortisol production blockade or receptor blockade, said Dr. Christofides. Medications that directly limit cortisol production include ketoconazole, osilodrostat (Isturisa), mitotane (Lysodren), levoketoconazole (Recorlev), and metyrapone (Metopirone). Mifepristone (Korlym, Mifeprex) is approved for people with Cushing’s who also have type 2 diabetes to block the effects of cortisol. Mifepristone does not lower the amount of cortisol the body makes but limits its effects. Pasireotide (Signifor) lowers the amount of ACTH from the tumor. Cabergoline is sometimes used off-label in the US for the same purpose.

Following surgery, people with Cushing’s need replacement steroids until their adrenal function resumes, when replacement steroids must be tapered. But Dr. Christofides said she believes that all physicians who prescribe steroids should have a clear understanding of when and how to taper patients off steroids.

“Steroid dosing for therapeutic purposes is cumulative in terms of body exposure and the risk of needing to taper. A single 2-week dose of steroids in a year does not require a taper,” she said. “It’s patients who are getting repeated doses of more than 10 mg of prednisone equivalent per day for 2 or more weeks multiple times per year who are at risk of adrenal failure without tapering.”

Physicians often underestimate how long a safe, comfortable taper can take, per Dr. Christofides. “It takes 6 to 9 months for the adrenals to wake up so if you’re using high-dose steroids more frequently, that will cause the patient to need more steroids more frequently,” she explained. “If you’re treating an illness that responds to steroids and you stop them without tapering, the patient’s disease will flare, and then a month from then to 6 weeks from then you’ll be giving them steroids again, engendering a dependence on steroids by doing so.”

When developing a steroid taper plan for postoperative individuals with Cushing’s (and others), Dr. Christofides suggests basing it on the fact that 5 mg of prednisone or its equivalent is the physiologic dose. “Reduce the dose by 5 mg per month until you get to the last 5 mg, and then you’re going to reduce it by 1 mg monthly until done,” she said. “If a patient has difficulty during that last phase, consider a switch to hydrocortisone because a 1 mg reduction of hydrocortisone at a time may be easier to tolerate.”

Prednisone, hydrocortisone, and the other steroids have different half-lives, so you’ll need to plan accordingly, adds Dr. Christofides. “If you do a slower taper using hydrocortisone, the patient might feel worse than with prednisone unless you prescribe it BID.” She suggests thinking of the daily prednisone equivalent of hydrocortisone as 30 mg to allow for divided dosing, rather than the straight 20 mg/day conversion often used.

What happens after a patient’s Cushing’s has been successfully treated? Cushing’s is a chronic disease, even in remission, Dr. Christofides emphasized. “Once you have achieved remission, my general follow-up is to schedule visits every 6 months to a year with scans and labs, always with the instruction if the patient feels symptomatic, they should come in sooner,” she said.

More on Cushing’s diagnosis and therapies.

https://www.medcentral.com/endocrinology/cushings-syndrome-a-clinical-update

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