Case Report Shows Rare Adrenal Tumors Associated with Cushing’s Disease

Posted on March 9, 2018 by MaryO

Pituitary tumors that produce too much adrenocorticotropic hormone (ACTH) have been associated with the development of rare tumors on the adrenal glands, called adrenal myelolipomas, for the first time in a case report.

The study, “Case report of a bilateral adrenal myelolipoma associated with Cushing disease,” was published in the journal Medicine.

Myelolipomas, composed of mature fat cells and blood-forming cells, are usually asymptomatic and do not produce hormones. In many cases, these tumors are detected by accident when patients undergo imaging scans for other conditions.

The cause of these tumors is unknown, but due to their benign nature, they do not spread to other parts of the body. However, they can grow up to 34 centimeters (about 13 inches), leading to tissue death and hemorrhage.

Researchers at Soon Chun Hyang University College of Medicine in Seoul, Korea, described the case of a 52-year-old man with myelolipoma possibly caused by an ACTH-secreting pituitary tumor.

During a routine checkup, researchers detected a mass in the patient’s spleen. Further abdominal evaluations identified tissue lesions in both adrenal glands consistent with myelolipoma. Besides the masses, the patient did not show any other Cushing-associated physical characteristics.

However, the patient’s ACTH levels were two times higher than the normal upper limit. Cortisol levels were also increased and unresponsive to low-dose dexamethasone treatment.

No additional lesions were found that could help explain the high ACTH and cortisol levels. But analysis of blood samples collected from the veins draining the pituitary glands revealed the right gland was producing too much ACTH, strongly suggesting Cushing’s disease.

Both the left adrenal gland and pituitary tumor were surgically removed. The samples collected during surgery confirmed the benign nature of the adrenal tumors, and the diagnosis of abnormal, ACTH-positive pituitary gland tissue.

Three days after the surgeries, hormone levels were back to normal. But a follow-up evaluation five months later again showed increased ACTH levels. Cortisol levels, however, were normal.

For the next seven years, the patient was evaluated every six months. During a five-year period, the size of the right adrenal gland was found to have grown. Imaging analysis confirmed the existence of small, new lesions in both pituitary glands.

“This case confers valuable information about the clinical course of adrenal myelolipoma associated with Cushing disease,” the researchers said. It also “supports the notion that ACTH can be associated with the development of bilateral adrenal myelolipomas.”

From https://cushingsdiseasenews.com/2018/03/08/bilateral-adrenal-myelolipoma-associated-with-cushing-disease-case-report/

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High Levels of MMP-9 Enzyme May Predict Tumor Recurrence in Cushing’s Patients

Posted on March 2, 2018 by MaryO

Measuring the levels of a specific enzyme in pituitary tumors producing excess adrenocorticotrophic hormone (ACTH) may help predict the recurrence of Cushing’s disease in patients, a study shows.

The study, “Expression of MMP-9, PTTG, HMGA2, and Ki-67 in ACTH-secreting pituitary tumors and their association with tumor recurrence,” was published in the journal World Neurosurgery.

Cushing’s syndrome is characterized by excess cortisol levels in the blood. In 70 percent of cases, this is caused by pituitary tumors making too much ACTH, a hormone that regulates cortisol production. This condition is called Cushing’s disease.

While transsphenoidal adenomectomy, a surgery to remove a pituitary gland tumor, is the first treatment choice, tumor recurrence rates can be as high as 45 percent.

Only a few studies have investigated the association between biomarkers and the risk of ACTH-secreting pituitary tumors recurring, leaving physicians with limited methods to predict which patients will have a recurrence.

Identifying biomarkers that can effectively predict the potential recurrence of Cushing’s disease would allow clinicians to look for early signs in patients and start appropriate follow-up and therapeutic protocols, avoiding long-term mortality.

Many studies have suggested that matrix metalloproteinase-9 (MMP-9) enzymes, the pituitary tumor transforming gene (PTTG), and high mobility group A 2 proteins (HMGA2) all play vital roles in the development of pituitary tumors.

Metalloproteinases (MMPs) are enzymes that work to degrade the cell’s extracellular matrix, which anchors the cell, thus enabling tumor invasion. PTTG is highly expressed in pituitary tumors, and is a marker of malignancy in many types of tumors. HMGA2 is overexpressed in various tumors, and is also associated with high malignancy.

However, whether levels of MMP-9, PTTG, and HMGA2 are related to ACTH-secreting tumor recurrence has not been investigated.

Researchers set out to determine the expression levels of MMP-9, PTTG, HMGA2, and Ki-67 (a marker of cell growth) in ACTH-secreting pituitary tumors, and evaluate their association with tumor behavior and recurrence.

They conducted a retrospective study that included 55 patients with sporadic Cushing’s disease with long-term remission after a transsphenoidal adenomectomy. Their tumor specimens were collected and examined.

Patients were divided into two groups based on whether or not they had tumor recurrence. There were 28 patients in the non-recurrent group, and 27 in the recurrent.

Results showed there was significantly increased expression of MMP-9 in tumor samples of recurrent patients, compared with the non-recurrent group. Levels of MMP-9 were also strongly associated with a shorter time period to recurrence (recurrence-free interval).

On the other hand, PTTG, HMGA2, and Ki-67 expression was not significantly different between the recurrent group and the non-recurrent group.

“ACTH-secreting pituitary tumors with higher levels of MMP-9 were associated with a higher recurrence rate and a shorter recurrence-free interval. MMP-9 could be a valuable tool for predicting recurrence of ACTH-secreting pituitary tumors,” the researchers concluded.

From https://cushingsdiseasenews.com/2018/03/02/mmp-9-enzyme-levels-may-predict-tumor-recurrence-in-cushings-study/

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Endoscopic and Microscopic Surgery Equally Effective in Cushing’s Disease

Posted on February 12, 2018 by MaryO

Using endoscopic or microscopic techniques to surgically remove the pituitary glands leads to similar remission and recurrence rates in Cushing’s disease patients, a review of 24 studies shows.

The study, titled “Outcome of endoscopic vs microsurgical transsphenoidal resection for Cushing’s disease,” was published in the journal Endocrine Connections.

In endoscopic transsphenoidal surgery, a surgeon uses a tiny camera as a guide, allowing for a panoramic surgical view with increased illumination of anatomic structures. In microsurgical transsphenoidal resection, a surgeon views through a microscope and uses minute instruments or lasers. Both procedures are used in transsphenoidal (TS) surgery to remove pituitary gland tumors, the root cause of Cushing’s disease. In transsphenoidal surgery, a surgeon accesses the pituitary gland through the nose and sinuses.

While endoscopic surgery seems to lead to better patient outcomes, it was unclear before this study if it has any advantages in patients with Cushing’s disease.

To gain more insight into the remission and recurrence rates of both techniques, researchers examined a total of 24 studies that included 1,670 adult patients with Cushing’s syndrome. Of these patients, 702 underwent endoscopic TS, and 968 underwent microsurgical TS.

The study’s authors found that remission rates were similar in both groups. In the endoscopic group, an average of 79.7 percent of patients experienced remission versus 76.9 percent in the microscopic group.

Patients who underwent endoscopic surgery experienced recurrence less often than those who underwent microscopic surgery, with recurrence rates of 11 percent and 15.9 percent, respectively. But researchers pointed out that follow-up times in the studies varied, making comparisons unreliable.

When recurrence rates were calculated by person per year, which takes follow-up time into account, both groups had a recurrence rate of approximately 4 percent per person per year.

Previous studies have shown that complications following either type of surgery occurred at comparable rates. These complications include hypothyroidism (underactivity of the thyroid gland), diabetes insipidus (a condition characterized by increased thirst), CSF leakage (leakage of fluid that normally bathes the brain and spinal cord), visual defects, hypocortisolemia (low cortisol blood levels), and hypogonadism (little or no hormones produced by the sex glands).

“We found that overall remission proportion was the same in CD patients who underwent endoscopic TS compared to patients who underwent microscopic TS. However, patients treated with the endoscopic approach for micro-adenomas were more likely to achieve remission than those treated microsurgically. Patients treated endoscopically were less likely to experience recurrence; however, when follow-up time is taken into account, this advantage disappears,” the researchers concluded.

 

From https://cushingsdiseasenews.com/2018/02/01/cushings-disease-transsphenoidal-surgery-study-finds-endoscopic-microscopic-procedures-equally-effective/

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Temozolomide May Partially Improve Aggressive Pituitary Tumors Causing Cushing’s Disease

Posted on February 10, 2018 by MaryO

The chemotherapy temozolomide partially improved a case of an aggressive pituitary tumor that caused symptoms of Cushing’s disease (CD), according to a new study in Poland. However, after tumor mass and cortisol levels were stabilized for a few months, the patient experienced rapid progression, suggesting that new methods for extending the effects of temozolomide are needed.

The study, “Temozolomide therapy for aggressive pituitary Crooke’s cells corticotropinoma causing Cushing’s Disease: A case report with literature review,” appeared in the journal Endokrynologia Polska.

Aggressive pituitary tumors are usually invasive macroadenomas, or benign tumors larger than 10 mm.

A very rare subset of pituitary adenoma — particularly corticotropinoma, or tumors with excessive secretion of corticotropin (ACTH) — exhibit Crooke’s cells. These tumors are highly invasive, have a high recurrence rate, and are often resistant to treatment.

Information is not widely available about the effectiveness of treating aggressive pituitary tumors, particularly those that cause Cushing’s disease. The management of these tumors usually requires neurosurgery, followed by radiotherapy, and pharmacotherapy. However, the chemotherapy medication temozolomide has been increasingly used as a first-line treatment after initial evidence of its effectiveness in treating glioblastoma, the most common form of brain cancer.

In this study, researchers at the Jagiellonian University, in Poland, discussed the case of a 61-year-old man with ACTH-dependent Cushing’s syndrome caused by Crooke’s cell corticotropinoma.

The patient first presented with symptoms of severe hypercorticoidism — the excessive secretion of steroid hormones from the adrenal cortex — in December 2011. He also showed advanced heart failure, severe headaches, and impaired vision, which had started two or three years before diagnosis. Examinations revealed osteoporosis and a fracture in the Th5 vertebra.

His morning ACTH levels were high. The same was observed for mean cortisol levels even after dexamethasone treatment, which was suggestive of a pituitary tumor secreting ACTH. MRIs showed the existence of a tumor mass, later identified as a macroadenoma with high cell polymorphism, the presence of Crooke’s cells, and ACTH secretion.

The patient was referred for transsphenoidal nonradical neurosurgery, performed through the nose and the sphenoid sinus, and bilateral adrenalectomy, or the surgical removal of the adrenal glands, in 2012-2013. However, he developed fast, postoperative recurrence of hypercorticoidism and tumor regrowth. This led to three additional transsphenoidal neurosurgeries and radiotherapy.

The patient’s clinical status worsened as he developed severe cardiac insufficiency. Doctors began temozolomide treatment in April 2015, which did not result in adverse effects throughout treatment.

The initial standard dose (150–200 mg/m2) was given once daily in the morning for five consecutive days, in a 28-day cycle. The patient also received 600 mg of ketoconazole, an antifungal medication. Ondansetron was administered to prevent nausea and vomiting.

Subsequent examinations revealed clinical and biochemical improvements, including a reduction in ACTH and cortisol levels. In addition, the patient also showed reduced cardiac insufficiency, less frequent and less severe headaches, visual field improvements, and better physical fitness and mood.

However, clinical symptoms worsened after the eighth temozolomide cycle. The tumor size also suddenly increased after the ninth cycle, reaching the inner ear. Temozolomide was then discontinued and ACTH levels increased by 28 percent one month later. The patient also demonstrated deteriorated vision, hearing loss, and strong headaches.

Clinicians then decided to start treatment with the Cushing’s disease therapy Signifor (pasireotide), but a worsening of diabetes was observed, and the patient died in February 2016.

“The most probable reason for death was compression of the brainstem, which had been observed in the last MRI of the pituitary,” the researchers wrote, adding that “due to the very short duration of treatment, any conclusions on the treatment with Signifor cannot be drawn.”

Overall, “the results of the presented case suggest that [temozolomide] treatment monotherapy could have only partial response in aggressive corticotroph adenoma causing Cushing’s disease, followed by sudden progression,” the investigators wrote. This contrasts with mostly responsive cases reported in research literature, they noted.

“Therefore, further research on the factors of responsiveness and on novel methods to extend the duration of the effect of [temozolomide] should be carried out,” they wrote.

From https://cushingsdiseasenews.com/2018/02/08/cushings-disease-case-study-poland-shows-temozolomide-temporarily-effective-treating-aggressive-pituitary-tumor/

Filed under: Cushing's, pituitary, Rare Diseases, Treatments | Tagged: , , , , , , , , | Leave a comment »

Pregnant Women with Hypertension and Hypercortisolism May Have Cushing’s

Posted on December 27, 2017 by MaryO

Pregnant woman with hypertension and significant signs of hypercortisolism (high cortisol levels) may have Cushing’s disease, according to a new case report.

The report, titled “A Case of Cushing’s Syndrome in Pregnancy,” was published in the Iranian Journal of Medical Sciences.

While Cushing’s rarely occurs in women during pregnancy, high cortisol levels can lead to major complications for both the mother and the fetus, such as premature birth and high fetal mortality.

However, it can be difficult to diagnose pathological hypercortisolism in these women as the symptoms might resemble other diseases that commonly occur during pregnancy, such as preeclampsia (high blood pressure during pregnancy) and gestational diabetes.

Unfortunately, there are no effective long-term medical therapies for Cushing’s. The most definitive therapy is the surgical removal of the pituitary or adrenal adenoma, if that is the case of hypercortisolism.

The case report details that a 29-year old women in the 27th week of pregnancy presented to the Ghaem Hospital clinic in Mashhad, Iran, with edema, weakness, and hypertension. Her symptoms also included truncal obesity, moon face (her face had a rounded appearance), purple steria on her upper and lower limbs and abdomen, excessive edema, and wet skin.

At first, she was hospitalized for suspected preeclampsia, but the diagnosis was later excluded.

The patient’s hormonal profile showed high levels of 24-hour urine cortisol. There were also low levels of adrenocorticotropic hormone (ACTH), which results from a negative feedback due to excessive cortisol. However, plasma cortisol is generally elevated during pregnancy, and therefore may not be the best method for diagnosis.

An abdominal ultrasonography revealed a well-defined mass in the right adrenal gland.

While hospitalized, the patient experienced two crises of blood pressure, and while preeclampsia was ruled out, the physicians could find no more plausible explanation than eclampsia (the onset of seizures in a women with preeclampsia).

Since eclampsia was suspected, the physicians terminated the pregnancy at 28th week of gestation using misoprostol. The woman delivered a male infant weighing 1.94 pounds.

Two days after birth, the physicians conducted a computed tomography (CT) scan and again found a mass in the right adrenal gland.

As a result, the patient underwent a laparoscopic right adrenalectomy to remove the mass one week after giving birth. The patient’s blood pressure normalized and cortisol levels declined. Her condition remained stable after surgery.

“Cushing’s syndrome should be considered in hypertensive pregnant patients with remarkable signs of hypercortisolism,” the researchers concluded. “The best results would be achieved through a collaboration between obstetricians, endocrinologists, and surgeons.”

From https://cushingsdiseasenews.com/2017/12/19/pregnant-women-hypertension-hypercortisolism-may-have-cushings-disease/

Filed under: adrenal, Cushing's, symptoms, Treatments | Tagged: , , , , , , , , , , | Leave a comment »

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