Pituitary Gland Resection May Help Manage Presumed Cushing’s Patients

 

The surgical removal of two-thirds of the pituitary gland is associated with high initial remission rates and low operative morbidity in patients with suspected Cushing’s disease, when no tumor is found on the gland during surgical exploration.

Cushing’s disease (CD) is caused by increased levels of glucocoticosteroids, such as adrenocorticotropic hormone (ACTH), circulating in the blood.

In nearly 70 percent of cases this happens as a result of benign tumors on the pituitary gland, which produce excess ACTH. In these patients, the most effective and first-line treatment is surgical removal of the pituitary gland tumor.

During the diagnostic stage, clinicians use several methods to identify and localize the source of excessive ACTH. But these methods can fail, and the presence of a tumor in the pituitary is not always confirmed. If the tumor remains unidentified during surgical exploration, it falls to the surgeon’s discretion about how to manage their patients.

Researchers at the University of Colorado Denver School of Medicine provided an overview of their experience on the management of patients with presumed Cushing’s disease who underwent surgical treatment.

The study, “Negative surgical exploration in patients with Cushing’s disease: benefit of two-thirds gland resection on remission rate and a review of the literature,” was published in the Journal of Neurosurgery.

“The diagnosis and treatment of CD is one of the most challenging entities that pituitary neurosurgeons, endocrinologists, and pathologists face,” the researchers wrote. “The ability to make a correct diagnosis and deliver a high likelihood of remission after surgery relies heavily on the performance of a meticulous workup and rational surgical strategy.”

The team retrospectively analyzed all cases that had been referred to the Department of Neurosurgery of CU School of Medicine between 1989 and 2011 for a potential ACTH-secreting pituitary tumor.

During this period, 161 cases of Cushing’s patients who underwent surgical tumor resection were reported. In 22 patients, the surgeon was unable to detect a tumor.

In these cases the surgical team decided to remove two-thirds of the gland, with resection of the lateral and inferior portions of the pituitary. All 22 patients were treated using a consistent technique performed by a single surgeon.

Posterior tissue analysis confirmed that six of these patients had pituitary ACTH-secreting tumors. In the remaining 16 patients, no tumor was identified. In three patients the team believed that overproduction of ACTH could be due to an overgrowth of ACTH-secreting cells rather than expansion.

The team believes that these findings underscore the difficulty of accurately diagnosing very small pituitary tumors pre- and post-operatively.

The 22 patients were followed for a mean time of 98.9 months, or 8.2 years. No remissions were observed in the six patients who had ACTH-secreting tumors or in 12 of the remaining patients. Blood analysis in follow-up exams confirmed these patients had normal levels of glucocoticosteroids.

Four patients continued to show persistent elevated amounts of ACTH. Additional clinical evaluations revealed that two patients had ACTH-secreting lung tumors, and one patient was suspected of having an ACTH-secreting tumor on a brain region close to the pituitary. There was one case where the clinical team was unable to identify the origin of elevated ACTH.

Only three patients required hormone replacement after the two-thirds gland removal to overcome a newly detected hormone deficit. The approach used by the surgical team was, overall, found to be safe with no severe side effects reported.

“Currently, when the neurosurgeon is faced with the inability to identify a discrete adenoma intraoperatively, there is little uniformity in the literature as to how to proceed,” the team wrote. “We believe this [pituitary resection] approach will be useful to help guide surgeons in the operative treatment of this particularly difficult group of patients.”

From https://cushingsdiseasenews.com/2017/12/14/pituitary-gland-resection-may-help-presumed-cushings-disease-patients/

2 Health Conditions That Can Cause Hyperpigmentation

Addison’s disease: Hyperpigmentation is a classic symptom of Addison’s disease, an endocrine disorder in which the adrenal glands fails to produce steroid hormone. The disease causes darkening of the skin in certain areas.

Cushing’s syndrome: The abnormal amount of cortisol in the human body causes a condition known as the Cushing’s syndrome. And one of the symptoms of the disorder is hyperpigmentation of the skin.

Adapted from http://www.thehealthsite.com/diseases-conditions/health-conditions-that-can-cause-hyperpigmentation/

Patients Undergoing Adrenalectomy Should Receive Steroid Substitutive Therapy

All patients who undergo removal of one adrenal gland due to Cushing’s syndrome (CS) or adrenal incidentaloma (AI, adrenal tumors discovered incidentally) should receive a steroid substitutive therapy, a new study shows.

The study, “Predictability of hypoadrenalism occurrence and duration after adrenalectomy for ACTH‐independent hypercortisolism,” was published in the Journal of Endocrinological Investigation.

CS is a rare disease, but subclinical hypercortisolism, an asymptomatic condition characterized by mild cortisol excess, has a much higher prevalence. In fact, subclinical hypercortisolism, is present in up to 20 percent of patients with AI.

The hypothalamic-pituitary-adrenal axis (HPA axis) is composed of the hypothalamus, which releases corticotropin-releasing hormone (CRH) that acts on the pituitary to release adrenocorticotropic hormone (ACTH), that in turn acts on the adrenal gland to release cortisol.

To avoid excess cortisol production, high cortisol levels tell the hypothalamus and the pituitary to stop producing CRH and ACTH, respectively. Therefore, as CS and AI are characterized by high levels of cortisol, there is suppression of the HPA axis.

As the adrenal gland is responsible for the production of cortisol, patients might need steroid substitutive therapy after surgical removal of AI. Indeed, because of HPA axis suppression, some patients have low cortisol levels after such surgeries – clinically known as post-surgical hypocortisolism (PSH), which can be damaging to the patient.

While some researchers suggest that steroid replacement therapy should be given only to some patients, others recommend it should be given to all who undergo adrenalectomy (surgical removal of the adrenal gland).

Some studies have shown that the severity of hypercortisolism, as well as the degree of HPA axis suppression and treatment with ketoconazole pre-surgery in CS patients, are associated with a longer duration of PSH.

Until now, however, there have been only a few studies to guide in predicting the occurrence and duration of PSH. Therefore, researchers conducted a study to determine whether HPA axis activity, determined by levels of ACTH and cortisol, could predict the occurrence and duration of PSH in patients who undergo an adrenalectomy.

Researchers studied 80 patients who underwent adrenalectomy for either CS or AI. Prior to the surgery, researchers measured levels of ACTH, urinary free cortisol (UFC), and serum cortisol after 1 mg dexamethasone suppression test (1 mg-DST).

After the surgery, all patients were placed on steroid replacement therapy and PSH was determined after two months. For those with PSH, levels of cortisol were determined every six months for at least four years.

Results showed that PSH occurred in 82.4 percent of CS patients and 46 percent of AI patients. PSH lasted for longer than 18 months in 50 percent of CS and 30 percent of AI patients. Furthermore, it lasted longer than 36 months for 35.7 percent of CS patients.

In all patients, PSH was predicted by pre-surgery cortisol levels after the 1 mg-DST, but with less than 70 percent accuracy.

In AI patients, a shorter-than-12-month duration of PSH was not predicted by any HPA parameter, but was significantly predicted by an absence of pre-surgery diagnosis of subclinical hypercortisolism.

So, this study did not find any parameters that could significantly predict with high sensitivity and specificity the development or duration of PSH in all patients undergoing adrenalectomy.

Consequently, the authors concluded that “the PSH occurrence and its duration are hardly predictable before surgery. All patients undergoing unilateral adrenalectomy should receive a steroid substitutive therapy.”

From https://cushingsdiseasenews.com/2017/12/08/therapy-cushings-patients-adrenalectomy/

Doctors Use Microwave Therapy on Cushing’s Patient Too Weak to Have Surgery

Microwave therapy improved the Cushing’s syndrome of a woman whose lungs had almost failed, allowing her to have the adrenal surgery needed to control her disease, a case study showed.

Lung infections had led to her near-respiratory failure.

Cushing’s syndrome stems from the pituitary gland producing excessive amounts of adrenocorticotropic hormone. Too much of the hormone leads to the adrenal glands generating excessive amounts of another hormone, cortisol — and that overproduction results in Cushing’s. The disease’s symptoms include increasing obesity, skin problems, muscle weakness, bone loss, fatigue, cognitive difficulties, and an inability to control emotions.

Doctors often remove patients’ adrenal glands to prevent cortisol production. But in this case, the patient was not in good enough condition to have the surgery. So doctors used microwave technology to reduce her cortisol levels to the point where surgeons could operate.

The case study, published in BMJ Case Reports, was titled “Ectopic ACTH syndrome complicated by multiple opportunistic infections treated with percutaneous ablation of the adrenal glands.

Excessive pituitary gland production of adrenocorticotropic hormone is the cause of 80 percent of Cushing’s cases.

In 5 to 10 percent of cases, a tumor in another part of the body also produces the hormone, leading to excessive amounts of it in the body. When a tumor is generating the hormone, the condition is called ectopic ACTH syndrome. The patient in the case study had ACTH syndrome.

The 63-year-old woman had complained to her family doctor about weight gain, headache, weakness, and flushing. When laboratory tests led to her being diagnosed with ectopic ACTH-dependent Cushing’s syndrome, she was admitted to a hospital’s internal medicine department.

Doctors planned surgery to remove her adrenal glands, but two days before the operation was scheduled, respiratory failure sent her to the hospital’s Intensive Care Unit. There, physicians treated her for two infections in her lungs, plus infections in her blood and urinary tract. She experienced serious medical complications while in the Intensive Care Unit.

After a month, she was in good enough condition to leave intensive chair but too frail for surgery. Instead, doctors used microwaves to destroy as much of her adrenal glands as they could.

Within two weeks, her condition was better. She had been unable to leave her hospital bed while in intensive care. After the microwave treatment, she engaged in physiotherapy that led to her being able to use a two-wheeled walker to go short distances. She could also make short excursions outside the hospital with her family.

Six months later she returned to the hospital for surgical removal of her adrenal glands.

There were no complications from the operation, and doctors discharged her two days later. Her cortisol levels have been at acceptable levels since then.

“Our experience demonstrates that percutaneous ablation is a viable alternative in patients with ectopic ACTH syndrome in whom medical therapy has failed and surgical adrenalectomy is not feasible,” the researchers wrote. “Further research comparing the efficacy and complication rates between percutaneous ablation [microwave therapy] and surgical adrenalectomy is needed.” In addition, “research is needed to determine the optimal method of percutaneous intervention,” the team wrote.

From https://cushingsdiseasenews.com/2017/12/01/case-study-shows-microwave-therapy-helped-cushings-patient-who-was-too-frail-for-surgery/

High Cortisol Levels, as Seen in Cushing’s, Can Lead to Greater Risk of Heart Disease, Study Finds

People with high cortisol levels have lower muscle mass and higher visceral fat deposits, putting them at a greater risk for cardiovascular disease, new research shows.

High levels of cortisol can result from a variety of reasons, including Cushing’s disease and adrenal tumors. Most adrenal tumors are found to be non-functioning, meaning they do not produce excess hormones. However, up to 47 percent of patients have mild autonomous cortisol excess (MACE).

The study, “Impact of hypercortisolism on skeletal muscle mass and adipose tissue mass in patients with adrenal adenomas,” was published in the journal Clinical Endocrinology.

Long-term studies have shown that as a group, patients with MACE tend to have increased cardiovascular risk factors, such as hypertension, type 2 diabetes mellitus (DM2), obesity, and high lipid levels, which are associated with higher cardiovascular death rates.

Abdominal adiposity, which refers to fat deposits around the abdomen and stomach, and central sarcopenia, referring to loss of skeletal muscle mass, are both known to be linked to higher cardiovascular risk and increased mortality.

Overt hypercortisolism is known to lead to increased visceral adiposity (body fat stored within the abdominal cavity) and muscle loss. However, little is known about the body composition of patients with adrenal adenomas and MACE.

Therefore, researchers set out to determine whether central sarcopenia and adiposity are present in patients with MACE, and whether they can be markers of disease severity in patients with adrenal adenomas. To determine this, researchers used body composition measurements of 25 patients with Cushing’s disease, 48 patients with MACE, and 32 patients with non-functioning adrenal tumors (NFAT) using abdominal CTs.

Specifically, researchers looked at visceral fat, subcutaneous fat, and total abdominal muscle mass. Visceral fat refers to fat around organs, and it is “deeper” than subcutaneous fat, which is closer to the skin.

Results showed that, compared to patients with non-functional tumors, those with Cushing’s disease had a higher visceral to total (V/T) fat ratio but a lower visceral to subcutaneous (V/S) fat ratio. In MACE patients, however, both ratios were decreased compared to patients with non-functional tumors.

Cushing’s disease patients also had 10 cm2  less total muscle mass, compared to patients with non-functional tumors.

An overnight dexamethasone suppression test was conducted in these patients to determine levels of cortisol in the blood. The next morning, cortisol levels were checked. High levels of cortisol indicate the presence of a disease, such as MACE or Cushing’s disease.

After administering the test, researchers determined that for an increase in cortisol in the morning, there was a correlating increase in the V/T ratio and the V/S fat ratio, and a decrease in the mean total muscle mass.

Therefore, the higher the degree of hypercortisolism, the lower the muscle mass and the higher the visceral adiposity.

These results could prove to be clinically useful as both visceral adiposity and low muscle mass are risk factors of a number of diseases, including cardiovascular disease.

“Body composition measurement may provide an additive value in making a diagnosis of clinically important MACE and aid in individualizing management of patients with ACAs and MACE,” the researchers concluded.

From https://cushingsdiseasenews.com/2017/11/30/cushings-disease-high-cortisol-levels-leads-to-greater-risk-heart-disease/

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