Endocrine Cancer

SAN FRANCISCO – The size of a pituitary tumor on magnetic resonance imaging in a patient with ACTH-dependent Cushing’s syndrome can’t differentiate between etiologies, but combining that information with biochemical test results could help avoid costly and difficult inferior petrosal sinus sampling in some patients, a study of 131 cases suggests.

If MRI shows a pituitary tumor larger than 6 mm in size, the finding is 40% sensitive and 96% specific for a diagnosis of Cushing’s disease as the cause of adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome, and additional information from biochemical testing may help further differentiate this from ectopic ACTH secretion, Dr. Divya Yogi-Morren and her associates reported at the Endocrine Society’s Annual Meeting.

Pituitary tumors were seen on MRI in 6 of 26 patients with ectopic ACTH secretion (23%) and 73 of 105 patients with Cushing’s disease (69%), with mean measurements of 4.5 mm in the ectopic ACTH secretion group and 8 mm in the Cushing’s disease group. All but one tumor in the ectopic ACTH secretion group were 6 mm or smaller in diameter, but one was 14 mm.

Because pituitary "incidentalomas" as large as 14 mm can be seen in patients with ectopic ACTH secretion, the presence of a pituitary tumor can’t definitively discriminate between ectopic ACTH secretion and Cushing’s disease, said Dr. Yogi-Morren, a fellow at the Cleveland Clinic.

That finding contradicts part of a 2003 consensus statement that said the presence of a focal pituitary lesion larger than 6 mm on MRI could provide a definitive diagnosis of Cushing’s disease, with no further evaluation needed in patients who have a classic clinical presentation and dynamic biochemical testing results that are compatible with a pituitary etiology (J. Clin. Endocrinol. Metab. 2003;88:5593-602). The 6-mm cutoff, said Dr. Yogi-Morren, came from an earlier study reporting that 10% of 100 normal, healthy adults had focal pituitary abnormalities on MRI ranging from 3 to 6 mm in diameter that were consistent with a diagnosis of asymptomatic pituitary adenomas (Ann. Intern. Med. 1994;120:817-20).

A traditional workup of a patient with ACTH-dependent Cushing’s syndrome might include a clinical history, biochemical testing, neuroimaging, and an inferior petrosal sinus sampling (IPSS). Biochemical testing typically includes tests for hypokalemia, measurement of cortisol and ACTH levels, a high-dose dexamethasone suppression test, and a corticotropin-releasing hormone (CRH) stimulation test. Although IPSS is the gold standard for differentiating between the two etiologies, it is expensive and technically difficult, especially in institutions that don’t regularly do the procedure, so it would be desirable to avoid IPSS if it’s not needed in a subset of patients, Dr. Yogi-Morren said.

The investigators reviewed charts from two centers (the Cleveland Clinic and the M.D. Anderson Cancer Center, Houston) for patients with ACTH-dependent Cushing’s syndrome seen during 2000-2012.

ACTH levels were significantly different between groups, averaging 162 pg/mL (range, 58-671 pg/mL) in patients with ectopic ACTH secretion, compared with a mean 71 pg/mL in patients with Cushing’s disease (range, 16-209 pg/mL), she reported. Although there was some overlap between groups in the range of ACTH levels, all patients with an ACTH level higher than 210 pg/mL had ectopic ACTH secretion.

Median serum potassium levels at baseline were 2.9 mmol/L in the ectopic ACTH secretion group and 3.8 mmol/L in the Cushing’s disease group, a significant difference. Again, there was some overlap between groups in the range of potassium levels, but all patients with a baseline potassium level lower than 2.7 mmol/L had ectopic ACTH secretion, she said.

Among patients who underwent a high-dose dexamethasone suppression test, cortisol levels decreased by less than 50% in 88% of patients with ectopic ACTH secretion and in 26% of patients with Cushing’s disease.

Most patients did not undergo a standardized, formal CRH stimulation test, so investigators extracted the ACTH response to CRH in peripheral plasma during the IPSS test. As expected, they found a significantly higher percent increase in ACTH in response to CRH during IPSS in the Cushing’s disease group, ranging up to more than a 1,000% increase. In the ectopic ACTH secretion group, 40% of patients did have an ACTH increase greater than 50%, ranging as high as a 200%-300% increase in ACTH in a couple of patients.

"Although there was some overlap in the biochemical testing, it is possible that it provides some additional proof to differentiate between ectopic ACTH secretion and Cushing’s disease," Dr. Yogi-Morren said.

In the ectopic ACTH secretion group, the source of the secretion remained occult in seven patients. The most common identifiable cause was a bronchial carcinoid tumor, in six patients. Three patients each had small cell lung cancer, a thymic carcinoid tumor, or a pancreatic neuroendocrine tumor. One patient each had a bladder neuroendocrine tumor, ovarian endometrioid cancer, medullary thyroid cancer, or a metastatic neuroendocrine tumor from an unknown primary cancer.

The ectopic ACTH secretion group had a median age of 41 years and was 63% female. The Cushing’s disease group had a median age of 46 years and was 76% female.

Dr. Yogi-Morren reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – The size of a pituitary tumor on magnetic resonance imaging in a patient with ACTH-dependent Cushing’s syndrome can’t differentiate between etiologies, but combining that information with biochemical test results could help avoid costly and difficult inferior petrosal sinus sampling in some patients, a study of 131 cases suggests.

If MRI shows a pituitary tumor larger than 6 mm in size, the finding is 40% sensitive and 96% specific for a diagnosis of Cushing’s disease as the cause of adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome, and additional information from biochemical testing may help further differentiate this from ectopic ACTH secretion, Dr. Divya Yogi-Morren and her associates reported at the Endocrine Society’s Annual Meeting.

Pituitary tumors were seen on MRI in 6 of 26 patients with ectopic ACTH secretion (23%) and 73 of 105 patients with Cushing’s disease (69%), with mean measurements of 4.5 mm in the ectopic ACTH secretion group and 8 mm in the Cushing’s disease group. All but one tumor in the ectopic ACTH secretion group were 6 mm or smaller in diameter, but one was 14 mm.

Because pituitary "incidentalomas" as large as 14 mm can be seen in patients with ectopic ACTH secretion, the presence of a pituitary tumor can’t definitively discriminate between ectopic ACTH secretion and Cushing’s disease, said Dr. Yogi-Morren, a fellow at the Cleveland Clinic.

That finding contradicts part of a 2003 consensus statement that said the presence of a focal pituitary lesion larger than 6 mm on MRI could provide a definitive diagnosis of Cushing’s disease, with no further evaluation needed in patients who have a classic clinical presentation and dynamic biochemical testing results that are compatible with a pituitary etiology (J. Clin. Endocrinol. Metab. 2003;88:5593-602). The 6-mm cutoff, said Dr. Yogi-Morren, came from an earlier study reporting that 10% of 100 normal, healthy adults had focal pituitary abnormalities on MRI ranging from 3 to 6 mm in diameter that were consistent with a diagnosis of asymptomatic pituitary adenomas (Ann. Intern. Med. 1994;120:817-20).

A traditional workup of a patient with ACTH-dependent Cushing’s syndrome might include a clinical history, biochemical testing, neuroimaging, and an inferior petrosal sinus sampling (IPSS). Biochemical testing typically includes tests for hypokalemia, measurement of cortisol and ACTH levels, a high-dose dexamethasone suppression test, and a corticotropin-releasing hormone (CRH) stimulation test. Although IPSS is the gold standard for differentiating between the two etiologies, it is expensive and technically difficult, especially in institutions that don’t regularly do the procedure, so it would be desirable to avoid IPSS if it’s not needed in a subset of patients, Dr. Yogi-Morren said.

The investigators reviewed charts from two centers (the Cleveland Clinic and the M.D. Anderson Cancer Center, Houston) for patients with ACTH-dependent Cushing’s syndrome seen during 2000-2012.

ACTH levels were significantly different between groups, averaging 162 pg/mL (range, 58-671 pg/mL) in patients with ectopic ACTH secretion, compared with a mean 71 pg/mL in patients with Cushing’s disease (range, 16-209 pg/mL), she reported. Although there was some overlap between groups in the range of ACTH levels, all patients with an ACTH level higher than 210 pg/mL had ectopic ACTH secretion.

Median serum potassium levels at baseline were 2.9 mmol/L in the ectopic ACTH secretion group and 3.8 mmol/L in the Cushing’s disease group, a significant difference. Again, there was some overlap between groups in the range of potassium levels, but all patients with a baseline potassium level lower than 2.7 mmol/L had ectopic ACTH secretion, she said.

Among patients who underwent a high-dose dexamethasone suppression test, cortisol levels decreased by less than 50% in 88% of patients with ectopic ACTH secretion and in 26% of patients with Cushing’s disease.

Most patients did not undergo a standardized, formal CRH stimulation test, so investigators extracted the ACTH response to CRH in peripheral plasma during the IPSS test. As expected, they found a significantly higher percent increase in ACTH in response to CRH during IPSS in the Cushing’s disease group, ranging up to more than a 1,000% increase. In the ectopic ACTH secretion group, 40% of patients did have an ACTH increase greater than 50%, ranging as high as a 200%-300% increase in ACTH in a couple of patients.

"Although there was some overlap in the biochemical testing, it is possible that it provides some additional proof to differentiate between ectopic ACTH secretion and Cushing’s disease," Dr. Yogi-Morren said.

In the ectopic ACTH secretion group, the source of the secretion remained occult in seven patients. The most common identifiable cause was a bronchial carcinoid tumor, in six patients. Three patients each had small cell lung cancer, a thymic carcinoid tumor, or a pancreatic neuroendocrine tumor. One patient each had a bladder neuroendocrine tumor, ovarian endometrioid cancer, medullary thyroid cancer, or a metastatic neuroendocrine tumor from an unknown primary cancer.

The ectopic ACTH secretion group had a median age of 41 years and was 63% female. The Cushing’s disease group had a median age of 46 years and was 76% female.

Dr. Yogi-Morren reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – The size of a pituitary tumor on magnetic resonance imaging in a patient with ACTH-dependent Cushing’s syndrome can’t differentiate between etiologies, but combining that information with biochemical test results could help avoid costly and difficult inferior petrosal sinus sampling in some patients, a study of 131 cases suggests.

If MRI shows a pituitary tumor larger than 6 mm in size, the finding is 40% sensitive and 96% specific for a diagnosis of Cushing’s disease as the cause of adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome, and additional information from biochemical testing may help further differentiate this from ectopic ACTH secretion, Dr. Divya Yogi-Morren and her associates reported at the Endocrine Society’s Annual Meeting.

Pituitary tumors were seen on MRI in 6 of 26 patients with ectopic ACTH secretion (23%) and 73 of 105 patients with Cushing’s disease (69%), with mean measurements of 4.5 mm in the ectopic ACTH secretion group and 8 mm in the Cushing’s disease group. All but one tumor in the ectopic ACTH secretion group were 6 mm or smaller in diameter, but one was 14 mm.

Because pituitary "incidentalomas" as large as 14 mm can be seen in patients with ectopic ACTH secretion, the presence of a pituitary tumor can’t definitively discriminate between ectopic ACTH secretion and Cushing’s disease, said Dr. Yogi-Morren, a fellow at the Cleveland Clinic.

That finding contradicts part of a 2003 consensus statement that said the presence of a focal pituitary lesion larger than 6 mm on MRI could provide a definitive diagnosis of Cushing’s disease, with no further evaluation needed in patients who have a classic clinical presentation and dynamic biochemical testing results that are compatible with a pituitary etiology (J. Clin. Endocrinol. Metab. 2003;88:5593-602). The 6-mm cutoff, said Dr. Yogi-Morren, came from an earlier study reporting that 10% of 100 normal, healthy adults had focal pituitary abnormalities on MRI ranging from 3 to 6 mm in diameter that were consistent with a diagnosis of asymptomatic pituitary adenomas (Ann. Intern. Med. 1994;120:817-20).

A traditional workup of a patient with ACTH-dependent Cushing’s syndrome might include a clinical history, biochemical testing, neuroimaging, and an inferior petrosal sinus sampling (IPSS). Biochemical testing typically includes tests for hypokalemia, measurement of cortisol and ACTH levels, a high-dose dexamethasone suppression test, and a corticotropin-releasing hormone (CRH) stimulation test. Although IPSS is the gold standard for differentiating between the two etiologies, it is expensive and technically difficult, especially in institutions that don’t regularly do the procedure, so it would be desirable to avoid IPSS if it’s not needed in a subset of patients, Dr. Yogi-Morren said.

The investigators reviewed charts from two centers (the Cleveland Clinic and the M.D. Anderson Cancer Center, Houston) for patients with ACTH-dependent Cushing’s syndrome seen during 2000-2012.

ACTH levels were significantly different between groups, averaging 162 pg/mL (range, 58-671 pg/mL) in patients with ectopic ACTH secretion, compared with a mean 71 pg/mL in patients with Cushing’s disease (range, 16-209 pg/mL), she reported. Although there was some overlap between groups in the range of ACTH levels, all patients with an ACTH level higher than 210 pg/mL had ectopic ACTH secretion.

Median serum potassium levels at baseline were 2.9 mmol/L in the ectopic ACTH secretion group and 3.8 mmol/L in the Cushing’s disease group, a significant difference. Again, there was some overlap between groups in the range of potassium levels, but all patients with a baseline potassium level lower than 2.7 mmol/L had ectopic ACTH secretion, she said.

Among patients who underwent a high-dose dexamethasone suppression test, cortisol levels decreased by less than 50% in 88% of patients with ectopic ACTH secretion and in 26% of patients with Cushing’s disease.

Most patients did not undergo a standardized, formal CRH stimulation test, so investigators extracted the ACTH response to CRH in peripheral plasma during the IPSS test. As expected, they found a significantly higher percent increase in ACTH in response to CRH during IPSS in the Cushing’s disease group, ranging up to more than a 1,000% increase. In the ectopic ACTH secretion group, 40% of patients did have an ACTH increase greater than 50%, ranging as high as a 200%-300% increase in ACTH in a couple of patients.

"Although there was some overlap in the biochemical testing, it is possible that it provides some additional proof to differentiate between ectopic ACTH secretion and Cushing’s disease," Dr. Yogi-Morren said.

In the ectopic ACTH secretion group, the source of the secretion remained occult in seven patients. The most common identifiable cause was a bronchial carcinoid tumor, in six patients. Three patients each had small cell lung cancer, a thymic carcinoid tumor, or a pancreatic neuroendocrine tumor. One patient each had a bladder neuroendocrine tumor, ovarian endometrioid cancer, medullary thyroid cancer, or a metastatic neuroendocrine tumor from an unknown primary cancer.

The ectopic ACTH secretion group had a median age of 41 years and was 63% female. The Cushing’s disease group had a median age of 46 years and was 76% female.

Dr. Yogi-Morren reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN DIEGO – Magnetic resonance-guided stereotactic laser ablation is a safe and effective option in the treatment of hypothalamic hamartoma, results from a multicenter pilot study showed.

At the annual meeting of the American Academy of Neurology, Dr. Daniel J. Curry reported results from 20 patients who have undergone treatment with a Food and Drug Administration–cleared neurosurgical tissue coagulation system called Visualase. Hypothalamic hamartoma (HH) is a rare disorder of pediatric epilepsy with an estimated prevalence of 1:50,000-100,000, said Dr. Curry, director of pediatric surgical epilepsy and functional neurosurgery at Texas Children’s Hospital, Houston.

"The main presentation is the mirthless laughter of gelastic seizures, but patients can have other seizure types," he said. "The diagnosis is frequently delayed, and high seizure burden in the brain can lead to epileptic encephalopathy. Seizures are notoriously resistant to medical managements necessitating surgical intervention ... open, endoscopic, or ablative."

To date, surgical intervention has been limited due to modest outcomes, with 37%-50% achieving seizure freedom. The location of HH tumors makes surgical intervention difficult, and as a result 7%-10% of patients have permanent surgical morbidity.

For the technique using the Visualase, Dr. Curry and his associates at four other medical centers in the United States performed the surgical technique through a single 4-mm incision, a 3.2-mm burr hole, and a 1.65-mm cannula trajectory with Visualase under real-time MR thermography, first with a confirmation test at about 3 W, followed by higher doses of 6-10 W for 50-120 seconds. Temperature limits were set to protect the hypothalamus and basilar artery and optic tract. The surgery had an immediate effect, and patients stayed in the hospital for a mean of 2 days.

The primary measure was seizure frequency at 1 year while the secondary measure was the complication profile of stereotactic laser ablation in epilepsy.

Of the 20 patients, 5 were adults, and the entire study population ranged in age from 22 months to 34 years. A total of 21 ablations were performed in the 20 patients. Dr. Curry reported that all but four patients were seizure free after the procedure. However, the rate of seizures diminished among the four who were not seizure free.

Seizures recurred in one of the pediatric patients. "We re-ablated him and he is now seizure free," Dr. Curry said.

Complications to date have included two missed targets, one case of IV phenytoin toxicity, one case of transient diabetes insipidus, two cases of transient hemiparesis, and one subarachnoid hemorrhage. Perioperative, temporary weight gain was detected in most patients. "With lack of hormonal disturbance, this is thought to be due to the perioperative, high-dose steroid use," Dr. Curry explained.

Postoperative interviews with parents of study participants "have revealed significant improvements in intellectual development, concentration, and interactiveness," he said. "Most families report improvement of mood, decreased behavioral disorders, and rage attacks."

To date, only two patients have completed formal postoperative neuropsychological testing. "There were no significant declines in memory in either patient," Dr. Curry said. One had improved math skills and reading comprehension while the other complained of memory dysfunction but was not below normal on testing.

"We have learned that laser ablation of hypothalamic hamartoma can be accomplished safely," Dr. Curry concluded. "More studies are needed to explain the antiepileptic effect in settings of incomplete radiologic destruction of the target and to advance thermal planning."

Dr. Curry said that he had no relevant financial conflicts to disclose.

[email protected]

SAN DIEGO – Magnetic resonance-guided stereotactic laser ablation is a safe and effective option in the treatment of hypothalamic hamartoma, results from a multicenter pilot study showed.

At the annual meeting of the American Academy of Neurology, Dr. Daniel J. Curry reported results from 20 patients who have undergone treatment with a Food and Drug Administration–cleared neurosurgical tissue coagulation system called Visualase. Hypothalamic hamartoma (HH) is a rare disorder of pediatric epilepsy with an estimated prevalence of 1:50,000-100,000, said Dr. Curry, director of pediatric surgical epilepsy and functional neurosurgery at Texas Children’s Hospital, Houston.

"The main presentation is the mirthless laughter of gelastic seizures, but patients can have other seizure types," he said. "The diagnosis is frequently delayed, and high seizure burden in the brain can lead to epileptic encephalopathy. Seizures are notoriously resistant to medical managements necessitating surgical intervention ... open, endoscopic, or ablative."

To date, surgical intervention has been limited due to modest outcomes, with 37%-50% achieving seizure freedom. The location of HH tumors makes surgical intervention difficult, and as a result 7%-10% of patients have permanent surgical morbidity.

For the technique using the Visualase, Dr. Curry and his associates at four other medical centers in the United States performed the surgical technique through a single 4-mm incision, a 3.2-mm burr hole, and a 1.65-mm cannula trajectory with Visualase under real-time MR thermography, first with a confirmation test at about 3 W, followed by higher doses of 6-10 W for 50-120 seconds. Temperature limits were set to protect the hypothalamus and basilar artery and optic tract. The surgery had an immediate effect, and patients stayed in the hospital for a mean of 2 days.

The primary measure was seizure frequency at 1 year while the secondary measure was the complication profile of stereotactic laser ablation in epilepsy.

Of the 20 patients, 5 were adults, and the entire study population ranged in age from 22 months to 34 years. A total of 21 ablations were performed in the 20 patients. Dr. Curry reported that all but four patients were seizure free after the procedure. However, the rate of seizures diminished among the four who were not seizure free.

Seizures recurred in one of the pediatric patients. "We re-ablated him and he is now seizure free," Dr. Curry said.

Complications to date have included two missed targets, one case of IV phenytoin toxicity, one case of transient diabetes insipidus, two cases of transient hemiparesis, and one subarachnoid hemorrhage. Perioperative, temporary weight gain was detected in most patients. "With lack of hormonal disturbance, this is thought to be due to the perioperative, high-dose steroid use," Dr. Curry explained.

Postoperative interviews with parents of study participants "have revealed significant improvements in intellectual development, concentration, and interactiveness," he said. "Most families report improvement of mood, decreased behavioral disorders, and rage attacks."

To date, only two patients have completed formal postoperative neuropsychological testing. "There were no significant declines in memory in either patient," Dr. Curry said. One had improved math skills and reading comprehension while the other complained of memory dysfunction but was not below normal on testing.

"We have learned that laser ablation of hypothalamic hamartoma can be accomplished safely," Dr. Curry concluded. "More studies are needed to explain the antiepileptic effect in settings of incomplete radiologic destruction of the target and to advance thermal planning."

Dr. Curry said that he had no relevant financial conflicts to disclose.

[email protected]

SAN DIEGO – Magnetic resonance-guided stereotactic laser ablation is a safe and effective option in the treatment of hypothalamic hamartoma, results from a multicenter pilot study showed.

At the annual meeting of the American Academy of Neurology, Dr. Daniel J. Curry reported results from 20 patients who have undergone treatment with a Food and Drug Administration–cleared neurosurgical tissue coagulation system called Visualase. Hypothalamic hamartoma (HH) is a rare disorder of pediatric epilepsy with an estimated prevalence of 1:50,000-100,000, said Dr. Curry, director of pediatric surgical epilepsy and functional neurosurgery at Texas Children’s Hospital, Houston.

"The main presentation is the mirthless laughter of gelastic seizures, but patients can have other seizure types," he said. "The diagnosis is frequently delayed, and high seizure burden in the brain can lead to epileptic encephalopathy. Seizures are notoriously resistant to medical managements necessitating surgical intervention ... open, endoscopic, or ablative."

To date, surgical intervention has been limited due to modest outcomes, with 37%-50% achieving seizure freedom. The location of HH tumors makes surgical intervention difficult, and as a result 7%-10% of patients have permanent surgical morbidity.

For the technique using the Visualase, Dr. Curry and his associates at four other medical centers in the United States performed the surgical technique through a single 4-mm incision, a 3.2-mm burr hole, and a 1.65-mm cannula trajectory with Visualase under real-time MR thermography, first with a confirmation test at about 3 W, followed by higher doses of 6-10 W for 50-120 seconds. Temperature limits were set to protect the hypothalamus and basilar artery and optic tract. The surgery had an immediate effect, and patients stayed in the hospital for a mean of 2 days.

The primary measure was seizure frequency at 1 year while the secondary measure was the complication profile of stereotactic laser ablation in epilepsy.

Of the 20 patients, 5 were adults, and the entire study population ranged in age from 22 months to 34 years. A total of 21 ablations were performed in the 20 patients. Dr. Curry reported that all but four patients were seizure free after the procedure. However, the rate of seizures diminished among the four who were not seizure free.

Seizures recurred in one of the pediatric patients. "We re-ablated him and he is now seizure free," Dr. Curry said.

Complications to date have included two missed targets, one case of IV phenytoin toxicity, one case of transient diabetes insipidus, two cases of transient hemiparesis, and one subarachnoid hemorrhage. Perioperative, temporary weight gain was detected in most patients. "With lack of hormonal disturbance, this is thought to be due to the perioperative, high-dose steroid use," Dr. Curry explained.

Postoperative interviews with parents of study participants "have revealed significant improvements in intellectual development, concentration, and interactiveness," he said. "Most families report improvement of mood, decreased behavioral disorders, and rage attacks."

To date, only two patients have completed formal postoperative neuropsychological testing. "There were no significant declines in memory in either patient," Dr. Curry said. One had improved math skills and reading comprehension while the other complained of memory dysfunction but was not below normal on testing.

"We have learned that laser ablation of hypothalamic hamartoma can be accomplished safely," Dr. Curry concluded. "More studies are needed to explain the antiepileptic effect in settings of incomplete radiologic destruction of the target and to advance thermal planning."

Dr. Curry said that he had no relevant financial conflicts to disclose.

[email protected]