Endocrine Cancer

The somatostatin analogue pasireotide reduced postoperative pancreatic fistula leak or abscess by 56%, compared with placebo, a randomized study has determined.

Pasireotide (Signifor) was effective after both pancreaticoduodenectomy and distal pancreatectomy, whether or not the pancreatic duct was dilated, Dr. Peter J. Allen and his colleagues wrote in the May 21 issue of the New England Journal of Medicine (N. Engl. J. Med. 2014;370:2014-22).

In those patients who did develop fistulas or leaks, pasireotide was associated with fewer grade 3 occurrences.

"These results suggest that ... not only were many leaks and fistulas prevented, but when they did occur they were less clinically relevant," wrote Dr. Allen of the Memorial Sloan Kettering Cancer Center, New York, and his coauthors.

The study randomized 300 patients to subcutaneous injections of either placebo or pasireotide twice daily for 7 days after pancreatic surgery. The primary endpoint was the development of a pancreatic leak, fistula, or abscess of at least grade 3. Secondary endpoints included the overall rate of pancreatic complications (all grades) and the rate of grade B or grade C pancreatic fistula.

Patients were a mean of 64 years old. Most (73%) underwent a pancreaticoduodenectomy. The average length of stay for these patients was about 10 days. The active group received 900 mcg of pasireotide subcutaneously twice daily for 7 days, beginning on the morning of surgery.

Mean postoperative serum glucose levels were significantly higher in patients taking pasireotide (258 mg/dL vs. 215 mg/dL). Readmission occurred in significantly fewer pasireotide patients (17% vs. 29%).

Significantly fewer of those taking the active drug were able to finish the entire course of 14 doses (76% vs. 86% given placebo). The lower completion rate was mostly due to nausea and vomiting, which caused 26 patients in the active group and 3 in the placebo group to withdraw from the study.

A leak or fistula of grade 3 or higher developed in 45 patients. The outcome was significantly less common among those taking pasireotide than among those on placebo (9% vs. 21%; relative risk, 0.44). "This corresponded to an absolute risk reduction of 11.7 percentage points," with a number needed to treat of 8, the investigators said.

Pasireotide was significantly more effective than placebo in surgical subgroups, including pancreaticoduodenectomy (RR, 0.49) and distal pancreatectomy (RR, 0.32). The effect was also positive whether the pancreatic duct was dilated (RR, 0.11) or nondilated (RR, 0.55).

The secondary outcome (grade B or C postoperative fistula) occurred in 37 patients (12%). In the pasireotide group, there were 12 grade B fistulas and no grade C fistulas. In the placebo group, there were 20 grade B and 5 grade C fistulas.

Overall 60-day mortality was 0.7% (one death in each treatment group). Grade 3 and 4 complications were common, occurring in 92% of the pasireotide group and 90% of the placebo group. Most of these were expected postoperative serum abnormalities.

The investigators said that the other approved somatostatin analogue, octreotide, has not been clearly associated with pancreatic leak reduction. They suggested that pasireotide may be more effective because it has a longer half-life and binds to four of the five somatostatin-receptor subtypes, rather than just two, as octreotide does.

They added that the octreotide studies were conducted before 2005, when there was no consistent definition of postoperative pancreatic fistula. Therefore, they concluded, the extant data cannot be used to identify octreotide efficacy in this application.

Pasireotide, which is made by Novartis Pharmaceuticals, is currently approved as an injection for the treatment of Cushing’s disease patients who cannot be helped through surgery.

Novartis Pharmaceuticals sponsored the trial. Dr. Allen received Novartis grant funding but had no other financial ties with the company.

[email protected]

The somatostatin analogue pasireotide reduced postoperative pancreatic fistula leak or abscess by 56%, compared with placebo, a randomized study has determined.

Pasireotide (Signifor) was effective after both pancreaticoduodenectomy and distal pancreatectomy, whether or not the pancreatic duct was dilated, Dr. Peter J. Allen and his colleagues wrote in the May 21 issue of the New England Journal of Medicine (N. Engl. J. Med. 2014;370:2014-22).

In those patients who did develop fistulas or leaks, pasireotide was associated with fewer grade 3 occurrences.

"These results suggest that ... not only were many leaks and fistulas prevented, but when they did occur they were less clinically relevant," wrote Dr. Allen of the Memorial Sloan Kettering Cancer Center, New York, and his coauthors.

The study randomized 300 patients to subcutaneous injections of either placebo or pasireotide twice daily for 7 days after pancreatic surgery. The primary endpoint was the development of a pancreatic leak, fistula, or abscess of at least grade 3. Secondary endpoints included the overall rate of pancreatic complications (all grades) and the rate of grade B or grade C pancreatic fistula.

Patients were a mean of 64 years old. Most (73%) underwent a pancreaticoduodenectomy. The average length of stay for these patients was about 10 days. The active group received 900 mcg of pasireotide subcutaneously twice daily for 7 days, beginning on the morning of surgery.

Mean postoperative serum glucose levels were significantly higher in patients taking pasireotide (258 mg/dL vs. 215 mg/dL). Readmission occurred in significantly fewer pasireotide patients (17% vs. 29%).

Significantly fewer of those taking the active drug were able to finish the entire course of 14 doses (76% vs. 86% given placebo). The lower completion rate was mostly due to nausea and vomiting, which caused 26 patients in the active group and 3 in the placebo group to withdraw from the study.

A leak or fistula of grade 3 or higher developed in 45 patients. The outcome was significantly less common among those taking pasireotide than among those on placebo (9% vs. 21%; relative risk, 0.44). "This corresponded to an absolute risk reduction of 11.7 percentage points," with a number needed to treat of 8, the investigators said.

Pasireotide was significantly more effective than placebo in surgical subgroups, including pancreaticoduodenectomy (RR, 0.49) and distal pancreatectomy (RR, 0.32). The effect was also positive whether the pancreatic duct was dilated (RR, 0.11) or nondilated (RR, 0.55).

The secondary outcome (grade B or C postoperative fistula) occurred in 37 patients (12%). In the pasireotide group, there were 12 grade B fistulas and no grade C fistulas. In the placebo group, there were 20 grade B and 5 grade C fistulas.

Overall 60-day mortality was 0.7% (one death in each treatment group). Grade 3 and 4 complications were common, occurring in 92% of the pasireotide group and 90% of the placebo group. Most of these were expected postoperative serum abnormalities.

The investigators said that the other approved somatostatin analogue, octreotide, has not been clearly associated with pancreatic leak reduction. They suggested that pasireotide may be more effective because it has a longer half-life and binds to four of the five somatostatin-receptor subtypes, rather than just two, as octreotide does.

They added that the octreotide studies were conducted before 2005, when there was no consistent definition of postoperative pancreatic fistula. Therefore, they concluded, the extant data cannot be used to identify octreotide efficacy in this application.

Pasireotide, which is made by Novartis Pharmaceuticals, is currently approved as an injection for the treatment of Cushing’s disease patients who cannot be helped through surgery.

Novartis Pharmaceuticals sponsored the trial. Dr. Allen received Novartis grant funding but had no other financial ties with the company.

[email protected]

The somatostatin analogue pasireotide reduced postoperative pancreatic fistula leak or abscess by 56%, compared with placebo, a randomized study has determined.

Pasireotide (Signifor) was effective after both pancreaticoduodenectomy and distal pancreatectomy, whether or not the pancreatic duct was dilated, Dr. Peter J. Allen and his colleagues wrote in the May 21 issue of the New England Journal of Medicine (N. Engl. J. Med. 2014;370:2014-22).

In those patients who did develop fistulas or leaks, pasireotide was associated with fewer grade 3 occurrences.

"These results suggest that ... not only were many leaks and fistulas prevented, but when they did occur they were less clinically relevant," wrote Dr. Allen of the Memorial Sloan Kettering Cancer Center, New York, and his coauthors.

The study randomized 300 patients to subcutaneous injections of either placebo or pasireotide twice daily for 7 days after pancreatic surgery. The primary endpoint was the development of a pancreatic leak, fistula, or abscess of at least grade 3. Secondary endpoints included the overall rate of pancreatic complications (all grades) and the rate of grade B or grade C pancreatic fistula.

Patients were a mean of 64 years old. Most (73%) underwent a pancreaticoduodenectomy. The average length of stay for these patients was about 10 days. The active group received 900 mcg of pasireotide subcutaneously twice daily for 7 days, beginning on the morning of surgery.

Mean postoperative serum glucose levels were significantly higher in patients taking pasireotide (258 mg/dL vs. 215 mg/dL). Readmission occurred in significantly fewer pasireotide patients (17% vs. 29%).

Significantly fewer of those taking the active drug were able to finish the entire course of 14 doses (76% vs. 86% given placebo). The lower completion rate was mostly due to nausea and vomiting, which caused 26 patients in the active group and 3 in the placebo group to withdraw from the study.

A leak or fistula of grade 3 or higher developed in 45 patients. The outcome was significantly less common among those taking pasireotide than among those on placebo (9% vs. 21%; relative risk, 0.44). "This corresponded to an absolute risk reduction of 11.7 percentage points," with a number needed to treat of 8, the investigators said.

Pasireotide was significantly more effective than placebo in surgical subgroups, including pancreaticoduodenectomy (RR, 0.49) and distal pancreatectomy (RR, 0.32). The effect was also positive whether the pancreatic duct was dilated (RR, 0.11) or nondilated (RR, 0.55).

The secondary outcome (grade B or C postoperative fistula) occurred in 37 patients (12%). In the pasireotide group, there were 12 grade B fistulas and no grade C fistulas. In the placebo group, there were 20 grade B and 5 grade C fistulas.

Overall 60-day mortality was 0.7% (one death in each treatment group). Grade 3 and 4 complications were common, occurring in 92% of the pasireotide group and 90% of the placebo group. Most of these were expected postoperative serum abnormalities.

The investigators said that the other approved somatostatin analogue, octreotide, has not been clearly associated with pancreatic leak reduction. They suggested that pasireotide may be more effective because it has a longer half-life and binds to four of the five somatostatin-receptor subtypes, rather than just two, as octreotide does.

They added that the octreotide studies were conducted before 2005, when there was no consistent definition of postoperative pancreatic fistula. Therefore, they concluded, the extant data cannot be used to identify octreotide efficacy in this application.

Pasireotide, which is made by Novartis Pharmaceuticals, is currently approved as an injection for the treatment of Cushing’s disease patients who cannot be helped through surgery.

Novartis Pharmaceuticals sponsored the trial. Dr. Allen received Novartis grant funding but had no other financial ties with the company.

[email protected]

BOSTON – Extensive surgery beyond lobectomy offers no survival advantage for small papillary thyroid cancers, according to a large database analysis.

Total thyroidectomy was not associated with an overall survival benefit over lobectomy for papillary thyroid cancers sized 1-2 cm (hazard ratio, 1.05; P = .61) or 2.1-4.0 cm (HR, 0.89; P = .21), even after adjusting for multiple patient and pathologic factors.

"Despite guidelines, our results call into question whether tumor size 1-4 cm should be an absolute determinant for extent of surgery," Dr. Mohamed Abdelgadir Adam said at the annual meeting of the American Surgical Association.

Current American Thyroid Association guidelines recommend lobectomy for tumors less than 1 cm in size and total thyroidectomy for those exceeding 1 cm.

Patrice Wendling/Frontline Medical News

"Using total thyroidectomy based on tumor size alone may unnecessarily subject patients to increased risks of complications without a survival benefit," he said. "In addition to tumor size up to 4 cm, other factors are important for determining extent of surgery such as nodal and distant metastases and patient preference."

The extent of surgery for papillary thyroid cancer, however, remains controversial. Recent analyses (Arch. Otolaryngol. Head Neck Surg. 2010;136:1055-61) have shown no survival difference between lobectomy and total thyroidectomy, while an earlier landmark study found improved overall survival with total thyroidectomy for tumors 1 cm or more (Ann. Surg. 2007;246;375-81). The latter study, however, has been criticized because it did not take into account patient comorbidities, multifocality, extrathyroidal extension, or completeness of resection, said Dr. Adam of Duke University School of Medicine, Durham, N.C.

The current analysis adjusted for age, gender, race, annual income, insurance status, hospital volume, patient comorbidities, tumor multifocality, extrathyroidal extension, lymph node involvement, metastases, surgical margins, and radioactive iodine ablation.

Discussant Dr. Blake Cady, professor emeritus of surgery at Harvard Medical School and Massachusetts General Hospital in Boston, said the current report is an important contribution to the controversy. It also supports his own bias against overtreatment of these mostly young patients with total thyroidectomy, which necessitates long-term medication and is accompanied by almost routine use of radioactive iodine, despite no evidence it improves outcomes in low-risk patients.

"In no other human cancer with a 99% 20-year survival is a policy of routine total primary organ removal practiced and routine systemic therapy used," he said. "Therefore, this report may help to scale back toward a more measured balance between treatment and morbidity."

Study coauthor Dr. Julie Ann Sosa, chief of endocrine surgery at Duke, challenged the audience to promote the growing body of evidence supporting equivalence in overall survival, such as a recent study described as coming the closest to a head-to-head comparison and having the longest follow-up at 18 years. It showed equivalence between lobectomy, without radioactive iodine, and total thyroidectomy for overall, progression-free, and disease-specific survival and risk of recurrence in tumors 40 mm or less (World J. Surg. 2014;38:68-79.

"In light of these data, I think it is probably high time for guidelines to potentially reconsider this issue," she said, noting that the American Thyroid Association will issue new guidelines later this spring or summer.

Dr. Sosa also advocated for "a more sophisticated approach" to preoperative evaluation and risk stratification for papillary thyroid cancer that distinguishes between low-, medium-, and high-risk tumors. The Duke study did not exclude most high-risk tumors, but rather adjusted for high-risk characteristics such as extrathyroidal extension, lymph node involvement, and distant metastases.

"When you adjust for these high-risk characteristics, the afforded overall survival benefit disappears," she said. "So what I think we would argue is that there is equivalence in outcome for the majority of patients for low- and medium-risk tumors. But for those patients who have high-risk tumors, as defined by some of these high-risk characteristics, then I think all of us would agree that total thyroidectomy, with or without radioactive iodine, would be indicated."

The study involved 61,775 patients in the National Cancer Database who underwent total thyroidectomy (n = 54,926) or lobectomy with or without isthmusectomy (n = 6,849) for papillary thyroid cancer from 1998 to 2006. Compared with the lobectomy group, the thyroidectomy group had more tumor multifocality (44% vs. 29%), positive surgical margins (27% vs. 7%), distant metastases (1% vs. 0.4%), and radioactive iodine (65% vs. 33%; P value less than .01 for all).

In multivariable analysis, nodal and distant metastases were associated with compromised survival, Dr. Adam said.

The complete manuscript of this study and its presentation at the American Surgical Association’s 134^th Annual Meeting, April 2014 in Boston, is anticipated to be published in the Annals of Surgery, pending editorial review.

The authors reported no conflicting interests

[email protected]

BOSTON – Extensive surgery beyond lobectomy offers no survival advantage for small papillary thyroid cancers, according to a large database analysis.

Total thyroidectomy was not associated with an overall survival benefit over lobectomy for papillary thyroid cancers sized 1-2 cm (hazard ratio, 1.05; P = .61) or 2.1-4.0 cm (HR, 0.89; P = .21), even after adjusting for multiple patient and pathologic factors.

"Despite guidelines, our results call into question whether tumor size 1-4 cm should be an absolute determinant for extent of surgery," Dr. Mohamed Abdelgadir Adam said at the annual meeting of the American Surgical Association.

Current American Thyroid Association guidelines recommend lobectomy for tumors less than 1 cm in size and total thyroidectomy for those exceeding 1 cm.

Patrice Wendling/Frontline Medical News

"Using total thyroidectomy based on tumor size alone may unnecessarily subject patients to increased risks of complications without a survival benefit," he said. "In addition to tumor size up to 4 cm, other factors are important for determining extent of surgery such as nodal and distant metastases and patient preference."

The extent of surgery for papillary thyroid cancer, however, remains controversial. Recent analyses (Arch. Otolaryngol. Head Neck Surg. 2010;136:1055-61) have shown no survival difference between lobectomy and total thyroidectomy, while an earlier landmark study found improved overall survival with total thyroidectomy for tumors 1 cm or more (Ann. Surg. 2007;246;375-81). The latter study, however, has been criticized because it did not take into account patient comorbidities, multifocality, extrathyroidal extension, or completeness of resection, said Dr. Adam of Duke University School of Medicine, Durham, N.C.

The current analysis adjusted for age, gender, race, annual income, insurance status, hospital volume, patient comorbidities, tumor multifocality, extrathyroidal extension, lymph node involvement, metastases, surgical margins, and radioactive iodine ablation.

Discussant Dr. Blake Cady, professor emeritus of surgery at Harvard Medical School and Massachusetts General Hospital in Boston, said the current report is an important contribution to the controversy. It also supports his own bias against overtreatment of these mostly young patients with total thyroidectomy, which necessitates long-term medication and is accompanied by almost routine use of radioactive iodine, despite no evidence it improves outcomes in low-risk patients.

"In no other human cancer with a 99% 20-year survival is a policy of routine total primary organ removal practiced and routine systemic therapy used," he said. "Therefore, this report may help to scale back toward a more measured balance between treatment and morbidity."

Study coauthor Dr. Julie Ann Sosa, chief of endocrine surgery at Duke, challenged the audience to promote the growing body of evidence supporting equivalence in overall survival, such as a recent study described as coming the closest to a head-to-head comparison and having the longest follow-up at 18 years. It showed equivalence between lobectomy, without radioactive iodine, and total thyroidectomy for overall, progression-free, and disease-specific survival and risk of recurrence in tumors 40 mm or less (World J. Surg. 2014;38:68-79.

"In light of these data, I think it is probably high time for guidelines to potentially reconsider this issue," she said, noting that the American Thyroid Association will issue new guidelines later this spring or summer.

Dr. Sosa also advocated for "a more sophisticated approach" to preoperative evaluation and risk stratification for papillary thyroid cancer that distinguishes between low-, medium-, and high-risk tumors. The Duke study did not exclude most high-risk tumors, but rather adjusted for high-risk characteristics such as extrathyroidal extension, lymph node involvement, and distant metastases.

"When you adjust for these high-risk characteristics, the afforded overall survival benefit disappears," she said. "So what I think we would argue is that there is equivalence in outcome for the majority of patients for low- and medium-risk tumors. But for those patients who have high-risk tumors, as defined by some of these high-risk characteristics, then I think all of us would agree that total thyroidectomy, with or without radioactive iodine, would be indicated."

The study involved 61,775 patients in the National Cancer Database who underwent total thyroidectomy (n = 54,926) or lobectomy with or without isthmusectomy (n = 6,849) for papillary thyroid cancer from 1998 to 2006. Compared with the lobectomy group, the thyroidectomy group had more tumor multifocality (44% vs. 29%), positive surgical margins (27% vs. 7%), distant metastases (1% vs. 0.4%), and radioactive iodine (65% vs. 33%; P value less than .01 for all).

In multivariable analysis, nodal and distant metastases were associated with compromised survival, Dr. Adam said.

The complete manuscript of this study and its presentation at the American Surgical Association’s 134^th Annual Meeting, April 2014 in Boston, is anticipated to be published in the Annals of Surgery, pending editorial review.

The authors reported no conflicting interests

[email protected]

BOSTON – Extensive surgery beyond lobectomy offers no survival advantage for small papillary thyroid cancers, according to a large database analysis.

Total thyroidectomy was not associated with an overall survival benefit over lobectomy for papillary thyroid cancers sized 1-2 cm (hazard ratio, 1.05; P = .61) or 2.1-4.0 cm (HR, 0.89; P = .21), even after adjusting for multiple patient and pathologic factors.

"Despite guidelines, our results call into question whether tumor size 1-4 cm should be an absolute determinant for extent of surgery," Dr. Mohamed Abdelgadir Adam said at the annual meeting of the American Surgical Association.

Current American Thyroid Association guidelines recommend lobectomy for tumors less than 1 cm in size and total thyroidectomy for those exceeding 1 cm.

Patrice Wendling/Frontline Medical News

"Using total thyroidectomy based on tumor size alone may unnecessarily subject patients to increased risks of complications without a survival benefit," he said. "In addition to tumor size up to 4 cm, other factors are important for determining extent of surgery such as nodal and distant metastases and patient preference."

The extent of surgery for papillary thyroid cancer, however, remains controversial. Recent analyses (Arch. Otolaryngol. Head Neck Surg. 2010;136:1055-61) have shown no survival difference between lobectomy and total thyroidectomy, while an earlier landmark study found improved overall survival with total thyroidectomy for tumors 1 cm or more (Ann. Surg. 2007;246;375-81). The latter study, however, has been criticized because it did not take into account patient comorbidities, multifocality, extrathyroidal extension, or completeness of resection, said Dr. Adam of Duke University School of Medicine, Durham, N.C.

The current analysis adjusted for age, gender, race, annual income, insurance status, hospital volume, patient comorbidities, tumor multifocality, extrathyroidal extension, lymph node involvement, metastases, surgical margins, and radioactive iodine ablation.

Discussant Dr. Blake Cady, professor emeritus of surgery at Harvard Medical School and Massachusetts General Hospital in Boston, said the current report is an important contribution to the controversy. It also supports his own bias against overtreatment of these mostly young patients with total thyroidectomy, which necessitates long-term medication and is accompanied by almost routine use of radioactive iodine, despite no evidence it improves outcomes in low-risk patients.

"In no other human cancer with a 99% 20-year survival is a policy of routine total primary organ removal practiced and routine systemic therapy used," he said. "Therefore, this report may help to scale back toward a more measured balance between treatment and morbidity."

Study coauthor Dr. Julie Ann Sosa, chief of endocrine surgery at Duke, challenged the audience to promote the growing body of evidence supporting equivalence in overall survival, such as a recent study described as coming the closest to a head-to-head comparison and having the longest follow-up at 18 years. It showed equivalence between lobectomy, without radioactive iodine, and total thyroidectomy for overall, progression-free, and disease-specific survival and risk of recurrence in tumors 40 mm or less (World J. Surg. 2014;38:68-79.

"In light of these data, I think it is probably high time for guidelines to potentially reconsider this issue," she said, noting that the American Thyroid Association will issue new guidelines later this spring or summer.

Dr. Sosa also advocated for "a more sophisticated approach" to preoperative evaluation and risk stratification for papillary thyroid cancer that distinguishes between low-, medium-, and high-risk tumors. The Duke study did not exclude most high-risk tumors, but rather adjusted for high-risk characteristics such as extrathyroidal extension, lymph node involvement, and distant metastases.

"When you adjust for these high-risk characteristics, the afforded overall survival benefit disappears," she said. "So what I think we would argue is that there is equivalence in outcome for the majority of patients for low- and medium-risk tumors. But for those patients who have high-risk tumors, as defined by some of these high-risk characteristics, then I think all of us would agree that total thyroidectomy, with or without radioactive iodine, would be indicated."

The study involved 61,775 patients in the National Cancer Database who underwent total thyroidectomy (n = 54,926) or lobectomy with or without isthmusectomy (n = 6,849) for papillary thyroid cancer from 1998 to 2006. Compared with the lobectomy group, the thyroidectomy group had more tumor multifocality (44% vs. 29%), positive surgical margins (27% vs. 7%), distant metastases (1% vs. 0.4%), and radioactive iodine (65% vs. 33%; P value less than .01 for all).

In multivariable analysis, nodal and distant metastases were associated with compromised survival, Dr. Adam said.

The complete manuscript of this study and its presentation at the American Surgical Association’s 134^th Annual Meeting, April 2014 in Boston, is anticipated to be published in the Annals of Surgery, pending editorial review.

The authors reported no conflicting interests

[email protected]

Elevated growth hormone levels had a negative impact on remission in acromegaly patients undergoing transsphenoidal adenomectomies, researchers from Emory University in Atlanta concluded after a retrospective, multivariate analysis of case studies.

To determine the impact of preoperative growth hormone (GH), Dr. Jeremy Anthony and his associates examined the case files of 79 acromegaly patients who underwent transsphenoidal adenomectomy between 1994 and 2013 at Emory and assigned them to two groups on the basis of their preoperative GH levels, using 40 ng/mL as the cutoff.

Biochemical remission was defined as normal insulin-like growth factor 1 (IGF-1) during follow-up of more than 3 months in the absence of adjuvant therapy. The results were released at the annual meeting of the American Association of Clinical Endocrinologists on May 15 in Las Vegas.

Group A, with preoperative GH levels greater than 40 ng/mL, comprised 19 patients with a mean age of 43 years and an average follow-up of 38 months. They had larger, more invasive tumors, higher preoperative IGF-1 levels, higher immediate postoperative GH, and more residual tumors at 3 months, compared with the 60 patients in group B, who had preop GH levels of 40 ng/mL or less, a mean age of 47 years, and 43 months of follow-up.

In group A, three patients (15%) had remission at 3 months, but two patients had recurrence within 2 years. In group B, 35 patients (58%) had remission at 3 months with no recurrence during follow-up.

On univariate analysis, lower preoperative GH was a predictor of remission. In a multivariate analysis, however, lack of cavernous sinus invasion was the only predictor of remission.

"The relationship of GH elevation and cavernous sinus invasion should be further defined, as should the molecular fingerprint and the potential role of preoperative medical treatment in this group of patients," Dr. Anthony and his associates wrote.

No disclosures were reported.

[email protected]

Elevated growth hormone levels had a negative impact on remission in acromegaly patients undergoing transsphenoidal adenomectomies, researchers from Emory University in Atlanta concluded after a retrospective, multivariate analysis of case studies.

To determine the impact of preoperative growth hormone (GH), Dr. Jeremy Anthony and his associates examined the case files of 79 acromegaly patients who underwent transsphenoidal adenomectomy between 1994 and 2013 at Emory and assigned them to two groups on the basis of their preoperative GH levels, using 40 ng/mL as the cutoff.

Biochemical remission was defined as normal insulin-like growth factor 1 (IGF-1) during follow-up of more than 3 months in the absence of adjuvant therapy. The results were released at the annual meeting of the American Association of Clinical Endocrinologists on May 15 in Las Vegas.

Group A, with preoperative GH levels greater than 40 ng/mL, comprised 19 patients with a mean age of 43 years and an average follow-up of 38 months. They had larger, more invasive tumors, higher preoperative IGF-1 levels, higher immediate postoperative GH, and more residual tumors at 3 months, compared with the 60 patients in group B, who had preop GH levels of 40 ng/mL or less, a mean age of 47 years, and 43 months of follow-up.

In group A, three patients (15%) had remission at 3 months, but two patients had recurrence within 2 years. In group B, 35 patients (58%) had remission at 3 months with no recurrence during follow-up.

On univariate analysis, lower preoperative GH was a predictor of remission. In a multivariate analysis, however, lack of cavernous sinus invasion was the only predictor of remission.

"The relationship of GH elevation and cavernous sinus invasion should be further defined, as should the molecular fingerprint and the potential role of preoperative medical treatment in this group of patients," Dr. Anthony and his associates wrote.

No disclosures were reported.

[email protected]

Elevated growth hormone levels had a negative impact on remission in acromegaly patients undergoing transsphenoidal adenomectomies, researchers from Emory University in Atlanta concluded after a retrospective, multivariate analysis of case studies.

To determine the impact of preoperative growth hormone (GH), Dr. Jeremy Anthony and his associates examined the case files of 79 acromegaly patients who underwent transsphenoidal adenomectomy between 1994 and 2013 at Emory and assigned them to two groups on the basis of their preoperative GH levels, using 40 ng/mL as the cutoff.

Biochemical remission was defined as normal insulin-like growth factor 1 (IGF-1) during follow-up of more than 3 months in the absence of adjuvant therapy. The results were released at the annual meeting of the American Association of Clinical Endocrinologists on May 15 in Las Vegas.

Group A, with preoperative GH levels greater than 40 ng/mL, comprised 19 patients with a mean age of 43 years and an average follow-up of 38 months. They had larger, more invasive tumors, higher preoperative IGF-1 levels, higher immediate postoperative GH, and more residual tumors at 3 months, compared with the 60 patients in group B, who had preop GH levels of 40 ng/mL or less, a mean age of 47 years, and 43 months of follow-up.

In group A, three patients (15%) had remission at 3 months, but two patients had recurrence within 2 years. In group B, 35 patients (58%) had remission at 3 months with no recurrence during follow-up.

On univariate analysis, lower preoperative GH was a predictor of remission. In a multivariate analysis, however, lack of cavernous sinus invasion was the only predictor of remission.

"The relationship of GH elevation and cavernous sinus invasion should be further defined, as should the molecular fingerprint and the potential role of preoperative medical treatment in this group of patients," Dr. Anthony and his associates wrote.

No disclosures were reported.

[email protected]

SAN FRANCISCO – A new chemotherapy regimen of capecitabine and temozolomide was highly active against advanced treatment-resistant neuroendocrine tumors, based on the interim results of a phase II trial.

Tumors shrank in 43% of the 28 patients with various types of differentiated metastatic neuroendocrine tumors given the regimen, which is abbreviated CAPTEM. Disease stabilized in 54%.

Responses were durable, with a median progression-free survival approaching 2 years, reported lead investigator Dr. Robert Fine of the department of medicine at New York Presbyterian Hospital–Columbia University Medical Center.

"In this study, we’re seeing patients who had been given 6 months to live and are still alive 8 years after starting CAPTEM," he said in a prepared statement. "The regimen was effective even in patients with tumors that hadn’t responded to any other standard treatment, including chemotherapy, high-dose octreotide, small molecule inhibitors, radiation, or surgery."

For example, 42% of the patients with carcinoid tumors had a complete or partial response, and the others had stabilization of their disease. Median progression-free survival in this subset exceeded 31 months.

"Pituitary tumors were extraordinarily sensitive – end-stage people on respirators who were intubated with pituitary masses [compressing the spinal cord] were 100% responsive to the regimen, he said. Two of three patients had a complete response and were able to come off the ventilator and remain disease free with ongoing treatment at nearly 4 years out. The other patient had a partial response.

Toxicities were mild, and none of the patients had to be hospitalized or died as a result of the treatment, Dr. Fine commented in a press briefing before the results were presented at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

Dr. Smitha S. Krishnamurthi of Case Western Reserve University, Cleveland, who was the press briefing moderator, concurred that the regimen offers a new treatment option to patients who have exhausted the standard options.

"This regimen of CAPTEM vs. TEM (temozolomide) is under study now in a cooperative group trial for patients with pancreatic neuroendocrine cancer," she noted.

Dr. Fine and his team enrolled patients in the trial who had well- or moderately differentiated neuroendocrine tumors and either experienced progression despite standard therapy with high-dose octreotide (Sandostatin) or were ineligible for this treatment because of a negative octreotide scan. Other prior treatments, with the exception of the two drugs being studied, were allowed.

CAPTEM contains capecitabine (Xeloda), currently approved by the Food and Drug Administration for the treatment of breast and colorectal cancers, and temozolomide (Temodar), currently approved for the treatment of anaplastic astrocytoma and glioblastoma multiforme.

The drugs are given in sequence to maximize efficacy, according to Dr. Fine, as the capecitabine depletes tumor thymidine stores, which dramatically potentiates the antitumor effect of the temozolomide.

Of the 28 patients, 12 had carcinoid tumors, 11 had pancreatic tumors, 3 had pituitary tumors, and 2 had medullary thyroid tumors.

The patients were treated with CAPTEM on 28-day cycles, with capecitabine alone for 9 days, both capecitabine and temozolomide for 5 days, and the next 14 days off.

Overall, 11% of patients had a complete response, 32% had a partial response, 54% had stable disease, and 3% had progressive disease. These values translated to a response rate of 43% and a clinical benefit rate of 97%.

Median progression-free survival exceeded 22 months, and median overall survival, although still maturing, exceeded 29 months.

"The toxicities were extraordinarily light," commented Dr. Fine, who disclosed that he receives research funding from Merck.

The most common grade 3 or 4 toxicities were lymphopenia (seen in 35% of patients), hyperglycemia (6%), thrombocytopenia (3%), and diarrhea (3%).

None of the patients were hospitalized, developed opportunistic infections, or died as a result of CAPTEM treatment.

SAN FRANCISCO – A new chemotherapy regimen of capecitabine and temozolomide was highly active against advanced treatment-resistant neuroendocrine tumors, based on the interim results of a phase II trial.

Tumors shrank in 43% of the 28 patients with various types of differentiated metastatic neuroendocrine tumors given the regimen, which is abbreviated CAPTEM. Disease stabilized in 54%.

Responses were durable, with a median progression-free survival approaching 2 years, reported lead investigator Dr. Robert Fine of the department of medicine at New York Presbyterian Hospital–Columbia University Medical Center.

"In this study, we’re seeing patients who had been given 6 months to live and are still alive 8 years after starting CAPTEM," he said in a prepared statement. "The regimen was effective even in patients with tumors that hadn’t responded to any other standard treatment, including chemotherapy, high-dose octreotide, small molecule inhibitors, radiation, or surgery."

For example, 42% of the patients with carcinoid tumors had a complete or partial response, and the others had stabilization of their disease. Median progression-free survival in this subset exceeded 31 months.

"Pituitary tumors were extraordinarily sensitive – end-stage people on respirators who were intubated with pituitary masses [compressing the spinal cord] were 100% responsive to the regimen, he said. Two of three patients had a complete response and were able to come off the ventilator and remain disease free with ongoing treatment at nearly 4 years out. The other patient had a partial response.

Toxicities were mild, and none of the patients had to be hospitalized or died as a result of the treatment, Dr. Fine commented in a press briefing before the results were presented at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

Dr. Smitha S. Krishnamurthi of Case Western Reserve University, Cleveland, who was the press briefing moderator, concurred that the regimen offers a new treatment option to patients who have exhausted the standard options.

"This regimen of CAPTEM vs. TEM (temozolomide) is under study now in a cooperative group trial for patients with pancreatic neuroendocrine cancer," she noted.

Dr. Fine and his team enrolled patients in the trial who had well- or moderately differentiated neuroendocrine tumors and either experienced progression despite standard therapy with high-dose octreotide (Sandostatin) or were ineligible for this treatment because of a negative octreotide scan. Other prior treatments, with the exception of the two drugs being studied, were allowed.

CAPTEM contains capecitabine (Xeloda), currently approved by the Food and Drug Administration for the treatment of breast and colorectal cancers, and temozolomide (Temodar), currently approved for the treatment of anaplastic astrocytoma and glioblastoma multiforme.

The drugs are given in sequence to maximize efficacy, according to Dr. Fine, as the capecitabine depletes tumor thymidine stores, which dramatically potentiates the antitumor effect of the temozolomide.

Of the 28 patients, 12 had carcinoid tumors, 11 had pancreatic tumors, 3 had pituitary tumors, and 2 had medullary thyroid tumors.

The patients were treated with CAPTEM on 28-day cycles, with capecitabine alone for 9 days, both capecitabine and temozolomide for 5 days, and the next 14 days off.

Overall, 11% of patients had a complete response, 32% had a partial response, 54% had stable disease, and 3% had progressive disease. These values translated to a response rate of 43% and a clinical benefit rate of 97%.

Median progression-free survival exceeded 22 months, and median overall survival, although still maturing, exceeded 29 months.

"The toxicities were extraordinarily light," commented Dr. Fine, who disclosed that he receives research funding from Merck.

The most common grade 3 or 4 toxicities were lymphopenia (seen in 35% of patients), hyperglycemia (6%), thrombocytopenia (3%), and diarrhea (3%).

None of the patients were hospitalized, developed opportunistic infections, or died as a result of CAPTEM treatment.

SAN FRANCISCO – A new chemotherapy regimen of capecitabine and temozolomide was highly active against advanced treatment-resistant neuroendocrine tumors, based on the interim results of a phase II trial.

Tumors shrank in 43% of the 28 patients with various types of differentiated metastatic neuroendocrine tumors given the regimen, which is abbreviated CAPTEM. Disease stabilized in 54%.

Responses were durable, with a median progression-free survival approaching 2 years, reported lead investigator Dr. Robert Fine of the department of medicine at New York Presbyterian Hospital–Columbia University Medical Center.

"In this study, we’re seeing patients who had been given 6 months to live and are still alive 8 years after starting CAPTEM," he said in a prepared statement. "The regimen was effective even in patients with tumors that hadn’t responded to any other standard treatment, including chemotherapy, high-dose octreotide, small molecule inhibitors, radiation, or surgery."

For example, 42% of the patients with carcinoid tumors had a complete or partial response, and the others had stabilization of their disease. Median progression-free survival in this subset exceeded 31 months.

"Pituitary tumors were extraordinarily sensitive – end-stage people on respirators who were intubated with pituitary masses [compressing the spinal cord] were 100% responsive to the regimen, he said. Two of three patients had a complete response and were able to come off the ventilator and remain disease free with ongoing treatment at nearly 4 years out. The other patient had a partial response.

Toxicities were mild, and none of the patients had to be hospitalized or died as a result of the treatment, Dr. Fine commented in a press briefing before the results were presented at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

Dr. Smitha S. Krishnamurthi of Case Western Reserve University, Cleveland, who was the press briefing moderator, concurred that the regimen offers a new treatment option to patients who have exhausted the standard options.

"This regimen of CAPTEM vs. TEM (temozolomide) is under study now in a cooperative group trial for patients with pancreatic neuroendocrine cancer," she noted.

Dr. Fine and his team enrolled patients in the trial who had well- or moderately differentiated neuroendocrine tumors and either experienced progression despite standard therapy with high-dose octreotide (Sandostatin) or were ineligible for this treatment because of a negative octreotide scan. Other prior treatments, with the exception of the two drugs being studied, were allowed.

CAPTEM contains capecitabine (Xeloda), currently approved by the Food and Drug Administration for the treatment of breast and colorectal cancers, and temozolomide (Temodar), currently approved for the treatment of anaplastic astrocytoma and glioblastoma multiforme.

The drugs are given in sequence to maximize efficacy, according to Dr. Fine, as the capecitabine depletes tumor thymidine stores, which dramatically potentiates the antitumor effect of the temozolomide.

Of the 28 patients, 12 had carcinoid tumors, 11 had pancreatic tumors, 3 had pituitary tumors, and 2 had medullary thyroid tumors.

The patients were treated with CAPTEM on 28-day cycles, with capecitabine alone for 9 days, both capecitabine and temozolomide for 5 days, and the next 14 days off.

Overall, 11% of patients had a complete response, 32% had a partial response, 54% had stable disease, and 3% had progressive disease. These values translated to a response rate of 43% and a clinical benefit rate of 97%.

Median progression-free survival exceeded 22 months, and median overall survival, although still maturing, exceeded 29 months.

"The toxicities were extraordinarily light," commented Dr. Fine, who disclosed that he receives research funding from Merck.

The most common grade 3 or 4 toxicities were lymphopenia (seen in 35% of patients), hyperglycemia (6%), thrombocytopenia (3%), and diarrhea (3%).

None of the patients were hospitalized, developed opportunistic infections, or died as a result of CAPTEM treatment.

SAN FRANCISCO – Measurements of prolactin levels during inferior petrosal sinus sampling did not help localize pituitary adenomas in patients with Cushing’s disease in a study of 28 patients, contradicting findings from a previous study of 28 patients.

The value of prolactin measurements in tumor localization using inferior petrosal sinus sampling (IPSS) remains unclear and needs further study in a larger, prospective study, Dr. Susmeeta T. Sharma said at the Endocrine Society’s Annual Meeting. The current and previous studies were retrospective analyses.

Although IPSS has been considered the standard test in patients with ACTH-dependent Cushing’s syndrome to differentiate between ectopic ACTH secretion and Cushing’s disease, there has been controversy about its value in localizing adenomas within the pituitary gland once a biochemical diagnosis of Cushing’s disease has been made. Various studies that used an intersinus ACTH ratio of 1.4 or greater before or after corticotropin-releasing hormone (CRH) stimulation have reported success rates as low as 50% and as high as 100% for tumor location.

A previous retrospective study of 28 patients with Cushing’s disease reported that adjusting the ACTH intersinus gradient by levels of prolactin before or after CRH stimulation, and combining the prolactin-adjusted ACTH intersinus ratio, improved pituitary adenoma localization. Magnetic resonance imaging (MRI) alone correctly localized the pituitary adenoma in 17 patients (61%), a prolactin-adjusted ACTH intersinus ratio of at least 1.4 improved the localization rate to 21 patients (75%), and combining MRI and the prolactin-adjusted ACTH intersinus ratio improved localization further to 23 patients, or 82% (Clin. Endocrinol. 2012;77:268-74).

The findings inspired the current retrospective study. The investigators looked at prolactin levels measured in stored petrosal and peripheral venous samples at baseline and at the time of peak ACTH levels after CRH stimulation for 28 patients with Cushing’s disease and ACTH-positive pituitary adenomas who underwent IPSS in 2007-2013. The investigators calculated prolactin-adjusted values by dividing each ACTH value by the concomitant ipsilateral prolactin value. They used an intersinus ACTH ratio of 1.4 or greater to predict tumor location.

At surgery, 26 patients had a single lateral tumor (meaning its epicenter was not in the midline), 1 patient had a central microadenoma, and 1 patient had a macroadenoma, reported Dr. Sharma of the National Institute of Child Health and Human Development, Bethesda, Md.

MRI findings accurately identified the location of 21 of the 26 lateral tumors (81%), compared with accurate localization in 18 patients using either the unadjusted ACTH intersinus ratio or the prolactin-adjusted ACTH intersinus ratio (69% for each), she said.

Incorrect tumor localization occurred with one patient using MRI alone and seven patients using either ratio. In four patients whose tumors could not be localized by MRI, the uncorrected and prolactin-adjusted ratios localized one tumor correctly and three tumors incorrectly. Only MRI correctly localized the one central microadenoma.

"We did not find any difference in localization rates by measurement of prolactin during IPSS," she said. The small size of the study and its retrospective design invite further research in a more robust study.

Dr. Sharma reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Measurements of prolactin levels during inferior petrosal sinus sampling did not help localize pituitary adenomas in patients with Cushing’s disease in a study of 28 patients, contradicting findings from a previous study of 28 patients.

The value of prolactin measurements in tumor localization using inferior petrosal sinus sampling (IPSS) remains unclear and needs further study in a larger, prospective study, Dr. Susmeeta T. Sharma said at the Endocrine Society’s Annual Meeting. The current and previous studies were retrospective analyses.

Although IPSS has been considered the standard test in patients with ACTH-dependent Cushing’s syndrome to differentiate between ectopic ACTH secretion and Cushing’s disease, there has been controversy about its value in localizing adenomas within the pituitary gland once a biochemical diagnosis of Cushing’s disease has been made. Various studies that used an intersinus ACTH ratio of 1.4 or greater before or after corticotropin-releasing hormone (CRH) stimulation have reported success rates as low as 50% and as high as 100% for tumor location.

A previous retrospective study of 28 patients with Cushing’s disease reported that adjusting the ACTH intersinus gradient by levels of prolactin before or after CRH stimulation, and combining the prolactin-adjusted ACTH intersinus ratio, improved pituitary adenoma localization. Magnetic resonance imaging (MRI) alone correctly localized the pituitary adenoma in 17 patients (61%), a prolactin-adjusted ACTH intersinus ratio of at least 1.4 improved the localization rate to 21 patients (75%), and combining MRI and the prolactin-adjusted ACTH intersinus ratio improved localization further to 23 patients, or 82% (Clin. Endocrinol. 2012;77:268-74).

The findings inspired the current retrospective study. The investigators looked at prolactin levels measured in stored petrosal and peripheral venous samples at baseline and at the time of peak ACTH levels after CRH stimulation for 28 patients with Cushing’s disease and ACTH-positive pituitary adenomas who underwent IPSS in 2007-2013. The investigators calculated prolactin-adjusted values by dividing each ACTH value by the concomitant ipsilateral prolactin value. They used an intersinus ACTH ratio of 1.4 or greater to predict tumor location.

At surgery, 26 patients had a single lateral tumor (meaning its epicenter was not in the midline), 1 patient had a central microadenoma, and 1 patient had a macroadenoma, reported Dr. Sharma of the National Institute of Child Health and Human Development, Bethesda, Md.

MRI findings accurately identified the location of 21 of the 26 lateral tumors (81%), compared with accurate localization in 18 patients using either the unadjusted ACTH intersinus ratio or the prolactin-adjusted ACTH intersinus ratio (69% for each), she said.

Incorrect tumor localization occurred with one patient using MRI alone and seven patients using either ratio. In four patients whose tumors could not be localized by MRI, the uncorrected and prolactin-adjusted ratios localized one tumor correctly and three tumors incorrectly. Only MRI correctly localized the one central microadenoma.

"We did not find any difference in localization rates by measurement of prolactin during IPSS," she said. The small size of the study and its retrospective design invite further research in a more robust study.

Dr. Sharma reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Measurements of prolactin levels during inferior petrosal sinus sampling did not help localize pituitary adenomas in patients with Cushing’s disease in a study of 28 patients, contradicting findings from a previous study of 28 patients.

The value of prolactin measurements in tumor localization using inferior petrosal sinus sampling (IPSS) remains unclear and needs further study in a larger, prospective study, Dr. Susmeeta T. Sharma said at the Endocrine Society’s Annual Meeting. The current and previous studies were retrospective analyses.

Although IPSS has been considered the standard test in patients with ACTH-dependent Cushing’s syndrome to differentiate between ectopic ACTH secretion and Cushing’s disease, there has been controversy about its value in localizing adenomas within the pituitary gland once a biochemical diagnosis of Cushing’s disease has been made. Various studies that used an intersinus ACTH ratio of 1.4 or greater before or after corticotropin-releasing hormone (CRH) stimulation have reported success rates as low as 50% and as high as 100% for tumor location.

A previous retrospective study of 28 patients with Cushing’s disease reported that adjusting the ACTH intersinus gradient by levels of prolactin before or after CRH stimulation, and combining the prolactin-adjusted ACTH intersinus ratio, improved pituitary adenoma localization. Magnetic resonance imaging (MRI) alone correctly localized the pituitary adenoma in 17 patients (61%), a prolactin-adjusted ACTH intersinus ratio of at least 1.4 improved the localization rate to 21 patients (75%), and combining MRI and the prolactin-adjusted ACTH intersinus ratio improved localization further to 23 patients, or 82% (Clin. Endocrinol. 2012;77:268-74).

The findings inspired the current retrospective study. The investigators looked at prolactin levels measured in stored petrosal and peripheral venous samples at baseline and at the time of peak ACTH levels after CRH stimulation for 28 patients with Cushing’s disease and ACTH-positive pituitary adenomas who underwent IPSS in 2007-2013. The investigators calculated prolactin-adjusted values by dividing each ACTH value by the concomitant ipsilateral prolactin value. They used an intersinus ACTH ratio of 1.4 or greater to predict tumor location.

At surgery, 26 patients had a single lateral tumor (meaning its epicenter was not in the midline), 1 patient had a central microadenoma, and 1 patient had a macroadenoma, reported Dr. Sharma of the National Institute of Child Health and Human Development, Bethesda, Md.

MRI findings accurately identified the location of 21 of the 26 lateral tumors (81%), compared with accurate localization in 18 patients using either the unadjusted ACTH intersinus ratio or the prolactin-adjusted ACTH intersinus ratio (69% for each), she said.

Incorrect tumor localization occurred with one patient using MRI alone and seven patients using either ratio. In four patients whose tumors could not be localized by MRI, the uncorrected and prolactin-adjusted ratios localized one tumor correctly and three tumors incorrectly. Only MRI correctly localized the one central microadenoma.

"We did not find any difference in localization rates by measurement of prolactin during IPSS," she said. The small size of the study and its retrospective design invite further research in a more robust study.

Dr. Sharma 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 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]