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Jamie J. Van Gompel, Todd B. Nippoldt, Dominique M. Higgins, and Fredric B. Meyer

Object

Obesity as a consequence of management of pediatric craniopharyngioma is a well-described phenomenon related to the degree of hypothalamic involvement. However, weight change and obesity have not been analyzed in adult patients. Therefore, the purpose of this study was 1) to evaluate the pattern of postoperative weight gain related to preoperative body mass index (BMI), 2) determine if postoperative weight gain is an issue in adult patients, and 3) develop an objective MR imaging grading system to predict risk of postoperative weight gain and obesity in adults treated for craniopharyngioma.

Methods

The authors retrospectively screened 296 patients with known craniopharyngioma for the following inclusion criteria: pathologically confirmed craniopharyngioma, index surgery at the authors' institution, and operative weight and height recorded with at least 3 months of follow-up including body weight measurement. Patients aged 18 years or younger were excluded, yielding 28 cases for analysis. Cases of craniopharyngiomas were compared with age- and sex-matched controls (pituitary adenoma patients) to evaluate the pattern and significance of perioperative weight changes.

Results

Mean age was 46 ± 17 years at surgery, and 64% of the patients were male. Complete resection was achieved in 71% of cases. There was no correlation of preoperative BMI and postoperative weight gain testing in a linear model. Sixty-one percent and 46% of patients had postoperative weight gains greater than 4 and 9%, respectively.

Comparing craniopharyngioma patients (cases) to age- and sex-matched controls, the preoperative BMIs were similar (p = 0.93) between cases (mean 28.9 [95% CI 30.9–26.9]) and controls (mean 29.3 [95% CI 31.9–26.7]). However, there was a trend to a greater mean postoperative weight change (percentage) in cases (10.1%) than in controls (5.6%) (p = 0.24). Hypothalamic T2 signal change and irregular contrast enhancement correlated and predicted higher-grade hypothalamic involvement. Furthermore, they can be used to objectively grade hypothalamic involvement as the authors propose. Progressive hypothalamic involvement correlated with larger postoperative weight gains (p = 0.022); however, hypothalamic involvement did not correlate with preoperative BMI (p = 0.5).

Conclusions

Postoperative weight gain in adult patients undergoing surgery for craniopharyngioma is a significant problem and correlates with hypothalamic involvement, as it does in pediatric patients. Finally, objective MR imaging criteria can be used to predict risk of postoperative weight gain and aid in grading of hypothalamic involvement.

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Dominique M. Higgins, Jamie J. Van Gompel, Todd B. Nippoldt, and Fredric B. Meyer

Object

Rathke cleft cysts (RCCs) are benign masses arising from the embryological Rathke pouch, and are commonly treated by transsphenoidal surgery. The authors retrospectively compared RCC extent of resection—either gross-total resection (GTR) or decompression—to the primary outcome measure, which was recurrences resulting in repeat surgery, and the secondary outcome measure, which was complications.

Methods

Seventy-four patients presenting to the neurosurgical department with RCC were analyzed retrospectively. Sixty-eight patients had a total of 78 surgical procedures, with the diagnosis of RCC confirmed by histological investigation; of these, 61 patients had adequate operative notes for the authors to evaluate extent of resection. Groups were separated into GTR (32 patients) or decompression (subtotal resection or fenestration into the sphenoid sinus; 29 patients) based on operative notes and postoperative imaging. The mean follow-up duration was 60.5 ± 72.1 months (the mean is expressed ± SD throughout).

Results

The average age at the time of the initial surgery was 42.8 ± 17.4 years, and 70% of patients were female. The mean cyst diameter preoperatively was 16.9 ± 17.8 mm. Eight patients had repeat surgery, our primary outcome measure; 3 repeat operations occurred in the GTR group, and 5 in the decompression group. There was no significant difference in recurrence when comparing groups (GTR 9%, decompression 17%; p = 0.36). There were no major complications; however, analysis of postoperative minor complications revealed that 11 (34%) GTRs resulted in surgical complications, whereas the decompression cohort accounted for only 3 complications (10%) (p = 0.03), with diabetes insipidus (6) and CSF leaks (5) being the most common. Gross-total resection also resulted in an increase in postoperative hyperprolactinemia compared with decompression (p = 0.03).

Conclusions

It appears that RCCs require repeat surgery in 13% of cases, and attempted GTR does not appear to reduce the overall rate of recurrence. However, more aggressive resections are associated with more complications in this series.

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Bruce E. Pollock, Jeffrey T. Jacob, Paul D. Brown, and Todd B. Nippoldt

Object

The authors reviewed outcomes after stereotactic radiosurgery for patients with acromegaly and analyzed factors associated with biochemical remission.

Methods

Retrospective analysis was performed for 46 consecutive cases of growth hormone (GH)–producing pituitary adenomas treated by radiosurgery between 1991 and 2004. Biochemical remission was defined as a fasting GH less than 2 ng/ml and a normal age- and sex-adjusted insulin-like growth factor–I (IGF-I) level while patients were not receiving any pituitary suppressive medications. The median follow up after radiosurgery was 63 months (range 22–168 months).

Twenty-three patients (50%) had biochemical remission documented at a median of 36 months (range 6–63 months) after one radiosurgical procedure. The actuarial rates of biochemical remission at 2 and 5 years after radiosurgery were 11 and 60%, respectively. Multivariate analysis showed that IGF-I levels less than 2.25 times the upper limit of normal (hazard ratio [HR] 2.9, 95% confidence interval [CI] 1.2–6.9, p = 0.02) and the absence of pituitary suppressive medications at the time of radiosurgery (HR 4.2, 95% CI 1.4–13.2, p = 0.01) correlated with biochemical remission. The incidence of new anterior pituitary deficits was 10% at 2 years and 33% at 5 years.

Conclusions

Discontinuation of pituitary suppressive medications at least 1 month before radiosurgery significantly improved endocrine outcomes for patients with acromegaly. Patients with GH–producing pituitary adenomas should not undergo further radiation therapy or surgery for at least 5 years after radiosurgery because GH and IGF-I levels continue to normalize over that interval.

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Bruce E. Pollock, Todd B. Nippoldt, Scott L. Stafford, Robert L. Foote, and Charles F. Abboud

Object. The goal of this study was to determine factors associated with endocrine normalization after radiosurgery is performed in patients with hormone-producing pituitary adenomas.

Methods. Between 1990 and 1999, 43 patients with hormone-producing pituitary adenomas underwent radiosurgery: 26 patients with growth hormone (GH)—producing tumors, nine with adrenocorticotrophic hormone—producing tumors, seven with tumors that produced prolactin (PRL) alone, and one with a tumor that secreted both GH and PRL. The median patient age was 42 years. Thirty-seven patients (86%) had undergone surgery earlier and in 30 (70%) there was tumor extension into the cavernous sinus. The product-limit method was used to calculate endocrine normalization while patients were not receiving any hormone-suppressive medication. The median follow-up period after radio-surgery was 36 months (range 12–108 months).

In 20 patients (47%) there was normalization of hormone secretion at a median of 14 months (range 2–44 months) after radiosurgery; no correlation was found between tumor type and cure. Actuarial cure rates were 20, 32, and 61% at 1, 2, and 4 years posttreatment. Multivariate analysis demonstrated that the absence of hormone-suppressive medications at the time of radiosurgery (relative risk 8.9, 95% confidence interval [CI] 1.2–68.7, p = 0.04) and maximum radiation doses greater than 40 Gy (relative risk 3.9, 95% CI 1.3–11.7, p = 0.02) correlated with an endocrine cure. A new anterior pituitary deficiency developed in seven patients (16%), temporal lobe necrosis was identified in two patients, an asymptomatic internal carotid artery stenosis was detected in two patients, and unilateral blindness occurred in one patient.

Conclusions. Radiosurgery provides an endocrine cure for many patients with persistent or recurrent hormone-producing pituitary adenomas. Further study is needed to determine whether pituitary hormone—suppressive medications have a radioprotective effect.

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John L. D. Atkinson, Jan L. Kasperbauer, E. Meredith James, John I. Lane, and Todd B. Nippoldt

✓ Ultrasonography has been used in neurosurgical operative procedures for several decades. The authors report the case of a large pituitary tumor that was subtotally resected using endoscopy via the transnasal—transsphenoidal approach, with the aid of transcranial real-time ultrasound. To our knowledge, this is the first reported case in which intraoperative transcranial—transdural real-time ultrasound was used to facilitate the resection of a skull base tumor.

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Yoshihiro Yamamoto, Dudley H. Davis, Todd B. Nippoldt, William F. Young Jr., John Huston III, and Joseph E. Parisi

✓ Inferior petrosal sinus sampling (IPSS) for adrenocorticotropic hormone (ACTH) levels in patients with Cushing's syndrome has become a useful method to distinguish ACTH-secreting pituitary tumors (Cushing's disease) from other causes of the syndrome, principally ectopic adrenocorticotropin secretion by an occult tumor. Although the test is generally regarded as highly specific, the authors recently encountered two patients whose IPSS measurements were false-positive for Cushing's disease. The results of IPSS suggested a pituitary origin of ACTH secretion in both patients, but transsphenoidal surgery failed to disclose a pituitary adenoma or to improve postoperative plasma cortisol levels. Both patients subsequently were found to have an ACTH-secreting carcinoid tumor of the lung. The false-positive IPSS studies were due to periodic hormonogenesis. The patients must be hypercortisolemic at the time IPSS is performed for the study to be valid.

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Christopher S. Graffeo, Avital Perry, Lucas P. Carlstrom, Fredric B. Meyer, John L. D. Atkinson, Dana Erickson, Todd B. Nippoldt, William F. Young Jr., Bruce E. Pollock, and Jamie J. Van Gompel

OBJECTIVE

Nelson-Salassa syndrome (NSS) is a rare consequence of bilateral adrenalectomy (ADX) for refractory hypercortisolism due to Cushing disease (CD). Although classically defined by rapid growth of a large, invasive, adrenocorticotropin hormone (ACTH)–secreting pituitary tumor after bilateral ADX that causes cutaneous hyperpigmentation, visual disturbance, and high levels of ACTH, clinical experience suggests more variability.

METHODS

The authors conducted a retrospective chart review of all patients 18 years and older with a history of bilateral ADX for CD, adequate pituitary MRI, and at least 2 years of clinical follow-up. Statistical tests included Student's t-test, chi-square test, Fisher's exact test, multivariate analysis, and derived receiver operating characteristic curves.

RESULTS

Between 1956 and 2015, 302 patients underwent bilateral ADX for the treatment of hypercortisolism caused by CD; 88 had requisite imaging and follow-up (mean 16 years). Forty-seven patients (53%) had radiographic progression of pituitary disease and were diagnosed with NSS. Compared with patients who did not experience progression, those who developed NSS were significantly younger at the time of CD diagnosis (33 vs 44 years, p = 0.007) and at the time of bilateral ADX (35 vs 49 years, p = 0.007), had larger tumors at the time of CD diagnosis (6 mm vs 1 mm, p = 0.03), and were more likely to have undergone external-beam radiation therapy (EBRT, 43% vs 12%, p = 0.005). Among NSS patients, the mean tumor growth was 7 mm/yr (SE 6 mm/yr); the median tumor growth was 3 mm/yr. Prevalence of pathognomonic symptoms was low; the classic triad occurred in 9%, while hyperpigmentation without visual field deficit was observed in 23%, and 68% remained asymptomatic despite radiographic disease progression. NSS required treatment in 14 patients (30%).

CONCLUSIONS

NSS is a prevalent sequela of CD after bilateral ADX and affects more than 50% of patients. However, although radiological evidence of NSS is common, it is most often clinically indolent, with only a small minority of patients developing the more aggressive disease phenotype characterized by clinically meaningful symptoms and indications for treatment. Young age at the time of CD diagnosis or treatment with bilateral ADX, large tumor size at CD diagnosis, and EBRT are associated with progression to NSS and may be markers of aggressiveness.