Nippoldt, Todd B.

Summary Objective We aimed to assess the prevalence of impulse control disorders ( ICD s) in patients with prolactin‐secreting adenomas treated with dopamine agonists ( DA s), to identify associated factors and to compare it with a group of patients with nonfunctioning pituitary adenoma. Subjects, Design and Measurement In a postal survey, 77 patients from Group A (patients with prolactinomas and present or past use of DA s) and 70 patients from Group B (patients with nonfunctioning pituitary adenoma and no history of DA therapy) responded to a questionnaire on compulsive shopping, pathologic gambling, hypersexuality and punding. Associated clinical information was obtained through the survey and review of medical electronic records. Results The total ICD prevalence was 24·68% in Group A and 17·1% in Group B ( P = 0·31). Group A had an increased rate of hypersexuality ( P = 0·03). Subgroup analysis revealed that men in Group A had a significantly increased frequency of total ICD s when compared with men in Group B (27·7 vs 3·7%, P = 0·01). No differences in rates of total ICD s were found between women of Groups A and B (20 vs 25·6%, P = 0·78). No association with type, dose or duration of treatment with DA was noted. Conclusions Males with prolactinomas treated with DA s were 9·9 times more likely to develop an ICD than their counterparts with nonfunctioning pituitary adenomas. Until prospective studies on the relationship of DA use in patients with prolactinoma and ICD s are available, the authors propose that patients with prolactinoma be forewarned of possible ICD development with DA therapy.

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.

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.

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.

AbstractBackgroundCushing’s syndrome (CS), due to multiple etiologies, is a disorder associated with the ravages of cortisol excess. The purpose of this review article is to provide a historical synopsis of surgery for CS, review a recent 10‐year period of operative management at a tertiary care facility, and to outline a practical approach to diagnosis and management.Materials and MethodsFrom 1996 to 2005, 298 patients underwent 322 operative procedures for CS at Mayo Clinic, Rochester, Minnesota. A retrospective chart review was carried out. Data was gathered regarding demographics, preoperative assessment, procedures performed, and outcomes. Data are presented as counts and percentages. Five‐year survival rates were calculated where applicable by the Kaplan‐Meier method. Statistical analysis was carried out with SAS, version 9 (SAS Institute, Inc., Cary, NC).ResultsTwo‐hundred thirty‐one patients (78%) had ACTH‐dependent CS and 67 patients (22%) had ACTH‐independent CS. One‐hundred ninety‐six patients (66%) had pituitary‐dependent CS and 35 patients (12%) had ectopic ACTH syndrome. Fifty‐four patients (18%) had cortisol‐secreting adenomas, 10 patients (3%) had cortisol‐producing adrenocortical carcinomas, and 1% had other causes. Cure rates for first time pituitary operations (transsphenoidal, sublabial, and endonasal) were 80% and 55% for reoperations. Most benign adrenal processes could be managed laparoscopically. Five‐year survival rates (all causes) were 90%, 51%, and 23% for adrenocortical adenomas, ectopic ACTH syndrome, and adrenocortical carcinomas, respectively.ConclusionsSurgery for CS is highly successful for pituitary‐dependent CS and most ACTH‐independent adrenal causes. Bilateral total adrenalectomy can also provide effective palliation from the ravages of hypercortisolism in patients with ectopic ACTH syndrome and for those who have failed transsphenoidal surgery. Unfortunately, to date, adrenocortical carcinomas are rarely cured. Future successes with this disease will likely depend on a better understanding of tumor biology, more effective adjuvant therapies and earlier detection. Clearly, IPSS, advances in cross‐sectional imaging, along with developments in transsphenoidal and laparoscopic surgery, have had the greatest impact on today’s management of the complex patient with CS.

Objective— To confirm insulinoma as the cause of hypoglycemia in a patient with NIDDM and determine the frequency of the co-occurrence of these two conditions. Research Design and Methods— The patient underwent an in-hospital prolonged fast (≤72 h), according to standard protocol, and an ultrasound examination of the pancreas. All cases of histologically confirmed insulinoma at this institution over the period of 1927–1992 were reviewed to determine the prevalence of pre-existent diabetes mellitus. Results— After 10 h of fasting, plasma glucose was low (1.89 mM); plasma insulin (258 pM) and C-peptide (1.39 nM) were elevated in the absence of sulfonylurea in the plasma. An insulinoma detected by ultrasonography was removed surgically with subsequent reoccurrence of insulin-requiring diabetes. Among 313 cases of insulinoma confirmed at this institution, this patient is the only one with pre-existent diabetes mellitus. Conclusions— Insulinoma occurs extraordinarily rarely in patients with pre-existing NIDDM.

Abstract To determine if replacement of GH improves BMD in adult-onset GHD, we administered GH in physiologic amounts to men and women with GHD. GH replacement significantly increased spine BMD in the men by 3.8%. Introduction: Growth hormone (GH) deficiency (GHD) acquired in adulthood results in diminished BMD; the evidence that replacement of GH improves BMD is not conclusive. We therefore performed a randomized, placebo-controlled trial to determine whether GH replacement would increase lumbar spine BMD in a combined group of men and women with adult-onset GHD. Materials and Methods: We randomized 67 men and women to receive GH (n = 33) or placebo (n = 34) for 2 yr. The GH dose was initially 2 μg/kg body weight/d, increased gradually to a maximum of 12 μg/kg/d and adjusted to maintain a normal IGF-I concentration for age and sex. BMD was assessed before treatment and at 6, 12, 18, and 24 mo of treatment. Fifty-four subjects completed the protocol. Results: BMD of the lumbar spine in the entire group increased by 2.9 ± 3.9% above baseline in the GH-treated subjects, which was significantly (p = 0.037) greater than the 1.4 ± 4.5% increase in the placebo-treated subjects. In a secondary analysis, spine BMD in GH-treated men increased 3.8 ± 4.3% above baseline, which was significantly (p = 0.001) greater than that in placebo-treated men (0.4 ± 4.7%), but the change in GH-treated women was not significantly different from that in placebo-treated women. Treatment with GH did not increase total hip BMD more than placebo treatment after 2 yr. Conclusions: We conclude that GH replacement in men who have adult-onset GHD improves their spine BMD, but we cannot draw any conclusions about the effect of GH replacement on spine BMD in women with adult-onset GHD.