Lucia Schwyzer, Robert M. Starke, John A. Jane Jr. and Edward H. Oldfield
Correlation between tumor volume and hormone levels in individual patients would permit calculation of the fraction of tumor removed by surgery, by measuring postoperative hormone levels. The goals of this study were to examine the relationship between tumor volume, growth hormone (GH), and insulin-like growth factor–1 (IGF-1) levels, and to assess the correlation between percent tumor removal and the reduction in plasma GH and IGF-1 in patients with acromegaly.
The 3D region of interest–based volumetric method was used to measure tumor volume via MRI before and after surgery in 11 patients with GH-secreting adenomas. The volume of residual tumor as a fraction of preoperative tumor volume was correlated with GH levels before and after surgery. Examination of this potential correlation required selection of patients with acromegaly who 1) had incomplete tumor removal, 2) had precise measurements of initial and residual tumor, and 3) were not on medical therapy.
Densely granulated tumors produced more peripheral GH per mass of tumor than sparsely granulated tumors (p = 0.04). There was a correlation between GH and IGF-1 levels (p = 0.001). Although there was no close correlation between tumor size and peripheral GH levels, after normalizing each tumor to its own plasma GH level and tumor volume, a comparison of percent tumor resection with percent drop in plasma GH yielded a high correlation coefficient (p = 0.006).
Densely granulated somatotropinomas produce more GH per mass of tumor than do sparsely granulated tumors. Each GH-secreting tumor has its own intrinsic level of GH production per mass of tumor, which is homogeneous over the tumor mass, and which varies greatly between tumors. In most patients the fraction of a GH-secreting tumor removed by surgery can be accurately estimated by simply comparing plasma GH levels after surgery to those before surgery.
Robert M. Starke, Brian J. Williams, John A. Jane Jr. and Jason P. Sheehan
Nonfunctioning pituitary macroadenomas often recur after microsurgery and thereby require further treatment. Gamma Knife surgery (GKS) has been used to treat recurrent adenomas. In this study, the authors evaluated outcomes following GKS of nonfunctioning pituitary macroadenomas and assessed predictors of tumor control, neurological deficits, and delayed hypopituitarism.
Between June 1989 and March 2010, 140 consecutive patients with nonfunctioning pituitary macroadenomas were treated using GKS at the University of Virginia. The median patient age was 51 years (range 21–82 years), and 56% of patients were male. Mean tumor volume was 5.6 cm3 (range 0.6–35 cm3). Thirteen patients were treated with GKS as primary therapy, and 127 had undergone at least 1 open resection prior to GKS. Ninety-three patients had a history of hormone therapy prior to GKS. The mean maximal dose of GKS was 38.6 Gy (range 10–70 Gy), the mean marginal dose was 18 Gy (range 5–25 Gy), and the mean number of isocenters was 9.8 (range 1–26). Follow-up evaluations were performed in all 140 patients, ranging from 0.5 to 17 years (mean 5 years, median 4.2 years).
Tumor volume remained stable or decreased in 113 (90%) of 125 patients with available follow-up imaging. Kaplan-Meier analysis demonstrated radiographic progression free survival at 2, 5, 8, and 10 years to be 98%, 97%, 91%, and 87%, respectively. In multivariate analysis, a tumor volume greater than 5 cm3 (hazard ratio = 5.0, 95% CI 1.5–17.2; p = 0.023) was the only factor predictive of tumor growth. The median time to tumor progression was 14.5 years. Delayed hypopituitarism occurred in 30.3% of patients. No factor was predictive of post-GKS hypopituitarism. A new or worsening cranial nerve deficit occurred in 16 (13.7%) of 117 patients. Visual decline was the most common neurological deficit (12.8%), and all patients experiencing visual decline had evidence of tumor progression. In multivariate analysis, a tumor volume greater than 5 cm3 (OR = 3.7, 95% CI 1.2–11.7; p = 0.025) and pre-GKS hypopituitarism (OR = 7.5, 95% CI 1.1–60.8; p = 0.05) were predictive of a new or worsened neurological deficit.
In patients with nonfunctioning pituitary macroadenomas, GKS confers a high rate of tumor control and a low rate of neurological deficits. The most common complication following GKS is delayed hypopituitarism, and this occurs in a minority of patients.
Stephen J. Monteith, Robert M. Starke, John A. Jane Jr. and Edward H. Oldfield
Subnormal postoperative serum cortisol levels indicate successful surgery and predict long-term remission of Cushing disease. Given the short serum half-lives of adrenocorticotropic hormone (ACTH) and cortisol, it is unclear why the decline in cortisol postoperatively is delayed for 18–36 hours. Furthermore, the relevance of the rate of cortisol drop immediately after surgery has not been investigated.
Patient data were analyzed from a prospectively accrued database. After surgery, cortisol replacement was withheld and serum cortisol measurements were obtained every 6 hours until values of 1.0–2.0 μg/dl or less were reached. The authors selected patients in whom serum cortisol dropped to 2 μg/dl or less after surgery (101 patients). Tumor resection was categorized as follows: 1) complete resection using the histological pseudocapsule as a surgical capsule, 2) complete piecemeal resection), 3) known incomplete resection, and 4) total hypophysectomy.
The median time to reach a cortisol level of less than or equal to 2.0 μg/dl was 9.9, 19.4, 25.3, and 29.5 hours with hypophysectomy, pseudocapsule, incomplete resection, and piecemeal techniques, respectively. Pseudocapsule resection produced a faster decline in cortisol than piecemeal techniques (p = 0.0001), but not as rapid a decline as hypophysectomy (p = 0.033).
Complete resection by other techniques is associated with delayed cortisol decline compared with pseudocapsule surgery, which may represent the product of residual tumor cells and therefore may explain the higher rate of recurrent disease associated with piecemeal techniques. The prompt drop in cortisol after hypophysectomy compared with patients with pseudocapsule surgery suggests that the corticotrophs of the normal gland can secrete ACTH for 10–36 hours after surgery despite prolonged and severe hypercortisolism.
Robert M. Starke, John A. Jane Jr., Ashok R. Asthagiri and John A. Jane Sr.
2010 AANS Annual Meeting Philadelphia, Pennsylvania May 1–5, 2010