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Edward H. Oldfield, John A. Jane Jr., Michael O. Thorner, Carrie L. Pledger, Jason P. Sheehan and Mary Lee Vance

OBJECTIVE

The relationship between growth hormone (GH) and insulin-like growth factor–1 (IGF-1) in patients with acromegaly as serial levels drop over time after treatment has not been examined previously. Knowledge of this relationship is important to correlate pretreatment levels that best predict response to treatment. To examine the correlation between GH and IGF-1 and IGF-1 z-scores over a wide range of GH levels, the authors examined serial GH and IGF-1 levels at intervals before and after surgery and radiosurgery for acromegaly.

METHODS

This retrospective analysis correlates 414 pairs of GH and IGF-1 values in 93 patients with acromegaly.

RESULTS

Absolute IGF-1 levels increase linearly with GH levels only up to a GH of 4 ng/ml, and with IGF-1 z-scores only to a GH level of 1 ng/ml. Between GH levels of 1 and 10 ng/ml, increases in IGF-1 z-scores relative to changes in GH diminish and then plateau at GH concentrations of about 10 ng/ml. From patient to patient there is a wide range of threshold GH levels beyond which IGF-1 increases are no longer linear, GH levels at which the IGF-1 response plateaus, IGF-1 levels at similar GH values after the IGF-1 response plateaus, and of IGF-1 levels at similar GH levels.

CONCLUSIONS

In acromegaly, although IGF-1 levels represent a combination of the integrated effects of GH secretion and GH action, the tumor produces GH, not IGF-1. Nonlinearity between GH and IGF-1 occurs at GH levels far below those previously recognized. To monitor tumor activity and tumor viability requires measurement of GH levels.

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Corey Raffel

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Mahmoud Messerer, Giulia Cossu, Roy Thomas Daniel and Emmanuel Jouanneau

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Neal F. Kassell, James C. Torner, John A. Jane, E. Clarke Haley Jr., Harold P. Adams and participants

✓ A prospective, observational clinical trial was conducted by the International Cooperative Study on the Timing of Aneurysm Surgery to determine the best time in relation to the hemorrhage for surgical treatment of ruptured intracranial aneurysms. Sixty-eight centers contributed 3521 patients in a 2½-year period beginning in December, 1980. Analysis by a prespecified “planned” surgery interval demonstrated that there was no difference in early (0 to 3 days after the bleed) or late surgery (11 to 14 days). Outcome was worse if surgery was performed in the 7 to 10-day post-bleed interval. Surgical results were better for patients operated on after 10 days. Patients alert on admission fared best; however, alert patients had a mortality rate of 10% to 12% when undergoing surgery prior to Day 11 compared with 3% to 5% when surgery was performed after Day 10. Patients drowsy on admission had a 21% to 25% mortality rate when operated on up to Day 11 and 7% to 10% with surgery thereafter. Overall, early surgery was neither more hazardous nor beneficial than delayed surgery. The postoperative risk following early surgery is equivalent to the risk of rebleeding and vasospasm in patients waiting for delayed surgery.

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Panagiotis Mastorakos, Davis G. Taylor, Ching-Jen Chen, Thomas Buell, Joseph H. Donahue and John A. Jane Jr.

OBJECTIVE

Cavernous sinus invasion (CSI) in Cushing’s disease (CD) negatively affects the probability of complete resection, biochemical cure, and need for adjuvant therapy. However, the prediction of CSI based on MRI findings has been inconsistent and variable. Among macroadenomas, the Knosp classification is the most widely utilized radiographic predictor of CSI, but its accuracy in predicting CSI and the probability of gross-total resection is limited in the setting of microadenomas or Knosp grade 0–2 macroadenomas. The authors noticed that the presence of a triangular shape of adenomas adjacent to the cavernous sinus on coronal MR images is frequently associated with CSI. The authors aimed to determine the correlation of this radiographic finding (“sail sign” [SS]) with CSI.

METHODS

The authors performed a retrospective review of all patients with a pituitary lesion < 20 mm and a biochemical diagnosis of CD treated with endoscopic or microscopic transsphenoidal resection from November 2007 to May 2017. Overall 185 patients with CD were identified: 27 were excluded for negative preoperative imaging, 32 for lacking tumors adjacent to the sinus, 7 for Knosp grade 3 or higher, and 4 for inadequate intraoperative assessment of the CSI. Following application of inclusion and exclusion criteria, 115 cases were available for statistical analysis. Intraoperative CSI was prospectively evaluated at the time of surgery by one of two neurosurgical attending surgeons, and MRI data were evaluated retrospectively by a neurosurgical resident and attending neuroradiologist blinded to the intraoperative results.

RESULTS

A positive SS was identified in 23 patients (20%). Among patients with positive SS, 91% demonstrated CSI compared to 10% without an SS (p < 0.001). Using the SS as a predictor of CSI provided a sensitivity of 0.7 and a specificity of 0.98, with a positive predictive value (PPV) of 0.91 and a negative predictive value of 0.9. Among patients with positive SS, 30% did not achieve immediate postoperative remission, compared to 3.3% of patients without an SS (p < 0.001).

CONCLUSIONS

The presence of a positive SS among Cushing’s adenomas adjacent to the CS provides strong PPV, specificity, and positive likelihood ratio for the prediction of CSI. This can be a useful tool for preoperative planning and for predicting the likelihood of long-term biochemical remission and the need for adjuvant radiosurgery.

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Neal F. Kassell, James C. Torner, E. Clarke Haley Jr., John A. Jane, Harold P. Adams, Gail L. Kongable and Participants

✓ The International Cooperative Study on the Timing of Aneurysm Surgery evaluated the results of surgical and medical management in 3521 patients between December, 1980, and July, 1983. At admission, 75% of patients were in good neurological condition and surgery was performed in 83%. At the 6-month evaluation, 26% of the patients had died and 58% exhibited a complete recovery. Vasospasm and rebleeding were the leading causes of morbidity and mortality in addition to the initial bleed. Predictors for mortality included the patient's decreased level of consciousness and increased age, thickness of the subarachnoid hemorrhage clot on computerized tomography, elevated blood pressure, preexisting medical illnesses, and basilar aneurysms. The results presented here document the status of management in the 1980's.

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Edward R. Laws, Adam S. Kanter, John A. Jane Jr. and Aaron S. Dumont

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Neurobehavioral outcome 1 year after severe head injury

Experience of the Traumatic Coma Data Bank

Harvey S. Levin, Howard E. Gary Jr., Howard M. Eisenberg, Ronald M. Ruff, Jeffrey T. Barth, Jeffrey Kreutzer, Walter M. High Jr., Sandra Portman, Mary A. Foulkes, John A. Jane, Anthony Marmarou and Lawrence F. Marshall

✓ The outcome 1 year after they had sustained a severe head injury was investigated in patients who were admitted to the neurosurgery service at one of four centers participating in the Traumatic Coma Data Bank (TCDB). Of 300 eligible survivors, the quality of recovery 1 year after injury was assessed by at least the Glasgow Outcome Scale (GOS) in 263 patients (87%), whereas complete neuropsychological assessment was performed in 127 (42%) of the eligible survivors. The capacity of the patients to undergo neuropsychological testing 1 year after injury was a criterion of recovery as reflected by a significant relationship to neurological indices of acute injury and the GOS score at the time of hospital discharge. The neurobehavioral data at 1 year after injury were generally comparable across the four samples of patients and characterized by impairment of memory and slowed information processing. In contrast, language and visuospatial ability recovered to within the normal range. The lowest postresuscitation Glasgow Coma Scale (GCS) score and pupillary reactivity were predictive of the 1-year GOS score and neuropsychological performance. The lowest GCS score was especially predictive of neuropsychological performance 1 year postinjury in patients who had at least one nonreactive pupil following resuscitation. Notwithstanding limitations related to the scope of the TCDB and attrition in follow-up material, the results indicate a characteristic pattern of neurobehavioral recovery from severe head injury and encourage the use of neurobehavioral outcome measurements in clinical trials to evaluate interventions for head-injured patients.

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Adam S. Kanter, Alfa O. Diallo, John A. Jane Jr., Jason P. Sheehan, Ashok R. Asthagiri, Rod J. Oskouian, David O. Okonkwo, Charles A. Sansur, Mary Lee Vance, Alan D. Rogol and EdwardR. Laws Jr

Object

Despite ongoing advances in surgical and radiotherapeutic techniques, pediatric Cushing's disease remains a diagnostic and therapeutic challenge. The authors report on the results of a single-center retrospective review of 33 pediatric patients with Cushing's disease, providing details with respect to clinical presentation, diagnostic evaluation, therapeutic course, complications, and outcomes.

Methods

There were 17 female and 16 male patients whose mean age was 13 years (range 5–19 years) in whom a diagnosis of Cushing's disease was based on clinical and biochemical criteria. Typical symptoms included weight gain (91%), prepubertal growth delay (83%), round facies (61%), hirsutism (58%), headache (45%), abdominal striae (42%), acne (33%), amenorrhea (24%), and hypertension (24%). In 67% of the cases, preoperative magnetic resonance images revealed a pituitary lesion and in 82% of the cases the imaging studies effectively predicted lateralization. Inferior petrosal sinus sampling was performed in seven patients (21%), and in all of these cases lateralization was 100% reliable. Fifty-five percent underwent selective adenomectomies and 45% underwent subtotal hypophysectomies.

Complications included one case of diabetes insipidus, one of persistent hypocortisolemia necessitating prolonged glucocorticoid replacement therapy, and one minor vascular injury that did not necessitate postoperative management modification or cause sequelae. There were no surgery-related deaths and no cases of postoperative cerebrospinal fluid leakage or meningitis. During a mean follow-up period of 44 months, clinical remission was ultimately achieved in 91% of patients: 76% after transsphenoidal surgery alone and an additional 15% after adjuvant radiosurgery and/or adrenalectomy following surgical failure. Three patients (12%) experienced disease recurrence and underwent a second surgical procedure at 18, 81, and 92 months, respectively; based on clinical and biochemical criteria a second remission was achieved in all. Three patients (9%) remain with persistent disease.

Conclusions

Pediatric Cushing's disease is a rare condition, often requiring a multidisciplinary diagnostic and a multimodal therapeutic approach for successful long-term remission.

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Alexandra M. Giantini Larsen, David J. Cote, Hasan A. Zaidi, Wenya Linda Bi, Paul J. Schmitt, J. Bryan Iorgulescu, Michael B. Miller, Timothy R. Smith, M. Beatriz Lopes, John A. Jane Jr. and Edward R. Laws Jr.

OBJECTIVE

The authors report the diagnosis, management, and outcomes of 6 cases of spindle cell oncocytoma (SCO) in an effort to guide clinical diagnosis and management of these uncommon lesions.

METHODS

This study is a retrospective review of cases involving adult patients who underwent resection of pituitary lesions at the authors’ institutions between January 2000 and October 2017. The authors identified patients with histopathological confirmation of SCO and collected clinical data, including preoperative, perioperative, and postoperative management, complications, and outcomes.

RESULTS

Six patients with SCO were identified. Clinical findings at initial presentation included visual disturbances, dizziness, and headache. All patients underwent resection. Four resections were initially performed by the transsphenoidal approach, and 2 resections were performed by craniotomy at an outside institution with subsequent transsphenoidal reoperations. Neither necrosis nor increased mitotic activity was seen in the tumor samples. All samples stained positive for S100 protein and thyroid transcription factor 1 and negative for glial fibrillary acidic protein and pituitary hormones. Five of the samples stained positive for epithelial membrane antigen. The average MIB-1 index was 8.3% (range 2–17). Postoperatively, 3 of the 6 patients received further treatment for progression of residual tumor or for recurrence, 2 have stable residual tumor, and 1 has had no recurrence after gross-total resection. Two patients developed postoperative complications of transient sixth cranial nerve palsy and diplopia. There were no other complications.

CONCLUSIONS

SCO poses both a diagnostic and therapeutic challenge. These tumors are often initially misdiagnosed as nonfunctional pituitary adenomas because of their sellar location and nonspecific symptomatology. Postoperatively, SCO must also be distinguished from other neoplasms of the posterior pituitary gland through histopathological examination. Resection of SCO can be challenging, given its highly vascular and adherent nature. Long-term follow-up is critical, as the tumor is associated with higher recurrence and progression rates compared to other benign neoplasms of the sella.