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Daniel F. Kelly

✓ Cushing's disease is a serious endocrinopathy that, if left untreated, is associated with significant morbidity and mortality rates. After diagnostic confirmation of Cushing's disease has been made, transsphenoidal adenomectomy is the treatment of choice. When a transsphenoidal adenomectomy is performed at experienced transsphenoidal surgery centers, long-term remission rates average 80% overall, surgical morbidity is low, and the mortality rate is typically less than 1%. In patients with well-defined noninvasive microadenomas, the long-term remission rate averages 90%. For patients in whom primary surgery fails, treatment options such as bilateral adrenalectomy, stereotactic radiotherapy or radiosurgery, total hypophysectomy, or adrenolytic medical therapy need to be carefully considered, ideally in a multidisciplinary setting. The management of Nelson's Syndrome often requires both transsphenoidal surgery and radio-therapy to gain disease control.

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Daniel F. Kelly, Edward R. Laws Jr. and Damirez Fossett

✓ Hyponatremia, usually attributed to the syndrome of inappropriate secretion of antidiuretic hormone, typically occurs in a delayed fashion following transsphenoidal removal of a pituitary adenoma. In a series of 99 consecutive patients who underwent transsphenoidal surgery for pituitary adenoma, nine patients developed delayed hyponatremia, seven of whom were symptomatic. Of these seven patients, four had been discharged from the hospital and required readmission on postoperative Day 7 to 9. In the nine patients who developed hyponatremia, on the average, serum sodium levels began to fall on Day 4 and reached a nadir on Day 7 (mean serum sodium nadir 123 mmol/L). The development of delayed hyponatremia was associated with the presence of a macroadenoma in eight of the nine patients.

Seven of the nine patients had serum sodium levels less than 130 mmol/L and required treatment. One patient was treated with fluid restriction alone and six were treated with both fluid restriction and intravenous urea therapy. Twenty-four and 48 hours after urea administration, serum sodium levels rose by an average of 6 and 10 mmol/L, respectively, and at discharge, levels averaged 136 mmol/L. Intravenous administration of urea provides a rapid yet safe means of correcting symptomatic hyponatremia when fluid restriction alone is inadequate. In this article, the authors discuss the pathogenesis of delayed hyponatremia.

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John A. Jane Jr.

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Gabriel Zada, Daniel F. Kelly, Pejman Cohan, Christina Wang and Ronald Swerdloff

Object. The direct endonasal approach performed with the aid of an operating microscope for removal of pituitary tumors has the potential advantage over the traditional sublabial route of minimizing postoperative rhinological complications, yet maintaining a high degree of efficacy and safety. To assess the effectiveness of this procedure, tumor remission rates and surgical complications were documented, and patients' postoperative complaints were recorded using a questionnaire.

Methods. One hundred consecutive patients underwent 109 endonasal operations for tumor removal. At a median follow-up period of 16 months (range 3–45 months), surgical remission rates were as follows: in 40 patients with endocrine-inactive macroadenomas, 95% for noninvasive and 40% for invasive tumors; in the 20 patients with prolactinomas, 75% for prolactinomas with an initial prolactin (PRL) level lower than 200 ng/ml, 33% for those with a PRL level between 200 and 600 ng/ml, and 0% for those with a PRL level higher than 1400 ng/ml; in the 15 patients with Cushing disease, 73% for microadenomas and 25% for macroadenomas; in the 10 patients with acromegaly, 75% for microadenomas and 50% for macroadenomas; in the five patients with Rathke cleft cysts, 80%; and in the five patients with craniopharyngiomas, 40%. There were seven major surgical complications and no operative deaths. Among the 78 patients who completed questionnaires (response rate 89%), the most common complaints concerned nasal packing (39%), removal of packing (36%), and mouth breathing (35%). At 3 months or longer after surgery, patients quantified sinonasal problems as follows: for facial pain, no problem in 83% and severe difficulty in 4%; for nasal congestion, no problem in 74%, and severe difficulty in 3%; for decreased nasal airflow, no problem in 77% and severe difficulty in 4%; for decreased sense of smell, no problem in 73% and severe difficulty in 4%; and for upper-lip numbness, no problem in 87% and severe difficulty in 1%. Twelve (86%) of 14 patients who had undergone sublabial surgery previously preferred the endonasal approach in terms of pain and ease of recovery.

Conclusions. The direct endonasal route for pituitary tumor removal has efficacy and complication rates comparable to those of the sublabial route. Patients generally recover rapidly from this minimally invasive procedure and have no or minimal sinonasal complaints. For patients requiring a repeated operation, the endonasal route appears to be less painful and easier to recover from than the sublabial route. Given the minimal nasal mucosal dissection required and the frequent patient complaints related to nasal packing, use of packing is no longer used for this procedure.

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Daniel F. Kelly, Irene T. Gaw Gonzalo, Pejman Cohan, Nancy Berman, Ronald Swerdloff and Christina Wang

Object. Recognition of pituitary hormonal insufficiencies after head injury and aneurysmal subarachnoid hemorrhage (SAH) may be important, especially given that hypopituitarism-related neurobehavioral problems are typically alleviated by hormone replacement. In this prospective study the authors sought to determine the rate and risk factors of pituitary dysfunction after head injury and SAH in patients at least 3 months after insult.

Methods. Patients underwent dynamic anterior and posterior pituitary function testing. Results of the tests were compared with those of 18 age-, sex-, and body mass index—matched healthy volunteers. The 22 head-injured patients included 18 men and four women (mean age 28 ± 10 years at the time of injury) with initial Glasgow Coma Scale (GCS) scores of 3 to 15. Eight patients (36.4%) had a subnormal response in at least one hormonal axis. Four were growth hormone (GH) deficient. Five patients (four men, all with normal testosterone levels, and one woman with a low estradiol level) exhibited an inadequate gonadotroph response. One patient had both GH and thyrotroph deficiency and another had both GH deficiency and borderline cortisol deficiency. At the time of injury, all eight patients with pituitary dysfunction had an initial GCS score of 10 or less and, compared with the 14 patients without dysfunction, were more likely to have had diffuse swelling, seen on initial computerized tomography scans (p < 0.05), and to have sustained a hypotensive or hypoxic insult (p = 0.07). Of two patients with SAH who were studied (Hunt and Hess Grade IV) both had GH deficiency.

Conclusions. From this preliminary study, some degree of hypopituitarism appears to occur in approximately 40% of patients with moderate or severe head injury, with GH and gonadotroph deficiencies being most common. A high degree of injury severity and secondary cerebral insults are likely risk factors for hypopituitarism. Pituitary dysfunction also occurs in patients with poor-grade aneurysms. Postacute pituitary function testing may be warranted in most patients with moderate or severe head injury, particularly those with diffuse brain swelling and those sustaining hypotensive or hypoxic insults. The neurobehavioral effects of GH replacement in patients suffering from head injury or SAH warrant further study.

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Daniel F. Kelly, Stefan M. Lee, Patty A. Pinanong and David A. Hovda

✓ Acute ethanol intoxication is a frequent complicating factor in human head injury, yet its impact on neurological outcome remains poorly defined. This study was undertaken to assess the effect of varying levels of preinjury ethanol on early postinjury mortality, recovery of motor function, and degree of neural degeneration after cortical contusion injury in the rat. Adult rats were pretrained on a beam-walking task, then randomized to one of five groups: low-dose ethanol and injury (1 g/kg, 16 animals); moderate-dose ethanol and injury (2.5 g/kg, 11 animals); high-dose ethanol and injury (3 g/kg, 17 animals); no ethanol and injury (nine animals); or ethanol and sham injury (seven animals). Forty minutes after intraperitoneal injection of ethanol or saline, the rats received a pneumatic piston—induced contusion injury of the left primary motor cortex. Their beam-walking ability was assessed daily for the next 7 days. At 4 weeks postinjury, the brains were sectioned and the dimensions of the cortical lesions were determined.

Preinjury ethanol administration was associated with an acute postinjury mortality rate of 29.5% (p < 0.05); the highest mortality rate (47.1%) occurred in the high-dose ethanol group, whereas no deaths occurred in the animals in the no ethanol or sham-injured groups (p < 0.01). However, injured animals receiving low- and moderate-dose ethanol had significantly less severe beam-walking impairment initially, and a more rapid return to normal beam-walking ability, compared to the no and high-dose ethanol groups (p < 0.05). Additionally, the mean lesion volumes were significantly smaller in the low- and moderate-dose ethanol treatment groups compared to the no and high-dose ethanol groups (23.2 ± 8 mm3 and 29 ± 6.7 mm3 vs. 52 ± 8.8 mm3 and 53.7 ± 10.9 mm3, respectively, p < 0.01). In this cortical contusion model, the presence of ethanol before injury appears to exert a potent neuroprotective effect when administered in low or moderate doses. This action is postulated to result from ethanol-induced inhibition of N-methyl-d-aspartate receptor-mediated excitotoxicity. The loss of neuroprotection and increased mortality rates observed with high-dose ethanol may be related to ethanol-induced hemodynamic and respiratory depression.

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Daniel F. Kelly

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Nancy McLaughlin, Amy A. Eisenberg, Pejman Cohan, Charlene B. Chaloner and Daniel F. Kelly

Object

Endoscopy as a visual aid (endoscope assisted) or as the sole visual method (fully endoscopic) is increasingly used in pituitary adenoma surgery. Authors of this study assessed the value of endoscopic visualization for finding and removing residual adenoma after initial microscopic removal.

Methods

Consecutive patients who underwent endoscope-assisted microsurgical removal of pituitary adenoma were included in this study. The utility of the endoscope in finding and removing residual adenoma not visualized by the microscope was noted intraoperatively. After maximal tumor removal under microscopic visualization, surgeries were categorized as to whether additional tumor was removed via endoscopy. Tumor removal and remission rates were also noted. Patients undergoing fully endoscopic tumor removal during this same period were excluded from the study.

Results

Over 3 years, 140 patients (41% women, mean age 50 years) underwent endoscope-assisted adenoma removal of 30 endocrine-active microadenomas and 110 macroadenomas (39 endocrine-active, 71 endocrine-inactive); 16% (23/140) of patients had prior surgery. After initial microscopic removal, endoscopy revealed residual tumor in 40% (56/140) of cases and the additional tumor was removed in 36% (50 cases) of these cases. Endoscopy facilitated additional tumor removal in 54% (36/67) of the adenomas measuring ≥ 2 cm in diameter and in 19% (14/73) of the adenomas smaller than 2 cm in diameter (p < 0.0001); additional tumor removal was achieved in 20% (6/30) of the microadenomas. Residual tumor was typically removed from the suprasellar extension and folds of the collapsed diaphragma sellae or along or within the medial cavernous sinus. Overall, 91% of endocrine-inactive tumors were gross-totally or near-totally removed, and 70% of endocrine-active adenomas had early remission.

Conclusions

After microscope-based tumor removal, endoscopic visualization led to additional adenoma removal in over one-third of patients. The panoramic visualization of the endoscope appears to facilitate more complete tumor removal than is possible with the microscope alone. These findings further emphasize the utility of endoscopic visualization in pituitary adenoma surgery. Longer follow-ups and additional case series are needed to determine if endoscopic adenomectomy translates into higher long-term remission rates.

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