Adrenocorticotropic Hormone-secreting Tumors Research Articles

THU531 A Case Of Cushing Syndrome Due To Ectopic ACTH Secreting Lung Neuroendocrine Tumor Treated With Cryoablation

Abstract Disclosure: S. Paknikar: None. J. McHugh: None. K. Rachmasari: None. I. Bancos: None. Introduction: Ectopic secretion of adrenocorticotropic hormone (ACTH) is a rare and severe form of Cushing Syndrome (CS) that requires an urgent specialized approach for diagnosis and management. Clinical Case: A 50-year-old woman was referred to endocrinology due to concern for CS. Over the previous year she had developed progressive weakness, edema, weight gain with abdominal fat redistribution, hypertension, and multiple compression fractures. On exam, she had a profound proximal myopathy, reported 10/10 pain along the spine, and was hypertensive (170/105 mm Hg) with normal other vitals. The patient's sodium was 141mmol/L [reference range 135-145 mmol/ L], potassium 4.1 mmol/L [3.6-5.2 mmol/L] while on spironolactone, and creatinine was 0.57 mg/dL [0.59-1.04 mg/dL]. Due to the severity of her symptoms, she was admitted to the hospital. Hormonal work up was consistent with an ACTH dependent CS: ACTH was 121pg/mL [7.2-63 pg/mL] and 24-hour urine cortisol was 645 mcg/24 hr [3.5-45 mcg/24 hr]. Workup for ACTH secreting tumor included a pituitary MRI which showed a 3 mm area of delayed enhancement in the pituitary gland, felt to be artifactual. A chest computed tomography (CT) showed a 1.3 cm low-density nodule in the right upper lobe concerning for a neuroendocrine tumor. A Gallium-68 DOTATATE Positron emission tomography/CT scan was performed and demonstrated that the nodule was highly DOTATATE avid (Krenning score of 3, scale of 0-4). These findings supported a diagnosis of ectopic CS caused by an ACTH secreting lung neuroendocrine tumor. Management of ectopic CS was twofold: addressing the underlying ACTH secreting lesion and urgent treatment of hypercortisolism and its consequences. In this case, this was achieved with CT-guided cryoablation of the right upper lobe nodule. The ACTH levels were monitored postoperatively, and when decreased (9.3pg/mL [ 7.2-63 pg/mL], glucocorticoid replacement therapy was initiated. As a result of prolonged hypercortisolism, the patient experienced multiple compression fractures and debility. Physical therapy was recommended for recovery from the compression fractures as well as proximal myopathy. Enoxaparin was initiated due to risk of venous thromboembolism from CS. From an osteoporosis standpoint, she was continued on calcium and vitamin-D supplementation and treated with weekly alendronate. Her hypertension improved allowing medication reduction. Postoperatively, she received education on adrenal insufficiency and biochemical monitoring for adrenal insufficiency recovery was implemented. Conclusion: Ectopic ACTH secreting tumors represent a rare cause of CS and effective management requires consideration of medical comorbidities to determine the approach: surgical, cryoablative, or medical therapy alone, mitigation of Cushing syndrome sequelae, and prompt recognition and treatment of glucocorticoid withdrawal. Presentation: Thursday, June 15, 2023

Effects of CRN04894, a Nonpeptide Orally Bioavailable ACTH Antagonist, on Corticosterone in Rodent Models of ACTH Excess

CRN04894 is an orally administered nonpeptide that is a potent and selective antagonist for adrenocorticotropic hormone (ACTH) acting at the melanocortin 2 receptor (MC2R) and is currently under development for the treatment of diseases of ACTH excess such as Cushing’s disease, congenital adrenal hyperplasia, and ectopic ACTH-secreting tumors. Cushing’s disease results from an adenoma derived from pituitary corticotropic cells that secrete excess ACTH, whereas ectopic ACTH syndrome arises from nonpituitary ACTH secreting tumors. Congenital adrenal hyperplasia is a genetic disease that results in cortisol deficiency leading to high levels of ACTH and adrenal androgens. Each of these indications is characterized by high ACTH levels that act on MC2R expressed in the adrenal cortex to drive pathological elevations of adrenally derived steroid hormones. CRN04894 blocks the action of ACTH at MC2R, providing a potential novel treatment for these diseases. Preclinical models of chronic hypercortisolemia include implantation of ACTH-secreting pituitary tumor cells in mice and continuous administration of ACTH via subcutaneously implanted osmotic pumps in rats. These models induce features consistent with human diseases of ACTH excess including hypercortisolemia and hypertrophy of the adrenal glands. We employed both rodent models to examine the pharmacodynamic effects of CRN04894 on corticosterone levels and adrenal gland morphology. In the mouse pituitary tumor model, subcutaneous inoculation of the ACTH-secreting mouse pituitary tumor cell line, AtT-20, into immunodeficient mice resulted in formation of tumors and increased plasma ACTH and corticosterone levels. Repeated daily oral administration of CRN04894 for 14 days dose-dependently and robustly suppressed plasma corticosterone levels in mice with AtT-20 tumors. In the rat model, subcutaneous implantation of osmotic pumps delivering ACTH resulted in increased corticosterone levels, reduction in body weight, and hypertrophy of the adrenal glands after 7 days. Daily oral administration of CRN04894 over 7 days dose-dependently suppressed corticosterone levels, mitigated the effect of ACTH excess on body weight, and rescued the adrenal gland hypertrophy. These findings provide evidence that CRN04894 functions as an effective ACTH antagonist at MC2R to suppress adrenal corticosterone secretion in both mouse and rat models of ACTH excess and hypercortisolemia, thus providing a strong rationale for its potential therapeutic utility in diseases of ACTH excess. This work was supported in part by an SBIR grant from the NIH awarded to Dr. Struthers (R43- DK115245)

Patient-Level Factors Influencing Hospital Costs and Short-Term Patient-Reported Outcomes After Transsphenoidal Resection of Sellar Tumors.

Identifying which factors influence treatment costs of transsphenoidal surgery for removal of sellar lesions can be complex. To identify which patient-level factors are associated with higher costs and evaluate the relationship between expenditures and short-term patient-reported outcomes. We used an institutional database tool to review prospectively collected data on patients (≥10 yr old) undergoing transsphenoidal sellar surgery. Hospital costs, demographic data, disease-specific variables, hospital-related measures, and patient-reported outcomes (Euro-QOL 5D [EQ-5D] responses) were collected for all patients. One hundred seventeen patients met the inclusion criteria. A multivariable logistic regression model for hospital costs showed a significant association between higher costs and adrenocorticotropic hormone-secreting tumors (odds ratio [OR] 86.34, 95% confidence interval [CI] 3.43-2176.42), larger tumor size (OR 1.13, 95% CI 1.01-1.28), and in-hospital complications (OR 14.98, 95% CI 2.21-101.68). The largest contributor to hospital costs in our cohort was facility cost (75%), followed by pharmacy (13%) and supply (7%) costs. Most patients (65.8%) had stable or improved EQ-5D responses at 1-mo follow-up. Stability or improvement in EQ-5D was more likely in patients with lower preoperative EQ-5D scores (P < .015) and with higher postoperative EQ-5D scores (P < .001) on univariate analysis. Most patients undergoing transsphenoidal surgery for sellar tumors experience stable or improved postoperative quality of life, even shortly after surgery. Factors associated with increased costs of surgery included larger tumor size and in-hospital complications. Using these data, further study can be directed at determining which interventions may improve the value of transsphenoidal surgery.

Pituitary-Directed Therapies for Cushing's Disease.

Cushing’s disease (CD) is caused by a pituitary corticotroph neuroendocrine tumor inducing uncontrolled hypercortisolism. Transsphenoidal surgery is the first-line treatment in most cases. Nonetheless, some patients will not achieve cure even in expert hands, others may not be surgical candidates and a significant percentage will experience recurrence. Many patients will thus require medical therapy to achieve disease control. Pharmacologic options to treat CD have increased in recent years, with an explosion in knowledge related to pathophysiology at the molecular level. In this review, we focus on medications targeting specifically pituitary adrenocorticotropic hormone-secreting tumors. The only medication in this group approved for the treatment of CD is pasireotide, a somatostatin receptor ligand. Cabergoline and temozolomide may also be used in select cases. Previously studied and abandoned medical options are briefly discussed, and emphasis is made on upcoming medications. Mechanism of action and available data on efficacy and safety of cell cycle inhibitor roscovitine, epidermal growth factor receptor inhibitor gefitinib, retinoic acid, and silibinin, a heat shock protein 90 inhibitor are also presented.

Clinical Outcomes After Endoscopic Endonasal Resection of Giant Pituitary Adenomas.

Giant pituitary adenomas represent a surgical challenge. We present the results of the endoscopic endonasal approach (EEA) for giant pituitary adenomas. We retrospectively reviewed the medical records of 55 patients with giant pituitary adenomas (>4 cm in maximum diameter) who underwent surgery with an EEA between 2008 and 2016. Factors affecting the extent of resection were evaluated. The mean patient age was 55.5 years. Tumors were nonfunctional in all but 4 patients, including 2 with growth hormone-secreting tumors, 1 with an adrenocorticotropic hormone-secreting tumor, and 1 with prolactinoma. Gross total resection was achieved in 24 patients (44%), and near-total resection (>90%) was achieved in 26 patients (47%). A multilobular configuration (P= 0.002) and cavernous sinus invasion (P= 0.044) negatively affected the extent of resection, whereas tumor size, intraventricular, and anterior or posterior fossa extension did not. Ten patients underwent adjuvant radiotherapy. All patients with hormone-secreting adenomas required adjuvant medical and/or radiotherapy to achieve biochemical remission. Postoperative vision was improved or normalized in 32 patients (66%), stable in 15 patients (31%), and worsened in 1 patient. A new hormonal deficit occurred in 8 patients (17%), whereas recovery of an existing hormonal deficit occurred in 6 patients (20%). The mean duration of follow-up was 41 months. Tumor recurrence/progression occurred in 6 patients (11%). Complications included apoplexy of residual tumor resulting in ischemic stroke in 1 patient, postoperative cerebrospinal fluid leak in 1 patient, and permanent diabetes insipidus in 4 patients (7%). Surgery with the EEA is an excellent option for managing giant pituitary adenomas. It results in superior clinical outcomes to those obtained using traditional microscopic transsphenoidal and transcranial approaches as reported in the literature.

301 Drivers and Components of Hospital Costs After Transsphenoidal Resection of Sellar Tumors

Abstract INTRODUCTION Assessing treatment costs of transsphenoidal surgery for removal of sellar lesions can be complex. Few data are available regarding what contributes to higher costs after these procedures. The goals of this study were to clarify cost drivers in transsphenoidal sellar surgery, to determine what categories contributed the most to these costs, and to evaluate the relationship between expenditures and short-term patient-reported outcomes. METHODS The authors used a proprietary institutional database tool the Value Driven Outcomes database to review prospectively collected data on transsphenoidal sellar surgery over a nearly 5-year period. Hospital costs, demographic data, disease-specific variables, hospital-related measures, and patient-reported outcomes in the form of Euro-QoL-5D (EQ-5D) responses were collected for all patients. RESULTS &gt;One hundred seventeen patients met the inclusion criteria. A multivariable logistic regression model for hospital costs showed a significant association between higher costs and adrenocorticotropic hormone secreting tumors (OR 30.409, 95% CI 2.695-343.121), larger tumor size (OR 1.084, 95% CI 1.026-1.146), and in-hospital complications (OR 4.209, 95% CI 1.268-13.968). The largest contributor to hospital costs in our cohort was facility cost (75%), followed by pharmacy (13%) and supply (7%) costs. Most patients (65.8%) had stable or improved EQ-5D responses at 1-month follow-up, with significantly lower preoperative EQ-5D scores than those who reported worsened quality of life (0.776 ± 0.209 vs. 0.867 ± 0.148, P = 0.015) and significantly higher postoperative EQ-5D scores (0.887 ± 0.144 vs. 0.759 ± 0.144, P &lt; 0.001) on univariate analysis. CONCLUSION Most patients undergoing transsphenoidal surgery for sellar tumors experience stable or improved postoperative quality of life, even shortly after surgery. Factors associated with increased costs of surgery included larger tumor size and in-hospital complications. Using these data, further study can be directed at determining which interventions may improve the value of transsphenoidal surgery.

Central Serous Chorioretinopathy in a Patient with Ectopic Adrenocorticotropic Hormone-secreting Tumor

Central Serous Chorioretinopathy in a Patient with Ectopic Adrenocorticotropic Hormone-secreting Tumor

Effect of repeated transsphenoidal surgery in recurrent or residual pituitary adenomas: A systematic review and meta-analysis.

Background:Recurrent or residual pituitary adenomas previously treated by transsphenoidal surgery are not uncommon. There are no strongly established guidelines to perform treatment of such cases. The objective of this study is to elucidate the effect of transsphenoidal reoperation in residual or recurrent pituitary adenomas.Methods:We made a systematic review of the literature to elucidate this effect through electronic search in MEDLINE/PubMed and Cochrane Central database. PRISMA statement was used as a basis for this systematic review and analysis of the risk of bias was made according to the Grading of Recommendations, Assessment, Development and Evaluation recommendations.Results:In this review, fifteen studies were finally pooled analyzed. Although remission rates (RRs) and follow-up periods varied widely, from 149 patients with growth hormone-secreting tumors the mean RR was 44.5%, from 273 patients with adrenocorticotropic hormone-secreting tumors the mean RR was 55.5% and among 173 patients with nonsecreting tumors, RR was 76.1%. There was significant higher RR in nonsecreting tumors. Mean follow-up was 32.1 months. No difference was found between microscopic and endoscopic techniques.Conclusions:A second transsphenoidal surgery is accompanied by a chance of remission in approximately half of cases with secreting tumors. In nonsecreting ones, success is higher.

Anesthetic Management of Emergent Laparoscopic Bilateral Adrenalectomy in a Patient with a Life-Threatening Cortisol Crisis

Cushing syndrome may rarely present with life-threatening hypercortisolism, manifested by hypertension, hypokalemia, hyperglycemia, and edema. If medical treatment proves ineffective in ameliorating the symptoms, emergent rescue adrenalectomy may be the only way to relieve the crisis. We describe the anesthetic management of a patient with an ectopic adrenocorticotropic hormone-secreting tumor, whose condition was rapidly deteriorating due to severe cortisol excess, and emergent adrenalectomy was the only available therapeutic modality. Despite severe metabolic derangement, edema, and incipient respiratory failure, emergent bilateral laparoscopic adrenalectomy was performed and the patient improved sufficiently to undergo surgery for the ectopic lesion without incident.

The postoperative monitoring of nonfunctioning pituitary adenomas

Clinically nonfunctioning pituitary tumors are common in tertiary endocrine practice. Although it is widely accepted that patients with these adenomas require long-term surveillance after surgery-particularly those with macroadenomas, which grow much more frequently than microadenomas-a consensus on postoperative monitoring and treatment strategies is lacking. The indications for radiotherapy, which has seen a decline in use over the past decade, are not clear, although most experts would agree that residual tumor mass after surgery, as well as tumor expansion into the cavernous sinus, indicate the need to consider postoperative radiotherapy. In patients not treated with radiotherapy after surgical treatment of a nonfunctioning adenoma, MRI of the tumor should be performed annually for the first 6 years and every 2 years thereafter. In addition, silent adrenocorticotropic hormone-secreting tumors can behave more aggressively if they recur, and tumor regrowth can also occasionally be found in patients after classical pituitary apoplexy, which suggests that individuals with these conditions should also be monitored carefully after surgery. However, at which point this scanning routine can be ceased remains the subject of debate, as few data on late recurrence of nonfunctioning pituitary adenomas exist.

TUMOR TISSUE IDENTIFICATION IN THE PSEUDOCAPSULE OF PITUITARY ADENOMA

The microsurgical pseudocapsule can be found in the transition zone between an adenoma and the surrounding normal pituitary tissue. We investigated the precise histology of the pseudocapsule. Furthermore, we evaluated the remission rate, the changes in pituitary function, and the recurrence rate after intensive resection of the pseudocapsule. In 616 patients with pituitary adenomas (Hardy Types I-III) over a period of 14 years, we introduced intensive resection of the microsurgical pseudocapsule to achieve complete tumor removal. A combined pituitary function test and radiological study were performed on the patients before surgery, 1 year after surgery, and at subsequent 1.5-year intervals 2 to 13 years postoperatively. Microsurgical pseudocapsules were identified in 343 (55.7%) of 616 patients, and the distinct microsurgical pseudocapsules were observed in 180 (52.5%) of these patients. In the remaining 163 patients, the microsurgical pseudocapsules were incompletely developed. Tumor cluster infiltration was present in the pseudocapsule in 71 (43.6%) of these patients. Aggressive resection of the microsurgical pseudocapsule was more often required in larger tumors than in smaller ones. The presence of a pseudocapsule was slightly more frequent in prolactin-secreting tumors (70.9%) than in growth hormone-secreting (55.0%) and adrenocorticotropic hormone-secreting (40.0%) tumors. In the 243 patients of the total resection group who underwent combined pituitary function tests more than 2 times after surgery, the surgical remission rate was 99.1% in clinically nonfunctional tumors, 88% in growth hormone-secreting, 70.6% in prolactin-secreting, and 100% in adrenocorticotropic hormone-secreting tumors. The surgical remission rate was 86.2% in the presence of a pseudocapsule and 94.3% in the absence of a pseudocapsule. Preoperative hypopituitarism improved in 140 patients (57.6%), persisted in 47 patients (19.3%), and was aggravated in 33 patients (13.6%). There was no statistical difference in improvement or deterioration of pituitary function according to the existence or absence of the pseudocapsule. The tumor recurrence rate was 0.8% in the total resection group and was 42.1% in the subtotal resection group. We have shown that tumor tissue is frequently present within the pseudocapsule, suggesting that any tumor remnant in the pseudocapsule could be a source of recurrence and an obstacle to achieving complete remission. These results indicate that intensive resection of the pseudocapsule could result in a higher remission rate without deteriorating pituitary function.

An Overlooked Tumor of the Lung in Cushing's Syndrome: Adrenocorticotropic Hormone-Secreting Carcinoid Tumor

An Overlooked Tumor of the Lung in Cushing's Syndrome: Adrenocorticotropic Hormone-Secreting Carcinoid Tumor

Pituitary tumors in children: clinical analysis of 21 cases

The aim of this study is to review the results of surgery for pituitary adenomas in children less than 18 years old. A retrospective review was done of pituitary adenoma patients with the age of less than 18 years who were treated in the period 1979-2003 at Dr. Shariati Hospital. Twenty-one patients (12 girls and 9 boys) were identified. The age range (mean) in girls and boys was 9-18 (15.8) and 9-17 (14.8) years, respectively. The duration of follow-up was 1-23 (13.4) years. Eight patients (38.1%) had adrenocorticotropic hormone-secreting tumors, 33.3% had prolactin-secreting tumors, 19% had growth hormone-secreting tumors, and 9.53% had nonfunctioning adenomas. Multidisciplinary management included surgery and, if necessary, reoperation with/without radiotherapy and pharmacotherapy. Eleven patients, mostly with prolactinomas, acromegaly, and nonfunctioning adenomas, needed reoperation and radiotherapy. There were two deaths, one of which was because of apoplexy. The biological behavior of pediatric pituitary adenomas seems more aggressive than adults' adenomas. The chance of pituitary apoplexy in pediatric invasive pituitary adenoma is high.

Radiosurgery for pituitary adenomas: Evaluation of its efficay and safety

11515 Background: Pituitary adenomas account for approximately 15% of all primary brain tumors. Multimodality treatment is often necessary and options include medical management, microsurgery, radiotherapy and radiosurgery (RS). Recently, RS has gained acceptance as a complementary treatment since it has been associated with a shorter latency for its effects and lesser morbidity than that of radiotherapy. The objective of this study was to assess the effects of RS on the radiological and hormonal control and its toxicity in the treatment of pituitary adenomas. Methods: It was done a retrospective analysis of the first 26 consecutive patients with pituitary adenomas treated with RS at our institution between 1999 and 2004. RS was delivered with a multiheaded cobalt unit (Gamma Knife). The median radiation dose was 20 Gy defined to the 50% isodose line. Almost 20% of tumors were non-secretory. The remaining were prolactinomas (31%), adrenocorticotropic hormone-secreting (34%) and growth hormone-secreting tumors (15%). Hormonal control was defined as hormonal response (decline of more than 50% from the pre-RS levels) and hormonal normalization. Radiological control was defined as stasis and shrinkage of the tumor. Hypopituitarism and visual deficit were the morbidity outcomes. Hypopituitarism was defined as the initiation of any hormone replacement therapy and visual deficit as loss of visual acuity or visual field after RS. Results: The median follow-up was 40,8 months.Tumor growth was controlled in 96% of the cases and tumor shrinkage ocurred in 8% of the cases. Hormonal control was observed in 14 of 20 (70%) and hormonal normalization in 7 of 20 (35%) patients after RS, with a median latency period of 28,2 months. The 3-year actuarial rate of hormonal control and normalization were 51% and 47,6%, respectively, and the 5-year actuarial rate were 74% and 68,6%, respectively. There were no patients with visual deficit or hypopituitarism after RS. Conclusions: RS is an effective and safe therapeutic option in the management of selected patients with pituitary adenomas. The short latency of the radiation response, the highly acceptable radiological and hormonal control and absence of complications at this early follow-up are consistent with literature. No significant financial relationships to disclose.

Gamma knife radiosurgery for benign cavernous sinus tumors: quantitative analysis of treatment outcomes.

We review our 8-year experience with gamma knife radiosurgery (GKRS) for the treatment of patients with benign cavernous sinus tumors and present a quantitative analysis of factors relevant to treatment outcomes. From 1994 to 2002, a total of 139 patients with benign cavernous sinus tumors were treated in 145 sessions. Their median age was 53 years, and the median follow-up was 3.5 years. The tumors included 57 meningiomas, 76 pituitary tumors (49 nonfunctional adenomas, 15 prolactinomas, 5 adrenocorticotropic hormone-secreting tumors, 6 growth hormone-secreting tumors, and 1 plurihormone-secreting tumor), 4 schwannomas, 1 hemangioma, and 1 paraganglioma. Sekhar tumor grades were as follows: I, n = 28 (20%); II, n = 42 (30%); III, n = 42 (30%); IV, n = 19 (14%); and V, n = 8 (6%). The median tumor volume was 3.4 cm(3), and the median prescribed dose was 15 Gy defined to the 50% isodose line. A total of 136 treated tumors (97.8%) were well controlled by GKRS, with low morbidity. For meningiomas, 29 tumors (51%) were unchanged and 26 (46%) were smaller at a median of 15.2 months. For pituitary tumors, 50 (66%) were unchanged and 25 (33%) were smaller at a median of 20.6 months. Improvement in cranial nerve (CN) function was seen in 19 (36.5%) of 52 patients with pre-GKRS deficits, and 3 patients (2.2%) developed new stable CN deficits after GKRS: 1 patient developed IVth CN palsy at 9 months, and 2 developed persistent VIth CN palsies at 43 and 45 months, respectively, that required surgical correction. Two patients developed transient VIth CN palsies at 48 months that self-resolved after another year. Endocrine function normalized for all 6 treated patients with a growth hormone-secreting tumor at a median of 18 months. One of the 5 adrenocorticotropic hormone-secreting tumors required retreatment after 17 months because of continued cortisol elevation. Thirteen (87%) of 15 prolactinoma patients had normalized prolactin levels within 2 years of the procedure; 2 patients relapsed by endocrine criteria at 18 and 22 months after GKRS. Two patients with normalized prolactin levels completed three normal pregnancies within 3 years of treatment. Six patients (4.3%) with a median tumor volume of 8 cm(3) developed radiation-induced injury at a median of 36 months after GKRS. Five of these patients also underwent external beam radiotherapy and received a median dose of 52.2 Gy in 30 fractions. Quantitative analysis revealed that the radiation dose to critical structures (optic apparatus and pons) is correlated with their distance from tumor margins. Underdosed tumor volume, tumor volume, and total treated volume are correlated with treatment outcomes. GKRS is a safe and effective treatment for selected patients with benign cavernous sinus tumors and is an important adjunct for treating postoperative tumor residual and/or recurrent tumor. Continued analysis of treated patients over an extended time is needed to evaluate long-term disease control and potential late GKRS complications.

Gamma knife radiosurgery for pituitary adenoma: early results.

In recent years, gamma knife radiosurgery (GKRS) has emerged as an important treatment modality in the management of pituitary adenomas. Treatment results after performing GKRS and the complications of this procedure are reviewed. Between 1994 and 2002, a total of 78 patients with pituitary adenomas underwent a total of 84 GKRS procedures in our medical center. This patient group comprised 46 men (59%) and 32 women (41%). All patients were treated for recurrent or residual disease after surgery or radiotherapy, with 83% presenting with extensive tumor involvement. The cavernous sinus was involved in 75 patients (96%), and 22 patients (28%) had hormone-secreting adenomas. This latter subset of patients included 12 prolactinomas (15%), 6 growth-hormone secreting tumors (8%), and 4 adrenocorticotropic hormone-secreting tumors (5%). The median tumor volume was 2.3 cm(3), and the median radiation dose was 15 Gy defined to the 50% isodose line. The mean and median follow-up periods were 41 and 36 months, respectively. GKRS was tolerated well in these patients; acute toxicity was uncommon and of no clinical significance. Late toxicity was noted in three patients (4%) and consisted of VIth cranial nerve palsy. In two patients, there was spontaneous resolution of this palsy, and in one patient, it persisted for the entire 3-year duration of follow-up. Of the 15 patients who presented with cranial nerve dysfunction, 8 (53%) experienced complete recovery and 3 (20%) showed major improvement within 12 months of therapy. Tumor volume reduction was slow, with 30% of patients showing decreased tumor volume more than 3 years after undergoing GKRS. None of the 56 patients with nonfunctioning tumors showed progression in the treated volume, and 4 (18%) of the 22 hormone-secreting tumors relapsed (P = 0.008). Of the four patients with adrenocorticotropic hormone-secreting adenomas, therapy failed in two of them. All six patients with growth hormone-producing tumors responded well to therapy. Of the 12 patients with prolactinomas 10 (83%) had normalization of hormone level and 2 patients experienced increasing prolactin level. Two patients with prolactinomas had three normal pregnancies after undergoing GKRS. GKRS is a safe and effective therapy in selected patients with pituitary adenomas. None of the patients in our study experienced injury to the optic apparatus. A radiation dose higher than 15 Gy is probably needed to improve control of hormone-secreting adenomas. Longer follow-up is required for a more complete assessment of late toxicity and treatment efficacy.

Adrenal surgery for hypercortisolism--surgical aspects.

Patients with endogenous hypercortisolism are thought to be at high risk for adrenalectomy and may experience significant postoperative surgical mortality/morbidity. From 1981 through 1991, 91 patients underwent adrenal resection for endogenous hypercortisolism. Causes were adrenal-dependent Cushing's syndrome (50%), pituitary-dependent Cushing's syndrome (27%), and an ectopic adrenocorticotropic hormone-secreting tumor (23%). Causes of adrenal-dependent Cushing's syndrome were adrenocortical adenoma (72%), bilateral nodular hyperplasia (20%), and adrenocortical carcinoma (8%). Comparative mean length of hospitalization for patients undergoing unilateral anterior versus posterior approach was 8 versus 6 days, and bilateral anterior versus posterior was 11 versus 6 days. Operative mortality was 2.6%. Only one patient had a wound infection, and no patient had either a venous thrombosis or a pulmonary embolism. Delayed wound healing occurred in three patients. (1) Adrenal surgery can be performed today with low morbidity/mortality. (2) Although there is an effect of hypercortisolism on wound healing, infection, diabetes, hypertension, coronary artery disease, and pulmonary embolism, it was possible to perform adrenalectomy surgically with acceptable morbidity and mortality. (3) These results may serve as a standard against which laparoscopic adrenalectomy may be compared.

Transsphenoidal surgery for pituitary adenomas in children.

The authors have reviewed the results of transsphenoidal surgery for pituitary adenomas done on 66 children (younger than 16 yr of age) between 1966 and 1992. Ninety-four percent (62 of 66) showed clinical evidence of pituitary hormonal hypersecretion. The most common type was the adrenocorticotropic hormone-secreting adenoma (n = 36), followed by the prolactinoma (n = 18) and the growth hormone-secreting types (n = 8). There were four cases of nonfunctioning adenomas. Adrenocorticotropic hormone-secreting tumors in children had presentations and surgical results similar to those seen in adults. Twenty-three of 33 patients with Cushing's disease had simple adenomectomy or subtotal hypophysectomy without symptomatic recurrence. Four of 10 initial treatment failures had subsequent successful surgical intervention, resulting in an overall cure rate of 78%. Postoperative hypocortisolism was suggestive of surgical success but was not absolute. Of three patients with Nelson syndrome, none were successfully treated with surgery alone and two developed invasive disease. Prolactin-secreting and growth hormone-secreting tumors in children occurred more commonly with suprasellar expansion than did their adult counterparts. Transsphenoidal surgery was capable of controlling disease in only 12% (1 of 8) of growth hormone-secreting tumors, and 67% (12 of 18) of prolactin-secreting tumors required postoperative medical therapy or radiotherapy for persistently elevated prolactin levels. Special difficulty was noted in boys with prolactinomas and in girls with primary amenorrhea. As in adults, preoperative prolactin levels correlated with ultimate surgical success rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Nelson's Syndrome

We present a case of Nelson's syndrome in which the clinical, radiographic, and surgical findings are indicative of a discrete microadenoma rather than of diffuse pituitary hyperplasia. Ultrastructural analysis reveals this to be the first example of a sparsely granulated lesion in Nelson's syndrome and only the second such adrenocorticotropic hormone-secreting tumor reported. Unfortunately, there do not seem to be any firm ultrastructural features that differentiate between hyperplasia and discrete adenoma. Separation of the two entities may be important in delineating the pathogenesis and treatment of Nelson's syndrome; these are discussed.

Nelson??s syndrome

We present a case of Nelson's syndrome in which the clinical, radiographic, and surgical findings are indicative of a discrete microadenoma rather than of diffuse pituitary hyperplasia. Ultrastructural analysis reveals this to be the first example of a sparsely granulated lesion in Nelson's syndrome and only the second such adrenocorticotropic hormonesecreting tumor reported. Unfortunately, there do not seem to be any firm ultrastructural features that differentiate between hyperplasia and discrete adenoma. Separation of the two entities may be important in delineating the pathogenesis and treatment of Nelson's syndrome; these are discussed.