Kalmon D. Post

Lymphocytic hypophysitis. Report of 3 new cases and review of the literature.

Lymphocytic hypophysitis is an uncommon but increasingly recognized disorder characterized by chronic inflammation and destruction of the anterior pituitary. Three new cases are presented here with a review of the 27 previously reported cases. The disease affects primarily young women in late pregnancy or in the postpartum period but also has been described in postmenopausal women and in one man. It presents as an expanding intrasellar mass or as partial or panhypopituitarism. The etiology may be autoimmune. The natural history of this entity begins with enlargement of the pituitary secondary to inflammatory infiltration and progresses to atrophy of the gland with destruction of pituitary tissue and replacement with fibrosis. At least 1 patient had documented recovery of pituitary function, and the overall potential incidence of recoverable function is unknown. Our improved understanding of this disease has led us to conclude that surgical intervention is not always necessary.

Clinical versus Subclinical Pituitary Apoplexy: Presentation, Surgical Management, and Outcome in 21 Patients

A retrospective review of 16 consecutive patients with pituitary apoplexy treated over a 10-year period is reported. Eight men and 8 women (mean age, 48 years) underwent transsphenoidal decompression after an average duration of symptoms of 19 days. The diagnosis of pituitary apoplexy was made by the sudden onset of headache (88%), nausea (56%), or meningismus (13%), with or without visual disturbances (75%), in the setting of a sellar tumor on computed tomographic or magnetic resonance imaging scans. Thirteen of 16 patients showed significant improvement of symptoms after surgery (average follow-up, 2.5 years). In addition, 5 patients with clinically silent yet extensive pituitary hemorrhage were treated. Although extensive pituitary hemorrhage often produced fulminant apoplexy, it also presented insidiously over many days with few, if any, clinical signs. Rapid diagnosis, endocrine replacement, and transsphenoidal decompression constituted effective therapy. Magnetic resonance imaging (after at least 12 hours of symptoms) was superior to computed tomography in detecting hemorrhage.

Depression of Circulating Blood Volume in Patients after Subarachnoid Hemorrhage: Implications for the Management of Symptomatic Vasospasm

The result of 42 blood volume determinations made with autologous red blood cells labeled with chromium-51 are reported. The subjects consisted of 11 control patients and 25 patients with recent subarachnoid hemorrhage (SAH). The mean red blood cell volume (RBCV) and the total blood volume (TBV) for female patients after SAH were significantly lower than corresponding control values (P less than 0.01). No depression of blood volume was found in males as a group. Seventy-two per cent of females had below-normal RBCV and 50% had below-normal TBV. Fifteen patients demonstrated angiographic vasospasm or signs of cerebral ischemia. Only 1 patient with asymptomatic vasospasm had a below-normal RBCV or TBV, whereas 6 of 7 patients with symptomatic vasospasm had a subnormal RBCV or TBV. The mean RBCV and mean TBV for female patients with symptomatic vasospasm were significantly lower than corresponding control values (P less than 0.02) and lower than values for female patients with asymptomatic vasospasm (P less than 0.05). The data suggest that volume status may be the important differential between asymptomatic and symptomatic vasospasm. Delayed ischemic deficits can be expected to develop in patients who have both spasm of the intracranial vessels and decreased TBV. Patients with normal blood volume are far less likely to experience cerebral ischemia, even if vasospasm develops.

Features at diagnosis of 324 patients with acromegaly did not change from 1981 to 2006: acromegaly remains under-recognized and under-diagnosed.

Background  Traditionally, acromegaly evaded diagnosis until in its clinically obvious later stages when treatment is more difficult. Over the last 25 years diagnostic tests have improved, but whether clinical disease detection also improved was unknown, so we tested if disease severity at diagnosis had changed from 1981 to 2006.

Clinical use of the optical digitizer for intracranial neuronavigation.

OBJECTIVE Computer-assisted frameless navigation techniques are used in many centers for intracranial neurosurgical procedures. In this study, we assessed the accuracy and the clinical usefulness of a frameless system based on the optical digitizer in a variety of intracranial procedures. METHODS The optical digitizer (StealthStation, Sofamor Danek, Memphis, TN) was used to perform 170 neurosurgical operations. Its accuracy was judged before and after each operation by comparing the computer-estimated error with the real estimated error measured on the patients anatomy. Several objective factors were evaluated to assess the clinical usefulness of the optical digitizer. For craniotomies, the intraoperative extent of resection based on computer-generated images was compared with that on postoperative images, and the length of hospital stay of patients undergoing frameless procedures was compared with that of patients undergoing conventional procedures. For needle biopsies, clinical usefulness was based on the rate of success in establishing a histological diagnosis. RESULTS The optical digitizer was accurate to within 2 mm for all procedures. The computer-estimated error was not significantly different from the real estimated error. The intraoperative extent of resection was accurate in 58 of 60 tumor resection patients, as confirmed on postoperative images. Patients undergoing frameless procedures had a significantly shorter hospital stay than those undergoing conventional procedures (7.5 +/- 1 versus 10.8 +/- 1.3 d, P < 0.05). All biopsies were diagnostic. CONCLUSION The optical digitizer is an accurate frameless device that offers clinical benefits. These include precise surgical resection, decreased hospitalization time, and accurate tissue diagnosis.

Clinical characteristics of silent corticotrophic adenomas and creation of an internet-accessible database to facilitate their multi-institutional study.

OBJECTIVESilent corticotrophic adenomas (SCAs) of the pituitary gland present as clinically nonfunctioning sellar lesions, with normal serum and urine hormone testing results, but stain positively for adrenocorticotropic hormone in immunohistochemical analyses. These tumors are now more readily recognized, but determination of their natural history and responses to treatment is difficult because of their rarity. We report the diagnoses and outcomes for a series of patients with SCAs, and we describe the creation of an Internet-accessible database (www.hsc.virginia.edu/neuro/neurosurgery/pituitary.html) for collection of multi-institutional data on these lesions. METHODSThe medical records of patients with documented SCAs who were treated at the University of Virginia between 1991 and 2002 were reviewed. A comprehensive data collection form was then created and posted online. RESULTSTwenty-seven patients with SCAs were identified, with a female predominance (70%, P = 0.04). Headache was the most common presenting symptom (70%), followed by visual field deficits (52%), acute or subacute pituitary apoplexy (33%), cavernous sinus syndrome (18.5%), and hypopituitarism (11.1%). Extrasellar extension was noted for 92.6% of patients on preoperative magnetic resonance imaging scans. Transsphenoidal surgery was performed for all patients. Follow-up information was available for all patients (median, 60 mo; range, 3–254 mo). Postoperatively, 33% of patients received radiotherapy. Recurrence was noted for 37% of all patients and 41.7% of patients who did not receive postoperative radiotherapy. CONCLUSIONSCAs, although clinically nonfunctioning, may behave like aggressive adrenocorticotropic hormone-secreting adenomas and therefore should receive vigorous follow-up monitoring, with consideration being given to the recommendation of radiotherapy in cases with residual tumor.

The historical evolution of transsphenoidal surgery: facilitation by technological advances

Over the past century, pituitary surgery has undergone multiple evolutions in surgical technique and technological advancements that have resulted in what practitioners now recognize as modern transsphenoidal surgery (TSS). Although the procedure is now well established in current neurosurgical literature, the historical maze that led to its development continues to be of interest because it allows a better appreciation of the unique contributions by the pioneers of the technique, and of the innovative spirit that continues to fuel neurosurgery. The early events in the history of TSS have already been well documented. This paper therefore summarizes the major early transitions along the timeline, and then further concentrates on some of the more recent advancements in TSS, such as the surgical microscope, fluoroscopy, endoscopy, intraoperative imaging, and frameless guidance. The account of each of these innovations is unique because they were each developed as a response to certain historical needs by the surgeon. An understanding of these more recent contributions, coupled with the early history, provides a more complete perspective on modern TSS.

Gender and age in the biochemical assessment of cure of acromegaly.

The principal biochemical criteria for cure in acromegaly are normalization of both glucose-suppressed GH levels and IGF-I levels. As we have reported previously, measurement of GH by highly sensitive assay in conjunction with IGF-I levels has led to are-appraisal of “normal” GH suppression criteria during an OGTT in subjects with acromegaly. In some patients with active acromegaly, glucose-suppressed GH levels as measured by highly sensitive assay are much lower than could previously be appreciated with less sensitive GH assays and some other patients in apparent remission have subtle abnormalities of GH suppression. A question to arise is whether gender differences in glucose-suppressed GH levels as found by others in young healthy subjects should be considered in our interpretation of OGTT criteria for cure in acromegaly. Therefore, we have evaluated parameters of GH secretion in a larger number of subjects from our cohort of postoperative patients with acromegaly and in healthy subjects in order to determine if gender or age associated differences in these parameters exist.Ninety-two subjects with acromegaly (49 men, 43 women) and 46 age-matched healthy subjects (26 men, 20 women) were evaluated with baseline GH and IGF-I levels and nadir GH levels after a 100 g. OGTT. GH was assayed by highly sensitive IRMA (DSL). Basal GH levels were higher in female than in male healthy subjects, but the fall in GH from baseline (%suppression) was also greater in females resulting in no significant difference in mean nadir GH levels in female vs. male healthy subjects (0.09 vs. 0.08 μg/L). In the subjects with acromegaly, there were no significant gender differences in basal, %GH suppression or nadir GH levels.Basal and nadir GH levels correlated significantly only in subjects with active disease (r = 0.84, p < .0001). Similarly, IGF-I levels correlated significantly with basal (r = 0.573, p = .0012), and nadir (r = .702, p < .0001) GH levels only in subjects with active disease. Gender differences in IGF-I levels were not apparent in any group of subjects. As expected, IGF-I levels declined with age in those groups of subjects with normal IGF-I levels. Nadir GH levels did not vary with age. In conclusion, we have not found significant gender or age-related differences in nadir GH levels and thus our data does not support separate OGTT criteria for cure in men and women with acromegaly.

Pituitary hemorrhage into a Rathke's cleft cyst.

This report describes a case of symptomatic pituitary hemorrhage into a Rathkes cleft cyst in a 25-year-old woman. The literature on pituitary hemorrhage in nonadenomatous sellar tumors is reviewed.

Prospective Study of Surgical Treatment of Acromegaly: Effects on Ghrelin, Weight, Adiposity, and Markers of CV Risk

CONTEXT Although epidemiological studies have found that GH and IGF-1 normalization reduce the excess mortality of active acromegaly to expected rates, cross-sectional data report some cardiovascular (CV) risk markers to be less favorable in remission than active acromegaly. OBJECTIVE The objective of the study was to test the hypothesis that remission of acromegaly after surgical therapy increases weight and adiposity and some CV risk markers and these changes are paralleled by a rise in ghrelin. DESIGN Forty-two adults with untreated, active acromegaly were studied prospectively. Changes in outcome measures from before to after surgery were assessed in 26 subjects achieving remission (normal IGF-1) and 16 with persistent active acromegaly (elevated IGF-1) after surgery. SETTING The study was conducted at tertiary referral centers for pituitary tumors. MAIN OUTCOME MEASURES Endocrine, metabolic, and CV risk parameters, anthropometrics, and body composition by dual-energy X-ray absorptiometry were measured. RESULTS Remission increased total ghrelin, body weight, waist circumference, C-reactive protein, homocysteine, high-density lipoprotein, and leptin and reduced systolic blood pressure, homeostasis model assessment score, triglycerides, and lipoprotein (a) by 6 months and for 32 ± 4 months after surgery. The ghrelin rise correlated with the fall in the levels of GH, IGF-1, and insulin and insulin resistance. Weight, waist circumference, and ghrelin did not increase significantly in the persistent active acromegaly group. Total body fat, trunk fat, and perentage total body fat increased by 1 year after surgery in 15 remission subjects: the increase in body fat correlated with the rise in total ghrelin. CONCLUSIONS Although most markers of CV risk improve with acromegaly remission after surgery, some markers and adiposity increase and are paralleled by a rise in total ghrelin, suggesting that these changes may be related. Understanding the mechanisms and long-term implications of the changes that accompany treatment of acromegaly is important to optimizing management because some aspects of the postoperative profile associate with the increased metabolic and CV risk in other populations.