Prolactinomas are the most common functional pituitary adenoma. Many prolactinomas can be treated with medication, but all patients should be evaluated at a neuroendocrine center including ...experienced neurosurgeons trained in transsphenoidal surgery. Surgery for prolactinomas is feasible and can be performed with low morbidity. Patients never previously treated with dopamine agonists should be considered for surgery if they have neurologic deficits, pituitary apoplexy, an uncertain diagnosis, or a significantly cystic prolactinoma. Patients previously treated with dopamine agonists should be considered for surgery in cases of intolerance or resistance. Recurrent and aggressive prolactinomas often require multimodal therapy.
Abstract
Context
In Cushing disease, the association between the rate of serum cortisol decline and recurrent disease after corticotroph adenoma removal has not been adequately characterized.
...Objective
To analyze postoperative serum cortisol and recurrence rates in Cushing disease.
Methods
Patients with Cushing disease and pathology-confirmed corticotroph adenoma were retrospectively studied. Cortisol halving time was estimated using exponential decay modeling. Halving time, first postoperative cortisol, and nadir cortisol values were collected using immediate postoperative inpatient laboratory data. Recurrence and time-to-recurrence were estimated and compared among cortisol variables.
Results
A total of 320 patients met inclusion/exclusion criteria for final analysis, and 26 of those patients developed recurrent disease. Median follow-up time was 25 months (95% CI, 19-28 months), and 62 patients had ≥ 5 years follow-up time. Higher first postoperative cortisol and higher nadir were associated with increased risk of recurrence. Patients who had a first postoperative cortisol ≥ 50 µg/dL were 4.1 times more likely to recur than those with a first postoperative cortisol < 50 µg/dL (HR 4.1, 1.8-9.2; P = .0003). Halving time was not associated with recurrence (HR 1.7, 0.8-3.8, P = .18). Patients with a nadir cortisol ≥2 µg/dL were 6.6 times more likely to recur than those with a nadir cortisol of < 2 µg/dL (HR 6.6, 2.6-16.6, P < .0001).
Conclusion
Postoperative nadir serum cortisol is the most important cortisol variable associated with recurrence and time-to-recurrence. Compared to first postoperative cortisol and cortisol halving time, a nadir < 2 µg/dL showed the strongest association with long-term remission and typically occurs within the first 24 to 48 hours after surgery.
Objective As interest and enthusiasm for the use of the endoscope in transsphenoidal anterior skull base and pituitary surgery increases, neurosurgeons are increasingly adopting endoscopic technology ...and associated novel concepts. Often this involves a transition from the standard operating microscope as the main means of visualization to the operating endoscope (2D or 3D) during surgery. Methods The authors' experience with this transition is described, including the rationale, advantages and disadvantages of the two surgical techniques. Results The successful use of endoscopic surgery for a large variety of pathological problems involving the anterior skull base and the pituitary region is presented. Perceived advantages for the patient and the surgeon are described, as is the occasional need for transition back to the microscopic approach. Conclusions The endoscopic approach and its allied technology are here to stay. They are useful and occasionally preferable methods for treating a variety of suitable lesions involving the anterior skull base. The importance of incorporating the basic principles of skull base surgery is emphasized.
Diabetes insipidus (DI) is a common complication of transsphenoidal surgery. The purpose of this study was to elucidate patient- and surgery-specific risk factors for DI.
The perioperative records of ...881 patients who had undergone transsphenoidal microsurgery at the authors' institution between January 1995 and June 2001 were reviewed. Among 857 patients without preoperative DI, the overall incidence of immediate postoperative DI was 18.3%, with 12.4% of patients requiring treatment with desmopressin at some point during their hospitalization. Persistent DI requiring long-term treatment with desmopressin was noted in 2% of all patients. An observable intraoperative cerebrospinal fluid (CSF) leak was strongly associated with an increased incidence of both transient (33.3%) and persistent (4.4%) DI. Craniopharyngioma and Rathke cleft cyst (RCC) were also associated with an increased incidence of transient and persistent DI, whereas repeated operation was not. Among patients with pituitary adenomas, those with Cushing's disease had an increased risk of transient (22.2%), but not persistent, DI. Patients with a microadenoma were more likely to suffer transient DI than those harboring a macroadenoma (21.6 compared with 14.3%) but were not more likely to experience persistent DI.
Diabetes insipidus remains a common complication of transsphenoidal surgery; however, it is most frequently transient in nature. Patients with an intraoperative CSF leak, a microadenoma, a craniopharyngioma, or an RCC appear to have an increased risk of transient DI. Risk factors for persistent DI include an intraoperative CSF leak, a craniopharyngioma, or an RCC.
Abstract Background Transsphenoidal surgery is a common neurosurgical procedure for accessing the pituitary and anterior skull base, yet few multicenter analyses have evaluated outcomes after this ...procedure. Study Design Patients undergoing transsphenoidal surgery from 2006 to 2015 were extracted from the ACS NSQIP database. Logistic regression was used to identify predictors of thirty-day complications. Results Of 1240 patients included in this analysis; 6.9% experienced a major complication, and 9.4% experienced any complication within 30 days. Other adverse events included death in 0.7% and non-routine hospital discharge in 5.3%. Most adverse events occurred within the first two weeks post-operatively; 82.9% of patients experienced their first complication during the initial hospital stay. Multivariable analysis demonstrated that predictors of hospital stay longer than four days included American Society of Anesthesiologists (ASA) classification III-V (P=0.015), insulin-dependent diabetes mellitus (P<0.001) and operative time in the third and fourth quartiles (both P<0.001). ASA classification III-V and operative time in the fourth quartile were also predictors of any adverse event (P=0.01 and P=0.005, respectively). Among these patients, 3.7% underwent reoperation, the most common reason for which was post-operative cerebrospinal fluid (CSF) leak (63.6%). Readmission occurred after 8.5% of cases at a median of 11.0 days post-discharge. The most common cause of readmission was hyponatremia (29.5%), followed by delayed post-operative CSF leak (16.0%). Conclusions Overall rates of adverse events in patients undergoing transsphenoidal surgery are relatively low, and most occur prior to discharge from the hospital. Post-discharge complications associated with transsphenoidal surgery include deep vein thrombosis, pulmonary embolism, and urinary tract infection. Delayed post-operative CSF leak is the major cause of reoperation, and hyponatremia is the major cause of readmission.
As demonstrated by histological and neuroimaging studies, pituitary adenomas have a capillary vascular density that differs significantly from that of surrounding structures. The authors hypothesized ...that intraoperative indocyanine green (ICG) fluorescence endoscopy could be used to visually differentiate tumor from surrounding tissues, including normal pituitary gland and dura.
After institutional review board approval, 16 patients undergoing endoscopic transsphenoidal surgery for benign pituitary lesions were prospectively enrolled in the study. A standard endoscopic endonasal approach to the sella was completed. Each patient then underwent endoscopic examination of the sellar dura and then the exposed pituitary adenoma after ICG bolus injection (12.5-25 mg). This examination was performed using a custom endoscope with a near-infrared light source and excitation wavelength filter.
The authors successfully recorded ICG fluorescence from sellar dura, pituitary, and surrounding structures in 12 of 16 patients enrolled. There were 3 technical failures of intraoperative ICG endoscopy, and 1 patient was excluded following discovery of a dye cross-allergy. A standard dose of 25 mg of ICG in 10 ml of aqueous solution optimized visualization of sellar region microvasculature within 45 seconds of peripheral bolus injection. Adenoma was less fluorescent than normal pituitary gland. Dural invasion by tumor was identifiable by a marked increase in fluorescence compared with native dura. The ICG endoscopic examination added 15-20 minutes of operative time under general anesthesia. There were no complications that resulted from use of ICG or the fluorescent light source.
Indocyanine green fluorescence endoscopy shows promise as an intraoperative modality to visually distinguish pituitary tumors from normal tissue and to visually identify areas of dural invasion, thereby facilitating complete tumor resection and minimizing injury to surrounding structures. These results support the continued development of fluorescence endoscopic resection techniques.
Context: Few studies have systematically analyzed the long-term recurrence rates of Cushing’s disease after initial successful transsphenoidal surgery.
Setting: This was a retrospective review of ...patients treated at the University of Virginia Medical Center.
Patients: A total of 215 subjects with Cushing’s disease who underwent initial transsphenoidal surgery for resection of a presumed pituitary microadenoma from 1992–2006 were included.
Main Outcome Measures: Remission and recurrence rates of Cushing’s disease were examined. Recurrence was defined as an elevated 24-h urine free cortisol with clinical symptoms consistent with Cushing’s disease.
Results: Of the 215 patients who underwent transsphenoidal surgery for Cushing’s disease, surgical remission was achieved in 184 (85.6%). The mean length of follow-up was 45 months. Actuarial recurrence rates of Cushing’s disease after initially successful transsphenoidal surgery at 1, 2, 3, and 5 yr were 0.5, 6.7, 10.8, and 25.5%, respectively. Among the 184 patients who achieved remission, 32 (17.4%) patients followed for more than 6 months ultimately had a recurrence of Cushing’s disease. The median time to recurrence was 39 months. Immediate postoperative hypocortisolemia (serum cortisol ≤ 2 μg/dl within 72-h surgery) was achieved in 97 (45.1%) patients. Patients who had postoperative serum cortisol of more than 2 μg/dl were 2.5 times more likely to have a recurrence than patients who had serum cortisol less than or equal to 2 μg/dl (odds ratio = 2.5; 95% confidence interval 1.12–5.52; P = 0.022).
Conclusions: A quarter of the patients with Cushing’s disease who achieve surgical remission after transsphenoidal surgery, recur with long-term follow-up. This finding emphasizes the need for continued biochemical and clinical follow-up to ensure remission after surgery.
Abstract
Pituitary tumors are the second most common adult primary brain tumor, with a variable clinical course. Recent work has identified a number of genetic determinants of pituitary tumor ...subtypes, which may augment traditional histopathologic classification schemes. We sought to determine whether pituitary tumors could be stratified based on objective molecular characteristics using a clinical genomics assay. We performed a retrospective analysis of patients operated on at the Brigham and Women's Hospital from 2012 to 2016 whose pituitary tumors were profiled using multiplexed next-generation sequencing. We analyzed 127 pituitary tumors, including 114 adenomas, 5 craniopharyngiomas, and 8 tumors of other histologies. We observed recurrent BRAFV600E
mutations in papillary craniopharyngiomas, CTNNB1 mutations in adamantinomatous craniopharyngiomas, and activating GNAS mutations in growth hormone–secreting adenomas. Furthermore, we validated the presence of two distinct genomic subclasses in adenomas (i.e., those with disrupted or quiet copy-number profiles) and the significant association of disruption with functional hormone status (P < 0.05). We report the clinical implementation of next-generation sequencing of pituitary tumors. We confirmed previously identified molecular subclasses for these tumors and show that routine screening as part of clinical practice is both feasible and informative. This large-scale proof-of-principle study may help to guide future institutional efforts for pituitary tumor classification as well as the incorporation of such techniques into prospective analysis as part of clinical trials.
We profiled 127 pituitary tumors with a clinical assay, confirming known mutations, uncovering undescribed alterations, and validating stratification of pituitary adenomas by copy-number alterations.
Abstract
Context
No studies have examined the association between body habitus and incidence of pituitary adenoma.
Objective
To determine if body mass index (BMI), waist circumference, body ...somatotype, or height are associated with risk of pituitary adenoma.
Design
Pooled analysis of 3 prospective cohort studies.
Setting
Population-based study.
Participants
Participants of the Nurses’ Health Study (NHS), Nurses’ Health Study II (NHSII), and the Health Professionals Follow-Up Study (HPFS), totaling 284 946 American health professionals.
Exposures
BMI, waist circumference, body somatotype, and height.
Outcome Measures
Self-reported incident pituitary adenoma. Multivariable (MV)-adjusted hazard ratios (HRs) of pituitary adenoma were estimated using Cox proportional hazards models.
Results
During 7 350 156 person-years of follow-up, 387 incident pituitary adenomas were reported. Comparing BMI of ≥30 to <25 kg/m2, higher adult BMI was associated with higher risk of pituitary adenoma (MV HR = 1.74; 95% CI, 1.33-2.28), as was higher maximum adult BMI (MV HR = 1.76; 95% CI, 1.34-2.30), higher waist circumference (MV HR = 1.06; 95% CI, 1.04-1.09 per inch), and higher BMI during early adulthood (at age 18 to 21, MV HR = 2.65; 95% CI, 1.56-4.49). Taller adult height was associated with pituitary adenoma (MV HR = 1.05; 95% CI, 1.01-1.09 per inch). Overall findings were similar in women and men, although power was limited in men (n = 62 cases). Sensitivity analyses demonstrated that the association between adult BMI and pituitary adenoma extended to at least 14 years prior to diagnosis and that the results were not affected when analyses were restricted to participants with similar healthcare utilization.
Conclusion
Higher BMI and waist circumference, from early adulthood to the time of diagnosis, were associated with higher risk of pituitary adenoma.
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