Jonathan J. Yun and John A. Jane Jr.
Lesheng Wang, Shengrong Long, and Qiangqiang Zhou
Kyle C. Wu, Edward R. Laws Jr., and John A. Jane Jr.
M. Harrison Snyder, David T. Asuzu, Dawn E. Shaver, Mary Lee Vance, and John A. Jane Jr.
Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common problem during the postoperative course after pituitary surgery. Although treatment of this condition is well characterized, prevention strategies are less studied and reported. The authors sought to characterize outcomes and predictive factors of SIADH after implementation of routine postoperative fluid restriction for patients undergoing endoscopic transsphenoidal surgery for pituitary adenoma.
In March 2018, routine postoperative fluid restriction to 1000 ml/day for 7 days was instituted for all patients who underwent surgery for pituitary adenoma. These patients were compared with patients who underwent surgery for pituitary adenoma between March 2016 and March 2018, prior to implementation of routine fluid restriction. Patients with preoperative history of diabetes insipidus (DI) or concern for postsurgical DI were excluded. Patients were followed by neuroendocrinologists and neurosurgeons, and sodium levels were checked between 7 and 10 days postoperatively. SIADH was defined by a serum sodium level less than 136 mmol/L, with or without symptoms within 10 days after surgery. Thirty-day readmission was recorded and reviewed to determine underlying reasons.
In total, 82 patients in the fluid-unrestricted cohort and 135 patients in the fluid-restricted cohort were analyzed. The patients in the fluid-restricted cohort had a significantly lower rate of postoperative SIADH than patients in the fluid-unrestricted cohort (5% vs 15%, adjusted OR [95% CI] 0.1 [0.0–0.6], p = 0.01). Higher BMI was associated with lower rate of postoperative SIADH (adjusted OR [95%] 0.9 [0.9–1.0], p = 0.03), whereas female sex was associated with higher rate of SIADH (adjusted OR [95% CI] 3.1 [1.1–9.8], p = 0.03). There was no difference in the 30-day readmission rates between patients in the fluid-unrestricted and fluid-restricted cohorts (4% vs 7%, adjusted OR [95% CI] 0.5 [0–5.1], p = 0.56). Thirty-day readmission was more likely for patients with history of hypertension (adjusted OR [95% CI] 5.7 [1.3–26.3], p = 0.02) and less likely for White patients (adjusted OR [95% CI] 0.3 [0.1–0.9], p = 0.04).
Routine fluid restriction reduced the rate of SIADH in patients who underwent surgery for pituitary adenoma but was not associated with reduction in 30-day readmission rate.
Matthew J. Shepard, M. Harrison Snyder, Sauson Soldozy, Leonel L. Ampie, Saul F. Morales-Valero, and John A. Jane Jr.
Early surgical intervention for patients with pituitary apoplexy (PA) is thought to improve visual outcomes and decrease mortality. However, some patients may have good clinical outcomes without surgery. The authors sought to compare the radiological and clinical outcomes of patients with PA who were managed conservatively versus those who underwent early surgery.
Patients with symptomatic PA were identified. Radiological, endocrinological, and ophthalmological data were reviewed. Patients with progressive visual deterioration or ophthalmoplegia were candidates for early surgery (within 7 days). Patients without visual symptoms or whose symptoms improved on high-dose steroids were treated conservatively. Log-rank and univariate analysis compared clinical and radiological outcomes between those receiving early surgery and those who underwent intended conservative management.
Sixty-four patients with PA were identified: 47 (73.4%) underwent intended conservative management, while 17 (26.6%) had early surgery. Patients receiving early surgery had increased rates of impaired visual acuity (VA; 64.7% vs 27.7%, p = 0.009); visual field (VF) deficits (64.7% vs 19.2%, p = 0.002); and cranial neuropathies (58.8% vs 29.8%, p < 0.05) at presentation. Tumor volumes were greater in the early surgical cohort (15.1 ± 14.8 cm3 vs 4.5 ± 10.3 cm3, p < 0.001). The median clinical and radiological follow-up visits were longer in the early surgical cohort (70.0 and 64.4 months vs 26.0 and 24.7 months, respectively; p < 0.001). Among those with VA/VF deficits, visual outcomes were similar between both groups (p > 0.9). The median time to VA improvement (2.0 vs 3.0 months, p = 0.9; HR 0.9, 95% CI 0.3–3.5) and the median time to VF improvement (2.0 vs 1.5 months; HR 0.8, 95% CI 0.3–2.6, p = 0.8) were similar across both cohorts. Cranial neuropathy improvement was more common in conservatively managed patients (HR 4.8, 95% CI 1.5–15.4, p < 0.01). Conservative management failed in 7 patients (14.9%) and required surgery. PA volumes spontaneously regressed in 95.0% of patients (38/40) with successful conservative management, with a 6-month regression rate of 66.2%. Twenty-seven patients (19 in the conservative and 8 in the early surgical cohorts) responded to a prospectively administered Visual Function Questionnaire-25 (VFQ-25). VFQ-25 scores were similar across both cohorts (conservative 95.5 ± 3.8, surgery 93.2 ± 5.1, p = 0.3). Younger age, female sex, and patients with VF deficits or chiasmal compression were more likely to experience unsuccessful conservative management. Surgical outcomes were similar for patients receiving early versus delayed surgery.
These data suggest that a majority of patients with PA can be successfully managed without surgical intervention assuming close neurosurgical, radiological, and ophthalmological follow-up is available.
David T. Asuzu, Rebecca M. Burke, Jeffrey Hakim, Dylan Coss, Min S. Park, Spencer C. Payne, and John A. Jane Jr.
Giant pituitary macroadenomas with a diameter >4 cm are rare tumors, accounting for only about 5% of pituitary adenomas. They are more difficult to maximally resect safely owing to limited access as well as encasement of adjacent structures. Acidophil stem cell adenomas are rare immature neoplasms proposed to derive from common progenitor cells of somatotroph and lactotroph cells. These adenomas comprise about 4.3% of surgically removed pituitary adenomas. No previous reports have described acidophil stem cell adenomas that grow to the size of giant macroadenomas. This rare entity poses special challenges given the need for maximal safe resection in an immature neoplasm.
The authors report a 21-year-old female who presented with 3 years of progressive visual decline and a giant macroadenoma. She underwent endoscopic transsphenoidal surgery for decompression. Given the tumor size and involvement of adjacent critical structures, gross-total resection was not achieved. The authors review the literature on giant pituitary adenomas and provide a discussion on clinical management for this rare entity.
The authors present a very rare case of a giant pituitary adenoma of acidophil stem cell origin and discuss the technical and management challenges in this rare entity.
Stephen T. Magill, John A. Jane Jr., and Daniel M. Prevedello
Mazin Elsarrag, Parantap D. Patel, Ajay Chatrath, Davis Taylor, and John A. Jane Jr.
Innovations in genomics, epigenomics, and transcriptomics now lay the groundwork for therapeutic interventions against neoplastic disease. In the past 30 years, the molecular pathogenesis of pituitary adenomas has been characterized. This enhanced understanding of the biology of pituitary tumors has potential to impact current treatment paradigms, and there exists significant translational potential for these results. In this review the authors summarize the results of genomics and molecular biology investigations into pituitary adenoma pathogenesis and behavior and discuss opportunities to translate basic science findings into clinical benefit.
The authors searched the PubMed and MEDLINE databases by using combinations of the keywords “pituitary adenoma,” “genomics,” “pathogenesis,” and “epigenomics.” From the initial search, additional articles were individually evaluated and selected.
Pituitary adenoma growth is primarily driven by unrestrained cell cycle progression, deregulation of growth and proliferation pathways, and abnormal epigenetic regulation of gene expression. These pathways may be amenable to therapeutic intervention. A significant number of studies have attempted to establish links between gene mutations and tumor progression, but a thorough mechanistic understanding remains elusive.
Although not currently a prominent aspect in the clinical management of pituitary adenomas, genomics and epigenomic studies may become essential in refining patient care and developing novel pharmacological agents. Future basic science investigations should aim at elucidating mechanistic understandings unique to each pituitary adenoma subtype, which will facilitate rational drug design.
Sepideh Amin-Hanjani, Nicholas C. Bambakidis, Fred G. Barker II, Bob S Carter, Kevin M. Cockroft, Rose Du, Justin F. Fraser, Mark G. Hamilton, Judy Huang, John A. Jane Jr., Randy L. Jensen, Michael G. Kaplitt, Anthony M. Kaufmann, Julie G. Pilitsis, Howard A. Riina, Michael Schulder, Michael A. Vogelbaum, Lynda J. S. Yang, and Gabriel Zada
Davis G. Taylor, Ajay Chatrath, Panagiotis Mastorakos, Gabriella Paisan, Ching-Jen Chen, Thomas J. Buell, and John A. Jane Jr.
Syringogenesis in Chiari malformation type I (CM-I) is thought to occur secondary to impaction of the cerebellar tonsils within the foramen magnum (FM). However, the correlation between the CSF area and syringogenesis has yet to be elucidated. The authors sought to determine whether the diminution in subarachnoid space is associated with syringogenesis. Further, the authors sought to determine if syrinx resolution was associated with the degree of expansion of subarachnoid spaces after surgery.
The authors performed a retrospective review of all patients undergoing posterior fossa decompression for CM-I from 2004 to 2016 at the University of Virginia Health System. The subarachnoid spaces at the FM and at the level of the most severe stenosis were measured before and after surgery by manual delineation of the canal and neural tissue area on MRI and verified through automated CSF intensity measurements. Imaging and clinical outcomes were then compared.
Of 68 patients, 26 had a syrinx at presentation. Syrinx patients had significantly less subarachnoid space at the FM (13% vs 19%, p = 0.0070) compared to those without syrinx. Following matching based on degree of tonsillar herniation and age, the subarachnoid space was significantly smaller in patients with a syrinx (12% vs 19%, p = 0.0015). Syrinx resolution was associated with an increase in patients’ subarachnoid space after surgery compared with those patients without resolution (23% vs 10%, p = 0.0323).
Syrinx development in CM-I patients is correlated with the degree to which the subarachnoid CSF spaces are diminished at the cranial outlet. Successful syrinx reduction is associated with the degree to which the subarachnoid spaces are increased following surgery.