pituitary_adenoma_case_series

Pituitary adenoma case series

Despite the widespread popularity of navigation and angled endoscopes in endonasal endoscopy, there are hardly few studies on their efficacy with the extent of resection or retreatment. This is probably the first study to assess the independent impact of these adjuncts among pituitary tumors. Patients with pituitary tumors undergoing endonasal endoscopy were prospectively studied for their demographics, clinico-radiological features, intraoperative use of navigation, and angled endoscopes, in relation to gross total resection (GTR), near total resection (NTR), endocrine remission, and retreatment. Pertinent statistical analyses were performed. Among a total of 139 patients, navigation and angled endoscopes could be used in 54 and 48 patients, respectively, depending upon their availability rather than chosen as per the case. There was no significant difference in baseline characteristics in relation to their use. The surgeon's perception of immediate benefit was noted among 51.9% while using navigation. The use of angled endoscopes towards the end of resection could help with additional tumor removal in 62.5% of patients. Overall, the use of navigation resulted in a significantly higher GTR (80.8% vs. 59.7%, OR 2.83, p = 0.01), a higher GTR/NTR (86.5% vs. 70.8%, OR 2.65, p = 0.04), and a lower retreatment rate (7.7% vs. 20.8%, OR 3.15, p = 0.05) than the others. In functioning tumors with cavernous sinus invasion, navigation had significantly increased remission rates (69.2% vs. 0%, p = 0.03). The use of angled endoscopes yielded a significantly higher GTR/NTR (91.7% vs. 70.6%, p = 0.04) and a lower retreatment rate (0% vs. 15.7%, p = 0.05) among only non-functioning adenomas. In multivariate analyses, the use of neuronavigation had a significant association with both GTR and retreatment rates (p values 0.005 and 0.02 respectively), independent of other confounding factors. The elective intraoperative use of navigation has a significant independent impact on the extent of resection and retreatment overall. While navigation results in better remission rates among functioning tumors with cavernous sinus invasion, angled endoscopy has a significant association with surgical outcomes in non-functioning tumors 1).


The aim of a study of Butenschoen et al. was to analyze the postoperative improvement of visual function after adenoma resection and to identify prognostic factors for the postoperative clinical recovery. They performed a retrospective analysis of all consecutive patients treated via a transsphenoidal approach for pituitary adenomas from April 2006 to December 2019 in a high-volume neurosurgical department. The primary outcome was postoperative visual acuity and visual field impairment; the clinical findings were followed up to 3 months after surgery and correlated with clinical and radiographic findings. In total, 440 surgeries were performed in our department for tumors of the sella region in a time period of 13 years via a transsphenoidal approach, and 191 patients included in the analysis. The mean age was 55 years, and 98% were macroadenomas. Mean preoperative visual acuity in patients with preoperative impairment (n = 133) improved significantly from 0.64/0.65 to 0.72/0.75 and 0.76/0.8 (right eye R/left eye L) postoperatively and at 3 months follow-up (p < 0.001). Visual acuity significantly depended on Knosp classification but not Hardy grading. The strongest predictor for visual function recovery was age. Transsphenoidal pituitary tumor resection remains a safe and effective treatment in patients with preoperative visual impairment. It significantly improves visual acuity and field defects after surgery, and recovery continues at the 3 months follow-up examination 2).


A retrospective analysis of 90-day outcomes of patients undergoing endoscopic pituitary adenomectomy from 2010 to 2019 by a neurosurgical/ENT team was performed. Tumor subtype, cavernous sinus invasion, extent of resection/early remission, endocrinology outcomes, complications, re-operations and readmissions were analyzed. A comparator cohort ≥ 65 years undergoing clinical surveillance without surgery was also analyzed.

Of 468 patients operated on for pituitary adenoma, 123 (26%) were ≥ 65 years (range 65-93 years); 106 (86.2%) had endocrine-inactive adenomas; 18 (14.6%) had prior surgery. Of 106 patients with endocrine-inactive adenomas, GTR was achieved in 70/106 (66%). Of 17 patients with endocrine-active adenomas, early biochemical remission was: Cushing's 6/8; acromegaly 1/4; prolactinomas 1/5. Gland function recovery occurred in 28/58 (48.3%) patients with various degrees of preoperative hypopituitarism. New anterior hypopituitarism occurred in 3/110 (2.4%) patients; permanent DI in none. Major complications in 123 patients were: CSF leak 2 (1.6%), meningitis 1 (0.8%), vision decline 1 (0.8%). There were no vascular injuries, operative hematomas, anosmia, deaths, MIs, or thromboembolic events. Median length of stay was 2 days. Readmissions occurred in 14/123 (11.3%) patients, 57% for delayed hyponatremia. Intra-cohort analysis by age (65-69, 70-74, 75-79, ≥ 80 years) revealed no outcome differences. Cavernous sinus invasion (OR 7.7, CI 1.37-44.8; p = 0.02) and redo-surgery (OR 8.5, CI 1.7-42.8; p = 0.009) were negative predictors for GTR/NTR. Of 105 patients evaluated for presumed pituitary adenoma beginning in 2015, 72 (69%) underwent surgery, 8 (7%) had prolactinomas treated with cabergoline and 25 (24%) continue clinical surveillance without surgery, including two on new hormone replacement.

This study suggests that elderly patients carefully selected for endoscopic adenoma removal can have excellent short-term outcomes including high resection rates, low complication rates and short length of stay. The experience supports a multidisciplinary approach and the concept of pituitary centers of excellence. Based on observations, approximately 25% of elderly patients with pituitary adenomas referred for possible surgery can be monitored closely without surgery 3).


A total of 140 children and adolescents with pituitary adenomas were admitted to Peking Union Medical College Hospital from December 1987 to December 2014, and their clinical manifestations, hormone secretions, images, pathological types, surgical complications and follow-up characteristics were analyzed. Fifty-eight (41.4%) males and 82 (58.6%) females with a mean age of 12.5 years old (range, 6-14 years old) were included. Regarding tumor type, adrenocorticotropic hormone (ACTH), prolactin (PRL), growth hormone (GH), non-functioning and multiple-secreting adenomas accounted for 35.7%, 25.7%, 12.2%, 25.7%, and 0.7% of the tumors, respectively. Microadenomas, macroadenomas and giant pituitary adenomas accounted for 33.6%, 60.0% and 6.4% of the patients, respectively. Approximately 19.3% of the adenomas included in this study were invasive. Transsphenoidal approach surgery (TSS) was commonly used and accounted for 97.9% of the cases in this study. Total resection was achieved in 93.6% of the patients, and subtotal resection was performed in the remaining patients. Finally, 113 patients underwent a full-term follow-up until 2 years after surgery, and tumors recurred in 32 patients. TSS is the most commonly used surgical procedure in patients younger than 14 years old. No significant differences in surgical outcomes, mortality during the perioperative period or complications were observed between patients younger than 14 years old and similar patients in the general population 4).


Pituitary adenomas from 203 patients were collected from January 2013 to April 2017, and immunohistochemical analysis was used to detect the expression of GLUT3 and GLUT1 in tumor specimens. GLUT3-positive expression in the cystic change group was higher than that in the non-cystic change group (P = 0.018). Proportions of GLUT3-positive staining of microadenomas, macroadenomas, and giant adenomas were 22.7% (5/22), 50.4% (66/131), and 54.0% (27/50), respectively (P = 0.022). In cases of prolactin adenoma, GLUT3-positive staining was predominant in cell membranes (P =0.000006), while in cases of follicle-stimulating hormone or luteotropic hormone adenoma, Mei et al. found mainly paranuclear dot-like GLUT3 staining (P = 0.025). In other hormonal adenomas, GLUT3 was only partially expressed, and the intensity of cell membrane or paranuclear punctate staining was weak. In contrast to GLUT3, GLUT1 expression was not associated with pituitary adenomas. Thus, the results indicate that the expression of GLUT3 in pituitary adenomas is closely related to cystic change and hormonal type. This study is the first to report a unique paranuclear dot-like GLUT3 staining pattern in pituitary adenomas 5).


Sixty-three consecutive female patients with a mean age of 29.5 ± 1.1 years. Based on magnetic resonance imaging findings before surgery, 31 (49.2%) patients had microadenoma, and the remaining 32 (50.8%) had macroadenoma. The median follow-up after transsphenoidal surgery was 53 (33-74) months, and long-term surgical remission was achieved in 50 (79.37%) patients with 28 (90.32%) microadenomas and 22 (68.75%) macroadenomas. No meningitis or persistent cerebrospinal fluid leaks occurred. Only one case suffered from persistent diabetes insipidus at follow-up. No severe pituitary dysfunction was observed in microprolactinoma patients. Of patients with menstrual disorders, 85% regained regular menstrual cycles after surgery. Nineteen patients in this cohort desired pregnancy and 15 of them successfully gave birth after surgery. All 17 microadenoma patients with modern surgical indications achieved normal prolactin levels and regular menstrual cycles with only one patient on drug therapy at follow-up.

Long-term follow-up showed a high remission rate in female prolactinoma patients, especially in microadenoma patients, after surgery. Transsphenoidal surgery performed by experienced neurosurgeons may offer a valuable approach to treat female microprolactinoma patients of child-bearing age with modern indications for surgery 6).


Pietro Mortini et al. from the Department of Neurosurgery and Gamma Knife Radiosurgery, IRCCS Ospedale San Raffaele, Milan published a total of 2145 consecutive patients undergoing first surgery for a pituitary adenoma (PA):

795 (37.1%) had a nonfunctioning pituitary adenoma (NFPA), 595 (27.7%) acromegaly, 496 (23.1%) Cushing's disease, 208 (9.7%) a prolactinoma, and 51 patients (2.4%) a Tyrotroph adenoma. Remission was achieved when strict hormonal and radiological criteria were met.

Early surgical remission was achieved in 66% of acromegalic patients, 79.6% of patients with Cushing's disease, 64.4% of prolactinomas, 74.5% of patients with a TSH-secreting adenoma, and 66.9% of NFPAs. The mean (±SE) follow-up was 60.1 ± 1.3 months. The recurrence-free survival at 10 years was 78.2% in acromegalic patients, 68.1% in prolactinomas, 74.3% in Cushing's disease, 70.3% in TSH-secreting adenomas, and 75.3% in NFPAs. Preoperative hypoadrenalism recovered in 35.3%, hypogonadism in 43.3% and hypothyroidism in 37.4% of patients with impaired function before surgery. The mortality rate was 0.2% and major morbidity 2.1%. New onset hypoadrenalism occurred after surgery in 2.5% of patients at risk, hypogonadism in 4.1%, and hypothyroidism in 1.8%. Permanent diabetes insipidus (DI) occurred in 0.9% of patients.

In experienced hands, transsphenoidal microsurgery for PAs achieves remission in most patients with a low complication rate. Pituitary function is preserved in most cases and can recover in more than one-third of patients with preoperative hypopituitarism 7).

2017

A total of 160 patients who underwent surgical resection of pituitary adenomas between February 2004 and December 2016 were reviewed. Eighty-one patients had hormone-secreting pituitary adenomas, and 79 patients had nonfunctioning pituitary adenoma. Among these 160 patients, cases with radiological calcifications on preoperative neuroimaging were included in this study, and clinical characteristics with intraoperative findings were analyzed, retrospectively.

Pituitary adenoma with calcification on preoperative neuroimaging was observed in only nine cases (5.6%). The study population consisted of these nine patients with nonfunctioning pituitary adenoma (n = 5), mixed growth hormone and prolactin-secreting pituitary adenomas (n = 3), and a prolactinoma (n = 1). In 89% of cases (n = 8), calcified pituitary adenoma was soft enough for suction despite the presence of a granular gritty texture intraoperatively. Besides, in a single patient (11%), evidence of hard thick capsular calcification was seen surrounding a soft tumor component; however, it did not interfere with adequate removal of the soft part, and tumor resection was possible in all cases without any complications.

Pituitary adenoma presenting with calcification is relatively rare, but should be kept in mind to avoid making a wrong preoperative diagnosis. As not all pituitary adenomas with calcification are hard tumors, preoperative radiological calcification should not affect decision-making regarding surgical indications 8).


Between 2004 and 2014, 94 patients with pituitary tumors were enrolled in this retrospective study. All patients underwent transsphenoidal surgery and received magnetic resonance imaging (MRI). The pre- and postoperative volumes calculated using the traditional formula were termed A1 and A2, and those calculated using the proposed method were termed O1 and O2, respectively. Wilcoxon signed rank test revealed no significant difference between the A1 and O1 groups (P = 0.1810) but a significant difference between the A2 and O2 groups (P < 0.0001). Significant differences were present in the extent of resection (P < 0.0001), high-grade cavernous sinus invasion (P = 0.0312), and irregular shape (P = 0.0116). Volume is crucial in evaluating tumor status and determining treatment. Therefore, a more scientific method is especially useful when lesions are irregularly shaped or when treatment is determined exclusively based on the tumor volume 9).

2016

Eighteen patients with pituitary macroadenomas underwent transsphenoidal surgery during 2013-2014 under low-field iMRI control (PoleStar N20, 0.15 T). Intrasellar balloons were used in all of them to assess the presence of tumoral remnants. They compared the findings in iMRI and postoperative high-field MRI control scans and also analyzed the number of intermediate imaging controls needed during surgery using this technique.

In total, of the 18 patients, 14 underwent a complete resection. In the remaining four patients, a safe maximal resection was performed, leaving a remnant because of cavernous sinus invasion. In all cases, the balloons were a major help in distinguishing the anatomical structures from the tumoral remnants. Fewer imaging controls were required, and there were no false-positives or negative intraoperative findings. No complications related to the technique were registered.

The “intrasellar balloon technique” is a useful tool that facilitates surgeons' intraoperative decision making. It is an important contribution to overcome the limitations of low-field iMRI as it provides a precise delineation of the resection margins, reduces false-positives and -negatives, and decreases the number of intermediate imaging controls required 10).


Thirty patients with pituitary adenoma were recruited from Huashan Hospital between September 2010 and January 2014. The examination included pupil examination, anterior and posterior segment examination, standard automated perimetry (SAP), RNFL and mfVEP. At three months and nine months after transsphenoid surgery, follow-up measurements were conducted in twenty-three patients, and at 18 months after surgery, the same examinations were performed in seven patients.

The average age of patients was 42.6±12.1years, with 23 males and 7 females. The mean score of SAP improved significantly: 1.75 before surgery; 0.62 at three months after surgery (p=0.00) and 0.50 at nine months after surgery (p=0.00). No significant improvement in RNFL thickness was observed at three months or nine months after surgery. The mean score of mfVEP also improved significantly: 0.85 before surgery; 0.53 at three months (p=0.00) and 0.38 at nine months after surgery (P=0.00). No statistical difference was observed in the outcome of patients at nine months of follow-up and 18 months of follow-up.

Visual field and mfVEP recovery with unchanged RNFL thickness was observed in patients after transsphenoid pituitary adenoma resection 11).


79 patients with pituitary adenomas underwent endoscopic transsphenoidal resection and completed the Headache Impact Test (HIT-6) and the 36-Item Short Form Health Survey (SF-36) QOL questionnaire preoperatively and at 6 weeks and 6 months postoperatively.

Preoperatively, 49.4% of patients had mild headache severity, 13.9% had moderate severity, 13.9% had substantial severity, and 22.8% had intense severity. Younger age and hormone-producing tumors predisposed greater headache severity, while tumor volume, suprasellar extension, chiasmal compression, and cavernous sinus invasion of the pituitary tumors did not. Preoperative headache severity was found to be significantly associated with reduced scores across all SF-36 QOL dimensions and most significantly associated with mental health. By 6 months postoperatively, headache severity was reduced in a significant proportion of patients. Of the 40 patients with headaches causing an impact on daily living (moderate, substantial, or intense headache), 70% had improvement of at least 1 category on HIT-6 by 6 months postoperatively, while headache worsened in 7.6% of patients. The best predictors of headache response to surgery included younger age, poor preoperative SF-36 mental health score, and hormone-producing microadenoma.

The results of this study confirm that surgery can significantly improve headaches in patients with pituitary adenomas by 6 months postoperatively, particularly in younger patients whose preoperative QOL is impacted. A larger multicenter study is underway to evaluate the long-term effect of surgery on headaches in this patient group 12).

2015

278 patients with PAs who underwent surgical interventions were evaluated. Most of the patients were aged 40-50 years with an average of 41 ± 14. The most prominent complaint was pressure effect, which was detected in 153 cases (55.2%). At the second place, hormonal disorders were observed in 125 cases (44.8%). Type of pituitary tumors were: Prolactinomas (29.1%), growth hormone (GH)-producing tumors (25%), nonfunctioning PAs (28.4%), adrenocorticotropic hormone (ACTH)-producing tumors (2.1%), thyroid stimulating hormone (TSH)-producing tumors (0.7%), GH/prolactin (13.6%), GH/ACTH (0.3%), and TSH/ACTH (0.3%). Fifty-seven patients presented with recurrent adenomas. Pituitary apoplexy was found in 11 patients. One case of Sheehan syndrome was recorded among these. The correlations between clinical symptoms and patients, age and sex were not significant.

The overview of demographic characteristics in Iranian patients with PAs with surgical indication has been discussed in the present investigation. The prevalence of different types of PAs and the most common clinical symptoms have been demonstrated 13).


1)
Patil NR, Dhandapani S, Sahoo SK, Chhabra R, Singh A, Dutta P, Walia R, Verma R, Gupta R, Virk RS, Ahuja CK, Dhandapani M, Chaudhary H, Jangra K, Gupta SK. Differential independent impact of the intraoperative use of navigation and angled endoscopes on the surgical outcome of endonasal endoscopy for pituitary tumors: a prospective study. Neurosurg Rev. 2020 Oct 22. doi: 10.1007/s10143-020-01416-x. Epub ahead of print. PMID: 33089448.
2)
Butenschoen VM, Schwendinger N, von Werder A, Bette S, Wienke M, Meyer B, Gempt J. Visual acuity and its postoperative outcome after transsphenoidal adenoma resection. Neurosurg Rev. 2020 Oct 10. doi: 10.1007/s10143-020-01408-x. Epub ahead of print. PMID: 33040306.
3)
Thakur JD, Corlin A, Mallari RJ, et al. Pituitary adenomas in older adults (≥ 65 years): 90-day outcomes and readmissions: a 10-year endoscopic endonasal surgical experience [published online ahead of print, 2020 Sep 16]. Pituitary. 2020;10.1007/s11102-020-01081-9. doi:10.1007/s11102-020-01081-9
4)
Zhao Y, Lian W, Xing B, Wang R. The characteristics of and surgical treatment for pituitary adenomas in patients under 14 years old. Clin Neurol Neurosurg. 2019 Jul 12;184:105423. doi: 10.1016/j.clineuro.2019.105423. [Epub ahead of print] Review. PubMed PMID: 31376772.
5)
Mei T, Zhang J, Wei L, Qi X, Ma Y, Liu X, Chen S, Li S, Wu J, Wang S. GLUT3 expression in cystic change induced by hypoxia in pituitary adenomas. Endocr Connect. 2018 Dec 1. pii: EC-18-0444.R1. doi: 10.1530/EC-18-0444. [Epub ahead of print] PubMed PMID: 30521480.
6)
Yi N, Ji L, Zhang Q, Zhang S, Liu X, Shou X, Lu B. Long-term follow-up of female prolactinoma patients at child-bearing age after transsphenoidal surgery. Endocrine. 2018 Jun 22. doi: 10.1007/s12020-018-1652-y. [Epub ahead of print] PubMed PMID: 29934876.
7)
Mortini P, Barzaghi LR, Albano L, Panni P, Losa M. Microsurgical therapy of pituitary adenomas. Endocrine. 2018 Jan;59(1):72-81. doi: 10.1007/s12020-017-1458-3. Epub 2017 Oct 24. PubMed PMID: 29067608.
8)
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9)
Chuang CC, Lin SY, Pai PC, Yan JL, Toh CH, Lee ST, Wei KC, Liu ZH, Chen CM, Wang YC, Lee CC. Different Volumetric Measurement Methods for Pituitary Adenomas and Their Crucial Clinical Significance. Sci Rep. 2017 Jan 18;7:40792. doi: 10.1038/srep40792. PubMed PMID: 28098212.
10)
Jiménez P, Brell M, Sarriá-Echegaray P, Roldán P, Tomás-Barberán M, Ibáñez J. “Intrasellar Balloon Technique” in intraoperative MRI guided transsphenoidal endoscopic surgery for sellar region tumors. Usefulness on image interpretation and extent of resection evaluation. Technical note. Acta Neurochir (Wien). 2016 Mar;158(3):445-9. doi: 10.1007/s00701-015-2697-9. Epub 2016 Jan 9. PubMed PMID: 26748503.
11)
Qiao N, Ye Z, Shou X, Wang Y, Li S, Wang M, Zhao Y. Discrepancy between structural and functional visual recovery in patients after trans-sphenoidal pituitary adenoma resection. Clin Neurol Neurosurg. 2016 Sep 6;151:9-17. doi: 10.1016/j.clineuro.2016.09.005. PubMed PMID: 27728836.
12)
Wolf A, Goncalves S, Salehi F, Bird J, Cooper P, Van Uum S, Lee DH, Rotenberg BW, Duggal N. Quantitative evaluation of headache severity before and after endoscopic transsphenoidal surgery for pituitary adenoma. J Neurosurg. 2016 Jun;124(6):1627-33. doi: 10.3171/2015.5.JNS1576. Epub 2015 Oct 23. PubMed PMID: 26495954.
13)
Zerehpoosh FB, Sabeti S, Sharifi G, Shakeri H, Alipour S, Arman F. Demographic study of pituitary adenomas undergone trans-sphenoidal surgery in Loghman Hakim Hospital, Tehran, Iran 2001-2013. Indian J Endocrinol Metab. 2015 Nov-Dec;19(6):791-6. doi: 10.4103/2230-8210.167551. PubMed PMID: 26693430.
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