Large Nonfunctioning Pituitary Adenomas Research Articles

Solid tumor size for prediction of recurrence in large and giant non-functioning pituitary adenomas

A subset of large non-functioning pituitary adenomas (lNFPA) and giant non-functioning pituitary adenomas (gNFPA) undergoes early progression/recurrence (P/R) after surgery. This study revealed the clinical and image predictors of P/R in lNFPA and gNFPA, with emphasis on solid tumor size. This retrospective study investigated the preoperative MR imaging features for the prediction of P/R in lNFPA (> 3 cm) and gNFPA (> 4 cm). Only the patients with a complete preoperative brain MRI and undergone postoperative MRI follow-ups for more than 1 year were included. From November 2010 to December 2020, a total of 34 patients diagnosed with lNFPA and gNFPA were included (median follow-up time 47.6 months) in this study. A total of twenty-three (23/34, 67.6%) patients had P/R, and the median time to P/R is 25.2 months. Solid tumor diameter (STD), solid tumor volume (STV), and extent of resection are associated with P/R (p < 0.05). Multivariate analysis showed large STV is a risk factor for P/R (p < 0.05) with a hazard ratio of 30.79. The cutoff points of STD and STV for prediction of P/R are 26 mm and 7.6 cm3, with AUCs of 0.78 and 0.79 respectively. Kaplan–Meier analysis of tumor P/R trends showed that patients with larger STD and STV exhibited shorter progression-free survival (p < 0.05). For lNFPA and gNFPA, preoperative STD and STV are significant predictors of P/R. The results offer objective and valuable information for treatment planning in this subgroup.

Post-Operative Use of Dopamine Agonist in Management of Remaining Nonfunctioning Pituitary Adenoma

Abstract Background: Complete tumor elimination via transsphe-noidal surgical operation is frequently hard for large non-functioning pituitary adenomas (NFPAs). A confirmed medical treating might be beneficial for their managing. Aim of Study: To investigate the effectiveness of dopamine agonist medication in decreasing or avoiding the re-growing of NFPA after ward surgical operation. Patients and Methods: This was a prospective, randomized, clinical trial done in Al-Azhar University Hospitals was conducted on 20 patients experienced primary transsphenoidal surgical operation for pituitary adenoma management, the study was carried out through a period of 12 months from March 2020 to March 2021. Results: Tumour reduction rate of remaining cancer mass was significantly higher in medically-treated group, while tumour growing rate of remaining tumour mass was signifi-cantly elevated in controls. Conclusion: Cabergoline (dopamine agonist was an ef-fective medication for the treatment of remaining NFPA, and its usage was accompanying with an elevated tumour shrink-agerates.

Adenomas hipofisarios y adenomas hipofisarios no funcionantes

Pituitary adenomas (PA) are a rare and heterogeneous group, mainly benign, of central nervous system lesions. Non-functioning pituitary adenomas (NFPAs) account for 25-35% of PA; in adulthood macroadenomas are the commonest. Silent gonadotroph adenomas are the most frequent AH's subtype (70-90% of all NFPAs). Symptoms are related with mass effects of the tumor on the surrounding tissues or with hypopituitarism. AHs are diagnosed by imaging tests, mainly contrast magnetic resonance imaging. In order to discard hormone disorders, endocrine analysis has to be performed. Neuro-ophthalmological study has to be carried out in adenomas involving optic chiasm and/or cavernous sinuses, as well as in patients with visual symptoms. Trans-sphenoidal surgery is the primary treatment for symptomatic or large NFPA.

Stereotactic Radiosurgery and Hypofractionated Stereotactic Radiotherapy for Nonfunctioning Pituitary Adenoma.

Objectives Hypofractionated stereotactic radiotherapy (HSRT) in two to five fractions may offer patients with large nonfunctioning pituitary adenomas (NFPAs) with chiasm involvement a safe and effective treatment over a single week. However, little has been reported regarding this novel approach. Design We compared the feasibility, outcomes, and toxicity of single-fraction stereotactic radiosurgery and HSRT. Setting This study was conducted at a tertiary academic referral center. Participants After approval by the institutional review board, we performed a retrospective cohort study of patients treated at our institution with stereotactic radiosurgery (SRS) and HSRT for NFPA. Selection for SRS or HSRT was based on clinicopathologic factors including tumor size and cavernous sinus invasion at the discretion of the treating physician. Main Outcome Measures Local control, endocrinopathy, and radiation-associated toxicity were evaluated by binary logistic regression and Cox's proportional hazards regression. Results A total of 45 patients with mean follow-up of 5 years were enrolled including 26 patients treated by HSRT with mean follow-up of 3 years and 19 patients treated by SRS with median follow-up of 6 years. Clinicopathologic characteristics were balanced between cohorts. Local failure at last follow-up was 5% in the SRS cohort and 8% in the HSRT cohort, and rates of post-SRS endocrinopathy were similar between each cohort. Late complications including radionecrosis, visual deficit, and secondary malignancy were minimal in either cohort. Conclusions HSRT is an appropriate treatment strategy for patients with NFPAs, particularly for optic pathway preservation in the setting of large tumors with chiasm involvement. Further studies are needed to optimize fractionated approaches and patient selection.

Clinical and Radiographic Characteristics Related to Hyperprolactinemia in Nonfunctioning Pituitary Adenomas

Hyperprolactinemia in patients with nonfunctioning pituitary adenomas (NFPAs) has been explained by the stalk compression of large pituitary adenomas. However, not all large NFPAs are associated with high serum prolactin levels. We aimed to elucidate and compare clinical, hormonal, and radiographic characteristics of NFPAs with and without hyperprolactinemia. We included 201 patients with clinically NFPAs who underwent transsphenoidal surgery performed by a single surgeon during 2010-2017 at a single center in Korea. We measured the three-dimensional diameters (anteroposterior [AP], width, height) and volumes of NFPA on magnetic resonance imaging. We conducted morning basal hormone measurements and dynamic tests preoperatively and 3 months postoperatively. All NFPAs were macroadenomas, and mean tumor volume was 10.4 ± 7.7 cm3. Of 201 patients, 59 (29.4%) had preoperative hyperprolactinemia. Hormone recovery rate was higher in patients with hyperprolactinemia compared with patients without hyperprolactinemia after age, sex, body mass index, tumor volume, and gross total resection adjustments (odds ratio [95% confidence interval]: 2.55 [1.10-5.92]). Tumor width/AP diameter ratio positively correlated with serum prolactin levels (r= 0.186, P= 0.008). Tumor volume was not significantly different between the 2 groups. Preoperative prolactin level is a useful marker to predict hormone recovery after surgery. Patients with NFPA and hyperprolactinemia tended to have a higher width/AP diameter ratio. Hyperprolactinemia of NFPA is more likely affected by tumor growth pattern, such as width/AP diameter ratio, than tumor volume.

Optimal management of non-functioning pituitary adenomas.

Transsphenoidal surgery is the treatment of choice for large non-functioning pituitary adenomas (NFPA) and symptomatic patients. The therapeutic strategies for the management of NFPA after surgery, i.e., watchful waiting, irradiation, or medical therapy have not been compared by randomized controlled trials. Slow re-growth is common, but the natural history of untreated tumors is variable. Conservative follow-up is associated with progression rates of over 40 %. Radiation is highly effective in preventing residual tumor growth, but has serious long-term side effects. Finally, no medications are currently approved for the treatment of NFPA. In this review, we present our view of the optimal management of these tumors, which includes risk stratification for the identification of high-risk patients suitable for active intervention, leaving low-risk patients for careful monitoring.

Commentary

The response to domperidone (a dopamine blocking agent) of serum prolactin (PRL) levels was compared in 3 patients with amenorrhea-galactorrhea without evidence of a pituitary tumor, 23 patients with prolactinomas (10 cases with histologic confirmation), 7 patients with histologically verified large nonfunctioning pituitary adenomas with normal or moderately elevated basal PRL levels, and 6 patients with histologically verified craniopharyngiomas (3 with normal basal PRL levels and 3 with elevated PRL levels). The response was compared with that of 10 patients with postpartum hyperprolactinemia and 14 normal women. Ten milligrams of intravenous domperidone induced a rapid rise in PRL that was maximal at 30 to 45 minutes in normal, postpartum, and amenorrhea-galactorrhea patients who had no sign of tumor. In contrast, domperidone failed to induce significant changes in PRL in cases of prolactinoma, nonfunctioning pituitary adenomas, and craniopharyngioma with or without elevated basal PRL levels. The results suggest that dopaminergic control on PRL secretion was impaired in all tumor cases. The mechanisms of this abnormal dopaminergic control, however, may be different. Whereas dopamine control in cases of prolactinoma is altered at the level of pituitary dopamine receptors, alternative explanations must be found for those tumors with normal basal PRL levels and lack of response to domperidone.

Radiotherapy for non-functioning pituitary adenomas.

The initial management of large non-functioning pituitary adenomas is surgical debulking. In some cases, postoperative radiotherapy (RT) is administered in order to reduce the likelihood of tumour regrowth. Historically, there have been concerns surrounding a number of potentially significant complications of pituitary RT. Recent contributions to the literature, however, suggest that pituitary RT may be less hazardous than was originally thought. This article reviews the evidence relating to the potential side-effects of RT and weighs these risks against the clinically beneficial effects of preventing pituitary tumour regrowth.

P-5-615 - Management of large nonfunctioning pituitary adenomas in staged surgery

P-5-615 - Management of large nonfunctioning pituitary adenomas in staged surgery

Recovery of visual and endocrine function following transsphenoidal surgery of large nonfunctioning pituitary adenomas

A series of 35 patients with non-functioning pituitary adenomas undergoing transsphenoidal surgery is presented. In most cases, the presenting symptoms were related to the mass effect of the tumor. There was no operative mortality. Before surgery, visual field defects were documented in 21 patients (60%). After surgery, excluding 3 patients with preoperative blindness, 28% regained normal vision and 67% showed variable improvement. Preoperatively, 24 patients (69%) had abnormal pituitary function, 24 (69%) had hypogonadism, 7 (20%) adrenal insufficiency, 8 (23%) hypothyroidism and 2 (6%) panhypopituitarism. After pituitary surgery, all but one patient with normal preoperative function retained it. Of the patients with hypopituitarism, 11 (46%) had variable improvement and 13 (54%) had persistent deficits. After surgery, 4 patients (57%) with adrenal insufficiency recovered normal adrenal function, 7 patients (29%) with hypogonadism recovered gonadal function and 1 patient (13%) with hypothyroidism recovered thyroid function. Prior to surgery, the presence of a normal or slightly elevated PRL and a rise in TSH after TRH and in LH after GnRH stimulation were of value in predicting possible recovery of pituitary function after surgery. These observations suggest the presence of viable pituitary tissue in these cases and point out that, in some instances, the mechanism of hypopituitarism may be compression of the portal circulation, rather than destruction of the normal pituitary gland.

Reversible hypopituitarism in patients with large nonfunctioning pituitary adenomas.

Detailed pituitary function studies were conducted on 26 patients with large nonfunctioning pituitary adenomas before and 2-3 months after transsphenoidal adenomectomy. Basal serum PRL, GH, TSH, LH, FSH, and ACTH levels were measured, and dynamic studies of their secretion were made. Preoperatively, GH deficiency was found in all 26 patients (100%), hypogonadism in 25 patients (96%), hypothyroidism in 21 patients (81%), and adrenal insufficiency in 16 patients (62%). Serum PRL levels were low (1.5-4 ng/ml) in 5 patients, normal (5-20 ng/ml) in 9 patients, and mildly elevated (21-53 ng/ml) in the remaining 12 patients. After selective adenomectomy, variable improvement in pituitary function occurred in 17 patients, worsening in 1 patient, and persistence of hypopituitarism in 8 patients. After surgery, normal thyroid function was documented in 12 of the 21 patients (57%) who were hypothyroid preoperatively. Similarly, 6 of the 16 patients (38%) with adrenal insufficiency recovered normal adrenal function, and 8 of the 25 patients (32%) with hypogonadism recovered normal gonadal function. GH deficiency persisted in all but 4 patients (15%). Serum PRL levels decreased in all patients, and only 5 had midly elevated levels after surgery. The presence of a normal or mildly elevated serum PRL level before surgery in these patients was of value in predicting possible recovery of pituitary function after surgery; none of the 5 patients with low preoperative serum PRL levels had any improvement in pituitary function after surgery. A rise in serum TSH levels after TRH administration before surgery also was helpful in predicting possible recovery from hypopituitarism. Most patients who had a rise in serum TSH level in response to TRH stimulation preoperatively recovered some pituitary function after adenomectomy. In contrast, no improvement in pituitary function occurred in patients who had blunted responses to TRH preoperatively. Improvement in pituitary function occurred more often in patients with tumors measuring 25 mm or less than in those with larger tumors. In conclusion, significant improvement in pituitary function may occur after surgical adenomectomy for nonsecreting pituitary tumors. A rise in serum TSH levels in response to TRH stimulation preoperatively suggested the presence of viable pituitary tissue in these patients with hypopituitarism. The presence of a normal or mildly elevated serum PRL level before surgery also suggested the presence of functioning pituitary lactotrophs. These observations suggest that compression of the portal circulation is a possible mechanism for hypopituitarism in this setting.(ABSTRACT TRUNCATED AT 400 WORDS)

Recovery of pituitary function following surgical removal of large nonfunctioning pituitary adenomas.

SUMMARYPituitary function was evaluated in eleven patients with large nonfunctioning pituitary adenomas before and 3 months after surgical adenomectomy. The longest anteroposterior dimension from the anterior wall to the dorsum of the sella on a lateral skull x‐ray ranged between 22 and 45 mm. All adenomas were confirmed histologically and had negative immunostaining for GH, PRL, ACTH and HCG.Based on the pre‐ and post‐operative pituitary function, the patients were divided into two groups. Group I included eight patients who had hypopituitarism pre‐operatively of whom five had partial recovery of pituitary function while three had persistent hypopituitarism. Group II included three patients who had normal pituitary function pre‐ and post‐operatively. Five patients of group I had high normal or slightly elevated serum PRL levels while one had a normal level and two patients had low levels pre‐operatively. TRH but not perphenazine resulted in a variable but definite rise in serum PRL preoperatively in patients with normal or elevated PRL level.In contrast, neither stimulus resulted in a rise in serum PRL in two patients with low basal levels. Serum PRL levels were normal in six patients and low in two others post‐operatively. Serum TSH levels were low in all eight patients with hypothyroidism. TRH resulted in a sustained release of TSH in three patients and was without effect in two patients pre‐operatively. Of eight patients with pre‐operative hypothyroidism, five recovered normal function and three remained hypothyroid. Of six patients with adrenal insufficiency pre‐operatively, two recovered normal pituitary—adrenal function while only two of eight patients recovered gonadal function post‐operatively. None of the eight patients recovered GH responsiveness to stimulation. All patients that recovered pituitary function had normal or slightly elevated serum PRL pre‐operatively. Our data indicate that recovery of pituitary function in patients with large pituitary adenomas and hypopituitarism may occur after surgical removal of the adenoma. One of the possible mechanisms of hypopituitarism in this setting would be interruption of the hypothalamic pituitary portal circulation by the large adenoma. An additional factor might be pressure necrosis and destruction of normal pituitary cells by the expanding adenoma. The extent of that might determine the degree of recovery of pituitary function.