Clinical characteristics and therapeutic outcomes of acromegalic patients with giant growth hormone-secreting pituitary adenomas: a single-center study of 67 cases.

PURPOSE: Acromegalic patients with giant growth hormone-secreting pituitary adenomas (GHPAs) (≥ 40 mm) are relatively rare, and their clinical characteristics and treatment outcome data are limited. This study aims to analyze the clinical practice experience of giant GHPAs. METHODS: Sixty-seven acromegalic patients with giant GHPAs and 67 patients with macro GHPAs (10-39 mm), matched for age and gender from the same hospital during the same period, were retrospectively recruited. The clinical characteristics, treatment, and outcomes were analyzed. RESULTS: Enlargement of the extremities and facial features were the most common symptoms in most patients (92.5%). Compared with the macroadenoma group, more frequent visual impairment (86.6% vs. 25.4%, P < 0.001) and gonadal axis dysfunction (49.3% vs. 34.3%, P = 0.008), higher preoperative fasting GH, nadir GH after OGTT and IGF-1 levels, and a higher proportion of extrasellar tumor invasion were seen in the giant adenoma group. As the adenoma size increases, the total resection rate decreases, and postoperative complications and multimodal treatment strategies increase significantly. Fasting and nadir GH levels remained higher at 1 week postoperatively, and there were more surgical complications and cases of anterior hypopituitarism in the giant group. After a median follow-up of 36 months, 12 patients (36.4%) in the giant GHPA group and 17 (36.2%) in the macro GHPA group achieved biochemical remission. Other factors such as age of onset, age of diagnosis, delayed diagnosis time, metabolic complications, p53 positive rate, and Ki-67 index showed no significant difference between the two groups. CONCLUSIONS: With aggressive multimodal therapy, the biochemical remission rate of acromegalic patients with giant GHPAs is comparable to that of patients with macro adenoma. However, postoperative complications and hypopituitarism need to be closely monitored.

Giant growth hormone-secreting pituitary adenomas from the endocrinologist's perspective.

OBJECTIVES: Since giant (≥40 mm) GH-secreting pituitary adenomas are rarely encountered, data on their characteristics and treatment outcomes are limited. We aimed to investigate the characteristics of giant GH-secreting pituitary adenomas and to compare their clinical, biochemical, imaging and histopathological features with non-giant macroadenomas. MATERIALS AND METHODS: We have evaluated 15 (six female/nine male) and 57 (29 female/28 male) patients with acromegaly in giant and <40 mm adenoma groups, respectively. Patients with <40 mm adenoma were further divided into subgroups with adenoma size 20-29 mm and 30-39 mm. RESULTS: In giant adenoma group, median (IQR) preoperative maximal diameter of adenoma was 40 mm (5 mm), median preoperative GH level was 40 (153.4) ng/mL and median baseline IGF-1 level was 2.19 (1.88) × ULN for age and sex. The number of surgeries was significantly higher in giant adenoma group (median 2, IQR 2) in which 66.7% of patients underwent repeated surgeries (p = 0.014). Residual tumor was detected after last operation in all patients with giant adenoma. Total number of treatment modalities administered postoperatively increased as adenoma size increased (p = 0.043). After a median follow-up duration of 10 years (IQR 10), hormonal remission was achieved in six patients (40%) of giant adenoma group, while the rate of hormonal remission in non-giant adenoma group was 37%. Although preoperative GH and IGF-1 levels and Ki-67 index tended to be higher with increasing adenoma size, there was no statistically significant difference between groups in terms of these variables, as well as age, sex and invasion status. CONCLUSION: Hormonal remission rates of acromegaly patients with ≥20 mm pituitary macroadenoma were comparable. However, giant GH-secreting pituitary adenomas require an aggressive multimodal treatment approach.

Size Matters: Rethinking of the Sizing Classification of Pituitary Adenomas Based on the Rates of Surgery: A Multi-institutional Retrospective Study of 29,651 Patients.

Objective Pituitary adenomas are historically classified into microadenoma or macroadenomas based on size less than or greater than/equal to 1c m. "Giant" adenomas describe tumors ≥4 cm. The aim of this study is to present an evidence-based approach to size classification based on national trends. Design The design involved is multi-institutional retrospective study. Participants A total of 29,651 patients were studied from National Cancer Institute's SEER program from 2004 to 2016 across the United States. Main Outcome Measures The main outcome measures include demographics, treatment characteristics, and overall survival in the population. Results At the 20-mm threshold, the likelihood of operation exceeds the likelihood of nonoperative management. Patients with adenoma size 1 to 19 mm had significantly longer overall survival compared with 20 to 50 mm (Log rank: p < 0.0001). No survival difference was found between size 20 to 29 mm and larger. There was no significant difference in the rate of surgery between 30 to 39 mm and 40 to 50 mm tumors( p = 0.5035). Surgery group had a higher overall survival compared with nonsurgically managed patients (Log rank: p < 0.0001). Conclusion Microadenoma has classically been used to describe pituitary tumors less than 1 cm, though no clinical significance of this threshold has been demonstrated. The current study suggests a size cut-off of 20 or 30 mm as more clinically relevant. Still, future studies are warranted to examine the significance of this classification by specific tumor type, and subclassified as appropriate. There is no difference in the rate of surgery or survival for adenomas between 30 and 50 mm, challenging the 4-mm cutoff threshold for "giant" adenoma.

Primary Endoscopic Management of Apoplexy in a Giant Pituitary Adenoma.

BACKGROUND: Sellar lesions with large suprasellar extension represent a neurosurgical challenge because of their nature and anatomic complexity. The goal of the extended transphenoidal-transtuberculum approach is enlarging the transsphenoidal route superiorly and laterally allowing for a surgical adequate exposure and offering a remarkable versatility in many sellar pathologies. CASE DESCRIPTION: We present the case of a 65-year-old man who suddenly developed blindness, right hemiparesis, and decreased alertness. The initial head computed tomography scan revealed a pituitary apoplexy of a giant adenoma associated with hydrocephalus resulting from obstruction of the foramen of Monro. The video shows a complete lesion removal through the sole endoscopic approach, with opening of the dural layer of sphenoidal plane and successful decompression of the third ventricle. Visual and functional improvement occurred in the immediate postoperative course. No lumbar drain has been used. CONCLUSIONS: This case demonstrates how the endoscopic approach can be attempted as a first and possibly stand-alone option for the surgical management of large sellar-suprasellar lesions. The endoscopic route is not associated with high rates of major complications and is safe when performed by experienced surgeons. In fact, it guarantees an enhanced control of the vascular feeders reaching the tumor from the anterior and middle fossa and results in a satisfactory manipulation of lesions invaginating into the floor of the third ventricle. A careful preoperative assessment of Knosp grade, tumor volume, hemorrhagic components, suprasellar extension, and sphenoid sinus invasion should always guide the management plan and suggest a staged or a combined (with transventricular or pterional approach) removal in particularly challenging cases.

Giant parathyroid adenoma: a rare cause of primary hyperparathyroidism mimicking a carcinoma.

Not required for Clinical Vignette.

Endoscopic Endonasal Approach for Complex Macroadenoma with Suprasellar and Retrochiasmatic Extension.

In this video, we describe the technical nuances of an endoscopic endonasal approach (EEA) for a complex macroadenoma with suprasellar and retrochiasmatic extension. The patient is a 51-year-old male with several years' history of progressive visual loss. Neuro-ophthalmology assessment revealed a profound visual loss with homonymous hemianopsia and left optic nerve atrophy. His pituitary hormonal profile was normal. The options for surgical approach included transcranial, endoscopic endonasal, or a combination of both. An EEA was the preferred surgical option, because it allows for early identification of the pituitary gland, and provides access to the suprasellar region including pre- and retrochiasmatic spaces, which facilitates tumor removal while minimizing manipulation of the optic apparatus. While most pituitary adenomas do not require extracapsular subarachnoidal dissection, there are complex adenomas with subarachnoidal invasion and multilobulated morphology, such as the one presented here, that require a combination of internal debulking, extracapsular and subarachnoidal dissection. The technique presented here allows for complete tumor resection, avoiding the risk of postoperative apoplexy of residual adenoma, and facilitates identification of perforating branches and neural structures that require meticulous preservation. Here, we also illustrate the proper management of reconstruction-related complications. Postoperative course was complicated with meningitis with necrotic nasoseptal flap and required surgical debridement, new inferior turbinate flap, fascia lata, lumbar drain, and 6-week antibiotic treatment. Imaging follow-up showed complete removal of tumor. The patient had significant improvement in visual fields and left visual acuity, and no postoperative hormonal dysfunction. The link to the video can be found at: https://youtu.be/9T5b167bVJA .

First Depiction of Flow Voids to Differentiate Pituicytomas from Giant Adenomas.

Pituicytomas are rare low-grade glial lesions of neurohypophysis or adenohypophysis. They are often misdiagnosed as adenomas due to their similar morphology. Previous reports have underlined their nonspecific aspect. In our experience, presence of flow voids on magnetic resonance, which usually indicate hypervascularized tumors with strong arterial supply, may be a useful sign to identify pituicytomas. Unlike adenomas, pituicytomas are highly vascularized tumors. Second, we emphasize the strong enhancement of these tumors when compared with normal hypophysis, which may be another sign of their hypervascularization. Indeed, adenomas, on the opposite side, present less enhancement than normal hypophysis. This observation is corroborated by previous histologic studies that showed adenomas present less vascular density than normal pituitary glands. However, in large tumors, the normal hypophysis can sometimes not be individualized and thus the enhancement gradient between the tumor and normal tissue cannot be properly assessed. Due to their rarity, no previous reports had ever emphasized the specific signs that could allow us to differentiate pituicytomas from adenomas; however, it seems crucial due to the potential hemorrhagic complications of pituicytoma surgery.

Endoscopic resection of large colorectal adenomas - clinical experience of a tertiary referral centre.

AIM: Colorectal cancer is a leading cause of cancer-related mortality. Adenomatous polyps are typically resected endoscopically to prevent cancer while giant and complex polyps are managed surgically. No criteria clearly define the indications for surgical vs endoscopic resection. Our aim was to evaluate factors associated with the short-term efficacy and safety of endoscopic resection of large (≥ 20 mm) and giant (≥ 40 mm) adenomas. METHOD: Consecutive cases with colonic adenomas larger than 20 mm resected endoscopically were included. Endoscopic, clinical and histological details of polyps were recorded as well as the need for surgical resection. RESULT: A total of 351 resections were included. The average adenoma diameter was 30.34 ± 10.66 mm. Surgery was recommended in 21 (5.98%) cases. In a multivariate analysis for efficacy, two variables were independent risk factors for surgery: adenoma size [OR 1.08 (95% CI: 1.04-1.12)] and caecal location [5.97(1.60-22.33)]. Postpolypectomy complications were documented in 85 (24.2%) cases: bleeding 69 (19.7%), perforations 8(2.3%) and significant discomfort 15(4.3%). Twenty-one patients (6.0%) developed serious complications requiring further hospitalization. In multivariate analysis for safety, independent risk factors for postpolypectomy complications included adenoma size [1.04 (1.06-1.01)], polyp morphology [sessile 2.55 (1.45-4.51), flat 2.40 (1.04-5.52)] and submucosal adrenaline injection [1.87 (1.11-3.20)]. Increments of 1 mm in adenoma diameter beyond 20 mm increased the need for surgery by 8% and the risk of complications by 4%. CONCLUSION: Resection of large or giant adenomas is generally a safe procedure. Although adenoma size and morphology are significant predictors of efficacy and safety, each case should be individually evaluated in a specialist unit for feasibility of endoscopic resection.

Endoscopic Endonasal Extended Approaches for the Management of Large Pituitary Adenomas.

The management of giant and large pituitary adenomas with wide intracranial extension or infrasellar involvement of nasal and paranasal cavities is a big challenge for neurosurgeons and the best surgical approach indications are still controversial. Endoscopic extended endonasal approaches have been proposed as a new surgical technique for the treatment of such selected pituitary adenomas. Surgical series coming from many centers all around the world are flourishing and results in terms of outcomes and complications seem encouraging. This technique could be considered a valid alternative to the transcranial route for the management of giant and large pituitary adenomas.

Early manifestation of communicating hydrocephalus after fractionated stereotactic radiotherapy for aggressive giant atypical prolactinoma.

Aggressive giant invasive pituitary adenomas refractory to standard surgical or medical treatment remain a genuine challenge. In addition, communicating hydrocephalus (CH) attributed to malabsorption of cerebrospinal fluid (CSF) developing after radiotherapy for pituitary adenomas has not been previously reported. Herein, we describe the case of a 48-year-old male presenting with a giant atypical prolactinoma refractory to previous therapies, including pharmacotherapy and repetitive surgery. He underwent image-guided fractionated stereotactic radiotherapy in 28 fractions, resulting in early manifestation of CH associated with undisputed, both radiological and hormonal response. He recovered well after a shunt placement, with otherwise favorable consequences such as sustained tumor regression, decreasing prolactin level, and retained visual function for a 22-month follow-up. Fractionated stereotactic radiotherapy would provide a viable treatment alternative for these refractory cases, while caution should be exercised regarding the possibility of iatrogenic CH.

Primary Hyperparathyroidism Caused by a Giant Parathyroid Adenoma: A case report

Primary hyperparathyroidism is a relatively rare disease entity in Korea. It is characterized by severe skeletal and renal changes due to hypersecretion of parathyroid hormone and rarely shows peptic ulceration, hypertension, pancreatitis and impaired mentality. Primary hyperparathyroidism is most commonly caused by an adenoma, or hyperplasia and rarely by cancer of the parathyroid gland. The authors experienced a case involving a giant parathyroid adenoma in a 62-year-old female. The main symptoms were general weakness, anorexia, and constipation. We detected the giant parathyroid adenoma on the anterior neck by using preoperative localization methods, such as ultrasonography, and a thallium-technetium subtraction scan. A parathyroidectomy was carried out, and the parathyroid adenoma measured 5.0 cm 3.2 cm in size and 12 gm in weight. Clinical laboratory reports and symptoms were normalized with no sequelae. We report this case with a review of the literature related to sizes and weights of adenomas.