Nonsecreting Pituitary Adenomas Research Articles

Cyberknife radio-neurosurgery for secreting pituitary adenomas treated with single fraction radio-neurosurgery: A systematic review and meta-analysis.

Stereotactic radiosurgery (SRS) is one of the treatment options for the management of residual or recurrent secreting pituitary adenomas (PA). While the role of radiosurgery (RS) by Gamma Knife (GK) has been clearly established, Cyberknife (CK) RS has been evaluated in fewer series. To perform a systematic review of the literature and meta-analysis, with the aim of focusing on the effect of CK RS on secreting PA. Using PRISMA guidelines, we reviewed articles published between January 1994 and January 2024. The inclusion criteria contained: single fraction RS, biochemical remission, tumor control and complication appearance (hypopituitarism). Were incorporated 8 studies including 152 secreting PA. Vast majority were treated in single fraction 115 (75.6%), with an overall rate of 59.9% (p<0.001). Total remission was encountered in 44/108 patients, for an overall rate of 50.2% (p<0.001). Partial remission was inconsistently reported among studies for 25/55 patients, for an overall rate of 38.8% (p=0.003). Uncontrolled disease was encountered in 36/108 patients, for an overall rate of 32.7% (p<0.001). Tumor control was not separately reported for secreting or non-secreting PA, but attained overall high rates. Single fraction CK radiosurgery is common practice for secreting PA. Our meta-analysis suggests high rates of both total and partial remission (as high as 89% if both taken together), with a complete remission rate of 50.2%. These results encourage the use of single fraction CK RS for secreting PA. To reach high rates of biochemical control, high doses of irradiation should be used.

Predictors of Subjective Olfactory Dysfunction and Sinonasal Quality-of-Life After Endoscopic Transsphenoidal Pituitary Surgery.

This is the largest study in North America investigating olfactory outcomes after pituitary surgery to date. Characterize factors associated with subjective olfactory dysfunction (OD) and worsened sinonasal quality-of-life (QOL) after endoscopic TSA. Patients undergoing primary TSA for secreting and non-secreting pituitary adenomas between 2017 and 2021 with pre- and post-operative SNOT-22 scores were included. Subjective OD was determined by the smell/taste dysfunction question on the SNOT-22 (smell-SNOT). 159 patients with pre- and post-operative SNOT-22 scores were included. Average total SNOT-22 scores worsened from pre-operative (16.91 ± 16.91) to POM1 (25.15 ± 20.83, P < .001), with no difference from pre-operative (16.40 ± 15.88) to POM6 (16.27 ± 17.92, P = .936) or pre-operative (13.63 ± 13.54) to POM12 (12.60 ± 16.45, P = .651). Average smell-SNOT scores worsened from pre-operative (0.40 ± 1.27) to POM1 (2.09 ± 2.01, P < .001), and pre-operative (0.46 ± 1.29) to POM6 (1.13 ± 2.45, P = .002), with no difference from pre-operative (0.40 ± 1.07) to POM12 (0.71 ± 1.32, P = .100). Female gender had a 0.9-point (95% CI 0.1 to 1.6) P = .021, increase in smell-SNOT at POM1, resolving by POM6 (0.1 [-0.9 to 1.1], P = .800) and POM12 (0.0 [-1.0 to 0.9], P = .942). Septoplasty with tunnel approach had a 1.1 [0.2 to 2.0] out of 5-point (P = .023) increase in smell-SNOT at POM1, resolving by POM6 (0.2 [-1.1 to 1.6], P = .764) and POM12 (0.4 [-0.9 to 1.6], P = .567). Female gender had a 9.5 (4.0 to 15.1)-point (P = .001) increase in SNOT-22 scores at POM1, resolving by POM6 (3.4 [-3.0 to 9.8], P = .292) and POM12 (6.4 [-5.4 to 18.2], P = .276). Intra-operative CSF leak had an 8.6 [2.1 to 15.1]-point (P = .009) increase in SNOT-22 scores at POM1, resolving by POM6 (5.4 [-1.7 to 12.5], P = .135), and POM12 (1.1 [-12.9 to 15.1], P = .873). Changes in subjective olfaction and sinonasal QOL after TSA may be associated with gender, operative approach, and intra-operative CSF leak, resolving 6-12 months post-operatively.

Open versus Endoscopic and Microscopic Pituitary Adenoma Excision– An Institutional Experience

Introduction: For symptomatic nonsecreting pituitary adenomas (PAs), surgical resection remains the treatment of choice. In this retrospective study, we compare the efficacy of open versus endoscopic and microscopic excision of pituitary adenoma, and to evaluate the merits and demerits of each approach. Material and Methods: This study is a retrospective analysis of patients who underwent surgical excision for symptomatic pituitary adenoma in institute of neurosurgery, madras medical college from January 2022 to December 2022. Various parameters were analyzed including the age, sex, type of surgical resection done, duration of surgery, average blood loss, extent of resection of tumors, and intra- and post-operative complication. Results: A total of thirty eight patients with pituitary adenoma were operated from January 2022 to December 2022. Six patients were operated by endonasal endoscopic transsphenoidal surgery and six patients were operated by microscopic transsphenoidal surgery, 26 patients were operated by Pterional craniotomy and excision of tumour. In an endoscopic and microscopic group, complete tumor excision was achieved in 8 patients (66.6%) and in open surgery group, it was achieved in 6 (23.1%) patients. In endoscopic and microscopic group, the mean operative time was 120 ± 25 min (ranged 80–135 min) and in open surgery group, it was 150 ± 15 min (ranged 130–175 min). In endoscopic and microscopic group, mean blood loss was 120 ± 30 ml (80–160 ml), and in open surgery group, it was 200 ± 15 (150–230 ml). Postoperative CSF leak from wound site was present in 1 case in open surgery group. There was no mortality in either group. Duration of hospital stay was 5 days in endoscopic and microscopic group and 14 days for open surgery group. Conclusion: Endoscopic and microscopic approach provides a wide surgical field and broad lateral vision making easier distinction of tumor tissues. Thus, there is less blood loss, less operative time, less postoperative complication, and early discharge from the hospital.

Non-secreting pituitary adenomas: clinical, biological, radiological and therapeutic aspects: a review of 17 cases

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Prolactinoma and Pregnancy Case report

Pregnancy in a patient with a secreting or non-secreting pituitary adenoma is a rare possibility in clinical practice. Management involves of both the consequences of pregnancy on the natural history of pituitary adenoma and the risks to the mother and fetus. We report the case of a patient who was followed for a pituitary adenoma prolactin and admitted to maternity in a clinical syndrome of intracranial hypertension.

PMON96 A Curious Case of Isolated Oculomotor Nerve Palsy From a Non-Functional Gonadotroph Adenoma

Abstract Introduction Pituitary adenoma typically presents with signs and symptoms of hormone hypersecretion and only 30% of cases present clinically as nonfunctioning adenomas. Furthermore, amongst these less than 5% are associated with ocular nerve palsies. We report a rare case of isolated, unilateral oculomotor nerve palsy due to a non-functional gonadotroph adenoma expanding into the left cavernous sinus. Case 48 years old male with a pertinent medical history of Type 2 Diabetes Mellitus presented to the ER with 3 days of intractable generalized headache associated with double vision, nausea, and increased lethargy. On initial examination, he had findings of oculomotor nerve palsy on the left eye (ptosis, the eye being down and out, and non-reactive pupil to direct or consensual light stimulation) while the rest of his examination was normal. His initial blood work was non-revealing and normal. He underwent extensive imaging including an initial CT scan showing a pituitary macroadenoma, followed by a pituitary-focused MRI brain revealing a hyperplastic pituitary lesion measuring 17.8 mm×22.5 mm in axial axis and 16.4 mm×14.4 mm in sagittal axis with extension into the left cavernous sinus. Biochemical workup was done to evaluate the pituitary function and it revealed a low total testosterone level (95 ng/ml) with a suppressed LH (2.1IU/l) and FSH (1.76 mIU/ml), a low fT4 (0.58 ng/dl) with a suppressed TSH (0.68 mIU/l), low cortisol (1.2 mcg/dl) with a suppressed ACTH of &amp;lt; 5 pg/ml and normal IGF-1 and prolactin levels. He was given stress dose steroids and underwent transsphenoidal resection of the pituitary mass. Pathology of the specimen showed immunoreactivity for SF1 and ASU which was suggestive of a gonadotroph adenoma. The patient showed no signs or symptoms of diabetes insipidus post-operatively, however, was managed for secondary adrenal insufficiency, hypothyroidism, and hypogonadism. He was discharged home on hydrocortisone, levothyroxine, and metformin. He followed up at the Neuroendocrine clinic within a week of discharge and maintained a regular outpatient follow-up where he showed gradual improvement in his symptoms. Conclusion Visual impairment from a non-secreting pituitary adenoma is usually from chiasmal compression. Very rarely, pituitary macroadenoma expands laterally into the cavernous sinus and compresses the oculomotor nerve causing signs and symptoms of third nerve palsy. This case highlights the importance of recognizing different presentations of nonfunctional pituitary adenoma early as this could improve both the morbidity and mortality associated with them. Reference Choong, K., Lee, S L. Pituitary Macroadenoma with invasion into the cavernous sinus, cranial nerve palsies (Endocrine Today) Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Extraocular Muscle Enlargement in Growth Hormone-Secreting Pituitary Adenomas.

While Graves disease is the most common cause of extraocular muscle enlargement, case reports have also associated growth hormone-secretory pituitary adenomas with this same phenomenon. We investigated the prevalence and response to treatment of extraocular muscle enlargement in patients with growth hormone-secretory pituitary adenomas. We retrospectively reviewed extraocular muscle sizes using MR imaging in patients with growth hormone-secretory pituitary adenomas who underwent a transsphenoidal surgical resection compared with a matched control group with nonsecretory pituitary adenomas. Descriptive and comparative statistics were used to evaluate patient characteristics and extraocular muscle sizes between the 2 groups. We identified 16 patients who presented with growth hormone-secreting pituitary adenomas and underwent transsphenoidal surgical resection from 2010 to 2019. The average diameter of the extraocular muscle at the time of diagnosis for the group with growth hormone-secretory pituitary adenomas was larger than that in the control group (4.7 versus 3.8 mm, P < .001). Nine patients achieved insulin-like growth factor 1 level normalization at a median of 11.5 months before their most recent MR imaging evaluation. The average size of the extraocular muscles of patients who achieved a normalized insulin-like growth factor 1 was smaller compared with those that did not (difference, 0.7 mm; 95% CI, 0.3-1.2 mm; P < .001), approaching the size of extraocular muscle in the control group. We describe a high prevalence of extraocular muscle enlargement in patients with growth hormone-secreting pituitary adenomas. Additionally, we note that the size of extraocular muscles decreased with associated improvement in the biochemical control of acromegaly.

Modern Linear Accelerator–Based Radiotherapy Is Safe and Effective in the Treatment of Secretory and Nonsecretory Pituitary Adenomas

Adjuvant radiotherapy (RT) can help achieve local control (LC) and reduce hormonal overexpression for pituitary adenomas (PAs). Prior reports involved Gamma Knife or older linear accelerator (LINAC) techniques. The aim of this study was to report long-term outcomes for modern LINAC RT. Institutional retrospective review of LINAC RT for PAs with minimum 3 years of magnetic resonance imaging follow-up was performed. Hormonal control was defined as biochemical remission in absence of medications targeting hormone excess. LC defined using Response Evaluation Criteria in Solid Tumors on surveillance magnetic resonance imaging. Progression-free survival defined as time alive with LC without return of or worsening hormonal excess from secretory PA. Kaplan-Meier and Cox proportional hazard models used. From 2003 to 2017, 140 patients with PAs (94 nonsecretory, 46 secretory) were treated with LINAC RT (105 fractionated RT, 35 radiosurgery) with median follow-up of 5.35 years. Techniques included fixed gantry intensity-modulated radiotherapy (51.4%), dynamic conformal arcs (9.3%), and volumetric modulated arc therapy (39.3%). Progression-free survival at 5 years was 95.3% for secretory tumors and 94.8% for nonsecretory tumors. Worse progression-free survival was associated with larger planning target volume on multivariable analysis (hazard ratio 2.87, 95% confidence interval 1.01-8.21, P= 0.049). Hormonal control at 5 years was 50.0% and associated with higher dose to tumor (hazard ratio 1.05, 95% confidence interval 1.02-1.09, P= 0.005) and number of surgeries (hazard ratio 1.74, 95% confidence interval 1.05-2.89, P= 0.032). Patients requiring any pituitary hormone replacement increased from 57.9% to 70.0% after RT. Modern LINAC RT for patients with PAs was safe and effective for hormonal control and LC. No difference in LC was noted for functional versus nonfunctional tumors, possibly owing to higher total dose and daily image guidance.

METTL3-mediated RNA m6A Hypermethylation Promotes Tumorigenesis and GH Secretion of Pituitary Somatotroph Adenomas.

Pituitary growth hormone-secreting (GH) pituitary adenomas (PAs) cause mass effects and dysregulated hypersecretion of GH. However, somatic mutation burden is low in PAs. While progress has been made in identifying the epigenetic changes involved in GH-PA initiation, the precise details of its tumorigenesis in GH-PA patients remains to be elucidated. As N6-methyladenosine (m6A) has been shown to often play a critical role in various tumors, it represents a possible initiation point for the tumorigenesis of pituitary adenomas. However, the role of RNA methylation in GH adenomas remains unclear. Protein expression of m6A regulators was measured by immunohistochemistry. Global levels and distribution of m6A methylation were separately analyzed by m6A enzyme-linked immunosorbent assay and m6A sequencing (m6A-seq). RNA interference and lentivirus knockdown system were used to investigate the role of methyltransferase-like 3 (METTL3) and its m6A- dependent regulatory mechanism in tumor progression and GH secretion. We show that both METTL3 messenger RNA and protein expression are elevated in GH-PA samples when compared with both normal pituitary tissue specimens and nonsecreting pituitary adenomas. Levels of m6A modification increased in GH-PAs, and hypermethylated RNAs are involved in hormone secretion and cell development. Knockdown of METTL3 in GH3 cell line resulted in decreased cell growth and GH secretion. Importantly, we found that GNAS and GADD45γ act as the downstream targets in this process. Our findings strongly suggest that m6A methyltransferase METTL3 promotes tumor growth and hormone secretion by increasing expression of GNAS and GADD45γ in a m6A-dependent manner. Thus, METTL3 and the methylated RNAs constitute suitable targets for clinical treatment of GH-PAs.

Stereotactic cryoablation of large tumors of the sellar region with intraoperative CT scans\u2014technical note

BackgroundCryoablation has been used by neurosurgeons in the past and is currently being used by other disciplines to treat kidney cancer, skin lesions, and cardiac conduction defects. Because the currently available cryogenic probes can safely create large lesions and the lesion generation (in the form of ice-ball) can be monitored on intraoperative CT images, cryoablation was used to treat large tumors in and around the sella. In this paper, the author describes a technique to perform this procedure.Main bodyThree large tumors in 3 patients were treated with this method. Age of the patients was 26–58 years with a male/female ratio of 2/1. Patient 1 had a non-secreting pituitary adenoma (measuring 8 × 8 cm) and presented with long-standing total visual loss in both eyes, severe headache, and seizures. She had previous resection and radiation therapy. Patient 2 had prolactinomas (measuring 5.1 × 4.6 cm) and presented with progressive loss of vision and diplopia. Patient 3 had recurrent craniopharyngioma (measuring 7.2 × 5 cm) with prior treatment with resection radiation and frequent drainage of the cyst. He presented with headache and progressive worsening of his vision.The procedure was done on the CT table with intraoperative scans, using Patil stereotactic frame and argon cryoablation probe (Healthtronics). 3-D images were used to plan targets and trajectories. The probe was placed at the target via a trans-nasal trans-sphenoidal route. One to 3 lesions measuring 2.5–3 cm in diameter were made to ablate the tumor. Ice-ball formation was monitored live on CT images.There is no complication. One patient had near-complete resolution of the tumor, two had partial resolution of their tumors, and all had resolution of their presenting symptoms at follow-up of 3–24 months (median 6 months). In one patient, symptoms reoccurred due to the formation of new tumor masses.Short conclusionCryoablation of intracranial tumors and can be done safely and effectively. Live monitoring of lesion generation using CT imaging is a major advantage of this technique.

Ultrasound Doppler examination in the surgical treatment of pituitary adenomas with cavernous sinus extension

Objective: To determine the effectiveness of intraoperative Doppler ultrasound in the surgical treatment of pituitary adenomas with invasive parasellar growth into the cavernous sinus Knosp 3 and Knosp 4. Material and Methods. During 2009–2017, 71 patients with pituitary adenomas (PA) with extension into the cavernous sinus Knosp 3 and Knosp 4 were retrospectively reviewed. According to the size PA were divided into pituitary macroadenomas, (from 10 to 40 mm) in 45 (63.4%) patients, and giant PA (over 40 mm) – in 26 (36.6%) patients. Cavernous sinus invasion Knosp 3 and 4 was identified in 47 (66.2%) and 24 (33.8%) patients respectively. Non-secreting PA - 43 (60.5%) patients and hormone-secreting PA - 28 patients (39.4%). Endoscopic endonasal trassphenoidal (EET) approach was used in all cases. Laterally expanded EET (LEEET) approach was used in 29 cases. Intraoperative Doppler ultrasound (IDUS) was used in 36 (51%) cases. Results. Intraoperative Doppler ultrasound was used in cases of Knosp 3 extension in 23 (32.4%) cases and in Knosp 4 - in 13 (18.3%) cases. Gross total resection, including extension into the cavernous sinus using IDUS was achieved in 22 (62.7%) patients. In cases where IDUS was not used, gross total resection was achieved in 19 (52.7%) cases. In cases where the IDUS was not used, recurrence rate was 7.3%, with IDUS - 5%. Biochemical remission was achieved in 22 (78.6%) cases. Liquorrhea nasalis after surgery was observed in 6 (8.4%) cases, meningoencephalitis - in 1 (1.4%) case, oculomotor palsy -3 (4.2%) cases. Conclusions. Intraoperative Doppler ultrasound is an informative method that provides safe resection of pituitary adenomas with cavernous sinus extension with a low level of possible postoperative complications. Parasellar extension of Pituitary adenomas into the cavernous sinus Knosp 4 significantly reduces the possibility of gross total resection. However, the use of intraoperative ultrasound makes it possible to determine safe boundaries for manipulation both medially and laterally from the internal carotid artery, increasing the level of radicality and the duration of clinical remission. Intraoperative Doppler ultrasound during endoscopic endonasal transsphenoidal surgery of pituitary adenomas with parasellar extension allows to identify the internal carotid artery in the tumor stroma with the existing changed skull base anatomy. Dura incision under intraoperative Doppler ultrasound reduces the risk of internal carotid artery injury.

RADT-36. PROSPECTIVELY ASSESSED TUMOR CONTROL AND TOXICITY OF BENIGN INTRACRANIAL PATHOLOGIES TREATED WITH AUTOMATED VMAT RADIOSURGERY – INITIAL 2 YEAR EXPERIENCE WITH FIRST 100 PATIENTS

Abstract BACKGROUND HyperArc is a treatment planning technology that automates treatment planning and delivery of single-isocenter VMAT radiosurgery (SRS). The technique generates high quality, rapidly deliverable plans. It is unknown whether HyperArc is effective for commonly-encountered, benign, intracranial conditions managed with SRS. Under IRB-approved prospective registry, we collected data on treatment planning/delivery, and clinical outcomes of non-malignant conditions managed with single-fraction or fractionated SRS since deployment in October 2017. METHODS Patients received either single-fraction or fractionated SRS with HyperArc™ (Varian Medical Systems) between October 2017 &amp; October 2019. Patients with &amp;lt; 3 months follow-up were censored. All patients treated received prescription dose to ≥ 99% of gross tumor volume without PTV expansion. All treatments were delivered on Varian Edge linac with 10MV flattening-filter free beam at 2400 MU/min with high-definition (2.5mm) multi-leaf collimator. Standard pathology-specific outcomes and toxicities were assessed. Significant CNS toxicity was defined as Grade 3 or higher event by CTCAE. RESULTS Total of 100 targets (min=0.13cc, max=58.9cc) were treated. 55 received single-fraction SRS (12-22Gy), two received 2-fraction fSRS boost (12Gy) following fractionated treatment, and 43 received 5-fraction fSRS (25-30Gy). The most common pathology was meningioma (n=55), followed by AVM (n=18), non-secretory pituitary adenoma (n=12), acoustic schwannoma (n=9), secretory pituitary adenoma (n=3), glomus tumor (n=2), pineocytoma (n=1), and paraganglioma (n=1). Follow-up ranged from 1.2 to 19.5 months (median 7.2). There were three local failures, all in atypical meningiomas. One patient in the cohort experienced ≥Gr3 toxicity. Each radiosurgery session used median of 3 arcs, with median treatment and beam-on time of 12.03 and 2.3 minutes. Plan quality was excellent; median RTOG conformity was 1.15, and median Paddick GI was 3.52. CONCLUSION Although HyperArc was developed for automated multiple-metastasis radiosurgery, we found it effective and efficient for benign intracranial indications too. Early clinical outcomes appear congruent with historical controls.

SAT-LB302 From Urolithiasis to Genetic Testing: An Unusual Presentation of MEN-4 Syndrome

Background:Germline mutations in the CDKN1B gene are responsible for Multiple Endocrine Neoplasia Type 4 (MEN 4) syndrome (Alrezk et al. 2017). Around 20 cases have been reported to date. Here, we report on a new MEN4 family which possibly extends the phenotypic spectrum attributable to germline mutations in CDKN1B. Clinical Case: A 56-year-old female presented with urolithiasis & was found to have hypercalcemia (serum calcium of 2.76 mmol/l ref. 2.12-2.62 mmol/l). Workup was in keeping with primary hyperparathyroidism (PHPT) (PTH 28.7 pmol/l ref. 1.50-9.30 pmol/l; phosphorus 0.89 mmol/l ref. 0.80-1.45 mmol/l). Sestamibi & US of the neck revealed no clear parathyroid adenoma. Two incidental thyroid nodules were benign on FNA cytology.The patient underwent neck exploration & a single enlarged parathyroid gland was removed. Pathology showed an enlarged hypercellular gland. Her calcium & PTH normalized after surgery but recurrence was documented a year later. Her family history was significant for PHPT in two brothers & a history of kidney stones in a third brother. Multi-gene panel testing (CASR, CDC73, CDKN1B, MEN1, RET, Invitae Corp.) revealed a pathogenic variant (PV) in CDKN1B (c.215delG). The patient underwent a 2 ½ parathyroidectomy with subsequent normalization of her calcium & PTH. Further work-up showed a 4.5mm non-secreting pituitary adenoma. Plasma metanephrines & NE were intermittently elevated. Serum gastrin was also mildly elevated 83 pmol/l (<53 pmol/l). A Ga68-DOTATATE PET scan was negative. Her 23-year-old daughter tested positive for the familial PV. She is asymptomatic & has normal calcium & PTH; pituitary function is normal except for an elevated IGF-1 at 63.9 nmol/l (ref 13.3- 42.6 nmol/l) with borderline growth hormone during OGTT (0.40 ug/l). Her pituitary MRI was normal. One brother with history of prostate cancer, PHPT & partial parathyroidectomy has tested positive for the familial CDKN1B variant. A second brother was also found to carry the familial variant & was clinically asymptomatic.Endocrinological workup has revealed he has PHPT, elevated chromogranin A at 196.2 ng/ml (ref <=82), calcitonin at 25 ng/l (normal <=9 ng/l), IFG1 (35.3 nmol/L ref. 13-21) but normal plasma metanephrines. An MRI of the sella shows an 8mm hypoenhancing lesion. On CT, a retroperitoneal hyperenhancing 4cm mass adjacent to the left ilio-psoas was seen, in keeping with a paraganglioma; additionally, he has a congenital left atrophic kidney & ureter. Two additional brothers; one with history of non-Hodgkin’s lymphoma, PHPT & partial parathyroidectomy & a second brother, also with prostate cancer & recurrent renal stones, have yet to be tested. Conclusions: A new MEN4 family is described here which expands the spectrum of clinical manifestations of this syndrome. Of great interest in our cases is the presence of paraganglioma, urological malformation, & pre-clinical GH/IGF1 elevation.

OR06-02 TBR-760, a Chimeric Somatostatin-Dopamine Compound, Arrests Aggressive Non-Functioning Pituitary Adenoma Growth In Vivo

TBR-760 is a chimeric dopamine (DA)-somatostatin (SST) compound with potent agonist activity at both DA type 2 (D2R; EC50 0.064nM) and SST type 2 (SSTR2; EC50 1.2nM) receptors. Prior studies have demonstrated that the chimeric DA-SST compounds are more potent and effective than either individual or combinations of individual DA and/or SST analogs in inhibiting secretion from pituitary adenomas. Non-functioning pituitary adenomas (NFPA) express high levels of D2R as well as lower levels of SSTRs, including the type 2 receptor (1), and thus have an appropriate receptor profile to respond to TBR-760. The present study examines the ability of TBR-760 to inhibit tumor growth in a mouse model of aggressive NFPA. Heterozygous and null mutant mice lacking one or both copies, respectively, of the pro-opiomelanocortin (POMC) gene (POMC-KO mice)(2) spontaneously develop aggressive, non-secreting pituitary adenomas (3). The POMC-KO mouse tumors have been shown to express D2R and SSTR2 at a similar level as human NFPAs (4). In addition, merging of microarray data (Affymetrix, U133 plus_2.0 and Mouse Genome 430 2.0 arrays), reveals 154 common gene signatures between human NFPAs and the POMC-KO mouse tumors. In an initial study, heterozygous POMC-KO mice with an established pituitary tumor of approx. 10mm3 (mean volume 8.9±0.3), as determined by MRI, were treated with a range of TBR-760 doses (0.125 to 12.5mg/kg, sc, QD) for 60 days. During that time, tumors in vehicle-treated mice increased in size by 890±0.7%, whereas all doses of TBR-760 tested resulted in a nearly complete inhibition of tumor growth from treatment initiation. We then compared the effect of the TBR-760 chimera with that of its individual SST agonist (SSTA) and DA agonist (DAA) components on tumor growth in the POMC-KO mice. As in the earlier study, TBR-760 treatment (1mg/kg, sc, QD), initiated when the mice had an established tumor of approx. 10mm3, completely arrested tumor growth during the 8 weeks of treatment (final mean tumor volume of 8.5±1.3mm3 vs. 54.61±10.6mm3 in vehicle-treated mice). Treatment with equimolar or 10x-higher doses of the individual SSTA or DAA, either alone or in combination, had no significant effect on tumor growth, except in the lower dose DAA group where a modest suppression of tumor growth was observed. These data demonstrate that only the dual DA-SST chimeric compound, TBR-760, completely arrested tumor growth in the POMC-KO mouse model of NFPA. Further, despite the highly aggressive nature of the POMC-KO tumors, significant tumor shrinkage was observed in 20% of the mice treated with TBR-760. These results support the development of TBR-760 as a medical therapy to prevent or arrest the growth of NFPAs and, potentially, to induce NFPA shrinkage.

Comparing Standard Performance and Outcome Measures in Hospitalized Pituitary Tumor Patients with Secretory versus Nonsecretory Tumors

Patient safety indicators (PSIs) and hospital-acquired conditions (HACs) are reported quality measures. We compared their prevalence in patients with secretory and nonsecretory pituitary adenoma using the National (Nationwide) Inpatient Sample (NIS), Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality. The NIS was queried for hospitalizations 2002-2014 involving pituitary adenomas. Prevalence of PSI, HAC, and 9 pituitary-related complications was determined using International Classification of Diseases, Ninth Revision codes. Patient risk factors were evaluated through multivariate analysis. A total of 20,743 patients with nonsecretory tumor and 3385 patients with secretory tumor were identified. Among patients with nonsecretory tumor, 3.79% experienced any PSI or HAC. Of patients with secretory tumor, 2.54% had any PSI or HAC. Before adjusting for covariation, secretory patients were less likely to have any PSI or HAC (odds ratio [OR], 0.652; P= 0.0002), experience any pituitary-related complication (OR, 0.804; P < 0.0001), have a poor outcome (hazard ratio [HR], 0.435; P < 0.0001), and die during hospitalization (HR, 0.293; P= 0.0015). Secretory patients had significantly shorter mean hospital length of stay (secretory/nonsecretory percent difference, -11.95%; P < 0.0001). However, inverse propensity score-weighted ORs comparing the groups' outcomes showed that there was no significant difference in the prevalence of any PSIs and HACs (OR, 0.963; P= 0.8570), pituitary-related complications (OR, 0.894; P= 0.1321), poor outcomes (HR, 0.990; P= 0.9287), in-hospital death (HR, 0.663; P= 0.2967), and length of stay (percent difference, -2.31%; P= 0.2967) between groups. Lack of significant difference in outcome measures after controlling for covariation is consistent with our finding that patients with nonsecretory tumor have more comorbidities on presentation for treatment. PSIs and HACs have limited ability to measure complications specific to pituitary tumors.

Patient-Reported Outcome (PRO) as an Addition to Long-Term Results after High-Precision Stereotactic Radiotherapy in Patients with Secreting and Non-Secreting Pituitary Adenomas: A Retrospective Cohort Study up to 17-Years Follow-Up.

High-precision radiotherapy has been established as a valid and effective treatment option in patients with pituitary adenomas. We report on outcome after fractionated stereotactic radiotherapy (FSRT) in correlation with patient-reported outcomes (PROs). We analyzed 69 patients treated between 2000 and 2019. FSRT was delivered with a median total dose of 54 Gy (single fraction: 1.8 Gy). PRO questionnaires were sent to 28 patients. Median overall survival was 17.2 years; mean local control was 15.6 years (median not reached). Median follow-up was 5.8 years. Twenty (71%) patients participated in the PRO assessment. Physicians reported symptoms grade ≥3 in 6 cases (9%). Of all, 35 (51%) patients suffered from hypopituitarism at baseline, and during follow-up, new or progressive hypopituitarism was observed in 11 cases (16%). Patients reported 10 cases of severe side effects. Most of these symptoms were already graded as CTCAE (Common Terminology Criteria for Adverse Events) grade 2 by a physician in a previous follow-up exam. PROs are an essential measure and only correlate to a certain extent with the physician-reported outcomes. For high-precision radiotherapy of pituitary adenomas, they confirm excellent overall outcomes and low toxicity. In the future, the integration of PROs paired with high-end treatment will further improve outcomes.

SAT-468 Conversion of a Non-Secreting to a Growth Hormone-Secreting Pituitary Adenoma: A Case of Rapid Development of Acromegaly

Introduction: Acromegaly is known to have a slow and insidious course. As a result, the diagnosis is made very late, and at the time of diagnosis most patients have macroadenomas. The average interval from onset of symptoms of acromegaly and diagnosis is approximately 12 years. In addition, conversion of a non-functioning to a functioning pituitary adenoma is very rare. We report a case of a documented non-secreting pituitary macroadenoma turning into a growth hormone secreting one resulting in symptomatic acromegaly in less than 4 years. Clinical Case: A 28 year old African American female presented for evaluation of headaches in 2014. Her past medical history is significant for headaches and childhood epilepsy since age 9. During her workup she was found to have a 1.2 cm pituitary macroadenoma on MRI. Her review of systems showed no evidence of vision changes, galactorrhea, hand enlargement, weakness, changes in body weight or skin pigmentation. Her exam was unremarkable, in particular she did not have any acromegaloid or cushingoid features. Her pituitary hormone work-up was unremarkable, showing no evidence of hormone excess or deficiency. Her IGF-1 was found to be 251 ng/dL (Normal: 78-270). She was evaluated by neurosurgery at that time, who recommended conservative approach with serial follow-up imaging. About 3 years and 8 months later, she was admitted to the hospital for her worsening symptoms of headaches, which were noted approximately 3 times weekly. On further questioning, examination and comparison with old pictures, she was noted to have coarsening of her facial features as well as increase in her ring size. Laboratory tests showed elevated IGF-1 levels on 2 separate occasions at 570 and 551 ng/dL. On repeat imaging, the pituitary macroadenoma was noted to be increased in size to 1.8 cm with increasing suprasellar extension and abutting the anterior aspect of the optic chiasm. She underwent endoscopic excision of pituitary adenoma and reconstruction of sellar floor. The pathology came back positive for human growth hormone staining. IGF-1 level decreased to 244 ng/mL in less than 4 months after surgery. Conclusion: Conversion of non-secreting pituitary adenoma to a growth hormone secreting one can happen over a relatively short time span, resulting in symptomatic acromegaly. We had a unique opportunity to observe this since the patient had previous imaging and biochemical work-up which we could use for comparison. This is contrary to the classic description of acromegaly where the clinical picture develops very slowly over many years or even decades.

How to Deal Pituitary Adenomas: A Retro prospective Study

Pituitary adenoma (PA) is a benign primary tumor that arises from the pituitary gland and is associated with ophthalmological, neurological and endocrinological abnormalities. However, causes that increase tumor progressing recurrence and invasiveness are still undetermined. Most adenomas are benign, approximately 35% are invasive and just 0.1% to 0.2% are carcinomas.Pituitary adenomas represent from 10% to 25% of all intracranial neoplasms and the estimated prevalence rate in the general population is approximately 17% Non-invasive and non-secreting pituitary adenomas are considered to be benign in the literal as well as the clinical sense; however a recent meta-analysis of available research has shown there are to date scant studies – of poor quality – to either support or refute this assumption. Etiology Adenomas which exceed 10 millimetres (0.39 in) in size are defined as macroadenomas, with those smaller than 10 mm referred to as microadenomas. Most pituitary adenomas are microadenomas, and have an estimated prevalence of 16.7% (14.4% in autopsy studies and 22.5% in radiologic studies). A majority of pituitary microadenomas often remain undiagnosed and those that are diagnosed are often found as an incidental finding, and are referred to as incidentalomas. Pituitary macroadenomas are the most common cause of hypopituitarism, and in the majority of cases they are non-secreting adenomas.While pituitary adenomas are common, affecting approximately one in 6 of the general population, clinically active pituitary adenomas that require surgical treatment are more rare, affecting approximately one in 1000 of the general population.

Regression of a nonfunctioning pituitary macroadenoma on the CDK4/6 inhibitor palbociclib: case report

A 71-year-old female patient was referred in 2013 for evaluation of an asymptomatic nonsecreting pituitary adenoma. The adenoma, measuring 13 mm in height by 10 mm in width, was discovered incidentally on imaging in 2012. Biochemical testing demonstrated a nonfunctioning adenoma. Given the relatively small lesion size and the lack of symptoms, observation was preferred over surgical intervention. The patient was monitored with routine MRI, which until 2016 demonstrated minimal growth. In early 2016, the patient developed recurrence of metastatic breast cancer and was treated with palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor. This inhibitor acts on a pathway believed to be involved in pituitary adenoma tumorigenesis. One year after starting palbociclib, routine imaging demonstrated significant regression of her pituitary adenoma. The authors hypothesize that inhibition of the CDK4/6 pathway by palbociclib contributed to adenoma regression in this patient, and that palbociclib may represent a possible adjuvant therapy for the treatment of nonfunctioning pituitary adenomas.

Short-term outcome of endoscopic versus microscopic pituitary adenoma surgery in a single center

Pituitary Adenomas (PA) are a group of benign tumors with diverse biological behavior including different hormonal secretion, cavernous sinus invasion and considerable rates of relapse. The aim of the study was to evaluate the benefits of the Endoscopic Endonasal Transsphenoidal (EET) approach for managing hormonal producing Pituitary Adenomas (PA) in terms of achieving clinical remission in comparison to the Microscopic Endonasal Transsphenoidal (MET) approach. During the period 2014 to 2017 a series of 128 patients with PA were operated on via MET (n=62) and EET (n=66) approach. Endocrinological, neuro-ophthalmic and MRI examinations were assessed preoperatively and postoperatively at 3rd and 12th month. Thirty-two patients were diagnosed with growth-hormone secreting adenomas (GH), 25 with Adrenocorticotropic Hormone secreting adenomas (ACTH), 17 with Prolactin-secreting adenomas (Prl) and 54 with non-secreting pituitary adenomas. The endoscopic group had higher levels of remission in comparison to the microscopic group (81.8% vs. 70.9%), however no significant difference was observed (?=0.128). PA with invasiveness to the cavernous sinus from the endoscopic group had significantly better remission rates opposed to the microscopic group (p<0.05). Macroadenomas not exceeding 40 mm in diameter had higher remission rates in the endoscopic group (p<0.05). Examination of postoperatiove complications showed similar incidence of postoperative diabetes insipidus and CSF leak (p>0.05). The use of endoscopic endonasal transphenoidal approach provides better remission rates in invasive PA compared to the conventional microsurgical approach. A long-term follow-up is still needed for further evaluation of our results.