Repeat Transsphenoidal Surgery Research Articles

Diagnostic characteristics and management outcome in patients with acromegaly: a 15-year experience at a tertiary care hospital in Pakistan

Objectives: To assess the diagnostic features of acromegaly, and analyse its management outcomes over a 15-year period in a tertiary care setting. Method: The descriptive, cohort, retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised data of adult patients of either gender diagnosed with acromegaly based on biochemical and radiological evidence between January 2005 and December 2019. Data was retrieved from the medical records. Data was analysed using SPSS 19. Results: Of the 84 subjects, 54(64.3%) were males and 30(35.7%) were female. The overall mean age was 38.69±13.52 years. The patients presented 5.43±4.3 years after the onset of symptoms, with somatic growth features, such as enlarged hands and feet which was the most common complaint 81(96.4%). Of all the patients, 73(86.9%) underwent trans-sphenoidal surgery for the removal of the pituitary adenoma, while 11(13.1%) opted out of the surgical option. Further, 9(12.3%) patients showed biochemical and radiological remission 6 months post-surgery. Out of the remaining 64(87.7%) patients, 38(59.4%) received radiosurgery or radiotherapy, 15(23.4%) underwent repeat trans-sphenoidal surgery, and 11(17.2%) chose medical treatment. Conclusion: Majority of patients failed to achieve remission after trans-sphenoidal surgery, which is the first line of treatment. Radiotherapy/repeat surgery was generally the options taken by those with persistent disease. Key Words: Acromegaly, Characteristics, Diagnosis, Management, Outcome, Pituitary tumour, Growth hormone.

Advances in surgical approaches for refractory pituitary adenomas.

Refractory pituitary adenomas are difficult to control tumors that progress through optimal surgical, medical, and radiation management. Repeat surgery is a valuable tool to reduce tumor volume for more effective radiation and/or medical therapy, and to decompress critical neurovascular structures. Advances in surgical techniques and technologies, including minimally invasive cranial approaches, intraoperative MRI suites, and cranial nerve monitoring, have improved surgical outcomes and expanded indications. Today, repeat transsphenoidal surgery has similar complications rates to upfront surgery in historical cohorts. The decision to operate on refractory adenomas should be made with multidisciplinary teams, balancing the benefit of tumor reduction with the potential for complications, including cranial nerve injury, carotid injury, and cerebrospinal fluid leak.

Sustained hypercortisolemia after bilateral adrenalectomy in Cushing's disease

Abstract Introduction Cushing's disease caused by pituitary corticotropin (ACTH)-secreting tumors. These tumors are almost always benign and are usually microadenomas. In 30 to 40 percent, the microadenoma is so small that it is not detectable by magnetic resonance imaging (MRI). Primary therapy consists of transsphenoidal surgery or pituitary irradiation. Patients who fail this first approach can be treated either by repeat transsphenoidal surgery, medical therapy, radiotherapy, or, as a final resort, surgical or medical adrenalectomy. Clinical Case A 38-year-old male patient presented with headache and fatigue. The laboratory examinations reviewed ACTH depending Cushing's syndrome. A suspicious lesion in the pituitary with no contrast enhancement was observed in Sella MRI. Cavernous sinus sampling consistent with central sources. He was operated in 2018 for pituitary Cushing's disease. Reticulin framework disrupted compatible with adenoma but, ACTH could not be stained in immunohistochemical staining for technical reasons. Due to the high cortisol levels of the patient in the postoperative follow-up, the patient underwent bilateral adrenalectomy in 2019. Because of active Cushing's disease, patient was re-evaluated in 2022. In laboratory examinations, HGB 16.6 g/dL, WBC 6400 /uL, NEU 3200 /uL, PLT 228000 uL, cre 0.76 mg/dL, TSH 1.5 mIU/L, FT4 1.2 ng/dl, FSH 4.6 U/L, LH 7.98 U/L, PTH 23.7 ng/L, PRL 17 µg/L, Total Testosterone 571 ng/dl, Progesterone 0.06 µg/L, GH 0.04 ug/L, IGF1 83 µg/L were detected. Basal cortisol was 35 ug/dl and ACTH 67 ng/L. Cortisol with 1 mg of DST resulted in 28 ug/dl. 2 mg DST resulted in cortisol 38 ng/L. Free cortisol in the urine was found to be 281 mg/day (n<130 mg/day). Empty sella was observed in sella MR. No prominent contoured lesion was observed in the pituitary gland. Adrenal gland was not observed in the Abdominal MRI. No tumor was detected in Thorax CT. The patient's pasireotide 0.3 mg 1×1 treatment was continued. Metyropane 250 mg 2×1 was added to the treatment. Conclusion In Cushing's disease, the ACTH-secreting adenoma may be too small to be detected.

PMON126 Null Cell Adenoma With Low Ki-67 Presenting as Recurrent Pituitary Mass

Abstract Background Pituitary adenomas account for 10% to 15% of all intracranial masses. Among these, approximately one-third are identified as nonfunctioning pituitary adenomas (NFPA) which have a heterogenous profile and an increased potential for relapse one to five years after pituitary surgery. In a retrospective analysis by Almeida et al,multiple surgical resections, elevated ki-67 and cavernous sinus invasion were predictive of recurrence. They typically present with symptoms of mass effect and most are macroadenomas at time of diagnosis. Clinical Case A 65-year-old female initially presented with bitemporal hemianopsia, galactorrhea and amenorrhea 28 years prior. She subsequently underwent transsphenoidal hypophysectomy with resolution of symptoms post operatively. She was clinically stable until 12 years after the surgery when she noted new onset peripheral visual field loss. Upon reevaluation, she was diagnosed with non-functioning pituitary macroadenoma for which she was advised gamma knife surgery but she opted a repeat transsphenoidal pituitary surgery. Her vision improved and she remained asymptomatic thereafter. Sixteen years after her second surgery, she developed blurring of vision. Cranial MRI was done which showed lobulated, heterogeneous hyperdense sellar-suprasellar mass measuring 55×36×47 mm extending to the bilateral sphenoid and ethmoid sinuses, left pterygopalatine fossa, left superior orbital fissure, probably the left foramen lacerum, and left cavernous sinus with encasement of the left internal carotid artery and associated erosion of the adjacent osseous structures. Visual field testing showed mild reduction in field sensitivity with consideration of media opacity and/or uncorrected error of refraction. Baseline hormonal work up was unremarkable. Hence, endoscopic endonasal transphenoidal, transethmoidal parasellar excision of sellar mass, with reconstruction via Hadad Flap was done. There were no intraoperative nor postoperative complications. The specimen was sent for histopathology with provisional anatomic diagnosis of pituitary adenoma. Immunohistochemistry stained negative for chromogranin and any of the pituitary hormones which was consistent with null cell adenoma. The Ki-67, an independent marker of tumor progression and recurrence, was low at less than 1%. However, after 1 month, repeat MRI showed  no significant change in the lobulated, heterogeneously enhancing mass centered in the sellar-suprasellar region. Thus, she received adjuvant radiotherapy with total dose of 5040cGy divided in 28 fractions and was advised close monitoring of pituitary MRI and/or development of any new symptoms. Conclusion In this case, although with low Ki-67, the presence of multiple surgeries and high Knosp grade were recognized as risk factors for its recurrence.Treatment of recurrent NFPA is multimodal which includes re-operation, radiosurgery and radiation therapy. A multidisciplinary team approach is required for its comprehensive management and long-term follow-up. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Surgery and perioperative management of patients with Cushing's disease.

Transsphenoidal surgery (TSS) is the initial treatment modality of first choice in Cushing's disease (CD). With microscopic TSS and endoscopic TSS, two operative techniques with equally favourable remission rates and operative morbidity are available. On average, remission is achieved with primary TSS in 80% of patients with microadenomas and 60% of patients with macroadenomas. The current literature indicates that remission rates in repeat TSS for microadenomas can also exceed 70%. Experience with TSS in CD plays an important role in the success rate and centralization in Pituitary Centres of Excellence has been proposed. Microadenoma stage, imaging-visible adenoma, confirmation of ACTH-positive adenoma on histopathology and noninvasiveness are positive predictors for postoperative remission. In postoperative management, a steroid-sparing protocol with early postoperative assessment of remission status is recommended. Convincing evidence suggests that prolonged postoperative prophylactic antithrombotic measures can significantly reduce the risk of postoperative thromboembolic events in CD. Prevention or successful treatment of cortisol withdrawal syndrome remains an unsolved issue that should be a focus of future research. The further development and broad availability of functional imaging hold promise for improved preoperative detection of microadenomas. Intraoperative identification of microadenomas by specific fluorescent targeting could be a promising future avenue for the treatment of patients with negative imaging.

Outcome in repeat transsphenoidal surgery in patients with persistent and recurrent Cushing's disease

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

Treatment of recurrent and persistent Cushing's disease after first transsphenoidal surgery: lessons learned from an international meta-analysis.

Transsphenoidal surgery (TSS) is the first-line treatment for patients with Cushing's Disease (CD). Recurrence rates after a first TSS range between 3 and 22% within 3years. Management of recurrent or persistent CD may include repeat TSS or stereotactic radiosurgery (SRS). We performed a meta-analysis to explore the overall efficacy of TSS and SRS for patients with CD after an initial surgical intervention. EMBASE, PubMed, SCOPUS, and Cochrane databases were searched from their dates-of-inception up to December 2021. Inclusion criteria were comprised of patients with an established diagnosis of CD who presented with persistent or biochemically recurrent disease after a first TSS for tumor resection and were treated with a second TSS or SRS. Search criteria yielded 2,116 studies of which 37 articles from 15 countries were included for analysis. Mean age ranged between 29.9 and 47.9years, and mean follow-up was 11-104months. TSS was used in 669 (67.7%) patients, while SRS was used in 320 (32.4%) patients, and remission rates for CD were 59% (95%CI 0.49-0.68) and 74% (95%CI 0.54-0.88), respectively. There was no statistically significant difference in the remission rate between TSS and SRS (P = 0.15). The remission rate of patients with recurrent CD undergoing TSS was 53% (95%CI 0.32-0.73), and for persistent CD was 41% (95%CI 0.28-0.56) (P = 0.36). Both TSS and SRS are possible approaches for the treatment of recurrent or persistent CD after a first TSS. Our data show that either TSS or SRS represent viable treatment options to achieve remission for this subset of patients.

AACE2021-A-1093: Diagnostic Characteristics and Management Outcome in Patients with Acromegaly: A 15-Year Experience at a Tertiary Care Hospital in Pakistan

Acromegaly is due to excess Growth hormone (GH) production, usually a result of pituitary adenoma. The diagnosis is often preceded by around 5 years of the active but unrecognized disease. Clinical expression of the disease in each patient depends on the levels of GH and Insulin-like Growth Factor-1 (IGF-1), age, tumor size, and the delay in diagnosis. Successful remission after Trans-sphenoidal surgery (TSS) is reported to be found in 52.5% of cases in the developed countries. It was a Descriptive cohort study. Total 84 patients with biochemical and radiological diagnoses of Acromegaly were included in the study between January, 2005 to December, 2019. Patients’ medical record files were reviewed & data recorded Of the 84 subjects, with a mean age of 38.69 ± 13.52 years, 54 (64.3%) were male while 30 (35.7%) were female. The patients presented at a mean duration of 5.43 ± 4.3 years after the onset of symptoms. The most frequent complaint was somatic growth features in the form of enlarged hands & feet noted by 81 (96.4%) pts. Overall, 73 (86.9%) patients underwent TSS for removal of pituitary adenoma while 11 (13.1%) patients refused to opt for the surgical option. Only 9 (12.3%) patients achieved biochemical & radiological remission after 6 months of surgery. Among 64 patients with persistent disease after TSS, 38 (59.4%) were treated with radiosurgery/radiotherapy, 15 (23.4%) underwent repeat TSS and 11 (17.2%) opted for medical treatment, mostly with Cabergoline. TSS is followed by the documentation of a high rate (88%) of failure to achieve remission and the majority of patients have to opt for radiotherapy/repeat TSS for the persistent disease. With the continuously improving surgical skills, we expect that the figures attaining remission after primary TSS will rise in the decades to come.

Surgical outcome of transsphenoidal surgery in Cushing's disease: a case series of 1106 patients from a single center over 30 years.

Transsphenoidal surgery (TSS) is the first-line treatment for patients with Cushing's disease (CD). However, the reported remission rates of patients who received TSS vary widely between different studies, and the predictors of surgical outcomes remain controversial. The present study analyzed the early outcome of TSS in a large population of patients with CD at a single center, and identified potential predictors of initial remission of TSS in patients with CD. The clinical features and surgical outcomes of CD patients who underwent TSS between 1988 and 2018 at Peking Union Medical College Hospital (PUMCH) were collected and analyzed from their medical records. Of the 1604 CD patients who underwent TSS at PUMCH between February 1988 and October 2018, 1106 patients had complete medical data and pathological results. After surgery, the overall postoperative initial remission rate was 72.5, and 27.5% of patients maintained persistent hypercortisolism. The initial remission rate of patients with preoperative noninvasive adenoma based on MRI (77.1%), intraoperative noninvasiveness (72.5%), microadenoma (74.3%), pathological confirmation (76.4%), and first TSS (73.9%) was significantly higher than that in patients with preoperative invasive adenoma (53.0%), intraoperative invasiveness (60.7%), macroadenomas (65.9%), pathologically negative (49.7%), and repeat TSS (56.0%), respectively (all P < 0.05). The initial remission rate in patients with pseudocapsule-based extracapsular resection (88.1%), MRI-visible adenoma (74.2%) was higher than that in patients without pseudocapsule-based extracapsular resection (77.1%), and with MRI-negative results (64.5%), respectively, but did not reach statistical significance (All P > 0.05). Striking, there was no significant differences in initial remission rates between patients who underwent selective adenomectomy and enlarged adenomectomy (P > 0.05). Whereas, the initial remission rates in patients who underwent partial hypophysectomy only was 51.0%, which was much lower than that in patients underwent selective adenomectomy and enlarged adenomectomy (P < 0.05). The TSS is a safe and effective procedure for the treatment of CD. Whereas, preoperative invasiveness based on MRI, intraoperative invasiveness, macroadenomas pathologically negative, and repeat TSS are related to lower initial remission rates.

Hypercoagulability in ACTH-Dependent Cushing Syndrome

Introduction: ACTH-dependent Cushing syndrome (CS) is associated with hypercoagulability; however, the incidence and timing of thrombosis during evaluation and management of CS is unclear.Objective: To evaluate the incidence and timing of thrombotic events in patients with ACTH-dependent CS following diagnosis and management.Methods: We performed a retrospective, longitudinal study of patients with ACTH-dependent CS seen at Stanford University Health Care from 1998 to 2020. Thrombotic events — deep vein thrombosis (DVT), pulmonary embolism (PE), cerebral vascular accident (CVA), and myocardial infarction (MI) — were recorded between diagnosis and 12 months following therapeutic intervention.Results: Of 108 patients with ACTH-dependent CS, 97 (89.8%) were women, and the mean age at diagnosis was 43.0 years (± 15.7 years). Sixty-eight (63%) patients had hypertension, 38 (35.2%) had diabetes mellitus, and 11 (10.2%) were active smokers. Of the 108 subjects, 97 (89.8%) had Cushing Disease (CD) and 11 (10.2%) had ectopic CS. Of the 97 patients with CD, 38 (39.2%) underwent inferior petrosal sinus sampling (IPSS), 59 (60.8%) underwent transsphenoidal surgery (TSS), 19 required repeat TSS (19.6%), and 15 underwent TSS and bilateral adrenalectomy (BAL) (15.4%). Of the 11 patients with ectopic CS, 3 (27.2%) underwent IPSS, 6 (54.5%) underwent BAL, and 1 (9.1%) underwent TSS and BAL.There were 10 thrombotic events among 7 (7.2%) CD patients, but no thrombotic events among ectopic CS patients. Of the thrombotic events, there were 7 (70%) DVT/PE, 2 (20%) CVA, and 1 (10%) cortical vein thrombosis. Six (60%) occurred within 30 days after TSS (range 3-25 days), 2 (20%) between 31 days and 1 year after TSS (range 59-165 days), 1 (10%) 26 days after IPSS but prior to TSS, and 1 (10%) in a patient who did not undergo IPSS or surgery. No thrombotic events were noted after BAL. Of the 8 postoperative thrombotic events, 5 (62.5%) occurred while patients received supraphysiologic glucocorticoid replacement (defined as >25mg hydrocortisone or equivalent daily) after curative surgery, 1 (12.5%) occurred after a patient was tapered to physiologic glucocorticoid replacement, and 2 (25%) occurred in patients who had persistent disease despite surgery. The degree of hypercortisolism at baseline was not associated with risk of thrombotic events.Conclusions: In this retrospective study, 6.5% of ACTH-dependent CS patients had a thrombotic event, all in patients with CD. The majority had venous thromboembolism with DVT/PE, and the highest incidence occurred up to 30 days after surgery. The degree of hypercortisolism at baseline did not correlate with subsequent thrombotic events. Therefore, it is important to monitor all patients with ACTH-dependent CS following surgical intervention for venous thromboembolism.

Treatment and outcomes of recurrent/persistent Cushing's disease: a single-center experience.

Although transsphenoidal adenomectomy is the first treatment choice for Cushing's disease (CD), tumor recurrence rates are as high as 45%, resulting in a therapeutic challenge for endocrinologists and neurosurgeons. For recurrent/persistent CD (RCD/PCD), Repeat transsphenoidal surgery (RTSS), radiotherapy, gamma knife radiosurgery (GKRS) or bilateral adrenalectomy may be considered. The purpose of the study was to report the treatments and outcomes of RCD/PCD in a single center. A retrospective study was performed on 55 RCD/PCD patients from a single center between 2000 and 2012 at Peking Union Medical College Hospital (PUMCH). Among the 55 RCD/PCD patients, 43 achieved remission (78%), and 11 maintained a PCD status (20%). The average times to recurrence after the initial treatment and Repeated treatment were 43.25±10.3 and 5.13±4.7 months, respectively (P=0.006); 17.6% of the patients experienced recurrence within the first year, and 52.9% of the patients experienced recurrence within 1.1-5.0 years. For the Repeated treatments, surgery was more effective for the biochemical remission of serum cortisol and adrenocorticotrophic hormone (ACTH) levels than radiotherapy. Delayed remission occurred in 28.9% (11/38) of the patients after Repeated surgery. Considering the previous biochemical levels after the initial surgery in RCD patients, 19.75% of patients experienced recurrence when serum cortisol levels were less than <3 µg/dL, and 51.4% of patients experienced recurrence under conditions of hypocortisolism and when 24-hour urinary free cortisol (24 UFC) was undetectable. RTSS remains a recommended treatment option for RCD/PCD patients while radiotherapy is suggested as an adjunctive treatment. Intensive follow-up is recommended, as patients with serum cortisol levels <3 µg/dL or undetectable 24 UFC levels can still experience recurrence after surgical treatment.

PET-guided repeat transsphenoidal surgery for previously deemed unresectable lateral disease in acromegaly.

The object of this study was to determine if revision transsphenoidal surgery (TSS), guided by 11C-methionine PET/CT coregistered with volumetric MRI (Met-PET/MRCR), can lead to remission in patients with persistent acromegaly due to a postoperative lateral disease remnant. The authors identified 9 patients with persistent acromegaly following primary intervention (TSS ± medical therapy ± radiotherapy) in whom further surgery had initially been discounted because of equivocal MRI findings with suspected lateral sellar and/or parasellar disease (cases with clear Knosp grade 4 disease were excluded). All patients underwent Met-PET/MRCR. Scan findings were used by the pituitary multidisciplinary team to inform decision-making regarding repeat surgery. Revision TSS was performed with wide lateral exploration as guided by the PET findings. Endocrine reassessment was performed at 6-10 weeks after surgery, with longitudinal follow-up thereafter. Met-PET/MRCR revealed focal tracer uptake in the lateral sellar and/or parasellar region(s) in all 9 patients, which correlated with sites of suspected residual tumor on volumetric MRI. At surgery, tumor was identified and resected in 5 patients, although histological analysis confirmed somatotroph tumor in only 4 cases. In the other 4 patients, no definite tumor was seen, but equivocal tissue was removed. Despite the uncertainty at surgery, all patients showed immediate significant improvements in clinical and biochemical parameters. In the 8 patients for whom long-term follow-up data were available, insulin-like growth factor 1 (IGF-1) was ≤ 1.2 times the upper limit of normal (ULN) in all subjects and ≤ 1 times the ULN in 6 subjects, and these findings have been maintained for up to 28 months (median 8 months, mean 13 months) with no requirement for adjunctive medical therapy or radiotherapy. No patient suffered any additional pituitary deficit or other complication of surgery. This study provides proof of concept that Met-PET/MRCR can be helpful in the evaluation of residual lateral sellar/parasellar disease in persistent acromegaly and facilitate targeted revision TSS in a subgroup of patients.

SAT-248 Cushing’s Disease with Two ACTH-Producing Pituitary Tumors

Objective: The objective of this case report is to discuss a case of Cushing’s disease with two ACTH-producing pituitary tumors and emphasize consideration of repeat surgery as a treatment modality for unsuccessful initial surgery. Methods: We present a case of a patient with Cushing’s disease with two ACTH-producing pituitary tumors and a literature review. Results: A 36 year-old female found to have left supraclavicular fossa swelling was screened for Cushing’s syndrome. Midnight salivary cortisol levels elevated at 0.636 ug/dL and 0.316 ug/dL (<0.010–0.090 ug/dL). 24-hour urine cortisol 162 ug/24 hr (0–50 ug/24 hr). 1-mg dexamethasone suppression test 14.0 ug/dL. Serum morning cortisol 26.4 ug/dL with corresponding ACTH 66.7 pg/mL (7.2–63.3 pg/mL). MRI brain with and without contrast showed a 7-mm relatively hypoenhancing lesion of the anterior pituitary gland. 8-mg dexamethasone suppression test 2.7 ug/dL. She underwent transsphenoidal surgery (TSS) and pathology was consistent with a pituitary adenoma staining positive for ACTH. No residual tumor was seen. Postoperative morning serum cortisol 17.0 ug/dL and ACTH 79 pg/mL (9–46 pg/mL). She had repeat TSS and the area of resection was clean with no residual tumor but a second adenoma was found that was not visualized on MRI and was distinct from the initial lesion. Postoperative morning cortisol 0.7 ug/dL and ACTH <9 pg/mL (9–46 pg/mL). Pathology was consistent with pituitary adenoma staining positive for ACTH. She is now on steroids for central adrenal insufficiency. Discussion: First-line treatment for Cushing’s disease is surgical resection of the primary lesion (Nieman LK, Biller BMK, et al. Treatment of Cushing’s syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2015; 100(8):2807–2831). Remission rates are 73–76% for selectively resected microadenomas but 43% for macroadenomas (Nieman et al. 2015). For patients who undergo a noncurative surgery, second-line therapies include repeat TSS, radiotherapy, medical therapy, and bilateral adrenalectomy. Repeat TSS is recommended particularly in patients who had evidence of incomplete resection or a pituitary lesion on imaging although this was not the case with our patient. Repeat TSS is cited to be successful in about 50–60% of cases (Patil CG, Veeravagu A, et al. Outcomes after repeat transsphenoidal surgery for recurrent Cushing’s disease. Neurosurgery. 2008;63(2):266–270) but carries an increased risk of hypopituitarism and lower likelihood of remission compared to initial surgery. Remission can be achieved more rapidly compared to other second-line treatments. Conclusion: In Cushing’s Disease with unsuccessful initial surgery, consideration for repeat TSS may be considered when there is access to an expert pituitary surgeon.

MON-255 Oral Contraceptive Pills Mask an Aggressive Crooke’s Cell Pituitary Adenoma

BackgroundCrooke’s cell tumors are rare and aggressive forms of pituitary adenomas. This variant of Cushing’s disease requires prompt diagnosis to avoid life-threatening complications. We report a unique case of Crooke’s cell tumor with longstanding history of irregular menstrual cycles, undiagnosed and later presented as acute unilateral ptosis and diplopia due to aggressive tumor invasion.Clinical Case23-year-old female presented to the ER with facial swelling, left eye droop and diplopia for 3 days. She had a past medical history of oligomenorrhea and hirsutism which was normalized by oral contraceptive pills (OCP)- a combination of ethinyl estradiol and drospirenone for the last 3 years. Years prior, workup of her oligomenorrhea showed normal androgenic profile with normal DHEA-S, testosterone and 17-OH progesterone. Current exam was also significant for elevated blood pressure 200/110mmHg, BMI 37, pigmented abdominal striae and terminal hair over her chin. Labs remarkable for hypokalemia K+ 2.7 mmol/L (3.5-5.3), elevated AM cortisol 51 mcg/dL (4-20), low TSH 0.152 mcUnit/mL (0.4-5.0), low IGF-1 170 ng/mL (222-566) and FSH 1.4 mUnit/mL (1.0-9.0), with normal prolactin 24.3 ng/mL (<0.5-25) and free T4 0.87ng/dL (0.8-1.8). MRI brain showed 2.8cm homogenous enhancing soft tissue mass involving the central skull base, sphenoid sinus, sella, suprasellar cistern, and parasellar regions; displacing the optic chiasm, and invading the cavernous sinuses bilaterally and orbital apices. Post trans-sphenoidal surgery (TSS) of the pituitary mass, her left eye ptosis and diplopia resolved. Post-op MRI showed subtotal resection of the extra-axial enhancing abnormality at the central skull base with extension to multiple other anatomic spaces. Pathology read consistent with aggressive Crooke’s cell adenoma, showing invasive biologic behavior without an elevated proliferation index with positive ACTH immunohistochemistry supportive of corticotroph cell adenoma. Post-op ACTH level 73 pg/mL (6-50) and cortisol 12.5 mcg/dL (4-20), while on dexamethasone. Repeat TSS was performed for residual adenoma. Cortisol remains elevated at 15.7mcg/dL despite high dose dexamethasone taper by the neurosurgery team for post-op development of right eye ptosis. She is currently awaiting proton beam radiation therapy.ConclusionCrooke’s cell tumors are an aggressive form of pituitary adenoma for which early diagnosis is crucial for its prognosis. Our case highlights the importance of maintaining a wide differential in evaluating young women with menstrual irregularities and to include screening for Cushing’s syndrome. Empiric treatment with OCPs can mask symptoms in the earlier course of Cushing’s disease as in our patient, causing recognition only after presentation with significant tumor growth. Earlier detection could have prevented adenoma invasion and potential neurological sequelae.

Outcomes After Repeat Transsphenoidal Surgery for Recurrent Cushing Disease: Updated.

Transspheniodal surgery (TSS) for Cushing disease (CD) is considered the first-line treatment; however, reported recurrence rates are high. To systemically review indications and outcomes for repeat TSS in recurrent CD. Retrospective review of patients undergoing TSS from 2008 to 2018 was performed. Patients undergoing repeat TSS for clinical and/or biochemically recurrent CD with follow-up at least 12 mo postoperatively were included. These data were analyzed in our "current cohort" and combined with our previously published data in a "combined cohort." The current cohort of patients undergoing operations from 2008 to 2018 with repeat surgery following a prior operation included 15 patients. Pathology at the time of first operation was positive for adrenocortiotrophic hormone (ACTH) adenoma in 13/15 (86.7%) and 9/15 (60%) had evidence of recurrence after a previous surgical procedure on preoperative magnetic resonance imaging (MRI). Remission was achieved immediately postoperatively in 13/15 (86.7%). Over an average follow-up of 34.7 mo (range: 12-116), 11/15 (68.8%) achieved persistent remission. When combined with the historical cohort that underwent an operation during 1992-2006, 44/51 (86.3%) patients had a prior operation demonstrating ACTH adenoma and 35/51 (68.6%) had evidence of recurrent disease on preoperative MRI. Thirty-five (68.6%) patients went into remission immediately postoperatively. Thirty one (60.8%) had continued remission at most recent reported follow-up. Recurrent CD can be a therapeutic challenge; however, these data demonstrate that in many patients repeat surgery can be an effective and safe next step prior to radiation or medical therapy.

SAT-LB084 Persistent Cushing Disease in a Prepubertal Pediatric Patient after Gross Total Resection: What to Expect

Cushing disease (CD), which is ACTH-dependent hypercortisolism is an exceedingly rare condition in pediatrics. The exact annual incidence is unknown but estimated to be approximately 0.7-2.4 cases per million people, with approximately 10% occurring in children, making the incidence in pediatrics <0.5 per million.(Lodish, et al. 2018; Sharma, et al. 2015) Of the pediatric cases, few are prepubertal. Of the pituitary tumors, microadenomas are most common. Pituitary macroadenomas accounts for 5-10% of all cases Cushing disease. The first line therapy is surgical resection of the adenoma. Remission rates are better with microadenomas (~75%) compared with macroadenomas (~43%).(Nieman et al. 2015) If a surgical resection is not curative, defined by the persistent elevation of morning serum cortisol > 5 μg/dl, then second-line therapies are required. We describe a 9-year-old African American female who initially presented with symptoms of significant weight gain, lower extremity edema and hypertension. Initial random (late-morning) serum cortisol level was 38.3 μg/dl and ACTH 99 pg/ml. Ultrasound of adrenal glands did not show any distinct masses. MRI brain showed 1.9 cm macroadenoma in the sella. She underwent transsphenoidal resection. Histology confirmed an ACTH-secreting tumor without atypical features: Ki67 <3%, P53 negative. Postoperatively, serum cortisol levels remained elevated to as high as 23.1 μg/dl. In the subsequent weeks following surgery, cortisol levels at different times of day demonstrated loss of normal diurnal rhythm. She also developed symptoms of headaches, anorexia and vomiting. Interestingly, repeat MRI brain was performed but did not show any residual tumor despite persistent biochemical CD. Persistent CD is defined as a sustained elevation in post-surgical cortisol levels. It may be secondary to residual tumor hidden within the gland, or invasion into the cavernous sinus or other neighboring spaces.(Nieman et al. 2015) The family should be included in the medical decision making regarding second line therapies given the long-term health related quality of life issues surrounding patients with CD. Second line therapies include repeat transsphenoidal surgery, radiotherapy, medical therapy, or bilateral adrenalectomy.(Nieman et al. 2015) Multiple comorbidities need to be addressed in the treatment of CD, on the one hand with persistent disease, hypertension, hyperglycemia, obesity and on the other hand with curative resection, possible panhypopituitarism and/or adrenal insufficiency. Patients may also suffer from “glucocorticoid withdrawal syndrome” secondary to relative deficiency of cortisol with symptoms of anorexia, nausea and fatigue and may require psychosocial support. (Nieman et al. 2015) Regardless of if the initial therapy was curative or not, patients with CD require long-term monitoring of secondary comorbidity outcomes. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Commentary: Surgical Outcomes Following Repeat Transsphenoidal Surgery for Nonfunctional Pituitary Adenomas: A Retrospective Comparative Study.

Commentary: Surgical Outcomes Following Repeat Transsphenoidal Surgery for Nonfunctional Pituitary Adenomas: A Retrospective Comparative Study.

Surgical Outcomes following Repeat Transsphenoidal Surgery for Nonfunctional Pituitary Adenomas: A Retrospective Comparative Study

Surgical Outcomes following Repeat Transsphenoidal Surgery for Nonfunctional Pituitary Adenomas: A Retrospective Comparative Study

Surgical outcomes in patients with Cushing's disease: the Cleveland clinic experience.

Transsphenoidal surgery (TSS) to resect a pituitary adenoma is considered first-line treatment for patients with Cushing's disease (CD). Early, post-operative remission rates >80% are expected for patients with a microadenoma (≤ 10mm) visible on magnetic resonance (MR) imaging. To report surgical outcomes and predictors of remission in a specialist center for patients with CD. Clinical data was obtained from a prospective CD database in addition to review of all electronic medical, laboratory and surgical patient records. Patients who underwent their first TSS by one neurosurgeon between 2004 and 2013, and had a minimum 1 year follow up, were evaluated. One hundred and one consecutive patients with CD (73F, 28M) underwent TSS. Median (range) age and follow-up were 47 (15-87) and 4.33 (1-9.8) years, respectively. At surgery, 74 (73.2%) patients had a microadenoma, 27 a macroadenoma; six of the latter patients had a planned, subtotal resection to control neurological signs due to mass effect. Initial remission rates were: microadenoma, 89% (66/74); macroadenoma, 63% (17/27); and 81% (17/21) in those macroadenomas where complete surgical removal was anticipated. Initial non-remission occurred in 18 patients, ten macro- and eight microadenoma; six of 18 had residual disease on most recent follow up. Six (2 macro, 4 micro) of the 83 patients with initial remission have had late (>12 months) recurrence of hypercortisolism that required either repeat TSS or adjunctive therapy, three of whom have persistent hypercortisolism. Macroadenoma (p = 0.003) and tumor invasion beyond the pituitary and sella (p < 0.001) were associated with failure to obtain remission with the initial TSS and greater likelihood of late recurrence. Patients in whom no lesion was seen on neuroimaging had rates of initial remission (21/25 or 84%) and a similar late recurrence rate of 4% (1/25) in comparison with those with MR-visible microadenomas (3/49, or 6%). A team-based approach, in a specialized pituitary center, can lead to initial and durable, long-term remission in patients with CD. The presence of a macroadenoma and tumor extension beyond the pituitary and sella were predictive of initial non-remission as well as risk of late recurrence.

Outcome of Microscopic Transsphenoidal Surgery in Cushing Disease: A Case Series of 96 Patients

To analyze the results of transsphenoidal surgery in patients with Cushing disease and outcome. Retrospective analysis of the records of 96 patients with Cushing disease from 1997 to 2012. There were 73 females and 23 males, with a mean follow-up of 44 months (range, 3-13 years). The sex ratio was significantly different in children and teenagers versus adults. Magnetic resonance imaging showed microadenoma, macroadenoma, and no adenoma in 66, 18, and 12 patients, respectively. There was no surgical mortality. Early remission (normal 24-hour urinary free cortisol and basal serum cortisol <5 μg/dL) was achieved in 94.8%. Regression analysis showed that only tumor size, cavernous sinus extension, and tumor consistency influenced remission. Recurrence was seen in 21.9%. Regression analysis showed that age, preoperative basal cortisol levels, and follow-up duration influenced recurrence. Correlation analysis showed that there was a significant negative correlation between patient age and the follow-up period. After detection of recurrence, 17 patients underwent repeat transsphenoidal surgery that resulted in remission in 12 patients (70.6%). The other 5 patients were referred for gamma knife radiosurgery or bilateral adrenalectomy. Transsphenoidal surgery is a safe and highly efficient procedure in the treatment of Cushing disease. Macroadenomas, cavernous sinus invasion, and harder tumor consistencies, however, are associated with lower remission rates (higher disease persistence) and younger age, higher preoperative cortisol levels, and longer follow-up periods are associated with higher recurrence.