Transsphenoidal Pituitary Surgery Research Articles

Risk Factors for Isolated Sphenoid Sinusitis after Endoscopic Endonasal Transsphenoidal Pituitary Surgery.

(1) Background: Transsphenoidal pituitary surgery can be conducted via microscopic or endoscopic approaches, and there has been a growing preference for the latter in recent years. However, the occurrence of rare complications such as postoperative sinusitis remains inadequately documented in the existing literature. (2) Methods: To address this gap, we conducted a comprehensive retrospective analysis of medical records spanning from 2018 to 2023, focusing on patients who underwent transsphenoidal surgery for pituitary neuroendocrine tumors (formerly called pituitary adenoma). Our study encompassed detailed evaluations of pituitary function and MRI imaging pre- and postsurgery, supplemented by transnasal endoscopic follow-up assessments at the otolaryngology outpatient department. Risk factors for sinusitis were compared using univariate and multivariate logistic regression analyses. (3) Results: Out of the 203 patients included in our analysis, a subset of 17 individuals developed isolated sphenoid sinusitis within three months postoperation. Further scrutiny of the data revealed significant associations between certain factors and the occurrence of postoperative sphenoid sinusitis. Specifically, the classification of the primary tumor emerged as a notable risk factor, with patients exhibiting nonfunctioning pituitary neuroendocrine tumors with 3.71 times the odds of developing sinusitis compared to other tumor types. Additionally, postoperative cortisol levels demonstrated a significant inverse relationship, with lower cortisol levels correlating with an increased risk of sphenoid sinusitis postsurgery. (4) Conclusions: In conclusion, our findings underscore the importance of considering tumor classification and postoperative cortisol levels as potential predictors of postoperative sinusitis in patients undergoing transsphenoidal endoscopic pituitary surgery. These insights offer valuable guidance for clinicians in identifying at-risk individuals and implementing tailored preventive and management strategies to mitigate the occurrence and impact of sinusitis complications in this patient population.

The Effect of the Coronavirus Disease 2019 Pandemic on Pituitary Surgery

PurposeAs the COVID-19 pandemic spread to the United States in 2020, there was an impetus towards postponing or ceasing non-urgent transsphenoidal pituitary surgeries to prevent spread of the virus. Some centers encouraged transcranial approaches for patients with declining neurologic function. However, no large-scale data exists evaluating the effects this had on national pituitary practice patterns. MethodsPituitary surgeries in the National Inpatient Sample were identified from 2017-2020. Surgeries in 2020 were compared to the three years prior to determine any differences in demographics, surgical trends/approaches and perioperative outcomes.In 2020, there was a decline in overall pituitary surgeries (34.2 vs. 36.3%, odds ratio (OR) 0.88, p<0.001) yet transsphenoidal approaches represented a higher proportion of interventions (69.0 vs. 64.9%, p<0.001). Neurosurgical complications were higher (51.9 vs. 47.4%, OR 1.13, p<0.001) and patients were less likely to be discharged home (86.4 vs. 88.5%, OR 0.84, p<0.001). This was especially true in April 2020 during the first peak in COVID-19 cases when transcranial approaches and odds of mortality/complications were highest. ConclusionsIn 2020, transsphenoidal surgery remained the preferred approach for pituitary tumor resection despite initial recommendations against the approach to prevent COVID-19 spread. Pituitary surgeries had a higher risk of periprocedural complications despite accounting for preoperative comorbidities, COVID-19 infection status, and surgical approach, suggesting that an overwhelmed hospital system can negatively influence surgical outcomes in non-infected patients.

The role of medical illustration in the evolution of transsphenoidal pituitary surgery.

Medical illustration played a crucial, yet often overlooked, role in the evolution of pituitary surgery. From the late 1800s to the present, many preeminent surgeons, in partnership with their surgical illustrator collaborators, developed and then shifted the paradigm of pituitary surgery, from an open procedure with high mortality and morbidity, to an endonasal approach with high success rates that is widely utilized today. This work aims to highlight the role of surgical illustrators as partners to their physician colleagues, creating artistically accessible road maps that shaped the development of the transsphenoidal approach.

Navigating the Surgical Landscape: A Comprehensive Analysis of Endoscopic vs. Microscopic Transsphenoidal Pituitary Surgery Outcomes.

Pituitary surgery, a critical intervention for various pituitary disorders, has sparked ongoing debates regarding the preference between endoscopic and microscopic transsphenoidal approaches. This systematic review delves into the outcomes associated with these techniques, taking into account the recent advancements in neurosurgery. The minimally invasive nature of endoscopy, providing improved visualization and reduced morbidity, stands in contrast to the well-established track record of the conventional microscopic method. Examining outcomes for disorders such as Cushing's disease and acromegaly, the review synthesizes evidence from Denmark, Bulgaria, and China. Noteworthy advantages of endoscopy encompass higher resection rates, shorter surgery durations, and fewer complications, endorsing its effectiveness in pituitary surgery. While emphasizing the necessity for prospective trials, the review concludes that endoscopic approaches consistently showcase favorable outcomes, influencing the ongoing discourse on the optimal surgical strategies for pituitary disorders.

Paediatric Cushing's disease: long-term outcome and predictors of recurrence.

Paediatric Cushing's disease (CD) is characterized by excess ACTH secretion from a pituitary adenoma, leading to hypercortisolism. It has approximately 5% of the incidence of adult CD and is a rare disorder in the paediatric age range. The four most specific presenting features of hypercortisolism are: change in facial appearance, weight gain, decreased linear growth and virilisation shown by advanced pubic hair for the stage of breast development or testicular volume. The main diagnostic priority is the demonstration of hypercortisolism followed by distinction between its ACTH-dependent and ACTH-independent origin, thus leading to identification of aetiology. All treatment options aim to resolve or control hypercortisolism. Consensus favours transsphenoidal (TSS) pituitary surgery with selective removal of the corticotroph adenoma. TSS in children with CD is now well established and induces remission in 70-100% of cases. External pituitary radiotherapy and bilateral adrenalectomy are second-line therapeutic approaches in subjects not responding to TSS. Long-term medical treatment is less frequently adopted. Recurrence in paediatric CD cases is low with factors predicting relapse being higher post-TSS cortisol and ACTH levels and rapid recovery of the hypothalamic-pituitary-adrenal axis after TSS. In summary, complete excision of the microadenoma with histological and biochemical evidence for this, predicts a low rate of recurrence of CD. Due to the need for rapid diagnosis and management to avoid the burden of prolonged exposure to hypercortisolism, tertiary university centres comprising both paediatric and adult endocrinology specialists together with experienced pituitary surgery and, eventually, radiotherapy units are recommended for referral of these patients.

P-61 From Cushing to Nelson Syndrome: Diagnostic challenges and Surgical Dilemma

Abstract Introduction Diagnosis of the origin of ACTH-dependent Cushing's syndrome (CS) can be difficult in some cases, especially when MRI of the pituitary gland does not reveal an adenoma. Inferior petrosal (IPSS) or cavernous sinus sampling (CSS) with CRH stimulation helps confirm the central origin in most cases. CSS also helps lateralize the tumor within the pituitary gland with a sensitivity of 80%. Because transsphenoidal pituitary surgery is successful in the majority of MRI-negative cases, bilateral adrenalectomy is performed less frequently. Even with advanced radiologic studies, the origin may not be detected. Adrenalectomy may be an option in these cases. However, loss of feedback inhibition of the hypothalamic-pituitary-adrenal axis; can lead to aggressive transformation of an existing ACTH-secreting pituitary adenoma into Nelson's syndrome within 1-5 years. Clinical Case A 46-year-old female patient complaining of hot flashes and unable to lose weight was evaluated for CS and referred to the Department of Neurosurgery for a pituitary adenoma (Table 1). Since the adenoma was &amp;lt;6mm CSS with CRH stimulation was performed. The results did not support central origin (Table 2). Ectopic ACTH secretion was considered, but without finding the origin of the tumor on radiological examination, and treatment with ketoconazole and metyrapone was started for CS. However the patient then discontinued outpatient follow-up. The patient presented to our clinic 6 years later with a new pituitary MRI showing tumor growth (Fig.1b). She complained of fatigue and obesity. She was depressed and anxious. The skin on her face, hands and hump was dark and patchy (Fig.1c). During these years, she consulted several endocrinologists. MRI was performed annually. Brain MRI had showed a fronto-basal extraaxial mass lesion. The patient underwent microsurgical resection and pathology revealed a microcystic meningioma (WHO grade I). 3 months later bilateral nodular hyperplasia of adrenal gland was detected; she underwent bilateral laparoscopic adrenalectomy (no neoplasia). ACTH gradually increased up to 418pg/ml; the diagnosis of Nelson's syndrome was established. The patient underwent endoscopic transsphenoidal adenomectomy. The ACTH level was found to be 12pg/ml on the 2nd postoperative day. Pathological examination revealed a ACTH secreting pituitary adenoma (Ki-67:7%). CS patients suffer from emotional lability due to the effects of elevated cortisol and to the physical changes of their body. Proximal muscle weakness and obesity causes fatigue symptoms. The diagnosis is often delayed until complications occur. Differential diagnosis could be difficult and challenging. Patient's emotional lability could adversely affect treatment/follow-up compliance. The presented case had meningioma resection which could be delayed until remission from CD and bilateral adrenalectomy which could be avoided by endoscopic pituitary surgery. This case is a good example of the need for pituitary centers of excellence.Figure.Fig.1.a. MRI scan of the pituitary gland at first admission shows (a) a lesion extending posteriorly inferior to the right half of the pituitary gland, hyperintense at T2-weighted, iso-hypointense at T1-w, with heterogeneous contrast enhancement consistent with pituitary microadenoma (4mm*2mm) Fig.1.b. Progression in size of the adenoma (6mm*4mm) Fig.1.c. Darkening of the skin due to hypersecretion of ACTH. Table 1.Cavernous sinus sampling with corticotropin-releasing hormone stimulation Table 2.Laboratory tests in different times

P-57 A case of pituitary carcinoma treated with osilodrostat for severe Cushing's syndrome

Abstract Introduction Pituitary carcinoma is a rare disorder accounting for 0.1–0.2% of pituitary tumors. We present a case of a male subject with ACTH-secreting pituitary carcinoma with metastasis to the spine, achieving eucortisolism on osilodrostat treatment. Clinical Case A 31-year-old male presented with complaints of pain in the rear-left thigh, numbness in the left-hand fingers and shoulder. MRI revealed an invasive pituitary tumor which had spread to the left frontal and temporal lobes with infiltration of the dura mater and compression of the left part of the optic chiasm, multiple formations in the large hemispheres, hemispheres of the cerebellum, in the right internal auditory meatus and at the level of the C1 vertebra compatible with metastasis. Spinal MRI showed a mass at Th6, L1-S2 level compatible with metastasis (Fig.1). The patient was diagnosed with Cushing's disease (CD) at 23 (late-night serum cortisol 1450 nmol/L (64–327), late-night salivary cortisol (LNSC) 66.4 nmol/L (0.5–9.65), 24hUFC 608 nmol/L (100–379), ACTH 107.3 pg/mL (7.2–63.3)) and underwent transsphenoidal pituitary surgery for pituitary macroadenoma 26×18×29 mm with biochemical remission. Two years later his symptoms of CD relapsed and he had a second transsphenoidal surgery. Histological examination showed an atypical corticotroph tumor with Ki67 – 11.6%. Two months after surgery, Kiber knife surgery was performed. However, 2 years later he had gradual deterioration of vision due to loss of lateral margins. A third transcranial adenomectomy was performed with following panhypopituitarism and diabetes insipidus. The tumor was positively stained for ACTH and also contained some atypical features including nuclear pleomorphism. Postoperative chemotherapy adjuvant treatment with Temozolomide and Carboplatin was prescribed. After 6 cycles, proton radiotherapy was done. In order to control hypercortisolism the patient received ketoconazole 800 mg per day, cabergoline 1 mg twice weekly and pasireotide 1.8 mg per day. However, it was not possible to achieve remission of hypercortisolism. As an adverse event of pasireotide, diabetes mellitus developed, which required insulin therapy and finally lead to pasireotide cessation. Ketoconazole and cabergoline were discontinued and osilodrostat treatment was initiated with a final dose of 5 mg daily over 2 years. He also received another course of radiation therapy at the age of 31 years. Over the past 2 years of observation, his ACTH level ranged from 37 pg/mL to 325.1 pg/ml. In spite of tumor progression and raised ACTH, the patient remains in eucortisolism (late-night serum cortisol 163.3 nmol/L, LNSC 5.21 nmol/L, 24hUFC 70.14 nmol/L) on osilodrostat 10 mg daily. Conclusion In this case osilodrostat was effective at controlling hypercortisolism, but its effects on the tumor are unknown. As this patient is the first described case of corticotroph carcinoma tumor treated with Osilodrostat, the results should be taken with caution.Figure 1.Pituitary and spinal MRI of the patientT1-weighted MRI demonstrating (A) chiasmal-sellar region formation, (B) formation in the rigt internal auditory meatus, (C) a highly invasive sacral L1–S2 metastasis

Perioperative growth hormone levels as an early predictor of new-onset secondary adrenal insufficiency following transsphenoidal pituitary tumor resection

ObjectiveThis study aims to predict new-onset secondary adrenal insufficiency (NOSAI) after transsphenoidal pituitary tumor resection surgery using perioperative growth hormone (GH) and prolactin (PRL) levels, among other factors. MethodsA cohort of 124 adult patients who underwent transsphenoidal resection for non-functioning pituitary adenoma, with routine perioperative glucocorticoid use, was used to develop the predictive regression model. An additional 46 patients served as the validation cohort. Generalized additive models were used to identify optimal cut-off points for the variables. ResultsThe GH level on postoperative day one (POD1) can be a simple predictor by implementing a cut-off point of 0.41 ng/ml. A value ≤ 0.41 ng/mL predicted NOSAI with 0.6316 sensitivity and 0.7810 specificity for the original cohort and 1.0000 sensitivity and 0.7143 specificity for the validation cohort. The multiple logistic regression model included perioperative PRL level difference, perioperative GH level difference, intraoperative cerebrospinal fluid (CSF) leakage, tumor size, and the combined effect of diabetes insipidus (DI) and relative perioperative GH level difference. The areas under the receiver operating characteristic curves were 0.9410 (original cohort) and 0.9494 (validation cohort) for the regression model. ConclusionEarly morning GH level on POD1 can predict NOSAI with fair accuracy when perioperative stress dose glucocorticoid is administered. Prediction accuracy can be improved by considering CSF leakage, DI, and perioperative changes in GH and PRL in the final regression model.

A prospective-randomized placebo-controlled trial comparing the effects of nebulized dexmedetomidine v/s dexmedetomidine-lignocaine mixture on intraoperative hemodynamics and surgical field quality in patients undergoing endoscopic transnasal transsphenoidal pituitary tumor surgery

Background: During transnasal transsphenoidal pituitary surgery (TNTSS), the primary objective is to maintain stable hemodynamics while ensuring ideal surgical conditions. This study aimed to investigate the effect of nebulized dexmedetomidine on hemodynamic parameters and the quality of the surgical field during TNTSS. Methods: Seventy-five patients scheduled for TNTSS were randomized into three groups of 25 each and received preoperative nebulization with 5 mL of nebulizing fluid consisting of 1.5 μg/kg of dexmedetomidine with saline in dexmedetomidine (D) group; 1.5 μg/kg of dexmedetomidine with 2% lignocaine in dexmedetomidine-lignocaine (DL) group and normal saline in the control (S) group. Heart rate (HR), mean blood pressure, Formmers score, anesthetic requirement, and emergence were evaluated for each group. Results: Group S had significantly higher HR and mean arterial pressure than the other two groups across various time points during surgery (P &lt; 0.01). The total requirements for fentanyl, propofol, sevoflurane, and labetalol and the incidence of delayed emergence were significantly higher in the S group compared to the other two groups (P &lt; 0.01). The D and DL groups exhibited significantly better surgical field conditions than the S group. In all the parameters assessed, patients in the D group outperformed those in the DL group. Conclusion: The administration of nebulized dexmedetomidine, both alone and in combination with lignocaine, resulted in stable hemodynamics, favorable operative conditions, reduced anesthetic requirement, and facilitated prompt emergence during TNTSS. Nebulized dexmedetomidine proved superior to its combination with lignocaine across all evaluated parameters.

Internal carotid artery injury during endoscopic transsphenoidal pituitary surgery: risk factors, management

BackgroundTranssphenoidal surgeons should try to avoid internal carotid artery (ICA) injury but also be prepared to manage it. We analyzed our experience with ICA injury during endoscopic transsphenoidal pituitary surgery and present associated risk factors and a management protocol. MethodsWe retrospectively reviewed and analyzed the medical records of 1596 patients who underwent endoscopic transsphenoidal surgery for pituitary tumor resection in our institution from January 2009 to October 2022. ResultsSix patients experienced an ICA injury. All received timely and effective hemostasis with immediate direct tamponade followed by endovascular treatment. No serious postoperative complications occurred. ConclusionsWe proposed a treatment plan for ICA injuries encountered during endoscopic transsphenoidal surgery and described our hemostasis process, methods of endovascular treatment, and means of postoperative follow-up in detail.

Association between urinary oxytocin secretion and natriuresis after transsphenoidal pituitary surgery.

Oxytocin (OXT) secretion has been shown to be abnormally elevated in patients who develop syndrome of inappropriate secretion of antidiuretic hormone (SIADH)-related hyponatremia after transsphenoidal pituitary surgery (TPS). While OXT was previously reported to increase natriuresis in the kidney, a potential role for this hormone in postoperative sodium balance and dysnatremias has not been studied. The objective of this study was to analyze the correlation between patients' urinary output of OXT and natremia and natriuresis after TPS. The authors measured and correlated the urinary output of OXT with natriuresis and natremia in 20 consecutive patients who underwent TPS. The ratio of urinary secretion of OXT between days 1 and 4 showed a strong, significant correlation with patient natriuresis at day 7 after pituitary surgery. Concomitantly, patient natremia showed a moderate, inverted correlation with OXT secretion in the urine. Together, these results show for the first time that urinary OXT secretion correlates with patient natriuresis and natremia after pituitary surgery. This observation suggests a notable role for this hormone in sodium balance.

Transsphenoid surgery outcomes in pituitary adenoma patients at Sumatera Utara University Hospital in 2022–2023: A prospective study

BackgroundAdenomas are common pituitary tumors, accounting for 10–15 % of all intracranial tumors. They are non-metastatic and benign, originating in the pituitary gland. The exact genetic mutations causing adenomas are not fully understood, but they involve tumor suppressor inactivator genes and protooncogene activator mutations. Transsphenoidal surgery is the preferred treatment for patients with neuro-ophthalmological symptoms to relieve pressure on the optic tract, resulting in visual improvement for around 80 % of patients. Surgery is recommended for patients with such symptoms or when the tumor invades the optic nerve. Risks of transsphenoidal surgery include diabetes insipidus, electrolyte imbalances, neurological deficits, and CSF rhinorrhea. Materials and methodsThis is a clinical trial study with a prospective cohort design to evaluate outcomes of pituitary adenoma patients who were undergone transsphenoid surgery at USU Hospital in 2022–2023. Total of 13 patients were included in the study. Preoperative and postoperative Na+, K+, and Cl− were measured to assess outcomes of transsphenoid surgery in pituitary adenoma patients. ResultVarious postoperative complications can be seen and be anticipated in transsphenoidal pituitary surgery. ConclusionWater and electrolyte imbalance is one of the most common complication found in patient who undergone transsphenoid surgery for pituitary adenoma. It can lead to secondary hospital admission and may be life-threatening if not treated adequately and immediately. Preoperative and postoperative laboratory Na+, K+, Cl− and urinary output are important parameters to be monitored in pituitary adenoma patient who undergone transsphenoid surgery.

Epidural Interlay Graft for Pituitary Surgery: A 4-Year Institutional Experience

Abstract Objective Sellar repair techniques with varying complexity and effectiveness have been employed to reduce the incidence of postoperative cerebrospinal fluid (CSF) leaks following endoscopic transsphenoidal pituitary surgery. This study describes our institutional experience with a minimalistic, highly effective approach to sellar repair. Methods The authors performed a retrospective review of consecutive cases of transsphenoidal pituitary surgery performed at our institution. All included subjects underwent sellar repair with an epidural interlay graft. Relationships between patient and tumor characteristics, incidence of CSF leak, adjunct repair techniques, and endocrine outcomes were examined. Results Three hundred and thirty-four (334) cases were included. Intraoperative CSF leak was encountered in 116 cases (34.7%), and postoperative CSF leak occurred only once (0.3%) early in the series. Seventy intraoperative CSF leaks were successfully repaired with an epidural interlay alone, including 13 high-flow leaks. Our rate of fat graft use (1.2%), nasoseptal flap (3.0%), and lumbar drain placement (6.6%) in the second half of the series showed a significant decline compared with the first half, indicating increased reliance on the interlay graft over time. Our 65% functional macroadenoma remission rate compares favorably with large historical series. Conclusions Simple sellar repair using an epidural interlay graft is highly effective in preventing postoperative CSF leaks, including cases of high-flow intraoperative leaks. More complex repair techniques are reserved for select high-risk cases or those with inadequate sellar bony ledges. With this technique, there has been no postoperative CSF leak at our institution in over 300 consecutive transsphenoidal pituitary surgeries.

Comparison of Cardiac Indices Using Two Different Concentrations of Topical Adrenaline during Endoscopic Transsphenoidal Pituitary Surgery: A Prospective Randomized Observational Study.

Introduction Adrenaline-soaked wicks are often employed to decongest nasal mucosa during transsphenoidal pituitary surgeries to ensure proper hemostasis and visibility of the operating field. Considerable debate exists regarding the optimum concentration of adrenaline that strikes a balance between hemostasis as well as the hemodynamic side effects of adrenaline. This study assessed cardiac indices like cardiac output and cardiac index using a FloTrac Vigileo cardiac output monitor to compare two different concentrations of adrenaline used for topical instillation. Materials and Methods 60 adult patients undergoing transsphenoidal pituitary surgery were randomly assigned to receive cotton wicks soaked in adrenaline solution (either 1:100,000 or 1:200,000) for nasal decongestion. Following a standardized anesthetic regime, a FloTrac Vigileo cardiac output monitor was attached with the invasive arterial line for precise monitoring and recording of cardiac indices (cardiac output and cardiac index). Additionally, quality of surgical field (as reported by the operating surgeon) blood loss, incidences of adverse hemodynamic events, and rescue drug usage were recorded. Results No difference in cardiac outputs and cardiac indexes of the patients was observed during baseline to 55 minutes and at 80 minutes and onward, whereas difference rose to statistical significance at the time points of 60 minutes and 70 minutes ( p < 0.05). Other parameters like stroke volume, stroke volume variation, and hemodynamic parameters were similar. Quality of the surgical fields (as reported by the surgeon), intraoperative bleeding, incidences of adverse effects, and frequency of rescue drugs usage were similar. Conclusion Instillation of 1:100,000 dilution of adrenaline solution compared with 1:200,000 for nasal decongestion is associated with significant rise in cardiac output and cardiac index at 60 and 70 minutes of the surgery with similar blood loss and hemodynamic variables. Therefore, the lower concentration of adrenaline can be recommended for usage during transsphenoidal pituitary surgeries.

Reversibility of Impaired Large-Scale Functional Brain Networks in Cushing’s Disease after Surgery Treatment: A Longitudinal Study

Introduction: Chronic exposure to excessive endogenous cortisol leads to brain changes in Cushing’s disease (CD). However, it remains unclear how CD affects large-scale functional networks (FNs) and whether these effects are reversible after treatment. This study aimed to investigate functional network changes of CD patients and their reversibility in a longitudinal cohort. Methods: Active CD patients (N = 37) were treated by transsphenoidal pituitary surgery and reexamined 3 months later. FNs were computed from resting-state fMRI data of the CD patients and matched normal controls (NCs, N = 37). A pattern classifier was built on the FNs to distinguish active CD patients from controls and applied to FNs of the CD patients at the 3-month follow-up. Two subgroups of endocrine-remitted CD patients were identified according to their classification scores, referred to as image-based phenotypically (IBP) recovered and unrecovered CD patients, respectively. The informative FNs identified by the classification model were compared between NCs, active CD patients, and endocrine-remitted patients as well as between IBP recovered and unrecovered CD patients to explore their functional network reversibility. Results: All 37 CD patients reached endocrine remission after treatment. The classification model identified three informative FNs, including cerebellar network (CerebN), fronto-parietal network (FPN), and default mode network. Among them, CerebN and FPN partially recovered toward normal at 3 months after treatment. Moreover, the informative FNs were correlated with 24-h urinary-free cortisol and emotion scales in CD patients. Conclusion: These findings suggest that CD patients have aberrant FNs that are partially reversible toward normal after treatment.

A post-operative fluid restriction protocol to reduce the incidence of delayed hyponatraemia following trans-sphenoidal pituitary surgery

A post-operative fluid restriction protocol to reduce the incidence of delayed hyponatraemia following trans-sphenoidal pituitary surgery

SAT625 The EGF-TBX19-EGFR Positive Feedback Loop Regulates The Expression Of The CD44v9/SLC7A11 Antioxidant System Within Corticotroph Pituitary Neuroendocrine Tumors

Abstract Disclosure: J. Chakrabarti: None. J. Eschbacher: None. K. Yuen: None. A.S. Little: None. Y. Zavros: None. Background: Stereotactic radiosurgery is a therapeutic modality considered in the adjuvant setting of patients with failed transsphenoidal surgery or recurrence of corticotroph pituitary neuroendocrine tumors (PitNETs), with variable biological remission rates ranging between 17% and 87%. Generated by alternative mRNA splicing (CD44v), CD44v9 is expressed in cancer stem cells and promotes resistance to reactive oxygen species (ROS) through the stabilization of the SLC7A11 (xCT) cystine glutamate transporter, but the role of this antioxidant system in PitNETs is unknown. TBX19 belongs to the T subfamily of TBX genes and is known to promote cancer cell metastasis. TBX19 is expressed within the pituitary gland and acts as a component of the proopiomelanocortin (POMC) gene activation program that works as a transcriptional activator. Epidermal Growth Factor Receptor (EGFR) via binding to its ligand Epidermal Growth Factor (EGF) signals to upregulate TBX19 expression via the ERK/NF-κB pathway. Within the pituitary, EGFR and its downstream pathway components (AKT, mTORC) are significantly increased in corticotroph PitNETs are associated with elevated ACTH secretion. Hypothesis: EGF/EGFR induces an EGF-TBX19-EGFR positive feedback loop that subsequently leads to the expression of the CD44v9/SLC7A11 antioxidant system within radiation-therapy resistant SOX2+ corticotroph PitNET cells. Methods: Human PitNET tissue was harvested during transsphenoidal pituitary surgery from CD patients to generate organoids (PitNETorg). Patient hPitNETsorg were pretreated with either Vandetanib (Vand), Rapamycin (Rapa, mTOR inhibitor), Erastin (xCT inhibitor), Mifepristone (Mife, glucocorticoid inhibitor) or Cabergoline (Caber, D2 receptor inhibitor) prior to 0, 4, 8 and 16Gy radiation doses. Functional analyses will be performed by spectral flow cytometry (Cytek™ Aurora), hormone secretion and high content confocal microscopy. Results: Decreased expression of CD44v9 and xCT correlated with increased apoptosis in hPitNETorg cultures in response to Vand, Rapa, and Erastin when compared to Veh, Mife and Caber pretreatments at an optimal radiation dose of 8Gy. Pretreatment of hPitNETorg with Rapa resulted in decreased expression CD44v9, a response mediated by of HIF-1α. Inhibition of TBX19 using a MEK inhibitor resulted in decreased expression of EGFR and downstream signaling components AKT and mTORC that correlated with decreased ACTH hPitNETorg secretion. Conclusions: The EGF-TBX19-EGFR positive feedback loop regulates CD44v9/xCT resistance to radiation therapy. Therefore, pretreatment of CD patients with drugs targeting the CD44v9/xCT antioxidant system may increase the efficacy, shorten latency time to remission, and decrease toxicity of stereotactic radiosurgery for the treatment of residual or recurrent functional corticotroph PitNETs. Presentation: Saturday, June 17, 2023

THU025 Acromegaly And Central Hyperthyroidism

Abstract Disclosure: A. Akhtar: None. M.A. Mahmood: None. Introduction: Pituitary adenomas are usually benign neoplasms that are the third most common type of central nervous system tumors. Although TSH releasing tumor accounts for 1% of pituitary adenomas, about one-third of the time it co-secretes Growth Hormone. Co-secretion of TSH and GH can further promote the prognosis of the tumor, therefore, must be immediately treated medically or surgically. Case Report: The case is of a 42 years old male patient who presented to his orthodontist with the complaint of loosening teeth and was referred to a primary care physician. According to the patient, he has observed an increase in his ring size up to 3 times his usual size, one and a half increase in his shoe size, some degree of joint pain, occasional visual blurriness, no weight loss, and snoring. He has no history of headaches, breast tenderness, or discharge. He works at a farm and has no family history of pituitary tumors. His laboratory findings in May 2021 show IGF-1 1028 ng/mL (normal less than 278 ng/mL), ACTH 72.2 pg/mL (normal &amp;lt;60pg/mL), Prolactin, TSH, LH and FSH levels were normal. These findings suggested an IGF-producing pituitary adenoma. During further workup, he had high levels of free T4 and free T3, 2.7 ng/dL and 8.2pg/mL (Normal 2.3 - 4.2pg/mL), respectively, along with elevated TSH levels, which were 8.1mIU/L (normal 0.27-4.2mIU/L). Magnetic resonance imaging showed a pituitary mass of 1.8cm x 2.0cm x 1.6cm in the suprasellar region, abutting the optic chiasm, and showed heterogeneous enhancement. There were no signs of hemorrhage. His visual field examinations were normal. He was prescribed to take 50mg of octreotide every 8 hours. In six weeks, the patient had improved levels of serum TSH which was lowered to 0.785mIU/L, and free T4 and free T3, which were 1.62pmol/L and 3.45pmol/L, respectively. He had transsphenoidal pituitary surgery. Pathology showed a 2.6 x 2.0 x 0.3 cm tumor of somatotropic type. Post-surgery MRI showed no tumor residues. Discussion: We report a middle-aged man with a rare case of the pituitary tumor with acromegaly and central hyperthyroidism. Thyrotropinomas, also known as TSHomas, are benign pituitary adenoma that produces thyroid stimulating hormones. Although rare, they are macroadenomas 80% of the times and 20-25% of the time co-secrete other pituitary hormones. These tumors may show elevated fT3, fT4, and TSH, and increased alpha-subunit. There is not enough evidence to proof the exact origin of the pathology, however, immunohistologically, the tumor cells arise from PIT1-lineage adenohypophyseal cells and could be associated with MEN 1 mutation on chromosome 11q13. Surgical removal of the tumor is a preferred approach to TSHomas, but recent studies have shown a significant improvement with medial therapy of somatostatin analogs by interacting with somatostatin receptors. Octreotide, a somatostatin analog has been clinically shown to bring the thyroid hormones to a normal level in 80% if cases and shrinkage of tumor size in pituitary adenoma in 60% of cases. It can be used as a pre-operative therapy to reduce the levels of free thyrotropin. It also reduces GH and serum IGF-1 levels. Co-secretion of TSH and GH promotes the prognosis of tumors which may be prevented with early diagnosis and treatment. Presentation: Thursday, June 15, 2023

THU011 Cushing’s Disease Diagnosis Challenge With Standard Pituitary MRI: A Clinical Case Report

Abstract Disclosure: E. Kasiri: None. N. Shah: None. Introduction: Cushing’s disease (CD); the most common cause of endogenous Cushing’s syndrome (CS) is mainly caused by an adrenocorticotropin (ACTH)-secreting pituitary adenomas. Although MRI remains the preferred imaging to detect these adenomas, still about 50% of microadenomas may be missed using standard 1.5-Tesla MRI and on the other hand higher resolution MRI with 3T magnets is not widely used. Here we present a case of Cushing’s disease with equivocal 1.5T MRI which made a next step of management rather challenging. Case presentation: A 57-year-old female with history of hypertension, type 2 diabetes mellitus and obesity (BMI: 34.41 kg/m2) presented to our endocrinology clinic to establish care. Her main complaint was difficulty losing weight. She denied taking any steroids or oral contraceptive pill. Vitals showed BP: 124/85 mm Hg, HR: 100 bpm and T: 98.3 °F. Physical exam was significant for moon facies, buffalo hump and abdominal obesity. She was screened for Cushing syndrome with 1mg overnight low dose dexamethasone test which resulted in abnormal cortisol response with a level of 2.1mcg/dl (&amp;lt;1.8 mcg/dl). A 24hr urine free cortisol: 7.3 mcg/dl (&amp;lt;45 mcg/dl) and two late night salivary cortisol measurements resulted in 0.388 and 0.229 mcg/dl (&amp;gt; 3 times upper limit of normal). Other labs showed elevated baseline ACTH :67.4 pg/ ml (7.2 - 63.3 pg/mL), cortisol :19.4 mcg/dl (4.5-23 mcg/dl) and normal DHEAS:1864.1ng/ml (650-3400 ng/mL). We decided to distinguish ectopic vs pituitary source of hypercortisolism by an 8 mg (high dose) dexamethasone suppression test which showed suppressed ACTH &amp;lt;1.5 pg/ml, Cortisol :2.6 mcg/dl (&amp;gt;50% suppression from baseline) suggesting pituitary origin. The standard pituitary 1.5T MRI with and without contrast as next step resulted in questionable microadenoma in the right aspect of pituitary gland and was equivocal. Within the multidisciplinary team decision was made to perform 3T pituitary MRI rather than invasive inferior petrosal sinus sampling (IPSS) which confirmed the pituitary microadenoma of 8.1 mm size with no mass effect and patient is scheduled for transsphenoidal pituitary surgery without needing further testing. Discussion: 3T MRI, with higher magnetic field than 1.5T allows to improve image quality and help with tumor detection in Cushing’s disease. It reportedly has higher sensitivity (80%) and specificity (∼100%) compared to 1.5T MRI which has overall sensitivity and specificity of 71% and 87% respectively. However, it is not the first to order by the clinicians when evaluating the ACTH secreting pituitary adenoma. In the case of equivocal 1.5 T MRI usually the next step is IPSS which is invasive. With availability of Corticotropin Releasing Hormone in the USA being difficult, limited studies of using DDAVP and limitations in finding tertiary centers to perform IPSS, a 3T MRI would be more feasible as a next step to identify a pituitary adenoma. Presentation: Thursday, June 15, 2023

THU096 When TSH Alone Is Not Enough

Abstract Disclosure: S.S. Awasty: None. L. Ghalib: None. Background: A Thyrotropinoma or TSHoma is the rarest of all pituitary adenomas approximately 1-2%. TSHomas are often only found due to symptoms from co-secreting tumors with TSHomas or routine laboratory testing. Misinterpretation of laboratory values can cause misdiagnosis and inappropriate treatment. Clinical Case: A 45-year-old female presented to her primary care physician for a routine appointment. The patient reported concerns regarding weight and a TSH was ordered, TSH 7.00 uIU/mL (0.49 - 4.67) with no other thyroid function values. The physician prescribed levothyroxine 50mcg treating for primary hypothyroidism and over the next 37 months the patient was prescribed increasing doses of levothyroxine based on TSH values. This patient was eventually referred to Endocrinology. At the initial Endocrinology visit TSH 7.59 uIU/mL (0.27 - 4.2 uIU/mL) and fT4 3.2 ng/dL (0.7 - 1.7) on levothyroxine 125mcg. Levothyroxine was discontinued and labs were repeated 6 weeks later TSH 5.9 uIU/mL (0.27 - 4.2), fT4 4.8 ng/dL (0.7 - 1.7), fT3 2.1 pg/mL (2 - 4.4), and alpha-subunit 1.5ng/mL (&amp;lt;=1.2 premenopausal female, &amp;lt;=1.8 postmenopausal female). A pituitary macroadenoma was discovered on MRI. The patient was referred to Pituitary Clinic and noted to have a prolactin of 53.8 ng/mL (non-pregnant females 2.8-29.2) and IGF-1 291.6 ng/mL (60.0 - 240.0). The patient underwent transsphenoidal pituitary surgery; pathology reported a plurihormonal subtype pituitary adenoma which stained positive for Prolactin, HGH, and TSH. One week after removal of the TSHoma, TSH 0.014 uIU/mL (0.550 - 4.780) fT4 0.65 ng/dL (0.89 - 1.76), and levothyroxine replacement was initiated with plans for continued outpatient monitoring to assess need for levothyroxine replacement. Conclusion: This case primarily demonstrates the importance of evaluating TSH levels in conjunction with free T4 levels to effectively interpret central versus primary causes of thyroid dysfunction. The high molar ratio of the alpha-subunit to the TSH level lends itself to a TSHoma differentiating it from a diagnosis of syndrome of resistance to thyroid hormone. While rare missing a TSHoma diagnosis could have devastating consequences. Checking other pituitary hormones pre-operatively even without symptoms also gave the indication that this was a co-secreting tumor. After adenoma removal rechecking pituitary hormones is of great importance as exemplified by pituitary-thyroid axis suppression noted post-operatively in this case. Presentation: Thursday, June 15, 2023