Inferior Petrosal Sinus Research Articles

Arterial spin labelling could detect the occlusion of inferior petrosal sinus for cavernous sinus dural arteriovenous fistula

Abstract Several reports indicate that arterial spin labelling (ASL) MRI is useful for the diagnosis, identification of cortical venous reflux, and assessment of therapeutic effect in dural arteriovenous fistula (dAVF). However, there is no reports indicating the utility of ASL in the identification of venous sinus obstruction. We herein report the case of a 72-year-old woman who presented with diplopia and right trigeminal neuralgia due to bilateral cavernous sinus dAVF. Digital subtraction angiography (DSA) showed temporal occlusion of the inferior petrosal sinus (IPS) and ASL indicated hyperintense signal in the IPS. The ASL signal could indicate venous stasis soon after the occlusion based on the serial changes of IPS patency and occlusion observed in the DSA.

12530 Inferior Petrosal Sinus Sampling In Cushing’s Disease

Abstract Disclosure: A. Gondhi: None. S. Antharam: None. I. Moledina: None. Inferior Petrosal Sinus Sampling in Cushing’s Disease Introduction: Cushing's disease (CD) is the most common cause of endogenous Cushing syndrome( CS) caused by ACTH secreting pituitary tumor. MRI is typically used for imaging, but standard MRI may only detect 50% of microadenomas. In these cases, inferior petrosal sinus sampling (IPSS) is the gold standard in detecting pituitary source of ACTH. Case presentation:A 53-year-old man presented with signs and symptoms of CS: fatigue, weight gain, decreased libido, mood swings, new onset prediabetes. Physical examination revealed cushingoid appearance with facial flushing, easy bruising, abdominal purple striae. Initial work up revealed ACTH dependent CS: elevated late night Salivary cortisol 0.39 mcg/dL (<0.09 mcg/dL), 24hr urine free cortisol 192 mcg/24 hour (4 – 50 mcg/24 hour)Non suppressed cortisol 8.1 mcg/dL (<1.8 mcg/dL) after 1mg dexamethasone suppression test8 AM ACTH 56 pg/ml (7.2 – 63 pg/ml), DHEAS 491 mcg/dL (38-318 mcg/dL)Pituitary hormonal work up: normal Prolactin 7.8 ng/mL (2.6-13.1 ng/mL)Low TSH 0.29 ng/ml (0.45-5.3 ng/ml) with normal Free T4 0.76 ng/dl (0.58-1.6 ng/dl)Low Total Testosterone 150 ng/dl (175-781 ng/dl), Low FSH<0.7 mInt units/ml(1.27-19.26 mInt units/ml), Low LH 1 mInt units/ml (1.24- 8.62 mInt units/ml), Normal IGF 180 ng/mL (65-222 ng/mL), A1C 6% (Prediabetes – 5.7-6.4) MRI Brain showed normal pituitary gland. IPSS was performed with DDAVP: +2, +5, +10, +15: Right/ periphery ratio- 31.8, 10.75, 7.6, 5.3. left/periphery ratio- 26.6, 18.8, 8.3, 7.5. All the ratios >=3, which showed clear central to peripheral gradient. and no left or right difference consistent with Cushing's disease. Subsequently, a transsphenoidal pituitary gland resection was performed. Suspicious tissue was excised from both sides during the surgery, showing positive ACTH immunostaining, consistent with pituitary microadenoma. Post-operative labs showed significant improvement with normalization of Cortisol 3.2 mcg/dl, ACTH 45 pg/ml, TSH 3.14 ng/ml, FT4 0.61 ng/dl, FSH 1.7 mInt units/ml, LH 2.4 mInt units/ml, Prolactin 7.1 ng/ml, A1C 5.4 %He was discharged on physiological dose of Hydrocortisone and passed cortisol stimulation test (3.4 mcg/dl ---> 18.1 mcg/dl) Conclusion: Distinguishing between CD and ectopic ACTH secretion is crucial due to the differing treatment options. The most accurate method for differentiation is IPSS, which boasts high sensitivity and specificity compared to other analyses. Despite its invasiveness, IPSS is associated with rare adverse events, making it a valuable tool in clinical practice. Presentation: 6/3/2024

6640 Utility of bilateral inferior petrosal sinus sampling for diagnosis and management of Cushing's disease in children ; a case report

Abstract Disclosure: V. leal: None. L. Socha: None. S.S. Awadalla: None. The causes of adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (CS) are Cushing's disease (CD) and ectopic ACTH syndrome (EAS). The differential diagnosis of CS and the localization of lesions in CD and EAS are often challenging. The utility of bilateral inferior petrosal sinus sampling (BIPSS), an important test in adults, is less defined in children.A 16-year-old girl was referred for evaluation and treatment of Cushing syndrome she experienced weight gain, secondary amenorrhea, and back pain. 24-hour urinary free cortisol and low-dose dexamethasone suppression tests suggested Cushing syndrome. Adrenocorticotropic hormone (ACTH) level and high-dose dexamethasone suppression test confirmed Cushing disease. Pituitary magnetic resonance reported a microadenoma. To rule ectopic ACTH syndrome, and localize the pituitary tumor, bilateral inferior petrosal sinus sampling (BIPSS) was performed with desmopressin to stimulate ACTH. Finally, the patient was diagnosed with Cushing disease due to right ACTH-secreting pituitary microadenoma and underwent endoscopic endo-nasal transsphenoidal surgery.In conclusion , BIPSS can be a valuable tool not only for discriminating between pituitary origin and ectopic ACTH-secreting Cushing syndrome, but also for providing precise localization of pituitary adenomas, thereby facilitating appropriate treatment. Presentation: 6/1/2024

7594 Diagnostic utility of 11C-Methionine PET-CT imaging in persistent or recurrent Cushing’s disease after transsphenoidal surgery

Abstract Disclosure: R. Furnica: None. F. Devuyst: None. C. Mathey: None. S. Constantinescu: None. C. De Herdt: None. L. Renaud: None. D.M. Maiter: None. Introduction: Equivocal or negative pituitary magnetic resonance imaging (MRI) findings pose a significant challenge in the management of persistent or recurrent Cushing’s disease (CD), compromising the chances of success of a further transsphenoidal surgery (TSS). The aim of our study was to determine the diagnostic utility of [1][1]C-methionine (MET) positron emission tomography coupled with computerized tomography (PET-CT) in localizing the residual corticotroph adenoma. Methods: We retrospectively analyzed the results of all MET-PET-CT performed between May 2002 and November 2023 in patients with a CD persisting or relapsing after TSS, and equivocal (n=14) or negative pituitary MRI findings (n=8). In 15 cases, images obtained from MET-PET were also co-registered with a high-resolution 3D pituitary MRI. All patients had a pathologically confirmed corticotroph tumor, and/or biochemical evidence of early postoperative remission after the first TSS, and/or proven ACTH-dependent Cushing’s syndrome with positive bilateral inferior petrosal sinus sampling. Results: Twenty-two patients were included (18 females and 4 males), with a mean age of 35.5 years at diagnosis. Initial tumors were mostly microadenomas with a mean tumor volume of 15 mm3. Thirteen out of the 22 patients had a suspect anomaly on conventional MRI that could however not be clearly distinguished from postsurgical changes, while the remaining 9 had a negative MRI. A significant MET standardized uptake value (SUV) in the suspected area of the tumor residue was defined as a ratio ≥ 1.80 relative to cerebellum SUV and was found in 12/22 patients (55%; 4 patients with negative pituitary MRI and 8 with equivocal findings). On the basis of positive imaging, repeat TSS was performed in 10 patients and was successful in 6, while Gamma Knife radiosurgery (GKRS) was performed in 2 patients allowing remission in both (total remission rate: 8/12). Among the 4 patients not cured by TSS, the presence of corticotroph adenoma in the resected tissue was found in 3 cases. Exploratory TSS was performed in 4 of the 10 PET negative patients, with no remission. Two patients were treated with GKRS, with remission in 1 case. Among the 4 other patients, bilateral adrenalectomy was performed in one case and adrenal steroidogenesis inhibitors were used in the remaining patients. Conclusions: [1][1]C-Methionine PET-CT imaging can provide valuable diagnostic information to detect a residual active corticotroph adenoma in about half of patients with a persistent or recurrent CD and equivocal or negative MRI results, thereby allowing targeted TSS or radiosurgery with a global success rate of 67% in this selected subpopulation. Presentation: 6/1/2024

8169 Bilateral Inferior Petrosal Sinus Sampling Using Metyrapone as a Reliable Alternative to Differentiate Between Cushing Disease and Ectopic ACTH Syndrome- A Single Center Experience

Abstract Disclosure: M. Azmath: None. S. Faisal: None. C. Caetano: None. T. Vedere: None. H. Aftab: None. B. Tendler: None. C. Malchoff: None. Introduction: Bilateral IPSS is a crucial test in accurately diagnosing Cushing disease (CD) and differentiating it from ectopic ACTH syndrome (EAS). [1] CRH stimulated IPSS is the gold standard technique but cannot be performed due to current shortage of CRH. Metyrapone is a safe and reliable alternative to CRH that can stimulate corticotrophs to secrete ACTH and hence used for IPSS. [2] We would like to share a single center experience using a novel low dose metyrapone protocol for IPSS that successfully helped differentiate CD and EAS. Methods: This was a retrospective analysis of patients presenting with Cushing syndrome. Initial diagnosis was confirmed based on standard testing including 24-hour urinary free cortisol (UFC), late night saliva concentrations (LNSC) and MRI. Metyrapone 500 mg every 4 hours for 3 doses was administered orally starting midnight prior to IPSS performed in the morning. ACTH levels drawn during initial evaluation for Cushing syndrome was compared to ACTH values post metyrapone from the peripheral vein sample to calculate a gradient. Ultimately, pituitary CD or EAS was confirmed based on cure following surgery and /or positive ACTH of tumor staining on pathology and/or concordant results with CRH stimulated IPSS. Results: There were 9 patients, out of which 5 had pituitary CD, and 4 had EAS. Pre ACTH levels for patients ranged between 14.5 and1164 pg/ml (normal reference range 6-50). Following metyrapone, ACTH level rose to 40-4705 pg/ml (normal reference range 6-50). The increase in ACTH levels ranged from 81-547% pre and post metyrapone. An average of 5-6 ACTH samples were drawn during IPSS. Catheterization was successful in all patients and was confirmed by IR. The mean central to peripheral (C/P) ACTH ratio for patients with confirmed CD was 20.53 in comparison with a ratio of 1.34 in patients with EAS. IPSS was confirmed to be diagnostic for pituitary CD if the peak ratio after metyrapone administration was more than 3. No adverse effects were observed during or after the procedure and no hospitalization was required pre-procedure. Discussion: We present single center experience with a novel low dose metyrapone protocol for IPSS. Our protocol was successful in increasing ACTH/cortisol secretion by tumorous cells as evidenced by increase in ACTH levels post metyrapone. It is an easy oral protocol which proved to be safe without the risk for adrenal insufficiency that can occur with higher doses. It also mitigates the small thromboembolic risk that can occur with DDAVP administration. A clear distinction in C/P ACTH ratios was observed in patients with CD versus EAS as early as the 3rd sample. In conclusion, our low dose metyrapone protocol was safe and reliable in accurately differentiating between CD and EAS in small sample of patients at our institution. Presentation: 6/1/2024

9272 Diagnostic utility of 11C-Methionine PET-CT imaging in persistent or recurrent Cushing’s disease after transsphenoidal surgery

Abstract Disclosure: R. Furnica: None. F. Devuyst: None. C. Mathey: None. S. Constantinescu: None. C. De Herdt: None. L. Renaud: None. D.M. Maiter: None. Introduction: Equivocal or negative pituitary magnetic resonance imaging (MRI) findings pose a significant challenge in the management of persistent or recurrent Cushing’s disease (CD), compromising the chances of success of a further transsphenoidal surgery (TSS). The aim of our study was to determine the diagnostic utility of [1][1]C-methionine (MET) positron emission tomography coupled with computerized tomography (PET-CT) in localizing the residual corticotroph adenoma. Methods: We retrospectively analyzed the results of all MET-PET-CT performed between May 2002 and November 2023 in patients with a CD persisting or relapsing after TSS, and equivocal (n=14) or negative pituitary MRI findings (n=8). In 15 cases, images obtained from MET-PET were also co-registered with a high-resolution 3D pituitary MRI. All patients had a pathologically confirmed corticotroph tumor, and/or biochemical evidence of early postoperative remission after the first TSS, and/or proven ACTH-dependent Cushing’s syndrome with positive bilateral inferior petrosal sinus sampling. Results: Twenty-two patients were included (18 females and 4 males), with a mean age of 35.5 years at diagnosis. Initial tumors were mostly microadenomas with a mean tumor volume of 15 mm3. Thirteen out of the 22 patients had a suspect anomaly on conventional MRI that could however not be clearly distinguished from postsurgical changes, while the remaining 9 had a negative MRI. A significant MET standardized uptake value (SUV) in the suspected area of the tumor residue was defined as a ratio ≥ 1.80 relative to cerebellum SUV and was found in 12/22 patients (55%; 4 patients with negative pituitary MRI and 8 with equivocal findings). On the basis of positive imaging, repeat TSS was performed in 10 patients and was successful in 6, while Gamma Knife radiosurgery (GKRS) was performed in 2 patients allowing remission in both (total remission rate: 8/12). Among the 4 patients not cured by TSS, the presence of corticotroph adenoma in the resected tissue was found in 3 cases. Exploratory TSS was performed in 4 of the 10 PET negative patients, with no remission. Two patients were treated with GKRS, with remission in 1 case. Among the 4 other patients, bilateral adrenalectomy was performed in one case and adrenal steroidogenesis inhibitors were used in the remaining patients. Conclusions: [1][1]C-Methionine PET-CT imaging can provide valuable diagnostic information to detect a residual active corticotroph adenoma in about half of patients with a persistent or recurrent CD and equivocal or negative MRI results, thereby allowing targeted TSS or radiosurgery with a global success rate of 67% in this selected subpopulation. Presentation: 6/1/2024

7667 Cushing’s Puzzle: Echinococcal Pituitary Cyst In A Rare Encounter

Abstract Disclosure: E. Sari: None. F. Erenler: None. Introduction: Echinococcus is a rare parasitic infection endemic in the Mediterranean, Middle East, South America and Africa, which can cause cystic disease in several organs. Central nervous system involvement is known to comprise 1-2% of all cystic echinococcal disease. Hereby, we report a case of an opportunistic pituitary echinococcus infection in a patient with hypercortisolism due to adrenocortical adenoma with initial misdiagnosis of Cushing’s disease. Clinical Case: A 40-year-old South American female with poorly controlled T2DM on oral agents and hypertension presented to the ER with abdominal pain and subsequent CT of the abdomen with contrast showed a right adrenal mass measuring up to 2.8 cm. A follow up CT with adrenal protocol confirmed 3.3 cm right adrenal mass, 46 HU in precontrast images with >50% washout. Review of records revealed that a recent MRI brain with contrast was performed for headache evaluation and showed an incidental 5x7x4 mm lesion in the pituitary gland. Endocrinology evaluation revealed 24-hour urine volume 1800 mL, elevated free cortisol levels 277.6 mcg/24hr (RR: 4.0-50.0 mcg/24hr), creatinine of 0.67g/24hr (RR: 0.50-2.15g/24hr). 1 mg dexamethasone suppression test showed AM cortisol of 28.7 mcg/dL. ACTH was elevated at 67 pg/mL (RR: 6-50 pg/mL). FSH, LH, and GH were normal. Presumed diagnosis of ACTH-dependent hypercortisolism was made and she underwent bilateral inferior petrosal sinus sampling with confirmed successful cannulation but this was inconclusive due to low ACTH levels. Follow-up MRI of the pituitary gland showed T1 bright, T2 isointense circumscribed lesion measuring 7x6x3 mm at anterior pituitary gland with a thin rim of peripheral enhancement consistent with cystic features. She underwent transsphenoidal resection of the pituitary lesion and the pathology specimen showed parasites consistent with echinococcosis. Infectious disease was consulted, and the patient started on albendazole. Post-operative laboratory evaluation was notable for persistently elevated AM cortisol, 24-hour urine free cortisol levels, and low ACTH levels, confirming ACTH independent hypercortisolism. She underwent right adrenal nodule resection and pathology was consistent with adrenocortical adenoma. Post-adrenalectomy AM cortisol levels were < 2 mcg/dL, indicating the resolution of hypercortisolism along with substantiating the diagnosis of primary adrenocortical hyperfunction. Conclusion: To the best of our knowledge, this is the first case report of an opportunistic echinococcus infection presenting as a pituitary lesion in the setting of Cushing Syndrome. We would like to highlight the importance of recognizing opportunistic infections, including Echinococcus as a potential etiology in the setting of hypercortisolism, especially for patients from endemic regions. Presentation: 6/2/2024

8036 A Rare Case of Cushing’s Syndrome Caused by a Pulmonary Carcinoid Tumor

Abstract Disclosure: A.C. Tep: None. F.M. Wolf: None. Introduction: The most common causes of ectopic ACTH (adrenocorticotropic hormone) syndrome include bronchial carcinoid tumors and other neuroendocrine tumors. Ectopic ACTH syndrome (EAS) can be difficult to diagnose. Differentiating Cushing’s disease and EAS is difficult, as ACTH-secreting tumors are often small and easily missed on imaging. Case Presentation: A 32-year-old male with a history of hypothyroidism presented with a 6-month history of facial rounding. He also noticed a dorsocervical fat pad, muscle weakness in the extremities, easy bruising, and elevated blood pressure progressing over the same period. A 24-hour urine free cortisol was elevated to 1797 mcg. Two salivary cortisol tests performed 1 hour after the patient’s usual bedtime had values of 4.4 ug/dl and > 1.000 ug/dl. Both the urine and salivary cortisol results were exceedingly high. ACTH was elevated (150 pg/ml). An MRI of the pituitary gland was normal without evidence of an adenoma. Frequently, ACTH-secreting pituitary adenomas are small enough that they are missed on MRI; however, given our patient’s rapid clinical presentation, additional imaging was performed to identify an ectopic source. A CT Chest/Abdomen/Pelvis showed a 1.2 cm nodule in the right middle lobe of the lung. The right middle lobe was resected, and pathology revealed a carcinoid tumor. His cortisol levels slowly decreased postoperatively and eventually normalized. At his one-month post-operative visit, his symptoms were all improving but not yet resolved. Discussion: This patient was found to have Cushing's syndrome due to ectopic ACTH production from a pulmonary carcinoid tumor. The patient demonstrated clinical improvement after resection of the tumor. Pulmonary carcinoid tumors are rare neuroendocrine epithelial tumors that account for 2-5% of all lung tumors. The annual incidence of these tumors is 2.3-2.8 cases per million people. Endogenous Cushing's syndrome is either ACTH-dependent or ACTH-independent. In ACTH-dependent Cushing's syndrome, the ACTH can either be from the pituitary or an ectopic source. Once ACTH-dependent disease is confirmed, a pituitary MRI is performed to evaluate for an ACTH-secreting pituitary adenoma; this is called Cushing’s disease. Some patients undergo inferior petrosal sinus sampling to confirm the source is central and to determine laterality before transsphenoidal resection of the adenoma. If the source of ACTH is not from the pituitary, obtaining a CT or MRI of the chest and abdomen locates tumors in most patients. At times a functional study, such as an octreotide or PET-DOTATE scan, is done to confirm the diagnosis before proceeding with surgical resection to avoid unnecessary removal of an incidental tumor. Ectopic ACTH production often causes a more rapid progression of Cushingoid features, which can be a clue to the diagnosis of this condition. Presentation: 6/1/2024

7277 Diabetic Ketoacidosis As The First Manifestation Of Ectopic Cushing’s Syndrome

Abstract Disclosure: R.S. Medeiros: None. Introduction: Ectopic Cushing’s Syndrome (ECS) represents 10-20% of all ACTH-dependent CS, and the majority of cases arise from lung carcinoids. These indolent lesions usually evolve clinically over 6-24 months, whereas carcinomas are associated with faster onset of ECS. Diabetic Ketoacidosis (DKA) as a presenting manifestation of Cushing’s Syndrome (CS) is very rare, with the few cases published to date related to Cushing’s disease. Clinical Case: A 42-year-old woman was admitted in the emergency room with DKA and COVID-19. During stabilization, florid CS was clinically suspected. She reported a 6-month history of secondary amenorrhea, lack of concentration and memory, easy bruising, proximal myopathy with frequent falls evolving to daily life dependency from relatives. She also reported a 2-month diagnosis of dyslipidemia, Diabetes and hypertension, and a diagnosis of atypical pneumonia 6 months ago. Physical exam showed typical cushingoid appearance, especially for marked limb sarcopenia and proximal myopathy. An overnight dexamethasone suppression test (morning cortisol: 25.7 ug/dL), 24h urinary free cortisol (UFC; 1072.5 ug/dL; reference: <176) and serum cortisol at 23h00 (25.5 ug/dL) confirmed CS. ACTH-dependent CS was diagnosed. She had non-suppressible serum cortisol in high dose dexamethasone suppression test, and CRH stimulation test was suggestive of Cushing’s disease only by a 20% rise of cortisol at 30 minutes. Pituitary MRI was normal. Inferior Petrosal Sinus sampling was postponed for several months due to healthcare strikes. The patient started 750 mg of metyrapone in three divided doses but rapidly decreased the dose and stopped it due to clinical resolution of CS, a dramatic improvement of all glucocorticoid-related comorbidities leading to discontinuation of statin, insulin, main oral anti-hyperglycemic and antihypertensive medications, and normal midnight salivary cortisol and 24h UFC. She remained in this eucortisolemic state for 12 months. Thoracic CT scan revealed thymic hyperplasia and a 25x15 mm well-defined nodule in the lingula. A 68Ga-DOTANOC PET/CT showed a single uptake in the same lung region. The patient underwent lingulectomy plus excisional biopsy of interlobar lymph nodes, and pathology revealed a low-grade neuroendocrine tumor (Ki67<2%, <2 mitosis) without involved lymph nodes. The patient is weaning off from physiologic doses of hydrocortisone. Conclusion: DKA can rarely be the presenting manifestation of severe CS, including ECS. Clinicians should suspect on this etiology of DKA based on clinical signs and cumulative morbidity not typical of a young patient. This hint would lead to the expedite implementation of targeted therapies for initial stabilization of the CS patient, and the timely institution of a proper diagnostic approach and definitive treatment of this challenging patients. Presentation: 6/2/2024

8356 Total Hypophysectomy in Cushing’s Disease: Results from a Terciary Center

Abstract Disclosure: M.V. Lopes: None. M.D. Severino: None. J. Rocha: None. C.R. Peixe: None. M.I. Alexandre: None. A. Gomes: None. M.J. Bugalho: None. Introduction: Transsphenoidal surgery (TSS) is the first line treatment for Cushing’s disease (CD), leading to remission in 70-80% of cases. Though selective adenomectomy is the preferred approach, total hypophysectomy may be needed. Objective: To describe 3 CD patients in which total hypophysectomy was performed. Clinical cases 1. A 58-year-old man with a history of type 2 diabetes (T2D) and obesity, was referred to the Endocrinology Clinic due to abdominal purple striae and facial plethora. Laboratory tests suggested ACTH dependent hypercortisolism, with normal serum ACTH, high 24h urinary cortisol and no cortisol suppression in the overnight 1mg dexamethasone suppression test (DST). The CRH test was suggestive of CD but no adenoma was found on pituitary MRI. Inferior petrosal sinus sampling (IPSS) was compatible with CD with right-sided lateralization. Right hypophysectomy was performed but no CD remission was achieved, so the patient underwent total hypophysectomy. Corticotroph hyperplasia was identified in histology. After 9 months of follow-up, he mantains CD remission. 2.A 37-year-old woman was diagnosed with ACTH dependent hypercortisolism after referral to the Endocrinology Clinic for alopecia, amenorrhea, hypertension and hirsutism. Laboratory tests showed severe hypokalemia, high plasma ACTH and 24h urinary cortisol and the MRI showed a right-sided macroadenoma. Nonetheless, considering the clinical severity, an IPSS was performed and definitely excluded an ectopic Cushing’s syndrome (CS) thus confirming the diagnosis of CD with right-sided lateralization. The patient underwent selective TSS, however, for lack of CD remission, total hypophysectomy was performed. Histology revealed an adenocorticotrophic adenoma. Yet, a year later, she maintains persistence of CD, although less severe, and is under treatment with metyrapone. 3.A 58-year-old woman with a history of T2D and class 3 obesity, was evaluated in our Endocrinology Clinic due to obesity. Her physical examination suggested CS, so this hypothesis was investigated. Laboratory tests suggested ACTH dependent hypercortisolism, with normal serum ACTH, elevated 24h urinary cortisol and no cortisol suppression in the overnight 1mg DST. The high dose DST was suggestive of CD but the pituitary MRI didn’t show an adenoma. IPSS was compatible with CD but it was not possible to determine lateralization. So, total hypophysectomy was performed. An adenocorticotrophic adenoma was identified in histology. Postoperative CD remission was achieved and persists 3 months later. Conclusions: These 3 cases highlight the challenge of treating CD and suggest that in certain cases total hypophysectomy may be the treatment of choice to cure or at least improve CD. Although it is associated with more complications than selective TSS, our patients had no complications, only developed panhypopituitarism and diabetes insipidus. Presentation: 6/1/2024

5165 Cushing’s Disease And Primary Aldosteronism Confounded By A Non-functioning Solitary Adrenal Incidentaloma

Abstract Disclosure: J.G. Friedman: None. W. Huang: None. Background: Adrenal incidentalomas are common, affecting ∼2% of the general population. The presence of adrenal incidentaloma necessitates biochemical testing for hypersecretion, however hypercortisolism and/or hyperaldosteronism may not necessarily originate from the nodule that prompted the initial workup. Clinical Case: A 53-year-old man with a history of obesity and hypertension was referred for workup of a 2.4 x 1.4 cm R adrenal nodule that was incidentally discovered on an abdominal CT to rule out pancreatitis. He was noted on examination to have some Cushingoid features. He was on three antihypertensives (amlodipine 10 mg, carvedilol 50 mg, and spironolactone 50 mg) with adequate blood pressure control and no hypokalemia. He denied spells nor exogenous steroid exposure. Initial testing for hypersecretion showed an elevated cortisol 8.7 ug/dL (<1.8) after 1 mg dexamethasone with adequate dexamethasone level, aldosterone concentration (PAC) 9 ng/dL (3-16), plasma renin activity (PRA) 0.7 ng/mL/h (0.25-5.82), potassium of 3.8 mmol/L (3.5-5.1), and normal plasma metanephrines. Further testing revealed elevated 24-hour urinary free cortisol 81.3 mcg/24h (4-50) and elevated late night salivary cortisol 0.10 and 0.13 mg/dL (<0.09). Baseline 8 AM ACTH was not suppressed 16.3 pg/mL (7.2-63.6). DDAVP stimulation resulted in an increase in cortisol and ACTH suggestive of Cushing’s disease, which was confirmed by inferior petrosal sinus sampling (IPSS). Pituitary MRI showed a 3.6 mm L-sided microadenoma. He underwent transsphenoidal resection with pathology consistent with an ACTH-staining pituitary adenoma. Immediate post-op cortisol nadir was 4.9 ug/dL. A few weeks after surgery, he underwent retesting for primary aldosteronism notable for PAC 14 ng/dL, PRA 0.58 ng/mL/h, and K 4.0 mmol/L. After oral salt loading, 24-hour urine aldosterone was 14.4 mcg/24h (<12) with urine sodium 247 mmol/L/24h (>200). He completed AVS which lateralized to the L adrenal gland despite a R adrenal nodule. He underwent L adrenalectomy with significant improvement in blood pressure which is now well-controlled on carvedilol monotherapy with normalization of PRA to 1.94 ng/ml/h. The R adrenal nodule remains stable in size and appearance on follow up imaging. Conclusion: The presence of an adrenal adenoma with concomitant biochemical evidence of hormonal excess cannot inherently be attributed to nodular autonomous function without further workup. Other hormonal assessment including ACTH level and localization studies are necessary prior to any surgical procedure to avoid missed diagnoses of Cushing’s disease and contralateral primary aldosteronism in the presence of a non-functioning adrenal nodule. Presentation: 6/1/2024

6917 Multiple Red Herrings Complicating the Diagnosis of Cyclic Cushing’s Syndrome

Abstract Disclosure: A. Grover: None. R. McGlotten: None. L.K. Nieman: None. Introduction: Cyclic Cushing’s syndrome (CCS) is a rare disorder characterized by intermittent hypercortisolemia. It may be caused by pituitary tumor (Cushing disease), ectopic ACTH tumor secretion (EAS), or primary adrenal disease. We present a case of CCS with multiple red herrings complicating the diagnosis. Case: A 57-year-old Cushingoid appearing woman presented elsewhere with weight gain, brain fog, weakness, hypertension, worsening diabetes, and OSA. Screening tests showed more than three episodes of hypercortisolism with interval eucortisolism: salivary and 24-urine cortisol (UFC) ranged from 0.06-0.34 µg/dL (reference range, RR, ≤0.09 µg/dL) and 59.7-137.1 µg/24 h (RR 4-50 µg/24 h) respectively. The patient was symptomatic throughout. Differential diagnosis was CCS vs a physiologic non-neoplastic condition. As she had no clear etiology for the latter, further testing was performed. ACTH was indeterminate (23-27 pg/mL, RR <46). Pituitary MRI showed a left 7 mm lesion. Inferior petrosal sinus sampling (IPSS) with Corticotropin Releasing Hormone (CRH) administration showed peripheral baseline ACTH levels of 9.0 and 10.0 pg/mL, suggesting that she had cycled out of a hypercortisolemic phase. The left petrosal baseline values were low (9 pg/mL,16 pg/mL), suggesting poor catheterization, which was confirmed by a low prolactin-normalized ACTH ratio. The petrosal levels were lower than expected (maximum 767 pg/ml), due to suppression of normal corticotropes vs poor tumor response. However, a central:peripheral step-up was consistent with Cushing's disease (CD) or pseudo-CS. She was referred to us for re-evaluation. A low FSH, LH, low normal TSH, and UFC of 160 µg/24h supported a diagnosis of CS. ACTH was 14.6 pg/mL. Pituitary MRI showed a 1.3 cm x 0.8 cm mass extending into the left cavernous sinus. She did not suppress cortisol during a dexamethasone suppression test (DST). After CRH administration ACTH levels doubled. Based on the macroadenoma and CRH response, CD was established; IPSS was not repeated. After transsphenoidal hypophysectomy, pathology revealed ACTH positive adenoma. Post-operative adrenal insufficiency required hydrocortisone replacement. Conclusion: CCS can pose a diagnostic challenge due to unpredictable duration and frequency of hypercortisolism. Intermittently elevated cortisol levels with CS symptoms should raise suspicion for CCS. In our case, low peripheral ACTH levels further suggested this possibility. DST may give spurious results in CCS owing to spontaneous falls or rises in cortisol at the time of testing. Prolonged hypercortisolism is required in all patients to ensure suppression of normal corticotropes, which if not complete, may confound results in patients with EAS. Finally, inadequate catheterization may affect accuracy of lateralization in any patient with CS and is ideally evaluated both by venography and prolactin measurement. Presentation: 6/1/2024

Endoluminal Sigmoid Sinus Occlusion During Jugular Foramen Tumor Surgery: Novel Technique, Operative Nuances, and Clinical Experience With 33 Patients.

Surgery of jugular foramen tumors (JFTs) often requires vascular control by means of ligating the internal jugular vein and sigmoid sinus (SS) to allow intrabulbar access. Occlusion of the SS traditionally involves presigmoid and retrosigmoid durotomies allowing introduction of ligature devices, predisposing to cerebrospinal fluid (CSF) leakage and pseudomeningoceles. We describe a simple and novel endoluminal sigmoid sinus occlusion (ESSO) technique with Gelfoam that is entirely extradural. An extended anterolateral infralabyrinthine approach with ESSO was performed in 33 patients with JFTs. After ligating the internal jugular vein, the SS is opened and Gelfoam is placed endoluminally into the proximal SS. Care is taken to avoid occlusion of the venous outflow of the vein of Labbe to avoid temporal lobe venous infarction. Hemostatic gelatin matrix is injected distally to stop venous backflow from the inferior petrosal sinus. The jugular venous system is isolated, and the outer jugular wall can be opened to expose the JFT for resection. There were no complications of temporal lobe venous infarction or postoperative hematoma observed. Four patients with intradural tumor extension developed pseudomeningoceles. For patients with purely extradural JFTs, none developed postoperative incisional CSF leaks and one had pseudomeningocele. This ESSO technique is fast and effective, permitting occlusion of the SS during JFT surgery. It has the advantage of being entirely extradural, avoiding durotomy which can result in postoperative CSF leak. It is important to keep the Gelfoam distal to the transverse-sigmoid junction to avoid occlusion of the vein of Labbe inlet and temporal lobe venous infarction.

An aggressive Cushing's syndrome originating from a rare thymic neuroendocrine tumor, controlled successfully with fluconazole and octreotide therapy before surgery.

Cushing's syndromes (CSs) due to the thymic neuroendocrine tumors are rarely seen. Here, a case of ectopic CS originating from an atypical neuroendocrine tumor has been presented. A 49-year-old woman was hospitalized with symptoms of fatigue, chest pressure, dyspnea, muscle weakness, and resistant hypertension. There was marked hyperpigmentation in the whole-body surface suggestive of adrenocorticotropic hormone (ACTH) excess and there were physical features of CS. There was deep hypokalemia. Basal hormone profile, dexamethasone suppression tests, midnight cortisol, and 24-hour urine cortisol levels were suggestive of ectopic CS. The pituitary magnetic resonance imaging revealed a 5 mm cystic lesion and the patient refused inferior petrosal sinus sampling. Thorax computerized tomography showed an anterior mediastinal mass. A fluorodeoxyglucose-positron emission tomography showed the same mediastinal lesion (suvmax: 11.4), and no other tumor focus was detected. There was an aggressive cortisol excess causing acute respiratory distress syndrome, making it difficult to perform the surgery. We immediately started fluconazole and octreotide therapy and were successful in lowering the cortisol level. Then a complete resection of the tumor had been able to be surgically performed and tumor cells showed strong cytoplasmic immunopositivity with ACTH. A definitive diagnosis of "ACTH secreting atypical thymic carcinoid tumor" was rendered based on the histopathological and immunohistochemical features. There was only surrounding vessel invasion, and no lymphoid or other organ metastases were detected. As there were surrounding vessel invasions, a two-cycle regimen cisplatin-etoposide chemotherapy and radiotherapy were employed. After surgical and medical therapy, the cortisol and ACTH levels turned to normal. The patient is in biochemical and clinical remission and has no tumor recurrence yet. Ectopic ACTH-producing thymic carcinoids are rare but life-threatening tumors because of the underlying malignancy and severe hypercortisolemia. It is important to consider this disease and perform appropriate treatment at the right time. Today, surgery is the standard therapeutic modality if it is possible to perform, but there is not a clear and constant recommendation for nonsurgical therapeutic modalities. Further studies are needed for the optimal treatment strategies.

Endovascular approaches for the treatment of dural carotid-cavernous fistulas: A systematic review.

Dural carotid-cavernous fistulas (dCCFs), also known as indirect carotid-cavernous fistulas, represent abnormal connections between the arterial and venous systems within the cavernous sinus that are typically treated via endovascular approach. We aim to investigate the clinical characteristics of patients with dCCFs based on the endovascular treatment approach and assess angiographic and clinical outcomes. A systematic review of the literature was performed. Data including number of patients, demographics, presenting clinical symptoms, etiology of fistula, Barrow classification, and embolization material were collected and evaluated. Outcome measures collected included degree of fistula occlusion, postoperative symptoms, complications, and mean follow-up time. A total of 52 studies were included examining four primary endovascular approaches for treating dCCFs: transarterial, transfemoral-transvenous (transpetrosal or other), transorbital (percutaneous or via cutdown), and direct transfacial access. Overall data was collected from 736 patients with 817 dCCFs. Transarterial approaches exhibit lower dCCF occlusion rates (75.6%) compared to transvenous techniques via the inferior petrosal sinus (88.1%). The transorbital approach via direct puncture or surgical cutdown offers a more direct path to the cavernous sinus, although with greater complications including risk of orbital hematoma. The direct transfacial vein approach, though limited, shows up to 100% occlusion rates and minimal complications. We provide a comprehensive review of four main endovascular approaches for dCCFs. In summary, available endovascular treatment options for dCCFs have expanded and provide effective solutions with generally favorable outcomes. While the choice of approach depends on individual patient factors and technique availability, traditional transvenous procedures have emerged as the first-line endovascular treatment. There is growing, favorable literature on direct transorbital and transfacial approaches; however, more studies directly comparing these general transvenous options are necessary to refine treatment strategies.

Cushing’s Disease Complicated with Multiple Thrombotic Phenomena Following Inferior Petrosal Sinus Sampling

Cushing’s syndrome is an endocrinologic disorder that occurs due to an excessive secretion of adrenal cortex-stimulating hormones or an overproduction of cortisol in the adrenal glands. Patients present with a variety of clinical symptoms such as obesity, hypertension, impaired glucose tolerance, and cardiovascular complications have been known for major contributors to the mortality. The inferior petrosal sinus sampling (IPSS) test is a useful diagnostic tool for identifying the source of Cushing’s disease. This procedure involves process of collecting samples through venous access and is generally considered safe. Here, we present 44-year-old patient diagnosed with Cushing’s disease presenting pulmonary thromboembolism and multiple embolic infarctions following IPSS.

Diagnostic Accuracy of the Desmopressin Stimulation Test in the Comprehensive Assessment of ACTH-Dependent Cushing’s Syndrome: A Comparative Analysis with BIPSS and TSS

ABSTRACT Background Cushing’s syndrome (CS) poses diagnostic challenges, particularly in distinguishing pituitary-dependent Cushing’s syndrome, Cushing’s disease (CD), from the ectopic ACTH syndrome (EAS). This study evaluated the diagnostic value of the desmopressin stimulation test (DST) in patients with ACTH-dependent CS in helping this discrimination. Methods Twenty-three ACTH-dependent CS patients underwent sequential DST, bilateral inferior petrosal sinus sampling (BIPSS), and transsphenoidal surgery (TSS). Two definitions of a positive DST results were applied. Diagnostic performance was assessed using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios. To avoid bias from predetermined criteria, we generated univariate receiver-operating characteristic (ROC) curves, plotting sensitivity against 1-specificity at various percentage cortisol and ACTH response levels. Results Against BIPSS, DST demonstrated robust sensitivity (Definition 1: 90.0%, Definition 2: 76.2%) and overall accuracy (Definition 1: 87.0%, Definition 2: 73.9%). PPV was high (Definition 1: 95.0%, Definition 2: 94.1%), but NPV indicated potential false negatives. Compared to TSS, DST showed good sensitivity (Definition 1: 90.9–77.3%) and PPV (100.0%) but limited NPV (16.7%). The likelihood ratios emphasized the diagnostic value of the test. Notably, against TSS, DST showed perfect discriminatory power (AUC 1.000 for percent ACTH, 0.983 for percent cortisol). Conclusion The desmopressin test shows promise in accurately identifying the underlying cause of ACTH-dependent CS, potentially reducing the reliance on invasive procedures and providing a practical solution for managing complex cases. Further research with larger cohorts is required to validate the utility of the DST in routine clinical practice.

Atypical presentation of Cushing's disease with weight loss and hypokalemia.

ACTH-secreting pituitary adenomas causing Cushing's disease (CD) typically present with weight gain, whereas weight loss and hypokalemia in endogenous Cushing's patients are suggestive of ectopic ACTH production. We report a case of CD presenting with atypical features of marked weight loss and hypokalemia. A 75-year-old female was admitted to the hospital with a history of profound weight loss, associated with uncontrolled hypertension, hyperglycemia, severe proximal muscle weakness, and hypokalemia. Subsequent investigations, including 24-h urinary free cortisol, 48-h low-dose dexamethasone suppression test, MRI of the sella, and bilateral inferior petrosal sinus sampling, confirmed CD without any evidence of ectopic ACTH production. She became eucortisolemic with medical therapy of ketoconazole and cabergoline, subsequently regained her weight, and became normokalemic. This case illustrates that patients with CD may present with symptoms and biochemical findings that would otherwise suggest ectopic ACTH production. Patients with CD do not always present with classical clinical features and may present with symptoms and biochemical findings that would otherwise suggest ectopic ACTH production. While most patients with CD typically lose weight after biochemical remission, some patients gain weight after the normalization of cortisol levels. This case highlights the need to entertain a broad differential in patients presenting with hypokalemia and weight loss and the need to exclude hypercortisolemia.

Proposal of a Classification System of Cavernous Sinus Dural Arteriovenous Fistulas and Treatment Strategies Based on Angioarchitecture: A Cohort Study of 116 Patients

Cavernous sinus (CS) dural arteriovenous fistulas (DAVFs) are commonly treated by transvenous embolization, but the details of treatment need to be more clearly defined. We propose a classification of CS-DAVF that can contribute to formulating endovascular treatment process. CS-DAVF was classified into seven categories based on the cumulative CS range and drainage patterns. CS-DAVF angioarchitecture, clinical characteristics, treatment strategies, and outcomes of CS-DAVF patients treated in our hospital from 2012 to 2021 were summarized and analyzed. Among the 116 patients with CS-DAVF: Type 1, 71 (61.2%); Type 2, 9 (7.8%); Type 3, 18 (15.5%); Type 4, 2 (1.7%); Type 5, 8 (6.9%); Type 6, 3 (2.6%); and Type 7, 5 (4.3%). Inter-CS or inferior petrosal sinus drainage was relatively rare in Types 1 and 6 (P < 0.001 and P < 0.001); basilar venous plexus drainage was more prevalent in Types 2, 5, and 7(P= 0.019). Inferior petrosal sinus occlusion was more commonly seen in Types 2, 3, and 5 (P= 0.005). The most frequent first symptoms and symptoms at admission in patients with CS-DAVF is ocular/orbital symptoms, occurring in 64 cases (55.2%) and 104 cases (89.7%), respectively. In this study, 108 patients (93.1%) underwent endovascular embolization. Among those who received endovascular embolization, 96 (88.9%) CS-DAVFs were treated via transvenous embolization. In long-term follow-up, 98 cases (84.5%) achieved cure, and 17 cases (14.7%) showed symptomatic improvement. Our proposed classification system based on cumulative CS range and drainage patterns can assist in formulating treatment strategies for transvenous embolization.

Maximizing the Sensitivity of Bilateral Inferior Petrosal Sinus Sampling.

Maximizing the Sensitivity of Bilateral Inferior Petrosal Sinus Sampling.