Somatostatin Receptor Scintigraphy Research Articles

7242 Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH) In A Patient With Recurrent Carcinoid

Abstract Disclosure: F. Woron: None. T.L. Anderson: None. P. Madhavan: None. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare generalized proliferation of pulmonary neuroendocrine cells. It is considered to be a pre-invasive lesion for pulmonary carcinoid, a rare neuroendocrine tumor (NET). DIPNECH is thought to be underdiagnosed, as patients can be asymptomatic or present with nonspecific cough and dyspnea, though it is also associated with fibrotic lung changes. Long-term annual surveillance imaging is recommended for due to the potential for development and metastasis of carcinoid tumors. We present a patient with recurrent pulmonary carcinoid later diagnosed with probable DIPNECH based on CT findings. The patient is a 72-year-old female with a prior 15 pack-year smoking history, who initially had a left lower lobe typical carcinoid tumor diagnosed and resected in 2018, with no evidence of lymph node metastasis. The patient’s medical history also includes pulmonary sarcoidosis, adrenal adenoma, thyroid nodule, hiatal hernia, and prediabetes. She has no family history of neuroendocrine tumors. Physical exam showed stable vitals with blood pressure of 112/70 mmHg in the right upper arm, heart rate of 84 bpm, and a body mass index of 39. Physical exam was unremarkable except for thyroid nodularity and obesity. Extensive biochemical evaluation for markers including chromogranin A and 24-hour urine 5-HIAA levels were within normal limits. In 2022, surveillance CT imaging showed a new 9 mm nodule in the right lobe within the bronchus, which was shown to be carcinoid on FNA. She complained of dyspnea and wheezing at this time, which has been managed with an albuterol inhaler. In 2023, PET/CT copper 64 dotatate scan showed a focal area of activity related to the nodule in the superior segment, also identified on recent CT scan, with the nodule measuring approximately 2.05 cm x 1.8 cm with a maximal SUV of 4.2. Interestingly, somatostatin receptor scintigraphy did not show any pick-up in the lung in 2018 or 2022. In 2023, the patient underwent right lower lobe superior segmentectomy after the nodule was found to have increased in size. Pathology showed G1, well-differentiated 1.1 cm typical carcinoid tumor with margins negative for invasive carcinoma. All 18 regional lymph nodes were negative for tumor. Immunohistochemical tests show that the tumor cells were positive for INSM1 and chromogranin with a low Ki-67 proliferation index (<2%), supporting the diagnosis. The patient is currently being monitored by yearly CT imaging and followed by both endocrinology and pulmonology. Given this case, we propose that DIPNECH should be considered as a differential in cases of pulmonary carcinoid, especially recurrent ones. Given that DIPNECH is thought to be underdiagnosed and a precursor for carcinoid associated with fibrotic lung changes, it is essential for this disease to be identified in order for patients to receive appropriate long-term monitoring. Presentation: 6/1/2024

6570 Treatment of Cushing’s With Levoketoconazole: A Case Series

Abstract Disclosure: N. Chamorro-Pareja: None. M. Haines: None. L.E. Dichtel: Consulting Fee; Self; Lumos Pharma. Research Investigator; Self; Recordati, NovoNordisk, Perspectum Ltd, Lumos Pharma, Pfizer, Inc.. Stock Owner; Self; Marea Therapeutics. Other; Self; Third Rock Ventures. B.M. Biller: Consulting Fee; Self; Xeris Pharmaceuticals, Recordati Rare Diseases, Sparrow, Lundbeck. Background: Endogenous Cushing’s syndrome (CS) is a rare condition of excess cortisol secretion; the most common cause is a pituitary corticotroph tumor (Cushing’s disease [CD]). Medical treatment for CD is primarily used to control hypercortisolism in patients with persistent or recurrent disease after transsphenoidal surgery (TSS). Levoketoconazole (LKCZ), a steroidogenesis inhibitor, was FDA approved in January 2022 for CS treatment. This reports 3 cases of patients who were treated with LKCZ for recurrent CS. Clinical Cases: Case 1: 44-year-old (yo) male (M) with a history of CD with urinary free cortisol (UFC) >26x upper limit of normal (ULN) who was treated preoperatively with ketoconazole (KCZ) 1000 mg/day with UFC improved to 6x ULN. KCZ was discontinued at TSS, and he achieved remission post-operatively. He was lost to follow-up and re-presented after several years with worsening hypertension, muscle weakness, edema, and anxiety with UFC 28x ULN and a recurrent pituitary lesion on MRI. He declined repeat TSS and underwent radiation therapy (RT) and medical treatment. LKCZ was initiated at 150 mg twice daily (BID) and increased to 300 mg BID. At LKCZ 300 mg BID, he had a low UFC and mild nausea but an adequate serum morning cortisol (10.4 ug/dL, ref:6-18.4 ug/dL); LKCZ was reduced to 150 mg BID with resolution of symptoms (sxs) and normal UFC. Case 2: 56 yo M with a history of CD (UFC >3x ULN) who underwent 2 TSSs and RT over 10 years prior with eventual remission, but later recurred. Sxs included brain fog and mood disturbances. He achieved control with pasireotide but discontinued due to abnormal liver function tests. He was then treated with KCZ 400 mg/day but remained hypercortisolemic (LNSC 1.1x ULN) and was interested in trying a new medication, so was switched to LKCZ 150 mg BID with significant improvement of sxs and normalization of LNSC. Case 3: 54 yo F with presumed cyclic CD (negative whole-body and octreotide scans) with UFC 1.7x ULN and LNSC 3x ULN. TSS was performed with negative pathology; she had persistent hypercortisolemia and sxs including insomnia, fatigue, and mood disturbances. She was intolerant to and/or uncontrolled on 4 medications, including KCZ at 1000 mg/day that was discontinued due to a rash. She was started on LKCZ 150 mg BID and achieved normal LNSC and UFC after about 1 month. The drug was discontinued due to the development of a rash similar to that with KCZ. Conclusion: LKCZ is a new option for the treatment of CS in patients whose disease persists after TSS. These 3 patients had improvement of sxs and normalization of cortisol levels while on LKCZ, although one patient discontinued LKCZ due to a rash that was previously experienced with KCZ. The other two patients are being carefully monitored for liver function test elevation, QTc abnormalities and adrenal insufficiency with no issues to date. To our knowledge, this is the first case series of CS patients treated clinically with LKCZ. Presentation: 6/1/2024

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

A retrospective study of paraganglioma of the urinary bladder and literature review.

To review and summarize the characteristics and therapy of paraganglioma of the urinary bladder (PUB). Patients who underwent the operation in Peking Union Medical College Hospital between January 2012 and December 2021 were reviewed for this retrospective study. A total of 29 patients, comprising 9 (31%) men and 20 (69%) women, were included. The main manifestations were hypertension, palpitation, and micturition syncope. Eight patients had an increased 24-h urinary catecholamine, and seven of them had increased norepinephrine. Normetanephrine in seven patients was increased. Six of 18 metaiodobenzylguanidine and 8 of 22 octreotide scans were positive. In total, 15 cases underwent laparoscopic partial cystectomy and 14 underwent transurethral resection of bladder tumor. In all patients, the immunohistochemical index of Melan-A, AE1/AE3, and α-inhibin were negative, and chromogranin A, S-100, and succinate dehydrogenase were positive. The Ki-67 of 28/29 cases was under 5%, and 1 case with a Ki-67 of 20% was diagnosed with malignant PUB. A total of 27 patients had a regular follow-up, 2 patients were lost during the follow-up, 3 patients had a recurrence, and 1 of these patients died within 1 year of surgery. The symptoms all disappeared or were relieved after the surgery. The transurethral surgery approach fits PUB tumors with a size <3 cm or that protrudes into the bladder and can significantly reduce the postoperative hospital stay. Early detection and treatment are effective, and regular review is necessary after the surgery.

Carcinoid Heart Disease Associated with Primary Ovarian Carcinoid Tumor: A Rare Presentation

Primary ovarian carcinoid tumors, an extremely rare subset of ovarian malignancies (&lt;0.1% of cases), typically manifest with abdominal pain and bloating. The occurrence of carcinoid heart disease (CHD) without classic carcinoid syndrome features is exceptionally uncommon. We report a 54-year-old female presenting with dyspnea and edema over months, lacking typical carcinoid syndrome signs. Initial assessments diagnosed heart failure, supported by elevated NT-Pro BNP, echocardiographic right ventricular dilation, and pulmonary/tricuspid valve regurgitation (normal left ventricular function). Right heart catheterization showed normal pulmonary/right ventricular pressures. Subsequent investigations (computed tomography thorax abdomen pelvis, 5-hydroxyindole acetic acid levels) strongly suggested carcinoid disease, confirmed by an octreotide scan revealing an octreotide-secreting ovarian carcinoid tumor. Surgical intervention included tricuspid and pulmonary valve repair, total abdominal hysterectomy, and bilateral salpingo-oophorectomy. Primary ovarian carcinoid tumors, though rare, may lead to unexpected complications like CHD. Timely diagnosis and intervention are pivotal for optimizing patient outcomes in such cases.

Combined visual and quantitative assessment of somatostatin receptor scintigraphy for staging and restaging of neuroendocrine tumors.

Somatostatin receptor scintigraphy (SRS) using 111In-DTPA-DPhe1-octreotide (pentetreotide) has become an integral part of neuroendocrine neoplasm management. The lack of precise quantification is a disadvantage of SRS. This study aimed to adapt the standardized uptake value (SUV) to SRS, establish the SUV range for physiological uptake in the liver, kidney, and spleen, and elucidate the utility of combined visual and quantitative SRS assessment for staging and restaging of neuroendocrine tumors (NETs). This study included 21 patients with NETs who underwent 111In-pentetreotide SRS. The SUV of physiological and pathological uptake was calculated using bone single-photon emission computed tomography (SPECT) quantitative analysis software (GI-BONE). For visual analysis, the primary and metastatic lesions were scored visually on planar and SPECT images using a five-point scale. We assessed the relationships between the SUVs of the liver, kidney, and spleen in the dual phase, and among quantitative indices, visual score, and pathological lesions classification. Sixty-three NEN lesions were evaluated. The mean ± standard deviation maximum SUVs (SUVmax) were liver: 4h, 2.6 ± 1.0; 24h, 2.2 ± 1.0; kidney: 4h, 8.9 ± 1.8; 24h, 7.0 ± 2.0; and spleen; 4h, 11.3 ± 4.5; 24h, 11.5 ± 7.6. Higher SUVmax was significantly associated with higher visual scores on dual-phase SPECT (4h, p < 0.001; 24h, p < 0.001) (4h: scores 3 and 4, p < 0.05; scores 3 and 5: p < 0.01; scores 4 and 5: p < 0.01; 24h: scores 3 and 4, p = 0.0748; scores 3 and 5: p < 0.01; scores 4 and 5: p < 0.01). We adapted the SUV to SRS and established the range of SUV for physiological uptake in the liver, kidney, and spleen. Combined visual and quantitative assessment is useful for imaging individual lesions in greater detail, and may serve as a new tumor marker of SRS for staging and restaging of NETs.

O-06 Efficacy of Lutetium-Peptide Receptor Radionuclide Therapy and osilodrostat treatment at achiving eucortisolism and tumour stabilization in a patient with metastatic ectopic ACTH-syndrome

Abstract Introduction Ectopic ACTH syndrome (EAS) is a rare cause of endogenous hypercortisolism. We present a case of a patient diagnosed with severe EAS, achieving eucortisolism and a favorable outcome of ACTH-producing metastatic pancreatic neuroendocrine tumor (NET) after 177Lu-DOTATATE and osilodrostat treatment. Clinical Case A female patient was admitted to our clinic at the age of 55 complaining of severe fatigue, facial and leg edema. Laboratory tests revealed a significant degree of ACTH-dependent hypercortisolemia (late-night serum cortisol 1856 nmol/L (64–327), late-night salivary cortisol (LNSC) 387.7 nmol/L (0.5–9.65), 24hUFC 8561 nmol/L (100–379), ACTH 332.8 pg/mL (7.2–63.3)), hypokalemia (1.88 mmol/L), increased liver enzymes (alanine aminotransferase (ALT) 303.2 U/L (0–55), aspartate aminotransferase (AST) 94.3 U/L (5–34)). MRI of the brain was negative for pituitary abnormalities. CT and somatostatin receptor scintigraphy with 99mTc-Tektrotyd revealed NET of the pancreas and multiple liver metastases. Subsequent biopsy confirmed NET grade 2, Ki67 – 7%. Treatment with lanreotide 120 mg every four weeks was initiated. In order to control hypercortisolism the patient received osilodrostat at a dose of 10 mg daily, which improved the patient's general condition in the first days of therapy. After 1 month of treatment, her hypercortisolism symptoms improved, LNSC dropped to 0.54 nmol/L and morning cortisol dropped from 1451 nmol/L (101–535) to 60.7 nmol/L, which could suggest adrenal insufficiency. She also had normalization of potassium and liver enzymes (ALT 18.4 U/L, AST 23 U/L). The dose of osilodrostat was firstly reduced and then discontinued. 177Lu-DOTATATE treatment was offered with four doses (7.4 GBq (200 mCi) every 8 weeks). The first dose was administered in January 2023. The SPECT-CT performed after the second dose demonstrated disease stabilization. At the time of writing, the patient remains in eucortisolism (LNSC 5,36 nmol/L, morning cortisol 140 nmol/L, ACTH 36.4 pg/ml) with tumor stabilisation after 4 doses of 177Lu-DOTATATE. However, the most recent routine blood test revealed thrombocytopenia (platelets 44×109/μl (150–400)), decreased white blood cell count (3.24×109/μl (4.5–11)), lymphocytes (0.71×109/μl (1.18–1.34)) and hemoglobin 98 g/L (117–160). Nevertheless, her general condition remains stable and significantly improved versus the initial investigation. Conclusion This observation highlights the feasibility and efficacy of a combined approach using osilodrostat and 177Lu-DOTATATE in the management of patients with metastatic ACTH-producing NET. This approach resulted in a substantially improved patient quality of life. Funding Russian Scientific Foundation 19-15-00398

Development of an individual display optimization system based on deep convolutional neural network transition learning for somatostatin receptor scintigraphy.

Somatostatin receptor scintigraphy (SRS) is an essential examination for the diagnosis of neuroendocrine tumors (NETs). This study developed a method to individually optimize the display of whole-body SRS images using a deep convolutional neural network (DCNN) reconstructed by transfer learning of a DCNN constructed using Gallium-67 (67Ga) images. The initial DCNN was constructed using U-Net to optimize the display of 67Ga images (493 cases/986 images), and a DCNN with transposed weight coefficients was reconstructed for the optimization of whole-body SRS images (133 cases/266 images). A DCNN was constructed for each observer using reference display conditions estimated in advance. Furthermore, to eliminate information loss in the original image, a grayscale linear process is performed based on the DCNN output image to obtain the final linearly corrected DCNN (LcDCNN) image. To verify the usefulness of the proposed method, an observer study using a paired-comparison method was conducted on the original, reference, and LcDCNN images of 15 cases with 30 images. The paired comparison method showed that in most cases (29/30), the LcDCNN images were significantly superior to the original images in terms of display conditions. When comparing the LcDCNN and reference images, the number of LcDCNN and reference images that were superior to each other in the display condition was 17 and 13, respectively, and in both cases, 6 of these images showed statistically significant differences. The optimized SRS images obtained using the proposed method, while reflecting the observer's preference, were superior to the conventional manually adjusted images.

Theranostics potential of somatostatin receptor scintigraphy in both small and non-small cell lung cancers: a preliminary study

Theranostics potential of somatostatin receptor scintigraphy in both small and non-small cell lung cancers: a preliminary study

Changes in tumor-to-blood ratio as a prognostic marker for progression-free survival and overall survival in neuroendocrine tumor patients undergoing PRRT

BackgroundHistorically, patient selection for peptide receptor radionuclide therapy (PRRT) has been performed by virtue of somatostatin receptor scintigraphy (SRS). In recent years, somatostatin receptor positron emission tomography (SSTR-PET) has gradually replaced SRS because of its improved diagnostic capacity, creating an unmet need for SSTR-PET-based selection criteria for PRRT. Tumor-to-blood ratio (TBR) measurements have shown high correlation with the net influx rate Ki, reflecting the tumor somatostatin receptor expression, to a higher degree than standardized uptake value (SUV) measurements. TBR may therefore predict treatment response to PRRT. In addition, changes in semiquantitative SSTR-PET parameters have been shown to predate morphological changes, making them a suitable metric for response assessment.MethodsThe institutional database of the Department of Nuclear Medicine (University Hospital Essen) was searched for NET patients undergoing ≥ 2 PRRT cycles with available baseline and follow-up SSTR-PET. Two blinded independent readers reported the occurrence of new lesions quantified tumor uptake of up to nine lesions per patient using SUV and TBR. The association between baseline TBR and changes in uptake/occurrence of new lesions with progression-free survival (PFS) and overall survival (OS) was tested by use of a Cox regression model and log-rank test.ResultsPatients with baseline TBR in the 1st quartile had a shorter PFS (14.4 months) than those in the 3rd (23.7 months; p = 0.03) and 4th (24.1 months; p = 0.02) quartile. Similarly, these patients had significantly shorter OS (32.5 months) than those with baseline TBR in the 2nd (41.8 months; p = 0.03), 3rd (69.2 months; p < 0.01), and 4th (42.7 months; p = 0.03) quartile. Baseline to follow-up increases in TBR were independently associated with shorter PFS when accounting for prognostic markers, e.g., RECIST response (hazard ratio = 2.91 [95%CI = 1.54–5.50]; p = 0.01). This was confirmed with regard to OS (hazard ratio = 1.64 [95%CI = 1.03–2.62]; p = 0.04). Changes in SUVmean were not associated with PFS or OS.ConclusionsBaseline TBR as well as changes in TBR were significantly associated with PFS and OS and may improve patient selection and morphological response assessment. Future trials need to assess the role of TBR for therapy monitoring also during PRRT and prospectively explore TBR as a predictive marker for patient selection.

SAT487 A Case of Mistaken Identity: A Rare Presentation of Ectopic Thyroid Tissue

Abstract Disclosure: N. Doshi: None. R. Azimzade: None. A. Rajpal: None. Background: Ectopic thyroid tissue (ETT) lateral to the midline is very rare, and its presence at the carotid bifurcation is exceedingly unique. Paraganglioma is the most common primary tumor at the carotid bifurcation, often called a carotid body tumor. We hereby present a case of lateral ETT with radiological features similar to paraganglioma. Case Description: A 72-year-old female with history of GERD was referred to us for evaluation of a well-circumscribed, slightly tender left neck mass. She has had the mass for approximately 15 years with previous evaluation with ultrasound in Yemen, where she was told to undergo surgery to remove it. She did not pursue surgery at that time. She moved to the U.S. one year ago and was re-evaluated for the neck mass. On examination, a firm mass was noted on the left side of the neck, followed by an ultrasound which demonstrated a 4.5 cm mass at the left carotid bifurcation and an enlarged right thyroid lobe of the same echogenicity with no tissue in the left thyroid bed. She had no clinical symptoms suggesting of hypo or hyperthyroidism. Laboratory examination showed suppressed TSH with elevated T3 suggesting thyrotoxicosis. CT neck was obtained for further characterization of the left neck mass which showed a hyper-enhancing, lobular soft tissue mass at the carotid bifurcation extending from the mandible to the level of the thyroid isthmus, concerning for carotid body paraganglioma or schwannoma. An I-123 scan demonstrated 24% (increased) uptake in the right thyroid lobe and minimal uptake in the carotid bifurcation tissue. The patient is currently being treated medically for thyrotoxicosis. Based on its ultrasonographic appearance, mild uptake on the I-123 scan, and no clinical suggestion of paraganglioma, the left neck mass is presumed to be ETT and no surgical intervention is being pursued. It is possible that the right lobe is thyrotoxic, suppressing iodine uptake in the ectopic tissue. Conclusion: This case demonstrates a unique presentation of ETT in the left carotid bifurcation with a thyrotoxic right lobe. It is difficult to distinguish the precise composition of neck masses at the carotid bifurcation, which has important implications for management. Often, an official diagnosis of thyroid tissue is made with histopathology only after the mass is surgically excised. Most ETT is benign in nature, and many times it is the only thyroid tissue available, thus surgery is not indicated. It is especially difficult to distinguish between ETT and paraganglioma on imaging itself. Somatostatin receptor scintigraphy, Ga-68/PET scanning, or iodine uptake scan can be useful to distinguish ETT from paraganglioma. Despite its rarity, lateral ETT must be included in the differential diagnosis of carotid body paraganglioma. Presentation Date: Saturday, June 17, 2023

THU016 Hiding In Plain Sight: Florid Cushing’s Disease Presenting As A Severe Extremity Cellulitis

Abstract Disclosure: C.M. Godar: None. E.B. Noble: None. N.O. Vietor: None. T.S. Knee: None. Background: Cushing’s syndrome may rarely present as an emergency known as Florid Cushing’s Syndrome. Patients can exhibit severe hyperglycemia, hypertension, hypokalemia, infections, and hypercoagulability. Cushing’s syndrome is a rare disease, and the constellation of clinical features can be overlooked if clinicians are not aware of the manifestations of hypercortisolism. We present the case of a patient with Cushing’s syndrome that went unrecognized with life-threatening sequelae. Case presentation: A 52-year-old woman with well-controlled type 2 diabetes and hypertension was admitted to the hospital for severe left lower extremity cellulitis. Prior to hospitalization she had noted rapid weight gain, fatigue, weakness, mental clouding, and moodiness. She was admitted for antibiotics and surgical debridement. The infection persisted despite broad spectrum antibiotics, multiple surgical debridements, and skin grafting. She became bacteremic, and extremity amputation was considered. She additionally developed hypertensive emergency, refractory hypokalemia, and hyperglycemia to 396 mg/dL. Exam was notable for facial plethora, supraclavicular fullness, dorsocervical fat pad, and violaceous abdominal striae. Cushing’s Syndrome was suspected, and labs revealed a significantly elevated random serum cortisol of 60.5mcg/dL (Ref 6.2-19.4), significantly elevated 24H urine cortisol of 2157mcg/24H (Ref 0-50), and ACTH elevated to 81.8pg/mL (Ref 7.2-63.3) that confirmed Cushing’s Disease. MRI sella and octreotide scans did not localize a lesion. Inpatient therapy included multiple antihypertensive agents, insulin drip, aggressive potassium repletion, and initiation of ketoconazole to reduce cortisol levels. Ketoconazole was maximally dosed and she underwent surgical exploration and removal of a small pituitary microadenoma. Following surgery, she developed transient adrenal insufficiency requiring hydrocortisone and she no longer required antihypertensives, insulin, or potassium therapy. Follow up 7 years later has revealed no recurrence of Cushing’s Disease. Discussion: Cushing’s Syndrome may present with a variety of clinical features and rarely may present as a medical emergency. Delay in diagnosis can lead to Florid Cushing’s Syndrome which carries high risk for morbidity and mortality. This case illustrates the need for clinician awareness of the features of Cushing’s Syndrome: hypertension, hyperglycemia, rapid weight gain, cushingoid exam features, hypokalemia, hirsutism, virilization, infection, and/or hypercoagulable state. Severe hypercortisolism was responsible for this patient’s refractory infection, and if not controlled, she likely would have endured a lower extremity amputation. Rapid detection with elevated random serum and/or urine cortisol and treatment with a cortisol-lowering agent is critical and lifesaving. Presentation: Thursday, June 15, 2023

THU537 A Case Of Aggressive NET With Extensive Bone Marrow Metastasis Presenting With Hypercalcemia

Abstract Disclosure: G. Kela: None. A.S. Gill: None. F. Kussaga: None. O. Olarinmoye: None. Introduction: A metastatic cancer that has no identifiable site of origin despite a thorough workup is termed cancer of unknown primary (CUP). Neuroendocrine tumors of unknown primary (NUP) are rare, making up less than 5% of all CUPs. This case demonstrates a rare presentation of a well-differentiated neuroendocrine tumor (NET) of an unclear primary site with extensive metastasis to the bone that initially presented with hypercalcemia of unclear cause. Case: We report a case of a 76-year-old-female with a history of depression and hypertension who was initially admitted for evaluation of hypercalcemia with a corrected calcium of 11.9, low normal PTH of 14.2, and PTHrP of 18, treated with zoledronic acid who presented again 3 months later with a 30lb weight loss for 2 months and bright red blood per rectum for one day. The patient had petechiae and flat dry purpura across her upper and lower extremities, lymphadenopathy, hepatosplenomegaly, and jaundice. Labs revealed a hemoglobin of 8.4g/dl (normocytic normochromic) and platelet count of 61,000/cm3, compared to 14.5g/dl and 269,000/cm3 respectively 4 months before admission. Colonoscopy and barium enema revealed internal hemorrhoids as the bleeding source. Laboratory workup for thrombocytopenia revealed no distinct etiology. Further workup with a right iliac bone marrow biopsy revealed a well-differentiated NET. The tumor cells expressed keratin 7, chromogranin, and synaptophysin, &amp; variably expressed INSM1. CT scan of the chest, abdomen, &amp; pelvis revealed a left thyroid nodule measuring 2.4 cm, suspicious for a NET on an octreotide scan. Biopsy of the left thyroid nodule, however, revealed follicular neoplasm which is not a NET. The patient was started on Lanreotide with no significant improvement. She remained severely anemic requiring multiple blood transfusions despite undergoing a hemorrhoidectomy. A repeat CT scan and MRI of the head done for increased confusion and disorganized speech 2 months later showed extensive metastatic disease involving the brain and skull. The patient could not tolerate further workup or cytotoxic chemotherapy and wished to proceed with hospice care. Discussion: NETs can arise from neuroendocrine cells located in any part of the body, most commonly in the gastrointestinal tract, lungs, or pancreas, and on extremely rare occasions from the bone. Conventionally, these tumors are indolent and accompanied by carcinoid symptoms. In this case, the bone biopsy was positive for tumor markers suggesting various primary sites including small bowel, stomach, and pancreas. However, despite extensive workup, the primary localization of the tumor was unsuccessful. The combination of the absence of a site of origin, the predominance of hematologic pathology (pancytopenia), and the highly invasive nature of this patient’s malignancy are suggestive of a well-differentiated NET with extensive metastasis into the bone. Presentation: Thursday, June 15, 2023

THU094 Multiple Endocrine Neoplasia Type 1 Tumor Recurrence After Loss To Follow Up

Abstract Disclosure: S.J. Sternlieb: None. K.G. Romo: None. R.S. Boothe: None. D. Englert: None. N. Manuel: None. Q.Z. Iqbal: None. Multiple Endocrine Neoplasia Type 1 Tumor Recurrence After Loss to Follow-up Sternlieb, S. J., Romo, K.G., Boothe, R., Manuel, N., Iqbal, Q.Z., Grissett, B., Englert, D. Background: MEN1 is a rare, autosomal dominant tumor disorder due to mutations in the MEN1 tumor suppressor gene. It is characterized by parathyroid, enteropancreatic and pituitary tumors. We present a young woman with MEN1 with prolactinoma, primary hyperparathyroidism and multiple pancreatic neuroendocrine tumors. Clinical Case: A 30-year-old woman with MEN1 presented with complaints of abdominal pain and GI bleeding (GIB). She was diagnosed with a prolactinoma at age 14 after presenting for primary amenorrhea and galactorrhea. She didn’t tolerate medical therapy with bromocriptine or cabergoline and required transphenoidal resection. At age 19, she presented with hypoglycemia and was found to have multiple pancreatic neuroendocrine tumors (NET) as well as a left (L) adrenal gland tumor. She underwent distal pancreatectomy and L adrenalectomy. Ten tumors in the pancreas stained variably for insulin, glucagon, gastrin and VIP. Multiple cortical adenomas were found in the adrenal gland. Post-operatively she developed a spinal cord hematoma related to placement of an epidural catheter for pain control, which led to permanent paraplegia. At age 21, she was diagnosed with primary hyperparathyroidism. She underwent left parathyroidectomy, then was lost to follow-up for 9 years. EGD showed multiple superficial duodenal ulcers. MRI brain identified a right (R) cavernous sinus mass inseparable from the R pituitary. CT abdomen showed a pancreatic head mass. Given the concern for neuroendocrine etiology, she underwent an EUS showing a pancreatic mass and a liver mass. Pancreatic mass pathology confirmed low-grade NET with Ki67 proliferation rate &amp;lt;1%, positive synaptophysin and chromogranin staining. After multidisciplinary discussion, the consensus was to continue PPI and sucralfate for GI ulcers, start lanreotide, and obtain somatostatin receptor scintigraphy. Surgery was not recommended unless significant GIB occurred on maximal therapy. She was referred to follow-up with GI, endocrinology, and NSGY. Since discharge, she has presented several times to other hospitals for abdominal pain, but has not adhered to follow-up. Conclusions: This case of recurrent neuroendocrine and pituitary tumors despite prior resections demonstrates the consequences of prolonged loss to follow-up with MEN1. Without routine surveillance, recurrence is likely. This patient lives in a rural area with lack of access to nearby subspecialty care, which is a barrier. More resources are needed to support patients with social barriers and progressive endocrinopathies. Key words: MEN1, prolactinoma, gastrinoma, NET, health care barriers Presentation: Thursday, June 15, 2023

Severe hypercalcemia due to metastatic pancreatic neuroendocrine tumor: a case report

BackgroundHypercalcemia of malignancy, as a paraneoplastic syndrome, is the most common metabolic disorder that accounts for 30% of malignancies and usually has a poor prognosis. Neuroendocrine tumors are uncommon and arise from neuroendocrine cells throughout the body. Actually, paraneoplastic hypercalcemia in neuroendocrine tumors is unusual and mostly associated with parathyroid hormone-related protein (PTHrP) secretion.Case presentationWe report a 51-year-old Iranian man who presented with nausea, vomiting, and significant weight loss for 1 month. Laboratory data revealed calcium of 26 mg/dl, accompanied by low level of PTH. Octreotide scan revealed a large donut-shaped octreotide avid lesion in the epigastric region at the right side of the mid-abdomen, with multiple varying size foci of abnormally increased radiotracer uptake in the epigastric region and both lobes of the liver. Endoscopic ultrasonography demonstrated a large heterogeneous mass lesion with irregular outline and good demarcation in the body of the pancreas with diffuse foci of calcification. Percutaneous biopsy of the liver mass demonstrated a well-differentiated neuroendocrine tumor (low grade) confirmed by immunohistochemistry with strongly positive chromogranin and synaptophysin stain. Hypercalcemia was treated with hydration, few sessions of hemodialysis, calcitonin, and denosumab injection. However, the patient developed symptomatic hypocalcemia. Oncology consultation led to prescription of long-acting octreotide 30 mg monthly and everolimus daily.ConclusionPancreatic neuroendocrine tumor could lead to malignant hypercalcemia; secretion of PTHrP is the most common cause, and signs and symptoms are usually milder than paraneoplastic syndrome due to hematologic and solid tumor. Generally, survival is better; however, its treatment is challenging, and primary debulking surgery is often required. A team approach to management is important at all points.

27 Neuroendocrine tumour of the breast: A case report &amp; Literature review

Abstract Introduction Neuroendocrine differentiation in breast carcinomas was first described by Feyrter and Hartmann in 1963, based on positive silver staining in mucinous carcinomas of the breast. NEBC are heterogeneous group of rare breast tumours which account for &amp;lt; 0.1 % of breast tumour and &amp;lt; 1% of neuroendocrine tumours. Case A 65-year-old female presented with a 12 x 10 cm non-tender hard globular slightly mobile mass in upper medial /inner quadrant of right breast with overlying 2 cm scar mark and bilateral axillary lymphadenopathy. Mammography revealed a BIRADS-4 lesion and FNAC showed atypical cells. Octreotide Scan showed that the mass was neuroendocrine in origin. Further CT imaging showed no other site for metastasis. She was managed with a Right sided modified radical mastectomy (MRM) after multidisciplinary team (MDT) decision. Biopsy of the Lesion showed ER, PR receptor &amp; synaptophysin receptor positivity, negative Her 2-neu status, ki-67 proliferation index of 10% &amp; grade II NET. Conclusion Primary neuroendocrine tumours of the breast are infrequent tumours that appear in women aged 60–70 years. Their diagnosis is complex as they lack defining clinical and radiological characteristics. Their low incidence makes it impossible to establish an optimal treatment protocol.

Diagnostic accuracy of 99mTc-HYNIC-TOC SPECT/CT for detecting osteomalacia-associated tumors.

Tumor-induced osteomalacia (TIO) is a rare acquired paraneoplastic disorder characterized by hypophosphatemia resulting from tumor-secreted fibroblast growth factor-23 (FGF23). Surgical resection of the culprit TIO is the first choice of treatment. However, TIO is difficult to detect with conventional diagnostic tools due to its small size and variable location in the body. Somatostatin receptor scintigraphy (SSR) has recently emerged as a functional molecular imaging choice for TIO detection and localization. This research was undertaken to evaluate the efficacy of 99mTc-labeled hydrazinonicotinyl-Tyr3-octreotide (99mTc-HYNIC-TOC) SPECT/CT in detecting TIO. 99mTc-HYNIC-TOC SPECT/CT and the available clinical data of 25 patients with suspected TIO were analyzed retrospectively. The 99mTc-HYNIC-TOC SPECT/CT findings were compared with the post-surgical pathology diagnosis and clinical follow-up results. Using 99mTc-HYNIC-TOC SPECT/CT, suspicious tumors were found in 18 of the 25 patients, and 15 of them underwent surgical resection. The post-operative pathology confirmed a TIO in those 13 patients whose symptoms and biochemical anomalies gradually resolved after the surgery. The remaining five patients were finally considered false positives. Moreover, the 99mTc-HYNIC-TOC SPECT/CT results were negative in seven patients, with six patients being true negative (4 patients were diagnosed with acquired Fanconi syndrome and 2 patients responded well to conservative therapy) and one being false negative. Therefore, the sensitivity and specificity values of 99mTc-HYNIC-TOC SPECT/CT in the evaluation of TIO were 92.9% (13/14) and 54.5% (6/11), respectively. The overall accuracy of 99mTc-HYNIC-TOC SPECT/CT for detecting TIO was 76.0% (19/25). The 99mTc-HYNIC-TOC SPECT/CT is an accurate imaging modality for locating culprit tumors in TIO.

Ectopic insulinoma: a systematic review.

Knowledge of ectopic insulinomas comes from single cases. We performed a systematic review through PubMed, Web of Science, Embase, eLibrary and ScienceDirect of all cases reported in the last four decades. We also describe one unreported patient. From 28 patients with ectopic insulinoma, 78.6% were female and mean age was 55.7 ± 19.2 years. Hypoglycaemia was the first symptom in 85.7% while 14.3% complained of abdominal pain or genital symptoms. Median tumour diameter was 27.5 [15-52.5] mm and it was localised by CT (73.1%), MRI (88.9%), [68Ga]Ga-DOTA-exedin-4 PET/CT (100%), 68Ga-labelled-DOTA-conjugated somatostatin analogue PET/TC (100%), somatostatin receptor scintigraphy (40%) and endoscopic ultrasound (50%). Ectopic insulinomas were located at duodenum (n = 3), jejunum (n = 2), and one respectively at stomach, liver, appendix, rectum, mesentery, ligament of Treitz, gastrosplenic ligament, hepatoduodenal ligament and splenic hilum. Seven insulinomas were affecting the female reproductive organs: ovary (n = 5), cervix (n = 2) and remaining tumours were at retroperitoneum (n = 3), kidney (n = 2), spleen (n = 1) and pelvis (n = 1). 89.3% underwent surgery (66.7% surgery vs. 33.3% laparoscopy) and 16% underwent an ineffective pancreatectomy. 85.7% had localized disease at diagnosis and 14.3% developed distant metastasis. Median follow-up time was 14.5 [4.5-35.5] months and mortality was reported in 28.6% with median time until death of 60 [5-144] months. In conclusion, ectopic insulinomas are presented as hypoglycaemia with female preponderance. Functional imaging [68Ga]Ga-DOTA-exedin-4 PET/CT and 68Ga-labelled-DOTA-conjugated somatostatin analogue PET/TC have very high sensitivity. Clinicians should be alert to the possibility of extra-pancreatic insulinomas when classic diagnostic tests and intraoperative pancreas exploration failed to locate the tumour.

Prognostic Implications of PET-Derived Tumor Volume and Uptake in Patients with Neuroendocrine Tumors.

Historically, molecular imaging of somatostatin receptor (SSTR) expression in patients with neuroendocrine tumors (NET) was performed using SSTR scintigraphy (SRS). Sustained advances in medical imaging have led to its gradual replacement with SSTR positron-emission tomography (SSTR-PET). The higher sensitivity in comparison to SRS on the one hand and conventional cross-sectional imaging, on the other hand, enables more accurate staging and allows for image quantification. In addition, in recent years, a growing body of evidence has assessed the prognostic implications of SSTR-PET-derived prognostic biomarkers for NET patients, with the aim of risk stratification, outcome prognostication, and prediction of response to peptide receptor radionuclide therapy. In this narrative review, we give an overview of studies examining the prognostic value of advanced SSTR-PET-derived (semi-)quantitative metrics like tumor volume, uptake, and composite metrics. Complementing this analysis, a discussion of the current trends, clinical implications, and future directions is provided.

Ectopic Cushing's syndrome from a corticotropin-releasing hormone-secreting medullary thyroid carcinoma: a rare pitfall of inferior petrosal sinus sampling.

This case report describes a rare presentation of ectopic Cushing's syndrome (CS) due to ectopic corticotropin-releasing hormone (CRH) production from a medullary thyroid carcinoma (MTC). The patient, a 69-year-old man, presented with symptoms of muscle weakness, facial plethora, and easy bruising. An inferior petrosal sinus sampling test (IPSS) demonstrated pituitary adrenocorticotrophic hormone (ACTH) secretion, but a whole-body somatostatin receptor scintigraphy (68Ga-DOTATOC PET/CT) revealed enhanced uptake in the right thyroid lobe which, in addition to a grossly elevated serum calcitonin level, was indicative of an MTC. A 18F-DOPA PET/CT scan supported the diagnosis, and histology confirmed the presence of MTC with perinodal growth and regional lymph node metastasis. On immunohistochemical analysis, the tumor cell stained positively for calcitonin and CRH but negatively for ACTH. Distinctly elevated plasma CRH levels were documented. The patient therefore underwent thyroidectomy and bilateral adrenalectomy. This case shows that CS caused by ectopic CRH secretion may masquerade as CS due to a false positive IPSS test. It also highlights the importance of considering rare causes of CS when diagnostic test results are ambiguous. Medullary thyroid carcinoma may secrete CRH and cause ectopic CS. Ectopic CRH secretion entails a rare pitfall of inferior petrosal sinus sampling yielding a false positive test. Plasma CRH measurements can be useful in selected cases.