ResearchPad - endocrine-neoplasia-case-reports-i Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[SUN-903 Insulinoma - a Tricker Diagnosis When Some Pieces Are Missing]]> Insulinoma is a rare pancreatic neuroendocrine tumour that secretes insulin, causing hypoglycemia. Because of the nonspecific symptoms, the diagnosis could constitute a challenge. Early detection is important to prevent serious consequences.

A 31-year old woman was admitted for prolonged fasting test. She had no relevant past medical or surgical history till eight months before, when she had an episode of generalized tonic-clonic seizure with loss of consciousness. At this time, she was taken to emergency, with identification of a hypoglycaemia of 33 mg/dL. Unfortunately this was undervalued and she was discharged with an appointment on a neurologist. After evaluation, she did an EEG, which was normal, and blood tests that identified a fasting glycemia of 50 mg/dL. By recommendation of her general practitioner, she began to monitor her glycemia during the day, identifying multiple glycemia <50mg/dL – in fasting and post-prandial period. After the first generalized seizure, she had multiple seizures, always associated with hypoglycaemia. During the night she had to wake up every two hours to eat, in order to prevent hypoglycaemia. Moreover, in the last 6 months, she augmented 12 Kg. She also described two episodes of behavioural changes with confusion and speech alteration.

She wasn’t under any medication that could be associated with hypoglycemias. Previous records showed she had a fasting glycemia of 50 mg/dL two years ago. When she was admitted to our department, besides she had eat one hour before, she had glycemia <55 mg/dL. Blood tests showed glucose level=22 mg/dL, insulin=39 μU/mL (normal range 2.6-24.9 μU/mL), C-Pep=0.90 ng/mL (normal range 1.1-4-4 ng/mL). Plasma B-hydroxybutyrate was negative. After Glucagon EV, glucose level increase to 53 mg/dL (>25 mg/dL). We also evaluated cortisol and growth hormone that were normal. Abdominal computed tomography scan with contrast demonstrated a well-defined hypervascular lesion involving pancreas tail. Abdominal MRI was also performed showing a hypervascular lesion involving pancreas tail with 11x21mm. Laparoscopic surgery to enucleate the lesion was made. Pathological evaluation revealed a well-differentiated neuroendocrine tumour (positive staining for synaptophysin, cromogranin and insulin) measuring 0.3 cm. The diagnosis of pancreatic insulinoma was confirmed. After surgery, the glucose level increased to the normal range. The patient is currently in 6 months follow-up with a good evolution.

The diagnosis of insulinoma requires high suspicion. In this case, the patient didn’t have the typical insidious neurogenic symptoms. There is a need to value neuroglycopenic symptoms associated with hypoglycemia, otherwise serious consequences can occur.

<![CDATA[SUN-917 Aggressive De Novo MEN1 Variant in a Child with Metastatic Pancreatic Acth and Crh Co-Secreting Neuroendocrine Tumor: Diagnosis and 10-Year Follow Up]]> Background:

In Multiple Endocrine Neoplasia type 1 (MEN1) only about 2% of pituitary adenomas are ACTH-secreting. Cushing Syndrome due to ectopic ACTH or CRH secretion from neuroendocrine tumors (NETs), carcinoid tumors, or pheochromocytomas is very rare, though patients with MEN1 are at increased risk for these three types of tumors, as well as autonomous adrenal secretion of cortisol. The 10-year follow up of a previously-reported case of a child with MEN1 and metastatic pancreatic ACTH/CRH-secreting NET is presented.

Clinical Case:

A previously-reported (J Clin Endocrinol Metab, 2015) now 21 yo female presented to the National Institutes of Health (NIH) at 11 yo with persistent hypercortisolemia despite transsphenoidal surgery for suspected Cushing Disease. However, the resected tissue revealed pituitary hyperplasia, and she remained hypercortisolemic. A CRH test was consistent with an ectopic source, and abdominal CT, PET scan, and Octreotide scan revealed a mass in the pancreatic tail. The patient underwent partial pancreatectomy at 11 yo with the resected tissue staining positive for ACTH and CRH. However, she remained hypercortisolemic, so bilateral adrenalectomy was performed. At 12 yo metastases were found, so Octreotide therapy was initiated. She continued to have elevated ACTH levels > 1000 pg/mL (5-46).

Additionally, a pituitary adenoma was noted at 12 yo, which has since increased in size. The patient also developed mild primary hyperparathyroidism, first noted at 19 yo. Sequencing of MEN1 for the patient and her parents revealed a de novo heterozygous c.1546dupC variant, consistent with sporadic MEN1. The patient also had a chromosome 8p23.2 duplication that was present in unaffected relatives.


While 2% of patients with MEN1 may develop Cushing Syndrome due to an ACTH-secreting pituitary adenoma, it is also important to consider ectopic secretion of ACTH/CRH from MEN1-associated NETs, carcinoid tumors, or pheochromocytomas, as well as autonomous adrenal secretion of cortisol. Given the early age and severe presentation of MEN1 features in this patient, the c.1546dupC heterozygous variant of MEN1, which has been previously reported in multiple other cases of MEN1, may represent a higher-risk causative variant of MEN1. Alternatively, expression of this variant may have been affected by the concurrent presence of an otherwise apparently benign chromosomal variant.


A. Karageorgiadis, G. Papadakis, J. Biro, M. Keil, C. Lyssikatos, M. Quezado, M. Merino, D. Schrump, E. Kebebew, N. Patronas, M. Hunter, M. Alwazeer, L. Karaviti, A. Balazs, M. Lodish, and C. Stratakis. Ectopic Adrenocorticotropic Hormone and Corticotropin-Releasing Hormone Co-Secreting Tumors in Children and Adolescents Causing Cushing Syndrome: A Diagnostic Dilemma and How to Solve It. Clin Endocrinol Metab, January 2015, 100(1):141–148

<![CDATA[SUN-905 A Case of Adrenal Cushings a Primary Hyperparathyroidism]]> We present the case of a 31 year old female referred with weight gain, secondary amenorrhea, facial plethora and buffalo hump x6-9/12. Background medical history of caesarean section. She was on no regular medications. She rarely consumed alcohol. There was no relevant family history.

She experienced secondary amenorrhea x6/12. Her menarche was at the age of 14 and had regular periods thereafter. She had gained 13kg over the previous 9/12. Examination revealed an intrascapular fat pad, abdominal striae and facial plethora. Her BP was 150/87.

Initial investigations were as follows: Overnight DST: Cortisol 642 nmol/L, DHEAS <0.4 µmol/L, hCG <1 U/L, TSH 0.71 mIU/L, FT4 15.1 pmol/L, Prolactin 380 mIU/L, IGF-I 152 µg/L, FSH 4.4 IU/L, LH 3.0 IU/L, oestradiol <100 pmol/L, 17-OH Progesterone <1.0 nmol/L. She then underwent a low dose 48 hour dexamethasone suppression test the results showed: Cortisol Day 1(time 0) 704 nmol/L, Day 2 (time 24 hours) 702nmol/L, Day 3 (time 48 hours) 703 nmol/L and paired ACTH 1.4ng/L.

She was admitted from clinic with BP 189/107 and was started on metyrapone and ramipril. On this admission her bloods showed calcium 2.70 mmol/L, iPTH 113.5 ng/L, 25 (OH) D27nmol/L. Ct abdomen and pelvis revealed a 3.3x2.2 cm right adrenal lesion with hounsfeld units <10 and unremarkable left adrenal. ARR, plasma metanephrines and HbA1c were all normal. The case was discussed at MDM and referred for retroperitoneal laprascopic right adrenalectomy. She was discharged day 2 post op off anti hypertensives and on hydrocortisone 10mg/5mg/5mg. Histology confirmed adrenocortical adenoma and Ki67 <5%.

Synacthen test done one month post operatively showed time 0 cortisol 35 nmol/L, time 30 cortisol 56 nmol/L, time 60 cortisol 60 nmol/L and time 0 ACTH 51 ng/L. Post operatively her menses returned.

When vitamin D replete, we re-evaluated her hypercalcemia. This revealed 2.77 mmol/L, iPTH 100.7ng/L, calcium: creatinine ratio 0.72 mmol/mol. She had an ultrasound neck and sestamibi which both lateralised to right lower lobe of thyroid. A synacthen test was repeated which revealed time 0 cortisol 183 nmol/L and ACTH 44 ng/L, time 30 cortisol 258 nmol/L and time 60 cortisol 302 nmol/L. She was referred for 4 gland exploration with intra operative PTH. Her baseline intra operative PTH was 193 ng/L and her 10 minute post excision value was 55 ng/L which demonstrates a 65% drop in concentration and intra operative PTH returned to within the reference interval.

The histology was atypical displaying extension of the tumour through the capsule and possible vascular extension. Ki 67 was <2%. It has been sent to St. Guy’s and Thomas’ for a second opinion. Her calcium and iPTH returned to normal post operatively. MEN1 and CDKN1B genes were negative. We’re awaiting gene sequencing on the following - RET, CDC73, CASR, CDKNIA, CDKN2C AND CDKN2B. This case represents a case of multiple endocrinopathies with no found genetic link.

<![CDATA[SUN-938 Rare Case of Ectopic Cushing Syndrome Caused by ACTH Secreting Thymic Neuroendocrine Tumor in a Patient with Multiple Endocrine Neoplasia Type 1]]> Introduction

Cushing syndrome (CS) represents an uncommon manifestation of MEN1 and can be caused by both ACTH dependent or independent etiologies. Among them, ectopic ACTH secretion from a Thymic neuroendocrine tumor (TNET) in MEN1 is rare, with very few cases reported so far in literature. We report a case of Ectopic Cushing syndrome (ECS) in a MEN1 patient (pt) with multiple tumors, secondary to ACTH-secreting TNET.

Case description:

A 44 year old male presented to our institution for nausea, vomiting, dizziness. He had initial workup which revealed multiple tumors (papillary thyroid cancer, thymic mass, parathyroid adenomas, bilateral adrenal nodules, macroprolactinoma, peripancreatic nodules). Given concern for MEN 1, genetic testing was performed which was confirmative. Hormonal workup at this time for adrenal nodules was negative including low dose dexamethasone suppression test(DST). The immobile thymic mass was found to be poorly differentiated NET on biopsy with Ki-67 >50% with vascular invasion and adhesions to lung/chest wall on VATS, not amenable to surgery. The pt declined chemotherapy and radiotherapy due to poor social support. Six months later, he presented with complaints of shortness of breath, proximal muscle weakness, anasarca. Evaluation revealed AM cortisol >60 ug/dL(range 6.7-22), high-dose DST Cortisol >60 ug/dL, 24hr urine free cortisol: 8511mcg (range 4-50) and ACTH level: 278pg/mL(range 6-50) confirming ACTH-dependent CS. Special stains from the previous TNET biopsy demonstrated positive staining for ACTH confirming ectopic ACTH secretion. Ketoconazole and chemotherapy with Etoposide and Carboplatin was started, however he clinically deteriorated and expired a few weeks after diagnosed of ECS.


TNET in MEN 1 is rare, with a prevalence of 3-8%. TNET are unusual neoplasms that account for 2% to 7% of all mediastinal tumors. TNET in MEN1 rarely secrete functional hormones with very few reported Ectopic ACTH secretion. MEN1 associated ECS from TNET is an aggressive disease with local invasion of adjacent mediastinal structures or metastasis being common, resulting in poor prognosis as demonstrated in few case reports including our case. Radical surgery of involved adjacent structures and adjuvant local RT can provide local disease control.


Our pt is a rare case of ECS from TNET in MEN1 with poor prognosis. A special feature of this case is that the patient had initial negative evaluation for hypercortisolemia, however 6 months later he presented with signs and symptoms of severe hypercortisolism, with evaluation confirming transformation into ACTH producing TNET. This conversion is very rarely found in literature and adds to the unique presentation of the case.

<![CDATA[SUN-925 Carcinoid: A Crisis in the Upside Down]]> Unrecognized carcinoid tumors can rarely present as a life-threatening condition known as carcinoid ‘crisis’ which typically presents as significant but transient hypotension if there is no appropriate preventive treatment. Somatostatin analogs such as Octreotide are agents of choice to avoid such crises. However, there is minimal literature and a lack of guidelines regarding the management of an active, labile carcinoid crisis in patients exhibiting both hypotension and hypertension, as will be presented here.

Case: A 76-year-old female with end-stage renal disease, status post kidney transplant on immunosuppressants, who was initially admitted for workup of hematuria. Abdominal CT revealed a bladder mass with various features concerning for malignancy and an incidental mesenteric mass, followed by bladder biopsy suggestive of neoplasm. The patient was taken to the OR where she first underwent resection of the bladder mass with subsequent proceeding to the removal of the mesenteric mass. Within minutes of manipulation of the mass, the patient became significantly hypotensive with a mild response to fluid resuscitation, requiring vasopressors. A frozen section suggested the possibility of a neuroendocrine tumor. Given concerns of carcinoid crisis the patient was started on Octreotide infusion achieving some degree of hemodynamic stabilization but soon developed extremely labile blood pressure with rapidly alternating hypotension (SBP <60mmHg) and hypertension (SBP >200mmgHg). During hypotensive episodes, the aid of adjunctive beta-adrenergic agents was required, while the doses for the Octreotide infusion were as high as 200mcg/hr. Initial Endocrinologic workup revealed a Chromogranin A level 1,178 ng/mL (25 - 140 ng/mL), VIP <50 pg/mL (<75 pg/mL), 24 hr 5HIAA 23.5 (<=6.0 mg/24 h), Serotonin 2,334 ng/mL (56 - 244 ng/mL) consistent with carcinoid. Repeat Serotonin levels 5 days after octreotide infusion was 674 ng/mL. The patient was successfully weaned from vasopressors but required continuation of Octreotide for additional 5 days due to intermittent episodes of hypotension.

Carcinoid crisis is a life-threatening condition associated with hypotension, and less commonly hypertension, from the release of vasoactive agents from tumor manipulation. Preparation with Octreotide before any manipulation or anesthesia is recommended to avoid a carcinoid crisis. However, if a crisis develops management is mainly with a continuous Octreotide infusion. The use of beta-adrenergic agents is debated, due to a possible “paradoxical effect” which could further worsen hypotension. Others argue that there is a role in preventing prolonged episodes of hypotension. In this case, it was required high doses and the infusion was needed for 5 days, probably related to the presence of ESRD which could have prolonged the bioavailability of the vasoactive agents.

<![CDATA[SUN-935 Invasive Neuroendocrine Breast Carcinoma Presenting as Liver Metastases]]> Introduction:

Primary neuroendocrine carcinoma of the breast is rare and must be differentiated from metastatic neuroendocrine carcinoma from the gastrointestinal tract.

Clinical Case:

A 66-year-old white female presented to the outpatient clinic complaining of abdominal fullness with unintentional weight loss of over 30 pounds over 3 months. She had no nausea, vomiting, diarrhea, or constipation. During initial evaluation, she had hepatomegaly with the liver edge palpable 4 cm below the costal margin. Laboratory studies are within normal limits except for elevated alkaline phosphatase at 369 U/L (n<130 U/L).

A CT scan of the abdomen and pelvis with contrast showed extensive malignant lesions involving the liver consistent with prior hepatocellular carcinoma versus metastatic disease. Patient had a colonoscopy and esophagogastroduodenoscopy in an attempt to identify a primary gastrointestinal malignancy, but both studies were unremarkable. Ultrasound guided biopsy of the liver masses revealed malignant cells with morphologic features that were suggestive of metastatic neuroendocrine carcinoma.

The patient was started on monthly intramuscular octreotide 30 mg. She had a Gallium-68 dotatate scan showing increased uptake in the area of several large heterogeneous necrotic tumors throughout the liver, and in the left sixth posterolateral rib. The maximum uptake was noted in a 3.7 cm x 3.5 cm ovoid mass in the right breast. The patient admitted to noticing a mass in her right breast which decreased in size after her initial dose of octreotide. She had not had a mammogram in several years and refused a breast exam during initial evaluation. The patient was sent for mammography and ultrasound as well as for biopsy of the breast lesion.

Results of the breast biopsy showed intermediate grade neuroendocrine tumor of the breast. The patient underwent right total mastectomy with lymph node staging, and intraoperative pathology identified neuroendocrine carcinoma of intermediate grade in the right breast and right axillary lymph nodes, and macrometastatic carcinoma in a right axillary tail lymph node. Immunohistochemistry showed the malignant cells were chromogranin and synaptophysin positive. They were also estrogen receptor positive. The cells were negative for progesterone receptor and human epidermal growth factor receptor 2.

The patient follows up regularly with oncology and continues to receive monthly doses of octreotide. She was also started on exemestane and had Yittrium-90 radioembolization of liver metastases.


Patients with neuroendocrine carcinoma of the breast rarely present with clinical conditions related to hormonal hypersecretion as in neuroendocrine carcinoma of the GI tract but respond to treatment with somatostatin analogs.

<![CDATA[SUN-932 Successful Response of Temozolomide (TMZ) in two Patients with Metastatic Pheochromocytoma/Paragangliomas (PPGLs)]]> Introduction: PPGLs are rare neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla or their neural crest progenitors, being able to secrete catecholamines. Its treatment is primarily surgical; however, for metastatic/inoperable tumors, effective treatments are lacking. The use of TMZ, an oral alkylating agent, has been scarcely reported with variable response rates. We report 2 patients with reasonable clinical, biochemical and structural responses.

Case Reports: Case 1) A 14-year old girl presented with neck pain, sweating, hypertension and tachycardia. Urinary hormonal profile revealed metanephrines 80 (up to 320 ug/24h) and normetanephrines 2983 (up to 390 ug/24h). Abdominal MRI showed a 10x6x5 cm retroperitoneal lesion in close contact with celiac trunk, superior mesenteric artery, renal arteries, aorta, left renal vein and vertebral bodies of T10, T11 and T12. A chest CT revealed multiple lung metastases. After 11 months, both the primary abdominal lesion and lung metastases increased in size.. Due to disease severity, after excluding surgical possibilities and confirming diagnosis by lesion biopsy, rescue treatment with TMZ was started for 5 days on a 28-day cycle. After 11 cycles, lung and abdominal lesions decreased more than 30% in size, and urinary metanephrines decreased 53.4%. After 21 cycles, there is no evidence of disease progression.

Case 2) A 44-year old female was first diagnosed at the age of 31 with a right adrenal mass invading the kidney and the inferior vena cava associated with hypertension, sweating, headaches and palpitations. She underwent right adrenalectomy and nephrectomy. Immunohistochemistry confirmed the diagnosis of pheochromocytoma. Seven years later, follow-up CT`s showed a 3 x 2 cm liver metastasis, which was resected, and two lung lesions, one located at the right inferior lobe (1.6 cm) and the other at the left superior lobe (0.9 cm), which initially were just followed-up. At this time, a 7-month sorafenib trial was performed but the drug was stopped due to intolerable side effects. After 3 years of follow-up, the lung lesions increased in size and the right lesion was resected, but the patient refused surgery for the remainder left lung lesion. After 1 year, left lung lesion increased to 2.4 cm and mediastinal and paratracheal lymphadenomegaly developed. TMZ in the same aforementioned schedule was prescribed and after 7 cycles a new chest CT revealed complete regression of the lung and lymph node metastases.. Urinary metanephrines were 2.1 times the upper limit of normal before TMZ and decreased to normal range.

Conclusion: These cases highlight the promising role of a well-tolerated single drug chemotherapy regimen in severe cases of metastatic and inoperable PPGLs. TMZ could be considered an alternative strategy for the treatment of these cases and, if possible, should be tested in adequate clinical trials.

<![CDATA[SUN-920 Familial Paraganglioma Syndrome: A Rare Case of Secondary Hypertension in Young People]]> Paragangliomas are rare tumors originating in the autonomic nervous system, whose clinical manifestations are the result of excessive production of catecholamines.

We present a case of a 26-year-old female with 5 years of disease characterized by episodic profuse sweating, headaches and high blood pressure refractory to antihypertensive treatment. She also had intermittent palpitations which intensified 1 month before admission. Patient was cataloged with diagnosis of endocrine hypertension. She had elevated urinary fractionated metanephrines, elevated plasma normethanephrin and plasma chromogranin A (CgA). Subsequently, an abdominal CT study was performed, finding a solid ovarian mass of defined edges located in retroperitoneal space, an intercave region immediately preceding the L2-L3 intervertebral disc that measured 26.2 x 23.9 x 28.8 mm. It was also found bilateral tumours at cervical level of 14 mm in right side and 10 mm in left side, suggestive of paranganglioma by magnetic resonance imaging (MRI).

With a suspected diagnosis of paraganglioma of Zuckerkandl’s organ, beta and alpha-adrenergic blockage were carried out and surgical intervention was done by a block resection of the tumour. Anatomopathological diagnosis confirmed the suspicion of well-delimited capsulated paraganglioma of 2.0 X 1.0 X 0.3 cm, with low mitotic index (<2) and a result of positive sinaptophisin by immunohistochemistry. She reached complete remission and normal determinations in urine of catecholamines and methanephrines. Currently the patient is in follow-up with favorable evolution and succinate dehydrogenase type B (SDHB) gene test is pending.

Despite infrequency of paragangliomas, it is important to take them into account in the differential diagnosis of hypertension, especially in young patients, due to their malignant potential and the effects of catecholamine secretion on the cardiovascular system.

<![CDATA[SUN-940 Carney Complex: A Case of a Rare Multiple Endocrine Neoplasia Misdiagnosed as Peutz-Jeghers Syndrome]]> Carney Complex (CNC) is an extremely rare multiple endocrine neoplasia caused by germline inactivating mutation in protein kinase A type I-alpha regulatory subunit (PRKAR1A gene). Mode of inheritance is mostly autosomal dominant; 25% of cases are due to de novo mutations. Only 750 world-wide cases have been reported. Most patients are diagnosed in the second or third decade. Clinical features include cutaneous myxomas, angiomyxoid nodules, lentiginous skin pigmentation, cardiac myxomas, and benign and rare malignant endocrine tumors. These endocrine tumors include and are not limited to prolactinomas, thyroid tumors, primary pigmented nodular adrenocortical disease (PPNAD), and large cell-calcifying Sertoli cell tumors (LCCSCT). Diagnosis is often challenging as disease manifestations can occur sporadically over a large span of time, and patients may present with various conditions such as Cushing syndrome, like our case. We present a case that demonstrates the importance of early recognition of this rare disorder.

A 28-year-old Caucasian male with PMH of HFrEF, HTN, Sertoli cell tumor status post orchiectomy, vertebral fractures, and surgical removal of lip angiomyxoma presented to clinic for hypogonadism. Physical examination revealed marked Cushingoid features and facial lentigines above his eyes and on his lips. His eclectic medical history and unique exam findings lead to finding of a unifying diagnosis. His labs revealed severe Cushing syndrome, and computed tomography (CT) of his abdomen was performed due to ACTH independent hypercortisolism, demonstrating a bilateral lobular appearance of the adrenal glands.

Combination of labs and physical exam findings of lentigines, skin myxomas, cushingoid features, rare angiomyxoma, LCCSCT and hypercortisolism lead to diagnosis of Carney Complex. He was misdiagnosed with Peutz-Jeghers in his adolescence due to LCCSCT and mucosal lentigines; therefore, hormonal screening was not routinely performed. Untreated Cushings led to severe osteoporosis with vertebral fractures and heart failure. Treatment included bilateral adrenalectomy. Pathology report confirmed rare PPNAD. PPNAD and LCCSCT are extremely rare tumors almost exclusively linked to Carney Complex. Interestingly, family history did not reveal endocrine disorders, cancers, or severe illnesses. Genetic testing returned positive for the PRKAR1A gene mutation. Given the consequences of untreated hormonal aberrations seen in this disorder, an early and accurate diagnosis is imperative.

<![CDATA[SUN-901 A Case of Coexisting Insulinoma and Islet Cell Hyperplasia]]> Introduction

Insulinoma is the most common neuroendocrine tumour of the pancreas and cause of endogenous hyperinsulinemia hypoglycaemia. Islet cell hyperplasia is a rare cause of hypoglycaemia in adults.

Clinical Case

A 42-year-old lady presented with hyperphagia, giddiness, decreased concentration and weight gain of 10 kg over one year. Her symptoms occurred both during fasting and postprandial. She did not have any medical conditions and did not take alcohol.

A 72-hour fast confirmed the presence of endogenous hyperinsulinemia; serum glucose of 2.4 mmol/L paired with insulin 8.14 mU/L and C -peptide 0.71 nmol/L occurring after 16 hours of fasting. Screening for sulphonylureas and meglitinides was negative. Serum beta-hydroxybutyrate was 0.1 mmol/L with a 1.6 mmol/L rise in serum glucose post 1 mg glucagon administration. Computed tomography (CT) of the abdomen showed a 13 X 11 X 15 mm exophytic lesion at the superior aspect of the pancreatic body and another exophytic projection measuring 9 X 8 X 6 mm arising from the tail. In view of possible multifocal insulinoma, a 68Ga-DOTATATE scan was performed and it showed an intensely DOTATATE-avid exophytic nodule arising from the pancreatic body and a second indeterminate DOTATATE-avid nodule close to the pancreatic tail. In addition, there was diffuse DOTATATE uptake in the tail of pancreas.

She underwent enucleation of pancreatic body nodule and spleen-saving distal pancreatectomy as the pancreatic tail nodule was not seen intra-operatively. Histology showed an insulinoma; a well-differentiated neuroendocrine tumour (Grade 1, pT1 N0 Mx) that was positively stained for synaptophysin, CD56, insulin, SSTR2 and SSTR5. The pancreatic tail nodule and distal pancreatectomy specimen showed islet cell hyperplasia; the pancreatic parenchyma showed multiple foci of well-circumscribed nests of bland islet cells with similar morphology to those seen in the insulinoma. She did not have further hypoglycaemia episodes post-operatively.

Concomitant presence of fasting and postprandial hypoglycaemia may suggest underlying dual pathology. Clinical and biochemical differentiation between insulinoma and islet cell hyperplasia is difficult. Therefore, imaging for diagnosis and precise preoperative localisation is important for successful resection of suspected lesions. 68Ga-DOTATATE scan can be as useful as 68Ga-DOTANOC and 68Ga-DOTATOC scan and is better than CT scan in localising not only insulinoma but also islet cell hyperplasia. In this case, islet cell hyperplasia-induced hyperinsulinemic hypoglycaemia may have persisted if distal pancreatectomy was not performed.


Adult-onset endogenous hyperinsulinemia hypoglycaemia can be caused by concurrent insulinoma and islet cell hyperplasia. 68Ga-DOTATATE scan may be a useful, non-invasive investigation, especially in cases where CT imaging suggests multifocal disease.

<![CDATA[SUN-919 Ectopic ACTH Syndrome: An Aggressive Presentation Due to Metastatic Liver Cancer of Unknown Primary]]> Background: Ectopic Cushing’s Syndrome is a rare but often aggressive condition caused by ACTH-hypersecretion from non-pituitary tumors. In patients with metastatic cancer, as well as those with occult tumors, the diagnosis and management can be extremely challenging. Clinical Case: A 25-year old woman recently diagnosed with poorly differentiated metastatic liver carcinoma of unknown primary was admitted for lower extremity edema and worsening fatigue for the preceding month. Since being diagnosed with liver cancer, she developed uncontrolled hypertension, persistent severe hypokalemia and facial “puffiness”. Physical exam was remarkable for moon facies and truncal obesity but no evidence of striae. An overnight 1-mg dexamethasone suppression test resulted in an elevated morning cortisol level of 93.4 mcg/dL and elevated ACTH of 299 pg/mL. A 24-hour urine cortisol was significantly elevated at 4,448 mcg/24 hours. These findings were consistent with hypercortisolism due to hypersecretion of ACTH. An MRI of the sella revealed no pituitary abnormality. A high-dose dexamethasone suppresion test (single 8 mg dose) was performed and her morning cortisol level remained elevated at 98.6 mcg/dL, consistent with ectopic ACTH secretion. She was treated for the underlying malignancy with carboplatin and paclitaxel. After a thorough discussion of therapeutic options, she was prescribed Ketoconazole with the plan to medically control the hypercortisolism potentially followed by bilateral adrenalectomy. Ketoconazole was up-titrated and Spironolactone was added resulting in significant improvement of hypokalemia and hypertension. Unfortunately, one week after discharge she was re-admitted due to worsening performance status, watery diarrhea and abdominal pain. A serum cortisol level was elevated at 124 mcg/dL and Metyrapone was added to her regimen. Unfortunately, her performance status continued to decline due to progression of cancer and uncontrolled hypercortisolism. As a result, she was deemed a poor surgical candidate for bilateral adrenalectomy. The patient’s condition rapidly deteriorated and she developed malignant ascites as well as altered mental status. In accordance with her wishes, a DNR order was placed and she passed away shortly thereafter. Conclusion: Ectopic ACTH-syndrome is the etiology of 10–20% of cases of Cushing’s syndrome. Clinical presentation is often sudden and rapidly progressive. Severe hypertension and hypokalemia are seen more commonly than in Cushing’s disease. Cases secondary to occult tumors or metastatic cancer can be particularly challenging to treat when it is not possible to eliminate the source of ACTH hypersecretion via surgical or medical treatment. In patients such as this, early bilateral adrenalectomy should be considered after starting medical therapy in order to reduce morbidity and mortality due to hypercortisolism.

<![CDATA[SUN-931 Characterization of an Ovarian Steroid Cell Tumor in a VHL Patient]]> Most ovarian steroid cell tumors arise sporadically. However, they can also be observed as a rare manifestation of von Hippel Lindau disease. Here, we present a clinical, pathological and molecular characterization of a steroid cell tumor in a VHL patient. A 14 year old girl with molecularly confirmed diagnosis of VHL developed hirsutism and amenorrhea. Initial clinical hormonal evaluation was notable for elevated 17-OHP of 406ng/dl, androstenedione 275ng/dl, and testosterone 102ng/dl. In order to exclude congenital adrenal hyperplasia as a common cause of hirsutism in adolescents, ACTH stimulation was performed, but no increase in 17-OHP was observed. Anti Muellerian hormone, inhibin (INH) A and INH B were normal. Imaging revealed a bilobed 6cm left adnexal mass. The mass was resected en bloc via a left oophorectomy. Pathological evaluation showed multinodular steroid cell tumor with clear cytoplasm and delicate vascular meshwork. Immunoprofiling demonstrated positivity for inhibin and calretinin; while renal cell carcinoma markers were negative. All laboratory values normalized post-surgery. In addition to clinical measurements pre- and post-surgery, steroid profiles were evaluated by LC-MS/MS. Quantitative RT-PCR analysis showed robust tumor expression of enzymes facilitating the production of androgens, but not estrogens. Further preliminary analysis by exome sequencing confirmed the known germline pathogenic variant in VHL, but no additional obvious somatic driver mutations were identified. Interestingly, the NGS analysis of different specimens from the same tumor revealed multiple different single base pair variants in the VHL gene as a second hit. In summary, hirsutism in VHL patients should raise the suspicion for unusual ovarian tumors. In contrary to the usual theory of a monoclonal expansion after loss of the wt VHL allele, this tumor appeared to be oligoclonal as evidenced by different somatic VHL mutations. This could be either explained by initial parallel occurrence of several clones or that the VHL second hit is not an initial event, but the mutation instead supports tumor expansion following initial steps of tumorigenesis.

<![CDATA[SUN-913 A MEN-2a Syndrome Index Case Presenting with Adrenergic Crisis and Cardiogenic Shock Due to Bilateral Pheochromocytoma]]> Background: MEN-2A syndrome is commonly asymptomatic at diagnosis. Withal, pheochromocytoma presenting as cardiogenic shock is a recognized but exceptional occurrence. Case: A healthy 26-year-old female presented to the emergency department with precordial discomfort, headache and shortness of breath, starting that morning. She had a gum corrective surgery in the day before, was medicated with ibuprofen, pantoprazole and amoxicillin/clavulanic acid, and had previous history of migraine and smoking. Her blood pressure was high, and she had pulmonary edema and respiratory failure. ECG: sinus tachycardia, left axis deviation, and negative T wave in aVL. Analytically: leukocytosis, elevated myocardial necrosis markers (troponin I 1.29 ng/mL, normal < 0 ng/mL), and hyperlactacidemia. Transthoracic echocardiogram: severe left ventricular dysfunction, akinesia of the basal mid segments of all walls; image of thickening immediately above the aortic valvular plane. CT angiography: bilateral adrenal masses (9.2x9.2x10.8 cm on the right; 2.3x2.8x3.3 cm on the left), suggestive of pheochromocytoma. Cardiogenic shock led to patient transfer to our hospital for ECMO, in which she was maintained for 14 days. Pheochromocytoma was confirmed (normetanephrine 15689 µg/24h [normal < 390 µg/24h], metanephrine 15000 [normal < 320 µg/24h]) and adrenergic blockade initiated. Hospitalization complications and surgical risk delayed bilateral adrenalectomy to 1 month after admission. She initiated glucocorticoid and mineralocorticoid replacement, was transferred to the ward stable, and started a rehabilitation program before hospital discharge. Phosphocalcic metabolism was normal (PTH 38.7 pg/mL, normal 10–65 pg/mL). High calcitonin levels (87 pg/mL, normal <5 pg/mL) lead to the diagnosis of medullary thyroid carcinoma, followed by total thyroidectomy. MIBG showed “No foci of radiopharmaceutical overaptation related to norepinephrine transporter overexpression lesions.”, and genetic study revealed heterozygous variant c.1900T>C [p. (Cys634Arg)] in exon 11 of the RET gene, confirming suspicion of MEN-2A syndrome. As there was no family history of endocrine neoplasias, she was referred to genetic counselling for evaluation of family members. She maintains follow-up, currently treated with hydrocortisone 7.5 + 5 + 2.5 mg od, fludrocortisone 0.1 mg od, and levothyroxine 137 mcg, with improvement of functional capacity and general state (weight gain of 13 kg), recovery of left ventricular function, normal urinary metanephrines, and calcitonin < 2.0 pg/mL. Conclusions: To our knowledge, MEN-2A syndrome presenting with cardiogenic shock due to pheochromocytoma was not yet described. Knowledge of unusual presentations of rare syndromes is important to arise suspicion and improve differential diagnosis in life-threatening conditions as cardiogenic shock.

<![CDATA[SUN-916 Novel Germline p.Gly42Arg MEN1 Missense Mutation in a Family Harboring Very Aggressive Pancreatic Tumor, Hyperparathyroidism and Pituitary Tumor]]> Background.Pancreatic neuroendocrine tumors ocurs in 30-80% of patients with MEN-1, and may be non-functioning and hormone secreting tumors. Non-functioning GEP-NETs are increasingly recognised due to advanced imaging modalities such as endoscopic ultrasound thus became the most common type in MEN1 patients. Several mutations MENIN gene were described, although patients with missense mutations are considered as low-impact mutation carriers.Case report.Index case, female, 47 years old, menarche at age of 16yo, amenorrhea until 23yo, when started continuous oral contraceptives. At age of 45 presented dizziness, paresthesia, cramps, had the diagnosis of Hyperparathyroidism related to multinodular parathyroid hyperplasia (Calcium 14mg/dL, PTH 117 pg/mL) and macroprolactinoma (prolactin 235 ng/mL; pituitary tumor 1.2 X 1.0 cm). All siblings and her mother were recruited and one brother, aged 45 years confirmed the diagnosis of hyperparathyroidism and nephrocalcinosis. Their mother, aged 77 years old, presented abdominal pain, and had the diagnosis of aggressivepancreatic tumor compressing bile duct causing intra and extra-pancreatic dilation, associated with metastatic lymph nodes. She was sunmitted to total pancreato-gastrectomy with esophagus jejunum anastomosis. Genetic screening:MEN1genetic screening for mutations was performed in all patients. In these probands, MLPA analysis was performed to detect large deletions of the MEN1gene, using SALSA MLPA probemix kit P017-D1 according to the manufacturer’s instructions (MRC-Holland, Amsterdam, The Netherlands).DNA was extracted from EDTA-Whole blood using MagNA Pure 24 (Roche). Sequencing libraries were qualified/quantified using TapeStation4200 (Agilent). Test method included coding regions ±10bp flanking intronic sequences of 3921 genes enriched using Kappa HyperPlus Library Preparation Kit (Roche) and SeqCap EZ inherited disease panel (Roche) and sequenced (2x75-bp Mid Output V2 Reagent) using NextSeq-500 (Illumina) (estimated mean coverage-100X). Read alignment, variant calling, variant filtration and annotation were performed with Varstation. SNVs and small indels (20bp) with total-read-depth,10X and variant-read-frequency more than20% found on AIP, APC, CDC73, CDKN1B, DICER1, FH, MAX, MEN1, MET, NF1, PRKAR1A, PTEN, RET, SDHA, SDHAF2, SDHB, SDHC, SDHD, TMEM127, TP53, VHL, WRN genes were analyzed.A missense mutation in exon 2, MEN1:c.124G.C:p.(GLY42Arg) was detected. Discussion and conclusion:MEN1-associated GEP-NETs seem to have a low proliferation rate and long survival has been reported, they should be of particular attention, since they are still the principal cause of death in MEN1 patients.Early screening and diagnosis are crucial for MEN-1 phenotypes.

<![CDATA[SUN-921 Indolent Presentation of Medullary Thyroid Cancer in a Patient with MEN Type 2B Due to a Germline RET M918T Mutationo]]> Background: MEN type 2B is rare and most commonly due to a germline methionine-to-threonine substitution at codon 918 (M918T) of the RET proto-oncogene. Medullary thyroid cancer (MTC) occurs in 100% of the patients affected with the mutation. This mutation is considered the highest risk and is typically associated with aggressive disease and worse overall survival. We describe a case of a late diagnosis of MEN 2B in a patient and his son, both with a relatively indolent presentation of MTC. Clinical Case: A 39-year-old man presented to an outside institution with difficult to control hypertension, headaches and anxiety and was found to have bilateral pheochromocytomas (left, 5.8 x 5.5 x 3.8 cm and right, 9 x 5.2 x 7.3 cm). Upon presentation to our institution, he was noted to have classic phenotypic features of MEN 2B with a marfanoid habitus and multiple mucosal neuromas. Genetic testing confirmed RET M918T mutation. His family history was negative for similar features in his parents and siblings. However, one of his three children, age 12, had similar phenotypic features and was found to have the same mutation. The patient subsequently underwent a successful bilateral adrenalectomy and pathology confirmed pheochromocytomas. Thyroid ultrasound showed multiple nodules with calcifications but no lateral nodal metastases. Calcitonin and carcinoembryonic antigen (CEA) levels were elevated (170 pg/mL, normal ≤10, and 180.4 ug/L, normal <3.8, respectively). He underwent a total thyroidectomy and bilateral central node dissection, with pathology confirming bilateral MTC (2.7 cm and 1.0 cm), metastatic in 4 of 10 positive lymph nodes (largest focus 2 mm). Whole body PET/CT post-operatively did not show metastatic disease. The patient’s son also had multiple thyroid nodules on ultrasound without lateral nodal metastases and elevated calcitonin and CEA levels (3015 pg/ml, normal ≤10, and 433 ng/mL, normal <2.5, respectively). MRI of the abdomen and pelvis was negative for pheochromocytomas. He underwent total thyroidectomy and bilateral central neck dissection, with pathology showing bilateral MTC (2.7 cm and 1.0 cm) with 0 of 14 positive lymph nodes. For both the patient and his son, calcitonin and CEA levels normalized following thyroidectomy and surveillance over a year later reveals no evidence of disease. Conclusion: Early diagnosis of MEN type 2B is important as MTC develops early in life and is the leading cause of death in these patients. When diagnosed early, prophylactic thyroidectomy in childhood is indicated and can improve long-term survival. There are salient phenotypic features associated with this disease which were unfortunately not recognized early in this patient and his son. Fortunately, their MTC presentations appear to be relatively indolent despite their late diagnoses, and they will continue to be closely monitored for recurrent disease.

<![CDATA[SUN-909 A Unique Presentation of Multiple Endocrine Neoplasia (MEN) Type 1 Mosaicism Caused by a Novel c.124G&gt;A Variant in the MEN1 Gene]]> The MEN1 gene is positioned on the long arm of chromosome 11 (11q13) and results in the production of menin. A classical tumour suppressor gene; the spectrum of reported germline MEN1 mutations occur throughout the gene with no strong genotype/phenotype relationship. Mosaicism is extremely rare, a recent report citing only 2 mosaic cases by next generation sequencing1. We describe a 43-year-old female with MEN1 mosaicism associated with parathyroid adenoma and probable gastrinoma.

Our patient initially presented with nephrolithiasis and nephrocalcinosis alongside biochemistry of primary hyperparathyroidism. Imaging confirmed a right lower pole parathyroid adenoma and the lesion was removed, pathology confirming the diagnosis (July 2018). Post operatively she remained hypercalcaemic. Repeat imaging suggested a further right sided culprit lesion.

One year previously (August 2017) she was admitted with a perforated duodenal ulcer within the first part of the duodenum (D1), ascribed to ibuprofen use, requiring surgical repair. Whilst awaiting repeat parathyroid surgery she represented with a further duodenal ulcer and perforation (February 2019) this time in the second part of the duodenum(D2). A second parathyroidectomy was performed and genetic investigations were instigated, given the presence of classical MEN1 phenotype. Again, pathology was consistent with a parathyroid adenoma (March 2019).

DNA was extracted for next generation sequencing which revealed mosaicism with a c.124 G>A variant detected in the MEN1 gene at a level of approximately 15%.

Further investigations have shown normal serum prolactin and pituitary and pancreatic MRI imaging. With no other family members testing positive (parents and 2/3 children) this mutation appears to be a de novo index case. Adjusted Calcium is normal 2.53 mmol/L (2.2-2.6 mmol/L) but serum Chromogranin A is elevated (2620 µg/L (ref range <95 µg/L)).

The c.124 G>A variant predicts an amino acid substitution p.(Gly42Ser) in menin structure, an amino acid change previously associated with MEN12. Given the paucity of MEN1 mosaicism reported within the literature with the presence of the two cell lines and only 15% mosaicism close monitoring will be crucial to determine the genotype/phenotype relationship in our patient.

1 Choppin et al 2019 Eur J Endocrinol 1; 180(2):L1-L3

2 Itoh et al 2017 Clin Pediatr Endocrinol 26;25-28

<![CDATA[SUN-937 A Case of Two Pathologies: Primary Hyperaldosteronism with a History of Pheochromocytoma]]> Background: In patients with system based diseases, multiple pathologies coexisting in the same organ can go undiagnosed. We present a case of a patient with long standing hypertension recently diagnosed with Primary hyperaldosteronism in the setting of known Pheochromocytoma. Case: A 43 year old male with a history of Von Hippel Lindau (VHL), Pheochromocytoma status post right subtotal adrenalectomy 18 years ago, renal cell carcinoma, prediabetes, bilateral renal cysts, and hypertension presented to the clinic for evaluation of suspected hyperaldosteronism. The patient had a history of medication refractory hypertension associated with hypokalemia requiring potassium supplementation. The patient’s VHL disease involved the pancreas, adrenal, brain and spine which required surgery to remove tumors in these areas. His Pheochromocytoma resolved status post subtotal adrenalectomy. Recent imaging and laboratory work up showed a stable left adrenal nodule (unchanged over the years), unremarkable right adrenal status post subtotal adrenalectomy with normal serum and urine metanephrines. In September 2019 he was seen by his Cardiologist for persistent Atrial Fibrillation and subsequent workup for suspected hyperaldosteronism showed a morning plasma aldosterone of 44.4ng/dL (normal range 4–21 ng/dL), plasma renin activity of <0.6 ng/ml/hr (normal range 0.6–4.3 ng/mL), 24 hour urine aldosterone of 21mcg/24hr (normal range 3–20 mcg/24hr), Urine sodium excretion of 236 mmol/24hr (normal range 40-217mmol/24hr), and potassium of 3.5mmol/L (normal range 3.6–5.0 mmol/L). The diagnosis of Primary hyperaldosteronism was confirmed and the patient was subsequently scheduled for adrenal venous sampling. Conclusion: This case demonstrates how multiple adrenal pathologies can present in the same individual. There is paucity of data in the literature as to the existence of both Pheochromocytoma and primary hyperaldosteronism in the same individual or the pathophysiological connection between them. When the diagnosis of a disease affecting a specific organ has already been made, the discovery of a secondary pathologic process affecting such organ may end up getting delayed. Clinicians should be aware of this possibility.

<![CDATA[SUN-929 An Unusual Presentation of Insulinomas-Profound Hypophosphatemia]]> <![CDATA[SUN-930 A Case of Acromegaly Secondary to Ectopic Growth Hormone-Releasing Hormone (GHRH) Secretion from a Bronchial Neuroendocrine Tumour]]> <![CDATA[SUN-928 Adrenal Plasmacytoma in Multiple Myeloma Patient-An Unusual Presentation]]>