SAT-018 Novel MEN1 Gene Mutation Related to a MEN1 Aberrant Phenotype.

Bilateral adrenal neuroblastoma (NB) is rare and is mainly stage 4S. Its incidence, presenting features, management, and outcome have not been fully defined yet. We searched the Italian NB Registry (RINB) for stage 4S NB infants with bilateral adrenal primary tumor to compare them with stage 4S NB with unilateral tumor. Between 1979 and 2016, the RINB enrolled 3731 NB patients aged 0-18 years including 317 infants (8.5%) diagnosed with stage 4S NB. Eleven/317 (3.5%) had a bilateral adrenal primary tumor (Group 1) and 190/317 (59.9%) had a unilateral tumor (Group 2). Group 1 infants were significantly younger (51 vs. 89 days) but were comparable with Group 2 for any other presenting features. In the absence of specific protocols, upfront treatment was based on symptoms, size of adrenal tumors, and biology, and consisted of observation in 5 cases, radiotherapy in one, chemotherapy in 2, and surgery in 3. Five/11 developed progression and 2 of them, both with MYCN amplification, died. The 5-year EFS rates of Group 1 and 2 were 54.5% vs. 73.3% (P=.14) and 5-year OSs were 81.8% and 89.4%, respectively (P=.44). Our data support the hypothesis that 4S NB infants with bilateral adrenal tumors can have favorable outcome with personalized therapeutic approach. The three patients with MYCN amplified tumor benefited from upfront aggressive chemotherapy, in accordance with current protocols. Because of the rarity of this intriguing form of neuroblastoma, collaborative prospective studies are warranted, especially in view of gaining a better insight on its biological and genetic features.

BackgroundCoexistence of a catecholamine-secreting tumor and an adrenal cortical tumor is quite rare which makes both diagnosis and management challenging. The purpose of this article is to describe the presence of this condition, share a stepwise approach for preoperative evaluation, and review the related literature.Case presentationA 44-year-old male patient had a history of hypertension and aggravating hypokalemia for years. Abdominal computed tomography incidentally found concomitant bilateral adrenal and left para-aortic tumors. Comprehensive adrenal hormone tests revealed a high aldosterone renin ratio and mildly elevated 24-h urine vanillylmandelic acid and norepinephrine levels. Subsequently, a metaiodobenzylguanidine scan showed uptake over the left para-aortic tumor, and NP-59 adrenal scintigraphy showed uptake over the left adrenal tumor. Further confirmatory tests, including captopril suppression, irbesartan suppression, and saline infusion, all confirmed the diagnosis of hyperaldosteronism. Adrenal venous sampling following 2 months of preparation with an alpha blocker demonstrated a left aldosterone-producing adrenal adenoma. Combining hormonal analysis, imaging studies, and adrenal venous sampling, the patient was diagnosed with left adrenal aldosteronoma, right adrenal nonfunctional tumor, and left para-aortic paraganglioma (PGL). Accordingly, laparoscopic left adrenalectomy and left PGL excision were performed smoothly under alpha blocker maintenance. The pathology report confirmed left adrenal cortical adenoma and left para-aortic PGL. Postoperatively, the blood pressure, biochemical tests, and adrenal hormone assays returned to normal, and related symptoms disappeared and were relatively stable during the follow-up period of two years.ConclusionsThis is the first case of left para-aortic PGL coexisting with an ipsilateral aldosterone-producing adenoma presenting as a left para-aortic tumor associated with bilateral adrenal tumors. Awareness of the rarity of this coexistence can avoid unexpected disasters during the process of evaluation and management.

According to some authors, a higher incidence of subclinical hypercortisolemia is found among patients with bilateral benign adrenal tumors than in those with unilateral tumors. It is still unknown whether all patients with bilateral adrenal tumors and subclinical hypercortisolemia should undergo surgery, and, if so, which tumor should be removed first. The aim of the study was to investigate whether unilateral adrenalectomy can lead to resolution of hypercortisolemia in patients with bilateral adrenal tumors and to improvement of their clinical status. The study group consisted of 25 patients with bilateral benign adrenal tumors and subclinical hypercortisolemia. In 24 patients, unilateral adrenalectomy was performed. The adrenal gland was selected for removal on the basis of scintigraphy and/or tumor diameter. Cortisol concentrations were measured before the surgery and at 1 and 6 months after the surgery at 8:00 AM, 10:00 PM, and after dexamethasone suppression. The morning blood levels of adrenocorticotropic hormone, dehydroepiandrosterone, 17‑hydroxyprogesterone, glycated hemoglobin, and lipid profile were determined. In all surgical patients, hypercortisolemia resolved after the surgery. However, only in 14 patients (58%), the clinical improvement was evident (improved control of diabetes and hypertension, body mass loss). Although subclinical hypercortisolemia resolved after surgery in all patients with bilateral adrenal tumors, only patients with poorly controlled diabetes and hypertension and a rapid increase in body mass benefited from the surgery.

Parathyroid adenoma weighing more than 3.5 g are referred as Giant parathyroid adenoma (GPA). These mainly present with primary hyperparathyroidism but have severe clinical presentations like severe hypercalcemia and significantly higher PTH levels. These features are sometimes indistinguishable from parathyroid carcinoma. We describe an interesting case and clinical course of a young woman with GPA. A 27 years old woman previously asymptomatic presented with pain in left leg along with difficulty in walking and was subsequently diagnosed to have fracture of neck of left femur and severe hypercalcemia. On evaluation, the patient was found to have PTH dependent hypercalcemia and severe osteoporosis. USG neck revealed well defined heterogenous hypoechoic lesion suggestive of parathyroid adenoma. Tc99 sestamibi scan showed tracer localization to inferior aspect of lower lobe of right thyroid gland. She underwent right inferior parathyroidectomy and a giant parathyroid adenoma (GPA) weighing 20 g was excised. Histology confirmed parathyroid adenoma with mainly chief type cells. The tumour excision resulted in significant decline in PTH levels. She developed severe hungry bone syndrome (HBS) in post operative period. She was treated aggressively for HBS with intravenous calcium gluconate, oral calcium supplements along with calcitriol. GPA present as distinct clinical entity with features different from both parathyroid adenoma and parathyroid carcinoma. We will highlight the distinguishing points of GPA from parathyroid adenoma and parathyroid carcinoma.

Adrenal-preserving laparoscopic surgery in selected patients with bilateral adrenal tumors

A. Saavedra-Simmons: None. L.A. Marion: None. P.M. Sadow: None. M.A. Blake: None. E.L. Blouch: None. R.A. Hodin: None. L.E. Dichtel: Research Investigator; Self; LED has received research support from Perspectum Ltd. and research support from Lumos Pharma, all per investigator-initiated request, and additional research support from Recordati and NovoNordisk. Other; Self; LED has equity in Marea Therapeutics and is a consultant for Lumos Pharma, LED is a fellow at Third Rock Ventures through the Mass General Brigham’s Innovation Fellows Program, but remains a full-time employee of Mass General Brigham during the course of this educational program (10/1/2022-9/30/2024). Background: Adrenal medullary hyperplasia (AMH) is a rare, benign condition that can present similarly to pheochromocytomas (PCC) clinically, biochemically and radiographically; differentiation requires histopathologic review. We present a case of a critically ill patient with bilateral adrenal masses and elevated catecholamines suspected of having PCC but ultimately diagnosed with AMH. CASE: A 54yo male with newly diagnosed acute myeloid leukemia presented with confusion and was incidentally found to have adrenal nodules measuring up to 2.8 cm (right) and 4.8 cm (left). Calcium was 15.9 mg/dL (8.5-10.5 mg/dL), PTH 312 pg/dL (10-60 pg/mL) and bilateral parathyroid lesions were found on imaging. Plasma normetanephrines (PNM) were 2.9 nmol/L (<0.90 nmol/L); urine normetanephrines (UNMs) were 5957 mcg/24h (<900 mcg/24h). Plasma and urine metanephrines were normal. Importantly, these tests were obtained in the intensive care unit, where the patient had developed disseminated intravascular coagulopathy. There was suspicion for an inherited syndrome given PTH-dependent hypercalcemia, bilateral parathyroid lesions and maternal history of PCC. After recovery from critical illness, bilateral adrenalectomy was performed for diagnostic purposes and medical optimization prior to planned bone marrow transplant. Surgical pathology unexpectedly revealed no adrenal masses and demonstrated only mild thickening of the bilateral adrenal medullas. Histopathology showed no pathological evidence for PCC, adrenal cortical neoplasia or neoplasia of the extra-adrenal paraganglia. Periadrenal fat was sectioned and appeared grossly normal. Postoperative PNM and UNM levels normalized, and there was no evidence of adrenal masses on follow-up CT. On retrospective review, the adrenal lesions on initial imaging were thought to be consistent with marked medullary hyperplasia that nearly halved on 3-week interval imaging, which could be consistent with resolution to mild AMH on pathology 7 weeks after the initial CT. Conclusion: We describe a case of a patient with significantly elevated catecholamine levels, PTH-dependent hypercalcemia with parathyroid lesions and family history of PCC who was incidentally found to have radiologic evidence of bilateral adrenal masses that on pathology demonstrated mild AMH. While there have been reports of similar cases in the literature of AMH appearing as adrenal masses on imaging, no explanation for the discrepancy in imaging and histopathology has been described. Animal studies suggest that the adrenal glands can become enlarged and hypertrophied during an acute stress event, possibly mediated by acute adrenal medullary hypersecretion. We thus hypothesize that AMH can mimic PCC on imaging in critical illness due to increased secretion of ACTH and catecholamines leading to hyperemia and adrenal thickening. AS and LAM contributed equally. Saturday, June 1, 2024

Adrenocortical cancer (ACC) is a rare malignancy. In the absence of metastatic disease, the suspicion of ACC is based on size and radiological appearance. The aim of this study was to analyse the long-term outcome of patients with large adrenal cortical tumours (>8 cm). A prospective database recorded clinical, biochemical, operative and histological data on patients operated for cortical adrenal tumours between January 2000 and February 2013. Out of 130 patients operated for cortical adrenal tumours, analysis was restricted to 37 cortical tumours >8 cm. There were 31 (84 %) ACCs and 6 (16 %) benign adenomas (p < 0.01). The most common presentation was that of an abdominal mass [17 (55 %) vs. 3 (50 %), ACC vs. benign, respectively]. There was no difference in size between stage II and stage III-IV tumours; however, there was a trend for tumours to be heavier in advanced stages (920 ± 756 vs. 1,435 ± 1,022 g, p = 0.08, stage II vs. stage III-IV, respectively). No mortality was observed in patients with benign tumours during a median follow-up of 70 months (range 36-99 months). Mortality in the ACC group occurred in 17/31 (55 %) patients. Mitotane was administered in 12 (71 %) patients with stage III-IV ACCs with a 5-year survival rate 25 % compared to 20 % in patients who did not receive Mitotane. In stage II ACC, eight (57 %) patients received Mitotane with a 50 % mortality at 5 years. The high incidence of ACC in cortical tumours >8 cm underlines the need for adequate surgical resection via open surgery aiming to avoid local recurrence. Beyond surgery, the impact of other therapies is not fully characterised and the efficacy of adjuvant Mitotane treatment is yet to be proven.

A Patient With Polyuria and Hypercalcemia

The Role of Calretinin, Inhibin, Melan-A, BCL-2, and C-kit in Differentiating Adrenal Cortical and Medullary Tumors: An Immunohistochemical Study

Parathyroid glands, minute endocrine glands, located in posterior aspect of thyroid glands secrete parathormone which plays an important role in maintaining calcium homeostasis in the body. The superior and inferior parathyroid glands originate from the 4th and 3rd branchial pouches respectively and migrate to occupy their normal positions in relation to the thyroid gland.1 Hyperparathyroidism is defined as hyper functioning of parathyroid gland and can be primary, secondary or tertiary. Primary hyperparathyroidism is due to parathyroid gland proliferative disorders which include parathyroid adenoma, parathyroid hyperplasia, parathyroid carcinoma or in association with other conditions in MEN syndrome. In more than 90 % patients, primary hyperparathyroidism is caused by a single parathyroid adenoma. Very rarely double parathyroid adenomas are seen. Secondary Hyperparathyroidism is caused in response to any chronic hypocalcaemic conditions like renal failure, gastrointestinal malabsorption, dietary rickets &amp; drugs, like phenytoin, phenobarbital &amp; laxative. Prolonged secondary hyperparathyroidism leads to tertiary hyperparathyroidism due to autonomous secretion. The clinical presentation of hyperparathyroidism is classically described as kidney stones, abdominal groans, painful bones, psychic moans, and fatigue overtones. In the initial course of the disease, the patients present with vague symptoms of fatigue, muscle and joint pain, frequent urination, nausea, constipation, and decreased appetite. If high index of suspicion is maintained, they can be conveniently diagnosed by routine blood tests which show increased calcium levels. However, in India still majority of people are diagnosed when they present with palpable neck mass, skeletal manifestations or deranged renal function. We hereby present 5 cases of parathyroid adenoma managed at our centre over a period of 2 years. P

Background: Co-occurrence of phaeochromocytoma and primary hyperparathyroidism is usually seen in patients of Multiple Endocrine neoplasia 2A(MEN2A) and is rare in Von Hippel Lindau disease (VHL). Parathyroid adenoma with pheochromocytoma in a genetically confirmed VHL has been reported only once till date (1). Clinical Case: A 30-year male was admitted for evaluation of hypertension and incidentally diagnosed adrenal mass on ultrasound. 9-years back, he was diagnosed as a case of VHL (right renal clear cell carcinoma, pancreatic cystadenoma, spinal hemangioblastoma and epididymal cysts). Right nephrectomy and pancreatic cyst excision had been done and past work-up for pheochromocytoma was normal. He also had been operated twice for recurrent renal calculi. Family history revealed surgery in mother for pancreatic mass. Current imaging revealed right adrenal mass (4.7*4.6 cm) with left renal cysts and calculi, pancreatic cysts and spinal- medullary hemangioblastoma and epididymal cysts. Fundus examination was normal. 24-hours urinary fractionated normetanephrines were elevated (2062 mcg/24 hours) and I131MIBG scan showed 4.7*4.6cm concentrating lesion in right renal fossa suggestive of right adrenal pheochromocytoma. However his biochemical evaluation revealed hypercalcemia (12.1 mg/dl), low phosphorus (3.2 mg/dl), low 25(OH) D (24.84 nmol/l), and raised PTH (121pg/ml). Ultrasound neck and Tc99m-Sestamibi localized left inferior parathyroid adenoma. DEXA scan showed severe osteoporosis. Genetic analysis confirmed VHL mutation in exon-1. Calcitonin and RET mutation were normal (ruled out MEN2A). Therapeutic approach was surgical excision of adrenal pheochromocytoma followed by parathyroidectomy. We report a case of pheochromocytoma with primary hyperparathyroidism (cause: left inferior parathyroid adenoma) in a patient of VHL (Renal clear cell carcinoma, pancreatic cystadenoma, epidydymal cysts and medullary and spinal hemangioblastoma). Hypercalcemia seen in patients of VHL is either due to bone metastasis/PTHrP/IL-6 secretion from RCC or due to PTHrP/PTH/calcitonin secretion from pheochromocytoma and rarely due to associated parathyroid adenoma. Literature search revealed four case reports of parathyroid adenoma with VHL. In only one of these, VHL had pheochromocytoma associated with parathyroid adenoma (1). Conclusion: Ours is the 2nd such case reported in literature of primary hyperparathyroidism in a genetically confirmed case of VHL with pheochromocytoma. This case highlights the overlap of tumorigenesis in two rare genetically divergent syndromes and importance of long-term follow-up for sequential development of new tumors. Reference: Arao T, Okada Yet al. A case of VHL disease with bilateral pheochromocytoma, renal cell carcinoma, pelvic tumor, spinal hemangioblastoma and primary hyperparathyroidism. Endocr J. 2002 Apr;49(2):181–8.

Precursor Lesions in Patients With Multiple Endocrine Neoplasia Type 1--Associated Duodenal Gastrinomas

Background: Familial adenomatous polyposis (FAP) is an autosomal dominant condition caused by germline mutation in the tumor suppressor gene APC. FAP occurs in 1 to 10.000 individuals, and is characterized by hundreds to thousands of colonic adenomatous polyps with a high risk of developing into colorectal cancer. Extracolonic manifestations can be malignant or benign. The major causes of morbidity and mortality in patients with FAP are abdominal desmoid tumors, with incidences ranging between 7% and 17%. Adrenal incidentaloma are frequently discovered in these patients, generally as benign lesions when they undergo abdominal CT-scan in the course of surveillance. Adrenal lesions in FAP ranged from 7.4% to 16%. We described an unusual patient with FAP, associated with autonomous cortisol production due to bilateral adrenal tumors and the development of aggressive desmoid tumor after unilateral adrenalectomy. Clinical Case: A 33-years-old female FAP-patient presented with abdominal pain, weight gain (10kgs), humor instability, paroxysmal of chest pain, dizziness and tremors. The abdominal MRI showed a heterogeneous, left adrenal mass (9.0 x 7.9 x 6.7cm), suspected for malignant tumor, and right adrenal mass with 3.6 x 1.8 cm suggestive of adenoma. Abdominal CT and PETCTFDG revealed on the left adrenal lesion with 33UH and maxSUV 3.9 and a right adrenal lesion 13UH and maxSUV 3.1. Serum hormone levels were as follows: cortisol after DST (1mg-dexamethasone) 4.8 ug/Dl, ACTH 8,8pg/Ml with no other abnormal hormone secretion detected. Patient underwent left adrenalectomy. Histological analysis revealed Weiss 1, modified Weiss 2 and Ki67 <1% compatible with adenoma. On follow-up, abdominal MRI revealed a 4.3cm-solid-homogeneous mass at the surgical incision, suspected of malignance. The mass progressively enlarged to 6.3 cm in diameter. Histological analysis of the biopsy identified a desmoid tumor. The contralateral adrenal tumor maintained stable during the follow-up; however, it began to produce cortisol autonomous secretion as observed on DST. The patient developed metabolic syndrome and did not present classical Cushing’ syndrome. Contralateral adrenalectomy was contraindicated because of concern of emergence of a new desmoid tumor. Discussion: FAP-associated with adrenal tumors can produce mineralocorticoids, corticosteroids, or both. Although adrenal cortical tumors have been reported frequently in FAP patients, the presence of bilateral commitment tumors on adrenal glands is extremely rare. Conclusion: We reported a woman with FAP and bilateral adrenal tumors with non-synchronic cortisol secretion associated with an aggressive desmoid tumor developing after the adrenalectomy. The patient is taking an adrenal inhibitor of steroidogenesis to control cortisol secretion and to provide clinical improvement.

Human multiple endocrine neoplasia subtype 2A (MEN 2A) is characterized by medullary thyroid carcinoma, pheochromocytoma and parathyroid hyperplasia or adenoma in the same individual. In this report, a case of a female Rottweiler with medullary thyroid carcinoma, bilateral pheochromocytoma and parathyroid adenoma was described. Clinical manifestations of muscle weakness, polydipsia, polyuria, diarrhea and weight loss were observed. Two adrenal neoplasms were identified incidentally by ultrasonography, and tumor in the left thyroid lobe was identified by palpation. Primary hyperparathyroidism was diagnosed by biochemical testing. Histopathology report was consistent with diagnosis of bilateral pheochromocytoma and parathyroid adenoma. Immunohistochemical staining was positive for calcitonin and synaptophysin, and negative for thyroglobulin, which confirmed medullary thyroid carcinoma. This case in a dog is presenting neoplastic characteristics similar to human MEN 2A and emphasizing the importance of using immunohistochemistry for confirmation.

BACKGROUND: Parathyroid adenomas are the main cause of primary hyperparathyroidism (PHPT). PHPT most often affects adults between ages 50-60 and is considered rare in children and adolescents, representing less than 5% of cases1. It is more common among females than among males in the proportion 3 to 1. During embryogenesis, both the superior and inferior parathyroid glands detach from their pharyngeal origin and migrate towards their final location, posteriorly to the thyroid gland. Migration can be faulty and ectopic glands can appear along the path of embryologic descent2. We present a case of an adolescent male who presented with symptomatic PHPT in the setting of an intrathymic parathyroid adenoma. CASE PRESENTATION: 17-year-old male with no significant past medical history developed symptoms of anxiety, nausea and fatigue. Laboratory values revealed calcium 14.3 mg/dL (8.6-10.3), PTH 227 pg/mL (15-65), 25-dihydroxyvitamin D (vit-D) 8.31 ng/mL (30-100), and phosphorus 1.5 mg/dL (2.5-5. 0). He denied any personal history of bone fractures or nephrolithiasis. CT parathyroid scan showed an enhancing oblong 1.7×0.6 cm lesion in the left upper mediastinal space suggestive of a parathyroid adenoma. Focal sestamibi uptake confirmed a 1.7×0.6 cm enhancing nodule in the left upper anterior mediastinum within the thymus. He was instructed to take 2,000 IU of vit-D daily. Repeat blood work one month later showed that his serum calcium decreased to 13.4 mg/dL and PTH decreased to 122 pg/mL. Additional labs revealed vit-D 16.81 ng/mL, 1,25-dihydroxyvitamin D (calcitriol) 160 pg/mL (19.9-79.3) and 24-hour urine calcium excretion of 409 mg (0-320). Patient underwent successful excision of an intrathymic hyperplastic parathyroid gland adenoma with a >50% drop in peak PTH levels intraoperatively at 10 minutes post excision, later confirmed by pathology. CONCLUSION: This case highlights an adolescent with symptomatic primary hyperparathyroidism due to an intrathymic parathyroid adenoma. Ectopic adenomas have been reported in approximately 4 to 16% of patients with hyperparathyroidism2. When embryological development of the parathyroid glands is defective, it can predispose to the formation of ectopic glands, which is an important cause of failed parathyroid exploration. Unfortunately, PHPT has greater morbidity in the younger age group since most of these patients develop complications from the hypercalcemia, such as kidney stones, hypercalciuria, bone disease and symptoms of abdominal pain/vomiting. This case emphasizes the importance for clinicians to be aware of ectopic parathyroid adenoma in adolescents who present with symptoms and labs consistent with primary hyperparathyroidism.