ResearchPad - adrenal-case-reports-i https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[SAT-183 Right Adrenal Mass: An Unusual Presentation]]> https://www.researchpad.co/article/elastic_article_8810 Background: Adrenal masses may be incidentally found on imaging done for other reasons. The prevalence is 4.4% and up to 10% in older patients. Malignancy is an uncommon cause in patients without a known diagnosis of cancer. The frequency of primary adrenal carcinoma in patients with adrenal incidentalomas is approximately 2.0 to 5.0%; another 0.7 to 2.5% have non-adrenal metastases to the adrenal gland.

Clinical Case: 54-year-old man with Hepatitis C, prior alcohol abuse, and cirrhosis was found to have an increase in the alpha-fetoprotein (AFP) level from normal to 244 ng/ml (nl<15.1) over a 6-month period. Liver MRI was consistent with a cirrhotic liver without focal enhancing lesions and showed a new indeterminate 7.6 cm right retroperitoneal lesion arising from the adrenal gland compared to a prior CT of the abdomen a year early. Further imaging confirmed a 9.6 x 9 x 7.6 cm heterogeneously enhancing right adrenal lesion with a necrotic center, concerning for a primary malignancy; up to 11.1cm a month later. Patient referred to Endocrine for further evaluation. There were no symptoms suggestive of Cushing’s, pheochromocytoma or primary hyperaldosteronism. On exam there were no hypertension, dorsal fat pad, supraclavicular fullness, skin thinning or purplish striae. Biochemical workup was consistent with a non-functioning adrenal mass. DHEA-S was 11 (38-313 mcg/dl). CT-guided core needle biopsy of right adrenal gland was consistent with metastatic hepatocellular carcinoma. CT pelvis with contrast re-demonstrated the right adrenal mass now measuring 11.4 x 10 x 10 cm with new enlarged retrocaval lymph node and no focal arterially enhancing lesions. During embolization of adrenal lesion/ hepatic angiogram, multiple liver lesions not previously identified were reported with the largest of 2.9cm size and enhancing lesions in the sacrum and bilateral iliac bones; decrease in size of the necrotic right adrenal mass measuring 8.2 x 9.1 x 9.1 cm 1-month post-embolization. Patient following with Oncology.

Conclusion:Unilateral isolated adrenal metastasis from occult hepatocellular carcinoma (HCC) is extremely rare. Adrenal gland is the second most common site of hematogenous spread from HCC after the lung and has been found in up to 8.4% of cases at autopsy. In our case, the adrenal metastasis was the first clinical presentation of HCC with no evident hepatic lesion until 9 months of adrenal finding; few cases have been reported. Fine needle aspiration/needle biopsy of suspected malignancy is useful to detect primary tumor in case of metastatic disease that is silent at this stage. Adrenal metastasis in HCC are seldom treated by surgery as by the time of diagnosis the tumor is usually far advanced and/or patients are poor surgical candidates. This case highlights the importance of suspecting underlying HCC in isolated adrenal mass in a patient with high risk factors.

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<![CDATA[SAT-231 A Case of Metastatic Pheochromocytoma Associated with Beckwith-Wiedemann Syndrome]]> https://www.researchpad.co/article/elastic_article_8711 Introduction:

Beckwith-Wiedemann Syndrome (BWS) is an autosomal dominant disorder of chromosome 11p15 that results in increased IGF-2 and CDK1NC. This leads to excessive cell proliferation and tumor formation. The following highlights a case of metastatic pheochromocytoma in a patient with BWS.

Clinical Case:

A 30-year-old male presented with sudden onset blurry vision without any associated complaints. His past medical history was significant for BWS. His family history was negative for uncontrolled hypertension, sudden death, thyroid cancer or hyperparathyroidism. Physical examination was notable for an elevated systolic blood pressure of 200/160 mm of hg and fundoscopy revealed features of hypertensive emergency. Laboratory investigations revealed an elevated plasma normetanephrine [10445 pg/ml (normal: <148)], metanephrine [93 pg/ml (normal: <57)], total metanephrine [10538 pg/ml (normal: <205)], epinephrine [134 pg/ml (normal:<50)], norepinephrine [23526 pg/ml (normal: 112-658), total catecholamine level [23660 (normal: 123-671pg/ml)] and dopamine [403 pg/ml (normal<30)] levels. His PTH, corrected serum calcium, gastrin, insulin, carcinoembryonic antigen, calcitonin levels and basal metabolic panel were all normal. MRI of the abdomen demonstrated bilateral adrenal nodules with a large mass encasing the celiac axis along with evidence of hepatic lesions. I-123 MIBG scan showed mild radioactive tracer uptake in the adrenal nodules and mass near the celiac axis but not in the hepatic lesions. PET scan confirmed MRI findings and was negative for any evidence of malignancy in the chest, pelvis and skeleton. MRI of the brain was negative for metastasis as well as pituitary abnormalities. Ultrasound-guided liver biopsy was positive for malignant cells that stained positive for chromogranin and synaptophysin confirming the diagnosis of metastatic pheochromocytoma. He was treated with phenoxybenzamine, diltiazem and lisinopril. He underwent cycles of cyclophosphamide, vincristine and dacarbazine. Genetic testing revealed a variant in SDHD gene which was of uncertain significance. Repeat biochemical testing on follow up after a year and a half showed a decreased plasma normetanephrine [487pg/ml] and metanephrine levels [110 pg/ml] in comparison to his levels on presentation. Repeat imaging revealed a decrease in tumor burden including bilateral adrenal nodules, celiac axis mass and hepatic metastases.

Conclusion:

This is an unusual case of malignant pheochromocytoma in the absence of SDHB mutation in a patient with BWS. Genetic causes in these patients are yet to be determined. However, genes H19 and KCNQ1OT1 have been implicated in addition to IGF-2 and CDK1NC

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<![CDATA[SAT-215 A Case of Polyglandular Autoimmune Syndrome]]> https://www.researchpad.co/article/elastic_article_8626 Background: Polyglandular autoimmune syndrome is defined by the presence of Addison’s disease, Autoimmune thyroid disease and Type 1 Diabetes Mellitus.

Clinical Case: This is a case presentation of a 56 year old female with a multitude of endocrine disorders, classified as polyglandular autoimmune syndrome, type 2, persistently elevated ACTH levels.

Over the years, the diagnoses of Primary Adrenal Insufficiency, Type 1 Diabetes, and Hypothyroidism, had revealed themselves, in this patient.

Her initial diagnosis upon establishment into our clinic was Addison’s disease and hypothyroidism for which she was getting adequate treatment. Her clinical course had been complicated by multiple admissions for DKA, along with adrenal crises.

Following the adrenal crisis, her ACTH levels had been noted to be persistently elevated, at 3362, despite hydrocortisone replacement at optimal dosing and normal AM cortisol levels. Her hyperpigmentation continued to worsen. A 1mg dexamethasone suppression test failed to lower the ACTH levels.

Concern for a possible ectopic ACTH secretion prompted further investigation with imaging studies such as an abdominal Cat scan which showed no adrenal pathology. Pituitary MRI was ultimately performed which showed no evidence of pituitary lesions.

These were following by an 8mg Dexamethasone suppression test which adequately decreased the ACTH level. However re-check of ACTH levels, after weeks of being on her physiological hydrocortisone dosing, showed that her ACTH levels had started to rise again. Given she had also had multiple admissions for adrenal crises, the concern was raised for possible malabsorption.

Given her risk for auto-antibody development, there was concern for another autoimmune process such as Celiac disease, as a potential cause for malabsorption. Her TTG IgA antibodies were checked, however they were absent.

At this point, the decision was made to use prednisone as a means of suppression of ACTH, and she was given three days of 40mg Prednisone daily, followed by ACTH level testing, which showed a decrease from 2009 to 708. These results prompted us to change her hydrocortisone to prednisone daily dosing instead, and we converted her to a slightly higher dose of Prednisone.

In the setting of underlying DM, this may pose an additional challenge with glycemic control, but we plan for close clinic follow up and repeat ACTH levels a few weeks after she has been on the new prednisone regimen.

Conclusion: This is a rare case of a patient with polyglandular autoimmune syndrome, type 2, with a persistently elevated ACTH level, requiring Prednisone, instead of hydrocortisone for treatment of primary adrenal insufficiency in efforts to reduce ACTH levels.

References: Neufeld M, Maclaren NK, Blizzard RM, Two types of autoimmune Addison’s disease associated with different polyglandular autoimmune (PGA) syndromes. Medicine (Baltimore). 1981;60(5):355.

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<![CDATA[SAT-219 Allgrove Syndrome: How to Suspect a Problem?]]> https://www.researchpad.co/article/elastic_article_8584 Background: Allgrove syndrome (triple A syndrome) is a rare autosomal recessive multisystem disease characterized by adrenal insufficiency, alacrimia and achalasia. It is caused by a mutation in the AAAS gene (12q13) encoding the protein ALADIN (1). This syndrome is often associated with neurological dysfunction disorders, amyotrophy, in such cases, it is named 4A and 5A syndrome, but sometimes there is also 2A syndrome. Prevalence:<1/1000000. The first description was in 1978. Clinical case: A 18-year patient A. complained of fatigue, weakness, darkening of the skin. From anamnesis of life: born from the first pregnancy without complications, weight 3200g. Parents often turned to the pediatrician with complaints: lethargy, frequent regurgitation, ARVI up to 6–7 times a year. Slow weight gain, dyspeptic syndrome (nausea, vomiting) was noted objectively. At the age of 3, the boy entered the surgical department with acute abdomen, fever, vomiting. Achalasia was revealed, reconstructive surgery was carried out. In the diagnostic search for the causes of body weight loss he was directed to the endocrinologist. There were an increase in ACTH 470 pg/ml (0,0-46 pg/ml), cortisol 0.05 µg/DL. Diagnosis: primary chronic adrenal insufficiency; the dose of hydrocortisone 10 mg/day did not change with age. An in-depth anamnesis found: the patient never cried with tears. Objectively: asthenic body type, BMI 16.5 kg/m2, hyperpigmentation of the palms, armpits; weakness in the proximal muscles of the limbs. Laboratory studies: ACTH 95 PG/ml, cortisol 0.1 µg/DL (3.7–19.4 µg/DL). The secretion of mineralocorticoids was evaluated: plasma aldosterone and renin levels were within the reference values. Ophthalmologist: injected conjunctiva, sclera. Schirmer’s test: mild alacrimia. It allowed to make the diagnosis: “Primary chronic adrenal insufficiency. Condition after surgery for achalasia (1997). Alacrimia. Allgrove Syndrome.” The dose of hydrocortisone was increased to 17.5 mg/day. In 2019, the patient complained of a sharp deterioration of health, darkening of the skin. The dose of hydrocortisone was increased to 25 mg/day (15 mg at 8.00, 10 mg in the afternoon). The ophthalmologist noted an increase in the severity of alacrimia, artificial tear drops was recommended. The diagnosis was confirmed by pathogenic mutation c.43C>T of the AAAS gene. Discussion: Despite the full clinical picture, the right diagnosis was made only after 14 years. We shown the difficulty of diagnosis is due to the lack of awareness of clinicians about the disease, the importance of interdisciplinary interaction, as well as the need for follow-up of such patients. Reference: (1) Handschug K, Sperling S, Yoon SJ, et al. Triple A syndrome is caused by mutations in AAAS, a new WD-repeat protein gene. Human Molecular Genetics. 2001;10:283–290.

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<![CDATA[SAT-223 Metastatic Pheochromocytoma in MEN2A: Clinical Features, Laboratory Data and Radiological Findings of a Rare Association - Case Report]]> https://www.researchpad.co/article/elastic_article_7115 Background: Multiple endocrine neoplasia type 2A (MEN2A) is an autosomal dominant syndrome caused by inactivating mutations in the RET proto-oncogene. It is characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO) and hyperparathyroidism (HPTH). MTC is one of the initial manifestations in 90% of patients. PHEO affects approximately 50% of patients, is almost always benign (98% of cases), usually bilateral and confined to the adrenal glands. HPTH occurs in 20-30% of patients. The clinical presentation, evolution and prognosis of metastatic PHEO associated with RET mutations are not yet well known.

Clinical Case: A previously healthy man was initially diagnosed with hypertension at 24 years of age. Two years later, after recurrent paroxysms of headache, tremors and tachycardia, the patient was suspected of having bilateral PHEO based on laboratory and radiological findings. Bilateral adrenalectomy was performed and the anatomopathological analysis confirmed the suspected diagnosis.

Soon afterward, although the patient was asymptomatic, with urinary metanephrines in the normal range, two possibly metastatic lesions were identified – one in the liver (9 x 8 mm) and one in the left adrenal bed. Some of the patient’s family members were also found to have PHEO and/or MTC, leading to the diagnosis of MEN2A. A RET germline mutation in codon 634 (p.Cys634Phe) of exon 11 was then found in the patient’s family pedigree. At the time, the patient (index case) had no evidence of MTC or HPTH.

Diagnostic 131I-MIBG scintigraphy showed increased uptake in the patient’s liver. The subsequent percutaneous liver biopsy confirmed the presence of metastatic PHEO. Interestingly, no significant 18F-FDG uptake was found on the 18F-FDG-PET/CT scan in the metastatic PHEO sites. For more than 10 years of follow-up with no specific treatment, the metastatic lesions demonstrated slow growth rates; metanephrine levels, although increased (total = 1422 mcg/24h, NR <1000; normetanephrine = 676 mcg/24h, NR <320; and metanephrine = 574 mcg/24h, NR <390), were relatively stable; blood pressure and adrenergic symptoms were under control with a few antihypertensive medications.

At 36 years of age, the calcitonin level was slightly increased (8.6 pg/mL, NR <8.4) and a minuscule thyroid nodule (3 x 3 x 2 mm) was identified on the ultrasound scan. Prophylactic thyroidectomy was performed, with a diagnosis of a 2.5-mm MTC. More recently, an increase in the metanephrine levels was found and treatment with iobenguane 131I may be an option.

Conclusion: Patients with metastatic PHEO caused by mutations in the RET proto-oncogene (MEN2A) may have a long survival time. In such patients, an 18F-FDG-PET/CT scan may exhibit low sensitivity for the diagnosis of metastasis and the onset of PHEO may precede that of MTC by many years.

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<![CDATA[SAT-185 Primary Adrenal Lymphoma Presenting with Symptomatic Hypercalcaemia]]> https://www.researchpad.co/article/elastic_article_7056 Introduction: Primary adrenal lymphoma (PAL) is a rare cause of adrenal enlargement with approximately 200 cases reported in the literature to date. It tends to affect elderly men and has a high incidence of bilateral involvement at diagnosis. We report the case of a 66 year old man, whose PAL manifested with symptomatic hypercalcaemia.

A 66 year old male, originally from the Philippines, was referred to the emergency department with nausea, vomiting, weight loss and right flank pain. His past medical history was significant for hypertension, gout and stage 3b chronic kidney disease. His medications were amlodipine, losartan and febuxostat. His family history was significant for hypertension. On examination he was hypertensive (blood pressure, 160/100 mmHg) and hyperpigmented. His laboratory investigations revealed; corrected calcium of 3.79 mmol/l, undetectable PTH, vitamin D 49 nmol/l. He was treated with intravenous (IV) 0.9% saline and IV zoledronic acid and his calcium levels improved.

To investigate causes of non-PTH mediated hypercalcaemia, computerised tomography of the thorax, abdomen and pelvis (CT TAP) as well as a positron emission tomography (PET) scan were performed. These demonstrated bilateral, large, metabolically active adrenal masses with no evidence of extra-adrenal disease. Differential diagnosis at this point included bilateral adrenal hyperplasia, metastases, lymphoma or adrenal TB. There were no radiological features of adrenocortical carcinoma (ACC) or phaeochromocytoma and subsequent biochemical investigations confirmed no evidence of cortisol, androgen or catecholamine excess. Adrenocorticotrophic hormone (ACTH) levels were elevated however, and a synacthen test revealed inadequate adrenal reserve (peak cortisol 214 nmol/l). The patient was commenced on maintenance steroids and with stress dose steroid cover, proceeded to adrenal biopsy. Histology confirmed diffuse large B cell non-Hodgkin’s lymphoma. Haematology became involved in his care and he commenced polychemotherapy in the form of R-CHOP, 1 week post confirmation of the diagnosis. His treatment is ongoing and he has tolerated it well with minimal side effects, except a flare of gout.

Learning points: PAL should be considered in the differential diagnosis in patients with bilateral adrenal masses. Image guided adrenal biopsy is the gold standard for diagnosis, though caution must be exercised and an ACC or phaeochromocytoma should be excluded prior to biopsy. The prognosis of PAL is poor and therefore early diagnosis and prompt initiation of treatment are required to improve outcomes.

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<![CDATA[SAT-196 The Use of <sup>11</sup>C-metomidate PET-CT to Detect Unilateral Primary Hyperaldosteronism]]> https://www.researchpad.co/article/elastic_article_6753 Background

Identifying causative adrenal lesions presents a significant diagnostic burden for physicians and radiologists. We describe the use of radiolabelled metomidate to lateralise primary hyperaldosteronism.

Case presentation

A 52-year old Chinese man with a 5-year history of hypertension was referred for hypokalemia [K 2.7 mmol/L (3.6 - 5.0)]. He had been on Telmisartan 80 mg and Amlodipine 10 mg daily and blood pressure at home ranged 110-120 / 70-80 mmHg. There was no history of poor oral intake, persistent diarrhea or vomiting, and he was not on any other prescription or alternative medications. There was no significant family history of hypertension or sudden cardiac death. Clinic blood pressure was 140/84 mmHg. There were no features suggestive of Cushing’s syndrome.

Repeat biochemical tests confirmed hypokalemia (K 3.1 mmol/L), and associated raised bicarbonate 37.3 mmol/L [19 - 29]. Magnesium and creatinine were normal. Aldosterone-renin Ratio was elevated at 8.1 (serum Aldosterone 611 pmol/L [97.3 - 834.0], active renin 2.7 pg/ml [1.8 – 59.4]). Post-saline infusion, non-suppressible serum aldosterone levels of 1137 pmol/L was demonstrated, consistent with autonomous aldosterone production.

A computed tomography of the adrenal revealed a 2.3 cm x 1.9 cm nodule on the left adrenal gland consistent with lipid rich adenoma.

Adrenal vein sampling (AVS) under continuous synacthen infusion was performed. Adrenal to peripheral cortisol ratio was ≥10 for either adrenal veins, confirming cannulation of the adrenal veins. Aldosterone-cortisol ratios showed lateralization to the left adrenal gland (lateralization ratio of 10.35). There was contralateral suppression of the right adrenal gland with ratio of 0.41.

11C-Metomidate PET-CT scan demonstrated a maximum standardised uptake value (SUVmax) of 26.8 over the left adrenal nodule, while the SUVmax of the right adrenal gland was 16.2. Ratio of the left to right adrenal gland SUVmax was 1.65 (above the threshold of 1.25); and was concordant with AVS. This confirmed that the patient had a left functional adrenal adenoma responsible for hyperaldosteronism.

Our patient underwent a left adrenalectomy, and histology was consistent with adrenal cortical adenoma. Prior to surgery he required 72 mmol/l of potassium supplementation daily to maintain K levels of 3.3 – 4.0 mmol/L. Two weeks post-operatively, he was normokalemic (K 4.9 mmol/L) without potassium supplementation. Serum aldosterone normalized to 159.3 pmol/L (active renin 9.3 pg/ml). Blood pressure is well controlled on amlodipine 5mg daily.

Conclusion

Targeted molecular imaging such as 11C-Metomidate PET-CT could aid localisation of functional adrenal disease to guide definitive surgical management. In the future, this could obviate the need for invasive and technically complex procedures like AVS.

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<![CDATA[SAT-205 POEMS: A Medical Odyssey]]> https://www.researchpad.co/article/elastic_article_6657 Introduction: POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes) syndrome is a rare disorder with poorly understood pathogenesis. The incidence of endocrinopathy associated with POEMS syndrome has been recognized more frequently in the last two decades, ranging between 67-84%. The cause of endocrine dysfunction associated with the syndrome is not known, but has been described to include hypogonadism, hypothyroidism, abnormalities of glucose metabolism, hyperprolactinemia, gynecomastia in men, hyperestrogenemia, calcium abnormalities and adrenal insufficiency (AI).

Case: A 38 y/o Hispanic male was initially referred to nephrology with complaint of leg swelling. Subsequently, the patient was referred to endocrinology for abnormal thyroid function studies and ongoing fatigue. Patient had prior medical history of recently diagnosed hypothyroidism treated with levothyroxine 100 mcg daily. The most bothersome complaint was pitting edema in the lower extremities with associated pain. He also endorsed right shoulder pain exacerbated by use of the right arm. He reported unintentional weight loss of about 30 pounds in the past 2-3 years, denying night sweats. He did endorse feeling fatigued, skin darkening, and erectile dysfunction. On exam patient was afebrile, BP 120/71 mm/Hg, HR 87 bpm, no goiter, no gynecomastia, skin hyperpigmentation, darkening creases of the palms, pitting edema in lower extremities. Work up showed abnormal lambda monoclonal bands in plasma and monoclonal lambda free light chain in urine. Bone survey showed lytic lesion in right scapula. [prolactin 15.6 ng/ml (normal (NL)= 0-25), free testosterone 23.1 pg/ml (NL= 35.0-155.0), total testosterone 205 ng/dl (NL= 250-1100), LH 8.2 MIU/ml (NL= 1.2-8.6), FSH 4.3 MIU/ml (NL=1.3-19.3), TSH 17.8 uIU/ml (NL= 0.45-5.33), free T4 0.62 ng/dl (NL= 0.58-1.64), free T3 3.05 pg/ml (NL=2.5-3.9), TPO antibody (AB) negative, IGF-1 41 ng/ml (NL=53-331), AM cortisol 8.2 ug/dl (NL=6.7-22.6), ACTH 99 pg/ml (NL=6-50), aldosterone 3 ng/dl (NL ≤28), renin activity 2.78 ng/ml/h (NL=0.25-5.82), 21-hydroxylase AB negative, 17-hydroxyprogesterone 54 ng/dl (NL=42-196), DHEA-S 88 mcg/dl (NL=106-464)]. ACTH stimulation test (250 mcg) was performed with basal cortisol 8.0 ug/dl (NL= 5.0- 21.0), basal ACTH 93 pg/ml (NL=6-50), 30min cortisol 9.7 ug/dl (NL=13.0-30.0), 60min cortisol 10.2 ug/dl (NL=14.0-36.0). Pt was diagnosed with primary AI and started on hydrocortisone. CT abdomen and pelvis with contrast showed normal adrenal glands.

Discussion: Physicians should be cognizant of a unifying diagnosis in a syndrome of such a broad presentation. Endocrinopathies vary in extent of dysfunction and may fluctuate during the course of POEMS syndrome. Multidisciplinary management as well as regular reassessment of endocrine function is integral in managing this complex disease.

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<![CDATA[SAT-227 Long-Term Outcomes of Two Siblings with X-Linked Congenital Adrenal Hypoplasia Due to a Mutation in NR0B1 (DAX1) Gene: Reproductive and Neuropsychiatric Aspects]]> https://www.researchpad.co/article/elastic_article_6624 Background: X-linked congenital adrenal hypoplasia (CAH) is a rare disease caused by mutations in the NR0B1 (DAX-1) gene. Non-classical manifestations have been described, including late-onset adrenal insufficiency (AI) and gonadotropin-independent precocious puberty (GIPP). We report long-term endocrine and neuropsychiatric outcomes of two siblings with CAH due to mutation in NR0B1.Case report: A 2-yr-old boy was referred due to progressive clinical signs of puberty since 6 months of age. At the age of 3 yr, AI was diagnosed, and the molecular analysis revealed a mutation in the NR0B1 (p.Cys65Leufs*6). Glucocorticoid replacement resulted in reduced testicular volume and decreased testosterone levels. At 11 yr, cyproterone acetate was indicated due to pubertal progression and bone age advancement. At 17 yr the patient had incomplete sexual development and no pubarche. Testosterone levels declined, despite pubertal levels of basal and GnRH-stimulated gonadotropin levels, indicating partial hypogonadotropic hypogonadism. Adult height was 156 cm (SDS: -2.7) within his target height of 161 cm (SDS: -2.1). This patient also presented a psychiatric diagnosis of mood disorder and attention-deficit/hyperactivity disorder (ADHD), and was under methylphenidate, topiramate and sertraline. Both the patient and his mother had SNP array performed, which excluded contiguous gene syndrome. His younger brother also harbored the same mutation in the NR0B1, confirmed shortly after birth. AI was diagnosed with 1 month of age. Cortisone acetate and fludrocortisone were initiated. At 11 months of age, he presented signs of pubertal development with an elevated ACTH and testosterone levels with suppressed gonadotropins, confirming the diagnosis of GIPP. He was treated with cyproterone acetate. At 8 yr, a pubertal response to the GnRH test was detected, and leuprorelin was added. At 9 yr, due to the low growth velocity and advanced bone age, rhGH was started. However, this patient presented a poor compliance and severe obesity (BMI 33 kg/m2). Treatment for GIPP and secondary CPP was stopped at 10 yr, with bone age of 13.5 yr and height of 151 cm (SDS: - 2.3). The diagnosis of ADHD and autism spectrum disorder was made after neuropsychiatric assessment and the patient received treatment with methylphenidate and sertraline. Conclusion: Pubertal development of patients with CAH due to NR0B1 mutations can be heterogeneous. However, the intriguing neuropsychiatric features in two siblings may suggest a role of NR0B1 in neuropsychological development or other still unknown underlying genetic defect.

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<![CDATA[SAT-229 Bilateral Pheochromocytoma as Incidental Finding in a Patient with Neurofibromatosis Type 1]]> https://www.researchpad.co/article/elastic_article_6611 Background.

In contrast to other genetic syndromes associated with Pheochromocytoma and Paraganglioma (PPGL) in which yearly biochemical screening is recommended, in neurofibromatosis due to the low penetrance of these tumors, screening is only recommended when there is clinical suspicion1. Given that signs and symptoms of catecholamine excess are vague and non-specific, clinicians should keep a low threshold for biochemical testing in these patients.

Clinical Case.

70 year old female with Neurofibromatosis type 1 (NF-1) diagnosed at age 24, hypertension and atrial fibrillation, was referred to our institution after being found incidentally with bilateral adrenal nodules. She had a 2 year history of poorly controlled, labile hypertension. Treatment at the time of presentation included doxazosin, metoprolol, valsartan and hydralazine. She denied other symptoms of catecholamine excess.

Further workup revealed elevated 24 hour urine normetanephrine at 2,530 mcg (ULN 500 mcg) and metanephrine at 1,325 mcg (ULN 290 mcg). Serum metanephrines were also elevated with free metanephrine of 1.6 nmol/L (ULN 0.5 nmol/L) and free normetanephrine of 4.1 nmol/L (ULN 0.9 nmol/L). Her biochemical metanephrine profile was consistent with pheochromocytomas in NF-1. MIBG uptake confirmed the presence of bilateral pheochromocytomas. She underwent a complete right adrenalectomy and a left cortical sparing adrenalectomy. Her adrenocortical function remains adequate. Post operatively while her blood pressures were no longer labile, she continued to require anti-hypertensive therapy.

Conclusion.

Patients who are at risk of developing pheochromocytomas and paragangliomas due to genetic syndromes or known germline mutations need ongoing clinical follow and biochemical testing for timely case detection. While in NF-1 pheochromocytomas are usually unilateral and present during early adulthood, they can present with bilateral disease and later in life2. During surgical treatment, even with unilateral disease, adrenocortical function should be preserved when possible3. Hypertension may persist despite complete surgical resection.

References

1. Lenders JWM, Duh Q-Y, Eisenhofer G, et al. Pheochromocytoma and Paraganglioma: An Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism. 2014;99(6):1915-1942.

2. Moramarco J, El Ghorayeb N, Dumas N, et al. Pheochromocytomas are diagnosed incidentally and at older age in neurofibromatosis type 1. Clinical endocrinology. 2017;86(3):332-339.

3. Neumann HPH, Tsoy U, Bancos I, et al. Comparison of Pheochromocytoma-Specific Morbidity and Mortality Among Adults With Bilateral Pheochromocytomas Undergoing Total Adrenalectomy vs Cortical-Sparing Adrenalectomy. JAMA network open. 2019;2(8):e198898.

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<![CDATA[SAT-191 A Case of Hypoplastic Left Heart Syndrome and Paraganglioma]]> https://www.researchpad.co/article/elastic_article_6519 INTRODUCTION:

Cyanotic heart disease and paragangliomas are two rare diagnosis. Co-occurrence of congenital cyanotic heart disease and pheochromocytomas/paragangliomas has been described, but the mechanism is unclear. In those patients where immediate cyanosis resulting from the congenital heart disease happens right after birth there is an association with an earlier detection of tumor compared to those with cyanotic heart disease later in life (26.6 years vs 46.3 years respectively) [1]. The objective of this case is to highlight this association, as a high degree of suspicion needs to be had when caring for individuals with cyanotic heart disease to pursue evaluation of these tumors. CASE: A 23-year-old man with a chief complaint of diffuse abdominal pain was found to have a 2.6 x 2.8 cm smoothly marginated soft tissue mass in the right lower quadrant on abdominal computed tomography. Patient had a known history of hypoplastic left heart syndrome (mitral atresia-aortic atresia) who had undergone a three-stage Norwood repair in childhood. In his adulthood was diagnosed with Central Adrenal Insufficiency, and Type 2 Diabetes Mellitus. At the time of presentation patient was short of breath, tachycardic (heart rate 115), and tender to palpation of his right lower quadrant. Plasma normetanephrines were 3.8 nmol/L (normal < 0.9 nmol/L), 24-hour urinary excretion of normetanephrine was 1117 mcg/24h (normal 103-390 mcg/24h). Plasma metanephrine levels were normal. A nuclear medicine whole body scan with metaiodobenzylguanidine (MIBG) scan confirmed a MIBG avid tumor in the right lower quadrant. Preoperative management was initiated with oral doxazosin. He underwent laparoscopic surgery with removal of a 3 cm pelvis mass resected from the retroperitoneal tissue deep to the peritoneum along the gonadal vein and ureter. Final pathology confirmed the diagnosis of a paraganglioma. Postoperatively, plasma normetanephrines were corrected at 0.86 nmol/L. Patient underwent genetic testing that was negative for FH, MAX, MEN1, NF1, RET, SDHA, SDHAF2, SDHB, SDHC, SDHD, TMEM127 and VHL. CONCLUSION: Multidisciplinary approach to these patients is essential given their complex hemodynamics. Long term follow up is necessary to monitor for tumor recurrence, review of case reports may suggest a higher risk of recurrence [1]. Of these case reports there has been no strong genetic association found, the most popular theory is a causal relationship from their cyanotic heart disease. References:

Zhao B, Zhou Y, Zhao Y et al (2018) Co-occurrence of pheochromocytoma-paraganglioma and cyanotic congenital heart disease: A case report and literature review. Front Endocrinol. https://doi.org/10.3389/fendo.2018.00165

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<![CDATA[SAT-208 An Adrenal Incidentaloma with Extramedullary Hematopoiesis]]> https://www.researchpad.co/article/elastic_article_6505 Introduction: Adrenal adenomas are incidentally noted during nonadrenal disease imaging at a rate up to 4%. Frequency of incidentalomas increases with age, most being adrenocortical adenomas. This case highlights an uncommon etiology of such an adrenal mass finding. Case Description: A 37-year-old with a history of hypertension, hypothyroidism, and tobacco use was admitted after post-operative complication. Prior to surgery, she had been experiencing right upper quadrant pain along with 70 lb weight loss and diarrhea. She otherwise had frequent palpitations. Patient had undergone cholecystectomy and common hepatic duct injury was noted. Imaging revealed a 5.3 x 3.5 cm right adrenal mass previously unknown prior to surgery. Hormonal workup was negative for overproduction of aldosterone, cortisol, DHEA-S or metanephrines. Discussion: Patient underwent successful resection of adrenal mass, revealing adrenal adenoma with osseous metaplasia and hematopoiesis. Extramedullary hematopoiesis is a usually discovered incidentally as in this case. Typical sites are the spleen and liver. Cases of adrenal gland manifestations have been reported in the presence of hemoglobinopathies (thalassemia, hereditary spherocytosis) or myelofibrosis. At four-month follow-up, laboratory testing on this patient didn’t suggest any erythrocytic or leukocytic disorder. Conclusion: This case highlights an uncommon finding of hematopoiesis in an adrenal incidentaloma without any underlying hematologic defect or disease. References: Motta, I., Boiocchi, L., Delbini, P., Migone De Amicis, M., Cassinerio, E., Dondossola, D., Rossi, G. and Cappellini, M. D. (2016), A giant adrenal myelolipoma in a beta‐thalassemia major patient: Does ineffective erythropoiesis play a role?. Am. J. Hematol., 91: 1281-1282. doi:10.1002/ajh.24446. Stewart P, Newell-Price J. (2016). The Adrenal Cortex. In Melmed S, Polonsky K, Larsen P, Kronenberg H, Williams Textbook of Endocrinology. (13th ed., pp 489-555). Philadelphia, PA: Elsevier

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<![CDATA[SAT-211 Is Doxazosin the Right Choice for Preoperative Management of Pheochromocytoma in Pregnancy?]]> https://www.researchpad.co/article/elastic_article_6488 Pheochromocytoma (PCC) in pregnancy is a very rare condition, with a reported incidence of less than 0.2 per 10.000 pregnancies (1), having fetal and maternal mortality of 50% if untreated (2). Choosing between selective vs. nonselective alpha blockers as preoperative management in pregnancy is controversial.

We report a case of a 39-year-old female having episodes of nervousness, hand tremors, palpitations, diaphoresis, and headaches since 2012; she also had a history of multiple miscarriages and uncontrolled hypertension(HTN) since 2018. In 2019, she was found to have plasma metanephrines 690pg/mL (0-62) and plasma normetanephrine of 3803pg/mL(0-145). Repeat labs showed: plasma metanephrines 2.071pg/mL(0-62), normetanephrine 6.289pg/mL(0-145), norepinephrine 4.268pg/mL(0-874), epinephrine 555pg/mL(0-62). CT abdomen showed a 6.2x5.1x6.4cm left adrenal mass, with 44 Hounsfield units and less than 50% of washout. She was started on Doxazosin 2mg/d, which eventually was increased to 6mg/d with optimal blood pressure (BP) control. After her preoperative workup, she was found to be 7 weeks pregnant. OB-GYN recommended left adrenalectomy before 14 weeks gestation. She had left open adrenalectomy, with normal range postoperative BP, off of antihypertensive medications.

The diagnosis of PCC in pregnancy should be considered in the setting of paroxysmal HTN, with no proteinuria, episodic palpitations, diaphoresis, facial flushing, and orthostatic hypotension. Anterior adrenalectomy early in pregnancy is recommended. The increased intraabdominal pressure, fetal movements, uterine contractions, delivery process, and abdominal surgical intervention can trigger the catecholamine release by the PCC, which could lead to placental abruption and miscarriage; and the rebound hypotension may lead to severe hypoxia, causing fetal demise (2). Definitive preoperative treatment between selective vs non-selective alpha-blockers remains controversial. Phenoxybenzamine, appeared to produce better attenuation of intraoperative HTN, however, it is associated with more maternal intraoperative/postoperative hypotension, and reflexive tachycardia. It crosses the placenta and accumulates in the fetus, increasing the risk of neonatal hypotension and respiratory depression (3,4,5). On the other hand, Doxazosin, can be displaced by high levels of catecholamines, but it is less associated with intraoperative/postoperative hypotension (6,7), with no reports of neonatal hypotension, and respiratory depression. Due to the lack of presynaptic a2-adrenoceptor blockade there is less reflex tachycardia, reducing the use of Beta-blockers (8). Doxazosin seems to be a safe, affordable alternative for preoperative management of PCC in pregnant patients.

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<![CDATA[SAT-192 Eletriptan (Relpaxa<sup>Tm)</sup> Causing False Positive Elevations in Urinary Metanephrine]]> https://www.researchpad.co/article/elastic_article_6444 Background:

The diagnosis of pheochromocytoma depends crucially on the demonstration of excessive production of catecholamines. This step, however, is fraught with several difficulties, in particular with false-positive test results. Drugs such as phenoxybenzamine and tricyclic antidepressants are the most frequently associated causes for false-positive results. Other medications are also known to cause a false positive elevation of urinary metanephrines. We are reporting a patient with markedly elevated urine metanephrines associated with the use of Eletriptan hydrobromide (RelpaxaTM), a drug commonly used for treating migraine.

Clinical Case:

A 29-year-old man with a history of migraine managed on ibuprofen and recently started Eletriptan presented to the emergency room complaining of a 24-hour history of progressively worsening headaches. At the time of initial evaluation his blood pressure was in the 220s/160s with a creatinine of 1.9 mg/dL with unknown baseline. He was managed on an IV nicardipine drip. Due to his young age he underwent an evaluation for secondary causes of his hypertension. Laboratory: normal aldosterone/renin level (ratio was 0.4), normal midnight salivary cortisol and normal thyroid function studies. Urine screening for drug abuse was also negative. A 24-hour urine metanephrine level, while the patient was taking Eletriptan, was markedly elevated (normetanephrine 1341mcg (ref 82–500) and metanephrine level of 2494 mcg (ref 45–290). In contrast, the plasma metanephrines were only mildly elevated (metanephrines level 27 pg/ml (ref 0–62) and normetanephrine level of 255 pg/ml (ref 0–145)). Adrenal CT did not reveal any evidence of adrenal nodules. Additionally a Gallium-68 PET/CT scan did not reveal any evidence of pheochromocytoma or paraganglioma. Eletriptan was discontinued and his blood pressure was controlled on oral medications. Within one week of stopping Eletriptan his urine metanephrines (metanephrine 76 mcg/ 24 hrs, normetanephrine 277 mcg/dL) and plasma metanephrines (metanephrine 39 pg/mL, normetanephrine 148 pg/mL) normalized.

Conclusion: The discrepancy between plasma and urine metanephrines in our patient suggests the possibility of a false positive test. Eletriptan, a second generation triptan drug, is a selective 5-hydroxytryptamine 1B/1D receptor agonist and has been shown to reduce carotid arterial blood flow, with only a small increase in arterial blood pressure at high doses. However, Eletriptan has no significant affinity or pharmacological activity at adrenergic α1, α2, or β; dopaminergic D1 or D2; muscarinic; or opioid receptors. It is also interesting to note that Eletriptan use is contraindicated in uncontrolled hypertension. It is possible Eletriptan may affect the assay of urine metanephrines. However, the exact mechanism of Eletriptan causing elevated urine metanephrines in our patient is not clear.

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<![CDATA[SAT-199 Diagnostic Dilemma: An Adrenal Incidentaloma in a Young Adult]]> https://www.researchpad.co/article/elastic_article_6293 Introduction:

In an adult endocrine clinic, the majority of patients referred for evaluation of an adrenal incidentaloma are older than 30 years of age. It is important to be reminded that a patient may be diagnosed with an adrenal mass at any age but the etiology may vary depending on the age at presentation.

Clinical case:

An 18 year-old African American female with no significant past medical problems presented with a 2 month history of flank and abdominal pain associated with nausea and vomiting. An abdominal CT scan and a dedicated adrenal CT showed a right adrenal mass measuring 2.2 x 2.6 cm. The noncontrast Hounsfield units were 23, enhanced Hounsfield units 210, and delayed Hounsfield units 72. The calculated washout was 44%, not consistent with an adrenal adenoma. An MRI of the abdomen showed a 2.5 cm right adrenal nodule. The lesion did not demonstrate significant loss of signal between in and out of phase imaging, therefore the characteristics were not consistent with a lipid rich adenoma. Laboratory tests included an ACTH of 31 pg/mL (6-48 pg/mL), cortisol 8.7 ug/mL at 10:57 am (7-9 am 5.27-22.45 ug/mL), aldosterone 10.1 ng/dL (6-48 ng/dL), renin 2.2 ng/mL/hr (upright 0.5-4.0 ng/mL/hr), DHEA-sulfate 129 ug/dL (44-248 ug/dL), plasma free metanephrine 0.10 nmol/L (0.00-0.49 nmol/L), and plasma free normetaneprhine 0.41 nmol/L (0.00-0.89 nmol/L). The 24-hour urine norepinephrine, epinephrine, and metanephrine were all normal, however the 24-hour urine dopamine was elevated, 824 ug/24 hrs (52-480 ug/24 hrs). Subsequently, plasma dopamine, norepinephrine, and epinephrine were all within the reference range. The patient had a robotic-assisted right adrenalectomy removing a 5.7 x 3.5 x 1.7 cm gland, weighing 16.3 grams. The pathology demonstrated a ganglioneuroma within the right adrenal gland measuring 2.2 x 2.0 x 2.7 cm, negative for neuroblastoma or blastic components. Focal hemorrhage was noted, there was no tumor necrosis, and no mitotic figures were present. The tumor appeared to be encapsulated in the adrenal gland and the Ki-67 stain was negative in ganglioneuroma cells.

Conclusion:

Adrenal adenomas that appear as incidentalomas in young adulthood are extremely rare. Evaluating younger versus older adults found to harbor an adrenal “incidentaloma“ requires a unique approach for each age group, as the differential diagnosis varies widely. In our patient, the imaging was extremely concerning and diagnostic considerations included neuroblastoma, adrenocortical malignancy, pheochromocytoma, or ganglioneuroma. Adrenal ganglioneuromas are most frequently diagnosed in fourth and fifth decades of life. In younger adults ganglioneuromas are usually found in the retroperitoneum and posterior mediastinum. For our patient, surgical resection of the adrenal mass confirmed the pathologic diagnosis and provided definitive cure.

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<![CDATA[SAT-203 Misleading Diagnosis of Cushing’s Syndrome on Pramipexole]]> https://www.researchpad.co/article/elastic_article_6218 We present an intriguing case of a patient incorrectly diagnosed with Cushing’s disease secondary to pramipexole use for restless leg syndrome (RLS). 61-year-old male with symptoms of 55 lb weight gain, progressive fatigue, and subjective muscle weakness presented to endocrinology office for work-up of possible Cushing’s syndrome. Physical exam was significant for mild facial plethora, purple striae, and central obesity. Patient’s history includes diagnosis of prolactin-producing pituitary microadenoma 30 years ago treated with bromocriptine with normalization of prolactin and resolution of adenoma. Patient notes ten years ago, he was started on pramipexole 1 mg TID for severe RLS. Given patient’s clinical symptoms he underwent hormonal testing which was notable for an abnormal 1 mg ONDST with morning cortisol 2.44 mcg/dL (normal &lt 1.8 mg/dL) and two abnormal late night salivary cortisol 0.177 mcg/dL and 0.199 mcg/dL (normal &lt 0.122). Repeat MRI showed a 0.4 cm hypoenhancing lesion in the left side of the anterior pituitary gland. Patient was referred for IPSS. His central-to-peripheral plasma ACTH ratio was as follows: before CRH administration: left 5.8, right 1.2; after CRH administration: left 16.4, right 2.7. These results demonstrated positive IPSS indicating centralization or a pituitary source of ACTH excess. Patient was going to be referred to neurosurgery for left pituitary adenoma resection, but literature search revealed a study showing pramipexole causing an increase in cortisol levels in physiologic studies involving healthy subjects. Due to these findings, labs were repeated while holding pramipexole. His morning cortisol and ACTH levels were normal. Late night salivary cortisol x3 were normal: 0.038, 0.071, and 0.024 mcg/dL (normal &lt 0.090 mcg/dL). The 24 hour urine free cortisol x2 was also normal. These negative biochemical findings showed no evidence of hypercortisolism off of pramipexole. This further complicated the case as the patient had positive IPSS. In order to help exclude the diagnosis of an ACTH secreting pituitary tumor, a DDAVP stimulation test was performed showing a normal response. Based on these tests it was concluded he does not have Cushing’s and that his hypercortisolism was related to pramipexole use. Repeat brain MRI showed no structural evidence of any pituitary lesion. We report a very rare case of pramipexole use leading to a false diagnosis of Cushing’s syndrome. This was fortunately identified prior to patient undergoing unnecessary surgery. We recommend awareness of pramipexole use associated with hypercortisolism to prevent incorrect diagnosis of Cushing’s syndrome.

Schilling, J. C., Adamus, W. S., & Palluk, R. (1992). Neuroendocrine and side effect profile of pramipexole, a new dopamine receptor agonist, in humans. Clinical Pharmacology & Therapeutics, 51(5), 541-548.

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<![CDATA[SAT-188 An Unusual Case Of Intra-adrenal Purely Norepinephrine Secreting Pheochromocytoma]]> https://www.researchpad.co/article/elastic_article_6141 Background: In 40% of pheochromocytoma/paraganglioma (PPGL) cases a causal germline mutation in a well-defined gene can be identified. The remainder are sporadic. The most common hereditary syndromes are NF1, MEN2 and VHL. Paragangliomas usually produce exclusively norepinephrine (NE) and are more likely to metastasize than adrenal tumors. Exclusively NE producing adrenal tumors are extremely rare and almost always associated with VHL or SDH syndromes (1).

Clinical Case: A 45-year-old South Asian woman with a 5-year history of HTN controlled on losartan presented emergently complaining of chest pressure. Cardiovascular workup was unrevealing. CT chest showed an incidental 3.2 x 2.4 cm lipid-poor left adrenal adenoma. No further follow-up done at that time. Two years later she presented with recurring episodes of chest pressure and uncontrolled HTN on amlodipine, metoprolol and losartan. She denied panic attacks, diaphoresis and other symptoms of anxiety. She denied personal and familial history of clinical features seen in NF1, MEN 2, VHL or SDH. Plasma metanephrines were 26 (<=57 pg/mL) and free normetanephrine 902 (<=148 pg/mL). 24-hour urine metanephrine was 178 (58-203 mcg/24h), normetanephrine 2422 (88-649 mcg/24h) and total metanephrine 2600 (182-739 mcg/24h) confirming the diagnosis of a solely NE secreting PPGL. MRI abdomen showed a well-circumscribed 3.3 cm lipid-poor left adrenal mass. MIBG scan and SPECT CT showed a focal area of intense radiotracer uptake corresponding to a 3.2 x 2.5 cm mass within the left adrenal gland. No extra-adrenal activity was demonstrated. Alpha blockade was started with doxazosin and the patient asked to salt/fluid load. She underwent left adrenalectomy. Pathology revealed a 5 x 2.5 x1.1 cm intra-adrenal pheochromocytoma; Chromogranin (+), synaptophysin (-), MIB1 low reactivity < 5%, S100 positive in sustentacular cells, keratin (-), EMA (-), Inhibin (-). Genetic testing for VHL, SDHD, SDHB, SDHC and MAX has been ordered per guidelines. One month post-operatively the patient had no symptoms of adrenergic overactivity and normal plasma metanephrine levels.

Clinical Lessons: This rare case of norepinephrine-only secreting pheochromocytoma is made even more unusual by absence of features of autosomal dominant hereditary syndromes. This may be sporadic or present a novel VHL, SDHD, SDHB, SDHC or MAX germline mutation (2).

1.

Eisenhofer, G., et al., Distinct gene expression profiles in norepinephrine- and epinephrine-producing hereditary and sporadic pheochromocytomas: activation of hypoxia-driven angiogenic pathways in von Hippel–Lindau syndrome. 2004. 11(4): p. 897.

2.

Ercolino, T., et al., Uncommon clinical presentations of pheochromocytoma and paraganglioma in two different patients affected by two distinct novel VHL germline mutations. Clinical Endocrinology, 2008. 68(5): p. 762-768.

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<![CDATA[SAT-210 When Acne, Hirsutism and Menstrual Irregularities Are More Than PCOS]]> https://www.researchpad.co/article/elastic_article_6111 Background: Polycystic ovarian syndrome (PCOS) mimics non-classic congenital hyperplasia (NCCAH), presenting with hyperandrogenic symptoms. NCCAH is usually diagnosed later in life, where 21-hydroxylase (21OHD) is the most common deficiency. There are more than 300 mutations in 21OHD, being V281L one of the described mutations.

Clinical Case: 23 y/o female patient G0P0 comes to the office complaining of irregular periods, frontal hair loss, weight gain, acne and hirsutism. She has had noticed these changes since menarche; however, her acne was getting worse. Was seen 2 months prior to presentation by her gynecologist who order a free Testosterone that was elevated (6.4 pg/mL, n<4.2 pg/mL), with normal TSH (1.1 uIU/mL, n,0.45-4.5). She was not taking any medication. Her mother has history of 2 spontaneous abortions and her sister has acne and hirsutism as well. On physical exam BMI was 26, it was noticed comedones and papules on her face, back and shoulders. Ferriman-Gallwey scale was >8. At the initial visit due to the clinical scenario, it was thought that she had hyperandrogenic syndrome, probably secondary to PCOS. Serum blood test were ordered and showed an elevated total testosterone (71 ng/dL, n,8-48ng/dL), free testosterone (8.4 pg/mL, n<4.2 pg/mL), 17- OH pregnenolone performed by liquid chromatography-tendem mass spectrometry (LC-MS/MS) was (429 ng/dL, n, 35-290 ng/dL luteal phase) and androstenedione LC-MS/MS (1941 ng/dL, n, 41-262 ng/dL) which confirmed NCCAH diagnosis due to 21OHD. She had no desire to become pregnant at the time of evaluation; however, was concern about fertility and genetics. Was started on OCPs and genetic testing was positive for V281L mutation in the CYP21A2 gene, being homozygous for this mutation. Three months after, her acne and frontal hair loss were better, and a trial of spironolactone 50 mg daily, was prescribed. For her sister and mother was suggested to consult endocrinology, due to possible same disease.

Conclusion: this case highlights the importance of recognizing NCCAH as a cause of hyperandrogenism. Molecular genetic analysis should be offered with genetic counseling to patients, since they can carry a severe allele which can affect their progeny. Clinicians should be aware of the importance of family history when diagnosing NCCAH on their patients; for detection, treatment and genetic counseling of NCCAH on family members as well, as found in this case.

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<![CDATA[SAT-224 Recurrent Co-Driver Mutation in CTNNB1-Mutant Aldosterone-producing Adenomas (APA), Causing Reversible Hypertension in Puberty, Pregnancy or Menopause]]> https://www.researchpad.co/article/elastic_article_6037 Background: Three patients with a syndrome of LH/HCG-activated primary aldosteronism in pregnancy or menopause carrying somatic CTNNB1 mutations were reported four years ago (Teo et al. NEJM 2015). This proved but half the story. Diagnosis of an APA in a 12-year old boy with severe hypertension revealed an apparently essential co-driver mutation. Methods: WES of tumour and blood was performed in the pubertal boy. Candidate genes were Sanger sequenced in other APAs from GB/Ireland, and France with known or suspected CTNNB1 mutations. LHCGR, GNRHR and CYP11B2 expression were measured in all available patients’ APAs and the adjacent adrenal gland (AAG) by RT-PCR. RNA and gDNA from the zona glomerulosa (ZG) of the proband’s AAG were collected by laser capture microdissection for Sanger sequencing of GNA11 and CTNNB1. Function of mutant genes was assessed by measurement of aldosterone production and LHCGR expression by immunofluorescence (IFC) in NCI-H295R adrenocortical cells and primary human APA cells. Results: The proband’s APA contained a p.(S45F) somatic mutation in CTNNB1, and a p.(Q209P) somatic mutation of the GTPase-activating residue (Q209) in GNA11. Mutations of Q209, to P or H, were also found in six other GB/Irish patients with previously identified mutations of CTNNB1 (S33C, G34R, T41A, S45F, or S45P). All seven patients remain normotensive 2-12 years post-adrenalectomy, including some with long-standing pre-operative hypertension. Four of the 13 French patients with CTNNB1 exon 3 mutant APAs have somatic mutation of Q209 of either GNA11 (n=3) or GNAQ. In comparison with their own AAG, the GB/Irish double mutant APAs showed an increase in expression of LHCGR, CYP11B2 and GNRHR by 32-166, 158-18980, and 1174-6642 fold, respectively. All four French double-mutants had >10 fold higher LHCGR than APAs with single mutations of CTNNB1 or other genes. Hyperplasia of ZG was observed in the ZG of the boy’s AAG but no APCC was detected. Homozygous or heterozygous Q209P mutation of GNA11 was detected in multiple ZG samples in RNA and/or gDNA but WT in CTNNB1 exon 3. H295R cells (CTNNB1 S45P) were GNA11 WT. Overexpression of GNA11 Q209 mutation increased aldosterone secretion to 465% of GNA11 WT overexpressing cells (n=6, P<0.001) and CYP11B2 expression was also increased several-fold. Smaller increases were seen in primary human adrenal cells after double-transfection by GNA11 and CTNNB1 mutants (n=3, P<0.001). This also caused membrane expression of LHCGR, visualised by IFC. Conclusions: APAs with double mutation of GNA11/GNAQ Q209 and CTNNB1 have a distinct phenotype, in which hypertension is triggered by high LH or HCG, and cured in all cases by adrenalectomy. GNA11/Q mediates the aldosterone response to ANGII, and the Q209 codon is analogous to the Q227 of GNAS, mutated in McCune Albright. Mosaicism for GNA11 may cause ZG hyperplasia.

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<![CDATA[SAT-216 Retroperitoneal Paraganglioma: Case Report]]> https://www.researchpad.co/article/Nf771c2c0-3c71-41f0-908e-c72ee3ed7160 Introduction: Paraganglioma (PGL) is a rare type of neuroendocrine neoplasm able to secrete neuropeptide and catecholamines. It can occur in any location between the neck and the pelvis. Most of the PGLs are diagnosed in the third to fifth decades and clinical presentation is variable and depends upon catecholamine secretion and tumor location. PGLs occur in the abdomen in 85% of cases. There are no unique imaging characteristics specific for PGLs, consequently, these tumors can be mistaken with other primary abdominal tumors.

Clinical-Case: We present the case of a 65-year-old woman with history of hypertension (diagnosis at 40 years) and dyslipidemia. She denied family history of hypertension. In the context of a recent diagnosis of type 2 Diabetes Mellitus, she underwent abdominal ultrasound which revealed a large, heterogeneous nodular formation with partial liquid content, measuring 12x15 cm, adjacent to the left hepatic border. Abdominal CT scan revealed an intra-abdominal mass, with 14cm (largest diameter), showing intimate contact, with no cleavage plan with the posterior wall of the gastric fundus, suggesting Gastrointestinal Stromal Tumor. A left adrenal nodule with 3.3 cm was also present, rounded, hypoechogenic, with regular margins and homogeneous. Echoendoscopy with biopsy of the retro-gastric mass showed a neuroendocrine neoplasia. At this point she was sent to an endocrinologist. When questioned she referred headache, diaphoresis and anxiety complaints for 3 years. At examination, a painless abdominal mass in the epigastrium and left hypochondrium was found. Laboratory evaluation revealed urinary metanephrines 11738 (64-302) ug/day, urinary normetanephrines 5832 (162-527) ug/day, renin 15.5 (1-8.2) pg/mL, aldosterone 28.6 (10-160)ng/dL, cortisol after 1 mg dexamethason 1,18 µg / dl (less than 1,8ug/dl) and chromogranin A 36.6 nmol / L (less than 3nmol/l). MIBG scintigraphy revealed fixation only in the large known retroperitoneal mass. The patient underwent excision of the retroperitoneal mass and of the left adrenal gland without complications. The histological diagnosis revealed, respectively, paraganglioma and adrenal cortical adenoma. Four weeks after surgery laboratory results were normal (urinary metanephrines 202 ug/24h and normetanephrines 382.0 ug /day; Chromogranin A 2.60 nmol/l). The results of the genetic tests including SDHB, SDHD, SDHC, VHL and MAX were negative.

Conclusion: This report emphasizes the necessity to include paraganglioma in the differential diagnosis and management of retroperitoneal tumors avoiding the risk of the biopsy in this kind of tumors.

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