ResearchPad - adrenal 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[MON-160 The Burdens of Adrenal Insufficiency: A Survey Study from Two Tertiary Care Centers in the United States]]> https://www.researchpad.co/article/elastic_article_8804 Background: Adrenal insufficiency (AI) is a chronic disorder necessitating life-long replacement. Patients’ quality of life and health outcomes depend on knowledge and comfort level with self-management.

Objective: To determine patients’ knowledge in regards to diagnosis and management, estimate burden of disease and to identify predictors of adverse outcomes in patients with AI

Methods: Survey study of patients with AI evaluated at two tertiary medical centers between 2015 and 2019. Collected variables included data on circumstances of AI diagnosis, symptoms, management, burden of disease, and overall well-being.

Results: Among 785 patients (mean age at diagnosis 44.2 ± 18.0, 64% women, and 92% Caucasian), 310 (40%) had primary AI (PAI), 255 (33%) had secondary AI (SAI) not related to glucocorticoid use, and 211 (27%) had steroid-induced AI (SIAI). Patients were diagnosed with AI after presenting with symptoms for a median of 1 year (0-6), 28% with symptoms lasting >2 years, 44% visiting emergency room (ER) at least once prior to diagnosis. A third of patients reported a discordant diagnosis from their medical record.

Baseline glucocorticoid replacement therapy included hydrocortisone (HC) in 447 (59%), median of 20 mg (IQR 15 - 25mg), prednisone in 190 (25%), median of 5 mg (IQR 4 - 7.5mg), other regimens in 38 (5%), and no steroids in the remainder (85, 11%); 197 (26%) patients reported daily equivalent HC dose of >25 mg. Overall, 549 (73%) of patients reported use of stress dose steroids at least once per year, higher in patients taking HC >25 mg/day (3.2 vs 2.7 times per year if HC<25mg/day, p=0.01). Improper use of stress steroids was reported in 193, 25% patients. Patients taking HC>25 mg /day reported a higher number of adrenal crises (1.6 vs 1.3 in patients on HC<25 mg/day, p=0.04). Among 314 (41%) patients who reported ER visits due to adrenal crisis, only a third received prompt glucocorticoids.

One third of patients described their general health as fair or poor. Predictors of negative perceptions of overall health included SIAI (OR 6.2 and 2.5, vs PAI and SAI respectively), poor understanding of diagnosis (OR 2.6), daily HC>25 mg (OR 2.1), and presence of at least one adrenal crisis (OR 2.3) (p<0.001 for all).

Conclusion: Patients with AI experience delay in diagnosis, and a third do not fully understand their diagnosis. In addition to patient education, interventions to improve general health and outcomes may include selecting a physiological glucocorticoid replacement therapy, prevention of adrenal crisis, and improving ER care.

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<![CDATA[SUN-188 Intra-Articular Triamcinolone Injections - a “Slipped” Cause of Cushing’s Syndrome]]> https://www.researchpad.co/article/elastic_article_8763 Background:

Triamcinolone injections are used to treat various orthopedic and rheumatologic conditions; their effects on the hypothalamic pituitary adrenal axis have not been well characterized.

Clinical Case:

A 14 yo female was referred to our clinic for evaluation of low TSH (0.16 µIU/mL) and possible hyperthyroidism. There was no goiter and she appeared euthyroid and had normal free T4 (1.01 ng/dl) but she had typical features of Cushing syndrome (CS), including round facies, thinning of hair, fatigue, truncal adiposity, violaceous striae, facial hirsutism and oligomenorrhea. She was previously healthy and participated in many sports. She did not report any history of exogenous glucocorticoid use but the fasting ACTH (4 pg/ml) and cortisol (0.1 µg/dl) levels were suppressed. Subsequent chart review revealed that she received intra-articular Triamcinolone (TA) to treat “slipping rib” syndrome. This included 3 injections of Kenalog 40 mg/mL, the last in July 2019. Her cumulative TA dose was 440 mg, the equivalent of prednisone 550 mg. Triamcinolone acetonide 1.4 mcg/dL (normal 0-0.1, analyzed by LC-MS/MS) was detected in the urine over 3 months after her last injection.

Conclusion:

- Levels of ACTH and cortisol can be suppressed for several months after intra-articular corticosteroid injections, placing the patient at subsequent risk for adrenal crisis

- In some cases, high doses of Triamcinolone administered by intra-articular injection can cause clinical Cushing syndrome

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<![CDATA[MON-208 Age-Dependent Progression of Renal Dysfunction After Adrenalectomy for Aldosterone-Producing Adenomas in Japan]]> https://www.researchpad.co/article/elastic_article_8761 Context: In patients with aldosterone-producing adenomas (APAs), adrenalectomy causes a rapid decrease in blood pressure and increase in blood potassium levels; however, the effects of these intensive metabolic changes on kidney function with age have not yet been examined in Japan.

Objective: To investigate factors related to the progression of kidney dysfunction after adrenalectomy in different age groups.

Participants: Fifty Japanese patients with APAs with 27,572 health check-up subjects as controls were examined.

Main Outcome Measures: We investigated changes in eGFR after adrenalectomy and characterized patients who progressed to chronic kidney disease (CKD).Results: Receiver Operating Characteristic and multivariate analyses revealed the postoperative cut-off age of CKD to be 50 years (sensitivity, 57%; specificity; 82%; AUC, 0.69) and identified age as a unique factor for the progression of CKD after adrenalectomy. Among preoperative patients with APAs, CKD was 6% for those younger than 50 years (<50) and 40% for those 50 years and older (≥50). As a control, in 27,572 health check-up subjects, the prevalence of CKD was 4.2% in men and 2.5% in women aged 41-50 years and 18.9% in men and 13.3% in women older than 61 years, clearly demonstrating the higher prevalence of CKD in patients with APAs than in healthy subjects, particularly those with APAs ≥50 years. In patients with APAs <50 years, median eGFR before and after adrenalectomy were 95 mL/min/1.73m2 and 88 mL/min/1.73m2, respectively, indicating that the percentage of the decrease in eGFR was -7%, which was not significant (paired t-test, p=0.13). In contrast, in patients with APAs ≥50 years, median eGFR after adrenalectomy decreased to 42 mL/min/1.73m2 from 67 mL/min/1.73m2 (adjusted by age, paired t-test, p=0.01) (percent decrease in eGFR, -24%) Patients with APAs ≥50 years who progressed to CKD showed higher preoperative aldosterone/renin ratios, lower potassium and chloride levels, lower BMI, and a higher incidence of a history of cardiovascular events and KCNJ5 mutation rates.Conclusion: Age is the most important predictor of the progression of kidney dysfunction after adrenalectomy in Japanese patients with APAs, particularly those with a history of cardiovascular events and positivity for KCNJ5 mutations.

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<![CDATA[SUN-163 Metastatic Spindle Cell Sarcoma Unmasked by Bilateral Adrenal Hemorrhage Resulting in Adrenal Insufficiency]]> https://www.researchpad.co/article/elastic_article_8759 Introduction:

Adrenal hemorrhage (AH) is rare and can be life-threatening when bilateral AH causes adrenal insufficiency (AI). Risk factors include trauma, stress, sepsis, anticoagulant and antiplatelet use, hematologic disorders, and underlying adrenal tumors. We describe a patient whose bilateral AH led to a diagnosis of an underlying malignancy and caused AI.

Clinical case:

A 71-year-old man with well-controlled HIV presented with fatigue, weight loss, and acute lower abdominal pain.

Four months prior to presentation, he underwent hip arthroplasty. His post-operative course was complicated by multiple pulmonary emboli and a new left 11.6 x 7.3 x 8.9 cm cystic retroperitoneal lesion with a density of 29 Hounsfield units on CT, thought to be a pancreatic pseudocyst or adrenal or retroperitoneal hemorrhage. Since the size remained stable on repeat CT three days later, he was discharged on rivaroxaban. On the day of presentation, he acutely developed severe abdominal and back pain. CT scan revealed a new 8.0 x 7.8 x 7.8 cm right adrenal collection and increased size of the prior left adrenal lesion to 13.1 x 10.6 x 13.0 cm. MRI confirmed bilateral adrenal masses with intralesional AH, as well as numerous peritoneal and retroperitoneal implants not noted on prior imaging.

He remained stable and was managed non-operatively. Sodium (Na) and potassium (K) ranged 134-138 mmol/L (135-145) and 3.7-4.3 mmol/L (3.5-5.1), respectively. On presentation, morning cortisol and ACTH were 11 ug/dL and 27 ng/L (6-50), respectively, with an undetectable aldosterone and PRA 0.65 ng/mL/hr (0.25-5.8). Subsequent ACTH levels were 71 and 102 ng/L, and cortisol levels were 12 and 14 ug/dL. ACTH-stimulated cortisol was 15 ug/dL and free cortisol was 0.88 ug/dL. Plasma metanephrines were normal. Hydrocortisone was started and anticoagulation was held indefinitely. Biopsy of a retroperitoneal implant revealed metastatic spindle cell sarcoma.

Three weeks later, given a persistently low Na of 134 mmol/L and increased K of 4.7 mmol/L, although blood pressure and heart rate were normal, he was empirically started on fludrocortisone. He followed up with oncology and was started on palliative chemotherapy.

Clinical lessons:

AH should prompt evaluation for an underlying etiology. In our patient, we suspect he already had a unilateral adrenal metastasis causing the initial unilateral AH, as he had no other risk factor. Four months later, the subsequent bilateral AH was likely caused by further metastatic spread and exacerbated by anticoagulation therapy.

This case also suggests that AH may preferentially affect the zona fasciculata of the adrenal cortex and cause glucocorticoid deficiency, a phenomenon which has been noted on prior case reports. Our patient only needed hydrocortisone replacement initially, followed by fludrocortisone replacement three weeks later.

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<![CDATA[SUN-155 A Complex Case of Adrenal Insufficiency Associated with NLRP1 Gene Mutation in a Patient with Myopathy and Mitochondrial Cytopathy]]> https://www.researchpad.co/article/elastic_article_8751 Most cases of Addison’s disease are due to an autoimmune response, with the most commonly associated genes belonging to human leukocyte antigen (HLA) complex. Genome wide association studies have shown a significant association of variants of Nuclear Localization Leucine-Rich-Repeat Protein 1 (NLRP1) with Addison’s disease. NLRP1 protein is involved in the assembly of inflammasome which promotes the secretion of interleukin-1β, interleukin-18 and downstream inflammatory responses to regulate inflammation. With underlying myopathy and mitochondrial disease, coexisting adrenal insufficiency may be challenging to identify. A 36-year-old female presented for evaluation of fatigue, myalgia, and dyspnea for several years. She carried a diagnosis of asthma, myopathy, gastroparesis requiring a gastric stimulator, and recently diagnosed adrenal insufficiency secondary to long term fluticasone use. Beside low blood pressure of 91/64 millimetres of mercury, physical exam was unremarkable. Lab findings were significant for dehydroepiandrosterone-sulfate (DHEAS) of 7.0 micrograms per deciliter (mcg/dL), Adrenocorticotropic hormone (ACTH) of 7.2 picograms per milliliter and cortisol of 1.4 mcg/dL. Adrenal insufficiency was confirmed with cosyntropin stimulation test. Methacholine challenge test showed worsening asthma. She was managed with empiric stress dose steroids when indicated. Muscle fatigue progressed despite taking ubiquinol, B100 and carnitine. She was further evaluated with muscle biopsy that showed type two fiber atrophy. Muscle coenzyme Q10 was 0.08 mcg/dL, and citrate synthase was 50% of normal, insufficient for electron transport complex I. Whole exome sequencing showed mutations in NLRP1 in addition to Myosin Heavy Chain 2 (MYH2) and Sodium voltage-gated Channel alpha subunit 4 (SCN4a) both of which are associated with myopathy. She was then started on a short-acting glucocorticoid regimen. While her adrenal insufficiency was initially thought to be secondary to inhaled steroids, subsequent mutation analysis suggested that she was prone to autoimmunity. This case illustrates the association of adrenal insufficiency with NLRP1 mutation. Furthermore, the symptoms of adrenal insufficiency and myopathy can overlap making it difficult to delineate. While so far most studies have dealt with mitochondrial myopathies due to deletions or point mutations in the mitochondrial deoxyribonucleic acid (DNA), a new field of investigation is that of syndromes due to mutations in the nuclear DNA.

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<![CDATA[OR03-04 The Study of Cell Senescence in Cortisol-Producing Adrenocortical Adenomas]]> https://www.researchpad.co/article/elastic_article_8739 Introduction Aging is associated with the pathogenesis of many endocrine disorders such as cardiovascular diseases and diabetes. Cell senescence has been reported as one of their mechanisms. In addition, stress responsiveness has been reported to be associated with cell senescence. In addition, some genetic abnormalities such as mitochondrial DNA (mtDNA) damages or telomere shortening, have been detected in some endocrine disorders. Cortisol is a well-known stress-induced hormone and closely associated with aging. We previously reported that cortisol-producing adenoma (CPA) more abundantly expressed cell senescent markers such as p16 and p21 than other hormone-producing adrenocortical adenomas. However, the detailed pathophysiology of cell senescence and its association with histological features in CPAs have remained virtually unknown. Therefore, we analyzed cell senescent markers (telomere length, mtDNA copy number, mtDNA deletion and p16 and p21 immunoreactivity) and analyzed their correlation with clinicopathological factors in CPA patients.

Methods & Materials Forty CPA cases was immunohistochemically evaluated. Twenty CPA, ten adjacent ZF and six non-functional adenoma (NFA) were examined for mtDNA abnormalities. mtDNA deletion was evaluated by nested-PCR and mtDNA copy number and telomere length were measured using real-time PCR.

Results p21 immunoreactivity was significantly higher in CPA than that of adjacent ZF (P=0.0001) and significantly inversely correlated with tumor size (P=0.0004). Telomere length was much longer in CPA than that in adjacent ZF(P=0.0038), and NFA (P=0.0018). mtDNA copy number of NFA was significantly higher than that of CPA and adjacent ZF (P=0.0038). mtDNA copy number of compact cells was significantly higher than that of clear cells (P=0.0432). mtDNA copy number of compact cells was positively correlated with urinary free cortisol (UFC) (P=0.0428) and plasma cortisol (F) (P=0.0609). mtDNA copy number of clear cells were inversely correlated with F (0.0497). 4977 bp mtDNA deletion was more frequently detected in CPA (54%) and in adjacent ZF (50%) than in NFA (17%).

Discussion Results of our present study did reveal that CPA harbored more senescent phenotype as demonstrated by abundant p16 and p21, marked telomere shortening, frequent mtDNA 4977bp deletion and relatively low mtDNA copy number, possibly caused by long-term exposure of excessive cortisol in situ compared to NFA. In addition, clear tumor cells could represent more senescent histological phenotype because of their lower mtDNA copy numbers. This is the first study to demonstrate that compact tumor cells were biologically more active than clear tumor cells and could reflect clinical cortisol biosynthesis, resulting in marked functional intratumoral heterogeneity in CPAs.

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<![CDATA[MON-213 Cardiac Damage and Related Risk Factors in Patients with Primary Aldosteronism]]> https://www.researchpad.co/article/elastic_article_8730 Primary aldosteronism (PA) is the most common cause of secondary hypertension. Overseas flow surveys show that compared with essential hypertension (EH), the risk of cardiovascular and cerebrovascular diseases and kidney damages in PA patients is increased, and the mortality rate of cardiovascular events is higher than that in EH patients, in addition,this effect is independent of elevated blood pressure. The difference of cardiac damage between PA and EH patients was analyzed by echocardiography. Methods From April 28, 2017 to April 28, 2019, patients with primary aldosteronism diagnosed by ICD in Department of Endocrinology and Metabolism, Department of Cardiology and Urology were extracted from the adrenal group database of the Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, and ICD diagnosis in Department of Endocrinology and Metabolism during the same period was also extracted. In patients with essential hypertension, the differences of clinical indicators and echocardiography between the two groups were compared, and the differences of cardiac damage and related risk factors between the two groups were explored. Results 295 patients were included in this study, including 148 patients in PA group (50.17%) and 147 patients in EH group (49.83%). There was no significant difference in gender, age, BMI, course of disease and average blood pressure between the two groups (P > 0.05). The levels of serum aldosterone and BNP in PA group were significantly higher than those in EH group, and the levels of serum renin and minimum blood potassium were significantly lower than those in EH group (P < 0.05). Left ventricular diameter (LV), left atrial diameter (LA), interventricular septal thickness (IVS), left ventricular posterior wall thickness (LVPW), ascending aorta diameter (AAO), end-diastolic diameter (EDD), end-diastolic volume (EDV) and stroke volume (SV) in PA group were significantly higher than those in EH group (P < 0.05). It was significantly higher than that in EH group (P < 0.05). The correlation analysis of variables with statistical significance between the two groups showed that serum renin activity level was negatively correlated with LV, AAO, EDD and SV, and the lowest serum potassium level was negatively correlated with LVPW and AAO. CONCLUSION Compared with EH of the same age, course of disease and blood pressure level, PA patients are more likely to suffer from cardiac damage, which is manifested by heart growth, ventricular septal thickening and cardiac function decline, and is closely related to the inhibition of serum renin activity and serum potassium level. Clinical attention should be paid to early screening and treatment of PA and its complications in order to reduce the risk of cardiac death.Key words: primary aldosteronism; echocardiography; cardiovascular 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[SUN-185 Severe Hyponatremia and Type 4 Renal Tubular Acidosis (Functional Hypoaldosteronism) Secondary to Trimethoprim]]> https://www.researchpad.co/article/elastic_article_8710 Introduction:

Trimethoprim-sulfamethoxazole (TMP-SMX) is a commonly used antibiotic. We present a case of severe hyponatremia and Type 4 renal tubular acidosis (functional hypoaldosteronism) in a patient treated with TMP-SMX.

Clinical Case:

A 62 year old gentleman with hypertension, dyslipidemia and a surgically repaired abdominal aortic aneurysm developed an aortic graft infection. He was admitted to hospital for acute right lower limb ischemia with embolic phenomena, and underwent surgical graft explantation. He required multiple courses of antibiotics post operatively.

He was initially referred to Endocrinology for severe hyponatremia, deemed likely to be from a salt losing nephropathy secondary to polymyxin. Thyroid function and morning cortisol levels were normal. He was managed with intravenous hypertonic saline and oral salt tablets. The hyponatraemia resolved a week after polymyxin was stopped.

Intravenous TMP-SMX was commenced the next day at 240 mg BD. A week later, the hyponatremia recurred, with concomitant hyperkalemia and a normal anion gap metabolic acidosis.

The serum sodium was 126 mmol/L (reference interval (RI) 135-145) and the serum osmolality 275 mmol/kg (RI 275- 305). Urine studies showed a high urinary sodium (154 mmol/L) and osmolality (481 mmol/kg), consistent with renal salt wasting. The serum potassium rose to a peak of 6.1 mmol/L (RI 3.5 - 5.0), with a normal anion gap metabolic acidosis (bicarbonate 17 mmol/L (RI 21 – 31)). A paired urine pH of 8 pointed to an inability to acidify the urine.

Given the clinical course and laboratory investigations, the diagnosis of TMP-associated hyponatremia and Type 4 RTA was made. Oral resonium was started to correct hyperkalemia, with a combination of oral sodium chloride and sodium bicarbonate used to treat the hyponatremia and metabolic acidosis. Fludrocortisone was not used given the concerns of causing hypertension in a patient with a diseased aortic graft.

The dose of TMP-SMX was gradually reduced with improvement of the acid-base and electrolyte abnormalities, lending weight to our diagnosis. After the dose of the TMP-SMX was reduced to 80 mg BD, the hyperkalemia and metabolic acidosis resolved. The oral sodium chloride and sodium bicarbonate were gradually tailed off and stopped after cessation of the TMP-SMX.

Clinical Lesson:

Trimethoprim blocks the epithelial sodium channel (ENaC) of the principal cells in the terminal portion of the nephron, similar to potassium sparing diuretics like amiloride and triampterene. The resulting hyponatremia, hyperkalemia and metabolic acidosis can be life threatening. Therefore, monitoring of electrolytes and acid base status is important, particularly in susceptible patients or in those where a high dose of trimethoprim is required.

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<![CDATA[SUN-219 Electron Transport Chain Complex 2 in Mitochondrial Pregnenolone Synthesis]]> https://www.researchpad.co/article/elastic_article_8708 The mitochondrial P450 family of enzymes (SCC), which require the electron transport chain (ETC) complexes III, IV and V, initiate steroidogenesis by cleaving the sidechain of cholesterol to synthesize steroid hormones, an essential component for mammalian survival. SCC is required for full-term gestation, and aberrant expression may cause pseudohermaphroditism, breast cancer or polycystic ovary syndrome. Complex II or succinate dehydrogenase (quinone) is shared with the TCA cycle and has no proton pumping capacity and no known role in steroid synthesis. We now show that succinate is an intermediate metabolite in the TCA cycle and plays a central role physiologically. Specifically, complex II is required for SCC activation, where the proton pump facilitates an active intermediate state conformation at the matrix, so that in the presence of succinate, ATP can add phosphate. A longer intermediate equilibrium state generates a transient stabilization to enhance the binding of phosphate anions in the presence of succinate anions, resulting in higher enthalpy and activity. An inhibition of the processing at the intermediate state stops phosphate addition and activity. We further describe that phosphate circulation brings the molten globule, an intermediate, to an active folded state. This is the first report showing that an intermediate state activated by succinate facilitates ETC complex II interaction with complexes III and IV for metabolism.

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<![CDATA[MON-LB44 Cushing’s Syndrome and Illegal Receptors]]> https://www.researchpad.co/article/elastic_article_8695 Case presentation: A 48-year-old female with HTN presented to the endocrinology clinic for the evaluation of incidental bilateral adrenal masses noted on chest CT for dyspnea workup. At the time of the presentation, she reported generalized fatigue, significant weight gain in the past year and shortness of breath. Her physical exam was remarkable for central obesity. Lab work showed elevated cortisol after 1 mg dexamethasone suppression test x 2 and elevated 24- hour urine cortisol. Plasma free metanephrine levels and aldosterone/ renin ratio were normal. MRI abdomen was done and showed bilateral adrenal masses (left: 5.6 cm, right: 3.2 cm). Patient was diagnosed with Cushing’s syndrome secondary to primary bilateral adrenal hyperplasia and was referred to endocrine surgery who recommended unilateral adrenalectomy. The decision was made to remove the larger left side adrenal mass. On post-operative day one her am cortisol decreased to 2.1 and she was started on hydrocortisone 20 mg in the morning and 10 mg in the evening.

Discussion: Primary bilateral adrenal hyperplasia is a rare cause (< 2 %) of endogenous Cushing’s syndrome, usually occurs in a bimodal age distribution, in childhood and in the fifth- sixth decades. Presentation is variable with most patients having no symptoms or subclinical Cushing’s. The theory is the larger nodule size corelates with the higher cortisol production. Studies have shown between 60-70% of cases has aberrant ectopic hormone receptors which leads to increased cortisol production not only from ACTH but also from other ligands such as serotonin and vasopressin. Aberrant receptor testing examines whether cortisol or other steroid production increases in response to either physiologic or pharmacologic stimulus. Multiple genetic mutations have been associated, the most frequent is mutations in the Armadillo repeat- containing 5 gene identified in 2013. Treatment can either be medical or surgical. Medical therapy can be initiated if testing for an aberrant receptor is positive. In recent years there has been a trend towards doing unilateral adrenalectomy instead of bilateral, with initial remission of symptoms reported in about 84% of cases after unilateral adrenalectomy although there is a small risk of recurrence. Post operatively after unilateral adrenalectomy patients should be monitored for adrenal insufficiency. Our patient declined aberrant receptor testing and opted for surgery and is doing well post operatively.

Conclusion: Primary bilateral adrenal hyperplasia is a rare cause of endogenous Cushing’s syndrome which can be treated either medically or surgically.

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<![CDATA[SAT-LB19 Is There a Need to Use Gadolinium Contrast for Pituitary MRI in the Evaluation of Pediatric Short Stature and Growth Hormone Deficiency?]]> https://www.researchpad.co/article/elastic_article_8684 Short stature is a common concern that necessitates pediatric endocrinology evaluation. Growth hormone (GH) deficiency is often included as an etiology. Brain and pituitary Magnetic Resonance Imaging (MRI) with gadolinium-based contrast agents (GBCAs) is the imaging modality of choice in assessing patients with GH deficiency. Given the significant strides made in MRI technology that allow improved spatial and contrast resolution, the necessity of using contrast material when obtaining brain and pituitary MRI in cases of short stature and isolated GH deficiency should be reassessed. We preformed a retrospective review of otherwise healthy patients with short stature and/or GH deficiency who underwent brain and pituitary MRI without and with contrast, to assess the benefit of contrast administration.

Introduction: Short stature is a common concern that necessitates pediatric endocrinology evaluation. The etiologies of short stature are diverse. GH deficiency is often included as an etiology although it accounts for only 1-2% of short stature cases. The prevalence of GH deficiency is reported to be ~ 1:3500. The vast majority of GH deficiency cases are idiopathic in nature with only 20% due to organic causes. The organic causes of GH deficiency include congenital central nervous system (CNS) anomalies, tumors and other pathologic conditions that involve the pituitary-hypothalamic region. As a result, the radiological assessment of the hypothalamic-pituitary region is considered standard of care for evaluating patients with GH deficiency. Although brain and pituitary MRI is the imaging modality of choice in assessing patients with GH deficiency, its yield in cases of isolated GH deficiency is very low. In a study of 40 otherwise normal patients with isolated GH deficiency, 35 (87.5%) had normal brain MRIs. The abnormal findings of brain MRI in the minority of isolated GH deficiency cases included pituitary hypoplasia, pituitary stalk agenesis, lack of the normal T1-weighted pituitary hyperintensity in the posterior part of the sella turcica, and the presence of a high-intensity signal at the infundibular level representing ectopic neurohypophysis. Traditionally, these brain and pituitary MRI images are obtained with the use of contrast material (gadolinium). The main purpose of using contrast material is for the evaluation of pituitary microadenomas. Given the fact that significant strides made in MRI technology and pituitary microadenomas are not appeared to be associated with GH deficiency, the necessity of using contrast material when obtaining brain and pituitary MRI in cases of short stature and isolated GH deficiency should be reassessed. GBCAs have been shown to deposit in different tissues including the kidneys and the brain. The risk increases with repeated doses. The clinical significance of this deposition is unclear at this time but warrants caution especially in pediatric population who have a longer expected lifespan to manifest any delayed effects. Allergic reactions and gastrointestinal symptoms in pediatric patients can occur with GBCA administration, although the incidence is low. Using contrast material also increases the total cost of the MRI study and prolongs the time needed to complete it. Moreover, in order to use contrast material, intravenous venous (IV) access is required which causes discomfort and additional stress to children and their families.

Therefore, we performed a retrospective review of otherwise healthy patients with short stature and/or growth hormone deficiency who underwent brain and pituitary MRI without and with contrast, to assess whether contrast administration led to diagnoses that would have otherwise been missed and/or impacted the patient’s clinical course.Objectives: - To compare the diagnostic yield of non-contrast MRI with pre and post-contrast MRI of the brain and pituitary in evaluation of pediatric patients with short stature and/or growth hormone deficiency.- A secondary objective is to measure the size of the pituitary gland and correlates it with peak growth hormone levels (using insulin/argenine).

Methodology: We included patients who underwent brain/pituitary MRI with/without contrast performed at our institution between Jan 2013-Dec 2018 who have short stature/GH deficiency. We excluded patients with known diagnosis of other pituitary hormone deficiencies prior to obtaining MRI studies, genetic and neurological disorders, known tumors/malignancies of any type, or renal failure. Two pediatric neuroradiologists independently reviewed the brain and pituitary MRI of these patients (each read 50% of the cohort) blinded to the clinical data and diagnoses. Each radiologist initially reviewed only the non-contrast portions of the studies, and subsequently, the same radiologist reviewed the entire study, including pre- and post-contrast portions in a separate session. The two sessions were 6 weeks apart to avoid recall bias. Several imaging findings including size and morphology of pituitary gland, presence of congenital anomalies or focal lesions and any associated intracranial findings systematically recorded, and subsequently analyzed.

Hypotheses: 1.The incidence of finding congenital pituitary cysts is the same when obtaining brain/pituitary MRI imaging using gadolinium contrast versus when not using contrast in patients with short stature and or isolate GH deficiency.

2.The incidence of discovering abnormal infundibulum is the same when obtaining brain/pituitary MRI imaging using gadolinium contrast versus when not using contrast in patients with short stature and or isolate GH deficiency. 3.Small pituitary size correlate with GH deficiency.

Results: -We identified 327 patients with short stature/GH deficiency from Jan 2013-Dec 2018-224 (68.5%) are males and 103 (31.5%) are females. -The mean age at the time of imaging is 10 years and the median is 11 years. -161 (49.24%) have height z-score < -2.25 and 166 (50.76%) have height z-score > -2.25.-82 (25.07%) have IGF1 z-score for age < -2, 102 (31.19%) have z-score ≥-2 to ≤ -1, 141 (43.12%) have z-score > -1 and 2 (0.62%) have no level done.-63 (19.27%) have GH peak <5, 87 (26.61%) have GH peak 5-7.99, 53 (16.21%) have GH peak 8-9.99, 30 (9.17%) have GH peak > 10 and 94 (28.75%) did not undergo GH provocative testing. -The kappa coefficient for pars intermedia cyst on pre vs. post contrast imaging is 0.74 and 0.55 for the infundibulum on pre vs. post contrast imaging. -The mean pituitary height for patients with IGF z-score < -2 is 3.9 mm, 4 mm for z-score ≥- 2 to ≤ -1 and 4.3 mm for z-score > -1-The mean pituitary height for patients with peak GH < 5 is 3.8 mm, 4.2 mm for peak 5-7.99, 4.3 mm for peak 8-9.99 and 4.4 mm for peak > 10.

Conclusion: This question has not been answered or even raised in the literature. Our findings suggest that the there is no added benefit to use gadolinium when obtaining brain/pituitary MRI for the evaluation of GH deficiency/short stature. Furthermore, it seems that there is an association between the pituitary height and the GH status of the cohort which is in line with previous published studies.

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<![CDATA[SUN-198 Metastatic Progression of Adrenocortical Carcinoma: Phenotypic Transformation to ACTH-Independent Cushing’s Syndrome]]> https://www.researchpad.co/article/elastic_article_8657 Background: Adrenocortical carcinoma (ACC) is a rare malignancy. Around 60% of adrenal carcinomas are functioning tumors and may present with distinctive phenotypes (1). Very rarely, as the disease progresses, changes in secretory patterns may be observed.

Clinical Case: A 39-year-old female presented to the hospital with a 1-month history of abdominal pain associated with hirsutism, weight gain, acne, and amenorrhea. Computed tomography of the abdomen showed a 7 cm left adrenal mass with areas of necrosis as well as presumptive metastatic disease involving the liver and lungs. Biopsy of the adrenal mass confirmed the diagnosis of adrenocortical carcinoma. Initial laboratories were compatible with hyperandrogenemia (increased 24-hour urine 17-ketosteroid level of 106.3 mg/24 hr (n 6.0-15.0) and mildly elevated testosterone of 65 ng/dL (n<45)). Aldosterone, renin, and metanephrines levels were normal. The patient underwent adrenalectomy after 1 month and was placed on hydrocortisone replacement. Follow-up biochemical testing showed a decrease in 17-ketosteroids level to 24.7 mg/24hr. DHEAS and testosterone were persistently elevated. Following discontinuation of hydrocortisone, her 24-hour urine cortisol was normal at 18 ug/24hr, (n 6-24) and ACTH was suppressed at 1.8 pg/mL (n 7-63). She was started on mitotane therapy shortly after.

Three months after initiation of treatment, she was admitted for a pulmonary embolism. At that time, she had clear signs of hypercortisolism, such as weight gain, hyperglycemia, easy bruising as well as purple striae. Progressive metastatic disease with enlarged lung and liver masses was observed in imaging. On this occasion, her morning cortisol was elevated at 35 ug/dL and ACTH was suppressed at 1 pg/mL. Th hyperandrogenemia was more evident this time with DHEAS of 778 ug/dl. Steroid supplementation was discontinued, and ketoconazole was started. An elevated 24-hour urinary cortisol (2085 ug/24hr) confirmed the diagnosis of Cushing Syndrome. Given the progression of disease while on mitotane, the patient was started on chemotherapy with etoposide, doxorubicin, and cisplatin.

Conclusion: This case represents an unusual example of the phenotypic transformation of adrenal cancer resulting in new-onset ACTH-independent Cushing’s syndrome while the patient was on treatment. Awareness of such changes in secretory pattern are important to guide therapy and minimize morbidity associated with hypercortisolism.

Reference: (1) Puglisi S, Perotti P, Pia A, Reimondo G, Terzolo M. Adrenocortical Carcinoma with Hypercortisolism. Endocrinol Metab Clin North Am. 2018 Jun;47(2):395-407.

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<![CDATA[SAT-LB44 WNT2B Regulates Adrenocortical Progenitor Cell Fate And Zona Glomerulosa Identity In Vivo]]> https://www.researchpad.co/article/elastic_article_8652 Dysregulation of normal adrenal structure and function contributes to a spectrum of diseases from hypoplasia to cancer. Peripheral adrenocortical progenitor cells in the zona glomerulosa (zG) centripetally migrate and differentiate to replenish steroidogenic cells of the zG and the inner cortex over time (1). Both the fate of progenitor cells and aldosterone production by steroidogenic cells in the zG are regulated by Wnt signaling (2,3), but the cell-specific effects of individual Wnt ligands in the adrenal are not fully understood. To further characterize Wnt signaling components crucial for progenitor cell maintenance and zG identity, we analyzed mouse adrenals using single molecule in situ hybridization (smISH), which revealed the previously unknown expression of Wnt2b exclusively in the adrenal capsule. Wnt2b is co-expressed with the Wnt signaling potentiator Rspo3, the loss of which causes zG depletion and reduced adrenal size in mice (4). Therefore, we hypothesized that capsular WNT2B activates Wnt signaling in the underlying cortex to maintain the undifferentiated state of progenitor cells. To define the role of WNT2B in these processes, we generated Wnt2b conditional knockout (cKO) mice by crossing a capsule-specific Gli1-CreERT2 driver (5) and a floxed Wnt2b allele (6). We administered tamoxifen to 6-week-old male mice and assessed the effects of Wnt2b loss 4 weeks later. Gli1-CreERT2 activation significantly decreased Wnt2b expression (P<0.001) and resulted in a lower adrenal to body weight ratio in Wnt2b cKOs compared to controls (P<0.05). Adrenocortical proliferation (Ki67) was significantly decreased in Wnt2b cKO mice (P<0.0001), suggesting that WNT2B may mediate progenitor cell self-renewal. To characterize the effect of WNT2B loss on Wnt signaling, we assessed activation of the primary Wnt effector β-catenin. High β-catenin activity in the zG observed in wild-type mice was disrupted in Wnt2b cKO mice, together with markedly reduced expression of adrenocortical Wnt target genes Axin2 and Wnt4. In addition, Wnt2b loss resulted in downregulation of steroidogenic genes Cyp11b2 (P=0.0139) and Hsd3b6 (P=0.0679). Together, these data suggest that capsule-derived WNT2B activates cortical Wnt signaling to maintain the identity of both undifferentiated progenitor cells and differentiated steroidogenic cells of the zG, which has important implications for adrenal homeostasis and disease, including both primary adrenal failure and neoplasia.

References: (1) King et al., PNAS, 2009 Dec 15;106(50):21185-90. (2) Berthon et al., Hum Mol Genet., 2010 Apr 15;19(8):1561-76. (3) Heikkila et al., Endocrinol., 2002 Nov;143(11):4358-65. (4) Vidal et al., Genes & Dev., 2016 Jun 15;30(12):1389-94. (5) Ahn & Joyner, Cell, 2004 Aug 20;118(4):505-16. (6) Tsukiyama & Yamaguchi, Neurosci Lett., 2012 Mar 14;512(1):48-52.

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<![CDATA[SAT-108 Growth Hormone Deficiency in a Patient with Ectodermal Dysplasia]]> https://www.researchpad.co/article/elastic_article_8640 Background information:

Ectodermal dysplasia (ED) is a rare heterogeneous group of genetic disorders of ectodermal derived tissues, characterized by abnormalities in skin, teeth, hair and eccrine glands. Growth failure in these children varies depending on the genetic mutation and has not been well characterized. This clinical case report presents a 11-year-old male with a heterozygous mutation in WNT 10 A, a variant of the hypohydrotic ED gene, who was found to have growth hormone (GH) deficiency and treated with GH.

Case report:

He was born at 35 weeks gestation by C-section with a birth weight of 5 lbs. 12 oz. to a mother who had invitro fertilization with donor eggs from the maternal aunt with ocular myasthenia gravis and sperm from the father. Pregnancy was complicated by twin gestation and polyhydraminos. He had transient myasthenia gravis and treated with pyridostigmine for 3 months for feeding problems and swallowing difficulty. He also had arthrogryposis of the distal upper extremities attributed to placental transfer of the maternal aunt’s myasthenia gravis antibodies.

He was referred to the endocrine clinic for evaluation of his growth failure around the age of 8 years. His growth chart indicated that he grew along the 5thpercentile until age 5 year with a gradual decline to the 3rd percentile by age 7 year and close to 2nd percentile by age 8 year. His BMI was at 7th percentile. Mid parental height was 5’9”. There was no history of delayed adolescence in the family. His twin sister had very mild form of arthrogryposis with dental delay but steady linear growth. He also had decreased exercise tolerance. His body tended to become hot during sports activities and had to wrap his face and neck with cold soaked towels. His other problems included delayed dental development with conical incisor, thin nail, missing teeth and hearing defects that raised suspicion for ectodermal dysplasia. Genetic testing at the age of 4 years had demonstrated a heterozygous mutation in the WNT 10A gene, an important gene for tooth development. Physical examination revealed a mild facial dysmorphism with conical incisor, missing teeth and high arched palate. He had contracture of the proximal inter phalangeal joints of the hands. Investigations revealed a normal thyroid function test, IGF-1 and IGFBP-3 level, CBC, sedimentation rate, chemistry panel and celiac titer. The bone age was concordant with his chronological age of 8 years. A GH stimulation study demonstrated a peak GH level of 4.94 ng/ml. An MRI of the brain revealed a normal pituitary gland. He was started on GH therapy with 0.3 mg/kg/week at age 9 year. His height improved from 2nd percentile at age 9 year to 20th percentile by age 11 year on growth hormone therapy. His exercise capacity and stamina also improved.

Conclusion:

Growth failure and GH axis should be evaluated in children with ED. GH therapy improves growth velocity and exercise capacity in patients with ED.

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<![CDATA[SAT-104 Unraveling the Connection Between Cortisol and Pediatric Idiopathic Intracranial Hypertension]]> https://www.researchpad.co/article/elastic_article_8633 Background: Idiopathic intracranial hypertension (IIH) is a condition of elevated intracranial pressure without identifiable secondary causes. The childhood incidence is 0.7 per 100,000 and increases with age, obesity, and female gender. Few case reports in the literature, and our own experience, suggest there may be an association between IIH and adrenal insufficiency (AI) but the real extent is unknown. Aim: To describe the prevalence of AI in children presenting with IIH to a large pediatric referral center. Methods: Retrospective chart review identified all children who presented with IHH and had cortisol measured between January 2010 and September 2019. Based on morning, random or 1 mcg ACTH stimulated cortisol levels, adrenal functioning was classified as: (1) deficient (peak cortisol <16 μg/dl, AM cortisol <5 μg/dl), (2) at risk (peak cortisol 16 - 20 μg/dl, AM cortisol 5 - 13 μg/dl or random < 13 μg/dl), or (3) sufficient (peak cortisol >20 μg/dl, AM or random cortisol >13 μg/dl). Descriptive data present mean (+/- standard deviation), and chi-squared (χ 2) tests of differences are used to examine differences between the adrenal functioning groups. Results: Participants (N=64) were 40.6% male, of mixed ancestry (61% non-Hispanic white; 19% African-American, 16% Hispanic White and 5% Asian), with a mean age of 10.8 (4.8) years. Cortisol levels were obtained at an average of 0.6 (1.9) years after diagnosis of IIH; 23% and 52% of patients had insufficient or at risk cortisol levels. The majority of those in the insufficient (70%) or at risk (80%) groups were exposed to topical, nasal or inhaled corticosteroids, but not systemic. Only 60% and 12 % of those with IIH and insufficient or at risk cortisol testing, respectively, underwent definitive testing with a stimulation test. Adrenal function did not differ by age, race/ethnicity, zBMI, nor prolong exposure to steroids (> 2 weeks), time between IIH diagnosis and cortisol testing (all P>.05). Those in the deficient group were less likely to be female (33%) than those in the at risk (61%; χ 2=3.07, df=1, P=.001) or sufficient (81%; χ 2=7.30, df=1, P<.001) groups. Those with AI were more likely to have history of asthma (53%; vs: 18% at risk and 12% normal; both P>.05) Conclusions: Steroid use and AI are common in IIH and need consideration as a cause of IIH development. Appropriate diagnosis and treatment of AI in children who present with IIH may lead to its resolution, significantly impacting clinical outcomes of these children. In our cohort, the majority had AI or at risk cortisol levels, and many did not undergo further testing. All young children who present with IIH should be evaluated for steroid exposure, including non-systemic steroids, and undergo evaluation for AI. Caution should be utilized in pediatric providers prescribing these medications. More prospective studies are required to evaluate the effects of steroid use in relation to IIH development.

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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[SUN-187 A Case of Adrenal Mass with Elevated ACTH and Cortisol in a Woman with No Cushingoid Features]]> https://www.researchpad.co/article/elastic_article_8608 Background

Adrenal incidentalomas can present with subclinical Cushing’s Syndrome (SCS), which is defined as elevated cortisol levels without overt clinical signs or symptoms. Inaccuracies in ACTH levels due to issues with the assay and non-classic presentation of Cushing’s Syndrome (CS) can delay appropriate diagnosis and timely intervention.

Clinical Case

A 50-year-old female with a history of an incidentally discovered 3.4 x 1.8 cm adrenal mass was referred for evaluation of hypercortisolism (midnight salivary cortisol 0.17 μg/dL, normal < 0.09 μg/dL) with lack of suppression of both ACTH (19 pg/mL, normal 6-50 pg/mL) and cortisol (13.1 μg/dL, normal 6.0-18.4 μg/dL) on overnight 1-mg dexamethasone suppression test (DST). Pheochromocytoma work up was negative.

Her medical history was remarkable for premature ovarian failure at age 40 and osteoporosis at age 48 (Lumbar spine T-score -3.6, Femoral neck T-score -3.7, Hip T-score -2.7).

She denied alcohol abuse and depression screening was negative. She reported high levels of stress and insomnia. She denied muscle weakness, acne, or change to body habitus. Fasting blood glucose was intermittently as high as 212 mg/dl but HbA1c was 5.5%. She did not have a history of hypertension or glucocorticoid use. Her BMI was 20 kg/m2 and she did not appear Cushingoid. A pitutiary MRI showed no evidence of pituitary lesions or enlargement.

Discussion and Follow up

A non-suppressed ACTH made an adrenal source of cortisol unlikely. The working diagnosis was pseudo-CS secondary to stress, loss of diurnal rhythm due to insomnia, or overlooked depression.

She was taking supplements, including biotin, and was asked to discontinue these for two weeks. Repeat 1-mg DST revealed an elevated cortisol of 9.8 μg/dL with a once again non-suppressed ACTH of 20 pg/mL. Her dexamethasone level was 109 ng/dL (normal after 1 mg dexamethasone 180-950 ng/dL), which may suggest slightly faster metabolism. All ACTH levels were run on Immulite assays, which has recently been suggested to be unreliable (1). When repeated using the Roche Assay, ACTH was low at 1.6 pg/mL. Given suppressed ACTH in conjunction with hypercortisolemia and osteoporosis, an adrenal source of CS was confirmed. Diagnosis was further solidified by a DHEA-S level of 11.4 μg/dL (normal 35.4 - 256 ug/dL). She underwent adrenalectomy and pathology revealed adrenal cortical adenomas.

Conclusion

The correct diagnosis of adrenal CS in this patient was delayed due to erroneously higher ACTH result by the Immulite assay. Similar cases have been reported in the literature with the use of Immulite assays for measurement of ACTH leading to invasive diagnostic procedures and even unnecessary pituitary surgery (1).

1.

Greene LW, Geer EB, Page-Wilson G, Findling JW, Raff H. Assay-Specific Spurious ACTH Results Lead to Misdiagnosis, Unnecessary Testing, and Surgical Misadventure-A Case Series. J Endocr Soc. 2019;3(4):763-72.

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<![CDATA[SAT-LB13 Clinical Utility of 21-Deoxycortisol in Congenital Adrenal Hyperplasia]]> https://www.researchpad.co/article/elastic_article_8602 Introduction Congenital Adrenal Hyperplasia (CAH) is most often caused by mutation of the 21-hydroxylase gene (CYP21), which results in underproduction of cortisol with overproduction of precursor steroids and their metabolites by the adrenal glands. Historically the most common biomarker used for detecting CAH in pediatric patients is 17-Hydroxyprogesterone (17OHP). Another less commonly used biomarker for 21-Hydroxylase deficiency is 21-deoxycortisol (21DOF), which increases from very low levels in normal patients to high levels in affected patients as 17OHP rises to very high levels. In this study we performed retrospective analysis of serum 21DOF concentration in specimens that had been genotyped for mutations in the CYP21A2 gene, or had been submitted to our laboratory for provocative adrenocorticotropin (ACTH / Cosyntropin) stimulation testing. Methods: Biochemical testing for 21DOF concentration was measured by LC-MS/MS. Briefly, a TX-4 HPLC system (Thermo-Fisher) with Agilent® 1100 pumps (Agilent Technologies, Inc.) and a Sciex® 5000 (Danaher) triple quadrupole mass spectrometer in positive mode atmospheric pressure chemical ionization (APCI) was used for detection in Multiple Reaction Monitoring (MRM) mode. Genetic testing was performed using the CAHDetx test, which detects the 12 most common small mutations and large gene deletions/conversions in CYP21A2. Genetic Correlations: 21DOF was quantifiable (above the LLOQ of the assay) in 4% (n=24/600) of specimens where no mutation was detected. 21-DOF was quantifiable in 42% (122/292) of specimens with 21-hydroxylase enzyme mutations as determined by the CAHDetx test. Those mutations included In2G, I172N, V281L and others. Some mutations such as Q318X did not result in a detectable increase in 21-deoxycortisol. ACTH Stimulation Response: 21-deoxycortisol was below the quantitation limit in both the baseline and stimulated samples in ~35% (52/148) of submitted samples. The 21-deoxycortisol was quantifiable in only the stimulation sample in ~45% (65/148) of ACTH stimulation submitted, and was quantifiable in both baseline and stimulated samples in the remaining ~20% (30/148) of ACTH stimulation pairings. The extent of 21-deoxycortisol increase ranged from 1.2-fold to 116-fold with a median 14-fold increase. Clinical Significance: The use of 21-deoxycortisol may be beneficial in reducing the rate of false positives in CAH diagnosis when used in concert with other steroid hormones, and may eventually reduce the need for provocative testing to confirm CAH diagnosis.

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