Cushingoid Features Research Articles

SAT-271 Block and Replace Therapy Successfully Improved Symptoms in Recurrent Cyclic Cushing’s Disease

BACKGROUND: Cyclic Cushing’s disease is rare and treatments have not been established for post-surgical recurrent cases. Here, we report a patient with recurrent cyclic Cushing’s disease, whose subjective symptoms improved by administration of metyrapone and hydrocortisone. Clinical Case: A 45‐year-old woman had exhibited face and peripheral edema, hyperphagia, weight gain, hair loss and limb numbness since September X-10. In May X-9, her ACTH and cortisol levels were high (87.8 pg/mL and 28.8 µg/dL, respectively), and she was referred to our department. A brain MRI revealed a pituitary adenoma of 7mm in diameter. Because blood ACTH and cortisol levels turned normal and typical Cushingoid features were absent at the admission to our department, cyclic Cushing’s disease was suspected. Later in September, because subjective symptoms recurred accompanied with blood cortisol level elevation, she was diagnosed as cyclic Cushing’s disease with the examinations including inferior petrosal sinus sampling. Transsphenoidal surgery was performed in November, and immunohistology confirmed ACTH-producing pituitary adenoma based on ACTH positivity. After the surgery, endocrine test results were normalized and subjective symptoms were ameliorated. In March X-3, the blood ACTH level increased again; however, no subjective symptoms were observed. From May X, she had experienced limb numbness, hyperphagia and weight gain again. MRI showed no apparent recurrence, but endocrine tests showed the activity of Cushing’s disease. Urinary free cortisol (UFC) increased to 300–400 µg/day in a 1-week cycle, indicating the recurrence of cyclic Cushing’s disease. Metyrapone treatment was initiated, and the patient was finally discharged after block and replace therapy with metyrapone 2,000 mg/day and hydrocortisone 15 mg/day. After metyrapone treatment, subjective symptoms improved and UFC was normalized. Conclusion: Block and replace therapy with metyrapone and hydrocortisone may be effective for recurrent cyclic Cushing’s disease, especially in cases with a very short cycle.

SAT-127 Localization and Treatment of the Ectopic ACTH Syndrome Using Somatostatin Analogues

Ectopic ACTH syndrome (EAS) is a rare disorder with a high morbidity and mortality due to the sequelae of severe hypercortisolism and possible underlying carcinoma. It is caused by various tumors, some originating from neuroendocrine cells. Optimal management includes localization and removal of the ectopic ACTH source. About 80% of these tumors have somatostatin (SS) receptors, so that SS analogues may be useful in the localization and treatment. This case demonstrates the use of SS analogues in localization and treatment of EAS.A 49-year-old female presented with 7 months of worsening Cushingoid features including rounded plethoric face, full supraclavicular fat pads, facial hair growth, multiple bruises, violaceous abdominal striae, kyphoscoliosis, 4+ peripheral edema, weight gain, hypertension (190/110 mmHg) and thoracic compression fractures. AM plasma ACTH concentration was 333 pg/mL (nl = 6 - 58 pg/mL); serum concentration cortisol was 71.4 mcg/dL (nl = 7 - 23 mcg/dL) and serum potassium concentration was 1.2 mmol/L (nl = 3.6 - 5.1 mmol/L). A 24-hour urine cortisol could not accurately be obtained. High dose 8 mg overnight dexamethasone testing demonstrated suppression of serum cortisol concentration from 71.4 to 6.3 mcg/dL, suggesting pituitary Cushing disease. Pituitary MRI scan revealed a 2.5 mm disc shaped cystic focus suggesting a Rathke’s cleft cyst. No central-to-peripheral ACTH gradient was present on bilateral inferior petrosal sinus sampling suggesting an ectopic ACTH source. There was a 1.2 x 1.0 cm nodule in the left lower lung lobe on CT chest. A gallium-68 dotatate PET/CT scan demonstrated enhancement of this same lung lesion and mild uptake in the left inferior hilum, suggesting a neuroendocrine lung tumor with possible metastases to lymph nodes. Biopsy and resection of the lesion was deferred until after control of her hypercortisolism. 30mg of Sandostatin LAR was started every 4 weeks to control the ectopic ACTH secretion and to confirm that the SS analogue positive lung lesion was the cause of the EAS. Sandsostatin LAR therapy over the next 12 weeks resulted in a steady clinical and biochemical improvement with a decrease in serum cortisol to 9.7 mcg/dL, control of hypertension (108/64 mmHg), weight loss of 6 pounds, and resolution of supraclavicular fat pads, hypokalemia, and peripheral edema. This confirmed our impression that the neuroendocrine lung tumor was the ACTH source.In summary, this patient with EAS had severe clinical manifestations of hypercortisolism and could not safely undergo surgical intervention. This case demonstrates the value of SS analogues (gallium-68 dotatate PET/CT and Sandostatin LAR) in localizing and confirming the source of ectopic ACTH production and markedly improving the clinical and biochemical features of the EAS.

SUN-160 Development of Adrenocortical Carcinoma in an Adrenal Nodule After Nine Years of Size Stability on Imaging: A Case for Critical Review of Efficacy of Radiographic Size Criteria

BACKGROUND: Current consensus guidelines for adrenal incidentalomas smaller than 4 cm recommend re-evaluation up to 2 years. Although there is no consensus for imaging surveillance beyond 2 years, in general, stability in size over time is considered a sign of benign nature. Clinical Case: A 50-year-old African-American woman presented to Endocrinology for resistant hypertension since age 30 and an enlarging right adrenal nodule. She was obese, weighing 138.8 kg with a BMI of 55.97 kg/m2, without clinical Cushingoid features. At her first visit she was taking the following antihypertensives: amlodipine, losartan, hydrochlorothiazide, and clonidine patch. She took no other prescription medications. Her baseline metabolic blood profile was normal. Further testing revealed a profile consistent with possible primary hyperaldosteronism and subclinical Cushing’s syndrome: plasma aldosterone 17 ng/dl, plasma renin activity 0.232 ng/ml/hour, ACTH 10 pg/ml, AM cortisol 8.3 mcg/dl, DHEAS 30 mcg/dl, and 1mg dexamethasone suppression test resulted in cortisol of 7.6 mcg/dl (normal < 1.8 mcg /dl) with a simultaneous dexamethasone level of 357 ng/dl (140 – 295 ng/dl). However, 24-hour urinary free cortisol and urinary metanephrines were within reference ranges. Further confirmatory tests were not performed due to her imaging findings, as described below.The earliest abdominal imaging was a CT abdomen with contrast in 2005 which measured a 2.1 cm right adrenal mass. For various reasons she had repeat CT contrast imaging in 2006, 2007, 2012, and 2014 demonstrating no changes in the dimensions of her adrenal nodule, noting all the studies were performed with contrast only and without Hounsfield unit (HU) measurements. In 2017, a CT abdomen with adrenal protocol demonstrated a right adrenal mass measuring 4 cm x 3.5 cm (increased from 2.1 X 1.2 cm in 2014), characterized by 43 HU pre-contrast, 71 HU post-contrast, and an absolute washout of 29%. Due to high suspicion for malignancy, a PET-CT was performed with FDG, which revealed high uptake in the right adrenal mass.She was referred for a right adrenalectomy and pathology showed adrenocortical carcinoma with some infiltration into adipose tissue. There was a high mitotic index (42 per 50 high powered fields) and Ki67 of 35%, classified as Stage III pT3NxM0. She was referred to oncology and treated with external radiation to the adrenal bed along with initiation of mitotane. Conclusion: This case infers that long-term size stability of an adrenal nodule does not confer full confidence of a benign process. Compared with previous reports in the literature describing long latencies for ACC, this is one of the longest records of size stability over 9 years followed by a size increase 3 years later.

Intralesional corticosteroid injections for the treatment of oral lichen planus: A systematic review

Background: Oral lichen planus is a chronic, immune-mediated disease that can impact the oral cavity significantly. Treatment options include topical and systemic corticosteroid therapy based on the disease severity. Intra-lesional corticosteroid injections (ILCI) have been incorporated in clinical practice as an effective modality to deliver treatment locally to expedite the healing process while limiting systemic toxicity. Purpose: The objective of this systematic review was to evaluate the role of ILCI in treating OLP. Methods: A systematic review of the literature was conducted in the PubMed and Web of Science databases following PRISMA protocol and up to September 2019. All English-language literature on ILCI for OLP was included. Relevant articles were systematically reviewed using multiple levels of elimination by title, abstract, and full text. Data from the included studies were extracted and analyzed. A total of six studies met the inclusion criteria. Results: Triamcinolone acetonide intra-lesional injection demonstrated efficacy and rapid healing of OLP lesions in three studies. Minor adverse events of secondary oral candidiasis and cushingoid features were reported. Conclusion: ILCI may be considered as an effective treatment option for OLP lesions with minimal side effects and risk of disease relapse.

ADRENAL ADENOMA WITH AUTONOMOUS CORTISOL SECRETION ACCOMPANIED BY HOMOLATERAL RENAL CELL CARCINOMA: A CASE REPORT.

Patients with renal malignancies present high risk of adrenal hyperplasia and adenoma, and part of these are primary lesions, mostly non-functional. Here we presented a case diagnosed as primary adrenal adenoma with autonomous cortisol secretion accompanied by homolateral renal cell carcinoma. A 79-year-old woman was referred for evaluation of a left adrenal mass, with a past medical history of severe hypertension, diabetes, and hyperlipidemia. On examination, no clinical signs of cushingoid features were found. Biochemical measurements showed plasma cortisol was 12.77 μg/dL and was not suppressed by 1 mg dexamethasone (DXM) overnight test (13.6 μg/dL). The contrast CT scan presented a 2.2 cm diameter adrenal mass and revealed, unfortunately, a hyperdense mass at the middle-upper pole of the left kidney. Laparoscopic nephrectomy with left adrenalectomy was performed and pathological examination indicated a final diagnosis of benign adrenocortical adenoma and renal clear cell carcinoma. At 2 months postoperatively, without replacement treatment of cortisol, a recovery of circadian rhythm of cortisol secretion was detected, indicated recovery of the hypothalamic-pituitary-adrenal axis. Patients with renal cancer might be accompanied with functional adrenal adenoma. Therefore, screening for adrenal function should be recommended in patients with renal tumors and/or adrenal incidentaloma.

Evidence of Systemic Absorption of Enteral Budesonide in Patients with Fontan-Associated Protein-Losing Enteropathy.

To evaluate for evidence of systemic glucocorticoid absorption in cases of Fontan-associated protein-losing enteropathy (PLE) treated with enteral budesonide, we reviewed the charts of 27 patients with Fontan-associated PLE followed at Children's Hospital Colorado from 2005 to 2018. Cases were excluded for lack of budesonide thserapy or a treatment duration of less than 6months. Charts were examined by two endocrinologists for review of prior biochemical endocrine evaluations, alterations in linear growth, and physical exam findings consistent with steroid excess. Twelve patients met inclusion criteria. Eight had prior documented cortisol screening. Three patients were tested while on treatment with a median fasting AM cortisol of 0.9 mcg/dL; two of these had a concomitantly measured ACTH, both below the detectable limit. Five patients were tested while weaning or having discontinued budesonide, with a median fasting AM cortisol of 9.1 mcg/dL. Eleven patients had decreases in height velocity associated with starting budesonide. Six patients had documentation of cushingoid features by an endocrinologist. In this cohort of children treated with budesonide for PLE following Fontan, clinical signs of systemic glucocorticoid absorption were frequent. Cortisol secretion was suppressed while on therapy, with adrenal recovery noted once budesonide was discontinued. Growth failure and cushingoid features were common findings. While these findings should be confirmed in larger cohorts, we recommend that the evaluation for systemic absorption of exogenous steroids be considered in patients treated with long-term enteral budesonide given the potential risk for adrenal crisis in times of physiologic stressors.

Over the counter medication: a study among dermatology outpatients

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Over-the-counter (OTC) medicine or non-prescription medicine refer to medicine that you can buy without a prescription from a health care professional. The prevalence, clinical patterns and causative agents of cutaneous drug reactions vary among different populations. The most widely used over the counter medication in dermatological practice are topical steroids. The main objective is to know awareness among the people about over the counter medication and clinical analysis of effects caused by them, to find the most commonly used OTC medication.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; Prospective questionnaire based study comprising of 453 cases of cutaneous effects due to over the counter medication was carried out for a period of 1 year. Diagnosis was made mainly based on clinical features.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; Super potent and high potent steroids were the most common OTC medication used which caused nodulocystic acne in 51.6% patients, atrophy in 3.97% patients, tinea incognito in 23.8% patients. Irritant contact dermatitis (due to hydroquinone, cotrimoxazole, neomycin) was seen in 18.5% patients. Fixed drug eruption was seen in 1.32% patients, cushingoid features in 0.66% patient.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Indiscriminate abuse of steroids by people due to lack of awareness should be stopped. This misuse and damage have serious effect on the quality of life of the patients in general and the skin of the face in particular. Management is difficult and necessitates psychological counselling as well as physical soothing of the sensitive skin. For the safety of people Indian association of Dermatology, Venereology and Leprology (IADVL) also started IADVL Task force Against Topical Steriod Abuse (ITATSA).&lt;/p&gt;

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Case Presentation: A 30-year-old female with no prior comorbidities presented to a nephrology center with polyuria and polydipsia of 2-weeks duration. Her 24-hour urine output was more than 6 L/day, and her serum sodium was 147 mEq/L, serum osmolality 302 mOsm/L, and urine osmolality 108 mOsm/L, consistent with a diagnosis of diabetes insipidus. Her glucose, potassium, and calcium levels were normal. Her thyroid-stimulating hormone was 1.13 mIU/L, thyroxine was 8.7 µg/dL, prolactin 34.6 ng/mL, and an 8 am cortisol was 3 µg/dL. She had two normal pregnancies, with last childbirth 8 years back. Her menstrual cycles were regular. Magnetic resonance imaging (MRI) of the brain showed a thickened stalk and enlarged pituitary gland (Fig. 1). On contrast, there was thickening and abnormal enhancement of the stalk and an enlarged pituitary measuring 15 mm, with abnormal heterogeneous enhancement with a peripheral rim of enhancement and a central nonenhancing area (Fig. 1). A diagnosis of infundibulo-hypophysitis was made, and a detailed set of investigations, including antinuclear antibodies, antineutrophil cytoplasmic autoantibodies (ANCA), IgG4, angiotensin-converting enzyme levels, chest X-ray, and skin tuberculin testing was done, with nonrevealing reports. She was started on intranasal desmopressin and prednisolone 60 mg/day with good resolution of symptoms. Desmopressin was stopped after 3 months; after being on high-dose steroids for 6 months, she presented to our center with weight gain and cushingoid features. A repeat MRI was unchanged. Due to a lack of resolution of the MRI features despite prolonged steroid therapy, a whole-body computed tomography scan with a transnasal biopsy of the pituitary gland was planned. Patient's prednisone dose was reduced to 15 mg/day. Patient presented a month later to the medical emergency with acute hypoxemic respiratory failure and acute renal failure, with serum creatinine of 4.75 mg/dL. Chest X-ray showed “white out” lungs, and urine analysis showed numerous red blood cells. A clinical diagnosis of pulmonary-renal syndrome was made, and the patient was started on high-dose steroids and plasma exchange was attempted. However, the patient succumbed within 48 hours of admission. What is the diagnosis?

Managing the challenging cases of pemphigus vulgaris with modified pulse therapy: case series

&lt;p class="abstract"&gt;In pemphigus vulgaris, pulse therapy is a promising modality to achieve better therapeutic response and to minimize the side effects of daily steroids. Here we report 5 different challenging situations where we successfully managed with modification of pulse therapy. Our first case had multiple comorbidities with persistent skin infections managed with dexamethasone and cyclophosphamide pulse (DCP) and interval pulse. The second case was unmarried hypertensive male with poor DLQI managed with Azathioprine pulse therapy. The third case was uncontrolled diabetic patient with pulmonary tuberculosis managed with rituximab. The fourth case was diabetic and hypertensive was managed with one day dexamethasone cyclophosphamide pulse therapy (DCP). The fifth case was not completed family with cushingoid features managed with dexamethasone azathioprine pulse therapy (DAP). Pulse therapy is effective in controlling disease activity in pemphigus. But it can be modified in some situations according to the patient needs.&lt;/p&gt;

SUN-463 Tumor Shrinkage with Preoperative Relacorilant Therapy in Two Patients with Cushing Disease Due to Pituitary Macroadenomas

Background: Relacorilant (RELA, Corcept Therapeutics) is a highly selective glucocorticoid receptor antagonist (GRA) that modulates the effects of excess cortisol, while showing no significant antagonism at the progesterone, mineralocorticoid, androgen, or estrogen receptors. It is currently being investigated for the treatment of patients with endogenous Cushing syndrome (CS) of any etiology. Results from the open-label Phase 2 study (NCT02804750) indicated that treatment with RELA was generally well tolerated and significantly improved glycemic and hypertension control in patients with endogenous hypercortisolism. In this Phase 2 study, two patients with Cushing disease (CD) showed evidence of tumor shrinkage on post-treatment MRIs performed after study completion. Cases: Two patients with de novo CD due to a macroadenoma were treated for 3 months with RELA prior to previously scheduled transsphenoidal pituitary surgeries. Pituitary imaging performed after treatment with RELA revealed significant shrinkage of the tumors. Patient 1 is a 50y/o woman with a pituitary macroadenoma measuring 10 x 6.3 mm on MRI. She presented with cushingoid features (moon face, dorsal & supraclavicular fat, plethora, central obesity, easy bruising, striae) and had confirmatory biochemical tests (ACTH 12.2 pmol/L (NR 1.3-11.1 pmol/L); UFC 177.7 nmol/d (NR 11.1-138 nmol/d); DST 156 ng/mL (15.6 mcg/dL). Patient 2 is a 43y/o man with a pituitary macroadenoma measuring 22 x 25 x 26 mm with suprasellar extension, right displacement of the pituitary stalk, and invasion of the left cavernous sinus on MRI. He also had cushingoid features and confirmatory biochemical tests (ACTH 20.9 pmol/L (NR 1.3-11.1 pmol/L); UFC 356.5 nmol/d (NR 11.1-138 nmol/d); DST 247 ng/mL (24.7 mcg/dL). After completing the 3-month study, pre-operative MRIs revealed reduction in the size of their tumors. The pituitary tumor for patient 1 decreased from 10 x 6.3 mm prior to treatment to 8.0 x 5.7 mm after treatment with RELA. The pituitary tumor for patient 2, decreased from 22 x 25 x 26 mm prior to treatment to 21 x 22 x 19 mm after treatment with RELA. Conclusion: Pituitary imaging performed as part of the pre-operative standard of care revealed tumor shrinkage in two patients with macroadenomas treated for 3 months with RELA. This unexpected finding will be formally investigated in an ongoing Phase 3 study with RELA (GRACE Study, NCT03697109). A potential explanation for this finding could be tumor sensitization to endogenous (hypothalamic) somatostatin via upregulation of somatostatin receptors type 2 (SSTR2) which are downregulated in patients with hypercortisolism. If confirmed, this finding may potentially support the role of RELA as pre-operative medical treatment in patients with CD with invasive macroadenomas.

MON-371 Giant Adrenal Myelolipoma: A Case Report

INTRODUCTION: Myelolipoma is a rare, benign tumor that primarily occurs in the adrenal gland. Through extensive review from different journal databases, there is only one case report published in the Philippines. CASE REPORT: A 48 year old Filipino female complained of left flank pain. She was normotensive, obese, with no Cushingoid features and had no history of weakness. CT scan with contrast showed a left 15cm adrenal mass with fatty component. Endocrine tests (excess of cortisol, catecholamines, and aldosterone) showed non functioning tumor with a normal DHEA-S. She underwent open adrenalectomy with an uneventful postoperative course. Initial histopathology was pheochromocytoma. Immunohistochemical staining revealed positive S100 expressing stromal fat cells and focal marrow precursor cell, LCA with expression of all mature leukocytes within the tumor, Melan-A showing residual adrenal glandular cells at the periphery of the tumor consistent with myelolipoma hence final diagnosis of adrenal myelolipoma. CONCLUSION: Adrenal myelolipomas present as large, hormonally inactive tumors with mass effects. Immunohistochemistry was important to confirm its diagnosis in this case.

SAT-221 False-Positive Urinary Free Cortisol with Oral Contraceptive Use

Introduction It is well-established that estrogen-containing oral contraceptives can raise serum cortisol levels and yield false-positive results on dexamethasone suppression testing, however it is less known that they can raise urinary free cortisol levels by an unknown mechanism. Case presentation A 47-year old woman taking microgestin 1/20 oral contraceptive (OC) was found incidentally to have osteopenia on chest X-ray. Subsequent DEXA scan demonstrated osteoporosis. During the work-up to determine the underlying etiology of her osteoporosis, she underwent a 24-hour urinary free cortisol, which was 207 ug/24 hours (0-50 ug/24 hours). Serum cortisol was 40.1 (6.2-19.4 ug/dL) and overnight 1mg dexamethasone suppression test yielded a cortisol of 2.7. After one week off her OC, serum cortisol was 24.6. After five weeks off her OC, urinary free cortisol was 19 and 1mg dexamethasone suppression test yielded a cortisol of 0.8. On exam, the patient did not have any cushingoid features. MRI of the brain showed a small hypoenhancing lesion, which was determined by neurosurgery to be insignificant. Ultimately, the cause of her osteoporosis was thought to be likely secondary to vitamin D deficiency and calcium malabsorption due to celiac disease. Discussion The biochemical diagnosis of hypercortisolism during treatment with estrogen-containing OCs remains a challenge. Prior studies have demonstrated that serum cortisol levels are typically elevated during OC use and that 1mg dexamethasone suppression testing may yield false-positive results in more than 50% of cases. This is thought to be due to an increase in the major binding protein for cortisol, corticosteroid-binding globulin. Although it is commonly thought that OCs do not affect urinary free cortisol measurements, a recent study showed that more than one-third of women taking OCs had a mild elevation of urinary free cortisol. There are a few hypotheses for the mechanism by which OC use leads to elevated urinary free cortisol, including direct effect on steroidogenesis in the adrenal glands. Our patient had a significantly elevated 24-hour urinary free cortisol and an equivocal 1mg dexamethasone suppression test while on OCs that normalized with OC discontinuation. Further, serum cortisol decreased with OC discontinuation. Conclusion The 24-hour urinary free cortisol level may be altered by oral contraceptive use and is therefore not a valid tool to evaluate for hypercortisolism in women on OCs. References Nickelsen T, et al. (1989). The dexamethasone suppression test and long-term contraceptive treatment. Experimental and Clinical Endocrinology, 94, 275–280. Paschali M, et al. (2013). False positives on both dexamethasone testing and urinary free cortisol in women on oral contraception. Clin Endocrinol, 79, 443-445. Trainer PJ. (2002). Corticosteroids and pregnancy. Seminars in Reproductive Medicine, 20, 375–280.

SAT-597 Diagnostic and Therapeutic Challenges of Riedel's Thyroiditis

Background: Riedel’s thyroiditis is an extremely rare condition characterized by an overgrowth of inflammatory fibrosis that destroys the thyroid follicular architecture. The presentation can mimic malignancy, and due to its rarity, the diagnosis can be delayed. Experience with treatment of this condition is limited, but glucocorticoids and tamoxifen have both been shown in case reports to be effective. Clinical Case: A 68 year old woman presented with dyspnea and weakness. Her exam showed a diffusely enlarged thyroid with a hard texture. Labs showed hypothyroidism for which she was started on levothyroxine, and imaging revealed a goiter with a dominant 3.1cm left thyroid nodule causing tracheal narrowing. Laryngoscopy showed R vocal fold paralysis. FNA of this nodule was non-diagnostic; therefore a core biopsy was attempted which showed no thyroid tissue but skeletal muscle and sclerotic fibro-connective tissue infiltrated by chronic inflammatory cells. Neck CT done 1 month after initial presentation showed a diffusely enlarged and heterogeneous thyroid gland encasing the R carotid artery, infiltrating the peri-thyroidal fat, and causing tracheal narrowing. Given ongoing concern for malignancy, she had open incisional thyroid biopsy showing dense fibrous tissue with chronic inflammation and entrapped skeletal muscle, but again no thyroid tissue was identified. Pathology was believed to be consistent with Riedel’s thyroiditis. She was started on prednisone 60mg daily with improvement in her symptoms, and the steroids were gradually tapered off after 9 months of treatment given stable imaging. The patient remained off steroids and without new symptoms for 1.5 years. She was then admitted for syncope and had further evidence of disease progression on CT scan, with continued growth of the mediastinal component as well as encasement of the bilateral internal carotid arteries, right brachiocephalic trunk, trachea, and upper esophagus. Repeat biopsy again showed dense fibrous tissue with scattered small lymphocytes and plasma cells. She was started back on prednisone 60 mg daily, and imaging done after 3 months of treatment showed shrinkage of the size of the neck and mediastinal mass. However, the patient was noted to have Cushingoid features, including moon facies and weight gain. Therefore, tamoxifen 10mg twice a day was started, and the glucocorticoids were successfully tapered off. To date, she remains asymptomatic without evidence of disease progression while on tamoxifen 10mg twice a day. Conclusion: Riedel’s thyroiditis is a rare chronic inflammatory disease characterized by an invasive fibrotic process that can mimic malignancy. Treatment with glucocorticoids and/or tamoxifen can result in improvement in symptoms and reduction of the size of the mass.

SAT-069 A Case of Congenital Hypoaldosteronism Due to Aldosterone Synthase Deficiency Misdiagnosed as Classic Congenital Adrenal Hyperplasia

Background: The clinical presentation of congenital hypoaldosteronism due to aldosterone synthase (aka corticosterone methyloxidase; CMO) deficiency varies with age and infants present with signs/symptoms of isolated mineralocorticoid deficiency. Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is characterized by combined glucocorticoid, mineralocorticoid deficiency and androgen excess. Clinical Case: A 6.8 y/o Female was referred for genetic testing for classic 21OHD CAH. Past History: Birth weight/length: 7.9 lbs/20 inches at term, uncomplicated pregnancy. Normal female genitalia. She presented within the 1st week of life with poor feeding and poor weight gain. Newborn screen - normal. Inpatient admission at 1 month for failure to thrive. Initial workup significant for Na 127 mg/dL (135 - 145), K 6.5 mg/dL (3.4 - 5.3), mildly elevated random 17hydroxyprogesterone (17OHP) 241 ng/dL (32 - 139) and cortisol 11.6 mcg/dL. She was diagnosed with CAH and initiated on hydrocortisone and fludrocortisone therapy. Medications: Hydrocortisone 2.5 mg twice daily (6.3 mg/m2/day), fludrocortisone 50 mcg daily. Family History: Non-contributory, mid-parental height 154.9 cm. Physical exam: Height 115.6 cm (20th %ile), weight 19.8 kg (18th %ile), BP 109/65 mmHg (95th/ 84th %ile). Well-appearing with no cushingoid features. Genital/pubertal exam: Prepubertal, normal female external genitalia. Laboratory tests: ACTH stimulation test was performed which showed - 0min: 17OHP 19 ng/dL, Cortisol 8 mcg/dL; 60min: 17OHP 155 ng/dL (<1000), Cortisol 23.4 mcg/dL (normal response >18), ruling out the diagnosis of classic 21OHD CAH. Hydrocortisone was discontinued. Further workup (holding fludrocortisone for 48hrs) showed mildly elevated plasma renin activity 3.5 ng/mL/hr (0.8 - 2), low aldosterone 1.8 ng/dL (3.5 - 124), normal 18-hydroxycorticosterone 11 ng/dL (6 - 85). 18-hydroxycorticosterone/aldosterone ratio 6.1 (ratio <10) - suggesting the diagnosis of CMO type I deficiency (1). Targeted genetic testing for CYP11B2 revealed a novel homozygous frameshift alteration in exon 3: p.Phe157Serfs*108 (c.451_469dup), a pathogenic variant predicted to lead to protein truncation and loss of function. Conclusions: This case demonstrates that the clinical presentation of isolated mineralocorticoid deficiency often overlaps features of combined glucocorticoid and mineralocorticoid deficiency. Normal newborn screen along with absence of virilization in a female infant should alert a clinician to consider isolated mineralocorticoid axis defects. The gold standard ACTH stimulation test should be performed to rule out classic CAH and avoid unnecessary glucocorticoid replacement and its long-term side effects. Reference: 1. Root AW, Disorders of aldosterone synthesis, secretion, and cellular function. Curr Opin Pediatr. 2014 Aug;26(4):480-6.

MON-133 Exacerbation of Lactic Acidosis During DKA in Adolescents with Type 1 Diabetes Mellitus with Mauriac Syndrome

Background: Glycogenic hepatopathy (GH: deposition of glycogen in the liver) and lactic acidosis (LA) in poorly controlled type 1 diabetes (T1D) can be the only presentation of Mauriac syndrome (hypercholesterolemia, growth retardation, delayed puberty, and cushingoid features). LA in the background of DKA is the result of poor tissue perfusion due to dehydration and hypophosphatemia. Intensive insulin therapy during management of DKA inhibits glycogenolysis and gluconeogenesis leading to the anaerobic conversion of pyruvate to lactate, thereby worsening the LA. Case series: Patient #1 had ten DKA admissions and had LA in two admissions nine months apart [mean + SD-age: 12.5+/-0.7 years; BMI-28.7+/-0.33 kg/m2, HbA1c:10.5 +/- 0.4%; duration of diabetes: 6.5+/-0.7 years]. Patient #2 had five DKA admissions (age:14 years; BMI: 23.7 kg/m2, HbA1c: 11.7; duration of diabetes: 6 years). Clinical and biochemical characteristics:- initial presentation- pH:7.11+/- 0.06; HCO3: 6.5+/- 0.6 mmol/l, glucose: 807+/-50.4 mg/dl, phos: 5.3+/-0.4, lactate: 3.11+/-1.33 with hepatomegaly on exam. DKA resolved in 27.6 +/- 2.5 hours. Lactate levels peaked to 7.8+/-0.3mmol/l at 13+/-11.5 hours after resolution of DKA and the anion gap at the time of the peak was 13.6 +/- 7.5mmol/l. Liver enzymes were within normal limits on admission and after [AST-21.6 +/-4.04; (5-34 U/L); ALT- 23.6 +/- 9.6 (0-55 U/L)]. Liver ultrasound showed hepatomegaly (18.65 +/-2.33 cm; Normal:8.5-14 cm) suggestive of glycogen versus fat deposition. Basal bolus insulin was continued and the lactate levels declined in 29+/-6.02 hours after the peak to 2.7 +/-1.18mmol/l at the time of discharge. Since the liver enzymes were normal and the LA was improving, no liver biopsy was performed in either of our patients. Conclusions: The lactate levels were high on admission and the levels continued to rise during and after resolution of the DKAin both the patients. Since the patients have a history of poorly controlled diabetes and had hepatomegaly on ultrasound, GH was considered the most likely cause of the hepatomegaly. Our cases illustrate the following points: a. hepatomegaly in poorly controlled T1DM is likely GH. b. elevated lactate levels favor GH as elevated lactate levels are not seen in steatohepatitis, the caveat being that ultrasound cannot discriminate between the two conditions c. DKA can unmask this lactic acidemia which can be present in half of the patients with Mauriac’s syndrome d. liver biopsy is the gold standard for diagnosis of GH though gradient-dual-echo liver MRI can be non-invasive alternative for diagnosis of GH.

SAT-468 Conversion of a Non-Secreting to a Growth Hormone-Secreting Pituitary Adenoma: A Case of Rapid Development of Acromegaly

Introduction: Acromegaly is known to have a slow and insidious course. As a result, the diagnosis is made very late, and at the time of diagnosis most patients have macroadenomas. The average interval from onset of symptoms of acromegaly and diagnosis is approximately 12 years. In addition, conversion of a non-functioning to a functioning pituitary adenoma is very rare. We report a case of a documented non-secreting pituitary macroadenoma turning into a growth hormone secreting one resulting in symptomatic acromegaly in less than 4 years. Clinical Case: A 28 year old African American female presented for evaluation of headaches in 2014. Her past medical history is significant for headaches and childhood epilepsy since age 9. During her workup she was found to have a 1.2 cm pituitary macroadenoma on MRI. Her review of systems showed no evidence of vision changes, galactorrhea, hand enlargement, weakness, changes in body weight or skin pigmentation. Her exam was unremarkable, in particular she did not have any acromegaloid or cushingoid features. Her pituitary hormone work-up was unremarkable, showing no evidence of hormone excess or deficiency. Her IGF-1 was found to be 251 ng/dL (Normal: 78-270). She was evaluated by neurosurgery at that time, who recommended conservative approach with serial follow-up imaging. About 3 years and 8 months later, she was admitted to the hospital for her worsening symptoms of headaches, which were noted approximately 3 times weekly. On further questioning, examination and comparison with old pictures, she was noted to have coarsening of her facial features as well as increase in her ring size. Laboratory tests showed elevated IGF-1 levels on 2 separate occasions at 570 and 551 ng/dL. On repeat imaging, the pituitary macroadenoma was noted to be increased in size to 1.8 cm with increasing suprasellar extension and abutting the anterior aspect of the optic chiasm. She underwent endoscopic excision of pituitary adenoma and reconstruction of sellar floor. The pathology came back positive for human growth hormone staining. IGF-1 level decreased to 244 ng/mL in less than 4 months after surgery. Conclusion: Conversion of non-secreting pituitary adenoma to a growth hormone secreting one can happen over a relatively short time span, resulting in symptomatic acromegaly. We had a unique opportunity to observe this since the patient had previous imaging and biochemical work-up which we could use for comparison. This is contrary to the classic description of acromegaly where the clinical picture develops very slowly over many years or even decades.

MON-396 Biochemically Silent Adrenal Mass in a Hypertensive Female

We describe a case of a biochemically silent pheochromocytoma, which raises the question about the appropriate pre-operative approach in cases of biochemically “silent” adrenal tumors. A 37-year-old white female was referred to our endocrinology clinic for evaluation of a large right sided adrenal incidentaloma. She was symptomatic for episodic severe migratory headaches, dizziness, intermittent orthostasis and anxiety. She was being treated for hypertension with labetalol 200mg twice daily. She denied any family history of pheochromocytomas or adrenal tumors. Her physical examination was unremarkable apart from BP 191/115, with regular heart rate of 93 beats per minute. Her BMI was 19 and she did not exhibit any cushingoid features. She had undergone biochemical testing 17 months prior, which included 24 hour urine fractionated metanephrines and catecholamines, 1mg overnight dexamethasone suppression test and aldosterone level, all of which were unremarkable. Biochemical work-up was again repeated and included fractionated metanephrines <0.20nmol/L (normal <0.50nmol/L), normetanephrines <0.70nmol/L (normal <0.90nmol/L), aldosterone 16ng/dl (normal <21ng/dl), renin activity 3.8ng/ml/hr (0.6-4.3ng/ml/hr), late night salivary cortisol <50ng/dl (normal <100ng/dl), total testosterone 26ng/dl (14-76ng/dl) and DHEA-S 3.1ng/ml (normal <10ng/ml). Results were consistent with a non-functional adrenal tumor. CT imaging was remarkable for 8.0 x 7.5 x 7.0 cm well defined heterogeneous solid and cystic mass involving the right adrenal gland, the central necrotic portion of the mass showed no enhancement, whereas the peripheral solid portion of the mass showed progressive enhancement with HU values of 50, 67 and 75 on unenhanced CT, arterial phase and portal venous phase respectively and no wash out findings. Patient was started on an alpha blocking agent with dramatic improvement in her blood pressure perioperatively. She underwent successful open right sided adrenalectomy. Pathology was remarkable for a pheochromocytoma. Pheochromocytomas are rare neuroendocrine tumors originating from chromaffin tissue, which can be associated with significant morbidity and mortality. It is not uncommon for these tumors to be clinically silent but it is rare for them to be biochemically silent. This case highlights the importance of reviewing the adrenal imaging phenotype and following clinical suspicion and treating perioperatively as a pheochromocytoma, despite a negative biochemical work-up. If untreated perioperatively with adequate alpha blockade, these cases can result in a perioperative hemodynamic instability, adrenergic crisis and potentially death.

MON-332 Metastatic Pancreatic Neuroendocrine Tumor: A Very Rare Cause of Ectopic ACTH Production (ACTHoma)

Introduction Ectopic ACTH syndrome (EAS)is responsible for 10% of Cushing’s syndrome. Multiple tumors, most commonly small cell carcinoma of lung are associated with EAS. Pancreatic neuroendocrine tumors (pNETs) are usually associated with secretion of pancreatic polypeptide, gastrinomas, insulinomas, glucagonomas and vasoactive intestinal peptide (VIPomas). EAS or “ACTHomas” are rarely associated with pNETs. Case 76y/o man with ah/o hairy cell leukemia, bladder cancer (both in remission), and stage M1 unresectable pNET tumor with liver metastases presented with generalized weakness. Discovery of his pNET was incidentally noted during routine surveillance with CT monitoring following successful bladder cancer treatment six years ago. Treatment of his pNET initially began with Everolimus and then switched to Lanreotide injections. No evidence of Cushing’s Syndrome at the time of diagnosis. The lesions remained stable in size and patient was doing well. Physical exam was notable for lethargy, frailty, and absence of Cushingoid features. Labs showed serum glucose 231mg/dl, sodium 141mEq/L, potassium 2.4mEq/L, AM cortisol 116 ug/dL (range 6.7-22.6ug/dl) and ACTH was 209.6pg/mL (range 7.2-63.3pg/mL). Renin-aldosterone levels were normal. Cortisol level did not suppress with low dose or high dose dexamethasone. His hospital course was significant for persistent hypokalemia despite aggressive supplementation, difficult to control blood glucose, and worsening kidney function. EAS with pNET is very refractory to management and may be rapidly progressive. They occasionally demonstrate classic manifestations of Cushingoid features. However, they often lack the traditional phenotypic features of Cushing syndrome. Treatment options for EAS in the setting of an unresectable tumor include medical management versus bilateral adrenalectomy. Metyrapone, a cortisol synthesis inhibitor, can be an effective therapy. Ketoconazole, an antifungal that inhibits cortisol production can be an alternative, but may need weeks to achieve control. Etomodate can rapidly reduce cortisol levels, but requires intensive care monitoring. Somatostatin analogs may be effective by reducing ectopic ACTH production and stabilize tumor growth. Medical versus surgical management of Cushing’s syndrome was discussed with the patient and family, but they opted for hospice care. Conclusion We present a case of pNET associated with late onset EAS without obvious signs of Cushing’s syndrome. To our knowledge this late presentation of ACTH secretion in the setting of a stable pNET has not been previously reported in the literature. EAS due to pNET is rare and metabolic abnormalities can occur rapidly without other Cushingoid manifestations which can pose significant management challenges. High index of suspicion is required for early diagnosis. Due to the aggressive nature, the 5 years survival rate is 16%.

SUN-387 ACTH-Independent Cushing Syndrome from Pregnancy-Induced Micronodular Hyperplasia

Background: Fewer than 200 cases of Cushing syndrome (CS) during pregnancy are reported in the literature, and most are patients who developed Cushing disease prior to pregnancy. Rare cases of pregnancy-induced ACTH-independent CS feature hCG stimulation of cortisol production from pre-existing adrenal adenomas with ectopic LH/hCG receptors (LHCGR). We describe a case of ACTH-independent CS from adrenocortical micronodular hyperplasia presenting during pregnancy. Case: A previously healthy 23-year-old G1P0 woman presented at 17 weeks gestational age (GA) with rapid 50-pound weight gain, diabetes, hypertension, proximal muscle weakness, violaceous abdominal and underarm striae, and facial swelling, which began shortly following conception. Biochemical analysis revealed a urinary free cortisol of 403 mcg/24 h, a midnight salivary cortisol of 0.71 mcg/dL and an ACTH of <5 pg/mL. She had no family history of CS or other endocrinopathies. MRI without contrast showed normal appearing adrenal glands without nodularity. Her presentation and biochemistry suggested ACTH-independent CS. Due to her severe clinical symptoms, absence of adenomas on imaging, and lack of affordable medical options, she underwent bilateral adrenalectomy at 20 weeks GA. In the weeks following bilateral adrenalectomy, the diabetes and cushingoid features resolved. She underwent urgent Caesarean section for non-reassuring fetal heart tones at 29 weeks GA, and the boy was discharged home after 2 months in the neonatal intensive care unit. Her adrenal tissue demonstrated multiple unpigmented 2-16 mm nodules, and immunohistochemistry showed increased expression of steroidogenic enzymes, including CYP11B1, HSD3B2, and CYP17A1 throughout the nodular tissue with suppressed expression in the non-nodular tissue. Similarly, transcriptional analysis of a nodule revealed 3.7- to 5.3-fold increased mRNA expression of CYP11B1, HSD3B2 and CYP17A1 compared to control normal adrenal tissue. LHCGR mRNA expression was 17.2-fold higher in the adrenal nodule compared to controls. When isolated adrenal cells derived from a nodule were treated with hCG, cortisol secretion increased 2.1-fold (to 86 pg/h/mg protein) from baseline but not in control adrenal cells, suggesting that elevated hCG due to pregnancy may have mediated the CS through stimulation of aberrantly expressed LHCGR in the patient’s adrenal glands. Significance: Pregnancy-induced ACTH-independent CS is a rare condition that may be caused by aberrant expression of LHCGR in the adrenal cortex, resulting in increased steroidogenesis and cortisol excess due to high hCG levels during pregnancy.

MON-410 Ectopic ACTH- Secreting Tumor Causing Rapidly Progressive Cushing’s Syndrome Remains an Elusive Localization Diagnosis

Background: 68Ga-DOTATATE PET-CT (DOTATATE-PET) has higher sensitivity and positive predictive value than other studies, reason for which it has become the imaging modality of choice for Neuroendocrine tumor (NET) localization, but data on ACTH-secreting NET is scarce. Case summary: 61 year old female with history of right hepatic lobe lipoma resection, T2DM (A1c 9.4%), HTN, and benign thyroid nodule that was evaluated for cushingoid features with facial and lower extremity edema, progressive generalized weakness, difficulty climbing stairs, 20 lbs weight loss and intermittent hypokalemia while on a diuretic plus three other antihypertensives over a six month period. ACTH-dependent hypercortisolism was confirmed with a non-suppressed ODST 11.27mcg/dL (normal <1.8), elevated 24 hr urine free cortisol 525 mcg/24h (RR 4.0-50.0, total volume 3.85 L, creatinine 0.92 g/24 hr), midnight salivary cortisol 1.13 mcg/dL(RR ≤0.09), and ACTH 122 pg/mL (RR 6-50). Additionally, plasma metanephrines were negative, aldosterone <1 ng/dl (RR ≤21) and renin activity 0.58 ng/mL/h (RR 0.25-5.82). Cushing’s disease was suspected since her 8am cortisol suppressed >50% after 8 mg dexamethasone (dexa) overnight (pre-dexa cortisol 33.78 mcg/dL, post-dexa cortisol 6.59 mcg/dL). However, MRI Sella did not show a pituitary adenoma and IPSS was compatible with Ectopic ACTH-secretion (EAS). CT chest, abdomen, pelvis with contrast did not reveal any frank lesion that could be the culprit of EAS. Octreoscan and FDG-PET were negative. DOTATATE-PET reported a mild focus of uptake on the medial aspect of the right upper lung lobe, thought to be a branching blood vessel since no anatomic lesion was seen on CT Chest that would correspond to the possible area of uptake. In the interim, she developed diffuse ecchymosis with worsening of her functional status, needing a walker and assistance with activities of daily living. She had several falls complicated by multiple lumbar compression fractures, rib, right pubic ramus and bilateral sacral insufficiency fractures for which she received reclast, a back brace and physical therapy. She was started on ketoconazole and titrated up, but due to rapid progression of her Cushing syndrome over five months without an identifiable source of EAS, the decision was made to proceed with bilateral adrenalectomy and perform surveillance imaging to identify growth of a possible occult NET. Conclusion: In our case, DOTATATE-PET did not help to localize an ACTH-secreting NET, suggesting that the sensitivity of this study might not be as good as reported for other types of NET. Therefore, Occult EAS remains a diagnostic challenge and clinicians may resort to bilateral adrenalectomy for permanent biochemical control and serial CT imaging to detect an incipient NET.