Ref Range Research Articles

PSAT278 A Curious Case of Thyroglossal Duct Cancer

Abstract Introduction Thyroglossal duct (TGD) cyst is a common congenital anomaly. Thyroid cancer rarely occurs in TGD cysts, affecting less than 1% of cysts. Here we present a case of TGD cancer presenting as a central neck mass. Case Presentation 60 y.o female presented to her primary care physician with a neck mass without any compressive symptoms. She had no history of head/neck radiation exposure and no family history of thyroid cancer. She was noted to have a non-tender central neck mass with palpable cervical lymphadenopathy. Neck ultrasound revealed a 5.7 cm multilobulated cystic and solid mass anterior to the thyroid gland. CT scan of the neck revealed a lobulated mixed solid cystic mass at the level of the thyroid cartilage projecting anteriorly, with an abnormal right submandibular lymph node measuring 2.2×1.0 cm. She was evaluated by ENT and underwent resection of the neck mass and the hyoid bone (Sistrunk's procedure). Level 1b lymph node was also removed. Operative findings were concerning for a malignant process. This was confirmed on pathology with findings of TGD papillary thyroid cancer (PTC) and level 1b lymph node demonstrating metastatic PTC with cystic features. She was then referred to endocrine. Thyroid ultrasound revealed multiple bilateral intermediate suspicion nodules. Left inferior thyroid nodule was noted to have high suspicion sonographic features with abnormal right sided level 2 and 3 lymph nodes. She was referred for total thyroidectomy, pathology revealed multifocal PTC with lymph node involvement with extra nodal extension and metastasis to the left sternohyiod muscle, pT2, pN1b, AJCC stage 2. 6-week post-surgical labs revealed TSH of 1.69 mIU/L (ref range 0.40-4.50), thyroglobulin level of 0.8 ng/ml (ref range athyrotic <0.1), with undetectable thyroglobulin antibodies <1 IU/ml (ref range < or = 1 IU/mL). She underwent RAI with 104.6 mci. I-131 Metastatic survey revealed increased uptake in the thyroid bed, otherwise no increased activity elsewhere. Stimulated TSH and Thyroglobulin levels were done but not collected appropriately and therefore not mentioned here. Repeat labs 12 weeks after RAI revealed a TSH of 2.86 mIU/L, Thyroglobulin level of 0.2 ng/ml, and undetectable Thyroglobulin antibody. Conclusion There are no standardized guidelines for management of TGD cancer given the rarity of this condition. FNAB (Fine need aspiration biopsy) may be associated with high false negatives due to inadequate sampling, given the cystic nature of these lesions. In majority of these cases definitive diagnosis of cancer is made after excision of the TGD cyst. Some experts favor a conservative approach via Sistrunk's procedure and pursuing total thyroidectomy if there is high suspicion of thyroid gland involvement as well. Whereas other authors have suggested a more aggressive approach with total thyroidectomy even without evidence of concomitant involvement of the thyroid gland. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PSUN346 TSHoma: A Rare Cause of Pituitary Adenoma

Abstract Introduction The TSH-producing adenoma (TSHoma) prevalence in the general population is 1 to 2 cases per million, accounting for less than 2% of all pituitary adenomas. Plurihormonal tumors account for about 30% of these cases, with the most common co-secreted hormone being GH. We present the case of a patient diagnosed with TSH adenoma many years after presentation. Case Presentation A 58 year old male with a history of incidentally diagnosed pituitary microadenoma on MRI in 2007, presented in 2014 following abnormal thyroid function testing (TFT), only reported symptoms being occasional headaches. TFT was significant for elevated TSH and FT4 (TSH 4.87—Ref range: 0.27-4.2. Free T4: 1.98–Ref range 0.7-1.7). Pituitary hormone profile was remarkable for a low IGF-1 and a borderline high Alpha subunit of glycoprotein hormone. A sellar MRI confirmed a 12mm pituitary macroadenoma. He was managed conservatively on beta blockers and low dose Methimazole, owing to a stable adenoma size and poor surgical candidacy with multiple comorbidities (e. g. Atrial fibrillation). Repeat labs in 2018 showed increasing TSH (12.85), with persistent elevations of FT3, FT4 and Thyroglobulin. He had follow up TFT monitoring and surveillance MRIs until 2021 when his lesion progressed to 14 mm with mass effect on right pre chiasmatic optic nerve and adjacent internal carotid artery. The patient underwent trans sphenoidal biopsy with debulking in 2021. The biopsy showed a plurihormonal adenoma (prolactin, GH and TSH secreting). Interestingly, prolactin, GH or IGF-1 were never elevated. Following surgery, MRI showed residual 13.2×9.7 mm tumor with no mass effect. His most recent labs showed a TSH: 2.5 and FT4: 1.7. Discussion The diagnosis of a TSHoma should be considered in all centrally hyperthyroid patients, to avoid complications and undue thyroid ablation. A TSHoma must be differentiated from Resistance to Thyroid Hormone (RTH)-beta, which occurs due to mutations in the Thyroid Hormone Receptor Beta gene. Serum a-subunit concentration and Sex Hormone Binding Globulin (SHBG) concentrations are normal in RTH-beta with no TSH suppression following somatostatin analog administration. The presence of a high TSH, FT3 and FT4, in the setting of an elevated a-subunit and pituitary macroadenoma on MRI is strongly suggestive of a TSHoma. Beta blockers are recommended for symptomatic individuals however anti thyroid drug therapy is not advisable for there is risk of thyroid hormone suppression with concomitant tumor overgrowth. Definitive therapy includes trans sphenoidal tumor resection with somatostatin analog therapy to achieve euthyroidism prior to surgery. Patients should be followed up with frequent monitoring of TFT's, along with MRIs every 2-3 years. For patients with residual disease following surgery, treatment with somatostatin analogs such as Octreotide or Lanreotide is favorable as opposed to pituitary irradiation. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

ODP584 Corticosteroid-binding Globulin Deficiency Independently Predicts Mortality and is Associated with Norepinephrine Requirements in Septic Shock.

Abstract Context: Hydrocortisone administration in septic shock remains controversial. Corticosteroid-binding globulin (CBG) transports cortisol to inflammatory sites and is depleted in septic shock. Objective To determine if severely deficient plasma CBG <200 nmol/L (Ref range 269-641 nmol/L) independently predicts septic shock mortality. Methods A prospective observational study in patients with septic shock. Patients were categorised into two groups: mean plasma CBG concentrations <200 nmol/L and ≥200 nmol/L (day 1/2), with additional categorisation by nadir CBG. Primary outcome was Intensive Care Unit (ICU) mortality. Secondary outcomes were 28- and 90-day mortality, norepinephrine requirements, renal-replacement therapy, and clinician-instituted hydrocortisone. Results 135 patients were included. Mortality rates in ICU were higher in the CBG <200 nmol/L vs the CBG ≥200 nmol/L group: 32.4% vs 13.9%; Odds ratio (OR), 2.97, (95% confidence intervals (CI) 1.19,7.41); P=0. 02: 28-days; OR 2.25 (95% CI 0.99,5.11): 90-days; OR 2.21 (95% CI 0.99,4.91). Multivariate analysis revealed 4 factors independently associated with ICU mortality: CBG <200 nmol/L (OR 3.23, 95% CI 1. 06,9.88), Acute Physiology and Chronic Health Evaluation (APACHE) II >25 (OR 3.58, 95% CI 1.20,10.68); Sequential [Sepsis-related] Organ Failure Assessment (SOFA) liver score (OR 1.98, 95% CI 1. 04,3.72); and renal-replacement therapy (OR 6.59, 95% CI 2.17,20. 01). Nadir CBG levels were associated with higher SOFA cardiovascular scores, norepinephrine total dose (ug) P<0. 01 and duration (days) P<0. 01. Plasma cortisol concentrations and hydrocortisone administration did not relate to ICU mortality. Conclusion Septic shock patients with CBG <200 nmol/L had higher norepinephrine requirements and 3.2-fold higher ICU mortality. CBG concentration was the only directly reversible independent mortality risk factor. Presentation: No date and time listed

S2944 Autoimmune Hepatitis Presenting With Concomitant Chronic Pancreatitis

Introduction: Autoimmune Hepatitis (AIH) is a progressive form of chronic hepatitis, with periods of remissions and exacerbations. Diagnosis includes abnormally high levels of immunoglobulins and multiple autoantibodies, with female predominance. Clinical presentation is variable, with a spectrum extending from asymptomatic cases to fulminant liver failure. Presenting symptoms may include abdominal pain, malaise, fatigue, and small joint arthralgia. We present a case of a 36 YO M with PMH of alcohol dependence and acute pancreatitis who was diagnosed with AIH. Case Description/Methods: A 36 YO AA M with PMH of alcohol dependence (in remission for 2 yrs), tobacco use, and pancreatitis, presented to the ED with non-radiating mid-epigastric abdominal pain 10/10 in severity, associated with NBNB emesis, exacerbated by movement for 2 days. The patient was hemodynamically stable and on exam he had icteric frenulum, abdominal distension, with liver span 12cm at mid-clavicular line, and absence of fluid wave, shifting dullness, rebound tenderness, or voluntary guarding. Labs notable for pancytopenia, elevated lipase, elevated ALP, elevated AST and ALT with 2:1 ratio, and hyperbilirubinemia. MRCP showed cirrhotic liver with splenomegaly and varices, as well as with free fluid in the lesser sac along the pancreatic head, duodenum, and right retroperitoneum (compatible with acute pancreatitis). Patient received IV fluids for pancreatitis. Additional labs were remarkable for elevated actin smooth muscle antibody at 26U (ref range: 0-19), ANA positive, with high alpha-1-antitrypsin levels and normal ceruloplasmin levels. The patient left against medical advice; and was given resources for Hepatology with referral for liver transplant (Figure). Discussion: There is limited data regarding patients with concomitant AIH and pancreatitis. Our pt presented with a AIH with secondary acute on chronic pancreatitis, in the absence of additional autoimmune manifestations. Mechanism of AIH remains poorly understood; however, there is an association between the HLA gene and AIH. Genetic studies have shown HLA-DRB1*0301 and HLA-DRB1*0401 as primary and secondary genotypes susceptible to AIH, as well as genetic variants with CARD10 and SH2B3. Products secondary to metabolism of ETOH such as alcohol dehydrogenase, malondialdehyde, and acetaldehyde, can lead to development of autoantibodies. Additional research is indicated to evaluate the relationship between AIH and acute pancreatitis.Figure 1.: A closer look at the case with images from the EGD, EUS, Right upper quadrant ultrasound and MRCP.

P33 The successful use of Belimumab in recurrent small bowel obstruction secondary to Lupus Enteritis

P33 The successful use of Belimumab in recurrent small bowel obstruction secondary to Lupus Enteritis

When All Is Not as It Seems: Recurrent Fever and New-onset Joint Pain in a 17-Month-old Girl.

When All Is Not as It Seems: Recurrent Fever and New-onset Joint Pain in a 17-Month-old Girl.

973-P: By How Much Does Red Blood Cell Status Affect the Accuracy of HbA1c?

Medical conditions can affect haematological factors altering relationship between HbA1c and glucose. Patients were recruited at hospital over 3 visits (*1/**2&3 only) comprising 20 with diabetes and in Fig 1 with liver disease (LD) & hepatitis C (HC) on ribavirin*, on dapsone*, with macrocytosis, and in Fig 2 LD & HC off ribavirin**, LD with nonalcoholic steatohepatitis and cirrhosis, rheumatoid arthritis, renal disease on erythropoietin (EPO) , renal disease off EPO and with microcytosis. Glucose and full blood count were measured with HbA1c on Tosoh G8 analysers, ref range 20-42mmol/mol. In Fig 1 HbA1c was more depressed relative to glucose than Fig 2, both p<0.001, with a combination of lower red blood cell (rbc) count & higher mean cell volume. The macrocytic nature of rbc implies faster turnover and less contact of haemoglobin with circulating glucose. Disclosure A. Karwath: None. J.A. Williams: None. R.A. Round: None. G. Gkoutos: None. G. Roberts: None. J. Webber: None. Funding Medical Research Council (MR/S003991/1) , MRC HDR UK (HDRUK/CFC/01) , NIHR Birmingham ECMC, NIHR Birmingham SRMRC, Nanocommons H2020-EU (731032) , MAESTRIA (Grant agreement ID 965286)

Renal allograft rejection with thrombotic microangiopathy associated with a Kidd blood group system alloantibody

Abstract Introduction/Objective The Kidd blood group antigens are urea transporters found on the surface of red blood cells, renal tubular epithelial cells, and endothelial cells in the renal medulla and vasa recta. While controversial, some reports have described an association between Kidd antigen donor/recipient mismatches and kidney transplant rejection when recipients possess or form anti-Kidd alloantibodies. To date, none of these reports have described development of a thrombotic microangiopathy (TMA) in the renal graft associated with these antibodies. We describe a case of fulminant renal transplant rejection associated with TMA in a patient with anti-Jk(a) alloantibodies who received a deceased-donor kidney transplant (DDKT). Methods/Case Report A 64-year-old woman with end-stage renal disease secondary to AL amyloidosis caused by plasma cell neoplasm received a DDKT associated with delayed graft function. No pre- or post-transplant donor specific antibodies (DSA) were detected, the flow crossmatch testing was negative, and a pre-operative type and screen identified anti-Jk(a) alloantibodies. On post-transplant day 5, her creatinine remained elevated at 6 mg/dL (ref range: 0.4–1.3 mg/dL) with an acute drop in platelets and undetectable haptoglobin. Allograft biopsy showed a combination of TMA with some additional evidence of acute cellular rejection. Tacrolimus was stopped to rule out drug-induced TMA, and the workup showed negative Shiga toxin, normal ADAMTS13 activity, negative atypical HUS genetic testing, and negative antiphospholipid syndrome testing. Genotyping of the donor kidney was positive for the Jk(a) antigen. Eculizumab, IVIG, and a trial of 8 sessions of therapeutic plasma exchange (TPE) were administered. Her creatinine improved (1.93–2.05 mg/dL), indicating a significant antibody-mediated etiology to her delayed graft function. About one month later, her creatinine worsened, and she received another trial of TPE with IVIG and eculizumab. Despite a mild decrease in her creatinine, repeat biopsies showed acute cellular rejection, persistent TMA, and chronic allograft injury. No DSAs were ever detected. Her creatinine never recovered, and she is now dialysis-dependent. Results (if a Case Study enter NA) NA Conclusion We speculate that anti-Jk(a) antibodies interacting with a Jk(a)-positive donor kidney account for graft TMA. This case underscores the potential importance of matching Kidd antigens in kidney transplantation.

THE CLOT THICKENS: DOES THE JOHNSON & JOHNSON COVID-19 VACCINE INCREASE THE RISK OF THROMBUS IN A HYPERCOAGULABLE STATE?

TOPIC: Pulmonary Vascular Disease TYPE: Fellow Case Reports INTRODUCTION: The 2019 coronavirus disease (COVID-19) has hematologic manifestations in addition to respiratory. COVID-19 is associated with a state of hypercoagulability. Evidence shows correlation with degree of hypercoagulability and severity of disease. Patients with severe COVID-19 were reported to have venous and arterial thrombi causing organ dysfunction and death. There was an urgent need for vaccination against SARS-CoV-2. Companies, including Johnson & Johnson (J&J), have released their vaccine. Recently, the Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) reported six cases of cerebral venous sinus thrombosis, which led to a pause in J&J vaccine administration. We present a case of a woman with antiphospholipid syndrome (APS) who developed acute deep venous thrombosis (DVT) after receiving the J&J vaccine while therapeutic with warfarin. CASE PRESENTATION: Ms G is a 54-year-old black woman with history of APS and severe COVID-19 infection. Prior APS panel for lupus anticoagulant antibody (Ab) on initial and repeat testing was positive. Anticardiolipin and beta-2 glycoprotein Ab were negative. Her complication from APS included chronic left lower extremity DVT since 2018. She was compliant with warfarin. She received the J&J vaccine twenty days prior to the present visit. Fifteen days after receiving the vaccine, she developed bilateral lower extremity swelling and calf pain, left worse than right. On exam, vital signs were within normal limits. She had 1+ non-pitting edema and tenderness in her left calf, worse compared to the right. Complete blood count showed platelets 172x10^9/L (ref range: 167-378x10^9/L). INR 3.03, prothrombin time 33 seconds (ref range: 9.8-12.9). COVID-19 IgG titer 8.08 index (S/C) (ref range: 0-1.39). Heparin-induced thrombocytopenia (HIT) screen was negative. Venous doppler ultrasound showed an acute femoral-to-peroneal DVT in the right leg and a chronic femoral DVT in the left leg. Due to recent joint statement by the CDC and FDA advising against heparin in patients with new thrombi after receiving the J&J vaccine due to HIT-like behavior of these thrombi, the patient was treated with rivaroxaban and is currently doing well. DISCUSSION: APS is an autoimmune disease that causes a chronic hypercoagulable state from antiphospholipid antibodies, which make patients prone to develop thrombi. Correlation has been shown between severity of COVID-19 and degree of inflammation. Severe illness leads to generation of excessive inflammatory cytokines and chemokines, endothelial dysfunction, and a host of other pathways to increase risk of thrombosis. CONCLUSIONS: With the recent discovery of the J&J vaccine potentially creating a HIT-like state, the risk of developing DVT in a patient with known hypercoagulable state (such as APS and severe COVID-19) appears elevated. Due to this finding, we recommend caution in giving the J&J vaccine. REFERENCE #1: Abou-Ismail, Mouhamed Yazan et al. "The hypercoagulable state in COVID-19: Incidence, pathophysiology, and management.” Thrombosis research vol. 194 (2020): 101-115. doi:10.1016/j.thromres.2020.06.029 DISCLOSURES: No relevant relationships by David Rutenberg, source=Web Response No relevant relationships by Yumeng Zhang, source=Web Response

Perplexing Infectious Etiology of a Case of Hypopituitarism and Central Diabetes Insipidus

Injury to the hypothalamus and both the anterior and posterior components of the pituitary gland is rare, but can result from infiltrative processes such as sarcoidosis, Langerhans cell histiocytosis, granulomatous with polyangiitis, and lymphocytic hypophysitis. Meningitis, pituitary infection, traumatic brain injury, and surgical instrumentation are other etiologies.A 40 year old man with mild cognitive impairment due to remote meningitis was evaluated for progressive somnolence. He was obtunded and cerebrospinal fluid (CSF) analysis revealed 11 WBC with lymphocytic pleocytosis (90% lymphocytes), highly elevated protein of 588 mg/dL (ref range 12-60 mg/dL), and low glucose of 17 mg/dL (ref range 40-70 mg/dL). MRI Brain revealed basilar meningitis/rhombencephalitis and suspected infectious vasculitis induced right middle cerebral artery territory stroke. Of note, there was substantial T2 hyperintense signaling in the hypothalamus and pituitary areas, which has been reported with tuberculosis (TB), Coccidioidomycosis (Cocci), and the aforementioned etiologies. He received broad antimicrobials, including TB treatment and fluconazole. He developed sinus bradycardia, hypotension, hypoglycemia, and hypothermia. Labs demonstrated inappropriately normal TSH of 1.4 mclU/mL (ref range 0.35-4.94 mclU/mL), low free T4 (fT4) of 0.50 ng/dL (ref range 0.7-1.48 ng/dL) with repeat fT4 undetectably low the following day, and AM cortisol less than 0.5mcg/dL (ref range 4-22 mcg/dL). Levothyroxine and steroids were initiated. He then developed central diabetes insipidus (DI) for which DDAVP was initiated. Comprehensive infectious and autoimmune meningoencephalitis workup was unrevealing. Serum and CSF tests for Listeria PCR, Cocci antibody and antigen, and TB were negative upon multiple, serial checks spanning weeks. CSF analysis one month later showed improvement in protein level (106 mg/dL), but still with elevated WBC (10 WBCs, 98% lymphocytes). MRI one month later demonstrated improvement in edema and the areas of ischemia and vasculitis were less. His adrenal insufficiency and central DI were transient and improved, no longer requiring steroids or DDAVP. He remains on levothyroxine for central hypothyroidism.The MRI and CSF findings point to an infectious etiology for hypopituitarism and central DI. We suspect an indolent bacteria such as Listeria or a fungus, likely Cocci, or TB meningitis. Cocci seemed to provide a unifying explanation as it classically creates infarcts and causes vasculitis. However, serial CSF tests were negative for Cocci, as well as for TB and Listeria. Marked improvement on follow up MRI also makes TB meningitis less likely as imaging would not resolve so quickly. This is a mysterious case; he improved on broad antimicrobial therapy and is being monitored closely in the outpatient setting.

Isolated Growth Hormone Deficiency as a Cause of Hypoglycemia Past Infancy

Introduction: Hypoglycemia is a common manifestation of Growth Hormone (GH) deficiency in infancy, but is rarely seen beyond 1 year of age. Here, we describe the case of a 5 year 6- month- old child with recurrent episodes of hypoglycemia due to GH deficiency in the setting of malnutrition. Experimental Methods / Case Presentation: Case report and literature review Results: A 5y6m girl with history of atypical teratoid rhabdoid tumor, status-post surgical resection and adjuvant therapy with CNS irradiation (50.4 gray), presented with recurrent hypoglycemia despite continuous G-tube feedings. Child had undergone surgery and irradiation approximately 3 years prior to presentation. She was initially followed at the cancer survivor clinic but had been lost to follow up for 2 years. At presentation, whole blood glucose was 51mg/dL. Height was 93.5cm (-4 SDS) and BMI 10.6 kg/m2 (- 7.75 SDS); she appeared malnourished on exam with minimal subcutaneous fat. She was admitted to the hospital where blood glucoses ranged from 59-68 mg/dL, despite continuous enteral feeds. On evaluation, blood ketones were mildly elevated at 0.67 mmol/L (ref range < 0.3mmol/L), growth factors were low: IGF1 15 ng/mL (ref range 37 - 272 ng/mL); IGF-BP3 1.1 mg/L (ref range 1.1 - 5.2 mg/L), and other pituitary hormones were within normal range [stimulation test cortisol peak 31.9 mcg/dL, TSH 2.4 mIU/mL(Ref range: 0.700 - 4.100 uIU/ML), Free T4 1.2 ng/dL (Ref range 1.0-2.4 ng/dL)]. Hypoglycemia resolved within 48 hours of initiating empiric treatment with GH (0.2mg/kg/week) and patient’s feeds were successfully compressed to 16 hours. Child was discharged home after passing an overnight 8-hour safety fast. Conclusion: Growth hormone deficiency can present as recurrent hypoglycemia outside the infantile period in the setting of malnutrition and needs to be considered in the differential diagnosis and evaluation of childhood hypoglycemia. ​

Idiopathic Hypophysitis

Introduction: Hypophysitis is a heterogeneous condition that leads to inflammation of the sella / suprasellar region, potentially resulting in hormonal deficiencies or mass effects. Prevalence of hypophysitis ranges from 0.2% to 0.88%. Annual incidence of hypophysitis is 1 case per 9 million individuals. We present an interesting case of idiopathic hypophysitis. Clinical Case: A 52-year-old female was evaluated for secondary hypothyroidism. Patient complained of excess fatigue, weight gain, headaches, polyuria with nocturia and vision changes. She was seen by ophthalmology for formal visual field testing revealing right superior quadrantanopia. Labs significant for TSH 4 uIU/mL (ref range 0.27-4.2uIU/mL), FT4 0.72ng/dL (ref range 0.93-1.7 ng/dL), Anti TPO ab negative, AM cortisol 8.9UG/dL, ACTH 18pg/mL, IGF1 127ng/mL, prolactin 7ng/mL, FSH 102MIU/mL, LH 41 MIU/mL. MRI sella revealed homogenous enhancement of the pituitary with convex superior margin - 0.8*1*0.9cm concerning for hyperplasia. Due to the concern for hypophysitis, an extensive inflammatory workup was pursued which was negative. She was started on thyroid hormone replacement and DDAVP. An empiric trial of high dose steroids failed to provide any relief. During workup, patient complained of transient right sided face and arm tingling, diagnosed with TIA and started on aspirin. Due to worsening headaches, a pituitary biopsy was pursued. Pathology significant for glandular tissue ruling out inflammatory, neoplastic, and infectious etiologies. Neurology diagnosed the patient with hemicrania continua. Patient is currently maintained on thyroid hormone replacement and DDAVP with close follow-up. Discussion: The incidence of hypophysitis has recently increased due to increased awareness and also due to the use of medications like ICI. Primary hypophysitis is mostly due to autoimmune etiology. Secondary hypophysitis could result from infections, neoplastic conditions or an adverse effect of medications. Clinical presentations ranges from being asymptomatic to having features of hypopituitarism. Usually presents with mass effect, visual symptoms due to the upward expansion of the pituitary gland impinging the dura mater and optic chiasm. This is followed by symptoms of hormone deficiency, central DI and hyperprolactinemia. Central AI has been reported in 20%-75%, central hypogonadism in 15%-60%, central hypothyroidism in 25%-58%, GH deficiency in 5%-41%, and prolactin deficiency in 13%-25%. Typical MRI findings include, homogeneous pituitary contrast enhancement, pituitary stalk thickening and loss of posterior pituitary bright spot, ‘figure of 8’ appearance, ‘dural tail’. Treatment consists of surgery, anti-inflammatory medications, and radiotherapy. Glucocorticoid treatment is the cornerstone for medical management; however, the overall recurrence rate is high.

Euglycemic DKA in Patients on SGLT2 Inhibitor and Potentially Ketotic State

Background: With mounting evidence demonstrating improved cardiovascular and renal outcomes with the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors, this class of newest antidiabetic agents is rapidly gaining favor. SGLT2 inhibition lowers the renal threshold for glucose excretion, resulting in renal glycosuria, a shift in substrate utilization from carbohydrate to fat oxidation and hyperglucagonemia and thus poses the risk of developing euglycemic DKA as a rare but serious adverse effect. Clinical Cases: the first case is A 36-year-old female was diagnosed with type 2 DM with an HbA1c of 10% and was started on multi-agent antihyperglycemic therapy including metformin 500 mg BID, extended release exenatide 2 mg once a week and empagliflozin 25 mg once daily which were all initiated simultaneously. 2 days after starting regimen, she complained of nausea, vomiting and was unable to tolerate oral diet and fluids by day 4 which potentially predisposed to starvation ketoacidosis. She presented to the ED with normal vitals, grossly normal physical exam and labs were significant for beta-hydroxybutyrate of over 7 mmol/L (ref range <0.28), bicarbonate of 10 mmol/L (22 - 33), anion gap 25 (7 - 17), arterial pH 7.16 (7.33 - 7.43), serum glucose 111 (7.33 - 7.43). GAD-65 antibody titer was <5 IU/mL (< 5). She was diagnosed with euglycemic DKA, transferred to ICU and started on DKA protocol to which she responded very well. Second patient is A 65 Years old male with past medical history of CAD, HTN, HDL, history of PE/DVT and Type 2 DM was on insulin and jardiance, started ketodiet while continuing taking the jardiance and stopped taking his insulin because his sugars were controlled presented to the ED with abdominal pain, nausea and vomiting, had relatively normal vitals and benign physical exam, labs showed Bicarbonate of 9 mmol/L (22 - 33), anion gap of 31 (7 - 17), venous pH of 7.07 (7.33 - 7.43) glucose was 189 (7.33 - 7.43), beta-hydroxybutyrate of over 7.7 mmol/L (ref range <0.28), patient was admitted to the ICU and started on insulin on DKA protocol Conclusion: SGLT2 inhibitors may be associated with DKA due to their ketogenic effects secondary to enhanced lipolysis and increased glucagon to insulin ratio. although not expected, euglycemic DKA could be much more present in cases where there is predisposition to increase ketones generation w/without appropriate clearance eg. starvation, ketotic diet, AKI, etc. These should be monitored for and the patient needs to be educated about accordingly to prevent both adverse outcomes and potential decrease in drug use if not strongly indicated. also,It would be prudent for prescribing clinicians to advise patients to withhold potentially harming medications temporarily if they cannot maintain adequate oral intake.

Immobilization Hypercalcemia (IH) in an Adult After Spinal Cord Injury

Background: Immobilization hypercalcemia (IH) is an uncommon diagnosis and little has been published about management of this condition. We present a case of IH and discuss clinical aspects of this unique bone metabolism state. Case: 32-year-old female with history significant for IV drug use, presented to the hospital with features of septic shock, Work up showed MRSA bacteremia associated with tricuspid endocarditis and septic pulmonary emboli. MRI of the spine done for progressive weakness of extremities revealed a cervical epidural abscess leading to spinal cord compression and myelomalacia. She underwent spinal abscess drainage and corpectomy, remained quadriplegic. 8 weeks later we were consulted to see her at inpatient rehabilitation facility for hypercalcemia. Labs showed Creat(0.6 mg/dl), hypercalcemia with corrected Calcium of 12.9 mg/dl f. Further workup showed suppressed PTH (< 6), V D-25 at (< 10 mg/dl). Phosphate (normal). ACE levels, PTHrp, Vit. D 1,25, SPEP, UPEP,and TSH were all normal. 24 hours urine calcium showed hypercalciuria, 400 mg/ml. Fasting Bone markers were elevated with serum N-telopeptide > 40 nM BCE, ref range (6.2–19.0) and C-Telopeptide is 2060 pg/ml ref range (60–650), which indicates increase bone turnover. IH was diagnosed and hydration attempted for few weeks. Serum calcium remained at 13 mg/dl, so she received a single slow infusion of pamidronate 30 mg. 4 days after infusion, calcium levels decreased to normal value of 10.2 mg/dl without any side effects. She remained normocalcemic 5 weeks post infusion. Discussion: IH is an uncommon condition but early recognition and intervention will minimize secondary long-term complications such as kidney stones, Osteoporosis or low bone mass, renal failure and acute pancreatitis. Albert, Fuller described IH in 1941(1). Most cases of IH had been reported in children and adolescents with high bone turn over following recent spinal cord injury(2–3). Very few reports have been published in young adults such as our patient,IH is attributed to prolonged immobilization from paralysis due to spinal cord injury,and other etiology (2–4), Proposed mechanism includes decreased mechanical stress on the bone which leads to increase bone resorption and remodeling and demineralization. To establish the diagnoses of IH, an exhaustive evaluation is warranted to rule out other causes of PTH dependent and independent hypercalcemia(5). Multiple treatment approaches have been used over the past few decades including early mobilization, hydration., saline diuresis, subcutaneous Calcitonin, glucocorticoids (6), IV sodium sulphate and phosphate (7). Bisphosphonates are the preferred pharmacological treatment of IH. Nonnitrogen containing bisphosphonates including clodronate and etidronate (8–9),. are not preferred due to concern for bone demineralization and osteomalacia. (10). Pamidronate has been used to treat IH due to its efficacy, safely and cost (11). Caution to be exercised in those patients with kidney disease.

“The Unusual Suspect” - Insulin Autoimmune Syndrome, an Extremely Rare Cause of Hypoglycemia

Background: Insulin autoimmune syndrome (IAS), also called Hirata syndrome, is a rare diagnosis which is characterized by hypoglycemia, normal or elevated fasting insulin level, and elevated anti-insulin antibody titers. Clinical Case: 45-year-old nondiabetic Caucasian female presented to the emergency department (ED) with chief complaint of near-syncope. She reported difficulty concentrating and feeling faint roughly 1 hour after consuming breakfast. Upon ED arrival, fingerstick glucose (FSG) was 47 mg/dL. Her symptoms resolved with ingestion of orange juice and repeat blood glucose (BG) 15 minutes later was 120 mg/dL. She reported similar symptoms in the last 5 years happening “every few months” without a predictable pattern; twice with witnessed loss of consciousness. Workup for syncope in the past included normal neurologic, cardiac, and tilt-table testing. She had no prior low FSG/BG recorded, no personal history of bariatric surgery or family history of diabetes mellitus and no access to antihyperglycemic medications. Past medical history included ulcerative colitis and medications included sulfasalazine and multivitamins. Pertinent review of systems was negative for weight loss, nausea, and diarrhea. Vital signs were within normal limits. Physical exam was unremarkable. Height was 165 cm, weight 67.8 kg and body mass index 24.9 kg/m2. Blood draw after overnight fast revealed BG of 78 mg/dL, C-peptide 0.7 ng/mL (ref range 0.8–3.5), insulin 10 µIU/mL (3–19), proinsulin <1.6 pmol/L (<8.0), insulin-like growth factor-2 (IGF-2) 339 ng/mL (180–580) and insulin antibody level 10.0 U/mL (0.0–0.4). She was managed conservatively with frequent small meals and patient has continued to do well without recurrence of symptoms. Conclusion: IAS is an exceedingly rare disease entity with about 460 cases described in literature, mostly in patients of Asian descent. Workup for hypoglycemia in non-diabetic patients should include insulin antibody titers to rule out IAS. There appears to be a genetic predisposition to developing IAS in patients with major histocompatibility complex (MHC) genes HLA-DQA1, HLA-DQB1 and HLA-DRB1. It is now being more frequently described in patients of non-Asian descent, particularly those with other autoimmune or plasma cell dyscrasias. It is also associated with drugs containing sulfhydryl groups and viral infections. Treatment should be tailored to severity of disease. Most drug induced IAS resolves after cessation of culprit drug. Conservative management is usually the first step with frequent, low carbohydrate meals with diazoxide or octreotide as adjunctive options. Immunosuppression (high-dose prednisolone or rituximab) and plasma exchanged are reserved severe or refractory cases.

Presentation of ACTH Independent Cushing’s as Severe Insulin Resistance During Pregnancy

Introduction: Cushing’s syndrome is very rare in pregnancy with around 200 cases reported in literature. It remains a diagnostic dilemma as pregnancy itself is a hypercortisolemic state. Several clinical characteristics of Cushing’s syndrome such as insulin resistance and hirsutism may overlap with normal variants of pregnancy and therefore leading to a missed diagnosis. We hereby present a case of a young pregnant woman with severe insulin resistance, with workup consistent with Cushing’s syndrome. Clinical Case: This was a 27-year-old pregnant woman with DM type 2 diagnosed about 7 years ago. During her pregnancy she was started on insulin and was later admitted to the hospital at 32 weeks for inpatient management of pre-eclampsia and uncontrolled hyperglycemia. Endocrine was consulted for severe insulin resistance and persistent hyperglycemia. On exam patient was noted to be obese with facial plethora, frontal balding and significant facial hirsutism. During the pregnancy she had noted significant weight gain with substantial worsening of frontal balding and hirsutism. Her current pregnancy was spontaneous but was after many years of trying to conceive. Prior pregnancy 8 years ago was uncomplicated with no history for GDM at that time. Review of recent pre-pregnancy imaging revealed left adrenal mass measuring 3.5 cm with 40 HU which measured around 2 cm 8 years ago. Biochemical work up revealed elevated 8 am cortisol at 35.4 ug/dL (ref range 6.2 - 19.4) with suppressed ACTH <5 pg/mL (6 – 50). Testosterone was high at 299 ng/dL (8 – 48) and DHEAS was low normal at 37 mcg/dL (18 – 391). Plasma and 24 hour urine metanephrine collection results were normal. 24-hour urine free cortisol was measured and was elevated at 628.5 mcg/24(4.0–50.0). Midnight salivary cortisol was 0.87 mcg/dL (<OR=0.09). Patient was managed conservatively with plan for surgical intervention post-delivery. Pregnancy was complicated by PPROM at 35 weeks with subsequent cesarean section. Baby was of average weight but developed mild hyperbilirubinemia which required short NICU stay. On reevaluation at 4-week postpartum period, repeat biochemical workup revealed elevated cortisol of 22.5 mcg/dL, ACTH <5 pg/ml, elevated 24-hour urine cortisol 163.9 mcg/24h with appropriate urinary creatinine. Testosterone level was improved postpartum to 9 ng/dL. DHEAS was 39 mcg/dL. Repeat imaging with CT with adrenal protocol revealed left adrenal mass measuring 2.3 cm with 20 HU with absolute washout of 79%. She was started on ketoconazole is now awaiting surgical intervention. Conclusion: We suspect that this patient may have had pregestational subclinical Cushing’s syndrome which eventually progressed to Cushing’s syndrome during pregnancy. Although this is a rare finding during pregnancy, workup for Cushing’s should be considered in pregnant women with severe insulin resistance, hirsutism, hypertension and pre-eclampsia.

820 An Unusual Case of Post-Traumatic Brain Injury Kleine-Levin Syndrome with Anti-GAD-65 Autoantibodies

Abstract Introduction Kleine-Levin Syndrome (KLS) is a rare clinical syndrome, and is precipitated by traumatic brain injury (TBI) in 9% of cases. An autoimmune component to KLS has previously been suggested. Autoantibody profiles in KLS are diverse and its overlap with autoimmune encephalitis is still not well described or understood. Here, a case of KLS in a patient with autoimmune diabetes with very high levels of serum autoimmune GAD-65 antibodies is presented. Report of case(s) A 36-year-old male Veteran with a history of alpha-thalassemia minor, prior history of insomnia with nightly sleep of 6 hours, prior history of mild OSA with AHI of 5.8 on PSG in 2018, sustained a mild TBI on 11/13/2019 after a 50-pound box fell on his head. CT head and cervical spine were normal. One week later, he developed recurrent episodes of hypersomnia, sleeping up to 80 hours continuously, waking briefly only to urinate or eat, with hyperphagia, irritability, and derealization present during episodes. One month after the TBI, he was diagnosed with Latent Autoimmune Diabetes in Adults (LADA) after blood glucose was found to be elevated at 566. Serum GAD-65 antibody level was very elevated at 10,594 U/mL (ref range: 0–5 U/mL), hemoglobin a1c was 7.7%, and insulin was started. Six months later, he was evaluated in the VA Sleep Clinic for continued hypersomnia, despite controlled diabetes. Neurological examination, MRI brain, and sleep-deprived EEG were normal. Cerebrospinal fluid testing was normal, with the exception of a CSF autoimmune encephalitis panel with a positive GAD-65 titer of 0.24 nmol/L (range &amp;lt;0.02 nmol/L) – non-diagnostic for autoimmune encephalitis. HLA-DQ1B status is pending. Conclusion Autoimmunity is an emerging topic of clinical significance in KLS. GAD-65 serum antibodies have both endocrine and neurologic significance, with high levels seen in autoimmune diabetes, encephalitis, stiff-person syndrome, and cerebellar ataxia. An autoantibody panel can be considered in patients with KLS, as the presence of autoimmune encephalitis may support the use of immunotherapy. Support (if any) Portland VA Research Foundation to Dr. Lim. The contents do not represent the views of the United States Government.

“Fueling the Fire” - Irish Sea-Moss Resulting in Jod-Basedow Phenomenon in a Patient With Grave’s Disease

Background: Jod-Basedow phenomenon is a rare cause of thyrotoxicosis due to excess iodine intake. Herbal supplements containing sea-moss have high iodine amount which may precipitate thyrotoxicosis in patients with underlying Grave’s disease or autonomous thyroid nodules. Clinical Case: A seemingly healthy 28-year-old female presented to the ED with chief complaint of fatigue with associated anxiety, palpitations and weight loss. On admission her temperature was 100.4 F, pulse 126 bpm and blood pressure 116/56 mmHg. Exam was unremarkable for thyroid goiter or orbitopathy. Labs revealed WBC count 3.4 x103/µL (ref range 4.0-11.0) with neutropenia, hemoglobin 4.3 g/dL (11.7-15.7), platelet 49 x103/µL (150-450). Liver transaminases (AST, ALT, and alkaline phosphatase) were elevated with levels up to 4 times the upper limit of normal. She was diagnosed with hemolytic anemia secondary to severe Vitamin B12 deficiency due to pernicious anemia. TSH was <0.01 mIU/L (0.27-4.20), free T4 2.46 ng/dL (0.8-1.9) and total T3 139 ng/dL (76-181). The patient subsequently endorsed remote history of hyperthyroidism diagnosed 7 years ago however she could not recall the underlying etiology or the name of medication she was treated with. She reportedly stopped this medication after 1 month due to developing goiter. She also endorsed intermittent use of store-bought supplement of Irish sea moss and bladderwrack in last 2 years. Further workup revealed elevated TSI and TBII antibody titers establishing diagnosis of Grave’s disease. Thyroid ultrasound showed normal sized heterogeneous hypervascular gland with no nodules. I-123 thyroid uptake and scan showed diffuse moderately elevated radioiodine uptake of 16.8% and 40.8% at 4 and 24 hours, respectively. Thionamide therapy was withheld due to concern of neutropenia and transaminitis. She was treated with beta-blocker after which her vital signs normalized. Labs 1 week after stopping sea moss showed TSH 0.01 mIU/L and free T4 1.4 ng/dL. Conclusion: Irish sea moss is a readily available herbal supplement with high, variable amounts of iodine. Despite little scientific evidence, it is often marketed to improve goiter amongst other health benefits. The recommended daily iodine intake per the FDA is 150 mcg. Higher amounts are expected to initially cause a short-lived suppression of thyroid function; the Wolff-Chaikoff effect, followed by “escape” and accelerated production of thyroid hormone in abnormal thyroid gland, known as Jod-Basedow phenomenon. In our case, the patient unknowingly worsened her underlying Grave’s disease due to the Jod-Basedow effect. Of note, apparantly she had a longer than expected course of Wolff-Chaikoff effect preceding the thyrotoxic state due to sporadic irregular intake of sea moss. Discontinuing sea moss led to clinical and biochemical improvement of hyperthyroidism without requiring thionamide therapy.

Tumor Induced Osteomalacia - Long Term Medical Treatment When Surgery Is Risky

Introduction: Tumor induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by bone pain, muscle weakness and fractures caused by production of a phosphaturic factor by rare mesenchymal bone or soft tissue tumors that causes isolated renal phosphate loss and osteomalacia. Low phosphate (iP), high bone alkaline phosphatase (BAP), and normal or low 125 dihydroxy D, are salient biochemical findings. Fibroblast derived growth factor (FGF 23) may be high or inappropriately normal. Gallium-68 Dotatate (DoT) imaging has become the imaging method of choice. Long term medical management may be required when removal of the tumor is risky or not feasable. Case Report: 65 yr old woman with carcinoid tumor of the right lung and a bony lesion in the T3 vertebral body diagnosed with TIO. She was initially screened for osteoporosis after traumatic rib fractures. Bone scan and SPECT-CT revealed numerous foci of increased uptake. She had elevated alkaline phosphatase 186 IU/L (0–140) and PTH 83 pg/ml (15–65) with a low phosphate 1.5 mg/dl (2.5–4.5), along with normal FGF23 level 102 RU/ml Ref Range < + 180 RU/ml. DoT and PET CT imaging for TIO evaluation showed a foci of increased uptake right lower lobe of her lung, and “osseous metastatic disease” in the right scapula, vertebral body, iliac, and pubic ramus. Sclerosis of T3 vertebral body was noted in the area of intense Gallium Dotatate uptake. Transbronchial excision of the lesion showed a well differentiated neuroendocrine carcinoma. Chromogranin A and 24 hour urine for 5HIAA were normal. She responded well to medical therapy with oral phosphate, calcium and calcitriol. Follow up, DoT and FDG PET showed persistent intense uptake in the sclerotic lesion on T3 vertebral body, while the rest of the hot spots resolved. Sclerotic T3 lesion is likely the primary lesion that is responsible for the TIO. Neuroendocrine tumor of the lung may be a mere association. Biopsy of the T3 lesion was not feasible and excision was considered risky to the patient. Discussion: Our case illustrates that awareness is the key to early diagnosis of TIO. FGF 23 in some TIO cases may be inappropriately normal in commercial assays and even in research labs. Measurement of fibronectin 1 (FN1) and FGF receptor 1 fusion gene which is noted in up to 60% of tumors are not commercially available. While DoT and PET CT are imaging modality of choice, CT and MRI may be useful to define the anatomy of the lesion. Long term medical management may be necessary when removal of primary lesion is not possible or risky. Most tumors are benign while some may prove to be malignant.

New Onset Autoimmune Diabetes Mellitus, Autoimmune Thyroiditis and Subsequent Autoimmune Hepatitis With Monoclonal Antibody to Programmed Cell Death-1 (PD-1) Protein Therapy in a Patient With Non Small Cell Lung Cancer: 18 Months Follow up Experience

Background: Monoclonal antibody to Programmed cell death-1 (PD-1) protein binds to PD-1 receptor and blocks its interaction with PD Ligand 1 and PD Ligand 2, which helps restore the immune response for various types of cancer treatment are used widely. These agents are associated with many auto immune diseases. We describe a case where a patient treated with PD-1 inhibitor manifested three autoimmune diseases. Clinical Case: A 62 year old female with past medical history of Non small cell adenocarcinoma stage IV with gluteal muscle metastasis was referred to endocrinology for new onset Diabetes Mellitus (DM). Family history was negative for thyroid and other autoimmune diseases, Her brother had type 2 DM. On physical examination: elderly female, thin built, BMI: 16.7 kg/m2 with a non-palpable thyroid and no skin lesions. Patient was started on Pembrolizumab every 3 weeks. During 2nd cycle, her basic metabolic panel revealed blood glucose level of 409 mg/dl, negative serum ketone, normal anion gap of 11 and HbA1c: 7.0 %, Anti TPO: positive; 9 (ref<9 IU/mL) with normal TSH, Ft4 and T3 level. C-peptide level was <0.1 (ref: 0.8- 3.85); Glutamic acid (GAD) antibody elevated: >250 (ref range<5), and Islet Cell Antibody was negative. CT scan of abdomen with contrast showed pancreas within normal limit. Prior to initiation of Pembrolizumab therapy her HbA1C was 5.3 and 8 am serum cortisol level was 19 ug/dl. She was started on multiple dose of subcutaneous insulin therapy for autoimmune DM. Her DM was well controlled on .77 units/ kg insulin dosage targeting a finger stick of 140–200 mg%. Following 16 cycles of Pembrolizumab patient was found to have elevated liver enzymes ALT 807 U/L, AST 1109 U/L, total bilirubin 2.1 mg/dL, with concerns for autoimmune hepatitis. A CT scan with contrast ruled out any metastatic lesion to liver, follow up labs with HbA1c 12.3%, TSH 1.09 uIU/mL, C-peptide remains<0.01 and TPO Ab remains positive: 60 IU/mL. Patient’s HLA pattern was heterozygous DR4-DQ8 and heterogyzous DR1-DQ5 haplotype. Conclusion: The loss of β cell function in our case appeared to be fulminant as suggested by the relatively low glycated hemoglobin level while C-peptide level was undetectable at diagnosis of autoimmune DM. High dose steroid therapy was not successful in reversing the condition and another case reported beta cell destruction was halted by stopping the check point inhibitor therapy. Recently, American society of Oncology article suggested measuring glucose at baseline and with each treatment cycle during induction for 12 weeks, then every 3–6 weeks thereafter risk factors for each subtype of DM to be assessed[1]. Reference: 1. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline, Journal of Clinical Oncology 2018 36:17, 1714–1768, DOI: 10.1200/JCO.2017.77.6385