bluuebunny/crossref_metadata_2025 huggingface dataset:
ODP580 A Case of New Onset Primary Adrenal Insufficiency in COVID Infection
Authors: Beshay Lauren , Yang Qin , Beshay Lauren
Published: November 2022

Background

Accumulating body of evidence shows that SARS-CoV-2 infection in COVID-19 is linked to a variety of autoimmune complications including autoimmune endocrinopathies. Here we report a case of newly diagnosed Addison's disease post-COVID-19 infection.

Case Description

A 23-year-old male with a history of three episodes of acute disseminated encephalomyelitis (ADEM) in childhood, was brought into the emergency department (ED) by EMS after being found down with a blood glucose of 28 at the field. Prior to presentation, he reported 3 days of sore throat, nausea, vomiting, fatigue, and chills. He takes no home medications, and is not vaccinated against COVID-19. In the ED, the physical exam is notable for temperature 39°C, pulse 145, BP 80/42, RR 39, and no mucocutaneous hyperpigmentation. Labs revealed a positive COVID test, serum sodium 125 mmol/L (135-145), potassium 3.1 mmol/L (3.5-4.1), and persistent hypoglycemia. TSH 1.89 μIU/mL (0.45-4.12). A morning baseline cortisol was 4 mcg/dl (ref: >18) with ACTH level of >1250 pg/ml (0-45). A high-dose 250 mcg ACTH stimulation test followed; with cortisol levels of 3, and 3 mcg/dl (ref: >18) at 30, and 60 minutes; respectively. Aldosterone <3. 0 ng/dl (4. 0-31. 0), and anti-21-hydroxylase antibody was positive (ref: negative). A CT scan of the abdomen with contrast demonstrated mildly atrophied bilateral adrenal glands. The hypotension and hyponatremia resolved after initiation of intravenous hydrocortisone, and he was discharged on hydrocortisone and fludrocortisone.

Conclusion

The patient's symptoms, elevated ACTH, low cortisol, and presence of 21-hydroxylase antibodies, are consistent with autoimmune Addison's disease. Since ADEM is an autoimmune condition, it is likely that the patient had underlying undiagnosed Addison's disease and COVID-19 triggered an adrenal crisis. There is also a possibility that SARS-CoV-2 infection may have induced a higher titer of adrenal antibody, leading to the exacerbation of Addison's disease. The case highlights the importance of considering adrenal insufficiency as a diagnostic differential in hemodynamically unstable COVID-19 patients, especially those with underlying autoimmune conditions.

Presentation: No date and time listed
LBODP104 Thyroid Plasmapheresis: An Alternative Option For Thyroid Storm
Authors: Khine Aye , Yin Ngwe
Published: November 2022

Introduction

Thyroid storm is a rare, life-threatening condition with a high mortality rate approaching 10-30%. The mainstay of treatment includes initiation of therapy directed against the thyroid, supportive intensive care, and treatment of any precipitating factors. We report three cases of patients with thyroid storm and successful therapeutic use of plasmapheresis when traditional therapy was contraindicated.

Clinical Cases Case 1

A 22-year-old male with no known past medical history, presented with fever, shortness of breath, and syncope. Labs showed TSH 0. 014 mIU/L (range 0.4-4.5), FT4 4.30 ng/dL (range 0.9-2.2), TSI 546% (range <140), and TPO 20 U/mL (range <60). He was diagnosed with thyroid storm due to Graves’ disease (Burch-Wartofsky score of 60). He was initially treated with propylthiouracil (PTU), hydrocortisone, propranolol, and Lugol's iodine solution. He developed transaminitis and shock liver so was not able to continue PTU or trial methimazole. He underwent 4 rounds of plasmapheresis with improvement in thyroid hormone levels and eventually had thyroidectomy.

Case 2

A 37-year-old female with known Graves’ disease (non-adherent to antithyroid drug), presented with shortness of breath and palpitations. Labs showed TSH <0. 01 mIU/L (range 0.4-4.5), FT4 4.83 ng/dL (range 0.9-2.2), and FT3 6. 0 pg/mL (range 2.3-4.2). Burch-Wartofsky score was 40 and supported the diagnosis of thyroid storm. She was initially treated with methimazole, hydrocortisone, propranolol, and Lugol's iodine solution. She developed transaminitis and there was also concern for methimazole-induced insulin autoimmune syndrome, so methimazole was discontinued. She underwent 3 rounds of plasmapheresis with improvement in thyroid hormone levels and eventually had thyroidectomy.

Case 3

A 31-year-old female with no known past medical history, presented with shortness of breath and altered mental status requiring intubation. Labs showed TSH <0. 01 mIU/L (range 0.4-4.5), FT4 4.65 ng/dL (range 0.9-2.2), FT3 25.2 pg/mL (range 2.3-4.2), TSI 467% (range <140), TPO 375 U/mL (range <60). She was diagnosed with thyroid storm due to Graves’ disease (Burch-Wartofsky score of 90). She was initially treated with methimazole, hydrocortisone, propranolol, and Lugol's iodine solution. She developed pulmonary alveolar hemorrhage and it was unclear if this was due to methimazole, thus methimazole was discontinued. She underwent 5 rounds of plasmapheresis with improvement in thyroid hormone levels and eventually had thyroidectomy.

Conclusion

Plasmapheresis can be an effective and safe treatment option in thyroid storm when there are contraindications for antithyroid drugs or when rapid normalization of thyroid hormone levels is needed. It should be considered as a stabilizing measure as it leads to marked improvement of thyrotoxicosis within 3-5 days, allowing thyroidectomy for definitive therapy.

Presentation: No date and time listed
ODP450 A Case of Metastatic Medullary Thyroid Cancer Presenting with Pathologic Hip Fracture
Authors: Watari Jessica , Miller Jeffrey
Published: November 2022

Introduction

Medullary thyroid cancer accounts for less than 5% of thyroid malignancies. Distant metastatic disease typically presents in lymph nodes, lung, liver and bone. We present a patient who initially presented with a pathologic hip fracture with bone biopsy revealing medullary thyroid carcinoma.

Case Description

A 44-year-old male with no past medical history presented to the emergency department for right hip pain following a mechanical fall. Imaging showed a right femoral neck pathologic fracture as well as lytic lesions within the right femoral neck and right ilium. Family history was significant for pancreatic cancer and breast cancer. The patient underwent bone biopsy of the right femur followed by total hip arthroplasty. Bone biopsy revealed metastatic medullary thyroid carcinoma. Thyroid ultrasound showed a 1.2 centimeter right solid hypoechoic nodule along with extensive cervical lymphadenopathy. Further imaging revealed metastatic disease throughout the thoracic spine, mediastinal lymphadenopathy, and a left 2.2 centimeter adrenal lesion with peripheral enhancement and possible necrosis. Carcinoembryonic antigen (CEA) level was 551 ng/mL (normal <4.7), calcitonin was 2,498 pg/mL (normal <10), and calcium levels were normal. Plasma free metanephrines were normal and plasma normetanephrines were less than two times the upper limit of normal. Genetic testing on the bone biopsy specimen revealed a RET p. C618S variant. Germline RET testing was collected. The patient was discharged with close follow-up with oncology to initiate systemic therapy and follow-up with endocrinology for the adrenal mass.

Discussion

Majority of cases of medullary thyroid carcinoma are sporadic. Patients typically present with a thyroid nodule with many having cervical lymph node involvement at diagnosis and 5-10% having distant metastatic disease. Our patient's initial presentation was unique in that he presented with a pathologic fracture. Bone metastases can be seen in about 30% of cases of metastatic medullary thyroid carcinoma. Calcitonin levels greater than 500 pg/mL require additional imaging to exclude metastatic disease. If RET mutational status is unknown, patients should be screened for primary hyperparathyroidism and pheochromocytoma. Screening for pheochromocytoma is critical in preoperative management of these patients. Treatment for patients with metastatic disease involves surgery, external beam radiotherapy, and kinase inhibitors.

Presentation: No date and time listed
ODP480 Failure to achieve remission post Radioactive iodine therapy
Authors: Paliou Maria , Tahir Marium , Trousdale Rhonda
Published: November 2022

Background

Radioactive iodine-131 (RAI) therapy is used to treat hyperthyroidism secondary to toxic multinodular goiter (TMNG) and Graves’ Disease (GD). The treatment failure (TF) rate for RAI as reported in previous studies is 8-16% (1). Most patients respond to RAI with normalization of thyroid function tests and improvement of clinical symptoms within 4–8 weeks. Previous studies also report higher TF rates amongst Black patients (2), but due to the low number of Blacks included in the study, identification of factors related to higher TF rates was difficult.

Study Purpose

Determine treatment failure rates in patients who underwent RAI treatment for hyperthyroidism and characteristics related to Treatment Failure.

Methods

This is a retrospective study that included patients treated with RAI for either TMNG or GD from 2014-2021 at an urban hospital. Patients with thyroid cancer, less than 18 years, or toxic adenoma were excluded. TF was defined as persistent hyperthyroidism 6 months after RAI. Remission was defined as euthyroid or hypothyroid state off of anti-thyroid hormones 6 months after RAI. Factors evaluated included age at RAI, gender, race, cause of hyperthyroidism, percentage uptake in pretreatment scan, peak Ft4 / Ft3 pre-treatment, RAI dose, and treatment with methimazole post RAI. Comparison of TF to those who achieved remission was performed using two-sample t-test or the Wilcoxon rank-sum test for continuous variables and fisher tests for categorical variables.

Results

66 patients were included in the analysis. Mean age was 49 years, majority female (76%), African (21%), African American (45%), GD (68%), TMNG (32%). 19 had TF (28.7%). There was no significant difference in characteristics between TF and remission groups prior to RAI. The RAI dose was not significantly different between the groups (21. 0;21.1mCi). However, patients given methimazole shortly after RAI were at significantly higher risk of TF compared to patients who did not receive methimazole after RAI (64% vs 89%, p=0. 04).

Conclusion

Previous studies report TF after RAI as high as 16%. Patients at our Hospital with TMNG or GD who underwent RAI had a higher TF rate of 28.7%. The high TF rate was not due to low RAI treatment dose. Randomized Controlled Trials have found 61%-86% (1) success with RAI dose ranging from 5.4 -15.7 mCi (1). In comparison, mean RAI dose at our hospital was high at 21. 0. Patients prescribed methimazole within 4 weeks of RAI were more likely to have TF at 6 months. Based on the results of this study, we will initiate a change in protocol at our institution to hold methimazole for at least 4 weeks after RAI to see if this lowers the TF rates.

References

1. Ross, Douglas S., et al. Thyroid 26.10 (2016): 1343–1421. 2. Mohamadien, N. R., & Sayed, M. H. (2020). American Journal of Nuclear Medicine and Molecular Imaging,10(5), 235.

Presentation: No date and time listed
ODP492 Longitudinal Prospective Study of Thyroid Function Tests In Pregnancy
Authors: Davern Recie , Hatunic Mensud
Published: November 2022

Current thyroid function test (TFT) reference ranges in pregnancy are obtained from TPO antibodynegative women in each trimester. Recent international recommendations suggest using specific reference ranges based on local and national population data. Our aim is to study a longitudinal prospective model of TFTs by classifying individuals into groups according to their differing trajectories of TSH and FT4 during pregnancy. We performed a prospective study of TFTs in each trimester in pregnant women attending a national maternity centre. We conducted TFT testing at 12 weeks, between 24-28 weeks and between 34-36 weeks’ gestation. TPO antibody were tested in the second trimester.490 women with no prior history of thyroid disorder have been recruited to date. Mean age was 34+/-5.3. Primiparity was 36.83%. First trimester TSH (median) was 1.44 mmol/L (0.9850-1.90), FT4 14.3 mmol/L (12.90-15.65), second trimester TSH 1.46 mmol/L (1. 09-1.91), FT4 12 mmol/L (10.95-13.15) and third trimester TSH 1.5 mmol/L (1.125-2. 015) and FT4 11.7 mmol/L (10.5-132.2). 20% of women were TPO antibody positive. There were 6 new hypothyroidism diagnoses, all TPO antibody positive and required treatment. Subclinical hypothyroidism was diagnosed in 13 participants with 76.9% TPO antibody positive and 10 requiring treatment. We made 7 new diagnoses of hyperthyroidism, 3 who were antibody positive and requiring treatment. Patients were grouped into three categories based on first trimester TSH: 4 with TSH <0. 05 mmol/L, 409 with TSH 0. 05-2.5 mmol/L and 77 with TSH >2.5 mmol/L. This represents the first longitudinal study of TFTs measured across each trimester of pregnancy in Irish women. 26/490 (5.3%) of women had TFT dysfunction with 19 requiring treatment during pregnancy. One fifth of women had TPO antibody positivity which is a higher proportion than reported in previous studies of thyroid disease in pregnancy.

Presentation: No date and time listed
ODP511 Relationship between TSH and Free Thyroxine in Outpatient Cancer Patient Population
Authors: Li Jieli , Alkhalaileh Hussam , Wei Ruhan , Lee Jason K Y , Williams JoAnna
Published: November 2022

Background

The inverse log-linear relationship between TSH and free thyroxine (FT4) is well established and reliably used for evaluation of hypothalamus-pituitary-thyroid axis function. However, there are limited data regarding pathophysiologic states in the TSH-FT4 relationship. The purpose of this study was to evaluate thyroid pituitary hypothalamic feedback regulation by the inverse log TSH and FT4 relationship in cancer patient population at the Ohio State University Comprehensive Cancer Center (OSUCCC-James).

Methods

This retrospective study analyzed the correlation between TSH and FT4 results from 13039 outpatient subjects collected in August 2019-November 2021 at Department of Family Medicine (OSU Wexner Medical Center), Department of Oncology and Department of Chemotherapy (OSUCCC-James). Time of collection for TSH and FT4 was from 7am to 7pm. Data were analyzed by morning (7am-12pm) and afternoon (12pm-7pm). Spearman correlation and non-linear fit were used for data analysis. Sex differences were analyzed as well in each group.

Results

No significant differences of TSH or FT4 results were found across all study groups and times in both males and females. Overall, an inverse correlation was observed between TSH and FT4 in the morning and afternoon for both male and female populations in all the three groups. Further analysis by non-linear model in log TSH and FT4 showed a worse fit in the group of Oncology compared to the group of Family Medicine, specifically in the morning data set in both males and females. Interestingly, the inverse non-linear relationship between log TSH and FT4 in the female group designated Chemotherapy showed a better fit in the afternoon, compared with other data sets in the same group.

Conclusions

In cancer patients, the inverse non-linear relationship between TSH and FT4 is weak, which might be resultant of malignancy or medication treatments, or other unknown reasons. The results advance understanding of the pathophysiology and challenges of laboratory diagnosis of thyroid disease in cancer patients. A better understanding of the complex nature of the TSH-FT4 relationship may need further study with better defining subclinical states of cancer patients.

Presentation: No date and time listed
PSAT265 Blood Glucose in Thyroid Eye Disease (TED) in Patients treated with Teprotumumab: Clinical Trials Data
Authors: Smith Terry J , Bhattacharya Rajib K , Hsu Kate , Kim Sun , Sile Saba , Barbesino Giuseppe , Holt Robert
Published: November 2022

Background

Teprotumumab, an FDA-approved insulin-like growth factor-1 receptor inhibitor for TED, improves proptosis, diplopia, inflammation, and quality of life. In the pooled phase 2 and 3 trial analysis, 8/84 (10%) teprotumumab-treated patients reported hyperglycemia adverse events (AEs) versus 1/86 (1.2%) in placebo. Here, we discuss perturbations in serum glucose data reported in patients from two pivotal clinical trials with teprotumumab.

Methods

Glycemia data from two randomized, double-masked, placebo-controlled multicenter trials were analyzed throughout 8 teprotumumab vs. placebo infusions. Blood glucose was measured at Weeks 1, 4, 15, and 21 in phase 2 study patients. In phase 3, all patients with pre-existing diabetes had blood glucose measured at each study visit. Patients without pre-existing diabetes had fasting blood glucose measurements at Weeks 1 and 4. The remainder of blood glucoses in non-diabetics were non-fasting. HbA1c levels were measured at baseline, 12 and 24 weeks, in all patients.

Results

The mean patient age was 51.4 years, with 73% female. At baseline, diabetic patients were controlled with oral and/or insulin therapies at primary investigator discretion. Mean baseline non-fasting blood glucose in teprotumumab patients was 98.3 mg/dl versus 100.5 mg/dl in placebo. Mean non-fasting blood glucose increased from baseline in teprotumumab-treated patients by 6.9 mg/dl but decreased by 6.5 mg/dl in those receiving placebo at 24 weeks. Nine hyperglycemia AEs were reported in 8 teprotumumab-treated patients; 6 resolved during the treatment period, 2 resolved after the last dose, and 1 continued after study completion. Five of 8 patients who had hyperglycemia had pre-existing diabetes in this pooled analysis. All reported hyperglycemic AEs were Grade 1 (>160mg/dl) or 2 (161 mg/dl to 250 mg/dl). In the teprotumumab group follow-up, two patients had hyperglycemia-related AEs. One resolved without medication. Neither led to study drug discontinuation. HbA1c increased by 0.22% (mean, N=72) with teprotumumab compared to 0.04% (N=71) with placebo. There were no cases of diabetic ketoacidosis or hyperosmolar hyperglycemic state.

Conclusion

Approximately 10% of teprotumumab treated patients compared to 1% receiving placebo had hyperglycemic events. Most hyperglycemic cases were easily controlled with medication. In addition, no treatment discontinuation or complications were associated with these elevated blood glucose levels. This analysis demonstrates no evidence for severe diabetogenesis with teprotumumab treatment, although blood glucose monitoring is recommended for all patients.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT288 Mucosa-associated Lymphoid Tissue Thyroid Lymphoma Presenting as a Rapidly Growing Neck Mass in an Asymptomatic Male Patient
Authors: Shrestha Nancy , Aguirre Lina E , Ekpe Victor , Dorin Richard I
Published: November 2022

A 77-year-old male was referred to endocrinology for a 2-month history of a rapidly enlarging painless left neck mass. His only other complaint was unintentional weight loss of 10 pounds over 12-months. On exam patient had a firm, smooth, nontender 2 cm thyroid/neck mass extending below left clavicle. No abnormalities were detected for right thyroid gland. There was no palpable lymphadenopathies or hepatosplenomegaly noted. No signs of tracheal, esophageal, or neck vein compression were noted. He did not have any history of radiation exposure, family history of thyroid-related disorders, or malignancy. Laboratory test including complete blood count, comprehensive metabolic profile and TSH were within normal limits. TPO antibody was positive. Ultrasound revealed a 7.7×4.1×4 cm hypoechoic spongiform mass replacing the left lobe of the thyroid, as well as scattered sub centimeter nodules. Contrasted CT of the neck confirmed 6.5×5.2×3.9 cm left thyroid mass causing mild rightward deviation of the trachea and extending into the superior mediastinum and no lymphadenopathy. FNA of the mass revealed presence of crushed lymphoid cells without thyroid follicular cells, which raised the possibility of chronic lymphocytic thyroiditis. FDG- PET scan showed intense, heterogeneous FDG uptake in the left neck mass (max SUV=10.7), likely arising from the left thyroid lobe concerning for thyroid malignancy without evidence of distant metastases. The patient underwent a left thyroid nodule core biopsy with subsequent left thyroid hemithyroidectomy. The pathology stains of the excised left thyroid lobe core biopsy showed extra nodal zone lymphoma of mucosa- associated lymphoid tissue (MALT Lymphoma) with extensive plasmocytic differentiation. Surgical path confirmed extra nodal zone lymphoma of mucosa-associated lymphoid tissue (MALT Lymphoma) with extensive plasmocytic differentiation and foci of chronic lymphocytic thyroiditis. Immunochemistry studies supported a diagnosis of plasma cell neoplasm or the plasma cell component of a B-cell lymphoproliferative disorder. Short-term follow-up FDG-PET and CT imaging demonstrated post-surgical changes without evidence of recurrence.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT297 Subacute Thyroiditis Following COVID-19 Vaccination
Authors: Alfares Khalid
Published: November 2022

Introduction

Subacute thyroiditis (SAT) precipitated by COVID-19 infection has been documented in the literature. However, we are now seeing patients develop SAT following the COVID 19 vaccine. Vaccine-related SAT have been reported in the literature, such as in the SARS vaccine. There are now several COVID-19 vaccines being used with benefits on morbidity and mortality. The mechanism of action leading to SAT from the vaccine has not been deciphered, however there are some theories. Here we present a case of COVID-19 vaccine-related SAT.

Case

42-year-old Caucasian gentleman with no past medical history, presented to the Endocrinology clinic with anterior neck pain around his thyroid area that started 3 days after his 2nd Pfizer COVID-19 vaccine. He described the pain as severe enough to wake him up from sleep. No weight loss, palpitation, heat intolerance or tremors. No prior exposure to stable iodine or radiation treatment. He takes no medications. He denies tobacco or alcohol use. Initial thyroid labs showed a T3 2.8 (2.5 - 4.4 pg/mL), T4 1.4 (0.61 - 1.44 ng/dL), TSH 1.4 (0.45 - 5.33 uIU/mL), TPO antibodies positive, thyroglobulin Ab undetectable, sedimentation rate of 42 (<30 mm/Hr). Ultrasound of the neck showed 1.7-centimeter TIRADS 4 nodules in the left lobe, and 0.9 cm on the right. The patient was noticing a discomfort in the right side of the neck. He was also having swallowing difficulties, low-grade fever, body ache, night sweats and unintentional weight loss. Though he initially presented with thyroid labs that were within the normal reference range, by the time he repeated them one month later, he was hyperthyroid. He was started on prednisone 20 mg and NSAID. At 2 weeks follow-up, his pain and swallowing difficulty have significantly improved. Over time, the patient's thyroid labs normalized and the pain in the neck subsided, repeat neck US 5 months later showed decreased nodule size. Steroids was stopped.

Discussion

The common side effects COVID-19 vaccines include pain in the injected site, skin reactions, flu-like symptoms, headache, fatigue and fever. SAT following viral vaccines has been reported previously. The association between SAT and COVID-19 vaccination has come to medical attention more recently due to widespread vaccinations. The mechanism for post-vaccination SAT remains unknown. However, adjuvants contained in vaccines may play a role in producing diverse autoimmune and inflammatory responses and the potential for cross-reactivity between the coronavirus spike protein target produced by the mRNA vaccine and healthy thyroid cells antigens. This case exemplifies the need to know about SAT and COVID 19 vaccine so that clinicians can advise patients to seek medical assistance if experiencing anterior neck pain, extended fever or palpitation so that they are treated properly and in a timely fashion.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
OR12-2 Inhibition of Basal and ACTH-stimulated Cortisol Secretion in Humans Using an Oral Nonpeptide ACTH Antagonist (CRN04894)
Authors: Betz Stephen , Ferrara-Cook Christine , Hernandez-Illas Martha , Luo Rosa , Madan Ajay , Miller Stephanie , Struthers Scott , Trainer Peter , Wang Yang , Krasner Alan
Published: November 2022

CRN04894 is a potent orally bioavailable MC2R (adrenal cortex specific ACTH receptor) antagonist (Kb=0.34 nM) that is >1000-fold selective for MC2R over other melanocortin receptor subtypes. In rats receiving continuous administration of ACTH via subcutaneously implanted osmotic pumps, oral administration of CRN04894 over 7 days has previously been shown to result in dose-dependent suppression of basal and ACTH stimulated corticosterone levels. This compound is in clinical development for the treatment of diseases of ACTH excess including congenital adrenal hyperplasia (CAH) and Cushing's Disease.

We report initial results from a randomized double-blinded, placebo-controlled single ascending dose study evaluating the safety, pharmacokinetics and pharmacodynamics of CRN04894 in 39 healthy volunteers. After an overnight fast, single doses of CRN04894 were administered at approximately 8 am, 2 hours prior to an IV bolus of ACTH 1-24 (cosyntropin). Serial cortisol over 600 minutes and pharmacokinetics over 168 hours post CRN04894 dose were measured. Two different challenge doses of ACTH 1-24 were studied: 250 μg (supra-pharmacological) and 1 μg (comparable to ACTH concentrations encountered in CAH and Cushing's Disease).

CRN04894 was rapidly orally absorbed (median tmax 0.5-1.5 hour), and demonstrated a dose dependent increase in systemic exposure, with an apparent terminal elimination t1/2 of approximately 20 hours.

Unstimulated (basal) cortisol measured 2 hours after CRN04894 administration fell in a dose-dependent manner, resulting in reduction near the theoretical maximum with the 80 mg dose cohort (-56.1% [SEM 4.0%, n=12] vs +17.4% in placebo [SEM=18.1%, n=9]). Dose-dependent cortisol suppression following a supra-pharmacological ACTH-stimulated (250 μg) was also observed, with a 41% reduction in the area under the curve (AUC60-600min) post-stimulation at the 80 mg dose. Furthermore, a single dose of 80 mg of CRN04894 reduced the cortisol response (AUC15-120 min) to a disease relevant 1 μg ACTH challenge by 48%, maintaining cortisol concentrations within the normal range seen prior to dosing in a basal unstimulated state. Single doses of CRN04894 were well tolerated with no need for glucocorticoid supplementation. All adverse events (AEs) were considered mild or moderate and there were no serious AEs.

The data from this single-dose, proof-of-concept study show that MC2R antagonist CRN04894 was well tolerated after oral delivery in healthy volunteers and demonstrated dose-dependent increases in exposure with lowering of basal and ACTH-stimulated cortisol secretion, including in the presence of disease relevant excess ACTH exposure. Multiple ascending dose evaluations are underway in anticipation of studies in patients with diseases of ACTH excess.

Presentation: Sunday, June 12, 2022 11:15 a.m. - 11:30 a.m.
PSAT364 High-Dose Levothyroxine to Exclude Malabsorption as a Cause of Refractory Hypothyroidism in Hospitalized Patients: Two Cases
Authors: Majumdar Sachin , Vangipuram Deepak
Published: November 2022

Introduction

Levothyroxine malabsorption is one of the causes of refractory hypothyroidism. Administration of a single large dose of levothyroxine can help distinguish this from refractory hypothyroidism due to other causes, but little is known about the utility of this test in patients hospitalized for severe hypothyroidism.

Case 1

A 42-year-old woman with Hashimoto's thyroiditis presented with symptomatic hypothyroidism. She reported being compliant with 150 mcg of levothyroxine daily. However, in the past year, her free T4 remained < 0.10 ng/dL on several occasions with TSH > 80 uIU/mL. On admission, free T4 was 0.58 ng/dL, total T4 was 4.9 ug/dL, and TSH was 57.06 uIU/mL. We administered 1000 mcg levothyroxine and found an increase in total T4 at 4 hours (12.1 ug/dL from 4.9 ug/dL). Absorption was found to be 100% at 4 hours implying that she was not taking her levothyroxine appropriately. She was counseled to take levothyroxine at 150 mcg on an empty stomach. At outpatient follow up in 3 weeks, free T4 improved to 1.44 ng/dL and TSH decreased to 1.050 uIU/mL.

Case 2

A 42-year-old woman with hypothyroidism, alcohol hepatitis, chronic pancreatitis and previous Roux-en-Y gastric bypass was admitted with progressive lower extremity edema and shortness of breath. She reported taking levothyroxine 175 mcg each morning with her other medications that included omeprazole and magnesium oxide, along with coffee and milk soon after. Her admission labs showed free T4 0.61 ng/dL, total T4 2.8 ug/dL and TSH 84.4 uIU/mL. After 1000 mcg of levothyroxine her total T4 increased from 2.6 ug/dL to 7.8 ug/dL in 4 hours, indicating 100% absorption. The reason for her inadequate outpatient response was probably the combined use of omeprazole, magnesium oxide and coffee with milk, being taken with levothyroxine. She was asked to continue levothyroxine 150 mcg on an empty stomach. Method: Patients were made NPO at midnight prior to the morning of the study. Baseline total T4 was obtained at 6: 00 AM and 1000 mcg of oral Levothyroxine was administered while the patient was monitored on telemetry. Total T4 was measured at 2 and 4 hours after administration.

Percentage absorption (% absorbed) = [[Increment TT4 (mcg/dL)×10 (dL/L)]/[total administered LT4 (mcg)]]×Vd (L)X100; Increment TT4 = [Peak TT4] - [Baseline TT4]; Vd (volume of distribution) = 0.442×BMI1

Conclusion

These cases indicate that a 1000 mcg T4 absorption study is safe and reasonable to perform in patients who are hospitalized for profound hypothyroidism when outpatient evaluation has been ineffective or challenging.

1 Gonzales KM, Stan MN, Morris JC 3rd, Bernet V, Castro MR. The Levothyroxine Absorption Test: A Four-Year Experience (2015-2018) at The Mayo Clinic. Thyroid. 2019 Dec;29(12): 1734-1742.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
LBODP108 Did You Follow Your Patient After ICI Cessation? A Case of Immune-Related Adverse Event 5 Months Following Completion Of Immunotherapy
Authors: Kedarisetti Sreekari , Vetrici Mariana , Tun Yin Nwe
Published: November 2022

Introduction

Immune checkpoint inhibitors (ICI) have been approved for use in cancer therapy for malignant melanoma, non-small cell lung cancer, and renal cell carcinoma in the last decade. Since their inception, immune-related adverse events (irAEs) have been well documented. We present a patient who developed 2 irAEs - grade 1 irAE during therapy and grade 3 irAE five months after completion of anti-CTLA-4 (Ipilimumab) and anti-PD-1 antibody (Nivolumab) therapy.

Case description

Our patient is a 65-year-old woman who was diagnosed in 2019 with Melanoma over the left knee which was resected in her home country. During follow-up here, she was started on immunotherapy with Ipilimumab and Nivolumab for metastatic disease. Her baseline labs including TFTs were normal before initiation of therapy. During treatment after 4 infusions, she developed hypothyroidism. At that time she was tolerating treatment well. Levothyroxine was initiated for this grade 1 irAE with the continuation of immunotherapy. She decided to move to her home country with a plan to pursue further immunotherapy upon her return. 7 months after discontinuation of therapy, the patient presented to our hospital with nausea, vomiting, and dizziness for 2 months. She was hypotensive and minimally responsive to intravenous fluids. Labs drawn were remarkable for hypothyroidism. Further workup demonstrated adrenal insufficiency with morning cortisol of 0.1 μg/dL and ACTH of <1.5 pg/ml. Pituitary hormones were within normal range except for elevated prolactin. A contrast-enhanced MRI of the pituitary was negative for any enlargement or mass. She was diagnosed with secondary adrenal insufficiency and managed with stress-dose corticosteroids with a resolution of symptoms. We were able to ascertain that our patient developed grade 3 irAE almost 5 months after her last immunotherapy.

Discussion

Cancer immunotherapy is associated with endocrinopathies such as hypophysitis, hypothyroidism, and adrenal insufficiency. As per a review done by González-Rodríguez E et al it has been found that the median time of onset from initiation for endocrine AEs was 7 - 20 weeks due to Ipilimumab and 11 weeks due to Nivolumab. In patients who received combined therapy, as per a retrospective study done by Nguyen et al, the median time from ICI administration to the diagnosis of immune-related hypophysitis was 35.8 weeks. In 2019, Ohara N reported a case of a patient with lung adenocarcinoma who developed isolated ACTH deficiency 4 months after discontinuation of Nivolumab therapy. Our patient developed two irAEs - during and after completion of immunotherapy. Symptoms can often be generalized and overlap with those of cancer progression making it difficult to diagnose. Our case highlights the need for continued surveillance of these patients by physicians probably even months after completion.

Presentation: No date and time listed
ODP538 A Case of Multiple Endocrine Neoplasia Type 2A with Malignant Paraganglioma
Authors: Ozawa Atsushi , Kondo Yuri , Horiguchi Kazuhiko , Yamada Masanobu
Published: November 2022

Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant hereditary cancer syndrome due to germline variants in the REarranged during Transfection (RET) proto-oncogene. There are two distinct clinical entities: MEN 2A and MEN 2B. MEN 2A is associated with medullary thyroid carcinoma (MTC), pheochromocytoma/paraganglioma and primary hyperparathyroidism.

Case presentation

At the age of 54, the patient became aware of a thyroid mass and went to the hospital. She was diagnosed as MTC by cytology. She was referred to our hospital for treatment. No thyroid cancer patients were found in her relatives. Her thyroid gland was elastic and soft, and a hard nodule about 1.5 cm in the lower pole of her left thyroid lobe was found. An Ultrasonography found the multiple nodules in both lobes of the thyroid gland, suggesting multiple or metastases of MTC. Although there was no family history, MEN2 was suspected, and screening of the abdominal organs by a CT scan revealed a 35 mm nodular lesion with calcification on the ventral side of the inferior vena cava (IVC). Multiple neoplastic lesions were found in her liver S2, S6 and S8 region. A CT scan also found the overall thickened right adrenal gland. An MIBG scintigraphy showed abnormal accumulations in these lesions. Laboratory data showed the increased the catecholamine metabolites both in blood and urine, and slightly increased CEA and calcitonin levels in the serum. After the genetic counselling, an informed consent was obtained and genetic test of RET oncogene was performed. A germline mutation was found in codon 634. Based on these findings, we diagnosed her as MEN2A with MTC, malignant paraganglioma and multiple liver metastases. First, IVC ventral lesions, multiple hepatic lesions, and right adrenal gland resection were performed. One month after the operation, total thyroidectomy and cervical lymph node dissection were performed. Pathologically, the IVC ventral tumor was a ganglion tumor covered with a pseudocapsule, with fibrous vitrification and coarse calcification inside. The histology of the liver regions were almost the same, and there was no finding suggesting the metastasis of MTC, and the histological image was consistent with the liver metastasis of paraganglioma. The right adrenal gland was diagnosed with adrenal medulla hyperplasia. Since then, she has been receiving continuous Cyclophosphamide Hydrate/ Vincristine Sulfate/Dacarbazine chemotherapy, and at the end of the 24th course, she has progressed without recurrence or the appearance of new metastases. It was reported that most Paragangliomas and pheochromocytomas in MEN2 with RET germline mutation are characterized by nonaggressive behavior, and paraganglioma was thought to be rare in onset than pheochromocytoma in MEN2A. In particular, cases of malignant paraganglioma in MEN2 with the RET634 germline mutation are extremely rare.

Presentation: No date and time listed
ODP557 PCSK9 Level Correlated with Disease Progression in Patient with Non-small Cell Lung Cancer
Authors: Iwabuchi Masayasu
Published: November 2022

Background

Hyperlipidemia may be present in cancer patients despite their debilitated general condition. It has also been reported that several types of cancer cells produce PCSK9, and that in advanced non-small cell lung cancer, chemotherapy with immune checkpoint inhibitors is effective in cases with low PCSK9 levels. We administered PCSK9 inhibitor to patients with advanced non-small cell lung cancer with hyperlipidemia according to the indications for hyperlipidemia. Chemotherapy with immune checkpoint inhibitors was performed, the patient's condition and the level of PSCK9 were observed. CASE: A woman in her 60s underwent surgery for lung cancer in 2017. The pathological diagnosis of squamous cell carcinoma of the left lower bronchus and the postoperative diagnosis of pT2bN2M0 stage IIIA were confirmed. Adjuvant chemotherapy with CDDP and VNR was started after surgery for her, but in 2018, recurrence of pulmonary lymph nodes was confirmed by intrabronchial induced transbronchial needle aspiration. The immunostaining result for PD-L1 was 50%. The first-line chemotherapy, the immune checkpoint inhibitor pembrolizumab, was started but was ineffective. She had high serum LDL levels of 174 mg/dL and high serum PCSK9 levels of 471 ng /mL (Norm: 47.4-225.2 ng/mL) despite exhaustion during her lung cancer treatment process. Her plasma PCSK9 levels were correlated with lung cancer status, suggesting PCSK9 production in lung cancer cells. Ezetimibe and statins were also discontinued because they were reported to increase serum PCSK9. The PCSC9K inhibitor evolocumab was administered at 140 mg every 2 weeks. Three months after the start of evolocumab, her serum PCSK9 level decreased slightly to 441 ng /mL. The immune checkpoint inhibitor nivolumab was then started, but the chemotherapy was ineffective, and her general condition worsened, correlating with her serum PCSK9 levels rising to 1635 ng/mL, and she died in 2021.

Discussion and Clinical Lessons

This is the first report on the clinical course of non-small cell lung cancer and the course of serum PCSK9 and the administration of PCSK9 inhibitors. Although PSCK9 is thought to be involved in cancer progression, the use of PCSK9 inhibitors at the same doses and doses as in the treatment of conventional hyperlipidemia failed to control cancer progression. The anti-PCSK9 vaccine has been experimentally shown to be effective against tumor progression. It is expected that PCSK9 inhibition by various methods will bring good results for cancer patients. Further research is needed to elucidate the exact mechanism by which PCSK9 regulates cancer cell proliferation and apoptosis. PCSK9 inhibitors, initially developed to treat hypercholesterolemia, may have significant involvement in the treatment of various cancers and their metastases. Therefore, collaboration between endocrinologists and oncologists is important in the laboratory and clinical practice.

Presentation: No date and time listed
PSUN370 Refractory Hypoglycemia Associated with a Metastatic Neuroendocrine Tumor Producing Multiple Hormones
Authors: Colon-Barreto Brigida , Liu Zhao , Steinberg Helmut , Karki Kanchan
Published: November 2022

Introduction

Neuroendocrine tumors are rare. They are derived from hormone-producing and nerve cells mostly found in GI tract, lung or pancreas. In about half of the cases, work-up does not detect any tumor-related hormone secretion. Even less common, the tumor produces several hormones which may be associated with clinical symptoms.

Clinical Case

A frail 81-year-old male with mild-to-moderate dementia and no history of diabetes presented to the emergency department with complaints of generalized weakness, fatigue, weight loss, poor appetite, diarrhea and shortness of breath for 1-2 weeks. Physical examination was pertinent for cachexia, general pallor, dry oral mucosa and having heme positive stool. Initial laboratory work-up found anemia (Hg 5.8g/dl), low glucose of 43 mg/dL, hypoalbuminemia (Alb 1.9 gm/dL). CT angiogram of abdomen did not show any active bleed but showed incidental diffuse hepatic lesions favoring metastatic disease, pancreatic ductal dilatation and fluid-filled loops of small and large bowel compatible with enteritis. Subsequent endoscopy and colonoscopy were negative for malignancy. Findings of multiple liver lesions prompted a CT-guided liver biopsy which showed a metastatic, well differentiated neuroendocrine tumor WHO grade II/III with positive stains for chromogranin A, synaptophysin, cytokeratin Oscar (Ki-67 less than 20%). MRCP abdomen examination of pancreas showed no focal pancreatic lesions but was suboptimal due to motion artefacts and lack of contrast. Workup for the tumor revealed increased serum serotonin (772 ng/ml), increased 5-HIAA (3,175 ng/ml), increased chromogranin A (48,436 ng/ml) and an increased 24hr Urine 5-HIAA (162mg/24hr). Further workup for the persistent and hypoglycemia showed a random cortisol 24.6mcg/dl. During hypoglycemia, insulin and C-peptide levels were 4.3 uU/L and 1.4ng/ml indicating inappropriately "normal" insulin production consistent with an insulinoma. IGF 1 and IGF 2 levels were withing the normal range.

The hypoglycemia was initially managed with continuous intravenous administration of dextrose and optimization of oral intake, glucagon and octreotide 50 mcg every 8 hours. However, the response to octreotide was insufficient and we were unable to wean the patient off the dextrose. Subsequently we started prednisone 20 mg oral daily and glucose tablets which allowed us to discontinue the intravenous dextrose and the octreotide. Patient was discharged home on hospice care.

Conclusion

Hypoglycemia is a potentially life-threatening condition necessitating prompt action including the administration of intravenous dextrose. The results of the workup indicate that the neuroendocrine tumor produced excessive amounts of both serotonin and insulin contributing to prolonged refractory hypoglycemia. Treatment of this rare condition is challenging and often empirical.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN240 A Case of Euglycemic DKA in Pregnancy
Authors: Grigoryan Seda , Oral Elif
Published: November 2022

Background

Euglycemic diabetic ketoacidosis (EKDA) is a rare diagnosis of exclusion occurring in a state of decreased hepatic production of glucose due to fasting state or enhanced urinary excretion of glucose. Pregnancy predisposes a woman to a state of accelerated starvation, where even short periods of fasting can lead to increased lipolysis and subsequent ketosis. DKA can develop quickly at lower serum glucose concentrations when triggers such as stress, pump malfunction, infection are present. EDKA is particularly important to recognize and treat in pregnant patients, as this increases risk of fetal demise. Diagnostic criteria of EKDA are elevated beta-hydroxybutyrate in serum or urine, decreased serum bicarbonate, glucose > 200 mg/dL, anion gap metabolic acidosis.Clinical case:26-year-old female G1P2 at 29-weeks’ gestation, with a medical history of type 1 diabetes mellitus on insulin pump, hypothyroidism, prior pregnancy complicated by pre-eclampsia presented as a transfer from an outside hospital after a low-impact motor vehicular accident. Patient was transferred with concern for DKA. At the time of presentation patient had been using her insulin pump per home settings, was NPO for at least 24 hours due to nausea and mild abdominal pain. BP was 140/77 mmHg, HR 114 beats/min, 97.6F, RR 16 with SpO2 99% on RA. Patient was alert and oriented, not in acute distress. Labs were notable for beta-hydroxybutyrate of 3.3 mmol/L, lactate 1.0 mmol/L, HbA1c 7.3%, TSH 3.16 mIU/L, Na 136 mmol/L, K 4 mmol/L, Cl 105 mmol/L, serum bicarbonate 18 mmol/L, glucose 97 mg/dL, creatinine 0.49 mg/dL, eGFR >90 mL/min/1.73m2, anion gap of 13 mmol/L. Patient was found to be in euglycemic DKA and was started on IV insulin with fluid resuscitation per protocol. Endocrinology was consulted as labs demonstrated worsening, with Na 135 mmol/L, serum bicarbonate 17 mmol/L, glucose 166 mg/dL. At this point patient had just started tolerating PO intake, no fetal distress was observed. We recommended continuation of treatment for a total of 24 hours, with subsequent normalization of labs and resolution of nausea. Patient was transitioned to home insulin pump with recommendation to snack frequently between meals and was discharged home with outpatient follow up. Upon follow up, patient did not experience recurrence of DKA but had been induced at 33 weeks due to pre-eclampsia, successfully giving birth to a live baby girl with Apgar scores of 5/6.

Conclusions

EDKA is a rare but easily missed diagnosis that is important to treat particularly in a pregnant patient, as risks of fetal demise are high. Serum or urine ketones should be checked in any hospitalized diabetic patient regardless of symptoms or other laboratory indicators. Triggers of EKDA in a state of pregnancy can include brief periods of fasting, infection, stress, and dehydration.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.