bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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 (&gt;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

Abstract
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

Abstract

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 (&lt;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.
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

Abstract

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 &lt; 0.10 ng/dL on several occasions with TSH &gt; 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

Abstract

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 &lt;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

Abstract

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

Abstract

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