Abnormal Thyroid Function Tests Research Articles

Identification of Iodotyrosines as Novel Substrates for the Thyroid Hormone Transporter MCT8.

Background: Monocarboxylate transporter 8 (MCT8) is the most specific thyroid hormone transporter identified to date, deficiency of which has been associated with severe intellectual and motor disability and abnormal serum thyroid function tests. However, it is presently unknown if MCT8, similar to other thyroid hormone transporters, also accepts additional substrates, and if disruption of their transport may contribute to the observed phenotype. Methods: In this study, we aimed to identify such substrates by applying liquid chromatography-mass spectrometry-based metabolome analysis in lysates of control and MCT8-overexpressing Xenopus oocytes. A subset of identified candidate substrates were validated by direct transport studies in transiently transfected COS-1 cells and human fibroblasts, which endogenously express MCT8. Moreover, transport characteristics were determined, including transport saturation and cis-inhibition potency of thyroid hormone transport. Results: Metabolome analysis identified 21 m/z ratios, corresponding to 87 candidate metabolites, with a 2.0-times differential abundance in MCT8-injected oocytes compared with controls. These metabolites included 3,5-diiodotyrosine (DIT) and several amino acids, including glutamate and glutamine. In accordance, MCT8-expressing COS-1 cells had 2.2-times lower intracellular accumulation of [125I]-DIT compared with control cells. This effect was largely blocked in the presence of 3,3',5-triiodothyronine (T3) (IC50: 2.5 ± 1.5 µM) or thyroxine (T4) (IC50: 5.8 ± 1.3 µM). Conversely, increasing concentrations of DIT enhanced the accumulation of T3 and T4. The MCT8-specific inhibitor silychristin increased the intracellular accumulation of DIT in human fibroblasts. COS-1 cells expressing MCT8 also exhibited a 50% reduction in intracellular accumulation of [125I]-3-monoiodotyrosine (MIT). In contrast, COS-1 cells expressing MCT8 did not alter the intracellular accumulation of [3H]-glutamate or [3H]-glutamine. However, studies in human fibroblasts showed a 1.5-1.9 times higher glutamate uptake in control fibroblasts compared with fibroblasts derived from patients with MCT8 deficiency, which was not affected in the presence of silychristin. Conclusions: Taken together, our results suggest that the iodotyrosines DIT and MIT can be exported by MCT8. MIT and DIT interfere with MCT8-mediated transport of thyroid hormone in vitro and vice versa. Future studies should elucidate if MCT8, being highly expressed in thyroidal follicular cells, also transports iodotyrosines invivo.

Abnormal thyroid function tests in a patient with history of breast cancer taking tamoxifen

Abnormal thyroid function tests in a patient with history of breast cancer taking tamoxifen

Does cranial bone ossification differ in children with developmental dysplasia of the hip?

This study aims to compare cranial bone ossification between patients with developmental dysplasia of the hip (DDH) and healthy individuals. Between September 2021 and April 2022, a total of 60 healthy female individuals (median age: 24.5 months; range, 18 to 36 months) and 56 female DDH patients (median age: 23 months; range, 18 to 35 months) were included. Age, head circumference, weight, height, and patency of the anterior fontanel were measured in groups. Percentiles were classified as very low, low, normal, high and very high. All patients were female and those with abnormal thyroid function test, vitamin D, calcium, phosphate and alkaline phosphatase values were not included in the study. For those diagnosed with DDH, they were included in the group regardless of the type of treatment. No statistically significant difference was found between the groups in terms of age and weight (p>0.05). The very low and very high head circumferences were more frequent, and the normal head circumferences were less frequent in the DDH group (p<0.05). There was no significant difference between groups in terms of fontanel closure (p>0.05). In open fontanels, no significant difference was found in both groups in terms of age (p>0.05). Our study results showed no significant difference between the fontanel ossifications of children with and without DDH; however, we found that the ossification of the skull bones of children with DDH was different compared to healthy children.

Diagnoses of obstetric and postpartum thyroid disease: a Danish validation study

Different diagnoses of thyroid disease are available in the 10th International Classification of Diseases (ICD-10), but the validity of diagnoses related to obstetric and postpartum thyroid disease is unknown. This was a retrospective cohort study of all patients in the North Denmark Region with a diagnosis of postpartum thyroiditis (PPT) (ICD-10: O905) from 2016 to 2019 or obstetric thyroid disease in 2019 (ICD-10: O992B (hypothyroidism) or O992C (hyperthyroidism)) registered in the Danish National Hospital Register. Information from nationwide registers and medical records were used to assess the validity. Among patients with an O905-diagnosis (n = 40), abnormal thyroid function test results were seen in all cases. A total of eight patients (20.0%) were positive for thyrotropin receptor antibodies postpartum, however, in low titers, and PPT was verified in 39 of 40 cases (97.5%). Altogether 45 of 50 patients with an O992B-diagnosis (90.0%) correctly had hypothyroidism, whereas hyperthyroidism was found in 25 of 39 patients with an O992C-diagnosis (64.1%). This is the first study to validate ICD-10 diagnoses of obstetric and postpartum thyroid disease. A high validity was seen for PPT (O905) and obstetric hypothyroidism (O992B), whereas for obstetric hyperthyroidism (O992C), the diagnosis could not be verified in one third of the cases.

The Impact of Physical Activity on Thyroid Health: Insights From Representative Data in Korea.

Thyroid hormones are essential for energy metabolism related to thermogenesis and oxygen consumption. This study evaluated the potential association of thyroid function including thyroid peroxidase antibodies (TPOAb) with physical activity in nationally representative data. This retrospective cohort study used data from the Korean National Health and Nutrition Examination Survey between 2013 and 2015. Physical activity (PA) was assessed using metabolic equivalents based on the validated Korean version of the International Physical Activity Questionnaire Short Form. PA level was categorized into 3 groups of high, moderate, and low. Participants with abnormal thyroid function test, restricted activity, or previous history of thyroid disease were excluded in the study. A total of 5372 participants was finally selected. The free T4 level was lowest in the low PA group, while TSH was not significantly different among the groups. TPOAb titers increased in the following order: moderate PA, low PA, and high PA. After adjustment for confounding factors, moderate PA was associated with a high T4 level and a decrease in TSH and TPOAb with significance. However, there were no significant changes in free T4, TSH, or TPOAb titer in the high PA group. In a subanalysis, females with moderate PA showed a significant decrease in TSH and TPOAb. In both males and females, insulin sensitivity was increased with moderate PA. In obese participants, TSH negatively correlated with PA, and free T4 levels decreased in the low PA. The sensitivity to thyroid hormone did not differ in our study. The present study found an association between thyroid function and moderate PA. Therefore, moderate-intensity PA should be recommended to improve thyroid function.

A challenging case of a pituitary macroadenoma and toxic thyroid adenoma with inappropriate TSH secretion.

Thyroid-stimulating hormone-secreting pituitary adenomas (TSHomas) are rare, accounting for less than 1% of all pituitary adenomas. We present a case of hyperthyroidism secondary to a likely TSHoma and coexisting functional thyroid adenoma. Laboratory errors and familial abnormalities in thyroid function tests were ruled out, and a diagnosis of the toxic thyroid adenoma was confirmed on a thyroid uptake scan. However, the triiodothyronine suppression test was contraindicated due to the patient's cardiovascular disease, and the thyrotropin-releasing hormone stimulation test, measurement of glycoprotein hormone alpha-subunit, and genetic testing were unavailable. Magnetic resonance imaging of the brain revealed a suprasellar pituitary macroadenoma measuring 40 mm × 20.3 mm × 17 mm. The patient was initiated on carbimazole; however, thyroid stimulating hormone and thyroxine levels remained elevated. The patient declined trans-sphenoidal surgery and was treated with radioactive iodine to manage the toxic thyroid adenoma, leading to reduced thyroxine levels and symptom improvement. Unfortunately, the patient passed away before long-acting somatostatin analogs became available. This case highlights the diagnostic and therapeutic challenges involved in managing thyrotoxicosis with dual etiology. Hyperthyroidism can have multiple etiologies, which can coexist in the same patient. Persistent discordant thyroid function tests warrant further investigation. The gold standard for diagnosis of TSHomas remains immunohistochemical analysis of the tumor tissue.

Effective TRIAC treatment of a THRβ-mutated patient with thyroid hormone resistance.

Resistance to thyroid hormone (RTH) is a rare autosomal dominant disease characterized by an alteration of thyroid hormone negative feedback, usually as a consequence of a mutation in the thyroid hormone receptor-b gene (THRβ). It is characterized by high variability of clinical manifestations, ranging from isolated abnormal thyroid function tests without symptoms to severe and impaired clinical conditions. Here we report the case of a woman who was diagnosed with RTHβ when she was 35 years old and was treated with 3,5,3-triiodiothyroacetic acid (TRIAC) because of the onset of clinical symptoms of hyperthyroidism. This therapy has been effective in controlling thyrotoxicosis for 5 years. After this time the patient developed an autoimmune hyperthyroidism, with TSH receptor autoantibodies appearance, which caused a loss of efficacy of the drug in controlling the disease. The development of different pathophysiological mechanisms of thyrotoxicosis, as in this case, could be the reason for both variability of disease manifestations and of loss of response to drug therapy.

Risk Factors for Thyroid Dysfunction in Pregnancy: An Individual Participant Data Meta-Analysis.

Background: International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p < 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; p < 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; p < 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; p < 0.001). Conclusions: The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction.

The prevalence of thyroid function test abnormalities and serum thyroid autoantibodies in vitiligo and alopecia areata patients in Saudi Arabian population

Background: Alopecia areata (AA) and vitiligo are immune-mediated inflammatory diseases characterized by hair loss and depigmented macules, respectively. It is often associated with other autoimmune conditions especially with autoimmune thyroid disorders indicating a potential role of autoimmunity in its development. Methods: A 222 patients, 113 AA and 109 vitiligo diagnosed, were retrospectively reviewed. We analyzed TG-Ab, TPO-Ab, Thyroid function tests (free T3, free T4, and TSH) in all patients. Results: In vitiligo patients, 11% (n=12) had elevated levels of anti-TG levels and 26.6% (n=29) had elevated levels of anti-TPO, Thyroid hormonal abnormalities were found in 15.6% (n=17) of vitiligo patients, and fT4 was elevated in 1.83% (n=2) patients. Within AA patients, 15.9% (n=18) had anti-TG elevation and 23.9% (n=27) had anti-TPO elevation, thyroid hormonal abnormalities were found in 16.8% (n=19), and fT4 was high in 0.88% (n=1) patient. No significant difference was found between the two groups for all measured parameters. No statistically significant correlation between the gender of the patients and the diagnosis, thyroid hormonal test, and thyroid autoantibody levels could be detected (p&gt;0.05) Conclusions: In our study, impaired thyroid functions and thyroid autoantibodies in vitiligo and AA patients were identified at similar rates of the previous studies. Moreover, we could not find differences in comparison to other ethnicities.

The Combined Effect of Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors on Thyroid Function.

Background: Recent successes with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) for the treatment of solid malignancies have paved the way for a new era of combined therapy. A common side effect seen with each of these classes of treatment is thyroid dysfunction, with rates estimated at 30-40% for TKI and 10-20% for ICI. However, little is known about the effect of combined ICI+TKI therapy on thyroid function. Therefore, this study evaluated the incidence, clinical features, and risk factors for developing thyroid abnormalities during ICI+TKI therapy and the relationship to cancer outcomes. Methods: We conducted a retrospective cohort study of patients treated with combination ICI+TKI cancer therapy at City of Hope Comprehensive Cancer Center from 2017 to 2023 who had pretreatment normal thyrotropin (TSH) levels. Primary analyses assessed the frequency, timing, and severity of thyroid function test abnormalities during ICI+TKI cancer therapy, and the requirement for thyroid hormone replacement. Secondary analyses evaluated risk factors for the development of thyroid dysfunction, including sex and drug regimen, and the association with cancer progression-free survival or overall survival. Univariable and multivariable models were used. Results: There were 106 patients who received ICI+TKI therapy with a median age of 63.5 years and a median follow-up of 12.8 months (interquartile range [IQR] 5.9-20.9). Notably, 63.2% (67/106) developed thyroid function abnormalities during ICI+TKI therapy, including 11 (10.4%) with hyperthyroidism, 42 (39.6%) with subclinical hypothyroidism (SCHypo), and 14 (13.2%) with overt hypothyroidism. The onset of thyroid dysfunction occurred at a median of 7 weeks (IQR 3.1-9.0) after start of ICI+TKI treatment for hyperthyroidism, 8.0 weeks (IQR 3.0-19.0) for SCHypo, and 8.1 weeks (IQR 5.9-9.1) for overt or worsening hypothyroidism. Hyperthyroidism resolved to hypothyroidism or normal TSH without intervention in all subjects, suggesting thyroiditis, and hypothyroidism was readily treated with thyroid hormone replacement. Conclusions: Thyroid dysfunction is a frequent adverse event in individuals treated with combination ICI+TKI therapy, with our data suggesting a rapid onset and higher incidence than previously seen with ICI or TKI therapy alone. Therefore, close monitoring of thyroid function during initial therapy and multidisciplinary care with endocrinology are recommended to facilitate early detection and initiation of thyroid hormone replacement in these patients.

THYROID FUNCTION ABNORMALITIES IN PATIENTS WITH METABOLIC SYNDROME: AN OBSERVATIONAL STUDY

Objective: The objective of the study is to study the presence of thyroid function abnormalities in cases with metabolic syndrome. Methods: This was a prospective observational study done in the department of biochemistry of a tertiary care medical college. 60 patients fulfilling the criteria for metabolic syndrome as per the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) criteria were included in this study. Demographic details of all the patients were noted. A detailed history was taken and thorough clinical examination was done. Thyroid function test was done in all cases. The presence of thyroid function test abnormalities was analyzed. Statistical analysis was done using SSPS 21.0 software and p&lt;0.05 was taken as statistically significant. Results: Out of these 60 cases, there were 37 (61.67%) males and 23 (38.33%) females with a M: F ratio of 1:0.62. The mean age of male and female patients was found to be 47.96±14.78 and 45.78±13.26 years, respectively. The mean age of male and female patients was found to be comparable with no statistically significant difference. Skin changes were present in 23 (38.33%) cases followed by tiredness (36.67%), constipation (25.00%), weight gain (21.67%), and pallor (15%). 29 (48.33%) were euthyroid whereas subclinical and clinical hypothyroidism was present in 18 (30%) and 10 (16.67%), respectively. 3 (5%) patients were found to have subclinical hyperthyroidism whereas there was no patient with clinical hyperthyroidism. Conclusion: Thyroid function abnormalities are common in patients with metabolic syndrome. It is therefore important to screen patients for thyroid function abnormalities so that appropriate interventions can be undertaken if necessary.

Increased Thyroidal Activity on Routine FDG-PET/CT after Combination Immune Checkpoint Inhibition: Temporal Associations with Clinical and Biochemical Thyroiditis.

FDG-PET/CT used for immune checkpoint inhibitor (ICI) response assessment can incidentally identify immune-related adverse events (irAEs), including thyroiditis. This study aimed to correlate the time course of FDG-PET/CT evidence of thyroiditis with clinical and biochemical evolution of thyroid dysfunction. A retrospective review was performed by two independent blinded nuclear medicine physicians (NMPs) of thyroidal FDG uptake in 127 patients who underwent PET/CT between January 2016 and January 2019 at baseline and during treatment monitoring of combination ICI therapy for advanced melanoma. Interobserver agreement was assessed and FDG-PET/CT performance defined by a receiver-operating characteristic (ROC) curve using thyroid function tests (TFTs) as the standard of truth. Thyroid maximum standardized uptake value (SUVmax) and its temporal changes with respect to the longitudinal biochemistry were serially recorded. At a median of 3 weeks after commencing ICI, 43/127 (34%) had a diagnosis of thyroiditis established by abnormal TFTs. FDG-PET/CT was performed at baseline and at a median of 11 weeks (range 3-32) following the start of therapy. ROC analysis showed an area under the curve of 0.87 (95% CI 0.80, 0.94) for FDG-PET/CT for detection of thyroiditis with a positive predictive value of 93%. Among patients with biochemical evidence of thyroiditis, those with a positive FDG-PET/CT were more likely to develop overt hypothyroidism (77% versus 35%, p < 0.01). In the evaluation of the index test, there was an almost perfect interobserver agreement between NMPs of 93.7% (95% CI 89.4-98.0), kappa 0.83. Increased metabolic activity of the thyroid on routine FDG-PET/CT performed for tumoral response of patients undergoing ICI therapy is generally detected well after routine biochemical diagnosis. Elevation of FDG uptake in the thyroid is predictive of overt clinical hypothyroidism and suggests that an ongoing robust inflammatory response beyond the initial thyrotoxic phase may be indicative of thyroid destruction.

Thyroid dysfunction and autoantibodies among patients infected with Covid 19 in Erbil city /IRAQ

Background and objectives: Autoimmune thyroid diseases or specifically Anti-thyroid peroxidase antibodies increasing after corona virus infection pandemic. This study investigating Anti-thyroperoxidase, anti-thyroid stimulating receptor antibodies in conjunction with traditional thyroid markers after corona virus infection hoping that this would aid in reduction of enduring morbidity and associated health concerns. Methods: This cross-sectional study was conducted in Rizgary Teaching Hospital and Erbil Teaching Hospital in Erbil, Iraq, within the period of February to September 2022. The study comprised hundred patients; 80 females and 20 males, these patients had clinical symptoms suspecting thyroid abnormalities and were suspected for having a sort of thyroid disease. They had abnormal thyroid function tests, with investigating thyroid autoantibodies and corona virus infection. Investigations include thyroid function test and antithyroid antibodies. Results: The level of Anti-thyroid peroxidase antibodies was positive among 75 hypothyroidism patients than among hyperthyroidism cases 2, p-value 0.012. Positive Anti-thyroperoxidase antibodies and hypothyroidism were significantly more common among corona virus infected cases, p-value 0.012 and 0.0109 respectively. However; anti-thyroid stimulating hormone receptor antibody was positive only among hyperthyroidism group (18%); p-value was significant 0.019. Conclusions: This study confirmed the correlation between thyroid function test, Anti-thyroperoxidase antibodies values and corona virus infection. Autoimmune thyroid diseases are more common among female cases, in addition; antithyroid antibodies especially Anti-thyroperoxidase antibodies were more common among female patients. There was high prevalence of both hypothyroidism and positive anti-TPO Ab in COVID-19 cases.

Prevalence and Associated Factors for Thyroid Dysfunction Among Patients On Targeted Therapy for Cancers: A Single-Center Study from Thailand.

This study aimed to explore the prevalence and associated factors of thyroid dysfunction among cancer patients treated with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). A cross-sectional study was done in patients who received TKIs at Rajavithi Hospital in 2019. For patients treated with ICI, a retrospective chart review for patients seen in 2018 to 2019 was conducted. If there were abnormal thyroid function tests (TFT), thyroid autoantibodies were tested. There were 144 patients on TKIs with a mean age of 56.0 years. Thyroid dysfunction was found in 14.6% of patients and most had subclinical hypothyroidism (n = 16, 11.1%). Imatinib (n = 11, 10.8%) and sunitinib (n = 4, 100%) were the 2 most common TKIs given to patients with thyroid dysfunction. Thyroid dysfunction was associated with male sex, chronic kidney disease and hepatitis B virus infection but not with previous thyroid disease and presence of thyroid autoantibodies.There were 18 patients who received ICIs. The mean age was 63.3 years. Twelve patients (66.7%) used programmed cell death protein-1 antibody (anti-PD1), mainly nivolumab. Thyroid dysfunction was found in 50%, which occurred at a median duration of 46 days. Most patients had overt hypothyroidism and 55.6% needed levothyroxine replacement. Thyroid dysfunctions from TKIs were mostly asymptomatic and mild in severity. Some types of TKIs might be associated with thyroid dysfunction. On the other hand, thyroid dysfunction from ICIs usually occurs within 6 months and requires levothyroxine replacement.

Thyroid Function Test Abnormalities in Children and Adolescents with COVID-19: A Case-Control Study

Background: There is a lack of conclusive evidence regarding thyroid function test (TFT) abnormalities in COVID-19, especially among children. Objectives: This study aimed to investigate TFT abnormalities in COVID-19 pediatric patients compared to healthy children. Methods: This study was conducted on 37 COVID-19-positive children who were admitted to Namazi Hospital from January 21 to March 1, 2022, compared with 37 healthy children. Within 48 h of positive real-time polymerase chain reaction (PCR) results for severe acute respiratory syndrome coronavirus 2, a blood sample was taken to measure serum levels of thyroid-stimulating hormone (TSH) and total thyroxine (tT4) in the two groups. Additional tests, including free and total triiodothyronine, free T4, and thyroperoxidase antibodies, were also conducted on cases. The chi-square, Pearson correlation coefficient, and analysis of variance tests were used for data analysis. Results: Twenty-five patients were male, and 49 were female, with a mean age of 7.99 ± 5.02. The abnormal TFT and TSH frequency was significantly higher in the case group than in the control group. Nevertheless, there was no significant difference between the case and control groups regarding tT4 abnormalities. We could not establish an association between the mean of TSH and tT4 and age groups in the two groups and between abnormalities of TFTs and COVID-19 severity. Conclusions: Although abnormalities of TFT were significantly more common among COVID-19 children, they were not associated with the disease severity. However, studies with larger sample sizes are recommended to evaluate thyroid abnormalities and their clinical course in COVID-19 children.

Abstract 17455: Heart in Crisis: Graves’ Thyrotoxicosis-Induced Cardiomyopathy

Background: We present a case of a young healthy male who presented with signs and symptoms of congestive heart failure and was subsequently diagnosed with dilated cardiomyopathy secondary to an unknown history of Graves’ disease. Case Presentation: A 40-year-old male with no medical history presented to the hospital with scrotal and bilateral lower leg edema for 4 days with associated shortness of breath. Physical examination was significant for an irregularly irregular heart rhythm. Electrocardiogram showed atrial fibrillation with a rapid ventricular response (Image B). Initial laboratory findings were elevated NT-proBNP of 1,240 pg/mL (&lt;125 pg/mL). Chest x-ray revealed significant cardiomegaly (Image A). Echocardiogram demonstrated an ejection fraction of 20% with a severely dilated bilateral atrium, left ventricle with severe diffuse hypokinesis of the left ventricle, and severe mitral regurgitation (Images C and D). Endocrine was consulted for abnormal thyroid function tests with TSH of &lt;0.010 mU/L (0.27-4.2 mU/L), free T4 of 6.06 ng/dL (.93-1.70 ng/dL), T3 of 258 ng/dL (80-200 ng/dL), thyroid-stimulating immunoglobulin of 9.51 IU/L (0.00-.55 IU/L) and TSH receptor antibody 14.00 IU/L (0.00-1.75 IU/L). The patient was started on methimazole and metoprolol with close follow-up with cardiology and endocrinology. Discussion: Severe Cardiomyopathy in adult patients with hyperthyroidism is rare occurring in approximately 6% of patients with less than 1% developing dilated cardiomyopathy with impaired left ventricular systolic function. Although the mechanism of dilated cardiomyopathy is still being researched it has been suggested that prolonged uncontrolled hyperthyroidism and autoimmunity as the potential causes. Further studies are needed to develop optimal management studies as it has been shown that the management of thyrotoxicosis can reverse cardiovascular manifestations and prevent irreversible cardiomyopathy.

Allan-Herndon-Dudley syndrome in Hong Kong: Implication for newborn screening

BackgroundAllan-Herndon-Dudley syndrome (MCT 8 deficiency) is an X-linked recessive condition caused by hemizygous pathogenic variants in SLC16A2 encoding the monocarboxylate transporter 8 (MCT8). Patients present with global developmental delay and neurological impairment, and abnormal serum thyroid function tests. The drug, 3,3′,5 triiodothyroacetic acid (TRIAC), was recently demonstrated to improve the endocrinological profile. Improvement in diagnostic approach is key to earlier start of treatment. Patient findingsWe described four Chinese patients with MCT8 deficiency undergoing different diagnostic odysseys. Their initial presentation included global developmental delay and dystonia. Patient 2 also had epilepsy. Patients 1 and 2 presented with two novel variants: (1)hemizygous NM_006517.4(SLC16A2):c.1170 + 2 T > A; p.(?), and (2)hemizygous NM_006517.4(SLC16A2):c.305dupT; p.(Val103GlyfsTer17) respectively. Patients 3 and 4 were biological brothers harboring hemizygous NM_006517.4(SLC16A2):c.305dupT; p.(Val103GlyfsTer17), which was first reported in 2004. We obtained the measurement of triiodothyronine (T3) and reverse T3 (rT3) from dried blood spot samples collected on Day 1 of life from Patient 1 and studied the biomarkers (rT3 and T3/rT3 ratio) proposed by Iwayama et al. for the detection of MCT8 deficiency at birth. Our data verified the significantly reduced rT3 level in Patient 1, compared with healthy newborns, although low T3 level and comparable T3/rT3 ratio with controls were detected. SummaryPatients with MCT8 deficiency often undergo diagnostic odysseys. An early diagnosis could be missed by a normal newborn thyroid function screening result based on biochemical measurement of TSH and/or T4/fT4. Early detection of rT3 is key to improving current diagnostic approach. ConclusionWe recommend that full thyroid function profile (TSH, T4/fT4, T3/fT3, rT3) be considered early for all pediatric patients presenting with unexplained developmental delay and/or dystonia. The potential inclusion of rT3 measurement in newborn screening may prove promising.

FRI400 A Rare Case Of Acute Sheehan's Syndrome In An Antepartum Patient

Abstract Disclosure: E. Jalal: None. C. Baldwin: None. Sheehan’s syndrome (SS) is a known complication of postpartum hemorrhage. It is typically diagnosed several years after birth given slow symptom onset related to hypopituitarism. We report a rare case of life-threatening antepartum pituitary ischemia secondary to hypotension, representing an acute presentation of SS. A 19-year-old primigravid woman at 31 weeks of gestation was admitted to the intensive care unit for septic shock secondary to Klebsiella pneumoniae pyelonephritis. Despite appropriate treatment, persistent hypotension prevented weaning of vasopressor support. Due to concurrent mild hyponatremia, the following studies were obtained: morning cortisol (2.46 mcg/dL [4.5-23 mcg/dL]), thyroid stimulating hormone (TSH) (0.379 IU/L [0.47-4.7 IU/L]), free triiodothyronine (2.1 pg/mL [2.8-5.3 pg/mL]), and free thyroxine (0.77 ng/dL [0.7-1.8 ng/dL]). Endocrinology was consulted for evaluation of adrenal insufficiency and abnormal thyroid function tests. Her prolactin was measured at 10.3 ng/mL, far below the expected range in a 3rd trimester pregnancy (35-600 ng/mL). Her remaining anterior pituitary hormone panel was unremarkable. MRI brain without contrast showed no evidence of an acute stroke or hemorrhage and commented that the prominence of the pituitary gland was likely related to current pregnancy. Stress dose hydrocortisone 100mg thrice daily and levothyroxine 50 mcg daily were initiated, allowing for weaning of vasopressor support. By discharge, she was titrated to levothyroxine 75mcg daily and hydrocortisone 20mg in the morning and 5mg in the afternoon. Repeat outpatient pituitary function testing found increase of prolactin to 397 ng/mL (35-600 ng/mL) and of IGF-1 to 486 ng/mL (113-408 ng/mL) as well as normalization of TSH to 3.210 (0.45-4.5IU/L), indicating likely recovery of pituitary axis. When readmitted at 38 weeks gestation for scheduled induction, she was given stress dose hydrocortisone 100mcg for labor. On discharge, she was tapered to prednisone 10mg daily and levothyroxine 50mcg daily. Appropriate hormone replacement and stress dose hydrocortisone resulted in an uncomplicated delivery and signs of clinical pituitary recovery postpartum as she was able to breastfeed without need for supplementation and maintain normotension after self-discontinuing prednisone and levothyroxine. The leading diagnosis to explain this patient’s hypopituitarism is acute SS, which is defined as symptom onset within 6 weeks postpartum. In our case, septic shock caused an abrupt onset of persistent hypotension leading to hormone levels suggestive of panhypopituitarism while the patient was pregnant at 31 weeks of gestation, which has not been reported in prior literature. While known as a chronic diagnosis in the postpartum population, further research should explore possible stunning effect of acute hypotension manifesting as acute SS in peripartum patients. Presentation: Friday, June 16, 2023

THU667 Severe Hypothyroidism With Paradoxically Elevated Direct Free T4 Due To Anti-thyroxine Antibodies

Abstract Disclosure: O. Magvanjav: None. M.J. McPhaul: None. I. Choucair: None. E. Holt: None. Introduction Laboratory interference may cause abnormal thyroid function test (TFT) results, leading to misdiagnosis and inappropriate patient care. There are several major types of interference. Here, we describe a hypothyroid patient with an elevated thyroid stimulating hormone (TSH) level with a paradoxically elevated direct free thyroxine (FT4) level caused by interference from anti-thyroxine autoantibodies (THAAB). Clinical Case Our patient is a 38-year-old man who was found to have markedly elevated TSH and FT4 levels during an outpatient workup for Lyme disease. The patient was overall well-appearing but reported some symptoms suggestive of hypothyroidism including excessive fatigue, non-pitting edema, and dry skin. Physical exam was notable elevated blood pressure (systolic blood pressure of 150 mmHg and diastolic blood pressure of 95 mmHg), normal temperature, normal heart rate (72 bpm), regular heart rhythm, and normal body mass index. He had non-tender thyromegaly without nodules, non-pitting edema of bilateral hands and legs, decreased leg hair over bilateral shins, and coarse, dry skin of his hands. Initial TSH level was &amp;gt;150 mIU/ml, with a paradoxically elevated direct FT4 of 10 ng/dl (normal range 0.80-1.70 ng/dL). The FT4 level by equilibrium dialysis was &amp;lt;0.2 ng/dl. Outside laboratory testing to eliminate the effect of heterophile antibodies using two different assays again returned with elevated FT4 levels. Screening for macro TSH confirmed the markedly elevated TSH level. Further investigations at a second outside laboratory revealed that he had THAAB. A repeat FT4 level by dialysis confirmed the markedly low FT4 levels. He was empirically started on low dose levothyroxine and after increasing the levothyroxine dose, he showed improvement in clinical symptoms and the expected decline in TSH. Conclusions Here we present a rare case of THAAB that caused laboratory interference during thyroid function testing, leading to falsely elevated thyroid hormone levels on immunoassays. This case shows the importance of suspecting interference when there is a discrepancy between clinical symptoms and laboratory results or between results obtained from different testing methods. Our patient likely had a genetic predilection for autoimmunity, and Lyme disease is a known trigger for various autoimmune conditions. Our case also emphasizes the importance of taking a systematic approach to investigate the cause of the laboratory interference. This will help prevent misdiagnosis of thyroid disorders that may lead to additional unnecessary testing and treatment. Presentation: Thursday, June 15, 2023

FRI476 Asymptomatic Thyrotropin-secreting Pituitary Microadenoma With Biochemical Secondary Hyperthyroidism: A Diagnostic Conundrum

Abstract Disclosure: G. Al-Naqeeb: None. R. Ghosh: None. P. Veeraraghavan: None. C. Cochran: None. J. Klubo-Gwiezdzinska: None. S. Gubbi: None. Background: Thyrotropin (TSH)-secreting pituitary adenomas (TSHAs) are often macroadenomas (&amp;gt;1 cm), and clinically present with secondary hyperthyroidism (SH), but clinically silent microTSHAs (&amp;lt;1 cm) with only biochemical SH pose a diagnostic challenge. Clinical Case: A 49-year-old, healthy male was referred to our center for evaluation of abnormal thyroid function tests (TFTs). Immunoassay (IA) measurements at an outside hospital had identified elevated free T4 (FT4), and an inappropriately normal TSH, and a pituitary magnetic resonance imaging (MRI) had noted an 8mm x 7mm non-invasive adenoma. The patient denied hyperthyroidism symptoms, medication/herbal supplement intake, radiation exposure, headaches, vision changes, and thyroid/pituitary disorders, or abnormal TFTs in relatives. Physical exam revealed no signs and symptoms of hyperthyroidism. No thyromegaly or cervical lymphadenopathy was felt. IA profile at our institute was consistent with an SH pattern [TSH: 3.32 mIU/L (NL: 0.4 - 4.7); FT4: 3 ng/dL (NL: 0.9 - 1.7); total T4: 14.5 mcg/dL (NL: 4.5 - 11.7); triiodothyronine: 266.6 ng/dL (NL: 80 - 200)], with similar values on repeat measurement. Equilibrium dialysis technique also yielded an elevated FT4 value. TSH-receptor, anti-thyroid peroxidase, and anti-thyroglobulin (Tg) antibody (Ab) titers, serum Tg, and thyroid binding globulin levels were normal. Dilution studies ruled out heterophile Ab interference. Familial dysalbuminemic hyperthyroxinemia was unlikely given the elevated FT4 values. Genetic testing revealed a normal THRB gene, thereby ruling out thyroid hormone resistance. THRA gene was not tested due to absence of behavioral or hearing issues. Markers of hyperthyroidism, including angiotensin converting enzyme, carotene, apolipoproteins, and osteocalcin levels were normal, except for an elevated sex hormone binding globulin of 104 nmol/L (NL: 11 - 78). Biochemical evaluation of other pituitary axes was normal. However, an elevated alpha sub-unit fraction (ASF) was noted on two separate measurements. Sonogram revealed a heterogeneous, hypervascular thyroid. Bone densitometry, echocardiogram, and Holter monitor studies were normal. The combination of biochemical SH, elevated ASF, pituitary adenoma, and exclusion of other etiologies causing SH pattern established the diagnosis of TSHA. An active surveillance approach was implemented. A pituitary MRI done 18 months later showed minimal (2mm in one axis) increase in the adenoma size, and the patient continued to demonstrate biochemical SH but remained asymptomatic. Conclusion: MicroTSHAs can present with asymptomatic SH. In this situation, excluding other biochemical SH etiologies is crucial to prevent unnecessary invasive procedures. But once TSHA diagnosis is established, due to the risk of tumor growth leading to symptomatic SH or mass effects, active surveillance is warranted. Presentation: Friday, June 16, 2023