Normal Thyroid-stimulating Hormone Levels Research Articles

Triiodothyronine/Thyroxine Ratio as a Marker of Clinical Response to Levothyroxine Replacement in Patients With Hypothyroidism.

Hypothyroidism is one of the most common endocrine disorders with a simple therapy, that is levothyroxine (LT4). A normal thyroid-stimulating hormone (TSH) measurement is used as a marker of optimal replacement. But, many patients still have symptoms. Triiodothyronine (T3), thyroxine (T4), and their ratio may correlate with clinical improvement. The study aims to assess the T3/T4 ratio as a marker of clinical response in patients with hypothyroidism. Method:A cross-sectional study was conducted from June to November 2022 at Faiha Specialized Diabetes, Endocrine, and Metabolism Center, in Basrah, southern Iraq. We included 48 adult patients with primary hypothyroidism on LT4 treatment only and TSH within the target reference range for at least within the last six months. Each patient was subjected to a questionnaire that was designed to capture hypothyroidism-related complaints in the form of a five-point Likert scale. Biochemical assessments were done with the measurement of TSH, T3, and T4. Despite having a normal TSH level, nearly all the patients had persistent and varying severity of clinical complaints of hypothyroidism. Tiredness, hair problems, weight gain, and cold intolerance were the most severely persistent symptoms. Patients with scores of two and more for weight gain, cold intolerance, and skin problems had significantly lower T3/T4 ratios (P = 0.04, 0.002, and 0.02, respectively), while in the remaining clinical symptoms, the T3/T4 ratio did not differ significantly. A low T3/T4 ratio was significantly associated with resistant symptoms of hypothyroidism and may be used as a marker for treatment efficacy with TSH rather than TSH value alone.

Thyroid hormone homeostasis in levothyroxine-treated patients: Findings from ELSA-Brasil.

The effectiveness of levothyroxine (LT4) in restoring thyroid hormone (TH) homeostasis, particularly serum thyroxine (T4) and triiodothyronine (T3) levels, remains debatable. To assess TH homeostasis in LT4-treated individuals using data from the Longitudinal Study of Adult Health in Brazil (ELSA-Brasil) study. The ELSA-Brasil study follows 15,105 adult Brazilians (aged 35 to 74 years) over 8.2 years (2008-2019) with 3 observation points assessing health parameters including serum thyroid stimulating hormone (TSH), free T4 (FT4), and free T3 (FT3) levels. We analyzed 186 participants that initiated treatment with LT4 during the study, and 243 individuals continuously treated with LT4 therapy. Initiation of therapy with LT4 resulted in a 11-19% decrease in TSH, a ∼19% increase in FT4, and a 7% reduction in FT3 serum levels (FT3 dropped >10% in ∼40% of the LT4-treated patients). This was associated with an increase in triglyceride levels and utilization of hypolipidemic and anti-diabetic medications. Participants continuously treated with LT4 exhibited a stable elevation in serum FT4 and, a reduction in serum FT3 and TSH levels. While 115 participants (47.3%) had at least one serum FT4 levels above the control reference range (>1.52 ng/dL), 38 participants (15.6%) had at least one serum FT3 below the reference range (<0.23 ng/dL). The present results challenge the dogma that treatment with LT4 for hypothyroidism restores TH homeostasis in all patients. A substantial number of LT4-treated patients exhibit repeated FT4 and FT3 levels outside the normal reference range, despite normal TSH levels. Further studies are needed to define the clinical implications of these findings.

Overt hypothyroidism in pregnancy and language development in offspring: is there an association?

Overt hypothyroidism during pregnancy is linked to various obstetric complications, such as premature birth and fetal death. While some studies have shown that maternal hypothyroidism can impact a child's Intelligence Quotient (IQ) and language development, findings are controversial. The aim of this study was to explore the connection between treated maternal hypothyroidism during pregnancy and offspring neurodevelopment, focusing on learning and language and examining related maternal obstetric complications. Group 1 included 31 hypothyroid women with elevated thyroid stimulating hormone (TSH) (> 10mU/L, > 10µIU/mL) during pregnancy, and Group 2 had 21 euthyroid women with normal TSH levels (0.5-2.5mU/L, 0.5-2.5µIU/mL). Children underwent neuropsycological assessments using the Griffiths-II scale. Pregnancy outcome showed an average gestational age at delivery of 38.2weeks for hypothyroid women, compared to 40weeks for controls, and average birth weight of 2855.6g versus 3285g for controls, with hypothyroid women having children with higher intrauterine growth restriction (IUGR) prevalence and more caesarean sections. The 1-min APGAR score was lower for the hypothyroid group's children, at 8.85 versus 9.52. Neuropsychological outcomes showed children of hypothyroid mothers scored lower in neurocognitive development, particularly in the learning and language subscale (subscale C), with a notable correlation between higher maternal TSH levels and lower subscale scores. Fetuses born to hypothyroid mothers appeared to be at higher risk of IUGR and reduced APGAR score at birth. Neurocognitive development seemed to affect language performance more than the developmental quotient. This alteration appeared to correlate with the severity of hypothyroidism and its duration.

Association of pro-atherogenic risk factors with thyroid-stimulating hormone level in women 25–44 years old

Thyroid hormones play an important role in regulating metabolism. A large body of literature suggests an increased risk of developing metabolic syndrome (MS) in individuals with hypothyroidism, but little data exists on the effects of high-normal levels of thyroid-stimulating hormone (TSH) on metabolism.Material and methods. The study was conducted on a representative sample of people aged 25–44 years (n = 1513, of which 840 were women). The analysis included the results of 343 women. A questionnaire, anthropometric and biochemical study were carried out. Biochemical parameters were analyzed in quartiles of TSH content. Determination of MS was carried out using the criteria of NCEP ATP III (2001), IDF (2005), VNOK (2009).Results. TSH content in the examined sample was 1.5 [1.0; 2.2] mU/l (median [lower quartile; upper quartile]). Among women 25–44 years old, women with highly normal TSH level (3.1 [2.7, 3.8] mU/l) have less favorable metabolic parameters. MS was detected in 31 % cases, with a predominant increase in the frequency of abdominal obesity – in 51 %, with increased triglyceride levels in 18 %. Women with hypertriglyceridemia had higher TSH content than those with normal triglyceride levels (2.4 ± 1.6 vs. 1.8 ± 1.3 mU/L, respectively, p = 0.007).Conclusions. In women 25–44 years of age, high-normal TSH content is more often associated with metabolic unhealth.

Evaluating the progression to abnormal thyrotropin in euthyroid preconception women: a population-based study

Background Abnormal preconception thyrotropin levels were associated with fecundability and adverse fetomaternal outcomes, however, little is known regarding the natural change of serum thyrotropin in euthyroid preconception women. Thus, we performed a population-based study to evaluate the progression to abnormal thyrotropin in euthyroid preconception women.Methods This retrospective cohort study used data from the National Free Prepregnancy Checkups Project (NFPCP) collected between 2010 and 2020. Female Han Chinese participants aged 20–49 years who had two repeated NFPCP participations with a time interval of 1.5–3.0 years, confirmed non-pregnant status within this duration, and normal thyrotropin levels during their first participation were included for the analysis of thyrotropin abnormalities during the second NFPCP examination. Data were analyzed between June 1 and October 1, 2023.ResultsThis study included 186,095 euthyroid women of reproductive age (mean ± SD, 26.72 ± 4.70 years) whose preconception thyrotropin levels were between 0.37 and 4.87 mIU/L. The median follow-up time was 2.13 (IQR, 1.85–2.54) years. A total of 8,497 (4.57%) women developed abnormal thyrotropin, including 4,118 (2.21%) subnormal thyrotropin and 4,379 (2.35%) supranormal thyrotropin. Compared with the reference group (thyrotropin 1.01–2.00 mIU/L), the lower baseline thyrotropin group had greater risk of developing subnormal thyrotropin, and the higher baseline thyrotropin group had greater risk of developing supranormal thyrotropin. Moreover, the restricted cubic spline analysis revealed a U-shaped dose–response association of baseline thyrotropin levels or thyrotropin multiples of the median (MOM) levels against risk of subnormal thyrotropin in the follow-up, and a J-shaped dose–response association against risk of supranormal thyrotropin levels in the follow-up. We further found that baseline thyrotropin outside of 1.43–1.93 mIU/L or baseline thyrotropin MOM outside 0.59–1.36 would hava a higher risk of developing of abnormal thyrotropin.ConclusionsBoth low and high baseline thyrotropin were associated with a significantly increased risk of developing abnormal thyrotropin outcomes. The optimal preconception baseline thyrotropin levels may be between 1.43 mIU/L and 1.93 mIU/L or baseline thyrotropin MoM between 0.59 and 1.36 to minimize progression toward abnormal thyrotropin after 1.5–3.0 years. These findings may help with counseling of preconception thyroid function monitoring.

Integrated Diagnostics of Thyroid Nodules.

Thyroid nodules are common findings, particularly in iodine-deficient regions. Our paper aims to revise different diagnostic tools available in clinical thyroidology and propose their rational integration. We will elaborate on the pros and cons of thyroid ultrasound (US) and its scoring systems, thyroid scintigraphy, fine-needle aspiration cytology (FNAC), molecular imaging, and artificial intelligence (AI). Ultrasonographic scoring systems can help differentiate between benign and malignant nodules. Depending on the constellation or number of suspicious ultrasound features, a FNAC is recommended. However, hyperfunctioning thyroid nodules are presumed to exclude malignancy with a very high negative predictive value (NPV). Particularly in regions where iodine supply is low, most hyperfunctioning thyroid nodules are seen in patients with normal thyroid-stimulating hormone (TSH) levels. Thyroid scintigraphy is essential for the detection of these nodules. Among non-toxic thyroid nodules, a careful application of US risk stratification systems is pivotal to exclude inappropriate FNAC and guide the procedure on suspicious ones. However, almost one-third of cytology examinations are rendered as indeterminate, requiring "diagnostic surgery" to provide a definitive diagnosis. 99mTc-methoxy-isobutyl-isonitrile ([99mTc]Tc-MIBI) and [18F]fluoro-deoxy-glucose ([18F]FDG) molecular imaging can spare those patients from unnecessary surgeries. The clinical value of AI in the evaluation of thyroid nodules needs to be determined.

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.

Temporary Thyroid Dysfunction and Catecholamine Excess Due to Mercury Poisoning in 6 Cases.

Mercury poisoning is a condition with multiple-organ dysfunction that has effects on the central nervous system, gastrointestinal system, cardiovascular system, skin, lungs, and kidneys. It can be fatal or may result in sequelae such as neurological disturbances, if treated late or left untreated. The endocrinological effects of mercury exposure are not well-known. We aimed to evaluate patients with mercury poisoning. A total of 6 cases of mercury poisoning from 3 families were included in the study. Clinical, laboratory, and follow-up data were recorded. Thyroid dysfunction was presented as high thyroid hormones and normal thyrotropin level (unsuppressed) in 5 cases (83.3%). On the other hand, pheochromocytoma-like syndrome was detected in 5 cases (83.3%) with hypertension. The 4 cases were the first to use methimazole for mercury poisoning due to tachycardia and hypertension despite antihypertensive treatment due to catecholamine excess and thyroid dysfunction. Hyponatremia was detected in 3 cases (50%). Mercury poisoning is difficult to diagnose because it is rare and presents with nonspecific physical and laboratory findings. Early diagnosis and providing appropriate treatment are essential in order to prevent sequelae. Mercury poisoning should be considered in patients with unexplained hypertension and tachycardia suggesting the involvement of thyroid hormones and catecholamines.

Anaemia-based screening for resistance to thyroid hormone alpha in children.

The hypothyroid phenotype associated with resistance to thyroid hormone alpha (RTH-α) is associated with a diverse clinical picture. On the other hand, thyroid-stimulating hormone (TSH) levels are normal. Free triiodothyronine (fT3) and free thyroxine (fT4) levels can also be normal; however, normo- or macrocytic anaemia is usually present in reported cases. Diagnosis is challenging and there is limited data regarding screening methods. The study aimed to assess the efficiency of a screening strategy for RTH-α. Out of a total of 6540 children evaluated at the outpatient clinics of paediatric neurology over 2 years and who underwent complete blood count and thyroid function tests, 432 were found to have anaemia. Within this group, we identified 42 children without an underlying specific neurological aetiology who exhibited normo- or macrocytic anaemia, normal TSH levels, fT3 levels in the upper half of the normal range or high, and fT4 levels in the lower half of the normal range or low. We excluded one patient who had already been diagnosed with RTH-α and nine patients could not be reached. Subsequently, clinical evaluation, biochemical assessment, and THRA sequencing analysis were conducted on 32 children. The findings were compared with those of the known RTH-α patients in our unit. The median age of the patients was 5.7 (5.1-7.4) years, and 22 of them were males (69%). The main reasons for assessment in paediatric neurology clinics were autism spectrum disorder (n = 12, 38%), epilepsy (n = 11, 34%), and delay in developmental stages (n = 8, 25%). Constipation was present in five of the cases (16%), while the closure of the anterior fontanelle and tooth eruption were delayed in two cases (6%) and one case (3%), respectively. The median length/height and weight standard deviation (SD) scores were 0.3 [(-0.8)-(1.1)] and -0.1 [(-0.8)-(0.3)], respectively. The median fT3, fT4, and TSH levels were 4.6 (4.2-5.0) pg/mL, 0.9 (0.8-1.0) ng/dL, and 2.2 (1.8-3.1) uIU/mL, respectively. Thirteen of the patients (41%) had high fT3 levels, while none of them had low fT4 levels. The normo- or macrocytic anaemia rate was 47% (normocytic/macrocytic, n = 8/7) at the time of reassessment. Serum creatine kinase (CK) was elevated in five patients (16%; one had anaemia). None of the subjects had a pathological variant in THRA. Known RTH-α patients had significantly lower median height SD score, higher rates of delayed tooth eruption and closure of the anterior fontanelle, lower haemoglobin levels, and higher mean corpuscular volume (MCV) and CK levels as compared to those found without RTH-α. This approach found one known patient with RTH-α but did not reveal any new cases. Notably, normo- or macrocytic anaemia did not persist in nearly half of the screened patients. A screening strategy that takes clinical findings and prominent laboratory features suggestive of RTH-α into account could lower unnecessary genetic analysis of THRA in patients presenting with neurological problems.

C-reactive Protein Levels in Patients With Autoimmune Hypothyroidism Before and After Levothyroxine Treatment.

Hypothyroidism is one of the most common endocrine disorders. Most patients with hypothyroidism have autoimmune thyroiditis (Hashimoto's), characterized by elevated concentrations of anti-thyroperoxidase (ATPO) antibodies. Both overt hypothyroidism (OH) and subclinical hypothyroidism (SH) have been associated with cardiovascular risk factors, including markers of inflammation. High-sensitivity C-reactive protein (hs-CRP) is a veridical marker of systemic inflammation. Even a minor increase in hs-CRP is considered a cardiovascular risk; therefore, evidence of a beneficial effect of levothyroxine treatment on hs-CRP could be an argument in favor of therapy for SH. To assess hs-CRP levels in patients with hypothyroidism and evaluate levothyroxine treatment's effect on hs-CRP. This is a cohort study in which patients with hypothyroidism were evaluated before and after treatment with levothyroxine. 37 patients (17 with OH and 20 with SH) and 38 healthy controls were included in the study. hs-CRP was measured at the baseline visit, then after 2 and 4 months of levothyroxine therapy at a dose necessary to achieve euthyroidism as evidenced by a normal level of thyroid-stimulating hormone (TSH). hs-CRP was significantly increased in OH (p < 0.001) and SH (p = 0.001) at baseline as compared to controls. hs-CRP significantly decreased in SH (2.2±1.6 mg/L at baseline visit, 1.4±1.1 mg/L after 2 months of levothyroxine treatment, P = 0.017) and tended to decrease in OH (2.3±1.6 mg/L at baseline visit, 1.6±1.1 mg/L after 4 months of levothyroxine treatment, P = 0.067*). Patients with hypothyroidism have increased hs-CRP levels compared to a healthy control group and, thereby, a moderately increased cardiovascular risk. Achievement of euthyroidism by levothyroxine treatment decreased the levels of hs-CRP in patients with hypothyroidism.

Effects of short- and long-term TSH suppression on lumbar bone mineral density in both genders using PET/CT

Iatrogenic subclinical hyperthyroidism is induced intentionally in patients with differentiated thyroid cancer to reduce the risk of tumor recurrence. This retrospective study aimed to investigate the effect of thyroid-stimulating hormone (TSH) suppressive therapy on bone mineral density in men and women. Two cohorts of endocrine cancer patients were compared. In cohort A, 42 patients with long-lasting suppressed serum TSH were assessed. Cohort B consisted of 41 euthyroid patients. Bone density was measured in the L1-L4 lumbar vertebrae of all patients using PET/CT scans performed for cancer staging. In 17 patients of cohort A who received a second PET/CT scan, bone density was measured again to provide longitudinal analysis. A non-significant difference in age (p = .572) and equal distribution of sex (p = .916) was determined when comparing both cohorts. A significant difference (p = .011) with a moderate effect (η2 = .08; 20.4%) was observed regarding higher bone mineral density (BMD^HU) in cohort B with normal TSH levels (M 160.63 ± 54.7 HU) versus cohort A under TSH suppression therapy (M 127.9 ± 59.5 HU) for a mean duration of 4.45 ± 2.64 years. Furthermore, no significant change in BMD^HU (p = .786) was found in those patients who received a second PET/CT scan after a mean observation time of 2.3 ± 1.2 years. In conclusion, long-lasting TSH suppression therapy caused a statistically significant decrease in BMD^HU while short-lasting therapy didn't. Therefore, we can assume a higher likelihood of osteoporosis in those patients under prolonged TSH suppression.

The negative impact of levothyroxine treatment on urinary luteinizing hormone measurements in pediatric patients with thyroid disease.

Previous studies suggest urinary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) measurements by immunofluorometric assays (IFMA) as noninvasive alternatives to serum assays for puberty assessment. However, these studies excluded patients with other endocrine disorders and those taking medications. Besides, the recent discontinuation of IFMA manufacturing is a concern. We explored the utility of luminometric assays (LIA) for urinary gonadotropins and thyroid-stimulating hormone (TSH) determinations in euthyroid patients with thyroid pathologies. We used LIA and IFMA assays to measure serum and first-morning-voided (FMV) urine LH, FSH, and TSH concentrations in euthyroid patients with various thyroid disorders. Of the 47 euthyroid patients with normal serum TSH (S-TSH) levels, 14 were receiving levothyroxine therapy. FMV total urinary LH (U-LH) concentrations correlated significantly with those measured in serum using either LIA (r=0.67, P<.001) or IFMA (r=0.83, P=.003) in patients not receiving levothyroxine treatment; however, no significant correlation could be detected in patients receiving levothyroxine regardless of the assay method (for LIA: r=0.50, P=.08 and IFMA r=0.44, P=.15). Urinary TSH (U-TSH) concentrations correlated poorly with those in serum in both the untreated and the treated groups (r=-0.13, P=.49, and r=-0.45, P=.11, respectively). FMV total U-LH determinations by LIA can be used to assess pubertal development in patients with thyroid pathology, provided the euthyroid patient is not on levothyroxine treatment. U-TSH measurements by LIA cannot replace invasive S-TSH measurements at least in patients with normal S-TSH levels. Further research may reveal the utility of U-TSH determinations in patients with elevated S-TSH levels.

Real Practice Assessment of Persistent Symptoms After Initiation of Levothyroxine

ObjectiveLevothyroxine (LT4) is the standard treatment for hypothyroidism. However, certain patients experience persistent symptoms even after achieving euthyroid status with LT4 therapy. We aimed to determine the frequency of persistent or new symptoms in patients with hypothyroidism after initiating LT4. MethodsThis retrospective study included patients with hypothyroidism who started on LT4 between January 2017 and December 2019 at Mayo Clinic in Rochester, Minnesota, USA. Five hundred patient charts were randomly selected for review. Patients with at least 1 documented follow-up encounter after LT4 initiation were evaluated for ≤3 follow-up visits regarding their biochemical status and symptoms. ResultsWe included 356 patients, a majority of whom were female (66.6%), white (92.3%), and obese (71.9%), with an average age of 59.5 years. At the baseline visit, approximately one-half of the patients (177/356, 47.7%) reported hypothyroid symptoms, with fatigue being the most common symptom. During the follow-up periods, we observed that 17.8% (28/157), 17.9% (19/106), and 19.3% (11/57) of patients had normal thyroid stimulating hormone (TSH) values but persistent symptoms, while 12.3% (19/156), 19.9% (16/107), and 8.9% (5/56) had normal TSH values but new symptoms. Overall, during each respective follow-up period, 26.7% (42/157), 27.3% (29/106), and 28% (16/57) of patients experienced persistent or new symptoms alongside normal TSH values, with fatigue being the most constant symptom. ConclusionOur findings indicate that approximately 1 in every 4 patients with hypothyroidism receiving LT4 therapy and achieving normal TSH levels experience persistent or new hypothyroid symptoms. The cause of these symptoms remains unclear, emphasizing the need for a better understanding of their underlying causes and the development of effective management strategies.

Laparoscopic Sleeve Gastrectomy: Impact on Body Mass Index and Thyroid Hormones in Euthyroid Obese Patients.

BACKGROUND Obesity is still a major global public health problem and its incidence is increasing. Obesity leads to deterioration in thyroid functions. Even when they are within normal ranges, high normal levels of thyroid-stimulating hormone (TSH) increase morbidity and mortality. This study aimed to evaluate the body mass index (BMI) and TSH levels in 300 euthyroid patients with obesity before and after laparoscopic sleeve gastrectomy (LSG). MATERIAL AND METHODS A total of 300 euthyroid patients who underwent LSG between 2019 and 2021 were included in the study. Body mass index (BMI), thyroid-stimulating hormone (TSH), and free triiodothyronine (FT) 3 and tetraiodothyronine (FT4) levels were recorded before surgery and at 6 and 12 months after surgery and subsequently analyzed. RESULTS Mean BMI values were significantly lower at 6 and 12 months after surgery (P<0.001). There was a significant difference between mean TSH and FT4 levels before surgery and those at 6 and 12 months after surgery (P<0.001). However, mean FT3 levels remained unchanged 1 year after surgery (P=0.005). CONCLUSIONS LSG is not only effective in terms of weight loss, but also exhibits improving effects on thyroid hormone homeostasis in obese patients and provides protection against further adverse effects of TSH.

The Relationship between Thyrotropin Serum Concentrations and Thyroid Carcinoma.

Thyroid Stimulating Hormone (TSH) is a hormone secreted by the pituitary gland and plays a role in regulating the production and secretion of thyroid hormones by the thyroid gland. This precise feedback loop is essential for maintaining a harmonious balance of thyroid hormones in the body, which are vital for numerous physiological processes. Consequently, TSH serves as a significant marker in assessing thyroid function, and deviations from normal TSH levels may indicate the presence of a thyroid disorder. Thyroid cancer (TC) is the malignant tumor within the endocrine system. In recent years, numerous experts have dedicated their efforts to discovering efficacious biomarkers for TC. These biomarkers aim to improve the accurate identification of tumors with a poor prognosis, as well as facilitate active monitoring of tumors with a more favorable prognosis. The role of TSH in the thyroid gland underscores its potential influence on the occurrence and progression of TC, which has garnered attention in the scientific community. However, due to the limited scope of clinical research and the dearth of high-quality foundational studies, the precise impact of TSH on TC remains unclear. Consequently, we present a comprehensive review of this subject, aiming to offer a valuable reference for future research endeavors.

SAT467 Monitoring TSH Over Time May Not Be Necessary in Patients With Thyroid Nodules

Abstract Disclosure: S. Kaul: None. A. Gupta: None. Introduction: A substantial number of patients with thyroid nodules receive monitoring of blood thyroid stimulating hormone (TSH) levels after the initial diagnosis. There is not enough literature supporting long-term monitoring of blood TSH levels in these patients with thyroid nodules. The objective of this study was to evaluate the change in blood TSH level in patients with known thyroid nodules over time and to determine if repeat blood TSH testing is required in these patients. We hypothesized that monitoring of blood TSH level is not warranted in patients with thyroid nodules in the absence of a history of medical conditions or medications that are known to affect thyroid hormone levels. Methods: We studied 100 patients aged 18 to 99 years at the Dayton VA Medical Center with at least one thyroid nodule on imaging studies from January 2010 to December 2016 with normal blood TSH level at time of the diagnosis of the thyroid nodule. Subjects with abnormal thyroid hormone level, history of hot thyroid nodule, autoimmune thyroid disease (on imaging or blood work), thyroid or pituitary surgery, radioactive iodine treatment, neck irradiation, or usage of thyroxine or any other medications known to affect thyroid hormone levels were excluded. Blood TSH level at the time of diagnosis of thyroid nodule and after were retrospectively studied and analyzed for 100 subjects. Normal blood TSH level range at time of diagnosis was noted to be 0.35-5.50 uIU/mL or 0.35-4.00 uIU/mL depending on the assay method used. Normal repeat blood TSH level range was noted to be 0.35-5.50 uIU/mL, 0.35-4.00 uIU/mL, or 0.55-4.78 uIU/mL depending on the assay method used. Results: 100 subjects with normal blood TSH at the time of diagnosis of their thyroid nodule had blood TSH level monitoring for an average time period of 5.74 years. Out of the 100, six subjects (6%, 95% CI [2.52%, 12.73%]) developed an abnormal blood TSH level in a mean time period of 6.94 years. One subject’s initial blood TSH level increased from 3.38 uIU/mL to 7.76 uIU/mL after 8.52 years. This subject did not receive treatment with thyroxine. In the other five subjects, blood TSH level decreased to below normal range in a mean time period of 6.63 years and ranged from 0.25-0.52 uIU/mL. Blood TSH level remained within normal range for 94 subjects in a mean time period of 5.67 years. Conclusion: Monitoring of blood TSH level over time may not be required in most patients with thyroid nodules in the absence of symptoms, medical conditions, or medications that are known to affect thyroid hormone levels. Presentation Date: Saturday, June 17, 2023

SAT617 Third Nerve Palsy As The Initial Presentation Of Pituitary Apoplexy, A Case Report

Abstract Disclosure: U. Siddiqui: None. M. Ahmad: None. K. Abiko: None. P. Ucciferro: None. Pituitary apoplexy is characterized by hemorrhage or infarction of the pituitary gland occurring after growth of a pre-existing adenoma. These adenomas are often asymptomatic, however, hemorrhage can compress surrounding cranial nerves and cause symptoms. We report a case of a 48-year-old male who presented with headache and third nerve palsy, found to have pituitary apoplexy despite negative initial CT imaging. Hospital Course: A 48-year-old man with a past medical history of asthma, cirrhosis, type 2 diabetes mellitus, hypertension and end stage renal disease presented to the emergency room for bitemporal headache. The headache was associated with right-sided blurry vision and ptosis. He was hypertensive to 166/79 mmHg, bradycardic to 58 beats per minute, afebrile with a temperature of 36.8 C with a respiratory rate of 18 breaths per minute. He was noted to have ptosis and inferolateral deviation of his right eye. Initial labs demonstrated the following: sodium 139 mmol/L, potassium 5.2 mmol/L, creatinine 8.44 mg/dL (baseline 6.5 mg/dL), bicarbonate 20 mmol/L, and hemoglobin 8.2 g/dL (baseline of 8-9 g/dL). The patient’s CT head without contrast and CT angiogram head and neck which were negative for acute infarct or hemorrhage, however, the patient’s MRI demonstrated a 2.1 x 2.1 x 1.4 cm macroadenoma with suprasellar extension and mild elevation of the optic chiasm. Further testing demonstrated a normal thyroid stimulating hormone level of 0.74 uIU/ml (normal 0.3-5.0 uIU/ml), low normal free t4 of 0.7 ng/dL (0.7-1.7 ng/dL), ACTH of &amp;lt;9 pg/ml (normal 9-46 pg/ml), morning cortisol of 1.3 mcg/dL (normal of &amp;gt;18 mcd/dL), total testosterone &amp;lt;10 ng/dL (normal 270-1070 ng/dL), follicular stimulating hormone of 2.2 mIU/ml (normal 1.5-12.4 mIU/mL) and a prolactin of 49 ng/ml (normal 0-19 mg/ml). Due to the patient’s symptoms and imaging findings he underwent transsphenoidal resection of tumor. Prior to the procedure he was placed on stress dosed steroids with IV hydrocortisone. After the procedure, the patient was weaned off IV hydrocortisone and continued on oral 15 mg of hydrocortisone in the morning and 5 mg in the evening. A repeat free T4 after the procedure was 0.9 ng/dl and the patient was not discharged on levothyroxine supplementation. He follows up with endocrinology as an outpatient and has had resolution of his right sided ptosis and vision changes. Discussion: Pituitary apoplexy presents in a variety of different ways including headache, nausea, altered mental status, and hormonal dysfunction. Third nerve palsy is a potential presentation of this uncommon condition and should be considered even with negative initial CT imaging. Through our case we hope to highlight this manifestation of pituitary apoplexy as, if the etiology of third nerve palsy remains elusive, pituitary apoplexy should be considered as a differential and further imaging should be obtained. Presentation: Saturday, June 17, 2023

FRI526 Geographic Trends In Thyroid Hormone Prescribing In The US: 2010 - 2020

Abstract Disclosure: M.D. Ettleson: None. N. Laiteerapong: None. W. Wan: None. A.C. Bianco: Consulting Fee; Self; Abbvie, Acella, Synthonics, Thyron, Madrigal. Introduction: Levothyroxine (LT4) is the first line treatment of hypothyroidism. However, some clinical guidelines suggest a trial of adding triiodothyronine (T3) therapy if LT4 monotherapy does not adequately resolve symptoms despite a normal thyrotropin (TSH) level. It is unknown how patterns of thyroid hormone (TH) prescribing (LT4 vs T3-containing therapy) differ across the US. Methods: We conducted a cross-sectional study of TH prescription data from a large, US-based claims database from January 1, 2010 to December 31, 2020. TH type (LT4, liothyronine [LT3], or desiccated thyroid extract [DTE]), geographic, and clinical data were collected. Only patients with a new TH prescription and a diagnosis of hypothyroidism were included. The study population was subdivided into 4 TH treatment classes: 1) LT4 monotherapy, 2) LT3 therapy with or without LT4, 3) DTE therapy with or without LT4, and 4) other. Statewide physician density and urban-rural classification were the primary geographic covariates analyzed. Other covariates included in the analytical models were age, sex, comorbidities, and co-prescribed medications. Results: A total of 524,818 adult patients accounted for 537,594 new TH prescriptions over the 11 year study period. Of the total population, 89.0% received LT4 monotherapy, 8.8% received DTE therapy, and 2.0% received LT3 therapy. The proportion of patients receiving DTE increased from 5.4% to 10.2% during the study period. DTE and LT3 prescriptions were not uniformly distributed throughout the US, with higher rates in the West and South regions. Residence in a state with higher endocrinologist density (3.0/100k population) was associated with a decreased likelihood of receiving LT3 or DTE therapy (adjusted OR 0.33, 95% CI [0.20 – 0.55], p &amp;lt;0.001; adjusted OR 0.18, 95% CI [0.08 – 0.41], p &amp;lt;0.001, respectively). Residence in large central metro zones was associated with an increased likelihood of receiving LT3 or DTE therapy (adjusted OR 1.32, 95% CI [1.22 – 1.42]; p &amp;lt;0.001; adjusted OR 1.05, 95% CI [1.01 – 1.10], p = 0.008, respectively). Conclusions: There do appear to be geographic disparities in the patterns of TH prescribing in the US. Differences in access to endocrine care may contribute to these disparities. Also, patients in more urban zones were more likely to receive LT3 or DTE therapies. Further investigation is necessary to understand the patient and physician-level factors underlying the geographic disparities identified. Presentation: Friday, June 16, 2023

The association between thyroid-stimulating hormone and thyroid nodules, goiter and thyroid antibody positivity.

The relationship between normal thyroid-stimulating hormone (TSH) levels and thyroid disease in adults remains controversial. This study aimed to investigate the correlation between serum TSH levels, particularly those falling within the normal range, and thyroid diseases in Chinese adults, including thyroid nodules (TN), goiter (GR), and thyroid antibody positivity. This research was a cross-sectional study conducted in an adult population in Tianjin, China. Thyroid volume (Tvol) and TN were assessed using thyroid ultrasonography. Fasting venous blood and spot urine samples were collected to evaluate thyroid function and iodine status. A total of 2460 subjects participated in the survey. The prevalence of thyroid dysfunction was 9.76%, and abnormal TSH levels were found to potentially increase the risk of GR and thyroid antibody positivity in adults. A total of 2220 subjects with TSH within the normal reference range were included in the further study. In these patients, Tvol decreased as TSH levels increased, in both men and women (P < 0.0001). Low TSH levels (0.27-1.41 IU/mL) were identified as a risk factor for TN (odds ratio [OR], 1.46; 95% CI: 1.14-1.87) and GR (OR 5.90, 95% CI 2.27-15.3). Upon stratification by sex and age, the risk of TN was found to be higher in women and elderly individuals (≥60 years old), while the risk of GR was found to be higher in men and younger individuals (<60 years old). High TSH levels (2.55-4.2 IU/mL) were identified as a risk factor for thyroid antibody positivity (OR, 1.53; 95% CI: 1.11-2.10). Men and younger individuals with high TSH levels exhibited a higher risk of thyroid antibody positivity. In adults with normal TSH levels, low TSH levels were associated with an increased risk of TN and GR, whereas high TSH levels were associated with thyroid antibody positivity. The research also suggests that adults whose TSH levels at upper or lower limits of the normal range should be reviewed regularly.

Alterations in neuroendocrine axes in brain-dead patients.

To identify changes in anterior pituitary gland hormone levels in brain-dead patients and alterations in free triiodothyronine (fT3), free thyroxine, cortisol, testosterone, and estradiol levels. Ten postmenopausal women and 22 men with brain death (BD) were included. Thefirst blood sample for determination of hormones (pre-BD) was collected when the clinician observed the first signs of BD. The second blood sample (BD day) was drawn after BD certification. Female patients exhibited lower follicle-stimulating hormoneand prolactin levels pre-BD and luteinizing hormone, follicle-stimulating hormone, and prolactin levels on BD day than the age-matched controls. Male patients' sex hormone levels were similar to those of the age-matched controls, except for testosterone levels, which were low in both consecutive measurements. All gonadotropins and prolactin levels were above the tests' lower detection limits (LDLs), except for one male patient with gonadotropin levels below the LDLs of the tests. Estradiol levels in both sexes ranged from normal to elevated. FT3 levels were significantly decreased in the two measurements. Thyroid-stimulating hormone (TSH)levels were low in eight patients and all low TSH levels were above the test's LDL. The remaining patients had normal or elevated TSH levels. The median adrenocorticotropic hormone (ACTH) and cortisol levels were within normal limits. All cortisol and ACTH levels were above the tests' LDLs, except for one patient with ACTH levels below the LDL in both measurements. This study supports the hypothesis that the anterior pituitary gland continues to function in the brain-dead state.