Levothyroxine Therapy Research Articles

Outcomes of Radiofrequency Ablation for Autonomously Functioning Thyroid Adenoma- Mayo Clinic Experience

Abstract Background Autonomously functioning thyroid nodules (AFTNs) constitute 5-7% of thyroid nodules and represent the second most common cause of hyperthyroidism following Graves’ Disease. Currently, radioactive iodine (RAI) and surgery are the standard treatment options, and both incur a risk of post-procedural hypothyroidism and other surgery and radiation- related complications. Methods This work aimed at assessing the efficacy of RFA, as an alternative treatment option, in resolving hyperthyroidism and also assess the nodule volume rate reduction (VRR) and its associated adverse events. Results A total of 22 patients underwent RFA for a solitary AFTN. 72% (n=16) had subclinical hyperthyroidism, 9% (n=2) had overt hyperthyroidism, and 18% (n=4) were biochemically euthyroid on anti-thyroid medication (ATD). Average pre-treatment TSH was 0.41 mIU/L (SD= 0.98) and free T4 1.29 ng/dl (SD= 0.33). Following a single RFA session, hyperthyroidism resolved in 90.9% (n= 20) and average VRR (61.13%) was achieved within 3-6 months following the ablation. Except for one nodule, none of the nodules grew during the follow-up period (16.5 months). Two patients (9%) developed transient tachycardia requiring short-term beta-blocker therapy, and two developed mild hypothyroidism requiring levothyroxine therapy. Two patients developed recurrent hyperthyroidism and elected to undergo lobectomy and repeat RFA respectively. No serious adverse effects were noted in this cohort. Conclusions RAI and/or surgery represent the standard of care for toxic adenomas but RFA shows excellent efficacy and safety profile. Therefore, at centers with RFA expertise it should be considered an alternative treatment strategy, avoiding radiation and surgery-related complications.

Investigating Associations between Subclinical Hypothyroidism and Pregnancy Outcomes and Effects of Levothyroxine Therapy on Improving Maternal and Infant Prognosis

Background: Current evidence shows subclinical hypothyroidism (SCH) is associated with increased risk of adverse pregnancy outcomes, though some controversies exist. However, little is known on the impacts and effectiveness of levothyroxine (LT4) therapy on pregnancy outcomes in women with SCH. Present study aims to investigate the associations between SCH and adverse pregnancy outcomes and clinical effects of levothyroxine (LT4) replacement therapy in patients with SCH. Methods: The clinical data of pregnant women (n = 635) with SCH who referred to Huai'an Maternal and Child Health Care Hospital, Huaian, China from June 2018 to December 2018 were retrospectively analyzed. Among them, 147 cases received standard thyroxine replacement therapy, 292 cases did not receive treatment and 150 cases who received irregular treatment or did not achieve the target or were lost to follow-up. 46 cases whose thyroid peroxidase antibody (TPOAb) was not checked during pregnancy were not included in the study. According to the TPOAb test results patients were divided into positive treatment (n = 14), negative treatment (n = 133), positive untreated (n = 19), or negative untreated (n = 273) subgroups. A total of 1876 pregnant women with normal thyroid function (TPOAb positive = 59; TPOAb negative = 1817) who delivered during the same period were selected as the control group. Pregnancy outcomes were assessed and compared between treated and control group, untreated and control group, TPOAb positive treatment subgroup and TPOAb positive and untreated subgroup, TPOAb negative treatment subgroup and TPOAb negative subgroup, and TPOAb positive and TPOAb negative subgroup. Results: Our data showed that the incidences of hypertensive disease, premature delivery, fetal growth restriction and fetal death during pregnancy in the untreated group were significantly higher than in the control group (p < 0.05). The incidence of preterm delivery in the treatment group was significantly lower compared to the untreated group and the control group (p < 0.05). Moreover, the incidence of premature birth in TPOAb positive treatment subgroup was significantly lower than their peers in TPOAb positive and untreated subgroup. The incidence of premature delivery in TPOAb negative treatment subgroup was significantly lower than TPOAb negative untreated subgroup and the difference was statistically significant (p < 0.05). There was no significant difference in the incidence of adverse pregnancy outcomes between TPOAb positive subgroup and TPOAb negative subgroup in the control group (p > 0.05). Conclusions: SCH during pregnancy is a risk factor for hypertensive disease during pregnancy, fetal growth restriction, premature delivery and fetal death. L-T4 replacement therapy improves maternal and infant outcomes in patients with SCH during pregnancy, regardless of whether or not TPOAb is positive.

12264 Myxedema Coma And The Impact Of Treatment Noncompliance

Abstract Disclosure: R. Subramani: None. H. Marasandra Ramesh: None. S. Yavuz: None. Introduction: Myxedema coma represents a critical medical condition marked by a heightened risk of both morbidity and mortality. It manifests as severe hypothyroidism, typically presenting with symptoms like lethargy, altered mental status, or potential obtundation. Various triggering factors, including infections, hypothermia, metabolic imbalances, surgery, and specific medications like amiodarone, lithium, and anesthetics, can precipitate this emergency. Here we outline a classic instance of myxedema coma stemming from non-adherence to levothyroxine treatment in the context of primary hypothyroidism. Case Summary: A 56-year-old woman with a medical history significant for primary hypothyroidism, hyperlipidemia, and mood disorder presented to the hospital exhibiting symptoms suggestive of a stroke. Upon arrival, she had a seizure episode and eventual unresponsiveness. Emergency intubation was performed due to a low Glasgow Coma Scale score and concern for airway protection. Further history revealed non-compliance with levothyroxine therapy. Laboratory findings included TSH of 150 uIu/ml, T4 of 1.1 ng/dl, T3 of 1.17 ng/dl, and cortisol of 21.9 ug/dl. Chest x-ray revealed complete atelectasis of the left lung with mediastinal shift initially before intubation. CT head and neck were unremarkable. A diagnosis of myxedema coma was made based on clinical presentation and a myxedema score of 75. Treatment included IV levothyroxine 50 mcg, increased to 100 mcg, nor-epinephrine drip for hypotension and 1000 mg of levetiracetam for seizures management. Pulmonary edema resolved following levothyroxine initiation. The patient was successfully extubated on day 3, weaned off oxygen, and discharged home after 8 days with counseling on medication adherence. Discussion: While encountering a case of myxedema coma is rare, it is crucial to maintain a low threshold for diagnosing this potentially fatal emergency. Early recognition, facilitated by a comprehensive history, physical examination, and prompt initiation of treatment, is essential for effective management. Despite early intervention, the mortality rate remains high, ranging from 50% to 60%. Wartofsky et al. advocate for the primary treatment approach with T4 alone, emphasizing its efficacy. Supportive measures such as warming, fluid resuscitation, mechanical ventilation, administration of antibiotics, vasopressors, and corticosteroids are also integral components of management. This case report underscores the considerable morbidity and mortality associated with myxedema coma. The most common trigger precipitating myxedema coma is non-compliance with levothyroxine therapy, particularly in elderly females with longstanding hypothyroidism. Therefore, counseling regarding strict adherence to levothyroxine is of paramount importance. Presentation: 6/1/2024

7915 A Case of Severe Hypothyroidism in a Patient with Nephrotic Syndrome presenting with Rhabdomyolysis requiring Levothyroxine and Liothyronine combination therapy

Abstract Disclosure: S.S. Mohammed: None. E.T. Ngo: None. S. Tadisina: None. B.M. Drees: None. Background: Nephrotic syndrome is known to worsen hypothyroidism via urinary loss of thyroid binding globulin, transthyretin, albumin and other proteins, often requiring escalating levothyroxine doses. Severe uncontrolled hypothyroidism can result in rhabdomyolysis, although this presentation is quite rare. Clinical case: We present a case of a 50-year-old male with long-standing Hashimoto’s hypothyroidism, biopsy-proven minimal change disease with nephrotic syndrome, dyslipidemia, and hypertension, who was admitted for generalized myalgia, weakness, and progressive swelling of bilateral hands and feet for one month. He had been off levothyroxine 3 months prior to presentation. He previously required large doses of oral levothyroxine, as high as 350mcg daily, but never achieved a euthyroid state despite reported adherence to therapy with the high levothyroxine doses.Laboratory workup showed severe hypothyroidism (free thyroxine <0.25ng/dL [0.6-1.6ng/dL] with markedly elevated thyroid stimulating hormone 282.03 mIU/mL [0.3-5.6mIU/mL]), along with acute kidney injury and rhabdomyolysis (Creatine kinase 4882 U/L[38-234U/L]). He was hemodynamically stable with intact mentation and was not deemed to be in myxedema coma. Physical examination was consistent with hypothyroidism with periorbital swelling, dry skin, deep hoarse voice, bilateral hand and feet edema, and delayed deep tendon reflexes. Thyroid function tests and clinical symptoms failed to improve after 8 days, despite high doses of levothyroxine IV (200mcg). Creatine kinase remained high at 4994 U/L [38-234U/L] despite adequate fluid hydration. Liothyronine 5mcg orally was started in addition to levothyroxine 200mcg IV. Repeat thyroid function tests after 2 days of combined IV levothyroxine and oral liothyronine therapy showed significant downtrend in TSH to 154.12 uIU/ml [0.3-5.6mIU/mL] and increase in free thyroxine to 0.44ng/dl [0.6-1.6ng/dL]. Creatine kinase also down trended to 3181U/L[38-234U/L] on D4 of IV levothyroxine 200mcg IV with liothyronine 5mcg daily. He was discharged stable and clinically improved on oral levothyroxine and liothyronine. Laboratory evaluation 10 days later showed further improvement in TFTs (TSH 66.0[0.3-5.6mIU/mL]), free thyroxine 0.6 [0.6-1.6ng/dL] Conclusion: This case presents a unique and unusual clinical course in symptomatic primary hypothyroidism with rhabdomyolysis and AKI. Rhabdomyolysis due to hypothyroidism, without an obvious precipitating factor, has been previously reported, but is very rare. There is limited evidence regarding combination treatment with levothyroxine and liothyronine in primary hypothyroidism; however, as demonstrated in this patient, combination therapy resulted in clinical and biochemical improvement of thyroid function. Presentation: 6/2/2024

8135 A Rare Case of Late Recurrence of Graves’ Disease Decades After Radioactive Iodine Therapy: Is it Really a Definitive Treatment?

Abstract Disclosure: K.S. Hill: None. R. Osman: None. Graves’ disease (GD) is the most common cause of hyperthyroidism in the US and worldwide. Radioactive iodine (RAI) therapy has excellent success rates in treatment of GD. Studies have demonstrated that RAI successfully treats GD with a single session in the majority of cases. Recurrence after RAI, if it occurs, is most commonly seen in the first year after RAI. However, this is rare particularly in patients who have developed evidence of successful treatment in the form of post-ablative hypothyroidism. Only a few case reports have demonstrated recurrence of GD more than 10 years after treatment of GD with RAI and development of post-ablative hypothyroidism. We report a case of GD recurrence approximately 30 years after ablation. A 69 y/o woman presented for evaluation of hyperthyroidism and newly discovered thyroid nodule. Her history was significant for GD with orbitopathy diagnosed in the early 1990s and treated with RAI. Following the ablation, she developed hypothyroidism and was managed for over 20 years on levothyroxine therapy. In recent years she began to develop symptoms of palpitations and heat intolerance with biochemical evidence of thyrotoxicosis despite reductions in her levothyroxine dose. She also developed recurrence of her orbitopathy, confirmed by ophthalmology. During this time, a neck CT incidentally described an atrophic thyroid gland with a 9 mm soft tissue nodule in the left thyroid bed. Follow up ultrasound showed a 1.1 cm nodule with increased vascularity in the left thyroid bed with an otherwise atrophic gland and no lymphadenopathy. Her levothyroxine was stopped for one month in preparation for a thyroid uptake scan, during which TSH increased to 15 mcU/mL. Scan showed overall severely decreased radioactive iodine uptake of the gland consistent with prior ablation although there was a faint uptake most focally conspicuous on the left side inferiorly. Thyroid stimulating immunoglobulin (TSI) was elevated at 1.35 IU/L (Ref 0.00-0.55). After discussion with the patient, the decision was made for surgical treatment with thyroidectomy. Pathology was benign. She was continued on her prior dose of levothyroxine 75 mcg daily however now with clinical and biochemical evidence of hypothyroidism requiring continued increase in levothyroxine dose to normalize TSH levels. GD is the most common cause of hyperthyroidism and RAI therapy is the most common definitive treatment for GD in the US. Recurrence of GD after ablative hypothyroidism is rare, particularly in the case of late recurrence decades after ablation. Only a few cases are reported in the literature, ours with the longest interval-to-relapse. Recurrence of orbitopathy may be the first clue. Our case highlights the need to continue to monitor clinically for recurrence of Graves’ disease long after RAI use. Presentation: 6/3/2024

7699 Unanticipated Harmony: PD-L1 Inhibitor Treatment for Urothelial Cancer Resolving Graves' Disease in a Patient - A Case of Immune Modulation Surprises

Abstract Disclosure: K. Tiwari: None. C.A. Resta: None. Introduction: Programmed death ligand 1(PD-L1) inhibitors constitute a class of immune checkpoint inhibitors (ICI) employed in treating various cancers. Thyroid-related immune-related adverse events (irAEs), such as hypothyroidism, are found to be in 3.9% of patients with PD L1 treatments. This case explores a unique scenario where a patient with pre-existing Graves' disease, undergoing PD-L1 inhibitor therapy for cancer, experienced an unexpected sequence of events leading to the default treatment of Graves' disease and subsequent progression to hypothyroidism. Case Presentation: A 59-year-old male, who had been effectively managed on methimazole for Graves' disease over two years and had chosen not to pursue definitive therapy for the condition, presented with tremors and a bilaterally enlarged thyroid gland during treatment for urothelial carcinoma. Laboratory findings included a TSH of 0.03 mIU/L (nl 0.40-4.50 mIU/L), fT4 of 3.4 ng/dL (nl 0.8-1.8 ng/dl), and tT3 of 284ng/dl (nl 76-181 ng/dl). The patient had recently started treatment with Avelumab, a PD-L1 inhibitor, as maintenance therapy following 4 cycles of gemcitabine/cisplatin cycles. Concerned about worsening Graves' disease, the methimazole dose was increased, and follow-up labs were performed after three weeks. These results showed low-normal fT4 of 0.8 ng/dL, TSH of 1.01 mIU/L(N), and low T3 of 58 ng/dL. TSI was mildly elevated at 168%. Due to rapidly changing thyroid function tests and suspicion of thyroiditis, methimazole was stopped. A PET scan a week later indicated diffuse thyroid uptake consistent with thyroiditis. Repeat labs 10 days later revealed a TSH of 67.36 mIU/L(H) and fT4 of 0.4 ng/dL(L), indicative of overt primary hypothyroidism. The patient exhibited symptoms including fatigue, constipation, and cold intolerance. The patient was initiated on levothyroxine therapy to address overt primary hypothyroidism, likely secondary to destructive thyroiditis from ICI. Discussion: Thyroid irAEs are typically incidentally discovered during routine monitoring of ICI treatment. It includes thyrotoxicosis, subclinical hypothyroidism, and overt hypothyroidism. These events commonly occur in patients lacking pre-existing thyroid conditions. In contrast, our patient, with a history of Graves' disease, experienced resolution of Graves' disease following treatment with PD-L1 inhibitor use with subsequent progression to hypothyroidism. Conclusion: This case emphasizes the importance of recognizing atypical presentations of thyroid irAEs in individuals with pre-existing thyroid disorders undergoing ICI treatment. Presentation: 6/3/2024

12387 Late New-onset Graves' Orbitopathy: 14 Years Post-radioactive Iodine Treatment Of Graves' Disease: Case Report

Abstract Disclosure: F.F. Altaleb: None. K. Alaybaa: None. N. Aljohani: None. Introduction: Graves' orbitopathy (GO) is an autoimmune condition affecting the orbit and retro-ocular tissues, often accompanied by hyperthyroidism associated with Graves' disease, but it is rarely observed in euthyroid or hypothyroid individuals. Radioactive iodine (RAI) therapy for Graves' disease and smoking are recognized risk factors for GO development and progression. Individuals who smoke and undergo RAI treatment are significantly more likely to experience ocular lesions and worsening of GO compared to non-smokers. The exacerbation of GO post RAI therapy is attributed to elevated levels of TSH receptor antibodies, which may persist for up to a year post-treatment. Our case presents a rare occurrence of severe new-onset GO manifesting 14 years after achieving prolonged euthyroid status and successful RAI treatment for Graves' disease, accompanied by persistent TSH receptor antibody positivity that is unlikely to be suppressed by long term levothyroxine therapy. Clinical case: A 55-year-old male who’s a smoker and previously diagnosed with Grave’s hyperthyroidism, received treatment with RAI ablation therapy 14 years ago. At the time of diagnosis, there were no symptoms or signs of GO, and no history of thyroid eye disease was detected. Following the RAI treatment, he developed hypothyroidism and was promptly started on a daily dosage of 100 mcg of levothyroxine.Upon ocular examination: Visual acuity: 20/30 in both eyes. Significant restriction in extraocular muscle movements, with reported diplopia and pain. Bilateral lid retraction, proptosis, right conjunctival chemosis, and injection of the bulbar conjunctiva and caruncle, as well as lagophthalmos, were evident. No relative afferent pupillary defect observed. Color vision: 3/15 in the right eye, 15/15 in the left eye. Intraocular pressure: 22 mmHg (right eye), 16 mmHg (left eye). Optic discs unremarkable. Proptosis measurements: 26 mm (right eye), 23 mm (left eye). Ophthalmopathy clinical activity score: 7.Our laboratory analysis indicated normal thyroid function test However, the TSH receptor antibody and TPO antibody returned positive.We initiated treatment with IV methylprednisolone at a dosage of 500 Mg weekly for a duration of 4 weeks. Additionally, we introduced local measures, along with selenium supplementation. Within a week of initiating treatment, the conjunctival chemosis resolved, and there was improvement in ocular movement, resulting in mild to moderate restriction in all directions of gaze. Conclusion: This case illustrates the unexpected development of GO in a patient who had been euthyroid and effectively cured of Grave's disease for a span of 14 years following RAI treatment. The presence of TSH receptor antibodies, which are likely unresponsive to suppression by levothyroxine, as well as smoking cigarette might have contributed to the late new onset of the disease. Presentation: 6/3/2024

A Randomized Clinical Trial Comparing 2 Levothyroxine Regimens During Ramadan Fasting in Thyroidectomized Patients.

For Muslim patients on levothyroxine (L-T4) therapy, the best approach for L-T4 intake during Ramadan fasting remains unclear. We compared 2 practical approaches for L-T4 intake during Ramadan. We randomly assigned 69 patients (21 males, 48 females, median age 44 years) with differentiated thyroid cancer (DTC) who underwent thyroidectomy in the past and are on stable LT4 doses to 2 arms. Arm A (33 patients) ingested their pre-Ramadan L-T4 dose at the evening meal and ate immediately. Arm B (36 patients) increased their pre-Ramadan dose by 25 µg if their regular L-T4 dose was ≤150 µg/day or by 50 µg if their pre-Ramadan dose was >150 µg/day and ate immediately. At the beginning of Ramadan (baseline), the median thyrotropin (TSH) level and the numbers of patients in euthyroidism, subclinical hyperthyroidism (Shyper), or subclinical hypothyroidism (Shypo) were comparable between the 2 arms (P = .69 and P = .65, respectively). At the end of Ramadan, in arm A there were 17 (51.5%), 3 (9.1%), and 13 (39.4%) patients in euthyroidism, Shyper, and Shypo compared with 17 (47.2%), 14 (38.9%), and 5 (13.9%) patients, respectively, in arm B (P = .005). The mean ± SD TSH levels in arms A and B at the end of Ramadan were 5.6 ± 6.0 mU/L and 1.67 ± 2.6 mU/L, respectively (P = .0001). No overt thyroid dysfunction developed but there were more cases of Shypo in arm A and Shyper in arm B. Arm B achieved desirable levels of TSH (normal or slightly suppressed) in 86% of cases and might be a preferable approach, especially for patients who need TSH suppression (eg, DTC).

Frequency and Determinants of Levothyroxine Therapy Initiation for Veterans with Subclinical Hypothyroidism.

Background/Objectives: There is evidence of overtreatment in patients with subclinical hypothyroidism (SCH). We aimed to identify the proportion of patients treated for SCH and the determinants of thyroid hormone therapy initiation. Methods: We included a random sample of adult Veterans diagnosed with SCH from 1 January 2016 to 31 December 2018 and conducted univariate and multivariable logistic regression to identify factors associated with levothyroxine initiation. Results: Out of 229 Veterans with SCH [90.0% male, 87.2% White, 99.1% non-Hispanic, median age (interquartile range; IQR) 68 (17) years], 27.5% were treated with levothyroxine. The treated group had a higher proportion of White patients (95.2% vs. 84.2%, p = 0.039), a higher thyrotropin level [median (IQR), 6.98 (2.06) mIU/L vs. 6.14 (1.10) mIU/L, p = 0.0002], a higher proportion of patients with thyrotropin level ≥ 10 mIU/L (11.1% vs. 3.0%, p = 0.021), a lower frequency of confirmatory thyroid testing before initiating levothyroxine (49.2% vs. 97.0%, p < 0.0001), and a similar frequency of thyroid autoimmunity testing (3.2% vs. 0.6%, p = 0.18) compared to the untreated group. In a multivariable logistic regression analysis, White race (OR = 4.50, 95% CI 1.19 to 17.08, p = 0.026) and index thyrotropin level [OR = 1.71, 95% CI 1.24 to 2.35, p = 0.001; for every SD increase (1.6 mIU/L)] were associated with higher odds of treatment. Conclusions: Three in 10 Veterans with SCH received levothyroxine, often based on a single abnormal thyroid test without autoimmunity assessment. White race and higher thyrotropin level were linked to increased odds of starting treatment, indicating potential disparities and the influence of SCH severity on decision-making.

Association between Subclinical Hypothyroidism and Adverse Pregnancy Outcomes in Assisted Reproduction Technology Singleton Pregnancies: A Retrospective Study.

Background/Objectives: Women with subclinical hypothyroidism (SCH) were reported to be at an increased perinatal risk. We aimed to investigate the relationship between SCH and perinatal outcomes in singleton pregnancies resulting from assisted reproduction technology (ART). Methods: We retrospectively examined the perinatal outcomes of ART singleton pregnancies in women who underwent thyroid function screening before conception and delivered at our hospital from January 2020 to July 2023. We defined SCH as thyroid-stimulating hormone (TSH) levels > 2.5 mU/L and normal free T4 levels. The patients were categorized into three groups: normal thyroid function (group A), SCH without levothyroxine therapy (group B), and SCH with levothyroxine therapy (group C). The risks of preterm birth, preeclampsia, fetal growth restriction, manual placental removal, and blood loss at delivery were compared among the three groups. Results: Out of the 650 ART singleton deliveries, 581 were assigned to group A, 34 to group B, and 35 to group C. The preterm birth rate at <34 weeks was significantly higher in group B and significantly lower in group C than in group A. The rate of preterm delivery at <34 weeks increased in correlation with TSH levels. Levothyroxine therapy was the significant preventive factor for preterm birth at <34 weeks. Conclusions: The preterm birth rate before 34 weeks was significantly higher in the SCH group. Levothyroxine therapy is a significant protective factor against preterm birth before 34 weeks. Universal screening for thyroid function and appropriate hormone therapy in pregnant women may help reduce perinatal risks, including preterm birth.

Triiodothyronine levels in athyreotic pediatric patients during levothyroxine therapy.

Levothyroxine (LT4) monotherapy is the current recommended approach for treating pediatric patients post-total thyroidectomy (TT) based on the assumption that peripheral conversion of thyroxine (T4) to triiodothyronine (T3) normalizes thyroid hormone levels. In adults, approximately 15% of post-TT patients on LT4 monotherapy have altered T4:T3 ratios with ongoing debate in regard to the clinical impact with respect to health-related quality of life (hrQOL). The ability to normalize T3 and T4 levels on LT4 monotherapy for pediatric patients' post-TT is important but not previously described. This study reports data on T3 levels in athyreotic pediatric patients to determine if a similar cohort of patients exists on LT4 monotherapy targeting normalization of TSH (LT4 replacement) or suppression (LT4 suppression). Thyroid function tests (TFTs) were retrospectively extracted from medical charts for patients <19 years old who underwent TT for definitive treatment of Graves' disease (GD) or differentiated thyroid cancer (DTC) between 2010-2021. LT4 dosing was selected to normalize the TSH in GD patients (LT4 replacement) or suppress TSH in DTC patients (LT4 suppression). Pre- and post-surgical TSH, T3 and T4 levels were compared. Of 108 patients on LT4 replacement (n=53) or LT4 suppression (n=55) therapy, 94% (102/108) of patients demonstrated T3 levels in the normal range post-TT. However, the majority of patients on LT4 replacement (44/53; 83%) and LT4 suppression (31/55; 56%) displayed post-TT T3 levels in the lower half of the normal range despite 50% (22/44) and 48% (15/31) of these patients, respectively, having post-TT fT4 levels above the upper limit of the normal range. A significant number of pediatric patients do not achieve similar T3 and T4:T3 levels pre- and post-TT. Future multi-center, prospective studies evaluating LT4 monotherapy in comparison to combined LT4/LT3 therapy are warranted to determine the potential clinical impact of altered T3 levels in athyreotic pediatric patients.

Hypothyroidism due to biallelic variants in IYD: description of 4 families and a novel variant.

Biallelic loss-of-function variants in the IYD gene cause hypothyroidism resulting from iodine wasting. We describe 8 patients (from 4 families in which the parents are first cousins) who are homozygous for a variant in IYD (including a novel missense deleterious variant, c.791C>T [P264L], in 1 family). Seven patients presented between 5 and 16 years of age with a large goiter, overt hypothyroidism, and a high serum thyroglobulin. The goiter subsided with levothyroxine therapy in most. Upon stopping levothyroxine in 5 patients, goiter and hypothyroidism reappeared in 3. In these 3 patients, a rising serum thyroglobulin concentration preceded hypothyroidism and goiter and urinary iodine excretion was low. In patients who remained euthyroid, urinary iodine was normal. In conclusion, these patients bearing biallelic pathogenic variants in IYD developed a large goiter, a high serum thyroglobulin, and overt hypothyroidism when their iodine intake was low.

Effect of Levothyroxine Therapy on the Lipid Profile of Patients With Hypothyroidism: A Systematic Review.

Hypothyroidism, also known as underactive thyroid, is a condition where the thyroid gland does not produce enough thyroid hormone. Deficiency or lack of thyroid hormone causes patients to have a slower metabolism, which may lead to secondary medical issues such as weight gain, fatigue, depression, and increased cardiovascular risk. This systematic review aims to explore the effect of levothyroxine therapy on the lipid profile of hypothyroid patients. Through a comprehensive search, 3096 articles were retrieved using keywords such as Hypothyroidism, Levothyroxine, Lipid, Dyslipidemia, and Cholesterol from PubMed, PubMed Central, Google Scholar, and ScienceDirect databases. The Medical Subject Headings (MeSH) strategy was also leveraged to extensively search the PubMed database. Research articles that were published from the year 2020 until May 2024, including randomized control trials, observational studies, meta-analyses, systematic reviews, literature reviews, and case reports, were included in the research. Research papers published before 2020, written in languages other than English, and animal studies were excluded. The 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria were used in the design of the systematic review. Levothyroxine therapy is the treatment of choice in patients suffering from hypothyroidism, and based on our review, the treatment has a positive impact, leading to a significant decrease in total cholesterol, low-density lipoproteins, and triglyceride values in hypothyroid patients. The research highlights the importance of starting timely levothyroxine therapy in hypothyroid patients to maintain normal lipid levels and reduce the associated cardiovascular risk.

Clinical efficacy of multigene panels in the management of congenital hypothyroidism with gland in situ.

Congenital hypothyroidism (CHT) is a diverse condition with various genetic etiologies. This study aimed to investigate the utility of next-generation sequencing (NGS) analysis in guiding treatment decisions and predicting prognosis for CHT patients with gland in situ (GIS). A retrospective analysis was conducted on 33 CHT patients with GIS who underwent NGS analysis at a single institution between 2018 and 2023. Patients were classified as having permanent (PCH), transient congenital hypothyroidism, or ambiguous congenital hypothyroidism (ACH) CHT based on their response to levothyroxine discontinuation at 3 years of age. Among the 33 patients, genetic variants were identified in 26, with the most prevalent variants found in DUOX2 (26.92%), TSHR (30.77%), TG (19.35%), and DUOXA2 (19.23%). Patients with high initial thyroid-stimulating hormone levels (>50 mIU/L) and low free thyroxine levels (<0.89 ng/dL) at diagnosis tended to have compound heterozygous or homozygous variants in DUOX2, DUOXA2, and TG, and were more likely to develop PCH. In contrast, patients with heterozygous variants in these genes often exhibited ACH. TSHR variants were associated with diverse clinical manifestations, ranging from PCH to ACH, and were more common in patients with initial thyroid-stimulating hormone levels <50 mIU/L. The study highlights the potential utility of NGS analysis in predicting the clinical course and guiding treatment decisions for CHT patients with GIS. Genetic analysis may aid in determining the appropriate duration of levothyroxine therapy and monitoring strategies, particularly in cases where traditional clinical indicators are inconclusive.

Diagnosis of Thyroid Nodules in Children and Adolescents with Subclinical Hypothyroidism and Their Outcomes after Early Thyroxine Treatment-A Longitudinal Study.

Pediatric thyroid nodules (TNs) present a higher malignancy rate compared to adults. We sought to diagnose the frequency and characteristics of TNs in children and adolescents with subclinical hypothyroidism (SH) and their outcomes after levothyroxine (LT4) therapy. A total of 256 children with TNs and SH were followed every semester from 2006 to 2018. All patients were treated with LT4. Clinical and radiologic findings, such as the size and texture of the nodules, were documented. Analysis included one-way ANOVA, Kruskal-Wallis, Chi-square, and Fisher's exact tests. After initial LT4 therapy, TNs disappeared in 85.5% and did not reappear throughout follow-up. In 14.5%, TNs remained the same or increased in size, but they decreased after subsequent LT4 administration with an increased dose. Thyroid disease family history (FHTD) was documented in 77.0%. In total, 64.5% developed a goiter, 46.0% exhibited thyroid heterogeneity on ultrasound, 23.4% had positive Anti-Tg, and 25.4% had positive anti-TPO autoantibodies. Our findings support the possible premise that early pharmacologic intervention with LT4 may be beneficial in children and adolescents with TNs and SH. The increased frequency of FHTD, goiter, thyroid heterogeneity, and Hashimoto in our patients emphasizes that thyroid ultrasounds may be warranted in children and adolescents with these characteristics in order to rule out the presence of TNs.

Investigating the effect of levothyroxine replacement on cholesterol levels in hypothyroid patients

ABSTRACT Introduction: Effects of levothyroxine therapy on the lipid profile of hypothyroid patients lead to decrease in the risk of cardiovascular diseases and mortality. Objective: Overt or subclinical hypothyroid dysfunction has negative effects on lipid metabolism and leads to hypercholesterolemia that in turn increases the risk of cardiovascular diseases and mortality. In this matter, several interventional studies investigated the effects of levothyroxine therapy on the lipid profile of hypothyroid patients, and conflicting results have been obtained. The current research aims to investigate the effect of levothyroxine replacement on cholesterol levels in hypothyroid patients. Methods: The present prospective study examined 112 patients (mean age of 43.80 ± 14.36 years) with overt hypothyroidism. To do so, 72.3% of patients were females. Levothyroxine replacement therapy was prescribed for patients, and they were examined monthly to evaluate the effects of therapy on their lipid profiles. After reaching normal thyroid stimulating hormone (TSH), the patients’ laboratory parameters, including TSH, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides, were surveyed. Results: After Levothyroxine therapy, there was a significant reduction in mean TSH (62.03 vs. 2.33 ± 1.95; P &lt; 0.0001), triglycerides (145.57 ± 88.65 vs. 121.91 ± 59.52, P = 0.002), cholesterol (203.90 ± 53.73 vs. 166.65 ± 40.07, P &lt; 0.0001), and serum LDL (123.61 ± 45.03 vs. 95.99 ± 24.20, P &lt; 0.0001), but the mean value of serum HDL did not show any significant change (54.18 ± 16.60 vs. 51.59 ± 18.38, P = 0.274). Conclusions: Levothyroxine therapy has beneficial effects on lipid profile in patients with overt hypothyroidism because it decreases serum triglyceride, total cholesterol, and LDL. However, levothyroxine therapy does not significantly change HDL levels.

Evaluation of Health-Related Quality of Life in Patients with Euthyroid Hashimoto's Thyroiditis under Long-Term Levothyroxine Therapy: A Prospective Case-Control Study.

Objectives: To investigate quality of life using the SF-12 scale in euthyroid Hashimoto's thyroiditis patients on levothyroxine therapy for at least three years. Methods: This prospective case-control study included 44 euthyroid Hashimoto's thyroiditis patients and 44 matched controls, conducted at a university hospital's endocrinology clinic from 6 November to 30 December 2023. Participants completed the SF-12 questionnaire; data were analyzed using Shapiro-Wilk, Student's t-test, Mann-Whitney U, Yates chi-squared, and Spearman's tests. Results: The study involved 88 participants (Hashimoto's group: 35 females, 9 males; control group: 31 females, 13 males), with average ages of 49.50 and 47.43 years old, respectively. Significant differences were observed in TSH, T4 levels, and family history (p < 0.05). The Hashimoto's thyroiditis group showed higher thyroid peroxidase antibodies (95.69 IU/mL) and lower scores on both physical and mental sub-dimensions of SF-12, with a significant difference in physical scores (p < 0.05). Significant correlations were found between age and Anti-TG; Anti-TPO and Anti-TG; BMI and T3; TSH and T4; HDL and triglycerides; MCS-12 and PCS-12; Anti-TPO and T3; cholesterol and T3; and LDL and cholesterol (p < 0.05). Other variables showed no significant correlations (p > 0.05). Conclusions: Our study shows that effective control of hypothyroidism is not sufficient to reduce the negative effects of Hashimoto's thyroiditis on patients' health-related quality of life. Beyond the normalization of hormone levels, comprehensive therapeutic strategies targeting the autoimmune aspects of the disease are essential for the management of Hashimoto's thyroiditis. This study provides a foundation for developing effective therapies that can enhance quality of life for patients with Hashimoto's thyroiditis.

Resistance To Thyroid Hormone Receptor Alpha Due to Heterozygous Pathogenic Variant in THRA Gene: A Case Report from India

Background: Thyroid Hormone Receptor Alpha (THRA) gene mutation is a thyroid hormone resistance syndrome characterized by non-responsiveness of target tissues to the active form of TH (T3). Clinical Description: We describe a heterozygous missense variant in exon 8 of THRA gene detected in a 2-month-old female with clinical phenotype of hypothyroidism, low free thyroxine, elevated free triiodothyronine &amp; normal levels of thyroid stimulating hormone. Management &amp; Outcome: Clinical improvement in linear growth, motor development domain, hypotonia &amp; constipation were noted with levothyroxine therapy but insufficiencies in cognitive and fine motor skills may remain. Conclusion: THRA gene mutation should be considered in patients with features of clinical hypothyroidism and elevated free T3, decreased/ normal free thyroxine &amp; normal thyroid-stimulating hormone levels.

Levothyroxine Therapy: Its Effect on Subclinical Hypothyroidism

Levothyroxine Therapy: Its Effect on Subclinical Hypothyroidism

Potential Risks and Benefits of Desiccated Thyroid Extract for the Treatment of Hypothyroidism: A Systematic Review.

Background: Desiccated thyroid extract (DTE) is no longer recommended for the treatment of hypothyroidism but is still in use. This review aimed to summarize the available literature on treatment with DTE in adult patients with hypothyroidism. Methods: The search was conducted up until January 6, 2024, in six electronic databases. Two reviewers independently screened all the search results. The retrieved studies compared DTE treatment with levothyroxine or combination therapy with liothyronine and levothyroxine. The primary outcome was quality of life (QoL), and the secondary outcomes included symptoms, treatment preference, adverse effects, thyroid hormone levels, thyroid autoantibodies, cardiovascular measures, and gene polymorphisms in deiodinase enzymes. Results: In the qualitative synthesis, we included nine nonrandomized studies of interventions (NRSIs), two randomized clinical trials (RCTs), and three case reports. The overall quality of evidence was moderate to very low for the various outcomes. The RCTs found no difference between treatments regarding QoL and symptom score assessments. In the NRSIs, symptom and QoL assessments were in favor of DTE. The included studies indicated that DTE may cause an increase in heart rate, lower body weight, and lower high-density lipoprotein compared with other treatment regimens, but results were conflicting. Conclusions: Most studies of DTE treatment are hampered by an inferior design, and data on long-term effects and side effects are lacking. Two RCTs could not demonstrate any difference in QoL or symptom scores when comparing DTE with other thyroid hormone substitutions. Future trials of DTE in patients with hypothyroidism should be based on adequate study designs, validated measures of QoL, patients with reduced QoL, and the assessment of biomarkers reflecting long-term adverse effects.