Thyrotropin (thyroid-stimulating hormone)-secreting pituitary adenomas are a rare cause of hyperthyroidism that frequently presents diagnostic and therapeutic challenges. This study characterizes the clinical, biochemical, radiological, and histopathological features of thyrotropin-secreting pituitary adenomas, evaluates long-term outcomes, and identifies factors influencing remission and recurrence. We retrospectively analysed 12 patients with thyrotropin-secreting pituitary adenomas treated between January 2003 and February 2025 at a tertiary endocrine referral centre. Clinical presentation, hormonal profiles, imaging characteristics, histopathology, management, and follow-up were reviewed. Diagnostic criteria included inappropriately normal or elevated thyroid-stimulating hormone levels with increased free thyroid hormones and pituitary imaging confirming an adenoma. Remission was defined as clinical and biochemical normalization without ongoing therapy. Subgroup analysis examined the impact of diagnostic delay on tumour size, invasiveness, and outcome. The cohort comprised nine men (75%) and three women (25%) with a mean age at diagnosis of 47.8±17.2 years. Excluding one multiple endocrine neoplasia type 1 case with early detection, the mean diagnostic delay was 42.5 months (range: 4-156). Magnetic resonance imaging revealed macroadenomas in 75% of patients and Knosp grade 3-4 invasion in 41.7%. Longer diagnostic delay was correlated with significantly larger tumours (17.9±3.6 mm vs 9.8±1.0 mm; p=0.004). All patients underwent surgery; 50% achieved remission, while 33.3% required additional therapy (somatostatin analogues and/or radiotherapy). At a median 7.8-year follow-up, 66.7% remained in sustained remission. No patient experienced thyroid storm; transient postoperative hypothyroidism occurred in 25%. Thyrotropin-secreting pituitary adenomas often present with heterogeneous and misleading biochemical profiles leading to diagnostic delay, larger and more invasive tumours, and a greater need for multimodal therapy. Early recognition of discordant thyroid function tests-elevated free T3/T4 with non-suppressed thyroid-stimulating hormone-is critical to avoid unnecessary thyroid ablation and improve surgical outcomes.

Nonfunctioning pituitary adenomas (NFPAs) have historically been characterized histologically based on hormonal immunostaining. The 2017 World Health Organization guidelines for pituitary neuroendocrine tumors further delineated NFPA classification based on biologically relevant transcription factors (TFs), including T-PIT, PIT-1, and steroidogenic factor 1 (SF-1). We sought to evaluate differences in NFPA immunohistochemistry (IHC) associated with biological sex and age according to new TF immunostaining criteria. A retrospective review of data from a single institution was conducted to identify patients who had undergone NFPA resection from 2012 to 2023. Patients grouped based on their biological sex and then further divided into age categories. Univariable statistics were used to identify associations between patient demographics and NFPA IHC. A total of 416 patients were included in the IHC-hormone analysis, and 154 patients were included in the IHC-TF analysis. Men were significantly less likely to have NFPAs with positive immunostaining for T-PIT (odds ratio [OR] = 0.15, 95% CI: 0.06-0.37) or adrenocorticotropic hormone (OR = 0.38, 95% CI: 0.22-0.64) and significantly more likely to have NFPAs stain positive for SF-1 (OR = 4.87, 95% CI: 2.24-10.6), follicle-stimulating hormone (FSH) (OR = 2.46, 95% CI: 1.64-3.69), luteinizing hormone (OR = 2.28, 95% CI: 1.26-4.13), thyroid-stimulating hormone (OR = 2.56, 95% CI: 1.05-6.26), or the alpha subunit (OR = 2.01, 95% CI: 1.36-2.97). Compared with the youngest age group, women in the oldest age group were more likely to have an NFPA stain positive for SF-1 (OR = 6.88, 95% CI: 1.86-25.4), FSH (OR = 2.32, 95% CI: 1.02-5.27), or the alpha subunit (OR = 2.14, 95% CI: 1.02-4.47). Similarly, men in the oldest age group were more likely to have an NFPA staining positive for FSH (OR = 4.16, 95% CI: 1.90-9.11) and the alpha subunit (OR = 2.36, 95% CI: 1.10-5.05); they were less likely to have positive immunostaining for adrenocorticotropic hormone (OR = 0.19, 95% CI: 0.04-0.79). There were no age-related differences in TF staining for male patients. This study demonstrates that sex and age are important demographic factors associated with immunostaining patterns and TF lineage subtypes for NFPAs. Underlying endocrine factors dictated by age and sex may represent a role in tumorigenesis or progression of NFPAs.

Background Thyroid-stimulating hormone pituitary adenomas (TSHomas) are a rare cause of central hyperthyroidism, characterized by abnormally high TSH levels, and typically respond to somatostatin analogue (SSA). We report a young patient with SSA-insensitive TSHoma where Lugol’s solution facilitated surgical preparation. Case presentation A 28-year-old male patient presented with a 1.5-year history of headache and visual loss. Thyroid function revealed elevated levels of free triiodothyronine (FT3) 45.87 pmol/L, free thyroxine (FT4) exceeding 100 pmol/L, and non-suppressed TSH 6.66 mIU/L. Magnetic resonance imaging (MRI) suggested a large pituitary adenoma (19 × 25 × 23 mm). Initial long-acting octreotide treatment was ineffective in controlling hyperthyroidism and was discontinued after 5 months. Approximately 1 year after the initial presentation, reassessment showed persistently elevated thyroid hormone levels. A TSH suppression test indicated octreotide sensitivity at 55%. An oral glucose tolerance test (OGTT) suggested concomitant growth hormone (GH) excess. Preoperatively, treatment with short-acting octreotide, methimazole, and Lugol’s solution effectively controlled thyroid hormone levels. The patient subsequently underwent transnasal adenomectomy. Histopathology confirmed a PIT-1-positive pituitary adenoma, with TSH, GH, and prolactin (PRL) positivity. At the 3-month follow-up, thyroid hormone, GH, and insulin-like growth factor-1 (IGF-1) levels had normalized. Conclusions This case highlights Lugol’s solution as a rescue therapy for SSA-insensitive TSH/GH co-secreting pituitary adenomas. Despite SSTR2/5 positivity, suboptimal response to octreotide suggests tumor heterogeneity or downstream signaling defects. Preoperative Lugol’s solution should be considered when SSAs and methimazole fail.

Androgen production in adrenocortical H295R cells is regulated by thyroid hormone T3 without reciprocal thyroid axis modulation in pediatric CAH.

IntroductionThe standard first-line treatment of hypothyroidism is oral levothyroxine (LT4) tablets usually at a dose of 1.6-1.8 μg/kg/day. Refractory hypothyroidism (RH) is defined as persistently elevated thyroid-stimulating hormone (TSH) levels despite LT4 doses ≥1.9 μg/kg/day, irrespective of symptoms. RH poses a clinical challenge due to diagnostic complexity, lack of clear guidelines, and risk of overtreatment. We report a case of RH successfully managed with intravenous (iv) LT4 and transitioned to soft-gel capsule LT4, resulting in sustained euthyroidism.Clinical CaseA 48-year-old woman with multinodular goiter underwent subtotal thyroidectomy for hyperthyroidism. Histopathology revealed a 1-cm encapsulated follicular variant papillary thyroid carcinoma. LT4 was started at 25 µg/day. Over the next 2 years, despite dose escalation up to 400 µg/day, she remained symptomatic with TSH levels between 30–96 mIU/L and fT4 ranging 2.5-6 pmol/L. Oral liothyronine and various LT4 formulations failed to improve thyroid function. Endoscopy revealed eosinophilic pangastritis; anti-endomysial antibodies were positive, but a gluten-free diet did not restore euthyroidism.At our center, she presented on LT4 800 µg/day with persistent hypothyroidism (TSH 82 mIU/L, fT4 <0.25 pmol/L fT3 3.1 pmol/L). Adherence was confirmed. Adrenal insufficiency was ruled out via ACTH stimulation. An LT4 absorption test confirmed true malabsorption. Intravenous LT4 was initiated and titrated up to 200 µg/day, resulting in gradual normalization of thyroid function. Further work-up demonstrated Helicobacter pylori–associated glandular atrophy, and eradication therapy was initiated. After two weeks of intravenous LT4, euthyroidism was achieved. Following the completion of Helicobacter pylori eradication therapy, oral LT4 as soft-gel capsules was initiated at a dose of 100 µg/day and titrated up to 300 µg/day. The patient remained clinically and biochemically euthyroid during follow-up. Diagnosis, management, and laboratory results of the patient are shown in Figure 1.ConclusionRH requires systematic evaluation to distinguish between noncompliance, drug interactions, and malabsorption. Gastrointestinal causes such as celiac disease, Helicobacter pylori infection, and atrophic gastritis are key pathological contributors. An LT4 absorption test is critical in confirming malabsorption when suspected. Intravenous LT4 is an effective bridge to restore thyroid levels while treating the underlying cause. Soft-gel LT4 may offer improved absorption post-intervention. Early diagnosis and individualized management are essential to avoid complications of under- or overtreatment.Figure 1:Diagnosis, management, and laboratory results of patient

IntroductionPituitary metastasis from a solid tumour is an extremely rare condition and is generally associated with a poor prognosis. Spontaneous regression is not typically expected, which further worsens the outlook. Here, we present a case of a patient with small-cell lung cancer (SCLC) who developed a pituitary mass. The marked regression of the lesion following chemotherapy strongly supported the likelihood of pituitary metastasis in this case.Clinical CaseA 59-year-old female patient, diagnosed with SCLC one month ago, was receiving radiotherapy and she also had a chemotherapy plan. When visual impairment and ptosis developed, cranial MRI was performed. She was referred to our outpatient clinic due to pituitary lesion. On physical examination blood pressure was 130/70 mmHg and a heart rate was 92/min. She was mildly dyspneic, had no signs of endocrine hyperfunction, nor polyuria or polydipsia. Obesity was also noted. Her medical history included hypertension and ischemic heart disease. In laboratory examination;ParameterResultReference RangeNa⁺140 mmol/L135–145 mmol/LK⁺4.9 mmol/L3.5–5.0 mmol/LBasal Cortisol30.3 μg/dL6.2–19.4 μg/dLACTH164 ng/L7.2–63.3 ng/LIGF-1471 μg/L62–186 μg/LTSH1.52 mIU/L0.27–4.8 mIU/LfT41.26 ng/dL0.79–1.59 ng/dLFSH9.6 IU/L3.5–12.6 IU/LLH4.08 IU/L2.4–12.6 IU/LProlactin20.3 μg/L2.8–29.2 μg/L1 mg Dexamethasone Suppression Test (DST)15.7 μg/dL—4 mg Dexamethasone Suppression Test (DST)18 μg/dL—Liver and Renal FunctionsNormal—Pituitary MRI revealed a 17×15×12 mm suprasellar mass lesion compressing the optic chiasm (Figure 1A-B). PET-CT demonstrated intense FDG uptake in the pituitary region, as well as involvement in the right lung’s lower, middle, and upper lobes, the left adrenal gland, and multiple lesions in the skeletal system. The patient was evaluated by a multidisciplinary pituitary board, and no clinical signs of acromegaly or Cushing’s syndrome were identified. Due to the high surgical risk given her condition, chemotherapy was promptly planned. Cisplatin and etoposide chemotherapy protocol was started, and the patient's visual impairment subsided following treatment. At the 3-month follow-up her visual complaints and ptosis completely resolved, basal cortisol decreased to 20 μg/dL, ACTH to 60 ng/L, and IGF-1 normalized. Control pituitary MRI releaved significant regression of the lesion (Figure 1C-D). In the first year of chemotherapy, during the pulmonology and oncology follow-up, she was hospitalized because of confusion following radiotherapy for brain metastases. It was later reported that the patient had passed away.ConclusionThe approach to pituitary metastases is generally palliative. On the other hand, if the primary tumor is expected to respond well to chemotherapy and surgery is considered high-risk, close monitoring may be considered to allow chemotherapy to be effective.Figure 1:A-B: Sagittal and coronal pituitary MRI images of the patient before chemotherapy. C-D: Sagittal and coronal pituitary MRI images of the patient 3 months after chemotherapy. Table 1:The patienteGFR: Estimated glomerular filtration rate, ACTH: Adrenocorticotropic hormone, IGF-1: Insulin-like growth factor 1, TSH: Thyroid stimulating hormone, fT4: Free thyroxine, FSH: Follicle-stimulating hormone, LH: Luteinizing hormone, E2: Estradiol, DST: Dexamethasone suppression test

IntroductionPrimary hypothyroidism is a frequently diagnosed endocrine disorder. Common signs and symptoms include asthenia, lethargy, cold sensitivity, rough voice, dry skin, constipation; however, some patients may present atypical signs and symptoms, which can result in diagnostic confusion. Primary hypothyroidism causes elevated thyrotropin-releasing hormone due to a loss of thyroxin feedback inhibition. Increased thyrotropin-releasing hormone levels can result in lactotroph hyperplasia and increasing prolactin. The degree of hyperprolactinemia is generally modest, and rarely exceeds 100 ng/mL.Clinical CaseWe report 18 years old female non pregnant patient presented with secondary amenorrhea 8 months ago, breast heaviness, with a presumptive diagnosis of a prolactinoma by her gynecologist based on amenorrhea and hyperprolactinemia. Referred to endocrinology consultation for hyperprolactinemia On clinical examination, her blood pressure was 110/70 mmHg with a pulse rate of 75beats/min. The thyroid gland was enlarged. Her serum prolactin that was 112 ng/mL, thyroid-stimulating hormone (TSH) was 145 mIU/L (0.3-6), FT4 was 0.2ng/dL(0.8-1.7). She was prescribed levothyroxine 100 mcg daily and 6 weeks later the patient presented with improved her general state and decreased breast heaviness. Her repeat blood testing showed normal thyroid stimulating hormone TSH level of 1.6 mIU/ml and normal serum prolactin level of 26ng/ml.Hypothyroidism is an important etiology of hyperprolactinemia. In overt hypothyroidism, the prevalence of hyperprolactinemia has been reported up to 40% Our case is primary hypothyroidism associated with hyperprolactinemia this cannot be only explained by the stimulatory effect of TRH on lactotrophs but also in primary hypothyroidism, pituitary cells also have reduced sensitivity to dopamine’s inhibitory effect. On the other hand, tri-iodothyronine (T3) was shown to decrease PRL mRNA levels in pituitary cells. Therefore, reduced thyroid hormone levels will increase prolactin synthesis. Prolactin clearance from circulation is also reduced in hypothyroidism. Hyperprolactinemia management depends on its etiology. In patients with prolactin-secreting pituitary adenoma, dopamine receptor agonists are used. However, in patients with hypothyroidism, thyroid hormone replacement can lead to the resolution of hyperprolactinemia without the need for additional interventions. Thyroid hormone replacement reversed the condition in our case and no need for treatment with dopaminergic agonists.ConclusionPrimary hypothyroidism is known to cause hyperprolactinemia. Clinicians must understand the effect of primary hypothyroidism on prolactin to avoid unnecessary treatment with dopaminergic agonists. Thyroid hormone replacement can reverse the condition.

IntroductionThyrotoxicosis is known to cause a high-output cardiac state and atrial fibrillation, but progression to biventricular dysfunction and secondary pulmonary hypertension is rare. Early diagnosis and definitive treatment of root cause are critical to prevent systemic complications, Herein we report an unusual case where prompt treatment reversed the cardiopulmonary effects of thyrotoxicosis.Clinical CaseA 42-year-old male presented with symptoms of thyrotoxicosis. His thyroid function tests demonstrated hyperthyroidism and anti-thyroglobulin antibodies were also significantly elevated.The patient developed atrial fibrillation and was later found to have biventricular dysfunction on echocardiogram.Patient was initially managed with antithyroid medication but was poorly compliant and later became refractory to treatment, and declined radioactive iodine therapy.Over time, he developed signs suggestive of pulmonary hypertension.Due to progression of his symptoms and treatment resistance, patient eventually underwent total thyroidectomy. Postoperatively, thyrotoxicosis resolved.Echo findings showed significant Improvements in Pulmonary HTN and Pulmonary Artery Systolic Pressure (PASP) Improvement from 37 mmHg + RAP (high probability of PH) to 22 mmHg (low probability of PH).ConclusionThis case illustrates an unusual but reversible complication of thyrotoxicosis, where delayed and refractory treatment led to cardiac decompensation and secondary pulmonary hypertension.Definitive management through thyroidectomy led to marked clinical improvement.Clinicians should be aware of this potential complication and consider early definitive therapy in non-compliant or treatment-refractory cases.Diagnosis is based on a detailed history, clinical examination, supplemented by relevant investigations (elevated free T4 and thyroid receptor antibodies, suppressed thyroid stimulating hormone (TSH) and imaging). Mainstay of treatment includes anti-thyroidal medications and if goal not achieved thyroidectomy and regular follow up electrocardiograms.

We aimed to comprehensively investigate the occurrence of thyroid nodules in a nationally representative population as well as in women of reproductive age from a geographic area with adequate iodine intake over the last two decades. This prospective cross-sectional study included 653 adult participants from three groups: a nationally representative gender-mixed group (205 participants) and women of reproductive age, including non-pregnant (306 participants) and pregnant (142 participants) women. For each participant, demographic data were collected, thyroid-stimulating hormone (TSH) levels were measured, thyroid volume was estimated, and the presence and size of thyroid nodules were recorded with high-resolution ultrasound. The ultrasound characteristics were analysed. Among the nationally representative participants, nodules were detected in 44.9%, with 39.0% larger than 5 mm and 13.7% larger than 0.5 mL. Among women of reproductive age, nodules were detected in 22.5%, with 14.1% larger than 5 mm and only 2.0% greater than 0.5 mL. The prevalence and size of nodules increased significantly with age in all groups, being significantly lower in non-pregnant women than in pregnant women, who were also older. In non-pregnant women of reproductive age, the number of nodules increased significantly after the age of 25, with the number of nodules larger than 5 mm increasing only after the age of 40. Thyroid nodules are prevalent in the population, but are rarely clinically significant. Therefore, screening for thyroid nodules in asymptomatic individuals with normal thyroid findings on clinical examination should be avoided.

Background: Pretibial dermopathy (PTD) is a rare, disfiguring manifestation of Graves’ disease. The shared pathophysiology with thyroid eye disease (TED), centered on fibroblast activation via a thyroid-stimulating hormone receptor and insulin-like growth factor-1 receptor (IGF-1R) complex, provides a strong rationale for using the IGF-1R inhibitor, teprotumumab. Methods: We present a case series of five patients with severe PTD and concomitant TED who were treated with teprotumumab. A review of reported cases in the literature was also conducted. Results: All patients experienced significant clinical improvement, including regression of skin thickening as well as enhanced functional capacity. Side effects included mild hearing loss, muscle cramps, and fatigue. One patient experienced a severe gastrointestinal event requiring treatment discontinuation, while those experiencing a recurrence of PTD, responded to a second course of therapy. Conclusions: Teprotumumab showed promising efficacy in the treatment of PTD. Further studies are needed to confirm its durability and safety.

Objective This study aimed to investigate the impact of a 10-week moderate intermittent walking training (MIWT) program on thyroid hormone levels and key cardiometabolic markers in obese postmenopausal women. Methods Thirty-six obese postmenopausal women (body mass index ≥ 30 kg.m−2, aged 50–60 years) were randomized to either the MIWT group (n = 18) or the control group (CG; n = 18). Participants performed the MIWT program for four sessions per week (five repetitions of the 6-min walking test [6MWT] at 60–80% of the distance covered in the 6-min walking test [6MWD], interspersed by 6 min of active recovery between repetitions). Body composition, thyroid hormones (thyroid stimulating hormone [TSH] and thyroxine-free [FT4]), lipid profile (triglycerides [TRG], total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C] and low-density lipoprotein cholesterol [LDL-C]), blood pressure and aerobic fitness (6MWT) were determined before and after the MIWT. Results The MIWT resulted in significant reductions in body composition (p < 0.05), TSH (−5.29%, p = 0.019, d = 0.16), FT4 (−1.84%, p = 0.032, d = 0.28), TRG (−7.29%, p = 0.003, d = 0.27), TC (−4.98%, p = 0.003, d = 0.31), LDL-C (−10.08%, p = 0.003, d = 0.51) and SBP (−2.57%, p = 0.035, d = 0.66), and significant increases in HDL-C (13.36%, p = 0.020, d = 0.52) and 6MWD (2.81%, p = 0.031, d = 0.51). Conclusions A 10-week MIWT program modestly improved thyroid hormones, cardiometabolic risk and functional capacity in obese postmenopausal women without adverse effects. MIWT is an accessible and low-impact intervention suitable for integration into routine clinical practice to prevent and manage thyroid-related and cardiometabolic disorders in this high-risk population.

Objective This study aimed to evaluate female sexual dysfunction (FSD) in postmenopausal women with and without type 2 diabetes (T2D) and its relationship with clinical, laboratory and socioeconomic parameters and quality of life (QoL). Method This cross-sectional study enrolled postmenopausal women with and without T2D not taking hormone replacement. Clinical and laboratory factors were assessed, and participants answered cardiovascular risk, socioeconomic, Short Form Health Survey 36 (SF-36) and Female Sexual Function Index (FSFI) questionnaires. Results Postmenopausal women without diabetes (n = 105) and with a previous T2D diagnosis (n = 110) were similar in age, marital status, race/ethnicity, employment status, alcohol use and body mass index. Women with T2D showed higher glycemia, glycated hemoglobin, cholesterol, thyroid-stimulating hormone and cardiovascular risk factors. SF-36 scores were significantly lower in women with T2D and sexual dysfunction compared to those without diabetes. FSFI scores below 26.55 were associated with higher odds of FSD with increasing age, whereas vitality showed an inverse association. Conclusion In postmenopausal women with T2D, reduced FSFI scores along with hypertension, hypothyroidism and elevated cardiometabolic risk were linked to poorer QoL. Age increased the odds of FSD, while vitality decreased them. These results underscore the multifactorial interaction of T2D, comorbidities and menopause in women’s sexual health and well-being.

To investigate serum xenopsin-related peptide (XRP) -1 levels in women with hyperemesis gravidarum (HEG) from the onset of pregnancy until the end of week 14. This cross-sectional study was conducted at the Antalya Training and Research Hospital Obstetrics Clinic, Türkiye, between July and December 2024. Forty-five pregnant diagnosed with HEG and 45 healthy pregnant were included. Venous blood samples for the XRP-1 test were collected from pregnant women and the collected serum samples were stored at -80 degrees until the day of analysis. Significant differences were observed between the HEG and healthy groups in terms of serum thyroid-stimulating hormone (1.86 ± 0.54 vs. 1.38 ± 0.67, respectively, p = 0.027), potassium (3.84 ± 0.45 vs. 3.58 ± 0.60, p = 0.010), and XRP-1 (4.33 ± 1.66 vs. 2.38 ± 1.32, p < 0.001) values. At receiver operating characteristic analysis, the area under the curve (AUC: 0.824) was statistically significant for serum XRP-1 (p < 0.001), with a cut-off value of ≥ 2.42 [95% confidence interval 0.731-0.917, 82.2% sensitivity, and 80.0% specificity]. The positive predictive value of serum XRP-1 was 80.0% and the negative predictive value was 81.0%. This study suggests that serum XRP-1 levels are elevated in HEG. Further studies are now needed to validate these findings.

To investigate the independent predictors of progression-free survival (PFS) after gemcitabine, cisplatin, and durvalumab (GCD) therapy for advanced biliary tract cancer (BTC), including the thyroid-stimulating hormone (TSH) ratio pre- and post-GCD. The subjects of this retrospective analysis were 29 patients receiving GCD for advanced BTC. The cutoff TSH ratios were determined by a receiver operating characteristic (ROC) curve for PFS. The independent predictors of PFS after GCD were determined by univariate and multivariate analyses. The median PFS was 4.9 (range, 0.9-16.8) months. The objective response and disease control rates were 13.0% and 52.2%, respectively. The cutoff values of the TSH ratio after one and two cycles were 0.97 [area under the ROC curve (AUROC): 0.86, 95% confidence interval (CI): 0.70-1.00], p = 0.02] and 1.2 (AUROC: 0.820, 95% CI: 0.664-0.976), respectively. Multivariate analysis identified pretreatment neutrophil-to-lymphocyte ratio (NLR) ≥ 5 [hazard ratio (HR): 6.27, 95% CI: 1.83-21.5, p = 0.004] and TSH ratio after two cycles of < 1.2 (HR: 3.25, 95% CI: 1.25-8.46, p = 0.02) as independent predictors of PFS. The TSH ratio after two GCD cycles of < 1.2 and a pretreatment NLR ≥ 5 are potential prognostic factors for poor PFS.

Thyroid-associated ophthalmopathy (TAO), a vision-threatening and disfiguring autoimmune orbital disorder, remains a therapeutic challenge due to the lack of therapies with orbital specificity, sustained efficacy, and minimal side effects. Herein, we present G4F7-CRISPR, a fluoropolymer-based CRISPR-Cas9 delivery platform engineered for localized and efficient disruption of thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor 1 receptor (IGF1R), two key mediators of TAO pathogenesis. G4F7-CRISPR achieved high insertion/deletion frequencies in primary orbital fibroblasts (Tshr: 37.2%; Igf1r: 42.8%) and mature adipocytes (Tshr: 22.4%; Igf1r: 24.3%), and maintained robust editing efficiency in orbital adipose tissue of TAO mouse models (Tshr: 30.7%; Igf1r: 32.4%). In both TAO mouse models and 3D human orbital organoids, dual-gene editing of Tshr and Igf1r via G4F7-CRISPR significantly suppressed orbital adipogenesis, inflammation, and fibrosis, demonstrating superior therapeutic efficacy over either single-gene approaches. Comprehensive off-target analyses in both TAO mouse models and orbital organoids revealed minimal off-target activity. Furthermore, G4F7-CRISPR exhibited excellent short- and long-term ocular and systemic safety in TAO mouse models. Notably, it outperformed teprotumumab-the FDA-approved therapy for TAO-in both therapeutic efficacy and safety, highlighting its potential clinical advantages. Collectively, these findings highlight the translational promise of G4F7-CRISPR as a safe, precise, and clinically viable gene therapy for TAO.

This study aimed to identify the clinical, biochemical, and pathological factors that predict the necessity of thyroid hormone replacement therapy following thyroid lobectomy (LT) and to assess their influence on postoperative hormone replacement requirements. This retrospective cohort study included 367 patients who underwent thyroid LT, with or without isthmectomy between 2012 and 2024. The collected data included demographic information, preoperative and postoperative thyroid function test results, thyroid ultrasound and pathological findings. Patients were followed-up postoperatively for an average duration of 45 months. Among the 367 patients, 22.6% (n = 83) required postoperative thyroid hormone replacement. Multivariate analysis identified several predictors for this requirement: a thyroid-stimulating hormone (TSH) level exceeding 2.53 µIU/mL at 6 to 8 weeks post-surgery (odds ratio [OR]: 1.125; P = .03), the presence of lymphocytic infiltration on pathological examination (OR: 2.624; P = .003), residual thyroid lobe volume of ≤5.234 cubic centimeters (cc) (OR: 1.17; P = .001), thyroiditis detected via preoperative ultrasound (OR: 3.771; P = .001). Receiver operating characteristic analysis demonstrated that a postoperative TSH level > 2.53 µIU/mL exhibited a sensitivity of 78.95% and a specificity of 71.76% (area under the curve = 0.786, P < .001), whereas a remaining lobe volume of ≤5.234 cc showed a sensitivity of 61.45% and a specificity of 74.30% (area under the curve = 0.686, P < .001). Our study suggests that TSH levels exceeding 2.53 µIU/mL, thyroid lobe volume ≤5.234 cc, lymphocytic infiltration, thyroiditis detected on preoperative ultrasound were identified as risk factors for the need for thyroid hormone replacement following thyroid LT. Individualized preoperative assessment coupled with long-term follow-up may be useful in determining the necessity of hormone replacement therapy after LT.

Fibrin interference can cause spurious immunoassay results, particularly in patients with coagulopathy or those receiving anticoagulant therapy. We report the case of an asymptomatic 79-year-old woman treated with apixaban, who presented spuriously elevated free thyroxine and free triiodothyronine levels, mimicking a syndrome of inappropriate secretion of thyroid-stimulating hormone. Plasma measurements revealed values within the reference range, which confirmed fibrin interference. To our knowledge, this is the first case to demonstrate fibrin interference in thyroid function testing during direct oral anticoagulant therapy. The relevant literature suggests a greater susceptibility to specific free thyroxine assay platforms. Clinicians should recognize this phenomenon to avoid unnecessary investigation of apparent thyroid dysfunction.

The commutability of thyroid-stimulating hormone international reference preparations plays an important role in metrological traceability.

Safety and regulatory assessment of heat-killed Lactiplantibacillus plantarum strain L-137 (HK L-137) as a food ingredient.

Aim: We aimed to compare the number and endocrine reasons of consultations between non-surgical departments (NSDs) and surgical departments (SDs). Material and Methods: Adult inpatient endocrine consultations during working hours for 7 consecutive months in our center were retrospectively reviewed. Patients who were discharged before consultation, consulted by the coronavirus disease 2019 (COVID-19) service, or referred for consultation for thyroid ultrasound, biopsy, and prescription were excluded. The patients' age and gender, the consultation department (NSDs and SDs), the endocrine issue for consultation, and preoperative or other consultations were recorded. If the consultation recommends a new medication, discontinuation of a medication, or a change in medication dosage, or provides advice on the preoperative management of endocrine diseases, such as suggesting a glucose-insulin infusion protocol, the consultation was considered improvement management (IM). If the consulted physician did not make a new diagnosis or prescribe a new therapy other than to support the present plan, it was accepted as no improvement management (NIM). Results: A total of 361 consultations were received, but data from 46 were excluded. The remaining 315 consultations and 214 patients were analysed. The rates of consultations that NIM were significantly higher in NSDs in all endocrine issues except bone and calcium metabolism. The department with the highest consultations was dermatology. The most consulted endocrine issue was diabetes in both NSDs and SDs, the second one was thyroid in NSDs and pituitary in SDs. The mean glycated hemoglobin (HbA1c) of consultations that NIM and the mean thyroid stimulating hormone (TSH) level of patients with repeated consultations were significantly low and high, respectively. Conclusion: Since the incidence of endocrine diseases is expected to increase in the future, training to be conducted according to the related endocrine issue, especially for consultations from the NSDs, could reduce NIM consultation rates.