Introduction: Accounting for less than 2% of all pituitary adenomas, TSHsecreting pituitary adenomas (TSHoma) are an uncommon cause of hyperthyroidism. Majority are macroadenomas with delayed diagnosis as most patients are unwittingly treated for primary hyperthyroidism. Recurring discordant thyroid function test (TFT) with elevated thyroidstimulating hormone (TSH) and Free T4 is a hint and warrants additional investigation to facilitate diagnosis. Case: We report a case of a 48-year-old female who was treated for primary hyperthyroidism since her late 20s with multiple admissions for recurrent congestive heart failure and atrial fibrillation. The cardiac issue was preceded by worsening thyrotoxicosis. Previous thyroid autoantibodies were negative. Of note, she had recurring discordant TFT results from two different assays (TSH:84.7, free thyroxine 4 [FT4]:75.43) (TSH:37.86, FT4:27.34) during admission, excluding assay interference and prompting toward TSHoma or Resistance to Thyroid Hormone (RTH). Examination revealed a large goiter (10 × 8 cm) hard in consistency, and pansystolic murmur over tricuspid area. No thyroid eye disease nor bitemporal hemianopia or clinical sign of acromegaly. Echocardiography showed dilated left atrium and mild to moderate tricuspid regurgitation with preserved ejection fraction. Thyroid-releasing hormone (TRH) stimulation test demonstrated blunted TSH response confirming TSHoma. Anterior pituitary hormone profile revealed normal insulin-like growth factor-1 level with suppressed sex hormones and prolactin, thus excluding co-secreting hormone. Sex hormone-binding globulin level, α-subunit, and T3 suppression test were not done due to unavailability. Magnetic resonance imaging pituitary uncovered pituitary mass measuring (2.6 × 3.3 × 2.2 cm) suggestive of macroadenoma with encasement of cavernous internal carotid arteries and cavernous sinus compression. Computed tomography neck revealed diffuse thyroid enlargement with compressive mass effects onto adjacent structure with trachea narrowing. After discussing with a multidisciplinary team, we planned her for total thyroidectomy followed by transsphenoidal surgery. Conclusion Late presentation and diagnosis in TSHoma remain a major challenge. TFT interpretation is fundamental in identifying the causes of secondary hyperthyroidism to avert detrimental sequalae and to guide optimal treatment.
Atrial Fibrillation ; Thyrotropin

Introduction: Macro-thyroid-stimulating hormone (macro-TSH) is a rare complex formed by monomeric TSH with anti-TSH autoantibodies. Macromolecules of TSH are not renally excreted due to its large size, leading to elevated TSH measurements without clinical consequences. This rare condition frequently mimics subclinical hypothyroidism, often leading to misdiagnosis and inappropriate levothyroxine therapy. Case: A 17-year-old female with major depressive disorder was biochemically diagnosed with subclinical hypothyroidism (TSH 39.06 mIU/L, free thyroxine 4 12.9 pmol/L, antithyroid peroxidase negative) and commenced on levothyroxine. Over 5 years, her TSH levels heavily fluctuated (0.48–82.59 mIU/L) and remained persistently elevated with high-normal free T4 levels despite treatment adherence. An endocrinology consult was obtained, and clinical evaluation revealed a clinically asymptomatic and euthyroid patient, with no family history of thyroid disease or supplement use, and there was no goiter. Assay interference was excluded by analyzing her thyroid function tests on a different platform, which yielded similar biochemical results. Subsequently, a polyethylene glycol (PEG) precipitation test was performed. Her pre-PEG TSH of 29.24 mIU/L decreased significantly to 2.78 mIU/L post-PEG. This yielded a remarkably low TSH recovery rate of 9.5%, strongly indicating the presence of macroTSH. Levothyroxine was then stopped, and she remained clinically euthyroid. Conclusion While gel filtration chromatography remains the gold standard for diagnosing this condition, PEG precipitation is a more accessible, cost-effective, and reliable screening method in clinical practice. A TSH recovery rate below 20% is considered highly suggestive of macro-TSH. Clinicians should maintain a high index of suspicion for macro-TSH in asymptomatic patients presenting with isolated TSH elevations that do not respond to thyroxine therapy. Prompt recognition prevents misdiagnosis and avoids the potential risks of unnecessary thyroid hormone replacement.
Hypothyroidism ; Thyrotropin

Introduction: Isolated hypothyroxinemia (IH) in pregnancy, characterized by low free thyroxine 4 (FT4) with normal thyroidstimulating hormone (TSH), has a reported prevalence of 1.3–8%. We present a diagnostically challenging case that initially mimicked central hypothyroidism before evolving into classic IH. Case: A 37-year-old G4P3 female at 22 + 3 weeks gestation with β-thalassemia trait presented with palpitations and tachycardia (150–184 bpm). A bedside echocardiogram showed volume depletion. Her heart rate improved to 108– 116 bpm following a 1.5 L normal saline bolus. Incidentally, thyroid function tests (TFTs) revealed both low FT4 6.04 pmol/L (7.86–14.41) and low TSH 0.009 mIU/L (0.38–5.33). Anti-thyroid peroxidase antibody was markedly elevated at 360 IU/mL (<35). At 24 + 4 weeks, TFTs showed persistently low FT4 (5.84 pmol/L) and TSH (0.022 mIU/L). Differential diagnoses included central hypothyroidism or assay interference. Tests were repeated using different platforms. Both the Beckman system (FT4: 5.73 pmol/L, TSH: 0.086 mIU/L) and Roche system (FT4: 8.83 pmol/L [12.0–22.0], TSH: 0.11 mIU/L [0.27–4.20]) confirmed low values, ruling out assay interference. Following endocrinology consultation and given her asymptomatic status, IH was considered most likely, and a plan for close monitoring was initiated. Serial follow-up demonstrated biochemical evolution. By 31 + 6 weeks, TFTs showed a low TSH (0.753 mIU/L) with an FT4 level (5.86 pmol/L) within the normal reference range, a pattern typical of IH in pregnancy. Repeat TFTs 6 weeks postpartum showed both TSH and FT4 within normal range. Conclusion This case illustrates a rare and unexpected biochemical progression of IH in pregnancy, initially presenting with a pattern indistinguishable from central hypothyroidism. It underscores that in an asymptomatic, fertile patient, IH can manifest with an atypical pattern early in gestation. The findings suggest that vigilant serial monitoring, rather than immediate extensive pituitary workup, may be a prudent initial approach in such scenarios, as the biochemical profile can normalize toward the classic IH pattern as pregnancy advances.
Female ; Pregnancy ; Thyrotropin

Introduction: Thyroid stimulating hormone (TSH) suppression following differentiated thyroid carcinoma is widely recommended to reduce recurrence risk. However, this strategy assumes cardiovascular tolerance to supraphysiologic thyroid hormone exposure. In patients with advanced structural heart disease, this assumption may fail, exposing a critical limitation of guideline-directed TSH suppression. Case: We report a 71-year-old male with end-stage renal failure on hemodialysis and severe ischemic cardiomyopathy (ejection fraction 23%) who presented with acute decompensation characterized by dyspnea, rapid atrial fibrillation, and non–ST-elevation myocardial infarction. He had a history of papillary thyroid carcinoma treated with total thyroidectomy and radioactive iodine over 20 years prior and was maintained on levothyroxine 200 mcg daily for TSH suppression. Despite biochemically euthyroid indices (TSH 1.8 mIU/L, free thyroxine 4 17 pmol/L), he developed recurrent arrhythmia with heart failure decompensation. This case highlights a dissociation between biochemical euthyroidism and tissue-level thyrotoxicity in a structurally compromised myocardium. Papillary thyroid carcinoma after definitive therapy typically follows an indolent course with low short-term mortality. In contrast, in severe left ventricular dysfunction, excess thyroid hormone increases adrenergic sensitivity and myocardial oxygen demand, precipitating arrhythmia and ischemia. This risk is amplified in end-stage renal disease, where altered hormone handling renders biochemical indices less reliable. Conclusion Biochemical euthyroidism does not equate to physiological safety. In patients with advanced cardiovascular disease, thyroid hormone therapy should be titrated to cardiovascular tolerance rather than oncologic targets alone, and routine TSH suppression may be inappropriate.
Thyroxine ; Heart Failure ; Thyrotropin

Introduction: Discordant thyroid function tests (TFTs), characterized by elevated free thyroxine 4 (FT4) with non-suppressed thyroid-stimulating hormone (TSH), pose a significant diagnostic challenge. Differentiating between Resistance to Thyroid Hormone (RTH) and TSH-secreting pituitary adenoma (TSH-oma) is essential, as management strategies differ substantially. Case: A female with a history of hyperthyroidism diagnosed in 2011 was treated with antithyroid drugs for 1 year before defaulting on follow-up. She was later found to have discordant TFTs at a private centre, where a brain computed tomography scan was reportedly normal. She was referred to our centre for optimization of thyroid function prior to planned thyroidectomy for a solitary large right thyroid nodule measuring 4.2 × 2.8 × 4.7 cm. Fine-needle aspiration cytology demonstrated a benign follicular lesion (Bethesda II). Despite restarting antithyroid medication, she remained clinically euthyroid with no overt thyrotoxic symptoms apart from intermittent palpitations without documented tachycardia. Antithyroid therapy was discontinued. Serial TFTs across multiple assay platforms consistently demonstrated elevated FT4 with inappropriately normal TSH levels. Thyroid autoantibodies, including TSH receptor and anti-thyroid peroxidase antibodies, were negative. Pituitary magnetic resonance imaging showed no evidence of adenoma, and serum α-subunit level was normal (0.3 ng/ mL), making TSH-oma unlikely. Dynamic testing was not performed as thyrotropin-releasing hormone stimulation was unavailable at our centre, while T3 suppression testing was deemed inappropriate due to symptomatic palpitations. Family screening was not possible as the patient was not in contact with her relatives. In the absence of pituitary pathology and given her largely euthyroid clinical status, RTH was considered the most likely diagnosis. Conclusion This case highlights the importance of considering RTH in patients with persistent discordant TFTs, particularly when clinical findings do not correlate with biochemical abnormalities. Early recognition and appropriate pituitary evaluation are essential to prevent misdiagnosis and avoid unnecessary antithyroid therapy or thyroidectomy.
Pituitary Neoplasms ; Thyroid Hormones ; Thyrotropin

OBJECTIVE: By analyzing the hormone secretion of the adenohypophysis, thyroid glands, gonads, and adrenal cortex in patients with hematological diseases before and after hematopoietic stem cell transplantation (HSCT), this study aims to preliminarily explore the effect of HSCT on patients' hormone secretion and glandular damage. METHODS: The baseline data of 209 hematological disease patients who underwent HSCT in our hospital from January 2019 to December 2023, as well as the data on the levels of hormones secreted by the adenohypophysis, thyroid glands, gonads and adrenal cortex before and after HSCT were collected, and the changes in hormone levels before and after transplantation were analyzed. RESULTS: After allogeneic HSCT, the levels of thyroid-stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (FT3) and estradiol (E2) decreased, while the levels of luteinizing hormone (LH) and follicle- stimulating hormone (FSH) increased. The T3 level of patients with decreased TSH after transplantation was lower than that of those with increased TSH after transplantation. In female patients, the levels of prolactin (PRL), progesterone (Prog), and testosterone (Testo) decreased after HSCT. Testo and PRL decreased when there was a donor-recipient sex mismatch, and the levels of adrenocorticotropic hormone (ACTH) and cortisol (COR) decreased when the HLA matching was haploidentical. The levels of T3, FT3, and PRL decreased after autologous HSCT. In allogeneic HSCT patients, the levels of TSH, T4, T3, FT3, and ACTH in the group with graft-versus-host disease (GVHD) were significantly lower than those in the group without GVHD. Logistic regression analysis showed the changes in hormone levels after transplantation were not correlated with factors such as the patient's sex, age, or whether the blood types of the donor and the recipient are the same. CONCLUSION HSCT can affect the endocrine function of patients with hematological diseases, mainly affecting target glandular organs such as the thyroid, gonads, and adrenal glands, while the secretory function of the adenohypophysis is less affected.
Humans ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Hematologic Diseases/blood* ; Follicle Stimulating Hormone/blood* ; Triiodothyronine/blood* ; Luteinizing Hormone/blood* ; Thyroid Gland/metabolism* ; Estradiol/blood* ; Thyrotropin/blood* ; Gonads/metabolism* ; Adult ; Middle Aged ; Adrenocorticotropic Hormone/blood* ; Hormones/metabolism* ; Adrenal Cortex/metabolism* ; Prolactin

OBJECTIVES: To analyze the results of neonatal screening for congenital hypothyroidism (CH) and hyperphenylalaninemia (HPA) in Zhejiang province from 1999 to 2022. METHODS: A total of 11 922 318 newborns were screened from September 1999 and December 2022 in Zhejiang province. The blood thyroid stimulating hormone (TSH) levels were measured by a fluorescence method and blood phenylalanine (Phe) levels were measured by fluorescence method or tandem mass spectrometry. TSH≥9 μIU/mL was considered positive for CH, while Phe>120 μmol/L and/or Phe/Tyr ratio>2.0 were considered positive for HPA. The positive newborns in screening were recalled, and the gene variations were detected by high-throughput sequencing and MassARRAY tests. RESULTS: The overall neonatal screening rate during 1999-2022 was 89.41% (11 922 318/13 333 929) and the screening rate was increased from 6.46% in 1999 to 100.0% in 2022. A total of 8924 cases of CH were diagnosed among screened newborns with an incidence rate of 1/1336. A total of 563 cases of HPA were diagnosed, including 508 cases of classic phenylketonuria (cPKU) and 55 cases of tetrahydrobiopterin deficiency (BH4D), with an incidence rate of 1/21 176. Ninety-seven out of 8924 cases of CH underwent genetic analysis. Gene mutations were detected in 9 CH related genes, the highest frequency mutations were found in DUOX2 gene (69.0%) with c.3329G>A (p.R1110Q) (18.2%) and c.1588A>T (p.K530X) (17.3%) as the hotspot mutations. There were 81 PAH gene variants detected in a total of 250 cases of cPKU, and c728G>A (p.R243Q) (24.4%), c.721C>T (p.R241C) (15.0%) were the hotspot mutations. Meanwhile 7 novel variants in PAH gene were detected: c.107C>A (p.S36*), c.137G>T (p.G46V), c.148A>G(p.K50E), c.285C>T (p.I95I), c.843-10delTTCC, exon4-7del and c.1066-2A>G. There were 12 PTS gene variants detected in 36 cases of BH4D, and c.259C>T (p.P87S) (31.9%) was the hotspot mutation. CONCLUSIONS The incident of CH has increased from 1999 to 2022 in Zhejiang province, and it is higher than that of national and global levels; while the incidence of HPA is similar to the national average. DUOX2 gene variation is the most common in CH patients; c.728G>A (p.R243Q) is the hotspot mutation in cPKU patients, while c.259C>T (p.P87S) is the hotspot mutation in BH4D patients.
Humans ; Infant, Newborn ; Neonatal Screening ; Dual Oxidases ; Congenital Hypothyroidism/genetics* ; Phenylketonurias/genetics* ; Thyrotropin

OBJECTIVE: To explore the mechanism of Radix Scrophulariae (RS) extracts in the treatment of hyperthyroidism rats by regulating proliferation, apoptosis, and autophagy of thyroid cell through the mammalian sterile 20-like kinase 1 (MST1)/Hippo pathway. METHODS: Twenty-four rats were randomly divided into 4 groups according to a random number table: control, model group, RS, and RS+Hippo inhibitor (XMU-MP-1) groups (n=6 per group). Rats were gavaged with levothyroxine sodium tablet suspension (LST, 8 μ g/kg) for 21 days except for the control group. Afterwards, rats in the RS group were gavaged with RS extracts at the dose of 1,350 mg/kg, and rats in the RS+XMU-MP-1 group were gavaged with 1,350 mg/kg RS extracts and 1 mg/kg XMU-MP-1. After 15 days of administration, thyroid gland was taken for gross observation, and histopathological changes were observed by hematoxylin-eosin staining. The structure of Golgi secretory vesicles in thyroid tissues was observed by transmission electron microscopy. The expression of thyrotropin receptor (TSH-R) was observed by immunohistochemistry. Terminal-deoxynucleoitidyl transferase mediated nick end labeling assay was used to detect cell apoptosis in thyroid tissues. Real-time quantity primer chain reaction and Western blot were used to detect the expressions of MST1, p-large tumor suppressor gene 1 (LATS1), p-Yes1 associated transcriptional regulator (YAP), proliferating cell nuclear antigen (PCNA), G₁/S-specific cyclin-D1 (Cyclin D1), B-cell lymphoma-2 (Bcl-2), Caspase-3, microtubule-associated proeins light chain 3 II/I (LC3-II/I), and recombinant human autophagy related 5 (ATG5). Thyroxine (T4) level was detected by enzyme-linked immunosorbent assay. RESULTS: The thyroid volume of rats in the model group was significantly increased compared to the normal control group (P<0.01), and pathological changes such as uneven size of follicular epithelial cells, disorderly arrangement, and irregular morphology occurred. The secretion of small vesicles by Golgi apparatus was reduced, and the expressions of receptor protein TSH-R and T4 were significantly increased (P<0.01), while the expressions of MST1, p-LATS1, p-YAP, Caspase-3, LC3-II/I, and ATG5 were significantly decreased (P<0.01). The expressions of Bcl-2, PCNA, and cyclin D1 were significantly increased (P<0.01). Compared with the model group, RS extracts reduced the volume of thyroid gland, improved pathological condition of the thyroid gland, promoted secretion of the secretory vesicles with double-layer membrane structure in thyroid Golgi, significantly inhibited the expression of TSH-R and T4 levels (P<0.01), upregulated MST1, p-LATS1, p-YAP, Caspase-3, LC3-II/I, and ATG5 expressions (P<0.01), and downregulated Bcl-2, PCNA, and Cyclin D1 expressions (P<0.01). XMU-MP-1 inhibited the intervention effects of RS extracts (P<0.01). CONCLUSION RS extracts could inhibit proliferation and promote apoptosis and autophagy in thyroid tissues through MST1/Hippo pathway for treating hyperthyroidism.
Rats ; Humans ; Animals ; Hippo Signaling Pathway ; Proliferating Cell Nuclear Antigen/metabolism* ; Cyclin D1/pharmacology* ; Caspase 3/metabolism* ; Protein Serine-Threonine Kinases/pharmacology* ; Apoptosis ; Hyperthyroidism/drug therapy* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Thyrotropin/pharmacology* ; Mammals/metabolism*

BACKGROUND: More than 75 million procedures with intravascular iodine-based contrast media (ICM) are performed worldwide every year, and some patients undergoing these procedures do not have normal thyroid function. The long-term effects of ICM in patients with mild thyroid dysfunction (TD) are unclear. METHODS: This prospective cohort study was conducted in China. Patients with stable angina pectoris with total triiodothyronine (TT3) reduction, normal thyroid-stimulating hormone, and reverse triiodothyronine (rT3) were enrolled and divided into high-dose (≥100 mL ICM) and low-dose groups (<100 mL ICM). We dynamically investigated the trends in thyroid function, rT3, and thyroid antibodies one year after ICM exposure. RESULTS: A total of 154 patients completed 6 months of follow-up and 149 completed 1 year of follow-up. Thyroglobulin antibody (TGAB) levels were elevated in 41 (26.6%) patients before ICM exposure, 11 (7.1%) of whom also had elevated thyroid peroxidase antibody levels. Transient subclinical TD occurred 6 months after ICM exposure; 75.5% (34/45) of post-operative TD occurred in the high-dose group. One patient developed severe hypothyroidism with myxedema, requiring drug intervention 1 year after ICM exposure. The level of rT3 showed no statistically significant changes during post-operative follow-up ( P  = 0.848). The TGAB level decreased at 6th month ( P  < 0.001), but increased at 1 year after ICM exposure ( P  = 0.002). CONCLUSIONS Patients with T3 reduction are at a risk of transient subclinical TD and hypothyroidism after a single large dose of ICM. Follow-up of this population at 9-12 months after ICM exposure is warranted.
Humans ; Contrast Media/adverse effects* ; Prospective Studies ; Hypothyroidism ; Triiodothyronine ; Iodine/adverse effects* ; Thyrotropin ; Thyroxine

OBJECTIVE: This study explored whether thyroglobulin and thyroid disease prevalence rates were higher in pregnant Chinese women with a median urinary iodine concentration of 100-149 µg/L, compared with those with a median urinary iodine concentration of 150-249 μg/L maintained through sustainable universal salt iodization. METHODS: This was a cross-sectional study in which 812 healthy pregnant women were enrolled to collect samples of their household edible salt, urine, and blood during their routine antenatal care in the 18 counties in Fujian Province, China. The levels of salt iodine concentration, urinary iodine concentration (UIC), free triiodothyronine (FT3), free thyroid hormone (FT4), thyroid-stimulating hormone (TSH), thyroglobulin (Tg), thyroid peroxidase antibody and thyroglobulin antibody were assessed during the routine antenatal care visits. RESULTS: The median UIC (mUIC) in pregnant women was 130.8 μg/L (interquartile range = 91.5-198.1 μg/L) in the counties with an mUIC of 100-149 μg/L (Group I), and 172.0 μg/L (interquartile range = 123.5-244.4 μg/L) in the counties with an mUIC of 150-249 μg/L (Group II). Goiter prevalence and thyroid nodule detection rates showed no difference between Group I and Group II ( P > 0.05). Except for FT4 values, the TSH, FT4, FT3, Tg and Tg values > 40 (μg/L) and the thyroid diseases prevalence rate (TDR) showed no significant differences between Group I and Group II ( P > 0.05), whether or not iodine supplementation measures were taken. CONCLUSION Compared with an mUIC of 150-249 μg/L, not only there was no difference in thyroid morphology, but also the Tg value, rate of Tg values > 40 µg/L, and TDR were not higher in pregnant women in the counties with an mUIC of 100-149 μg/L achieved through sustainable universal salt iodization in Fujian Province, China.
Female ; Humans ; Pregnancy ; Cross-Sectional Studies ; Iodine/urine* ; Pregnant Women ; Sodium Chloride, Dietary ; Thyroglobulin ; Thyroid Gland ; Thyrotropin ; East Asian People