BACKGROUND

Thyroid storm (TS) continues to be a diagnostic and therapeutic challenge. It is a life-threatening severe thyrotoxicosis characterized by organ decompensation. This study aims to determine if there are any changes in this present century about TS diagnosis and management. Furthermore, it aims to describe the clinical profile, precipitants, and outcomes of patients with TS seen at the University of Santo Tomas Hospital (USTH) and assess the association of patient characteristics with mortality.

This is a retrospective cohort analysis of patients with TS admitted at USTH from 2009 through 2018. Logistic regression analysis was used to determine the association of age, Burch Wartofsky-Point Scale (BWPS) score, clinical manifestations, and precipitating factor with mortality.

A total of 21 cases were identified. Majority of the patients were female (90.48%) with a mean age of 42.90 years old. The overall mean BWPS was 49.52 (16.35) while those who expired had higher mean score of 61.67 (5.77). TS as the first clinical presentation was seen in only one patient (4.7%) while majority were previously diagnosed with hyperthyroidism, (95.24%). Graves’ disease (90.48%) was the most common etiology of thyrotoxicosis. Cardiac manifestations were predominant and tachycardia was the most common clinical manifestation (80.95%) with thyrotoxic heart disease as a comorbidity (23.81%). The most common precipitant was infection (52.38%) followed by noncompliance with treatment. The mean hospital length of stay was four days with two patients needing intubation, and both expired afterward. There were three mortalities (14.29%) due to multiple organ dysfunction and fatal arrythmia.

TS remains a life-threatening condition. Aggressive treatment is justified once with suspicion of TS. Age, BWPS on admission, clinical manifestation and precipitants did not predict the likelihood of mortality. Since predictive features are still not thoroughly identified due to its infrequency, it remains for us to be vigilant and not delay crucial treatment to improve the morbidity and mortality associated with TS.

INTRODUCTION

Hyperthyroidism was thought to lower thyroid cancer risk due to TSH suppression, potentially leading to overlooked diagnoses. This study examines clinical factors linked to thyroid cancer in hyperthyroid patients who have undergone thyroidectomy.

This study determined the clinical factors associated with malignancy among patients with hyperthyroidism who underwent thyroidectomy in a tertiary hospital.

This analytical cross-sectional study reviewed electronic biopsy results of adult patients who underwent thyroidectomy from January 2009 to December 2019 for hyperthyroidism secondary to Graves’ Disease, Solitary Toxic Adenoma or Multinodular Toxic Goiter. It considered factors linked to thyroid cancer, its prevalence, and clinical features associated with aggressive tumor behavior.

Sixty hyperthyroid patients who underwent thyroidectomy were included, 12 of whom have thyroid cancer. Each increase in the initial free thyroxine (FT4) leads to increased likelihood of thyroid cancer by 1.02 times (95% CI 1.001-1.03, p=0.044). The presence of thyroid nodule is associated with 24 times (95% CI 2.67-3275.62, p=0.002) higher risk of thyroid cancer, while every unit increase in mm for nodule diameter increases thyroid cancer odds by 1.04 times (95% CI 1.01-1.07, p=0.022). An FNAB pre-op diagnosis of malignancy is associated with having histopathologic diagnosis of thyroid cancer increased by 40 times (95% CI 2.42-6668.98, p=0.007). Although aggressive tumor behavior was noted among those with a younger age on average (36.35 vs 46.75 years), higher initial FT4 (95.97 vs 23.55 pmol/L), and those with sizeable diameter of multinodular goiter (95 mm vs 20 mm), only the high FT4 was statistically significant.

Initial FT4, thyroid nodules, nodule size, and pre-operative FNAB finding of a malignancy were the factors associated with thyroid cancer in hyperthyroid patients who underwent thyroidectomy. Furthermore, those with aggressive tumor behavior had higher initial FT4 levels.

We report a case of an uncommonly aggressive presentation of the rare entity of synchronous papillary (PTC) and follicular thyroid carcinomas (FTC) in a 67-year-old woman initially presenting with thyrotoxicosis from Graves’ disease. She was found to have two thyroid nodules with extensive intra-cardiac tumour thrombus, symptomatic left pelvis bony metastasis with pathological fracture, pulmonary metastases and mediastinal lymph node metastases. Further investigations suggested a diagnosis of synchronous papillary and metastatic follicular thyroid cancer. Treatment with radical surgery followed by adjuvant therapeutic radioiodine ablation was proposed, but the patient declined all forms of cancer-specific therapy and was elected solely for a palliative approach to treatment. We discuss the diagnostic considerations in arriving at the diagnosis of synchronous thyroid malignancy – in this case the clear features of PTC and the strong probability of FTC due to invasiveness and metastatic follicular lesions. This case underscores potential limitations of the ACR TI-RADS system, notably with certain ultrasonographic features suggesting malignancy that might not be adequately captured. Notably, the aggressive presentation of DTC in this case may be contributed by the concurrent presence of Graves’ Disease, suggesting heightened vigilance when assessing potential thyroid malignancies in such patients.
Papillary Thyroid Carcinoma ; Thyroid Cancer, Papillary ; Follicular Thyroid Carcinoma ; Adenocarcinoma, Follicular ; Graves Disease

OBJECTIVES

This study aimed to determine the clinical profile of non thyroidal cancer patients with thyroid dysfunction associated with tyrosine kinase inhibitor (TKI) therapy at the University of Santo Tomas Hospital (USTH), Philippines.

This is a retrospective observational study of TKI initiated adult non-thyroidal cancer patients with thyroid function testing from 2013 to 2018.

Forty percent (95% CI: 26.2% - 58.61%) of the sixty individuals who had thyroid function tests (TFT) had incident thyroid dysfunction. Thirty percent had hypothyroidism (i.e., 25% overt [mean TSH 16.64 uIU/mL]; 5% subclinical [mean TSH 6.62 uIU/mL]). The median time at risk was 8 and 16 months for overt and subclinical hypothyroidism, respectively. Fifty-six percent had persistent hypothyroidism (median TSH 16.75, p = 0.009). The average time to recovery of transient hypothyroidism was 39 months. Ten percent had hyperthyroidism with a median time at risk of 1.5 months. Non-small cell lung cancer and renal cell carcinoma were possible associated risk factors of thyroid dysfunction.

TKI-induced thyroid dysfunctions are common. Screening and monitoring for thyroid abnormalities during TKI therapy is important.

Restless legs syndrome （RLS） is a common sensory-motor disorder of the nervous system， and its mechanism remains unknown， which may be related to neuropsychiatric diseases， nutritional and metabolic diseases， kidney diseases， and pregnancy. We report a special case of RLS which was diagnosed prior to hyperthyroidism and experienced worsening of the RLS symptoms. We aim to discuss the mechanism of hyperthyroidism aggravating RLS， helping clinicians have a better understanding of the influencing factors for RLS.
Hyperthyroidism ; Comorbidity

Humans ; Thyrotoxicosis/chemically induced* ; Amiodarone

OBJECTIVE: To report the clinical and genetic characteristics of a rare case of Gitelman syndrome with comorbid Graves disease and ACTH-independent adrenocortical adenoma. METHODS: A patient who had presented at the Nanchong Central Hospital on December 21, 2020 was selected as the study subject. Clinical data of the patient was collected. Whole-exome sequencing was carried out on DNA extracted from peripheral venous blood samples from the patient and her family members. RESULTS: The patient, a 45-year-old woman, was found to have Graves disease, ACTH-independent Cushing syndrome, hypokalemia and hypomagnesemia following the discovery of an adrenal incidentaloma. MRI scan had revealed a 3.8 cm × 3.2 cm mass in the left adrenal gland. The mass was removed by surgery and confirmed as adrenocortical adenoma. DNA sequencing revealed that the patient and her sister have both harbored compound heterozygous variants of the SLC12A3 gene, namely c.1444-10(IVS11)G>A and c.179(exon1)C>T (p.T60M), which were respectively inherited from their father and mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.1444-10(IVS11)G>A and c.179(exon1)C>T (p.T60M) were respectively classified as a variant of uncertain significance (PM2_Supporting+PP3) and a likely pathogenic variant (PM3_Strong+PM1+PP3). CONCLUSION The conjunction of Gitelman syndrome with Graves disease and adrenal cortex adenoma is rather rare. The newly discovered c.1444-10(IVS11)G>A variant of the SLC12A3 gene, together with the heterozygous variant of c.179(exon1)C>T (p.T60M), probably underlay the pathogenesis in this patient.
Humans ; Female ; Middle Aged ; Gitelman Syndrome/genetics* ; Adrenocortical Adenoma ; Hypokalemia ; Graves Disease/genetics* ; Mothers ; Mutation ; Solute Carrier Family 12, Member 3

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*

OBJECTIVES: Graves' ophthalmopathy (GO) is a multifactorial disease, and the mechanism of non coding RNA interactions and inflammatory cell infiltration patterns are not fully understood. This study aims to construct a competing endogenous RNA (ceRNA) network for this disease and clarify the infiltration patterns of inflammatory cells in orbital tissue to further explore the pathogenesis of GO. METHODS: The differentially expressed genes were identified using the GEO2R analysis tool. The Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology analysis were used to analyze differential genes. RNA interaction relationships were extracted from the RNA interactome database. Protein-protein interactions were identified using the STRING database and were visualized using Cytoscape. StarBase, miRcode, and DIANA-LncBase Experimental v.2 were used to construct ceRNA networks together with their interacted non-coding RNA. The CIBERSORT algorithm was used to detect the patterns of infiltrating immune cells in GO using R software. RESULTS: A total of 114 differentially expressed genes for GO and 121 pathways were detected using both the KEGG and gene ontology enrichment analysis. Four hub genes (SRSF6, DDX5, HNRNPC,and HNRNPM) were extracted from protein-protein interaction using cytoHubba in Cytoscape, 104 nodes and 142 edges were extracted, and a ceRNA network was identified (MALAT1-MIR21-DDX5). The results of immune cell analysis showed that in GO, the proportions of CD8⁺ T cells and CD4⁺ memory resting T cells were upregulated and downregulated, respectively. The proportion of CD4 memory resting T cells was positively correlated with the expression of MALAT1, MIR21, and DDX5. CONCLUSIONS This study has constructed a ceRNA regulatory network (MALAT1-MIR21-DDX5) in GO orbital tissue, clarifying the downregulation of the proportion of CD4⁺ stationary memory T cells and their positive regulatory relationship with ceRNA components, further revealing the pathogenesis of GO.
Humans ; CD8-Positive T-Lymphocytes ; RNA, Long Noncoding/genetics* ; Algorithms ; CD4-Positive T-Lymphocytes ; Down-Regulation ; Graves Ophthalmopathy/genetics* ; Gene Regulatory Networks ; MicroRNAs/genetics* ; Serine-Arginine Splicing Factors ; Phosphoproteins

OBJECTIVES: Dysthyroid optic neuropathy (DON) is a class of diseases that makes seriously endanger to the vision of patients with thyroid-associated ophthalmopathy. This study aims to observe the visual function changes in patients with DON, and to evaluate the diagnostic value of indicators diagnosing DON. METHODS: A retrospective study was conducted on 98 eyes of 49 patients with dysthyroid optic neuropathy (DON) who were treated in Xiangya Hospital of Central South University from January 2017 to December 2019. All patients were received the examination of best corrected visual acuity (BCVA), Humphrey visual field, visual evoked potential (VEP), and contrast sensitivity. Ninety-eight eyes were divided into a DON group (45 eyes) and a non-DON group (53 eyes). T-test was used to compare the related indicators between the 2 groups. The sensitivity and specificity of each indicator were analyzed by receiver operating characteristic (ROC) curve. RESULTS: The BCVA and visual field index (VFI) of the DON group were significantly lower than those of the non-DON group (all P<0.05). The mean deviation (MD) and pattern standard deviation (PSD) of the DON group were significantly higher than those of the non-DON group (all P<0.05). The low frequency contrast sensitivity (CSL), medium frequency contrast sensitivity (CSM), and high frequency contrast sensitivity (CSH) of the DON group were significantly lower than those of the non-DON group (all P<0.05), with CSH being particularly prominent. Compared with the non-DON group, at spatial frequencies of 15°, 30°, and 60°, the amplitude of N135 wave was significantly reduced, and the latency of N75 wave, P100 wave, and N135 wave was significantly prolonged in the DON group (all P<0.05); at spatial frequencies of 15° and 30°, the amplitude of P100 wave was significantly reduced in the DON group (P<0.05). The ROC curve analysis results showed that the area under the curve (AUC) of VFI, CSL, CSM, CSH and 15° P100 amplitude diagnosing DON were 0.812, 0.841, 0.880, 0.784, and 0.791, respectively, with CSM possessing the highest sensitivity and specificity. CONCLUSIONS The visual function of patients with DON is decreased. VFI, contrast sensitivity of low, medium, and high frequency, and 15° P100 wave amplitude might be effective indicators for early diagnosis of DON.
Humans ; ROC Curve ; Optic Nerve Diseases/complications* ; Retrospective Studies ; Evoked Potentials, Visual ; Graves Ophthalmopathy