scholarly journals Cytokine/Chemokine/Growth Factor Profiles Contribute to Understanding the Pathogenesis of the Salivary Gland Dysfunction in Euthyroid Hashimoto’s Thyroiditis Patients

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
K. Morawska ◽  
M. Maciejczyk ◽  
S. Zięba ◽  
Ł. Popławski ◽  
A. Kita-Popławska ◽  
...  

Hashimoto’s thyroiditis (HT) is one of the most common autoimmune diseases. It is suggested that, in addition to thyroid gland dysfunction, HT is responsible for impaired secretion from the salivary glands. The aim of this study was to evaluate the extent of symptoms of salivary gland dysfunction. We also assessed the relationship between the levels of selected cytokines, chemokines, and growth factors in unstimulated whole saliva (UWS) and the rate of UWS secretion and symptoms of xerostomia in HT patients. The study group consisted of 25 female patients diagnosed with Hashimoto’s disease in its spontaneous euthyroid state who had never received hormonal treatment. In more than half of the examined patients, we observed the level of UWS secretion below 0.2 mL/min, indicating impaired secretory function of the salivary glands. Moreover, we demonstrated that the clinical symptoms of salivary gland dysfunction worsen with disease duration. Nevertheless, the inflammatory changes occurring in these glands are independent of general inflammation in the course of HT. Our results clearly indicate an abnormal profile of cytokines, chemokines, and growth factors in the UWS of HT euthyroid women as well as the fact that concentrations of IL-6 and IL-1 as well as INF-γ, TNF-α, and IL-12 may be potential biomarkers for salivary gland dysfunction in the course of HT. Furthermore, salivary IL-12 (p40) may be helpful in assessing the progression of autoimmunity-related inflammation in the course of HT. In conclusion, secretory dysfunction of the salivary glands is closely related to autoimmunity-related inflammation in the course of HT, which leads to objective and subjective symptoms of dry mouth.

Author(s):  
Christina Winter ◽  
Roman Keimel ◽  
Markus Gugatschka ◽  
Dagmar Kolb ◽  
Gerd Leitinger ◽  
...  

The intact function of the salivary glands is of utmost importance for oral health. During radiotherapy in patients with head and neck tumors, the salivary glands can be damaged, causing the composition of saliva to change. This leads to xerostomia, which is a primary contributor to oral mucositis. Medications used for protective or palliative treatment often show poor efficacy as radiation-induced changes in the physico-chemical properties of saliva are not well understood. To improve treatment options, this study aimed to carefully examine unstimulated whole saliva of patients receiving radiation therapy and compare it with healthy unstimulated whole saliva. To this end, the pH, osmolality, electrical conductivity, buffer capacity, the whole protein and mucin concentrations, and the viscoelastic and adhesive properties were investigated. Moreover, hyaluronic acid was examined as a potential candidate for a saliva replacement fluid. The results showed that the pH of radiation-induced saliva shifted from neutral to acidic, the osmolality increased and the viscoelastic properties changed due to a disruption of the mucin network and a change in water secretion from the salivary glands. By adopting an aqueous 0.25% hyaluronic acid formulation regarding the lost properties, similar adhesion characteristics as in healthy, unstimulated saliva could be achieved.


2020 ◽  
Author(s):  
Xiao-an Pang ◽  
Zhi-xiao Wei ◽  
Jun-hong Li ◽  
Xiao-qi Pang

Abstract Background Hashimoto’s thyroiditis (HT) may cause salivary dysfunction in patients resulting in xerostomia, but little is known about changes in salivary function in patients with no obvious dry mouth symptoms. In this study we assessed salivary function in women with HT, who had not experienced xerostomia and, for the first time, evaluated the effects of thyroid auto-antibodies on this function. Methods Sixty consecutive subjects were included, comprising 32 women (mean age, 36 ± 12 years) diagnosed with HT accompanied by differentiated thyroid cancer (DTC) in the study group (HT group), along with a control group (DTC group) of 28 women (mean age, 40 ± 12 years) diagnosed with DTC only. Salivary gland scintigraphy was used to assess salivary function with the semi-quantitative parameters of maximum absorption ratio and maximum secretion ratio, the decrease of which indicate impaired salivary function. Moreover, the HT and DTC groups were divided into four subgroups (Anti– HT, Anti+ HT, Anti– DTC, and Anti+ DTC), based on the presence of anti-thyroid peroxidase antibody (TPOAb) and anti-thyroglobulin antibody (TgAb). Finally, salivary gland semi-quantitative parameters were correlated with levels of thyroid-stimulating hormone (TSH), TGAb, and TPOAb in the HT and DTC groups. Results None of the semi-quantitative parameters examined in parotid or submandibular glands differed significantly between the HT and DTC groups. However, the maximum secretion ratio for the parotid and submandibular glands were significantly different in the subgroup comparison (p < 0.05). Furthermore, the TgAb, TPOAb, and TSH values correlated significantly with salivary excretive function (p ≤ 0.05). Conclusion Women with HT without xerostomia may not have salivary functional impairment during hypothyroidism. Serum thyroid autoantibody and TSH levels may mainly influence salivary excretive function but not uptake function.


1987 ◽  
Vol 66 (1_suppl) ◽  
pp. 660-666 ◽  
Author(s):  
W. H. Schwarz

The rheology of saliva affects the coating and lubrication of oral surfaces and the consistency of ingested foods. Salivary gland dysfunction can cause tissue damage and dysphagia. Therefore, we have considered the problem of designing a synthetic saliva for medical management. Also, we have measured certain rheological properties [shear-dependent viscosity η (k)] and the frequency-dependent moduli [G′(f) and η′(f)] of normal stimulated whole saliva. Analysis of the rheological data and consideration of requirements for using artificial saliva have resulted in a better understanding of the rheological functions of natural saliva and the desirable characteristics of synthetic saliva. In addition, we have measured rheological properties of two commercial saliva substitutes for comparison.


Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2139
Author(s):  
Mirco Schapher ◽  
Michael Koch ◽  
Daniela Weidner ◽  
Michael Scholz ◽  
Stefan Wirtz ◽  
...  

Salivary gland stones, or sialoliths, are the most common cause of the obstruction of salivary glands. The mechanism behind the formation of sialoliths has been elusive. Symptomatic sialolithiasis has a prevalence of 0.45% in the general population, is characterized by recurrent painful periprandial swelling of the affected gland, and often results in sialadenitis with the need for surgical intervention. Here, we show by the use of immunohistochemistry, immunofluorescence, computed tomography (CT) scans and reconstructions, special dye techniques, bacterial genotyping, and enzyme activity analyses that neutrophil extracellular traps (NETs) initiate the formation and growth of sialoliths in humans. The deposition of neutrophil granulocyte extracellular DNA around small crystals results in the dense aggregation of the latter, and the subsequent mineralization creates alternating layers of dense mineral, which are predominantly calcium salt deposits and DNA. The further agglomeration and appositional growth of these structures promotes the development of macroscopic sialoliths that finally occlude the efferent ducts of the salivary glands, causing clinical symptoms and salivary gland dysfunction. These findings provide an entirely novel insight into the mechanism of sialolithogenesis, in which an immune system-mediated response essentially participates in the physicochemical process of concrement formation and growth.


2006 ◽  
Vol 51 (12) ◽  
pp. 1055-1060 ◽  
Author(s):  
H. Inoue ◽  
K. Ono ◽  
W. Masuda ◽  
Y. Morimoto ◽  
T. Tanaka ◽  
...  

1987 ◽  
Vol 66 (1_suppl) ◽  
pp. 680-688 ◽  
Author(s):  
M. M. Schubert ◽  
K. T. Izutsu

Saliva is important for maintaining oral health and function. There are instances when medical therapy is intended to decrease salivary flow, such as during general anesthesia, but most instances of iatrogenic salivary gland dysfunction represent untoward or unavoidable side-effects. The clinical expression of the salivary dysfunction can range from very minor transient alteration in saliva flow to a total loss of salivary function. The most common forms of therapy that interfere with salivation are drug therapies, cancer therapies (radiation or chemotherapy), and surgical therapy. These therapies can affect salivation by a number of different mechanisms that include: Disruption of autonomic nerve function related to salivation, interference with acinar or ductal cell functions related to salivation, cytotoxicity, indirect effects (vasoconstrictiondilation, fluid and electrolyte balance, etc.), and physical trauma to salivary glands and nerves. A wide variety of drugs is capable of increasing or decreasing salivary flow by mimicking autonomic nervous system actions or by directly acting on cellular processes necessary for salivation; drugs can also indirectly affect salivation by altering fluid and electrolyte balance or by affecting blood flow to the glands. Ionizing radiation can cause permanent damage to salivary glands, damage that is manifest as acinar cell destruction with subsequent atrophy and fibrosis of the glands. Cancer chemotherapy can cause changes in salivation, but the changes are usually much less severe and only transient. Finally, surgical and traumatic injuries interfere with salivation because of either disruption of gland innervation or gross physical damage (or removal) of glandular tissue (including ducts).


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16522-16522
Author(s):  
M. Yokokawa ◽  
N. Uchida ◽  
A. Wada ◽  
A. Kawaguchi ◽  
M. Notani ◽  
...  

16522 Background: For head and neck cancer (HNC) patients who receive curative irradiation (RT), RT-induced xerostomia is a frequent and troublesome adverse event diminishing quality of life. In this prospectve study, morphological changes in salivary glands were evaluated by means of MR volume calculation and examination of the functional changes in MR-sialography as compared with subjective symptoms. Materials and Methods: Sixteen HNC patients (15 squamous cell carcinomas and 1 lymphoma) scheduled to receive more than 44 Gy to the primary tumor were registered (median dose to salivary glands: 60 Gy). MRI was performed prior to start of RT (pre-RT), as well as 2–4 weeks after completion of RT (post-RT). Evaluations were undertaken as follows: 1) Subjective symptoms of oral dry sensation were scaled by visual analogue scale (pre-RT VAS, post-RT VAS); 2) Changes in depictions of MR-sialography (heavy T2WI) following tartaric acid stimulation were graded into three categories (good,fair, poor); and, 3) Changes in salivary gland volume were measured as reduction ratio(%) = (pre-RT volume - post -RT volume) / pre-RT volume × 100. Results: Post-RT VAS of oral dry sensation was greater than that of pre-RT (p=0.001). Clinical symptoms (changes in VAS) did not correlate with salivary gland reduction ratio nor radiation dosage for either the parotid (PG) or submandibular glands (SG). RT dosage and reduction ratio correlated well (r=0.62). Reactivity of MR-sialography stimulated by tartaric acid became poor after RT. The mean RT dosages to PG and SG of the poor group were higher than those of the good group (p<0.05). Conclusions: MR-sialography after RT showed a poor response to secretion stimulation, which correlated with RT dosage. Moreover, MR- sialography with secretion stimulation may have the potential to be a non-invasive and sensitive method by which to assess the severity of xerostomia of each gland separately as ‘functional MR - sialography‘. More cases and longer follow up, and dose-volume histogram evaluation of each salivary gland are required to confirm the results. No significant financial relationships to disclose.


2006 ◽  
Vol 91 (11) ◽  
pp. 4497-4500 ◽  
Author(s):  
Junichi Tajiri

Abstract Context: Hashimoto’s thyroiditis is an autoimmune disease that can produce marked clinical symptoms when patients have large diffuse goiters. Design: This retrospective cohort study was designed to evaluate whether radioactive iodine (RAI) is effective for Hashimoto’s thyroiditis with a large goiter. Starting in November 1999, 13 Hashimoto’s patients with large goiters, whose thyroiditis was refractory to TSH suppression therapy with thyroid hormone administration [two men and 11 women with a mean age of 61.2 ± 8.9 yr (50–79 yr)], were recruited for the present study. The duration of symptomatic goiter before undergoing RAI was 12.0 ± 7.9 yr (4–33 yr). Thirteen millicuries of 131I was administered two to six times, at an interval of 1–6 months on an outpatient basis. Thyroid weight was measured ultrasonographically, or by computed tomography if ultrasound was not possible due to the large size of the goiter. Results: RAI was administered an average of 4.7 ± 1.4 times (two to six times), with a total dose of 59.8 ± 17.3 mCi (25.0–78.0 mCi). The observation period was 47.9 ± 13.4 months (26–66 months) after the first RAI. The average weight of the thyroid gland was 125.3 ± 57.7 g (42.9–269.4 g) before the first RAI, decreasing significantly to 49.7 ± 25.8 g (18.3–93.3 g) after the last RAI (P &lt; 0.001, paired Student’s t test). The percent reduction from baseline was 58.7 ± 14.2% (35.7–84.0%). None of the patients showed an increase in goiter size or complained of a pressure sensation after any of the RAI treatments. Conclusion: RAI is effective in Hashimoto’s thyroiditis with a large goiter.


Author(s):  
Lauren Gayle Meeks ◽  
Diogo De Oliveira Pessoa ◽  
Jessica Anne Martinez ◽  
Kirsten H. Limesand ◽  
Megha Padi

Radiation therapy for head and neck cancer causes damage to the surrounding salivary glands, resulting in salivary gland hypofunction and xerostomia. Current treatments do not provide lasting restoration of salivary gland function following radiation; therefore, a new mechanistic understanding of the radiation-induced damage response is necessary for identifying therapeutic targets. The purpose of the present study was to investigate the metabolic phenotype of radiation-induced damage in parotid salivary glands by integrating transcriptomic and metabolomic data. Integrated data were then analyzed to identify significant gene-metabolite interactions. Mice received a single 5 Gy dose of targeted head and neck radiation. Parotid tissue samples were collected 5 days following treatment for RNA sequencing and metabolomics analysis. Altered metabolites and transcripts significantly converged on a specific region in the metabolic reaction network. Both integrative pathway enrichment using rank-based statistics and network analysis highlighted significantly coordinated changes in glutathione metabolism, energy metabolism (TCA cycle and thermogenesis), peroxisomal lipid metabolism, and bile acid production with radiation. Integrated changes observed in energy metabolism suggest that radiation induces a mitochondrial dysfunction phenotype. These findings validated previous pathways involved in the radiation-damage response, such as altered energy metabolism, and identified robust signatures in salivary glands, such as reduced glutathione metabolism, that may be driving salivary gland dysfunction.


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