Association Between Hashimoto’s Thyroiditis and Periodontal Disease: A Narrative Review

Abstract

Objective: This review aims to elucidate the link between Hashimoto’s thyroiditis (HT) and periodontal disease (PD) and to substantiate whether the autoimmune mechanisms involved in the pathogenesis of HT influence the integrity of oral tissues, eventually inducing the development of PD. Methods: The present article is a narrative review that has been composed conforming to the Scale for the Assessment of Narrative Review Articles (SANRA) guidelines on the topic ‘Association between HT and PD’. Results: Eight studies, including four case–control studies, one cross-sectional study, two case reports, and one bidirectional Mendelian randomization study, were cited. These studies were filtered by language (all in English) and relevance to the topic and were sourced from the Google Scholar and PubMed databases. The results suggest a potential link between HT and PD, indicating that HT may have a direct impact on oral tissues. Conclusion: Existing research shows limited but probable evidence associating HT with PD; nevertheless, further large-scale studies with refined methodologies are required to assess this hypothesis and elucidate the precise mechanisms by which HT may contribute to PD pathogenesis.

1. Introduction

Hashimoto’s thyroiditis (HT) is an autoimmune disorder characterised by the presence of specific antibodies, such as thyroid peroxidase (TPO) and thyroglobulin (TG) antibodies. This autoimmune response prompts lymphocytic infiltration, notably involving T cells, in response to the presence of these antibodies. Over time, this immune-mediated process results in gradual destruction and fibrosis of the thyroid gland [1]. Consequently, there is an elevation in thyroid-stimulating hormone (TSH) levels and a reduction in triiodothyronine (T3) and thyroxine (T4) hormone production, which are characteristic hallmarks of hypothyroidism [2]. The prevalence of HT exhibits regional and socioeconomic disparities, with a higher incidence among females than among males [3]. Diagnosis primarily involves quantifying antibodies against TPO and TG along with the assessment of thyroid ultrasound to check for the presence of decreased echogenicity [4].

Periodontal disease (PD) involves the periodontium including the gingiva, cementum, periodontal ligament and alveolar bone. Gingivitis is the earliest form of PD which can be reversed upon improvement in oral hygiene. Gingival inflammation occurs due to the accretion of bacteria and debris, also called dental plaque. This subsequently leads to the formation of soft tissue pockets between the tooth root and gingiva. Gingivitis, if left untreated, can progress into a chronic, destructive, irreparable inflammatory condition called periodontitis. Periodontitis leads to detachment of gingiva from the cemental surface of tooth root and resorption of the alveolar bone which can eventually result in tooth loss. PD can be caused by several factors including smoking, poor oral hygiene, pregnancy, and age. Inadequate oral hygiene is the most important factor in the initiation of PD because it can lead to the accumulation of microbial plaque, leading initially to gingivitis which frequently progresses to periodontitis if not treated [5].

In 2017, the American Academy of Periodontology (AAP) and the European Federation of Periodontology (EFP) jointly introduced a new Classification for Periodontal and Peri-implant Diseases and Conditions at the World Workshop [6,7,8]. This was intended to replace the Armitage 1999 classification of PD, which has been in use for almost 20 years. The 1999 classification was updated to address concerns about its complexity and to better align with current understanding [9,10]. The new classification categorises PD and conditions into three forms: (1) periodontal health, gingival diseases and conditions, (2) periodontitis and (3) other conditions affecting periodontium. The first category includes periodontal health and gingival health as well as gingivitis (dental-biofilm-induced) and gingival diseases (non-dental-biofilm-induced). Similarly, the second category encompasses necrotising periodontal diseases, periodontitis and periodontitis as a manifestation of systemic disease. The third category includes systemic diseases or conditions affecting the periodontal supporting tissues, periodontal abscesses and endodontic–periodontal lesions, mucogingival deformities and conditions, traumatic occlusal forces, and tooth and prosthesis-related factors [6,7,8].

This scheme merged the previously recognised forms of “chronic” and “aggressive” periodontitis under a single category called “periodontitis”. This category was further characterised using a multidimensional staging and grading system. The staging indicates the severity and extent of the disease, while the grading reflects the rate of disease progression and associated risk factors, such as diabetes and smoking [6,7,8]. Additionally, distinct categories for necrotising periodontal diseases, endodontic–periodontal lesions, and periodontal abscesses are maintained [6]. Systemic diseases and developmental conditions are also recognised for their impact on periodontium [11]. These updates aim to improve diagnostic accuracy and treatment outcomes for patients and provide a more comprehensive and clinically useful framework. Furthermore, a new emphasis has been placed on peri-implant conditions, recognising the importance of peri-implant health and the classification of peri-implant mucositis and peri-implantitis [7]. The classification of PDs has been a long-standing dilemma, with periodic updates reflecting new knowledge and technologies.

There is strong evidence in the literature that validates the association between PDs and certain systemic diseases such as osteoporosis [12,13], cardiovascular disorders [14,15,16], stroke [17], type 2 diabetes [18,19,20,21], chronic obstructive pulmonary disease, cognitive disorders such as Alzheimer’s disease, and certain cancers [21]. Additionally, PD can be attributed to autoimmune disorders, revealing a strong association with rheumatoid arthritis [22,23] and systemic lupus erythematosus [24,25].

Similarly, the autoimmune mechanism of HT may affect the integrity of oral supporting tissues, leading to the development of PD. Multiple studies have suggested a direct influence of thyroid antibodies on oral tissues. Possible mechanisms include modifications in the capillary microstructure of the interdental papilla, emphasising that HT patients have a characterised microcapillary structure due to the increased serum inflammatory biomarkers [26] or a positive correlation found between free thyroxine (fT4) and gingival index (GI) and fT4 and probing pocket depth (PPD), implying a potential association between periodontal inflammation and HT [27]. The reported repercussions and abuse of periodontal tissues owing to endocrine fluctuations have also been of vital significance in conceiving the idea that a plausible association exists between the two.

Table 1. Important clinical aspects of Hashimoto’s thyroiditis and periodontal disease.

Hashimoto’s Thyroiditis	Periodontal Disease
1. Autoimmune Nature and Pathogenesis ▪ HT is characterised by the presence of thyroid-specific autoantibodies, specifically against TG and TPO [1,28,29,30]. ▪ The disease comprises lymphocytic infiltration and damage to thyroid follicles, resulting in atrophy and fibrosis [1,28,29].	1. Diagnostic Criteria and Clinical Signs ▪ PD diagnosis involves assessing clinical signs such as BOP, periodontal pockets, gingival recessions, furcation involvement, and radiographic bone loss. Patient-reported outcomes like increased tooth mobility and migration are also crucial [31]. ▪ The new classification system groups periodontitis into a single category with a staging and grading system based on disease severity and complexity of management [6].
2. Symptoms and Clinical Presentation ▪ Common symptoms include neck pain, voice changes, throat discomfort, dyspnoea, dysphagia, and goitre-related symptoms [30,32,33]. ▪ HT can present with a range of thyroid function states, from euthyroid to hypothyroid, and occasionally hyperthyroid phases [29,30].	2. Pathogenesis and Progression ▪ Periodontitis is initiated by dental plaque accumulation, leading to an inflammatory response that causes microbial alterations and tissue damage. Chronic inflammation can result in irreversible loss of attachment and alveolar bone [34,35,36]. ▪ The disease involves a dysbiosis of the oral microbiota and an over-aggressive immune response, which includes upregulation of proinflammatory cytokines and reactive oxygen species, contributing to tissue destruction [35,37].
3. Diagnosis ▪ Diagnosis is based on clinical features, the presence of antithyroid antibodies, and decreased echogenicity on thyroid ultrasound [28,29,30,38]. ▪ FNAC is a valuable diagnostic tool, revealing lymphocytic infiltration and other characteristic cytological features [38].	3. Systemic Associations ▪ Periodontitis is associated with several systemic diseases, including diabetes, cardiovascular diseases, chronic obstructive pulmonary disease, rheumatoid arthritis, certain cancers, and cognitive disorders like Alzheimer’s disease. These associations highlight the importance of periodontal health in overall systemic health [21,35,37].
4. Associated Conditions ▪ HT is frequently associated with other autoimmune diseases such as T1D, alopecia, vitiligo and coeliac disease [1,30]. ▪ There is a noted association between HT and papillary thyroid carcinoma, with HT patients having a higher prevalence of this malignancy [28,39,40].	4. Risk Factors ▪ Both modifiable (e.g., smoking, diet) and non-modifiable (e.g., genetic susceptibility) risk factors influence the severity and progression of PD. Environmental and host factors play significant roles in disease pathogenesis [35].
5. Management ▪ The primary treatment for hypothyroidism resulting from HT is synthetic levothyroxine [1,28,29,30]. ▪ Surgery may be needed for large goitres causing compressive symptoms or when malignancy cannot be ruled out [29,40]. ▪ Nutritional and micronutrient management, including vitamin D and selenium supplementation, may benefit some patients, although evidence is still emerging [39].	5. Treatment and Management ▪ Treatment includes scaling, antiseptic rinses, systemic antibiotics, and occasionally surgical interventions. New treatment modalities being explored include antimicrobial therapy, host modulation therapy, laser therapy, and tissue engineering [36]. ▪ Maintaining periodontal health requires daily oral hygiene and professional removal of microbial biofilm. Patient self-care, including the use of oral rinses, is critical for managing periodontal health [36].

BOP (bleeding on probing); FNAC (fine needle aspiration cytology); HT (Hashimoto’s thyroiditis); PD (periodontal disease); T1D (type 1 diabetes); TG (thyroglobulin); TPO (thyroid peroxidase).

demonstrates the important clinical aspects of HT and PD.

A convincing amount of work has been conducted regarding the correlation between hypothyroidism and its impact on periodontal health [41,42,43,44]. However, studies on compromised periodontium in the context of HT are scarce. Furthermore, the presence of immune dysregulation, chronic inflammation, and vascular endothelial dysfunction in both HT and PD and the impact of hypothyroidism on bone metabolism (which may affect alveolar bone) suggest a strong possibility of an association between both disorders. Therefore, this review aimed to further assess the linkage between HT and PD by gathering the latest explorations on this subject and calling attention to the gap in existing research work in order to substantiate this hypothesis.

2. Materials and Methods

The present study is a narrative review composed in accordance with the guidelines provided by the Scale for the Assessment of Narrative Review Articles (SANRA) [45], of the scientific literature on the topic “Association between Hashimoto’s thyroiditis and periodontal disease” obtained by the research question: “Is periodontal disease a manifestation of systemic effects of autoimmune Hashimoto’s thyroiditis?”

The search for studies was carried out in August 2023 using PubMed and Google Scholar. The keywords used in the topic addressed included “Hashimoto’s disease” OR “Hashimoto’s thyroiditis” OR “chronic autoimmune thyroiditis” OR “thyroid antibodies” OR “autoimmune hypothyroidism” AND “periodontal lesions” OR “periodontitis”. After refining the inclusion criteria of articles, a literature review was established to include those publications that, upon reading the title and abstract, contained present knowledge related to the affiliation between HT and PD.

The search results revealed a total of 3278 articles (3183 from PubMed and 95 from Google Scholar), of which 3270 were excluded, resulting in a total of eight articles (including four case–control studies, one cross-sectional study, two case reports, and one bidi-rectional Mendelian randomization study), selected to participate in the composition of this review.

Table 2. Criteria for inclusion and exclusion of studies in this narrative review.

Inclusion Criteria	Exclusion Criteria
Articles with titles and abstracts indicating relevance to the HT-PD association.	Articles not answering the research question.
Primary research including cross-sectional studies, case–control studies, case reports/case series and clinical trials.	Secondary research including systematic reviews and narrative reviews.
Articles in English language.	Articles in non-English language.
Full text available for review.	Articles whose full texts were not available.

HT (Hashimoto’s thyroiditis); PD (periodontal disease).

presents the inclusion and exclusion criteria of this narrative review.

3. Hashimoto’s Thyroiditis

HT, also recognised as autoimmune thyroiditis or chronic lymphocytic thyroiditis, is an autoimmune disorder of the thyroid gland. It typically features an enlarged thyroid gland (goitre), infiltration of lymphocytes, and high levels of autoimmune antibodies in the blood. HT is a prevalent reason for hypothyroidism in regions with sufficient iodine levels, which upsurges the malignancy risk [46].

3.1. Risk Factors

HT is said to be a combination of environmental risk factors and genetic susceptibility, resulting in immune system failure due to an autoimmune attack on the thyroid. Several studies have identified a genetic predisposition to HT. Marwaha et al. (2003) have suggested that 34% of immediate family members of children with HT might also have the condition, in contrast to only 13% of immediate family members of children without HT [47]. Villanueva et al. (2003) used data from the NHANES-3 survey and found a sibling recurrence risk ratio (λs) of 28, indicating a substantial genetic involvement in the onset of HT [48]. Furthermore, Dittmar et al. (2011) revealed that brothers and sisters of individuals with HT have a 21-times higher chance of contracting the disease [49].

Some environmental factors contribute to a higher risk of HT. Increased iodine consumption can trigger thyroid autoimmunity. In areas where iodine levels are high, 25% of individuals have thyroid antibodies [50], compared to 13% in iodine-deficient regions [51], and 18% in regions with adequate iodine levels [52]. Certain medications, such as interferon-alpha for chronic hepatitis, cause 40% of the patients to develop thyroid antibodies [53]. Likewise, interleukin (IL)-2, which is used for melanoma and neural carcinoma, also increases thyroid antibody positivity [54]. Infections such as hepatitis C can also trigger thyroid autoimmunity [53]. A study by Wasserman et al. on pregnant women’s sera found a connection between previous Toxoplasma gondii infection and higher levels of TPO antibodies [55].

3.2. Pathogenesis

Autoimmune thyroid disease is primarily marked by the invasion of the thyroid gland by lymphocytes, with T cells being notably predominant. This involves the activation and conversion of B-cells into antibody-producing plasma cells, a process aided by follicular helper T cells (Tfh cells). Increased activity in HT contributes to the production of thyroid-specific autoantibodies, which target and damage thyroid cells, while T regulatory (Treg) cells dampen the immune response. Failure to do so leads to inadequate control of autoreactive immune responses. The thyroid gland becomes infiltrated with T and B cells [56]. This invasion causes slow destruction of the thyroid tissue, resulting in atrophy and fibrosis of thyroid cells. Lymphocytic infiltration also triggers the production of various cytokines. For instance, Figueroa-Vega et al. (2010) revealed that IL-17 and IL-22 are overexpressed in individuals with HT compared to those with Graves’ disease (GD) [57]. Additionally, Bai et al. (2014) observed a correlation between TPO antibodies and IL-22 levels in individuals with HT, indicating a possible involvement of this cytokine in producing antibodies [58]. IL-23, produced by cells of the body’s initial defence mechanisms, was also observed to be increased in HT patients [59]. IL-14 and IL-16 were found in individuals with GD as well as HT [60]. Furthermore, an earlier study by Ruffilli et al. (2014) suggested the involvement of interferon gamma-inducible protein 10, a chemokine, in immune-mediated destruction observed in HT [61]. All these cytokines cause further activation of T and B cells, as well as thyroid gland destruction (Figure 1).

Prior research has demonstrated that substances emitted by dead or dying cells promote the formation of a sterile inflammatory environment, which triggers the immune system [62]. It has been demonstrated that innate immunity is activated upon the release of genomic DNA [63]. An inflammatory response and impaired activity of important thyroid proteins, such as sodium-iodide symporter (NIS), were linked to thyroid cell death in culture leading to the release of genomic DNA [64]. The researchers showed in a series of sophisticated tests that histone H2B was the primary trigger for activating the innate immune response. As a result, thyroid autoimmunity appears to be initiated by sterile thyroid injury alone.

Small noncoding RNA segments known as microRNAs (miRNAs) have also been linked to the pathophysiology of thyroid immunity. It has been demonstrated that different miRNA regulates both innate and adaptive immune responses [65]. When fine needle aspiration was used, HT tissue was found to have lower concentrations of miR-155_2, and increased concentrations of miR-200a1, compared to thyroid tissue from healthy individuals [66]. Apart from tissue samples, blood miRNA was examined using miR-22, miR-375, and miR-451, which revealed elevated concentrations in patients with GD and HT in comparison to controls [67]. Further studies are necessary to fully investigate the potential of miRNAs as innovative treatment options for autoimmune thyroid diseases, with a focus on HT.

Histological features of HT include a variety of components, such as lymphoplasmacytic invasion, the presence of fibrotic tissue, degeneration of parenchymal tissue, and abundance of enlarged cells with eosinophilic granules in lymphoid follicles, known as Hurthle cells (Figure 2). However, these histological characteristics are not unique to HT [28].

3.3. Clinical Presentation

In HT patients, the clinical presentation can vary, with patients presenting as euthyroid, subclinical thyroid, or clinical hypothyroid, which depends on the intensity of the immunological reaction [69]; however, it typically involves thyroid gland’s diffuse enlargement (goitre) with no other discernible reason. Patients may develop single or multiple nodules, which can be either benign or malignant [70] and are often located above the isthmus [69]. Malignancies can include papillary carcinoma [70] or thyroid lymphoma [71]. Reduced echogenicity on thyroid sonograms was observed in the patients with appropriate clinical features [29].

3.4. Diagnosis

HT can be diagnosed through clinical examination, antibody assessment, and thyroid function tests [70]. Patients with HT often report a sensation of constriction and swelling in the neck while neck pain is an uncommon symptom. Physical examination of these patients typically reveals regular, non-tender goitre. The results showed that the white blood cell (WBC) count and erythrocyte sedimentation rate (ESR) were both within usual limits [71].

Confirmation of the diagnosis involves testing for thyroid autoantibodies, which serve as the primary indicators of HT. These include TG, TPO, and thyrotropin receptor antibodies (TRAb). Notably, an elevated level of antibody is not unique to HT; it can also be present in other thyroid conditions including multinodular goitre and thyroid malignancy. However, the existence of antithyroid microsomal antibodies exceeding a 1:6400 ratio or anti-TPO antibodies at levels greater than 200 IU per ml indicates a strong likelihood of chronic autoimmune thyroiditis [71].

TPO and TG antibodies can be found in both blood serum and saliva, which are identified using enzyme-linked immunosorbent assay (ELISA) kits. The detection of these antibodies confirms the autoimmune nature of the disease. In some cases, when TSH receptor-blocking antibodies are present in a person, especially female, it may lead to severe congenital hypothyroidism in their offspring. Additionally, patients exhibit high TSH levels and low thyroid hormones (T3 and T4). Radioactive iodine uptake (RAIU) results can vary, the level can be either normal or elevated depending on the degree of follicular destruction [71]. Thyroid ultrasonography and/or thyroid uptake and scanning are included in imaging studies which can be conducted if the thyroid antibody test is negative or if a nodule is detectable [69].

4. Periodontal Disease

PD, a prevalent dental disease, is characterised by inflammation of the periodontium and gradual degradation of periodontal ligaments and alveolar bone [72]. The most common cause of PD is microbial plaque build-up on the surface of teeth due to inadequate oral hygiene. The disease process begins with “gingivitis”, which is characterised by inflammation and bleeding gums. Gingivitis can be reversed with good oral care however if not treated, it may advance to “periodontitis”. Periodontitis refers to the gradual breakdown of the periodontium, which involves both hard and soft tissues. Clinically, patients with periodontitis show the presence of dental calculus (both supragingival and subgingival), swollen bleeding gums, halitosis, and diastema. PD is marked by the extension of normal gingival sulcus into a “periodontal pocket”, along with the degradation of supporting fibres and bone loss, resulting in clinical attachment loss. In advanced stages, periodontitis can cause tooth mobility due to severe bone loss visible on radiographs. Pus from the periodontal pockets can also be observed [73].

Similar to periodontitis, peri-implantitis is a condition that affects the soft and hard tissues surrounding a dental implant. It is characterised by symptoms such as bleeding on probing (BOP), which may be followed by pus formation and bone loss, and sometimes requires implant removal. The primary cause is a microbiological biofilm that invades the sulcular epithelium, leading to the accumulation of polymorphonuclear cells, monocytes, and macrophages [74]. The inflammatory response triggers the production of cytokines, similar to those observed in periodontitis. In addition to causing localised inflammation, peri-implantitis induces a systemic host response, evident by elevated levels of C-reactive protein (CRP), IL-6, and WBCs, and increased local production of tumour necrosis factor α (TNF-α) and IL-17.

Although peri-implantitis shows a significant inflammatory infiltrate in the mucosa, it usually affects fewer sites with a smaller inflamed area than periodontitis. However, it remains a greater inflammatory trigger than periodontitis [75].

4.1. Staging and Grading of Periodontitis

The new classification system for PD provides a comprehensive framework for diagnosing and managing periodontitis by incorporating both the staging and grading criteria discussed below.

4.1.1. Staging of Periodontitis

Periodontitis is staged from I to IV based on the severity of periodontal breakdown (e.g., attachment loss and bone loss) and the complexity of managing the disease (e.g., pocket depth, furcation involvement, and tooth mobility), whereas the extent of the periodontitis is described as either localised or generalised [6,8,76].

4.1.2. Grading of Periodontitis

Grading is categorised into three levels (A, B, and C) based on the rate of disease progression, i.e., slow, moderate, and rapid. Grading also considers risk factors such as smoking and diabetes, which can modify the grade [6,8,76].

4.1.3. Implementation and Reliability

Studies have shown moderate to high inter-examiner reliability in using the staging and grading system among specialists, postgraduate students, and general dentists. Moreover, the new classification system has been shown to predict periodontal-related tooth loss, with higher stages and grades associated with increased risk of tooth loss, demonstrating predictive capability [77,78,79].

4.1.4. Clinical Application

This system provides a comprehensive framework that extends beyond severity to include biological features, aiding in precision medicine approaches for periodontitis management [6,8]. Also, the staging and grading system is used to guide treatment planning, ensuring the conservation of teeth and preservation of alveolar bone in implant therapy [76].

4.2. Pathogenesis

The onset and progression of PD are due to dysbiosis of the subgingival microbiota, which comprises approximately 700 species. However, the main bacteria responsible for disease advancement are Porphyromonas gingivalis and Fusobacterium nucleatum. These bacteria within the subgingival biofilm induce an inflammatory response by generating virulence factors for instance lipopolysaccharides (LPS), peptidoglycans, lipoteichoic acids, proteases, as well as toxins [80]. These virulence factors act via the Toll-like receptor signalling pathway activating this subsequently triggers the intracellular nuclear factor kappa-B ligand (NF-κB), resulting in an elevation in IL production, particularly IL-8 [81]. TNF-α and prostaglandin E2 (PGE2) are also emitted by gingival tissue in reaction to pathogens [80]. Additionally, the count of T and B cells has increased in response to chronic inflammation [81]. Among them, T helper cells and Treg cells are responsible for the further release of the inflammatory mediators. All of these mediators perform a pivotal role in attracting immune cells, such as neutrophils and macrophages. They also cause overexpression of proteolytic enzymes, such as matrix metalloproteinases (MMPs) and the receptor activator of nuclear factor kappa-B ligand (RANKL), leading towards periodontal tissue damage by pathological breakdown of its extracellular matrix and alveolar bone resorption, respectively [80,81,82,83] (Figure 3).

4.3. Prevalence

PD is a prevailing infectious oral condition that manifests in approximately 20–50% of the global population. One key factor in its development is economic status. People with lower incomes have 1.81 times higher susceptibility to suffer from periodontitis compared to people with higher earnings because they often have dental insurance and receive better dental care.

In developing countries, there is a higher prevalence of calculus deposits in adolescents (35–70%), while in developed countries, this percentage is lower, ranging from 4% to 34%. In developed countries, 14–47% of adults have calculus deposits, whereas in developing countries, this figure ranges from 36% to 63%. Notably, individuals in developing nations show a greater proportion of periodontal pockets measuring 4–5 mm [84]. Older people have a higher chance of developing PD because of their relatively weaker immune system, making them more prone to inflammation [85]. Furthermore, reduced frequency of regular tooth brushing in older adults is also a contributing factor to the onset of PD. A review indicated that as age advances, the incidence of extreme PD also increases and the prevalence of severe PD escalates with age, culminating around 40 years, after which it remains relatively stable. In addition, the connection between age and PD is not solely predicated on chronological years but is rather intertwined with the extended duration of untreated PD, as often seen in elderly people, playing a pivotal role [86].

4.4. Risk Factors

PD is characterised by the gradual damage of tissues in periodontium. The damage is facilitated through the mutual influence among imbalanced colonies of microorganisms and atypical immune reactions within oral structures. Pivotal microbial agents and persistent gingival inflammation play crucial roles in PD progression. Furthermore, biological processes, external influences (such as lifestyle and diet food habits), autoimmune disorders, diabetes, tobacco smoking, stress, obesity, osteoporosis, cardiovascular disorders, and other factors increase the risk of PD [87].

Understanding these risk factors is crucial in clinical practice. Over 700 phylotypes of bacteria, including almost 400 species, are found in plaque which is present beneath the gum line. Plaque present in deep pockets of the periodontium contains many bacteria, especially Gram-negative bacteria. These microbes have a strong association with the progression of periodontitis in adults. Consumption of tobacco also harms periodontium and enhances PD progression [87].

Many studies have shown a link among diabetic patients and an elevated tendency towards infections of the oral cavity, such as PD. PD progresses more quickly in patients with poorly controlled diabetes [88]. Osteopenia also plays a part in PD development, as determined by a review. It showed a clear link between osteopenia of skeletal and lower jaws and reduced alveolar bone height and loss of teeth in menopausal women. The factors that cause osteopenia and periodontal disease may be similar, as they directly affect or regulate processes in both conditions [89].

PD is also influenced by diet, lifestyle, physical activity, and obesity. The aggravated pro-inflammatory condition in patients with obesity might enhance susceptibility to pathogenic bacteria in gingival tissues, thereby potentially influencing periodontal disease. Age, pregnancy, and low socioeconomic status are other risk factors. PD is a multifactorial disease, and effective care of those factors which increase the probability of PD demands comprehensive knowledge of these factors [90].

4.5. Evidence-Based Guidelines to Treat Periodontitis

The EFP has developed S3-level clinical practice guidelines (CPGs) to provide evidence-based recommendations for periodontitis treatment. These guidelines aim to standardise care, improve treatment outcomes, and address the complexities of managing the different stages of the disease.

4.5.1. Stepwise Approach to Treatment

The EFP guidelines recommend a stepwise approach for treating stages I–III periodontitis, which includes behavioural changes, supragingival and subgingival biofilm control, risk factor management, and supportive periodontal care [91,92].

4.5.2. Adjunctive Systemic Antimicrobials

Systemic antimicrobials can be used as adjuncts in the treatment of periodontitis, mostly in cases where subgingival instrumentation alone is inadequate. Nevertheless, their use is limited due to concerns about antibiotic resistance [93].

4.5.3. Interdisciplinary Treatment for Stage IV

For stage IV periodontitis, the guidelines emphasise the need for interdisciplinary treatment approaches, including orthodontic tooth movement, tooth splinting, occlusal adjustment, and both tooth- and implant-supported prostheses [94].

4.5.4. Personalized and Minimally Invasive Care

These guidelines advocate personalised treatment plans that consider individual risk profiles and aim to be minimally invasive. This includes tailored maintenance and supportive care to extend the benefits of initial treatments [92].

4.5.5. Adaptation to Local Contexts

The EFP guidelines have been adapted for use in different countries, such as the United Kingdom and Taiwan, to account for local healthcare environments and specific anatomical considerations [91,95].

4.5.6. Prevention and Management of Peri-Implant Diseases

The guidelines also cover the prevention and treatment of peri-implant diseases, recommending a structured peri-implant care program and specific interventions to manage peri-implant mucositis and peri-implantitis [96].

The EFP S3-level CPGs provide a comprehensive, evidence-based framework for the treatment of periodontitis. They recommend a stepwise, personalised approach to care, the cautious use of systemic antimicrobials, and the importance of interdisciplinary treatment for advanced stages. These guidelines are adaptable to different healthcare settings and also address the prevention and management of peri-implant diseases.

5. Association Between HT and PD: Evidence from the Studies

Table 3. Overview of research findings showing the association between Hashimoto’s thyroiditis and periodontal disease.

Author	Study Design	Participants	Diagnostic Test	Result
Gao et al. [97]	MR method	Population-wide study	IVW	There is no association between genetically predisposed periodontitis and autoimmune thyroid condition. Moreover, thyroid function variations do not pose a risk of periodontitis.
Duda-Sobczack et al. [98]	Case-control study	264	TSH levels were assessed by ECLIA, and GI for periodontitis	Autoimmune thyroiditis has a negative correlation with plaque accumulation and hence a positive association with better gingival status in T1D patients.
Ay et al. [27]	Case-control study	60	Endocrinologic Evaluations (fT4, anti-TPO, TSH), intra- and extra-oral examinations (BOP, GI, PI, PPD)	A positive correlation between fT4 and GI and PPD proposes that periodontal inflammation might be related to HT.
Song et al. [99]	Cross-sectional study	5468	Serum TSH levels, CPI	Decreasing periodontitis prevalence and increasing anti-TPO prevalence imply an inverse relationship between HT and PD.
Al-Hindawi. and Al-Ghurabi [100]	Case-control study	60	ELISA Test	TPO and TG antibodies are indicated in autoimmune hypothyroidism, but their salivary levels may not reflect serum concentrations accurately.
Nagaraj [101]	Case report	1	Nuclear Scintigraphy	The progression of periodontal disease in association with the development of HT indicates a possible link between the two.
Patil et al. [102]	Case report	1	Thyroid scintigraphy	HT is positively associated with significantly higher odds for PD.
Scardina and Messina [26]	Case-control study	30	Gingival capillaroscopy	Characteristic interdental papilla patterns in HT patients indicate that it may be a risk factor for PD.

anti-TPO (anti-thyroid peroxidase); BOP (bleeding on probing); CPI (community periodontal index); ECLIA (electrochemiluminescence immunoassay); ELISA (enzyme-linked immunosorbent assay); fT4 (free thyroxine 4); GI (gingival index); HT (Hashimoto’s thyroiditis); IVW (inverse variance weighted); MR (Mendelian randomization); PD (periodontal disease); PI (periodontal index); PPD (probing pocket depth); TG (thyroglobulin); TPO (thyroid peroxidase); TSH (thyroid stimulating hormone); T1D (type 1 diabetes).

summarises the key research findings that helped establish the association between HT and PD.

Gao et al. assessed the bidirectional causal association between periodontitis and thyroid function (fT4 and TSH levels) and dysfunction (hyperthyroidism, hypothyroidism, and autoimmune thyroid disease) by conducting a bidirectional Mendelian randomisation (MR) study. The inverse variance weighted (IVW) method was used to derive genetic instruments from large-scale genome-wide association studies. The results revealed that individuals who are genetically predisposed to periodontitis may also suffer hypothyroidism; however, variations in thyroid function did not lead to an increased risk for periodontitis. Also, no causal relationship between periodontitis and hyperthyroidism or autoimmune thyroid disease (HT, GD, or other autoimmune thyroid diseases) has been established [97].

Duda-Sobczack et al. investigated how thyroiditis correlates with gingival health in adults diagnosed with type 1 diabetes (T1D). They included 264 patients subdivided into two groups: those with or without autoimmune thyroiditis. T1D was confirmed by the existence of characteristic symptoms at the beginning, level of glucose in the blood and having one or more antibodies among islet cells, glutamic acid decarboxylase (anti-GAD), and insulinoma-associated tyrosine phosphatase (IA-2A) antibodies. Diabetic management and the existence of diabetic neuropathy and retinopathy were also assessed along with blood tests and serum lipid, creatinine, and glycated haemoglobin (HbA1C) levels. Serum TSH levels were assessed using electrochemiluminescence immunoassay (ECLIA) Elecsys analysers; only cases having documented anti-TPO and TG antibodies were part of this study. Examination of periodontal status was performed using the WHO Health Organization probe, and gingival severity was assessed using GI. The conclusion stated that immune-mediated thyroiditis correlates with reduced accretion of dental plaque and enhanced gingival health in T1D patients than in those without thyroid disease. Additional studies are necessary to evaluate the causative factors of these outcomes [98].

Ay et al. evaluated the periodontal health status of adolescents (12–18 years) with HT. The study consisted of 60 adolescent girls grouped into HT (n = 30) and control (n = 30) groups. Evaluation of endocrinological (anti-TPO, fT4, TSH), intra- and extra-oral, and periodontal parameters including BOP percentage, GI, periodontal index (PI), and PPD, were performed. The HT group was revealed to exhibit significantly elevated levels of anti-TPO and TSH. Although no considerable differences were detected between the two groups regarding periodontal parameters, the significant positive correlation between fT4 (used in the investigation of HT) and GI (indicator of gingival inflammation), and fT4 and PPD led the authors to deduce that periodontal inflammation might be associated with HT [27].

Song et al. examined the connection between thyroid dysfunction and periodontitis and analysed findings on thyroid function status and Community Periodontal Index (CPI) scores. A sample of 5468 Koreans was categorised into three tertiles according to serum TSH levels. The ranges of serum TSH levels were <1.76 mIU/L for the first tertile, 1.76–2.83 mIU/L for the second tertile, and >2.83 mIU/L for the third tertile. Serum anti-TPO antibody concentrations were also measured. The data showed a gradual rise in the occurrence of anti-TPO antibodies across tertiles, with 3.1% in the first tertile, 2.7% in the second tertile, and a notable jump to 7.9% in the third tertile. Conversely, the prevalence of periodontitis decreased from 26.5% in the first tertile to 20.9% in the third tertile, suggesting a potential inverse relationship between tertile groups and periodontitis occurrence. The increase in the prevalence of anti-TPO antibodies along tertiles and the decrease in the occurrence of periodontitis suggest a potential inverse relationship between anti-TPO antibodies and periodontitis prevalence [99].

In a case–control study by Al-Hindawi and Al-Ghurabi, thyroid antibodies were measured in the serum and saliva samples of 60 individuals with hypothyroidism. Patients were allotted into two groups: 30 patients with PD and 30 patients without PD. Thirty volunteers were included as the controls. When comparing hypothyroid patients with or without PD to the control group, no substantial difference was observed in salivary TPO antibody levels, while when measuring TG antibody levels, no notable differences were observed. However, in serum samples, TPO antibody concentrations were substantially elevated in individuals with hypothyroidism with or without PD relative to the control group. Similarly, the TG antibody levels were significantly elevated. Conversely, there was no marked difference in these antibodies between patients with hypothyroidism with and without PD. These findings indicate that TPO and TG antibodies may contribute to hypothyroidism in autoimmune conditions. However, the levels of these antibodies in saliva do not correspond to their levels in blood [100].

A case report by Anitha and Nagaraj reported the impact of HT on periodontitis. A 43-year-old woman reported experiencing mobile teeth and bleeding gums at the Periodontics department. Clinical examinations revealed poor oral hygiene, BOP, generalised pockets, and tooth mobility. Routine blood investigations and glucose levels in the blood were unremarkable. Consequently, chronic periodontitis was diagnosed. Post-treatment, the patient showed no BOP, reduced PPD and improved oral hygiene. However, after 1 year, the patient reported loose teeth. The onset of HT was indicated by her medical history. Reports containing nuclear scintigraphy and levels of T4 validated the diagnosis of HT. Despite maintaining good oral hygiene, radiographic findings revealed vertical defects. These progressive findings suggest a potential relationship between periodontitis and HT [101].

In a clinical case report by Patil and Giri, a female aged 42 years visited the department of periodontology with a complaint of bleeding gums. Surgical treatment was performed following a diagnosis of chronic periodontitis. After 6 months there was no BOP, and the patient exhibited good oral hygiene. The patient visited the department after a year interval with mobile teeth. The patient consulted a gynaecologist because of menstrual irregularities, which were later found to be caused by HT. Radiographic findings revealed significant bone loss, despite good oral hygiene. TSH levels were elevated, and thyroid scintigraphy revealed diffuse thyromegaly with an organification defect. Deep PPD, measuring 10 mm, were found in the molars and premolars regions. These findings suggest a possible relationship between periodontitis and HT [102].

Scardina and Messina evaluated histological variations in the microcirculatory vascular pattern of the interdental papilla between patients with HT and healthy patients. A total of 30 subjects were examined: 15 with HT (case) and 15 healthy individuals (control), using computerised video microscopic techniques. Each participant was examined for visibility, course, tortuosity, average calibre of capillary loops, and number of visible capillary loops per square millimetre. The results revealed a characteristic capillaroscopic interdental papilla pattern in HT patients with reduced calibre and a greater number and tortuosity of capillaries, thus indicating the possible influence of HT on periodontal structures. These findings demonstrate that these modifications could be a potential risk factor for the complex activity associated with PD [26].

6. Possible Molecular Relationship Between HT and PD

In recent years, the relationship between systemic conditions and PD has attracted significant interest. Among these systemic conditions, HT has been suggested to have a potential association with PD. This section explores the probable molecular mechanisms that underlie this association.

6.1. Common Immunological Mechanisms

Both HT and PD are characterised by chronic inflammation and dysregulation of the immune system. One of the key commonalities is the involvement of T helper cells, particularly T helper 1 (Th1) and T helper 17 (Th17) cells. These cells play a critical role in the pathogenesis of both diseases by promoting inflammatory responses. In HT, Th1 and Th17 cells contribute to the autoimmune destruction of thyroid tissue, whereas in PD, they are involved in the inflammatory response that results in periodontal tissue destruction [103,104].

6.2. Vascular Endothelial Dysfunction

Another shared mechanism is the dysfunction of the vascular endothelium, specifically in the gingival microcirculation. Endothelial dysfunction is a common feature of HT, due to chronic inflammation and autoimmune activity. This dysfunction can impair blood flow and nutrient delivery to the periodontal tissues, aggravating PD. Similarly, in PD, endothelial dysfunction contributes to the progression of the disease by promoting inflammation and tissue damage [103].

6.3. Bone Metabolism and Alveolar Bone Loss

Hypothyroidism, a common result of HT, has a significant impact on bone metabolism. It can lead to reduced bone density and increased susceptibility to bone loss. This is especially relevant to PD, where alveolar bone loss is a critical feature. The influence of hypothyroidism on bone metabolism may therefore exacerbate the bone loss seen in PD, creating a vicious cycle of inflammation and tissue destruction [103].

6.4. Autoimmune Basis

The autoimmune nature of both diseases provides another layer of connection. In HT, the immune system mistakenly attacks the thyroid gland, while in PD, the immune response to bacterial plaque can become dysregulated, resulting in tissue destruction. The presence of autoantibodies and the chronic inflammatory state in HT may predispose individuals to a heightened immune response in the periodontium, thereby associating the two conditions on an autoimmune basis [104].

7. Limitations and Future Research Directions

The present narrative review is subject to several limitations that should be addressed in future. Firstly, the review included only studies published in English, potentially excluding relevant research available in other languages. This language bias limits the comprehensiveness of the findings. Additionally, the review was restricted to two databases, PubMed and Google Scholar, which may have led to the omission of valuable studies. Another significant limitation is the small number of studies reviewed; only eight studies were included. This limited sample size restricts the strength of the conclusions and underscores the need for more research on this topic. Added to that, the included studies showed heterogeneity in terms of methodology, study designs and outcomes assessed, making it difficult to perform a systematic review.

To improve the scope and quality of future reviews, several directions are recommended. Expanding the inclusion criteria to encompass non-English studies would provide a more comprehensive understanding of the topic. Future reviews should also incorporate additional databases to capture a wider range of studies and reduce publication bias. Conducting systematic reviews and meta-analyses is suggested to offer a more detailed and quantitative synthesis of the available evidence. There is also a clear need for more high-quality primary studies especially randomized controlled trials on a larger scale and better resources with refined methodologies to fill gaps and validate existing findings, given the limited number of studies identified. Also, the molecular background linking HT and PD involves several shared mechanisms, including the role of Th1 and Th17 cells, vascular endothelial dysfunction, and the impact of hypothyroidism on bone metabolism. While these potential mechanisms provide biological plausibility for an association between the two conditions, further research is needed to establish a definitive causal relationship. Addressing these limitations and pursuing these future research directions will advance the field towards more comprehensive and reliable knowledge.

8. Conclusions

Various studies have suggested that HT has an unfavourable effect on the periodontal health of patients and therefore, suggests probable association between the two disorders. Nevertheless, additional research is crucial to elaborate on the systemic impact of HT on PD. This understanding will help dental professionals, enabling them to effectively manage HT and PD patients with adequate diagnosis and treatment plans.