A holistic approach to hypothyroidism and Hashimoto’s thyroiditis

Thyroid disorders, particularly Hashimoto’s thyroiditis, are among the most common endocrine conditions encountered in clinical practice. Conventional treatment protocols, typically centred around levothyroxine (T4) replacement and monitoring thyroid-stimulating hormone (TSH) levels, are effective for many patients, but leave a significant subset with persistent symptoms despite normalised biochemical markers.¹ These patients often report continued fatigue, cognitive impairment, weight gain, and mood disturbances, among other symptoms, even with TSH levels within the reference range.

A more comprehensive approach to thyroid care, focusing not just on TSH but also on triiodothyronine (T3) levels, thyroid antibodies, adrenal health, gut function, sleep, and stress management, is critical for improving clinical outcomes. This well-rounded methodology recognises that thyroid disease, particularly Hashimoto’s, is not merely a thyroid disorder, but often a manifestation of broader systemic dysfunction, particularly involving the immune system and other hormonal axes. This article will explore the limitations of conventional thyroid management, the role of T3 in clinical outcomes, the importance of addressing autoimmunity in Hashimoto’s thyroiditis, and the value of an all-inclusive approach in managing these complex cases.

Hypothyroidism vs Hashimoto’s: Understanding the difference

In a clinical setting, there is very little distinction made between the diagnosis of Hashimoto’s and hypothyroidism. It is understood the two are effectively the same, which is why they are managed clinically in the same way. However, to appropriately manage them, it is incumbent that two diagnoses be properly understood.

Hypothyroidism refers to the general condition in which the thyroid gland does not produce enough thyroid hormone (T3 and T4), resulting in a reduction of the metabolism of the body. This slowdown is caused by a number of factors including iodine deficiency, radiation/chemotherapy treatment, medications, infective disorders, and a host of unknown drivers.

More rarely, dysfunction of the pituitary gland or hypothalamus can also directly impact hormone production in the thyroid gland. There are over 400 symptoms associated with an underactive thyroid, but the most common tend to be fatigue, brain fog, depression/anxiety, cold intolerance, constipation, weight gain, and hair loss (eyebrows in particular).

Hashimoto’s, known also as Hashimoto’s thyroiditis or Hashimoto’s disease, is a specific autoimmune condition wherein the thyroid gland is directly impacted. The usual case is when the immune system mistakenly attacks the thyroid gland, leading to inflammation and gradual destruction of the thyroid tissue. Over time, if the process is not curtailed, the damage reduces the gland’s ability to produce thyroid hormones, resulting in hypothyroidism.

Hashimoto’s is the most common form of hypothyroidism in the developed world and is characterised by the combination of underactive thyroid symptoms, the presence of thyroid antibodies (anti-thyroid peroxidase antibodies and anti-thyroglobulin antibodies), and/or the presence of a positive ultrasound for chronic inflammatory changes.

Thyroid physiology and the limitations of conventional management

The thyroid gland secretes T4 and T3 as the main thyroid hormones. T4 is converted to the active hormone T3, primarily in the liver, kidneys, muscles, and other peripheral tissue. T3 exerts the main metabolic effects at the cellular level, affecting the cell at all levels and stimulating cellular DNA to increase metabolism and thermogenesis. TSH is secreted by the anterior pituitary and acts as a regulatory signal for thyroid hormone production. Conventional management of hypothyroidism relies heavily on monitoring serum TSH and adjusting T4 replacement accordingly. This approach is rooted in the assumption that normalising TSH will restore euthyroid status across all tissues, a hypothesis that holds for many, but not all, patients.

TSH and free thyroxine (FT4) measurements, while useful, do not always reflect the intracellular availability of T3, the biologically active thyroid hormone. A significant number of patients on T4 monotherapy fail to convert adequate amounts of T4 to T3, leaving them with persistent hypothyroid symptoms despite normal TSH levels. This phenomenon, often referred to as ‘tissue hypothyroidism’, highlights the need for a more nuanced approach to thyroid hormone replacement therapy.

The role of T3: Beyond TSH and T4

T3, the metabolically active form of thyroid hormone, is responsible for binding to nuclear receptors and regulating gene expression involved in metabolic processes, thermogenesis, and cognitive function. Research has shown that a subset of patients, especially those with low peripheral conversion capacity (T4 to T3), continue to exhibit hypothyroid symptoms on levothyroxine monotherapy due to suboptimal T3 levels. The failure to adequately convert T4 to T3 can be attributed to several factors, including chronic inflammation, insulin resistance, nutrient deficiencies (selenium and zinc), and genetic polymorphisms such as those affecting the deiodinase enzymes (particularly DIO1 and DIO2). ^2,3,4

Clinical trials suggest that combination therapy using both T4 and T3 may offer symptom relief for patients who fail to thrive on T4 monotherapy. A meta-analysis of randomised controlled trials has demonstrated that a subset of patients report improved quality of life and symptom relief with combination therapy compared to T4 alone, despite equivalent serum TSH levels.

Another randomised clinical trial showed use of T3 medication reduced body weight and resulted in greater thyroid hormone action on lipid metabolism, without detected differences in cardiovascular function or insulin sensitivity.⁵ Furthermore, reverse T3 (rT3), an inactive isomer of T3, can competitively inhibit the binding of T3 to its receptor, further exacerbating symptoms in patients with elevated rT3. Conditions such as chronic stress, critical illness, and systemic inflammation can increase rT3 production, leading to functional hypothyroidism at the tissue level, despite normal serum T4 and TSH.

Hashimoto’s thyroiditis: Autoimmunity at the core

Hashimoto’s thyroiditis, the most common cause of hypothyroidism in developed nations, is an autoimmune condition characterised by lymphocytic infiltration and destruction of the thyroid gland. The conventional approach to Hashimoto’s often overlooks the autoimmune nature of the disorder, focusing instead on managing hypothyroidism solely through thyroid hormone replacement via levothyroxine. However, thyroid hormone replacement does not address the underlying immune dysregulation that drives the progression of Hashimoto’s, leaving patients at risk for continued thyroid destruction and the potential development of additional autoimmune conditions like asthma, lupus, and type 2 diabetes, to name a few.

Measuring thyroid antibodies – thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb) – is essential for diagnosing Hashimoto’s, yet these tests are not always included in routine thyroid screening. The most common method of testing is to screen for only TPOAb to confirm the diagnosis of Hashimoto’s, while ignoring the TgAb.

To properly diagnose Hashimoto’s, either the TPOAb or the TgAb must be present in the blood results, in addition to hypothyroid symptoms. Elevation of either thyroid antibodies indicates an ongoing autoimmune process, even when TSH remains within the reference range. In patients with elevated antibodies, addressing the immune dysfunction is critical to halting or slowing the progression of thyroid damage.

A comprehensive approach: Addressing immune dysregulation, inflammation, and the gut-thyroid axis

To effectively manage Hashimoto’s thyroiditis, it is necessary to address the autoimmune component of the disease. The immune system’s attack on the thyroid gland must be mitigated through a combination of dietary, lifestyle, and therapeutic interventions aimed at reducing inflammation, supporting immune tolerance, and restoring gut integrity.

1. Gut health and the gut-thyroid axis
The gut plays a pivotal role in both thyroid hormone metabolism and immune system function. Approximately 20 per cent of T4 is converted to T3 in the gut, and intestinal dysbiosis or increased intestinal permeability (‘leaky gut’) can impair this conversion. Moreover, the gut-associated lymphoid tissue is a major regulator of immune function, and disruptions in gut health are linked to the development and exacerbation of autoimmune diseases, including Hashimoto’s thyroiditis.⁶

Several studies have established the connection between gut permeability and autoimmune thyroid disease. Zonulin, a marker of intestinal permeability, is often elevated in patients with Hashimoto’s, suggesting that addressing gut integrity may play a crucial role in modulating the immune response. Dietary interventions, such as the removal of gluten or dairy (which shares molecular mimicry with thyroid tissue), can reduce intestinal inflammation and lower antibody levels in some patients.⁷

2. Adrenal function and the hypothalamic-pituitary-adrenal (HPA) axis
Chronic stress and adrenal dysfunction can significantly impact thyroid function. Elevated cortisol levels, commonly seen in states of chronic stress, inhibit the conversion of T4 to T3, reduce the efficiency of T3 receptor interaction, and increase rT3 production. This creates a state of functional hypothyroidism at the cellular level, even if serum T4 and TSH are within the reference range.

Supporting adrenal health through stress reduction techniques, adequate sleep, and nutritional supplementation (eg, adaptogens, B vitamins, vitamin C) is essential for optimising thyroid function in patients with hypothyroidism or Hashimoto’s. The interplay between the HPA axis and thyroid function underscores the importance of evaluating adrenal health in any patient with thyroid dysfunction. Symptoms such as fatigue (not associated with mineral deficiency), disrupted circadian rhythm, and difficulty coping with stress may suggest underlying adrenal dysregulation, which, if unaddressed, can perpetuate thyroid dysfunction.

3. Dietary and lifestyle interventions
Dietary modifications are a cornerstone of managing autoimmune thyroid disease. A nutrient-dense, anti-inflammatory diet rich in antioxidants, omega-3 fatty acids, and micronutrients (such as selenium, zinc, iodine, and vitamin D) can help modulate the immune response and support thyroid function. Selenium, in particular, has been shown to reduce TPOAb levels and improve thyroid function in patients with Hashimoto’s. Similarly, optimising vitamin D levels is crucial for immune regulation, as vitamin D deficiency is common in patients with autoimmune conditions and is associated with increased disease severity.^8,9

In addition to dietary interventions, lifestyle modifications that reduce systemic inflammation and support immune function are equally important. Regular physical activity, sufficient sleep, and stress management techniques (eg, mindfulness, meditation, conflict resolution techniques) have all been shown to positively impact autoimmune disease progression and overall thyroid function.

T3-based therapy and combination treatment: Clinical considerations

Given the role of T3 in cellular metabolism and its critical importance for symptom resolution, clinicians should consider combination therapy (T4 + T3) in patients who remain symptomatic on levothyroxine monotherapy. The addition of T3, either in the form of synthetic liothyronine or natural desiccated thyroid (NDT) preparations, can provide patients with the active hormone they need for symptom relief.

NDT is a good alternative for patients as it is substantially preferred over levothyroxine alone.¹⁰ Careful monitoring of both serum T3 and reverse T3 levels is essential when adjusting therapy to avoid overmedication of symptoms (similar to hyperthyroid symptoms) and potential adverse cardiovascular effects.

Combination therapy has been shown to improve psychological wellbeing, cognitive function, and overall quality of life in certain patient populations. Clinicians should individualise thyroid treatment based on the patient’s clinical presentation, biochemical markers, and response to therapy, with an emphasis on optimising T3 availability at cellular level.

Conclusion

The management of hypothyroidism and Hashimoto’s thyroiditis require a paradigm shift from a purely biochemical approach to one that addresses the full spectrum of thyroid health, including the role of T3, immune system dysfunction, gut health, adrenal function, and lifestyle factors.

A comprehensive, functional approach not only targets thyroid hormone optimisation, but also addresses the underlying causes of thyroid dysfunction, particularly autoimmunity and systemic inflammation. By expanding the clinical focus to include these critical elements, clinicians can achieve better outcomes and provide patients with lasting symptom relief.