Hyperthyroidism and Thyrotoxicosis: Causes, Symptoms, and Thyroid Treatment

What are hyperthyroidism and thyrotoxicosis?

The thyroid gland is a small but vital organ located in the neck that produces hormones regulating the body's metabolism. When the thyroid produces too many of these hormones, a condition known as hyperthyroidism occurs. This leads to the acceleration of many bodily functions.

Thyrotoxicosis is a broader term describing a clinical syndrome caused by an excess of thyroid hormones in the blood, regardless of their origin. Hyperthyroidism is one of the most common causes of thyrotoxicosis. Autoimmune thyroid diseases (AITD) are the most common organ-specific diseases of this gland [6].

Causes of hyperthyroidism and thyrotoxicosis

Excess thyroid hormones can be caused by various factors, including autoimmune processes, side effects of certain medications, and other conditions.

Autoimmune diseases

• Graves' disease: This is the most common cause of hyperthyroidism, in which the immune system mistakenly attacks the thyroid gland, producing stimulating antibodies to the thyroid-stimulating hormone (TSH) receptor. These antibodies cause the gland to produce excessive amounts of hormones [6].
• Hashimoto's thyroiditis: Although Hashimoto's thyroiditis most often leads to hypothyroidism (underactive thyroid function) due to progressive cell destruction [6], it can begin with a short-lived hyperthyroidism phase [1]. This disease is characterized by the presence of antibodies against thyroid peroxidase and thyroglobulin, as well as lymphocyte infiltration of the thyroid gland [6]. Hashimoto's thyroiditis is frequently associated with other autoimmune conditions such as alopecia, vitiligo, celiac disease, and type 1 diabetes mellitus [1].

Autoimmune thyroid diseases are the most common autoimmune disorder among women of reproductive age and can affect fertility and the outcomes of assisted reproductive technologies (ART) [5].

Drug-induced thyrotoxicosis

Certain medications can cause thyroid dysfunction, including thyrotoxicosis:

• Antineoplastic agents: Newer anticancer drugs, such as targeted therapy and immunotherapy (e.g., tyrosine kinase inhibitors, ipilimumab, tremelimumab), can cause thyroid dysfunction in 20-50% of patients. Although hypothyroidism is more common, cases of thyrotoxicosis have also been described [2].
• Tirzepatide: This dual GLP-1/GIP agonist used for obesity treatment was associated with the development or worsening of thyroid disorders in 5.3% of patients in one study. The most frequent diagnoses were nodular/goitrous thyroiditis and drug-induced thyroiditis [3].
• Interferon-alpha: Used for treating various conditions, including chronic hepatitis C, interferon-alpha can cause thyroiditis in up to 40% of patients. It can present as autoimmune thyroiditis (similar to Hashimoto's or Graves' disease) or as non-autoimmune destructive thyroiditis, which often begins with an early thyrotoxic phase and then progresses to hypothyroidism [8].

Symptoms: How does excess thyroid hormone manifest?

Symptoms of hyperthyroidism can be diverse and affect many body systems due to accelerated metabolism. They include:

• Rapid heartbeat (tachycardia) and arrhythmias.
• Nervousness, irritability, anxiety.
• Unexplained weight loss despite a normal or increased appetite.
• Increased sweating and heat intolerance.
• Hand tremors (tremor).
• Muscle weakness and fatigue.
• Sleep disturbances.
• Changes in the menstrual cycle in women.
• Protruding eyes (exophthalmos) in Graves' disease.

It is important to note that in cancer patients, symptoms of thyroid dysfunction such as fatigue, weakness, or depression may be mistakenly attributed to the underlying disease or its treatment, complicating timely diagnosis [2].

Diagnosis and associated conditions

Diagnosis of hyperthyroidism and thyrotoxicosis typically begins with a blood test for TSH and thyroid hormone levels (free T4 and T3). A low TSH level combined with high T4 and/or T3 levels indicates hyperthyroidism.

• To diagnose Hashimoto's thyroiditis, a characteristic ultrasound pattern and the presence of thyroid antibodies are used [1].
• Special attention is paid to TSH levels in women of reproductive age planning pregnancy or undergoing ART, as autoimmune thyroid diseases can affect fertility [5].

Modern approaches to treating hyperthyroidism

The goal of hyperthyroidism treatment is to normalize thyroid hormone levels and eliminate symptoms. The choice of treatment method depends on the cause, severity of the condition, patient age, and presence of comorbidities.

Drug therapy

The mainstay therapy for hyperthyroidism is antithyroid drugs, which reduce thyroid hormone production [4]. These include:

• Methimazole (MMI): A frequently used medication.
• Propylthiouracil (PTU): Preferred in certain cases, especially during the first trimester of pregnancy [4].

Special cases: Pregnancy and lactation

Untreated or poorly controlled hyperthyroidism in the mother can negatively impact pregnancy outcomes, causing fetal and neonatal problems such as hypo- or hyperthyroidism [4].

• In the first trimester of pregnancy, PTU is preferred due to a lower risk of teratogenic effects compared to MMI. However, PTU is associated with a risk of maternal hepatotoxicity. After the first trimester, switching to MMI is recommended, which is associated with a risk of choanal and esophageal atresia in the fetus when used in the first trimester [4].
• During lactation, antithyroid drugs can be used under strict medical supervision, taking into account their excretion into breast milk [4].

Other treatment methods

• Radioactive iodine therapy: Used to destroy part of the thyroid gland, reducing hormone production.
• Surgery (thyroidectomy): Removal of part or all of the thyroid gland may be recommended in cases where medical treatment is ineffective, for large goiters, or when malignancy is suspected.

In subclinical hypothyroidism, often accompanying AITD, levothyroxine treatment is generally recommended when TSH levels are above 4.0 mIU/L. However, the benefit of treatment at lower TSH thresholds (2.5–4.0 mIU/L) remains a subject of debate [5]. Immunomodulatory therapy, such as glucocorticoids or intravenous immunoglobulin, does not yet have compelling evidence of efficacy for improving ART outcomes in women with AITD [5].

Conclusion

Hyperthyroidism and thyrotoxicosis are conditions requiring careful diagnosis and adequate treatment. Timely consultation with an endocrinologist and adherence to medical recommendations allow for effective control of thyroid hormone levels, prevention of complications, and significant improvement in patients' quality of life. Given the complexity of the clinical picture, especially in patients with comorbid conditions or undergoing specific therapies, an individual and comprehensive approach to each case is crucial.

Sources

• [1] Clinical aspects of Hashimoto's thyroiditis. https://pubmed.ncbi.nlm.nih.gov/25231451/
• [2] Thyroid dysfunction from antineoplastic agents. https://pubmed.ncbi.nlm.nih.gov/22010182/
• [3] Impact of Tirzepatide Therapy on Thyroid Disease: Understanding Risks and Emerging Insights. https://pubmed.ncbi.nlm.nih.gov/42145153/
• [4] Management of hyperthyroidism during pregnancy and lactation. https://pubmed.ncbi.nlm.nih.gov/21389085/
• [5] Autoimmune thyroid disease in infertility and assisted reproductive technology: A review. https://pubmed.ncbi.nlm.nih.gov/41287632/
• [6] Autoimmunity, New Potential Biomarkers and the Thyroid Gland-The Perspective of Hashimoto's Thyroiditis and Its Treatment. https://pubmed.ncbi.nlm.nih.gov/38731922/
• [7] Management of chronic hand and foot eczema. An Australia/New Zealand Clinical narrative. https://pubmed.ncbi.nlm.nih.gov/32776537/
• [8] Interferon induced thyroiditis. https://pubmed.ncbi.nlm.nih.gov/19942147/

The information provided in this article is for reference purposes only and cannot replace professional medical advice. Always consult a qualified specialist for the diagnosis and treatment of diseases.