How the Thyroid Gland Works and Regulates Hormones

Thyroid gland is an organ located in the lower front part of the neck. The main function of the thyroid gland is to produce triiodothyronine (T3) and thyroxine (T4). Thyroid hormones are key regulators of basal energy expenditure and metabolism, regular cell development and differentiation, neurodevelopmental processes in the first years of life, linear growth, body composition, and weight. Normal thyroid function is regulated by the hypothalamic thyrotropin-releasing hormone (TRH) that stimulates the release of the thyroid-stimulating hormone (TSH) from the pituitary gland. In turn, TSH drives the synthesis and secretion of thyroid hormones from the thyroid gland. TSH and TRH levels increase when circulating thyroid hormone levels are low, and vice versa. Serum TSH and free thyroxine (FT4) concentrations are routinely used to assess thyroid function of an individual in everyday clinical practice. Free T3 or free T4 measures an active thyroid hormone which is not bound to protein, and is able to affect body tissues. Total T3 or total T4 measures the bound and free hormone, which can be influenced by protein levels in the blood. Tests measuring free hormones more accurately reflect how the thyroid gland is functioning.

Common Thyroid Disorders: Hypothyroidism and Hyperthyroidism

Hypothyroidism: Causes, Symptoms and Treatment

Hypothyroidism is a condition characterized by reduced production and secretion of thyroid hormones. In primary hypothyroidism, the thyroid gland cannot produce adequate thyroid hormones. The less commonly seen secondary hypothyroidism results from abnormal pituitary gland function. The main indicator of the hypothyroid condition is a low level of thyroid hormones and an elevated TSH level. The most common cause of hypothyroidism is Hashimoto’s thyroiditis. Patients with hypothyroidism require lifelong thyroid hormone replacement treatment with levothyroxine. The primary goal of treatment is to provide the appropriate daily dose of thyroid hormone to restore normal thyroid function for each individual patient.

Hashimoto’s Thyroiditis as a Cause of Hypothyroidism

Hashimoto’s thyroiditis is an autoimmune disease in which a dysfunctional immune system leads to chronic damage of thyroid tissue, followed by replacement of the damaged areas with scar tissue and lymphocytes. This diagnosis is more common in women, and its prevalence increases with age. The disease is characterized by positive antibodies against thyroglobulin and thyroid peroxidase. Metabolism slows down due to a decline in hormone levels. Patients most often complain of fatigue, poor concentration and memory, sensitivity to cold, constipation, weight gain, hair loss, low mood, a sensation of choking or tightness in the neck, and lack of motivation.

Hyperthyroidism: Symptoms, Risks and Management

Hyperthyroidism is a condition of excessive production and secretion of thyroid hormones into the blood. The main indicators are elevated levels of thyroid hormones and a decreased level of TSH. An accelerated metabolism of substances and nutrients in the body may lead to the development of other health problems after a prolonged period of hyperthyroidism. In most cases, the cause of hyperthyroidism is Basedow–Graves disease, but other possible causes include multinodular toxic goiter, toxic adenoma, and thyroid inflammation. Untreated hyperthyroidism can cause cardiac arrhythmias, congestive heart failure, osteoporosis, adverse obstetric outcomes, and metabolic derangements such as increased resting energy expenditure and gluconeogenesis. Treatment should be patient-centered and individualized, taking into account age, comorbidities, severity of hyperthyroidism, likelihood of remission, plans for pregnancy, available surgical expertise, and patient preferences.

Basedow–Graves Disease and Autoimmune Hyperthyroidism

Basedow–Graves disease is an autoimmune disorder that occurs more frequently in younger women. It is manifested by diffuse enlargement of the thyroid gland, which can be accompanied by bulging eyes. A hallmark of the disease is the presence of antibodies against thyroglobulin, thyroid peroxidase, and TSH receptor. Patients most commonly complain of palpitations, accelerated digestion, weight loss despite increased appetite, feeling hot and sweating, insomnia, changes in the menstrual cycle and sexual desire, nervousness, and trembling hands. In patients with Graves’ disease, treatment should focus on controlling hyperthyroidism with the anticipated eventual remission of Graves’ disease with antithyroid drugs. Antithyroid drugs decrease thyroid hormone synthesis and secretion. In patients who do not achieve remission, or in those whose hyperthyroidism remits and then recurs, definitive therapy with radioactive iodine or thyroidectomy should be considered.

Multinodular Toxic Goiter and Toxic Adenoma

Multinodular toxic goiter is a disease characterized by multiple nodules in the thyroid gland that secrete thyroid hormones excessively without regulation by the pituitary gland. A toxic adenoma is a type of benign tumor that similarly excessively secretes thyroid hormones. Toxic nodular goitre and toxic adenoma are mostly treated with radioactive iodine or thyroidectomy.

Thyroid Tumors and Thyroid Cancer

A tumor is an abnormal accumulation of tissue. Tumors can be benign or malignant. The etiology of thyroid carcinoma is not fully understood. However, it is known that a higher risk is present in females, individuals with a family history of cancer, those who have been exposed to radiation, and that it occurs more frequently after the age of thirty.

Benign Thyroid Tumors: Follicular Adenoma

Follicular adenoma is the most common epithelial benign tumor. It occurs in all age groups, but more often in young adults. These are solitary, spherical formations with a diameter of less than 3 cm. Adenomas may be functional (toxic) or non-functional. Functional adenomas produce thyroid hormones uncontrollably, without activation of the pituitary gland.

Malignant Thyroid Tumors: Types and Treatment Options

Malignant tumors of the thyroid gland are very rare and account for about 1% of all malignant tumors. They can be differentiated (papillary and follicular) or undifferentiated (medullary and anaplastic). Differentiated tumor cells resemble normal tissue cells. Tumors made up of such cells respond better to treatment. Undifferentiated tumors are made up of cells that do not resemble normal tissue, so they behave more aggressively and require a more aggressive approach to treatment. Malignant tumors occur somewhat more frequently in women, typically between 30 and 45 years of age. Treatment options are determined by the type and stage of thyroid cancer. Surgically removing the thyroid gland is a common approach. Any remaining cancer cells are then treated with radioactive iodine therapy. After surgical removal of the thyroid gland, patients need to take thyroid hormone replacement therapy for the rest of their lives to maintain normal physiological processes. External beam radiation therapy may be an option for individuals whose aggressive or advanced thyroid tumors do not respond to standard care.

Papillary Thyroid Carcinoma

Papillary carcinoma is the most common thyroid cancer. This type of cancer has the best prognosis. It is more often diagnosed before the age of 40. It can remain localized in the gland for years, but in some patients, metastases to the cervical lymph nodes are already present at the time of diagnosis.

Follicular Thyroid Carcinoma

Follicular carcinoma is the second most common type of thyroid cancer. It occurs mainly in middle-aged and older individuals. This type of cancer is more aggressive than papillary thyroid carcinoma, but likewise has a good prognosis for recovery.

Medullary Thyroid Carcinoma

Medullary carcinoma is a rare type of thyroid cancer. It occurs in middle and late adulthood, usually sporadically as a solitary thyroid nodule. The prognosis of medullary thyroid cancer is usually not as favorable as that of differentiated thyroid cancers.

Anaplastic Thyroid Carcinoma

Anaplastic carcinoma is the rarest histological type of thyroid cancer, but it is extremely aggressive. Compared with other types of thyroid carcinoma, it unfortunately has the worst prognosis.

Current Research and Advances in Thyroid Disease Treatment

Since thyroid disorders are largely a consequence of a hectic lifestyle, it is important to introduce some changes in an individual’s daily life. In the treatment of thyroid disease, in addition to medication, the importance of a proper diet is also emphasized. The diet should be varied and balanced, with frequent fluid intake. There is no specific diet therapy for thyroid problems, but the Mediterranean diet is recommended, as it has proven to be extremely beneficial for a wide range of health problems. It is important to emphasize the importance of consuming minimally processed foods or avoiding industrially prepared foods that are abundant in stores. Selenium and selenoproteins are important in the creation and metabolism of thyroid hormones. They have an anti-inflammatory effect, can reduce the titer of thyroid peroxidase antibodies, have a positive effect on hypothyroidism, and result in a reduction in the required dose of levothyroxine.

In addition to existing diagnostic methods, additional research is being conducted for the purpose of earlier detection of diseases, personalized medicine, and better treatment methods. The association of various inflammatory parameters with thyroid disorders is being investigated to serve as additional diagnostic tools. The involvement of various genes in thyroid diseases is also being examined, which could be useful in a personalized approach to patients in the future. Several international ultrasound-based thyroid nodule risk stratification systems have been developed with the goal of reducing unnecessary biopsies. Less invasive alternatives to surgery for low-risk thyroid cancer, such as active surveillance and minimally invasive interventions, are being explored. New systemic therapies are now available for patients with advanced thyroid cancer. The progress of targeted therapy and biomarker research in thyroid cancer represents a possible change in therapeutic methods aimed at precision and individualization.

Author: Marija Banović (Polyclinic Leptir)

References

1. Patil N, Rehman A, Anastasopoulou C, et al. Hypothyroidism. [Updated 2024 Feb 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK519536/
2. Mathew P, Kaur J, Rawla P. Hyperthyroidism. [Updated 2023 Mar 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537053/
3. Guo M, Sun Y, Wei Y, Xu J and Zhang C. (2024) Advances in targeted therapy and biomarker research in thyroid cancer. Front. Endocrinol. 15:1372553. doi: 10.3389/fendo.2024.1372553
4. Brčić L, Barić A, Gračan S, Brdar D, Torlak Lovrić V, Vidan N, Zemunik T, Polašek O, Barbalić M, Punda A, Boraska Perica V. (2016): Association of established thyroid peroxidase autoantibody (TPOAb) genetic variants with Hashimoto’s thyroiditis, Autoimmunity, DOI: 10.1080/08916934.2016.1191475