Hypothyroidism – Symptoms and Treatment

Definition of the Disease. Causes of the Condition

Hypothyroidism is a disorder of the endocrine system that occurs due to prolonged low levels of thyroid hormones produced by the thyroid gland, and problems with their impact on the body primarily at the tissue level.

Annually, 0.6-3.5% of individuals are affected by hypothyroidism per thousand people. This disorder can occur at any age, but it usually occurs in elderly individuals over 60 years old. Among newborns, hypothyroidism occurs in one case out of 4-5 thousand.

Risk factors include:

  • Autoimmune thyroiditis;
  • Hyperthyroidism;
  • Subacute and postpartum thyroiditis;
  • Autoimmune diseases (B1-deficient anemia, Addison’s disease, type I diabetes);
  • Head and neck tissue cancer (treated);
  • Smoking;
  • Thyroid gland diseases in relatives;
  • Use of radioactive iodine in the treatment of thyroid cancer;
  • Taking certain medications (amiodarone, α-interferon, lithium carbonate, iodine-, bromine-containing, and other drugs).

In 80% of cases, hypothyroidism is associated with a weakening of the body’s defenses, i.e., autoimmune thyroiditis. It is the leading cause of primary hypothyroidism in adults.

The risk of autoimmune thyroiditis depends on the age and gender of the patient: in women aged 40-50, it occurs 10-15 times more often than in men.

In autoimmune thyroiditis, even against the background of prolonged remission, the functional state of the thyroid gland can vary significantly at different times. Thus, with age, destructive changes in the thyroid gland gradually increase. This factor, as well as the presence of thyroid autoantibodies, can provoke the transition from subclinical (hidden) hypothyroidism, which occurs against the background of autoimmune thyroiditis, to overt hypothyroidism. The frequency of such cases is about 5% per year.

Symptoms of Hypothyroidism

The symptoms of hypothyroidism are extremely deceptive, varied, and not always noticeable. Their manifestation depends on the degree of severity of the disease.

The main clinical manifestations include:

  • Metabolic-hypothermic syndrome. Characterized by constant feeling of cold, decreased body temperature, and weight gain.
  • Dysfunction of the nervous system and sensory organs. A person becomes lethargic, sluggish, experiences drowsiness, memory impairment, nasal congestion, and hearing impairment. The voice becomes low and hoarse, and speech becomes slow. Dense swelling may occur on the face and limbs. The skin thickens, becomes dry and cold, acquiring a pale color with a yellowish tint. Hair becomes dull and brittle, prone to falling out.
  • Cardiovascular system disorders. Decreased or normal blood pressure is observed. Some patients experience mild diastolic hypertension.
  • Gastrointestinal changes. Intestinal peristalsis slows down, constipation occurs, changes in the gallbladder and its ducts, decreased appetite, up to the development of anorexia.
  • Anemic syndrome. Due to a lack of thyroid hormones, depression of hematopoiesis occurs, often resulting in B12-deficient and post-hemorrhagic anemia, with increased bleeding time.
  • Kidney dysfunction. Renal blood flow and glomerular filtration rate decrease, as does the efficiency of renal plasma flow, and the level of glucose and sodium in the blood decreases below normal.
  • Reproductive system disorders. Women experience ovulation disorders, menstrual cycles become short and rare, leading to infertility. In most cases, secondary hyperprolactinemia develops, accompanied by spontaneous milk leakage from the breast and absence of menstruation. Pregnancy rarely occurs against the background of decompensated hypothyroidism. Decreased libido is observed in individuals of both sexes. Erectile dysfunction and spermatogenesis disorders may develop in men.
  • Musculoskeletal system disorders. Bone remodeling is usually slowed down, the intensity of bone resorption and bone formation decreases. Decreased bone density and rhabdomyopathy often occur, both with muscle hypertrophy and atrophy.

Pathogenesis of Hypothyroidism

Thyroid hormones produced by the thyroid gland are called “triiodothyronine” (T3) and “thyroxine” (T4). They influence almost all processes occurring in the body. Their stimulating effect is exerted by the thyroid-stimulating hormone of the pituitary gland (TSH).

The synthesis of thyroid hormones begins after the thyroid gland captures iodine. It acts as a regulator of hormonogenesis and proliferation of thyrocytes – cells of the thyroid gland epithelium. Once inside thyrocytes, iodide is oxidized to its active form with the help of thyroperoxidase – a microsomal antigen to which antibodies are formed, especially in autoimmune thyroiditis. The level of iodine intake alters the sensitivity of thyrocytes to the effects of TSH, which is enhanced in iodine deficiency.

Interaction of thyroid hormones of the thyroid gland with thyroid-stimulating hormone of the pituitary gland

Based on this mechanism of thyroid hormone formation, hypothyroidism is pathogenetically divided into four types:

  • Primary (thyrogenic);
  • Secondary (hypopituitary);
  • Tertiary (hypothalamic);
  • Peripheral (tissue).

Primary hypothyroidism occurs in 80-95% of cases and is often due to disorders in the overall structure of the thyroid gland, which can be congenital or acquired, as well as dysfunction of its secretory cells.

Secondary and tertiary hypothyroidism occur in 3-4% of cases. They are associated with diseases of such brain areas as the adenohypophysis or hypothalamus, resulting in persistent thyroid hormone deficiency and disruption of TSH secretion from the pituitary gland.

Peripheral hypothyroidism develops extremely rarely – in 0-1% of cases. Its main factor is resistance of target tissues (such as the brain, pituitary, heart, bones, liver) to T4 and T3 hormones.

Type of Hypothyroidism

  • Underdevelopment or absence of a lobe of the thyroid gland
  • Congenital disorders of thyroglobulin synthesis
  • Chronic lymphocytic thyroiditis
  • Severe iodine deficiency
  • Subacute lymphocytic thyroiditis in the hypothyroid stage
  • Loss of thyroid tissue mass
  • Surgical interventions
  • Radioactive iodine therapy for thyrotoxicosis
  • Radiation therapy for neck tumors
  • Medication intake
  • Inorganic or organic iodine
  • Antithyroid drugs
    (thionamides, potassium perchlorate, potassium thiocyanate)


  • Hypopituitarism
  • Isolated TSH deficiency
  • Hypothalamic developmental defects
  • Infections (encephalitis)
  • Tumors, sarcoidosis
  • Generalized (partial) peripheral resistance
    to thyroid hormones – T4 and T3.

In the pathogenesis of autoimmune thyroid diseases, genetic and environmental factors interact. However, the exact role of both is not determined. Cell mechanisms, i.e., cytotoxic effects of autoreactive T lymphocytes, are given primary importance in the death of thyrocytes in these diseases. The absence of classical signs of purulent inflammation (pain, swelling, and others) usually accompanying massive tissue necrosis in autoimmune thyroid damage suggests a different mechanism of thyrocyte death in such cases. In recent years, it has been established that T lymphocytes are capable of inducing target cell death not only by necrosis but mainly by inducing their destruction.

Classification and Stages of Hypothyroidism

In the International Classification of Diseases, Tenth Revision, two forms of hypothyroidism are distinguished:

  1. Subclinical (hidden) hypothyroidism, developed due to iodine deficiency.
  2. Other forms of hypothyroidism:
  • Congenital hypothyroidism with diffuse goiter;
  • Congenital hypothyroidism without goiter;
  • Hypothyroidism caused by medication and other exogenous substances;
  • Post-infectious hypothyroidism;
  • Atrophy of the thyroid gland (acquired);
  • Other specified hypothyroidisms;
  • Unspecified hypothyroidism.

Primary hypothyroidism is divided into three major groups:

  1. Congenital hypothyroidism.
  2. Hypothyroidism associated with a decrease in the amount of functioning thyroid tissue:
  • Developing after surgery;
  • Developing after radiation;
  • Caused by autoimmune thyroid disorders;
  • Associated with viral thyroid disease;
  • Developing in the presence of thyroid neoplasms.
  1. Hypothyroidism associated with impaired production of thyroid hormones:
  • Endemic goiter – occurs in areas with iodine deficiency;
  • Sporadic goiter with hypothyroidism – develops in case of hormone biosynthesis defects;
  • Drug-induced hypothyroidism – appears due to the intake of thionamides and other drugs;
  • Goiter and hypothyroidism developed due to the consumption of products containing harmful substances.

Recently, a classification of primary hypothyroidism has been developed based on the severity of symptoms and hormonal test results (with the determining factor being the TSH level). It includes:

  1. Subclinical (hidden) hypothyroidism – symptoms are vague or absent, TSH level is elevated, and T4 content is normal.
  2. Manifested hypothyroidism – typical clinical presentation of hypothyroidism, elevated TSH level, and decreased T4 concentration:
  • Compensated.
  • Decompensated.
  1. Complicated – cretinism, heart failure, serous cavity effusion, secondary pituitary adenoma, develop.

Complications of Hypothyroidism

Myxedema coma, a life-threatening condition, more commonly develops in elderly individuals who have had severe hypothyroidism for a prolonged period without treatment. The main precipitating factors for such a complication include:

  • – Hypothermia;
  • – Cardiovascular diseases;
  • – Acute infections;
  • – Trauma;
  • – Blood loss;
  • – Surgical interventions;
  • – Alcohol intake or medications suppressing the central nervous system function;
  • – Stressful situations.

In myxedema coma, body temperature typically drops to 24-32.2°C, accompanied by seizures and respiratory depression. Treatment of such a condition must commence immediately. However, even with timely detection and prompt treatment of the complication, death can occur in 25-60% of cases.

Complications can arise not only from untreated hypothyroidism but also from improper medication therapy. For instance, drug overdose can lead to excessive synthesis of thyroid hormones and cardiovascular system pathologies. Hence, it is crucial to follow all physician recommendations for disease treatment and refrain from self-medication.

Diagnosis of Hypothyroidism

Diagnosing hypothyroidism involves detailed patient history, examination, and laboratory investigations. Since the symptoms of hypothyroidism are nonspecific, it may be masked by other conditions. Therefore, laboratory tests play a crucial role in identifying hypothyroidism. They are indicated for all patients with thyroid disorders and involve assessing TSH and free T4 levels. Determining the level of T3 in the blood is generally not informative, as it remains normal in primary hypothyroidism.

High levels of TSH and low levels of free T4 in the blood indicate overt hypothyroidism. In subclinical hypothyroidism, TSH levels are elevated, while free T4 levels are within the normal range. After confirming the presence of hypothyroidism, the nature of the disease and possible complications are assessed using TSH levels. In most cases, TSH levels also help evaluate the adequacy of the therapy, with a persistent normal TSH level in the blood indicating effective treatment.

In rare cases, a thyrotropin-releasing hormone stimulation test may be conducted to assess autoimmune thyroid disorders.

Additional diagnostic methods, such as thyroid ultrasound, scintigraphy, or fine-needle aspiration biopsy, are used to refine the nature and severity of the disease.

As cases of nodular goiter increase with age, significant cervical kyphosis may displace the trachea posteriorly and downward, complicating the palpation assessment of the thyroid gland and hindering the timely diagnosis of the disease.

Treatment of Hypothyroidism

The goal of treating hypothyroidism is to maintain TSH levels within the range of 0.5-1.5 mIU/L.

The only method of treatment is lifelong replacement therapy. Initiation of therapy is recommended when TSH levels exceed 10 mIU/L, along with high titers of antibodies to thyroid peroxidase (TPO) and other indicators. Preferably, levothyroxine sodium preparations are used. Their use is contraindicated only in cases of untreated thyrotoxicosis, adrenal insufficiency, acute myocardial infarction, allergy, and individual intolerance to the drug.

Treatment is usually administered in a hospital setting. Indications for hospitalization of patients with hypothyroidism include:

  • Severe disease;
  • Presence of significant cardiac pathology;
  • Myxedema coma.

Replacement therapy for primary (manifest) hypothyroidism is indicated lifelong with the administration of levothyroxine at an average dose of 1.6-1.8 mcg/kg. For patients with cardiac pathology, the dose is calculated at 0.9 mcg/kg. It should be noted that due to decreased metabolism of thyroid hormones, the need for them decreases with age.

The doses of levothyroxine depend on the etiology and pathogenesis of the disease. The requirement for the drug is higher in individuals with spontaneous hypothyroidism compared to those with hypothyroidism occurring after surgery or radioactive iodine therapy.

The TSH level at the time of hypothyroidism diagnosis is directly related to the optimal replacement dose of levothyroxine: for most women, it is 75-100 mcg, and for men, up to 150 mcg per day.

The first TSH level control after initiating treatment is performed after 2-3 months, then once every six months (with the mandatory condition of patient compliance with the treatment regimen).

Subclinical hypothyroidism carries the risk of developing the manifest form of the disease with all its characteristic manifestations. Clear hypothyroidism occurs in 20-50% of patients within 4-8 years, and the presence of antithyroid antibodies increases the risk to 80%. Therefore, individuals with subclinical hypothyroidism should be closely monitored by specialists for an extended period.

Challenges in the Treatment of Hypothyroidism

Treatment with thyroxine is safe, simple, and relatively inexpensive. However, despite years of experience in its use, several problems may arise. The main issue is related to patients not adhering to the treatment regimen. For instance, simultaneous increases in T4 and TSH levels likely indicate that the patient did not follow the prescribed treatment regimen in the days leading up to their doctor’s visit.

The reduction in the effectiveness of the established levothyroxine dose is often associated with lower hormone content in the tablets (e.g., in generic formulations) or drug interactions when other medications are taken simultaneously.

Insufficient dosage may also result from reduced levothyroxine absorption, disruption of enterohepatic circulation, accelerated metabolism of thyroxine, decreased thyroxine-binding globulin levels, or slow decline in thyroid function after hyperthyroidism treatment.

Other specific issues and problems in hypothyroidism treatment include:

FactorsAssociated Conditions and Issues
Drug interactions during concurrent medicationReduced absorption of levothyroxine
Acceleration of levothyroxine metabolismReduction in thyroid hormone-binding globulin levels
Heart diseases exacerbation of underlying ischemic heart diseaseAngina
Bone mineral density adverse effects of levothyroxine overdosePregnancy may require an increase in levothyroxine dosage
Hypothyroidism in elderly patients difficulty in diagnosisInitial lower replacement doses of levothyroxine
Transient hypothyroidismTemporary levothyroxine administration may be recommended
Mixedema coma difficulty in levothyroxine or triiodothyronine dosage adjustmentNecessary thorough follow-up investigations are required
Adrenal insufficiency combination of adrenal and thyroid insufficiencyReduction in TSH levels with corticosteroid therapy alone
Need for thyroxine and corticosteroid administration in some cases of hypopituitarismNo need to compensate for hypothyroidism before impending surgery
Hypothyroidism may increase sensitivity to usual doses of anesthetics and sedativesLung diseases association of hypothyroidism with sleep apnea
Worsening of asthma during levothyroxine treatmentMental illnesses association of hypothyroidism with psychiatric disorders
Possible remission with levothyroxine treatment

The best criterion for adjusting levothyroxine dosage in autoimmune thyroiditis is the evaluation of TSH and free T4 levels. Treatment aims to compensate for hypothyroidism through replacement therapy and reduce goiter with suppressive therapy. The effectiveness of treatment is judged by:

  • Reduction in goiter volume
  • Decrease in thyroid gland density
  • Reduction in antibody titer to normal levels
  • Maintenance of TSH levels within the normal range

Prescribing thyroid hormone preparations for autoimmune thyroiditis without impaired thyroid function is not advisable, and surgery may lead to a condition that significantly impairs the patient’s quality of life, with the potential for severe hypothyroidism and disability.