Hyperthyroidism

Introduction and Facts

Hyperthyroidism (Graves' disease, PG) or also called thyrotoxicosis is a condition due to increased levels of free thyroid hormone in the blood. PG was first reported by Parry in 1825, then Graves in 1835 and followed by Basedow in 1840. The distribution of sex and age in hyperthyroidism varies greatly from clinic to clinic. The ratio of women and men obtained at the Palembang Hospital was 3.1 : 1 at the RSCM Jakarta was 6 : 1, at the RS. Dr. Soetomo 8 : 1 and at RSHS Bandung 10 : 1.1 While the distribution of age at RSUP Palembang is mostly at the age of 21 - 30 years (41.73%), but according to several other authors, the peak is between 30-40 years.

There are several known diseases that can cause hyperthyroidism with the most common causes being toxic diffuse goiter and toxic nodular goiter, both multinodular and solitary types. Several other causes of hyperthyroidism can be found in subacute thyroiditis, chronic autoimmune thyroiditis, thyroid carcinoma, goiter ovary, exogenous hyperthyroidism, hyperthyroidism due to iodine use. Of the various causes of hyperthyroidism, Graves' disease (PG) or Basedow's disease or Parry's disease is the most common cause.

Pathophysiology

Hyperthyroidism is a clinical condition caused by excessive secretion of thyroid hormones, namely thyroxine (T4) and triiodothyronine (T3). There was also an increase in triiodothyronine (T3) production as a result of increased thyroxine (T4) conversion in peripheral tissues.

Under normal circumstances, thyroid hormone affects tissue metabolism, tissue oxidation processes, growth processes and protein synthesis. These thyroid hormones affect all cells in the body through the mechanism of transport of amino acids and electrolytes from extracellular fluid into cells, activation/synthesis of protein enzymes in cells and enhancement of intracellular processes.

In adult mammals the efficacy of thyroid hormone is seen, among others:

 - increased lipolytic activity in adipose tissue

 - modulation of gonadotropin secretion

 - maintain growth of cell proliferation and hair maturation

 - stimulates the sodium pump and glycolytic pathway, which results in calorigenesis and oxidative phosphorylation in liver, kidney and muscle tissue.

With increasing levels of this hormone, tissue metabolism, protein synthesis and others will be affected, this situation will be clinically seen with palpitations, tachycardia, atrial fibrillation, weakness, sweating, increased appetite, decreased body weight. Sometimes the only clinical symptoms are weight loss, heart failure, muscle weakness and frequent bowel movements for unknown reasons.

The pathogenesis of PG is still unclear. It is suspected that the increase in thyroid hormone levels is caused by a thyroid activator that is not TSH which causes the thymid gland to be hyperactive. This activator is an antibody against the TSH receptor, so it is called a TSH receptor antibody. This antibody is often referred to as thyroid stimulating immunoglobulin (TSI). And it turns out that this TSI is found in almost all patients with PG.

In addition, in PG, antibodies to thyroglobulin and anti-microsomes are often found. Further studies showed that these two antibodies have a role in the occurrence of damage to the thyroid gland. These microsomal antibodies can be found in almost 60-70% of patients with PG, even with radioassay examination can be found in almost all patients, while thyroglobulin antibodies can be found in 50% of patients. The formation of these autoantibodies is thought to be due to the effect of immunologic control (immunoregulation), this defect is influenced by genetic factors such as HLA2 and environmental factors such as infection or stress. In toxic nodular goiter, the increase in thyroid hormone levels is caused by the autonomization of the associated nodule with excessive function, while the rest of the gland functions normally or decreases.

Clinical Symptoms and Complications

The clinical picture of hyperthyroidism can be mild with complaints that are difficult to distinguish from anxiety reactions, but can be severe to life-threatening for the patient because of the onset of hyperpyrexia, circulatory disorders and collapse. The chief complaint is usually one of increased nervousness, palpitations or fatigue. From research on a group of patients, 10 prominent symptoms were found, namely:

 - Nervousity

 - Fatigue or muscle weakness

 - Moderate weight loss, good appetite

 - Diarrhea or frequent bowel movements

 - Intolerance to hot air

 - Excessive sweating

 - Changes in menstrual pattern

 - Tremor

 - Pounding

 - Eye and neck protrusion

The symptoms of hyperthyroidism can last from a few days to several years before the patient goes to the doctor, and often a patient is not aware of the disease.

Diagnosis

On clinical examination, a typical picture was obtained, namely: a patient is tense with rapid speech and behavior, signs in the eyes, wet and warm palms, tremors, onchlysis, vitiligo, neck enlargement, rapid pulse, arrhythmias, pulse pressure. height and shortened Achilles reflex time. On the basis of these clinical signs, a clinical diagnosis can be established.

For areas where specific laboratory tests for thyroid hormone cannot be performed, the use of the Wayne and New Castle indices is helpful in establishing the diagnosis of hyperthyroidism. Basal metabolic measurement (BMR), if the BMR is > ± 30, it is very likely that a person has hyperthyroidism.

To confirm the diagnosis, it is necessary to do a thyroid function test, such as T4 and T3 levels, free T4 levels or free thyroxine index (FT41). Other tests that can help establish the diagnosis include: thyroid antibody examination, which includes anti-thyroglobulin and antimicrosomes, measurement of serum TSH levels, radioactive iodine uptake test and thyroid scanning.

Management and Care

General Treatment:

1) Rest. This is necessary so that the patient's hypermetabolism does not increase. Patients are advised not to do any work that is tiring/disturbing the mind either at home or at work. In severe cases, total bed rest is recommended at the hospital.

2) Diets. The diet should be high in calories, protein, multivitamins and minerals. This is partly due to: an increase in metabolism, a negative nitrogen balance and a negative calcium balance.

3) Sedatives. Given the frequent occurrence of anxiety in PG, then a sedative can be given. In addition, it is also necessary to provide psychotherapy.

Special Treatment.

1. Anti-thyroid medication. These medications slowly relieve the symptoms of hyperthyroidism by preventing the thyroid gland from producing too much hormone. Anti-thyroid drugs include methimazole and propylthiouracil. Symptoms usually begin to improve within a few weeks to months. Treatment with anti-thyroid drugs usually lasts 12 to 18 months. After that, the dose can be reduced or stopped slowly if the symptoms have disappeared and if the blood test results show that thyroid hormone levels have returned to the standard range. For some people, anti-thyroid drugs put hyperthyroidism into long-term remission. But others may find that hyperthyroidism returns after this treatment. Although rare, serious liver damage can occur from both anti-thyroid drugs. However, because propylthiouracil has caused more cases of liver damage, it is generally only used if the patient cannot take methimazole. A small number of people who are allergic to these drugs may experience skin rash, itching, fever, or joint pain and may increase the risk of infection.
2. Iodine. Iodine administration will inhibit hormone synthesis acutely but within 3 weeks the effect will disappear due to an escape mechanism from the gland in question, so that even though secretion is inhibited, synthesis is still present. As a result, there is an accumulation of hormones and when iodine is stopped, excessive secretion occurs and the symptoms of hyperthyroidism intensify.
3. Beta Blockers (Beta Blockers). The occurrence of complaints and symptoms of hyperthyroidism is caused by hypersensitivity to the sympathetic system. The increased stimulation of the sympathetic system is thought to be due to the increased sensitivity of receptors to catecholamines.
4. Ablation of adenoids. Performing surgical ablation or administration of I131.

• Surgery. The main indications for surgery are those who are young and fail or are allergic to antithyroid drugs. Surgery in the form of a subtotal thyroidectomy is also recommended in patients with conditions that cannot be treated with I131.
• Ablation with I131. Since the discovery of I131 there has been a change in the field of hyperthyroidism treatment. Although there are many complications that arise after treatment, but because it is cheap and easy to administer, this method is widely used.

References:

1. Jonathan S, Damayanti T, Antariksa B. Patofisiologi emfisema. Jurnal Respirologi Indonesia. 2019:39(1):60-9
2. Hermawan AG . Pengelolaan dan pengobatan hipertiroid. Cermin Dunia Kedokteran 1990:63:51-5.
3. Mayo Clinic. Hyperthyroidism (overactive thyroid) [Internet]. 2022. Available from: https://www.mayoclinic.org/diseases-conditions/hyperthyroidism/diagnosis-treatment/drc-20373665