Last updated date: 07-May-2023
Originally Written in English
The thyroid gland is a bilobed organ found between the cricoid cartilage and the suprasternal notch in the front side of the trachea. A thyroid isthmus joins each lobe of the thyroid. The superior thyroid artery, which branches from the external carotid artery, and the inferior thyroid artery, a branch of the thyrocervical trunk, supply it. The word "hyperthyroidism" refers to a condition characterized by excessive thyroid hormone production.
It is a prevalent misperception that the terms thyrotoxicosis and hyperthyroidism are interchangeable. Excess thyroid hormone exposure to tissues is referred to as "thyrotoxicosis." Although hyperthyroidism and thyrotoxicosis are related and can be used interchangeably, it is vital to distinguish between the two.
The word "hyperthyroidism" refers to a condition characterized by excessive thyroid hormone production. In other words, the thyroid gland is hyperactive. Another word for this condition is thyrotoxicosis, which refers to elevated thyroid hormone levels in the bloodstream regardless of the cause.
Thyroid gland physiology
The thyroid gland is covered by a thin layer of connective tissue that penetrates the gland and splits it into compartments. The thyroid gland is made up of spherical, polarized follicular cells that surround a thyroglobulin-rich gel-like colloid. Thyroglobulin is the organic precursor for thyroid hormones, and it requires iodide to be converted into thyroid hormone.
After being converted to iodide by the thyroid peroxidase enzyme, dietary iodine is delivered into thyroid follicular cells through the sodium-iodide symporter. The incorporation of iodide into monoiodotyrosine (MIT) or diiodotyrosine (DIT) molecules is known as organification, and the process is generally self-regulated. The Wolff-Chaikoff effect occurs when low dietary iodide facilitates upregulation of the sodium-iodide symporter and high dietary iodide temporarily slows the organification process.
The peroxidase enzyme is responsible for the incorporation of iodide into the thyroid hormone precursors, MIT and DIT. The organic coupling of one MIT molecule with one DIT molecule produces triiodothyronine (T3), whereas the coupling of two DIT molecules produces thyroxine (T4).
Thyroxine (T4) is secreted by the thyroid gland in response to thyroid-stimulating hormone (TSH) released by the anterior pituitary gland. Deiodinase enzymes convert the released T4 to the more powerful triiodothyronine (T3). Although the thyroid gland has the inherent potential to produce T3, the majority of the conversion of T4 to T3 occurs outside of the thyroid.
In response to low circulating thyroid-stimulating hormone (TSH), T3, or T4, the hypothalamus produces thyrotropin-releasing hormone (TRH). TRH stimulates anterior pituitary release of thyroid-stimulating hormone (TSH), which stimulates thyroid gland T4 output. T4 and T3 regulate both the hypothalamus and the anterior pituitary.
Graves disease is the most frequent cause of hyperthyroidism in the United States and other Western nations. Because Graves disease is autoimmune in nature, this kind of hyperthyroidism is more common in younger people. Toxic multinodular goiter is the most prevalent cause of hyperthyroidism in the elderly.
Although Graves disease and toxic multinodular goiter are the most common causes of hyperthyroidism, iodine-induced hyperthyroidism (Jod-Basedow phenomenon), thyroid adenomas, de Quervain thyroiditis (subacute thyroiditis), postpartum thyroiditis, and factitious thyroiditis are also causes of hyperthyroidism (thyrotoxicosis factitia).
Factitious thyroiditis is hyperthyroidism caused by the inadvertent or excessive use of pharmaceutical thyroid hormone. Thyroxine has the potential for abuse due to a well-received side effect of weight loss, and every history of a hyperthyroid patient should include a drug list and an assessment of potential misuse.
Ectopic foci of thyroxine-secreting tissue are another cause of hyperthyroidism. The more common (albeit rare) variant of this etiology is struma ovarii, which consists of ectopic and functioning thyroid tissue in the ovary.
Iodine-associated hyperthyroidism or thyrotoxicosis can be caused by amiodarone or other iodine-containing drugs. The Jod-Basedow phenomenon refers to iodine-induced hyperthyroidism (Jod is the German word for iodine).
The incidence of hyperthyroidism varies by ethnic group, but in Europe, the frequency is controlled by dietary Iodine intake, and some instances are linked to autoimmune illness. Subclinical hyperthyroidism affects women more than males after the age of 65, but overt hyperthyroidism affects 0.4 per 1000 women and 0.1 per 1000 men and varies with age.
Any investigation of the worldwide epidemiology of hyperthyroidism will distinguish between iodine-sufficient and iodine-deficient locations. While an overabundance of iodine can cause hyperthyroidism, a lack of iodine can cause both hypothyroidism and hyperthyroidism.
Graves disease is particularly frequent in younger individuals and is the leading cause of hyperthyroidism in that age group. Toxic multifocal goiter is most frequent in elderly people and is the most common cause of hyperthyroidism in this age group. Graves disease and toxic multifocal goiter are both more common in women and are often found in individuals with relevant familial and personal medical histories.
The Whickham Survey, conducted in 1977 in County Durham, northern England, assessed the range of thyroid problems. Although the Whickham Study's demographics comprised of main inhabitants of a village in northern England (and so had weak extrapolation ability), the survey did offer noteworthy hyperthyroidism results. According to the Whickham Survey, women had nearly ten times the prevalence of hyperthyroidism as males.
The pathophysiology of hyperthyroidism varies depending on the kind of hyperthyroidism. The underlying cause of Graves disease is autoimmune, namely the development of thyroid-stimulating immunoglobulins that bind to the TSH receptor and mimic the actions of TSH. Graves disease is distinguished by two extra-thyroidal symptoms that are not observed in other types of hyperthyroidism. Graves disease ophthalmopathy is distinguished by edema of retro-orbital tissues, resulting in anterior protrusion of the ocular globes. Pretibial myxedema is a plaque-like thickening of the skin anterior to the tibia caused by dermal glycosaminoglycan infiltration.
Toxic multinodular goiter is characterized by palpable thyroid nodules. It is the major cause of hyperthyroidism, especially among the elderly. Toxic multinodular goiter causes increased thyroid hormone production from autonomous ectopic tissue, resulting in clinical thyrotoxicosis.
Thyroid adenoma, as contrast to toxic multinodular goiter, which can appear with numerous nodules, normally presents with a single papillary lesion that has the potential to cause hyperthyroidism. The clinical appearance of hyperfunctioning thyroid adenomas distinguishes them from thyroid carcinomas. Thyroid hormone production by thyroid carcinomas is minimal, and thyroid hormone levels are not high enough to generate overt hyperthyroidism. As a result, thyroid adenomas are usually harmless.
Thyroiditis-related hyperthyroidism causes a transitory rise in circulating thyroid hormone due to mechanical rupture of thyroid follicles. Subacute thyroiditis (De Quervain thyroiditis) usually occurs after an acute illness, such as an upper respiratory infection. It is a granulomatous inflammatory condition that results in a delicate thyroid gland.
Painless thyroiditis is a kind of hyperthyroidism that is most common in the postpartum period. It is lymphocytic thyroiditis, and it may be separated from subacute thyroiditis by the clinical history and thyroid gland palpation.
Iodine-induced hyperthyroidism (Jod-Basedow phenomenon) is usually caused by the injection of iodine-containing drugs such as contrast media or amiodarone. As previously stated, the conversion of iodide residues into precursor thyroid hormone molecules is generally self-regulating.
The Wolff-Chaikoff effect occurs when there is an excess of circulating iodide, which prevents organification. Professionals think that in individuals with iodine-induced hyperthyroidism, regions of autonomous function allow for increased thyroid hormone release in the presence of high iodide levels.
Discontinuation of the problematic agent usually results in hyperthyroidism remission. There are two forms of amiodarone-induced thyrotoxicosis: type 1 and type 2. The history, diagnostic findings, and therapy all point to a differentiation between the two kinds. Patients with type 1 amiodarone-induced thyrotoxicosis often have pre-existing thyroid disease, limited RAI absorption, and increased thyroid parenchymal blood flow.
Typically, anti-thyroid medication is used to treat the condition. In contrast, patients with amiodarone-induced thyrotoxicosis type 2 may not have a history of thyroid illness. Diagnostic tests may reveal poorer RAI uptake and decreased thyroid parenchymal blood flow. Steroids are frequently used to treat type 2 variation. While amiodarone therapy can result in hyperthyroidism due to increased iodine exposure, amiodarone itself can be directly cytotoxic, adding to thyroid damage.
Excessive amounts of chorionic gonadotropin, as found in trophoblastic tumors, can produce hyperthyroidism via weak stimulation of the TSH receptors. This etiology of hyperthyroidism, however, is far more uncommon than the previously described causes of hyperthyroidism.
Symptoms of Hyperthyroidism
Weight loss despite increased hunger, palpitation, agitation, tremors, dyspnea, fatigability, diarrhea or increased GI motility, muscular weakness, heat sensitivity, and diaphoresis are all symptoms of hyperthyroidism. Thyroid hormone exposure to peripheral tissues manifests as signs and symptoms of a hypermetabolic condition. A patient with hyperthyroidism often has signs and symptoms consistent with this condition of elevated metabolic activity.
Unintentional weight loss despite unaltered oral intake, palpitations, diarrhea or increased frequency of bowel movements, heat sensitivity, diaphoresis, and/or menstrual abnormalities are common symptoms that a patient may describe.
A thyroid check may or may not detect an enlarged thyroid (referred to as goiter). The thyroid gland might be diffusely enlarged, or one or more nodules could be palpated. The thyroid gland might be asymptomatic or highly painful to even gentle probing.
Thyroid stimulating hormone (TSH) is the preferred first diagnostic test and is regarded as the best screening test for evaluating thyroid pathology and monitoring thyroid replacement medication. Increased T3 and/or elevated T4 will produce lower TSH production from the anterior pituitary gland due to the negative feedback that T3 and T4 impose on the pituitary gland. An abnormal TSH level is frequently followed by a free T4 and/or free T3 assay. Concerns about an autoimmune disorder, such as Graves disease, will necessitate additional investigation, which will include testing blood levels of TSH-receptor antibodies.
TSH levels should be read with caution in the setting of acute sickness since they are significantly more vulnerable to the effects of illness.
Because hyperthyroidism is a prevalent cause of atrial fibrillation, further workup with an ECG may be necessary, especially if the patient complains of palpitations. Obtaining troponin levels is not usual unless the clinical presentation, such as active chest discomfort, demands additional cardiac ischemia workup.
Chest x-rays, for example, have minimal diagnostic use in the treatment of hyperthyroidism. Ultrasound is not effective in detecting hyperthyroidism, although the ultrasound findings of nodules may help pinpoint an etiology.
Because the majority of cases of hyperthyroidism are caused by Graves disease or toxic multinodular goiter, the diagnosis can be confirmed based on history, clinical findings, and thyroid palpation. A 24-hour radioactive iodine uptake (RAIU) is required to differentiate Graves disease from other hyperthyroidism etiologies in situations of diffuse goiter or no thyroid enlargement. The percentage of iodine-131 retained by the thyroid after 24 hours is referred to as radioactive iodine absorption. The usual range of RAIU for the typical western diet is typically 10% to 30%.
Graves disease, toxic multinodular goiter, and thyroid adenoma are causes of hyperthyroidism with elevated RAIU, indicating increased thyroid hormone production. Subacute thyroiditis, painless thyroiditis, iodine-induced hyperthyroidism, and factitious hyperthyroidism all resulted in lower RAIU levels. Thyroiditis is characterized by the destruction of thyroid follicles and the resultant release of thyroid hormone. Thyroiditis causes a decrease in RAIU because there is no increased production of thyroid hormone.
If RAIU is not accessible or is contraindicated, thyroid receptor antibodies can be measured as an alternate test for Graves disease diagnosis.
A radioisotope thyroid scan is a type of diagnostic imaging that uses technetium-99m pertechnetate as a radioactive tracer. The sodium-iodide symporter transports technetium-99m pertechnetate to the thyroid gland. The scan itself evaluates thyroid nodule functional activity, categorizing them as "cold" (hypofunctioning), "warm" (isofunctioning), or "hot" (hyperfunctioning). "Cold" nodules raise concerns for probable malignancy due to inefficient iodide absorption and thyroid hormone production, as seen in thyroid carcinomas.
The treatment of hyperthyroidism is separated into two groups based on the underlying etiology: symptomatic therapy and definitive therapy. Hyperthyroidism symptoms such as palpitations, anxiety, and tremor can be managed with a beta-adrenergic antagonist such as atenolol. Calcium channel blockers, like as verapamil, can be used as a second-line treatment in individuals who are intolerant to beta-blockers or have contraindications to beta-blocker medication.
Transient types of hyperthyroidism, such as subacute thyroiditis or postpartum thyroiditis, should be treated solely with symptomatic medication because the hyperthyroidism is self-limiting in these clinical settings.
Radioactive iodine therapy (RAI), thionamide therapy, and partial thyroidectomy are the three final therapies for hyperthyroidism, all of which predispose the patient to long-term hypothyroidism. Clinical evaluation and monitoring of free T4 levels are essential for individuals undergoing any of these medications.
TSH monitoring is ineffective after final treatment because TSH stays lowered until the patient becomes euthyroid. As a result, TSH monitoring for thyroid function is not advised soon after final medication.
The etiology influences the choice of definitive treatment modality. Because of its excellent effectiveness, RAI therapy is considered the treatment of choice in practically all Graves disease patients. Despite its relative safety and excellent effectiveness, RAI is not recommended for pregnant or nursing individuals.
RAI treatment involves the administration of radioactive iodine-131 and the subsequent destruction of thyroid tissue. A single dosage is enough to manage hyperthyroidism in a considerable proportion of patients, and the effects on other regions of the human body are basically insignificant due to the radioactive iodine-131's strong thyroid absorption.
Prior to starting RAI therapy in a female patient with reproductive potential, it is strongly advised to take a beta-hCG to rule out pregnancy. Any patient using a thionamide (methimazole or propylthiouracil) should be told to stop taking it about a week before starting RAI therapy since thionamides can interfere with the therapeutic efficacy of RAI therapy.
Several months of post-RAI treatment are usually required to achieve euthyroid state. Patients are typically examined every 4 to 6 weeks, with longer time intervals for stable, plasma-free T4 levels. Failure to achieve euthyroidism following RAI therapy may signal the necessity for repeat RAI therapy (for symptomatic hyperthyroidism) or the start of thyroxine medication (for hypothyroidism).
RAI treatment includes the release of thyroid hormone that has been stored, resulting in transitory hyperthyroidism. Although this temporary hyperthyroidism is often well tolerated, it is cause for worry in those with substantial heart problems. Pretreatment with a thionamide to deplete the stored hormone is indicated for individuals with cardiac disease to minimize the possible aggravation of cardiac illness.
Thionamide therapy is used as a last treatment for hyperthyroidism in patients who are hesitant to undertake RAI therapy or who have contraindications to RAI therapy, such as allergy or pregnancy. Methimazole and propylthiouracil both impede thyroid peroxidase-mediated thyroid hormone production.
Thyroid peroxidase is the enzyme in charge of converting dietary iodine to iodide. Propylthiouracil (PTU) also reduces active thyroid hormone availability in peripheral tissues by inhibiting the extrathyroidal conversion of T4 to T3. Thionamide medication has little long-term effect on thyroid function, and patients who cease thionamide therapy frequently experience hyperthyroidism remission.
Typically, it takes many months after starting thionamide medication to achieve euthyroid state. Although methimazole and PTU are both effective, methimazole is chosen due to a lower risk of side effects. This suggestion is deviated from in pregnant individuals, for whom PTU is suggested. Methimazole has been linked to an increased risk of congenital abnormalities, hence PTU is favored in the treatment of gestational hyperthyroidism.
Agranulocytosis, hepatitis, vasculitis, and drug-induced lupus are among side effects of thionamide treatment. Although these are uncommon adverse effects, patients should be cautioned of their possibility. Patients should also be urged to stop taking thionamide immediately and to tell their doctor if signs of agranulocytosis develop (fever, chills, rapidly progressive infection, sore throat, among others).
Due to the quick development of agranulocytosis, routine monitoring of leukocyte counts is not indicated when beginning a patient on a thionamide. Due to the possibility of hepatitis, a baseline complete metabolic panel (CMP) to test hepatic function would not be unjustified.
Subtotal thyroidectomy is used to treat hyperthyroidism on a long-term basis. Pretreatment with methimazole to attain approximately euthyroid state is part of the patient's preparation for a subtotal thyroidectomy. Supersaturated potassium iodide is then administered daily for about 2 weeks before surgery and then withdrawn. To lower resting heart rate, atenolol can be begun 1 to 2 weeks before surgery. Supersaturated potassium iodide is also administered and then withdrawn. The goal of these management approaches is to decrease problems related with perioperative hyperthyroidism exacerbation.
Hypothyroidism, caused by T4's reduced secretory potential, is one of the complications following partial thyroidectomy. The most prevalent consequence of partial thyroidectomy is hypothyroidism. Because the parathyroid glands are so close to the thyroid gland, they might be removed together with the thyroid tissue, resulting in hypoparathyroidism.
Vocal cord paralysis is a consequence of partial thyroidectomy due to the likelihood of iatrogenic damage to the recurrent laryngeal nerve. All of these issues should be discussed with the patient, and the conversation should be documented.
Hyperthyroidism is characterized by nonspecific signs and symptoms such as palpitations, increased frequency of bowel motions, and weight loss. Other disorders that might explain the patient's symptoms should be checked out.
Differential diagnoses for hyperthyroidism etiologies can be formed based on physical abnormalities of the thyroid gland. When a normal thyroid gland is palpated in the setting of hyperthyroidism, it might be related to Graves disease, painless thyroiditis, or factitious hyperthyroidism (thyrotoxicosis factitia). Graves disease can sometimes manifest as an enlarged, non-tender thyroid.
A painful, enlarged thyroid on palpation may be symptomatic of De Quervain thyroiditis (subacute thyroiditis). Palpation of a single thyroid nodule indicates thyroid adenoma, but palpation of several thyroid nodules indicates toxic multinodular goiter.
Because of the high success rates of definitive therapy and the efficiency of symptom management, hyperthyroidism attributable to Graves disease or toxic multinodular goiter has an overall favourable prognosis. As with any condition, the prognosis of a specific pathology is patient-centered and reflects management, response to therapy, and adherence to prescribed therapies.
Untreated or mismanaged hyperthyroidism can result in thyroid storm, a severe episode of hyperthyroidism. Thyroid storm is characterized by tachycardia, increased GI motility, diaphoresis, anxiety, and fever, all of which reflect the hypermetabolic condition of hyperthyroidism. Thyroid storm is a potentially fatal consequence of hyperthyroidism that need prompt medical treatment. Thionamide therapy should be used in the treatment of thyroid storm or a high degree of suspicion of thyroid storm (methimazole or propylthiouracil). PTU, in particular, is beneficial because it inhibits peripheral T4 to T3 conversion. Beta blockade can also be used to treat symptoms.
Except for thyroid storm, hyperthyroidism is seldom life-threatening, although it can have a considerable impact on a patient's daily routine. Hyperthyroidism can cause a variety of symptoms and, if left untreated, can lead to a reduced quality of life. Because there are several causes of hyperthyroidism, the illness is best addressed by a multidisciplinary team.
Patients should be educated on the significance of medication adherence by primary care clinicians, including the nurse practitioner. Furthermore, the pharmacist should tell the patient that some items, including as contrast dyes, expectorants, dietary supplements, and seaweed pills, may contain high quantities of iodine and hence interfere with therapy.
The presence of thyroid storm may demand consultation with an endocrinologist and probable admission to the critical care unit owing to potentially life-threatening consequences such as tachycardia and hypertensive crisis. Nurses who provide patient care should be aware of the signs and symptoms of a thyroid storm.
As previously stated, any consideration of RAI therapy in a female of reproductive potential should be preceded by a negative beta-hCG, as pregnancy is an absolute contraindication to RAI therapy. Incorporating a mandated pregnancy test as part of a comprehensive treatment plan might aid in avoiding possibly harmful radiation exposure.
Patients with Graves disease will need to see an ophthalmologist. Thyroidectomy patients must take levothyroxine for the rest of their lives. Pharmacists are critical in reviewing prescriptions, checking for medication interactions, and educating patients.