What Does the Thyroid Do? — The Letter That Sets the Body's Pace, the Reminder That Grows When It Runs Short

"They Say My Thyroid Levels Are a Bit High"

A person who gets their health checkup results hears that "their thyroid levels are a bit high." Another person gets an ultrasound of their neck and hears that "a small nodule is visible." It is confusing right from the start whether a high level means the thyroid is working too much or too little.

In Korea, stories often circulated that thyroid cancer was unusually common there. During the period when incidence rates were soaring, the thyroid cancer incidence rate in Korea was more than four times that of Koreans living in the United States (PMID 38727257).

This article follows what the thyroid does, why we read thyroid lab values backward, and what happens to the body when the thyroid works too little or too much. We look at Korean data regarding the high rate of thyroid cancer detections and the story of a dining table rich in seaweed.

This is the final article in this series following letters carried in the blood. In the first article, which covered how letters sent by the body via the blood work, we saw the gland in the front of the neck and the two layers below the brain exchanging letters, and the task of reading that pairing on a lab report was deferred to here.

A Letter Sent by the Gland in Front of the Neck

A hormone is a substance made in one part of the body that travels through the blood to a distant place, changing what the cells there do. If you compare a hormone to a letter, the blood is the postal route the letter travels on.

The thyroid is a gland in the front of the neck that makes thyroid hormone and releases it into the blood. Thyroid hormone is the hormone made and released by the thyroid, a name used together for two things: T4, also called thyroxine, and T3.

Thyroid hormone is essential for the growth of the brain and nerves, for growing taller, and for using energy to generate heat. This hormone also regulates how the liver handles nutrients, the balance of water inside the body, and the work of the heart and vessels (PMID 27347897). The places that read this letter most are the brain, liver, muscles, heart, and adipose tissue (PMID 38671149).

Grouping these tasks into a single word gives us metabolism. Metabolism is the overall work of the body producing energy from what it gets from food, and using that energy to build and break down what the body needs. Thyroid hormone is a core hormone that regulates body development and metabolism (PMID 38671149). Many of the symptoms that appear in a person lacking thyroid hormone are due to slowed metabolism (PMID 40900603).

The two hormones have different roles. T4 in the blood is about one hundred times more abundant than T3, but the receiving side catches T3 more easily. T4 is converted into T3 through the hands of enzymes in tissues outside the thyroid (PMID 27347897). Most letters are sent as T4, and rewritten into T3, which is read more easily near the receiving end.

The receiving side is the receptor. A receptor is a protein located on a cell that recognizes and grabs only a specific hormone.

There is an ingredient that always goes into this letter. Iodine is an element strictly necessary for making thyroid hormone, also called iodide. Without iodine, thyroid hormone cannot be made, and thyroid cells gather iodine and use it to make the hormone (PMID 38870258, PMID 36834802).

Thyroid hormone is a letter telling various organs of the body to adjust the speed of metabolism, and the ingredient of that letter is iodine.

The Urging from Upstairs, the Reply from Downstairs

The thyroid does not decide on its own how much hormone to make. Two places upstairs decide. The hypothalamus is a small region deep beneath the front of the brain that receives nerve signals and releases hormones, and the pituitary gland is a gland dangling from a thin stalk right below the hypothalamus, releasing hormones into the blood that tell other glands what to do.

Thyroid-stimulating hormone is a letter the pituitary gland sends to the thyroid telling it to "make and release hormones". On a lab report, it is written as TSH, taking the capital letters from the English name. A letter from the hypothalamus draws this letter out of the pituitary, and this letter spurs every step by which the thyroid makes and releases hormones (PMID 27347897). It is an urging letter sent by upstairs to downstairs.

Urging brings a reply. Feedback is a method where, as the results of a letter accumulate, those effects reach the sender of the letter and notify them to "stop sending them now". T4 and T3 in the blood reach the hypothalamus and pituitary to reduce the letters from upstairs. When the thyroid itself does less work so that thyroid hormones in the blood decrease, the letters from upstairs increase, and when thyroid hormones overflow, they decrease in reverse (PMID 27347897).

Therefore, when TSH is high, we read it first as the thyroid side lacking hormones, causing upstairs to increase its urging. This is because among cases where thyroid function drops, the most common is trouble in the thyroid itself (PMID 35589725). However, a slightly high TSH frequently returns to normal when measured again (PMID 34766382), and it rises due to age alone even when there is no disease in the thyroid (PMID 31287527). Even a slight change in thyroid hormones makes TSH move significantly. Because that large signal is easy to measure, TSH is the value looked at first when checking thyroid function (PMID 31662841).

Next to TSH, a value called free T4 is commonly written together. Carrier proteins are proteins that hold and carry hormones through the blood, and free T4 is the portion among T4 in the blood that floats free without sticking to carrier proteins. The urging from upstairs and the reply from downstairs, written side by side, are the two lines on the lab report.

A range is written next to each line. The reference range is the range where the middle 95% falls, gathered by collecting the values of healthy people and trimming off the top and bottom 2.5% each. This range is a line drawn by statistics, not a line drawn by weighing the risk of disease or death (PMID 37696273).

Where to set the upper end of the TSH reference range is itself a subject of debate (PMID 31662841). Co-occurring diseases, medications taken, age, sex, iodine status, and even the time of blood draw and season are many things that move the TSH value (PMID 31662841). Because of TSH rising as people age, one review considers that if older standards are applied as-is to people past age 70, people with only a slightly high TSH would have been counted higher than reality (PMID 31287527).

Because TSH is an urging letter that increases when thyroid hormones are lacking and decreases when they overflow, the two lines on the lab report are placed together and read in reverse.

When There Aren't Enough Letters

Hypothyroidism is a condition where there is a shortage of thyroid hormone. It is a common disease, more common in women and older people, and how common it is depends heavily on how much iodine the people in that region eat (PMID 40900603).

In places with plenty of iodine, the most common cause comes from immunity. Autoimmunity is when the immunity that protects the body mistakenly recognizes its own body's cells as enemies and attacks them. Hashimoto's thyroiditis is a long-standing inflammation of the thyroid where autoimmunity targets the thyroid. In regions where people eat plenty of iodine, up to 85% of hypothyroidism cases stemming from trouble in the thyroid itself are Hashimoto's thyroiditis (PMID 40900603). A severe lack of iodine can also cause hypothyroidism, but in regions with sufficient iodine, the autoimmune side is a more common cause (PMID 35589725). A family history, neck surgery or radiation therapy, and certain drugs also raise the risk (PMID 40900603).

When letters are short, the body leans toward slowing down. Hypothyroidism usually starts silently, and symptoms may only appear in the late stages of the disease (PMID 35589725). Symptoms caused by a slowed metabolism appear—such as easily fatiguing, gaining weight, having blurred memory or concentration, and irregular periods—none of which are symptoms exclusive to the thyroid (PMID 40900603). Therefore, whether it is hypothyroidism is sorted out through blood tests. When TSH is high and free T4 is low, it is overt hypothyroidism originating from trouble in the thyroid itself (PMID 40900603).

Review articles have also noted their positions on screening people without symptoms in advance. Screening is a test intended to find people with a disease in advance among those without symptoms. The same review notes that it does not recommend hypothyroidism screening for people without symptoms, and recommends selective testing for those considered to be at high risk (PMID 40900603). Since the test that sorts out hypothyroidism in this review is a blood test, the screening mentioned here is also a blood test checking thyroid function. Another review also cites the limitations of the TSH test and leans toward opposing population-wide screening with TSH until randomized trials weighing benefits and harms emerge (PMID 31662841). Ultrasounds to find lumps in the neck will be covered separately later.

Untreated hypothyroidism can invite serious complications like heart failure, and if it worsens very severely, body temperature and blood pressure drop and consciousness clouds, resulting in a condition that requires intensive care unit treatment. The mortality rate in this state reaches as high as 30% (PMID 40900603).

The foundation of treatment is returning TSH to the normal range with a drug that supplements thyroid hormone, and since using too little or too much both carries heart and blood vessel risks, TSH is adjusted by measuring it again (PMID 40900603). Most people improve once the levels return, but quite a few people continue to feel discomfort, and the reasons for that and better methods remain matters that still require more research (PMID 34766382, PMID 35589725).

When the Letters Overflow

There is also a breakdown in the opposite direction. Hyperthyroidism is a state where the thyroid produces and releases too much thyroid hormone (PMID 27038492, PMID 37847271). The most common cause is Graves' disease, followed by cases where a part of the thyroid makes hormones on its own, regardless of the urging from upstairs.

Graves' disease is a condition where antibodies created by autoimmunity attach to the thyroid-stimulating hormone receptor, turning that receptor on (PMID 39039206). A fake urging letter that the pituitary gland never sent is stuck to the receiving site, and the thyroid reads that letter and makes excessive hormones. Graves' disease is much more common in women (PMID 37847271).

When the letters overflow, the body tilts toward speeding up. Common symptoms include anxiety, difficulty falling asleep, a pounding heart, unexpected weight loss, and difficulty tolerating the heat (PMID 37847271). Confirmation is again done with a blood test. When TSH is suppressed and low, and free T4 or T3 is high, it is clear hyperthyroidism (PMID 38278171).

Untreated hyperthyroidism can lead to arrhythmias where the heart rhythm is disrupted, heart failure, and osteoporosis where bones become weak, and it is also associated with an increased risk of mortality (PMID 37847271). Treatments include medications that cause the thyroid to make fewer hormones, radioactive iodine, and surgery, and which one to choose is decided individually for each person (PMID 37847271).

When thyroid hormones are lacking, the body tilts toward slowing down, and when they overflow, it tilts toward speeding up, and which direction it is is told apart by a blood test.

When Only the Numbers Are Slightly Off

It is quite common to find that only TSH is slightly high on a lab report while free T4 is within the range. Up to roughly one in ten adults (PMID 31287527). Subclinical hypothyroidism is a condition where TSH is higher than the reference range, but free T4 remains within the reference range. It is also called subclinical hypothyroidism. The word "subclinical" in the name points to what the test looks like, and symptoms can still be present in this condition. The most common cause is Hashimoto's thyroiditis, and in middle age, vague symptoms such as fatigue or mood changes may accompany it (PMID 31287527).

This condition frequently resolves on its own. Because 62% of high TSH readings can return to normal by themselves, one review notes that it is advisable to retest and check after at least about two months (PMID 34766382). Conversely, some people progress to overt hypothyroidism, and that risk is greater if antibodies targeting the thyroid are present in the blood (PMID 31287527).

So, would taking medication to supplement thyroid hormones make it better. There is a trial that randomly divided 737 people aged 65 or older who had this persistent condition into two groups. One group took the medication, and the other took a placebo (PMID 28402245). A placebo is a fake medicine that looks the same but has no active pharmacological ingredient.

The average age of the participants was 74 years, and the initial TSH averaged 6.4. A year later, TSH was lower in the medication group, but there was no difference between the two groups in changes in hypothyroid symptom scores and fatigue scores, and no benefit was seen in other outcomes either. Pre-specified serious side effects were not clearly more frequent in the medication group. The researchers concluded that medication did not confer a clear benefit in subclinical hypothyroidism in those aged 65 and older (PMID 28402245).

The question this trial answered was about symptoms and fatigue over one year in those aged 65 and older. In a post-hoc analysis that re-analyzed data from two trials in the same age group later, medication also had no effect on cardiac and metabolic indicators, including blood lipid levels. However, in 27 people whose initial TSH was 10 or higher, changes toward improvement were seen, though that change was not distinct when adjusted for multiple testing (PMID 41965091). There is also evidence on the side of harm. One review notes that this medication can cause a state of excess thyroid hormones, particularly in older people (PMID 31287527).

Guidelines view this evidence differently. Based on a review pooling 21 trials, a guideline panel in 2019 composed of patients, clinicians, and methodologists strongly recommended against using thyroid hormones in adults with subclinical hypothyroidism. The panel noted that there was no consistent meaningful benefit in quality of life and symptoms, and also weighed the burden of lifelong management and uncertainty about harms. The panel added that this recommendation does not apply to women preparing for pregnancy and people with a TSH over 20, and may not fit people with severe symptoms or young adults aged 30 or younger. The panel noted that it recommends monitoring whether thyroid function worsens or resolves instead of medication (PMID 31088853).

One review considers that most people with subclinical hypothyroidism can be monitored without treatment, while noting that treatment may be necessary for people with a TSH of 10 or higher or young and middle-aged adults with mild hypothyroid symptoms (PMID 31287527). Recommendations on what to do for older people differ across international guidelines. One review covering those aged 65 and older suggests considering treatment when TSH is persistently 7 or higher, and leaning away from starting treatment if it is lower than that (PMID 34953533).

There is a trial showing that medication did not improve symptoms and fatigue in subclinical hypothyroidism in those aged 65 and older, and guideline judgments diverge depending on age, symptoms, numerical values, and pregnancy plans.

Lumps in the Neck, and Thyroid Cancer in Korea

When getting a neck ultrasound, lumps in the thyroid are commonly seen. A thyroid nodule is a distinct mass formed inside the thyroid that differs from the surrounding tissue, commonly referred to as a lump in the thyroid. Nodules that can be felt by hand account for 4 to 7% of the population, but when including nodules incidentally found on ultrasound, studies widely report them in 19 to 67% of people (PMID 12588078). The increasing frequency of imaging tests for reasons unrelated to the thyroid appears to be the reason why nodules are commonly discovered (PMID 29509871). Most are asymptomatic and benign. Clinically meaningful cancers are around one in ten (PMID 29509871, PMID 40916877).

When examining a nodule, its shape is first observed via ultrasound. Fine-needle aspiration is a test that uses a thin needle to extract a small number of cells from a nodule, examining them under a microscope to distinguish whether they are benign or malignant. Large or suspicious nodules on ultrasound have their cells examined through this test. Ultrasound risk stratification alone can make needle biopsies unnecessary in many cases (PMID 39152228). Symptomatic or suspicious nodules remain targets for further examination with ultrasound and cytological tests today (PMID 40916877).

The story of how thyroid cancer surged in Korea is connected to these common nodules. Overdiagnosis is the finding and diagnosing of a disease that would have passed without trouble if left unfound. For overdiagnosis to occur, two things must be present: there must be a disease that remains silent without producing symptoms, and there must be an activity that uncovers it (PMID 20413742).

The incidence rate of thyroid cancer in Korea increased tenfold from 1999 to 2012 (PMID 33979040). During the period of rapid increase, the incidence rate among Koreans living in the United States was less than a quarter of that in Korea, and the speed of the increase was similar to other groups in the United States. Researchers concluded that Korea's high incidence rate is not explained by genetics and is likely due to factors in the healthcare system (PMID 38727257).

What increased was almost a single type of cancer. Papillary thyroid cancer is the type that accounts for the largest share among thyroid cancers. In a study examining 25 countries, papillary thyroid cancer was the only type that consistently increased in every country, and the incidence rate of papillary thyroid cancer in women was highest in Korea. Researchers interpreted that this type exists in an asymptomatic form and is easily found when the thyroid is closely scrutinized (PMID 33662333).

Meanwhile, the thyroid cancer mortality rate did not rise. In Korea's national cancer registry and mortality data, the thyroid cancer mortality rate for the overall population actually began to decline from the early 2000s (PMID 33979040). Globally as well, while incidence rates rose sharply, mortality rates remained relatively unchanged. One review attributes a substantial portion of the increased incidence to the overdiagnosis of small, slow-growing papillary thyroid cancer, citing the widespread and sometimes inappropriate use of thyroid and neck ultrasounds as the underlying cause. The same review notes that, to a lesser degree, advanced thyroid cancers also increased over the past 40 years, contributing to this trend (PMID 40903496).

A study looking at data from 63 countries estimated that overdiagnosis accounted for more than 85% of thyroid cancer cases in South Korean women in the mid-2010s (PMID 39389067). Another study comparing South Korea, China, and Japan found that South Korea had the largest share estimated to be due to overdiagnosis (PMID 37488752). Both percentages from the two studies are estimates produced through statistical methods.

Korea's incidence rate declined starting in 2012. The aforementioned 85% is an estimate from the mid-2010s, after that decline began. Because this is earlier than 2014, when the overdiagnosis debate began in earnest, researchers believe that changes in nodule testing guidelines may have influenced this drop, and the debate may have accelerated the decline (PMID 33979040). Researchers from the 63-country study concluded that even though some countries like Korea have seen incidence rates stall or decline, the magnitude of overdiagnosis remains very large, and overdiagnosis is rapidly spreading to other countries (PMID 39389067). A research team in Korea noted that while the decrease in adults is likely due to reduced screening, childhood thyroid cancer has continued to rise, and its causes may involve a mix of screening effects and a genuine increase (PMID 34054738).

Data worth noting also emerged after diagnoses decreased. In a study examining about 430,000 thyroid cancer patients using South Korean health insurance data, the incidence rate rapidly decreased after 2012 and then remained at that level. However, the thyroid cancer mortality rate analyzed by year of diagnosis decreased for a while and then increased starting in the mid-2010s. Because this mortality rate is calculated with patients diagnosed with thyroid cancer as the denominator, the population being measured differs from the overall population mortality rate seen earlier. This abstract does not state whether the number of people dying from thyroid cancer increased, or why this ratio rose. Citing the rise in thyroid cancer mortality rates among patients diagnosed after 2015, the researchers concluded that it is important to properly diagnose and treat thyroid cancers with a high risk of progression, while simultaneously needing efforts to reduce overdiagnosis and overtreatment of low-risk thyroid cancers (PMID 38874484).

The reason overdiagnosis is harmful is because of what happens after discovery. Even overdiagnosed cancers lead to treatment, leaving behind the risk of complications, and the diagnosis itself leaves behind anxiety and a financial burden (PMID 36687223). For some cancers meeting specific conditions, active surveillance without immediate surgery has also become an option (PMID 39152228).

A review examining breast, prostate, and thyroid cancer screening together summarizes that many screening programs simultaneously produce the benefit of reducing disease-specific mortality and the harms of overdiagnosis and overtreatment. This abstract does not state whether thyroid cancer screening alone reduced mortality (PMID 28104314).

Thyroid nodules are common and mostly benign, and multiple studies estimate that the sharp increase in thyroid cancer in Korea was mostly due to an increase in detection. Although Korea's incidence rate has turned downward since 2012, properly diagnosing and treating cancers with a high risk of progression while reducing overdiagnosis and overtreatment of low-risk cancers remain challenges that must be solved together (PMID 38874484).

Dietary Iodine, Too Little or Too Much

30% of the world's population remains at risk of iodine deficiency (PMID 36079737). When iodine is severely lacking, even as the thyroid tries harder to gather more, there is not enough to make hormones; the thyroid grows larger and hypothyroidism develops. When deficiency happens in childhood, cognition and growth are impaired (PMID 25591468).

When deficiency is mild, the thyroid works harder so that most people maintain normal function. The trade-off is that a thyroid stimulated for a long time develops more self-made hormone-producing nodules, increasing the frequency of hyperthyroidism in that population (PMID 25591468).

There is also the opposite extreme, of excess. People usually tolerate high dietary intake or exposure to iodine well. However, when a large amount enters all at once, hypothyroidism or hyperthyroidism can develop in some vulnerable individuals, with hospital contrast agents being a common source (PMID 38870258). An iodine-excess state is also linked to hypothyroidism and thyroid autoimmunity (PMID 24926457).

South Korea is a country with high iodine intake (PMID 24926457). Due to culinary culture and geography, Koreans eat more iodine-rich sea vegetables than Westerners do (PMID 40809894).

In the 2013–2015 Korea National Health and Nutrition Examination Survey, the median urinary iodine concentration of Koreans fell into the "above requirements" category based on World Health Organization standards (PMID 29766681). Another study analyzing the same data found that roughly one in seven people had deficient or excessive levels respectively, and the group with higher urinary iodine also had a higher average TSH. The researchers concluded that the overall iodine nutritional status in South Korea is very good (PMID 29188371).

Whether excessive intake is harmful to the thyroid of Koreans remains an unanswered question. A study of approximately 190,000 South Korean adults found that the group consuming the most iodine did not have more thyroid disease than the group consuming the least. However, because this was a cross-sectional study that estimated intake via dietary questionnaires at a single point in time, the researchers noted that longer-term follow-up studies are still needed (PMID 40809894).

Iodine can cause trouble for the thyroid whether it is deficient or excessive, South Korea is a country leaning toward excessive intake, and what that intake does to the thyroid of Koreans is not yet definitively established.

Reading the Two Lines on the Test Report

Let us imagine three people receiving their health checkup reports on the same day. All three look at the two lines: TSH and free T4.

The first person has a high TSH and a low free T4. The letters from downstairs are in short supply, and upstairs has increased its urging as replies have dwindled (PMID 27347897). This is the pattern of overt hypothyroidism, where the trouble lies within the thyroid gland itself (PMID 40900603). Where iodine is sufficient, the most common cause is Hashimoto's thyroiditis (PMID 40900603).

The second person has a suppressed, low TSH and a high free T4. The letters from downstairs overflow so that upstairs has nearly stopped urging, and this is the test pattern of overt hyperthyroidism (PMID 38278171). The same test pattern can appear even when the thyroid is not making extra hormone—such as in thyroiditis—so further distinction of the cause is needed (PMID 38278171). Whether the cause is Graves' disease is further distinguished by tests like antibodies attaching to the TSH receptor (PMID 37847271).

The third person has a TSH slightly above the reference range and a free T4 within the range. This is the pattern of subclinical hypothyroidism. All the considerations we saw earlier follow this person. Re-testing can show that a significant number return to normal (PMID 34766382), TSH rises even without thyroid disease if a person is older (PMID 31287527), and trials have found that in those 65 and older, medication did not relieve symptoms and fatigue (PMID 28402245). Conversely, some people progress to overt hypothyroidism (PMID 31287527). If a person is young, has severe symptoms, a much higher value, or is preparing for pregnancy, the guidance diverges in its judgment (PMID 31088853, PMID 31287527).

This upside-down reading is for the most common case—that is, when the trouble originates in the thyroid gland itself. Hypothyroidism is divided according to the site of trouble into the thyroid gland itself, the pituitary or hypothalamus, and the tissues of the body, with trouble in the thyroid gland itself being the most common (PMID 35589725). Hypothyroidism caused by trouble in the pituitary or hypothalamus is tricky to diagnose in its own right, and becomes even harder if trouble in other hormone chains upstairs overlaps (PMID 33549603). That upstairs chain was covered in the article on how hormones work.

The two lines are a starting point, nothing more. Because TSH shifts due to many circumstances such as concurrent illnesses, medications taken, and age, one review takes the position that all of a person's circumstances must be examined before jumping into treatment based solely on a slightly high TSH (PMID 31662841).

Where to Look Further

There are also questions that remain unsolved. What a slight deviation of TSH from the reference range means for the body a long time later is not yet clear (PMID 31662841).

You can follow the upper tier of the thyroid chain, feedback, and carrier proteins in more detail in "How Hormones Work — Letters Only the Addressee Reads, Replies That Say Stop". What test results actually tell you, and why the same result is read differently depending on who it came from, is covered by "What a Test Actually Tells You — An Introduction to Sensitivity, Specificity, and Pretest Probability". The disruption of rhythm that hyperthyroidism can bring, and the benefits and burdens of finding a disease without symptoms in advance, can also be met in "What Atrial Fibrillation Is — The Upper Chambers That Lost the Beat, and the Blood That Pools There".

With this piece, we close the "Hormones and Blood Sugar — Letters Carried in the Blood" series. Starting from how hormones work, passing through the two letters that keep a grip on blood sugar, diabetes where those letters break down, the numbers of a blood sugar test, obesity and GLP-1, and all the way to the thyroid, six pieces have followed a single letter carried in the blood.

Source Papers

• "Thyroid Cancer Incidence Among Korean Individuals: A Comparison of South Korea and the United States." (2024) — PMID 38727257 — The thyroid cancer incidence rate in South Korea from 1999 to 2014 (48.05 per 100,000 person-years) was higher and its rate of increase (17.9% per year) was much faster than among ethnic Koreans living in the United States (11.12), suggesting healthcare system factors rather than genetics.
• "Hypothalamus-Pituitary-Thyroid Axis." (2016) — PMID 27347897 — TRH stimulates TSH, which in turn stimulates the pre-steps of thyroid hormone synthesis and secretion; negative feedback by T4 and T3 occurs; hypothyroidism leads to increased TRH and TSH, with the reverse in hyperthyroidism; involvement in neural development, growth, energy metabolism, thermogenesis, hepatic nutritional metabolism, fluid balance, and cardiovascular regulation via nuclear receptors mediating gene expression; T4 has 1/100th the potency of T3 and is converted to T3 outside the thyroid, with transporters and deiodinases regulating T3 availability.
• "Metabolic Messengers: Thyroid Hormones." (2024) — PMID 38671149 — Thyroid hormones are core hormones regulating development and metabolism in mammals, with human target tissues primarily including the brain, liver, muscle, heart, and adipose tissue.
• "Hypothyroidism: A Review." (2025) — PMID 40900603 — A disease of thyroid hormone deficiency, with prevalence varying by iodine intake and commonly seen in women and the elderly; Hashimoto's disease accounts for up to 85% of primary hypothyroidism in iodine-sufficient regions; nonspecific symptoms due to decreased metabolism (fatigue, weight gain, cognitive changes, irregular menstruation); untreated cases risk heart failure, myxedema coma (intensive care unit admission, mortality up to 30%); high TSH plus low free T4 indicates overt primary hypothyroidism; levothyroxine normalizes TSH; both under- and overtreatment carry cardiovascular risks.
• "Risks of Iodine Excess." (2024) — PMID 38870258 — Iodine is a trace element necessary for thyroid hormone synthesis; excessive intake or exposure is generally well tolerated, but acute loads can trigger hypo- or hyperthyroidism in some vulnerable individuals; contrast media are a common source in medical settings.
• "Selenium, Iodine and Iron-Essential Trace Elements for Thyroid Hormone Synthesis and Metabolism." (2023) — PMID 36834802 — Iodine is accumulated into thyroid cells via NIS, oxidized, and bound to thyroglobulin, while TSH stimulates the entire process of thyroid hormone synthesis and secretion.
• "Challenges in Interpreting Thyroid Stimulating Hormone Results in the Diagnosis of Thyroid Dysfunction." (2019) — PMID 31662841 — TSH is the primary indicator of thyroid function, showing an amplified response to small changes in thyroid hormones; the upper limit of the reference range itself is controversial; comorbidities, medications, age, sex, iodine status, time of day, and seasonality affect TSH; the long-term prognosis of small deviations is unclear, and all factors must be considered before intervening based on a borderline TSH alone.
• "The optimal healthy ranges of thyroid function defined by the risk of cardiovascular disease and mortality: systematic review and individual participant data meta-analysis." (2023) — PMID 37696273 — TSH and free T4 reference intervals are statistically defined by the 2.5th to 97.5th percentiles and do not account for the risk of clinical outcomes.
• "Subclinical Hypothyroidism: A Review." (2019) — PMID 31287527 — Definition (elevated TSH and normal free T4), affecting up to 10% of adults, with Hashimoto's as the most common cause; TSH rises with age even without thyroid disease, potentially overestimating prevalence in those over 70; middle-aged individuals may have nonspecific symptoms; most can be observed without treatment; treatment is considered for a TSH above 10 or in younger and middle-aged adults with symptoms.
• "Treating hypothyroidism is not always easy: When to treat subclinical hypothyroidism, TSH goals in the elderly, and alternatives to levothyroxine monotherapy." (2022) — PMID 34766382 — 62% of high TSH results can normalize spontaneously, warranting re-evaluation after 2 months or more; the upper TSH limit is age-dependent (under 40: 3.6, over 80: 7.5).
• "Hypothyroidism." (2022) — PMID 35589725 — Classification into primary, central, and peripheral, with acquired primary being the most common; severe iodine deficiency can be a cause, but chronic autoimmune thyroiditis is more common in iodine-sufficient regions; usually begins insidiously with late symptoms; levothyroxine is one of the most prescribed drugs worldwide; significant symptoms persist in many patients even after normalization, and further research is needed on reference ranges and combination therapy.
• "Hyperthyroidism." (2016) — PMID 27038492 — Hyperthyroidism involves increased thyroid hormone synthesis and secretion, with Graves' disease as the most common cause, followed by toxic multinodular goiter.
• "Hyperthyroidism: A Review." (2023) — PMID 37847271 — The most common cause is Graves' disease (2% of women, 0.5% of men), and toxic nodules feature autonomous function; common symptoms include anxiety, insomnia, palpitations, weight loss, diarrhea, and heat intolerance; untreated cases are associated with increased rates of arrhythmia, heart failure, osteoporosis, and death; causes are identified via clinical presentation, thyroid function tests, and TSH receptor antibodies, while treatment options include antithyroid drugs, radioactive iodine, and surgery, personalized to the individual.
• "Graves disease: latest understanding of pathogenesis and treatment options." (2024) — PMID 39039206 — The primary mechanism of Graves' disease involves autoantibodies that bind to and activate the TSH receptor.
• "Hyperthyroidism." (2024) — PMID 38278171 — Diagnosis relies on a suppressed TSH with elevated free T4 and T3 (overt) or levels within the reference range (subclinical).
• "Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism." (2017) — PMID 28402245 — A double-blind, placebo-controlled RCT of 737 adults aged 65 and older with persistent subclinical hypothyroidism (mean age 74.4, mean TSH 6.40) found no difference in hypothyroid symptoms or fatigue scores after 1 year, no benefit in secondary outcomes, and no significant excess in serious adverse events of special interest; conclusion: no clear benefits of levothyroxine in older adults with subclinical hypothyroidism.
• "Levothyroxine treatment response of cardiometabolic biomarkers in older adults with subclinical hypothyroidism." (2026) — PMID 41965091 — A post-hoc analysis of two RCTs in adults aged 65 and older (286 participants) showed no effect on cardiometabolic markers; a trend toward lipid improvement in the baseline TSH $\ge$ 10 subgroup (27 participants) was not significant after correcting for multiple testing.
• "Thyroid hormones treatment for subclinical hypothyroidism: a clinical practice guideline." (2019) — PMID 31088853 — GRADE guideline panel based on a systematic review of 21 trials involving 2,192 participants issued a strong recommendation against thyroid hormones for adults with subclinical hypothyroidism, citing no benefit in quality of life or symptoms alongside the burden of lifelong management and uncertain harms; women planning pregnancy and those with TSH > 20 were excluded; the recommendation may not apply to individuals with severe symptoms or young adults under 30.
• "Subclinical hypothyroidism in older individuals." (2022) — PMID 34953533 — International guideline recommendations for managing subclinical hypothyroidism in the elderly vary.
• "Thyroid nodules: diagnosis and management." (2024) — PMID 39152228 — Nodule prevalence is approximately 25%, and ultrasound risk stratification can often make biopsies unnecessary; large or suspicious nodules undergo fine-needle aspiration cytology, and some are managed with active surveillance or focal ablation.
• "The Diagnosis and Management of Thyroid Nodules: A Review." (2018) — PMID 29509871 — Nodules are found in up to 65% of the general population (due to increased imaging), mostly benign and clinically insignificant, with clinically significant cancers accounting for about 10%.
• "Diagnosis and management of thyroid nodule." (2025) — PMID 40916877 — Incidental nodules are mostly (over 90%) benign, while symptomatic or suspicious nodules undergo further evaluation via ultrasound and cytopathology, with active surveillance as an option for some malignant nodules.
• "Overdiagnosis in cancer." (2010) — PMID 20413742 — Overdiagnosis is the diagnosis of cancers that would never lead to symptoms or death, requiring two preconditions: a pool of quiet disease and an activity that detects it, with thyroid cancer suggesting such overdiagnosis.
• "Thyroid cancer incidence trends by histology in 25 countries: a population-based study." (2021) — PMID 33662333 — Between 1998 and 2012, papillary cancer was the only histological type that systematically increased across all countries; from 2008 to 2012, South Korean women had the highest incidence of papillary cancer, a subtype prone to detection via intensive screening in asymptomatic forms.
• "Unravelling the rise in thyroid cancer incidence and addressing overdiagnosis." (2026) — PMID 40903496 — Rapid incidence rise and relatively stable mortality since the 1980s; a substantial portion of the increase is due to the overdiagnosis of small, slow-growing papillary cancers driven by the widespread and sometimes inappropriate use of ultrasound, with advanced-stage increases also contributing to a lesser degree.
• "Evolving epidemiological patterns of thyroid cancer and estimates of overdiagnosis in 2013-17 in 63 countries worldwide: a population-based study." (2024) — PMID 39389067 — Following a rise until the early 2010s in countries like South Korea, rates declined; more than 85% of thyroid cancer cases in South Korean women between 2013 and 2017 were estimated to be overdiagnosed, and overdiagnosis remains large while spreading to transition countries.
• "Trends in incidence and overdiagnosis of thyroid cancer in China, Japan, and South Korea." (2023) — PMID 37488752 — Among China, Japan, and South Korea from 1998 to 2012, South Korea had the highest incidence and estimated proportion of overdiagnosis (men: 90.3%, women: 94.9%).
• "Trends in Childhood Thyroid Cancer incidence in Korea and Its Potential Risk Factors." (2021) — PMID 34054738 — Adult thyroid cancer incidence in Korea has recently decreased (likely due to reduced screening), whereas childhood thyroid cancer continued to increase from 1999 to 2017, potentially driven by actual increase factors such as excess iodine, medical radiation, and obesity alongside screening effects.
• "Mitigating Cancer Overdiagnosis." (2022) — PMID 36687223 — Overdiagnosis leads to unnecessary treatments and their complications, risk of death, anxiety, and financial hardship, with thyroid cancer cited as an example.
• "Breast, prostate, and thyroid cancer screening tests and overdiagnosis." (2017) — PMID 28104314 — Many screening tests produce both benefits (reductions in disease-specific mortality) and harms (overdiagnosis and overtreatment), necessitating balanced discussions.
• "Iodine and Iodine Deficiency: A Comprehensive Review of a Re-Emerging Issue." (2022) — PMID 36079737 — Salt iodization has reduced deficiency, but 30% of the global population remains at risk.
• "Iodine deficiency and thyroid disorders." (2015) — PMID 25591468 — Early-life deficiency impairs cognition and growth, severe deficiency causes goiter and hypothyroidism, and mild-to-moderate deficiency triggers increased thyroid activity to maintain normal function in most people at the cost of increased toxic multinodular goiter and hyperthyroidism.
• "Iodine and thyroid function." (2014) — PMID 24926457 — Iodine excess is linked to hypothyroidism and thyroid autoimmunity, with South Korea primarily experiencing excess and North Korea experiencing deficiency, requiring further research on the optimal intake range on the Korean Peninsula.
• "The association between iodine intake and thyroid disease in iodine-replete regions: the Korean Genome and Epidemiology Study." (2025) — PMID 40809894 — Due to dietary culture and geography, Koreans consume iodine-rich seaweeds more than Westerners; a cross-sectional analysis of 190,524 participants using a semi-quantitative food frequency questionnaire showed that high intake was not associated with increased thyroid disease, though long-term longitudinal studies are needed.
• "Evaluation of Thyroid Hormone Levels and Urinary Iodine Concentrations in Koreans Based on the Data from Korea National Health and Nutrition Examination Survey VI (2013 to 2015)." (2018) — PMID 29766681 — The median urinary iodine concentration among Koreans in KNHANES VI was 294 μg/L, categorized as "above requirements" by WHO standards.
• "Urinary iodine concentration and thyroid hormones: Korea National Health and Nutrition Examination Survey 2013-2015." (2019) — PMID 29188371 — Among 8,318 participants, 14.0% had iodine deficiency and 13.4% had excess; subgroups with higher median urinary iodine had higher average TSH levels; author conclusion: overall very good iodine nutritional status.
• "Thyroid nodules." (2003) — PMID 12588078 — Palpable nodules are found in 4–7% of the population, whereas incidental nodules found via ultrasound reach 19–67%, most are asymptomatic, and about 5% of palpable nodules are malignant.
• "Decreasing trends in thyroid cancer incidence in South Korea: What happened in South Korea?" (2021) — PMID 33979040 — National cancer registry and mortality data from 1999 to 2016 show age-standardized incidence rose from 6.3 (1999) to 63.4 (2012) before declining; the decline began in 2012, ahead of the overdiagnosis debate in 2014; mortality began declining in the early 2000s, distant-stage incidence in 2010, and localized-stage incidence in 2012; changes in nodule screening guidelines may have influenced the inflection point, and the debate may have accelerated the decline.
• "Thyroid cancer-specific mortality during 2005-2018 in Korea, aftermath of the overdiagnosis issue: a nationwide population-based cohort study." (2024) — PMID 38874484 — Among 434,228 thyroid cancer patients in health insurance data, incidence increased until 2012, dropped sharply through 2015, and stabilized through 2018; cancer-specific mortality among patients grouped by diagnosis year decreased until 2013 and then increased through 2018; conclusion: balancing efforts to properly diagnose and treat cancers with a high risk of progression while reducing the overdiagnosis and overtreatment of low-risk cancers is crucial.
• "The hypothalamus-pituitary-thyroid (HPT)-axis and its role in physiology and pathophysiology of other hypothalamus-pituitary functions." (2021) — PMID 33549603 — The diagnosis of central hypothyroidism is complex on its own and becomes even more difficult when abnormalities of other hypothalamus-pituitary axes overlap.