Can antibiotics cause thyroid problems



Tetracycline, first marketed by Lederle Laboratories in 1953, was frequently prescribed for treatment of acne vulgaris. Due to clinical advantages over tetracycline (e.g. simpler dosing schedule and improved digestive tolerability)7 doxycycline (1967) and minocycline (1972) became preferred, although their own adverse effects include gastrointestinal symptoms, photosensitivity, and pigment accumulation in nails, skin, sclerae and teeth. In addition, minocycline can induce autoimmune conditions including systemic lupus erythematosus, autoimmune hepatitis and less commonly, serum sickness and vasculitis8–10; doxycycline also can induce autoimmune hepatitis.11

Although black pigmentation of the thyroid appears to occur commonly with exposure to minocycline or doxycycline, thyroid dysfunction manifesting as hyper- or hypothyroidism has been reported rarely. Proposed mechanisms include (1) competitive inhibition of TPO-induced iodination of tyrosine moieties in thyroglobulin, (2) inhibition of TPO-catalyzed coupling of iodotyrosine residues, (3) cytotoxic damage to follicular cells leading to release of preformed thyroid hormone, (4) indirect or direct antibody-mediated destruction of follicular cells.6, 12, 13

Proposed mechanisms of tetracycline-class drug-induced pigmentation accumulation include (1) degradation from drug interaction with lipofuscin, (2) oxidation of the drug, (3) interaction via TPO with tyrosine metabolism (needed for melanin and neuromelanin), and (4) lysosomal dysfunction.14–16 Pigmentation seems to occur rapidly and is enduring.14 Although black discoloration often is considered pathognomonic for minocycline exposure, less common etiologies include cystic fibrosis, ochronosis, mucoviscidosis, ceroid storage disease, bruising, hemorrhage, hemochromatosis and effects of other drugs including doxepin, lithium, and tricyclic antidepressants (via lysosomal accumulation).17–20

One in vitro study of minocycline effects on thyroid hormone synthesis found that only the combined presence of minocycline and TPO led to black pigmentation changes as well as disruption of synthesis steps. Specifically, minocycline appeared to inhibit TPO-catalyzed iodination at a potency similar to or greater than13 the anti-thyroid drugs methimazole and propylthiouracil. Inhibition of iodination was dose-dependent; at low concentrations (25 μM), minocycline competitively inhibited of TPO-induced iodination, whereas at high concentrations (100uM), it acted reversibly to inhibit iodination independent of inactivation of TPO.

The three cases described herein illustrate that minocycline and doxycycline can result in more severe thyroid dysfunction in children and adolescents than previously demonstrated. Prior pediatric cases have been associated with evidence of autoimmunity.5, 6 The second novel observation from our cases is that concurrent autoimmunity is not a necessary component of tetracycline-induced clinical and laboratory-evident thyroid dysfunction. Thus, thyroiditis from minocycline in these cases appears to be a non-autoimmune chemical thyroiditis resulting in cytotoxic damage sufficient to cause marked release of thyroid hormone and, in some cases, subsequent persistent hypothyroidism. That being said, this chart review also found that it is not uncommon for tetracycline-antibiotic treated adolescents to have evidence for autoimmune thyroid dysfunction. It is possible that family history of autoimmunity in two of the three cases could point to a latent familial predisposition without detectable autoimmunity in the individual.

In spite of these potential clinically significant effects on thyroid function, a warning about thyroid dysfunction is not included in the package insert for doxycycline,21 and is mentioned only as “cases of abnormal thyroid function have been reported” for minocycline.22 Routine clinical and laboratory evaluation of thyroid function is not currently recommended when prescribing these medications for treatment of acne.

Tetracycline antibiotic-induced thyroid dysfunction may be more common, serious, and persistent than previously realized and should be considered in the differential diagnosis for pediatric cases of antibody-negative thyroid dysfunction. Minocycline and doxycycline can cause a non-immune chemical thyroiditis leading to severe hyperthyroidism. Following removal of offending antibiotics, this chemical thyroiditis can evolve into persistent hypothyroidism. Although doxycycline and minocycline are commonly prescribed to youth for treatment of acne vulgaris, the frequency of non-autoimmune thyroiditis related to minocycline or doxycycline is unknown. It is likely that the majority of cases escape clinical detection and diagnosis and therefore prospective studies are needed to determine the prevalence, clinical significance and severity of cases. Additional investigation is needed to determine whether routine screening of thyroid function in youth receiving long-term treatment with these antibiotics is warranted.

Can Drugs Cause Hypothyroidism?

Most people who have an under-performing thyroid gland, known as hypothyroidism, got the disease because their immune system started attacking their thyroid gland. However, hypothyroidism can also be triggered by certain medications for unrelated conditions.

On Lithium? Check Your Thyroid

A common offender is lithium, especially in people who have an underlying or undiagnosed thyroid problem, said Leonard Wartofsky, MD, MPH, chairman of the department of medicine at MedStar Washington Hospital Center in Washington, D.C.

Lithium, primarily to treat episodes of mania in people with bipolar disorder, works by decreasing abnormal activity in the brain. It is also prescribed for certain blood disorders, depression, and schizophrenia.

Anyone prescribed lithium should have their thyroid blood levels checked regularly to make sure there is no lithium-induced hypothyroidism.

If the thyroid gland is functioning normally, lithium used to treat these other conditions should have no effect on the amount of thyroid hormone released, Dr. Wartofsky said. But if you have Hashimoto’s, another subclinical thyroid disorder, or even a genetic predisposition to hypothyroidism, “lithium becomes a great burden to the gland that cannot be overcome.”

Iodine: Too Much of a Good Thing Is No Good

The thyroid gland needs iodine to function properly.

According to a 2012 paper published in the journal Endocrine Practice, iodine deficiency is the most common cause of hypothyroidism in the world.

However, in the United States and other developed countries, there is usually plenty of iodine in the basic diet to keep the thyroid functioning normally.

Even though the thyroid needs iodine, “too much of a good thing is no good,” Wartofsky said. Iodine supplements — often seaweed-based and offered as a powder, tablet, or capsule — are advised only for people diagnosed with iodine deficiency. For anyone else, the iodine intake can become excessive and affect thyroid function, especially if you are predisposed to the disease either through genetics or a subclinical condition.

Other Drugs and Hypothyroidism

Other, less common medications that can lead to hypothyroidism in people already predisposed include:

Amiodarone: most commonly prescribed for heart rhythm disorders and containing large amounts of iodine, it also can cause thyroid inflammation that initially causes thyroid hormone levels to rise, explained Jeffrey Garber, MD, associate professor of medicine at Harvard Medical School, immediate past president of the American College of Endocrinology, and chief of endocrinology at Harvard Vanguard Medical Associates in Boston. “After this resolves, the thyroid gland is depleted and hypothyroidism, which may or may not be permanent, ensues.”

Interferon alpha: Used to treat hepatitis C and some cancers, Dr. Garber said that it may cause inflammation of the thyroid gland, known as thyroiditis, which can lead to hypothyroidism.

Interleukin-2:Used to boost the immune system in cancer therapy, it can cause thyroiditis.

Thalidomide: Although the onset of hypothyroidism from this cancer drug used to treat multiple myeloma is rare, thalidomide also may cause thyroiditis, Garber said.

Bexarotene: best known for treating for cutaneous T cell lymphoma.

Ipilimumab: used to treat melanoma by activating the immune system.

Tyrosine kinase inhibitors: including the cancer drugs sunitinib and sorafenib.

Since several medications can lead to diseases of the thyroid, Garber advised patients to help protect themselves by asking their doctor whether a prescribed medication could possibly interfere with thyroid function before taking it.

5 Anti-Thyroid Side Effects Of Antibiotics You Need To Know

Drugs are not always the answer, especially when it comes to a compromised immune system in people with hypothyroidism and Hashimoto’s.

Antibiotics have been used for decades as a medication that kills or slows the growth of bacteria. This class of drugs is among the most frequently prescribed medications today. They are useful in the treatment of infections, pneumonia, allergies and skin problems.

Thousands of children, adults and animals are being treated with antibiotics every year and they are successfully curing different diseases. Whether it is just a gut trickling episode of infective diarrhea or a life-threatening infection antibiotics are considered as the go to magic-pills.

However, it doesn’t mean that antibiotics come without side effects. Recent studies revealed that the side effects and long-term consequences of antibiotic use are much worse than it was previously thought.

Furthermore, antibiotics could be doing significant black magic to your thyroid especially if you are already taking thyroid medication.

In fact, there are 5 anti-thyroid side effects of antibiotics that are seldom taken into consideration by both – patients and doctors:

Table of Contents

1. Use of antibiotics changes gut micro-flora and can make you more hypothyroid

There are two major types of antibiotics based on the area of action – broad and narrow spectrum. For example, Erythromycin the most widely used antibiotic of all, is a broad-spectrum antibiotic that doesn’t work against any specific pathogen. It tries to kill them all and also eradicates the friendly flora of our intestines. Narrow spectrum antibiotics such as Vancomycin target a specific family of bacteria.

Studies show that not only overuse or an unjustified use of antibiotics disrupt the gut flora and cause disbyosis. But also even a single course of antibiotics creates an imbalance between friendly and not-so-friendly micro flora that can affect thyroid hormone pathway and how your body uses and utilizes thyroid medication.

There are two types of thyroid hormones in our body, inactive form T4 and active T3. Every cell of your body needs thyroid hormones for normal function, however they are able to use the T3 form only. A conversion of T4 to T3 peripherally, a major part of which occurs in the liver, muscles, brain and the thyroid gland itself, ensures that you get an adequate supply of T3 to your cells.

In addition, up to 20% of T4 to T3 conversion happens in your digestive tract but only in the presence of specific good gut bacteria. This process requires an enzyme named sulfatase and this is exactly where intestinal bacterias come into the picture. There is no other source of this enzyme except those micro-friends that are considered as enemies by antibiotics which wipe them out.

Reduced levels of T3 precipitates a state of hypothyroidism and this can happen despite abundant reserves of T4 and iodine in the body. Further harm is caused by suppression of the Hypothalamus-Pituitary-Adrenal or HPA axis through surplus of T4 that is not converted into T3.

HPA axis operates via a classical feedback system. Positive feedback to hypothalamus secretes Thyroid Releasing Hormone (TRH) which in turn stimulates the anterior part of the pituitary gland to produce Thyroid Stimulating Hormone (TSH).

Having an excess of T4 peripherally sends a negative feedback suppressing thyroid hormone synthesis and aggravating the already created hypothyroid state. This clearly translates into unresolved hypothyroid symptoms because no amount of thyroid medication can help you if the inherent mechanism operated with the help of gut bacterias is dysfunctional in the first place.

2. Antibiotics can affect efficacy and potency of thyroid drugs

There are two polar types of interactions between drug compounds, synergism and antagonism. While synergism means enhancing the effect of a particular drug, antagonistic drugs reduce the efficacy and potency of each other.

Two commonly prescribed antibiotic drugs such as Ciprofloxacin and Rifampicin are known to change the efficacy of thyroid medication. Here is how:

  • Ciprofloxacin which is prescribed for acute diarrhea has an antagonistic effect on thyroid medications and reduces efficacy of thyroid drugs making patients more hypothyroid.

  • Rifampicin which is an anti-tubercular drug increases the effect of thyroid drugs and yields synergistic output that can result in hyperthyroid symptoms.

Both of these medications thus, create an imbalance between circulating T4 and T3 levels affecting the HPA axis.

3. Some antibiotics reduce absorption of thyroid medication

Another and more direct mechanism that affects thyroid medication is the presence of fluoride which is an element that is found in our teeth, bones and toothpastes as well as in antibiotics of fluoroquinolones or quinolones family.

A chemical fluoride is used as a stabilizer for medications, however it actually de-stabilizes thyroid hormone balance in our body in two ways:

  • By directly reducing absorption of medications prescribed for hypothyroidism and Hashimoto’s disease

  • By competing with iodine which is a building block that is necessary for thyroid hormone production

Taking quinolone antibiotics along with Levothyroxine may lead to reduced absorption of thyroid drugs and cause noticeable changes in TSH.

4. Autoimmune diseases, allergies and many other health issues are predictable consequences of antibiotics

Intestinal walls of your digestive system have a protective barrier called epithelium. While this epithelium is chiefly concerned with the absorption of food and drugs into bloodstream, it is not the sole purpose.

It creates a boundary between gut and the abdominal cavity, preventing the communication between what is inside and outside gut. When that protection is breached, an exaggerated exposure to those alien colonies occurs and this guarantees an immune response within the body.

This is what exactly happens with the use of antibiotics. Some of these drugs are very aggressive and have the ability to damage the intestinal epithelial cells and unleash those bacterias which are supposed to be contained in a protected space. This phenomena is called increased intestinal permeability and is proposed to be one of major causes of autoimmune disease including Hashimoto’s thyroiditis.

These triggers an immune mediated reaction and leads to the production of auto-antibodies, a major step-up in the progression of Hashimoto’s disease and many other autoimmune conditions.

In addition, when the normal bacterial biofilms of the intestinal lining becomes disrupted by antibiotic use and there are not enough good gut bacteria, it compromises the development of T regulatory cells of the immune system.

Shifts in the immune system and immuno-suppression create a whole new set of troubles, leading to more infections, allergies, autoimmune diseases and intake of more antibiotics to fight them. This is a vicious cycle indeed.

5. Antibiotic resistance can trigger and worsen Hashimoto’s and hypothyroidism

The modern era of antibiotics started with the discovery of penicillin by Alexander Fleming in 1928. However, the first cases of antibiotic resistant bacteria were identified soon after in the United Kingdom in 1962 and in the United States in 1968.

Since then pharmaceutical companies have developed and introduced many new antibiotics to solve the resistance problem. However, despite these efforts persistent bacterial infections still remain a big threat especially for people with a compromised immune system.

Antibiotic resistance occurs when bacteria become “resistant” to the therapeutic doses of antibiotics and continue to multiply because medication has lost its ability to control and kill bacterial growth effectively. This happens due to overuse and misuse of antibiotics but also because of negative side effects of antibiotics to the gut flora as already mentioned earlier in this article.

Today, a whopping 80% of the antibiotics sold in the US are used in farm animals mainly to prevent infections and promote growth. As a result even if you are not taking antibiotics you still can develop antibiotics resistance through the food supply.

In people with Hashimoto’s and hypothyroidism antibiotic resistance can be a trigger and a contributing factor that worsens the disease. It opens the door to a host of infections linked to thyroid disease that your immune system is unable to fight effectively. Some of them include H pylori, E. coli, Epstein-Barr Virus (EBV), Yersinia enterocolitica and Borrelia burgdorferi to just name a few.

The problem is that in conventional medicine all these infections are treated with even more antibiotics. For example, a treatment for H pylori involves not only one antibiotic but a triple and quadruple therapy when 3 or 4 antibiotics are used to erradicate this bacteria. Antibiotic resistance and weak immune system make this approach ineffective.

However, there are natural substances that are often even more effective than antibiotics. Often natural compounds for H pylori remain the only option for people who have already developed an antibiotic resistance.

7 Steps To Avoid Negative Antibiotic Impact On Your Thyroid

1. Use antibiotics responsibly. They are designed to fight infections and are absolutely useless for a common cold and flu.

2. Check if antibiotics contain fluoride as one of ingredients and are on the list of fluoroquinolones or quinolones family that is well-known to reduce absorption of thyroid medication.

The quinolones include the following antibiotics: Ciprofloxacin, Cipro, Ciloxan eye drops, Levofloxacin, Levaquin, Quixin, Moxifloxacin, Avelox, Vigamox eye drops, Norfloxacin, Noroxin, Ofloxacin, Ocuflox, Floxin, Floxin Otic, Floxacin, Trovafloxacin, Trovan and alatrofloxacin.

3. Ask for a less aggressive type of antibiotics that cause less damage to your intestinal walls.

4. Repair your gut damage and restore flora after antibiotic use.

Doctors prescribe antibiotics but they fail to take measures to repair damage that these drugs cause to your gut flora. As a result, the gut flora of most patients treated with antibiotics never fully recover.

Constipation, indigestion and bloating are very common symptoms of severe dysbiosis and a weak immune system that is unable to fight infections. Unfortunately, probiotics alone are only bandaids and do not fully replenish the gut flora with all good bacteria. It is important not only to re-populate the intestines with beneficial bacteria but also restore the variety of species.

5. Watch for antibiotics in your food, especially animal products like dairy, eggs, fish and meats.

6. Get tested for persistent infections if you continue to struggle with low grade inflammation, Hashimoto’s and hypothyroidism symptoms that just don’t go away.

7. Consider a natural alternative to antibiotics.

As you see antibiotics are not always the best available solution, especially when it comes to a compromised immune system in people with hypothyroidism and Hashimoto’s and those who already developed antibiotic resistance.

The good news is that there are powerful natural herbal alternatives available that use different mechanisms of action. As such, plant antibiotic choices can help with many common alignments without further contributing to resistance issues and help to recover from the damage caused by antibiotic use.

Look into available natural alternatives to antibiotics and other drugs and use them whenever possible.

P.S. Learn about a life-changing holistic treatment for hypothyroidism and Hashimoto’s disease in our free online Hypothyroidism Seminar: The Right And Wrong Ways To Heal

Ciprofloxacin and Rifampin Have Opposite Effects on Levothyroxine Absorption. Goldberg, A. et. al. Thyroid, October, 2013

Cohen, S. Thyroid Healthy. 2014

The Antibiotic Resistance Crisis: Part 1: Causes and Threats. Ventola CL. Pharmacy and Therapeutics. 2015;40(4):277-283.

At a Glance

The thyroid gland produces two related hormones, thyroxine (T4) and triiodothyronine (T3), which play a critical role in thermogenic and metabolic homeostasis. T3 and T4 are normally synthesized and released in response to a combined hypothalamic pituitary signal mediated by thyroid stimulating hormone (TSH) from the pituitary and thyrotropin releasing hormone from the hypothalamus. There is a negative feedback from thyroid hormone concentration, primarily T3, to TSH production causing total T4, total T3, free T4, and free T3 concentrations to move in opposition to TSH concentration.

Hypothyroidism is a condition in which the thyroid gland is functionally inadequate. Causes of hypothyroidism include autoimmune disorders, such as Hashimoto’s thyroiditis, atrophic thyroiditis, and postpartum thyroiditis; iodine deficiency, the most common cause of hypothyroidism in underdeveloped areas; congenital defects; medications or treatments that can result in hypothyroidism; central hypothyroidism in which the thyroid is not stimulated by the pituitary or hypothalamus; and infiltrative processes that damage the thyroid, pituitary, or hypothalamus. These different causes of hypothyroidism are often interrelated. Usually the exact cause of the hypothyroidism cannot be definitively determined.

Drug-induced hypothyroidism is an under active thyroid gland caused by certain medications. The medications that can cause hypothyroidism may be drugs normally used to treat hyperthyroidism or that are related to thyroid function and a group of nonthyroid related drugs. The drugs used to treat hyperthyroidism or are related to thyroid function that can result in drug-induced hypothyroidism are propylthiouracil, radioactive iodine, potassium iodide, and methimazole. Iodides, in general, alter thyroid function. Total T3 and total T4 are 3 and 4 iodinated tyrosines. Even iodide containing solutions used for sterilization or iodides used in dyes and contrast media can cause hypothyroidism. Iodide can also causes hyperthyroidism.

The group of drugs not used to treat thyroid dysfunction, which can result in drug-induced hypothyroidism includes amiodarone, nitroprusside, sulfonylureas, thalidomide, interleukin, lithium, perchlorate, and interferon-alpha therapy.

Drug-induced hypothyroidism presents with the same signs and symptoms as are seen with other hypothyroid conditions (i.e., fatigue, cold intolerance, weight gain, depression, and dry skin).

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

TSH and free T4 are the usual laboratory diagnostic tools in the diagnosis of hypothyroidism. In hypothyroidism due to drug-induced hypothyroidism, free T4 will be decreased and TSH will be increased in an effort to provide the body with adequate thyroid hormones. T3 is not as reliable in the diagnosis of hypothyroidism. However, measuring TSH, free T4, or other analytes will not identify the cause of the hypothyroidism as drug induced.

In a patient with stable thyroid status, TSH is the more sensitive test in the diagnosis of hypothyroidism, since the relationship between TSH and free T4 is log/linear. Intraindividual variation for free T4 is quite small, so any small deficiency of free T4 will be sensed by the anterior pituitary relative to the individual’s set point and cause an amplified, inverse response in TSH.

In a patient with unstable thyroid status, free T4 is the more reliable indicator.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Interferences may obscure the diagnosis of drug-induced hypothyroidism or complicate the monitoring of the effectiveness of thyroid replacement therapy.

Most thyroid testing today is performed by either immunoassay in which labeled and unlabeled ligands compete for a limited number of antibody sites, or immunometric assays in which an antibody is bound to a solid surface rather than an antibody. Cross reactivity of autoantibodies or heterophilic antibodies can affect diagnostic accuracy of competitive binding based tests. The term heterophilic antibodies is often loosely applied to relatively weak antibodies with multiple activity sites, known as autoantibodies, seen in auto immune disorders; broadly reactive antibodies induced by infections or exposure to therapy containing monoclonal mouse antibodies (HAMA); or human anti-animal immunoglobulins produced against well defined, specific antigens following exposure to therapeutic agents containing animal antigen or by coincidental immunization through exposure to animal antigens.

The latter, Human Anti-Animal Antibodies (HAAA), are strong reactors. HAMA and HAAA affect immunometric assays more than simple competitive immunoassays. In immunometric assays, HAMA and HAAA can form a bridge between the capture and signal antibodies. Autoantibodies and heterophilic antibody interferences can sometimes be detected by simply using a different manufacturer’s method employing a slightly different antibody. Tests in which dilutions are acceptable, such as total T4, total T3, or TSH, but not free T4 or free T3, may be checked for linearity of response to help identify heterophilic antibody interference.

Most circulating thyroid hormones are bound to protein. Only the hormone that is free is biologically active. Variations in binding protein will cause variations in concentrations of total hormones. In general, serum TSH is less affected by binding issues than T3 and T4, and T4 is bound more tightly than T3. T3 and T4 circulate in the body bound to thyroid binding globulin (TBG); transthyretin, formally known as thyroixine binding prealbumin; and serum albumin. Physiological shifts toward greater total hormone binding will decrease available free hormone. Theoretically, free T3 and free T4 are not affected analytically by binding. In reality, all of the free methods are binding dependent to varying degrees.

Phenytoin, carbamazepine, aspirin, and furosimide compete with thyroid hormone for protein binding sites and, thus, acutely increase free hormone and reduce total hormones. Eventually, a normal equilibrium is reestablished where free levels normalize at the expense of total levels.

Heparin stimulates lipoprotein lipase, liberating free fatty acids, which inhibit total T4 protein binding and elevate free T4.

Free fatty acids are known to affect some methods.

Estrogens increase TBG increasing total thyroid hormones.

What Lab Results Are Absolutely Confirmatory?

There are no confirmatory tests for drug-induced hypothyroidism, as drug-induced hypothyroidism cannot be differentiated from other hypothyroidisms, other than by implication. If a drug known to cause drug-induced hypothyroidism is present and/or if the hypothyroidism is corrected with the removal of the implicated drug, then the hypothyroidism is presumed drug induced.

Otherwise, it has been suggested that the best confirmation of hypothyroidism, in general, is an evaluation of response to a trial administration of thyroxine supplement in patients with symptoms of hypothyroidism.

Patients with positive thyroperoxidase antibodies (TPOAbs) are at an increased risk of developing drug-induced hypothyroidism with several of the nonthyroid related drugs. Patients with positive TPOAbs are at particular risk when a preexisitng Hashimoto’s thyroiditis is present or when taking amiodarone. Amiodarone is an iodine containing antiarrhythmic.

The National Academy of Clinical Biochemistry has specific guidelines for patients taking amiodarone. These guidelines recommend:

  • if TSH is abnormal, a complete physical examination with baseline TSH, TPOAb, free T4, and free T3 should be undertaken prior to amiodarone therapy initiation

  • thyroid status should be monitored every 6 months via TSH after amiodarone initiation.

  • TPOAb is a risk factor for developing drug-induced hypothyroidism at any time during amiodarone therapy

Amiodarone induced hyperthyroidism (AIH) can also occur.

Symptoms of hypothyroidism may include brittle fingernails, coarsening and thinning of hair, puffy eyes, weakness, and constipation. Symptoms expressing themselves later in the course of the disease are hoarseness; menstrual disorders; puffy hands, face, and feet; thickening of the skin; thinning of eyebrows; increased cholesterol levels; muscle and/or joint aches and stiffness; slowed speech; and decreased hearing.

A combination of high free T4 and high TSH may be an indication of therapeutic noncompliance. Acute ingestion of missed levothyroxine (L-T4) just prior to a clinic visit will raise the free T4 but fail to normalize the TSH because of a “lag effect.” Free T4 is the short-term indicator, whereas TSH is a long-term indicator. Since TSH is the long-term indicator, it is not influenced by time of L-T4 ingestion.

When testing free T4, the daily dose of L-T4 should be withheld until after sampling, as free T4 is significantly increased above baseline for up to 9 hours after ingesting L-T4. Ideally, L-T4 should be taken prior to eating, at the same time each day, and at least 4 hours apart from other medications. Many medications, and even vitamins and minerals, can influence L-T4 absorption. L-T4 should not be taken with iron supplements. Patients should not switch from brand to brand of L-T4, and prescriptions should not be written generically, as doing so will allow brand to brand switches. Although stated concentrations of L-T4 may be the same, slight variations exist between pharmaceutical manufacturers in terms of bioavailability.

Medication storage recommendations should be scrupulously followed. Medication should be stored away from humidity, light, and increased temperatures. When ordering medication, it is best to avoid the summer for shipping.

TSH or free T4 levels may be diagnostically misleading during transition periods of unstable thyroid function. Often, these transition periods occur in the early phase of treating hyper- or hypothyroidism or changing the L-T4 dose. It takes 6-12 weeks for pituitary TSH secretion to reequilibrate to the new thyroid hormone status. Similar periods of unstable thyroid status may occur following an episode of thyroiditis.

TSH or free T4 levels may be diagnostically misleading in cases of abnormalities in hypothalamic or pituitary function in which the usual negative feedback is not seen and TSH may remain within normal ranges.

Free T4 and TSH have reduced specificity in hospitalized patients with nonthyroid illness. Most hospitalized patients have low serum total T3 and free T3. These abnormalities are seen with both acute and chronic nonthyroid illness and are thought to be the malfunction of central inhibition of hypothalamic releasing hormone.

The National Academy of Clinical Biochemistry guidelines for testing of hospitalized patients with nonthyroid illness recommendations indicate:

  • Acute or chronic nonthyroid illness has complex effects on thyroid function testing. Whenever possible, diagnostic testing should be deferred until the illness has resolved, except in cases in which there is a suggestion of presence of thyroid dysfunction.

  • Physicians should be aware that some thyroid tests are inherently not interpretable in severely ill patients or patients receiving multiple medications.

  • TSH in the absence of dopamine or glucocorticoid therapy is the more reliable test.

  • TSH testing in the hospitalized patient should have a functional sensitivity of less than 0.02 mIU/L; otherwise, sick, hyperthyroid patients with profoundly low TSH cannot be differentiated from patients with mild transient TSH suppression caused by nonthyroid illness.

  • An abnormal free T4 in the presence of serious somatic disease is unreliable. In hospitalized patients, abnormal free T4 testing should reflex to total T4. If both free T4 and total T4 are abnormal in the same direction, a thyroid condition may exist. Discordant free T4 and total T4 abnormalities are more likely the result of illness, medication, or a testing artifact.

  • Total T4 abnormalities should be considered in conjunction with the severity of the patient illness. A low T4 in patients not in intensive care is suspicious of hypothyroidism, since low total T4 levels in nonthyroid illness in hospitalized patients are most often seen in sepsis. If a low total T4 is not associated with an elevated TSH and the patient is not profoundly sick, hypothyroidism secondary to pituitary or hypothalamic deficiency should be considered.

  • Reverse T3 formed by the loss of an iodine group from T4 where the position of the iodine atoms on the aromatic ring is reversed is rarely helpful in the hospital setting, because paradoxically normal or low values can result from impaired renal function and low binding protein concentrations.

During pregnancy, estrogens increase TBG to 2 or 3 times prepregnancy levels. This shifts binding such that total T3 and total T4 are approximately 1.5 times nonpregnant levels at 16 weeks gestation.

TSH is also altered during pregnancy. TSH is decreased in the first trimester because of the thyroid stimulating activity of human chorionic gonadotropin (HCG). The decline in TSH is associated with a modest increase in free T4 from the increased TBG. In approximately 2% of pregnancies, the increase in free T4 leads to a condition known as gestational transient thyrotoxicosis. This condition may be associated with hyperemesis.

In the second and third trimester, free hormone levels decrease 20-40% below reference ranges.

Pregnant patients receiving L-T4 replacement may require increased dose to maintain a normal TSH and free T4.

TSH has a very short half-life of 60 minutes and is subject to circadian and diurnal variation peaking at night and reaching a nadir between 10 AM and 4 PM. T4 has a much longer half-life of 7 days.

It should be noted that there is a continuous decrease in the TSH/free T4 ratio from the middle of gestation through completion of puberty. In adulthood, TSH increases in the elderly. Age related reference ranges, or at least ratio adjusted reference ranges, should be used for these analytes.

For a change in value to have clinical significance, the difference should take into consideration analytical and biological variabilities. The magnitude of difference in thyroid testing values reflecting a clinical significance when monitoring a patient’s response to therapy are:

  • T4 28 nmol/L (2.2 μg/dL)

  • free T4 6 pmol/L (0.5 ng/dL)

  • T3 0.55 nmol/L (35 ng/dL)

  • free T3 1.5 ( pmol/L (0.1 ng/dL)

  • TSH 0.75 mIU/L

When depression starts in the neck

Treating an underactive thyroid gland may improve mood.

Updated: June 5, 2019Published: July, 2011

When someone develops depression, the brain usually becomes the focus of attention. But other organs can be the source of the problem. A common example is when the thyroid gland produces too little hormone — a condition known as hypothyroidism.

Over 10 million Americans suffer from hypothyroidism. The condition is much more common in women than in men, and becomes more prevalent with age. As many as one in five women will develop hypothyroidism by age 60.

Although researchers aren’t entirely sure why there is a link between hypothyroidism and depression, it is likely that some people are taking antidepressants when they should really be taking thyroid medication. Here is a brief review of when clinicians and patients should consider hypothyroidism as a possible cause of low mood — and what to do next.

Front view: Thyroid gland

The mighty thyroid

The thyroid gland is a small butterfly-shaped structure that sits low in the neck, below the Adam’s apple (a protrusion made of cartilage that both women and men have). Although it weighs less than an ounce, the thyroid exerts a powerful influence throughout the body. It does so by secreting hormones that affect metabolism, a chemical activity that controls how fast and efficiently cells convert nutrients into energy. By regulating metabolism, the thyroid indirectly affects every cell, tissue, and organ in the body — from muscles, bones, and skin to the digestive tract, heart, and brain.

The thyroid, in turn, is regulated by the pituitary or “master” gland. The pituitary gland (a pea-sized gland that sits beneath the brain) constantly monitors blood levels of hormones, including those produced by the thyroid. When blood levels of thyroid hormones fall, the pituitary gland uses a chemical signal known as thyroid-stimulating hormone (TSH) to prompt the thyroid to pump up production. In response, the thyroid uses iodine from food to produce two hormones. Triiodothyronine, known as T3, contains three iodine atoms, while thyroxine, or T4, contains four. A normally functioning thyroid gland, working in conjunction with the pituitary gland, secretes T3 and T4 into the bloodstream at a steady pace.

In a person with hypothyroidism, however, the thyroid gland does not fully respond to TSH, so blood levels of T3 and T4 remain low. Assuming the pituitary is functioning normally, TSH levels rise; physicians often use the TSH level to help make a diagnosis of hypothyroidism.

When thyroid hormone levels are low, many organs and internal systems slow down, creating a wide range of symptoms — including depression. People over 60 may have only one symptom — such as mood impairment or difficulty concentrating.

Distinguishing depression from hypothyroidism*

Shared symptoms

  • Depressed mood

  • Fatigue

  • Weight gain

  • Reduced sexual desire

  • Trouble concentrating

More typical of depression

More likely hypothyroidism

  • Insomnia

  • Restlessness and inability to sit still

  • Feelings of worthlessness

  • Inappropriate guilt

  • Thoughts of death or suicide

  • Planning or attempting suicide

  • Feeling chilled or overly sensitive to cold temperatures

  • Constipation

  • Muscle cramps or stiffness

  • Dry skin and hair

  • Hair loss

  • Hoarseness

  • Slowed heart rate

*Blood tests measuring thyroid function are necessary to confirm a diagnosis of hypothyroidism.

Causes of hypothyroidism

The thyroid gland is a small butterfly-shaped structure that sits low in the neck, below the Adam’s apple (a protrusion made of cartilage that both women and men have). Although it weighs less than an ounce, the thyroid exerts a powerful influence throughout the body. It does so by secreting hormones that affect metabolism, a chemical activity that controls how fast and efficiently cells convert nutrients into energy. By regulating metabolism, the thyroid indirectly affects every cell, tissue, and organ in the body — from muscles, bones, and skin to the digestive tract, heart, and brain.

The thyroid, in turn, is regulated by the pituitary or “master” gland. The pituitary gland (a pea-sized gland that sits beneath the brain) constantly monitors blood levels of hormones, including those produced by the thyroid. When blood levels of thyroid hormones fall, the pituitary gland uses a chemical signal known as thyroid-stimulating hormone (TSH) to prompt the thyroid to pump up production. In response, the thyroid uses iodine from food to produce two hormones. Triiodothyronine, known as T3, contains three iodine atoms, while thyroxine, or T4, contains four. A normally functioning thyroid gland, working in conjunction with the pituitary gland, secretes T3 and T4 into the bloodstream at a steady pace.

In a person with hypothyroidism, however, the thyroid gland does not fully respond to TSH, so blood levels of T3 and T4 remain low. Assuming the pituitary is functioning normally, TSH levels rise; physicians often use the TSH level to help make a diagnosis of hypothyroidism.

When thyroid hormone levels are low, many organs and internal systems slow down, creating a wide range of symptoms — including depression. People over 60 may have only one symptom — such as mood impairment or difficulty concentrating.

Diagnosing and treating hypothyroidism

Unless the pituitary gland is malfunctioning, a simple blood test to measure TSH provides a definitive test for hypothyroidism. Typically a clinician also feels a patient’s neck to assess the size of the thyroid gland and checks for other physical signs of hypothyroidism, such as brittle nails and dry skin.

Treatment usually involves taking a medication once a day to restore thyroid hormone levels to normal. Several options exist.

Levothyroxine. The most commonly prescribed drug is a purified form of synthetic T4, levothyroxine (Levothroid, Synthroid, others). Levothyroxine works in the same way natural thyroid hormone does, provides stable levels of hormone, and is well absorbed.

All brands are equally effective, but each brand or generic formulation contains slight variations of ingredients that may affect the amount of drug in the blood. The issue is not one of quality, because generic drugs undergo the same potency tests that brand-name drugs do. Instead, the problem is that pharmacies may substitute one generic for another. Therefore it’s important to consult with your doctor if, for any reason, you receive a new brand.

Clinicians determine the initial dose of levothyroxine based on a patient’s weight, age, severity of hypothyroidism, and other medical conditions or medications. In older people, for example, raising thyroid hormone levels too quickly may place stress on the heart — so clinicians usually begin with a low dose and increase it gradually. All people metabolize drugs in different ways, making the same dose more effective in one person than another. Certain medications — such as the mood stabilizer carbamazepine (Tegretol) and the antidepressant sertraline (Zoloft) — may reduce the effectiveness of levothyroxine. Given all these factors, clinicians order periodic blood tests to monitor how effective a thyroid medication is for each individual, and make adjustments based on the results.

Other options. Liothyronine (Cytomel), a synthetic version of T3, is eliminated from the system faster than T4, so levels fluctuate more. Another option is liotrix (Thyrolar), which combines both T3 and T4 in one pill. Both of these drugs may require more careful dosing to avoid raising thyroid hormone levels too far. Yet some people respond better to these medications.

Combining antidepressants and thyroid medications

Thyroid medications are sometimes added to antidepressant treatment to improve mood — even when thyroid function is normal. Clinicians usually recommend liothyronine (T3 hormone) to augment antidepressant therapy, but in some cases they recommend levothyroxine (T4). One theory is that thyroid drugs act in concert with antidepressants in the brain. Another idea is that thyroid pills boost chemical activity in the brain, improving mood and concentration.

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study evaluated the combination of T3 thyroid hormone and antidepressants in people who had not improved after two previous treatments. About 25% of those taking T3 thyroid hormone saw additional improvement in their symptoms.

Chances of hyothroidism recovery

Most people with hypothyroidism respond positively to treatment and find that depression and other bothersome symptoms subside with time. How long that takes is an individual matter, ranging from weeks to months. Elderly people may take longer to respond, since doses of thyroid medications need to be increased slowly to avoid putting any strain on the heart.

As a service to our readers, Harvard Health Publishing provides access to our library of archived content. Please note the date of last review on all articles. No content on this site, regardless of date, should ever be used as a substitute for direct medical advice from your doctor or other qualified clinician.

The thyroid is the gland in your neck associated with metabolism—the processes by which your body makes use of energy. Autoimmune thyroid disease is common in lupus. It is believed that about 6% of people with lupus have hypothyroidism (underactive thyroid) and about 2% have hyperthyroidism (overactive thyroid). A thyroid gland that is functioning improperly can affect the function of organs such as the brain, heart, kidneys, liver, and skin. Hypothyroidism can cause weight gain, fatigue, depression, moodiness, and dry hair and skin. Hyperthyroidism can cause weight loss, heart palpitations, tremors, heat intolerance, and eventually lead to osteoporosis. Treatment for both underactive and overactive thyroid involves getting your body’s metabolism back to normal.

Thyroid Hormone Replacement

Thyroid replacement is used to treat people with underactive thyroid, whether it is caused by autoimmune disease, radioactive iodine treatment, or surgical removal. The main medication used to treat hypothyroidism is levothyroxine sodium (Synthroid, Levoxyl, and Levothroid), a synthetic version of thyroxine (T4), a thyroid hormone your body produces naturally. Other medications are also available, namely liothyronine, a synthetic version of another thyroid hormone called triiodothronine (T3); liotrix, a synthetic combination of T4 and T3; and desiccated natural thyroid (natural thyroid hormone prepared from dried porcine thyroid). Since these medications simply supplement a hormone that is missing, the only real safety concern is ensuring that you take the right amount. Therefore, your doctor will need to regularly check your thyroid and TSH levels to make sure you are receiving the correct dosage.

Thyroid hormone stays in your body for a long time, so you will only need to take it once a day, usually in the morning. It is important to take this medication without food, because food can affect your body’s absorption of the hormone. In addition, remember to take your thyroid medication at the same time of day, and do not stop taking your medication without first discussing the decision with your doctor. Many people need to take thyroid medication for the rest of their lives.

Remember to tell your doctor about any other medications you may be taking, since certain drugs can interact with your thyroid medication. These include oral contraceptives, estrogen, testosterone, certain anti-seizure medications, cholesterol-lowering medications (statins) and some antidepressants. Certain foods can also interfere with your body’s absorption of thyroid hormone, including iron, calcium, and soy.

If you are pregnant or may become pregnant, it is perfectly safe to continue taking your thyroid medication. It is important for pregnant women to maintain appropriate levels of thyroid hormone in the body to provide the healthiest environment for fetal development. When you first learn that you are pregnant, you should contact your doctor so that s/he can check your thyroid hormone and TSH levels; these levels should also be checked once during each trimester.

Anti-thyroid Medications

Propylthioracil (PTU)
Methimazole (Tapezole)

Propylthioracil (PTU) and methimazole (Tapezole) are medications used to treat overactive thyroid. They work by slowing down the production of thyroid hormone and do not cause permanent damage. When taken appropriately, these medications can control hyperthyroidism in just a few weeks; however, the main problem with anti-thyroid medications lies with the fact that the underlying problem returns once they are discontinued. Therefore, many people are encouraged to seek more permanent treatments, such as radioactive iodine treatment or surgical removal. Side effects of anti-thyroid medications include skin rash, upset stomach, drowsiness, and a bitter aftertaste. Rare but serious side effects include sore throat, fever, chills, jaundice, decreased white blood cells, and liver disease.

Your doctor may also prescribe a medication called a beta blocker (a drug usually given for high blood pressure) to block the action of thyroid hormone in your body. While beta blockers will not change the levels of thyroid hormone in your blood, they will make you feel better by reducing some of the symptoms of hyperthyroidism, including increased heart rate, shakes, and nervousness. These drugs work within hours and may help to quell these symptoms before other drugs have a chance to take effect. However, speak to your doctor if you have Raynaud’s phenomenon (color changes in the fingers and toes with cold exposure), since beta blockers worsen this condition.

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