The Molecule That Replaced an Organ
Levothyroxine is the most prescribed drug in the United States. This is the sixty-four-year relay — from sheep glands to pharmaceutical-grade synthesis — that made it possible.
Written by Seth Collins, Pharm.D.
Updated on May 22, 2026
Drug History
3 viewsLevothyroxine is the most prescribed drug in the United States. The numbers shift slightly depending on methodology, but the position at the top does not. Between 150 and 180 million prescriptions annually. It is a synthetic version of a hormone the human thyroid gland has been producing since before vertebrates had spines.
Every pharmacist dispenses it constantly. It comes in twelve tablet strengths, from 25 micrograms to 300, because the dosing is precise enough that a 12-microgram difference changes a patient's lab values measurably. It has a half-life of seven days. Patients take it on an empty stomach, wait thirty minutes before eating, avoid calcium and iron supplements within four hours, and repeat this indefinitely. The molecule itself is simple: four iodine atoms attached to a pair of linked tyrosine rings. A structure a chemistry undergraduate could draw in ten minutes.
It took humanity roughly forty years to figure out what it was.
The Disease Nobody Could Name
On October 24, 1873, a surgeon named William Gull presented a paper to the Clinical Society of London describing something he had observed in several adult women. They had become slow, mentally and physically. Their faces were puffy. Their skin coarse, their hair thin, their reflexes delayed in a way he had not encountered before. They were cold when the room was not cold. They moved as though pushing through resistance no one else could see.
Gull called it a "cretinoid state" in adults. The word cretinism already existed for children born with severe developmental delay and stunted growth, children born without functional thyroid glands or in iodine-deficient regions. The connection between adult and childhood syndromes was not yet obvious. The thyroid gland was known to anatomists, but its function was unknown. It had no duct and secreted nothing anyone had identified. A reasonable physician in 1873 could have concluded it was vestigial.
The Clinical Society convened a committee. They gathered sixty-one cases and eighteen autopsies. The 1888 report documented the clinical picture precisely and named it myxedema. They confirmed the thyroid was consistently abnormal in autopsied cases. They did not know what to do about it.
That problem fell to a physician in Middlesbrough named George Redmayne Murray.
Murray and the Sheep
Murray was twenty-five years old in 1891 when he read the Clinical Society report and reached a direct conclusion: if the thyroid does something essential and patients with myxedema have no functioning thyroid, what happens if you give them someone else's?
He extracted glycerine from sheep thyroid glands, prepared an injectable solution, and on April 13, 1891, began administering it to a forty-six-year-old woman who had been severely myxedematous for years. She improved substantially. Her puffiness decreased, her reflexes returned, her mental clarity came back. He published the case in the British Medical Journal in October 1891, six months after beginning treatment.
The case report is worth reading for what it documents at the end. His original patient, Mrs. S., continued thyroid extract injections and later oral preparations for the remaining twenty-eight years of her life. When she died in 1919 at age seventy-four, Murray calculated she had consumed around five liters of thyroid extract derived from approximately 870 sheep. Murray had not cured her. He had replaced a function her body had lost, using material from another species, and it worked every day for nearly three decades.
Within a few years, desiccated thyroid tablets, dried and powdered gland from pigs and cattle, were being produced commercially. Patients swallowed them and stabilized. Nobody knew why, because nobody had identified what in the gland was actually doing the work.
Kendall at Mayo, 1914
Edward Calvin Kendall arrived at the Mayo Clinic in Rochester, Minnesota, in 1914 with a specific objective: isolate the active substance from thyroid tissue. He had already attempted this at Parke-Davis in Detroit and failed. The molecule was unstable and extraction attempts destroyed it.
Working through Christmas 1914, Kendall processed 6,500 pounds of hog thyroid glands using alkaline hydrolysis followed by careful precipitation and recrystallization. He had fallen asleep in the laboratory while evaporating ethanol from a partially purified extract and awoke to find a white crust had formed in a glass beaker. On Christmas Day, he repeated the extraction and confirmed what he had. He called it thyroxine. It was iodine-containing, and it was the substance that had been doing what desiccated thyroid had done empirically since Murray's sheep experiments twenty-three years earlier.
Kendall later won the Nobel Prize, but not for thyroxine. He won it for cortisone, the same glucocorticoid whose post-1949 long-term toxicity data eventually drove other researchers toward finding a non-steroidal anti-inflammatory. His Nobel biography notes that his name "will always be associated with his isolation of thyroxine," and then the citation moves on. His thyroid work, which had been immediately useful to far more patients for far longer, received no prize. It appears as a footnote.
Harington and the Structure
What Kendall had done was isolate the molecule. He did not know its chemical structure. He knew it worked.
Charles Robert Harington arrived at University College Hospital Medical School in London in the mid-1920s to determine the structure and synthesize the molecule from scratch. He examined Kendall's thyroxine, its iodine content, optical activity, and hydrolysis products, and identified a tyrosine backbone: two tyrosine-derived rings linked by an oxygen bridge, with four iodine atoms distributed across them. He worked out the structure analytically, then built it with George Barger of the University of Edinburgh.
The synthesis was published in the Biochemical Journal in 1927. This was academic chemistry done at a bench with limited equipment, published because that was what you did. Harington and Barger did not profit significantly from it. The molecule they assembled from component parts in London was identical to the one Kendall had extracted from 6,500 pounds of hog glands in Minnesota.
One thing Harington did not fully resolve was the isomer problem. The synthesized thyroxine was a racemic mixture, equal parts of two mirror-image forms of the molecule: L-thyroxine and D-thyroxine. The L-form is the biologically active one. The body makes only L-thyroxine. The D-form has minimal biological activity. Harington understood this, but the purification technology to separate them reliably at scale did not yet exist. That would take another thirty years.
The Second Hormone
Between Murray's injections in 1891 and the commercial introduction of pure synthetic levothyroxine in 1955, tens of millions of patients were treated with desiccated thyroid. Armour Thyroid became the standard. It worked, and physicians learned to dose it.
The problem was consistency. Desiccated thyroid is a biological product. The iodine content of an animal's thyroid varies with diet, health, and processing method. Potency shifted between batches. For a hormone where dosing precision mattered, where a 12-microgram difference registers in laboratory values, that variability was not trivial.
The other problem was ratio. Human thyroid glands produce mostly T4, which is thyroxine, alongside a small amount of T3, or triiodothyronine. Porcine glands produce a higher proportion of T3 than humans make. Patients on desiccated thyroid were receiving a hormone blend that did not match human physiology. Nobody fully understood why this mattered until 1952, when a biochemist at the National Institute for Medical Research in London named Rosalind Pitt-Rivers, working with a Canadian postdoctoral fellow named Jack Gross, identified the unknown iodine-containing compound in human plasma as 3:5:3'-L-triiodothyronine. They published the finding in The Lancet in March 1952.
T3 is what T4 becomes in the body. The liver and other tissues strip one iodine atom from circulating thyroxine, converting it to T3, which then acts on cells. Thyroxine functions largely as a prohormone, and T3 does most of the metabolic work. This finding restructured how thyroid physiology was understood. Pitt-Rivers was elected a Fellow of the Royal Society in 1954. The discovery itself was gradually attributed in shorthand to Gross alone in the literature, then absorbed into background knowledge without consistent attribution to either of them. She continued working at the NIMR, eventually heading its Division of Chemistry, until retirement in 1972. She died in January 1990.
Synthroid, 1955
In 1955, Flint Laboratories introduced Synthroid: synthetic levothyroxine sodium, the pure L-isomer, at consistent pharmaceutical-grade potency.
This was the practical endpoint of a sixty-four-year relay. Murray's sheep experiments in 1891. Kendall's isolation in 1914. Harington and Barger's synthesis in 1927. Now a stable, manufacturable, bioidentical form of what the human thyroid gland produces, without batch variation, without D-isomer contamination, without porcine T3 ratios mismatched to human biology.
Physicians began switching patients. The transition was not immediate. Desiccated thyroid had a loyal clinical following, and patients stable on it for decades were reluctant to change. Some still prefer it, and that debate has never fully resolved. What synthetic levothyroxine did over the following decades was become quietly indispensable. Hypothyroidism affects somewhere between four and ten percent of the population depending on how subclinical cases are counted. It is more common in women and more common with age. In a country of 330 million people with functional healthcare access, the number of patients requiring thyroid replacement every day for the rest of their lives is very large. The prescription volume followed from the math.
The Boots Study
In 1987, Boots Pharmaceuticals, which had acquired the Synthroid brand from Flint, commissioned a researcher at UCSF named Betty Dong to conduct a bioequivalence study. The question was straightforward: was Synthroid meaningfully different from generic levothyroxine, or were the products clinically interchangeable?
The study ran five years. Dong enrolled twenty-two women with stable hypothyroidism and compared Synthroid against three alternative levothyroxine preparations in a four-way crossover design. By 1990, she had her answer: the products were bioequivalent. No significant differences among the four preparations.
This was the finding Boots had funded the study to generate. It was not, apparently, the finding Boots wanted.
Boots had argued publicly that its brand was superior and had priced accordingly. When Dong completed the study, the company alleged methodological problems that a UCSF investigation found to be minor and correctable. Boots then invoked a contract clause giving them control over publication. The paper was accepted by the Journal of the American Medical Association in 1994. Under legal threat, Dong withdrew the manuscript. JAMA held the paper.
On April 25, 1996, the Wall Street Journal ran a front-page story on the suppression. The exposure changed the calculation. JAMA published the study in April 1997, seven years after Dong had the results. An accompanying editorial by JAMA Deputy Editor Drummond Rennie described the episode in plain terms. The FDA responded by classifying levothyroxine products as "new drugs" requiring formal approval and bioequivalence data, not because the drug was problematic, but because the agency had allowed the regulatory standard to go unset for the most widely prescribed drug in the country. Knoll Pharmaceutical, which had acquired Boots and Synthroid during the suppression period, settled a consumer class action for $135 million and later paid an additional $41.8 million to thirty-seven states to resolve charges of deceptive marketing.
Dong had done the work correctly. It was buried for seven years by the company that paid for it because the answer was commercially inconvenient. The FDA's current regulatory framework for levothyroxine products descends directly from the aftermath of that suppression.
What the Number Represents
Levothyroxine does one thing. It replaces a hormone the body is failing to produce in sufficient quantity. There is no dramatic mechanism here, no repurposed accident like a molecule synthesized for arthritis that turned out to close fetal heart vessels in neonatal units. It is substitution therapy: take the molecule the thyroid makes, synthesize it at pharmaceutical purity, give it to the person whose thyroid cannot make enough. Multiply that by 150 million prescriptions per year in the United States alone.
The relay that produced it ran from a physician in Middlesbrough injecting sheep thyroid into a woman with myxedema, through a chemist in Minnesota processing 6,500 pounds of hog glands to isolate crystalline thyroxine on Christmas Day, through two chemists who determined the structure and built it from scratch in London, through a biochemist whose name mostly disappeared from the discovery she helped make, through a manufacturer who solved the final production problem in the 1950s, and through a researcher in San Francisco who spent five years collecting data that a pharmaceutical company spent seven years trying to prevent from reaching physicians.
Mrs. S. took sheep thyroid preparations every day for twenty-eight years and died at seventy-four in 1919.
A patient started on levothyroxine today will take a tablet every morning before breakfast for the rest of their life, wait thirty minutes, and go about their day. The tablet costs a few cents. The alternative is the condition William Gull described in London in 1873: the slow face, the cold intolerance, the mind moving through resistance no one else can see.
Some molecules are not dramatic. They are necessary, every day, for everyone who needs them, and it turns out that is a very large number of people.
Sources
Gull WW. On a cretinoid state supervening in adult life in women. Transactions of the Clinical Society of London. 1874;7:180–185.
Ord WM (chairman). Report of a committee of the Clinical Society of London nominated December 14, 1883, to investigate the subject of myxoedema. Trans Clin Soc Lond. 1888;21(suppl):1–215.
Murray GR. Note on the treatment of myxoedema by hypodermic injections of an extract of the thyroid gland of a sheep. British Medical Journal. 1891;2(1606):796–797. doi:10.1136/bmj.2.1606.796.
Murray GR. The life history of the first case of myxoedema treated by thyroid extract. British Medical Journal. 1920;1:359–360.
Kendall EC. The isolation in crystalline form of the compound containing iodin, which occurs in the thyroid. JAMA. 1915;64(25):2042–2043.
Harington CR, Barger G. Chemistry of thyroxine: constitution and synthesis of thyroxine. Biochemical Journal. 1927;21(1):169–183. doi:10.1042/bj0210169.
Gross J, Pitt-Rivers R. The identification of 3:5:3'-L-triiodothyronine in human plasma. The Lancet. 1952;259(6705):439–441. doi:10.1016/S0140-6736(52)91952-1.
Dong BJ, Hauck WW, Gambertoglio JG, et al. Bioequivalence of generic and brand-name levothyroxine products in the treatment of hypothyroidism. JAMA. 1997;277(15):1205–1213.
Rennie D. Thyroid storm. JAMA. 1997;277(15):1238–1243.
Lindholm J. Hypothyroidism and thyroid substitution: historical aspects. Journal of Thyroid Research. 2011. doi:10.4061/2011/809341.
The Pillars is a series on the foundational molecules of modern medicine. Written by Seth Collins, Pharm.D.
Every pharmacist dispenses it constantly. It comes in twelve tablet strengths, from 25 micrograms to 300, because the dosing is precise enough that a 12-microgram difference changes a patient's lab values measurably. It has a half-life of seven days. Patients take it on an empty stomach, wait thirty minutes before eating, avoid calcium and iron supplements within four hours, and repeat this indefinitely. The molecule itself is simple: four iodine atoms attached to a pair of linked tyrosine rings. A structure a chemistry undergraduate could draw in ten minutes.
It took humanity roughly forty years to figure out what it was.
The Disease Nobody Could Name
On October 24, 1873, a surgeon named William Gull presented a paper to the Clinical Society of London describing something he had observed in several adult women. They had become slow, mentally and physically. Their faces were puffy. Their skin coarse, their hair thin, their reflexes delayed in a way he had not encountered before. They were cold when the room was not cold. They moved as though pushing through resistance no one else could see.
Gull called it a "cretinoid state" in adults. The word cretinism already existed for children born with severe developmental delay and stunted growth, children born without functional thyroid glands or in iodine-deficient regions. The connection between adult and childhood syndromes was not yet obvious. The thyroid gland was known to anatomists, but its function was unknown. It had no duct and secreted nothing anyone had identified. A reasonable physician in 1873 could have concluded it was vestigial.
The Clinical Society convened a committee. They gathered sixty-one cases and eighteen autopsies. The 1888 report documented the clinical picture precisely and named it myxedema. They confirmed the thyroid was consistently abnormal in autopsied cases. They did not know what to do about it.
That problem fell to a physician in Middlesbrough named George Redmayne Murray.
Murray and the Sheep
Murray was twenty-five years old in 1891 when he read the Clinical Society report and reached a direct conclusion: if the thyroid does something essential and patients with myxedema have no functioning thyroid, what happens if you give them someone else's?
He extracted glycerine from sheep thyroid glands, prepared an injectable solution, and on April 13, 1891, began administering it to a forty-six-year-old woman who had been severely myxedematous for years. She improved substantially. Her puffiness decreased, her reflexes returned, her mental clarity came back. He published the case in the British Medical Journal in October 1891, six months after beginning treatment.
The case report is worth reading for what it documents at the end. His original patient, Mrs. S., continued thyroid extract injections and later oral preparations for the remaining twenty-eight years of her life. When she died in 1919 at age seventy-four, Murray calculated she had consumed around five liters of thyroid extract derived from approximately 870 sheep. Murray had not cured her. He had replaced a function her body had lost, using material from another species, and it worked every day for nearly three decades.
Within a few years, desiccated thyroid tablets, dried and powdered gland from pigs and cattle, were being produced commercially. Patients swallowed them and stabilized. Nobody knew why, because nobody had identified what in the gland was actually doing the work.
Kendall at Mayo, 1914
Edward Calvin Kendall arrived at the Mayo Clinic in Rochester, Minnesota, in 1914 with a specific objective: isolate the active substance from thyroid tissue. He had already attempted this at Parke-Davis in Detroit and failed. The molecule was unstable and extraction attempts destroyed it.
Working through Christmas 1914, Kendall processed 6,500 pounds of hog thyroid glands using alkaline hydrolysis followed by careful precipitation and recrystallization. He had fallen asleep in the laboratory while evaporating ethanol from a partially purified extract and awoke to find a white crust had formed in a glass beaker. On Christmas Day, he repeated the extraction and confirmed what he had. He called it thyroxine. It was iodine-containing, and it was the substance that had been doing what desiccated thyroid had done empirically since Murray's sheep experiments twenty-three years earlier.
Kendall later won the Nobel Prize, but not for thyroxine. He won it for cortisone, the same glucocorticoid whose post-1949 long-term toxicity data eventually drove other researchers toward finding a non-steroidal anti-inflammatory. His Nobel biography notes that his name "will always be associated with his isolation of thyroxine," and then the citation moves on. His thyroid work, which had been immediately useful to far more patients for far longer, received no prize. It appears as a footnote.
Harington and the Structure
What Kendall had done was isolate the molecule. He did not know its chemical structure. He knew it worked.
Charles Robert Harington arrived at University College Hospital Medical School in London in the mid-1920s to determine the structure and synthesize the molecule from scratch. He examined Kendall's thyroxine, its iodine content, optical activity, and hydrolysis products, and identified a tyrosine backbone: two tyrosine-derived rings linked by an oxygen bridge, with four iodine atoms distributed across them. He worked out the structure analytically, then built it with George Barger of the University of Edinburgh.
The synthesis was published in the Biochemical Journal in 1927. This was academic chemistry done at a bench with limited equipment, published because that was what you did. Harington and Barger did not profit significantly from it. The molecule they assembled from component parts in London was identical to the one Kendall had extracted from 6,500 pounds of hog glands in Minnesota.
One thing Harington did not fully resolve was the isomer problem. The synthesized thyroxine was a racemic mixture, equal parts of two mirror-image forms of the molecule: L-thyroxine and D-thyroxine. The L-form is the biologically active one. The body makes only L-thyroxine. The D-form has minimal biological activity. Harington understood this, but the purification technology to separate them reliably at scale did not yet exist. That would take another thirty years.
The Second Hormone
Between Murray's injections in 1891 and the commercial introduction of pure synthetic levothyroxine in 1955, tens of millions of patients were treated with desiccated thyroid. Armour Thyroid became the standard. It worked, and physicians learned to dose it.
The problem was consistency. Desiccated thyroid is a biological product. The iodine content of an animal's thyroid varies with diet, health, and processing method. Potency shifted between batches. For a hormone where dosing precision mattered, where a 12-microgram difference registers in laboratory values, that variability was not trivial.
The other problem was ratio. Human thyroid glands produce mostly T4, which is thyroxine, alongside a small amount of T3, or triiodothyronine. Porcine glands produce a higher proportion of T3 than humans make. Patients on desiccated thyroid were receiving a hormone blend that did not match human physiology. Nobody fully understood why this mattered until 1952, when a biochemist at the National Institute for Medical Research in London named Rosalind Pitt-Rivers, working with a Canadian postdoctoral fellow named Jack Gross, identified the unknown iodine-containing compound in human plasma as 3:5:3'-L-triiodothyronine. They published the finding in The Lancet in March 1952.
T3 is what T4 becomes in the body. The liver and other tissues strip one iodine atom from circulating thyroxine, converting it to T3, which then acts on cells. Thyroxine functions largely as a prohormone, and T3 does most of the metabolic work. This finding restructured how thyroid physiology was understood. Pitt-Rivers was elected a Fellow of the Royal Society in 1954. The discovery itself was gradually attributed in shorthand to Gross alone in the literature, then absorbed into background knowledge without consistent attribution to either of them. She continued working at the NIMR, eventually heading its Division of Chemistry, until retirement in 1972. She died in January 1990.
Synthroid, 1955
In 1955, Flint Laboratories introduced Synthroid: synthetic levothyroxine sodium, the pure L-isomer, at consistent pharmaceutical-grade potency.
This was the practical endpoint of a sixty-four-year relay. Murray's sheep experiments in 1891. Kendall's isolation in 1914. Harington and Barger's synthesis in 1927. Now a stable, manufacturable, bioidentical form of what the human thyroid gland produces, without batch variation, without D-isomer contamination, without porcine T3 ratios mismatched to human biology.
Physicians began switching patients. The transition was not immediate. Desiccated thyroid had a loyal clinical following, and patients stable on it for decades were reluctant to change. Some still prefer it, and that debate has never fully resolved. What synthetic levothyroxine did over the following decades was become quietly indispensable. Hypothyroidism affects somewhere between four and ten percent of the population depending on how subclinical cases are counted. It is more common in women and more common with age. In a country of 330 million people with functional healthcare access, the number of patients requiring thyroid replacement every day for the rest of their lives is very large. The prescription volume followed from the math.
The Boots Study
In 1987, Boots Pharmaceuticals, which had acquired the Synthroid brand from Flint, commissioned a researcher at UCSF named Betty Dong to conduct a bioequivalence study. The question was straightforward: was Synthroid meaningfully different from generic levothyroxine, or were the products clinically interchangeable?
The study ran five years. Dong enrolled twenty-two women with stable hypothyroidism and compared Synthroid against three alternative levothyroxine preparations in a four-way crossover design. By 1990, she had her answer: the products were bioequivalent. No significant differences among the four preparations.
This was the finding Boots had funded the study to generate. It was not, apparently, the finding Boots wanted.
Boots had argued publicly that its brand was superior and had priced accordingly. When Dong completed the study, the company alleged methodological problems that a UCSF investigation found to be minor and correctable. Boots then invoked a contract clause giving them control over publication. The paper was accepted by the Journal of the American Medical Association in 1994. Under legal threat, Dong withdrew the manuscript. JAMA held the paper.
On April 25, 1996, the Wall Street Journal ran a front-page story on the suppression. The exposure changed the calculation. JAMA published the study in April 1997, seven years after Dong had the results. An accompanying editorial by JAMA Deputy Editor Drummond Rennie described the episode in plain terms. The FDA responded by classifying levothyroxine products as "new drugs" requiring formal approval and bioequivalence data, not because the drug was problematic, but because the agency had allowed the regulatory standard to go unset for the most widely prescribed drug in the country. Knoll Pharmaceutical, which had acquired Boots and Synthroid during the suppression period, settled a consumer class action for $135 million and later paid an additional $41.8 million to thirty-seven states to resolve charges of deceptive marketing.
Dong had done the work correctly. It was buried for seven years by the company that paid for it because the answer was commercially inconvenient. The FDA's current regulatory framework for levothyroxine products descends directly from the aftermath of that suppression.
What the Number Represents
Levothyroxine does one thing. It replaces a hormone the body is failing to produce in sufficient quantity. There is no dramatic mechanism here, no repurposed accident like a molecule synthesized for arthritis that turned out to close fetal heart vessels in neonatal units. It is substitution therapy: take the molecule the thyroid makes, synthesize it at pharmaceutical purity, give it to the person whose thyroid cannot make enough. Multiply that by 150 million prescriptions per year in the United States alone.
The relay that produced it ran from a physician in Middlesbrough injecting sheep thyroid into a woman with myxedema, through a chemist in Minnesota processing 6,500 pounds of hog glands to isolate crystalline thyroxine on Christmas Day, through two chemists who determined the structure and built it from scratch in London, through a biochemist whose name mostly disappeared from the discovery she helped make, through a manufacturer who solved the final production problem in the 1950s, and through a researcher in San Francisco who spent five years collecting data that a pharmaceutical company spent seven years trying to prevent from reaching physicians.
Mrs. S. took sheep thyroid preparations every day for twenty-eight years and died at seventy-four in 1919.
A patient started on levothyroxine today will take a tablet every morning before breakfast for the rest of their life, wait thirty minutes, and go about their day. The tablet costs a few cents. The alternative is the condition William Gull described in London in 1873: the slow face, the cold intolerance, the mind moving through resistance no one else can see.
Some molecules are not dramatic. They are necessary, every day, for everyone who needs them, and it turns out that is a very large number of people.
Sources
Gull WW. On a cretinoid state supervening in adult life in women. Transactions of the Clinical Society of London. 1874;7:180–185.
Ord WM (chairman). Report of a committee of the Clinical Society of London nominated December 14, 1883, to investigate the subject of myxoedema. Trans Clin Soc Lond. 1888;21(suppl):1–215.
Murray GR. Note on the treatment of myxoedema by hypodermic injections of an extract of the thyroid gland of a sheep. British Medical Journal. 1891;2(1606):796–797. doi:10.1136/bmj.2.1606.796.
Murray GR. The life history of the first case of myxoedema treated by thyroid extract. British Medical Journal. 1920;1:359–360.
Kendall EC. The isolation in crystalline form of the compound containing iodin, which occurs in the thyroid. JAMA. 1915;64(25):2042–2043.
Harington CR, Barger G. Chemistry of thyroxine: constitution and synthesis of thyroxine. Biochemical Journal. 1927;21(1):169–183. doi:10.1042/bj0210169.
Gross J, Pitt-Rivers R. The identification of 3:5:3'-L-triiodothyronine in human plasma. The Lancet. 1952;259(6705):439–441. doi:10.1016/S0140-6736(52)91952-1.
Dong BJ, Hauck WW, Gambertoglio JG, et al. Bioequivalence of generic and brand-name levothyroxine products in the treatment of hypothyroidism. JAMA. 1997;277(15):1205–1213.
Rennie D. Thyroid storm. JAMA. 1997;277(15):1238–1243.
Lindholm J. Hypothyroidism and thyroid substitution: historical aspects. Journal of Thyroid Research. 2011. doi:10.4061/2011/809341.
The Pillars is a series on the foundational molecules of modern medicine. Written by Seth Collins, Pharm.D.
Tags
Issue 002
Drug History
Levothyroxine
Pharmacology