When was synthroid discovered

One other report assessed issues with substituting LT4 products in a more indirect way This was a survey that was e-mailed to endocrinologists to evaluate potency and consistency issues with LT4.

The study analyzed reports of adverse events associated with changes in TSH values and found that However, this report did not directly compare generic and brand-name LT4, and it was inherently limited by the lack of knowledge of the total number of cases of change in the source of the LT4 in all of the patients treated by the survey respondents. Our study has several limitations. First, it was retrospective, and drug choice was not randomly assigned.

Hence, there may be a number of unknown and unmeasured confounders not accounted for that influence both drug assignment and patient outcomes.

Second, whether the patient was taking generic LT4 or Synthroid was determined by prescription records in their chart, which may not reflect what they actually received from the pharmacy. Although we contacted the pharmacies of all subjects to verify that they did in fact receive only generic LT4 or only Synthroid, in a few cases of the subjects on Synthroid, the record of what was dispensed was not available for the entire duration of therapy.

In addition, for patients on generic LT4, the record of which manufacturer the LT4 came from was incomplete or missing for nearly half the cases. Additionally, due to the retrospective nature of the study, there is no way to verify a standard method of administering the LT4 pills, such as taking at the same time of day or on an empty stomach.

In fact, because of the young age of the patients, the time of day of pill administration may be quite variable and often is very close to the time of a feeding. However, we would not expect this to be different between the groups. Along the same line, compliance with treatment could not be verified, although we attempted to assess this by examining the patient histories, and no difference between the groups was observed.

Finally, TSH and free T 4 assays were not always done at our center, and this may have contributed some to the variability observed because there was a trend toward this more often in the Synthroid group than in those taking generic LT4. In conclusion, our data suggest that in young children with congenital hypothyroidism, generic LT4 is therapeutically interchangeable with Synthroid. Given the small number of subjects and the retrospective nature of the study, our data certainly need to be confirmed.

Further study to assess bioequivalence of generic and brand-name LT4 in older children and adults with hypothyroidism in a prospective fashion is warranted. Murray GR. Note on the treatment of myxoedema by hypodermic injections of an extract of the thyroid gland of a sheep. Br Med J. Google Scholar. Kendall FC. The isolation in crystalline form of the compound containing iodine, which occurs in the thyroid.

Lindholm J , Laurberg P. Hypothyroidism and thyroid substitution: historical aspects. J Thyroid Res. Docket no. Prescription drug products: levothyroxine sodium. Fed Regist.

Hennessey JV. Levothyroxine a new drug? Since when? How could that be? Stockigt J. Testing the bioavailability of oral L-thyroxine by studying its absorption: smoke or mirrors?

Toft A. Which thyroxine? Food and Drug Administration. Guidance for industry: levothyroxine sodium tablets—in vivo pharmacokinetic and bioavailability studies and in vitro dissolution testing. Accessed August 8, Prescription drug product list. Orange Book. Therapeutic equivalence evaluation codes. Are bioequivalence studies of levothyroxine sodium formulations in euthyroid volunteers reliable? FDA acts to ensure thyroid drugs don't lose potency before expiration date. Accessed August 15, For many years, desiccated animal thyroid was the source of T 4 used by doctors and was touted as a near-perfect medical therapy.

But, as researchers have discovered, the complete biochemical picture of the thyroid's most important ingredient, thyroxine, is far more complex. Even today, the medical community debates the role of thyroxine and the best way to use it. Doctors and researchers recognized the thyroid's role in metabolism as far back as the late s.

Then, preeminent surgeon Theodor Kocher, who won a Nobel Prize in Physiology or Medicine in for his perfection of surgical thyroidectomy techniques, noted that many of his patients after surgery eventually developed the classic symptoms of hypothyroidism. Soon, doctors found that injecting these patients with thyroid extracts from sheep reversed the symptoms. Even better, they found that patients could take the extracts orally to the same effect.

In the early s, biochemist Edward C. Kendall isolated thyroxine from thyroid extract. He also shared a Nobel Prize in Physiology or Medicine, in , for his discovery of the activity of cortisone. T 4 was eventually synthesized by biochemist Charles R. Harington in Thyroxine is formed there by thyroperoxidase enzymes, which affix iodine atoms to the rings of tyrosine residues of the protein thyroglobulin.

While most of the T 4 remains bound to thyroglobulin, small amounts break free with the help of proteases and circulate throughout the body to act on its metabolism. In the s, researchers discovered another major thyroid hormone, triiodothyronine, or T 3. This far more potent hormone is largely synthesized from T 4 by deiodinase enzymes outside the thyroid. These include grapefruit juice, soy foods such as tofu and soybeans, espresso coffee, and walnuts.

The most common side effects from levothyroxine are:. Ask your pharmacist which side effects they see most often, and what factors make you more likely to develop certain side effects. Find out which side effects warrant a call to your doctor.

Some of the more serious side effects from thyroid hormone include:. While you may assume that your doctor knows all the answers to your hypothyroidism treatment, your pharmacist can be just as helpful. Asking the right questions may make the difference between starting a medication that you rightly thought you were prescribed to getting on a generic brand.

Whether you've just been diagnosed with hypothyroidism or have been living with it for some time, there are certain things you should know about…. Experts say excessive doses of Benadryl can cause serious health issues, including death in some instances. Myxedema is a result of undiagnosed or untreated hypothyroidism, or when someone stops taking their thyroid supplements. Learn more. Understand the link between your stress levels and your thyroid.

Armour Thyroid is a natural desiccated thyroid extract for treating hypothyroidism. Used for over a century, this type of thyroid medication can cause…. Symptoms of hypothyroidism underactive thyroid can disrupt several parts of your life. Weight gain, for example, often causes significant distress….

A better understanding of the comparative effectiveness of generic compared with brand-name levothyroxine preparations may help physicians optimize their decisions about levothyroxine treatment.

In turn, the findings may affect the management of hypothyroidism in millions of patients in the United States and the costs of levothyroxine use. This cohort study adhered to the International Society for Pharmacoeconomics and Outcomes Research ISPOR reporting guideline for defining, reporting, and interpreting nonrandomized studies of treatment effects using secondary data sources. Pharmacy claims include information on medications dispensed, including amount and dates of prescriptions.

Laboratory data, available for a subset of the cohort on the basis of data sharing agreements, include test names, logical observation identifier names, and test results. Study data were accessed using techniques compliant with the Health Insurance Portability and Accountability Act of Because this study involved analysis of preexisting, deidentified data, the Mayo Clinic institutional review board declared it exempt from board approval and informed consent.

We identified 2 cohorts. Patients were required to have at least days of continuous medical and pharmacy benefits coverage before treatment initiation index date and 90 days after initiation. We applied a number of cohort exclusions. We excluded patients who filled any thyroid preparation within the days before the index data ie, only new users were included.

We also excluded patients who were not adherent to levothyroxine therapy. Adherence was measured by the proportion of days covered at 90 days, and patients were considered adherent if the proportion of days covered was greater than To assess thyroid status, we further limited our study to patients who had linked thyrotropin results at both baseline within 90 days before drug initiation and follow-up within weeks after initiation.

Only patients with baseline thyrotropin values ranging from 4. Finally, we excluded patients with conditions that require specific thyrotropin targets that may fall outside of the reference range, such as pregnancy, thyroid cancer, and hypopituitarism, or patients exposed to medications known to affect thyroid hormone levels during the baseline and follow-up periods a list of medications and International Classification of Diseases codes for excluded conditions is found in eTable 1 in the Supplement.

Cohort 2 was a subset of cohort 1. We included only patients from cohort 1 who had a normal follow-up thyrotropin level within 3 months and a subsequent follow-up thyrotropin level measured 6 to 12 weeks after the thyrotropin test with normal findings. Given that these patients had a previous normal thyrotropin value, the individuals were likely to be receiving the same dose of levothyroxine.

We also excluded patients who switched from generic to brand-name or from brand-name to generic levothyroxine within days 6 months of treatment initiation.

We characterized whether the index pharmacy fill was for a generic or a brand-name thyroid hormone drug. We used First Databank to categorize each fill as brand-name or generic.

First Databank categorizes pharmacy products as generic if they are sold under a generic pharmacy label, which includes authorized generic products. The brand-name products included Synthroid AbbVie; [ The generic manufacturers included Mylan Pharmaceuticals [ We examined the effectiveness of levothyroxine based on attained thyrotropin levels measured in the outpatient setting.

For assessment of effectiveness, we examined the proportion of individuals who initiated use of either generic or brand-name levothyroxine and who attained a normal thyrotropin level within 3 months, clinically meaningful abnormal thyrotropin level within 3 months, and stable thyrotropin level s within 3 months after thyrotropin fell into the normal range Figure 2. We defined a normal thyrotropin level as ranging from 0. Using thyrotropin values beyond 3 months of therapy may not be an accurate surrogate for effectiveness because the values might reflect changes in doses rather than the comparative effectiveness between brand-name and generic levothyroxine.

Moreover, levothyroxine dose adjustments may not be reliably obtained retrospectively from the OptumLabs Data Warehouse, because physician-directed medication adjustments may involve pill splitting and alternate-day dosing. We defined stable thyrotropin levels as a normal thyrotropin level within 3 months after thyrotropin levels fell into the normal range. When there were multiple thyrotropin level measurements during this period of time, we used the one closest to the first thyrotropin measurement Figure 2.

We used propensity scores to minimize confounding. Patients receiving generic levothyroxine were matched with patients receiving brand-name levothyroxine using nearest-neighbor matching with a caliper of 0.

We developed a propensity score model with the binary outcome of initiating treatment with brand-name levothyroxine. The model included demographics, comorbidities, and baseline thyrotropin values shown in Table 1 cohort 1 and Table 2 cohort 2.

Variables within these models were selected based on clinical relevance and evidence from prior studies. For each cohort, we evaluated the balance among the treatment groups by comparing standardized mean differences of baseline covariates between the groups. We used SAS software, version 9. The comparative effectiveness of generic and brand-name levothyroxine among new users could be influenced by the presence of endogenous production of thyroid hormone patients with a functional thyroid gland.

Therefore, we examined whether outcomes differed among patients with and without endogenous thyroid hormone production. Because the mean full replacement dose of levothyroxine in adults is approximately 1. Propensity score matching shrinks the sample to produce groups of the same size.

Therefore, we used an alternative propensity score method, inverse probability of treatment weighting IPTW , to preserve the data lost during matching to confirm our findings. Inverse probability of treatment weighting is an alternative method of incorporating propensity scores to isolate treatment effects used in observational studies. Contrary to propensity score matching, in which the resulting conditional model for the outcomes is fitted though matching, IPTW uses weighting.

Most patients 15 [ Patients who received generic levothyroxine were older mean [SD] age, After propensity score matching, no significant differences were apparent between generic and brand-name levothyroxine groups with respect to all of the measured variables Table 1. Among propensity score—matched patients mean [SD] age, Among matched pairs of patients, the proportion of patients who achieved a normal thyrotropin value within 3 months of filling their first levothyroxine prescription was similar for patients who received generic vs brand-name levothyroxine [ Among these matched pairs of patients, 94 4.

A total of patients from cohort 1 had a normal follow-up thyrotropin level within 3 months and underwent subsequent follow-up thyrotropin level measurement 6 to 12 weeks after the normal thyrotropin test result. Similar to the baseline characteristics of patients in cohort 1, most patients used generic levothyroxine [