Metal coordinated poly-zinc-liothyronine provides stable circulating triiodothyronine levels in hypothyroid rats
Open accessAbstract
BACKGROUND: Liothyronine (LT3) has limited short-term clinical applications, all of which aim at suppressing thyrotropin (TSH) secretion. A more controversial application is chronic administration along with levothyroxine in the treatment of hypothyroidism. Long-term treatment with LT3 is complicated by its unique pharmacokinetics that result in a substantial triiodothyronine (T3) peak in the blood three to four hours after oral dosing. This is a significant problem, given that T3 levels in the blood are normally stable, varying by <10% throughout the day. METHODS: O])n, known as poly-zinc-liothyronine (PZL), was synthesized and loaded into coated gelatin capsules for delivery to the duodenum where sustained release of T3 from PZL occurs. Male Wistar rats were made hypothyroid by feeding on a low iodine diet and water containing 0.05% methimazole for five to six weeks. Rats were given a capsule containing 24 μg/kg PZL or equimolar amounts of LT3. Blood samples were obtained multiple times from the tail vein during the first 16 hours, and processed for T3 and TSH serum levels. Some animals were treated daily for eight days, and blood samples were collected daily. RESULTS: Rats given LT3 exhibited the expected serum T3 peak (about fivefold baseline) at 3.5 hours, followed by a rapid decline, with serum levels almost returning to baseline values by 16 hours. In contrast, serum T3 in PZL-treated rats exhibited about a 30% lower T3 peak at nine hours. Furthermore, the plateau time, that is, the time-span during which the serum T3 concentration is at least half of T3 peak, increased from 4.9 to 7.7 hours in LT3- versus PZL-treated rats, respectively. Serum TSH dropped in both groups, but PZL-treated rats exhibited a more gradual decrease, which was delayed by about four hours compared to LT3-treated rats. Chronic treatment with either LT3 or PZL restored growth, lowered serum cholesterol, and stimulated hepatic expression of the Dio1 mRNA and other T3-dependent markers in the central nervous system. CONCLUSION: Capsules of PZL given orally restore T3-dependent biological effects while exhibiting a reduced and delayed serum T3 peak after dosing, thus providing a longer period of relatively stable serum T3 levels compared to capsules of LT3.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Poly-zinc-LT3 is a copolymer of zinc and T3 that forms a supramolecular complex with mucoadhesive properties, which, coupled with its hydrolysis behavior, make it a slow-release formulation of T3.
“This copolymer of zinc and T3 forms a supramolecular complex that has mucoadhesive properties, which, when coupled with its hydrolysis behavior, make it a slow-release formulation of T3 (63).”
From Emerging Therapies in Hypothyroidism (2024) · cites this paper as [63]
The Discussion (page not available) describes PZL as a zinc–T3 polymeric complex with a supramolecular structure that promotes intestinal mucoadhesion and slower T3 delivery. It attributes the extended absorption to mucoadhesion and ligand exchange, not to hydrolysis behavior; that mechanism in the citing sentence is unsupported by our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn hypothyroid rats, T3 clearance rate did not differ between poly-zinc-LT3 and LT3 treatment.
“The T3 clearance rate did not show differences between poly-zinc-LT3- and LT3-treated rats.”
From Emerging Therapies in Hypothyroidism (2024) · cites this paper as [63]
In rats, daily administration of poly-zinc-LT3 for 8 days produced pharmacodynamics similar to LT3, including reduction of serum cholesterol, restoration of growth rate, and induction of T3-dependent genes in heart, liver, and brain.
“Daily administration of poly-zinc-LT3 for 8 days showed pharmacodynamics similar to LT3 treatment in rats, such as reduction of serum cholesterol, restoration of growth rate, and induction of T3-dependent genes in the heart, liver, and brain (63).”
From Emerging Therapies in Hypothyroidism (2024) · cites this paper as [63]
In hypothyroid rats, poly-zinc-LT3 produced an approximately 30% lower peak serum T3 (Cmax) that was delayed (longer Tmax) by ~6 h compared with equimolar LT3.
“Remarkably, the serum T3 levels exhibited favorable pharmacokinetics (PK) (63), i.e., an approximately 30% lower peak (lower Cmax) that was delayed (longer Tmax) by ~6 h as compared to serum T3 levels in rats given equimolar amounts of LT3.”
From Emerging Therapies in Hypothyroidism (2024) · cites this paper as [63]
In hypothyroid rats, the decline in elevated TSH after poly-zinc-LT3 was delayed by ~4 h compared with LT3.
“TSH levels, which were elevated, declined rapidly after LT3 administration, but the decline was delayed by ~4 h in poly-zinc-LT3-treated rats.”
From Emerging Therapies in Hypothyroidism (2024) · cites this paper as [63]
Da Conceicao and colleagues synthesized poly-zinc-liothyronine (PZL) and loaded it into gelatin capsules.
“More recently, Da Conceicao and colleagues synthesized poly-zinc-liothyronine (PZL) and loaded it into gelatin capsules (179).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [179]
An animal study demonstrated that PZL capsules had an approximately 30% lower Cmax, an approximately 6 hour later time to peak serum concentration (Tmax), and a plateau time that was approximately 3 hours longer than conventional T3 capsules.
“An animal study demonstrated an ∼30% lower Cmax, a ∼6 hour later time to peak serum concentration (Tmax), and a plateau time that was ∼3 hours longer than in conventional T3 capsules.”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [179]
After oral administration, PZL can leak out from capsules and adhere to the mucosa of the gastrointestinal tract like a drug depot, and T3 is then released into the intestinal lumen and ultimately absorbed into the bloodstream.
“After oral administration, PZL can leak out from capsules and adhere to the mucosa of the gastrointestinal tract like a “drug depot” (Fig. 6C). T3 is then released into the intestinal lumen and ultimately absorbed into the bloodstream.”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [179]
A large proportion of articles on LT4 nanomaterials only extended the studies to in vitro experiments and few proceeded to animal or human studies.
“However, a large proportion of articles only extended the studies to in vitro experiments and few of them proceeded to animal or human studies (179, 180, 272).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [179]
The pharmacokinetic properties and biocompatibility of LT4 nanomaterials remained untested.
“The pharmacokinetic properties and biocompatibility remained untested.”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [179]
PZL slows down its gut transit time and forms a "depot" for slow release of T3 which is then absorbed into the blood stream.
“This slows down its gut transit time and in essence forms a “depot” for slow release of T3 which is then absorbed into the blood stream (63).”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Jonklaas, J., Bianco, A. C., Bauer, A. J., Burman, K. D., Cappola, A. R., Celi, F. S., Cooper, D. S., Kim, B. W., Peeters, R. P., Rosenthal, M. S., et al. (2014) · Thyroid® · doi:10.1089/thy.2014.0028 · Cited by 1,928 · see citing works
Self-citationBianco, A. C., Salvatore, D., Gereben, B., Berry, M. J., & Larsen, P. R. (2002) · Endocrine Reviews · doi:10.1210/edrv.23.1.0455 · Cited by 1,853 · see citing works
Self-citationLow Serum Thyrotropin Concentrations as a Risk Factor for Atrial Fibrillation in Older Persons
Sawin, C. T., Geller, A., Wolf, P. A., Belanger, A. J., Baker, E., Bacharach, P., Wilson, P., Benjamin, E. J., & D'Agostino, R. B. (1994) · New England Journal of Medicine · doi:10.1056/nejm199411103311901 · Cited by 1,259 · cited 1× · see citing works
“Long-term studies indicate that having even minimally elevated thyroid hormone levels places patients at a significantly greater risk for cardiovascular events (17,18) and hip fractures (19).”
The basics and underlying mechanisms of mucoadhesion
SMART, J. (2005) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2005.07.001 · Cited by 1,167 · see citing works
Chaker, L., Bianco, A. C., Jonklaas, J., & Peeters, R. P. (2017) · The Lancet · doi:10.1016/s0140-6736(17)30703-1 · Cited by 1,159 · see citing works
Self-citationRisk for fracture in women with low serum levels of thyroid-stimulating hormone
Bauer, D. C., Ettinger, B., Nevitt, M. C., Stone, K. L., & for the Study of Osteoporotic Fractures Research Group (2001) · Annals of Internal Medicine · doi:10.7326/0003-4819-134-7-200104030-00009 · Cited by 467 · see citing works
Williams Textbook of Endocrinology
Niculescu, D. (2008) · Acta Endocrinologica (Bucharest) · doi:10.4183/aeb.2008.127 · Cited by 373 · see citing works
Levothyroxine Monotherapy Cannot Guarantee Euthyroidism in All Athyreotic Patients
Gullo, D., Latina, A., Frasca, F., Le Moli, R., Pellegriti, G., & Vigneri, R. (2011) · PLoS ONE · doi:10.1371/journal.pone.0022552 · Cited by 307 · see citing works
Escobar-Morreale, H. F., Obregón, M. J., Escobar del Rey, F., & Morreale de Escobar, G. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118353 · Cited by 287 · see citing works
Escobar-Morreale, H. F., del Rey, F. E., Obregón, M. J., & de Escobar, G. M. (1996) · Endocrinology · doi:10.1210/endo.137.6.8641203 · Cited by 261 · see citing works
An Online Survey of Hypothyroid Patients Demonstrates Prominent Dissatisfaction
Peterson, S. J., Cappola, A. R., Castro, M. R., Dayan, C. M., Farwell, A. P., Hennessey, J. V., Kopp, P. A., Ross, D. S., Samuels, M. H., Sawka, A. M., et al. (2018) · Thyroid · doi:10.1089/thy.2017.0681 · Cited by 231 · see citing works
Self-citationRussell, W., Harrison, R. F., Smith, N., Darzy, K., Shalet, S., Weetman, A. P., & Ross, R. J. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-2674 · Cited by 219 · see citing works
Bianco, A. C., Anderson, G., Forrest, D., Galton, V. A., Gereben, B., Kim, B. W., Kopp, P. A., Liao, X. H., Obregon, M. J., Peeters, R. P., et al. (2014) · Thyroid · doi:10.1089/thy.2013.0109 · Cited by 205 · cited 2× · see citing works
“This is expected, given the positive effects of T3 on growth hormone and insulin growth factor 1 secretion (28).”
Self-citationSILVA, J. E., DICK, T. E., & LARSEN, P. R. (1978) · Endocrinology · doi:10.1210/endo-103-4-1196 · Cited by 189 · see citing works
Werneck de Castro, J. P., Fonseca, T. L., Ueta, C. B., McAninch, E. A., Abdalla, S., Wittmann, G., Lechan, R. M., Gereben, B., & Bianco, A. C. (2015) · Journal of Clinical Investigation · doi:10.1172/jci77588 · Cited by 184 · see citing works
Self-citationIs a Normal TSH Synonymous With “Euthyroidism” in Levothyroxine Monotherapy?
Peterson, S. J., McAninch, E. A., & Bianco, A. C. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-2660 · Cited by 182 · see citing works
Self-citationGalton, V. A., Schneider, M. J., Clark, A. S., & St. Germain, D. L. (2009) · Endocrinology · doi:10.1210/en.2008-1572 · Cited by 181 · see citing works
Coordination of hypothalamic and pituitary T3 production regulates TSH expression
Fonseca, T. L., Correa-Medina, M., Campos, M. P. O., Wittmann, G., Werneck-de-Castro, J. P., Arrojo e Drigo, R., Mora-Garzon, M., Ueta, C. B., Caicedo, A., Fekete, C., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci61231 · Cited by 155 · see citing works
Self-citationDefending plasma T3 is a biological priority
Abdalla, S. M., & Bianco, A. C. (2014) · Clinical Endocrinology · doi:10.1111/cen.12538 · Cited by 147 · cited 2× · see citing works
“Maintaining fairly stable serum T3 levels is a priority for the HPT axis, given that T3 levels are kept quite stable within the normal reference range, even in animals that are genetically modified not to convert T4 to T3 (4–6).”
Self-citationType 1 iodothyronine deiodinase is a sensitive marker of peripheral thyroid status in the mouse
Zavacki, A. M., Ying, H., Christoffolete, M. A., Aerts, G., So, E., Harney, J. W., Cheng, S.-Y., Larsen, P. R., & Bianco, A. C. (2005) · Endocrinology · doi:10.1210/en.2004-1392 · Cited by 138 · see citing works
Self-citationThe history and future of treatment of hypothyroidism
McAninch, E. A., & Bianco, A. C. (2016) · Annals of Internal Medicine · doi:10.7326/m15-1799 · Cited by 118 · see citing works
Self-citationBianco, A. C., & Silva, J. E. (1987) · Endocrinology · doi:10.1210/endo-120-1-55 · Cited by 102 · see citing works
Self-citationSaravanan, P., Siddique, H., Simmons, D., Greenwood, R., & Dayan, C. (2007) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-2007-973071 · Cited by 100 · see citing works
Hennemann, G., Docter, R., Visser, T. J., Postema, P. T., & Krenning, E. P. (2004) · Thyroid · doi:10.1089/105072504323030924 · Cited by 90 · see citing works
Samuels, M. H., Kolobova, I., Smeraglio, A., Peters, D., Purnell, J. Q., & Schuff, K. G. (2016) · Thyroid · doi:10.1089/thy.2015.0345 · Cited by 87 · see citing works
Christoffolete, M. A., Arrojo e Drigo, R., Gazoni, F., Tente, S. M., Goncalves, V., Amorim, B. S., Larsen, P. R., Bianco, A. C., & Zavacki, A. M. (2007) · Endocrinology · doi:10.1210/en.2006-1042 · Cited by 62 · see citing works
Self-citationGORMAN, C. A., JIANG, N.-S., ELLEFSON, R. D., & ELVEBACK, L. R. (1979) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-49-1-1 · Cited by 56 · see citing works
Jonklaas, J., & Burman, K. D. (2016) · Thyroid® · doi:10.1089/thy.2015.0629 · Cited by 41 · see citing works
New insights into the variable effectiveness of levothyroxine monotherapy for hypothyroidism
McAninch, E. A., & Bianco, A. C. (2015) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(15)00325-3 · Cited by 39 · see citing works
Self-citationBiondi, B., Fazio, S., Palmieri, E. A., Tremalaterra, R., Angellotti, G., Bonè, F., Riccio, G., Cittadini, A., Lombardi, G., & Saccà, L. (1999) · PubMed · Cited by 38 · see citing works
Role for inner ring deiodination preventing transcutaneous passage of thyroxine
Santini, F., Vitti, P., Chiovato, L., Ceccarini, G., Macchia, M., Montanelli, L., Gatti, G., Rosellini, V., Mammoli, C., Martino, E., et al. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021439 · Cited by 37 · see citing works
Santini, F., Giannetti, M., Ricco, I., Querci, G., Saponati, G., Bokor, D., Rivolta, G., Bussi, S., Braverman, L. E., Vitti, P., et al. (2014) · Endocrine Practice · doi:10.4158/ep13331.or · Cited by 31 · see citing works
Risks and safety of combination therapy for hypothyroidism
Jonklaas, J. (2016) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2016.1182019 · Cited by 27 · see citing works
The one-dimensional chain polymer of aqua(tyrosinato)zinc(II)
Li, D.-Q., Zhou, J., & Liu, X. (2007) · Acta Crystallographica Section C Crystal Structure Communications · doi:10.1107/s010827010703185x · Cited by 11 · see citing works
Kinetic Analysis of Drug Release from Compounded Slow-release Capsules of Liothyronine Sodium (T3).
(2017) · PubMed · Cited by 9 · see citing works
do Nascimento, B. P. P., Bocco, B. M. L. C., Fernandes, G. W., Fonseca, T. L., McAninch, E. A., Cardoso, C. V., Bondan, E. F., Nassif, R. J., Cysneiros, R. M., Bianco, A. C., et al. (2018) · Endocrinology · doi:10.1210/en.2018-00146 · Cited by 7 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 4
- [14]Peterson SJ, Cappola AR, Castro MR, Dayan CM, Farwell AP, Hennessey JV, Kopp PA, Ross DS, Samuels MH, Sawka AM, Taylor PN, Jonklaas J, Bianco AC. 2018. An online survey of hypothyroid patients captured predominantly dissatisfied individuals. Thyroid 28:707–721 [DOI] [PMC free article] [PubMed] [Google Scholar]
- [24]Price JD, Piccariello T, Palmer S. 2014. Metal-coordinated pharmaceuticals. Drug Dev Deliv 14:34–39 [Google Scholar]
- [28]Bianco AC, Anderson G, Forrest D, Galton VA, Gereben B, Kim BW, Kopp PA, Liao XH, Obregon MJ, Peeters RP, Refetoff S, Sharlin DS, Simonides WS, Weiss RE, Williams GR. 2014. American Thyroid Association guide to investigating thyroid hormone economy and action in rodent and cell models. Thyroid 24:88–168 [DOI] [PMC free article] [PubMed] [Google Scholar]
- [36]Bianco AC, Silva JE. 1987. Nuclear 3,5,3′-triiiodothyronine (T3) in brown adipose tissue: receptor occupancy and sources of T3 as determined by in vivo techniques. Endocrinology 120:55–62 [DOI] [PubMed] [Google Scholar]
Cited by
Sorted by citations
Deiodinases and their intricate role in thyroid hormone homeostasis
Luongo, C., Dentice, M., & Salvatore, D. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0218-2 · Cited by 332 · see citing works
Optimal thyroid hormone replacement
Jonklaas, J. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnab031 · Cited by 89 · see citing works
Levothyroxine: conventional and novel drug delivery formulations.
Liu, H., Li, W., Zhang, W., Sun, S., & Chen, C. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnac030 · Cited by 63 · see citing works
The relevance of T3 in the management of hypothyroidism
Salvatore, D., Porcelli, T., Ettleson, M. D., & Bianco, A. C. (2022) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(22)00004-3 · Cited by 44 · see citing works
Self-citationIndividualised requirements for optimum treatment of hypothyroidism: complex needs, limited options
Hoermann, R., Midgley, J. E. M., Larisch, R., & Dietrich, J. W. (2019) · Drugs in Context · doi:10.7573/dic.212597 · Cited by 40 · see citing works
Emerging Therapies in Hypothyroidism
Bianco, A. C. (2024) · Annual Review of Medicine · doi:10.1146/annurev-med-060622-101007 · Cited by 36 · see citing works
Self-citationSustained release T3 therapy: animal models and translational applications
Idrees, T., Price, J. D., Piccariello, T., & Bianco, A. C. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00544 · Cited by 30 · see citing works
Self-citationThe Swinging Pendulum in Treatment for Hypothyroidism: From (and Toward?) Combination Therapy
McAninch, E. A., & Bianco, A. C. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00446 · Cited by 24 · see citing works
Self-citationCombination Thyroid Hormone Replacement; Knowns and Unknowns
Taylor, P. N., Eligar, V. S., Muller, I., Scholz, A., Dayan, C. M., & Okosieme, O. E. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00706 · Cited by 21 · see citing works
Dumitrescu, A. M., Hanlon, E. C., Arosemena, M., Duchon, O., Ettleson, M., Giurcanu, M., & Bianco, A. C. (2022) · Thyroid · doi:10.1089/thy.2021.0304 · Cited by 20 · see citing works
Self-citationPhysiological Role and Use of Thyroid Hormone Metabolites - Potential Utility in COVID-19 Patients
Fröhlich, E., & Wahl, R. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.587518 · Cited by 20 · see citing works
M’bitsi-Ibouily, G. C., Marimuthu, T., Kumar, P., Choonara, Y. E., du Toit, L. C., Pradeep, P., Modi, G., & Pillay, V. (2019) · Scientific Reports · doi:10.1038/s41598-019-40538-1 · Cited by 15 · see citing works
Köhrle, J., & Richards, K. H. (2020) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/a-1175-4610 · Cited by 7 · see citing works
Role of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism
Jonklaas, J. (2022) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2021.12.003 · Cited by 7 · see citing works
Premawardhana, L. D., Taylor, P. N., Okosieme, O. E., Adlan, M. A., Obuobie, E. K., & Dayan, C. M. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1282608 · Cited by 6 · see citing works
Shared Decisionmaking in the Treatment of Hypothyroidism
Bianco, A. C. (2025) · Clinical Endocrinology · doi:10.1111/cen.15228 · Cited by 5 · see citing works
Self-citationJonklaas, J. (2025) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2025.2492789 · Cited by 2 · see citing works
Phase 1 Clinical Trial of Poly-Zinc-Liothyronine Demonstrates Slow-Release Serum T 3 Kinetics
McAninch, E. A. (2022) · Clinical Thyroidology · doi:10.1089/ct.2022;34.9-12 · Cited by 2 · see citing works
Advances in hypothyroidism management: rethinking therapy beyond levothyroxine
Ditshego, R., Pick, J., & Ncube, K. N. (2025) · SA pharmaceutical journal. · doi:10.36303/sapj.3267 · Cited by 1 · see citing works
Clinician's Review of Thyroid and Parathyroid Disease
Loftley, A. (2020) · Journal of Diabetes and Clinical Research · doi:10.33696/diabetes.1.017
Design and evaluation of metal-liganded bioactive delivery system for enhanced oral bioavailability
M’bitsi-Ibouily, G. C. (2019)
Delivery of liothyronine by microneedle patch for the treatment of hypothyroidism
Gomaa, Y. A., Hasin, T., Griffin, M. N., Nguyen, T. C., Noel, R. K., O’Farrell, L., McAninch, E. A., Kaiser, A. M., Wood, L. B., & Prausnitz, M. R. (2026) · Drug Delivery and Translational Research · doi:10.1007/s13346-026-02214-6
- Authors
- Da Conceição, R. R., Fernandes, G. W., Fonseca, T. L., Bocco, B. M. L. C., & Bianco, A. C.
- Affiliations
- Division of Endocrinology and Metabolism, Rush University Medical Center, Chicago, Illinois.
- University of Chicago (US)
- Division of Endocrinology, University of Chicago, Chicago, Illinois.
- Corresponding author
- Bianco, Antonio C.
- Venue
- Thyroid
- Publisher
- SAGE Publications
- Published
- 2018-11
- Volume
- 28
- Issue
- 11
- Pages
- 1425-1433
- ISSN
- 1050-7256 (ISSN-L)
- 1557-9077
- PMC
- PMC7207055
- OpenAlex
- W2896972411
- Cited by
- 23
- References
- 36
- Citations by year
- 2026: 1 · 2025: 3 · 2023: 2 · 2022: 4 · 2021: 4 · 2020: 2 · 2019: 7
- FWCI
- 2.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Thyroid (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R44DK116396)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Keywords
- liothyronine, triiodothyronine, hypothyroidism, sustained drug release, thyroid-stimulating hormone, low iodine diet, methimazole, serum cholesterol, rats
- MeSH terms
- Animals, Hypothyroidism, Male, Thyrotropin, Triiodothyronine, Treatment Outcome, Rats, Wistar, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
