Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Endocrine
Published in: Endocrine 1/2017

01-01-2017 | Review

The emergence of levothyroxine as a treatment for hypothyroidism

Author: James V. Hennessey

Published in: Endocrine | Issue 1/2017

Login to get access

Abstract

Objective

To describe the historical refinements, understanding of physiology and clinical outcomes observed with thyroid hormone replacement strategies.

Methods

A Medline search was initiated using the search terms, levothyroxine, thyroid hormone history, levothyroxine mono therapy, thyroid hormone replacement, combination LT4 therapy, levothyroxine Bioequivalence. Pertinent articles of interest were identified by title and where available abstract for further review. Additional references were identified in the course of review of the literature identified.

Results

Physicians have intervened in cases of thyroid dysfunction for more than two millennia. Ingestion of animal thyroid derived preparations has been long described but only scientifically documented for the last 130 years. Refinements in hormone preparation, pharmaceutical production and regulation continue to this day. The literature provides documentation of physiologic, pathologic and clinical outcomes which have been reported and continuously updated. Recommendations for effective and safe use of these hormones for reversal of patho-physiology associated with hypothyroidism and the relief of symptoms of hypothyroidism has documented a progressive refinement in our understanding of thyroid hormone use. Studies of thyroid hormone metabolism, action and pharmacokinetics have allowed evermore focused recommendations for use in clinical practice. Levothyroxine mono-therapy has emerged as the therapy of choice of all recent major guidelines.

Conclusions

The evolution of thyroid hormone therapies has been significant over an extended period of time. Thyroid hormone replacement is very useful in the treatment of those with hypothyroidism. All of the most recent guidelines of major endocrine societies recommend levothyroxine mono-therapy for first line use in hypothyroidism.
Literature
1.
E.C. Kendall, The isolation in crystalline form of the compound containing iodin, which occurs in the thyroid: its chemical nature and physiologic activity. J. Am. Med. Assoc. 64, 2042–2043 (1915)CrossRef
2.
3.
4.
5.
J. Gross, R. Pitt-Rivers, The identification of 3:5:3′-L-triiodothyronine in human plasma. Lancet 1(6705), 439–441 (1952). doi:S0140-6736(52)91952-1PubMedCrossRef
6.
7.
J. Roche, S. Lissitzky, R. Michel, The metabolism of triiodothyronin and its biosynthesis as a thyroid hormone. C. R. Seances Soc. Biol. Fil. 146(19-20), 1474–1477 (1952)PubMed
8.
L.E. Braverman, S.H. Ingbar, K. Sterling, Conversion of thyroxine (T4) to triiodothyronine (T3) in athyreotic human subjects. J. Clin. Invest 49, 855–864 (1970)PubMedPubMedCentralCrossRef
9.
A.C. Bianco, D. Salvatore, B. Gereben, M.J. Berry, P.R. Larsen, Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocr. Rev. 23(1), 38–89 (2002)PubMedCrossRef
10.
J. Jonklaas, B. Davidson, S. Bhagat, S. SJ, : Triiodothyronine levels in athyreotic individuals during levothyroxine therapy. JAMA 299(7), 769–777 (2008)PubMedCrossRef
11.
A. Pilo, G. Iervasi, F. Vitek, M. Ferdeghini, F. Cazzuola, R. Bianchi, Thyroidal and peripheral production of 3,5,3′-triiodothyronine in humans by multicompartmental analysis. Am J. Physiol. 258(4 Pt 1), E715–726 (1990)PubMed
12.
S. Snyder, R.E. Listecki, Bioidentical thyroid replacement therapy in practice: Delivering a physiologic T4:T3 ratio for improved patient outcomes with the Listecki-Snyder protocol. Int. J. Pharm. Compd. 16(5), 376–380 (2012)PubMed
13.
14.
F. Semon, In discussion of ‘A typical case of myxedema’. In: Drewitt, F.D. (ed.) Proceedings of the Clinical Society of London, London, GB 1883, Vol. ii, pp. 1072–1074. BMJ
15.
C.T. Sawin, The invention of thyroid therapy in the late nineteenth century. Endocrinol. 11(1), 1–3 (2001)CrossRef
16.
Report on myxoedema. In, vol. Suppl 1. Transactions of the clinical society of London, (1888)
17.
R. Bettencourt, S. J-A, Un cas de myxoedeme traite par la greffe hypodermique du corps thyroide d’um mouton. La. Sem. Med. 1884(10), 294 (1890)
18.
R. Bettencourt, J.-A. Serrano, Un cas de myxoedeme (cachexie pachydermique) traite par la greffe hypodermique du corps thyroide d’um mouton. In: l’Association Francaise puor l’Advancement des Sciences, Limoges 1890, pp. 683–690 (1891)
19.
A.M. Bettencourt-Rodrigues. Communicacoes scientificas. In: C.b. Sawin (ed.) Lisbon Society of Medical Sciences. J. Soc. Sci. Med. Lisboa, Lisbon, p. 114 (1890)
20.
G.R. Murray, Note on the treatment of Myxoedema by hypodermic injections of an extract of the thyroid gland of a sheep. British Medical Association. (BMJ, Bournemouth), p. 796 (1891)
21.
G.R. Murray, Remarks on the treatment of myxedema with thyroid juice, with notes on four cases. In: 60th Annual Meeting of the British Medical Association 1892, pp. 449–451. BMJ
22.
23.
H.W.G. Mackenzie, A case of myxedema treated with great benefit by feeding with fresh thyroid glands. BMJ 1892(ii), 940–941 (1892)CrossRef
24.
G.R. Murray, The life-history of the first case of myxedema treated by thyroid extract. BMJ 1920(i), 359–360 (1920)CrossRef
25.
26.
H.W.G. Mackenzie, A case of myxoedema treated with great benefit by feeding with fresh thyroid glands. Br. Med. J. 2 (1892)
27.
B. Bramwell, The thyroid treatment of myxoedema and sporatic cretinism, with notes of twenty-three cases of myxoedema and five cases of sporadic cretinism, treated by thyroid extract. Edinburgh Hosp. Rep. 1895(3), 116–249 (1895)
28.
H.A. Selenkow, M.S. Wool, A. New, Synthetic thyroid hormone combination for clinical therapy. Ann. Intern. Med. 67(1), 90–99 (1967)CrossRef
29.
G.J. Canaris, J.F. Steiner, E.C. Ridgway, Do traditional symptoms of hypothyroidism correlate with biochemical disease? J. Gen. Intern. Med. 12(9), 544–550 (1997)PubMedPubMedCentralCrossRef
30.
G.J. Canaris, N.R. Manowitz, G.H. Mayor, E.C. Ridgway, The colorado thyroid disease prevalence study. Arch. Intern. Med. 160(4), 526–534 (2000)PubMedCrossRef
31.
A. Carle, I.B. Pedersen, N. Knudsen, H. Perrild, L. Ovesen, P. Laurberg, Hypothyroid symptoms and the likelihood of overt thyroid failure: a population-based case-control study. Eur. J. Endocrinol. 171(5), 593–602 (2014). doi:10.​1530/​EJE-14-0481 PubMedCrossRef
32.
33.
R.F. Farquharson, A.H. Squires, Inhibition of secretrion of thyroid gland by continued ingestion of thyroid substance. Tr. Am. Phys. 56, 87–97 (1941)
34.
35.
36.
E.A. Novak, J.M. Holthaus, R.O. Ogborn, Clinical study of levo-thyroxine and aged desiccated thyroid in euthyroid subjects. Am. J. Med. Sci. 247, 336–343 (1964)PubMedCrossRef
37.
38.
39.
40.
M.I. Surks, A.R. Schadlow, J.H. Oppenheimer, A new radioimmunoassay for plasma L-triiodothyronine: measurements in thyroid disease and in patients maintained on hormonal replacement. J. Clin. Invest. 51(12), 3104–3113 (1972). doi:10.​1172/​JCI107137 PubMedPubMedCentralCrossRef
41.
J. Chalmers, G. Dickson, J. Elks, et al. The synthesis of thyroxine and related substances. Part V. A synthesis of L-thyroxine from l-tyrosine. J. Chem. Soc. 3424–3422 (1949)
42.
43.
B.A. Sachs, L. Wolfman, G. Murthy, Lipid and clinical response to a new thyroid hormone combination. Am. J. Med. Sci. 256(4), 232–238 (1968)PubMedCrossRef
44.
R.N. Smith, S.A. Taylor, J.C. Massey, Controlled clinical trial of combined triiodothyronine and thyroxine in the treatment of hypothyroidism. Br. Med. J. 4(5728), 145–148 (1970)PubMedPubMedCentralCrossRef
45.
I.M. Jackson, W.E. Cobb, Why does anyone still use desiccated thyroid USP? Am. J. Med. 64(2), 284–288 (1978)PubMedCrossRef
46.
R. Penny, S.D. Frasier, Elevated serum concentrations of triiodothyronine in hypothyroid patients. Values for patients receiving USP thyroid. Am. J. Dis. Child 134(1), 16–18 (1980)PubMedCrossRef
47.
M.S. LeBoff, M.M. Kaplan, J.E. Silva, P.R. Larsen, Bioavailability of thyroid hormones from oral replacement preparations. Metabolism. 31(9), 900–905 (1982)PubMedCrossRef
48.
A. Lev-Ran, Part-of-the-day hypertriiodothyroninemia caused by desiccated thyroid. JAMA 250(20), 2790–2791 (1983)PubMedCrossRef
49.
S.R. Smith, Desiccated thyroid preparations. Obsolete therapy. Arch. Intern. Med. 144(5), 926–927 (1984)PubMedCrossRef
50.
C.T. Sawin, A. Geller, J.M. Hershman, W. Castelli, P. Bacharach, The aging thyroid. The use of thyroid hormone in older persons. JAMA 261(18), 2653–2655 (1989)PubMedCrossRef
51.
K. Petersen, C. Bengtsson, L. Lapidus, G. Lindstedt, E. Nystrom, Morbidity, Mortality and quality of life for patients treated with levothyroxine. Arch. Intern. Med. 150(10), 2077–2081 (1990)PubMedCrossRef
52.
G. Mercuro, M.G. Panzuto, A. Bina, M. Leo, R. Cabula, L. Petrini, F. Pigliaru, S. Mariotti, Cardiac function, physical exercise capacity, and quality of life during long-term thyrotropin-suppressive therapy with levothyroxine: effect of individual dose tailoring. J. Clin. Endocrinol. Metab. 85(1), 159–164 (2000)PubMedCrossRef
53.
J.V. Hennessey, K.D. Burman, L. Wartofsky, The equivalency of two L-Thyroxine preparations. Ann. Intern. Med. 102, 770–773 (1985)PubMedCrossRef
54.
55.
M. Maeda, N. Kuzuya, Y. Masuyama, Y. Imai, H. Ikeda, Changes in serum triiodothyronine, thyroxine, and thyrotropin during treatment with thyroxine in severe primary hypothyroidism. J. Clin. Endocrinol. Metab. 43(1), 10–17 (1976). doi:10.​1210/​jcem-43-1-10 PubMedCrossRef
56.
R.L. Rosenbaum, U.S. Barzel, Levothyroxine replacement dose for primary hypothyroidism decreases with age. Ann. Intern. Med. 96(1), 53–55 (1982)PubMedCrossRef
57.
C.T. Sawin, T. Herman, M.E. Molitch, M.H. London, S.M. Kramer, Aging and the thyroid. Decreased requirement for thyroid hormone in older hypothyroid patients. Am. J. Med. 75(2), 206–209 (1983)PubMedCrossRef
58.
I.E. Brajkovich, K. Mashiter, G.F. Joplin, J. Cassar, Serum T4, T3, and TSH levels in primary hypothyroidism during replacement therapy with thyroxine. Metabolism 32(8), 745–747 (1983). doi:0026-0495(83)90101-4PubMedCrossRef
59.
F.B. Davis, R.S. LaMantia, S.W. Spaulding, R.E. Wehmann, P.J. Davis, Estimation of a physiologic replacement dose of levothyroxine in elderly patients with hypothyroidism. Arch. Intern. Med. 144(9), 1752–1754 (1984)PubMedCrossRef
60.
J.V. Hennessey, J.E. Evaul, Y.-C. Tseng, K.D. Burman, L. Wartofsky, L-thyroxine dosage: A reevaluation of therapy with contemporary preparations. Ann. Intern. Med. 105, 11–15 (1986)PubMedCrossRef
61.
L.H. Fish, H.L. Schwartz, J. Cavanaugh, M.W. Steffes, J.P. Bantle, J.H. Oppenheimer, Replacement dose, metabolism, and bioavailability of levothyroxine in the treatment of hypothyroidism. N. Engl. J. Med. 316, 764–770 (1987)PubMedCrossRef
62.
J.V. Hennessey, L. Wartofsky, Thyroxine preparations. Ann. Intern. Med. 101(1), 140 (1984)CrossRef
63.
C.T. Sawin, M.I. Surks, M. London, R. Chingleput, P.R. Larsen, Oral thyroxine: variation in biologic action and tablet content. Ann. Intern. Med. 100, 641–645 (1984)PubMedCrossRef
64.
J.R. Garber, R.H. Cobin, H. Gharib, J.V. Hennessey, I. Klein, J.I. Mechanick, R. Pessah-Pollack, P.A. Singer, K.A. Woeber, Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Thyroid 22(12), 1200–1235 (2012). doi:10.​1089/​thy.​2012.​0205 PubMedCrossRef
65.
J. Jonklaas, A.C. Bianco, A.J. Bauer, K.D. Burman, A.R. Cappola, F.S. Celi, D.S. Cooper, B. Kim, R. Peeters, M.S. Rosenthal, A. Sawka, Guidelines for the treatment of hypothyroidism. Thyroid (2014). doi:10.​1089/​thy.​2014.​0028
66.
J.V. Hennessey, Levothyroxine a new drug? Since when? How could that be?. Thyroid 13(3), 279–282 (2003)PubMedCrossRef
67.
68.
D.A. Escalante, N. Arem, R. Arem, Assessment of interchangeability of two brands of levothyroxine preparations with a third-generation TSH Assay. Am. J. Med. 98, 374–378 (1995)PubMedCrossRef
69.
R.W. Rees-Jones, A.R. Rolla, P.R. Larsen, Hormonal content of thyroid replacement preparations. JAMA 243(6), 549–550 (1980)PubMedCrossRef
70.
B.J. Dong, V.R. Young, B. Rapoport, The nonequivalence of levothyroxine products. Drug Intell. Clin. Pharm. 20, 77–78 (1986)PubMed
71.
S.S. Stoffer, W.E. Szpunar, Potency of current levothyroxine preparations evaluated by high-performance liquid chromatography. Henry Ford Med. J 36(1), 64–65 (1988)
72.
J.M. Jacobsen, A. Ramos-Gabatin, R.L. Young, S.G. Watkins, M.L. Brown, Nonequality of brand name thyroxine products. JAMA 243(8), 733 (1980)CrossRef
73.
A. Ramos-Gabatin, J.M. Jacobson, R.L. Young, In vivo comparison of Levothyroxine preparations. JAMA 247(2), 203–205 (1982)PubMedCrossRef
74.
N. Lowy, Regulatory Issues regarding slow release T3, extracts, and compunded T4/T3. Paper presented at the Treatment of Hypothyroidism; Exploring the Possibilities, Westin City Center, Washington DC, 25 April 2013
75.
Docket Number 97N-0314, Prescription drug products; levothyroxine sodium. Fed. Regist. 62(157), 43535–43538 (1997)
76.
Guidance for industry: Levothyroxine sodium tablets- In vivo pharmacokinetic and bioavailability studies and invitro dissolution testing. U. S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), 1–8 (2000)
77.
Guidance for Industry: Levothyroxine Sodium Products Enforcement of August 14, 2001; Compliance Date and Submission of New Applications.: In: U. S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). pp. 1–6. (2001)
78.
Guidance for Industry: Bioavailability and Bioequivalence Studies for Orally Administered Drug Products- General Considerations (Draft Guidance). (2002)
79.
V.A. Blakesley, W. Awni, C. Locke, T. Ludden, G.R. Granneman, L.E. Braverman, Are bioequivalalence studies of levothyroxine sodium formulations in euthyroid volunteers reliable?. Thyroid 14(3), 191–200 (2004)PubMedCrossRef
80.
81.
82.
83.
M.G. Santaguida, C. Virili, S.C. Del Duca, M. Cellini, I. Gatto, N. Brusca, C. De Vito, L. Gargano, M. Centanni, Thyroxine softgel capsule in patients with gastric-related T4 malabsorption. Endocrine 49(1), 51–57 (2015). doi:10.​1007/​s12020-014-0476-7 PubMedCrossRef
84.
R. Vita, S. Benvenga, Tablet levothyroxine (L-T4) malabsorption induced by proton pump inhibitor; a problem that was solved by switching to L-T4 in soft gel capsule. Endocr. Pract. 20(3), e38–41 (2014). doi:10.​4158/​EP13316.​CR PubMedCrossRef
85.
P.J. Kim, I. Sachmechi, Levothyroxine malabsorption induced by diabetic gastroparesis exacerbated during pregnancies: effect of intramuscular levothyroxine injections and levothyroxine soft gel capsules. AACE Clin. Case Rep. 1, e73–e78 (2015)CrossRef
86.
R. Vita, G. Saraceno, F. Trimarchi, S. Benvenga, A novel formulation of L-thyroxine (L-T4) reduces the problem of L-T4 malabsorption by coffee observed with traditional tablet formulations. Endocrine 43(1), 154–160 (2013). doi:10.​1007/​s12020-012-9772-2 PubMedCrossRef
87.
T.M. Grant, T. Zhu, C. Brandquist, N.S. Teuscher, M.J. Lamson, Randomized, open-label, single-dose, two-way crossover study to determine the relative bioavailability of a reformulated levothyroxine tablet compared with the commercial tablet (levoxyl(R)) in healthy volunteers. Clin. Pharmacol. Ther. 85(Suppliment 1), S95 (2009). PIII-85
88.
P. Colucci, P. D’Angelo, G. Mautone, C. Scarsi, M.P. Ducharme, Pharmacokinetic equivalence of a levothyroxine sodium soft capsule manufactured using the new food and drug administration potency guidelines in healthy volunteers under fasting conditions. Ther Drug Monit 33(3), 355–361 (2011). doi:10.​1097/​FTD.​0b013e318217b69f​ PubMedCrossRef
89.
J.V. Hennessey, The FDA revises requirements for levothyroxine products. Thyroid 18(5), 487–490 (2008)PubMedCrossRef
90.
J.V. Hennessey, A.O. Malabanan, B.R. Haugen, E.G. Levy, Adverse event reporting in patients treated with levothyroxine: results of the pharmacovigilance task force survey of the american thyroid association, american association of clinical endocrinologists, and the endocrine society. Endocr. Pract. 16(3), 357–370 (2010)PubMedCrossRef
91.
D.S. Ross, G.H. Daniels, D. Gouveia, The use and limitations of a chemiluminescent thyrotropin assay as a single thyroid function test in an out-patient endocrine clinic. J. Clin. Endocrinol. Metab 71(3), 764–769 (1990)PubMedCrossRef
92.
L. Somwaru, A.M. Arnold, N. Joshi, L.P. Fried, A.R. Cappola, High frequency of and factors associated with thyroid hormone over-replacement and under-replacement in men and women Aged 65 and Over. J. Clin. Endocrinol. Metab. 94(4), 1342–1345 (2009)PubMedPubMedCentralCrossRef
93.
J.J. Diez, Hypothyroidism in patients older than 55 years: an analysis of the etiology and assessment of the effectiveness of therapy. J. Gerontol. A Biol. Sci. Med. Sci. 57(5), M315–320 (2002)PubMedCrossRef
94.
J.G. Hollowell, N.W. Staehling, W.D. Flanders, W.H. Hannon, E.W. Gunter, C.A. Spencer, Serum TSH, T4, and Thyroid Antibodies in the United States Population(1988 to 1994): National Health and Nutrition Survey (NHANES III). J. Clin. Endocrinol. Metab. 87, 489–499 (2002)PubMedCrossRef
95.
J.V. Parle, J.A. Franklyn, K.W. Cross, S.R. Jones, M.C. Sheppard, Thyroxine prescription in the community: serun thyroid stimulating hormone level assays as an indicator of undertreatment or overtreatment. Br. J. Gen. Pract. 43(368), 107–109 (1993)PubMedPubMedCentral
96.
R.W. Flynn, S.R. Bonellie, R.T. Jung, T.M. MacDonald, A.D. Morris, G.P. Leese, Serum thyroid-stimulating hormone concentration and morbidity from cardiovascular disease and fractures in patients on long-term thyroxine therapy. J. Clin. Endocrinol. Metab. 95(1), 186–193 (2010). doi:10.​1210/​jc.​2009-1625 PubMedCrossRef
97.
J.S. Mammen, J. McGready, R. Oxman, C.W. Chia, P.W. Ladenson, E.M. Simonsick, Thyroid hormone therapy and risk of thyrotoxicosis in community-resident older adults: findings from the baltimore longitudinal study of aging. Thyroid 25(9), 979–986 (2015). doi:10.​1089/​thy.​2015.​0180 PubMedPubMedCentralCrossRef
98.
D.J. Lips, M.T. van Reisen, V. Voigt, W. Venekamp, Diagnosis and treatment of levothyroxine pseudomalabsorption. Neth. J. Med. 62(4), 114–118 (2004)PubMed
99.
R.M. Bagattoli, M. Vaisman, J.S. Lima, L.S. Ward, Estudo de Adesao ao Tratamento do Hipotiroidismo. Arq. Braz. Endocrinol. Metab. 44(2), 483–487 (2000)
100.
F. Vaisman, C.M. Coeli, L.S. Ward, H. Graf, G. Carvalho, R. Montenegro Jr., M. Vaisman, How good is the levothyroxine replacement in primary hypothyroidism patients in Brazil? Data of a multicentre study. J. Endocrinol. Invest. 36(7), 485–488 (2013). doi:10.​3275/​8810 PubMed
101.
102.
103.
K.W. Wenzel, Optimization of levothyroxine treatment. Dosage dependence on the existing parenchymal mass, age, body weight and fasting intake. Dtsch. Med. Wochenschr. 111(36), 1356–1362 (1986). doi:10.​1055/​s-2008-1068634 PubMedCrossRef
104.
M.J. Lamson, C.L. Pamplin, R.L. Rolleri, I. Klein, Quantitation of a substantial reduction in levothyroxine absorption by food. Thyroid 14, 876 (2004)
105.
T.G. Bach-Huynh, B. Nayak, J. Loh, S. Soldin, J. Jonklaas, Timing of levothyroxine administration affects serum thyrotropin concentration. J. Clin. Endocrinol. Metab. 94(10), 3905–3912 (2009)PubMedPubMedCentralCrossRef
106.
107.
S.A. Irving, T. Vadiveloo, G.P. Leese, Drugs that interact with levothyroxine: an observational study from the Thyroid Epidemiology, Audit and Research Study (TEARS). Clin. Endocrinol. (Oxf) 82(1), 136–141 (2015). doi:10.​1111/​cen.​12559 CrossRef
108.
A. Stagnaro-Green, M. Abalovich, E. Alexander, F. Azizi, J. Mestman, R. Negro, A. Nixon, E.N. Pearce, O.P. Soldin, S. Sullivan, W. Wiersinga, Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid 21(10), 1081–1125 (2011). doi:10.​1089/​thy.​2011.​0087 PubMedPubMedCentralCrossRef
109.
C. Virili, G. Bassotti, M.G. Santaguida, R. Iuorio, S.C. Del Duca, V. Mercuri, A. Picarelli, P. Gargiulo, L. Gargano, M. Centanni, Atypical celiac disease as cause of increased need for thyroxine: a systematic study. J. Clin. Endocrinol. Metab. 97(3), E419–422 (2012). doi:10.​1210/​jc.​2011-1851 PubMedCrossRef
110.
111.
M. Cellini, M.G. Santaguida, I. Gatto, C. Virili, S.C. Del Duca, N. Brusca, S. Capriello, L. Gargano, M. Centanni, Systematic appraisal of lactose intolerance as cause of increased need for oral thyroxine. J. Clin. Endocrinol. Metab. 99(8), E1454–1458 (2014). doi:10.​1210/​jc.​2014-1217 PubMedCrossRef
112.
M. Asik, F. Gunes, E. Binnetoglu, M. Eroglu, N. Bozkurt, H. Sen, E. Akbal, C. Bakar, Y. Beyazit, K. Ukinc, Decrease in TSH levels after lactose restriction in Hashimoto’s thyroiditis patients with lactose intolerance. Endocrine 46(2), 279–284 (2014). doi:10.​1007/​s12020-013-0065-1 PubMedCrossRef
113.
S. Checchi, A. Montanaro, L. Pasqui, C. Ciuoli, V. De Palo, M.C. Chiappetta, F. Pacini, L-thyroxine requirement in patients with autoimmune hypothyroidism and parietal cell antibodies. J. Clin. Endocrinol. Metab. 93(2), 465–469 (2008). doi:10.​1210/​jc.​2007-1544 PubMedCrossRef
114.
M. Centanni, L. Gargano, G. Canettieri, N. Viceconti, A. Franchi, G. Delle Fave, B. Annibale, Thyroxine in goiter, Helicobacter pylori infection, and chronic gastritis. N. Engl. J. Med. 354(17), 1787–1795 (2006)PubMedCrossRef
115.
V. Fonseca, M. Thomas, A. Katrak, P. Sweny, J.F. Moorhead, Can urinary thyroid hormone loss cause hypothyroidism? Lancet 338(8765), 475–476 (1991). doi:0140-6736(91)90546-2PubMedCrossRef
116.
117.
J.M. Carswell, J.H. Gordon, E. Popovsky, A. Hale, R.S. Brown, Generic and brand name L-thyroxine are not bioequivalent for children with severe congenital hypothyroidism. J. Clin. Endocrinol. Metab. (2013)
118.
C.J. Worell, Sandoz Introduces Levothyroxine Sodium Tablets, USP, A Bioequivalent Alternative Product to Synthroid and Levoxyl. In. Sandoz, a Novartis Company, Advertisement to Physicians, (2004)
119.
120.
H.M. Robertson, A.K. Narayanaswamy, O. Pereira, S.A. Copland, R. Herriot, A.W. McKinlay, J.S. Bevan, P. Abraham, Factors contributing to high levothyroxine doses in primary hypothyroidism: an interventional audit of a large community database. Thyroid 24(12), 1765–1771 (2014). doi:10.​1089/​thy.​2013.​0661 PubMedCrossRef
121.
H.T. Stelfox, S.B. Ahmed, J. Fiskio, D.W. Bates, An Evaluation of the adequacy of outpatient monitoring of thyroid replacement therapy. J. Eval. Clin. Pract. 10(4), 525–530 (2004)PubMedCrossRef
122.
J. Jonklaas, Sex and age differences in levothyroxine dosage requirement. Endocr. Pract. 16(1), 71–79 (2010)PubMedCrossRef
123.
A.A. Ismail, P.L. Walker, J.H. Barth, K.C. Lewandowski, R. Jones, W.A. Burr, Wrong biochemistry results: two case reports and observational study in 5310 patients on potentially misleading thyroid-stimulating hormone and gonadotropin immunoassay results. Clin. Chem. 48(11), 2023–2029 (2002)PubMed
124.
125.
G. Brenta, M. Vaisman, J.A. Sgarbi, L.M. Bergoglio, N.C. Andrada, P.P. Bravo, A.M. Orlandi, H. Graf, Clinical practice guidelines for the management of hypothyroidism. Arq. Bras. Endocrinol. Metabol. 57(4), 265–291 (2013). doi:S0004-27302013000400003PubMedCrossRef
126.
127.
P.S. Jellinger, Acquired hypothyroidism after switching from thyroid USP to levothyroxine. Clin. Cornerstone 7(Suppl 2), S22–24 (2005). doi:S1098-3597(05)80055-9PubMedCrossRef
128.
T.D. Hoang, C.H. Olsen, V.Q. Mai, P.W. Clyde, M.K. Shakir, Desiccated thyroid extract compared with levothyroxine in the treatment of hypothyroidism: a randomized, double-blind, crossover study. J. Clin. Endocrinol. Metab. 98(5), 1982–1990 (2013). doi:10.​1210/​jc.​2012-4107 PubMedCrossRef
129.
P. Saravanan, W.-F. Chau, N. Roberts, K. Vedhara, R. Greenwood, C.M. Dayan, Psychological well-being in patients on “adequate” doses of L-thyroxine: results of a large, controlled community-based questionaire study. Clin. Endocrinol. 57, 577–585 (2002)CrossRef
130.
,R. Bunevicius, G. Kazanavicius, R. Zalinkevicius, A.J. Prange, Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism. N. Engl. J. Med 340, 424–429 (1999)PubMedCrossRef
131.
W. Siegmund, K. Spieker, A.I. Weike, T. Giessmann, C. Modess, T. Dabers, G. Kirsch, E. Sanger, G. Engel, A.O. Hamm, M. Nauck, W. Meng, Replacement therapy with levothyroxine plus triiodothyronine (bioavailable molar ratio 14: 1) is not superior to thyroxine alone to improve well-being and cognitive performance in hypothyroidism. Clin. Endocrinol. (Oxf) 60(6), 750–757 (2004). doi:10.​1111/​j.​1365-2265.​2004.​02050.​x CrossRef
132.
H.F. Escobar-Morreale, J.I. Botella-Carretero, F. Escobar Del Ray, G. Morreale De Escobar, Review: treatment of hypothyroidism with combinations of levothyroxine plus liothyronine. J. Clin. Endocrinol. Metab. 90(8), 4946–4954 (2005)PubMedCrossRef
133.
S. Grozinsky-Glasberg, A. Fraser, E. Nahshoni, A. Weizman, L. Leibovici, Thyroxine-triiodothyronine combination therapy versus thyroxine monotherapy for clinical hypothyroidism: meta-analysis of randomized controlled trials. J. Clin. Endocrinol. Metab. 91(7), 2592–2599 (2006)PubMedCrossRef
134.
Metadata
Title
The emergence of levothyroxine as a treatment for hypothyroidism
Author
James V. Hennessey
Publication date
01-01-2017
Publisher
Springer US
Published in
Endocrine / Issue 1/2017
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-016-1199-8

Other articles of this Issue 1/2017

Endocrine 1/2017 Go to the issue

Original Article

Vitamin D status in primary hyperparathyroidism: effect of genetic background

Letter to the Editor

Comment on “Long-term exposure to electromagnetic radiation from mobile phones and Wi-Fi devices decreases plasma prolactin, progesterone, and estrogen levels but increases uterine oxidative stress in pregnant rats and their offspring”

Original Article

Thyroglobulin levels measured at the time of remnant ablation to predict response to treatment in differentiated thyroid cancer after thyroid hormone withdrawal or recombinant human TSH

Original Article

Ramadan fasting in patients with adrenal insufficiency

Original Article

Long-term outcome of multimodal therapy for giant prolactinomas

Meta-Analysis

Continuous subcutaneous insulin infusion versus multiple daily injections in individuals with type 1 diabetes: a systematic review and meta-analysis

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits