Serum Ferritin, Iron Metabolism & Thyroid Status
Posted: Sun Jul 21, 2024 1:36 am
Moved from Anemia forum on February 12, 2026
da Conceição RR, Giannocco G, Herai RH, Petroski LP, Pereira BG, Oliveira KC, Chiamolera MI, Sato MA, Maciel RM, de Souza JS - "Thyroid dysfunction alters gene expression of proteins related to iron homeostasis and metabolomics in male rats" Mol Cell Endocrinol 579:112086 (2024) doi: 10.1016/j.mce.2023.112086
https://linkinghub.elsevier.com/retriev ... 23)00237-X
"Research suggests that THs can influence iron homeostasis by affecting mRNA and protein expression, such as ferritin and transferrin. Our study focused on male rats to assess mRNA expression of iron homeostasis-related proteins and metabolomics in thyroid dysfunction. We found altered gene expression across various tissues (liver, duodenum, spleen, and kidney) and identified disrupted metabolite patterns in thyroid dysfunction. These findings highlight tissue-specific effects of thyroid dysfunction on essential iron homeostasis proteins and provide insights into associated metabolic changes."
Deshpande UR, Nadkarni GD - "Relation between thyroid status and ferritin metabolism in rats" Thyroidology 4(3):93-7 (1992)
https://pubmed.ncbi.nlm.nih.gov/1285038/
"It appears from the present data that ferritin metabolism is influenced by thyroid hormone as well as by iron. Thus, the raised serum ferritin in hyperthyroid patients may be partially attributed to increased ferritin synthesis in the liver and its possible leakage into circulation."
Fischli S, von Wyl V, Trummler M, Konrad D, Wueest S, Ruefer A, Heering K, Streuli R, Steuer C, Bernasconi L, Recher M, Henzen C - "Iron metabolism in patients with Graves' hyperthyroidism" Clinical Endocrinology 87(5):609-616 (2017)
https://doi.org/10.1111/cen.13450
Gianoukakis AG, Leigh MJ, Richards P, Christenson PD, Hakimian A, Fu P, Niihara Y, Smith TJ - "Characterization of the anaemia associated with Graves' disease" Clinical Endocrinology 70(5):781-787 (2009)
https://doi.org/10.1111/j.1365-2265.2008.03382.x
"GD anaemia is common, resembles the anaemia of chronic disease, and is associated with markers of inflammation. It corrects promptly with return to the euthyroid state following treatment."
Gierach M, Rudewicz M, Junik R - "Iron and ferritin deficiency in women with hypothyroidism and chronic lymphocytic thyroiditis - systematic review" Endokrynol Pol 75(3):253-261 (2024) doi: 10.5603/ep.97860
https://journals.viamedica.pl/endokryno ... 3/ep.97860
"Assessing iron status along with ferritin should be an integral part of additional diagnostic measures in cases of hypothyroidism, particularly Hashimoto's disease."
Hernik A, Szczepanek-Parulska E, Filipowicz D, Czarnywojtek A, Wrotkowska E, Kramer L, Urbanovych A, Ruchala M - "Hepcidin and iron homeostasis in patients with subacute thyroiditis and healthy subjects" Mediators of Inflammation 2019:5764061 (2019)
https://doi.org/10.1155/2019/5764061
"HepcidinEL in SAT patients correlated with CRP (r = 0.614, p = 0.003), ferritin (r = 0.815, p < 0.001), and aTPO (r = -0.491, p = 0.024). On multiple regression, the correlation between hepcidinEL and ferritin was confirmed (p < 0.001). Conclusions. SAT is accompanied by a significant increase in hepcidin, which reflects an acute-phase inflammatory process. Parameters of iron homeostasis improved significantly while inflammatory indices got lower following recovery."
Hernik A, Szczepanek-Parulska E, Filipowicz D, Abdolall A, Borowczyk M, Wrotkowska E, Czarnywojtek A, Krasiński Z, Ruchała M - "The hepcidin concentration decreases in hypothyroid patients with Hashimoto's thyroiditis following restoration of euthyroidism" Scientific Reports 9(1):16222 (2019)
https://doi.org/10.1038/s41598-019-52715-3
Hepcidin decreased as patients moved from hypothyroidism to euthyroidism, alongside changes in iron homeostasis and correlations involving ferritin and hepcidin.
https://doi.org/10.1186/s13044-016-0031-0
"Thyroid stimulating hormone had significant negative correlation with hemoglobin (r = −0.337, p < 0.001) and transferrin saturation (r = −0.204, p = 0.002)."
Kubota K, Tamura J, Kurabayashi H, Shirakura T, Kobayashi I - "Evaluation of increased serum ferritin levels in patients with hyperthyroidism" Clinical Investigator 72(1):26-29 (1993)
https://doi.org/10.1007/BF00231112
"Thus it is concluded that the increase in serum ferritin levels in patients with hyperthyroidism may be due to the direct action of thyroid hormones on its synthesis, while in some cases complicated with anemia impaired iron utilization by erythropoietic cells may also be involved."
Leedman PJ, Stein AR, Chin WW, Rogers JT - "Thyroid hormone modulates the interaction between iron regulatory proteins and the ferritin mRNA iron-responsive element" Journal of Biological Chemistry 271(20):12017-12023 (1996)
https://doi.org/10.1074/jbc.271.20.12017
"We conclude that T3 can functionally regulate the IRE binding activity of the IRP. These observations provide evidence of a novel mechanism for T3 to up-regulate hepatic ferritin expression, which may in part contribute to the elevated serum ferritin levels seen in hyperthyroidism."
Maldonado-Araque C, Valdés S, Lago-Sampedro A, Lillo-Muñoz JA, Garcia-Fuentes E, Perez-Valero V, Gutierrez-Repiso C, Goday A, Urrutia I, Peláez L, Calle-Pascual A, Castaño L, Castell C, Delgado E, Menendez E, Franch-Nadal J, Gaztambide S, Girbés J, Ortega E, Vendrell J, Chacón MR, Chaves FJ, Soriguer F, Rojo-Martínez G - "Iron deficiency is associated with Hypothyroxinemia and Hypotriiodothyroninemia in the Spanish general adult population: Di@bet.es study" Sci Rep 8(1):6571 (2018) doi: 10.1038/s41598-018-24352-9
https://pmc.ncbi.nlm.nih.gov/articles/PMC5919900/
Saïd R - "Hyperthyroidism: a cause of serum ferritin elevation" Review of Internal Medicine 21(12):1129-1131 (2000)
https://doi.org/10.1016/S0248-8663(00)00275-7
Swapnika TG, Sabitha Rani SS, Dipankar S, Itagi ABH, Vamshidhar IS - "A Comparative Study of Iron Status in Subclinical Hypothyroid and Euthyroid Subjects in a Tertiary Care Hospital" Cureus 16(1):e52007 (2024) doi: 10.7759/cureus.52007
"The prevalence of anemia in subclinical hypothyroidism is significantly elevated, and considering the absence of significant clinical manifestations in the early stages, it is recommended to routinely conduct investigations for early detection, facilitating prompt management. Consequently, our study emphasizes that both overt and subclinical hypothyroidism should be recognized as risk factors for the development of iron deficiency anemia."
Takamatsu J, Majima M, Miki K, Kuma K, Mozai T - "Serum ferritin as a marker of thyroid hormone action on peripheral tissues" Journal of Clinical Endocrinology and Metabolism 61(4):672-676 (1985)
https://doi.org/10.1210/jcem-61-4-672
Intraindividual ferritin decreased as Graves' patients became euthyroid; ferritin rose when hypothyroid patients achieved euthyroidism; short-term T3 increased ferritin in euthyroid subjects, with blunted responses in thyroid hormone resistance.
https://doi.org/10.1074/jbc.M002354200
“These data link two different cell receptor systems to common signaling pathways that regulate IRP binding and ferritin expression.”
(NOTE: In this paper, the TRH effect on IRP binding is explicitly described as PKC-dependent, which is the canonical downstream arm of Gq/11 signalling.)
Tiwari R, Saharia GK, Mangaraj M - "Evaluation of Serum Ferritin and Anti-Thyroid Peroxidase Antibody Status in Newly Diagnosed Subclinical Cases of Hypothyroidism" Endocr Metab Immune Disord Drug Targets 21(8):1453-1458 (2021) doi: 10.2174/1871530320666200925125404
https://www.eurekaselect.com/article/110234
"Ferritin concentrations were decreased in anti-TPO negative hypothyroidism, but in the case of anti-TPO positive hypothyroidism the ferritin concentrations are raised. Hence, hypothyroidism should not always be considered as an iron deficiency state."
Van de Vyver FL, Blockx PP, Abs RE, Van den Bogaert WG, Bekaert JL - "Serum ferritin levels in hyperthyroidism" Annals of Internal Medicine 97(6):930-931 (1982)
https://doi.org/10.7326/0003-4819-97-6-930_3
"Our initial investigation included 38 hyperthyroid patients, studied before and during therapy. A decrease of serum ferritin during antithyroid therapy was noted in most patients; 18 of the 20 patients, reaching the euthyroid state during this preliminary study, showed a fall in serum ferritin level. Our study currently includes 44 hyperthyroid patients who became euthyroid. In all but four patients, serum ferritin levels decreased during treatment."
Vinayagamoorthi R, Dhiman P, Kollipaka R, Sabita P, Hemavathy V - "Association of Hypothyroidism With Low Serum Ferritin Levels and Iron-Deficiency Anemia During the First Trimester of Pregnancy" Cureus 14(8):e28307 (2022) doi: 10.7759/cureus.28307
"There was a significant increase in TSH levels and a significant decrease in the levels of FT4, FT3, ferritin, iron, and hemoglobin (Hb) in hypothyroid pregnant women compared to euthyroid pregnant women. The correlation and regression analysis revealed a significant negative association of TSH and a positive association of FT4 with ferritin, iron, and Hb."
Zwirska-Korczala K, Buntner B, Sobieraj H, Ostrowska Z, Kniazewski B, Swietochowska E - "Serum ferritin, iron and transferrin in women with thyrotoxic Graves' disease before and after methimazole treatment" Acta Physiol Pol 41(7):163-8 (1990)
https://pubmed.ncbi.nlm.nih.gov/2136311/
da Conceição RR, Giannocco G, Herai RH, Petroski LP, Pereira BG, Oliveira KC, Chiamolera MI, Sato MA, Maciel RM, de Souza JS - "Thyroid dysfunction alters gene expression of proteins related to iron homeostasis and metabolomics in male rats" Mol Cell Endocrinol 579:112086 (2024) doi: 10.1016/j.mce.2023.112086
https://linkinghub.elsevier.com/retriev ... 23)00237-X
"Research suggests that THs can influence iron homeostasis by affecting mRNA and protein expression, such as ferritin and transferrin. Our study focused on male rats to assess mRNA expression of iron homeostasis-related proteins and metabolomics in thyroid dysfunction. We found altered gene expression across various tissues (liver, duodenum, spleen, and kidney) and identified disrupted metabolite patterns in thyroid dysfunction. These findings highlight tissue-specific effects of thyroid dysfunction on essential iron homeostasis proteins and provide insights into associated metabolic changes."
Deshpande UR, Nadkarni GD - "Relation between thyroid status and ferritin metabolism in rats" Thyroidology 4(3):93-7 (1992)
https://pubmed.ncbi.nlm.nih.gov/1285038/
"It appears from the present data that ferritin metabolism is influenced by thyroid hormone as well as by iron. Thus, the raised serum ferritin in hyperthyroid patients may be partially attributed to increased ferritin synthesis in the liver and its possible leakage into circulation."
Fischli S, von Wyl V, Trummler M, Konrad D, Wueest S, Ruefer A, Heering K, Streuli R, Steuer C, Bernasconi L, Recher M, Henzen C - "Iron metabolism in patients with Graves' hyperthyroidism" Clinical Endocrinology 87(5):609-616 (2017)
https://doi.org/10.1111/cen.13450
Gianoukakis AG, Leigh MJ, Richards P, Christenson PD, Hakimian A, Fu P, Niihara Y, Smith TJ - "Characterization of the anaemia associated with Graves' disease" Clinical Endocrinology 70(5):781-787 (2009)
https://doi.org/10.1111/j.1365-2265.2008.03382.x
"GD anaemia is common, resembles the anaemia of chronic disease, and is associated with markers of inflammation. It corrects promptly with return to the euthyroid state following treatment."
Gierach M, Rudewicz M, Junik R - "Iron and ferritin deficiency in women with hypothyroidism and chronic lymphocytic thyroiditis - systematic review" Endokrynol Pol 75(3):253-261 (2024) doi: 10.5603/ep.97860
https://journals.viamedica.pl/endokryno ... 3/ep.97860
"Assessing iron status along with ferritin should be an integral part of additional diagnostic measures in cases of hypothyroidism, particularly Hashimoto's disease."
Hernik A, Szczepanek-Parulska E, Filipowicz D, Czarnywojtek A, Wrotkowska E, Kramer L, Urbanovych A, Ruchala M - "Hepcidin and iron homeostasis in patients with subacute thyroiditis and healthy subjects" Mediators of Inflammation 2019:5764061 (2019)
https://doi.org/10.1155/2019/5764061
"HepcidinEL in SAT patients correlated with CRP (r = 0.614, p = 0.003), ferritin (r = 0.815, p < 0.001), and aTPO (r = -0.491, p = 0.024). On multiple regression, the correlation between hepcidinEL and ferritin was confirmed (p < 0.001). Conclusions. SAT is accompanied by a significant increase in hepcidin, which reflects an acute-phase inflammatory process. Parameters of iron homeostasis improved significantly while inflammatory indices got lower following recovery."
Hernik A, Szczepanek-Parulska E, Filipowicz D, Abdolall A, Borowczyk M, Wrotkowska E, Czarnywojtek A, Krasiński Z, Ruchała M - "The hepcidin concentration decreases in hypothyroid patients with Hashimoto's thyroiditis following restoration of euthyroidism" Scientific Reports 9(1):16222 (2019)
https://doi.org/10.1038/s41598-019-52715-3
Hepcidin decreased as patients moved from hypothyroidism to euthyroidism, alongside changes in iron homeostasis and correlations involving ferritin and hepcidin.
Khatiwada S, Gelal B, Baral N, Lamsal M - "Association between iron status and thyroid function in Nepalese children" Thyroid Research 9:2 (2016)A positive correlation was observed between hepcidin and fT3 (p = 0.033, r = 0.465) at T0. In the females, the level of hepcidin positively correlated with ferritin concentration before (p < 0.001, r = 0.928) and after treatment (p < 0.001, r = 0.835). A statistically significant difference was observed in RDW-CV (red blood cell distribution width - coefficient of variation) between the hypothyroid and euthyroid states. In conclusion, a decrease in hepcidin concentration during the transition from the hypothyroid state to euthyroidism in patients with HT is associated with the observed dynamics in iron homeostasis, mainly reflected by improvement in RDW-CV and significant correlations between ferritin and hepcidin as well as between hepcidin and fT3.
https://doi.org/10.1186/s13044-016-0031-0
"Thyroid stimulating hormone had significant negative correlation with hemoglobin (r = −0.337, p < 0.001) and transferrin saturation (r = −0.204, p = 0.002)."
Kubota K, Tamura J, Kurabayashi H, Shirakura T, Kobayashi I - "Evaluation of increased serum ferritin levels in patients with hyperthyroidism" Clinical Investigator 72(1):26-29 (1993)
https://doi.org/10.1007/BF00231112
"Thus it is concluded that the increase in serum ferritin levels in patients with hyperthyroidism may be due to the direct action of thyroid hormones on its synthesis, while in some cases complicated with anemia impaired iron utilization by erythropoietic cells may also be involved."
Leedman PJ, Stein AR, Chin WW, Rogers JT - "Thyroid hormone modulates the interaction between iron regulatory proteins and the ferritin mRNA iron-responsive element" Journal of Biological Chemistry 271(20):12017-12023 (1996)
https://doi.org/10.1074/jbc.271.20.12017
"We conclude that T3 can functionally regulate the IRE binding activity of the IRP. These observations provide evidence of a novel mechanism for T3 to up-regulate hepatic ferritin expression, which may in part contribute to the elevated serum ferritin levels seen in hyperthyroidism."
Maldonado-Araque C, Valdés S, Lago-Sampedro A, Lillo-Muñoz JA, Garcia-Fuentes E, Perez-Valero V, Gutierrez-Repiso C, Goday A, Urrutia I, Peláez L, Calle-Pascual A, Castaño L, Castell C, Delgado E, Menendez E, Franch-Nadal J, Gaztambide S, Girbés J, Ortega E, Vendrell J, Chacón MR, Chaves FJ, Soriguer F, Rojo-Martínez G - "Iron deficiency is associated with Hypothyroxinemia and Hypotriiodothyroninemia in the Spanish general adult population: Di@bet.es study" Sci Rep 8(1):6571 (2018) doi: 10.1038/s41598-018-24352-9
https://pmc.ncbi.nlm.nih.gov/articles/PMC5919900/
Saïd R - "Hyperthyroidism: a cause of serum ferritin elevation" Review of Internal Medicine 21(12):1129-1131 (2000)
https://doi.org/10.1016/S0248-8663(00)00275-7
Swapnika TG, Sabitha Rani SS, Dipankar S, Itagi ABH, Vamshidhar IS - "A Comparative Study of Iron Status in Subclinical Hypothyroid and Euthyroid Subjects in a Tertiary Care Hospital" Cureus 16(1):e52007 (2024) doi: 10.7759/cureus.52007
"The prevalence of anemia in subclinical hypothyroidism is significantly elevated, and considering the absence of significant clinical manifestations in the early stages, it is recommended to routinely conduct investigations for early detection, facilitating prompt management. Consequently, our study emphasizes that both overt and subclinical hypothyroidism should be recognized as risk factors for the development of iron deficiency anemia."
Takamatsu J, Majima M, Miki K, Kuma K, Mozai T - "Serum ferritin as a marker of thyroid hormone action on peripheral tissues" Journal of Clinical Endocrinology and Metabolism 61(4):672-676 (1985)
https://doi.org/10.1210/jcem-61-4-672
Intraindividual ferritin decreased as Graves' patients became euthyroid; ferritin rose when hypothyroid patients achieved euthyroidism; short-term T3 increased ferritin in euthyroid subjects, with blunted responses in thyroid hormone resistance.
Thomson AM, Rogers JT, Leedman PJ - "Thyrotropin-releasing hormone and epidermal growth factor regulate iron-regulatory protein binding in pituitary cells via protein kinase C-dependent and -independent signaling pathways" J Biol Chem 275(41):31609-31615 (2000)Serum ferritin measurements were evaluated as a marker of thyroid hormone action on peripheral tissues. Mean serum ferritin concentrations were not significantly different in euthyroid, thyrotoxic, and hypothyroid subjects due to a wide spread in ferritin levels among individuals.
Intraindividual changes in serum ferritin, however, occurred with changing thyroid function. All 18 patients with thyrotoxic Graves' disease had a decrease in serum ferritin levels when they became euthyroid during antithyroid drug therapy. Furthermore, a significant intraindividual correlation between serum levels of ferritin and T4 or T3 was found in 2 patients with thyrotoxic Graves' disease in whom levels were measured serially throughout the course of therapy. Similarly, serum ferritin levels increased in all 12 hypothyroid patients with Hashimoto's disease when euthyroidism was achieved with L-T4 therapy.
Administration of 75 μg T3 daily for 1 week to 11 euthyroid subjects resulted in a 23–243% (mean ± SD, 117 ± 70%) increase i n serum ferritin above basal values. In contrast, in 3 patients with thyroid hormone resistance, the same treatment produced rises in serum ferritin concentrations of only 2%, 5%, and 15%.
Our data suggest that alterations in thyroid status in a given individual produce changes in serum ferritin levels. Measurement of this protein before and after T3 therapy may prove useful in the diagnosis of thyroid hormone resistance.
https://doi.org/10.1074/jbc.M002354200
“These data link two different cell receptor systems to common signaling pathways that regulate IRP binding and ferritin expression.”
(NOTE: In this paper, the TRH effect on IRP binding is explicitly described as PKC-dependent, which is the canonical downstream arm of Gq/11 signalling.)
Tiwari R, Saharia GK, Mangaraj M - "Evaluation of Serum Ferritin and Anti-Thyroid Peroxidase Antibody Status in Newly Diagnosed Subclinical Cases of Hypothyroidism" Endocr Metab Immune Disord Drug Targets 21(8):1453-1458 (2021) doi: 10.2174/1871530320666200925125404
https://www.eurekaselect.com/article/110234
"Ferritin concentrations were decreased in anti-TPO negative hypothyroidism, but in the case of anti-TPO positive hypothyroidism the ferritin concentrations are raised. Hence, hypothyroidism should not always be considered as an iron deficiency state."
Van de Vyver FL, Blockx PP, Abs RE, Van den Bogaert WG, Bekaert JL - "Serum ferritin levels in hyperthyroidism" Annals of Internal Medicine 97(6):930-931 (1982)
https://doi.org/10.7326/0003-4819-97-6-930_3
"Our initial investigation included 38 hyperthyroid patients, studied before and during therapy. A decrease of serum ferritin during antithyroid therapy was noted in most patients; 18 of the 20 patients, reaching the euthyroid state during this preliminary study, showed a fall in serum ferritin level. Our study currently includes 44 hyperthyroid patients who became euthyroid. In all but four patients, serum ferritin levels decreased during treatment."
Vinayagamoorthi R, Dhiman P, Kollipaka R, Sabita P, Hemavathy V - "Association of Hypothyroidism With Low Serum Ferritin Levels and Iron-Deficiency Anemia During the First Trimester of Pregnancy" Cureus 14(8):e28307 (2022) doi: 10.7759/cureus.28307
"There was a significant increase in TSH levels and a significant decrease in the levels of FT4, FT3, ferritin, iron, and hemoglobin (Hb) in hypothyroid pregnant women compared to euthyroid pregnant women. The correlation and regression analysis revealed a significant negative association of TSH and a positive association of FT4 with ferritin, iron, and Hb."
Zwirska-Korczala K, Buntner B, Sobieraj H, Ostrowska Z, Kniazewski B, Swietochowska E - "Serum ferritin, iron and transferrin in women with thyrotoxic Graves' disease before and after methimazole treatment" Acta Physiol Pol 41(7):163-8 (1990)
https://pubmed.ncbi.nlm.nih.gov/2136311/
Abstract
We investigated iron metabolism in 47 women with thyrotoxic Graves' disease. Serum iron, ferritin, transferrin, triiodothyronine and thyroxine concentrations were RIA measured before and after methimazole treatment when patients became euthyroid. The control group consisted of 52 healthy women. We noted that serum ferritin levels and the ferritin to transferrin ration were significantly lower while the iron to ferritin ratio was higher in patients before and after methimazole therapy. Iron concentration as well as the iron to transferrin and the iron to thyroid hormone ratios were decreased only before treatment.