Interesting - patients found to have reduced FT4 and reduced FT3 associated with lower ferritin levels. But without change of TSH.
Surely, if the TSH test is so exquisitely sensitive and is the best test for hypothyroidism, it would reveal the lower FT4 and FT3 levels regardless of ferritin level?
It certainly seems to imply that ferritin measurement (preferably full iron assessment) is required for proper assessment. Indeed, it also seems to suggest that TSH, FT4 and FT3 should be tested in those with low ferritin. Although I am usually highly critical of labs changing what is tested, in this case, automatically doing TSH, FT4 and FT3 might not be a bad idea. (Trouble, of course, if lab has no idea of patient background.)
Odd that it should crop up in what appears to be diabetes research...
Hypothyroxinemia = low T4 blood level
Hypotriiodothyroninemia = low T3 blood level
Sci Rep. 2018 Apr 26;8(1):6571. doi: 10.1038/s41598-018-24352-9.
Iron deficiency is associated with Hypothyroxinemia and Hypotriiodothyroninemia in the Spanish general adult population: Di@bet.es study.
Maldonado-Araque C1, Valdés S2,3, Lago-Sampedro A1,4, Lillo-Muñoz JA5, Garcia-Fuentes E6,7, Perez-Valero V5, Gutierrez-Repiso C1,8, Goday A9, Urrutia I4,10, Peláez L1, Calle-Pascual A4,11, Castaño L4,10, Castell C12, Delgado E13,14,15, Menendez E13,14,15, Franch-Nadal J4,16, Gaztambide S4,17, Girbés J18, Ortega E7,19, Vendrell J4,20, Chacón MR21, Chaves FJ4,22, Soriguer F1,4, Rojo-Martínez G1,4.
1 Department of Endocrinology and Nutrition, Hospital Regional Universitario de Málaga, IBIMA, Málaga, Spain.
2 Department of Endocrinology and Nutrition, Hospital Regional Universitario de Málaga, IBIMA, Málaga, Spain. firstname.lastname@example.org.
3 Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain. email@example.com.
4 Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.
5 UGC de Laboratorio (Bioquímica). Hospital Regional Universitario de Málaga, Málaga, Spain.
6 UGC de Aparato Digestivo. Hospital Universitario Virgen de la Victoria, IBIMA, Málaga, Spain.
7 CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
8 UGC de Endocrinología y Nutrición. Hospital Universitario Virgen de la Victoria. IBIMA, Málaga, Spain.
9 Department of Endocrinology and Nutrition, Hospital del Mar, Barcelona, Spain.
10 Hospital Universitario Cruces, BioCruces, UPV/EHU, Barakaldo, Spain.
11 Department of Endocrinology and Nutrition, Hospital Universitario S. Carlos de Madrid, Madrid, Spain.
12 Public Health Agency of Catalonia, Department of Health, Barcelona, Spain.
13 Endocrinology and Nutrition Service, Hospital Universitario Central de Asturias, Oviedo, Spain.
14 Department of Medicine, University of Oviedo, Hospital Central de Asturias, Oviedo, Spain.
15 Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain.
16 EAP Raval Sud, Institut Català de la Salut, Red GEDAPS, Primary Care, Unitat de Suport a la Recerca (IDIAP - Fundació Jordi Gol), Barcelona, Spain.
17 Department of Endocrinology and Nutrition, Hospital Universitario Cruces - UPV-EHU, Baracaldo, Barcelona, Spain.
18 Diabetes Unit, Hospital Arnau de Vilanova, Valencia, Spain.
19 Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Barcelona, Spain.
20 Department of Endocrinology and Nutrition, Hospital Universitario Joan XXIII, Institut d'Investigacions Sanitaries Pere Virgili, Tarragona, Spain.
21 Joan XXIII University Hospital. IISPV., Tarragona, Spain.
22 Genomic Studies and Genetic Diagnosis Unit, Fundación de Investigación del Hospital Clínico de Valencia-INCLIVA, Valencia, Spain.
Previous studies have suggested that iron deficiency (ID) may impair thyroid hormone metabolism, however replication in wide samples of the general adult population has not been performed. We studied 3846 individuals free of thyroid disease, participants in a national, cross sectional, population based study representative of the Spanish adult population. Thyroid stimulating hormone (TSH), free thyroxin (FT4) and free triiodothyronine (FT3) were analyzed by electrochemiluminescence (E170, Roche Diagnostics). Serum ferritin was analyzed by immunochemiluminescence (Architect I2000, Abbott Laboratories). As ferritin levels decreased (>100, 30-100, 15-30, <15 µg/L) the adjusted mean concentrations of FT4 (p < 0.001) and FT3 (p < 0.001) descended, whereas TSH levels remained unchanged (p = 0.451). In multivariate logistic regression models adjusted for age, sex, UI, BMI and smoking status, subjects with ferritin levels <30 µg/L were more likely to present hypothyroxinemia (FT4 < 12.0 pmol/L p5): OR 1.5 [1.1-2.2] p = 0.024, and hypotriiodothyroninemia (FT3 < 3.9 pmol/L p5): OR 1.8 [1.3-2.6] p = 0.001 than the reference category with ferritin ≥30 µg/L. There was no significant heterogeneity of the results between men, pre-menopausal and post-menopausal women or according to the iodine nutrition status. Our results confirm an association between ID and hypothyroxinemia and hypotriiodothyroninemia in the general adult population without changes in TSH.
29/04/2018 08:14 Edited to add from the full paper:
ID may alter the synthesis of thyroid hormones by multiple mechanisms: ID induces ineffective erythropoiesis, thus reducing the transport of oxygen to the different tissues required for multiple enzymatic reactions. ID has also been shown to increase in-vitro hepatic reverse triiodothyronine deiodination, suggesting that under conditions of ID, thyroid hormones tend to be metabolized by an inactivating route. Also, ID may lower thyroperoxidase activity and therefore interfere with the synthesis of thyroid hormones. Although these mechanisms described could be explanatory, our results suggest the implication of additional hypothalamic-pituitary mechanisms, given the lack of TSH response to the decrease in the levels of peripheral hormones. Accordingly, the experiments carried out by Tang et al. in iron deficient rats subjected to low temperatures, showed decreased levels of TSH, FT4 and FT3, which reverted to normal if stimulated with synthetic thyrotropin releasing hormone (THR), suggesting that ID may impair the hypothalamic secretion of THR. In line with this observation, the study from Eftekhari in Iranian adolescents with ID, showed that despite increases in FT3 and FT4 concentrations, the TSH concentration was unaffected by iron supplementation. Since no separate mechanism on its own fully explains the results found in our study, it is likely that a combination of mechanisms may be involved.
Link to full paper:
29/04/2018 10:26 - Added this older abstract which appears relevant:
Effects of cold exposure or TRH on the serum TSH levels in the iron-deficient rat.
Tang F1, Wong TM, Loh TT.
1 Department of Physiology, Faculty of Medicine, University of Hong Kong.
Normal and iron-deficient rats were exposed to cold at 4 degrees C for 1 hr or 5 hrs and the serum TSH, T3 and T4 levels were compared with those in rats kept at room temperature (20 degrees C). There was a rise in serum TSH, T3 and T4 levels in response to 1 hr and 5 hrs of cold exposure in normal, but not in iron-deficient rats. Although pituitary TSH contents were lower in iron-deficient rats, the increases in serum levels of TSH following administration of TRH were similar in both normal and iron-deficient rats. The results suggest that the inability to respond to cold in iron-deficient rats may be due to a reduction in the release of TRH from the hypothalamus.