Should women with abnormal serum thyroid stimulating hormone undergo screening for anemia?
Article Type: Letter to the editor
Authors: Sahin, Mustafa
Toprak, Selami Kocak
Altintas, N. Defne
Pub Date: 08/01/2009
Publication: Name: Archives of Pathology & Laboratory Medicine Publisher: College of American Pathologists Audience: Academic; Professional Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2009 College of American Pathologists ISSN: 1543-2165
Issue: Date: August, 2009 Source Volume: 133 Source Issue: 8
Accession Number: 230247096
Full Text: We read with great interest the Letter to the Editor by Lippi et al, (1) which reported that screening for anemia in women with abnormal serum thyroid stimulating hormone (TSH) would be unnecessary if it is not supported by a reasonable clinical suspicion. However, no data are provided on outpatient recruitment criteria. This information is needed to appraise the practical implications of the results. The reason for hospital admission may affect both TSH and hemoglobin levels; the results may include abnormal TSH values related to euthyroid sick syndrome. Data on drug history (for anemia and thyroid disease as well as others) and alcohol intake, which may have affected TSH values and erythrocyte indices, are missing.

Plasma glucose levels, alone, may alter erythrocyte indices even if the patient is not anaemic. (2) Hence, the presence of diabetes may have been a confounding factor in the statistical analysis. Subjects should also be grouped according to age, which may affect TSH levels. No data were given regarding the details of the multivariate analysis.

As well, vitamin B12 deficiencies are reported to be frequent in hypothyroidism. (3) Besides, menorrhagia is reported in severe hypothyroidism, and it is associated with iron deficiency anemia, which requires iron replacement for treatment. (4)

It would have been more helpful if the patients were categorized as subclinical hypothyroidism, clinical hypothyroidism, or subclinical hyperthyroidism and clinical hyperthyroidism, regarding the decision to screen for anemia. Sideropenia has been reported to be a common finding in women with subclinical hypothyroidism, and it is suggested that ferritin levels should routinely be screened in such patients. (5) Conversely, it has been documented that resistance to oral iron treatment or erythropoietin treatment in patients with anemia can be the result of abnormal thyroid function. (6,7) Finally, in hyperthyroid patients, it is well known that antithyroid drugs are a cause of anemia, and patients should be screened for anemia during follow-up, even if they are not screened initially. (8)

MUSTAFA SAHIN, MD

Department of Endocrinology

Gaziantep State Hospital

Gaziantep, Turkey 27010

SELAMI KOCAK TOPRAK, MD

Department of Hematology

Gaziantep State Hospital

Gaziantep, Turkey 27010

N. DEFNE ALTINTAS, MD

Department of Internal Medicine

Medicana International Ankara Hospital

Ankara, Turkey 06520

(1.) Lippi G, Montagnana M, Salvagno GL, Guidi GC. Should women with abnormal serum thyroid stimulating hormone undergo screening for anemia? Arch Pathol Lab Med. 2008;132(3): 321-322.

(2.) Koga M, Morita S, Saito H, Mukai M, Kasayama S. Association of erythrocyte indices with glycated haemoglobin in pre-menopausal women. Diabet Med. 2007;24(8):843-847.

(3.) Jabbar A, Yawar A, Wasim S, et al. Vitamin B12 deficiency common in primary hypothyroidism. J Pak Med Assoc. 2008;58(5):258-261.

(4.) Krassas GE, Pontikides N, Kaltsas T, Papadopoulou P, Paunkovic N, Duntas LH. Disturbances of menstruation in hypothyroidism. Clin Endocrinol (Oxf). 1999;50(5):655-659.

(5.) Duntas LH, Papanastasiou L, Mantzou E, Koutras DA. Incidence of sideropenia and effects of iron repletion treatment in women with subclinical hypothyroidism. Exp Clin Endocrinol Diabetes. 1999;107(6):356-360.

(6.) Cinemre H, BilirC, Gokosmanoglu F, Bahcebasi T. Hematologic effects of levothyroxine in iron-deficient subclinical hypothyroid patients: a randomized, double-blind, controlled study [published online ahead of print November 4, 2008]. J Clin Endocrinol Metab. 2009;94(1): 151-156.

(7.) Kaynar K, Ozkan G, Erem C, et al. An unusual etiology of erythropoietin resistance: hyperthyroidism. Ren Fail. 2007;29(6):759-761.

(8.) Thomas D, Mosidis A, Tsiakalos A, Alexandraki K, Syriou V, Kaltsas G. Antithyroid drug-induced aplastic anemia. Thyroid. 2008;18(10): 1043-1048.

The authors have no relevant financial interest in the products or companies described in this article.

In Reply.--We are thankful to the authors of this letter because it provides a further opportunity to discuss the relationship between thyroid dysfunction and anemia. A shortage of resources afflicts health care systems worldwide, and additional expenditures from unnecessary or unjustified testing would contribute to worsening this already precarious situation. In addition, identification of presumptive disease (anemia in the current case) in otherwise asymptomatic patients poses a clinical dilemma (to treat or not to treat) and the resultant potential patient risks associated with such treatment or nontreatment (eg, psychologic effects of being diagnosed with anemia). Thus, there are additional caveats to that of cost that should further prevent the unnecessary testing of patients. As clearly mentioned in our letter, (1) the study was designed to investigate the rationale of performing a widespread screening for anemia in women with abnormal serum thyroid stimulating hormone (TSH) results, when a reasonable clinical suspicion was lacking.

The first criticism raised about our letter concerned the lack of outpatient recruitment criteria, which is more philosophic than practical. In fact, there was no "reason for hospital admission" in our population because the study population comprised outpatient women referred to our laboratory for routine blood testing; thus, the prevalence of any confounding factors would be expected to be equally distributed among the test groups. Indeed, we cannot rule out the presence of comorbidities or concomitant therapies, but this is commonplace when performing population screenings. According to our study design, we aimed to establish a potential epidemiologic association between abnormal values of TSH and anemia, regardless of the underlying conditions causing TSH and/or red blood cell abnormal findings, that is, irrespective of the clinical reasoning for the test requests. We cautiously concluded that widespread population screening seems unjustified, but we would agree that the presence of diabetes, other comorbidities (eg, vitamin B12 or iron deficiency), or therapeutic treatments would radically change this scenario. In such cases, however, hematologic testing would be justified by the underlying conditions rather than by the presence of a finding of thyroid abnormalities.

There is a clear drawback in the next consideration by the authors. Although sideropenia has been reported to be a common finding in women with subclinical hypothyroidism, so that the authors suggest screening for ferritin levels routinely in such patients, the diagnosis of anemia, according to the World Health organization, is defined as a qualitative or quantitative deficiency of hemoglobin, and is, thus, independent from the parameters of iron metabolism. (2) Therefore, screening for vitamin B12, folic acid, or ferritin might be unjustified in nonanemic individuals, at least until hemoglobin levels fall below the conventional thresholds. (2)

We do agree that TSH distribution progressively shifts toward higher concentrations with age, thus justifying the use of age-specific ranges for TSH. (3) Unfortunately, however, the most recent recommendations by the Guidelines Committee of the National Academy of Clinical Biochemistry (4) do not consider this issue and still suggest the use of a generic interval of between 0.2 and 2.5 mU/L. When age-specific ranges become universally agreed upon and available, we would be happy to reanalyze our data accordingly.

Although it has been occasionally suggested that clinical thyroid dysfunction might be associated with some forms of anemia, especially in childhood, the prevalence of this association varies widely in adults, (4) thus raising reasonable doubts as to the cost effectiveness for screening a large population of patients presenting with abnormal TSH values but no specific clinical symptoms, as was the case in our study. The other caveats mentioned in our opening paragraph also need to be carefully considered.

Finally, we agree that antithyroid drugs are a cause of anemia, and patients should be monitored for anemia during the follow-up. However, the term screened is used inappropriately in this context. once the patient is being treated for thyroid abnormalities, hematologic testing would assume the meaning of monitoring, rather than population screening, as was our study intent.

GIUSEPPE LIPPI, MD

Sezione di Chimica Clinica

Dipartimento di Scienze

Morfologico-Biomediche

Universita degli Studi di Verona

Verona, Italy 37121

(1.) Lippi G, Montagnana M, Salvagno GL, Guidi GC. Letters to the editor: should women with abnormal serum thyroid stimulating hormone undergo screening for anemia? Arch Pathol Lab Med. 2008;132(3):321-322.

(2.) Beutler E, Waalen J. The definition of anemia: what is the lower limit of normal of the blood hemoglobin concentration? Blood. 2006; 107(5):1747-1750.

(3.) Surks MI, Hollowell JG. Age-specific distribution of serum thyrotropin and antithyroid antibodies in the US population: implications for the prevalence of subclinical hypothyroidism. J Clin Endocrinol Metab. 2007;92(12):4575-4582.

(4.) Baloch Z, Carayon P, Conte-Devolx B, et al. Guidelines Committee, National Academy of Clinical Biochemistry. Laboratory medicine practice guidelines: laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid. 2003;13(1):3-126.

(5.) Weissel M. Disturbances of thyroid function in the elderly. Wien Klin Wochenschr. 2006; 118(1-2):16-20.

The author has no relevant financial interest in the products or companies described in this article.
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