Kadgi, Chauhan, and Nakate: Hematological changes in hypothyroidism and hyperthyroidism in adults


Introduction

Thyroid hormones are one of the essential hormones. These are required for the normal development, differentiation, metabolic balance and physiological function of virtually all tissues. Thyroid function disorders are among the most common endocrine diseases.1 Thyroid diseases are common worldwide. In India too, there is a significant burden of thyroid diseases. In India the prevalence of hypothyroidism is 10.95% and hyperthyroidism is 1.3%. Our country at present harbours 42 million individuals who suffer from one or more forms of thyroid disorders. Despite a high disease burden, thyroid gland disorders have failed to receive due attention. Even after the promotion of iodized salt since 1983, prevalence rates have failed to reduce to statistically significant levels.2, 3 Hypothyroidism is common among the disorders of the endocrine system. Thyroid hormones are not produced in proportion of body requirement by thyroid gland in hypothyroidism. The confirmed diagnosis of the hypothyroidism can be made by measuring blood levels of thyroid stimulating hormone (TSH) and thyroxine levels. Women are affected more with hypothyroidism than men. 4 Hyperthyroidism is a condition in which thyroid gland is hyperfunctioning which leads to an excessive amount of thyroid hormones circulating in the blood.4 Hypothyroidism can cause certain forms of anemia.5 One of the studies suggested that there is an essential relationship between the hypothyroid state and low levels of iron, vitamin B12, and folic acid in the human body.6 In contrast, hyperthyroid patients do not show anemia frequently, whereas erythrocytosis is fairly common.7, 8 As far as white blood cells and thrombocytes are concerned, a slightly depressed total leucocyte count, neutropenia, and thrombocytopenia have been observed in hypothyroid patients.9 Furthermore, increased, normal, or slightly decreased total leucocyte counts have been found in hyperthyroid patients, with only a relatively reduced neutrophils and a relatively increased eosinophils and mononuclear cells. Nevertheless, Axelrod reported hyperplasia and hypoplasia of all myeloid cell lines in hyperthyroidism and hypothyroidism respectively.10 With reference to lymphocytes, triidothyronine (T3) has been demonstrated to regulate pro-B-cell proliferation and thus a prerequisite for normal B-cell production in the bone marrow. These observations confirmed the association between thyroid gland dysfunction and Hematopoiesis.11, 12, 13

Materials and Methods

Study design

This was a cross-sectional descriptive study conducted in tertiary care center during the period from March 2018 to October 2019 to evaluate the correlation between thyroid disease and hematological changes.

Study population

For study 100 patients of hypothyroidism, 80 patients of hyperthyroidism and 100 euthyroid patients attending endocrinology OPD at tertiary care center were selected.

Inclusion criteria

The present study included cases of thyroid dysfunction attending the endocrinology OPD above the age of 14 years irrespective of sex.

Exclusion criteria

Cases of thyroid dysfunction attending the endocrinology OPD having infectious diseases, history of recurrent infections, asthma, allergy or using any drugs and age below 14 years were excluded from the study.

Ethical consideration

Permission was taken from ethical committee of the institute and all the participants were explained the purpose of study and informed written consent was taken from them.

Statistical analysis

Data was entered into Microsoft Excel and analyzed using SPSS (Statistical Package for Social Sciences) Software 20. Categorical variables were expressed in terms of frequency and percentage and continuous were expressed in terms of mean and SD. ANOVA test was applied to see any significant difference in continuous variables (RBC, WBC, TFT variables and platelet) among study groups (Hypothyroid, hyperthyroid and control group) Bonferroni post hoc correction was applied to see any difference between hypothyroid and control as well as hyperthyroid and control group with p<0.05 as statistically significant value.

Procedure

  1. Detail clinical histories were recorded

  2. A specific protocol was followed which included patients’ particulars, clinical features, biochemical parameters and clinical diagnosis.

  3. Informed written consent was taken.

  4. Collection of two separate blood samples was done from each patient, 3 ml in plain vacutainer and 2 ml in EDTA vacutainer.

  5. Sample collected in plain vacutainer was used for serum TSH assay by electrochemiluminescence immunoassay method.

  6. Normal serum TSH level is 0 27 to 4 2 μIU/ml

  7. Serum TSH level less than 0 27 μIU/ml was labeled as hyperthyroidism

  8. Serum TSH level more than 4 2 μIU/ml was labeled as hypothyroidism

  9. Complete blood count and peripheral blood smear preparation were done from the sample collected in EDTA vacutainer.

  10. Complete blood count was done on automated cell counter Sysmex 5 part differential for red cell indices and blood cell counts.

  11. Peripheral blood smears were made by wedge method and then those were air dried

  12. Staining of peripheral blood smears was done by Leishman stain and then it was dried and mounted with DPX.

  13. Stained smears then were observed under microscope for the type of anemia

  14. The relationship between serum TSH levels and complete blood count as well as serum TSH levels and peripheral blood smear were studied in detail to determine the hematological changes.

Table 1

Age-wise distribution and Male: Female ratio among study groups (n=280)

Age group

Hypothyroid (n=100)

Hyperthyroid (n=80)

Control (n=100)

Total (n=280)

14-20yrs

1(1%)

0(0%)

3(3%)

4(1.4%)

21-30yrs

18(18%)

13(16.2%)

26(26%)

57(20.4%)

31-40yrs

36(36%)

17(21.2%)

36(36%)

89(31.8%)

41-50yrs

20(20%)

12(15%)

12(12%)

44(15.7%)

51-60yrs

6(6%)

7(8.8%)

2(2%)

15(5.4%)

61-70yrs

15(15%)

24(30%)

15(15%)

54(19.3%)

71-80yrs

4(4%)

7(8.7%)

6(6%)

17(6.0%)

Total

100(100%)

80(100%)

100(100%)

280(100%)

Male:Female

2.3:1

1.6:1

1.3:1

1.7:1

Table 2

Comparison of TFT variables among study groups

Variables

Hypothyroid

Hyperthyroid

Control

P value

(n=100)

(n=80)

(n=100)

p1= p value of hypothyroid

Mean +/-Std Deviation

Mean +/-Std Deviation

Mean +/-Std Deviation

p2= p value of hyperthyroid

TSH (µIU/ml)

20.96+/-29.3

0.13+/-0.062

2.17+/-1.14

p1=0.0001

p2=0.0001

T3 (ng/dl)

1.06+/-0.31

2.56+/-3.63

1.55+/-0.5

p1=0.0001

p2=0.0001

T4 (µg/dL)

6.04+/-3.18

11.88+/-4.33

8.17+/-2.07

p1=0.0001

p2=0.0001

Table 3

Comparison of RBC indices among study groups

RBC Indices

Hypothyroid

Hyperthyroid

Control

P value

Mean+/- Std. Deviation

Mean+/- Std. Deviation

Mean+/- Std. Deviation

p1= p value of hypothyroid

p2= p value of hyperthyroid

RBC(N x 106/µl)

3.4+/-0.79

3.93+/-0.72

4.58+/-0.63

p1=0.0001

p2=0.0001

Haemoglobin

(gm %)

9.44+/-2.26

11.3+/-2.31

13.76+/-1.78

p1=0.0001

p2=0.0001

Haematocrit (%)

28.72+/-6.03

33.91+/-6.68

41.23+/-5.56

p1=0.0001

p2=0.0001

MCV (fl)

80.67+/-7.40

81.59+/-4.54

83.58+/-8.38

p1=0.012

p2=0.188

MCH (pg)

27.23+/-3.48

28.48+/-2.14

29.12+/-1.41

p1=0.003

p2=0.267

MCHC (g/dl)

29.72+/-3.38

29.76+/-2.35

30.17+/-1.19

p1=0.351

p2=0.373

RDW (%)

13.55+/-0.3

13.74+/-0.66

12.53+/-0.66

p1=0.001

p2=0.0001

Results

Our findings showed that hypothyroidism was more common among younger and hyperthyroidism was common in elderly population with overall female predominance (Table 1) and hypothyroid group showed raised TSH with depressed T3 and T4 levels and hyperthyroid group showed depressed TSH with raised T3 and T4 levels (Table 2). Hypothyroid group showed statistically significant reduction in Mean RBC count, hemoglobin, hematocrit, MCV and MCH and increased RDW whereas hyperthyroid group showed reduction in Mean RBC count, hemoglobin, hematocrit and increased RDW when compared with control group. There was no statistically significant difference in MCV and MCH in hyperthyroid group. MCHC results were statistically insignificant in both hypothyroid and hyperthyroid group as compared with control group (Table 3). There was no statistically significant difference in total leukocyte count and platelets count among hypothyroid and control as well as hyperthyroid and control group.

Table 4

Comparison of total WBC count and differential leucocyte count among study groups

WBC Indices

Hypothyroid

Hyperthyroid

Control

P value

Mean+/- Std. Deviation

Mean+/- Std. Deviation

Mean+/- Std. Deviation

p1= p value of hypothyroid

p2= p value of hyperthyroid

TLC (Nx103/µl, )

7.98+/-2.38

7.14+/-2.21

8.19+/-2.35

p1=0.719

p2=1.000

Neutrophil %

59.87+/-6.17

60.54+/-5.99

66.07+/-4.84

p1=0.0001

p2=0.0001

Lymphocyte%

35.13+/-5.29

34.98+/-5.83

30.08+/-5.08

p1=0.0001

p2=0.0001

Monocyte%

2.18+/-1.42

2.03+/-1.05

1.51+/-0.79

p1=0.0001

p2=0.007

Eosinophil%

2.43+/-1.16

2.64+/-1.23

2.1+/-1.147

p1=0.150

p2=0.008

Basophil%

-

-

-

NA

Table 5

Comparison of Platelet findings among study groups

TFT Group

Mean platelet

Std. Deviation

P value

(Nx103/µl)

(Nx103/µl)

p1= p value of hypothyroid

p2= p value of hyperthyroid

Hypothyroid

(n=100)

188.89

89.01

p1=0.081

Hyperthyroid

(n=80)

296.78

381.78

p2=0.729

Control

(n=100)

258.11

107.54

Table 6

Comparison of Platelet findings among study groups

PBS

Hypothyroid (n=100)

Hyperthyroid (n=80)

Control (n=100)

Total (n=280)

MC HC anaemia

17(17%)

18(22.5%)

6(6%)

41(14.6%)

NC HC anaemia

5(5%)

0(0%)

0(0%)

5(1.8%)

NC NC anaemia

70(70%)

26(32.5%)

5(5%)

101(36.1%)

Within Normal Limit

8(8%)

36(45%)

89(89%)

133(47.5%)

Total

100(100%)

80(100%)

100(100%)

280(100%)

[i] [MC HC – Microcytic Hypochromic, NC HC – Normocytic Hypochromic, NC NC – Normocytic Normochromic]

In differential leukocyte count both hypothyroid and hyperthyroid group showed statistically significant difference in neutrophil, lymphocyte and monocyte count. In addition hyperthyroid group also had significant difference in eosinophil count (Table 4, Table 5). Peripheral Blood Smears (PBS) showed anemia in 92% of hypothyroid and 55% of hyperthyroid subjects. The most common type of anemia noted was Normocytic Normochromic followed by Microcytic Hypochromic anemia (Table 6).

Discussion

The thyroid gland is the largest endocrine gland in the body. It weighs about 14-18 grams. Thyroid gland is bigger in females than in males. The Thyroid hormones, T4 and T3, are synthesized in the thyroid gland. T3 is more potent hormone than T4.1, 2, 3 Thyroid hormones play a vital role in cell differentiation during development and maintain metabolic homeostasis in adults. Thyroid gland also has a significant effect on erythropoiesis. It induces erythropoietin secretion and proliferation of erythroid progenitors.14, 15 Thyroid diseases are common worldwide. In India too, there is a significant burden of thyroid diseases.2, 3 Thyroid dysfunctions affect red blood cells and cause anemia. These dysfunctions importantly include hypothyroidism and hyperthyroidism. They may also cause pancytopenia. Association of alteration in hematological parameters such as Red blood cell (RBC) count, hemoglobin (Hb), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), white blood cell (WBC) count and platelet count with thyroid dysfunction is also observed. 16 So, this cross sectional descriptive study was done in Tertiary care center to determine the correlation between thyroid diseases and hematological changes. In our study, statistically significant reduction in Mean RBC count, hemoglobin, hematocrit, MCV and MCH was observed in hypothyroid group with increased RDW whereas hyperthyroid group showed decrease in Mean RBC count, hemoglobin, hematocrit and increased RDW when compared with control group (P-value 0.05). There was no statistically significant difference in MCV and MCH in hyperthyroid group. MCHC results were statistically insignificant in both hypothyroid and hyperthyroid group as compared with control group (P-value 0.05). Total leukocyte count and platelets count did not show statistically significant difference among hypothyroid and hyperthyroid and control group (P-value 0.05). In differential leukocyte count both hypothyroid and hyperthyroid group showed statistically significant relative neutropenia with relative lymphocytosis and monocytosis. In addition hyperthyroid group also had relative increase in eosinophil count (P-value 0.05). Anemia was noted on PBS examination of both hypothyroid and hyperthyroid subjects, most commonly with hypothyroid group.

A study by Das K.C. et al. also noted anemia on peripheral blood smears examination in both hypothyroid and hyperthyroid patients.14 Dorgalaleh et al. conducted study to correlate hematological parameters with thyroid hormones and found out statistically significant difference in Hb, HCT, MCV, MCH, MCHC and RDW but no difference in red cell count, total leucocyte count and platelet count among hypothyroid and hyperthyroid groups when compared with control group.17 In a study by Geetha J P et al., results revealed that RDW and MCV in hypothyroid and hyperthyroid groups of patients in comparison to euthyroid individuals have statistically significant difference but Hb and HCT did not show any significant difference in comparison with euthyroid group.18

Kawa MP et al. study reported that RBC, Hb, HCT,MCV,MCH and MCHC in patients with hyperthyroidism and hypothyroidism had statistically significant difference in comparison with control group.16

Conclusion

Hematological analysis, which was the strength of our study, showed that all subjects with hypothyroidism and hyperthyroidism have a direct effect on most of the red blood cells indices.

Thyroid hormones in more than one way play a crucial role in regulating the various hematological parameters. Their presence could steer towards subclinical thyroid dysfunction allowing its early management. So, it is important not to ignore the evaluation of thyroid hormones in cases of unexplained anaemias in the female reproductive age group. So, in conclusion we can say that all the patients with hypothyroidism and hyperthyroidism should be periodically evaluated for probable hematological changes.

Source of Funding

None.

Conflict of Interest

None.

References

1 

PM Yen Physiological and Molecular Basis of Thyroid Hormone ActionPhysiol Rev200181310971142

2 

AG Unnikrishnan S Kalra RK Sahay G Bantwal M John N Tewari Prevalence of hypothyroidism in adults: An epidemiological study in eight cities of IndiaIndian J Endocr Metab20131764752

3 

AG Unnikrishnan UV Menon Thyroid disorders in India: An epidemiological perspectiveIndian J Endocr Metab201115Suppl S27881

4 

GA Brent Clinical practice. Graves' diseaseNew Engl J Med20083582425942605

5 

L Horton RJ Coburn JM England RL Himsworth The haematology of hypothyroidismQ J Med19764517710123

6 

JD Hines CH Halsted RC Griggs JW Harris Megaloblastic anemia secondary to folate deficiency associated with hypothyroidismAnn Intern Med1968684792805

7 

HG Fein RS Rivlin Anemia in thyroid diseasesMed Clin North Am197559511334510.1016/s0025-7125(16)31963-0

8 

R Corrocher M Querena AM Stanzial G De Sandre Microcytosis in hyperthyroidism: haematological profile in thyroid disordersHaematologica198166677986

9 

CSP Lima DEZ Wittmann V Castro MA Tambascia I Lorand-Metze STO Saad Pancytopenia in untreated patients with Graves' diseaseThyroid20061644039

10 

AR Axelrod L Berman The bone marrow in hyperthyroidism and hypothyroidismBlood19516543653

11 

MP Foster E Montecino-Rodriguez K Dorshkind Proliferation of bone marrow pro-B cells is dependent on stimulation by the pituitary/thyroid axisJ Immunol199916311588390

12 

C Arpin M Pihlgren A Fraichard Effects of T3Rα1 and T3Rα2 gene deletion on T and B lymphocyte developmentJ Immunol2000164115260

13 

K Grymuła E Paczkowska V Dziedziejko The influence of 3, 3′, 5-triiodo-L-thyronine on human haematopoiesisCell Proliferation200740330215

14 

KC Das M Mukherjee TK Sarkar Erythropoiesis and erythropoietin in hypo and hyperthyroidismJ Clin Endocrinol Metab197540221120

15 

DW Golde N Bersch IJ Chopra MJ Cline Thyroid hormones stimulate erythropoiesis in vitroBr J Haematol1977372173710.1111/j.1365-2141.1977.tb06833.x

16 

MP Kawa K Grymuła E Paczkowska M Baśkiewicz-Masiuk E Dąbkowska M Koziołek Clinical relevance of thyroid dysfunction in human haematopoiesis: biochemical and molecular studiesEur J Endocrinol20101622295305

17 

A Dorgalaleh M Mahmoodi B Varmaghani F Kiani Node O Saeeidi Kia S Alizadeh Effect of thyroid dysfunctions on blood cell count and red blood cell indiceIran J Pediatr Hematol Oncol201332737

18 

JP Geetha R Srikrishna Role of red blood cell distribution width (RDW) in thyroid dysfunctionInt J Biol Med Res20123214768



jats-html.xsl

© This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


  • Article highlights
  • Article tables
  • Article images

Article History

Received : 27-10-2021

Accepted : 02-09-2021

Available online : 23-11-2021


View Article

PDF File   Full Text Article


Copyright permission

Get article permission for commercial use

Downlaod

PDF File   XML File   ePub File


Digital Object Identifier (DOI)

Article DOI

https://doi.org/10.18231/j.ijpo.2021.094


Article Metrics






Article Access statistics

Viewed: 66

PDF Downloaded: 12



Wiki in hindi