Rare case of autoimmune hypothyroidism presenting with pancytopenia

Abstract

Hypothyroidism can involve any organ system in the body with the involvement of haematopoietic system seen in about 30% of the cases. Anaemia is the most common haematological involvement with the affection of other cell lines being exceedingly rare and limited to occasional case reports. Here we present a case of a 14-year-old boy who presented with fever and pancytopenia and was later diagnosed to be a case of autoimmune hypothyroidism.

Background

Hypothyroidism can affect any organ system of the body. Involvement of the haematopoietic system being seen in about 30% of cases with anaemia being the the most common presentation and affection of other cell lines being exceedingly rare.¹ To our best knowledge, there are only a few case reports available. We hereby describe a case of autoimmune hypothyroidism presenting with pancytopenia.

Case presentation

A 14-year-old boy presented with complaints of low-grade intermittent fever, a maximum temperature recorded up to 101^oF, for the past 1 month without any definite localising symptoms. He also complained of gaining weight, generalised dryness and coarsening of the skin, easy fatigability and feeling breathless while playing with his peers and climbing stairs for the last 2 to 3 months. However, there was no history of cough, chest pain, orthopnoea, paroxysmal nocturnal dyspnoea or any blood loss. He denied any history of malar rash, photosensitivity, oral ulcers or joint symptoms. Physical examination revealed bodyweight of 41 kg with height being 132 cm and body mass index (BMI) 23.5 kg/m², vitals stable (pulse rate of 88 beats/min, blood pressure of 106/60 mm Hg, respiratory rate of 12/min, moderate pallor, generalised dry and coarse skin, few wet purpuras inside the oral cavity, grade 2 thyromegaly, no lymphadenopathy (figure 1A). Systemic examination findings were within normal limits.

Figure 1.

(A) Photograph of patient showing dry skin and grade 2 thyromegaly. (B) Photomicrograph of bone marrow (H&E stained, 40X) showing hypoplastic marrow with replacement by fat cells.

Investigations

His blood investigations showed pancytopenia with a high erythrocyte sedimentation rate with the rest of the parameters being within the normal limit (table 1). Peripheral blood film showed a normocytic normochromic picture without any blasts or, any abnormal cells. Further investigations showed sterile blood culture, 6 to 8 pus cells/high power field in urine microscopy with urine culture showing a growth of Escherichia coli. Chest radiograph showed cardiomegaly without any lung parenchymal abnormality and echocardiography showed mild pericardial effusion with good biventricular systolic function. Contrast-enhanced CT (CECT) of chest and abdomen showed mild ascites, minimal bilateral pleural effusion without any other abnormality.

Table 1.

Investigations

Parameters (normal range)	At baseline	At 2 weeks	At 6 weeks
Haemoglobin (mmol/L) (8.7–11.3 mmol/L)	4.22	5.03	5.65
Total leucocyte count (109/L) (4.0–11.0 x 109/L)	2.2	4.3	5.6
Platelet count (109/L) (150–400 x 109/L)	110	170	210
Erythrocyte sedimentation rate (1–13 mm/1st hour)	115 mm/1st hour
C reactive protein (mg/L) (<5 mg/L)	2.0
Serum procalcitonin (ng/mL) (0.01–0.5 ng/mL)	0.2
Serum urea (mmol/L) (2.5–10.7 mmol/L)	7.14
Serum creatinine (mmol/L) (0.053–0.106 mmol/L)	0.071
Serum bilirubin (μmol/L) (3.4–17.1 μmol/L)	8.55
SGPT (IU/L) (5–40 IU/L)	26
SGOT (IU/L) (5–40 IU/L)	30
Total protein (gm/L) (60–83 g/L)	68
Albumin (gm/L) (34–48 g/L)	38
Serum procalcitonin (<0.15 ng/mL)	0.05 ng/mL
Prothrombin time (13 s)	13.2 s
Serum iron (μg/dL) (50–150 µg/L)	102
Serum ferritin (μg/L) (50–200 µg/L)	300
Transferrin saturation (30%–50%)	50%
Total iron binding capacity (μg/dL) (300–360 µg/dL)	300
Serum B12 (pg/mL) (200–950 pg/mL)	1300
Serum folate (ng/mL) (5–21 ng/mL)	20
Body weight (kg)	41	40	38

SGOT, Serum glutamic-oxaloacetic transaminase; SGPT, Serum glutamic-pyruvic transaminase.

Differential diagnosis

With these available investigations, a haematological disorder like aplastic anaemia, leukaemia or, lymphoma, any connective tissue disease, infective diseases like tuberculosis (TB) and leishmaniasis was kept as possible differentials. However, CECT of the chest and abdomen did not show any significant lymphadenopathy or, any other features suggestive of TB or, lymphoma. Tuberculin skin test and rapid testing for leishmania antigen (RK 39) were negative. Anti-nuclear antibody by indirect immunofluorescence also came out to be negative, making any possibility of any connective tissue disease less likely. Serum iron profile, B₁₂ and folate were normal. Bone marrow examination showed hypocellular marrow, normal erythroid–myeloid ratio without any atypical cells or leishmania-donovan bodies (figure 1B) with marrow culture being sterile, thus further ruling out the possibility of primary haematological disorder, TB or leishmaniasis. Thyroid profile, done because of history of thyromegaly, weight gain and dry skin features, showed low free T4 (0.11 ng/dL) and high thyroid stimulating hormone (TSH) (>100 μIU/mL). Anti-thyroid peroxidase antibody level was 734.2 IU/mL (normal level <5.61 IU/mL). Serum erythropoietin level was also done which came out to be low (2.8 U/L; reference range 4–27 U/L). Taking all the things together, his cause of pancytopenia was suspected to be due to hypothyroidism, although infectious aetiology like atypical viral infection causing transient marrow suppression could not be ruled out.

Treatment

He was started on injectable antibiotics as per urine culture sensitivity report with which he became afebrile in 3 to 4 days. Repeat urine culture was sterile. Antibiotics stopped after 7 days. However even then pancytopenia persisted. Later with diagnosis of hypothyroidism, he was also started on levothyroxine (62.5 mcg/day).

Outcome and follow-up

He gradually improved, repeat count after 2 weeks revealed resolution of cytopenia with further follow-up after 6 weeks showing significant improvement in all parameters (table 1).

Discussion

Anaemia, being the most common haematological abnormality in hypothyroidism, is usually normocytic normochromic, less commonly macrocytic due to coexistent vitamin B₁₂/folate deficiency or, microcytic due to excess blood loss, especially in women.² The exact pathophysiology of normocytic anaemia is not clear, however, ferrokinetic studies have shown decreased maximum Fe95 utilisation by red blood cells suggesting hypothyroidism can affect cellular needs for oxygen and its utilisation, thus affecting erythropoiesis. Plasma erythropoietin has been shown to be low in contrast to other causes of anaemia where it is usually increased due to tissue hypoxia.³ Our case also showed similar findings.

Pancytopenia, although uncommon, has rarely been reported in the literature, although limited to case reports.⁴ An associated autoimmune disorders like pernicious anaemia or, an autoimmune reaction to bone marrow causing marrow hypoplasia has been implicated as a cause.^{5 6} It is usually responsive to thyroid replacement with B₁₂, folate supplement needed in case of pernicious anaemia. Rarely steroid therapy has also been found to be beneficial. In our case, no evidence of megaloblasts in peripheral smear or bone marrow rules out pernicious anaemia. Rather, hypoplastic marrow and response to thyroid supplement establish autoimmune reaction to bone marrow as the possible cause, been rarely reported in the literature.

Besides, infection can also cause pancytopenia either by transient bone marrow suppression or, via secondary haemophagocytic lymphohistiocytosis.⁷ Numerous bacteria, virus, fungi can cause such episode of pancytopenia which often can be self-limited. Although, in our case pancytopenia persisted even after treatment completion for urinary tract infection and there was no other features to suggest severe sepsis, but possibility of infection causing marrow suppression, could not be ruled out with certainty.

However, considering temporal course of the illness with recovery of pancytopenia with starting of levothyroxine, autoimmune hypothyroidism seems more plausible explanation.

To conclude, though pancytopenia is a relatively rare manifestation of hypothyroidism, it should be kept in possible differentials as it is well responsive to treatment in comparison to other aetiologies like aplastic anaemia.

Learning points.

• Anaemia is the most common haematological involvement of hypothyroidism, seen in up to 30% of the cases, usually normocytic, normochromic; however, can be macrocytic or, microcytic also.

• Pancytopenia can rarely be seen in hypothyroidism, due to association with pernicious anaemia or, as a result of an autoimmune reaction to bone marrow.