Endocrine Abstracts (2009) 19 P90

On adequate thyroxine replacement and still symptomatic

MS Kamaruddin & SH Pearce


Royal Victoria Infirmary, Newcastle Upon Tyne, UK.


Hypothyroid patients often present with non-specific symptoms and some of these may persist despite adequate thyroxine replacement, including weakness, poor memory, paraesthesia and numbness or coldness of the extremities. In patients on thyroxine who have been referred due to persistent symptoms, we routinely look for vitamin B12 deficiency, if symptoms persist once thyroxine replacement has been optimised.

We present three patients who remained symptomatic despite adequate thyroxine replacement. Patient A and B described joint pains with mood swings. Patient C however described symptoms of poor balance and poor concentration. All of them had markedly subnormal plasma B12 levels, which were confirmed before treatment with intramuscular hydroxycobalamin. Surrogate markers including antibodies and macrocytosis were negative in all three cases. All had significant improvement in their symptoms.

Patient: sex, ageTSH 0.3–4.7 mU/lFree T4 11–23 pmol/lThyroid peroxidase antibodies 0–60 KU/lB12 170–700 ng/lMCV (pre) (post) 83–101 flIntrinsic factor & parietal cell antibodies
A: M,510.2223>130010595.4 94.0Negative
B: F,290.93164013891.3 86.0Negative
C: F,371.33186812486.8 84.8Negative

Pernicious anaemia is present more frequently in subjects with primary autoimmune hypothyroidism, with reports of association in up to 12%. As vitamin B12 is an essential cofactor in different enzymatic processes involving the nervous system and haematopoiesis, deficiency in one system is possible without evidence of insufficiency in the other. Thus, macrocytosis, as an indirect marker of B12 status can be absent. Similarly, intrinsic factor & parietal cell antibody tests may lack sensitivity, making it difficult to identify such patients unless plasma vitamin B12 levels are measured. We recommend screening hypothyroid patients with persistent symptoms (particularly of neurocognitive change) despite adequate thyroxine, by direct measurement of plasma B12.

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