Intolerance to Levothyroxine

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Diarrhoea

soon after levothyroxine replacement therapy

1.

A. Elâ€Houni,

2.

N. Younis,

3.

H. Soran and

4.

D. Bowenâ€

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Author Affiliations

1.

Department of Diabetes &

Endocrinology, Arrowe Park Hospital, Wirral

Sir,

A 57â€year old woman presented with tiredness, dry skin and weight

gain. Examination revealed a smooth goitre with dry greasy skin. Biochemical

investigations were consistent with primary hypothyroidism with raised

thyroidâ€stimulating hormone (TSH) 16.8 mU/l (normal range 0.5–5.5 mU/l) and a

low total thyroxine 55 nmol/l (normal range 60–180 nmol/l). Thyroid peroxidase

autoantibodies were raised, at a titre of 1:1106 (normal range <1:10); other

organâ€specific autoantibodies were not detected and full blood count and

electrolytes were normal. 50 mcg of levothyroxine was commenced soon after she

become unwell with nausea, vomiting and bloating, associated with watery

diarrhoea. She had a normal lactoseâ€containing diet.

Further investigations revealed a normal cortisol response to a

short synacthen test, excluding 's disease. An oesophagoâ€gastroduodenoscopy

and multiple duodenal biopsies were normal, with no evidence of villous

atrophy. IgA endomysial and antiâ€gliadin autoantibodies were not detected and

IgA was normal. Intestinal fluid and stool microscopy and culture were normal.

Neither amoebae nor giardiasis were detected, and a 3â€day faecal fat collection

was normal. Barium enema studies and sigmoidoscopy revealed no abnormalities.

Levothyroxine was discontinued, as symptoms were intolerable. Her

gastrointestinal symptoms disappeared and diarrhoea had completely resolved

after 24 h. Further reâ€challenge of levothyroxine at a dose of 25 mcg resulted

in a recurrence of symptoms. She was tried on a purified, speciallyâ€formulated

thyroxine product containing levothyroxine without any additives or inactive

ingredients as intolerance to the inactive ingredients was suspected.1

This she tolerated with no untoward effects and no gastrointestinal symptoms.

At followâ€up 4 months later, she was well without further symptoms, and

clinically and biochemically euthyroid.

Thyroxine is available in variety of preparations, the commonest

being levothyroxine. These contain in addition to sodium thyroxine, lactose,

magnesium stearate, povidine and colour additives. Our patient could not

tolerate even the smallest dose available, resulting in nausea and diarrhoea

symptoms, which disappeared after discontinuation and reoccurred after

reâ€challenging. Her symptoms did not recur on taking a purified thyroxine

preparation, suggesting intolerance to the inactive ingredients of standard

levothyroxine tablets. Thyroxine is absorbed in the small intestine, and

disorders such as coeliac disease and short bowel syndrome can result in

malabsorption and subâ€optimal treatment.2,,3

Our patient had a normal lactoseâ€containing diet, and had no evidence to

suggest malabsorption or lactose intolerance.

Drug intolerance is a reproducible adverse reaction to a specific

ingredient that is not psychologically based. Allergy is a form of intolerance

in which there is evidence that the response is caused by an immunological

reaction. Other mechanisms of intolerance include enzyme defects (e.g. lactase

deficiency), pharmacological effects (e.g. histamine release), toxic properties

(e.g. haemagglutinating lectins) and irritants (e.g. spices). Our case is rare

and has not been reported in the literature to the best of our knowledge,

despite hypothyroidism being a very common condition. Nonâ€compliance is the

commonest cause of failure to respond to levothyroxine treatment, and it is

possible some cases may be caused by thyroxine intolerance.

We suggest that with hypothyroid patients who are intolerant of

thyroxine, in addition to considering adrenal insuffiency and myocardial

ischaemia, the role of additives in the standard tablets should be considered,

particularly in patients with gastrointestinal symptoms. Purified forms of

thyroxine, although not easily available, should be considered as an

alternative therapy.

·

© Association of Physicians

References

1.

↵

dales Pharmacy, London.

2.

↵

Counsell CE, Taha A, Ruddell WS. Coeliac disease and autoimmune

thyroid disease. Gut1994; 35:844–6.

Abstract/FREE Full Text

3.

↵

Topliss DJ, JA, Volpe R. Increased requirement for

thyroid hormone after a jejunoileal bypass operation. Can Med Assoc J1980; 123:765–6.

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