Q J Med 2002; 95: 125-126
© 2002 Association of Physicians
Correspondence |
Diarrhoea soon after levothyroxine replacement therapy
Department of Diabetes & Endocrinology, Arrowe Park Hospital, Wirral
Sir,
A 57-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 thyroid-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 organ-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 lactose-containing diet.
Further investigations revealed a normal cortisol response to a short synacthen test, excluding Addison's disease. An oesophago-gastroduodenoscopy and multiple duodenal biopsies were normal, with no evidence of villous atrophy. IgA endomysial and anti-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 3-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 re-challenge of levothyroxine at a dose of 25 mcg resulted in a recurrence of symptoms. She was tried on a purified, specially-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 follow-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 re-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 sub-optimal treatment.2,3 Our patient had a normal lactose-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. Non-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.
References
1. Martindales Pharmacy, London.
2.
Counsell CE, Taha A, Ruddell WS. Coeliac disease and autoimmune thyroid disease. Gut1994; 35:844–6.
3. Topliss DJ, Wright JA, Volpe R. Increased requirement for thyroid hormone after a jejunoileal bypass operation. Can Med Assoc J1980; 123:765–6.[Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||