Clinical review

Deterioration of symptoms after start of thyroid hormone replacement

Jonathan Stephen Murray, medical student ^a, Rubaraj Jayarajasingh, medical student ^a, Petros Perros, consultant endocrinologist ^b. 

^a Medical School, Newcastle upon Tyne NE2 4HH, ^b Freeman Hospital, High Heaton, Newcastle upon Tyne NE7 7DN

Correspondence to: P Perros Petros.Perros{at}ncl.ac.uk

Doctors often arrange thyroid function tests for patients presenting with general symptoms of tiredness, and in some cases hypothyroidism is subsequently diagnosed. Lack of clinical response to thyroxine replacement is not uncommon in cases of "subclinical hypothyroidism." A deterioration of symptoms, however, may signify a potentially life threatening alternative diagnosis.

	Case reports

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Case 1
A 26 year old woman with type 1 diabetes, presented with a five week history of lethargy, nausea, feeling lightheaded on standing, occasional vomiting, and four unexplained severe hypoglycaemic episodes. The hypoglycaemic episodes occurred unexpectedly (no change in dietary intake, amount of physical exertion, amount of alcohol ingestion, or dose or timing of insulin therapy).

Case 2
A 51 year old woman presented with a two month history of cold intolerance, weight gain, and constipation. Hypothyroidism was suspected and was confirmed biochemically by her general practitioner (results unavailable), and the patient was started on thyroxine 50 µg daily. A few weeks later the patient's general practitioner advised her to increase her thyroxine dose to 100 µg daily as the results of her thyroid function tests continued to be abnormal (serum concentration of thyroid stimulating hormone 6.59 mU/l, free thyroxine 16 pmol/l).

	Discussion

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Hypothyroidism is a common disease with a lifelong risk in women that approaches 10%. ^{1 2} The treatment of hypothyroidism is usually simple, and referral to secondary care is unnecessary. ^{3 4} Patients with hypothyroidism may have other autoimmune diseases such as type 1 diabetes, Addison's disease, or pernicious anaemia.⁵ Addison's disease is rarer than hypothyroidism, with an estimated prevalence of 60 cases per million population,⁵ but as many as 25% of patients with Addison's disease have hypothyroidism.⁶ Combined thyroid and adrenal insufficiency may also result from pituitary failure, though in such cases a low serum thyroxine concentration in association with a normal or low serum concentration of thyroid stimulating hormone should alert the clinician to the underlying diagnosis. The coexistence of thyroid and adrenal insufficiency therefore is greater than may be expected from the individual prevalences of these diseases. Furthermore, raised serum concentrations of thyroid stimulating hormone in the absence of primary thyroid failure can be a feature of adrenal insufficiency⁷ and may resolve after glucocorticoid replacement.⁸ Several factors can lead to misdiagnosis of hypothyroidism in patients with Addison's disease: symptoms of both conditions may be similar and non-specific; skin pigmentation in Addison's disease may not be recognised by the patient or relatives because of its insidious development, and may even be absent⁹; hypothyroidism is common, whereas Addison's disease is rare; thyroid function tests are easily accessible, cheap, and easy to interpret. The biochemical diagnosis of Addison's disease usually requires more sophisticated tests more appropriate in a secondary care setting; the serum concentration of thyroid stimulating hormone is often raised in adrenal failure.

It is both unrealistic and unnecessary to screen every patient with a raised serum concentration of thyroid stimulating hormone for Addison's disease. In our experience, however, most patients presenting in this manner have additional clinical features that should alert the clinician to this possibility. They include skin and mucosal pigmentation, postural hypotension, weight loss, and hyperkalaemia. Failure to reach a correct diagnosis in patients with a raised serum concentration of thyroid stimulating hormone who have Addison's disease (even in patients with only borderline adrenal failure, as in case 2) can lead to an adrenal crisis if thyroxine is introduced before glucocorticoid replacement.¹⁰ It is imperative that Addison's disease be excluded when a patient's clinical state deteriorates shortly after the introduction of thyroxine.

	Acknowledgments

   Contributors: JSM and RJ collated the clinical data, reviewed the literature, and helped to write the manuscript. PP verified the clinical data, helped to write the manuscript, and is the guarantor for the article.

	Footnotes

Funding: None.

Competing interests: None declared.

	References

Top Case reports Discussion References

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9.	Barnett AH, Espiner EA, Donald RA. Patients presenting with Addison's disease need not be pigmented. Postgrad Med J 1982; 58: 690[Abstract].
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(Accepted 25 May 2001)