Clinical Review Lesson of the week

Deterioration of symptoms after start of thyroid hormone replacement

BMJ 2001; 323 doi: (Published 11 August 2001) Cite this as: BMJ 2001;323:332
  1. Jonathan Stephen Murray, medical studenta,
  2. Rubaraj Jayarajasingh, medical studenta,
  3. Petros Perros (, consultant endocrinologistb
  1. a Medical School, Newcastle upon Tyne NE2 4HH
  2. b Freeman Hospital, High Heaton, Newcastle upon Tyne NE7 7DN
  1. Correspondence to: P Perros
  • Accepted 25 May 2001

Suspect Addison's disease if a patient's symptoms worsen after thyroxine is given for suspected hypothyroidism

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

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).

Thyroid function tests showed a serum concentration of thyroid stimulating hormone of 37.30 mU/l (reference range 0.5-5.7 mU/l) and free thyroxine 12.7 pmol/l (9-22 pmol/l). The patient was started on 25 µg thyroxine daily. This resulted in an immediate exacerbation of symptoms, which prompted a referral to an endocrinologist. On examination she was pigmented and had orthostatic hypotension (92/50 mm Hg supine, 86/60 mm Hg standing). She was hyponatraemic (serum sodium 121 mmol/l) and hyperkalaemic (serum potassium 5.5 mmol/l). Basal serum cortisol was undetectable (<20 nmol/l) and failed to respond to …

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