A 40 years old man with a diagnosis of Adrenoleukodystrophy (ALD) was referred for evaluation of symptoms suggestive of hypogonadism. He had a past medical history of ALD associated adrenal insufficiency and osteoporosis. He took regular hydrocortisone and a trial medication, MD1003.
Following review, post clinic blood tests revealed a testosterone 24.5 nmol/l (7.631.4), LH 8.8 IU/l (1.78.6) and FSH 1.5 IU/l (1.512.4). Thyroid function tests had been reported urgently with an elevated FT4>100 pmol/l (1222), FT3 12.3 pmol/l (4.66.8) and a suppressed TSH 0.02 mIU/l. The patient was not clinically thyrotoxic, had no goitre and no opthalmopathy. Assay interference was suspected and so the sample was sent to the supra-regional assay service laboratory (Cambridge) to be analysed by DELFIA immunoassay. The results confirmed assay interference with a FT4 19.5 pmol/l (1019.8), FT3 6.8 pmol/l (3.56.5) and a normal TSH 1.23 mIU/l (0.355.0). The likely causative agent was the trial medication, MD1003. The MD1003 Biotin European AMN Trial is a study of ultra-high dose biotin in patients with ALD. Biotin interference, particularly with thyroid function testing, has been highlighted recently and may occur in samples analysed by Roche cobas immunoassays used in our institution. Typically, this may cause positive interference in competitive immunoassays (FT4 and FT3) and negative interference sandwich immunoassays (TSH).
Given biotin interference was likely to be an issue in all of our immunoassays, we turned our attention to his gonadotrophins axis. Analysis by a different immunoassay (Siemens Centaur) confirmed likely assay interference with a testosterone of 13.1 nmol/l, LH 30.7 IU/l (1.56.3) and FSH 13 IU/l (1.010.1). He is now being considered for testosterone replacement.
This case highlights i) The importance of detailed history and clinical assessment where laboratory tests are discordant with the clinical picture. ii) The need to recognised biotin interference in Roche cobas immunoassays, which if missed, can lead to unnecessary referrals; investigations; treatment or treatment delays. iii) Interference may affect multiple immunoassays, either raise or lower hormone levels and cause marked (thyroid function) or mild discrepancies (gonadotrophins).
01 Jan - 31 Dec 2017
Society for Endocrinology