Falsely raised TSH levels due to human anti-mouse antibody interfering with thyrotropin assay

Abstract

The case of a 39-year-old woman who was referred for weight gain and amenorrhoea is reported. Laboratory evaluation showed high levels of thyroid-stimulating hormone (TSH). The patient was started on increasing doses of levothyroxine for subclinical hypothyroidism. TSH remained persistently raised and the patient became thyrotoxic. Evaluation at another laboratory showed normal levels of TSH, raising the possibility of interfering substances. TSH levels were normalised with the addition of mouse serum to the patient's sample, confirming the presence of human anti-mouse antibodies as the interfering substance in the TSH assay. S ubclinical hypothyroidism refers to mildly increased serum thyroid-stimulating hormone levels in the presence of normal free thyroxine (T4) and triiodothyronine (T3).1 In the US National Health and Examination Survey, 2 4.3% of 16 533 people had subclinical hypothyroidism. Progression to overt hypothyroidism is reported to vary from 3% to 20%, the risks being greater in those patients with goitre or thyroid antibodies.3 Although subclinical hypothyroidism is often asymptomatic, potential risks include progression to overt hypothyroidism, cardiovascular effects, hyperlipidaemia and neuropsychiatric effects. Treatment of subclinical hypothyroidism remains controversial. It is suggested that treatment of subclinical hypothyroidism will reduce cardiovascular risk factors, improve lipid profile and minimise neurobehavioural abnormalities. 4 It is recommended that patients with TSH .10 or TSH level between 5 and 10 in conjunction with goitre or positive anti-thyroid peroxidase should be treated. 1 We present a patient treated for hypothyroidism, it was later found that human anti-mouse monoclonal antibody (HAMA) had interfered with the TSH assay.A 39-year-old Hispanic woman was referred to the Division of Endocrinology, Metropolitan Hospital Center, New York, for evaluation of weight gain, increased appetite and amenorrhoea for 5 months. She denied any blurring of vision, headache, hoarseness of voice or intolerance to cold. Medical history showed hypertension, depression and schizophrenia treated for several years, and excision of an ovarian cyst. Her drugs included fosinopril, imipramine, olanzapine, haloperidol, benzatropine, fluphenazine, paroxetine and hydroxyzine. Family history was notable for breast cancer in her mother. Examination was unremarkable except for a weight of 196 pounds (89 kg). Initial laboratory evaluation showed a TSH concentration of 13.86 (range 0.35-5.50) mU/ l, a total T4 concentration of 8.4 (range 3-13) mg/dl and a T3 concentration of 1.03 (range 0.6-1.18) ng/ml. Anti-microsomal antibody titre was normal (,2 U/ml). On the basis of these results, a diagnosis of subclinical hypothyroidism was made and the patient was started on levothyroxine. She was followed up every 4-6 weeks and the thyroid function was monitored. During this period, she was given increasing doses of levothyroxine without adequate suppression of TSH. Prolactin level was raised at 135 ng/ml (range ...

Diagnosis and management of treatment-refractory hypothyroidism: an expert consensus report

“…In addition, a normal TSH should not always be considered a reliable indicator for euthyreosis, especially in patients presenting with symptoms consistent with thyroid deficiency [ 40 ]. Several conditions such as age, pregnancy, and the presence of thyroid hormone antibodies may complicate the interpretation of TSH values [ 6 , 8 , 18 ]. In spite of these limitations, TSH remains the best means of assessing thyroid function in over 80% of patients.…”

Utility of a canine TSH assay for diagnosis and monitoring of feline hyperthyroidism

“…This finding was later confirmed by other authors [8] [16] and is corroborated by the current study. Possible reasons for this conflicting combination include interfering antibodies falsely raising TSH concentrations (as has been described in human patients [21] [22]), hyperthyroidism not severe or chronic enough to completely suppress pituitary TSH secretion [2], laboratory error [17], and tumors of the thyrotrophs that have ▶Fig. 2 Boxplot of TSH concentrations (ng/mL) in the respective groups depicted as median, interquartile range and full range.…”

“…This finding was later confirmed by other authors 8 , 16 and is corroborated by the current study. Possible reasons for this conflicting combination include interfering antibodies falsely raising TSH concentrations (as has been described in human patients 21 , 22 ), hyperthyroidism not severe or chronic enough to completely suppress pituitary TSH secretion 2 , laboratory error 17 , and tumors of the thyrotrophs that have so far only been described in humans 23 . Interfering heterophile (poorly defined antibodies that cause interference by non-competitive binding mostly to the Fc region of assay antibodies) 24 or anti-animal antibodies (antibodies binding to proteins and antibodies of specific species) are the most likely explanation in 2 cats of this study, as elevated TSH was verified by repeated analyses on separate occasions and T4 was very high.…”

Heterophilic Interference of Rheumatoid Factor in TSH Immunometric Assay: A Cross-Sectional Observational Study

“…Immunometric assays are particularly more vulnerable to such interference. There have been numerous case reports of heterophilic interference in thyroid function tests,[ 2 3 4 5 6 7 8 9 10 11 12 13 14 15 ] with Thyroid Stimulating Hormone (TSH) as the most common analyte affected. Although currently, manufacturers routinely add blocking agents to their assay formulations, not all heterophile interference can be blocked as suggested by some case reports.…”