Time-dependent changes in FT4 and FT3 levels measured using mass spectrometry after an acute ingestion of excess levothyroxine in a case with hypothyroidism.

Congenital hypothyroidism Excess levothyroxine Free thyroid hormone Immunoassay Mass spectrometry Thyrotoxicosis

Journal

Thyroid research
ISSN: 1756-6614
Titre abrégé: Thyroid Res
Pays: England
ID NLM: 101469037

Informations de publication

Date de publication:
2020
Historique:
received: 04 02 2020
accepted: 13 04 2020
entrez: 8 5 2020
pubmed: 8 5 2020
medline: 8 5 2020
Statut: epublish

Résumé

Thyrotoxicosis is common disorder among endocrine dysfunctions. It is not rare that the free thyroid hormone level exceeds the measurement range of immunoassay. Such extreme high concentration of free thyroid hormone is generally considered to be impossible to measure correctly because of changes in the balance between free hormones and binding proteins by dilution of serum. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), however, higher concentrations are able to be determined. We present a case of a 21-year-old female with congenital hypothyroidism who had taken a total of 5 mg levothyroxine over three consecutive days following discontinuance of the medication for a month. Immunoassay performed 3 hours after the last ingestion showed that the patient's free thyroxine (FT4) was over 100 pmol/L and her free triiodothyronine (FT3) was 24.5 pmol/L. With a temporary cessation of levothyroxine, the patient was kept for observation without any other medication. Two days after the last ingestion, FT4 was still over 100 pmol/L and FT3 was increased to 28.8 pmol/L. After an additional 4 days, both FT4 and FT3 levels decreased. Through this period, no thyrotoxic symptom or physical sign had appeared. We also measured FT4 and FT3 levels in her cryopreserved serum by ultrafiltration LC-MS/MS. Her FT4 level measured by ultrafiltration LC-MS/MS on the visiting day and 2 days later were 160.0 and 135.5 pmol/L, respectively, indicating that the toxic dose of levothyroxine was partly changed to T3 during the 2 days. The FT3/FT4 ratios were revealed to be low, accounting for the patient's benign clinical course despite temporal toxic exposure to levothyroxine. It is implied that prior discontinuation of supplementary levothyroxine increases potential vacant binding sites for thyroid hormone as a buffer to prevent toxic T3 effect. It was helpful to clarify the time dependent changes in free thyroid hormone levels by ultrafiltration LC-MS/MS in discussing the clinical course in this case. Though mass spectrometry has a disadvantage in speed for routine laboratory use, its accurate measurement, particularly of levels exceeding the measurable range of the immunoassay, provides valuable information for more appropriate management of extreme thyrotoxicosis.

Sections du résumé

BACKGROUND BACKGROUND
Thyrotoxicosis is common disorder among endocrine dysfunctions. It is not rare that the free thyroid hormone level exceeds the measurement range of immunoassay. Such extreme high concentration of free thyroid hormone is generally considered to be impossible to measure correctly because of changes in the balance between free hormones and binding proteins by dilution of serum. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), however, higher concentrations are able to be determined.
CASE PRESENTATION METHODS
We present a case of a 21-year-old female with congenital hypothyroidism who had taken a total of 5 mg levothyroxine over three consecutive days following discontinuance of the medication for a month. Immunoassay performed 3 hours after the last ingestion showed that the patient's free thyroxine (FT4) was over 100 pmol/L and her free triiodothyronine (FT3) was 24.5 pmol/L. With a temporary cessation of levothyroxine, the patient was kept for observation without any other medication. Two days after the last ingestion, FT4 was still over 100 pmol/L and FT3 was increased to 28.8 pmol/L. After an additional 4 days, both FT4 and FT3 levels decreased. Through this period, no thyrotoxic symptom or physical sign had appeared. We also measured FT4 and FT3 levels in her cryopreserved serum by ultrafiltration LC-MS/MS. Her FT4 level measured by ultrafiltration LC-MS/MS on the visiting day and 2 days later were 160.0 and 135.5 pmol/L, respectively, indicating that the toxic dose of levothyroxine was partly changed to T3 during the 2 days. The FT3/FT4 ratios were revealed to be low, accounting for the patient's benign clinical course despite temporal toxic exposure to levothyroxine. It is implied that prior discontinuation of supplementary levothyroxine increases potential vacant binding sites for thyroid hormone as a buffer to prevent toxic T3 effect.
CONCLUSION CONCLUSIONS
It was helpful to clarify the time dependent changes in free thyroid hormone levels by ultrafiltration LC-MS/MS in discussing the clinical course in this case. Though mass spectrometry has a disadvantage in speed for routine laboratory use, its accurate measurement, particularly of levels exceeding the measurable range of the immunoassay, provides valuable information for more appropriate management of extreme thyrotoxicosis.

Identifiants

pubmed: 32377234
doi: 10.1186/s13044-020-00078-7
pii: 78
pmc: PMC7193347
doi:

Types de publication

Case Reports

Langues

eng

Pagination

4

Informations de copyright

© The Author(s) 2020.

Déclaration de conflit d'intérêts

Competing interestsThe authors declare that they have no competing interests.

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Auteurs

Yuko Ito (Y)

1Department of Laboratory Medicine, School of Medicine, Fukushima Medical University, Hikarigaoka, Fukushima, Fukushima 960-1295 Japan.
2Thyroid and Endocrinology Center, Fukushima Medical University Hospital, Fukushima, 960-1295 Japan.

Satoru Suzuki (S)

2Thyroid and Endocrinology Center, Fukushima Medical University Hospital, Fukushima, 960-1295 Japan.

Yoshiko Matsumoto (Y)

2Thyroid and Endocrinology Center, Fukushima Medical University Hospital, Fukushima, 960-1295 Japan.
3Department of Thyroid and Endocrinology, School of Medicine, Fukushima Medical University, Fukushima, 960-1295 Japan.

Chiyo Ohkouchi (C)

2Thyroid and Endocrinology Center, Fukushima Medical University Hospital, Fukushima, 960-1295 Japan.
3Department of Thyroid and Endocrinology, School of Medicine, Fukushima Medical University, Fukushima, 960-1295 Japan.

Satoshi Suzuki (S)

2Thyroid and Endocrinology Center, Fukushima Medical University Hospital, Fukushima, 960-1295 Japan.
3Department of Thyroid and Endocrinology, School of Medicine, Fukushima Medical University, Fukushima, 960-1295 Japan.

Manabu Iwadate (M)

2Thyroid and Endocrinology Center, Fukushima Medical University Hospital, Fukushima, 960-1295 Japan.
3Department of Thyroid and Endocrinology, School of Medicine, Fukushima Medical University, Fukushima, 960-1295 Japan.

Sanae Midorikawa (S)

2Thyroid and Endocrinology Center, Fukushima Medical University Hospital, Fukushima, 960-1295 Japan.
4Department of Radiation Health Management, School of Medicine, Fukushima Medical University, Fukushima, 960-1295 Japan.

Susumu Yokoya (S)

2Thyroid and Endocrinology Center, Fukushima Medical University Hospital, Fukushima, 960-1295 Japan.

Shinichi Suzuki (S)

2Thyroid and Endocrinology Center, Fukushima Medical University Hospital, Fukushima, 960-1295 Japan.
3Department of Thyroid and Endocrinology, School of Medicine, Fukushima Medical University, Fukushima, 960-1295 Japan.

Hiroki Shimura (H)

1Department of Laboratory Medicine, School of Medicine, Fukushima Medical University, Hikarigaoka, Fukushima, Fukushima 960-1295 Japan.
2Thyroid and Endocrinology Center, Fukushima Medical University Hospital, Fukushima, 960-1295 Japan.

Classifications MeSH