Thyroxine (T4) Metabolism in an Athyreotic Patient Who Had Taken a Large Amount of T4 at One Time.

Abstract

Abstract. As we had an opportunity to take blood samples from a totally thyroidectomized patient who had attempted suicide by taking 2,000 tg of Levothyroxine (L-T4), the serum levels of thyroid hormones were sequentially measured to investigate the metabolism of circulating thyroid hormones in an athyreotic human. The serum concentrations of most thyroid hormones reached a peak on the second day, but the serum T3 level showed a peak one day later. The maximum concentrations of T4 (315 µg/l), FT4 (48.8 ng/l) and rT3 (0.80 µg/l) were very high, while the peak T3 level (1.92 jug/l) did not exceed the upper limit of the normal range. The serum T4 and rT3 levels returned to their normal range 13-17 days after the suicide attempt. The TSH level was suppressed rapidly and reached its nadir (0.044 mU/I) on the 6th day. During this period, the T112 and MCR of serum T4 were 10.4 days and 0.64 1/day, respectively, which values were almost equivalent to those observed during 15 days after discontinuation of the maintenance L-T4 therapy. In summary, the oral intake of a large amount of L-T4 at one time does not induce a proportional increase in the T3 level in an athyreotic person. The MCR of serum T4 is decreased and the T112 of serum T4 is prolonged, probably due to the lack of intrathyroidal deiodination. These findings support the conclusion that the D1 activity in the thyroid is one of the major determinants in the metabolic clearance of serum T4. Wenzel et al. [5] reported that the maximum concentration of serum T3 after oral intake of an excessive dose (3000 ,ug) of Levothyroxine (L-T4) at one time did not exceed the upper limit of normal range in normal subjects.Nevertheless, the contribution of the thyroid to systemic T4 metabolism is not clear and the precise consequence has not been well documented in reference to the high T3 level in patients with hyperthyroid Graves' disease. In order to evaluate the effect of the thyroid on the metabolism of circulating thyroid hormones, we examined the metabolism of thyroid hormones in an athyreotic patient who had taken an excessive dose of L-T4 at one time.

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

“…Ishihara T et al reported an athyreotic patient having taken 2 mg of levothyroxine at one time, with serum concentrations of T4, FT4 and reverse T3 (rT3) that reached a peak on the second day, while the serum T3 level peaked one day later [7]. FT3 level in the present case also peaked later,…”

“…Levothyroxine is a commonly prescribed medication for hypothyroidism, and many cases of acute ingestion of excess levothyroxine have been reported, such as young children ingesting tablets by accident [3], adults attempting to commit suicide [5] [6] [7]. Edmundo K et al described an adult case of accidental intoxication with 50 mg/day instead of 50 µg/day of levothyroxine over 9 days, due to pharmacist error in the preparation of the capsules, leading to an FT4 level of 74.1 ng/dL (955.90 pmol/L) measured by an automated chemiluminescence system.…”

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

“…Ishihara T et al reported an athyreotic patient having taken 2 mg of levothyroxine at one time, with serum concentrations of T4, FT4 and reverse T3 (rT3) that reached a peak on the second day, while the serum T3 level peaked one day later [7]. FT3 level in the present case also peaked later, indicating that the toxic dose of levothyroxine partly changed to T3 during the two days.…”

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

“…Levothyroxine is a commonly prescribed medication for hypothyroidism, and many cases of acute ingestion of excess levothyroxine have been reported, such as young children ingesting tablets by accident [3], adults attempting to commit suicide [4][5][6][7]. Edmundo K et al described an adult case of accidental intoxication with 50 mg/day instead of 50 μg/day of levothyroxine over 9 days, due to pharmacist error in the preparation of the capsules.…”

“…The patient presented with a stuporous mental state, atrial fibrillation and acute respiratory failure, but treatment with charcoal hemoperfusion was successful [8]. In most of the cases mentioned above, the patients was not in critical condition in spite of the excessive intake of levothyroxine, ranging from 2 mg to 720 mg. FT4 levels in those cases ranged from 38.7 pmol/L to > 167 pmol/L [3][4][5][6][7]. These reports suggested that clinical course severity did not always depend on the amount of levothyroxine ingested or on the patient's free thyroid hormone level, though pre-hospital deaths were not included.…”