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CASE REPORT
Year : 2020  |  Volume : 17  |  Issue : 3  |  Page : 146-148

Accidental levothyroxine ingestion in children: Review of four cases


1 Department of Endocrinology, Ramaiah Medical College and Hospital, Bengaluru, Karnataka, India
2 Department of Paeditrics, Ramaiah Medical College and Hospital, Bengaluru, Karnataka, India

Date of Submission28-Feb-2020
Date of Acceptance25-Jun-2020
Date of Web Publication20-Jan-2021

Correspondence Address:
Dr. Pramila Kalra
Department of Endocrinology, Ramaiah Medical College and Hospital, Bengaluru, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/trp.trp_9_20

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  Abstract 


Incidence of accidental levothyroxine ingestion in children has been increasing in recent times, mainly because of increasing prescriptions. We present four such cases, who presented to the pediatrics department in the past year. Four children aged 2–14 years presented to the emergency department with accidental consumption of levothyroxine tablets, total strength ranging from 1000 to 3000 μg. All were reported within half an hour to 8 h of consumption. Three of them were asymptomatic at presentation and one had one episode of vomiting. Gastric lavage was done and activated charcoal was given to all. Vitals were normal, except one had tachycardia for which the child received propranolol tablet for 1-week duration to control heart rate. Baseline free T4 was high and thyroid-stimulating hormone was normal in all. They were admitted for observation for 2–6 days and later followed on an outpatient basis. Ingestion of large doses of levothyroxine in children typically follows a benign course. Patients may be asymptomatic or have thyrotoxic symptoms and rarely significant complications, including seizures and arrhythmias. The severity of symptoms does not correlate with plasma levels of T4, and the onset of symptoms can be delayed for up to 6–11 days. Asymptomatic children can be monitored at home following gastrointestinal decontamination. In cases with severe symptoms, children should be monitored in the hospital for cardiac or neurological instability. Propranolol is used in the presence of features of toxicity. Levothyroxine is colorful and palatable that can be attractive to young children. Gastric lavage and activated charcoal is the mainstay of treatment in accidental levothyroxine ingestion in children.

Keywords: Levothyroxin poisoning, levothyroxin overdose, thyroxin overdose


How to cite this article:
Maddukuri HR, Kalra P, Karunakara B P, Venugopal P. Accidental levothyroxine ingestion in children: Review of four cases. Thyroid Res Pract 2020;17:146-8

How to cite this URL:
Maddukuri HR, Kalra P, Karunakara B P, Venugopal P. Accidental levothyroxine ingestion in children: Review of four cases. Thyroid Res Pract [serial online] 2020 [cited 2021 Jun 22];17:146-8. Available from: https://www.thetrp.net/text.asp?2020/17/3/146/307564




  Introduction Top


Acute ingestion of excess thyroid hormone preparations is frequently reported to poisoning control centers. The American Association of Poison Control Centres Annual Report 2014 documents, 9301 exposures to thyroid hormone preparations in United States of America. Of these, 4444 (47.8%) occurred in children younger than 6 years, 722 (7.8%) in persons aged 6–19 years and 3597 (38.7%) in persons aged older than 19 years[1] In the Netherlands 181 cases of levothyroxine intoxications in children younger than 12 years were reported in 2009. Usually, levothyroxine intoxication in children has a mild course in general.[2],[3] In some cases, serious events such as seizures, thyroid storm, and even coma may be caused by low dosages of levothyroxine.[4] In this article, we present four cases of levothyroxine ingestion in children, of which three were accidental, and one was a part of a suicide attempt [Table 1]. All the cases reported to the emergency department of our hospital within the first 8 h of ingestion with very few symptoms.
Table 1: Clinical details of all cases

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  Clinical History, Physical Examination, Laboratory Findings, and Management Top


Four children, mean age 5 years, presented to the emergency department with accidental consumption of levothyroxine tablets. Total dose ranged from 1500 to 3750 μg. All presented to the emergency unit within half an hour to 8 h of consumption. Three of them were asymptomatic at presentation, and one had one episode of vomiting. Baseline T4 was high and thyroid-stimulating hormone (TSH) was normal in all [Table 2].
Table 2: Laboratory findings of all cases

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Administration of activated charcoal and prophylactic administration of propranolol is recommended as the initial treatment. We treated our patients with activated charcoal to decontamination. Thereafter, we started with propranolol to prevent possible complications of the levothyroxine intoxication, such as tachycardia and hypertension in case 2. Other treatments such as propylthiouracil, steroids, iopanoic acid, cholestyramine, sodium idopate, and hemoperfusion lack evidence.[2],[3],[4],[5],[6] For the management of children at risk, monitoring of vital signs and laboratory data are most important. Reviewing the scarce literature and national and international databases (www.toxbase.org and Poisindex [Micromedex]), Patients should be closely monitored for the clinical course during 48–72 h postingestion in those children who have ingested >0.1 mg levothyroxine/kg, children with a short interval since ingestion, symptomatic presentation. Monitoring of vital signs until 14 d postingestion is recommended based on the elimination half-life of levothyroxine and the fact that 2 weeks are needed in this case to normalize levels of TSH, fT3, and fT4.

We believe that children who do not fulfill these criteria can be discharged after informing the parents/caregivers about possible (delayed onset of) symptoms and complications. As such, we think both high- and low-risk children with levothyroxine intoxication should watch for any adverse events.

Follow-up

All patients were followed up on the OPD basis for the next month.


  Discussion Top


Ingestion of large doses of levothyroxine in children generally follows a benign course. Patients may be asymptomatic or have thyrotoxic symptoms, including mild fever, tachycardia, hypertension, loose stools, and irritability.[2] Seizures may be one of the manifestations in some cases.[3] The severity of symptoms does not correlate with plasma levels of T4, and the onset of symptoms may be delayed for up to 6–11 days.[4] Asymptomatic children can be monitored at home following gastrointestinal decontamination. In cases with severe symptoms, children should be observed in the hospital for cardiac or neurological instability. Treatment for acute levothyroxine ingestion-include gastrointestinal decontamination, and administration of activated charcoal, that can decrease systemic absorption if instituted within 1-h postingestion.[7] The same protocol was followed in our cases. Our case series also followed a benign course with doses of levothyroxine ranging from 1500 to 3750 μg. None of the children had any serious adverse event.

Pharmacokinetics of thyroid hormones

Levothyroxine is thyroxine (T4) analog, which is the predominant circulating form of thyroid hormone. In the peripheral tissues, T4 is partially converted to liothyronine (T3), a more biologically active thyroid hormone. Since T4 is pharmacologically inactive, T3 is the substance responsible for the development of toxic symptoms. It is clear that if any symptoms appear, they are delayed in onset as levothyroxine must achieve peripheral conversion to T3.

Pharmacological data also show that Tmax of levothyroxine is reached at 5–6 h after oral intake. Elimination half-life (T1/2) is 7 d for T4 and 0.8 d for T3. Exogenously administered thyroid hormone indirectly suppresses the thyroid gland activity, decreases the TSH level.

Lewander et al.[2] specifically studied the pharmacokinetics of T4 and T3 in acute T4 intoxication in 7 patients. Their findings indicate a mean T1/2 for T4 of 2.8 d, which is shorter than the T1/2 observed in physiologic concentrations (7 d in children) and a T1/2 for T3 of 6 d, which is almost five times longer than in physiologic concentrations. Furthermore, the peak concentration of T3 is reached at >24 h after the ingestion. This favors the conclusion that delay in onset of symptoms and duration of toxicity is due to the conversion from levothyroxine to T3 and prolonged elimination time of T3 in acute overdose. In our patient, the peak concentration of T3 was on day 2, with T3 reaching normal values after 14 days. This explains the occurrence of a delay in symptoms after levothyroxine overdose.

The usual dose of levothyroxine in hypothyroid pediatric patients is 2–6 μg/kg/d in one dose. Our patients ingested 50 μg/kg to 200 μg/kg, 25–35 times the standard dose, and they were all euthyroid. All patients T4, T3 blood levels were increased at the 2nd day. Despite a high dose of ingested levothyroxine and very high thyroid hormone levels, patients showed mild clinical symptoms, limited to a tachycardia.

Children seem to be more tolerant of massive overdoses of levothyroxine when compared with adults but can develop moderate-to-severe toxicity following acute levothyroxine ingestions. It is suggested that higher production of reverse T3 (rT3) is responsible for the decreased risk of a thyroid storm after a levothyroxine overdose. rT3 is an isomere T3, which is also derived from T4 deionization. It binds to the thyroid hormone receptors and thereby blocks the action of T3.[7] The activated charcoal might have protected by binding levothyroxine to cations and thus decreasing absorption.[8]

Comparison of the clinical course with previously reported cases

The majority of previously reported studies have described mild symptoms in acute levothyroxine overdose, despite high amounts of levothyroxine taken (dosages up to 18 mg levothyroxine).[2],[3],[4],[5] Symptoms include tachycardia, fever, irritability, hyperactivity, diarrhea, abdominal pain, and hypertension. Tunget et al.[8] even suggested that acute ingestions of levothyroxine <5 mg T4 equivalent require no decontamination or aggressive management since only mild symptoms occur sporadically in this range. However, Tsutaoka et al.[4] reported a case of a tonic-clonic seizure in a 3.5-year-old boy on the 3rd day after ingestion of a maximum of 3.6 mg levothyroxine (about 0.22 mg/kg). Rarely, massive thyroid hormone overdose has led to grand mal seizures,[4] thyroid storm, and even coma,[6] particularly in adults. Overall, previous reports suggest that there is no dose-response relationship between the occurrence or severity of symptoms and the amount levothyroxine ingested. Even patients with a relatively low dose of levothyroxine potentially develop seizures, and it is not possible to predict which patients will become symptomatic.


  Conclusions Top


Levothyroxine tablet is colorful and palatable that can be attractive to young children. Gastric lavage and activated charcoal are the mainstays of treatment in accidental levothyroxine ingestion in children.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Mowry JB, Spyker DA, Brooks DE, McMillan N, Schauben JL. 2014 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 32nd Annual Report. Clin Toxicol (Phila) 2015;53:962-1147.  Back to cited text no. 1
    
2.
Lewander WJ, Lacouture PG, Silva JE, Lovejoy FH. Acute thyroxine ingestion in pediatric patients. Pediatrics 1989;84:262-5.  Back to cited text no. 2
    
3.
Willgerodt H, Keller E, Sorger D, Hoepffner W. Acute ingestion of thyroxine and triiodothyronine in young children. Eur J Pediatr 2003;162:639-41.  Back to cited text no. 3
    
4.
Tsutaoka BT, Kim S, Santucci S. Seizure in a child after an acute ingestion of levothyroxine. Pediatr Emerg Care 2005;21:857-9.  Back to cited text no. 4
    
5.
Lehrner LM, Weir MR. Acute ingestions of thyroid hormones. Pediatrics 1984;73:313-7.  Back to cited text no. 5
    
6.
Kreisner E, Lutzky M, Gross JL. Charcoal hemoperfusion in the treatment of levothyroxine intoxication. Thyroid 2010;20:209-12.  Back to cited text no. 6
    
7.
Shilo L, Kovatz S, Hadari R, Weiss E, Nabriski D, Shenkman L. Massive thyroid hormone overdose: Kinetics, clinical manifestations and management. Isr Med Assoc J 2002;4:298-9.  Back to cited text no. 7
    
8.
Tunget CL, Clark RF, Turchen SG, Manoguerra AS. Raising the decontamination level for thyroid hormone ingestions. Am J Emerg Med 1995;13:9-13.  Back to cited text no. 8
    



 
 
    Tables

  [Table 1], [Table 2]



 

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