Clinical insights into levothyroxine overdose: A systematic review

Table 1 Baseline demographics and clinical characteristics of 95 patients with levothyroxine toxicity from published case reports, series, and more extensive studies with individualizable data, n (%)/median (25^th-75^th percentiles)

Characteristic	n	Results
Age (years)	87	20 (3.5-42)
Gender	62
Female		41 (66.13)
Male		21 (33.87)
Comorbidities	95
Psychiatric disorder		9 (9.47)
Diabetes mellitus		4 (4.21)
Chronic kidney disease		3 (3.16)
Heart failure		2 (2.11)
COPD/asthma		1 (1.05)
Highest heart rate (beats/minute)	47	110 (89-128)
Highest systolic blood pressure (mm Hg)	41	115 (100-130)
Highest diastolic blood pressure (mm Hg)	40	70 (61.5-80)
Lowest potassium level (mmol/L)	7	3.6 (2.4-4.3)
Highest temperature (°C)	29	36.7 (36.4-37)
Highest creatinine (mmol/L)	16	0.039 (0.026-0.057)
Cumulative amount of levothyroxine (μg)	54	4250 (1250-10000)
Time from overdose to presentation (hours)	48	4.5 (1.5-24)

COPD: Chronic obstructive pulmonary disease.

Table 2 Symptoms and complications in 95 patients with levothyroxine toxicity from published case reports and series¹

Variable	Frequency (%)
Tachycardia	37 (38.95)
Confusion	22 (23.16)
Fever	18 (18.95)
Tremors	13 (13.68)
Palpitations	12 (12.63)
Diarrhea	10 (10.53)
Vomiting	8 (8.42)
Heat intolerance	7 (7.37)
Sweating	6 (6.32)
Shortness of breath	6 (6.32)
Atrial fibrillation	5 (5.26)
Dizziness	4 (18.18)
Weight loss	3 (3.16)
Periodic paralysis	3 (3.16)
Bradycardia	2 (2.11)
Heart failure	2 (2.11)
Ophthalmopathy	1 (1.05)
In-hospital mortality	1 (1.05)

¹Some patients experienced multiple symptoms or complications; therefore, the total percentage exceeds 100%.

Table 3 Comparative analysis of patient characteristics and clinical outcomes based on levothyroxine use for non-suicidal vs intentional suicidal purposes, n (%)/median (25^th-75^th percentiles)/mean ± SD¹

Characteristic/outcome	Not for suicide (n = 47)	Intentional for suicide (n = 46)	P value
Age (years)	3.5 (1.5-18)	35.5 (19-49)	< 0.001
Highest heart rate (beats/minute)	119 (100-140)	100 (85-120)	0.02
Highest systolic BP (mm Hg)	110 (95-123)	120 (110-132)	0.06
Highest diastolic BP (mm Hg)	66.39 ± 11.74	78.35 ± 12.05	0.003
Highest AST/SGOT (U/L)	35.5 (31-40)	22 (17.5-47.5)	0.05
Highest ALT/SGPT (U/L)	18 (13-24)	13 (11-19)	0.25
Cumulative levothyroxine dose (μg)	4054 (1000-14000)	4250 (1485-9700)	0.802
Treatment
Activated charcoal	15 (31.91)	12 (26.09)	0.53
Gastric lavage	4 (8.51)	1 (2.17)	0.36
Cholestyramine	1 (2.13)	3 (6.52)	0.36
Steroids	11 (23.4)	6 (13.04)	0.19
Beta blockers	20 (42.55)	11 (23.91)	0.057
Methimazole	2 (4.26)	1 (2.17)	1
Propylthiouracil	3 (6.38)	3 (6.52)	1
Plasmapheresis	7 (14.89)	0
Intubation	2 (4.26)	0
In hospital mortality	1 (2.13)	0

¹Some patients received more than one treatment, resulting in a total treatment count exceeding the total number of patients in the respective groups.

AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; SGOT: Serum glutamic-oxaloacetic transaminase; SGPT: Serum glutamic-pyruvic transaminase; BP: Blood pressure.

Table 4 Summary of clinical characteristics, treatment strategies, and outcomes in larger-scale studies of levothyroxine toxicity

Ref.	n	Age group	Key presentations	Reason for ingestion	LTX dose ingested	Treatment and complications
Litovitz et al[35]	78	0-12 years (0-5: 75; 5-12: 3)	74 Asymptomatic (94.9%), 3 fever, 1 vomiting, 1 diarrhea	Not specified	0.5 mg or less: 35 patients; 0.6-3.0 mg: 27 patients; > 3.0 mg: 6 patients	75 (96.1%) managed at home; 26 (33.3%) received no treatment; 38 (48.7%) received ipecac; 3 patients were hospitalized, 1 required propranolol treatment (2.5 mg every 6 hours)
Binimelis et al[4]	6	46-74 years	6 fever, tremors, heat intolerance, tachycardia	Unintentional	70-1200 mg ingested over 2-12 days	All patients received propranolol (120-140 mg/day) and hydrocortisone (400 mg/day). Patients 4-6 received propylthiouracil (400-1200 mg/day) and plasmapheresis. All patients developed neurological complications (e.g., coma, hemiparesis, aphasia). Patients 1-2 had left ventricular failure; others had rhythm disturbances. 1 patient died
Seidel et al[40]	54	< 28 days	42 Asymptomatic (77.8%). 1 tachypnea, 1 weight loss, 3 diarrhea, 6 restlessness	Not specified	< 30 µg/kg: 36 patients (87% asymptomatic); 30-50 µg/kg: 14 patients (79% asymptomatic); 50-60 µg/kg: 4 patients (75% asymptomatic)	Gastric lavage, Beta-blockers
Kandasamy et al[26]	5	Not specified	3 asymptomatic (60%). 2 hypertension with transient ECG changes	Unintentional	Maximum dose: 500 μg	No active treatment
Nygaard et al[41]	181	1-14 years	153 asymptomatic (84.5%)	Suicide: 44 (24.3%); unintentional: 134 (74.0%)	300-18000 μg	Not available
Roth et al[39]	11189	0-5 years: 6668 (59.6%); > 5 years: 4521 (40.4%)	112 vomiting (1.0%), 78 restlessness (0.7%), 123 tachycardia (1.1%)	10742 (96.0%) unintentional	Not specified	Activated charcoal in 392 patients (3.5%); gastric decontamination: Ipecac-induced emesis followed by activated charcoal administration in 134 patients (1.2%)

LTX: Levothyroxine; ECG: Electrocardiogram.