Pediatric TRIAC case series

19 evidence topics · 1 source

Objective

Stated objective

“The objective of this study was to assess the clinical, imaging, biochemical, and genetic characteristics of patients with MCT8 deficiency treated with TRIAC, the doses used, and the response to treatment.” (opens the source at this quote in a new tab)

Location and study date

Institution and enrollment period

Characteristic	Value
Institution	“Hospital de Pediatría S.A.M.I.C. Prof. Dr. Juan P. Garrahan, City of Buenos Aires, Argentina”

“During the period from January 2019 to November 2022, 4 patients from 4 different families were diagnosed with MCT8 deficiency and treated with triac at Hospital J. P. Garrahan.” (opens the source at this quote in a new tab)

Study design

Single-center case series

“Here we report a case series of patients with MCT8 deficiency assessed at Hospital J. P. Garrahan and treated with TRIAC between January 2019 and December 2022.” (opens the source at this quote in a new tab)
“At the beginning of treatment and at the last control, age, weight and height progression, heart rate, blood pressure, feeding difficulty, neurological examination focused on neurodevelopment, and muscle tone and mass were assessed.” (opens the source at this quote in a new tab)

Eligibility criteria

Genetic confirmation and consent

“Molecular studies revealed pathogenic variants in all studied patients.” (opens the source at this quote in a new tab)
“The parents of all patients signed the informed consent for the use of TRIAC.” (opens the source at this quote in a new tab)

Treatment

Dose and time to treatment initiation

“The mean time from diagnosis to initiation of TRIAC was 2.7 months (±2.2 months).” (opens the source at this quote in a new tab)
“All patients received a daily intake, with a mean dose of 19 μg/kg (±6.8 SD).” (opens the source at this quote in a new tab)

Treatment start date and current daily dose by participant

Participant	Start date	Current dose
Participant 1	“Nov-2019”	“22 μg/kg”
Participant 2	“Jun-2020”	“18 μg/kg”
Participant 3	“Jan-2022”	“10 μg/kg”
Participant 4	“Jun-2022”	“26 μg/kg”

Regulatory access in Argentina

“In Argentina, the use of triac was approved by the National Drug, Food and Technology Administration of Argentina (Administración Nacional de Medicamentos, Alimentos y Tecnología Médica, ANMAT) in April 2015.” (opens the source at this quote in a new tab)

Study outcomes

Rationale for using serum t3 concentration as a biochemical outcome

Elevated T3 as the biochemical marker of MCT8 deficiency

“Intrathyroidal T4 is low because it is rapidly converted to T3 which is elevated, this being the main biochemical marker.” (opens the source at this quote in a new tab)
“If it is clinically suspected, a complete thyroid profile should be requested because elevated T3 levels are a characteristic biochemical marker.” (opens the source at this quote in a new tab)

Thyroid hormone assays

“TSH, free T4, and total T3 were measured using the CMIA method on Abbott’s Architect i4000 Immunoassay Analyzer.” (opens the source at this quote in a new tab)
“Total T4 and SHBG were analyzed by chemiluminescence on the Immulite 2000 XPi system, and the reference intervals proposed by Elmlinger et al.8,9 were applied.” (opens the source at this quote in a new tab)

Statistical analysis description

Number of participants (Planned and analyzed)

Included participants

Population	Participants
Children treated with tiratricol	“4”

Description of analysis sets

No evidence found.

Results

Participant disposition

Follow-up and treatment duration by participant

Participant	Follow-up duration	Treatment duration
Participant 1	“3 years and 6 months”	“32 months”
Participant 2	“2 years and 6 months”	“22 months”
Participant 3	“1 year and 1 month”	“6 months”
Participant 4	“7 months”	“5 months”

Baseline characteristics

Age, sex, and clinical presentation at diagnosis

“All patients were male, with a median age at diagnosis of 1.38 years (range: 0.58–7.16).” (opens the source at this quote in a new tab)
“The most frequent clinical manifestations were axial hypotonia, spasticity, and overall developmental delay secondary to central hypothyroidism.” (opens the source at this quote in a new tab)
“Signs of peripheral hyperthyroidism were observed in 50% of patients; a lack of weight progression was the most frequent clinical manifestation.” (opens the source at this quote in a new tab)
“None had cardiovascular signs.” (opens the source at this quote in a new tab)
“In 2 patients, the MRI showed alterations in myelination.” (opens the source at this quote in a new tab)

Thyroid function at diagnosis

“Elevated T3 levels (3.19–4,7 ng/mL) were observed in 100% of patients.” (opens the source at this quote in a new tab)
“T4 and free T4 determinations were low in 3 patients and normal in 1 (receiving levothyroxine).” (opens the source at this quote in a new tab)
“All patients had elevated SHBG.” (opens the source at this quote in a new tab)

Efficacy results

Biochemical response

“T3 levels decreased in all patients, and even 3/4 reached normal values, over a mean time of 2.5 months.” (opens the source at this quote in a new tab)
“T4 and free T4 levels remained low in all cases and TSH levels were normal while receiving treatment.” (opens the source at this quote in a new tab)

Total T3 at diagnosis and at the last control by participant

Participant	Total T3 at diagnosis, ng/mL	Total T3 at last control, ng/mL
Participant 1	“3.3 (NV: 0.29–2.26)”	“2.7 (NV: 0.29–2.26)”
Participant 2	“3.19 (NV: 1.03–2.3)”	“2.12 (NV: 1.03–2.3)”
Participant 3	“4.7 (NV: 0.99–2.14)”	“1.52 (NV: 0.99–2.14)”
Participant 4	“3.56 (NV: 0.29–2.26)”	“2.08 (NV: 0.29–2.26)”

Clinical response

“In our population, the main benefit was the improvement in spasticity, muscle tone, and developmental delay.” (opens the source at this quote in a new tab)
“The 2 children with malnutrition showed an improvement in weight.” (opens the source at this quote in a new tab)

Health-related quality of life and patient-reported outcomes

No evidence found.

Safety results

Reported adverse reactions

“No adverse reactions to TRIAC were reported during follow-up.” (opens the source at this quote in a new tab)

Study limitations

Summary

The series included four participants from a single hospital and did not include a concurrent control group. Treatment duration ranged from 5 to 32 months. The authors describe retrospective data collection and unequal access to developmental stimulation therapies. The observed biochemical response and absence of reported adverse reactions in four participants cannot establish comparative effectiveness, quantify uncommon harms, or separate treatment effects on development from concomitant supportive care.

Limitations stated by the authors

“The limitations of this study are its retrospective nature and the limited number of patients, who were from different families with unequal access to stimulation therapies, which are a fundamental aspect in the progression of neurodevelopment.” (opens the source at this quote in a new tab)