Product information and disease description Place of product in therapy Approaches to treatment Current treatment options and standard of care

Combined levothyroxine and propylthiouracil

9 evidence topics · 3 sources

Guideline position on levothyroxine monotherapy and on combined levothyroxine and propylthiouracil

“Post-natal treatment with levothyroxine monotherapy is not recommended” (opens the source at this quote in a new tab)
“If thyroid hormone analogs are unavailable, we suggest that a combination of levothyroxine and PTU treatment could be considered” (opens the source at this quote in a new tab)
“Given the rare but potentially severe and life-threatening side effects of PTU and the unknown long-term effects of thyroid hormone analogs, we acknowledge that the risks versus benefits of such therapies should be considered carefully, particularly in patients whose baseline liver function is already deranged” (opens the source at this quote in a new tab)

Published outcomes of levothyroxine alone and with propylthiouracil

“Treatment with levothyroxine in a wide dose range (2.5–15 mcg/kg/day), commenced at the age of 0.5 to 36 months, did not improve neurodevelopment and, in some cases even aggravated the hyperthyroid state in peripheral tissues” (opens the source at this quote in a new tab)
“Combination therapy with propylthiouracil (PTU− given to block T4 to T3 conversion) and levothyroxine reduced signs of hyperthyroidism in peripheral tissues in some patients, increasing body weight, reducing heart rate, and serum sex hormone-binding globulin (SHBG) concentrations, but had no beneficial effects on neurocognitive development” (opens the source at this quote in a new tab)

Conventional antithyroid drugs

“Conventional antithyroid drugs such as carbimazole or methimazole are not recommended in MCT8 deficiency, as the thyrotoxic state is not driven by primary TH overproduction, and their use may exacerbate central hypothyroidism.” (opens the source at this quote in a new tab)

Combined treatment case series: objective and population

“To evaluate the combined administration of propylthiouracil (PTU) and levothyroxine (LT4) in managing monocarboxylate transporter 8 (MCT8) deficiency and identify optimal therapeutic dosages.” (opens the source at this quote in a new tab)
“This multicenter case series involved 12 male patients with MCT8 deficiency whose parents/guardians consented to PTU and LT4 treatment. Data were collected from January 2008 to June 24, 2024.” (opens the source at this quote in a new tab)
“At the beginning of treatment, the median age was 18 months (IQR: 9–28 months), and a median of 40 months (IQR: 25–88 months) at the last encounter.” (opens the source at this quote in a new tab)

Combined treatment case series: biochemical outcomes

“Patients showed a significant reduction in serum total triiodothyronine (TT3) concentration and TT3/TT4 ratio, with increased serum TT4 and free T4 (fT4) concentrations. The use of PTU effectively reduced TT3 concentration by 25% at an average dose of 6.8 mg/kg/day, while LT4 increased fT4 concentration by 40% from baseline at an average dose of 4.3 µg/kg/day.” (opens the source at this quote in a new tab)
“Combined treatment with PTU and LT4 normalized serum T3, fT4, and TT4 in patients with MCT8 deficiency.” (opens the source at this quote in a new tab)

Combined treatment case series: baseline and last-encounter values

Parameter	Baseline	Last encounter	p value
Total T3, ng/dL	“337.7 ± 66”	“237 ± 91”	“<0.001”
Free T4, pmol/L	“8.9 ± 2.8”	“27.7 ± 15.3”	“0.003”
SHBG, nM/L	“242 ± 64.9”	“212.1 ± 73.4”	“0.170”
Heart rate, bpm	“102.7 ± 14.6”	“108.7 ± 21.13”	“0.433”

Combined treatment case series: metabolic and physical outcomes

“No statistical differences were observed in metabolic and physical parameters between baseline and last encounter overall for the group, but six of eight patients for whom these data were available had an increase in weight (z-score).” (opens the source at this quote in a new tab)

Combined treatment case series: hepatic and hematologic safety

“There were no adverse effects on liver function or granulocyte numbers noted throughout the period of observation.” (opens the source at this quote in a new tab)
“In our limited study, we did not find any evidence of liver toxicity; however, close monitoring of liver function tests is indicated given the concern and the relatively high doses of PTU used.” (opens the source at this quote in a new tab)

Combined treatment case series: limitations stated by the authors

“The number of patients in this study is not sufficiently powered to detect significant differences in peripheral tissue markers of TH action due to the variable baseline. Furthermore, the length of treatment was variable. Direct comparisons to other treatments such as DITPA and TRIAC are not possible in this report.” (opens the source at this quote in a new tab)