Propylthiouracil
| Evidence Level: L4 | Predicted Indications: 2 |
Table of Contents
- Propylthiouracil
- Pharmacist Assessment Report
- Propylthiouracil: Resistance to thyroid hormone due to a mutation in thyroid hormone receptor beta
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Australia Market Information
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Propylthiouracil: Resistance to thyroid hormone due to a mutation in thyroid hormone receptor beta
One-Sentence Summary
Propylthiouracil (PTU) is an antithyroid drug originally used to treat hyperthyroidism, Graves disease, thyrotoxicosis and thyroid crisis. The TxGNN model’s top-ranked prediction is resistance to thyroid hormone due to a THRB mutation, but there are no registered clinical trials and only 4 publications (case reports and mouse models), none showing benefit from PTU. The prediction is best regarded as a network artefact rather than a credible new use.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Resistance to thyroid hormone due to a mutation in thyroid hormone receptor beta |
| TxGNN Prediction Score | 0.9966 |
| Evidence Level | L4 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not currently available. Based on known information, PTU is a thionamide that inhibits thyroid peroxidase and so reduces thyroid hormone synthesis. Its efficacy in hyperthyroidism is established.
In resistance to thyroid hormone (RTH), tissues respond poorly to high circulating hormone levels. Lowering hormone output is generally not appropriate and may cause hypothyroid-like symptoms or TSH-driven goitre enlargement. The retrieved literature supports this caution. In one Thai case, the patient’s goitre enlarged after 9 months of PTU given for presumed thyrotoxicosis. The high TxGNN score (0.9966) comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence, and it is not a therapeutic rationale.
Other Predictions Reviewed
| Rank | Predicted Indication | Score | Evidence Level | Comment |
|---|---|---|---|---|
| 3 | Hyperthyroxinemia | 0.9908 | L4 | Many forms are euthyroid or tissue-resistant, so treatment is not indicated. One MCT8 case report suggests a niche benefit. |
Clinical Trial Evidence
Currently no related clinical trials are registered for the top-ranked prediction.
Trials found for other predictions are summarised below, because they bear on the antithyroid drug class rather than on a new indication:
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT05118542 | Phase 3 | Completed | 36 | Single-blind comparison of PTU and methimazole in Graves disease, measuring atherosclerosis markers (indirect outcome) |
| NCT03066076 | Phase 3 | Unknown | 60 | Total thyroidectomy versus thionamides in Graves ophthalmopathy (PTU not confirmed as the specific comparator) |
| NCT01056419 | Phase 4 | Unknown | 40 | Early total thyroidectomy versus antithyroid drugs in Graves orbitopathy (surgical focus) |
| NCT03433352 | N/A | Unknown | 90 | Gut microbiota and methimazole response in Graves disease (does not involve PTU) |
| NCT03447093 | N/A | Unknown | 120 | Observational oral microbiota study in autoimmune thyroiditis (no PTU intervention) |
No ANZCTR identifiers were found in the data compiled for this report.
Literature Evidence
Publications for the top-ranked prediction (RTH due to THRB mutation):
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 22919057 | 2012 | Animal model | Endocrinology | Role of TSH in thyroid carcinoma in mice carrying a THRB mutation |
| 12201835 | 2002 | Case report | Clin Endocrinol | Neonatal thyrotoxicosis and maternal infertility in RTH (M313T mutation) |
| 10724359 | 1999 | Case report | Endocr J | Thai woman with RTH was treated with PTU for presumed thyrotoxicosis and her goitre enlarged |
| 21909131 | 2012 | Animal model | Oncogene | Thyroid hormone activates tumour cell proliferation in a mouse model of follicular thyroid carcinoma |
Selected supporting publications for other predictions:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 30283735 | 2018 | Guideline | Eur Thyroid J | ETA guideline supports thionamides in Graves hyperthyroidism, with methimazole first-line |
| 24622372 | 2013 | Review | Lancet Diabetes Endocrinol | Hyperthyroidism in pregnancy |
| 31345521 | 2019 | Review | Endocrinol Metab Clin North Am | High-risk patients receive PTU in the first trimester, then may transition to methimazole |
| 18334584 | 2008 | Case report | J Clin Endocrinol Metab | PTU plus L-thyroxine was beneficial in a patient with an MCT8 mutation |
| 16450313 | 2006 | Case report | Exp Clin Endocrinol Diabetes | Thyrotoxicosis-induced Prinzmetal angina resolved after PTU restored euthyroidism |
| 26321810 | 2015 | Case report | Indian J Crit Care Med | PTU-induced autoimmune disease (safety signal) |
| 19196368 | 2009 | Clinical study | Int J Clin Pract | ANCA positivity in Graves patients treated with PTU |
| 2090674 | 1990 | Case report | J Endocrinol Invest | Neonatal hepatitis after placental transfer of PTU |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 13836F | PTU | Tablet 50 mg (oral) | Not recorded in the data compiled for this report |
The single entry is a valid, single-ingredient product.
Safety Considerations
Contraindications and risk conditions (from the knowledge graph, not label text):
- Haematological: thrombocytopenia, leukopenia, pancytopenia, agranulocytosis, neutropenia (including congenital and idiopathic forms)
- Thyroid: hypothyroidism, myxedema, congenital hypothyroidism
- Hepatic: drug-induced liver injury, hyperbilirubinaemia, Gilbert syndrome
- Respiratory: interstitial lung disease
Drug interactions: 83 interactions were identified. The main ones are:
- Major: deferiprone
- Moderate: warfarin, dicoumarol, theophylline, aminophylline, oxtriphylline, naltrexone, iodide I-131, iodide I-123, macimorelin
- Other listed interactions have an unclassified severity (for example omeprazole, pantoprazole, rosuvastatin, clopidogrel and several corticosteroids)
Safety signals from the literature: hepatotoxicity, ANCA-associated vasculitis and autoimmune disease, and neonatal hepatitis after placental transfer. For these reasons PTU is generally reserved for the first trimester of pregnancy, thyroid storm or methimazole intolerance.
Please refer to the TGA-approved Product Information (PI) for authoritative warnings and contraindications. Label-based safety data could not be retrieved.
Conclusion and Next Steps
Decision: Hold
Rationale: The top-ranked prediction has no clinical trials and only case reports and mouse models, and the mechanism argues against use because suppressing hormone synthesis is inappropriate in RTH. PTU’s hepatotoxicity also limits its role.
To proceed, the following is needed:
- TGA Product Information, to establish label warnings, contraindications and the approved indication text
- Detailed mechanism of action data
- For neonatal thyrotoxicosis, a focused review of PTU use in pregnancy and neonates, weighing hepatotoxicity against methimazole alternatives
- Direct clinical evidence of PTU benefit for any proposed new indication, which is currently absent
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.