Levothyroxine
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Levothyroxine: From Thyroid Hormone Replacement to Endemic Goiter
One-Sentence Summary
Levothyroxine is a synthetic thyroid hormone, conventionally used to replace thyroid hormone. The SAHPRA record supplied does not state its approved indication text. The TxGNN model predicts it may be effective for endemic goiter, but only 1 registered clinical trial was retrieved (it tests a non-levothyroxine intervention), and the literature is mostly iodine-deficiency epidemiology and iodine prophylaxis. Evidence for this specific indication is therefore weak.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Thyroid hormone replacement (general pharmacology; the SAHPRA record supplied contains no indication text) |
| Predicted New Indication | Endemic goiter |
| TxGNN Prediction Score | 99.81% |
| Evidence Level | L4 |
| South Africa Market Status | Marketed |
| Number of SAHPRA Registrations | 1 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, levothyroxine is a thyroid hormone replacement. It suppresses TSH, and TSH drives thyroid growth, so it could in theory reduce goiter size.
Endemic goiter is caused mainly by iodine deficiency, which raises TSH. Iodine repletion is the causal, first-line intervention, and thyroid hormone treats only the downstream TSH drive. The retrieved literature reflects this. It is dominated by iodized oil, iodized salt and maternal iodine supplementation, and contains no controlled levothyroxine efficacy data for this indication.
The one directly relevant paper is a 1988 German multicentre study (PMID 3278876). It compared levothyroxine alone with levothyroxine plus iodide in 74 patients with diffuse endemic goiter. It is old and small, and this pack contains no result data or classification for it.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT04482907 | N/A | Completed | 68 | Placebo-controlled study of dill (Anethum graveolens) in thyroiditis and nodular goiter. Not a levothyroxine trial, so it is likely linked to this prediction only by a shared condition keyword. |
No SANCTR or PACTR registrations were retrieved.
Literature Evidence
No paper retrieved reports controlled levothyroxine efficacy data in endemic goiter. Most study types below are taken from titles and abstracts, because the pack has not classified them.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 3278876 | 1988 | Multicentre comparative study | Dtsch Med Wochenschr | Levothyroxine 150 µg vs levothyroxine 100 µg + iodide in 74 patients with diffuse endemic goiter, followed by iodide prophylaxis |
| 7704809 | 1994 | Review | Curr Ther Endocrinol Metab | Overview of endemic goiter |
| 2031356 | 1991 | Review | World J Surg | Iodine deficiency is the established primary cause. Iodine prophylaxis is the established prevention and treatment, though implementation is difficult. |
| 36839362 | 2023 | Review | Nutrients | Update on iodine deficiency and iodine prophylaxis |
| 25629792 | 2015 | Interventional/cohort | Curr Med Res Opin | Maternal iodine supplementation and thyroid function in 460 pregnant women in goiter-endemic areas |
| 4312017 | 1969 | Interventional field study | Am J Clin Nutr | Iodized oil for prophylaxis and treatment in rural Ecuador and Peru |
| 2997259 | 1985 | Longitudinal study | J Clin Endocrinol Metab | Oral iodized oil reduced goiter prevalence in Sudanese schoolchildren (67% to 36%) |
| 6309889 | 1983 | Interventional study | J Clin Endocrinol Metab | Iodized oil in 58 goitrous patients in Greece reduced goiter size |
| 8121602 | 1993 | Case series | Minerva Ginecol | 38 pregnant women with endemic goiter, 4 of whom received levothyroxine 50–100 µg/day |
| 6304776 | 1983 | Physiology study | Prog Clin Biol Res | TSH is raised in endemic goiter and correlates inversely with T4 |
South Africa Market Information
| Registration Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| Reg. No. 56/21.3/0331 | Roidace 25 | Tablet (oral) | Not stated in the record supplied |
Safety Considerations
Please refer to the SAHPRA-approved Professional Information (PI) for safety information. Report adverse drug reactions to SAHPRA.
The DrugBank interaction query returned no results, which means no data, not proof of no interactions.
For related goiter indications, the pack notes that TSH-suppressive levothyroxine carries known risks, including bone loss and atrial fibrillation. Any goiter use would need careful patient selection.
Conclusion and Next Steps
Decision: Hold
Rationale: There is no levothyroxine-specific trial or controlled evidence for endemic goiter. The literature supports iodine repletion as the causal first-line treatment. The one registered trial is unrelated to levothyroxine.
The pack lists two other goiter predictions with stronger evidence (both L2, decision stage S2, “Research Question”):
- Nodular goiter: randomized levothyroxine-relevant trials, including the placebo-controlled Phase 4 trial NCT00277589 (n=1024) and the lobectomy trial NCT00941551 (n=150).
- Nontoxic goiter: the randomized trial of levothyroxine vs radioactive iodine (PMID 11238476).
Three other predictions (renal hypodysplasia/aplasia, bilateral renal agenesis, Potter sequence) have no plausible mechanism and no evidence. They are most likely knowledge-graph artifacts.
To proceed, the following is needed:
- The SAHPRA package insert (warnings, contraindications, approved indication), which is currently missing and blocks the safety screening
- Mechanism of action data from DrugBank
- Full-text review of PMID 3278876 to see whether levothyroxine reduced goiter volume in endemic goiter
- Local data on iodine status in South Africa, to establish whether endemic goiter is relevant to the local population
- Consideration of shifting the research question to nodular or nontoxic goiter, where randomized evidence exists
This report is for research reference only and does not constitute medical advice. Repurposing candidates require clinical validation before use.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.