DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for atrophy of thyroid — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAtrophy of thyroid maps to a 3-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
approvedSunitinibApproved drug
Structures already discussed alongside atrophy of thyroid in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
KIT kinase domain — Sunitinib has a real, experimentally solved structure in complex with this target (PDB 3G0E, 1.6 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet b49drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3G0E · 1.6 Å · ligand Sunitinib (B49). Experimental structure, not a prediction.
What the evidence adds up to
In 17 patients with metastatic renal cell carcinoma treated with sunitinib, median thyroid volume reduction was 30% at last evaluation. Eight patients had more than 50% volume reduction, and hypothyroidism was significantly more frequent in that group. Half of those with high reduction showed transient thyroid-stimulating hormone suppression suggesting thyrotoxicosis. Autopsy histology showed atrophy of thyroid follicles and degeneration of follicular epithelial cells without major loss of vascular volume. The authors concluded that sunitinib-induced thyroid atrophy may result from thyrotoxicosis or direct follicular cell damage.
Among 325 Graves’ disease patients treated with radioiodine, 76% were treated successfully. Success was associated with smaller thyroid, lower free thyroxine, and shorter antithyroid drug withdrawal before treatment. Hypothyroidism occurred in 41% of patients overall, and early hypothyroidism was more likely with lower 24-hour iodine uptake, lower total iodine dose, and higher iodine dose per gram of thyroid tissue. A separate review notes that antithyroid drug therapy has a relapse rate above 50%, and that current treatment strategies aim at ablating the thyroid to induce permanent hypothyroidism rather than targeting the underlying autoimmune stimulation.
A randomised trial of 60 thyrotoxicosis patients (51 with Graves’ disease, 9 with toxic multinodular goiter) compared carbimazole with radioiodine over one year. Bone mineral content at lumbar spine and femoral neck improved similarly in both groups, as did body weight, protein, and fat content. No difference was observed between the two therapies. In 143 athyreotic patients on levothyroxine replacement, those with low tri-iodothyronine levels had significantly lower body weight than those with normal tri-iodothyronine, suggesting lean body mass influences peripheral conversion of thyroxine to tri-iodothyronine.
What is still missing is prospective data on whether any drug can reverse established thyroid atrophy rather than merely induce it as a side effect. No trial has tested a repurposed agent specifically for thyroid atrophy in humans. The existing evidence is limited to small observational studies and retrospective analyses, with no randomised controlled trial designed to restore thyroid volume or function. Patient stratification by baseline thyroid volume, autoantibody status, and lean body mass has not been incorporated into any interventional study. Funding for such a trial is absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
British Journal of Cancer · 2010 · 57 citations · open access
The incidence and mechanism of sunitinib-induced thyroid atrophy in patients with metastatic renal cell carcinoma
AbstractBACKGROUND: To elucidate the incidence and mechanisms of sunitinib-induced thyroid atrophy, we investigated serial volumetric and functional changes, and evaluated histological changes of the thyroid gland in metastatic renal cell carcinoma patients who received sunitinib. METHODS: Thyroid volume (by computed tomography volumetry) and thyroid function were measured at baseline, during the treatment, and at post-treatment periods. Histological evaluation of the thyroid gland was performed in four autopsied patients. RESULTS: The median reduction rate in thyroid volume at last evaluation during sunitinib treatment was 30% in all 17 patients. The incidence of hypothyroidism during sunitinib treatment was significantly higher in the high reduction rate group (n=8; more than 50% reduction in volume) than in the low reduction rate group (n=9; less than 50% reduction in volume). Half of the patients in the high reduction rate group exhibited a transient thyroid-stimulating hormone suppression, suggesting thyrotoxicosis during sunitinib treatment. Histological evaluation demonstrated atrophy of thyroid follicles and degeneration of follicular epithelial cells without critical diminution of vascular volume in the thyroid gland. CONCLUSION: Thyroid atrophy is frequently observed following sunitinib treatment and may be brought about by sunitinib-induced thyrotoxicosis or the direct effects of sunitinib that lead to degeneration of thyroid follicular cells.
Nuclear Medicine Communications · 2017 · 40 citations · open access
Prognostic factor analysis in 325 patients with Graves’ disease treated with radioiodine therapy
AbstractINTRODUCTION: I therapy is a choice for Graves' hyperthyroidism. Several factors that affect the success of I treatment in Graves' disease (GD) patients have been put forward. The aim of this retrospective study was to evaluate the factors influencing the success of I therapy and the occurrence of hypothyroidism after I therapy. PATIENTS AND METHODS: We reviewed 325 GD patients, who were well documented out of 779 cases, treated with I in the First Affiliated Hospital of Xi'an Jiaotong University between 2010 and 2016. We collected the potential influencing factors, including demographic data (age, sex, family history), iodine intake state, antithyroid drugs (ATD) taking, thyroid texture, complications of hyperthyroidism, physical and laboratory examinations [thyroid weight, effective I half-life time (Teff), 24-h iodine uptake rate, tri-iodothyronine, thyroxine, free tri-iodothyronine (FT3), free thyroxine, thyroid-stimulating hormone, thyroglobulin antibody, thyroid microsome antibody, thyrotropin receptor antibody], and final administered dosages according to Quimby formula. The correlations between the prognosis of GD patients and these factors were analyzed by logistic regression analysis. RESULTS: Out of 325 patients, 247 (76.00%) were treated successfully with radioiodine. GD patients who were cured by I therapy were more likely to have smaller thyroid [odds ratio (OR)=0.988, 95% confidence interval (CI)=0.980-0.996, P=0.002], lower FT4 levels (OR=0.993, 95% CI=0.988-0.997, P=0.002), and shorter time of ATD withdrawal before I treatment (OR=0.985, 95% CI=0.975-0.996, P=0.002). Hypothyroidism occurred in 132 (41.00%) out of 325 patients. There was an increased risk of early hypothyroidism in patients with lower 24-h iodine uptake (OR=0.964, 95% CI=0.941-0.988, P=0.004), and treated with a lower total dose of iodine (OR=0.892, 95% CI=0.824-0.965, P=0.005) and a higher iodine dose per garm of thyroid tissue (OR=5.414E+14, 95% CI=45.495-6.444E+27, P=0.027). CONCLUSION: Our results showed that I treatment was more successful in patients with lower weight of the thyroid, lower free thyroxine level, and shorter ATD taking period. Furthermore, early hypothyroidism after radioiodine treatment was more likely to occur in patients with lower 24-h iodine uptake, lower total dose of iodine, and higher iodine dose per garm of thyroid tissue.
Tamoxifen Therapy in Steroid-Resistant Riedels Disease
AbstractRiedels thyroiditis is a rare chronic inflammatory disorder characterised by extensive fibrosis of the thyroid gland and sometimes the surrounding tissues. We report a case of Riedels Thyroiditis in a middle aged female presenting with goitre, stridor and dyspnoea. She initially responded to corticosteroid treatment and subsequently to tamoxifen. The rationale for these treatments are discussed.
Indian Journal of Endocrinology and Metabolism · 2013 · 6 citations · open access
Indefinite antithyroid drug therapy in toxic Graves′ disease: What are the cons
AbstractExisting treatment modalities for Graves' disease includes antithyroid drugs (ATDs), radioactive iodine, and surgery. There has been a lack of general agreement as to which therapy is the best as none is ideal since all effectively restore euthyroidism, but with some limitations. Previously, therapies were selected with the goal of achieving euthyroidism. Instead, hypothyroidism is now the goal of treatment, to ensure that hyperthyroidism does not recur. Current evidences suggest that high relapse rate and not so rare fatal side effects seen with ATD therapy compel one to consider other definite modes of treatment like radiotherapy and surgery for toxic Graves' disease after discussing this with the patient.
Indian Journal of Endocrinology and Metabolism · 2017 · 5 citations · open access
Effect of antithyroid therapies on bone and body composition: A prospective, randomized, clinical study comparing antithyroid drugs with radioiodine therapy
AbstractBACKGROUND: Thyrotoxicosis is associated with loss of body weight and bone mineral content (BMC). Antithyroid drugs (ATD) and radioiodine therapy (RIT) are the common options for the management of thyrotoxicosis. We evaluated the effect of ATD and RIT on BMC and body composition. MATERIALS AND METHODS: In this prospective study, we randomized 60 patients of thyrotoxicosis (20-50 years, treatment naïve, males) to receive either ATD (Group 1) using carbimazole or RIT (Group 2). We excluded patients with significant ophthalmopathy and thyroid malignancy. The patients were followed serially for 1 year. Body composition was analyzed using the bioimpedance method and BMC by dual-energy X-ray absorptiometry technique. The data were analyzed using appropriate statistical measures. RESULTS: The patients had a mean age of 33 ± 4.2 years and mean symptoms duration of 8.2 ± 2.7 months before the diagnosis. A total of 51 patients had Graves' disease, and the remaining 9 had toxic multinodular goiter. BMC at lumbar spine and femoral neck improved with both the therapies similarly at the end of 1 year. The body weight, protein, and fat content also increased after 1 year of observation similar between the two groups. None of the observed parameters showed a difference with regard to the mode of ATD. CONCLUSION: ATD and RIT have comparable effects on the bone and body composition in the management of thyrotoxicosis. Further long-term studies are needed to confirm the observed findings.
Abstract• Thyroid acropachy (TA) developed in a 48-year-old man at least six years prior to clinically evident and symptomatic hyperthyroidism. The TA prompted a clinical workup for acromegaly on two occasions, with negative results. It usually develops after diagnosis or treatment of hyperthyroidism and usually occurs in conjunction with exophthalmos. In our patient, TA preceded the diagnosis and treatment of hyperthyroidism and was not associated with exophthalmos. (<i>Arch Dermatol</i>116:205-206, 1980)
Journal of Korean Medical Association · 2018 · 1 citations · open access
Treatment of relapsed hyperthyroidism
AbstractGraves disease is the most common disease that causes hyperthyroidism. It is an autoimmune disease characterized by the overproduction of thyroid hormones due to continuous stimulation of the thyroid gland by thyroid-stimulating hormone receptor antibody. Therapeutic modalities for Graves disease include antithyroid drugs (ATDs), radioactive iodine, and thyroidectomy. ATDs are the most preferred therapeutic option by physicians in most countries except North America. However, current treatment strategies are unfortunately aimed at inhibiting thyroid hormone production or ablating the thyroid to induce permanent hypothyroidism, not at inhibiting thyroid-stimulating hormone receptor antibody. ATD therapy has a high relapse rate (more than 50%), and morbidity and mortality increase in cases of relapse. Therefore, the proper and prompt management of relapsed patients is very important.
Endocrinology and Metabolism · 2010 · 0 citations · open access
Factors Influencing Peripheral Conversion of Thyroxine to Tri-Iodothyronine in Athyreotic Individuals during Levothyroxine Replacement
AbstractBACKGROUNDTri-iodothyronine (T3) is the main active hormone, and 20% of this is derived from the thyroid gland and 80% is from the peripheral tissue according to 5'-monodeiodination of thyroxine (T4). In the previous studies, normal T3 levels were achieved with traditional levothyroxine (LT4) therapy alone in athyreotic patients, but there has been no data about the factors influencing peripheral conversion of LT4. The aim of this study was to determine the factor(s) influencing peripheral conversion of LT4 to T3 in athyreotic patients during LT4 replacement. METHODS: The patients who underwent total-thyroidectomy for any cause, and mostly for thyroid cancers, at Asan Medical Center between 2000 and 2008 were enrolled. The free T4, T3 and thyroid stimulating hormone (TSH) levels and age, gender, weight, height, body mass index (BMI) and the T4 dose were measured. Only patients with normal ranges of free T4 and TSH were included in the analysis. RESULTS: A total of 143 patients were enrolled. The mean T3, free T4 and TSH levels were 143.7 ng/dL, 1.4 ng/dL and 1.6 microU/mL, respectively. The mean weight and BMI were 62.9 kg and 24.6 kg/m2, respectively. We divided them into two groups according to the serum T3 level and we compared the characteristics of the groups. There were no differences in age, the gender distribution, the T4 dose/weight and the BMI between the low T3 group (T3 < or = 122 ng/dL, n = 14) and the normal T3 group (T3 > 122 ng/dL, n = 129). In the low T3 group, the mean body weight was significantly lower than that of the normal T3 group (59.0 +/- 6.0 vs. 63.4 +/- 9.9, respectively, P = 0.025). CONCLUSION: Lean body mass seems to be an important factor for determining the peripheral conversion of T4 to T3 in human. This suggest that a combination of T3/T4 is better than T4 only when we treat the patients with hypothyroidism and who have a negligible amount of functioning thyroid tissue, if they have a low lean body mass.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
