DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Thyrotoxicosis — screening already-approved drugs against its 37-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleThyrotoxicosis maps to a 37-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 thyrotoxicosis 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
A single case report describes transient overt thyrotoxicosis followed by hypothyroidism in a patient receiving sunitinib, a tyrosine kinase inhibitor for renal cell carcinoma and gastrointestinal stromal tumours. Another case report describes a 21-year-old woman who developed atrial fibrillation after a 10 mg levothyroxine overdose; she was treated with propylthiouracil, propranolol, hydrocortisone, and hemoperfusion, and recovered.
In a UK cost-effectiveness study of 135 patients with thyrotoxicosis (62% Graves’ disease, 7% nodular disease, 5% thyroiditis, 27% unknown aetiology), 74 patients received an 18-month course of thionamide therapy, 43 received radioiodine, and 5 had a thyroidectomy. At 30 months, 73% of the thionamide group were cured (euthyroid), compared to 95% in the radioiodine group at 24 months and 100% in the thyroidectomy group at 24 months. Cost per cure was £3,763 for thionamides, £1,375 for radioiodine, and £6,551 for thyroidectomy. The authors concluded radioiodine was the most cost-effective primary treatment. A 1951 report on 46 patients treated with thiouracil, propylthiouracil, or aminothiazole noted that these goitrogenic compounds are inexpensive and readily available, and that tolerance does not develop; patients were selected for prolonged treatment based on likelihood of sustained remission, postoperative recurrence, or refusal of surgery.
Thyrotoxic storm occurs in 1–2% of hospital admissions for thyrotoxicosis and carries high mortality even when diagnosed and treated. Management includes volume repletion, cooling, beta-blockade (propranolol or esmolol), large doses of antithyroid drugs (crushed and given by nasogastric tube or per rectum if needed), stable iodine (Lugol’s solution) after antithyroid drugs are started, and dexamethasone. In severe cases, peritoneal dialysis, plasmapheresis, or cholestyramine resin may be used. For patients with a compromised gastrointestinal tract, non-oral routes for thionamides, beta-blockers, iodine solutions, and glucocorticoids are recommended; plasmapheresis is a temporary bridge if conventional therapy fails. A 1973 symposium opening address and a 2012 discussion of radioiodine dosing note that there is no consensus on the optimal dose, with the author’s practice being 400 MBq for Graves’ disease and 800 MBq for large multinodular goitre.
What remains missing are prospective trials comparing fixed versus calculated radioiodine doses, data on long-term outcomes of non-oral drug regimens in thyrotoxic storm, and any randomised evidence for the use of plasmapheresis or hemoperfusion in severe thyrotoxicosis. Patient stratification by aetiology and severity is not standardised in the available studies.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Thyroid · 2007 · 54 citations
Sunitinib (Sutent)-Induced Thyrotoxicosis Due to Destructive Thyroiditis: A Case Report
AbstractNumerous drugs have been associated with destructive thyroiditis (subacute thyroiditis). Sunitinib, a tyrosine kinase inhibitor employed in renal cell carcinoma and gastrointestinal stromal tumors, has recently been linked to destructive thyroiditis with resultant hypothyroidism. We report a patient with transient overt thyrotoxicosis followed by hypothyroidism, apparently related to sunitinib therapy.
The Cost Effectiveness of Treatment Modalities for Thyrotoxicosis in a U.K. Center
AbstractOBJECTIVE: This study determined the cost effectiveness of treating thyrotoxicosis using thionamide therapy, radioiodine or surgery in the United Kingdom. DESIGN: One hundred thirty-five patients diagnosed with thyrotoxicosis (62% Graves' disease, 7% nodular disease, 5% thyroiditis, and 27% unknown aetiology) referred in 12 months were offered a fully informed choice of treatment modality. Thirteen patients with transient thyrotoxicosis were subsequently excluded from the analysis. Seventy-four patients (61%) received an 18-month course of thionamide therapy, 43 received radioiodine therapy (35%), and 5 had a thyroidectomy (4%) within the first year of diagnosis as their primary treatment. A successful outcome ("cure") was defined as euthyroidism 12 months after thionamide therapy or euthyroidism or hypothyroidism on thyroxine replacement at 24 months following radioiodine or thyroidectomy. Costs were calculated for outpatient attendances, laboratory tests, and initial and subsequent treatments. MAIN OUTCOME: In the thionamide group 73% were "cured" at 30 months after initiating treatment compared to 95% in the radioiodine group and 100% treated by thyroidectomy at 24 months. Cost per "cure" was calculated to be 3,763 pounds (5,644 dollars) per patient who received thionamides, 1,375 pounds (2,063 dollars) per patient given radioiodine and 6,551 pounds (9,826 dollars) per patient who underwent thyroidectomy. CONCLUSION: The most cost-effective primary treatment modality for thyrotoxicosis is radioiodine.
Management of Severe Thyrotoxicosis When the Gastrointestinal Tract Is Compromised
AbstractBACKGROUND: The management of patients with severe thyrotoxicosis in the absence of a functional gastrointestinal tract represents an uncommon but significant clinical challenge associated with a high mortality rate. This article offers a literature review and discussion of the available management options in this setting. SUMMARY: Treatment of severe thyrotoxicosis in patients unable to ingest medications by the oral route should focus on normalization of thyroid hormone levels utilizing conventional medical therapy for thyrotoxicosis, administered via non-oral routes. This includes thionamides, beta-blockers, iodine containing solutions, and glucocorticoids. When conventional medical therapy fails, plasmapheresis should be considered as a temporary therapeutic bridge until conventional therapies can be instituted effectively or emergent surgery performed. CONCLUSION: Although a rare scenario, the management of patients with severe thyrotoxicosis in the absence of a functional gastrointestinal tract represents a challenging clinical situation. Endocrinologists and critical care physicians should be apprised of the available treatment modalities which must be instituted swiftly in order to avoid a catastrophic outcome.
World Journal of Clinical Cases · 2022 · 12 citations · open access
Thyrotoxicosis after a massive levothyroxine ingestion: A case report
AbstractBACKGROUND: The literature on thyrotoxicosis caused by excessive ingestion of exogenous thyroid hormone is limited, and most cases reported have involved pediatric clinical studies. CASE SUMMARY: A 21-year-old woman initially presented with palpitation and chest tightness after an overdose of levothyroxine (10 mg). The patient transiently lost consciousness and developed atrial fibrillation during hospitalization. We used propylthiouracil to decrease the peripheral conversion of T4 to T3 and inhibit the synthesis of endogenous thyroxine, propranolol to control heart rate, hydrocortisone to correct severe thyrotoxicosis, and hemoperfusion to increase levothyroxine clearance. The patient recovered and was discharged. CONCLUSION: For patients with thyrotoxicosis after taking excess levothyroxine, it is critical to monitor vital signs and initiate effective treatment.
Journal of Intensive Care Medicine · 2002 · 11 citations
Thyrotoxic Storm
AbstractThyrotoxic storm is a syndrome of exaggerated thyrotoxicosis with systemic decompensation seen in 1-2% of hospital admissions for thyrotoxicosis. The diagnosis is based on recognition of typical cardinal manifestations, but even when diagnosed and treated, mortality rates are high. Results of thyroid function tests may be no more abnormal than those seen in uncomplicated thyrotoxicosis. Often, there is a history of partially treated thyrotoxicosis, and/or decompensation related to a precipitating event such as infection, stroke, pulmonary embolism, or radioiodine therapy. Treatment must be aggressive and includes volume repletion with i.v. glucose and saline, and pressor agents may be needed. Patients belong in an intensive care unit, with a cooling blanket for hyperpyrexia. Appropriate cardiac medications are employed to control ventricular rate in those with atrial fibrillation. The thyroid is blocked by large doses of antithyroid agent. In patients unable to swallow, tablets can be crushed and given by nasogastric tube or per rectum. After antithyroid drugs are started, stable iodine as Lugol's solution is given to block further hormone release from the gland. Sodium ipodate can be used instead of iodine and has the advantage of inhibiting conversion of T4 to T3. In severe cases, thyroid hormone may be removed from the circulation by peritoneal dialysis or plasmapheresis, and cholestyramine resin may be used to bind T4 and T3 within the gastrointestinal tract. β-adrenergic antagonists such as propranolol are given, or the very short-acting β-adrenergic blocker, esmolol, has also been used with success. A Swan-Ganz catheter is used to monitor central hemodynamics, especially in patients receiving high-dose propranolol, pressors, digoxin, diuretics, and fluids. Large doses of dexamethasone have been given based on presumed increased glucocorticoid requirements in thyrotoxicosis and because adrenal reserve may be reduced. Therapy must be continued until a normal metabolic state is achieved, at which time iodine is progressively withdrawn and plans made for definitive treatment.
The Journal of Clinical Endocrinology & Metabolism · 1951 · 8 citations
LATE RESULTS IN THE TREATMENT OF THYROTOXICOSIS WITH GOITROGENIC COMPOUNDS
AbstractSINCE the first report by Astwood(l) in 1943 of the clinical use of thiourea in thyrotoxicosis, many goitrogenic compounds have been tried in this disorder. At present two thiouracil compounds, 6N propylthiouracil and methylthiouracil, are the most widely used by physicians in general practice. Such compounds have these advantages,—they are inexpensive, readily available, and tolerance or “fastness” to them does not develop. Because of their widespread use it seems desirable to report followup observations on a selected group of patients with unquestionable thyrotoxicosis treated with several goitrogenic substances and followed for intervals ranging from two to more than six years. This report deals with 46 such patients. Nineteen received thiouracil, 19 received propylthiouracil, 2 received aminothiazole, and 6 received thiouracil followed by propylthiouracil. All were selected for prolonged treatment because (a) the clinical picture suggested the probability of obtaining a sustained remission (mild to moderate severity of symptoms without marked thyroid enlargement), (b) because they presented postoperative recurrences of thyrotoxicosis, or (c) because they refused thyroidectomy. Initially the total daily dosage was divided into three equal parts. This was gradually reduced to a single daily maintenance dose as remission developed. The average daily initial dose of thiouracil was 0.7 Gm.; of propylthiouracil, 0.15 Gm.; and of aminothiazole, 0.6 Gm. The average daily maintenance doses were 0.1, 0.04 and 0.1 Gm., respectively. Data pertaining to age, sex distribution and types of goiter are shown in Table 1.
Symposium on modern trends in the management of thyrotoxicosis. Opening address
AbstractJournal Article Symposium on modern trends in the management of thyrotoxicosis. Opening address Get access W Michie W Michie Aberdeen Royal Infirmary Search for other works by this author on: Oxford Academic Google Scholar British Journal of Surgery, Volume 60, Issue 10, October 1973, Pages 757–758, https://doi.org/10.1002/bjs.1800601002 Published: 07 December 2005
Indian Journal of Endocrinology and Metabolism · 2012 · 1 citations · open access
Thyrotoxicosis and radioiodine therapy: Does the dose matter?
AbstractThere are 3 treatment options for thyrotoxicosis: Antithyroid drugs, Surgery and radioiodine. The choice of treatment varies geographically. Radioiodine therapy is preferred in the United States. The aim of radioiodine is to destroy sufficient thyroid tissue to cure the hyperthyroidism. There is a lack of consensus towards what dose of radioiodine should be used. Several methods are used to determine the dose. In our practice we administer 400 MBq to patients with Graves and in patients with large multinodular goiter, we would administer 800 MBq.
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.
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