DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for multinodular goiter — screening already-approved drugs against its 40-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleMultinodular goiter maps to a 40-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
No approved-drug candidate for multinodular goiter is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
inositol-tetrakisphosphate 1-kinase (ITPK1) — ITPK1 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet anpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2Q7D · 1.6 Å · ligand PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER (ANP). Experimental structure, not a prediction.
What the evidence adds up to
Shear wave elastography was tested against histology in 146 nodules from 93 patients, of which 29 (19.9%) were malignant. Mean elasticity index was 150±95 kPa in malignant nodules versus 36±30 kPa in benign ones (P<0.001). At a cutoff of 65 kPa, sensitivity was 85.2% and specificity 93.9% for a positive predictive value of at least 80%. Adding elastography to conventional ultrasound scoring raised sensitivity from 51.9% to 81.5% while keeping specificity at 97.0%. The authors concluded the technique may be applicable to multinodular goiters but called for larger prospective studies to define its place relative to ultrasound and fine-needle aspiration.
Radioiodine therapy in 130 consecutive patients with multinodular toxic goiter produced cure with one or two treatments in 119 patients (92%), with 68 (52%) euthyroid within three months. Median thyroid volume fell from 44 mL to 25 mL, a 43% reduction, 24 months after the last dose. Hypothyroidism developed in 14% within five years, but was significantly more common in patients who received antithyroid drug pretreatment (20% versus 6%, P<0.005). The authors recommended iodine-131 as the treatment of choice for multinodular toxic goiter.
A 47-year-old Japanese woman with hyperthyroidism and a large multinodular goiter, whose paternal history included goiter, was found to carry a germline heterozygous KEAP1 mutation (c.1448 G>A, p.R483H). Total thyroidectomy removed a 209 g benign gland. Nuclear accumulation of NRF2 was much higher in her nodules than in nodules from four unrelated multinodular goiter patients. No additional germline mutations were found in genes known to be associated with multinodular goiter.
A retrospective cohort of 33 patients with substernal goiter treated by thyroidectomy through a single neck incision reported no definitive recurrent laryngeal nerve lesions and no definitive hypoparathyroidism. Two patients had transient recurrent nerve paresis and two required re-operation for neck hematoma. A case report described a 54-year-old man with a 20-year multinodular goiter found to harbour coexistent papillary and anaplastic thyroid carcinoma (T3 N0 M0, stage IVA) after total thyroidectomy; he received external beam radiation and showed no progression at 12 weeks, but was then lost to follow-up. A 1911 surgical series reported no mortality in 167 consecutive goiter operations, attributing safety to early recognition and operation.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The Journal of Clinical Endocrinology & Metabolism · 2010 · 423 citations
Shear Wave Elastography: A New Ultrasound Imaging Mode for the Differential Diagnosis of Benign and Malignant Thyroid Nodules
AbstractCONTEXT: Elastography uses ultrasound (US) to assess elasticity. Shear wave elastography (SWE) is a new technique that estimates tissue stiffness in real time and is quantitative and user independent. OBJECTIVES: The aim of the study was to assess the efficiency of SWE in predicting malignancy and to compare SWE with US. DESIGN: Ninety-three patients and 39 control subjects were included in the study. Predictive value of SWE was assessed by correlation between elasticity, US parameters, and histology. Elasticity index (EI) was first analyzed alone. Scores have been constructed with echographic parameters, i.e. vascularity, hypoechogenicity, and microcalcifications (Score 1=US Score), and with the same parameters plus EI (Score 2=US+SWE Score). For statistical analysis, univariate and multivariate analysis and receiver operating characteristic curves were used. RESULTS: A total of 146 nodules from 93 patients were analyzed. Twenty-nine nodules (19.9%) were malignant. Mean (±sd) EI was 150±95 kPa (range, 30-356) in malignant nodules vs. 36±30 (range, 0-200) kPa in benign nodules (P<0.001, Student's t test). For a positive predictive value of at least 80%, characteristics of tissue elasticity (cutoff, 65 kPa) were: sensitivity=85.2%, and specificity=93.9%. Characteristics of the US Score were: sensitivity=51.9% [95% confidence interval (CI), 33.1; 70.7], and specificity=97% (95% CI, 93.6; 1). Characteristics of the US+SWE Score were: sensitivity=81.5% (95% CI, 66.9; 96.1), and specificity=97.0% (95% CI, 93.6; 1). CONCLUSION: Promising results have been obtained with SWE. This technique may be applied to multinodular goiters. Larger prospective studies are needed to confirm these results and to define the respective places of SWE, US, and FNA.
Archives of Internal Medicine · 1999 · 121 citations · open access
Radioiodine Therapy for Multinodular Toxic Goiter
AbstractBACKGROUND: Radiolabeled iodine 131 therapy is used for treatment of multinodular toxic goiter, but long-term follow-up studies are lacking. METHODS: A prospective study of 130 consecutive patients (115 women) treated with 131I for multinodular toxic goiter and followed by evaluation of thyroid volume (determined using ultrasound) and thyroid function variables. RESULTS: The patients were observed for a median of 72 months (range, 12-180 months). Sixty-six patients received antithyroid drug pretreatment; 64 did not. Iodine 131 treatment (3.7 MBq/g thyroid tissue corrected to a 100% 24-hour 131I uptake) was given as a single dose in 81 patients, 2 doses in 38, and 3 to 5 doses in 11. One or 2 treatments cured 119 patients (92%), and 68 (52%) became euthyroid within 3 months after 131I treatment. The median 131I dose was 370 MBq (range, 93-1850 MBq). Forty-nine patients needing more than 131I dose had a reduction in median thyroid volume from 56 mL (range, 21-430 mL) to 44 mL (range, 15-108 mL), representing a 24% reduction related to the insufficient 131I dose. In all patients, the initial median thyroid volume of 44 mL (range, 16-430 mL) decreased to 25 mL (range, 8-120 mL) (P<.005), representing a median reduction of 43%, 24 months after the last 131I dose. Hypothyroidism evaluated using life-table analysis developed in 6% of patients who did not receive antithyroid pretreatment and 20% who did (P<.005) after a median of 42 months (range, 3-60 months), the total hypothyroidism frequency being 14% within 5 years of treatment. CONCLUSIONS: Ninety-two percent of patients with multinodular toxic goiter were cured with 1 or 2 treatments. The thyroid volume was reduced by 43%, with few side effects. Iodine 131 should be the choice of treatment in patients with multinodular toxic goiter.
Frontiers in Endocrinology · 2016 · 24 citations · open access
A Novel Germline Mutation of KEAP1 (R483H) Associated with a Non-Toxic Multinodular Goiter
AbstractBACKGROUND: gene was reported as a novel genetic abnormality associated with familial multinodular goiter. That report was limited, and the pathogenic features were not well established. PATIENT FINDINGS: We report a 47-year-old Japanese woman who presented with hyperthyroidism and a large multinodular goiter. The family history was notable for a paternal history of goiter. Graves' disease was diagnosed based on positive TRAb, but scintiscan imaging showed that the patient's radioiodine uptake was restricted in the non-nodular areas, indicating largely cold nodules. A total thyroidectomy was performed. The resected thyroid tissue weighed 209 g, and subsequent pathological findings were benign. The patient had a germline heterozygous KEAP1 mutation, c. 1448 G > A, resulting in an amino acid substitution (p.R483H). A next-generation sequencing analysis covering all known genes associated with multinodular goiter showed no additional germline mutation. The nuclear accumulation of NRF2, a protein associated with KEAP1, was shown at much higher rates in the patient's nodules compared with nodules obtained from four unrelated patients with multinodular goiters. CONCLUSION: gene was associated with the development of a non-toxic multinodular goiter.
Brazilian Journal of Otorhinolaryngology · 2009 · 12 citations · open access
A critical analysis of 33 patients with substernal goiter surgically treated by neck incision
AbstractUNLABELLED: The possibility of needing a combined access, with neck and chest incisions makes the treatment of substernal goiter a challenge both in the pre-op and the intraoperative. We hereby, discuss a standardization of the surgical technique to minimize the need for a chest approach, making the substernal goiter a surgically treatable disease, through a single neck incision, and with low indices of complication. AIM: To assess the substernal goiter surgically approach through a neck incision and to analyze the surgical complications. MATERIALS AND METHODS: We carried out a historical cohort by retrospective analysis of the charts of patients submitted to thyroidectomy, and 33 of them (10.4%) had substernal goiter. RESULTS: All 33 patients were surgically treated through a neck incision without the need for sternotomy. We did not observe definitive lesions in the inferior laryngeal nerve or definitive hypoparathyroidism. Only 2 patients had recurrent nerve paresis; and 2 patients were re-operated because of a neck hematoma. CONCLUSION: Patients with substernal goiter can be safely treated surgically through a single neck incision, bearing low complication rates.
Annals of Medicine and Surgery · 2020 · 5 citations · open access
A rare coexistence of papillary carcinoma and anaplastic carcinoma of thyroid in multinodular goitre: Case report and literature review
AbstractINTRODUCTION: Multinodular goiter is defined as multiple discrete nodules in the thyroid gland. The incidence of Papillary carcinoma thyroid was found to be highest out of total Multinodular Goiter cases while that of Anaplastic carcinoma was the least. We report a rare coexistence of Papillary carcinoma and Anaplastic carcinoma in adult patient with a long-standing Multinodular Goiter. CASE PRESENTATION: Here we present a case of 54 years male with huge anterior neck swelling for 20 years with a gradual increase in size. Computerized tomography of neck revealed solidocystic mass lesion without any significant lymphadenopathy, features suggesting Multinodular goiter with differential diagnosis of Carcinoma Thyroid. Cytological examination showed Papillary thyroid Carcinoma. He underwent total thyroidectomy with central neck dissection. Postoperative period was uneventful. Histopathological report revealed features suggestive of mixed tumor of Papillary thyroid Carcinoma and Anaplastic Carcinoma thyroid TNM Staging T3 N0 M0, Stage IVA. After the final reports patient was sent for adjuvant therapy three weeks later where he received megavoltage external beam radiation and he was followed up till 12th week. He was assessed radiologically which showed no signs of physical progression of the disease. However, he was lost to follow up after that visit. DISCUSSION: Long-standing benign conditions of thyroid can transform into malignant forms in the undefined duration of time. CONCLUSION: Regular follow up and early management of multinodular goiter at the right time can save a patient from undue stress and complication like the conversion into malignancy.
FACTORS INFLUENCING THE SAFETY OF OPERATION FOR GOITER
AbstractNo form of treatment for goiter has stood the test of years as has surgery since 1885, when Kocher reported the first considerable number of operations. Numerous patients treated for years by drugs, serums and other measures have later sought relief in surgery, and the number of enlightened internists who, like Osler, refer their patients for operation after three months' unavailing medical treatment is rapidly increasing. A further increase in the amount of goiter surgery will depend on our success in convincing the general practitioner and the patient of the safety of operation. A study of my recent methods with no mortality in 167 consecutive cases in comparison with earlier work, which was much less successful, may offer some suggestions to those interested in this subject. <h3>EARLY OPERATION FOR SAFETY</h3> As in many pathologic conditions, the safety of the patient may depend in large part on the early recognition and
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works using Disease Ontology synonyms, 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.
