DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for hypoparathyroidism — screening already-approved drugs against its 8-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHypoparathyroidism maps to a 8-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
approvedCalcitriolApproved drug
Structures already discussed alongside hypoparathyroidism in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Crystal Structure Of The Nuclear Receptor For Vitamin D Ligand Binding Domain — Calcitriol has a real, experimentally solved structure in complex with this target (PDB 1IE9, 1.4 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 vdxdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1IE9 · 1.4 Å · ligand Calcitriol (VDX). Experimental structure, not a prediction.
What the evidence adds up to
Hypoparathyroidism is a disorder of hypocalcaemia caused by insufficient parathyroid hormone secretion. The prevalence is estimated at 37 per 100,000 person-years in the United States and 22 per 100,000 person-years in Denmark, with an incidence in Denmark of 0.8 per 100,000 person-years. The most common cause is postsurgical, followed by autoimmune and rare genetic disorders. In a Dutch multicentre cohort of 200 patients who underwent total or completion thyroidectomy, 15% developed persistent hypoparathyroidism, defined as the need for active vitamin D with or without calcium supplementation longer than one year after surgery. The incidence varied from 14.5% to 28.5% depending on the definition used. In a separate nationwide cohort of 260 patients with permanent hypoparathyroidism after total thyroidectomy, 15% were not adequately controlled, meaning they had symptoms of hypocalcaemia, low serum calcium, or high urinary calcium excretion. Those patients required higher doses of oral calcium and calcitriol, had a higher rate of hospitalisation during follow-up (35.9% vs 10.9%), and had lower postoperative PTH concentrations.
Chronic hypoparathyroidism is conventionally treated with oral calcium, calcitriol or other active vitamin D analogues, and sometimes thiazide diuretics. Standard therapy can control the disease, but high doses may be needed, with poor compliance and risk of long-term complications such as renal insufficiency, kidney stones, posterior subcapsular cataracts, and intracerebral calcifications. Hypoparathyroidism does not appear to increase overall mortality, cardiovascular disease, fractures, or malignancy. In a prospective study comparing subtotal parathyroidectomy and total parathyroidectomy with autotransplant for secondary hyperparathyroidism in 43 dialysis patients, definitive hypoparathyroidism occurred in 8.3% of the subtotal group and 5.26% of the total-with-autotransplant group; the difference was not statistically significant.
In an early real-world analysis of 123 patients in a U.S. expanded access programme, palopegteriparatide (TransCon PTH) was administered at a starting dose of 18 μg/day and titrated alongside conventional therapy. Nearly all patients (95.1%) had previously been treated with short-lived PTH therapy. Over 12 months, the proportion of patients achieving independence from conventional therapy (no calcitriol and ≤600 mg/day elemental calcium) increased. Mean serum calcium remained within the reference range, and no new safety signals were identified. Two families with dominantly transmitted isolated hypoparathyroidism were found to have heterozygous splice-altering mutations in TBX1, with reduced penetrance and variable expressivity. What remains missing are uniform evidence-based treatment guidelines that enable comparison of interventions, prospective data on long-term outcomes with newer agents, and studies that stratify patients by aetiology or genetic subtype to predict which treatments might work for whom.
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 · 2016 · 353 citations · open access
Epidemiology and Diagnosis of Hypoparathyroidism
AbstractCONTEXT: Hypoparathyroidism is a disorder characterized by hypocalcemia due to insufficient secretion of PTH. Pseudohypoparathyroidism is a less common disorder due to target organ resistance to PTH. This report summarizes the results of the findings and recommendations of the Working Group on Epidemiology and Diagnosis of Hypoparathyroidism. EVIDENCE ACQUISITION: Each contributing author reviewed the recent published literature regarding epidemiology and diagnosis of hypoparathyroidism using PubMed and other medical literature search engines. EVIDENCE SYNTHESIS: The prevalence of hypoparathyroidism is an estimated 37 per 100 000 person-years in the United States and 22 per 100 000 person-years in Denmark. The incidence in Denmark is approximately 0.8 per 100 000 person-years. Estimates of prevalence and incidence of hypoparathyroidism are currently lacking in most other countries. Hypoparathyroidism increases the risk of renal insufficiency, kidney stones, posterior subcapsular cataracts, and intracerebral calcifications, but it does not appear to increase overall mortality, cardiovascular disease, fractures, or malignancy. The diagnosis depends upon accurate measurement of PTH by second- and third-generation assays. The most common etiology is postsurgical hypoparathyroidism, followed by autoimmune disorders and rarely genetic disorders. Even more rare are etiologies including parathyroid gland infiltration, external radiation treatment, and radioactive iodine therapy for thyroid disease. Differentiation between these different etiologies is aided by the clinical presentation, serum biochemistries, and in some cases, genetic testing. CONCLUSIONS: Hypoparathyroidism is often associated with complications and comorbidities. It is important for endocrinologists and other physicians who care for these patients to be aware of recent advances in the epidemiology, diagnosis, and genetics of this disorder.
JAMA Otolaryngology–Head & Neck Surgery · 2021 · 44 citations · open access
Persistent Postthyroidectomy Hypoparathyroidism in the Netherlands
AbstractImportance: Hypoparathyroidism is one of the most common complications after total or completion thyroidectomy. The reported incidence rate of hypoparathyroidism in the literature is highly variable. Data that provide a better understanding of the magnitude of this postoperative complication are warranted and can provide a stepping stone for further collaborations that aim to reduce complication rates and establish uniform treatment protocols. Objective: To evaluate the incidence of postoperative, persistent hypoparathyroidism after total or completion thyroidectomy in patients who were referred to university hospital centers and assess the association of different definitions with the incidence of hypoparathyroidism. Design, Setting, and Participants: This retrospective multicenter cohort study conducted throughout 2016 in 7 Dutch university hospital centers included 200 patients who were undergoing a total or completion thyroidectomy. Data analysis was conducted in January 2021. Main Outcomes and Measures: We report on the incidence of persistent hypoparathyroidism, defined as the need for active vitamin D with or without calcium supplementation longer than 1 year after surgery. Results: A total of 200 patients (143 women [71.5%]; mean [IQR] age, 49.0 [37.0-62.0] years) were included and 30 patients (15.0%) developed persistent hypoparathyroidism. The incidence of persistent hypoparathyroidism varied between 14.5% (calcium and active vitamin D 1 year postsurgery) to 28.5% (calcium and/or active vitamin D 6 months postsurgery) depending on the definition used. Conclusions and Relevance: In this cohort study, the risk of persistent hypoparathyroidism after total or completion thyroidectomy was 15% in patients who were referred to university hospital centers. The high rate of persistent hypoparathyroidism warrants efforts to reduce this complication rate. There is discrepancy in the definition and treatment of persistent hypoparathyroidism, and use of uniform evidence-based treatment guidelines enables comparison of interventions.
Endokrynologia Polska · 2016 · 19 citations · open access
Częściowe usunięcie przytarczyc versus całkowite usunięcie przytarczyc z autoprzeszczepem we wtórnej nadczynności przytarczyc — jednoośrodkowe, prospektywne badanie w grupie 43 pacjentów
AbstractINTRODUCTION: The need for parathyroidectomy remains high in the group of patients on long-term dialysis with medically refractory secondary hyperparathyroidism (sHPT). We aim to compare the results after subtotal parathyroidectomies (sPtx) and total parathyroidectomies with autotransplant (tPtx + AT) performed for sHPT at a single referral centre. MATERIAL AND METHODS: This prospective study comparatively analysed sPtx and tPtx + AT performed in our department between February 2010 and December 2014. We followed-up both surgical techniques, with respect to the main clinical symptoms, laboratory data, mortality, and recurrent disease. RESULTS: Forty-three patients on whom we performed 26 sPtx and 19 tPtx + AT were entered in the study. There were no statistically significant differences between groups as far as demographic and preoperative clinical data are concerned. We did not encounter postoperative mortality in either of the groups. The follow-up period was significantly longer for the sPtx group (p = 0.04). The immediate postoperative serum calcium levels were significantly lower in the tPtx + AT group (p = 0.009). Definitive hypoparathyroidism was encountered in two patients in the sPtx group (8.3%) and in one from the tPtx + AT group (5.26%). Four patients from the sPtx group (16.6%) and three from the tPtx + AT group (15.78%) died during the follow-up due to causes unrelated to parathyroidectomy. Overall we had two recurrences in the sPtx group and none in the tPtx + AT group (p = 0.57). CONCLUSIONS: In our opinion both techniques have comparable results concerning the clinical and laboratory outcomes and rates of postoperative hypoparathyroidism, at least in short- and medium-term follow-up.
The Journal of Clinical Endocrinology & Metabolism · 2018 · 18 citations · open access
Heterozygous Mutations in TBX1 as a Cause of Isolated Hypoparathyroidism
AbstractContext: Most cases of autosomal dominant isolated hypoparathyroidism are caused by gain-of-function mutations in CASR or GNA11 or dominant negative mutations in GCM2 or PTH. Objective: To identify the genetic etiology for dominantly transmitted isolated hypoparathyroidism in two multigenerational families with 14 affected family members. Methods: We performed whole exome sequencing of DNA from two families and examined the consequences of mutations by minigene splicing assay. Results: We discovered disease-causing mutations in both families. A splice-altering mutation in TBX1 (c.1009+1G>C) leading to skipping of exon 8 (101 bp) was identified in 10 affected family members and five unaffected subjects of family A, indicating reduced penetrance for this point mutation. In a second family from France (family B), we identified another splice-altering mutation (c.1009+2T>C) adjacent to the mutation identified in family A that results in skipping of the same exon; two subjects in family B had isolated hypoparathyroidism, whereas a third subject manifested the clinical triad of the 22q11.2 deletion syndrome, indicative of variable expressivity. Conclusions: We report evidence that heterozygous TBX1 mutations can cause isolated hypoparathyroidism. This study adds knowledge to the increasingly expanding list of causative and candidate genes in isolated hypoparathyroidism.
Permanent postoperative hypoparathyroidism: an analysis of prevalence and predictive factors for adequacy of control in a cohort of 260 patients
AbstractBackground: Recent guidelines for the treatment of hypoparathyroidism emphasize the need for long-term disease control, avoiding symptoms and hypocalcaemia. Our aim has been to analyze the prevalence of poor disease control in a national cohort of patients with hypoparathyroidism, as well as to evaluate predictive variables of inadequate disease control. Methods: From a nation-wide observational study including a cohort of 1792 patients undergoing total thyroidectomy, we selected 260 subjects [207 women and 53 men, aged (mean ± SD) 47.2±14.8 years] diagnosed with permanent hypoparathyroidism. In every patient demographic data and details on surgical procedure, histopathology, calcium (Ca) metabolism, and therapy with Ca and calcitriol were retrospectively collected. A patient was considered not adequately controlled (NAC) if presented symptoms of hypocalcemia or biochemical data showing low serum Ca levels or high urinary Ca excretion. Results: Two hundred and twenty-one (85.0%) patients were adequately controlled (AC) and 39 (15.0%) were NAC. Comparison between AC and NAC patients did not show any significant difference in demographic, surgical, and pathological features. Rate of hospitalization during follow-up was significantly higher among NAC patients in comparison with AC patients (35.9% vs. 10.9%, P<0.001). Dose of oral Ca and calcitriol were also significantly higher in NAC subjects. In a subgroup of 129 patients with serum parathyroid hormone (PTH) levels available, we found that NAC patients exhibited significantly lower postoperative PTH concentrations than AC patients [median (interquartile range) 3 (1.9–7.8) vs. 6.9 (3.0–11) pg/mL; P=0.009]. Conclusions: In a nation-wide cohort of 260 subjects with definitive hypoparathyroidism, 15% of them had poor disease control. These patients required higher doses of oral Ca and calcitriol, had higher rate of hospitalization during follow-up and showed lower PTH concentrations in the postoperative period.
Frontiers of hormone research · 2018 · 7 citations
Conventional Treatment of Hypoparathyroidism
AbstractThe treatment of hypoparathyroidism depends on the severity of hypocalcemia, how rapidly the hypocalcemia developed, and the symptomatology. Chronic hypoparathyroidism is usually treated with oral supplementations, including calcium, calcitriol, or other active vitamin D analogs, and at times, thiazide diuretics. Although the standard therapy can adequately control patients with this disease, sometimes very high doses are required to maintain serum calcium levels in the normal range, with poor compliance and risk of long-term complications.
Endocrine Practice · 2025 · 3 citations · open access
Early U.S. Real-World Treatment Patterns and Outcomes in Palopegteriparatide Treatment for Patients With Hypoparathyroidism
AbstractOBJECTIVE: To examine the impact of palopegteriparatide (YORVIPATH; TransCon PTH) on real-world clinical outcomes in adult patients with hypoparathyroidism. METHODS: Adult patients with hypoparathyroidism who enrolled in the U.S. expanded access program as of October 2024 and provided consent were included in the analysis. Palopegteriparatide was administered at a recommended starting dose of 18 μg/day and titrated alongside conventional therapy (calcitriol and calcium). Conventional therapy requirements, palopegteriparatide dosing, serum calcium levels, and adverse events were assessed up to 12 months of treatment. RESULTS: Among 135 patients enrolled in the expanded access program who received at least 1 dose of palopegteriparatide, 123 provided consent for data use and were included in analysis. Nearly all patients (95.1%, 117/123) were previously treated with short-lived parathyroid hormone (PTH) therapy (primarily teriparatide or recombinant human PTH [1-84]), and 50.4% (62/123) switched directly from short-lived PTH or PTH-related protein therapy to palopegteriparatide. There was no clinically meaningful difference (>3 μg) in palopegteriparatide dose between direct switch and nondirect switch patients, with a similar trend over time. With palopegteriparatide treatment, the proportion of patients achieving independence from conventional therapy (defined as taking no calcitriol and ≤600 mg/day of elemental calcium) increased over 12 months. Mean serum calcium levels remained within the reference range (8.3-10.6 mg/dL) with palopegteriparatide, and no new safety signals were identified with up to 12 months of treatment. CONCLUSION: This real-world analysis of palopegteriparatide treatment of hypoparathyroidism outside of a clinical trial setting reaffirms its efficacy and safety profile and provides insights into outcomes associated with different treatment transition practices.
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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