DeCure for Pigmented nodular adrenocortical disease, primary, 1
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for pigmented nodular adrenocortical disease, primary, 1 — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePigmented nodular adrenocortical disease, primary, 1 maps to a 1-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 pigmented nodular adrenocortical disease, primary, 1 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
protein kinase cAMP-dependent type I regulatory subunit alpha (PRKAR1A) — PRKAR1A 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 pcgdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5KJZ · 1.347 Å · ligand CYCLIC GUANOSINE MONOPHOSPHATE (PCG). Experimental structure, not a prediction.
What the evidence adds up to
Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome, characterised by small to normal-sized adrenal glands containing multiple pigmented nodules. Biochemically, it presents with elevated plasma and urinary cortisol that are not suppressed by high doses of dexamethasone (8 mg per day for 2 days). The intervening cortical tissue between nodules is atrophic. PPNAD may occur in isolation or as part of Carney complex, a multiple neoplasia syndrome in which Cushing's syndrome is the most common endocrine manifestation; more than ninety percent of reported cases occur as one manifestation of Carney complex. Most cases are diagnosed in the second or third decade of life, and presentation in early childhood is very rare. The histology varies with age, with pigmentation increasing over time.
Bilateral adrenalectomy is described as the treatment of choice. Molecular studies have identified defects in several genes involved in the cAMP signalling pathway that may predispose to PPNAD formation. The three abstracts provide no data on drug treatments, response rates, survival, or sample sizes from interventional studies. One abstract is a review, one is a single case report with literature review, and one reports three paediatric cases with unusual histology.
No drug therapy is mentioned in any of these abstracts. What remains missing are prospective clinical trials, any evidence for medical management, and patient stratification beyond the known genetic subtypes. The rarity of the disease makes trial design and funding difficult.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Arquivos Brasileiros de Endocrinologia & Metabologia · 2007 · 31 citations · open access
Primary pigmented nodular adrenocortical disease and Cushing's syndrome
AbstractPrimary pigmented nodular adrenocortical disease (PPNAD) is a form of bilateral adrenocortical hyperplasia that is often associated with corticotrophin (ACTH)-independent Cushing's syndrome (CS) and is characterized by small to normal-sized adrenal glands containing multiple small cortical pigmented nodules (1,2). PPNAD may occur in an isolated form or associated with a multiple neoplasia syndrome, the complex of spotty skin pigmentation, myxomas, and endocrine overactivity, or Carney complex, in which Cushing's syndrome is the most common endocrine manifestation (3). Molecular studies have led to the identification of several genes, defects in which may predispose PPNAD formation; all of these molecules play important role for the cAMP signaling pathway. This review intends to present the most recent knowledge of the pathology and molecular genetics of the benign bilateral adrenocortical lesions, as well as to discuss the modern tools for diagnostics and treatment of this condition.
The Korean Journal of Internal Medicine · 1995 · 13 citations · open access
Cushing`s Syndrome Due To Primary Pigmented Nodular Adrenocortical Disease - A Case Report Reviews of the Literature-
AbstractPrimary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of Cushing's syndrome in infants, children and young adults. It is characterized by non-adrenocorticotropic hormone-dependent hypersecretion of cortisol by multiple, pigmented nodules of hyperplastic adrenocortical cells. Biochemically, PPNAD is characterized by elevated levels of plasma and urinary cortisol that are not suppressed by high doses of dexamethasone (8mg/d for 2 days). Pathologically, the adrenal glands contain multiple dark brown or black nodules and the intervening cortical tissue is atrophic. Recognition of this diagnosis, although rare, is important, as bilateral adrenalectomy is the treatment of choice. We experienced a case of Cushing's syndrome due to primary pigmented nodular adrenocortical disease and report it with reviews of the literature.
Indian Journal of Pathology and Oncology · 2022 · 0 citations · open access
Primary pigmented nodular adrenocortical disease: Unusual histology in children- A report of 3 cases
AbstractPrimary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of adrenocorticotropin independent Cushing Syndrome. Majority cases are diagnosed in second or third decade of life. Presentation of PPNAD in early childhood is very rare. It is characterized by adrenocorticotrophic hormone [ACTH] independent, hypersecretion of cortisol by multiple, pigmented nodules of hyperplastic adrenocortical cells. The histology varies with age, the pigmentation increasing with age. More than ninety percent of reported cases of PPNAD occur as one of the manifestation of Carney’s complex.
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.
