DeCure for Pigmented nodular adrenocortical disease, primary, 4
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for pigmented nodular adrenocortical disease, primary, 4 — 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, 4 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
approvedAdenosine monophosphateApproved drug
Structures already discussed alongside pigmented nodular adrenocortical disease, primary, 4 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 CobT from Methanocaldococcus jannaschii — Adenosine monophosphate has a real, experimentally solved structure in complex with this target (PDB 6PT8, 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 aamdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6PT8 · 1.4 Å · ligand Adenosine monophosphate (AAM). Experimental structure, not a prediction.
What the evidence adds up to
Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of Cushing syndrome in infants, children, and young adults, characterised by non-adrenocorticotropic hormone-dependent hypersecretion of cortisol from multiple pigmented nodules. Biochemically, it is defined by elevated plasma and urinary cortisol that is not suppressed by high doses of dexamethasone (8 mg per day for two days). Pathologically, the adrenal glands contain multiple dark brown or black nodules with atrophic intervening cortical tissue. More than ninety percent of reported cases occur as part of Carney complex. In one series of four patients aged 10 to 38 years with germline inactivating mutations of the PDE11A4 gene, three had small adrenal glands with pigmented micronodules deep in the cortex, while the fourth had slightly enlarged glands due to diffuse hyperplasia of the superficial cortex extending into the epi-adrenal fat.
A 1999 study described a paradoxical response to dexamethasone as a diagnostic feature of PPNAD. The histology varies with age, with pigmentation increasing over time. Presentation in early childhood is very rare. Bilateral adrenalectomy is considered the treatment of choice. The disease is potentially deadly, though the abstracts do not provide specific survival or mortality figures. No drug therapy is mentioned in any of the abstracts; the only intervention discussed is surgical removal of both adrenal glands.
The abstracts provide no data on response rates to any pharmacological treatment, no survival statistics, and no controlled trials. What is missing is any evidence for a drug that could replace or delay adrenalectomy, any prospective trial design, and any stratification of patients by genetic subtype (such as PDE11A4 versus PRKAR1A mutations) that might guide future therapy.
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 American Journal of Surgical Pathology · 2010 · 36 citations · open access
Familial Micronodular Adrenocortical Disease, Cushing Syndrome, and Mutations of the Gene Encoding Phosphodiesterase 11A4 (PDE11A)
AbstractWe present the pathologic findings in the adrenal glands of 4 patients, aged 10 to 38 years, with Cushing syndrome and germline inactivating mutations of the gene PDE11A4 that encodes phosphodiesterase11A4. The gene is expressed in the adrenal cortex and catalyses the hydrolysis of cyclic adenosine monophosphate and cyclic guanosine monophosphate. Two of the patients were mother and daughter; the third had no affected relative; the fourth patient inherited the mutation from her father. Three of the group, including the mother and daughter, had the same pathology, primary pigmented nodular adrenocortical disease, a disorder known to be caused by inactivating mutations of the PRKAR1A gene. In these cases, the adrenal glands were small and the pathologic change was deep in the cortex in which numerous pigmented micronodules developed. In the remaining patient, the glands were slightly enlarged primarily owing to a diffuse hyperplasia of the superficial cortex that extended into the epi-adrenal fat.
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.
American journal of diseases of children · 1964 · 8 citations
Pigmentation in Addison's Disease
AbstractPigmentation may occur as an isolated clinical manifestation in adults with Addison's disease. It may be present for years before the appearance of the other characteristic manifestations of adrenocortical failure. Soffer, Dorfman, and Gabrilove<sup>1</sup>reported a patient with Addison's disease who had pigmentation as the only sign for 18 years; five others were abnormally pigmented for ten, seven, six, five, and four years, respectively, before the appearance of other evidence. The presence of pigmentation as the sole manifestation of Addison's disease in adults has been well documented by Abu Haydar et al2 and by Smith.<sup>3</sup> Pigmentation is a frequent finding in children with Addison's disease. Of the 62 proven cases reviewed by Jaudon,<sup>4</sup>93.3% had pigmentation. To our knowledge, no documented case of Addison's disease in a child with pigmentation as the only manifestation has been reported. Six of the cases quoted by Jaudon<sup>4</sup>had a
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.
