DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Adrenocorticotropic hormone deficiency — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAdrenocorticotropic hormone deficiency maps to a 2-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 adrenocorticotropic hormone deficiency 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.
What the evidence adds up to
Two patients with isolated ACTH deficiency were described in 1960, a 58-year-old woman and a 28-year-old man, both with weight loss and weakness; the woman died of adrenal insufficiency, and postmortem showed small but intact adrenals, an intact pituitary and a normal hypothalamus, with the specific cause of the ACTH deficiency unknown. A 2008 report describes a peripubertal girl with isolated ACTH deficiency and a normal TPIT gene who presented with an acute neurologic emergency, noting that early-onset forms have been linked to TPIT mutations but the genetic basis of juvenile- or late-onset IAD is unknown. A 2017 paper presents two cases of isolated ACTH deficiency with different outcomes, listing possible causes including autoimmune lymphocytic hypophysitis, traumatic brain injury, tumours, pituitary irradiation, and ischemic brain insult, and emphasises that the condition is not always permanent.
A 2009 case report describes a 69-year-old woman with isolated ACTH deficiency who developed Takotsubo cardiomyopathy during acute adrenal crisis; replacement therapy with hydrocortisone sufficiently improved her cardiomyopathy. A 2022 retrospective study of nine patients with adrenal histoplasmosis in eastern India found that 77.8% had signs of adrenal insufficiency, all had bilateral adrenal mass, and one patient died (11.1%); treatment with antifungal agents with or without hydrocortisone or fludrocortisone was effective in most, but adrenocortical function did not recover completely and many required long-term hydrocortisone supplementation.
The 1960 report notes that neither patient had hyperpigmentation, both had normal thyroidal and gonadal function, and no evidence of intracranial tumour or prior glucocorticoid therapy. The 2022 study reports that 44.4% of patients had predisposing immunocompromised conditions (diabetes or chronic alcoholism) while the rest were immunocompetent, and that mineralocorticoid deficiency was not permanent. What remains missing are prospective studies with larger sample sizes, systematic genetic screening for juvenile- and late-onset cases, and trials that stratify patients by aetiology to determine which cases of isolated ACTH deficiency are reversible and which require lifelong replacement.
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 · 1960 · 45 citations
HYPOADRENOTROPISM: THE ISOLATED DEFICIENCY OF ADRENOTROPIC HORMONE
AbstractTwo patients with an isolated deficiency of adrcnotropic hormone are presented. One was a female patient, aged 58, who had a six-year history of profound weight loss, weakness and loss of axillary and pubic hair. The second was a male patient, aged 28, who suffered from weight loss, weakness and spontaneous hypoglycemic attacks. Neither patient had the hyperpigmentation characteristic of primary adrenal insufficiency and both were shown to have adrenal insufficiency that changed to a state of normal adrenal function during treatment with ACTH. Thyroidal and gonadal functions were normal. Neither patient had evidence of an intracranial tumor, and neither had received previous glucocorticoid therapy. The female patient died of adrenal insufficiency, and postmortem studies revealed small but intact adrenals, an intact pituitary and a normal hypothalamus. These patients suffered from a deficiency of circulating ACTH but the specific etiology of this deficiency is unknown.
Internal Medicine · 2009 · 30 citations · open access
Takotsubo Cardiomyopathy during Acute Adrenal Crisis due to Isolated Adrenocorticotropin Deficiency
AbstractWe report a 69-year-old woman who had isolated adrenocorticotropic hormone (ACTH) deficiency. Subsequently, she had Takotsubo cardiomyopathy during acute adrenal crisis. Replacement therapy with hydrocortisone sufficiently improved her cardiomyopathy. We conclude that her myocardial dysfunction was closely related to adrenal insufficiency and suggest that in certain circumstances, adrenal crisis may cause Takotsubo cardiomyopathy.
Journal of Pediatric Endocrinology and Metabolism · 2008 · 6 citations
Isolated Adrenocorticotropic Hormone Deficiency Presenting as an Acute Neurologic Emergency in a Peripubertal Girl
AbstractIsolated adrenocorticotropic hormone (ACTH) deficiency (IAD) is extraordinarily rare, and the clinical manifestations of its accompanying adrenal insufficiency are diverse. Early-onset forms of IAD have been linked to mutations in the Tpit transcription factor gene TPIT; however, the genetic basis of juvenile- or late-onset IAD is unknown. Herein, we describe a case of a peripubertal girl with IAD and a normal TPIT gene who presented with an acute neurologic emergency, demonstrating both the variable clinical presentation of IAD and the need for continued investigation into the molecular mechanisms underlying juvenile- and late-onset IAD.
Adrenal Histoplasmosis: an Eastern Indian Perspective
AbstractContext: The clinical presentation of histoplasmosis is varied. Due to its propensity for adrenal involvement, histoplasmosis is an important differential diagnosis in any patient presenting with adrenal mass, bilateral in particular. Objective: Data on clinical presentation, pattern of adrenal involvement, radiological appearance and long-term follow-up of adrenal histoplasmosis are relatively sparse; hence we looked at it. Design: This record based single-centre retrospective study was conducted in one of the tertiary care hospitals, situated in eastern India catering the Gangetic delta. Subjects and methods: Data on demographic characters, presenting manifestations, biochemical & hormonal parameters and radiological appearance of confirmed adrenal histoplasmosis cases (n=9), admitted between 2015-2019 have been retrieved. The treatment outcome and condition of patients after 1-4 years of follow-up has also been discussed. Results: Four out of the nine (44.4%) patients had predisposing immunocompromised conditions in the form of diabetes and/or chronic alcoholism while rest were immunocompetent. Seven out of nine patients (77.8 %) had signs and symptoms suggestive of adrenal insufficiency, while two (22.2%) presented with only pyrexia of unknown origin. All of them had bilateral adrenal mass, though the radiologically appearances were different. All patients received anti-fungal agents with/without hydrocortisone and/or fludrocortisone. One patient died (11.1%), while majority responded favourably to treatment. Adrenocortical function did not recover completely. Conclusions: The possibility of adrenal histoplasmosis should always be considered in patients presenting with bilateral adrenal mass, irrespective of adrenal morphology. Treatment is effective, but many of them require supplemental hydrocortisone for quite a long period, if not lifelong. Mineralocorticoid deficiency, however, is not permanent.
International Clinical Pathology Journal · 2017 · 0 citations · open access
Isolated Adrenocorticotropic Hormone Deficiency not Always Permanent
AbstractIsolated Adrenocorticotrophic hormone (ACTH) deficiency is rare but could be a lifethreatening condition characterized by hypocortisolism. Most causes are secondary to autoimmune process such as lymphocytic hypophysitis. It may also occur after traumatic brain injury, tumors, pituitary irradiation and ischemic brain insult. Genetic causes are not infrequent. We present two causes of Isolated Adrenocorticotrophic Hormone (ACTH) deficiency who experienced different outcomes and highlight the importance of understanding the various possible aetio-pathophysiology.
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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