# Síndrome Cushing endógena

> Página oficial: https://raras.org/doenca/sindrome-cushing-endogena
> Fonte: Raras.org — Banco de Dados de Doenças Raras em Português (CC BY-NC-SA 4.0)
> Última atualização: 2026-05-07

## Identificadores

- **ORPHA**: 641613 — https://www.orpha.net/en/disease/detail/641613
- **OMIM**: none — https://omim.org/entry/none

## Descrição clínica

Grupo raro de distúrbios endócrinos causados ​​por níveis de exposição prolongados e altos a glicocorticoides de origem endógena (produção do córtex adrenal). As características clínicas típicas são obesidade facial e troncular, síndrome hipercatabólica (pele mais fina, estrias roxas, equimoses, hematomas sem trauma óbvio, fraqueza muscular proximal com amiotrofia, osteoporose) e, em crianças, ganho de peso com diminuição da velocidade de crescimento.

## Epidemiologia e herança


## Sinais e sintomas (126 fenótipos HPO)

- **Insônia** — HPO: HP:0100785
- **Livedo reticularis** — HPO: HP:0033505
- **Compressão do nervo óptico** — HPO: HP:0007807
- **Necrose avascular** — HPO: HP:0010885
- **Defeito do campo visual** — HPO: HP:0001123
- **Cefaleia** — HPO: HP:0002315
- **Carcinoma pulmonar de pequenas células** — HPO: HP:0030357
- **Sela túrcica grande** — HPO: HP:0002690
- **Hipergastrinemia** — HPO: HP:0500167
- **Pancreatoblastoma** — HPO: HP:0100757
- **Tumor carcinoide pulmonar** — HPO: HP:0030445
- **Neoplasia do timo** — HPO: HP:0100521
- **Fragilidade capilar** — HPO: HP:0025017
- **Comportamento atípico** — HPO: HP:0000708
- **Ataque de pânico** — HPO: HP:0025269
- **Câncer de próstata** — HPO: HP:0012125
- **Ideação suicida** — HPO: HP:0031589
- **Rubor** — HPO: HP:0031284
- **Infecções fúngicas cutâneas recorrentes** — HPO: HP:0011370
- **Tumores malignos do trato gastrointestinal** — HPO: HP:0006749
- **Acidente vascular cerebral** — HPO: HP:0001297
- **Contagem de eosinófilos diminuída** — HPO: HP:0031891
- **Fraqueza fatigável dos músculos proximais dos membros** — HPO: HP:0030200
- **Carcinoma medular de tireoide** — HPO: HP:0002865
- **Úlcera cutânea** — HPO: HP:0200042
- **Anormalidade do sistema respiratório** — HPO: HP:0002086
- **Hiperpigmentação intraoral** — HPO: HP:0010284
- **Imunodeficiência** — HPO: HP:0002721
- **Leucocitose** — HPO: HP:0001974
- **Anormalidade do sistema cardiovascular** — HPO: HP:0001626
- **Amenorreia** — HPO: HP:0000141
- **Infarto do miocárdio** — HPO: HP:0001658
- **Amenorreia secundária** — HPO: HP:0000869
- **Linfopenia** — HPO: HP:0001888
- **Fraqueza muscular** — HPO: HP:0001324
- **Feocromocitoma** — HPO: HP:0002666
- **Demência** — HPO: HP:0000726
- **Tumor carcinoide pulmonar atípico** — HPO: HP:0030446
- **Tumor endócrino pancreático** — HPO: HP:0030405
- **Edema periférico** — HPO: HP:0012398
- _...e mais 86 sintomas. Ver https://raras.org/doenca/sindrome-cushing-endogena._

## Genes associados (10)

- **GNAS** — Protein ALEX [Disease-causing germline mutation(s) in]
  - Função: May inhibit the adenylyl cyclase-stimulating activity of guanine nucleotide-binding protein G(s) subunit alpha which is produced from the same locus in a different open reading frame
- **CDH23** — Cadherin-23 [Candidate gene tested in]
  - Função: Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells. CDH23 is required for establishing and/or maintaining t
- **USP48** — Ubiquitin carboxyl-terminal hydrolase 48 [Candidate gene tested in]
  - Função: Deubiquitinase that recognizes and hydrolyzes the peptide bond at the C-terminal Gly of ubiquitin. Involved in the processing of polyubiquitin precursors as well as that of ubiquitinated proteins (Pub
- **BRAF** — Serine/threonine-protein kinase B-raf [Candidate gene tested in]
  - Função: Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus (Probable). Phosphorylates MAP2K1, and thereby activates the MAP kinase signal transduction pathw
- **NR3C1** — Glucocorticoid receptor [Candidate gene tested in]
  - Função: Receptor for glucocorticoids (GC) (PubMed:27120390, PubMed:37478846). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mi
- **TP53** — Cellular tumor antigen p53 [Candidate gene tested in]
  - Função: Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775
- **ATRX** — Transcriptional regulator ATRX [Candidate gene tested in]
  - Função: Involved in transcriptional regulation and chromatin remodeling. Facilitates DNA replication in multiple cellular environments and is required for efficient replication of a subset of genomic loci. Bi
- **KDM1A** — Lysine-specific histone demethylase 1A [Candidate gene tested in]
  - Função: Histone demethylase that can demethylate both 'Lys-4' (H3K4me) and 'Lys-9' (H3K9me) of histone H3, thereby acting as a coactivator or a corepressor, depending on the context (PubMed:15620353, PubMed:1
- **ARMC5** — Armadillo repeat-containing protein 5 [Candidate gene tested in]
  - Função: Substrate-recognition component of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that terminates RNA polymerase II (Pol II) transcription in the promoter-proximal region of genes (PubMed:39504960,
- **USP8** — Ubiquitin carboxyl-terminal hydrolase 8 [Disease-causing germline mutation(s) in]
  - Função: Hydrolase that can remove conjugated ubiquitin from proteins and therefore plays an important regulatory role at the level of protein turnover by preventing degradation. Converts both 'Lys-48' an 'Lys

## Ensaios clínicos ativos (2)

- **NCT06430528** [RECRUITING]: A Block-and-Replace Therapy With Osilodrostat and Concomitant Glucocorticoid Replacement — https://clinicaltrials.gov/study/NCT06430528
- **NCT03604198** [ACTIVE_NOT_RECRUITING]: Extension Study to Evaluate the Safety of Long-Term Use of Relacorilant in Patients With Cushing Syndrome — https://clinicaltrials.gov/study/NCT03604198
- **NCT03697109** [COMPLETED]: A Study of the Efficacy and Safety of Relacorilant in Patients With Endogenous Cushing Syndrome — https://clinicaltrials.gov/study/NCT03697109
- **NCT06131580** [UNKNOWN]: Canadian Continuation of Roll-over Study in Patients With Endogenous Cushing's Syndrome — https://clinicaltrials.gov/study/NCT06131580

## Doenças relacionadas (por similaridade fenotípica)

- [Síndrome Cushing dependente de ACTH](https://raras.org/doenca/sindrome-cushing-dependente-de-acth) — ORPHA:99892 — 102 sintomas em comum
- [Síndrome Cushing por secreção ectópica de ACTH](https://raras.org/doenca/sindrome-cushing-por-secrecao-ectopica-de-acth) — ORPHA:99889 — 83 sintomas em comum
- [Adenoma hipofisário isolado familiar](https://raras.org/doenca/adenoma-hipofisario-isolado-familiar) — ORPHA:314777 — 81 sintomas em comum
- [Doença Cushing](https://raras.org/doenca/doenca-cushing) — ORPHA:96253 — 77 sintomas em comum
- [Síndrome Cushing suprarrenal](https://raras.org/doenca/sindrome-cushing-suprarrenal) — ORPHA:647758 — 55 sintomas em comum
- [Síndrome Cushing por doença adrenocortical macronodular bilateral](https://raras.org/doenca/sindrome-cushing-por-doenca-adrenocortical-macronodular-bilateral) — ORPHA:189427 — 55 sintomas em comum
- [Neoplasias endócrinas múltiplas](https://raras.org/doenca/neoplasias-endocrinas-multiplas) — ORPHA:100094 — 28 sintomas em comum
- [Neoplasia endócrina múltipla](https://raras.org/doenca/neoplasia-endocrina-multipla) — ORPHA:276161 — 27 sintomas em comum
- [Hiperparatireoidismo genético](https://raras.org/doenca/hiperparatireoidismo-genetico) — ORPHA:208596 — 25 sintomas em comum
- [Hiperparatireoidismo primário familiar](https://raras.org/doenca/hiperparatireoidismo-primario-familiar) — ORPHA:2207 — 24 sintomas em comum

## Importante

O Raras **não diagnostica e não prescreve**. Esta página é educativa e informativa.
Pacientes devem consultar profissionais de saúde qualificados para decisões clínicas.

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