# Doença Cushing

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

## Identificadores

- **ORPHA**: 96253 — https://www.orpha.net/en/disease/detail/96253
- **CID-10**: E24.0
- **OMIM**: OMIM:219090 — https://omim.org/entry/219090

## Descrição clínica

Forma de síndrome Cushing dependente da hormona adrenocorticotrófica (ACTH), uma síndrome Cushing (SC) endógena, caracterizada pela secreção excessiva crónica da hormona adrenocorticotrófica (ACTH) devido a um adenoma corticotrófico hipofisário.

## Epidemiologia e herança

- **Prevalência**: 1-9 / 100 000
- **Padrão de herança**: Not applicable

## Sinais e sintomas (79 fenótipos HPO)

- **Linfopenia** — HPO: HP:0001888 (Frequente (79-30%))
- **Herança autossômica dominante** — HPO: HP:0000006
- **Herança autossômica recessiva** — HPO: HP:0000007
- **Hipocalemia** — HPO: HP:0002900
- **Atrofia do músculo esquelético** — HPO: HP:0003202
- **Mentação psicótica** — HPO: HP:0001345
- **Corpos vertebrais bicôncavos** — HPO: HP:0004586
- **Cifose** — HPO: HP:0002808
- **Nefrolitíase** — HPO: HP:0000787
- **Comportamento anormal relacionado a medo/ansiedade** — HPO: HP:0100852
- **Eritema facial** — HPO: HP:0001041
- **Alcalose** — HPO: HP:0001948
- **Obesidade** — HPO: HP:0001513
- **Adenoma hipofisário** — HPO: HP:0002893
- **Intolerância à glicose** — HPO: HP:0001952
- **Edema** — HPO: HP:0000969
- **Úlcera cutânea** — HPO: HP:0200042 (Ocasional (29-5%))
- **Adenoma de células corticotróficas hipofisárias** — HPO: HP:0008291 (Muito frequente (99-80%))
- **Imunodeficiência** — HPO: HP:0002721 (Frequente (79-30%))
- **Aumento do nível circulante de ACTH** — HPO: HP:0003154 (Frequente (79-30%))
- **Infecções fúngicas cutâneas recorrentes** — HPO: HP:0011370 (Ocasional (29-5%))
- **Anormalidade do sistema respiratório** — HPO: HP:0002086 (Ocasional (29-5%))
- **Equimose** — HPO: HP:0031364 (Ocasional (29-5%))
- **Hiperpigmentação da pele** — HPO: HP:0000953 (Frequente (79-30%))
- **Defeito do campo visual** — HPO: HP:0001123 (Raro (<5%))
- **Edema pedal** — HPO: HP:0010741 (Raro (<5%))
- **Amiotrofia proximal** — HPO: HP:0007126 (Frequente (79-30%))
- **Paranoia** — HPO: HP:0011999 (Raro (<5%))
- **Amenorreia** — HPO: HP:0000141 (Frequente (79-30%))
- **Hirsutismo** — HPO: HP:0001007 (Frequente (79-30%))
- **Amenorreia secundária** — HPO: HP:0000869 (Ocasional (29-5%))
- **Hiperpigmentação intraoral** — HPO: HP:0010284 (Frequente (79-30%))
- **Fraqueza muscular** — HPO: HP:0001324 (Frequente (79-30%))
- **Suscetibilidade a hematomas** — HPO: HP:0000978 (Frequente (79-30%))
- **Labilidade emocional** — HPO: HP:0000712 (Frequente (79-30%))
- **Fraqueza fatigável dos músculos proximais dos membros** — HPO: HP:0030200 (Frequente (79-30%))
- **Osteoporose** — HPO: HP:0000939 (Frequente (79-30%))
- **Diabetes mellitus** — HPO: HP:0000819 (Frequente (79-30%))
- **Comportamento atípico** — HPO: HP:0000708 (Frequente (79-30%))
- **Estrias distensas** — HPO: HP:0001065 (Frequente (79-30%))
- _...e mais 39 sintomas. Ver https://raras.org/doenca/doenca-cushing._

## Genes associados (8)

- **CDH23** — Cadherin-23 [Major susceptibility factor 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
- **AIP** — Small ribosomal subunit protein bS22, mitochondrial [MENDELIAN]
  - Função: May act as a negative regulator of Aurora-A kinase, by down-regulation through proteasome-dependent degradation
- **USP48** — Ubiquitin carboxyl-terminal hydrolase 48 [Disease-causing somatic mutation(s) 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
- **NR3C1** — Glucocorticoid receptor [Disease-causing somatic mutation(s) 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
- **ATRX** — Transcriptional regulator ATRX [Disease-causing somatic mutation(s) 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
- **BRAF** — Serine/threonine-protein kinase B-raf [Disease-causing somatic mutation(s) 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
- **TP53** — Cellular tumor antigen p53 [Disease-causing somatic mutation(s) 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
- **USP8** — Ubiquitin carboxyl-terminal hydrolase 8 [Disease-causing somatic 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 (15)

- **NCT03831958** [RECRUITING]: Long-Term Follow-Up of Survivors of Pediatric Cushing Disease — https://clinicaltrials.gov/study/NCT03831958
- **NCT04569591** [RECRUITING]: DDAVP for Pituitary Adenoma — https://clinicaltrials.gov/study/NCT04569591
- **NCT00001595** [RECRUITING]: An Investigation of Pituitary Tumors and Related Hypothalmic Disorders — https://clinicaltrials.gov/study/NCT00001595
- **NCT07463625** [RECRUITING]: Evaluation of Positron Emission Tomography (PET) With [18F]FET for the Detection of ACTH-Secreting Corticotroph Pituitary Neuroendocrine Tumors. — https://clinicaltrials.gov/study/NCT07463625
- **NCT06471829** [RECRUITING]: A Trial of Lu AG13909 in Adult Participants With Cushing's Disease — https://clinicaltrials.gov/study/NCT06471829
- **NCT07335315** [RECRUITING]: Evaluation of Intraoperative Contrast Enhanced Ultrasound for the Identification of Pituitary Adenoma in Cushing's Disease Compared to Other Pituitary Tumors — https://clinicaltrials.gov/study/NCT07335315
- **NCT03364803** [RECRUITING]: Collecting Information About Treatment Results for Patients With Cushing's Syndrome — https://clinicaltrials.gov/study/NCT03364803
- **NCT03774446** [RECRUITING]: Multicenter Study of Seliciclib (R-roscovitine) for Cushing Disease — https://clinicaltrials.gov/study/NCT03774446
- **NCT05971758** [RECRUITING]: Fimepinostat, Combination HDAC and Pi3-kinase Inhibitor Tumor-Directed Therapy for Cushing Disease — https://clinicaltrials.gov/study/NCT05971758
- **NCT05804669** [RECRUITING]: A Study to Evaluate the Safety and PK of CRN04894 for the Treatment of Cushing's Syndrome — https://clinicaltrials.gov/study/NCT05804669

## Doenças relacionadas (por similaridade fenotípica)

- [Adenoma hipofisário isolado familiar](https://raras.org/doenca/adenoma-hipofisario-isolado-familiar) — ORPHA:314777 — 77 sintomas em comum
- [Síndrome Cushing dependente de ACTH](https://raras.org/doenca/sindrome-cushing-dependente-de-acth) — ORPHA:99892 — 77 sintomas em comum
- [Síndrome Cushing endógena](https://raras.org/doenca/sindrome-cushing-endogena) — ORPHA:641613 — 77 sintomas em comum
- [Síndrome Cushing por secreção ectópica de ACTH](https://raras.org/doenca/sindrome-cushing-por-secrecao-ectopica-de-acth) — ORPHA:99889 — 59 sintomas em comum
- [Síndrome Cushing suprarrenal](https://raras.org/doenca/sindrome-cushing-suprarrenal) — ORPHA:647758 — 29 sintomas em comum
- [Síndrome Cushing por doença adrenocortical macronodular bilateral](https://raras.org/doenca/sindrome-cushing-por-doenca-adrenocortical-macronodular-bilateral) — ORPHA:189427 — 29 sintomas em comum
- [Alteração do metabolismo e transporte de ferro](https://raras.org/doenca/alteracao-do-metabolismo-e-transporte-de-ferro) — ORPHA:309842 — 16 sintomas em comum
- [Porfiria hepática](https://raras.org/doenca/porfiria-hepatica) — ORPHA:659694 — 16 sintomas em comum
- [Lipodistrofia parcial familiar](https://raras.org/doenca/lipodistrofia-parcial-familiar) — ORPHA:98306 — 15 sintomas em comum
- [Hipoparatireoidismo genético](https://raras.org/doenca/hipoparatireoidismo-genetico) — ORPHA:208593 — 13 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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**Citação sugerida**: Raras.org — Doença Cushing. Disponível em: https://raras.org/doenca/doenca-cushing
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