# Deficiências combinadas de hormônios hipofisários, formas genéticas

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

## Identificadores

- **ORPHA**: 95494 — https://www.orpha.net/en/disease/detail/95494
- **CID-10**: E23.0
- **OMIM**: none — https://omim.org/entry/none

## Descrição clínica

O hipopituitarismo congénito é caracterizado por deficiência múltipla de hormonas hipofisárias, incluindo deficiências somatotróficas, tireotróficas, lactotróficas, corticotróficas ou gonadotróficas. O hipopituitarismo congénito é raro em comparação com a elevada incidência de hipopituitarismo induzido por adenomas hipofisários, cirurgia transesfenoidal ou radioterapia.

## Epidemiologia e herança

- **Prevalência**: Unknown
- **Padrão de herança**: Autosomal dominant, Autosomal recessive, X-linked recessive

## Sinais e sintomas (161 fenótipos HPO)

- **Escoliose** — HPO: HP:0002650
- **Cifoescoliose toracolombar** — HPO: HP:0003423
- **Deficiência do hormônio liberador de hormônio luteinizante hipotalâmico** — HPO: HP:0012287
- **Deficiência de gonadotrofina** — HPO: HP:0008213
- **Pescoço curto** — HPO: HP:0000470
- **Autismo** — HPO: HP:0000717
- **Anormalidade do eixo hipotálamo-hipófise** — HPO: HP:0000864
- **Nistagmo** — HPO: HP:0000639
- **Aplasia/Hipoplasia do cerebelo** — HPO: HP:0007360
- **Hipo-hidrose** — HPO: HP:0000966
- **Pele seca** — HPO: HP:0000958
- **Anosmia** — HPO: HP:0000458
- **Deficiência auditiva neurossensorial** — HPO: HP:0000407
- **Morfologia anormal do sistema cardiovascular** — HPO: HP:0030680
- **Polidipsia** — HPO: HP:0001959
- **Hemiplegia/hemiparesia** — HPO: HP:0004374
- **Criptorquidia** — HPO: HP:0000028
- **Anormalidade do sono** — HPO: HP:0002360
- **Atresia esofágica** — HPO: HP:0002032
- **Obesidade** — HPO: HP:0001513
- **Fissura palatina** — HPO: HP:0000175
- **Fístula traqueoesofágica** — HPO: HP:0002575
- **Hipoplasia do pênis** — HPO: HP:0008736
- **Deficiência visual** — HPO: HP:0000505
- **Hipercalemia** — HPO: HP:0002153
- **Insuficiência adrenal deficiente em adrenocorticotrofina** — HPO: HP:0011735
- **Hiponatremia** — HPO: HP:0002902
- **Hepatite** — HPO: HP:0012115
- **Enrugamento prematuro da pele** — HPO: HP:0100678
- **Massa muscular diminuída** — HPO: HP:0003199
- **Voz anormalmente aguda** — HPO: HP:0001620
- **Hipopituitarismo anterior** — HPO: HP:0000830
- **Fácies de boneca** — HPO: HP:0000295
- **Microfalos** — HPO: HP:0030260
- **Genu valgum** — HPO: HP:0002857
- **Cabelo esparso** — HPO: HP:0008070
- **Acromicria** — HPO: HP:0031878
- **Micropênis** — HPO: HP:0000054
- **Anormalidade do metabolismo/homeostase** — HPO: HP:0001939
- **Resposta reduzida de TSH ao teste de estimulação com hormônio liberador de tireotrofina** — HPO: HP:0033082
- _...e mais 121 sintomas. Ver https://raras.org/doenca/deficiencias-combinadas-de-hormonios-hipofisarios-formas-geneticas._

## Genes associados (20)

- **PROP1** — Homeobox protein prophet of Pit-1 [Disease-causing germline mutation(s) in]
  - Função: Possibly involved in the ontogenesis of pituitary gonadotropes, as well as somatotropes, lactotropes and caudomedial thyrotropes
- **PROKR2** — Prokineticin receptor 2 [Candidate gene tested in]
  - Função: Receptor for prokineticin 2. Exclusively coupled to the G(q) subclass of heteromeric G proteins. Activation leads to mobilization of calcium, stimulation of phosphoinositide turnover and activation of
- **SOX2** — Transcription factor SOX-2 [Candidate gene tested in]
  - Função: Transcription factor that forms a trimeric complex with OCT4 on DNA and controls the expression of a number of genes involved in embryonic development such as YES1, FGF4, UTF1 and ZFP206 (By similarit
- **ARNT2** — Aryl hydrocarbon receptor nuclear translocator 2 [Candidate gene tested in]
  - Função: Transcription factor that plays a role in the development of the hypothalamo-pituitary axis, postnatal brain growth, and visual and renal function (PubMed:24022475). Specifically recognizes the xenobi
- **ELF4** — ETS-related transcription factor Elf-4 [Candidate gene tested in]
  - Função: Transcriptional activator that binds to DNA sequences containing the consensus 5'-WGGA-3'. Transactivates promoters of the hematopoietic growth factor genes CSF2, IL3, IL8, and of the bovine lysozyme
- **FGFR1** — Fibroblast growth factor receptor 1 [Candidate gene tested in]
  - Função: Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation a
- **TBX19** — T-box transcription factor TBX19 [Disease-causing germline mutation(s) in]
  - Função: Transcriptional regulator involved in developmental processes. Can activate POMC gene expression and repress the alpha glycoprotein subunit and thyroid-stimulating hormone beta promoters
- **GHRHR** — Growth hormone-releasing hormone receptor [Disease-causing germline mutation(s) in]
  - Função: Receptor for GRF, coupled to G proteins which activate adenylyl cyclase. Stimulates somatotroph cell growth, growth hormone gene transcription and growth hormone secretion
- **BTK** — Tyrosine-protein kinase BTK [Disease-causing germline mutation(s) in]
  - Função: Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling (PubMed:19290921). Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling tha
- **RNPC3** — RNA-binding region-containing protein 3 [Disease-causing germline mutation(s) in]
  - Função: Participates in pre-mRNA U12-dependent splicing, performed by the minor spliceosome which removes U12-type introns. U12-type introns comprises less than 1% of all non-coding sequences. Binds to the 3'
- **SOX3** — Transcription factor SOX-3 [Disease-causing germline mutation(s) in]
  - Função: Transcription factor required during the formation of the hypothalamo-pituitary axis. May function as a switch in neuronal development. Keeps neural cells undifferentiated by counteracting the activit
- **ROBO1** — Roundabout homolog 1 [Disease-causing germline mutation(s) in]
  - Função: Receptor for SLIT1 and SLIT2 that mediates cellular responses to molecular guidance cues in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of
- **GH1** — Somatotropin [Disease-causing germline mutation(s) in]
  - Função: Plays an important role in growth control. Its major role in stimulating body growth is to stimulate the liver and other tissues to secrete IGF1. It stimulates both the differentiation and proliferati
- **LHX3** — LIM/homeobox protein Lhx3 [Disease-causing germline mutation(s) in]
  - Função: Transcription factor. Recognizes and binds to the consensus sequence motif 5'-AATTAATTA-3' in the regulatory elements of target genes, such as glycoprotein hormones alpha chain CGA and visual system h
- **POU1F1** — Pituitary-specific positive transcription factor 1 [Disease-causing germline mutation(s) in]
  - Função: Transcription factor involved in the specification of the lactotrope, somatotrope, and thyrotrope phenotypes in the developing anterior pituitary. Specifically binds to the consensus sequence 5'-TAAAT

## Ensaios clínicos ativos (5)

- **NCT07412782** [RECRUITING]: REMS25: Study on the Use of REMS Technology in Diseases Commonly Associated With Reduced Bone Mineral Density (BMD) — https://clinicaltrials.gov/study/NCT07412782
- **NCT04020913** [COMPLETED]: Skeletal Muscle Effects of GH in Boys — https://clinicaltrials.gov/study/NCT04020913
- **NCT06294860** [COMPLETED]: Biological Age in Children With GH Deficiency Undergoing Hormone Replacement Therapy — https://clinicaltrials.gov/study/NCT06294860
- **NCT00209235** [RECRUITING]: Albright Hereditary Osteodystrophy: Natural History, Growth, and Cognitive/Behavioral Assessments — https://clinicaltrials.gov/study/NCT00209235
- **NCT03812913** [RECRUITING]: Neuropsychological Assessment of Children and Adolescents With Turner Syndrome — https://clinicaltrials.gov/study/NCT03812913

## Doenças relacionadas (por similaridade fenotípica)

- [Deficiência de hormônio do crescimento isolada não-adquirida](https://raras.org/doenca/deficiencia-de-hormonio-do-crescimento-isolada-nao-adquirida) — ORPHA:631 — 56 sintomas em comum
- [Hipotireoidismo congênito](https://raras.org/doenca/hipotireoidismo-congenito) — ORPHA:442 — 51 sintomas em comum
- [Hipotireoidismo congênito permanente](https://raras.org/doenca/hipotireoidismo-congenito-permanente) — ORPHA:226292 — 44 sintomas em comum
- [Hipotireoidismo central](https://raras.org/doenca/hipotireoidismo-central) — ORPHA:226298 — 41 sintomas em comum
- [Pan-hipopituitarismo](https://raras.org/doenca/pan-hipopituitarismo) — ORPHA:90695 — 40 sintomas em comum
- [Monossomia parcial do braço curto do cromossomo 1](https://raras.org/doenca/monossomia-parcial-do-braco-curto-do-cromossomo-1) — ORPHA:261857 — 36 sintomas em comum
- [Espectro clínico de displasia septo-óptica](https://raras.org/doenca/espectro-clinico-de-displasia-septo-optica) — ORPHA:3157 — 36 sintomas em comum
- [Monossomia parcial do cromossomo 19](https://raras.org/doenca/monossomia-parcial-do-cromossomo-19) — ORPHA:261841 — 36 sintomas em comum
- [Síndrome aneuploidia variada em mosaico](https://raras.org/doenca/sindrome-aneuploidia-variada-em-mosaico) — ORPHA:1052 — 36 sintomas em comum
- [Deficiência de hormônio pituitário adquirida](https://raras.org/doenca/deficiencia-de-hormonio-pituitario-adquirida) — ORPHA:95502 — 36 sintomas em comum

## Importante

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Pacientes devem consultar profissionais de saúde qualificados para decisões clínicas.

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**Citação sugerida**: Raras.org — Deficiências combinadas de hormônios hipofisários, formas genéticas. Disponível em: https://raras.org/doenca/deficiencias-combinadas-de-hormonios-hipofisarios-formas-geneticas
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