Leuprolide Acetate Therapy in Luteinizing Hormone–Dependent Cushing's Syndrome

Lacroix, André; Hamet, Pavel; Boutin, Jean-Marie

doi:10.1056/nejm199911183412104

Cited by 220 publications

(161 citation statements)

References 33 publications

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“…The LH/hCGR was present in a non-mutated form and its expression was not increased compared with normal adrenal tissue. In the same patient, cisapride and metoclopramide, two serotonin 5-HT 4 receptor agonists also stimulated plasma cortisol (55). Some cases of aberrant receptors for LH/hCG in combination with serotonin or other receptors have been reported (16,56,57).…”

Section: Lh/hcg-responsive Aimahmentioning

confidence: 86%

“…Administration of the long-standing GnRH analog leuprolide acetate led to suppression of endogenous LH and normalization of cortisol production (55). The LH/hCGR was present in a non-mutated form and its expression was not increased compared with normal adrenal tissue.…”

Section: Lh/hcg-responsive Aimahmentioning

confidence: 94%

“…The aberrant adrenal function of LH/hCG receptor was first identified in a woman with transient CS during sequential pregnancies; persistent CS and AIMAH developed only after the post-menopausal sustained elevation of endogenous LH (55). Administration of the long-standing GnRH analog leuprolide acetate led to suppression of endogenous LH and normalization of cortisol production (55).…”

Section: Lh/hcg-responsive Aimahmentioning

confidence: 98%

“…In catecholamine-dependent CS in AIMAH, β-adrenergic receptor antagonists were efficient in the long-term control of hormonal hypersecretion (42,72). In LH/hCG-dependent AIMAH and CS, suppression of endogenous LH levels with long-acting leuprolide acetate controlled steroid secretion and avoided bilateral adrenalectomy (15,55). It is possible that tumor regression might not occur, despite complete blockade of the aberrant receptors, because other genetic events (other than aberrant receptors) inducing proliferation can appear over time (30,41).…”

Section: Management Of Aimahmentioning

confidence: 99%

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Cushing's syndrome secondary to ACTH-Independent macronodular adrenal hyperplasia

Costa

Lacroix

2007

Arq Bras Endocrinol Metab

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ACTH-Independent macronodular adrenal hyperplasia (AIMAH) is a rare cause of endogenous Cushing's syndrome (CS), in which clinical features usually become apparent only after several decades of life. This form of adrenal hyperplasia typically produces excess cortisol with overt or subclinical CS, but concurrent secretion of mineralocorticoids or sexual steroids can also occur. The diagnosis is suspected by bilateral adrenal nodules larger than 1 cm on incidental imaging studies or following the demonstration of ACTH-independent hormonal hypersecretion. The pathophysiology of this entity is heterogeneous and has been intensely explored in recent years. Several G-protein coupled receptors aberrantly expressed in the adrenal cortex have been implicated in the regulation of steroidogenesis and in the initial cell proliferation in AIMAH. Several familial cases of AIMAH have been recently described with the same pattern of aberrant hormone receptors in all affected members of the family. It is probable that additional somatic genetic events related to cell cycle regulation, adhesion and transcription factors occur in addition over time in the various nodules; other mechanisms, as Gsp or ACTH receptor mutations and paracrine adrenal hormonal secretion have been rarely identified as the molecular mechanism in some cases. When systematically screened, most patients with AIMAH exhibit an in vivo aberrant cortisol response to one or various ligands suggesting the presence of aberrant adrenal receptors. The identification of these receptors creates the possibility of a specific pharmacological treatment isolated or associated with adrenalectomy. A hiperplasia adrenal macronodular independente de ACTH (AIMAH) é uma causa rara de síndrome de Cushing (SC) endógena, na qual alguns aspectos clínicos só se tornam evidentes depois de várias décadas de vida. Esta forma de hiperplasia adrenal caracteristicamente produz excesso de cortisol resultando na síndrome de Cushing franca ou subclínica, embora a secreção concomitante de mineralocorticóide, estrógeno e andrógenos também possa ocorrer. A suspeita diagnóstica é feita pela presença de nódulos adrenais bilaterais maiores que 1 cm, como achado incidental em exames de imagem ou pela demonstração de hipersecreção hormonal independente de ACTH. A fisiopatologia desta doença é heterogênea e tem sido intensamente estudada nos últimos anos. Vários receptores acoplados à proteína G, com expressão aberrante no córtex adrenal, têm sido implicados na regulação da esteroidogênese e no início da proliferação celular que ocorre na AIMAH. Diversos casos familiais de AIMAH foram recentemente descritos, e um mesmo padrão de expressão anormal dos receptores aberrantes foi observado em todos os membros afetados das famílias investigadas. Ao longo do tempo, é provável que ocorram, nos nódulos, eventos genéticos adicionais relacionados à regulação do ciclo celular, adesão e fatores de transcrição. Outros mecanismos moleculares, como mutações nos genes da proteína Gsα e do receptor de ACTH, ou ...

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Section: Lh/hcg-responsive Aimahmentioning

confidence: 86%

Section: Lh/hcg-responsive Aimahmentioning

confidence: 94%

Section: Lh/hcg-responsive Aimahmentioning

confidence: 98%

Section: Management Of Aimahmentioning

confidence: 99%

See 2 more Smart Citations

Cushing's syndrome secondary to ACTH-Independent macronodular adrenal hyperplasia

Costa

Lacroix

2007

Arq Bras Endocrinol Metab

Self Cite

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show abstract

“…Lastly, the identification of ectopic or abnormal hormone receptors in adrenal cortisol-secreting nodular hyperplasias has given rise to new opportunities to use specific pharmacological therapies (68)(69)(70).…”

Section: Therapymentioning

confidence: 99%