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

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 Gsa e do receptor de ACTH, ou secreção hormonal parácrina na adrenal, têm sido raramente identificados em alguns casos. A maioria dos pacientes com AIMAH, quando sistematicamente investigados, desenvolve uma produção anormal de cortisol em resposta a vários ligantes, sugerindo a presença de receptores adrenais aberrantes. A identificação destes receptores cria a possibilidade para um tratamento farmacológico específico isolado ou associado à adrenalectomia.

Cushing's syndrome secondary to ACTH-independent macronodular adrenal hyperplasia.

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.

Endocrinología gastroenterológica: aspectos básicos / Gastrointestinal endocrinology: basic aspects

El presente artículo revisa los aspectos básicos y generales de la endocrinología del tracto gastrointestinal, conocimientos que facilitan la comprensión de sus aspectos fisiológicos y clínicos. Las células del tracto digestivo producen diversos mensajeros químicos que son liberados por mecanismos endocrinos, neurocrinos y paracrinos; la interrelación de estos eventos hormonales con eventos neuronales, van a regular los procesos de absorción, secreción, y de motilidad digestiva

[Gastroenterologic endocrinology: basic aspects]. / Endocrinología gastroenterológica: aspectos básicos.

Gastrointestinal cells produce several substances which act as messengers in the various biochemical processes of the body. These substances are released by endocrine, paracrine and neurocrine mechanisms. Both, hormonal and neuronal phenomenaregulate the absorptive, secretory and motility activity of the gastrointestinal tract. This paper goes over basic and general aspects of hormones secreted in the gastrointestinal system in order to make easier the understanding of their influence in the health and disease.

Modulation of the membrane potential of the Schwann cell of the squid giant nerve fiber.

1. The involvement of second messengers and of other chemical mediators, in the modulation of the membrane potential of the Schwann cell of the giant nerve fiber of the Tropical squid Sepioteuthis sepioidea is described. 2. The involvement of the cyclic nucleotide adenosine 3', 5' monophosphate (cAMP) in mediating the actions of the nicotinic Ach receptors of the Schwann cells is suggested. 3. The presence of octopaminergic receptors in the Schwann cells, mediating their actions through the activation of adenylate cyclase, is also described. 3. Receptors for vasoactive intestinal peptide (VIP) are also present on the Schwann cells, and their actions are mediated via a second messenger system that does not involve the activation of adenylate cyclase. 5. The three independent receptor systems referred above are able to interact in a complex way, which involves both their direct actions on the Schwann cell membrane potential and modulatory effects between the systems.