Somatostatin analogs in ectopic corticotropin production

Werder, Klaus von; Müller, O. A.; Stalla, G. K.

doi:10.1016/s0026-0495(96)90107-9

Cited by 35 publications

(24 citation statements)

References 15 publications

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“…Several drugs can be used for this, including ketoconazole, aminoglutethimide, metyrapone and mitotane (106). In case of ectopic ACTH syndrome, treatment with somatostatin analogues may be considered for amelioration of ACTH secretion and glucocorticoid excess (107,108). Such treatment is unlikely to exert an important anti-tumoural effect.…”

Section: Treatmentmentioning

confidence: 99%

Cyclic Cushing’s syndrome: a clinical challenge

Meinardi¹,

Wolffenbuttel²,

Dullaart³

2007

eur j endocrinol

126

134

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Cyclic Cushing's syndrome (CS) is a rare disorder, characterized by repeated episodes of cortisol excess interspersed by periods of normal cortisol secretion. The so-called cycles of hypercortisolism can occur regularly or irregularly with intercyclic phases ranging from days to years. To formally diagnose cyclic CS, three peaks and two troughs of cortisol production should be demonstrated. Our review of 65 reported cases demonstrates that cyclic CS originates in 54% of cases from a pituitary corticotroph adenoma, in 26% from an ectopic ACTH-producing tumour and in about 11% from an adrenal tumour, the remainder being unclassified. The pathophysiology of cyclic CS is largely unknown. The majority of patients with cyclic CS have clinical signs of CS, which can be either fluctuating or permanent. In a minority of patients, clinical signs of CS are absent. The fluctuating clinical picture and discrepant biochemical findings make cyclic CS extremely hard to diagnose. Clinicians should therefore be aware of this clinical entity and actively search for it in all patients with suspected CS but normal biochemistry or vice versa. Frequent measurements of urinary cortisol or salivary cortisol levels are a reliable and convenient screening tool for suspected cyclic CS. Cortisol stimulation or suppression tests may give spurious results owing to spontaneous falls or rises in serum cortisol at the time of testing. When cyclic CS is biochemically confirmed, further imaging and laboratory studies are guided by the presence or absence of ACTH dependency. In cases of suspected ectopic ACTH production, specific biochemical testing for carcinoids or neuroendocrine tumours is required, including measurements of serotonin in platelets and/or urine, chromogranin A and calcitonin.European Journal of Endocrinology 157 245-254

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Section: Treatmentmentioning

confidence: 99%

Cyclic Cushing’s syndrome: a clinical challenge

Meinardi¹,

Wolffenbuttel²,

Dullaart³

2007

eur j endocrinol

126

134

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“…Recent reports have shown significant efficacy of selective D 2 -receptor agonists, such as cabergoline, and of a multiligand SS analogue with high sst 5 affinity (pasireotide/SOM230) in the medical management of pituitary-dependent Cushing's syndrome (Pivonello et al 2004, Boscaro et al 2008, Pivonello et al 2008. The use of sst 2 -or D 2 -targeting agonists has also been advocated in cases of Cushing's syndrome due to ectopic ACTH production by neuro-endocrine tumours (von Werder et al 1996, Pivonello et al 2007.…”

Section: Introductionmentioning

confidence: 99%

Differential regulation of human dopamine D2 and somatostatin receptor subtype expression by glucocorticoids in vitro

Bruin¹,

Feelders²,

Waaijers³

et al. 2008

Journal of Molecular Endocrinology

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Dopamine agonists (DA) and somatostatin (SS) analogues have been proposed in the treatment of ACTH-producing neuroendocrine tumours that cause Cushing's syndrome. Inversely, glucocorticoids (GCs) can differentially influence DA receptor D 2 or SS receptor subtype (sst) expression in rodent models. If this also occurs in human neuro-endocrine cells, then cortisollowering therapy could directly affect the expression of these target receptors. In this study, we investigated the effects of the GC dexamethasone (DEX) on D 2 and sst expression in three human neuro-endocrine cell lines: BON (carcinoid) and TT (medullary thyroid carcinoma) versus DMS (small cell lung cancer), which is severely GC resistant. In BON and TT, sst 2 mRNA was strongly down-regulated in a dose-dependent manner (IC 50 0 . 84 nM and 0 . 16 nM), whereas sst 5 and especially D 2 were much more resistant to DEX treatment. Sst 2 down-regulation was abrogated by a GC receptor antagonist and reversible in time upon GC withdrawal. At the protein level, DEX also induced a decrease in the total number of SS (K52%) and sst 2 -specific (K42%) binding sites. Pretreatment with DEX abrogated calcitonin inhibition by sst 2 -preferring analogue octreotide in TT. In DMS, DEX did not cause significant changes in the expression of these receptor subtypes. In conclusion, we show that GCs selectively down-regulate sst 2 , but not D 2 and only to a minor degree sst 5 in human neuro-endocrine BON and TT cells. This mechanism may also be responsible for the low expression of sst 2 in corticotroph adenomas and underwrite the current interest in sst 5 and D 2 as possible therapeutic targets for a medical treatment of Cushing's disease.

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“…in metastatic disease or in the case of occult tumors). Tumor-directed therapy involves an individualized approach, and can include somatostatin analogues, systemic chemotherapy, interferon-α, chemoembolization, radiofrequency ablation, and radiation therapy (21)(22)(23)(24). In the present case, surgery for tumor resection was attempted three times, but the tumor was locally invasive since diagnosis.…”

Section: Treatment and Managementmentioning

confidence: 85%

A rare case of Cushing syndrome by cyclic ectopic-ACTH

Farage

Costa²,

Godoy-Matos

2012

Arq Bras Endocrinol Metab

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SUMMARYACTH-dependent Cushing syndrome (CS) due to ectopic ACTH production is most times difficult to manage. The identification of the source of ACTH may take many years. Surgery or chemotherapy for the primary tumor is not always possible. Control of Cushing symptoms is many times achieved using medication, or bilateral adrenalectomy in refractory cases. This case presents a Brazilian male who showed severe hypertension, mood changes, muscle weakness, darkening of skin, and increased abdominal fat. An investigation for Cushing syndrome was carried out and, after a four-year follow-up, a carotid glomus tumor (chemodectoma) was confirmed, a rare ectopic ACTH-producing tumor. Besides, the patient presented cyclic Cushing syndrome that was exacerbated by diverticulitis episodes. This case presents interesting pitfalls on diagnosis and management of ACTH-dependent CS. This is the only report of a chemodectoma that produced ACTH in the literature. Arq Bras Endocrinol Metab. 2012;56(5):324-30 SUMÁRIO A síndrome de Cushing ACTH-dependente causada por produção ectópica de ACTH é, muitas vezes, difícil de diagnosticar e conduzir. A identificação da fonte produtora de ACTH pode demorar muitos anos. A cirurgia ou quimioterapia para o tumor primário nem sempre é possível, sendo o controle do hipercortisolismo alcançado com uso de fármacos ou adrenalectomia bilateral, nos casos refratários. Este caso apresenta um homem com hipertensão grave, mudança de humor, fraqueza proximal, escurecimento da pele e aumento de gordura abdominal. A investigação para síndrome de Cushing foi feita e, após quatro anos de acompanhamento, confirmou--se um tumor de glomus carotídeo (quemodectoma), causa rara de tumor secretor de ACTH. Nesse período, o paciente apresentou síndrome de Cushing cíclica, exacerbada por crises de diverticulite. O caso ilustra pontos importantes no diagnóstico, no acompanhamento e na condução da síndrome de Cushing ACTH-dependente, sendo este o único caso de tumor de glomus de carótida produzindo ACTH descrito na literatura médica. Arq Bras Endocrinol Metab. 2012;56(5):324-30

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Somatostatin analogs in ectopic corticotropin production

Cited by 35 publications

References 15 publications

Cyclic Cushing’s syndrome: a clinical challenge

Cyclic Cushing’s syndrome: a clinical challenge

Differential regulation of human dopamine D2 and somatostatin receptor subtype expression by glucocorticoids in vitro

A rare case of Cushing syndrome by cyclic ectopic-ACTH

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