Clinically Silent Corticotroph Tumors of the Pituitary Gland

Scheithauer, Bernd W.; Jaap, Alan J.; Horváth, Éva; Kovács, Kálmán; Lloyd, Ricardo V.; Meyer, Fredric B.; Laws, Edward R.; Young, William F.

doi:10.1227/00006123-200009000-00039

Cited by 46 publications

(96 citation statements)

References 13 publications

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“…In addition, in one third of the reported cases the initial presentation consisted of mass effects of a silent adenoma and Cushing's syndrome evolved only in the course of the disease. This is in contrast with findings of Scheithauer et al [62] who report 23 cases with a benign silent corticotrophic adenoma at pathology reports, but in these cases no symptoms of hypercortisolim occurred during the course of the disease. Although data are scarce, the evolvement of Cushing's syndrome after initial presentation of a silent corticotrophic adenoma might thus be considered as indicative of possible future malignant behaviour of the pituitary tumor.…”

Section: Discussioncontrasting

confidence: 93%

Malignant pituitary corticotroph adenomas: report of two cases and a comprehensive review of the literature

et al. 2008

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Corticotroph pituitary carcinomas are tumors, defined by the presence of distant metastases that determine their poor prognosis. The diagnosis and therapy of malignant corticotroph adenomas remains a clinical challenge. The molecular mechanisms of malignant transformation of pituitary adenomas are unclear, although they are believed to arise in an adenoma-to-carcinoma sequence. We describe two cases of malignant Cushing's disease with metastases in liver and bone, respectively. The primary pituitary tumors were treated by a combination of radiotherapy and transsphenoidal surgery, but recurred several times in both patients. The time interval between the diagnosis of Cushing's disease and the discovery of metastases was 32 and 17 years, respectively. In the first case the patient died within 6 months after diagnosis of metastasis, whereas the second patient is alive at a followup of 2 years after the discovery of the metastasis. Furthermore, we reviewed all available cases of corticotroph pituitary carcinomas reported in the literature and analyzed their clinical features and therapeutical management. In conclusion, frequent relapses of Cushing's disease, aggressive growth of macroadenoma, Nelson's syndrome after adrenalectomy or persistently high ACTH levels should prompt the clinician to consider the possibility of pituitary corticotroph carcinomas.

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Section: Discussioncontrasting

confidence: 93%

Malignant pituitary corticotroph adenomas: report of two cases and a comprehensive review of the literature

et al. 2008

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“…Although SCA patients in our study showed no clinical signs and symptoms of Cushing's syndrome, the metabolic phenotype of Cushing's syndrome, such as hypertension, impaired glucose tolerance and obesity, did not differ between SCAs and NFAs. Furthermore, the present endocrine ACTH (fold increase) 3) 6.0 ± 4.1 3.4 ± 2.9 Cortisol (fold increase) 3) 2.0 ± 0.7 2.0 ± 1.3 Dexamethasone suppression test 4) ACTH (pg/ml) 1) 13.0 ± 6.93 7.0 ± 1.67 Cortisol (µg/dl) 1) 2.04 ± 0.73 1.10 ± 0.38 data that SCA patients showed normal diurnal rhythm of ACTH/cortisol secretion with suppressibility to lowdose dexamethasone and responsiveness to CRH stimulation, suggest normal regulation of ACTH secretion in SCA. Despite no difference of tumor size by imaging data between SCAs and NFAs, the recurrence rate (66.7%) was higher in SCA patients, suggesting its aggresiveness.…”

Section: Discussionmentioning

confidence: 61%

“…Their clinical and endocrine manifestations are poorly understood and the reasons for the lack of Cushingoid features in SCA remain unknown. Although these tumors may recur more frequently postoperatively [1] and behave more aggressively [3,4], there are conflicting reports as well [2]. Furthermore, studies on the long-term follow-up and preoperative clinical diagnosis of SCAs are very limited [5].…”

mentioning

confidence: 99%

Defective Expression of Prohormone Convertase 1/3 in Silent Corticotroph Adenoma

et al. 2007

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Abstract. Silent corticotroph adenoma (SCA) is defined as an ACTH-producing pituitary tumor not associated with clinical and endocrine feartures of Cushing's syndrome, but its underlying molecular mechanism(s) remains unknown thus far. We tested the hypothesis that reduced expression of prohormone convertase (PC) 1/3 responsible for proteolytic processing of proopiomelanocortin (POMC) in SCA may lead to production of unprocessed, biologically inactive POMC and/or precursor of ACTH. Among 30 non-functioning pituitary macroadenomas (NFA) examined, we found 6 SCAs by immunohistochemical study using anti-ACTH antibody. Preoperative endocrine and diagnostic image tests did not reveal any differences between SCA and the remaining NFA except for the higher recurrence rate of SCA. While steady-state PC1/3 mRNA levels determined by RT-PCR were almost comparable between SCAs and NFAs, immunohistochemical study showed negative immunostaining for PC1/3 in all 6 SCAs. Our data suggest that defective PC1/3 expression may lead to preferential production of unprocessed, biologically inactive ACTH variants in SCA.

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“…The sex predominance, as reported in neurosurgical series, remains unclear. Thus, Webb et al (7) suggested that it is more common in females (70.4%) whereas Scheithauer et al (8) found a male/female ratio of 69.9/30.5.…”

Section: Adenomas Corticotróficos Silenciososmentioning

confidence: 99%

“…Currently, two distinct pathologic subtypes of SCAs are recognised (8). A third type of SCA, initially proposed in 1980 (2), is now thought to be unrelated to the SCA spectrum and is simply referred to as "silent type 3 adenoma".…”

Section: Pathology and Pathogenesismentioning

confidence: 99%

Silent corticotroph adenomas

Karavitaki

Ansorge

Wass

2007

Arq Bras Endocrinol Metab

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Silent corticotroph pituitary adenomas (SCA) are defined as pituitary adenomas showing positive staining for adrenocorticotrophic hormone in immunohistochemical studies, but not associated with perioperative clinical or laboratory features of hypercortisolaemia. They account for 1.1-6% of surgically removed pituitary adenomas. Currently, two distinct pathologic subtypes of SCA are recognised. Their pathogenesis remains unclear. They present with local mass effects (headache, visual deterioration, cranial nerve palsies, endocrine dysfunction). The lack of manifestations of cortisol excess has not been conclusively explained. In surgical series, most tumours are macroadenomas with suprasellar extension present in 87-100% of the cases; this is in contrast to Cushing's disease, which is mostly attributed to microadenomas. Surgery remains the main therapeutic approach. Attempts to identify predictors of recurrence have not been successful. Management and follow-up protocols should be planned taking into account their potential aggressive behaviour, particularly upon recurrence. The development of florid pituitary Cushing's syndrome and local recurrence followed by metastatic disease (occasionally outside the central nervous system) have been rarely reported. Adenomas corticotróficos silenciosos (ACS) são definidos como adenomas hipofisários que apresentam coloração positiva para o hormônio adrenocorticotrófico em estudos imuno-histoquímicos, mas não são associados com achados clínicos ou laboratoriais peri-operatórios de hipercortisolemia. São responsáveis por 1,1-6% dos adenomas hipofisários removidos cirurgicamente. Atualmente, dois subtipos patológicos distintos de ACS são reconhecidos, mas sua patogênese permanece obscura. Eles se apresentam com efeitos de massa local (cefaléia, deterioração visual, paralisia de nervos cranianos, disfunção endócrina). A ausência de manifestações de excesso de cortisol não é suficientemente explicada. Em séries cirúrgicas, a maioria dos tumores são macroadenomas com extensão suprasselar, presente em 87-100% dos casos, em contraste com a doença de Cushing, que é principalmente atribuída a microadenomas. A cirurgia continua a principal ação terapêutica. A tentativa de se identificar preditores de recorrência tem sido mal sucedida. Protocolos de manejo e acompanhamento devem ser planejados levando-se em consideração o seu comportamento potencialmente agressivo, particularmente na recorrência. Raramente tem sido reportado o desenvolvimento de síndrome de Cushing hipofisária florida e recorrência local, seguida de doença metastática (ocasionalmente fora do sistema nervoso central).

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Clinically Silent Corticotroph Tumors of the Pituitary Gland

Cited by 46 publications

References 13 publications

Malignant pituitary corticotroph adenomas: report of two cases and a comprehensive review of the literature

Malignant pituitary corticotroph adenomas: report of two cases and a comprehensive review of the literature

Defective Expression of Prohormone Convertase 1/3 in Silent Corticotroph Adenoma

Silent corticotroph adenomas

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