Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement.

Growth hormone (GH) has been used for over 35 years, and its safety and efficacy has been studied extensively. Experimental studies showing the permissive role of GH/insulin-like growth factor 1 (IGF-I) in carcinogenesis have raised concerns regarding the safety of GH replacement in children and adults who have received treatment for cancer and those with intracranial and pituitary tumours. A consensus statement was produced to guide decision-making on GH replacement in children and adult survivors of cancer, in those treated for intracranial and pituitary tumours and in patients with increased cancer risk. With the support of the European Society of Endocrinology, the Growth Hormone Research Society convened a Workshop, where 55 international key opinion leaders representing 10 professional societies were invited to participate. This consensus statement utilized: (1) a critical review paper produced before the Workshop, (2) five plenary talks, (3) evidence-based comments from four breakout groups, and (4) discussions during report-back sessions. Current evidence reviewed from the proceedings from the Workshop does not support an association between GH replacement and primary tumour or cancer recurrence. The effect of GH replacement on secondary neoplasia risk is minor compared to host- and tumour treatment-related factors. There is no evidence for an association between GH replacement and increased mortality from cancer amongst GH-deficient childhood cancer survivors. Patients with pituitary tumour or craniopharyngioma remnants receiving GH replacement do not need to be treated or monitored differently than those not receiving GH. GH replacement might be considered in GH-deficient adult cancer survivors in remission after careful individual risk/benefit analysis. In children with cancer predisposition syndromes, GH treatment is generally contraindicated but may be considered cautiously in select patients.

Ectopic ACTH syndrome

Ectopic adrenocorticotropic secretion (EAS) is responsible for 12-17 percent of cases of Cushing's syndrome (CS) and covers a range of tumours, from undetectable benign lesions to widespread metastases. The syndrome is often associated with severe hypercortisolaemia, which aggravates the underlying condition. EAS requires a complete workup that includes the establishment of endogenous CS, diagnosis of adrenocorticotropic hormone (ACTH) dependency, localization of the source of ACTH secretion and rapid biochemical control of hypercortisolaemia. Dynamic endocrine tests should include inferior petrosal sinus sampling with CRH stimulation. Localization studies depend on the availability of reliable high-resolution cross-sectional imaging. This systematic review of the largest published series of patients with EAS (over 380 patients) reveals the common trends in the prevalence and management of this syndrome. The concept of 'occult' EAS has been revisited and the terms 'overt' and 'covert' EAS introduced. In addition to small cell lung carcinoma, the most common causes of ectopic EAS are bronchial carcinoids, thymic tumours, islet cell tumour of the pancreas, medullary thyroid carcinomas, and phaeochromocytomas. Their prevalence and the best localization modalities are presented. Medical and surgical management is discussed on the basis of the extensive experience of major referral centres.

A secreção ectópica de ACTH (SEA) é responsável por 12-17 por cento dos casos de síndrome de Cushing (SC), cobrindo uma variedade de tumores, desde lesões benignas indetectáveis a metástases disseminadas. A SEA está freqüentemente associada com hipercortisolemia grave, que agrava a condição de base e requer uma avaliação completa, que inclui a confirmação da SC endógena, o diagnóstico da dependência ao ACTH, a localização da fonte da secreção de ACTH e o controle bioquímico rápido da hipercortisolemia. Testes endócrinos dinâmicos devem incluir a coleta de amostras do seio petroso inferior com estímulo pelo CRH. O estudo da localização da fonte depende da disponibilidade de procedimentos de imagem de alta-resolução confiáveis. A revisão sistemática das maiores séries publicadas de pacientes com SEA (mais de 380 pacientes) revela tendências comuns na prevalência e manejo dessa síndrome. O conceito de SEA "oculta" está sendo revisado e os termos SEA "manifesta" e "latente" são introduzidos. Além do carcinoma pulmonar de pequenas células, as causas mais comuns de SEA são os carcinóides brônquicos, tumores tímicos, tumor de ilhotas pancreáticas, carcinoma medular de tiróide e feocromocitoma; sua prevalência e as melhores modalidades para localização são apresentadas. O manejo clínico e cirúrgico é discutido com base na vasta experiência dos principais centros de referência.

Ectopic ACTH syndrome.

Ectopic adrenocorticotropic secretion (EAS) is responsible for 12-17% of cases of Cushing's syndrome (CS) and covers a range of tumours, from undetectable benign lesions to widespread metastases. The syndrome is often associated with severe hypercortisolaemia, which aggravates the underlying condition. EAS requires a complete workup that includes the establishment of endogenous CS, diagnosis of adrenocorticotropic hormone (ACTH) dependency, localization of the source of ACTH secretion and rapid biochemical control of hypercortisolaemia. Dynamic endocrine tests should include inferior petrosal sinus sampling with CRH stimulation. Localization studies depend on the availability of reliable high-resolution cross-sectional imaging. This systematic review of the largest published series of patients with EAS (over 380 patients) reveals the common trends in the prevalence and management of this syndrome. The concept of 'occult' EAS has been revisited and the terms 'overt' and 'covert' EAS introduced. In addition to small cell lung carcinoma, the most common causes of ectopic EAS are bronchial carcinoids, thymic tumours, islet cell tumour of the pancreas, medullary thyroid carcinomas, and phaeochromocytomas. Their prevalence and the best localization modalities are presented. Medical and surgical management is discussed on the basis of the extensive experience of major referral centres.