Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course

Novel concept of antisurvival factor (ASF) therapy produces an objective clinical response in four patients with hormone-refractory prostate cancer: Case report

BACKGROUND. Osteoblasts and osteoblast-derived survival growth factors, such as insulin-like growth factor I (IGF I), inhibit chemotherapy apoptosis of prostate cancer cells, thereby producing cytotoxic drug-resistant tumor growth, in vitro. METHODS. We tested a novel therapeutic approach, referred to as antisurvival factor (AFS) therapy, that aimed at reduction of osteoblast-derived IGFs, using dexamethasone (4 mg per os, qD) and growth hormone (GH)-dependent liver-derived IGFs, using a somatostatin-analog (lanreotide, 30 mg, intramuscularly (IM), q14D) in combination with triptorelin (3.75 mg, intramuscularly, q28D) to produce a clinical response in 4 patients with progressing hormone-refractory prostate cancer. RESULTS. The patients given ASF therapy exhibited an excellent improvement of clinical performance and a decline of prostate-specific antigen (PSA) within 2 months of ASF therapy. One of them experienced excellent clinical response (normalization of PSA), two experienced good clinical response (decline of PSA of more than 50%), and one experienced stabilization (decline of PSA of less than 50%). CONCLUSIONS. We conclude that this novel concept of combination therapy, using ASF with hormone ablation, is a promising salvage therapy that should be further assessed with a randomized clinical trial

Diabetes insipidus, secondary hypoadrenalism and hypothyroidism after traumatic brain iInjury: Clinical implications

Adequate ADH secretion, adrenal and thyroid functions are vital during the acute and post-acute phases of TBI. Deficiencies of these functions as a result of TBI are increasingly recognized. During the acute phase of TBI the incidence of severe DI is 2.9%; the incidence of less severe forms of DI is 21.6-26%. The development of DI seems to correlate with the severity of trauma. In most occasions DI is transient, but persisting DI may develop with an incidence of 6.9-7.5% amongst TBI victims. The assessment of the adequacy of adrenal function during the acute phase of TBI remains a diagnostic challenge. A few studies demonstrated an incidence of hypoadrenalism of 15-16% uring the early phase of TBI. It should be noted that early hypoadrenalism may be due to either a structural damage at the level of the hypothalamo-pituitary unit or it may develop in the context of the so-called "relative adrenal insufficiency", a functional abnormality that is currently increasingly recognized during the course of severe illness. Secondary hypoadrenalism during the late phases of TBI appears with an incidence of 7.1-12.7%. The "low-T3 syndrome" compromises the assessment of thyroid function during the acute phase of TBI; the incidence of TSH insufficiency during the recovery phase varies widely between 1-21%. In summary, diabetes insipidus, secondary hypoadrenalism and hypothyroidism may develop in a small albeit significant proportion of patients during the course of TBI. Therefore, assessment of the integrity of ADH secretion, hypothalamic-pituitary adrenal (HPA) axis and thyroid axis is crucial to ensure survival and optimal rehabilitation of TBI patients. © Springer Science + Business Media, Inc. 2006

Recurrent and/or metastatic thyroid cancer: therapeutic options.

Thyroid cancer is relatively rare, accounting for 0.5 - 10 cases per 100,000 individuals per year. Despite their generally favourable prognosis, patients with differentiated thyroid cancer are at risk of tumour recurrence for decades after diagnosis. The optimal management remains controversial even in the low-risk patients because of the high cure rates, long natural history and rarity of these tumours. Therapeutic interventions in recurrent and metastatic differentiated thyroid cancer depend on the type of initial treatment, the site and the extent of disease. Surgical excision of the amenable-to-surgery lesions and radioiodine administration remain the first approach. External radiotherapy may be given to patients with inoperable lesions or those not concentrating radioiodine. Chemotherapy has not provided consistently successful results. Various therapeutic approaches for anaplastic carcinoma give poor results, making the development of novel treatments necessary. Innovative strategies, including recombinant human thyroid stimulating hormone, retinoic acid redifferentiation therapy and gene therapy, may lead to further improvement in the management of thyroid cancer arising from follicular cells