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OBJECTIVE Some authors proposed to lower the present postglucose GH nadir cut-off (i.e. 0.26 microg/l in 24 patients (Group B). Group B had only slightly higher IGF-1 SDS (0.4 +/- 1.0 vs.- 0.1 +/- 1.0, P = ns) and lower body mass index (BMI) than Group A (26.2 +/- 2.4 vs. 30.6 +/- 4.5 kg/m(2), P < 0.005). GH nadir positively correlated with IGF-1 (P < 0.05, r = 0.32) and negatively with BMI (P < 0.05, r = 0.42). In Phase 2, all patients had IGF-1 levels in the normal range and GH nadir < 1 microg/l, both parameters being even lower than those found at the time of remission. No patient had either clinical or neuroradiological evidence of disease recurrence. CONCLUSIONS The current GH nadir limit is still adequate to define both short- and long-lasting remission of acromegaly, independently of the type of definitive treatment. Patients with the lowest GH nadir should probably be monitored long-term for adequacy of their GH secretion.

Summary Objective Long-term effects of trans-naso-sphenoidal surgery (TNS) or long-acting somatostatin analogs (SSA) on the function of hypothalamic–pituitary–adrenal (HPA) axis have been poorly investigated. Aim of this study was to evaluate HPA axis integrity during the follow-up in patients with GH-secreting pituitary adenomas and preserved HPA function post-TNS or prior SSA. Design and patients This retrospective study investigated 36 acromegalic patients (16M and 20F, age: 47 ± 13 years), 20 of whom cured by TNS and 16 controlled by SSA therapy (12 previously operated and 4 in primary medical therapy), before and after long-term follow-up (median: 72 months, range: 12–240). No patient previously underwent radiotherapy. Measurements HPA function was studied by morning circulating cortisol and ACTH levels, 24-h urinary free cortisol (UFC) and cortisol response to low-dose short Synacthen test (LDSST, 1 µg) with a peak > 500 nmol/l as cut-off for normal function. Results Serum basal cortisol, ACTH and UFC levels were in the normal range and did not significantly change over time. As far as the cortisol peak after LDSST is concerned, 12 patients (32%, 8 TNS and 4 SSA) developed biochemical hypoadrenalism. None of the patients in primary medical therapy showed cortisol peak

ObjectiveIt is still unknown whether prolonged treatment with somatostatin analogs (SSTa) may cause a long-lasting disease remission in GH-secreting adenomas after drug discontinuation. The aim of the present study was to investigate the evolution of GH/IGF-I secretion and tumor mass after SSTa withdrawal in patients affected by acromegaly.Patients and DesignA total of 27 patients with acromegaly (12de novoand 15 previously operated) were treated with SSTa for a median period of 48 months and considered optimally controlled in hormonal and neuroradiological terms. None of them were previously irradiated.MethodsBasal GH, post-glucose GH nadir, IGF-I, clinical signs/symptoms, and metabolic parameters were evaluated after 12–16 weeks from drug withdrawal. Only patients who met the current criteria for disease remission remained in drug suspension being periodically re-evaluated for biochemical/clinical data and neuroradiological imaging.ResultsAfter 12–16 weeks withdrawal, 15 of the 27 patients had disease relapse and restarted SSTa, while 12 were considered ‘in disease remission’ (44% of total). Glucose metabolism improved in both euglycemic and diabetic patients after short-term SSTa discontinuation. Only one of the ten patients who reached 24 weeks withdrawal showed biochemical disease recurrence. On the whole, five of the patients still in remission after 6 months have already prolonged the follow-up over 12 months (median: 24 months), without clinical and biochemical/neuroradiological evidence of disease recurrence.ConclusionsThese preliminary data indicate a successful withdrawal of SSTa at least in a subset of well-responsive patients with acromegaly and challenge the previously held concept that medical therapy is always a lifelong requirement.

Some authors proposed to lower the present postglucose GH nadir cut-off (i.e.1 microg/l) to that obtained in healthy subjects to establish remission of acromegaly. The aim of the study was to correlate GH nadir with hormonal and metabolic parameters and to confirm the adequacy of the current limit to define disease remission.Retrospective study of 40 acromegalic patients cured by surgery, followed by radiotherapy when appropriate, studied at the time of disease remission (Phase 1) and re-evaluated after at least 3 years' follow-up (median 6.5 year, Phase 2). GH nadir was evaluated in 44 sex- and age-matched controls.Symptom score, pituitary function, neuroradiological imaging, metabolic parameters (BMI, glucose metabolism, insulin sensitivity, lipid profile, blood pressure).The upper limit of the 'normal' GH nadir was fixed at 0.26 microg/l (mean + 2SD of controls). In Phase 1, GH nadir was0.26 microg/l in 16 patients (Group A) and0.26 microg/l in 24 patients (Group B). Group B had only slightly higher IGF-1 SDS (0.4 +/- 1.0 vs.- 0.1 +/- 1.0, P = ns) and lower body mass index (BMI) than Group A (26.2 +/- 2.4 vs. 30.6 +/- 4.5 kg/m(2), P0.005). GH nadir positively correlated with IGF-1 (P0.05, r = 0.32) and negatively with BMI (P0.05, r = 0.42). In Phase 2, all patients had IGF-1 levels in the normal range and GH nadir1 microg/l, both parameters being even lower than those found at the time of remission. No patient had either clinical or neuroradiological evidence of disease recurrence.The current GH nadir limit is still adequate to define both short- and long-lasting remission of acromegaly, independently of the type of definitive treatment. Patients with the lowest GH nadir should probably be monitored long-term for adequacy of their GH secretion.