Objective. This prospective open trial aimed to evaluate the efficacy and safety of isotretinoin (13-cis-retinoic acid) in patients with Cushing's disease (CD). Methods. Sixteen patients with CD and persistent or recurrent hypercortisolism after transsphenoidal surgery were given isotretinoin orally for 6–12 months. The drug was started on 20 mg daily and the dosage was increased up to 80 mg daily if needed and tolerated. Clinical, biochemical, and hormonal parameters were evaluated at baseline and monthly for 6–12 months. Results. Of the 16 subjects, 4% (25%) persisted with normal urinary free cortisol (UFC) levels at the end of the study. UFC reductions of up to 52.1% were found in the rest. Only patients with UFC levels below 2.5-fold of the upper limit of normal achieved sustained UFC normalization. Improvements of clinical and biochemical parameters were also noted mostly in responsive patients. Typical isotretinoin side-effects were experienced by 7 patients (43.7%), though they were mild and mostly transient. We also observed that the combination of isotretinoin with cabergoline, in relatively low doses, may occasionally be more effective than either drug alone. Conclusions. Isotretinoin may be an effective and safe therapy for some CD patients, particularly those with mild hypercortisolism.

Summaryobjectives An estimated 15 million persons suffer from lymphoedema of the leg in filariasis-endemic areas of the world. A major factor in the progression of lymphoedema severity is the incidence of acute dermatolymphangioadenitis (ADLA), which is triggered by bacteria that gain entry through damaged skin, especially in the toe web spaces ('interdigital skin lesions'). Little is known about the epidemiology of these skin lesions or about patients' awareness of them.methods We interviewed and examined 119 patients (89% women) with lymphoedema of the leg in Recife, Brazil, an area endemic for bancroftian filariasis.results We detected 412 interdigital skin lesions in 115 (96.6%) patients (mean, 3.5 lesions per patient, range 0-8). The number of interdigital skin lesions was significantly associated with lymphoedema stage (P < 0.001) and frequency of ADLA (P < 0.0001). Only 20 (16.8%) patients detected their own interdigital skin lesions or considered them abnormal. Patients reported a mean of 3.6 ADLA episodes during the previous 12 months (range, 0-20); reported ADLA incidence was associated with lymphoedema stage (P < 0.0001) and the number of interdigital skin lesions detected by the examining physician (P < 0.0001).conclusions These data suggest that interdigital skin lesions are a significant risk factor for ADLA and that persons with lymphoedema in filariasis-endemic areas are unaware of their presence or importance. Prevention of ADLA through prompt recognition and treatment of interdigital skin lesions will require that patients be taught to identify lesions, especially between the toes and to recognize them as abnormal.

Somatostatin analogs (SSAs) represent the mainstay of therapy in acromegaly. One of the potential disadvantages is the expected need to maintain therapy indefinitely in previously non-irradiated patients. The aim of this multicenter prospective open trial was to evaluate the likelihood of successful discontinuation of SSA therapy in well-controlled acromegalic patients who fulfilled very strict criteria: two or more years of treatment with the long-acting SSA octreotide LAR (OCT-LAR), a stable dose and injections interval every 4 weeks or longer for the previous year, GH levels <2.5 ng/ml and normal IGF-1 levels for age, a tumor remnant <10 mm, no history of radiotherapy, and no use of cabergoline or pegvisomant over the previous 6 months. Disease recurrence was defined as an increase of IGF-1 to levels above 1.2-fold the upper limit of normal (ULN). Out of 220 patients, 20 patients (12 women and 8 men; mean age, 48.1 ± 10.3 years; age range, 27-64) treated for 2.74 ± 0.64 years (range, 2.0-4.4) were included in this prospective study and OCT-LAR therapy was stopped. Four patients (20 %) remained without clinical and biochemical/neuroradiological evidence of disease recurrence after 12-18 months of follow-up. Sixteen patients (80 %) relapsed biochemically within 9 months after drug withdrawal and restarted OCT-LAR at the same previous dose. Compared to recurring subjects, non-recurring patients had significantly lower mean IGF-1 (× ULN) levels but there were some overlapping values in both groups. No other characteristic could be identified as a predictor of successful OCT-LAR discontinuation. Our findings demonstrated that OCT-LAR withdrawal, though rare, is possible in well-selected acromegalic patients treated for at least 2 years and considered optimally controlled in hormonal and neuroradiological terms.

Successful discontinuation of cabergoline (CAB) treatment has been reported in 31–75% of prolactinomas patients treated for at least 2 years. In contrast, it is not well established whether CAB therapy can be successfully withdrawn after a failed first attempt. This prospective open trial was designed to address this topic and to try to identify possible predictor factors. Among 180 patients with prolactinomas on CAB therapy, the authors selected those who fulfilled very strict criteria, particularly additional CAB therapy for at least 2 years, normalization of serum prolactin (PRL) levels following CAB restart, no tumor remnant >10 mm, no previous pituitary radiotherapy or surgery; and current CAB dose ≤1.0 mg/week. Recurrence was defined as an increase of PRL levels above the upper limit of normal. A total of 34 patients (70.6% female) treated with CAB for 24–30 months were recruited. Ten patients (29.4%) remained without evidence of recurrence after 24–26 months of follow-up. Twenty-four patients (70.6%) recurred within 15 months (75% within 12 months) after drug withdrawal and ~80% were restarted CAB. Median time to recurrence was 10.5 months (range, 3–15). Despite overlapping values, non-recurring patients had significantly lower mean PRL levels before withdrawal. Moreover, the recurrence rate was lower in subjects without visible tumor on pituitary magnetic resonance imaging (MRI) than in those with small remnant tumor (60 vs. 79%), though the difference was not statistically significant (P = 0.20). No other characteristic could be identified as a predictor of successful CAB discontinuation. In conclusion, a second attempt of CAB withdrawal after two additional years of therapy may be successful, particularly in patients with lower PRL levels and no visible tumor on pituitary MRI. Close monitoring of PRL level is mandatory, especially within the first year after withdrawal, where most recurrences are detected.