Remissão da acromegalia após suspensão do tratamento farmacológico: estudo prospectivo multicêntrico

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Casagrande, Alessandra [UNIFESP]
Abucham Filho, Julio Zaki [UNIFESP]
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Artigo 1: Context: Long-term remission of acromegaly after somatostatin analogs withdrawal has been reported in 18-42% of patients in studies with relatively small number of patients using different inclusion and remission criteria. Objectives: To establish the probability and predictive factors for short-and long-term remission (normal IGF-1 for age/sex: IGF-1?1.00 xULN) after octreotide- LAR withdrawal in a larger population of well controlled patients with acromegaly (normal mean IGF-1 in the last 24 months). Design: Prospective, multicenter. Settings and Participants: Fifty-eight well controlled patients with acromegaly receiving only octreotide-LAR as primary or post-surgical treatment were included in 14 University centers in Brazil. All patients had been on stable doses and dose intervals of octreotide-LAR in the last year and no one had been submitted to radiotherapy. Intervention: Withdrawal of octreotide-LAR. Main outcome measurement: Serum IGF-1 after 8 (short-term) and 60 weeks (long-term) of octreotide-LAR withdrawal. Results: Seventeen of 58 patients (29%) were in remission in the short-term, but only four achieved long-term remission after treatment withdrawal. Kaplan-Meier estimated remission probability at 60 weeks was 7% and decreased to 5% at 72 weeks. Short-term remission rate was significantly higher (44%, P=0.017) in patients with pre-treatment IGF-1<2.4 xULN. No other predictive factor for short- or long- term remission was found. Conclusion: Long-term remission of acromegaly after octreotide-LAR withdrawal was an uncommon and frequently unsustainable event. In contrast, the much higher probability of short-term remission suggests that increasing dose intervals should be emphasized and routinely attempted in well controlled patients. Artigo 2: Purpose: Remission of acromegaly has been reported after somatostatin analogs withdrawal, but not after withdrawal of combination therapy with cabergoline, and only sporadically in patients controlled by cabergoline alone. Methods: To establish the remission rates (normal IGF-1 for age/sex: IGF- 1?1.00 xULN) after withdrawal of combined treatment with octreotide-LAR and cabergoline and cabergoline alone we prospectively studied 16 patients with acromegaly controlled by those treatments in the preceding two years as part of a larger study on remission of acromegaly after withdrawal of different medical treatments. Results: Among 97 patients with controlled acromegaly included in the entire study, only 16 patients had been on combination therapy (n=12) or cabergoline alone (n=4). At eight weeks after treatment withdrawal, three patients (19%) were in remission (short-term remission). At 60 weeks (long-term remission), IGF-1 levels were still in the normal range in two patients (12.5%) and remained normal up to 108 weeks after treatment withdrawal (last visit). One patient had been treated with cabergoline alone and another one with combination of octreotide and cabergoline before treatment withdrawal. Those two patients represent, respectively, 25% and 8.5% of remission rates according to type of previous treatment. Conclusion: Remission of acromegaly after withdrawal of treatment can also occur in patients with acromegaly controlled by cabergoline alone or cabergoline combined with octreotide.
CASAGRANDE, Alessandra. Remissão da acromegalia após suspensão do tratamento farmacológico: estudo prospectivo multicêntrico. 2016. 64 f. Tese (Doutorado em Endocrinologia Clínica) – Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2016.