Correlation analysis between short-term insulin-like growth factor-I and glucose intolerance status after transsphenoidal adenomectomy in acromegalic patients: a large retrospective study from a single center in China

ABSTRACT Objectives: Our study aimed to investigate the associations of glucose tolerance status with insulin-like growth factor-I (IGF-I) and other clinical laboratory parameters of acromegalic patients before and after the patients underwent transsphenoidal adenomectomy (TSA) by conducting a single-center, retrospective study. Subjects and methods: A total of 218 patients with acromegaly who had undergone TSA as the first treatment were retrospectively analyzed. Serum IGF-I, growth hormone (GH) and glucose levels were measured before and after surgery. Results: The follow-up levels for random GH, GH nadir, and the percentage of the upper limit of normal IGF-I (%ULN IGF-I) were decreased significantly. The percentages of normal (39.0%), early carbohydrate metabolism disorders (33.0%) and diabetes mellitus (28.0%) changed to 70.2%, 16.5% and 13.3%, respectively, after TSA. %ULN IGF-I at baseline was higher in the diabetes mellitus (DM) group than in the normal glucose tolerance group and impaired glucose tolerance (IGT) /impaired fasting glucose (IFG) groups before TSA, and the DM group exhibited a greater reduction in %ULN IGF-I value after surgery. The follow-up %ULN IGF-I value after surgery was significantly lower in the improved group, and Pearson's correlation analysis revealed that the reductions in %ULN IGF-I corresponded with the reductions in glucose level. Conclusion: This study examined the largest reported sample with complete preoperative and follow-up data. The results suggest that the age- and sex-adjusted IGF-I level, which reflects altered glucose metabolism, and the change of it are associated with improved glucose tolerance in acromegalic patients both before and after TSA.

Resultados do tratamento cirúrgico na acromegalia com um único neurocirurgião e meta-análise cumulativa / Outcome of surgical treatment for acromegaly performed by a single neurosurgeon and cumulative meta-analysis / Outcome of surgical treatment for acromegaly performed by a single neurosurgeon and cumulative meta-analysis

Avaliamos retrospectivamente os resultados da cirurgia transesfenoidal num grupo de acromegálicos operados por um único neurocirurgião, comparando-os com uma meta-análise cumulativa de 10 séries (1.632 pacientes) publicadas entre 1992-2005. Estudamos 28 pacientes (17M/11F; 44,1 ± 12,7 anos; 27 com macroadenomas, sendo 86 por cento invasivos), acompanhados por 21,4 ± 17,6 meses após a cirurgia; eles foram classificados de acordo com a atividade da acromegalia em: 1) doença controlada (DC): GH basal ou médio < 2,5 ng/ml ou GH nadir no TTOG < 1ng/ml e IGF-1 normal; 2) não controlada (DNC): GH basal ou médio > 2,5 ng/ml ou nadir no TTOG > 1 ng/ml e IGF-1 elevado; 3) inadequadamente controlada (DIC): GH normal e IGF-1 elevado ou GH elevado e IGF-1 normal. Após a cirurgia, os níveis de GH reduziram de 61,7 ± 101,1 ng/ml para 7,2 ± 13,7 ng/ml (p< 0,001), e os de IGF-1 de 673,1 ± 257,7 ng/ml para 471,2 ± 285 ng/ml (p= 0,01). A taxa de remissão bioquímica foi de 57 por cento [10 pacientes (35,5 por cento) com DC e 6 (21,5 por cento) com DIC], similar àquela obtida na meta-análise de cirurgias de macroadenomas. Sete dos 28 pacientes foram submetidos à re-intervenção (4 operados em outro hospital e 3 pelo nosso neurocirurgião), sendo 5 (71,5 por cento) classificados como DC no pós-operatório. Invasão de seio cavernoso foi mais prevalente nos DNC e DIC, e desvio de haste hipofisária no grupo DNC. A taxa de remissão foi maior nas séries em que apenas um único cirurgião realizou os procedimentos (66 por cento vs. 49 por cento; p< 0,05). Em conclusão, esses dados comprovam que a experiência do neurocirurgião pode aumentar significativamente as taxas de remissão do tratamento cirúrgico da acromegalia, especialmente em tumores maiores e mais invasivos, e que a re-intervenção realizada por cirurgião experiente deve ser considerada nos algoritmos de abordagem terapêutica desta doença.

The aim of this retrospective study was to evaluate the results of transsphenoidal surgery in a group of patients with acromegaly who were operated by the same neurosurgeon. Our results were compared to those from a cumulative meta-analysis of 10 series (1,632 patients) published between 1992­2005. We followed 28 patients (17M/11F; 44.1 ± 12.7 yr; 27 with macroadenomas; 86 percent being invasive) during 21.4 ± 17.6 months after treatment. Patients were classified according to disease activity as follows: 1) controlled (CD): basal or mean GH < 2.5 ng/ml or nadir GH (OGTT) < 1 ng/ml and normal IGF-1; 2) uncontrolled (UCD): basal or mean GH > 2.5 ng/ml or nadir GH > 1 ng/ml and elevated IGF-1; 3) inadequately controlled (ICD): normal GH and elevated IGF-1 or elevated GH and normal IGF-1. After surgery, GH levels decreased from 61.7 ± 101.1 ng/ml to 7.2 ± 13.7 ng/ml (p< 0.001) and mean IGF-1 from 673.1 ± 257.7 ng/ml to 471.2 ± 285 ng/ml (p= 0.01). Biochemical remission rate was 57 percent [10 (35.5 percent) patients with CD and 6 (21.5 percent) with ICD], similar to the mean remission rate observed in the meta-analysis of surgical outcome of macroadenomas. Seven of 28 patients were submitted to surgical re-intervention (4 had been previously operated elsewhere and 3 by our neurosurgeon), with CD observed in 5 (71.5 percent) on follow-up. Cavernous sinuses invasion was more prevalent in UCD and ICD, whereas infundibular stalk deviation occurred only in patients with UCD. Remission rate was significantly higher in series where all surgical procedures were performed by the same surgeon (66 percent vs. 49 percent; p< 0.05). Thus, the surgeon's experience significantly improves the surgical outcome in acromegaly, especially in patients harboring large and invasive tumors, and re-intervention performed by an experienced surgeon should be considered in the algorithms for clinical management of this disease.