Les adénomes somatotropes: etude clinique, biologique et neuroradiologique portant sur 85 cas d'acromégalie suivis à l'Hôpital de la Timone.

Introduction
Selective acromegaly for acromegaly may have a wide range of remission rates, ranging from 40 to 80% in published series. These heterogeneous results rely not only on the surgeon experience, but also depend on the use of different biochemical remission criteria.
Aim of the work
The first part of this study is to evaluate clinical, biochemical and radiological data in a consecutive series of 85 patients diagnosed with acromegaly and followed-up by the endocrine team of Prof Jaquet in La Timone University Hospital (Marseille, FRANCE). The aim of the second part of this study is to settle a predictive model of surgical remission , after univariate and multivariate analysis of this clinical, biochemical, radiological and pathological data.
Methods
Biological criteria of acromegaly surgical remission included: normal IGF1 values according to age and sex, mean GH values <2µg/L and GH<1µg/L after 75g OGTT. In mixed somatotroph adenomas, remission criteria also included prolactin and alpha subunit hypersecretion normalization at last follow up.
Results
The first part of the study included 85 acromegalics (39 males, 46 females). Mean age at diagnosis was 43,5 years (range 13-68) and mean delay of acromegaly diagnosis was 6,2± 4,7 years.Mean follow up was 29 ±32 months. Among the 85 patients: 52/85 had headaches, 33/80 had a visual impairment (scotomas= 22, quadrantopsias= 2, hemianopsias= 9). Mean hormonal values at diagnosis were: GH=66,5µg/L (range 1-1730), IGF1=769 (range 300-1900 µg/L), PRL=27,3 µg/L (range 9-130, n=67), alpha subunit=4,4 UI/L (range 0,2-60). Pituitary MRI identified 3/19 microadenomas (frontal diameter<10 mm) invading cavernous sinus and 49/66 macroadenomas (frontal diameter equal or > 10 mm) with invading features. Frontal diameter had a good correlation with cavernous sinus invasion (r=0,48 , p<0,01) and sphenoidal sinus extension (r=0,46,p<0,01). GH hypersecretion had a good positive correlation with tumoral diameter (r=0,46 , p<0,01).
In the second part of the study, there were 72 acromegalic patients that underwent transphenoidal surgery by the same neurosurgeon (Prof F. Grisoli), with a mean post surgical follow up of 26 months. Using astringent biochemical remission criteria, there were 27 patients (38%) in remission and 45 patients not cured. In univariate analysis none of the following criteria was predictive of remission: age, sex, headaches, visual disturbances, adenoma immunostaining.
Pathological data included: 29 GH adenomas, 18 mixed GH/alpha SU, 12 mixed GH/prolactin, 11 GH/prolacti/alpha SU and two mixed GH (with TSH and/or LH staining). In univariate and multivariate analysis MRI radiological signs of invasion (carotideal extension) and mean tumoral diameter>22 mm independently predicted surgical failure (p<0,0001 and p=0,00054 respectively).

Conclusions
In this series GH nadir <1 µg/L is highly specific (89%) as an early surgical remission criteria (day 8) , whereas normalization of IGF1 is not predictive. Using astringent biochemical remission criteria, only 38 % of patients were in remission. Our multivariate predictive model identified MRI radiological cavernous sinus invasion and tumor diameter as main failure presurgical predictive factors.In GH tumors which diameter was >30 mm, surgical failure was 100%. Clinicians should integrate these parameters when evaluating surgical treatment in acromegaly.