Our study presents one of the largest series of patients treated with PEETS by single neurosurgeon in such a short time period and is the first to analyze remission, endocrinological and anatomical complications, and hypopituitarism improvement in the same series of patients treated with PEETS. In all other studies on PEETS, the authors focused only on remission (the extent of tumor removal), anatomical complications and diabetes insipidus, constantly ignoring anterior pituitary function. In addition, this is the largest series of patients with prolactinomas initially treated with PEETS.
Overall postoperative remission in our series was achieved in 83.8% (98/117) of patients; 69.8% with macroadenomas (44/63) and 100% with microadenomas (54/54). Remission was achieved in 80.6% of patients with nonfunctioning adenomas and in 84.9% with functioning adenomas. It is extremely difficult to compare these results with other studies due to a wide variety of remission criteria. However, a metaanalysis on remission and anatomical complications consisting of eight studies reported an overall remission rate of 78% (14
). Similar results were reported in a more recent study, which obtained an overall remission rate of 79.3% (83% for nonfunctioning and 76.3% for functioning adenomas) after a median follow-up of 61.5 months (15
). Studies that evaluated initial remission in functioning adenomas reported the rates of 63%-75.6% (16
). Our results are slightly better than those reported in all previous studies, possibly due to a larger proportion of patients with microprolactinomas in our series, which might have a more favorable outcome.
A total of 20.5% (24/117) of complications was recorded, endocrinological in 17.1% (20/117) and anatomical in 3.4% of cases. Complication rates (especially anatomical) were slightly lower when compared with Gondim’s series, in which 26.9% (81/301) of complications was observed, 17.9% endocrinological and 8.97% anatomical (18
). Anatomical complication rates in our series are similar to those reported by Zhang et al (3%, 21/678) (19
). We observed low rates of postoperative cerebrospinal fluid leaks (0.8% in our series compared to 2.6% reported by Gondim). In the metaanalysis conducted by Tabee, postoperative cerebrospinal fluid leak occurred in 2% and permanent diabetes insipidus in 1% of patients (14
). Lower rates of cerebrospinal fluid leak in our series are not in accordance with previous studies reporting on higher rates of cerebrospinal fluid leak after PEETS (16
). A total of 17.1% of endocrinological complications in our series is in accordance with Gondim’s study (18
), which is the single reported study on endocrinological complications after PEETS. Endocrinological complications differ tremendously between hormonal deficiencies in our series. We recorded far more adrenal insufficiencies than other hormonal deficiencies. This is possibly due to different methodology for the analysis of adrenal insufficiency, which was analyzed indirectly through the necessity for hydrocortisone treatment over the first 18 months after surgery, unlike other hormonal deficiencies that were analyzed on the seventh postoperative day. This different approach toward the assessment of adrenal axis is due to empirical hydrocortisone therapy, which needed to be administered routinely to all patients prior and three months after the surgery, since there are no reliable predictors of sufficient adrenal function (20
). Additional explanation of this discrepancy might be in the fact that routine hydrocortisone therapy by itself might potentially influence adrenal axis recovery via inhibition of corticotropin secretion. Our results confirm that microadenoma patients recover their pituitary function faster than macroadenoma patients. The majority of microadenoma patients require hydrocortisone replacement only within the first six months after surgery.
It is considered that pituitary deficiencies in patients with pituitary adenomas are caused by compression and destruction of the normal pituitary gland by the expanding mass and possibly due to focal necrosis after compression of the portal circulation (12
). In Webb's series, in 48% of patients with hypopituitarism at least one hormone deficiency was improved (12
). In another series, growth hormone deficiency recovered in 15%-47%, hypogonadism improved in 29%-32%, adrenal insufficiency in 38-5, and hypothyroidism in 13%-57% of the cases (8
). In our series, 35.3% of hormonal deficiencies improved after surgery: in 26.7% of patients with hypogonadism, 50.0% with growth hormone deficiency, 42.1% with adrenal insufficiency, and 12.5% with hypothyroidism. However, our results are hardly comparable with those in previous studies, due to different periods after surgery in which hormonal status was assessed. Hypopituitarism progressively improves after surgery (23
). Arafah and Webb evaluated recovery one to six months postoperatively, unlike in our study where hypogonadism, GH deficiency, and hypothyroidism improvement were assessed on the seventh postoperative day (12
). But nevertheless, improvement rates in our series were only slightly inferior to theirs. These data emphasize the role of increased intrasellar pressure in the pathophisiology of hypopituitarism caused by pituitary adenoma. Recovery of adrenal insufficiency in our series was assessed within 18 months after surgery, similar to Berg’s study (23
), in which hypocortisolism was evaluated by insulin-tolerance test 12 months after surgery. Recovery rate of 42.1% in our series is comparable to that reported by Berg (recovery in 55% of patients 12 months postoperatively), despite the difference in criteria in these two studies (23
Since we were the first to analyze the outcomes of PEETS in large series of patients with prolactinomas, we wish to discuss the role of PEETS in prolactinoma treatment. DA are first-line treatment for prolactinomas (7
). However, up to one third of patients treated with bromocriptine experienced systemic side-effects, 12% did not tolerate the drug in therapeutic doses, and 5%-10% showed minimal or no response to treatment (24
). Cabergoline has been shown to be more effective in normalizing PRL levels, with significant reduction of adverse effects (26
), but its use is limited in developing countries due to relatively high costs. Transsphenoidal surgery improved substantially over the last 20 years. In Turner’s study on microsurgical treatment of 32 microprolactinomas published twelve years ago, remission rates were 78% with 13 (40%) hormonal deficiencies developed after the surgery (27
). In the most recent study, Babey reported remission rates of 94% in 34 small prolactinomas with one case of newly developed hypogonadism (complete hormonal status was not determined) (11
). This is similar to Kreutzer’s study with remission rates of 91.3% in 56 microprolactinoma patients and overall endocrinological complication rates of 8.8% in 171 prolactinoma patients (micro-, macro-, giant adenomas) (10
). We achieved remission in 100% (39/39) of patients with microprolactinomas, along with only one case of transient diabetes insipidus, without permanent hormonal deficiencies. Endocrinological complications were recorded in 3 (4.9%) macroprolactinoma patients, with one case of permanent hypocortisolism (1.6%). Our results are slightly superior to all previously published data, suggesting that PEETS might be a valuable alternative to DA therapy. There is no doubt that medical treatment of prolactinomas is the first-line treatment. However, since the majority of prolactinomas are detected in the stage of microadenoma (7
), treatment with PEETS in experienced specialized centers might be a reasonable alternative to DA treatment.
Our study has some limitations: the data are largely descriptive and it is a non-randomized, single institutional study. Also, due to a small number of patients, statistical analysis could not be performed between certain groups. In conclusion, patients with microadenomas have higher remission and lower complication rates following PEETS, emphasizing the necessity for early detection and treatment of pituitary adenomas. PEETS is a discussion-worthy method for microprolactinoma treatment.