Noninvasive Macroadenomas Research Articles

Transsphenoidal Approach for Sellar Region Tumor : A Case Series

Introduction: Transsphenoidal approaches to the sellar region, with endoscopic or microscopic techniques, are regularly used to treat a diverse collection of pathologies. Case Description: Three patients with presenting symptoms visual disturbance and headache were evaluated with MRI that showes sellar region masses. All patients were undergo transphenoid tumor removal. Post operation evaluation show improvement in visual disturbance and headache with no adverse event after procedure. Discussion : Transsphenoidal endoscopic surgery (TSS) for functional pituitary adenomas yields better endocrinologic results for noninvasive macroadenomas. However, the rate of postoperative CSF leakage was greater with the endoscopic method. In patients with pituitary adenomas, younger age, dense visual field defect, and the preoperative absence of central or bilateral visual field abnormalities were predictive factors of visual field recovery following transsphenoidal approach-tumor excision. Overall survival rates are generally high, ranging from 91% to 98%. Conclusion: Transphenoid approach was a good surgical method for sellar region masses and show good outcomes after operation. Keyword : Sellar region masses; Surgical; Transsphenoid approach

Clinical Characteristics and Outcomes of Prolactinomas in Children and Adolescents: A Large Retrospective Cohort Study.

Prolactinoma, the most common subtype of pituitary adenoma, is rare in children and adolescents. Clinical presentation and treatment outcomes of prolactinomas in this population have been evaluated insufficiently. To summarize the clinical features, both medication and surgical outcomes of prolactinomas in children and adolescents in a large retrospective cohort from China. A cohort of patients with prolactinomas aged ≤20 years at diagnosis between 2012 and 2021 in Peking Union Medical College Hospital were retrospectively analyzed. The cohort comprised 170 patients (115 females and 55 males, median age 16.6 years), with 20.0% (23/115) girls without menarche and 33.3% (18/54) boys in prepuberty. The median maximal diameter was 15.0 mm (61.2% macroadenomas and 4.6% giant adenomas), and the median baseline prolactin (PRL) level was 211.0 ng/mL. Larger sizes and higher PRL levels were observed in girls without menarche at diagnosis and in boys. Most girls presented with menstrual disturbance (86.7%), and boys were frequently bothered by headaches (42.6%), reduced height velocities (25.9%), and delayed puberty (18.2%). Dopamine agonists (DAs) were used as first-line treatment in 133 patients, and the resistance rate was 22.5% (25/111), independently associated with maximal tumor diameters (P = .035). Surgery was performed in 76 patients. Long-term surgical remission rates were 32.9% (25/76) overall, negatively associated with cavernous sinus invasion independently (P = .025), 59.4% (19/32) in noninvasive tumors (64.0% in 25 noninvasive macroadenomas), and 5.0% (1/20) in invasive tumors. Pediatric prolactinomas exhibited more severe clinical characteristics in boys and in patients diagnosed during earlier stages of pubertal developments. Given the overall efficacy of PRL normalization by medication and considerable surgical remission rate in noninvasive tumors, DAs remain the first-line recommendation for prolactinomas in children and adolescents, while surgery might be viable for noninvasive tumors.

Cell proliferation, apoptosis, and angiogenesis in non-functional pituitary adenoma: association with tumor invasiveness.

Non-functioning pituitary adenoma (NFPA) is the most prevalent pituitary macroadenoma. No prognostic marker has been found to explain the behavior of these tumors. We aimed to explore cell proliferation, apoptosis, proangiogenic markers, and microvascular density (MVD) in noninvasive and invasive NFPAs. Adenoma invasiveness was defined according to Knosp and Hardy classifications based on preoperative magnetic resonance imaging scans. Cell proliferation was examined using Ki67 and P53. Tissue expression of Bcl-2 was used to assess the antiapoptosis pathway. CD34 and CD105 were measured to evaluate MVD, while VEGF expression was assessed as an indicator of pro-angiogenesis. Moreover, VEGF, bFGF, endocan, and endostatin were measured on preoperative serum samples. Tissue and serum markers were examined in 18 patients with invasive and 21 patients with noninvasive NFPAs. Ki67 less than 3% was reported in 10 invasive and 14 noninvasive NFPAs (P = 0.752). P53 staining was negative in all subjects. In addition, Bcl-2 staining was negative in 15 and 20 subjects, respectively (P = 0.718). VEGF-A expression 2+ or 3+ was reported in 9 invasive and 11 noninvasive macroadenomas (P = 0.83). Moreover, CD34 and CD105 positivity were comparable between the two groups. Furthermore, the comparison of serum markers showed no significant differences. Cell proliferation, apoptosis, and angiogenesis play a limited role in NFPA behavior.

Management of Pituitary Adenomas: Mononostril Endoscopic Transsphenoidal Surgery.

Introduction:The endoscopic transsphenoidal approach for pituitary adenomas and other sellar lesions is quickly becoming the procedure of choice in their surgical management. The most common approach is binostril three-hand technique which requires a large exposure and subjects both nasal cavities to potential trauma. To reduce nasal morbidity, we employ a mononostril two-hand technique with the help of the endoscope holder. In this research, we review our series to determine efficacy of this approach in the management of pituitary adenomas.Methods:We performed a retrospective analysis of our initial series of 64 consecutive patients with pituitary adenomas operated by the same surgical team from 2008 till 2014 using a mononostril endoscopic approach. After categorizing the lesions into microadenomas, noninvasive macroadenomas, and invasive macroadenomas, we reviewed the radiological and biochemical outcomes of the surgeries after 3 months, 12 months, and 18 months. We also assessed recurrences and complications. Extent of resection was divided into gross total resection, near total resection (>90% resection), and partial resection for the remaining.Results:Our results show resection rates comparable to most series in the literature, with a gross total resection of 87% in non-invasive macroadenomas, and surgical disease control in 75% of invasive nonfunctioning adenomas. The remission rate in Cushing’s disease was 81%, where it achieved up to 58% surgical remission in growth hormone secreting pituitary adenomas (including the invasive adenomas). The complication rate was very low.Conclusion:We conclude that the mononostril endoscopic approach is well suited for most pituitary tumor operations and carries comparable remission and resection rates to most endoscopic series with minimal complications and nasal morbidity.

Diagnosis and treatment of TSH-secreting adenomas: review of a longtime experience in a reference center.

TSH-secreting pituitary adenomas are among the less prevalent pituitary tumors, corresponding to 0.9-1.5% of all pituitary adenomas in surgical series. A series of 11 patients with TSH-secreting and cosecreting adenomas diagnosed and treated in the last 25years in a single center is described. The mean age at diagnosis was 37 years (range 18-80years; median 23years); the ratio of male-to-female patients was similar (6M:5F). Only three patients was the correct diagnosis established shortly after the initial medical evaluation. Other four patients were initially diagnosed with other pituitary adenomas (prolactinoma, acromegaly, and non-secreting pituitary tumor) and another four diagnosed with primary hyperthyroidism. There was a mean diagnostic delay of 6.0years (range 0.5-25years; median 2years). Nine patients had macroadenomas and two patients had microadenomas. Seven patients underwent pituitary surgery which controlled the disease in only two (one micro- and one noninvasive macroadenoma). The other treatments were directed to the thyroid gland (surgery or 131I radiotherapy), pituitary radiotherapy, and somatostatin analog. In spite of its relatively straightforward diagnosis, which includes clinical/subclinical hyperthyroidism with or without goiter, increased free thyroxine and nonsuppressed TSH levels, and pituitary mass, the diagnosis of TSH-secreting and cosecreting adenomas was frequently unrecognized and thus much delayed. Serum alpha-subunit levels were high in nearly all patients with TSH-secreting adenomas and useful in excluding other conditions in the differential diagnosis. Proper indication and interpretation of simple laboratory tests should be emphasized in medical education to improve diagnostic accuracy.

Efficacy of transsphenoidal surgery in achieving biochemical cure of growth hormone-secreting pituitary adenomas among patients with cavernous sinus invasion: a systematic review and meta-analysis

Objectives: Growth hormone-secreting pituitary adenomas in adults can result in severe craniofacial disfigurement and potentially fatal medical complications. Surgical resection leading to remission of the disease is dependent on complete surgical resection of the tumor. Lesions that invade the cavernous sinus may not be safely accessible via an endonasal transsphenoidal surgery (TSS), and the rates of biochemical remission of patients with residual disease vary widely in the literature. We conducted a meta-analysis to examine the prevalence of biochemical remission after TSS among patients with growth hormone-secreting pituitary adenomas with and without cavernous sinus invasion.Methods: Embase, PubMed, and Cochrane Library databases were searched for relevant publications. Fourteen studies with 972 patients with biochemically confirmed growth hormone-secreting pituitary adenomas were included in the meta-analysis.Results: The overall remission prevalence under a fixed-effect model was 47.6% (95% CI = 40.8–54.4%) for patients with invasive macroadenomas (I2 = 74.6%, p < 0.01); 76.4% (95% CI = 72.2–80.1%) for patients with non-invasive macroadenomas (I2 = 59.6%, p = 0.03); and 74.2% (95% CI = 66.3–80.7%) for patients with non-invasive microadenomas (I2 = 36.4, p = 0.10). The significant difference among the three groups resulted from the difference between patients with or without cavernous sinus invasion (p = 0.01) and not from the size of adenomas among those without cavernous sinus invasion (p = 0.66).Discussion: The prevalence of biochemical remission in patients with cavernous sinus invasion was lower than in patients without cavernous sinus invasion after TSS for acromegaly.

Endoscopic Endonasal versus Microsurgical Transsphenoidal Approach for Growth Hormone–Secreting Pituitary Adenomas—Systematic Review and Meta-Analysis

The pituitary adenoma causing acromegaly is typically resected through a transsphenoidal approach and visualized with an operating microscope or endoscope. We undertook a systematic review and meta-analysis examining the clinical efficacy of endoscopic and microsurgical approaches. Relevant studies using either endoscopic or microscopic transsphenoidal approaches for growth hormone pituitary adenomas were identified until February 2016. Data were extracted and analyzed according to predefined clinical end points. We identified 31 studies, in which 950 patients underwent endoscopic transsphenoidal resection and 2137 patients underwent microsurgical transsphenoidal resection. Patients undergoing microsurgery were less likely to present with hypothyroidism (10.7% vs. 19.1%, P= 0.033, 462 vs. 156 patients) and less likely to have macroadenomas (66.9% vs. 83.8%, P ≤ 0.001, 1484 vs. 884 patients); adenomas with cavernous sinus invasion (21.3% vs. 44.4%, P= 0.036, 592 vs. 558 patients); and a lower mean tumor volume (17.84 vs. 20.54 mm3, P= 0.012, 158 vs. 248 patients). Patients treated via the endoscopic approach were more likely to achieve remission for noninvasive macroadenomas (83.8% vs. 66.9%, P ≤ 0.001, 115 vs. 365 patients). Sinusitis (15.6% vs. 2.6%, P < 0.001, 241 vs. 295 patients) and intraoperative cerebrospinal fluid leak (21.6% vs. 1.0%, P= 0.022, 697 vs. 127 patients) were more common in patients treated endoscopically, and meningitis (0.7% vs. 1.7%, P= 0.027, 511 vs. 1513 patients) was more common in patients undergoing a microsurgical approach. Our study shows the clinical utility of the endoscopic approach and demonstrates potential benefits including increased remission rates with noninvasive macroadenomas and a lower rate of meningitis.

Remisión bioquímica de pacientes acromegálicos sometidos a cirugía endoscópica

&lt;span&gt;Objetivo. La cirugía transnasal hernia transesfenoidal endoscópica es la base del tratamiento para la acromegalia en nuestro centro. Realizamos un estudio retrospectivo de 2008-2011 para determinar si este abordaje induce remisión bioquímica, y comparamos nuestras observaciones con series publicadas. Métodos. Analizamos retrospectivamente nuestra base de datos, e identificamos los pacientes sometidos a cirugía transnasal transesfenoidal endoscópica como tratamiento primario de acromegalia. Valoramos las imágenes y perfiles endocrinológicos pre-operatorios, y utilizamos los criterios del Consenso de Acromegalia de 2009 para determinar la remisión bioquímica. Resultados. Ocho pacientes recibieron adenomectomía endoscópica primaria. Uno tenía un microadenoma, uno un macroadenoma no invasivo, y seis presentan macroadenomas invasivos. La media de los niveles del factor de crecimiento similar a la insulina tipo I tres meses post-cirugía fueron 633 ng/mL (199 ng/ml-1600 ng/mL), mientras que los de la hormona de crecimiento fueron 10,20ng/mL (0,96ng/mL-16,60ng/mL). Dos pacientes cumplieron criterios de remisión; un macroadenoma no invasivo y un microadenoma. Cuatro de los pacientes restantes tuvieron remisión con análogos de somatostatina. Conclusiones. Este es el primer reporte de cirugía transnasal transesfenoidal endoscópica como terapia primaria de acromegalia en Costa Rica. La cura en pacientes con macroadenomas grandes e invasivos puede ser difícil y requiere de terapia multimodal.&lt;/span&gt;

Primary Endoscopic Transnasal Transsphenoidal Surgery for Magnetic Resonance Image–Positive Cushing Disease: Outcomes of a Series over 14 Years

There are scant data of endoscopic transsphenoidal surgery (ETS) with adjuvant therapies of Cushing disease (CD). To report the remission rate, secondary management, and outcomes of a series of CD patients. Patients with CD with magnetic resonance imaging (MRI)-positive adenoma who underwent ETS as the first and primary treatment were included. The diagnostic criteria were a combination of 24-hour urine-free cortisol, elevated serum cortisol levels, or other tests (e.g., inferior petrosal sinus sampling). All clinical and laboratory evaluations and radiological examinations were reviewed. Forty consecutive CD patients, with an average age of 41.0 years, were analyzed with a mean follow-up of 40.2 ± 29.6 months. These included 22 patients with microadenoma and 18 with macroadenoma, including 9 cavernous invasions. The overall remission rate of CD after ETS was 72.5% throughout the entire follow-up. Patients with microadenoma or noninvasive macroadenoma had a higher remission rate than those who had macroadenoma with cavernous sinus invasion (81.8% or 77.8% vs. 44.4%, P = 0.02). After ETS, the patients who had adrenocorticotropic hormone-positive adenoma had a higher remission rate than those who had not (76.5% vs. 50%, P = 0.03). In the 11 patients who had persistent/recurrent CD after the first ETS, 1 underwent secondary ETS, 8 received gamma-knife radiosurgery (GKRS), and 2 underwent both. At the study end point, two (5%) of these CD patients had persistent CD and were under the medication of ketoconazole. For MRI-positive CD patients, primary (i.e., the first) ETS yielded an overall remission rate of 72.5%. Adjuvant therapies, including secondary ETS, GKRS, or both, yielded an ultimate remission rate of 95%.

Clinical applications of somatostatin analogs for growth hormone-secreting pituitary adenomas

Excessive growth hormone (GH) is usually secreted by GH-secreting pituitary adenomas and causes gigantism in juveniles or acromegaly in adults. The clinical complications involving cardiovascular, respiratory, and metabolic systems lead to elevated morbidity in acromegaly. Control of serum GH and insulin-like growth factor (IGF) 1 hypersecretion by surgery or pharmacotherapy can decrease morbidity. Current pharmacotherapy includes somatostatin analogs (SAs) and GH receptor antagonist; the former consists of lanreotide Autogel (ATG) and octreotide long-acting release (LAR), and the latter refers to pegvisomant. As primary medical therapy, lanreotide ATG and octreotide LAR can be supplied in a long-lasting formulation to achieve biochemical control of GH and IGF-1 by subcutaneous injection every 4–6 weeks. Lanreotide ATG and octreotide LAR provide an effective medical treatment, whether as a primary or secondary therapy, for the treatment of GH-secreting pituitary adenoma; however, to maximize benefits with the least cost, several points should be emphasized before the application of SAs. A comprehensive assessment, especially of the observation of clinical predictors and preselection of SA treatment, should be completed in advance. A treatment process lasting at least 3 months should be implemented to achieve a long-term stable blood concentration. More satisfactory surgical outcomes for noninvasive macroadenomas treated with presurgical SA may be achieved, although controversy of such adjuvant therapy exists. Combination of SA and pegvisomant or cabergoline shows advantages in some specific cases. Thus, an individual treatment program should be established for each patient under a full evaluation of the risks and benefits.

Endoscopic transsphenoidal pituitary surgery: a good and safe primary treatment option for Cushing's disease, even in case of macroadenomas or invasive adenomas

Although the endoscopic technique of transsphenoidal pituitary surgery (TS) has been widely adopted, reports on its results in Cushing's disease (CD) are still scarce and no studies have investigated long-term recurrence rates. This is the largest endoscopic series published till now. To gain insight into the role of endoscopic TS as a primary treatment option for CD, especially in patients with magnetic resonance imaging (MRI)-negative CD and (invasive) macroadenomas. Retrospective cohort study. The medical records of 86 patients with CD who underwent endoscopic TS were examined. Data on preoperative and postoperative evaluation, perioperative complications, and follow-up were collected. Remission was defined as disappearance of clinical symptoms with a fasting plasma cortisol level ≤ 50 nmol/l either basal or after 1 mg dexamethasone. The remission rate in different adenoma subclasses varied significantly: 60% in MRI-negative CD (n=20), 83% in microadenomas (n=35), 94% in noninvasive macroadenomas (n=16), and 40% in macroadenomas that invaded the cavernous sinus (n=15). The recurrence rate was 16% after 71 ± 39 months of follow-up (mean ± S.D., range 10-165 months). Endoscopic TS is a safe and effective treatment for all patients with CD. Recurrence rates after endoscopic TS are comparable with those reported for microscopic TS. Our data suggest that in patients with noninvasive and invasive macroadenomas, the endoscopic technique of TS should be the treatment of choice as remission rates seem to be higher than those reported for microscopic TS, although no comparative study has been performed.

Clinical and diagnostic characteristics of hyperprolactinemia in childhood and adolescence

Pituitary adenoma is the most common cause of hyperprolactinemia, which is a rare endocrine disorder encountered in pediatric patient care. Epidemiological and clinical information about hyperprolactinemia in childhood and adolescence is limited. Clinical signs of hyperprolactinemia are very heterogeneous. In girls, disturbances in menstrual function and galactorrhea may be seen, whereas in boys, headache, visual disturbances, delayed pubertal development and hypogonadism are often present. Owing to the ease of ordering a serum prolactin measurement, an evidence-based, cost-effective approach to the management of this endocrine disorder is required. Before a diagnosis of hyperprolactinemia is made, drug use, renal insufficiency, hypothyroidism, and parasellar tumors should be excluded. The main objectives of treatment are normalization of prolactin level, adenoma shrinkage, and recovery from clinical signs related to hyperprolactinemia. In patients with microadenoma, invasive or non-invasive macroadenoma, and even in patients with visual field defects, dopamine agonists are the first-line treatment. Surgical treatment is indicated in patients who are unresponsive or intolerant to medical treatment or who have persistent neurological signs. Radiotherapy should be considered as a supportive treatment for patients in whom surgery fails or medical response is not achieved.

Outcomes after a purely endoscopic transsphenoidal resection of growth hormone–secreting pituitary adenomas

Using strict biochemical remission criteria, the authors assessed surgical outcomes after endoscopic transsphenoidal resection of growth hormone (GH)-secreting pituitary adenomas and identified preoperative factors that significantly influence the rate of remission. A retrospective review of a prospectively maintained database was performed. The authors reviewed cases in which an endoscopic resection of GH-secreting pituitary adenomas was performed. The cohort consisted of 26 patients who had been followed for 3-60 months (mean 24.5 months). The thresholds of an age-appropriate, normalized insulin-like growth factor-I concentration, a nadir GH level after oral glucose load of less than 1.0 μg/l, and a random GH value of less than 2.5 μg/l were required to establish biochemical cure postoperatively. Overall, in 57.7% of patients undergoing a purely endoscopic transsphenoidal pituitary adenectomy for acromegaly, an endocrinological cure was achieved. The mean clinical follow-up duration was 24.5 months. In patients with microadenomas (4 cases) the cure rate was 75%, whereas in patients harboring macroadenomas (22 cases) the cure rate was 54.5%. Cavernous sinus invasion (Knosp Grades 3 and 4) was associated with a significantly lower remission rate (p = 0.0068). Hardy Grade 3 and 4 tumors were also less likely to achieve biochemical cure (p = 0.013). The overall complication rate was 11.5% including 2 incidents of transient diabetes insipidus and 1 postoperative CSF leak, which were treated nonoperatively. A purely endoscopic transsphenoidal approach to GH-secreting pituitary adenomas leads to similar outcome for noninvasive macroadenomas compared with traditional microsurgical techniques. Furthermore, this approach may often provide maximal visualization of the tumor, the pituitary gland, and the surrounding neurovascular structures.

Fully endoscopic transsphenoidal surgery for functioning pituitary adenomas: A retrospective comparison with traditional transsphenoidal microsurgery in the same institution

Background The efficacy and the minimally invasive nature of the fully transnasal endoscopic procedure in the treatment of pituitary adenomas and other lesions of the sellar area have been widely reported in the literature. Many authors observed similar results in terms of the correction of hormonal hypersecretion in functioning pituitary adenomas using endoscopic endonasal surgery or the traditional microscopic technique. We report the endocrinologic outcome in 2 series of patients operated on at the same institution for functioning pituitary adenomas using these 2 different techniques. Methods This study includes 2 successive series of 60 consecutive patients presenting with a hormonally active pituitary adenoma operated on by the same surgeon. The surgical results obtained in the most recently operated group using a fully endoscopic endonasal technique were compared with those obtained previously using the traditional microsurgical transsphenoidal procedure. The classification of tumors into 4 grades according to Hardy was based on modern MRI and intraoperative findings. Results The overall remission rate of hypersecretion was 63% in the endoscopic group compared with 50% in the microsurgical group. The most obvious difference between the 2 groups was observed in noninvasive macroadenomas. In this specific grade of tumors, the remission rate of hypersecretion obtained using endoscopy was 78% compared with 43% using microsurgery. The endocrinologic results achieved for microadenomas were similar in the 2 groups. Postoperative CSF leaks occurred more frequently (6 cases) in the endoscopic group. Conclusions In our experience, fully endoscopic transsphenoidal surgery for functioning pituitary adenomas leads to a better endocrinologic outcome for noninvasive macroadenomas compared to the traditional microsurgical technique. However, morbidity with the endoscopic technique was higher in terms of the rate of postoperative CSF leaks.

High incidence of low O6-methylguanine DNA methyltransferase expression in invasive macroadenomas of Cushing's disease

Crooke's cell adenoma (CCA), characterized by massive Crooke's hyaline change in corticotroph adenoma, causes a rare subtype of Cushing's disease. In contrast to ordinary corticotroph adenomas, CCAs are generally aggressive and present as invasive macroadenomas, which are refractory to both surgery and radiotherapy and have a high-recurrence rate. Moreover, some patients with CCA present with distant or craniospinal metastases. Currently, there are no effective standard therapies for CCA. We report a patient with Crooke's cell carcinoma who presented with local invasion and liver metastases, which was refractory to conventional therapeutic modalities including transsphenoidal surgery, radiosurgery, medications, and hepatic transcatheter arterial embolization. After all these treatments failed, the patient had monthly temozolomide administrations, resulting in gradual clinical improvement and biochemical data that were consistent with tumor shrinkage. In glioblastoma, low O(6)-methylguanine DNA methyltransferase (MGMT) expression is associated with epigenetic gene silencing and predicts a better response to temozolomide. We thus investigated MGMT expression, immunohistochemically, in seven CCAs (five invasive macroadenomas and two invasive microadenomas) and 17 ordinary-type adenomas (OTAs; three noninvasive macroadenomas, 12 noninvasive microadenomas, and two invasive microadenomas) from patients with Cushing's disease. In seven CCAs, all five invasive macroadenomas exhibited low MGMT expression, defined as <5% nuclear MGMT staining. In 17 OTAs, only one adenoma showed low MGMT expression. In Cushing's disease, invasive macroadenomas including CCA usually have low-MGMT expression. Temozolomide thus may be a new therapeutic option for invasive macroadenomas such as CCA particularly when conventional treatments are ineffective.

Surgical Reintervention in Acromegaly: is it Still worth trying?

There has not been a formal evaluation of how frequently and to what extent surgical reintervention in patients with persistently active acromegaly may achieve significant, albeit incomplete, reductions in growth hormone (GH) and insulinlike growth factor-I (IGF-I) levels. Of importance, recent studies suggest that the response to radiotherapy and pharmacotherapy is better with lower degrees of hypersomatotropism. The objective of this study was to evaluate the outcome of surgical reintervention in patients with active acromegaly at our institution between 1995 and 2005. We retrospectively evaluated the outcome in 53 patients with active acromegaly (49 with macroadenomas) who underwent a second operation a mean of 24.1 +/- 25.2 months after the first intervention. Basal and postglucose GH as well as IGF-I levels were analyzed at diagnosis and after the first and second pituitary procedures. Basal GH decreased in 38 patients (72%): to <10 ng/mL in 17 and to <2.5 ng/mL in 11. The mean IGF-I index and basal GH decreased significantly after surgical reintervention: 1.7 +/- 0.4 to 1.4 +/- 0.4 (P = .0001) and 13.0 +/- 12.8 to 8.3 +/- 11.3 ng/mL (P = .0001), respectively. Some decrement in IGF-I was observed after surgical reintervention in 30 patients (57%), being greater than 30% in 9 (17%). Only 5 patients (9%) achieved complete biochemical cure (normal IGF-I and a postglucose GH level of <1 ng/mL). Reoperation achieved a significant decline in basal and postglucose GH levels as well as in IGF-I index only in patients with noninvasive macroadenomas. Pituitary surgical reintervention in patients with acromegaly results in a low percentage of biochemical cure. If a remnant of a noninvasive macroadenoma is visible and accessible, however, such a procedure may significantly reduce GH and IGF-I levels.

Does first-line surgery still have its place in the treatment of acromegaly?

Transsphenoidal surgery is currently the first-line treatment of acromegaly. Remission is observed in 80 to 90% microadenomas, 50 to 60% non-invasive macroadenomas, and less than 20% invasive macroadenomas. Predictive factors include age, maximal size of the adenoma, cavernous sinus invasion, initial hormone levels and neurosurgeon's experience. Complications are rare, with about 5% definitive diabetes insipidus and 10% of new anterior pituitary hormone deficits. Somatostatin agonist pretreatment can be proposed as it decreases tumor volume in about 25% cases and might reduce the rate of immediate postsurgical complications; however, there is no obvious difference in surgical remission rate whether patients are pretreated or not. Debulking surgery can also be proposed in very large macroadenomas incompletely controlled by somatostatin agonists or resistant to medical treatment, as it was shown to facilitate somatostatin agonist efficacy in more than 50% cases.

La chirurgie de première intention a-t-elle encore une place dans le traitement de l’acromégalie ?

Transsphenoidal surgery is currently the first-line treatment of acromegaly. Remission is observed in 80–90% of microadenomas, 50–60% of noninvasive macroadenomas, and less than 20% of invasive macroadenomas. Predictive factors include age, maximal size of the adenoma, cavernous sinus invasion, initial hormone levels and neurosurgeon's experience. Complications are rare, with about 5% definitive diabetes insipidus, and 10% of new anterior pituitary hormone deficits. Somatostatin agonist pretreatment can be proposed, as it decreases tumor volume in about 25% of cases and might reduce the rate of immediate postsurgical complications; however, there is no obvious difference in surgical remission rate whether patients are pretreated or not. Debulking surgery can also be proposed in very large macroadenomas incompletely controlled by somatostatin agonists, or resistant to medical treatment, as it was shown to facilitate somatostatin agonist efficacy in more than 50% of cases.

Transsphenoidal surgery for acromegaly: endocrinological follow-up of 98 patients.

Transsphenoidal surgery is the preferred treatment modality for growth hormone (GH)-secreting pituitary adenomas. In many series, the reported postoperative remission is based mainly on achievement of GH levels less than 2 ng/ml. Strict criteria for insulin-like growth factor I normalization and even lower GH levels (<1 ng/ml) are now suggested to define cure of acromegaly, but the evidence does not yet support such low GH levels in epidemiological follow-up. We analyzed our postoperative results in a large cohort of patients with acromegaly. Ninety-eight patients harboring GH-secreting adenomas (46 microadenomas and 52 macroadenomas) underwent transsphenoidal surgery between 1990 and 1999. Ninety-one patients were operated for the first time, and 12 patients underwent reoperations because of previous surgical failure (7 had undergone surgery elsewhere previously). Biochemical remission was defined as a repeated fasting or glucose-suppressed GH level of 2 ng/ml or less, and a normal insulin-like growth factor I level. Remission was achieved in 74% of all patients after one operation, including 84% of patients with microadenomas and 64% of patients with macroadenomas. Seventy-three percent of patients with macroadenomas 11 to 20 mm in size achieved remission, as compared with a 20% remission rate for patients with adenomas larger than 20 mm. Patients with preoperative random GH levels lower than 50 ng/ml had a better outcome (85% remission), whereas GH greater than 50 ng/ml was associated with remission in 30% of the patients. Only one of the patients (8%) with postoperative active disease who underwent a second operation achieved remission. Recurrence was rare (one patient), and all failed surgical attempts could be detected during the immediate postoperative evaluation. On the basis of strict postoperative GH and insulin-like growth factor I criteria to define remission, our series demonstrates the efficacy of transsphenoidal surgery for acromegalic patients with microadenomas and noninvasive macroadenomas. However, patients with large adenomas (>20 mm) and preoperative GH greater than 50 ng/ml have a poor prognosis and require adjunctive medical or radiation therapy to control GH hypersecretion.

Pharmacotherapy or surgery as primary treatment for acromegaly?

In recent years important progress has been made in the management of acromegaly due to the availability of effective and well tolerated drugs and to improved surgical techniques, resulting in a broader choice of therapeutic interventions. Although surgery in the hands of an experienced surgeon still represents the primary option for the majority of patients, the new formulations of somatostatin analogues and dopamine agonists have partially modified the primary therapeutic approach to this severe and disabling chronic disease. Therapy with somatostatin analogues has been shown to reduce morbidity and the mortality rate in patients with acromegaly, and currently in some patients this medical approach may be preferable to surgery. Although in selected patients individualised pharmacotherapy might represent the primary therapy, trans-sphenoidal surgery of microadenomas and noninvasive macroadenomas remains the primary option, since the remission rate is very high and the costs are relatively low in comparison with lifelong therapy with somatostatin analogues. However, the treatment schedule in acromegaly should consider criteria additional to tumour size and invasiveness, such as the age and the general clinical condition of the patient. Presurgical treatment with somatostatin analogues has been reported to reduce surgical complications and time of hospitalisation after the operation. Moreover, a multidisciplinary team of well trained specialists is needed in order to guarantee the most optimal quality of life and life expectancy for patients with acromegaly.