Preoperative Growth Hormone Levels Research Articles

Outcome of endoscopic transsphenoidal surgery for acromegaly: Comparison of using and not using the floor standing pneumatic powered endoscope-holder system

IntroductionEndoscopic transsphenoidal surgery can be performed by two surgeons, including an endoscopist (PE/2S), and by a single surgeon with an endoscope-holder system (PE/1S + H). We analyzed the surgical outcome, and outcome predictors in acromegaly patients in endoscopic transsphenoidal surgery using floor standing pneumatic endoscope-holder system. MethodsEndoscopic transsphenoidal surgery was performed with PE/1S+H (n = 51) and PE/2S (n = 20). Postoperative remission was evaluated by the 2010 consensus criteria for acromegaly. We compared the surgical results of PE/2S style and PE/1S+H style, and investigated the factors associated with favorable surgical outcomes. ResultsThere was no difference in clinical background between the PE/2S and the PE/1S + H groups. The remission rates for PE/2S and PE/1S+H were 65.0% and 82.4%, respectively, with no significant difference (p = 0.128). In consecutive 71 cases, statistically useful predictors of remission were low preoperative growth hormone (GH) level (<12 ng/mL), low Knosp grade (0–2), and low revised Knosp grade (0–3A). In the conventional Knosp grade 0–2 and 3/4, the sensitivity was 0.76 and the specificity was 0.81. In the revised Knosp grade 0–3A and 3B/4, the sensitivity was 0.96 and the specificity was 0.44. ConclusionThe outcome of GH-producing pituitary neuroendocrine tumors surgically removed by PE/1S+H could be almost equivalent to that by PE/2S. Preoperative low GH level and Knosp grades, including revised Knosp grades, are useful preoperative predictors for surgical remission of acromegaly.

Management of growth hormone-secreting pituitary adenomas causing acromegaly: a practical review of surgical and multimodal management strategies for neurosurgeons.

This review aimed to highlight the history, diagnostic criteria, preoperative prognostic factors, surgical management, and multimodal adjuvant therapies recommended to provide a comprehensive and multifaceted understanding of and clinical approach to treating growth hormone-secreting pituitary adenomas (GHPAs) in patients with acromegaly. The authors collated and reviewed published studies, many written by skull base neurosurgeons, endocrinologists, and radiation oncologists with expertise in pituitary adenoma management, to produce a practical and contemporary update pertaining to the optimal management of acromegaly for neurosurgeons. Acromegaly is a debilitating disease for which surgery can be curative in more than two-thirds of patients. Recent rates of hormonal remission by the authors' group and others following the resection of GHPAs are on the order of 70%-80%, and these increase to more than 85% with the addition of medical therapy in a minority of patients who do not achieve remission with surgery alone. Most tumors are accessible via a direct endoscopic endonasal transsphenoidal approach, which can be augmented with a variety of extended approaches to gain access to suprasellar, clival, and parasellar compartments as needed. Preoperative growth hormone levels, cavernous sinus invasion, and pituitary adenoma consistency are important factors in determining the extent of resection. In most patients with residual or recurrent disease, medical therapy (e.g., somatostatin analogs and dopamine agonists) can be used to help achieve hormonal remission. Repeat surgery can be safely performed in most cases if needed, whereas stereotactic radiosurgery is usually reserved for medically resistant tumors in surgically inaccessible compartments. The neurosurgeon has a primary and often definitive role in the management of acromegaly. The involvement of an integrated and multidisciplinary team consisting of experts from neurosurgery, otolaryngology, endocrinology, and radiation oncology optimizes the chances for a biochemical cure, even in large and aggressive GHPAs.

Endocrine Outcomes and Associated Predictive Factors for Somatotrophin Pituitary Adenoma after Endoscopic Endonasal Transsphenoidal Surgery: 10 Years of Experience in a Single Institute.

Objective Biochemical remission rates of endoscopic endonasal transsphenoidal surgery (EETS) and its associated predictive factors were evaluated in patients with somatotrophin pituitary adenomas. Methods The patients who underwent EETS in Jinling Hospital were identified between 2011 and 2020. The surgeons' experience, preoperative insulin-like growth factor 1 (IGF-1), basal growth hormone (GH) levels, nadir GH levels, and the tumor characteristics were analyzed for their relationships with endocrine outcomes. Total 98 patients were included for single factor analysis and regression analysis. They were divided into three groups according to the admission chronologic order. Results The overall remission rate of the patients was 57% (56/98) for all the patients over 10 years. In the single factor analysis, we found that the tumor size, cavernous invasion, and sellar invasion were valuable to predict the endocrine outcome after surgery. As for the suprasellar invasion, no significant difference was found between the noninvasive group and the invasive group. The preoperative IGF-1 level ( p = 0.166), basal GH level ( p = 0.001), and nadir GH level ( p = 0.004) were also different between the remission group and the nonremission group in the single factor analysis. The logistic regression analysis indicated that the preoperative nadir GH (odds ratio = 0.930, 95% confidence interval = 0.891-0.972, p = 0.001) was a significant predictor for the endocrine outcomes after surgery. Conclusion The surgeons' experience is an important factor that can affect the patients' endocrine outcomes after surgery. The macroadenomas with lateral invasion are more difficult to cure. Patients with higher preoperative nadir GH levels are less likely to achieve remission.

Predictors of Remission of Acromegaly following Surgical Treatment in Growth Hormone-Secreting Pituitary Adenoma.

Background and Objective Surgery is the treatment of choice for growth hormone (GH)-secreting pituitary adenoma. The remission of random GH depends on various factors. We aimed to evaluate the predictors related to remission of random GH following surgical treatment. Methods We collected the data retrospectively from the chart review from a single unit of neurosurgery. The diagnostic criteria for remission were a random GH < 1 ng/mL or nadir GH < 0.4 ng/mL after an oral glucose tolerance test. Results Data from a total of 110 (females 62 [56.4%]) patients were available for follow-up and were analyzed. The mean age was 36.5 years (14-69 years). Vision impairments were seen in 39 (35.5%) patients. The mean duration of symptoms before surgery was 34 months. The mean volume of the tumor was 7.2 mL (0.44-109.8 mL). Knosp grade 3 and 4 tumors were seen in 41.5% of cases. The mean preoperative random GH level was 68.9 ng/mL. Transsphenoidal surgery was done in 107 (97.3%) cases. The gross total resection could be done in 36 (32.7%) cases. At 3 months, 25 (26%) patients had a biochemical remission. In univariable analysis, lower Knosp grade, preoperative GH level < 40 ng/mL, gross total resection, and male gender were associated with remission at 3 months. In regression analysis, preoperative GH and male gender were related to remission at 3 months. Conclusion The preoperative GH level < 40 ng/mL is associated with higher chances of remission after surgery for GH-secreting pituitary adenoma.

Self-reported symptoms in patients with acromegaly: a 6-month follow-up in a single neurosurgical center.

Acromegaly is characterized by hypersecretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), accompanied by a compromise in the perception of wellness. The Patient-Assessed Acromegaly Symptom Questionnaire (PASQ) is relevant to assessing signs and symptoms but is mainly used to evaluate the efficacy of a pharmacological intervention. To explore the perioperative variation in symptom severity, the divergence between subgroups stratified according to clinical outcomes or treatment modalities, and the interaction between symptom scores and clinical indices, we prospectively recruited 106 patients with acromegaly from 2016 to 2018. Oral glucose tolerance and GH tests were performed, and PASQ was administered before treatment and 6 months postoperatively. Patients were divided into active (n = 49) and remission (n = 57) groups according to postoperative GH and IGF-1 levels. PASQ scores and GH and IGF-1 levels decreased significantly postoperatively in both groups. A significantly higher preoperative headache score and greater extent of decrease in arthralgia were seen in the active and remission groups, respectively. No significant variation in PASQ scores was found between patients receiving surgery alone and those receiving preoperative somatostatin analogs. Preoperative fasting GH (GH0) levels were positively correlated with preoperative excessive perspiration. Further regression analyses validated the variation in GH0 as a noteworthy determinant of the extent of change in soft-tissue swelling, excessive perspiration, fatigue, and total PASQ scores. Patient-reported symptoms were substantially alleviated after surgery, independent of endocrine remission or use of preoperative somatostatin. A GH level decrease was a notable coefficient for PASQ scores.

The Prognostic-Based Approach in Growth Hormone-Secreting Pituitary Neuroendocrine Tumors (PitNET): Tertiary Reference Center, Single Senior Surgeon, and Long-Term Follow-Up

Postoperative deserved outcomes in acromegalic patients are to normalize serum insulin-like growth factor (IGF-1), reduce the tumoral mass effect, improve systemic comorbidities, and reverse metabolic alterations. Pituitary neuroendocrine tumors (PitNET) are characterized to present a heterogeneous behavior, and growth hormone (GH)-secreting PitNET is not an exception. Promptly determining which patients are affected by more aggressive tumors is essential to guide the optimal postoperative decision-making process [prognostic-based approach]. From 2006 to 2019, 394 patients affected by PitNET were intervened via endoscopic endonasal transsphenoidal approach by the same senior surgeon. A total of 44 patients that met the criteria to be diagnosed as acromegalic and were followed up at least for 24 months (median of 66 months (26-156) were included in the present study. Multiple predictive variables [age, gender, preoperative GH and IGF-1 levels, maximal tumor diameter, Hardy's and Knosp's grade, MRI. T2-weighted tumor intensity, cytokeratin expression pattern, and clinicopathological classification] were evaluated through uni- and multivariate statistical analysis. Sparse probability of long-term remission was related to younger age, higher preoperative GH and- or IGF-1, group 2b of the clinicopathological classification, and sparsely granulated cytokeratin expression pattern. Augmented recurrence risk was related to elevated preoperative GH levels, tumor MRI T2-weighted hyperintensity, and sparsely granulated cytokeratin expression pattern. Finally, elevated risk for reintervention was related to group 2b of the clinicopathological classification, Knosp's grade IV, and tumor MRI T2-weighted hyperintensity. In this study, the authors determined younger age, higher preoperative GH and- or IGF-1 levels, group 2b of the clinicopathological classification, Knosp's grade IV, MRI T2-weighted tumor hyperintensity and sparsely granulated cytokeratin expression pattern are related to worse postoperative outcomes in long-term follow-up patients affected with GH-secreting PitNET.

Delayed postoperative hyponatremia in patients with acromegaly: incidence and predictive factors.

Delayed postoperative hyponatremia (DPH) is a unique complication of transsphenoidal surgery (TSS) in pituitary tumors. Growth hormone (GH) enhances renal sodium reabsorption; however, the association between postoperative GH reduction and DPH in acromegaly is unclear. This study was performed to clarify the incidence of and the predictive factors for DPH in patients with acromegaly who underwent TSS. Ninety-four patients with active acromegaly were examined retrospectively. During the postoperative course, patients with serum sodium levels ≤ 134mEq/L were classified into the DPH group. We compared basic clinical characteristics, tumor characteristics, and preoperative and postoperative examination findings between the DPH and non-DPH groups. DPH occurred in 39 patients (41.5%), and the lowest serum sodium levels were generally observed during postoperative days (PODs) 7-9. They needed a 3-day longer hospital stay than those without DPH. The DPH group had lower preoperative body weight and body mass index. In addition, a transient increase in body weight during PODs 5-7 occurred with a transient decrease in urinary volume in the DPH group. Preoperative and postoperative GH and insulin-like growth factor-1 levels did not differ between the twogroups. The findings suggested that lower preoperative weight and a postoperative transient gain in body weight are associated with an increased risk of DPH in acromegaly patients undergoing transsphenoidal surgery.

High Prevalence of Vertebral Fractures Associated With Preoperative GH Levels in Patients With Recent Diagnosis of Acromegaly.

Osteopathy and morphometric vertebral fractures (VFs) are emerging complications in acromegaly. However, the prediction of VFs in this clinical setting is still a matter of uncertainty, and it is debated whether they are an early event in the natural history of the disease. We aimed to evaluate the prevalence and determinants of morphometric VFs in patients with recently diagnosed acromegaly. We enrolled 92 patients (43 men/49 women) on admission to the neurosurgery unit before transsphenoidal surgery, and compared them with control individuals without secondary forms of osteoporosis and pituitary disorders. We performed a VF assessment on preoperative chest x-ray images and collected biochemical, demographic, and clinical data. We detected a significantly higher prevalence of VFs (33.7%) in patients with acromegaly than in controls (P = .001). Among the patients with acromegaly and VFs, 12 (38.7%) showed multiple VFs, and 5 (16.1%) showed moderate/severe VFs. Patients with VFs had higher random serum growth hormone (GH) levels than those with no VFs (P = .03), but there was no difference in insulin-like growth factor-1 (IGF-1) (P = .07) and IGF-1/Upper Normal Limit ratio (P = .08). Free 3,5,3'-triiodothyronine was slightly lower in patients with acromegaly and VFs than in those without VFs (P = .05). In multiple logistic analysis, GH was independently associated with risk for VFs (P = .003). The preoperative serum GH cutoff value that predicted VFs was 12 ng/mL. For the first time, high prevalence of radiological VFs is reported in patients with recent diagnosis of acromegaly. Therefore, we can hypothesize that VFs are an early phenomenon of acromegaly and related to GH levels. VF assessment should be included in the workup at the diagnosis of acromegaly.

Predictors of postoperative biochemical remission in acromegaly.

Acromegaly is a rare neuroendocrine condition that can lead to significant morbidity. Despite China's vast population size, studies on acromegaly remain sparse. This study aimed to investigate the clinical characteristics and predictors of biochemical remission after surgery for acromegaly using the China Acromegaly Patient Association (CAPA) database. A retrospective nationwide study was conducted using patient-reported data from CAPA database between 1998 and 2018. The principal component analysis (PCA) and logistic regression analysis were employed to determine independent predictors of biochemical remission at 3months in patients after surgery. Of the 546 surgical cases (mean age: 36.8years; 59.5% females), macroadenomas and invasive tumors (Knosp score 3-4) were 83.9% and 64.1%, respectively. Ninety-five percent of patients were treated with endonasal surgery and 36.8% exhibited biochemical remission at 3-months postoperatively. The following independent predictors of biochemical remission were identified: preoperative growth hormone (GH) levels between 12 and 28μg/L [odds ratio (OR) = 0.58; 95% confidence interval (CI), 0.37-0.92; p = 0.021], preoperative GH levels > 28μg/L (OR = 0.55; 95% CI, 0.34-0.88; p = 0.013), macroadenoma (OR = 0.56; 95% CI, 0.32-0.96; p = 0.034), giant adenomas (OR = 0.14; 95% CI, 0.05-0.38; p < 0.001), Knosp score 3-4 (OR = 0.37; 95% CI, 0.24-0.57; p < 0.001), and preoperative medication usage (OR = 2.32; 95% CI, 1.46-3.70; p < 0.001). In this nationwide study spanning over two decades, we highlight that higher preoperative GH levels, large tumor size, and greater extent of tumor invasiveness are associated with a lower likelihood of biochemical remission at 3-months after surgery, while preoperative medical therapy increases the chance of remission.

Impact of tumor characteristics and pre- and postoperative hormone levels on hormonal remission following endoscopic transsphenoidal surgery in patients with acromegaly.

Acromegaly is a disease of acral enlargement and elevated serum levels of insulin-like growth factor-1 (IGF-1) and growth hormone (GH), usually caused by a pituitary adenoma. A lack of consensus on factors that reliably predict outcomes in acromegalic patients following endoscopic endonasal transsphenoidal surgery (EETS) warrants additional investigation. The authors identified 52 patients with acromegaly who underwent an endoscopic endonasal approach (EEA) for resection of a GH-secreting pituitary adenoma. Preoperative and postoperative tumor and endocrinological characteristics such as tumor size, invasiveness, and GH/IGF-1 levels were evaluated as potential indicators of postoperative hormonal remission. Endocrinological remission was defined as postoperative IGF-1 levels at or below the age- and sex-normalized values. The 52 patients had a mean age of 50.7 ± 13.4 years and a mean follow-up duration of 24.4 ± 19.1 months. Ten patients (19%) had microadenomas and 42 (81%) had macroadenomas. Five patients (9.6%) had giant adenomas. Forty-four tumors (85%) had extrasellar extension, with 40 (77%) exhibiting infrasellar invasion, 18 (35%) extending above the sella, and 7 (13%) invading the cavernous sinuses. Thirty-six patients (69%) underwent gross-total resection (GTR; mean maximal tumor diameter 1.47 cm), and 16 (31%) underwent subtotal resection (STR; mean maximal tumor diameter 2.74 cm). Invasive tumors were significantly larger, and Knosp scores were negatively correlated with GTR. Thirty-eight patients (73%) achieved hormonal remission after EEA resection alone, which increased to 87% with adjunctive medical therapy. Ninety percent of patients with microadenomas and 86% of patients with macroadenomas achieved hormonal remission. Preoperative IGF-1 and postoperative day 1 (POD1) GH levels were inversely correlated with hormonal remission. Postoperative CSF leakage occurred in 2 patients (4%), and none experienced vision loss, death, or injury to internal carotid arteries or cranial nerves. Endoscopic transsphenoidal resection of GH-secreting pituitary adenomas is a safe and highly effective treatment for achieving hormonal remission and tumor control in up to 87% of patients with acromegaly when combined with postoperative medical therapy. Patients with lower preoperative IGF-1 and POD1 GH levels, with less invasive pituitary adenomas, and who undergo GTR are more likely to achieve postoperative biochemical remission.

MON-310 Factors Associated with Remission After Surgery for Acromegaly

Background: Acromegaly is a disorder characterized by excessive growth hormone (GH) secretion, which, in most cases, is caused by a GH secreting adenoma. Surgical removal of the tumor via a transsphenoidal approach is the first choice treatment for most patients. The remission rate after an initial resection is 80 to 90 percent for microadenomas and less than 50 percent for macroadenomas. Objective: To analyze predictive factors of remission in acromegaly patients who underwent transsphenoidal surgery for GH secreting adenoma. Methods: From January 2006 to October 2019, 75 patients with GH secreting pituitary adenoma were evaluated at our center. Patients who had undergone medical treatment or radiotherapy as first treatment were excluded. A total of 60 patients were included in the analysis. Remission was defined as normal serum insulin-like growth factor-1 (IGF-1) age and sex adjusted and a random serum GH less than 1 ng/mL and/or nadir GH during oral glucose tolerance test <0.4 ng/mL. Results: We evaluated 60 patients (41 females and 19 males), with a mean age at diagnosis of 49.6 (ranged from 23 to 77 years). Mean initial IGF-1 was 905.3 ng/mL (range 100-324) and mean initial GH was 25.0 ng/mL (<2.5). Macroadenomas were more common than microadenomas (48 vs 12). The average maximum tumor diameter was 15.6 mm and 21 patients were graded as Knosp 3 or 4, which indicated cavernous sinus invasion. Patients were follow for 11.8 years. Overall, the remission rate was 50.0% after surgery. Mean age of patients in surgical remission (51.6 years) was higher than those patients not in remission (47.5 years) (p=0.439). Remission rates for microadenomas and macroadenomas were 75.0% and 44.9%, respectively (p=0.04). Patients who achieved remission had smaller tumors compared with those who failed to attain remission (mean diameter 11.6mm versus 17.8 mm). Using the Knosp classification system and preoperative magnetic resonance images to determine cavernous sinus invasion, Knosp grade 3 to 4 tumors were found in 5 patients in remission and in 16 patients with persistence of disease (p=0.003). Patients who achieved remission had a significantly lower preoperative IGF-1 level (650.5 ng/mL) compared with those who did not (1211.0 ng/mL) (p=0.04). Preoperative GH levels were lower for the patients who achieved remission (18.7 ng/mL) than for those who did not (32.5 ng/mL, p=0.006). Conclusions: In our study, predictors of biochemical remission after surgery were smaller tumor size, lower Knosp grade, and lower preoperative GH and IGF-1 levels.

Morphometric Alterations of the Sphenoid Ostium and other Landmarks in Acromegaly: Anatomical Considerations and Implications in Endoscopic Pituitary Surgery.

The sphenoid ostium (SO) is an important landmark for the endoscopic surgeon. Changes in size and position of the SO and variations in other skull base landmarks in acromegalics have not been adequately evaluated. The authors evaluated the morphometry and location of the SO and other landmarks in acromegaly and compared these findings with those in nonfunctioning pituitary adenomas (NFPAs). In this retrospective case-control study, the dimensions and location of the SO and other skull base landmarks were radiologically evaluated in 18 patients with growth hormone (GH)-secreting adenomas. These findings were analyzed in relation to preoperative GH levels and compared with 18 age- and sex-matched controls with NFPAs. The dimensions of the SO were significantly larger in the GH-adenoma group (P < 0.05). The SO was further from the midline (P = 0.04) and closer to the sphenopalatine foramen (SPF) (P = 0.02) in the GH-adenoma group, and this finding correlated with increasing preoperative GH levels. Acromegalics demonstrated larger intracavernous carotid diameters (P = 0.05) and smaller intercarotid distances than the patients with NFPAs (P = 0.02). The SO is larger and located higher up in the sphenoid face and closer to the SPF in patients with GH adenomas. Increasing GH levels in these patients correlate with the upward and lateral displacement of the SO. These patients demonstrate larger intracavernous carotid diameters and smaller intercarotid distances than patients with NFPAs. These morphological alterations are of particular relevance to the pituitary surgeon.

Long-term outcomes of transsphenoidal surgery for management of growth hormone-secreting adenomas: single-center results.

Transsphenoidal surgery is advocated as the first-line management of growth hormone (GH)-secreting adenomas. Although disease control is defined by strict criteria for biochemical remission, the length of follow-up needed is not well defined in literature. In this report, the authors present their long-term remission rate and identify various predictive factors that might influence the clinical outcome. The authors conducted a single-institute retrospective analysis of all transsphenoidal procedures for GH-secreting adenomas performed from January 2000 to June 2016. The primary outcome was defined as biochemical remission according to the 2010 consensus criteria and measured at the 1-year postoperative mark as well as on the last recorded follow-up appointment.Secondary variables included recurrence rate, patterns of clinical presentation, and outcome of adjuvant therapy (including repeat surgery). Subgroup analysis was performed for patients who had biochemical or radiological "discordance"-patients who achieved biochemical remission but with incongruent insulin-like growth factor 1 (IGF-1)/GH or residual tumor on MRI. Recurrence-free survival analysis was conducted for patients who achieved remission at 1 year after surgery. Eighty-one patients (45 female and 36 male) with confirmed acromegaly treated with transsphenoidal surgery were included. In 62 cases the patients were treated with a pure endoscopic approach and in 19 cases an endoscopically assisted microscopic approach was used.Primary biochemical remission after surgery was achieved in 59 cases (73%) at 1 year after surgery. However, only 41 patients (51%) remained in primary surgical remission (without any adjuvant treatment) at their last follow-up appointment, indicating a recurrence rate of 31% (18 of 59 patients) over the duration of follow-up (mean 100 ± 61 months). Long-term remission rates for pure endoscopic and endoscopically assisted cases were not significantly different (48% vs 52%, p = 0.6). Similarly, no significant difference in long-term remission was detected between primary surgery and repeat surgery (54% vs 33%, p = 0.22).Long-term remission was significantly influenced by extent of resection, cavernous sinus invasion (radiologically as well as surgically reported), and preoperative and early postoperative GH and IGF-1 levels (within 24-48 hours after surgery) as well as by clinical grade, with lower remission rates in patients with dysmorphic features and/or medical comorbidities (grade 2-3) compared to minimally symptomatic or silent cases (grade 1). The long-term surgical remission rate appears to be significantly less than "early" remission rates and is highly dependent on the extent of tumor resection. The authors advocate a long-term follow-up regimen and propose a clinical grading system that may aid in predicting long-term outcome in addition to the previously reported anatomical factors. The role of repeat surgery is highlighted.

Effect of growth hormone and somatomedin-C axis on fracture healing

Aim: Many studies have examined the effects of different calciotropic hormones on fracture healing, whereas few studies focus on growth factors. Local detection of somatomedin C (IGF-1) in fracture callus, application of growth hormone (GH) and IGF-1 as non-union treatment, and low GH and IGF-1 levels in osteoporotic fractures indicate that these hormones are effective in fracture healing. However, most of these studies are based on post fracture GH and IGF-1 levels. GH and IGF-1 are also involved in acute phase response and can change due to trauma. The aim of this study is to investigate the change in GH and IGF-1 levels in patients treated with osteotomy, in which an iatrogenic fracture is created, and to evaluate the effect of these hormones on fracture healing by comparing the results before and after the fractures. Methods: Patients who were diagnosed with developmental dysplasia of the hip and underwent surgery between 2014-2015 were prospectively followed for this cohort study. Forty-one patients were included, and two groups were formed. Patients who underwent open reduction and soft tissue release without osteotomy (n=20) were included in the first group. Patients who underwent pelvic osteotomy (n=21), in which iatrogenic fractures were created, were included in the second group. Blood samples were obtained from all patients pre-operatively and on the 1st and 28th postoperative days. Friedman and Mann-Whitney U tests were used for statistical analysis. Results: Mean age of the first group, comprising 19 females (95%) and 1 male (5%), was 11.25 months (Range: 6-25 months). Mean age of the second group, including 17 females (85.7%) and 4 males (14.3%), was 74.4 months (Range: 24-120 months). While there was no significant difference between pre- and postoperative GH values in the first group (P=0.05), postoperative GH levels were significantly higher than preoperative GH levels in the second group (P&lt;0.001). Postoperative IGF-1 levels were significantly lower than preoperative IGF-1 levels in both groups (P&lt;0.001). When the difference of preoperative and postoperative 1st day GH and IGF-1 values were compared between two groups, GH changes were found significantly higher in the second group (P&lt;0.001) whereas serum IGF-1 changes were significantly lower in the second group (P=0.043). Conclusion: IGF-1 is inadequate in the investigation of fracture healing due to its short half-life and local production. On the other hand, GH plays an active role in fracture healing and increases significantly in comparison to pre-fracture values. Considering the GH increase during fracture healing, it may be beneficial to support patients with pathological fracture healing with growth hormone.

Clinical Characteristics and Postoperative Recovery of Hypopituitarism in Patients with Nonfunctional Pituitary Adenoma

To investigate the clinical characteristics of hypopituitarism and its reversibility after surgery for nonfunctional pituitary adenoma (NFPA); analyze the correlation between tumor size and hypopituitarism incidence; and predict hypopituitarism by tumor volume and maximum diameter. We retrospectively reviewed 164 patients with NFPA who underwent surgical treatment at Peking Union Medical College Hospital from January 2016 to December 2016. Demographic, imaging, and endocrine data were collected during preoperative, postoperative, and long-term follow-up (21.1 ± 3.3 months) periods. Differences in hormone levels were analyzed by paired and independent samples t-tests. The cut-off values of tumor size and volume to predict hypopituitarism were calculated by receiver operating characteristic curves. In total, 80.4% (132/164) of patients had anterior pituitary hypofunction and 48.4% patients had hypogonadism; the recovery rate of luteinizing hormone was 80.9%, and follicular-stimulating hormone was 60%. In total, 36.5% of patients had hypothyroidism; the recovery rate of thyroxine was 85%, free thyroxine was 87.8%, and thyroid-stimulating hormone was 100.0%. Finally, 27.4% of patients had insulin-like growth factor 1 (IGF-1)/growth hormone (GH) hypofunction, and the recovery rate of IGF-1 was 77.8%. The preoperative free thyroxine, thyroxine, GH, IGF-1, follicular-stimulating hormone, and luteinizing hormone levels were significantly lower in the giant adenoma group (n= 43) than in the large adenoma group (n= 121). The hypopituitarism predictive cut-off value of tumorvolume was 3105.1 mm3 and that of tumor diameter was 23.5 mm. NFPA has a significant influence on gonadal hormone, IGF-1/GH, and thyroid hormone. NFPA can cause single- or multiple-hormone reduction in each pituitary target gland. Tumor size is positively correlated with the incidence and degree of hypopituitarism. NFPA-induced hypopituitarism is significantly recovered after surgical treatment.

Endoscopic Endonasal Approach to the Growth Hormone–Secreting Pituitary Adenomas: Endocrinologic Outcome in 68 Patients

The endoscopic endonasal approach has recently become an acceptable option for resection of all pituitary adenomas. We assessed biochemical outcome of endoscopic endonasal surgery in growth hormone (GH)-secreting adenomas, including remission rate, predictors of remission, and associated complications. Sixty-eight consecutive patients with acromegaly who underwent endoscopic endonasal surgery were analyzed prospectively. Tumors were classified according to size, Knosp grade, and Hardy-Wilson classification. Biochemical remission was defined as normal serum insulin-like growth factor 1 level and either a suppressed GH serum level less than 0.4 μg/L during an oral glucose tolerance test or a random GH level less than 1.0 μg/L at least 3 months after surgery. Total biochemical remission rate was 64.7%. Gross total resection was achieved in 61 of the 68 patients (89.7%). Remission was achieved in 12 of 16 microadenomas (75%) and 32 of 52 macroadenomas (61.5%). Based on univariate logistic regression analysis, preoperative variables predictive of remission were age (P=0.004), Knosp grade (P= 0.023), and preoperative GH levels (P= 0.042). Three patients (4.4%) experienced postoperative panhypopituitarism, and permanent diabetes insipidus was seen in 4 patients (5.9%). Two patients (2.9%) developed cerebrospinal fluid leaks, which were treated by lumbar puncture in one case and early surgical repair in the other case. Endoscopic endonasal adenoma resection leads to a high rate of endocrinologic remission in GH-secreting adenomas with a low complication rate. Patients with older age, higher preoperative GH levels, and higher Knosp grades are less likely to achieve remission.

Somatotrophic Adenoma in Children Younger than 14 Years: Clinical Features and Treatment of 22 Cases at a Large Pituitary Center.

To investigate the clinical features of somatotrophic adenoma in children younger than 14 years and to evaluate the short-term and long-term outcomes of transsphenoidal surgery. This single-center retrospective study included 22 patients with somatotrophic adenoma who were admitted to our institution between January 1997 and January 2017. The patients' demographics, hormone levels, imaging characteristics, surgical outcomes, and follow-up data were summarized. The average age of patients at diagnosis was 10.3 years, and the average disease duration was 42.5 months. Growth acceleration was observed in 90.9% of patients. Mixed somatolactotrophic adenoma was identified in 36.4% of patients. In total, 77.3% of tumors on imaging were macroadenomas or giant adenoma, and 50% were invasive. Twenty-one patients underwent tumor resection, and the remission rate after a single transsphenoidal surgery was 45%. Preoperative growth hormone levels (P= 0.017), growth hormone nadir (P= 0.003), and tumor size (P= 0.026) were the most likely influencing factors associated with the surgical remission rate. Postoperative cerebral spinal fluid leakage (15%) was the main complication of transsphenoidal surgery. During a median follow-up period of 42.5 months, 72.7% of the patients obtained remission after monotherapy or combined treatment, and no recurrence was observed. Somatotrophic adenomas in children younger than 14 years tend to be macroadenomas with a shorter disease duration than that observed in adults. Transsphenoidal surgery is safe and effective and could represent a preferred treatment option. The combination of surgery, medication, and radiation is recommended to achieve optimal long-term outcomes.

Endoscopic therapy and curative effect in pituitary adenoma patients complicated by acromegalic cardiomyopathy.

The study aimed to retrospectively analyze the clinical characteristics of patients with pituitary adenomas complicated by acromegalic cardiomyopathy and to evaluate the effect of endoscopic surgery. Eighty-six pituitary adenoma patients complicated by acromegalic cardiomyopathy who were treated with endoscopic surgery in the First Affiliated Hospital of Soochow University from January 2010 to December 2016 were enrolled. We noted patient clinical characteristics and explored the relationships with surgical treatment. Before and after surgery, all patients underwent an examination of pituitary endocrinology, brain magnetic resonance (MR), and echocardiography. The serum levels of growth hormone (GH), left ventricular end-diastolic diameter (LVIDd), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left ventricular ejection fraction (EF), and mitral valve (E/A ratio) were examined with non-invasive methods, and the results were compared. Of the 86 patients, there were 23 with microadenomas, 27 with large adenomas, and 36 with giant adenomas. There were 28 patients with invasive adenomas and 58 with non-invasive adenomas. The pre-operative mean GH level was 71.23 ± 3.29μg/L, which was positively correlated with tumor volume (r = 0.751, P < 0.01). Via trans-sphenoidal endoscopic pituitary adenoma resection, 51 patients underwent total tumor resections, 25 underwent subtotal resections, 8 underwent major part resections, and 2 underwent partial resections. After surgery, the GH mean level was 3.81 ± 1.03μg/L, which was significantly different (t = 3.72, P < 0.01) from the pre-operative level. Cardiac function indices, including LVIDd, IVST, LVPWT, E/A, and EF, were significantly improved. The long-term curative rate was 39.17% and the remission rate was 77.29%. For pituitary adenoma patients complicated by acromegalic cardiomyopathy, endoscopic surgery resulted in a good curative effect and the growth hormone levels were maintained, which can significantly improve cardiac structure and function.

Endoscopic Transsphenoidal Approach for Acromegaly with Remission Rates in 401 Patients: 2010 Consensus Criteria.

Transsphenoidal surgery is the first-choice treatment for acromegaly. Postoperative remission is an important predictor of outcome. Various factors have been described as markers of remission: preoperative mean growth hormone (GH) and insulin-like growth factor-1 levels, cavernous sinus invasion, tumor size, extrapseudocapsular resection, and experience of the surgeon. A total of 401 patients underwent 432 endoscopic transsphenoidal surgeries between August 1997 and June 2016 at the Pituitary Research Centre of Kocaeli University. The remission rates were evaluated according to the 2010 consensus criteria using preoperative and postoperative data including overall remission, cavernous sinus invasiveness, extrapseudocapsular resection, resection rate, and preoperative and postoperative GH levels. Total resection was performed in 311 (77.56%) of 401 patients according to early (24-hour) postoperative magnetic resonance imaging. Overall, remission was achieved in 273 (68.1%) of 401 patients. Remission was achieved in 186 (63.3%) of 294 patients with macroadenomas, 87 (81.3%) of 107 patients with microadenomas, and 35 (40.7%) of 86 patients with cavernous sinus invasion. Remission was seen in 21 (75%) of 28 patients who underwent pseudocapsular resection. According to preoperative GH levels, remission was achieved in 205 (72.4%) of 273 patients with GH levels below 20 ng/mL but decreased to 11 (37.9%) of 29 patients with GH levels over 60 ng/mL. There was, conversely, a very strongly significant correlation with cavernous sinus invasion (P < 0.001; r:-0.953) and also a very strongly significant correlation with extrapseudocapsular resection (P < 0.001; r: 0.810). However, remission was very weakly but reversely significantly correlated with adenoma size and volume. The most significant factors for remission are cavernous sinus invasion and extrapseudocapsular resection. Higher remission rates can be achieved with the removal of small remnants by meticulous sweeping and by total resection. Preoperative and postoperative GH levels are predictive of remission.

Reoperation for growth hormone-secreting pituitary adenomas: report on an endonasal endoscopic series with a systematic review and meta-analysis of the literature.

OBJECTIVE Surgery is generally the first-line therapy for acromegaly. For patients with residual or recurrent tumors, several treatment options exist, including repeat surgery, medical therapy, and radiation. Reoperation for recurrent acromegaly has been associated with poor results, with hormonal control usually achieved in fewer than 50% of cases. Extended endonasal endoscopic approaches (EEAs) may potentially improve the results of reoperation for acromegaly by providing increased visibility and maneuverability in parasellar areas. METHODS A database of all patients treated in the authors' center between July 2004 and February 2016 was reviewed. Cases involving patients with acromegaly secondary to growth hormone (GH)-secreting adenomas who underwent EEA were selected for chart review and divided into 2 groups: first-time surgery and reoperation. Disease control was defined by 2010 guidelines. Clinical and radiological characteristics and outcome data were extracted. A systematic review was done through a MEDLINE database search (2000-2016) to identify studies on the surgical treatment of acromegaly. Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, the included studies were reviewed for surgical approach, tumor size, cavernous sinus invasion, disease control, and complications. Cases were divided into reoperation or first-time surgery for comparative analysis. RESULTS A total of 44 patients from the authors' institution were included in this study. Of these patients, 2 underwent both first-time surgery and reoperation during the study period and were therefore included in both groups. Thus data from 46 surgical cases were analyzed (35 first-time operations and 11 reoperations). The mean length of follow-up was 70 months (range 6-150 months). The mean size of the reoperated tumors was 14.8 ± 10.0 mm (5 micro- and 6 macroadenomas). The patients' mean age at the time of surgery was younger in the reoperation group than in the first-time surgery group (34.3 ± 12.8 years vs 49.1 ± 15.7 years, p = 0.007) and the mean preoperative GH level was also lower (7.7 ± 13.1 μg/L vs 25.6 ± 36.8 μg/L, p = 0.04). There was no statistically significant difference in disease control rates between the reoperation (7 [63.6%] of 11) and first-time surgery (25 [71.4%] of 33) groups (p = 0.71). Univariate analysis showed that older age, smaller tumor size, lower preoperative GH level, lower preoperative IGF-I level, and absence of cavernous sinus invasion were associated with higher chances of disease control in the first-time surgery group, whereas only absence of cavernous sinus invasion was associated with disease control in the reoperation group (p = 0.01). There was 1 case (9%) of transient diabetes insipidus and hypogonadism and 1 (9%) postoperative nasal infection after reoperation. The systematic review retrieved 29 papers with 161 reoperation and 2189 first-time surgery cases. Overall disease control for reoperation was 46.8% (95% CI 20%-74%) versus 56.4% (95% CI 49%-63%) for first-time operation. Reoperation and first-time surgery had similar control rates for microadenomas (73.6% [95% CI 32%-98%] vs 77.6% [95% CI 68%-85%]); however, reoperation was associated with substantially lower control rates for macroadenomas (27.5% [95% CI 5%-57%] vs 54.3% [95% CI 45%-62%]) and tumors invading the cavernous sinus (14.7% [95% CI 4%-29%] vs 38.5% [95% CI 27%-50%]). CONCLUSIONS Reoperative EEA for acromegaly had results similar to those for first-time surgery and rates of control for macroadenomas that were better than historical rates. Cavernous sinus invasion continues to be a negative prognostic indicator for disease control; however, results with EEA show improvement compared with results reported in the prior literature.