Long-term outcomes of neuroendoscopic cyst partial resection combined with stereotactic radiotherapy for craniopharyngioma.

PURPOSE: The aim of this study was to evaluate the treatment outcomes of neuroendoscopic cyst partial resection (ECPR) combined with stereotactic radiotherapy (SRT) for cystic craniopharyngiomas. METHODS: In this retrospective study, 22 craniopharyngioma patients undergoing ECPR combined with SRT were included. This combination therapy was indicated for suprasellar cystic craniopharyngiomas in patients whose pituitary function was preserved but would be difficult to preserve in direct surgery. The outcomes of combination therapy, including tumor control and postoperative visual and pituitary functions, were investigated. RESULTS: ECPR was safely performed, and cyst shrinkage was accomplished in all cases. After ECPR, visual function improved in 12 of 13 patients (92%) with visual field disturbance and did not deteriorate in any patients. Pituitary function was preserved in 14 patients (64%) and deteriorated in eight patients (36%) after ECPR. As a complication of ECPR, meningitis occurred because of a wound infection in one patient. In 18 of 22 patients (82%), the tumor was controlled without further treatment 19 - 87 months (median, 33 months) after SRT. Hypopituitarism was an adverse event after SRT in two of the 18 patients who achieved tumor control. Four patients (18%) had enlarged cysts after SRT. Postoperative pituitary function was significantly more likely to deteriorate in cases of extensive detachment from the ventricular wall, and retreatment was significantly more common in cases with hypothalamic extension. CONCLUSION: Although limited to some cases, ECPR combined with SRT is a less invasive and useful therapeutic option for suprasellar cystic craniopharyngiomas. However, its long-term prognosis requires further evaluation.

Clinical Factors Affecting Daily Dosage of Desmopressin Orally Disintegrating Tablets in Arginine Vasopressin Deficiency.

CONTEXT: Desmopressin orally disintegrating tablets (ODTs) are widely used to treat arginine vasopressin deficiency (AVP-D). However, limited information is available on the dosage regimen; the dosage for each patient is selected based on their response to the initiation dose. OBJECTIVE: To investigate the relationships between clinical characteristics and the daily dose of ODTs and to identify factors that affect ODT dosages. METHODS: This retrospective study included 209 adult patients with AVP-D. Patients were administered ODTs sublingually and instructed to restrict eating and drinking for 30 minutes after taking ODTs using a patient leaflet. ODT dose titration was conducted during hospitalization with close monitoring of urine output, body weight, and serum sodium levels. Multivariable linear regression models were applied to identify clinical factors associated with the daily dose of ODTs at discharge. We also evaluated the dosage at 1 year in 134 patients who were followed up in our hospital. RESULTS: The median daily dose of ODTs at discharge was 90 µg (IQR 60-120 µg). Multivariable linear regression models identified sex, age, and estimated creatinine clearance (eCCr) as significant factors associated with the daily dose of ODTs, with eCCr having the strongest effect. After excluding patients recovering from AVP-D, 71% of those followed up at our hospital took the same daily dose at 1 year after discharge. CONCLUSION: To achieve the safe and stable treatment of AVP-D, the daily dose of ODT needs to be selected based on a patient's sex, age, and eCCr under appropriate sublingual administration by patient education.

Ipsilateral Visual Loss Caused by Optic Nerve Compression between a Tuberculum Sellae Meningioma and the Internal Carotid Artery.

We report a rare case of ipsilateral visual loss caused by compression of the optic nerve between a tuberculum sellae meningioma (TSM) and the internal carotid artery (ICA). The patient was a 70-year-old female who presented with a 2-year history of left visual disturbance with a TSM on magnetic resonance imaging. No tumor infiltration to the optic canal was identified in the preoperative images. Extended endoscopic transsphenoidal surgery was performed and showed no infiltration to the optic canal. The tumor was removed completely, and optic nerve compression was found between the TSM and atherosclerotic ICA. This report shows an atypical case in which compression of the optic nerve between a TSM and the ICA caused ipsilateral visual loss despite no infiltration to the optic canal.

Immunohistochemical and ultrastructural review of six cases previously diagnosed as null cell PitNETs.

Pituitary neuroendocrine tumors (PitNETs) lacking lineage affiliation are termed "null cell" PitNETs (NCTs). NCTs are characterized as being immunonegative for pituitary hormones as well as transcription factors. We analyzed the ultrastructure and immunohistochemistry of six hormone-negative and transcription factor (TPIT, PIT1, SF1)-negative PitNETs, with less than 1% immunoreactive cells. Histologically, three cases presented a perivascular pattern and pseudorosettes; the other three showed a solid pattern with oncocytic changes. Electron microscopic examination revealed poorly differentiated tumor cells with sparsely scattered secretory granules and intracellular organelles in all null cell tumors when compared with hormone-positive PitNETs. Two cases harbored a honeycomb Golgi (HG) structure, and three oncocytic tumors showed mitochondrial accumulation. The two HG cases were immunopositive for newly obtained TPIT (CL6251) and showed some adrenocorticotropic hormone-positive cells, while the remaining four were diffusely immunopositive for GATA3, with two SF1-positive cases identified in subsequent immunostaining. Thus, these six cases may be classified as two sparsely granulated corticotroph PitNETs, two gonadotroph PitNETs with SF1 re-staining, and two likely gonadotroph PitNETs with GATA3 immunostaining. No "true NCT" was detected among 1071 PitNETs, demonstrating the importance of precise diagnosis following the most recent criteria to improve therapeutic success.

The Development of Primary Effusion Lymphoma-Like Lymphoma in a Patient with Preexisting Essential Thrombocythemia.

A 71-year-old Japanese male was diagnosed with essential thrombocythemia (ET) with the JAK2 V617F mutation variation, in April 2011. He was mainly treated with hydroxyurea following which the number of platelets was maintained within the normal limit. At age 80, he was hospitalized due to cardiac tamponade. Computed tomography showed no evidence of tumor masses or lymphadenopathy. Pericardial drainage was performed, and cytopathologic examination of the fluid revealed atypical lymphoid cells consistent with an effusion lymphoma of B cell lineage. The pericardial effusion was completely drained, and complete remission was achieved. Ultimately, the patient was diagnosed with primary effusion lymphoma-like lymphoma (PEL-LL). To the best of our knowledge, this is the first report of PEL-LL following ET.

GH-induced LH hyporesponsiveness as a potential mechanism for hypogonadism in male patients with acromegaly.

Male patients with acromegaly frequently have hypogonadism. However, whether excess GH affects gonadal function remains unclear. We retrospectively compared clinical features affecting total testosterone (TT) and free testosterone (FT) levels between 112 male patients with acromegaly and 100 male patients with non-functioning pituitary adenoma (NFPA) without hyperprolactinemia. Median maximum tumor diameter (14.4 vs. 26.5 mm) and suprasellar extension rate (33 vs. 100%) were lower in acromegaly, but LH, FSH, TT, and FT were not significantly different. In acromegaly, TT was less than 300 ng/dL in 57%, and FT was below the age-specific reference range in 77%. TT and FT were negatively correlated with GH, IGF-1, and the tumor size, and positively correlated with LH. In NFPA, they were positively correlated with IGF-1, LH, FSH, ACTH, cortisol, and free T4, reflecting hypopituitarism. Multiple regression analysis showed that TT and FT had the strongest correlation with GH in acromegaly, and with LH in NFPA. Surgical remission was achieved in 87.5% of 56 follow-up patients with acromegaly. TT and FT increased in 80.4 and 87.5%, respectively, with a significant increase in LH. In acromegaly, the degree of postoperative increase in TT(FT) correlated with the fold increase of TT(FT)/LH ratio, a potential parameter of LH responsiveness, but not with fold increase of LH, whereas in NFPA it correlated with both. These results suggest that excessive GH is the most relevant factor for hypogonadism in male acromegaly, and may cause impaired LH responsiveness as well as the suppression of LH secretion.

Challenges in the functional diagnosis of thyroid nodules before surgery for TSH-producing pituitary adenoma.

SUMMARY: A 50-year-old woman with thyroid-stimulating hormone (TSH)-producing pituitary adenoma (TSHoma) was diagnosed due to symptoms of thyrotoxicosis. Preoperatively, she showed thyrotoxicosis with the syndrome of inappropriate secretion of TSH (SITSH) and had a 5 cm nodule in her thyroid gland. Octreotide was administered preoperatively, which helped lower her serum TSH level but not her thyroid hormone level. These findings were atypical for a patient with TSHoma. The TSHoma was completely resected, and the TSH level dropped below the sensitivity limit shortly after surgery. Interestingly, however, thyroid hormone levels remained high. A clear clue to the aetiology was provided by consecutive thyroid scintigraphy. Although preoperative thyroid scintigraphy did not show a hot nodule and the mass was thought to be a non-functional thyroid nodule, the nodule was found to be hot in the postoperative phase of TSH suppression. By focusing on the atypical postoperative course of the TSHoma, we were able to conclude that this was a case of TSHoma combined with an autonomously functioning thyroid nodule (AFTN). LEARNING POINTS: The diagnosis of autonomously functioning thyroid nodules (AFTNs) depends on suppressed serum TSH levels. If thyroid hormones are resistant to somatostatin analogue therapy or surgery for TSHoma, complications of AFTN as well as destructive thyroiditis need to be considered. It is important to revisit the basics when facing diagnostic difficulties and not to give up on understanding the pathology.

Immunohistochemistry or Molecular Analysis: Which Method Is Better for Subtyping Craniopharyngioma?

Craniopharyngioma (CP) is mainly classified into two pathological subtypes: adamantinomatous (ACP) and papillary (PCP). CTNNB1 (ß-catenin) mutations are detected in ACPs, and the BRAF V600E mutation is detected in PCPs. However, genetic analysis is not always possible in general medical practice. In this study, we investigated whether immunohistochemistry could replace genetic analysis as an aid in subtype diagnosis. Here, 38 CP patients who had undergone their first tumor resection were included. Among the 38 cases, 22 were morphologically diagnosed as ACP, 10 cases were diagnosed as PCP, and six cases were diagnosed as undetermined CP that were morphologically difficult to classify as either ACP or PCP. Results of immunohistochemistry and genetic analysis and clinical features were compared. Based on the immunohistochemistry, 26 (22 ACPs and four undetermined CPs) showed nuclear ß-catenin expression, 11 (nine PCPs and two undetermined CPs) exhibited positive BRAF V600E immunostaining, and one PCP showed membranous ß-catenin expression and negative BRAF V600E immunostaining. Among the 26 nuclear ß-catenin expression cases, 11 had CTNNB1 mutations; however, 15 cases had mutations of neither CTNNB1 nor BRAF V600E. All 11 BRAF V600E immunopositive cases had BRAF V600E mutations. When comparing clinical features, pediatric patients and those with tumor calcification and less solid components on MRI more commonly had nuclear ß-catenin expression tumors than BRAF V600E immunopositive tumors, reflecting the differences in clinical features between ACP and PCP. Accordingly, immunohistochemistry can replace genetic analysis as an aid to determine the subtype diagnosis of CP in general medical practice.

Diagnosis and Surgical Management of Exophytic Suprasellar Pituitary Adenoma Extending Over the Diaphragma Sellae and Mimicking Craniopharyngioma: A Case Report.

Pituitary adenomas developing from the lateral surface of the pituitary gland are referred to as exophytic pituitary adenomas. When an exophytic pituitary adenoma extends into the suprasellar region, the tumor exhibits an atypical growth pattern that makes it difficult to distinguish it from craniopharyngiomas or other parasellar lesions on MRI. A 53-year-old woman who presented with general malaise and visual disturbances was diagnosed with a brain tumor. MRI showed a suprasellar tumor presenting as superior lobulation with reticular enhancement and partial calcification. Subsequently, endoscopic transsphenoidal surgery was performed on the patient. The suprasellar tumor was found to originate from the superior surface of the normal pituitary gland and it extended into the supra-diaphragm region. Subtotal tumor resection was achieved, and her clinical symptoms subsequently improved. Exophytic suprasellar pituitary adenomas (SPAs) are extremely rare and may be mistaken for ectopic SPAs in some cases. Contrast-enhanced fast imaging employing steady-state acquisition (CE-FIESTA) can clearly depict the connection between an exophytic SPA and the normal pituitary gland via a diaphragma sellae defect. During surgery, it was seen that the exophytic SPA and anterior lobe of the pituitary gland connected with each other directly. The tumor originated from the superior surface of the pituitary gland and extended into the supra-diaphragm region. These findings clearly confirmed the difference between exophytic SPAs and ectopic SPAs. In surgical management, an exophytic SPA needs careful consideration for resecting the tumor from encased surrounding structures without vascular and nerve injury. Ultrasonic aspiration devices may be useful for safely resecting the tumor from important structures due to tissue selection. Exophytic SPAs are distinguished from ectopic SPAs with respect to the direct connection between the tumor and the normal pituitary gland. These findings can be clearly depicted using CE-FIESTA and should be confirmed during surgery. Clinicians should be aware of the risk that exophytic SPA may extend into the supra-diaphragm region and of the difficulties of resecting the tumor encasing surrounding structures in the suprasellar region.

[Successful management of cold agglutinin syndrome developing subsequent to rheumatoid arthritis with immunosuppressive therapy].

A 58-year-old man was admitted with shortness of breath in September 2019. He had a severe hemolytic anemia with a high cold agglutinin (CA) titer. He also had arthralgia and finger deformation. He was diagnosed with cold agglutinin syndrome (CAS) secondary to rheumatoid arthritis (RA) based on the clinical course. Occasionally, CAS has been reported to occur in parallel with collagen disease, infectious disease, or malignant tumor. CAS developing secondary to collagen disease occurs less frequently than that to infectious disease or malignant tumors. Furthermore, CAS caused by RA is very rare, even among patients with collagen diseases. Our patient was effectively treated with immunosuppressive therapy including abatacept, which attenuated the symptoms of CAS and RA.

Magnetic Resonance Angiography-based Prediction of the Results of Balloon Test Occlusion.

Precautious balloon test occlusion (BTO) is sometimes performed in cases of high-risk intraoperative internal carotid artery injury. We investigated whether magnetic resonance angiography (MRA) findings could predict BTO results to thus avoid the use of precautious BTO. This retrospective study, included 96 patients who underwent BTO, eight of whom underwent bilateral BTO. The relationship between the BTO results for 104 internal carotid arteries and the MRA findings obtained in 96 patients were retrospectively evaluated. On MRA, anterior cerebral artery (A1)-anterior communicating artery-A1 was defined as anterior collateral circulation (ACC), and posterior cerebral artery-posterior communicating artery was defined as posterior collateral circulation (PCC). BTO was tolerated in all 27 sides with thick ACC regardless of PCC thickness. In 31 of 44 cases with a thin ACC, the tested sides were BTO-tolerant (70.5%). Of these 44 tested sides, all five with a thick PCC were BTO-tolerant, but eight with a thin PCC and 31 with an invisible PCC showed results other than tolerance. Among cases with an invisible ACC, 10 of 33 tested sides were BTO-tolerant (30.3%). Among these 33 tested sides, outcomes other than tolerance were observed regardless of PCC thickness. Thick, thin, and invisible ACCs were assigned 3, 1, and 0 points, respectively; and thick, thin, and invisible PCCs were assigned 2, 1, and 0 points, respectively. A sum of 3 points in the ACC and PCC indicated that all sides were BTO-tolerant. In conclusion, a thick ACC or a thin ACC with a thick PCC indicates BTO-tolerance. The BTO prediction score is useful for predicting results of BTO.

Outcomes of three-Tesla magnetic resonance imaging for the identification of pituitary adenoma in patients with Cushing's disease.

Pituitary adenoma has been reported to be detectable in only 36-63% of Cushing's disease (CD) patients by magnetic resonance imaging (MRI). In this study, we investigate the outcomes and problems associated with tumor identification using 3-Tesla (3-T) MRI, which provides clearer images than ≤1.5-T MRI, in 115 patients who were initially diagnosed with CD. Before surgery, 31 macroadenomas (27%) and 54 microadenomas (47%) were identified by 3-T MRI, but pituitary adenoma was invisible on MRI in the remaining 30 cases (26%). The smallest tumor diameter amenable to a definitive diagnosis was 2 mm, and spoiled gradient-echo was the best sequence for diagnosing microadenomas. In 14 of 30 cases of MRI-invisible CD, the pituitary adenoma was identified during surgery. Nine of these 14 tumors that developed from outside the pituitary gland were retrospectively identified on MRI by comparison with surgical findings. The remaining 16 cases of MRI-invisible CD in which the pituitary adenoma was not identified during surgery involved partial hypophysectomy. Seven cases were hormonally remitted, but another nine cases experienced persistent disease after surgery. The sensitivity and specificity of the pituitary adenoma diagnosis in CD patients after the introduction of 3-T MRI were 80% and 100%, respectively. However, the sensitivity decreased to 72% when macroadenomas were excluded. Some adenomas associated with CD are still undetectable on 3-T MRI due to tumor size, location and intensity. However, sensitivity can be improved by monitoring tumors that develop outside the pituitary gland.

Endoscopic Endonasal Surgery for Subdiaphragmatic Type Craniopharyngiomas.

Subdiaphragmatic type craniopharyngiomas are tumors that originate within the sella. They are divided into two types; those localized within an enlarged sella (intrasellar type) and those accompanying a suprasellar extension (suprasellar extended type). The clinicopathological features and the recent outcomes of endoscopic endonasal surgery were retrospectively reviewed in 32 patients, with 11 surgeries for recurrence. These tumors showed a preponderance in young patients (19 patients were younger than 18-year-old) and suprasellar extended type (25 cases), were mostly composed of a large cyst (96.9%) and were frequently adamantinomatous type (68.8%). Combined transcranial-endoscopic endonasal surgery was applied in three patients with extremely large tumors and significant frontal extension. Total tumor resection and stalk preservation were achieved in 26 and 17 patients, respectively. No complications developed after surgery apart from pituitary dysfunction and visual deterioration. 5 of 6 patients with subtotal tumor resection and 6 of 7 patients with no improvement or deterioration of visual function were in the recurrent cases. Although this type is basically an extraarachnoidal tumor, the suprasellar portion of the tumor showed adherence to important tissues in some patients with recurrence. Pituitary function remained normal in only one third of patients with stalk preservation. To avoid pituitary dysfunction after surgery, sharp excision of firm adherence to the stalk should be considered in some patients.

Postoperative growth hormone dynamics in clinically nonfunctioning pituitary adenoma.

Growth hormone deficiency (GHD) is an endocrine disorder characterized by insufficient production of growth hormone (GH). Non-functioning pituitary adenoma (NFPA) is one of common causes of GHD. Although most patients with NFPA have transsphenoidal surgery, the time-dependent changes in GH after operation have yet to be investigated. In this study, we analyzed patients with NFPAs that underwent transsphenoidal surgery. Postoperatively, GH secretion was evaluated in response to GH-releasing peptide-2 (GHRP2) infusion. We also investigated how several factors affected GH dynamics. Of 119 patients analyzed, 94 (79.0%) had peak GH levels less than 9.0 ng/mL and were diagnosed with severe GHD (sGHD) immediately after surgery. Of those patients, 27 (28.7%) recovered from sGHD within 1-2 years after surgery. Univariate analyses confirmed that sGHD recovery improved significantly in patients that were younger, had only undergone a single primary surgery, had not had anterior hormone deficiency except GH, and had cystic adenoma or normal insulin-like growth factor-1 (IGF1) standard deviation score (SD-S) levels immediately after surgery. Multivariate analyses confirmed that younger age and absence of hormone replacement therapy significantly predicted sGHD recovery within 1-2 years after surgery. Taken together, our results indicated that postoperative sGHD should be assessed by GHRP2 infusion, regardless of IGF1 SD-S levels. Furthermore, recovery from sGHD occurs more frequently at 1-2 years after surgery especially in younger patients and/or those with GH deficiency alone. These patients, therefore, should be reassessed for GHD by appropriate tests including GHRP2 test at 1-2 years after surgery.

Low-Grade Glioma of the Neurohypophysis: Clinical Characteristics and Surgical Outcomes.

BACKGROUND: Low-grade glioma (LGG) of the neurohypophysis is an extremely rare tumor arising from the pituicytes of the posterior pituitary or the infundibulum. The preoperative imaging findings of these tumors mimic those of pituitary adenomas, and radical resection is often challenging in affected patients due to the hypervascularity of the tumor. Here we describe the clinical and radiologic features of this clinical entity. METHODS: We identified 8 patients with LGG of the neurohypophysis who underwent surgery at Toranomon Hospital between January 2007 and March 2017. We retrospectively reviewed the clinical and radiologic data for these patients. RESULTS: The patient cohort comprised 5 men and 3 women, with a mean age of 57 years. The presenting symptoms included visual disturbance in 7 patients and anterior pituitary dysfunction in 7 patients. No patient had diabetes insipidus (DI). Preoperative magnetic resonance imaging (MRI) showed a thick anterior pituitary gland located anterior to the tumor in 3 patients and flow voids on T2-weighted images in 6 patients. All patients underwent transsphenoidal surgery, and gross total resection was achieved in 4 patients. Postoperative morbidities included deterioration of anterior pituitary function in 4 patients and permanent DI in 3 patients. CONCLUSIONS: Anterior displacement of a thick anterior pituitary by a tumor combined with evidence of flow voids on preoperative MRI is helpful in the preoperative diagnosis of LGG of the neurohypophysis. Radical resection should be attempted in these tumors, especially during primary surgery, even though it is associated with postoperative pituitary dysfunction.

Therapeutic outcomes of transsphenoidal surgery in pediatric patients with craniopharyngiomas: a single-center study.

OBJECTIVE The aim of this study was to analyze the outcomes of transsphenoidal surgery (TSS) in a single-center clinical series of pediatric craniopharyngioma patients treated with gross-total resection (GTR). METHODS The authors retrospectively reviewed the surgical outcomes for 65 consecutive patients with childhood craniopharyngiomas (28 girls and 37 boys, mean age 9.6 years) treated with TSS (45 primary and 20 repeat surgeries) between 1990 and 2015. Tumors were classified as subdiaphragmatic or supradiaphragmatic. Demographic and clinical characteristics, including extent of resection, complications, incidence of recurrence, pre- and postoperative visual disturbance, pituitary function, and incidence of diabetes insipidus (DI), as well as new-onset obesity, were analyzed and compared between the primary surgery and repeat surgery groups. RESULTS Of the 45 patients in the primary surgery group, 26 (58%) had subdiaphragmatic tumors and 19 had supradiaphragmatic tumors. Of the 20 patients in the repeat surgery group, 9 (45%) had subdiaphragmatic tumors and 11 had supradiaphragmatic tumors. The only statistically significant difference between the 2 surgical groups was in tumor size; tumors were larger (mean maximum diameter 30 mm) in the primary surgery group than in the repeat surgery group (25 mm) (p = 0.008). GTR was accomplished in 59 (91%) of the 65 cases; the GTR rate was higher in the primary surgery group than in the repeat surgery group (98% vs 75%, p = 0.009). Among the patients who underwent GTR, 12% experienced tumor recurrence, with a median follow-up of 7.8 years, and recurrence tended to occur less frequently in primary than in repeat surgery patients (7% vs 27%, p = 0.06). Of the 45 primary surgery patients, 80% had deteriorated pituitary function and 83% developed DI, whereas 100% of the repeat surgery patients developed these conditions. Among patients with preoperative visual disturbance, vision improved in 62% but worsened in 11%. Visual improvement was more frequent in primary than in repeat surgery patients (71% vs 47%, p < 0.001), whereas visual deterioration was less frequent following primary surgery than repeat surgery (4% vs 24%, p = 0.04). Among the 57 patients without preoperative obesity, new-onset postoperative obesity was found in 9% of primary surgery patients and 21% of repeat surgery patients (p = 0.34) despite aggressive resection, suggesting that hypothalamic dysfunction was rarely associated with GTR by TSS in this series. However, obesity was found in 25% of the repeat surgery patients preoperatively due to prior transcranial surgery. Although there were no perioperative deaths, there were complications in 12 cases (18%) (6 cases of CSF leaks, 3 cases of meningitis, 2 cases of transient memory disturbance, and 1 case of hydrocephalus). Postoperative CSF leakage appeared to be more common in repeat than in primary surgery patients (20% vs 4.4%, p = 0.2). CONCLUSIONS The results of TSS for pediatric craniopharyngioma in this case series suggest that GTR should be the goal for the first surgical attempt. GTR should be achievable without serious complications, although most patients require postoperative hormonal replacement. When GTR is not possible or tumor recurrence occurs after GTR, radiosurgery is recommended to prevent tumor regrowth or progression.

Growth hormone-producing pituitary adenomas in childhood and young adulthood: clinical features and outcomes.

PURPOSE: Growth hormone (GH)-producing pituitary adenomas (PAs) in childhood or young adulthood are rare, and the details surrounding these tumors remain enigmatic. We present the clinical, pathological and genetic features of this disease. METHODS: We identified 25 patients aged 20 years or younger with GH-producing PAs who underwent surgery between 2003 and 2016 at Toranomon Hospital in Tokyo. We retrospectively reviewed the clinical data, treatment outcomes and pathological features of these patients to shed light on childhood acromegaly. RESULTS: The cohort comprised 14 male and 11 female patients whose average age at the time of surgery was 17.3 years. Germline AIP mutations were present in 5 of 13 patients examined, and Carney complex was identified in 2 of 25 patients. The mean maximum tumor diameter was 26.7 mm, and total resection assessed during surgery was achieved in 17 patients. Based on their respective pathological findings, patients were divided into the following 4 groups: sparsely granulated adenomas (5), densely granulated (DG) adenomas (6), plurihormonal adenomas (9), and silent subtype 3 (SS3) adenomas (5). During the mean follow-up period of 50.3 months, complete endocrinological remission was achieved in 14 of 25 patients (56%) by surgery alone and in 19 patients (76%) after postoperative adjuvant therapy. CONCLUSIONS: GH-producing PAs in young patients are intriguing and difficult to treat due to their distinct tumor characteristics, including a lower incidence of the DG subtype and a higher incidence of SS3 adenomas and genetic abnormalities. Therefore, multi-modal therapies are essential to achieve optimal clinical outcomes.

Pitfalls in early biochemical evaluation after transsphenoidal surgery in patients with acromegaly.

Although the current remission criteria for acromegaly are clear and concise, some pitfalls have been reported in early endocrinological evaluation after surgery. To evaluate the long-term (>4 year) outcome and to detect the pitfalls in early evaluation, we retrospectively reviewed 128 patients with acromegaly who underwent primary transsphenoidal surgery during 2011 and 2012. These included 66 men and 62 women, aged from 7 to 76 (mean 46) years old. 49 patients (38.3%) were preoperatively treated with somatostatin analog (SSA). Follow-up period ranged from 52 to 75 (63) months. Long-term remission using the current consensus criteria was achieved in 107 patients (83.6%), 105 of which patient had achieved remission in early evaluation. In 5 patients with preoperative SSA treatment, IGF-1 levels re-elevated more than one year after surgery. Five female patients without pretreatment with SSA showed delayed normalization of IGF-1 between 13 to 27 months postoperatively, two of which patients satisfied the remission criteria. In conclusion, the long-term results can be reliably predicted by the remission criteria early after surgery in most patients with acromegaly. For the accurate evaluation within a year after surgery, however, influence of preoperative treatment with SSA, delayed normalization of IGF-1, and poor GH suppression due to low insulin resistance must be considered, particularly in women.

Inherent Tumor Characteristics That Limit Effective and Safe Resection of Giant Nonfunctioning Pituitary Adenomas.

BACKGROUND: Surgical treatment of giant pituitary adenomas is sometimes challenging. We present our surgical series of giant nonfunctioning adenomas to shed light on the limitations of effective and safe tumor resection. METHODS: The preoperative tumor characteristics, surgical approaches, outcome, and histology of giant nonfunctioning adenoma (>40 mm) in 128 consecutive surgical patients are reviewed. The follow-up period ranged from 19 to 113 months (mean 62.2 months). RESULTS: A transsphenoidal approach was used in the treatment of 109 patients and a combined transsphenoidal transcranial approach in 19 patients. A total of 93 patients (72.7%) underwent total resection or subtotal resection apart from the cavernous sinus (CS). The degree of tumor resection, excluding the marked CS invasion, was lower in tumors that were larger (P = 0.0107), showed massive intracranial extension (P = 0.0352), and had an irregular configuration (P = 0.0016). Permanent surgical complications developed in 28 patients (22.0%). Long-term tumor control was achieved in all patients by single surgery, including 43 patients with adjuvant radiotherapy. Most tumors were histologically benign, with a low MIB-1 index (<3.0%) beside a few tumors mainly silent adenomas of pituitary-specific transcription factor lineage. CONCLUSIONS: Irrespective of the surgical approach, massive intracranial extension, an irregular configuration, and marked CS invasion are inherent factors that independently limit effective resection. These high-risk tumors require an individualized therapeutic strategy.