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.

A case of isolated hypothalamitis with a literature review and a comparison with autoimmune hypophysitis.

Idiopathic hypothalamitis is a rare condition that can cause anterior pituitary dysfunction and central diabetes insipidus (CDI), occasionally accompanied by a disturbance of autonomic regulation known as hypothalamic syndrome. This condition has been described as a subtype of autoimmune (lymphocytic) hypophysitis; however, some cases of isolated hypothalamic involvement with no inflammatory lesions in either the pituitary gland or infundibulum have been reported. The detailed epidemiology and pathophysiology of isolated hypothalamitis have not been clarified. We herein report a case of a solitary hypothalamic lesion in a young woman who showed spontaneous development of CDI and panhypopituitarism accompanied by hyperphagia. The hypothalamic lesion increased from 11 × 7 to 17 × 7 mm over 16 months based on the sagittal slices of magnetic resonance imaging examinations. The negative results for anti-pituitary antibodies and anti-Rabphilin-3A antibodies suggested that upward extension of lymphocytic adenohypophysitis or infundibulo-neurohypophysitis was unlikely. Infectious disease, granulomatosis, Langerhans cell histiocytosis, vasculitis, and systemic neoplastic diseases were excluded by the findings of a laboratory investigation, cerebrospinal fluid examination, and imaging studies. To make a definitive diagnosis, we performed a ventriculoscopic biopsy of the hypothalamic lesion. Histology revealed an infiltration of nonspecific lymphoplasmacytes with no evidence of neoplasm, which was consistent with a diagnosis of idiopathic hypothalamitis. Subsequently, the patient was treated with methylprednisolone pulse therapy followed by oral prednisolone. The hypothalamic lesion improved and remained undetectable after withdrawal of the prednisolone, suggesting that the glucocorticoid treatment was effective for isolated hypothalamitis while the patient remains dependent on the replacement of multiple hormones.

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.

MSH6/2 and PD-L1 Expressions Are Associated with Tumor Growth and Invasiveness in Silent Pituitary Adenoma Subtypes.

Mismatch repair genes mutS homologs 6/2 (MSH6/2) expressions are involved in tumor growth and programmed cell death 1 ligand 1 (PD-L1) expression in tumor immunity, but the direct association with pituitary adenomas (PAs) is not well understood. We aimed to clarify the effects of MSH6/2 and PD-L1 expression on tumor proliferation and invasiveness in nonfunctioning (NF) PAs. We performed immunohistochemistry to classify the NFPAs into gonadotroph adenoma (GAs), silent corticotroph adenomas (SCAs), null cell adenoma (NCAs), and pituitary transcription factor 1 (PIT1) lineage PAs. We evaluated MSH6/2 and PD-L1 mRNA expressions in NFPAs by real-time PCR (n = 73), and statistically analyzed the expressions and clinicopathological factors. We also investigated the effect of MSH6 knockout on PD-L1 expression in AtT-20ins and GH3. MSH6/2 expressions were significantly lower in invasive NFPAs than in non-invasive NFPAs, and lower in SCAs and NCAs than in GAs. MSH6/2 expressions were positively associated with PD-L1 expression. PD-L1 expression was significantly lower in invasive NFPAs than in non-invasive NFPAs, and lower in SCAs and NCAs than in GAs. Although MSH6/2 expressions also tended to be lower in PIT1 lineage PAs than in GAs, PIT1 lineage PAs expressed PD-L1 equivalently to GA, which was unlike SCAs and NCAs. MSH6 knockout in AtT-20ins and GH3 significantly decreased PD-L1 expression (75% and 34% reduction, respectively) with cell proliferation promotion. In conclusion, differences in MSH6/2 and PD-L1 expressions of SCAs, NCAs, and PIT1-lineage PAs from those of GAs appear to contribute to their clinically aggressive characteristics, such as more proliferation and invasiveness.

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.

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.

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.

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.

Low insulin resistance after surgery predicts poor GH suppression one year after complete resection for acromegaly: a retrospective study.

Remission of acromegaly is defined as a nadir in GH <1.0 ng/mL during a 75-g oral glucose tolerance test (75gOGTT) and insulin-like growth factor-1 (IGF-1) normalization. Recently, a lower cut-off value for GH nadir (<0.4 ng/mL) has been proposed. We retrospectively evaluated the prevalence and clinical characteristics of postoperative cases with normalized IGF-1 levels and a GH nadir of 0.4-1.0 ng/mL one year after complete resection of GH-secreting pituitary adenoma (GHoma). We included 110 cases of acromegaly with complete adenoma resection, no preoperative treatment, preoperative glycosylated hemoglobin <6.5%, preoperative basal plasma glucose <126 mg/dL, GH nadir <1.0 ng/mL during a 75gOGTT, and normalized IGF-1 at the first postoperative year evaluation, whereupon patients were divided into two groups: control (GH nadir <0.4 ng/mL) and high GH (GH nadir >0.4 ng/mL). Clinical parameters, including measures of insulin secretion and resistance, were compared between groups. The high GH group included 10 patients (9.1%) and had a lesser level of insulin resistance immediately following surgery and at the first postoperative year evaluation. On single regression analysis, insulin resistance immediately following surgery was predictive of and correlated with the GH nadir at the first postoperative year evaluation. The GH nadir at the first postoperative year evaluation may be insufficient in patients with normalized IGF-1 with low insulin resistance immediately following complete resection of GHoma. Careful evaluation is needed to assess remission in such patients.

A new multilayer reconstruction using nasal septal flap combined with fascia graft dural suturing for high-flow cerebrospinal fluid leak after endoscopic endonasal surgery.

This study aimed to evaluate the usefulness and reliability of a new endoscopic multilayer reconstruction using nasal septal flap (NSF) to prevent high-flow cerebrospinal fluid leak after endoscopic endonasal surgery. This study was a retrospective review on 97 patients who underwent multilayer reconstructions using NSF combined with fascia graft dural suturing after endoscopic endonasal surgery between July 2012 and March 2014. Patients were divided into two groups, third ventricle opening group and nonopening group, based on the presence of a direct connection between the third ventricle and the paranasal sinus after tumor removal. Furthermore, we compared this procedure with our previous reconstruction after resection of craniopharyngioma. Finally, we checked the patients who had postoperative prolonged discomfort of the nasal cavity for over a year. Postoperative cerebrospinal fluid (CSF) leak occurred in three patients (3.1 %): one from the third ventricle opening group and the remaining two from the nonopening group. External lumbar drain was performed after surgery in only seven patients (7.2 %). The incidence of postoperative CSF leak was similar in both groups, whereas the rate of craniopharyngioma in the third ventricle opening group was significantly higher. The incidence of postoperative CSF leak after resection of craniopharyngioma was not statistically significant but obviously higher in the previous group (12.2 %) compared with that in the present group (2.3 %). Twelve patients (12.4 %) had postoperative nasal discomfort of the nasal cavity for over a year. Multilayer reconstruction using NSF combined with fascia graft dural suturing is a more reliable method for preventing postoperative high-flow CSF leakage after endoscopic endonasal surgery even if there is a direct connection between the third ventricle and the paranasal sinus. However, we should pay close attention especially to prolonged discomfort of the nasal cavity after harvesting NSF.

Short-term preoperative octreotide treatment for TSH-secreting pituitary adenoma.

Preoperative control of hyperthyroidism in patients with TSH-secreting pituitary adenomas (TSHoma) may avoid perioperative thyroid storm. Perioperative administration of octreotide may control hyperthyroidism, as well as shrink tumor size. The effects of preoperative octreotide treatment were assessed in a large number of patients with TSHomas. Of 81 patients who underwent surgery for TSHoma at Toranomon Hospital between January 2001 and May 2013, 44 received preoperative short-term octreotide. After excluding one patient because of side effects, 19 received octreotide as a subcutaneous injection, and 24 as a long-acting release (LAR) injection. Median duration between initiation of octreotide treatment and surgery was 33.5 days. Octreotide normalized free T4 in 36 of 43 patients (84%) and shrank tumors in 23 of 38 (61%). Length of octreotide treatment did not differ significantly in patients with and without hormonal normalization (p=0.09) and with and without tumor shrinkage (p=0.84). Serum TSH and free T4 concentrations, duration of treatment, incidence of growth hormone (GH) co-secretion, results of octreotide loading tests, form of administration (subcutaneous injection or LAR), tumor volume, and tumor consistency did not differ significantly in patients with and without hormonal normalization and with and without tumor shrinkage. Short-term preoperative octreotide administration was highly effective for TSHoma shrinkage and normalization of excess hormone concentrations, with tolerable side effects.

Therapeutic outcomes in patients undergoing surgery after diagnosis of Cushing's disease: A single-center study.

This study aimed to investigate early and late outcomes of patients who underwent neurosurgical procedures for the preoperative diagnosis of Cushing's disease (CD). Clinical, endocrine, imaging, and histologic data from 252 patients undergoing pituitary surgery at Toranomon Hospital through the end of 2012 were entered into a database and statistically analyzed. In 22 of these patients (8.7%; positive venous sampling in 15 and negative venous sampling in 7 patients), tumors were invisible on magnetic resonance imaging (MRI) and 42.9% of them achieved remission. In the remaining 230 patients, 93.5% of those with microadenomas (n=154) and 71.1% of those with macroadenomas (n=76) achieved early postoperative remission, with recurrence rates of 2.7% and 14.8%, respectively, during a 72.5-month median follow-up. In multivariate analyses, cavernous sinus invasion (CSI; odds ratio [OR], 13.0), type of surgery (OR, 4.0), and tumor size (OR, 2.7) were significant preoperative factors affecting early postoperative results, whereas peak cortisol levels ≥9.4 µg/dL in response to corticotropin-releasing hormone (CRH) and CSI were significant factors predicting recurrence. Tumor recurrence was more common in patients with non-densely granulated adenomas than in patients with densely granulated adenomas. We propose that the higher remission and lower recurrence rates in this series are due to our surgical strategies, including extracapsular tumor removal, aggressive resection of tumors with CSI, extended transsphenoidal surgery (TSS), or a combined approach for large/giant adenomas. Appropriate multimodal treatments, including radiotherapy, medication, and repeated surgery in patients with persistent or recurrent CD, could result in better overall outcomes than previously achieved.

Transsphenoidal cyst cisternostomy with a keyhole dural opening for sellar arachnoid cysts: technical note.

A less invasive transsphenoidal approach with a keyhole dural opening for intrasellar arachnoid cysts is described. This approach was used to address seven sellar cystic lesions with suprasellar extension; they were six intrasellar arachnoid cysts (IACs) and one Rathke's cleft cyst (RCC). In all cases, preoperative MRI revealed cerebrospinal fluid (CSF) intensity on both T1- and T2-weighted images. On preoperative contrast-enhanced MRI, five of the six IACs manifested posterior displacement of the flattened pituitary gland toward the dorsum sellae; one of the six IACs and the RCC exhibited a flattened pituitary gland on the anterior surface of the cyst. Wide cyst cisternostomy through a keyhole dural opening was carried out safely using a microscope with the support of a thin angled endoscope (30° and/or 70°, diameter 2.7 mm). As we aimed to avoid iatrogenic injury of the pituitary function, we found it difficult to obtain a sufficiently wide and precise opening of the cyst wall when the pituitary gland was located on the anterior surface of the cyst wall. Our approach facilitates safe cyst cisternostomy as wide as that obtainable by transcranial manipulation. In addition, CSF leakage is prevented by dural plasty using the fascia lata and stitching with 6-0 monofilament sutures. This technique can be adapted to address various sellar cystic lesions. However, as the posterior or anterior displacement of the normal pituitary gland in the presence of IACs or RCCs, respectively, affects the width of the cyst opening, our technique is more suitable for IACs than RCCs.

A handmade eye movement monitor using a piezoelectric device during transsphenoidal surgery.

We describe a handmade eye movement monitor featuring a piezoelectric device for use during transsphenoidal surgery (TSS). The sensor consists of a piezoelectric device, condensers, resistors, and several inexpensive parts. Eyeball movements elicited by surgical manipulations during TSS for cavernous sinus tumor are detected by small disc-shaped sensors taped to the eyelids. The responses could be monitored as sharp waves on an electroencephalograph. After we started using this monitor, both the incidence and the severity of cranial nerve injuries during TSS for cavernous sinus tumor decreased. Our device is especially useful at operations to remove functioning pituitary adenomas invading the cavernous sinus and contributes to their favorable endocrine outcomes. None of our patients manifested the postoperative swelling of the eyelids or conjunctival congestion generally seen in patients subjected to the insertion of needle sensors for the acquisition of electromyograms of the extraocular muscles, which is widely used during surgery to identify the cranial nerves responsible for eye movement. Our monitor is less expensive and easier to use than any commercially available sensor devices. As our method does not require the insertion of needle sensors, it is less invasive than electromyography of the extraocular muscles.

Remote extradural haematomas following extended transsphenoidal surgery for a craniopharyngioma--a case report.

We present the first recorded case of a remote extradural haematoma following extended transsphenoidal surgery (eTSS) for craniopharyngioma. We believe that this is a unique complication related to rapid and excessive intracranial hypotension caused by acute overdrainage of cerebrospinal fluid (CSF) during the eTSS procedure.

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.

A Prospective, Multicenter, Observational Study of Surgical vs Nonsurgical Management for Pituitary Apoplexy.

CONTEXT: Pituitary apoplexy (PA) has been traditionally considered a neurosurgical emergency, yet retrospective single-institution studies suggest similar outcomes among patients managed medically. OBJECTIVE: We established a multicenter, international prospective registry to compare presentation and outcomes in PA patients treated with surgery or medical management alone. METHODS: A centralized database captured demographics, comorbidities, clinical presentation, visual findings, hormonal status, and imaging features at admission. Treatment was determined independently by each site. Key outcomes included visual, oculomotor, and hormonal recovery, complications, and hospital length of stay. Outcomes were also compared based on time from symptom onset to surgery, and from admission or transfer to the treating center. Statistical testing compared treatment groups based on 2-sided hypotheses and P less than .05. RESULTS: A total of 100 consecutive PA patients from 12 hospitals were enrolled, and 97 (67 surgical and 30 medical) were evaluable. Demographics, clinical features, presenting symptoms, hormonal deficits, and imaging findings were similar between groups. Severe temporal visual field deficit was more common in surgical patients. At 3 and 6 months, hormonal, visual, and oculomotor outcomes were similar. Stratifying based on severity of visual fields demonstrated no difference in any outcome at 3 months. Timing of surgery did not affect outcomes. CONCLUSION: We found that medical and surgical management of PA yield similar 3-month outcomes. Although patients undergoing surgery had more severe visual field deficits, we could not clearly demonstrate that surgery led to better outcomes. Even without surgery, apoplectic tumor volumes regress substantially within 2 to 3 months, indicating that surgery is not always needed to reduce mass effect.

Scalp hair loss after transsphenoidal adenomectomy in patients with acromegaly.

OBJECTIVE: Scalp hair loss is often encountered in clinical practice in Japan after successful surgery for acromegaly. However, this intriguing issue has not been addressed in the literature. The aim of this study was to examine scalp hair loss after surgery for acromegaly. METHODS: Postoperative scalp hair loss was surveyed using a mail-back questionnaire given to 511 patients undergoing primary surgery for acromegaly, 484 of whom constitute the patient pool in this study. RESULTS: Of the 484 patients, 263 (54%) patients noticed varying degrees of hair loss between 3 and 6 months after surgery [the degree of alopecia was minimal in 50 patients (10%), moderate in 117 patients (24%), and severe in 96 patients (20%)], although postoperative hair loss was noticed only in six (3·6%) of 167 patients with nonfunctioning adenomas. Postoperative hair loss was significantly more common in female patients, cured patients and patients with severe postoperative growth hormone deficiency. Among those 263 patients, full recovery was reported by 85 patients (32%), incomplete recovery by 88 patients (34%), and hardly any recovery by 90 patients (34%). A lack of hair recovery was significantly more common in male patients or in patients with severe hair loss after surgery. CONCLUSIONS: This, the first large-scale, single-centre, clinical study to shed light on the issue of postoperative hair loss after surgery for acromegaly, shows that it is important to prospectively inform patients that varying degrees of hair loss occur in a large number of acromegalic patients, especially after successful surgery.

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.