Pituitary

AcroVoice: the controversial values in reflecting acromegaly disease activity

Correction to: Rathke’s cleft cysts: a 6-year experience of surgery vs. observation with comparative volumetric analysis The original version of this article unfortunately contained errors in legend numbers of Figure 2 caption.

Ectopic pituitary adenomas: common presentations of a rare entity Abstract Purpose Ectopic pituitary adenomas (EPA) are rare tumors thought to arise from embryological remnants along the route of normal pituitary migration. Clinically, these tumors vary in hormonal activity and can exert mass effect based on location and size. Methods We performed a single-center retrospective analysis of patients with diagnosis of ectopic pituitary adenoma from 2001 to 2018. Results Five patients were identified with EPA: a 48-year-old woman with suprasellar EPA treated with transsphenoidal removal of the tumor, a 44-year-old woman with cavernous EPA treated with transsphenoidal removal of the tumor, a 48-year-old woman with sphenoid EPA treated with cabergoline, a 45-year-old man with clival EPA treated with cabergoline and transsphenoidal surgical resection, and a 54-year-old man with clival EPA treated with cabergoline therapy. Conclusions EPA should be considered as a differential diagnosis of juxta-sellar lesions. Appropriate hormonal testing may lead to early diagnosis, avoidance of unnecessary biopsy or surgery, and improved outcomes.

Functional survival of rat pituitary gland in hypothermic storage for pituitary transplantation Abstract Purpose Deteriorated pituitary function can lead to serious complications that might need lifelong hormone replacement therapy. However, long-term hormone administration can have significant adverse effects. Thus, it would be more desirable to restore pituitary function by pituitary transplantation. In this study, we investigated functional preservation of extracted pituitary gland in special preservation solution under hypothermic condition for pituitary transplantation. Methods We obtained nineteen pituitary glands from 250–300 g male Sprague–Dawley rats via parapharyngeal approach. These extracted glands were divided into three pieces and stored in histidine-tryptophan-ketoglutarate (HTK) solution at 4 °C and compared to their corresponding glands stored in phosphate buffer saline (PBS). Light and electron microscopic examinations were performed to identify morphological changes of pituitary gland at 0,3, and 7 days after storage. TUNEL assay to confirm cell viability, and adenosine-triphosphate (ATP) concentration were also serially examined. Results Tissue architecture and cellular viability of specimens preserved in HTK solution for 3 days were considerably maintained and similar to those in normal pituitary gland (0 day specimen). In contrast, specimens stored in PBS were markedly destroyed after 3 days of storage. After 7 days of storage, significant degeneration occurred in tissues stored in both HTK and PBS. However, tissue architecture was preserved more in specimens stored in HTK solution than those stored in PBS. ATP concentration decreased more rapidly in specimens stored in PBS solution, but there was no statistical significance (p= 0.055). Conclusions Extracted rat pituitary gland supplemented with special preservation solution could be preserved for 3 days under hypothermic condition.

Cushing’s disease due to somatic USP8 mutations: a systematic review and meta-analysis Abstract Purpose Cushing’s disease (CD) is a severe illness generally caused by microcorticotropinomas (MICs) and in approximately 7–20% of patients by macrocorticotropinomas (MACs). USP8-mutations have been identified as a major genetic cause of CD (~ 50%). Few studies have reported the distribution between MICs–MACs related to USP8-mutations and their genotype–phenotype correlations. Therefore, we aimed to evaluate USP8-mutations in a cohort of MICs–MACs from a unique center and to perform a systematic review and meta-analysis. Methods DNA-tumor-tissues from 47 corticotropinomas (16 MICs and 31 MACs) were sequenced. Clinical-biochemical data, radiological imaging data and remission/recurrence rates were evaluated. In addition, we performed a meta-analysis of nine published series (n = 630). Results We identified four different USP8-mutations previously described, in 11 out of 47 (23.4%) corticotropinomas; 8 out of 11 were MACs. The urinary cortisol levels of our patients with corticotrophin USP8-mutated-alleles were lower than those of patients with wild-type (WT) alleles (p ≤ 0.017). The frequency of USP8-mutated-alleles among the series was approximately 30% with a higher prevalence in female-patients (p < 0.1 × 10−4). Among the 5 series, the remission rates were higher in patients with USP8-mutated-alleles than in those with the USP8-WT-alleles (p < 0.1 × 10−4). Conclusion Our data, as well as the retrospective review of CD series associated with USP8-mutated alleles, show heterogeneous findings among the series. Several drawbacks included the lack of a systematic protocol to evaluate these patients before surgery and follow-up. Further prospective studies using a systematic protocol will provide more consistent information about the influence of the corticotropinomas with USP8-mutated alleles on the phenotype, responses to treatment and outcome of patients with CD.

Assessment of static and dynamic plantar data of patients with acromegaly Abstract Purpose To determine both static and dynamic plantar data of acromegalic subjects while barefoot. Methods Seventy acromegalic patients and 48 age-, sex-, weight- and height-matched healthy controls were included. Plantar variables were measured using the footscan gait system. The data included the width and length of each foot, relative force distribution in each quadrant, mean force applied to each foot and maximum pressure while walking. Maximum pressure data were obtained from ten parts of the foot. Injury risk assessments of five different regions were performed. To analyze balance, center of pressure (CoP) measurements were performed. The patients with acromegaly were compared with the controls. Furthermore, a comparison of patients with active and controlled acromegaly was performed. Results The foot was wider in acromegalic patients. The mean force on each foot was higher in cases of acromegaly (acromegaly: 1027 ± 180 N, control: 908 ± 180 N, p = 0.001). In the acromegalic individuals, the maximum pressure in the midfoot was higher, while the medial heel maximum pressure was lower (midfoot maximum pressure acromegaly: 11.3 ± 3.5 N/cm2, control: 8.9 ± 3.7 N/cm2, p = < 0.001). Injury risk was similar. CoP measurements elicited intact balance. In terms of static and dynamic plantar data, there was no difference between patients with active and controlled acromegaly. Conclusions This is the first study to demonstrate that compared with healthy controls, patients with acromegaly experience great force on their feet while standing and high pressure in the midfoot during walking. Podiatric evaluation, custom molded orthotics and individualized rehabilitation programs for acromegalic patients may provide better force and pressure distribution throughout the foot and improve gait and skeletal symptoms.

Preoperative visual evoked potential in the prediction of visual outcome after pituitary macroadenomas surgery Abstract Objective The purpose of the present study is to investigate longitudinal changes in Visual evoked potential (VEP) parameters as an objective test after transsphenoidal surgery, its correlation with subjective tests and clinical value of VEP in the prediction of visual outcome. Methods Fifty patients with pituitary macroadenoma who underwent surgical removal of the tumor recruited in this study. All the patients underwent ophthalmic examination, static automated perimetry (SAP), VEP and magnetic resonance imaging (MRI) preoperatively and 3 months after surgery. Results Fifty patients with pituitary macroadenoma (size: 25.1 ± 9.9 mm) were recruited in the study. Before surgery, the pattern of VEP showed a prolonged latency with reduced amplitude in eyes with abnormal visual acuity or abnormal visual field. The P100 wave latencies and amplitudes showed significant correlation with visual acuity and SAP scores. After surgery, visual acuity and visual field improvements were seen in 51% and 65.6% of eyes, respectively. Mean SAP and visual acuity scores increased significantly (p < 0.01), P100 wave latency declined and amplitude improved after surgery but not significantly. The mean age of patients, size of tumors and preoperative P100 wave latency were significantly lower in eyes with visual field and acuity improvement. Conclusion VEP is a helpful quantitative and objective complementary test to visual acuity and SAP exams for assessing pre-operative visual abnormalities and post-operative visual outcome in patients with pituitary macroadenoma.

Role of gamma knife radiosurgery in the treatment of prolactinomas Abstract Purpose Stereotactic radiosurgery is one of the treatment options for prolactinomas, the most commonly used being Gamma Knife Radiosurgery (GKRS). GKRS is indicated mainly in the treatment of dopamine agonist (DA)-resistant prolactinomas. In our study, we report on our experience in treating prolactinoma patients by GKRS. Methods Twenty-eight patients were followed-up after GKRS for 26–195 months (median 140 months). Prior to GKRS, patients were treated with DAs and 9 of them (32.1%) underwent previous neurosurgery. Cavernous sinus invasion was present in 16 (57.1%) patients. Indications for GKRS were (i) resistance to DA treatment (17 patients), (ii) drug intolerance (5 patients), or (iii) attempts to reduce the dosage and/or shorten the length of DA treatment (6 patients). Results After GKRS, normoprolactinaemia was achieved in 82.1% of patients, out of which hormonal remission (normoprolactinaemia after discontinuation of DAs) was achieved in 13 (46.4%), and hormonal control (normoprolactinaemia while taking DAs) in 10 (35.7%) patients. GKRS arrested adenoma growth or decreased adenoma size in all cases. Two patients (8.3%) developed hypopituitarism after GKRS. Prolactinoma cystic transformation with expansive behaviour, manifested by bilateral hemianopsia, was observed in one patient. Conclusions GKRS represents an effective treatment option, particularly for DA-resistant prolactinomas. Normoprolactinaemia was achieved in the majority of patients, either after discontinuation of, or while continuing to take, DAs. Tumour growth was arrested in all cases. The risk of the development of hypopituitarism can be limited if the safe dose to the pituitary and infundibulum is maintained.

Antibody array strategy for human growth factor secretome profiling of GH-secreting adenomas Abstract Purposes To test if the antibody array strategy could be utilized to simultaneously detect the secretion of multiple growth factors by human pituitary GH-adenomas and to measure octreotide-induced alterations. Methods Specimens of human pituitary adenomas were cultured and incubated with or without octreotide for 24 h. Conditional media were analyzed by human growth factor antibody array and VEGF concentrations were measured by ELISA. Media were also analyzed for GH concentrations. p21 expression levels were examined by Western blot of the specimens lysates. Results The antibody arrays successfully identified growth factors secreted by GH-adenomas in vitro. Octreotide treatment induced both elevations and reductions in growth factors secretion. GH response to octreotide was measured, and in this small-sized study resistant and sensitive GH-adenomas presented with no unique secretome pattern of each of the groups. Octreotide-induced VEGF alterations analyzed by the antibody array and by ELISA were not fully matched. Conclusions This study suggests that the broad proteomic strategy of antibody arrays may be utilized to study the growth factors secretion pattern of GH-adenomas and its regulation by somatostatin analogs or other compounds.

Rathke’s cleft cysts: a 6-year experience of surgery vs. observation with comparative volumetric analysis Abstract Background Rathke’s cleft cysts (RCCs) are common sellar lesions. Their management remains controversial, particularly when small or asymptomatic. Herein we review a consecutive series of RCC patients managed with surgery or observation. Methods All patients with a new diagnosis of presumed RCC, based on MRI, from February 2012–March 2018 were retrospectively divided into observational and surgical cohorts based on an intent-to-treat model. The cohorts were compared for clinical presentation, and cyst volume. The observational cohort was followed for change in cyst size. The surgical cohort was followed for changes in endocrinopathy, visual symptoms, headache and recurrence. Results Of 90 patients (mean age 36.7 ± 19.4 years; 68% female), 60% (n = 54) were in the observational cohort and 40% (n = 36) in the surgical cohort. Average follow-up was 13 ± 23 months in the observational cohort and 24 ± 19 months in the surgical group. In comparing the cohorts, mean ages were similar with more women in the surgical group (81% vs. 56%, p = 0.04). Most patients in the observational cohort had incidentally-discovered RCCs (n = 50, 88%) as opposed to the surgical cohort (n = 6, 17%). The surgical cohort had higher rates of headache (89% vs 26%, p < 0.001), endocrinopathy (36% vs 0%, p < 0.001), and visual dysfunction (19% vs 0%, p = 0.001). Mean cyst volume and maximal cyst dimensions were greater in the surgical cohort (0.94 ± 0.77 cm3 and 14.2 ± 4.1 mm), compared to the observational cohort (0.1 ± 0.14 cm3 and 6.4 ± 3 mm), (p < 0.001). Among the 53% (n = 30/54) of patients in the observational group with follow-up, 3 (10%) had spontaneous RCC shrinkage, 1 (3%) had modest asymptomatic growth (at 10 months from initial MRI), and 87% had stable cyst size. Of the 36 patients recommended to have surgery, 89% (n = 32) did so. Post-operatively, complete or partial resolution of headache, endocrinopathy and visual dysfunction were documented in 90% (n = 28/30), 75% (n = 10/12), and 100% (n = 7/7), respectively. On follow-up MRI, 8 (22%) patients had some cyst reaccumulation, of whom 3 (8%) were symptomatic and underwent uneventful reoperation. No major complications such as hematoma, CSF leak, new endocrinopathy or visual deficits occurred. Conclusion From this consecutive series, a majority (60%) of RCCs do not appear to warrant surgical intervention and have a low risk of cyst progression. However, surgical cyst removal appears to be indicated and safe for patients with larger, symptomatic RCCs. Simple cyst drainage has a high rate of improvement in pituitary gland function, visual function and headache resolution with low complication rates and symptomatic recurrence risk. These findings stress the importance of careful case selection and potential utility of volumetric assessment for patients with RCCs.