Changes in cardiovascular risk factors in patients with acromegaly after trans-sphenoidal adenomectomy.

The surgical treatment of acromegaly reduces mortality, however its impact on cardiovascular risk factors is unclear. This study was carried out to determine the changes in cardiovascular risk factors in patients with acromegaly who received trans-sphenoidal surgery. We recruited 127 patients with acromegaly who received trans-sphenoidal adenomectomy between August 2003 and May 2014 and follow-up for 12 months. Fasting GH and IGF-1 levels were evaluated every 3 months, and cardiovascular risk factors were assessed before and 12 months after surgery. The main outcomes were changes in cardiovascular risk factors after surgery. One year after trans-sphenoidal adenomectomy, 68 patients (53.5%) had a fasting GH level <2.0 ng/mL, IGF-1 was normalized in 74 patients (58.3%), and both fasting GH and IGF-1 were under control in 51 patients (40.2%). Levels of glycated hemoglobin (HbA1c) (8.57 ± 3.19 vs. 6.66 ± 0.90%, p = 0.001) and triglycerides (130.6 ± 61.5 vs. 108.0 ± 47.5 mg/dL, p = 0.027) were significantly decreased and serum creatinine was significantly increased (0.665 ± 0.222 vs. 0.754 ± 0.223 mg/dL, p = 0.001) after trans-sphenoidal adenomectomy. However, there were no significant changes in body weight, systolic blood pressure, diastolic blood pressure, total cholesterol, high-density lipoprotein cholesterol and cardiovascular risk score after trans-sphenoidal adenomectomy. In the patient with high cardiovascular risk before surgery, systolic blood pressure, total cholesterol, fasting glucose, triglycerides and high-density lipoprotein cholesterol improved after trans-sphenoidal adenomectomy. In this study, HbA1c and triglycerides were significantly decreased after trans-sphenoidal adenomectomy in the patients with acromegaly irrespective of endocrinological outcomes. The other traditional cardiovascular factors might be improved after trans-sphenoidal adenomectomy in the patients with a high cardiovascular risk.

Clinical and Pathological Aspects of Silent Pituitary Adenomas.

CONTEXT: Silent pituitary adenomas are anterior pituitary tumors with hormone synthesis but without signs or symptoms of hormone hypersecretion. They have been increasingly recognized and represent challenging diagnostic issues. EVIDENCE ACQUISITION: A comprehensive literature search was performed using MEDLINE and EMBASE databases from January 2000 to March 2018 with the following key words: (i) pituitary adenoma/tumor and nonfunctioning; or (ii) pituitary adenoma/tumor and silent. All titles and abstracts of the retrieved articles were reviewed, and recent advances in the field of silent pituitary adenomas were summarized. EVIDENCE SYNTHESIS: The clinical and biochemical picture of pituitary adenomas reflects a continuum between functional and silent adenomas. Although some adenomas are truly silent, others will show some evidence of biochemical hypersecretion or could have subtle clinical signs and, therefore, can be referred to as clinically silent or "whispering" adenomas. Silent tumors seem to be more aggressive than their secreting counterparts, with a greater recurrence rate. Transcription factors for pituitary cell lineages have been introduced into the 2017 World Health Organization guidelines: steroidogenic factor 1 staining for gonadotroph lineage; PIT1 (pituitary-specific positive transcription factor 1) for growth hormone, prolactin, and TSH lineage, and TPIT for the corticotroph lineage. Prospective studies applying these criteria will establish the value of the new classification. CONCLUSIONS: A concise review of the clinical and pathological aspects of silent pituitary adenomas was conducted in view of the new World Health Organization classification of pituitary adenomas. New classifications, novel prognostics markers, and emerging imaging and therapeutic approaches need to be evaluated to better serve this unique group of patients.

Ganglioglioma of the adenohypophysis mimicking pituitary adenoma: A case report and review of the literature.

INTRODUCTION: Ganglioglioma is a generally benign tumor, mostly occurring in patients <30 years old. Temporal lobe is most frequently involved. Up to now, only 3 cases were reported of ganglioglioma in the pituitary gland, all being confined to the neurohypophysis. Here, we are the first to report an adenohypophysis ganglioglioma. CASE PRESENTATION: A 43-year-old woman presented with chronic headache was referred to our hospital. Magnetic resonance imaging (MRI) indicated pituitary adenoma. Endoscopic transnasal transsphenoidal surgery was performed. The tumor was rich in blood supply, with tough texture, therefore only subtotal resection was conducted. Pathology analysis revealed an adenohypophysial tumor composed of dysplastic ganglion cells and neoplastic glial cells collided with nonspecific hyperplasia of pituitary cells. Immunohistochemistry revealed positive staining of synaptophysin, glial-fibrillary acidic protein, and CD34. The results were consistent with the diagnosis of ganglioglioma. After the surgery the patient recovered well except developing cerebrospinal fluid rhinorrhea, which was controlled by lumbar drainage. MRI 6 months later did not show any sign of progression. CONCLUSION: According to the findings of our case, concerns should be raised considering ganglioglioma as a differential diagnosis of mass located in the sellar region. Furthermore, an ideal management strategy for pituitary ganglioglioma is not known; therefore, more cases and long-term follow-up are needed to enrich our knowledge of the diagnosis, treatment, and prognosis of this rare intracranial lesion.

Spindle cell oncocytoma: Report of two cases with massive bleeding and review of the literature.

Spindle cell oncocytoma (SCO) is a rare pituitary tumor, classified as a WHO grade I neoplasm. Due to its rarity, SCO is often preoperatively misdiagnosed as a pituitary macroadenoma. In the present study we report two recent cases of SCO, a 61-year-old male and a 65-year-old female presenting at Treviso General Hospital between March 2014 and April 2015. Tumor resection was achieved by endoscopic transsphenoidal approach but massive hemorrhagic events hampered surgery, endangering the patient's life in both cases. Both tumors featured fascicles of spindle cells with eosiniphilic cytoplasm expressing vimentin, S-100 and thyroid transcription factor-1 (TTF-1). The diagnosis of SCO was confirmed by second opinion in both cases. Extensive review of available literature, about 30 cases from 2002 to 2015, provided valuable clinical data for preoperative diagnosis and surgical removal of SCO tumors.

Radiosurgery for infundibulum adenoma: stalk dose implications.

Treating pituitary adenomas in the infundibulum with stereotactic radiosurgery (SRS), achieving tumor volume control while preserving pituitary endocrine function and visual function, is challenging. We present a case of a recurrent remnant infundibular lesion treated with Gamma Knife surgery (GKS). The mass was treated with microsurgical resection twice, and the residual stalk lesion was treated with single-session SRS employing a margin dose of 15 Gy to the infundibulum. Five years after GKS, tumor regression persists without visual dysfunction or hypopituitarism. Radiosurgical doses of 30 Gy to the pituitary stalk may be tolerated by patients while maintaining endocrine function.

Spindle cell oncocytoma of the adenohypophysis: two case reports and a review of the literature.

Spindle cell oncocytoma (SCO) of the adenohypophysis is a rare tumor in the sellar region. Due to its rarity, little information is available regarding SCO. It is often misdiagnosed as another type of sellar tumor. In the present study, two cases of SCO were reported. One patient was a 35-year-old female presenting with decreased visual acuity, amenorrhea and lactation. The other patient was a 62-year-old female with no clear symptoms or signs. Cranial magnetic resonance imaging (MRI) revealed a suprasellar mass with marked homogeneous enhancement in the two cases. A craniotomy was performed to completely resect the tumors. The tumors were immunopositive for vimentin, epithelial membrane antigen (EMA), S-100 and thyroid transcription factor-1 (TTF-1). The tumors were pathologically diagnosed as SCO. No recurrence occurred during the follow-up period of 15-21 months. In the present study, the literature was reviewed and the clinical data, imaging features, intraoperative findings and recurrence of 24 cases were analyzed in the literature as well as the present two cases. The average age of the SCO patients was 58.5 years and no gender preference was observed for the disease. The tumor exhibited homogeneous enhancement on the MRI. The intraoperative assessment revealed that the tumor had a rich blood supply and the SCO tumors were immunopositive for vimentin, S-100, EMA and TTF-1. These findings provided valuable clinical data for the preoperative diagnosis and surgical removal of SCO tumors.

Pituitary image: pituicytoma.

INTRODUCTION: Pituicytoma is a rare tumor arising from the neurohypophysis or pars intermedia of the adenohypophysis. CASE REPORT: A 36 year old male came to our observation presenting polydipsia, polyuria, polyphagia, decreased libido and altered sleep-wake rhythm. The biochemical tests showed hypotonic urine, mild hyperprolactinemia, hypogonadotropic hypogonadism, central hypothyroidism. Magnetic resonance revealed an expansive lesion of the suprasellar region (slightly isointense on T1, hyperintense on T2, impregnating contrast medium), that was partially removed by trans-cranial neurosurgical approach. The histopathological diagnosis was pituicytoma. After surgery, in addition to endocrine disorders, the patient presented severe neurological sequelae and hyperthermia, likely due to damage of the hypothalamus, followed by a progressive metabolic syndrome. The residual tumor was monitored by MRI, and, due to the early gradual increase in volume, was treated by stereotactic radiosurgery. DISCUSSION/CONCLUSIONS: Pituicytomas are often difficult to distinguish from other hypothalamic or pituitary lesions. However, their identification would be preferable in a pre-operative setting in order to optimize the work-up and to initiate a proactive management of the expected complications.

Human kallikrein 10 expression in surgically removed human pituitary corticotroph adenomas: an immunohistochemical study.

Human kallikrein 10 (hk10), a secreted serine protease, was reported to function as a tumor suppressor. hK10 immunoexpression has been demonstrated in lactrotrophs and corticotrophs of the nontumorous human adenohypophysis. In the present study, for the first time we report hK10 immunoexpression in various surgically removed corticotroph adenoma subtypes. Specimens were fixed in formalin and embedded in paraffin. Immunostaining was performed using the streptavidin-biotin-peroxidase complex method with an hK10-specific rabbit polyclonal antibody. Results showed that the endocrinologically active adrenocorticotropic hormone (ACTH)-producing pituitary tumors and the silent subtypes were immunopositve for hK10. Intensity of staining varied between the different subtypes. Intensity was lowest in the silent subtypes (silent corticotroph subtypes 1 and 2) compared with nontumorous human adenohypophysial corticotrophs, whereas the endocrinologically active subtypes (ACTH-secreting adenomas, corticotroph carcinomas, Crooke cell adenomas, Crooke cell carcinomas), showed the highest hK10 immunoexpression. Immunopositivity in the nuclei of the ACTH-secreting adenomas and carcinomas, as well as dual cytoplasmic and nuclear localization of hK10 in some of the secreting tumor types was an intriguing finding. Immunoexpression of hK10 in the ACTH-secreting tumors as well as in the Crooke cell tumors was significantly increased when compared with the nonfunctioning tumors and in the corticotrophs of nontumorous pituitaries.

Incidencia de adenomas hipofisiarios en pacientes ingresados al servicio de neurocirugía del Hospital Roosevelt. Guatemala, enero 2010 a diciembre 2011 / Incidence of pituitary adenomas in patients admitted to the neurosurgery department of Roosevelt Hospital. Guatemala, January 2010 to December 2011

Introducción: Los adenomas de hipófisis sonneoplasias benignas que afectan más a adultosde sexo femenino. No se cuenta con tasa deincidencia anual de adenomas hipofisarios anivel nacional. Se realizó un estudio descriptivocon el fin de determinar la incidencia local deadenomas hipofisarios. Metodología: Se realizóun estudio descriptivo transversal en pacientesque ingresaron al Departamento de Neurocirugíadel Hospital Roosevelt para intervención quirúrgicadurante enero 2010 a diciembre 2011. Lasvariables estudiadas fueron edad, sexo, tipo deadenoma hipofisario, síntomas y signos clínicos,complicaciones postoperatorias tempranas,estancia en cuidados críticos y mortalidad. El plande análisis estadístico incluyó la recolección de lainformación, el ordenamiento de datos y uso delprograma Epi Info 3.5.6 para el análisis estadísticode medidas de frecuencia y proporciones. Se utilizóMicrosoft Excell para la elaboración de tablas ygráficas. Resultados: La tasa de incidencia deadenomas hipofisarios fue de 15 casos por cada 100tumores. El predominio del tumor fue en pacientesfemeninas y en edades comprendidas entre los 31-65 años. La disminución de la agudeza visual y lacefalea fueron los signos y síntomas más frecuentes(81% y 77% respectivamente). La complicaciónpostoperatoria inmediata más frecuente fue ladiabetes insípida (4/10 casos). El 54% de los casospermaneció en cuidados intensivos por un periodoentre uno y tres días. Para este estudio la tasa demortalidad fue cero...

Introduction: Pituitary adenomas are benignneoplasms affecting more female adults. Thereis no annual incidence of pituitary adenomasnationwide. A descriptive study was conducted todetermine the local incidence of pituitary adenomas.Methodology: A descriptive cross-sectional studyin patients admitted to the Department of Neurosurgeryat Roosevelt Hospital for surgery injanuary 2010 to december 2011. The variablesstudied were age, sex, type of pituitary adenoma,clinical signs and symptoms, early postoperativecomplications, hospital stay and mortality in criticalcare. The statistical analysis plan included collectinginformation , the ordering of data and use of Epi Info3.5.6 program for statistical analysis of frequencymeasurements and proportions. Microsoft Excelwas used to produce tables and graphs. Results:The incidence of pituitary adenomas was 15 casesper 100 tumors. The prevalence of the tumor was infemale patients and aged 31-65 years. Decreasedvisual acuity and headache were the most commonsigns and symptoms (81% and 77% respectively).The most common immediate postoperative complicationwas diabetes insipidus (4 /10 cases) 54%of the cases remained in intensive care for a periodof one to three days. For this study, the mortality ratewas zero...

Approach to testing growth hormone (GH) secretion in obese subjects.

Identification of adults with GH deficiency (GHD) is challenging because clinical features of adult GHD are not distinctive and because clinical suspicion must be confirmed by biochemical tests. Adults are selected for testing for adult GHD if they have a high pretest probability of GHD, ie, if they have hypothalamic-pituitary disease, if they have received cranial irradiation or central nervous system tumor treatment, or if they survived traumatic brain injury or subarachnoid hemorrhage. Testing should only be carried out if a decision has already been made that if deficiency is found it will be treated. There are many pharmacological GH stimulation tests for the diagnosis of GHD; however, none fulfill the requirements for an ideal test having high discriminatory power; being reproducible, safe, convenient, and economical; and not being dependent on confounding factors such as age, gender, nutritional status, and in particular obesity. In obesity, GH secretion is reduced, GH clearance is enhanced, and stimulated GH secretion is reduced, causing a false-positive result. This functional hyposomatotropism in obesity is fully reversed by weight loss. In conclusion, GH stimulation tests should be avoided in obese subjects with very low pretest probability.

Regulation of intestinal immune response by selective removal of the anterior, posterior, or entire pituitary gland in Trichinella spiralis infected golden hamsters.

The influence of anterior pituitary hormones on the gastrointestinal tract of humans and animals has been previously reported. Hypophysectomy (HYPOX) in the rat causes atrophy of the intestinal mucosa, and reduction of gastric secretion and intestinal absorption, as well as increased susceptibility to bacterial and viral infections. However, to our knowledge, no findings have been published concerning the immune response following HYPOX during worm infection, particularly that which is caused by the nematode Trichinella spiralis. The aim of this work was to analyze the effects of total or partial HYPOX on colonization of T. spiralis in the intestinal lumen, together with duodenal and splenic cytokine expression. Our results indicate that 5 days post infection, only neurointermediate pituitary lobectomy (NIL) reduces the number of intestinally recovered T. spiralis larvae. Using semiquantitative inmunofluorescent laser confocal microscopy, we observed that the mean intensity of all tested Th1 cytokines was markedly diminished, even in the duodenum of infected controls. In contrast, a high level of expression of these cytokines was noted in the NIL infected hamsters. Likewise, a significant decrease in the fluorescence intensity of Th2 cytokines (with the exception of IL-4) was apparent in the duodenum of control and sham infected hamsters, compared to animals with NIL surgeries, which showed an increase in the expression of IL-5 and IL-13. Histology of duodenal mucosa from NIL hamsters showed an exacerbated inflammatory infiltrate located along the lamina propria, which was related to the presence of the parasite. We conclude that hormones from each pituitary lobe affect the gastrointestinal immune responses to T. spiralis through various mechanisms.

Observation of the neurohypophysis, pituitary stalk, and adenohypophysis during endoscopic pituitary surgery: demonstrative findings as clues to pituitary-conserving surgery.

BACKGROUND: High-definition imaging in endoscopic transsphenoidal pituitary surgery accounts for significantly better identification of anatomic structures. This report presents the clinical images of the adenohypophysis and neurohypophysis under high-definition endoscopic observation, and provides some clues for pituitary-sparing surgery. METHODS: Ten demonstrative cases of pituitary lesions, including three cases of gonadotropin-producing pituitary adenoma, two cases of somatotropin-secreting pituitary adenoma, and five cases of Rathke's cleft cysts, were entered in this study. From these cases, we extracted helpful intraoperative findings that affected the surgeon's decision about surgical procedures and led to favorable results. RESULTS: The extracted findings contain the following lessons: (1) to find a boundary plane that separate a lesion from the pituitary; (2) to mark the difference of color between the adenohypophysis and the neurohypophysis; (3) to identify the location of the pituitary stalk connecting to the neurohypophysis; (4) to observe the color change of the pituitary induced by decompression; (5) to know pathological findings of the pituitary surface; (6) to distinguish the parenchyma of the neurohypophysis from pathological tissues; and (7) to recognize the intrasellar findings at the completion of removal. Recognition of these findings led to an excellent result in each case. CONCLUSIONS: Despite being shown in a limited number of cases, on the basis of HD endoscopic images, accurate identification of the neurohypophysis and the pituitary stalk as well as adenohypophysis during surgery contributes to pituitary-conserving operations.

Spindle cell oncocytoma of the adenohypophysis with marked hypervascularity. Case report.

A 68-year-old male presented with a very rare case of spindle cell oncocytoma (SCO), a recently identified very rare neoplasm of the anterior pituitary, manifesting as panhypopituitarism and visual field defect. The pituitary tumor with suprasellar extension was only partially resected via transsphenoidal surgery because of the tumor consistency and bleeding. Histological diagnosis was consistent with schwannoma. The tumor regrew and angiography revealed hypervascularity, so a transcranial approach was employed for the re-operation which only achieved partial resection because of intraoperative extensive bleeding. The tumor cells showed similar histological and immunohistochemical profiles to the previous specimen, but electron microscopy demonstrated that cytoplasm abundantly filled with mitochondria. The final diagnosis of SCO was established and the patient received postoperative conventional radiation therapy of 50 Gy. Only 15 cases of SCO have been reported, and the diagnosis was mistaken in many cases as schwannoma, oncocytic pituitary adenoma, or craniopharyngioma, and multiple surgeries followed by radiation therapy were required.

Regulation of intestinal morphology and GALT by pituitary hormones in the rat.

Here, the effects of neurointermediate (NIL), anterior (AL), and total hypophysectomy (HYPOX) on ileal mucosa cells and gut-associated lymphoid tissue (GALT) are reported. Compared with the sham-operated (SHAM) rats, the villi height and goblet cells numbers were significantly decreased in all groups. Lamina propria area decreased in AL and HYPOX, but not in NIL animals. CD8(+) but not CD4(+) lymphocytes decreased in the HYPOX and NIL groups. Paneth cells did not change, while IgA cells, IgM cells, and secretory IgA were significantly decreased in all groups. NIL but not AL animals lost significant numbers of IgA cells and secretory IgA. In summary, pituitary hormones exert lobe-specific regulatory effects on the gut and on GALT.

Neuron precursor features of spindle cell oncocytoma of adenohypophysis.

CONTEXT: Spindle cell oncocytoma of the adenohypophysis (SCO) is a non-endocrine neoplasm with few recurrent forms described. It arises from the folliculo-stellate cells of the adenohypophysis. OBJECTIVE: We describe a case of SCO in a 24-year-old woman and provide pathogenetic information. DESIGN: Hematoxylin-eosin (H&E), and immunohistochemistry, with controls, for S100, SMI-311, neurofilament, EMA, CD68, GFAP, chromogranin, synaptophysin, and Ki67 were performed. CD44, nestin, Gli2, p-Akt(Ser 473) and p-mTOR(Ser 2448) antibodies were applied, and each analyte's cellular distribution and intensity were noted. RESULTS: H&E showed a proliferation of spindle and polygonal cells with a fascicular pattern, without mitoses. There was reactivity for SMI-311, CD44, nestin, S100, EMA, and vimentin. Neurofilament, CD68, chromogranin, synaptophysin, and GFAP were not expressed. p-Akt and p-mTOR were expressed suggesting mTORC2. Gli2 showed nuclear expression in the tumoral cells. CONCLUSIONS: These findings suggest that SCO has neuron-like precursor cells. Sonic hedgehog and mTOR pathways are activated.

Intra-pituitary administration revisited: development of a novel in vivo approach to investigate the ovine hypophysis.

The anterior pituitary gland regulates physiological processes via the secretion of hormones, which are under the control of factors produced either in the hypothalamus or the pituitary gland itself. Studies investigating how the pituitary gland functions have employed both in vitro and in vivo approaches. Although in vitro analysis has the advantage that it is pituitary specific, the results may be incomplete because the tissue is isolated from other physiological inputs that could affect function under natural conditions. Without vascular input, such studies are inherently of short duration. Conversely, in vivo experiments that rely upon systemic hormone injections require high doses, are non-target specific and the precise hormone concentrations reaching the pituitary gland are difficult to control. Intracerebroventricular hormone infusions are reliant on assumptions that factors are transported to the pituitary gland from the cerebrospinal fluid and are without cerebral effects. Here we describe an innovative method to investigate anterior pituitary function in conscious sheep by direct infusion of peptides into the pituitary tissue surrounding the hypophyseal portal blood vessels. This approach is an adaptation of the hypophyseal portal cannulation technique whereby an indwelling cannula provides direct access to the rostral aspect of the adenohypophysis. Peptide infusions were achieved by insertion of a needle through the implanted cannula such that it penetrated the pituitary. Using this technique, infusion of TRH (17 ng/1 µl/min for up to 6h) induced a sustained rise in systemic prolactin levels that lasted for the duration of the infusion.

A case of corticotroph carcinoma that caused multiple cranial nerve palsies, destructive petrosal bone invasion, and liver metastasis.

A 52-year-old woman experienced sudden onset of double vision due to a right abducens nerve palsy and was diagnosed as having a pituitary macroadenoma that invaded into the right cavernous sinus. Otherwise, she was asymptomatic despite marked elevation of ACTH (293 pg/ml) and cortisol (24.6 µg/dl) levels. The patient underwent transsphenoidal surgery followed by γ-knife radiosurgery (GKR), which healed the diplopia and ameliorated the hypercortisolemia. The excised tumor was diffusely stained for ACTH with a high (15%) Ki-67 labeling index. Early tumor recurrence occurred twice thereafter, producing right lower cranial nerve palsies with petrosal bone destruction at 8 months and an ipsilateral oculomotor nerve palsy at 12 months after GKR; all palsies resolved completely with the second and third GKRs. Hypercortisolemia worsened rapidly soon after the third GKR, and the patient developed marked weight gain, hypokalemia, and hypertension. Multiple liver lesions were incidentally detected with computer tomography and identified as metastatic pituitary tumor on immunohistochemistry. An ACTH-producing adenoma should be followed carefully for early recurrence and/or metastatic spread when the tumor is an invasive macroadenoma with a high proliferation marker level. The unique aggressive behavior and high potential for malignant transformation of this case are discussed.