Prognostic Factors for Invasiveness and Recurrence of Pituitary Adenomas: A Series of 94 Patients.

(1) Background: The aim of the current study is to evaluate the immunohistochemical expression of Ki-67, CD-56, Cyclin-D1 and E-Cadherin in the tissues samples of pituitary adenomas (PAs) and its association with PAs clinical manifestation tumor size, invasiveness and the risk of recurrence. (2) Materials and Methods: Ninety-four patients who underwent endoscope transsphenoidal excision of PAs were included in our study. The immunohistochemical expression of the Cyclin-D1, CD-56, E-Cadherin and Ki-67 markers was analyzed in paraffin-embedded tissue samples. (3) Results: The expression of Cyclin-D1 and Ki-67 index levels was positively correlated with the size (p < 0.001, r = 0.56 and p < 0.001, r = 0.43, respectively), the recurrence (p < 0.001, r = 0.46 and p = 0.007 r = 0.3, respectively), the extrasellar extension (p < 0.001, r = 0.48 and p < 0.001, r = 0.4, respectively) and the cavernous sinus invasion of (p < 0.001, r = 0.39 and p < 0.001, r = 0.3, respectively). No correlation was found between CD-56 and E-Cadherin expression with the size, the invasiveness and the recurrence of PAs. (4) Conclusion: Cyclin-D1 and Ki-67 are promising immunohistochemical markers in predicting the invasive behavior and recurrence of PAs in contrast to E-Cadherin and CD-56 which did not seem to be associated with PAs behavior post-surgery. However, larger studies are required in order to establish their role in the routine evaluation of PAs.

MGMT immunohistochemistry in pituitary tumors: controversies with clinical implications.

INTRODUCTION: Temozolomide (TMZ) is currently considered as a rational therapeutic option for patients with progressively aggressive pituitary adenomas and carcinomas not responding to conventional therapies. Administration of TMZ results in clinical response and improvement in survival of many of these patients depending upon the expression of the DNA repair enzyme O-6 methylguanine DNA transferase (MGMT). Low or negative MGMT immunoreactivity predicts responsiveness to TMZ therapy. Therefore, MGMT serves as a criterion to select candidate patients anticipating response to treatment. MATERIALS AND METHODS: The MGMT expression was investigated in 25 pituitary adenomas with Ki-67 labeling index more that 3% and p53 expression, using various antigen retrieval protocols. After direct application of the antibody, only one adenoma yielded positive for MGMT. However, after pretreatment of tissue sections with antigen retrieval protocols, another 3 adenomas, initially negative turned to positive. CONCLUSIONS: These findings could explain lack of response to TMZ treatment in patients with false negative MGMT immunohistochemistry. Evaluation of tumor samples for MGMT expression should carefully be carried-out using the optimum immunohistochemical protocol to obtain consistent and reliable results that help to identify patients that could respond to TMZ therapy.

High incidence of thyroid cancer among patients with acromegaly.

PURPOSE: Several studies have suggested that patients with acromegaly have an increased risk of thyroid, colorectal, breast and prostate cancers. In this study we determined the prevalence of malignant neoplasms in patients with acromegaly. METHODS: Cancer risk was evaluated in a cohort of 110 patients (M/F 48/62, age 58.63±13.8 years, range 30-86) with acromegaly. Mean age at diagnosis of acromegaly was 46.37±13.11 years. Mean period of time since diagnosis of acromegaly was 12.26+9.6 years. RESULTS: From 110 patients, cancer was diagnosed in 26 (23.6%) patients. Thyroid cancer was the most common cancer and was diagnosed in 13 patients (11.8%); other cancers encountered were gastric cancer (N=2), endometrial cancer (N-2), and breast cancer, colon cancer, prostate cancer (N-2), myelodysplastic syndrome, renal cell carcinoma, lung cancer and pancreatic carcinoma, one case each. Age, gender, age at the time of diagnosis of acromegaly, tumor size of pituitary adenoma and duration of disease were not associated with cancer development. CONCLUSIONS: This study suggests that patients with acromegaly have an increased risk of thyroid cancer and therefore they should undergo regular screening with hormonal and ultrasound evaluation of the thyroid and FNAB when required.

Pituitary abscess: a case report and review of the literature.

UNLABELLED: Pituitary abscess is a rare life-threating entity that is usually misdiagnosed as a pituitary tumor with a definite diagnosis only made postoperatively. Over the last several decades, advances in healthcare have led to a significant decrease in morbidity and mortality due to pituitary abscess. We report a case of a 34-year-old woman who was admitted to our department for investigation of a pituitary mass and with symptoms of pituitary dysfunction, headaches and impaired vision. During her admission, she developed meningitis-like symptoms and was treated with antibiotics. She eventually underwent transsphenoidal surgery for excision of the pituitary mass. A significant amount of pus was evident intraoperatively; however, no pathogen was isolated. Six months later, the patient was well and had full recovery of the anterior pituitary function. Her menses returned, and she was only on treatment with desmopressin for diabetes insipidus that developed postoperatively. LEARNING POINTS: Pituitary abscess is a rare disease and the reported clinical features vary mimicking other pituitary lesions.The diagnosis of pituitary abscess is often very difficult to make and rarely included in the differential.The histological findings of acute inflammatory infiltration confirm the diagnosis of pituitary abscess.Medical and surgical treatment is usually recommended upon diagnosis of a pituitary abscess.

Young adult patient with headache, fever and blurred vision.

BACKGROUND AND IMPORTANCE: This case highlights the fact that acute pituitary apoplexy may be misdiagnosed due to being confused with other entities exhibiting similar symptoms, such as meningitis or subarachnoid hemorrhage. CLINICAL PRESENTATION: A patient in his late 30s presented with sudden and severe frontal headache, fever, blurred vision, nausea, confusion, as well as oculomotor palsy (CN III) with partial ptosis of the left eyelid, dilated left pupil and left eye globe deviation inferiorly and laterally. The final diagnosis was acute pituitary apoplexy complicating a pituitary macroadenoma. In this setting, headache is usually present due to stretching and irritation of the dura mater, and fever due to meningeal irritation or upward expansion leading to hypothalamic dysfunction. Decreased visual acuity and defects in visual fields are caused by upward expansion, which compresses the optic chiasm. Ophthalmoplegia can also be observed due to lateral expansion with invasion of the cavernous sinus. CONCLUSION: Medical professionals involved in emergency care should be aware of this clinical entity and collaborate with endocrinologists using a multidisciplinary team approach for prompt diagnosis and optimal treatment of such patients.

De novo intracranial collision tumour in previously evacuated intracerebral haematoma site.

The authors report the rare and first documented case of intracranial collision tumour occurrence in a previously evacuated intracerebral haematoma site. Surgery trauma could predispose to collision tumour occurrence. Research efforts should try to reveal the possible pathogenesis of this condition.

Aseptic meningitis after transsphenoidal management of Rathke's cleft cyst: case report and review of the literature.

Aseptic meningitis after transsphenoidal surgery (TSS) for treatment of Rathke's cleft cyst (RCC) is a rare complication caused by the leakage of the cyst contents within the subarachnoid space. We present a case of aseptic meningitis occurring after TSS for a RCC. During surgery, the cyst wall was subtotally removed, and intraoperative cerebrospinal fluid (CSF) leakage was observed. The patient developed meningeal signs and symptoms on the first postoperative day. CSF examinations were highly suggestive of aseptic meningitis. Histological examination confirmed a granulomatous inflammatory reaction of the RCC wall. Preexisting inflammation, subtotal cyst wall resection, intraoperative erosion of the diaphragma sellae and placement of a lumbar drain may be risk factors for the development of aseptic meningitis.

Non-adenomatous sellar lesions: experience of a single centre and review of the literature.

Non-adenomatous sellar lesions represent a diagnostic and occasionally a therapeutic challenge. The purpose of the study was to provide an overview of the clinical and radiographic characteristics of non-adenomatous sellar lesions operated at our department, with emphasis on treatment options. In our transsphenoidal surgical series of 300 cases, 29 non-adenomatous sellar lesions (9.7%) were identified by histology. Medical files and imaging findings were retrospectively analysed. Clinical presentation was usually a result of local mass effect. Imaging features were not always diagnostic. Of 29 non-adenomatous sellar lesions, total tumour excision with transsphenoidal surgery was achieved in 17, and no supplemental treatment was needed. Lesions partially resected were further treated with reoperation, radiation therapy, or medical therapy, tailored to individuals. In our experience, non-adenomatous sellar lesions represent a more prevalent clinical entity than expected. Pituitary surgeons should be aware of their existence to reconstruct treatment strategy, proceeding to adjuvant therapy when necessary.

Thyrotoxic periodic paralysis as the first manifestation of a thyrotropin-secreting pituitary adenoma.

Thyrotoxic Periodic Paralysis (TPP) is a rare manifestation of hyperthyroidism characterized by muscle weakness and hypokalemia. Thyroid-Stimulating Hormone (TSH)-secreting pituitary adenoma is a rare cause of hyperthyroidism. Even more rare is the occurrence of TPP as the first manifestation of a TSH-secreting pituitary adenoma. We report a 31-year-old Asian male patient suffering from TPP caused by a TSH-secreting adenoma, who was evaluated for persistent episodes of muscle paralysis. Laboratory investigation revealed hypokalemia as well as elevated levels of both thyroid hormones and TSH. The Magnetic Resonance Imaging (MRI) of the pituitary gland revealed a microadenoma, thus suggesting the presence of a TSH-secreting adenoma. The patient underwent transphenoidal resection and the pathological investigation confirmed the diagnosis of TSH-secreting pituitary adenoma. After the adenomectomy and the restoration of euthyroidism, the patient did not experience any episode of hypokalemic paralysis or weakness. Despite its rarity, TSH-secreting pituitary adenoma should be included in the differential diagnosis of TPP.

Collision sellar lesions: experience with eight cases and review of the literature.

The concomitant presence of a pituitary adenoma with a second sellar lesion in patients operated upon for pituitary adenoma is an uncommon entity. Although rare, quite a great variety of lesions have been indentified coexisting with pituitary adenomas. In fact, most combinations have been described before, but an overview with information on the frequency of combined pathologies in a large series has not been published. We present a series of eight collision sellar lesions indentified among 548 transsphenoidally resected pituitary adenomas in two Neurosurgical Departments. The histological studies confirmed a case of sarcoidosis within a non-functioning pituitary adenoma, a case of intrasellar schwannoma coexisting with growth hormone (GH) secreting adenoma, two Rathke's cleft cysts combined with pituitary adenomas, three gangliocytomas associated with GH-secreting adenomas, and a case of a double pituitary adenoma. The pertinent literature is discussed with emphasis on pathogenetic theories of dual sellar lesions. Although there is no direct evidence to confirm the pathogenetic relationship of collision sellar lesions, the number of cases presented in literature makes the theory of an incidental occurrence rather doubtful. Suggested hypotheses about a common embryonic origin or a potential interaction between pituitary adenomas and the immune system are presented.

Localisation of cervical spinal cord compression by TMS and MRI.

The authors set out to study the role of transcranial magnetic stimulation (TMS) in the pre-surgical assessment of patients with cervical spondylotic myelopathy. Central motor conduction time (CMCT) was calculated in 50 patients and 50 controls by recording muscle evoked potentials from upper limb muscles. The level of spinal cord compression was determined according to the pattern of CMCT prolongation and compared with the level disclosed by MRI. Direct comparison of the TMS and MRI results was possible in 42 cases and agreement was noted in 25 (59.5%). In the 23 patients in whom the two methods did not give convergent findings, post-operative data were used in order to determine the actual level of compression. This level was correctly indicated by TMS in 87.5% of cases and by MRI in 12.5%. TMS is a neurophysiological tool that can complement existing methods for determining the level of cervical spinal cord compression.

Suicide attempt by jumping: a study of gonadal axis hormones in male suicide attempters versus men who fell by accident.

Low plasma total testosterone (T) levels may influence the sense of well-being and produce depressive symptomatology, increasing the risk of suicide. In a previous study, we reported reduced serum T levels in male psychiatric patients after a suicide attempt. The reduction was more pronounced in subjects who used violent attempt methods, and we discussed the possible influence of stress of hospitalization, serious medical condition and treatment. In order to minimize the influence of such factors, we compared in this study the levels of plasma sex hormones of 15 psychiatric patients (10 suffering from schizophrenia and 5 from depression) who had attempted suicide by jumping with those of a group of 18 male subjects who were hospitalized after accidentally falling from a high height. Compared with a healthy control group of 40 males, both accident and attempt groups had lower T levels. The attempt group showed a trend toward lower T levels compared with levels in the accident group. In the accident group, luteinizing hormone (LH) levels were elevated compared with levels in healthy controls, indicating a normal function of the hypothalamic-pituitary-gonadal (HPG) axis. This was not the case for the attempt group, where low T levels were not accompanied by increases in LH. Cortisol and prolactin were similarly elevated in both patient groups, but were not related to the low T levels. The results indicate that male psychiatric patients who attempt suicide by violent methods may have low total plasma T levels, possibly due to a dysfunction of the HPG axis at the hypothalamic-pituitary level. Monitoring HPG axis function in future studies could prove to be a predictor of suicide at least for male psychiatric attempters, and could lead to preventive strategies.

Intra-sellar schwannoma co-existing with GH-secreting pituitary adenoma.

BACKGROUND: We present a unique example of an intra-sellar schwannoma co-existing with a growth hormone (GH)-secreting pituitary adenoma. METHOD AND FINDINGS: The patient presented with acromegaly and magnetic resonance imaging (MRI) revealed an intra-sellar mass. The tumour was totally resected via a sub-labial trans-sphenoidal approach. Histopathology demonstrated the presence of a GH-secreting adenoma as well as a schwannoma at the periphery of the adenoma. After surgical excision, remission of the acromegaly occurred. Follow-up monitoring showed no evidence of recurrence of the adenoma two years after surgery. CONCLUSION: To the best of our knowledge, this is the first example of an intra-sellar schwannoma co-existing with a GH-secreting pituitary adenoma.

CSF neurotransmitter metabolites and neuropsychiatric symptomatology in patients with normal pressure hydrocephalus.

Patients with normal pressure hydrocephalus (NPH) may exhibit certain neuropsychiatric symptomatology, possibly related to alterations in central neurotransmitter activity. The aim of this study was to relate psychiatric distress, as expressed by the scores in the SCL-90 subscales, to CSF levels of the main metabolites of noradrenaline (MHPG), serotonin (5-HIAA), and dopamine (HVA) in NPH patients. The metabolite levels were estimated in CSF samples taken during the tap test in 19 patients with probable NPH, and compared to 19 sex- and age-matched controls. Cognitive impairment was evaluated by the MMSE. Compared to controls, NPH patients had similar MHPG and 5-HIAA levels, and significantly elevated HVA levels, a notable difference from patients with dementias. There were no significant correlations of metabolite levels to the scores in the nine SCL-90 subscales. MMSE score was not related either to metabolite levels, or to the SCL-90 subscale scores. Patients scored higher than controls in most SCL-90 subscales, more pronounced being the difference in obsessive-compulsive symptomatology. Serotonergic neurotransmitter activity seems not to be altered in NPH patients, and this may explain the reported lack of beneficial effect of serotonergic drugs for obsessive-compulsive symptoms in NPH patients.