Neuro-Endocrine Recovery After Pituitary Apoplexy: Prolactin as a Predictive Factor.

OBJECTIVE: Pituitary apoplexy is a serious medical complication of a pre-existing pituitary adenoma characterized by a variety of clinical symptoms ranging from mild headache to neurologically impaired and finally comatose patients. Management options are surgery or conservative treatment (e. g., with dexamethasone). Surgery is commonly performed in case of severe acute neurological and visual symptoms. However, prospective studies demonstrating a benefit of surgery over conservative treatment in terms of visual, neurological and even endocrine outcomes are lacking. Decision making is still controversial, and recommendations for surgery are based on low evidence grades and focus on visual impairment. Endocrine function and especially markers identifying patients with potential for pituitary recovery after surgery are not well described in the literature. PATIENTS AND DESIGN: We analysed data from 24 patients (m:f/16:8) with a median age of 64 yrs (38 to 83yrs) that underwent surgery for pituitary apoplexy regardless of time from symptom onset. Apoplexies were necrotic in 14 cases and haemorrhagic in 10 cases. RESULTS: Preoperatively, 7 patients (29.2%) showed complete anterior pituitary insufficiency, 16 patients (66.6%) had partial anterior pituitary insufficiency and one patient (4.17%) had normal pituitary functions. Persistent panhypopituitarism was found in 7 patients (29.2%), whereas an overall improvement of pituitary function was noted in 13 (57.1%) patients. Preoperative prolactin (PRL) levels were significantly associated with recovery of endocrine functions, whereas specifically all patients with preoperative PRL levels of at least 8.8 ng/ml recovered partially or fully. Time to surgery (0-7 days vs. 1-4 weeks vs.>4 weeks) was not significantly associated with outcome. CONCLUSIONS: Our data emphasize that normal and high preoperative PRL levels are associated with better endocrine outcome after surgery. We conclude that patients benefit from surgical intervention even after delayed diagnosis with the serum PRL levels is being a valid biomarker for clinical decision making.

Postoperative Neurologic Outcome in Patients with Pituitary Apoplexy After Transsphenoidal Surgery.

OBJECTIVE: Pituitary apoplexy can cause severe neuro-ophthalmologic or endocrinologic sequelae, requiring timely treatment. The present study was performed to evaluate postoperative neurologic outcomes and to identify their risk factors in patients who underwent transsphenoidal surgery for pituitary apoplexy. METHODS: Forty-one consecutive patients with pituitary apoplexy who underwent transsphenoidal surgery were reviewed retrospectively. The initial rates of visual acuity (VA) decrease, visual field (VF) defect, and ocular palsy were 34.1%, 46.3%, and 68.3%, respectively. The median maximal diameter and tumoral volume was 2.6 cm (range, 2.0-4.6 cm) and 5.3 cm3 (range, 2.4-38.8 cm3), respectively. Seventeen patients (41.5%) underwent surgery within 7 days. The median follow-up duration was 45 months (range, 12-196 months). RESULTS: At the last follow-up, 62.9% (22/35) of patients had made a full recovery from preoperative neurologic deficits, with partial recovery observed in the remaining patients. The rates of improvement and full recovery from VA decrease were 92.9% and 57.1%, respectively; those from VF defect were 94.7% and 36.8%, respectively; and those from ocular palsy were 100.0% and 96.4%, respectively. On multivariate analysis, initial visual impairment score (≥20) was the only significant risk factor for postoperative neurologic sequelae (P < 0.001; odds ratio, 40.8). Surgical timing was not associated with postoperative neurological recovery (P = 0.733). CONCLUSIONS: Ocular palsy was fully recovered in 96.4% patients with pituitary apoplexy after transsphenoidal surgery. Initial visual impairment status was found to be more strongly associated with postoperative neurologic recovery than surgical timing.

Apoplexy of pituitary adenomas: the perfect storm.

OBJECT: Pituitary adenomas occasionally undergo infarction, apoplexy, which often destroys much of the tumor. It is well known that apoplexy can be precipitated by several acute factors, including cardiac surgery, other types of surgery, trauma, insulin infusion, and stimulation with administration of hypothalamic releasing factors. METHODS: The prior focus on mechanisms underlying pituitary apoplexy has been on these acute events. Less attention has been given to the endogenous features of pituitary tumors that make them susceptible to spontaneous infarction, despite that most pituitary apoplexy occurs in the absence of a recognized precipitating event. The authors examine intrinsic features of pituitary adenomas that render them vulnerable to apoplexy-features such as high metabolic demand, paucity of angiogenesis, and sparse vascularity, qualities that have previously not been linked with apoplexy-and argue that it is these features of adenomas that underlie their susceptibility to spontaneous infarction. The sensitivity of freshly cultured pituitary adenomas to hypoglycemia is assessed. RESULTS: Adenomas have high metabolic demand, limited angiogenesis, and reduced vessel density compared with the normal gland. Pituitary adenoma cells do not survive in the presence of reduced or absent concentrations of glucose. CONCLUSIONS: The authors propose that the frequent ischemic infarction of pituitary adenomas is the product of intrinsic features of these tumors. These endogenous qualities create a tenuous balance between high metabolic demand and marginal tissue perfusion. Thus, the tumor is vulnerable to spontaneous infarction or to acute ischemia by any event that acutely alters the balance between tumor perfusion and tumor metabolism, events such as acute systemic hypotension, abruptly decreased supply of nutrients, hypoglycemia with insulin administration, or increase in the tumor's metabolic demand due to administration of hypothalamic releasing factors. It may be possible to take advantage of these intrinsic features of pituitary adenomas by using aspects of this vulnerability for development of new approaches for treatment.

Clinical features and surgical outcome of clinical and subclinical pituitary apoplexy.

The clinical features of pituitary hemorrhage vary from asymptomatic to catastrophic. Clinical symptomatic pituitary apoplexy is a well-described syndrome characterized by sudden headaches, visual impairment, hypopituitarism and, at times, impaired consciousness. Subclinical pituitary apoplexy is characterized by minimal atypical clinical manifestations and, as a result, may be misdiagnosed or inappropriately treated. The purpose of the study was to evaluate the clinical manifestations, surgical outcome and post-operative pituitary function in patients who had clinical or subclinical pituitary apoplexy. We retrospectively identified 65 patients (30 men, 35 women; age range 21-87 years, mean age 48.4 years) who underwent transsphenoidal surgery. Of these, 25 patients were diagnosed as having clinical apoplexy, while the remaining 40 patients were classified as having subclinical pituitary apoplexy. The follow-up period ranged from 21 to 73 months (mean 44 months). Vision improved in 14 of 22 patients with clinical apoplexy (64%) and in 26 of 28 patients with subclinical apoplexy (93%) (p=0.017); the total resection rate was 57% and 42%, respectively (p=0.285). After 2 years of follow-up, hormone replacement therapy was needed in only 26% and 36% of patients, respectively (p=0.149). Our findings suggest that the incidence of subclinical pituitary apoplexy is higher than that of clinical pituitary apoplexy. Both the tumor resection rate and mean age were higher in those with clinical pituitary apoplexy, while those who had subclinical pituitary apoplexy demonstrated better visual improvement. During long-term follow-up, the need for hormonal replacement decreased in both groups.

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Clinical features and immunohistochemical changes of pituitary apoplexy.

The clinical features of 426 pituitary adenomas were retrospectively analyzed, focusing on the factors that affect the development of pituitary apoplexy. Immunohistochemical analysis was used to define the different hormone types of the tumors and the expression of various immunologic targets, including the pituitary tumor transforming gene, basic fibroblast growth factor-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and proliferating cell nuclear antigen. Of the 426 patients, 83 presented with pituitary apoplexy (19.48%). Among them, 43 patients (43/83, 51.82%) developed apoplexy in the absence of any obvious precipitating factor. Clinical manifestations included headaches (80/83, 96.38%), vision loss (69/83, 83.13%), pituitary function change (51/83, 61.45%), visual field defects (41/83, 49.39%), and nausea and vomiting (34/83, 40.96%). Male patients and patients with functional adenoma had a higher probability of developing apoplexy. Complicated immunological expression patterns were found in adenomas associated with pituitary apoplexy, with adenomas of different hormone types identified.

Immunohistochemical expression of nestin in adenohypophysial vessels during development of pituitary infarction.

OBJECTIVES: The aim of this work was to investigate the immunohistochemical expression of nestin, a member of the intermediate filament family, in adenohypophysial vasculature during development and progression of pituitary infarction. METHODS: Forty-five nontumorous adenohypophyses and 34 pituitary adenomas of various types, all exhibiting acute or healing infarcts, were examined immunohistochemically using the streptavidin-biotin-peroxidase complex method. RESULTS: In both adenohypophyses and pituitary adenomas without infarction, nestin was expressed in only a few capillaries and endothelial cells. In acute infarcts without a vascular response, no nestin was demonstrable within necrotic capillaries (50 cases). In organizing infarcts, newly formed vessels spreading into necrotic zones showed nestin expression in all capillaries and practically every endothelial cell (25 cases). In the hypocellular, fibrotic scar phase, only a few vessels (4) were apparent, and immunoreactivity was focal and mild. CONCLUSIONS: Nestin is strongly expressed in newly formed capillaries and is downregulated when infarcts transform to fibrous tissue. Nestin expression may provide valuable insight into the process of pituitary angiogenesis.

Pituitary apoplexy and inappropriate ADH secretion.

Pituitary apoplexy may be associated with visual deterioration that may be severe in some cases. Misdiagnosis of this condition is not uncommon, resulting in delayed treatment, which may adversely affect the outcome and visual prognosis. We present a case of pituitary apoplexy, who presented with features of syndrome of inappropriate anti-diuretic hormone secretion (SIADH) and monocular blindness. He had remarkable improvement to normal vision along with normalisation of serum sodium following emergency trans-sphenoidal surgery.

[An interesting case of pituitary apoplexy showing abnormality in water-electrolyte before and after surgery].

Cases which present abnormality in water-electrolyte before and after operation of pituitary adenoma are occasionally reported. The authors have encountered a case in which neurological symptoms became aggravated abruptly with pituitary apoplexy after admission, hyponatremia was noted before operation and polyuria, not hypotonic urine was observed after operation. As a result of an endocrinological examination which may have an influence on water-electrolyte (ADH, aldosterone, ANP, etc.) the ADH level in hyponatremia before operation was high at 6.8 pg/ml; so, it was taken as SIADH. According to a study at the time of polyuria after operation, the ADH level was normal at 2.4 pg/ml, the ANP level was abnormally high at 140 pg/ml and the specific gravity of the urine was kept at 1.010 or more. So, polyuria was considered due to abnormally increased content of serum ANP. In polyuria due to abnormally increased content of serum ANP, the osmotic pressure of the urine is maintained relatively well, which is a clinical feature evidently different from diabetes insipidus. After operation for pituitary adenoma, water-electrolyte should be controlled with polyuria due to abnormally increased content of serum ANP in addition to diabetes insipidus taken into consideration.