OBJECTIVE: Serum PRL levels at presentation may be useful in distinguishing between disconnection hyperprolactinemia in non-secretory pituitary adenomas and prolactinomas in order to guide appropriate therapy; however, there is a debate regarding the discriminatory PRL thresholds. We aimed to examine PRL concentrations at presentation in a cohort of histologically proven non-functioning pituitary adenomas (NFPA).
DESIGN AND METHODS: Retrospective case note analysis was performed. Clinical, biochemical, histopathological and radiological data were recorded and analyzed. Complete data were available for 250 subjects with NFPA.
RESULTS: Of the study population, 44.8% were hyperprolactinemic at presentation, 55.3% of whom were female. Of those with hyperprolactinemia, 73.2% had PRL<1000 mIU/l on presentation, 24.1% had PRL between 1000 and 1999 mIU/l. Only 2.7% (no.=3 females, 1.2% whole cohort) had PRL>2000 mIU/l (94.3 ng/ml), 2 of whom were pregnant. No male subject and no subjects with an intrasellar macroadenoma had serum PRL>1000 mIU/l (47.2 ng/ml). Overall, serum PRL was not higher among 43 subjects taking medications known to raise PRL.
CONCLUSIONS: Our data support recent evidence that the serum PRL concentration is rarely >1000 mIU/l in males, or >2000 mIU/l in females, with non-functioning macroadenomas and that, once other contributing factors to the hyperprolactinemia have been excluded, a trial of dopamine agonist therapy for such lesions is indicated.
Introduction: 'Silent' somatotropinomas are defined as GH-immunopositive pituitary adenomas without clinical symptoms of acromegaly and GH elevation in peripheral blood. Such tumours used to be considered as rare. However, recent data has indicated that they are more frequent than previously thought. The present paper shows that pituitary adenomas, diagnosed before surgery as nonfunctioning, often display GH immunopositivity. Material and methods: Fifty six patients with pituitary adenomas were included in the study. All the patients underwent transphenoidal adenectomy. In 37 patients before the surgery, clinically nonfunctioning pituitary adenomas (CNFPAs) were diagnosed. In 19 patients, acromegaly was diagnosed. All the excised tumours were examined immunohistochemically using the primary antibodies against the pituitary hormones or their subunits. Results: All the adenomas in the patients with acromegaly were immunopositive for GH. Among the pituitary tumours diagnosed before the surgery as clinically nonfunctioning, 45.9% showed GH immunopositivity. Both somatotropinomas with acromegaly and 'silent' GH-immunopositive adenomas most often co-expressed prolactin, whereas GH-immunonegative nonfunctioning adenomas expressed mainly LH and/or FSH. In three cases of 'silent' somatotropinomas, IGF-1 levels were slightly elevated, suggesting that these patients may present a 'low-symptomatic' acromegaly. Conclusions: GH-immunopositivity occurs in nearly half of 'clinically' nonfunctioning pituitary adenomas. Because of that, IGF-1 determination in blood before the surgery, and immunohistochemical examination of adenoma for GH after the surgery, should be performed as standard in all patients suffering from pituitary tumours, irrespective of the presence or absence of acromegaly symptoms.
PRINCIPLES: During the past years our group built a care network for patients with pituitary tumours with referrals from the midlands and the central part of Switzerland, comprising about 1.6 million inhabitants. The purpose of this retrospective observational study with longitudinal data is to review the experience of pituitary surgery and the operative outcome within this Swiss-wide largest network.
METHODS: A total of 182 patients operated at the Neurosurgical Department of the Kantonsspital Aarau 2005-2010 were included in this study. The follow-up was 3.6±1.6 years.
RESULTS: The following lesions were found: non-functioning adenoma (n = 114; 63%); macroprolactinoma (n = 18; 10%); microprolactinoma (n = 11; 6%); acromegaly (n = 11; 6%), Cushing's disease (n = 7; 4%); Rathke's cleft cyst (RCC; n = 9; 5%); others (n = 12; 7%). Intraoperative MRI (iMRI) was used in 115 (63%) patients. Preoperatively, hypopituitarism was found in 105 (58%) patients. Postoperative recovery of defunct axes was detected in 48%. Visual field and visual acuity deficits due to optic pathway compression by tumour were detected in 48% and 41% of the patients, respectively. Postoperative recovery of visual function was seen in 89%. The increase of total resection rate by iMRI was statistically significant (p = 0.0007). Recurrent tumour growth was seen in 5 (3%) patients during follow-up.
CONCLUSIONS: Transsphenoidal surgery is the primary treatment for most sellar lesions. The use of iMRI may lead to higher gross total resection rates. In Switzerland close cooperation between specialised centres is a very positive experience both to support operative case loads and to optimise patient follow-up.
A prospective study was performed to evaluate the presentation, therapeutic management, and clinical outcome of nonfunctioning pituitary adenomas (NFPAs). In most of 385 consecutive patients, NFPAs were macroadenomas. The mean follow-up duration was 5.5 ± 1.4 years. Presentation was dominated by headache, visual disturbance, and hypopituitarism. Pituitary apoplexy (clinical and subclinical) was observed in 88 patients. Appropriate steroids replacement was given before surgery. Endoscope-assisted transsphenoidal surgery (TSS) was performed, and was well tolerated by all patients. At discharge, visual disturbances were improved in 215 (87.6%) patients who had complained of visual impairment preoperatively. The shorter the time from presentation of pituitary apoplexy to surgery, the better the outcome in visual function. Seventy-two (18.7%) patients developed transient diabetes insipidus (DI) and 85 (22.1%) patients developed hyponatremia, but all these improved within six weeks. Hypocortisolism was confirmed in 84 (21.8%) patients with an abnormal postoperative day 2 (POD2) 0800 serum cortisol level and in 122 (31.7%) patients with an abnormal POD6 0800 serum cortisol level. Hypothyroidism occurred in 135 (35.1%) patients. Steroids replacement was thus given immediately. Eight (2.1%) patients needed lifetime hormone substitution. No adrenal crisis occurred. Five (1.3%) patients died within six weeks. Residual tumors were confirmed in 79 patients (20.8%) by postoperative four-month enhanced MR imaging. Tumor recurrence or regrowth occurred in 56 patients (14.7%) during the follow-up period. These patients required repeat TSS or radiosurgery. The findings of this study support the use of TSS as a feasible initial treatment for NFPAs. With appropriate perioperative management of abnormal fluid, electrolyte, and endocrinological function, TSS was associated with minimum morbidity and was well tolerated by patients regardless of age. However, close screening of pituitary function and adequate neuroradiological follow-up should be performed after surgery for detection of tumor recurrence or regrowth. The indications for repeat TSS and postoperative radiosurgery in residual or recurrent NFPAs should be better defined.
OBJECTIVE: This study is an updated review of a Southeast Brazilian experience NFPA, emphasizing clinical features, laboratorial and imaging assessment, therapeutic management and outcome.
DESIGN AND METHODS: Retrospective study, in which 104 patients with NFPA were evaluated by the same team of endocrinologists and neurosurgeon. Patients underwent biochemical evaluation, radiological studies and visual field assessment.
RESULTS: Hypopituitarism and neuro-ophthalmological defects were observed in 89%. We observed GH deficiency (81.4%), hypogonadism (63.3%), adrenal hypofunction (59.5%), hypothyroidism (20.4%), high (38.5%) and low (16.7%) prolactin levels. Preoperative imaging classified 93% of the tumors as macroadenomas. Extra-sellar expansion was observed in 83.8%. Varying degrees of visual disturbance were observed in 74%. Primary treatment was transsphenoidal surgery (75%). Clinical control was achieved with one surgery in 37.5 % of patients. The majority of patients needed a second therapeutic approach, radiotherapy or other surgeries. Immunohistochemistry resulted negative for pituitary hormones in 43%. Improvement of neuro-ophthalmological symptoms was observed in 61% of the patients after treatment.
CONCLUSIONS: Our data confirm elevated prevalence of mass effect and hypopituitarism in patients harboring NFPA. Recurrence due to invasion or incomplete resection of the tumor is quite common, which frequently leads to a second therapeutic option.
OBJECTIVE: Transsphenoidal adenomectomy carries the possibility of new pituitary failure and recovery. Herein, we present rates and determinants of postoperative hormonal status.
METHODS: All consecutive patients who underwent endonasal transsphenoidal adenoma removal over an 8-year period were analyzed. Those with previous sellar radiotherapy were excluded. Pre- and postoperative hormonal status (at least 3 mo after surgery) were determined and correlated with clinical parameters using a multivariate statistical model.
RESULTS: Of 444 patients (median age 45 years, 75% macroadenoma, 19% with multiple operations), 9 had preoperative panhypopituitarism. Of the remaining 435 patients, new hypopituitarism occurred in 5.5% of patients (anterior loss in 5%; permanent diabetes insipidus in 2.1%; including 2 patients who had total hypophysectomy). Of 346 patients with preoperative hormonal dysfunction, 170 (49%) had improved function. "Stalk compression" hyperprolactinemia resolved in 73% of 133 patients; recovery of at least 1 other anterior axis (excluding isolated hypogonadism associated with "stalk compression" hyperprolactinemia) occurred in 24% of 209 patients. Multivariate analysis showed that new hypopituitarism was most strongly associated with larger tumor diameter (P = 0.04). Of 223 patients with an endocrine-inactive adenoma, new hypopituitarism was seen in 0, 7.2, and 13.6% of patients with tumor diameters of <20, 20 to 29, and >or=30 mm, respectively (P = 0.005). Multivariate analysis revealed that resolution of hypopituitarism was related to younger age (39 versus 52 years, P < 0.0001), absence of an intraoperative cerebrospinal fluid leak and, in patients with an endocrine-inactive adenoma, absence of systemic hypertension (24% versus 6%, P = 0.009).
CONCLUSION: After transsphenoidal adenomectomy, new unplanned hypopituitarism occurs in approximately 5% of patients, whereas improved hormonal function occurs in 50% of patients. The likelihood of new hormonal loss or recovery appears to depend on several factors. New hypopituitarism occurs most commonly in patients with tumors larger than 20 mm in size, whereas hormonal recovery is most likely to occur in younger, nonhypertensive patients and those without an intraoperative cerebrospinal fluid leak.
BACKGROUND AND AIMS: The aim of the present study was to evaluate the clinical presentation, characteristics and post-surgical outcome of non-functioning pituitary macroadenomas (NFPM) in elderly patients.
METHODS: 27 patients (65-81 years; 13 Males, 14 Females) with NFPM (20-45 mm in diameter) were studied. The symptoms prompting neuroradiological studies were vision alterations in 52%, and dizziness, loss of memory, confusion, headache and depression in 29%; in 19% of patients, the disease was incidentally discovered during computed tomography (CT) or magnetic resonance imaging (MRI) for head trauma or cerebral ischemic attacks.
RESULTS: Endocrinological evaluation on diagnosis showed global anterior hypopituitarism in 33% and partial hypopituitarism in 37% of patients. Immunohistochemistry showed signs of neurosecretion in most NFPM (chromogranin-A in 55%, gonadotropins in 19%, ACTH in 3.7%). Ki-67 antigen expression was indicative of low proliferative activity. Surgery was highly effective in improving alterations in vision and compressive symptoms, but was unable to restore normal pituitary function in established hypopituitarism in most cases. Eight patients (31%) were free of disease on subsequent MRI (follow-up 1-6 years). In 18 (69%) patients, a post-surgical residue was present. Of these, 6 (33%) underwent radiotherapy in the following years, owing to an increase in the volume of the remnants, and six (33%) underwent additional surgical treatment, followed by radiotherapy for further signs of growth in two. In the remaining patients, a small intrasellar remnant was stable on yearly MRI.
CONCLUSIONS: in elderly patients, the development of hypopituitarism is often overlooked and the initial diagnosis of NFPM may be delayed. This can expose patients to the risks of unrecognized hypopituitarism and jeopardize post-surgical outcome.
OBJECTIVE: Transsphenoidal surgery is the treatment of choice for nonfunctioning pituitary macroadenomas (NFMA). In this study we evaluated the long-term effects of a treatment strategy in which postoperative radiotherapy was not routinely applied to patients with NFMA.
DESIGN: This was a retrospective follow-up study.
PATIENTS: We included 109 consecutive patients (age 56 +/- 13 yr) operated for NFMA between 1992 and 2004.
RESULTS: Radiological imaging revealed a macroadenoma in all patients, with suprasellar extension in 96% and parasellar/infrasellar extension in 36% of cases. Visual field defects were present in 87% of the patients and improved in 84% of these patients after surgery. Only six patients received postoperative radiotherapy. Ten patients died during the follow-up period. Ninety-seven patients could be assessed for tumor regrowth or tumor recurrence after a mean follow-up period of 6.0 +/- 3.7 yr. In nine patients there was evidence for tumor regrowth, and in one patient tumor recurrence was observed. The mean time to tumor growth/recurrence after initial therapy was 6.9 (range 3-12) yr. Follow-up duration was found to be an independent predictor for tumor regrowth.
CONCLUSION: Transsphenoidal surgery without postoperative radiotherapy is an effective and safe treatment strategy for NFMA, without evidence for tumor regrowth in 90% of all patients, at least for the duration of follow-up presented in this study. Additional studies are required to exclude higher regrowth and recurrence rates during prolongation of the duration of follow-up.
BACKGROUND: The differentiation of a pituitary non-functioning macroadenoma from a macroprolactinoma is important for planning appropriate therapy. Serum PRL levels have been suggested as a useful diagnostic indicator. However, values between 2500 and 8000 mU/l are a grey area and are currently associated with diagnostic uncertainty.
OBJECTIVE: We wished therefore, to investigate the serum PRL values in a large series of patients presenting with apparently non-functioning pituitary macroadenomas.
PATIENTS AND METHODS: All patients presenting to the Department of Endocrinology in Oxford with clinically non-functioning pituitary macroadenomas (later histologically verified) between 1990 and 2005 were studied. Information documented in the notes on the medications and on the presence of conditions capable of affecting the serum PRL levels at the time of blood sampling was also collected.
RESULTS: Two hundred and twenty-six patients were identified (median age at diagnosis 55 years, range 18-88 years; 146 males/80 females; 143 gonadotroph, 46 null cell, 25 plurihormonal and 12 silent ACTH adenomas). All tumours had suprasellar extension. At the time of blood sampling 41 subjects were taking medications capable of increasing serum PRL. Hyperprolactinaemia was found in 38.5% (87/226) of the patients. The median serum PRL values in the total group were 386 mU/l (range 16-3257) (males: median 299 mU/l, range 16-1560; females: median 572 mU/l, range 20-3257) and in those not taking drugs capable of increasing serum PRL 363 mU/l (range 16-2565) (males: median 299 mU/l, range 16-1560; females: median 572 mU/l, range 20-2565). Serum PRL < 2000 mU/l was found in 98.7% (223/226) of the total group and in 99.5% (184/185) of those not taking drugs. Among the three subjects with serum PRL > 2000 mU/l, two were taking oestrogen preparations.
CONCLUSIONS: Based on a large series of histologically confirmed cases, serum PRL > 2000 mU/l is almost never encountered in nonfunctioning pituitary macroadenomas. Values above this limit in the presence of a macroadenoma should not be surrounded by diagnostic uncertainty (after acromegaly or Cushing's disease have been excluded); a prolactinoma is the most likely diagnosis and a dopamine agonist should be considered as the treatment of choice.
INTRODUCTION: The aim of this study was to define the impact of surgery on pituitary function in a large consecutive series of patients harbouring non-functioning pituitary adenomas.
MATERIALS AND METHOD: Between December 1982 and December 2000, a total of 822 patients underwent primary surgery in the authors' department. In 721 cases a complete set of endocrinological data was available. Functions of the pituitary-gonadal, pituitary-thyroid and pituitary-adrenal axes were assessed immediately before surgery and again one week, 3 months and 1 year after the operation, utilizing standardized tests and commercially available assays.
RESULTS: There was some degree of pre-operative hypopituitarism in 561 (85%) and 53 (86.3%) of the patients belonging to the transsphenoidal and the transcranial groups, respectively. Prior to transsphenoidal [transcranial] surgery, 163 (31%) [34 (55.7%)] of the patients had secondary adrenal deficiency, 463 (76.6%) [49 (89%)] had hypogonadism and 105 (19.1%) [14 (25.4%)] were hypothyroid. Preoperatively, prolactin levels were mildly elevated in 167 patients (25.3%), whereas 1 year after surgery, levels were elevated in only 5 patients. Permanent diabetes insipidus occurred in 4 patients, 2 from the transsphenoidal group (0.3%) and 2 from the transcranial group (3.2%). Following transsphenoidal surgery 110 (19.6%) of patients had normal pituitary function [versus 0% after transcranial surgery], 169 (30.1%) [6 (11.3%)] showed improvement, 274 (48.9%) [49 (73.7%)] had persistent deficits and 8 (1.4%) [8 (15%)] showed deterioration of pituitary function.
DISCUSSION: These data indicate that transsphenoidal surgery for non-functioning pituitary adenomas in expert hands is, relatively, far less detrimental to patients compared with transcranial surgery. The latter carries a much greater risk of post-operative deterioration in pituitary function.
Serum PRL levels at presentation may be useful in distinguishing between disconnection hyperprolactinemia in non-secretory pituitary adenomas and prolactinomas in order to guide appropriate therapy; however, there is a debate regarding the discriminatory PRL thresholds. We aimed to examine PRL concentrations at presentation in a cohort of histologically proven non-functioning pituitary adenomas (NFPA).
DESIGN AND METHODS:
Retrospective case note analysis was performed. Clinical, biochemical, histopathological and radiological data were recorded and analyzed. Complete data were available for 250 subjects with NFPA.
RESULTS:
Of the study population, 44.8% were hyperprolactinemic at presentation, 55.3% of whom were female. Of those with hyperprolactinemia, 73.2% had PRL<1000 mIU/l on presentation, 24.1% had PRL between 1000 and 1999 mIU/l. Only 2.7% (no.=3 females, 1.2% whole cohort) had PRL>2000 mIU/l (94.3 ng/ml), 2 of whom were pregnant. No male subject and no subjects with an intrasellar macroadenoma had serum PRL>1000 mIU/l (47.2 ng/ml). Overall, serum PRL was not higher among 43 subjects taking medications known to raise PRL.
CONCLUSIONS:
Our data support recent evidence that the serum PRL concentration is rarely >1000 mIU/l in males, or >2000 mIU/l in females, with non-functioning macroadenomas and that, once other contributing factors to the hyperprolactinemia have been excluded, a trial of dopamine agonist therapy for such lesions is indicated.