The natural course of non-functioning pituitary macroadenomas

OBJECTIVE: The natural history of non-functioning pituitary macroadenomas (NFMA) has not been completely elucidated. Therefore, we evaluated pituitary function, visual fields, and tumor size during long-term follow-up of non-operated patients with NFMA. DESIGN: Follow-up study. PATIENTS: Twenty-eight patients (age 55 +/- 3 years) with NFMA, not operated after initial diagnosis, were included. RESULTS: Initial presentation was pituitary insufficiency in 44%, visual field defects in 14%, apoplexy in 14%, and chronic headache in 7% of the patients. The duration of follow-up was 85 +/- 13 months. Radiological evidence of tumor growth was observed in 14 out of 28 patients (50%) after duration of follow-up of 118 +/- 24 months. Six patients (21%) were operated, because tumor growth was accompanied by visual field defects. Visual impairments improved in all the cases after transsphenoidal surgery. Spontaneous reduction in tumor volume was observed in eight patients (29%). No independent predictors for increase or decrease in tumor volume could be found by regression analysis. CONCLUSION: Observation alone is a safe alternative for transsphenoidal surgery in selected NFMA patients, without the risk of irreversibly compromising visual function.     

Cushing Disease After Treatment of Nonfunctional Pituitary Adenoma: A Case Report and Literature Review

We describe a very rare case of nonfunctional pituitary adenoma (NFPA) that exhibited corticotrophic activity after resection and radiotherapy. The possible mechanisms of the transformation from NFPA to Cushing disease (CD) are discussed.A 43-year-old man presented with impaired vision, bilateral frontal headaches, and hyposexuality. He had no symptoms suggestive of hypercortisolism, and 8 am plasma cortisol concentration was 67.88 ng/mL. Brain imaging revealed a 15 × 15 × 21-mm sellar mass suggestive of a macroadenoma. The tumor was resected by transsphenoidal surgery and identified by immunohistochemical analysis as a chromophobic adenoma that did not stain for pituitary hormones. The patient was treated with prednisone and levothyroxine replacement therapy. After a third recurrence, the patient presented with clinical features and physical signs of Cushing syndrome. Plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations were elevated, and there was a loss of circadian rhythms. Inferior petrosal sinus sampling after desmopressin showed the central–peripheral ACTH ratio was greater than 3:1. A repeat transsphenoidal resection was undertaken. Immunohistochemistry revealed ACTH positivity. Three months following surgery, imaging showed little residual tumor, but plasma ACTH remained elevated. He was referred for postoperative Gamma Knife radiotherapy.The immunological activity and biological features of the hormones secreted from a pituitary adenoma vary with time. Because long-term outcomes are unpredictable, postoperative follow-up is essential to detect postoperative transformation from NFPA to CD.     

Endoscopic endonasal approach for pituitary adenoma: surgical complications in 301 patients

The authors investigate the complications of transnasal transsphenoidal endoscopic surgery in the treatment of 301 patients with pituitary adenomas. A retrospective analysis of complications in 301 patients submitted to transsphenoidal transnasal endoscopic surgery at the General Hospital of Fortaleza, Brazil between January 1998 and December 2009. The complications were divided in two groups: anatomical (oronasofacial, sphenoid sinus, intrasellar, suprasellar and parasellar) and endocrinological complications (anterior and posterior pituitary dysfunctions). We observed a total of 81 complications (26.9%) in our series. Anatomical complications occurred in 8.97% (27 cases): 8 CSF postoperative leaks (2.6%), 6 cases (1.9%) of delayed nasal bleeding, 5 cases (1.6%) of sphenoidal sinusitis, 3 cases (0.9%) of carotid artery lesion, 2 cases of meningitis (0.6%) and one case (0.3%) of each of the uncommon following complications: intrasella-suprasella hematoma, pontine hematoma and chiasmaplexy. Endocrinological complications occurred in 17.9% (54 cases): additional postoperative anterior lobe insufficiency in 35 cases (11.6%), and postoperative diabetes insipidus in 19 cases (6.3%). In our series, 3 cases of deaths (not directly related to the procedure) were also observed. Endoscopic transsphenoidal surgery represents an effective option for the treatment of patients with pituitary tumor. Complications still occur and must be reduced as much as possible. Successful endoscopic pituitary surgery requires extensive training in the use of an endoscope and careful planning of the surgery. Additional improvement can be expected with greater experience and new technical developments.     

Olfactory Function and Quality of Life Following Microscopic Endonasal Transsphenoidal Pituitary Surgery

Olfactory outcomes as well as oronasal postoperative complications of transsphenoidal pituitary surgery have not been well studied. The objective of this study was to investigate nasal symptoms including olfactory function as well as quality of life following transsphenoidal pituitary surgery.The study is designed as a prospective cohort study set in a single tertiary hospital.A total of 53 patients with pituitary adenomas were included.All patients underwent pituitary surgery with the right-sided endonasal transsphenoidal approach.Outcomes were assessed with the Chinese version of the Medical Outcomes Study Short Form-36 (SF-36) to survey patient health, the Chinese version of the 22-item Sinonasal Outcome Test (SNOT-22), and a Toyota and Takagi (T&T) olfactometer. Assessments were carried out before surgery and at 1 week, and 1 and 4 months after surgery.The overall SF-36 scores were significantly lower, but the SNOT-22 scores were higher at 1 week and 1 month postoperatively compared with baseline (all P < 0.001). The results of T&T olfactometer testing showed that there was a significant decline in the ability to detect odors postoperatively, even at 4 months. Multivariate linear regression analysis showed that lower education level, partial tumor removal, and longer duration of surgery were independent risk factors for a higher SNOT-22 score at 1 week after surgery.The findings show that microscopic endonasal transsphenoidal pituitary surgery impairs olfactory function in most patients for at least 4 months after surgery.     

Postoperative assessment of the patient after transsphenoidal pituitary surgery

While most transsphenoidal pituitary surgery is accomplished without complication, monitoring is required postoperatively for a set of disorders that are specific to this surgery. Postoperative assessments are tailored to the early and later postoperative periods. In the early period, which spans the first few weeks after surgery, both monitoring of anterior and posterior pituitary function and managing neurosurgical issues are the focus of care. Potential disruption of pituitary-adrenal function is covered with perioperative glucocorticoids. Various strategies exist for ensuring the integrity of this axis, but typically this is done by measuring a morning cortisol on the 2nd or 3rd postoperative days. Patients with levels <10 μg/l should continue therapy with reassessment in the later postoperative period. Monitoring for water imbalances, which are due to deficiency or excess of ADH (DI or SIADH, respectively), is accomplished by continuous accounting of fluid intake, urine output and specific gravities coupled with daily serum electrolyte measurements. DI is characterized by excess volumes of inappropriately dilute urine, which can lead to hypernatremia. Most patients maintain adequate fluid intake and euvolemia, but desmopressin therapy is required for some. SIADH, which peaks in incidence on 7th postoperative day, presents with hyponatremia that can be severe and symptomatic. Management consists of fluid restriction. Neurosurgical monitoring is primarily for disturbances in vision or neurological function, and although uncommon, for CSF leak and infections such as meningitis. In the later postoperative period, the adrenal, thyroid and gonadal axes are assessed. New persistent hypopituitarism is rare when transsphenoidal surgery is performed by an experienced surgeon. Various strategies are available for assessing each axis and for providing replacement therapy in patients with deficiencies. Long term monitoring with assessments of visual, neurological and pituitary function coupled with pituitary imaging is necessary for all patients who have undergone surgery, irrespective of the hormone status of their tumors.     

Pituitary adenomas in adolescence--ten-year experience and literature review

Pituitary adenomas account for less than 6% of all intracranial tumors in adolescence. Between November 1987 and October 1996, 8 patients were treated by transsphenoidal resection at Kaohsiung Medical College Hospital. This series included 4 girls and 4 boys with ages ranging from 14 to 19 years. Symptoms reflecting endocrine dysfunction such as scanty pubic hairs in males and amenorrhea in females, were more often found than neurological problems in all adolescents at presentation. Macroadenoma occurred in five of our eight cases (62%) of adolescent pituitary adenoma. In one case (12%), the tumor was plurihormonal tumor. Long-term follow-up (mean 4.5 +/- 2.7 years) revealed the majority of patients had good endocrine function. Significant operative morbidity included steroid-induced psychosis in one patient and transient diabetes insipidus in three, which resolved in all three within two weeks. Our study showed that 1) pituitary tumors in children were uncommon, and when they occurred they were frequently large and invasive; 2) the endocrine disturbance caused by pituitary adenomas alerted the patients to seek medical help more often than neurological deficit; 3) in adolescence, almost all pituitary adenomas were functioning; nonfunctioning pituitary adenomas were rare in adolescence; and 4) transsphenoidal surgery was feasible and safe in adolescence, even with poor pneumatization of the sphenoid sinus, which remains controversial in the literature.     

Effect of transsphenoidal surgery on decreased visual acuity caused by pituitary apoplexy

We treated 12 patients with pituitary apoplexy out of 103 patients with pituitary tumors from August 1994 to March 2008 in the Nishi-Kobe Medical Center. The male to female ratio was 1:2 and the average age was 43 years old, ranging from 19 to 73. The symptoms on presentation were a decrease of visual acuity in nine, headache in seven, endocrinological disturbance in six, visual field defect in seven, a febrile state in six, vomiting in four, oculomotor disturbance in two, abducens palsy in one, and transient altered consciousness in one. All patients underwent transsphenoidal surgery and, in four of these, surgery was conducted within 7 days after onset. All nine patients with a decrease in the visual acuity recovered (100%) and, in addition, complete or near-complete vision recovery was noted in six out of eight patients (75%), excluding one patient whom we were unable to examine accurately. Emergent surgery was performed for only two patients with an acute deterioration of the visual acuity, with one finally developing complete blindness. Based on this study, we conclude that decompressive surgery is very useful for decreased visual acuity caused by pituitary apoplexy, but it is not necessary to perform emergent surgery for pituitary apoplexy in the absence of severe visual deterioration.     

Non-functioning pituitary adenomas: endocrinological and clinical outcome after transsphenoidal and transcranial surgery.

AIM: To study improvement of anterior pituitary function after transsphenoidal and transcranial surgery of non-functioning (NF) pituitary macro- and microadenomas. METHODS: We retrospectively examined 155 patients with NF adenomas preoperatively and 3 months, 1 year and 2 years postoperatively. 130 patients harboured a macroadenoma, 109 underwent transsphenoidal (group one), 21 transcranial surgery (group two). 25 patients presented a microadenoma (transsphenoidal surgery, group three). Endocrine studies included basal serum levels and dynamic testing of anterior pituitary partial function. Clinical symptoms and hormone replacement therapy were documented. RESULTS: Preoperatively, in group one, two and three, somatotropic function was impaired in 85, 90 and 80 %, gonadotropic in 61, 57 and 24 %, corticotropic in 31, 38 and 28 %, thyreotropic in 32, 38 and 12 % and lactotropic in 22, 38 and 32 % cases, respectively. Pituitary functions did not improve significantly after transsphenoidal or transcranial surgery. Presurgically, 63, 62 and 0 % patients complained about visual impairments, 60, 48 and 40 % about headache, 53, 24 and 36 % about fatigue and 28, 33 and 20 % about disturbance of cycle or potency. After transsphenoidal surgery, impaired vision, headache and fatigue improved within 3 months; after transcranial surgery, only headache improved. Preoperatively, pituitary malfunctions were treated adequately. Postsurgically, more patients received adrenal and thyroid hormone substitution, less patients received sex hormones than examinations proved necessary. CONCLUSION: Anterior pituitary function of NF adenoma patients did not improve significantly after transsphenoidal or transcranial surgery. After transsphenoidal surgery, most clinical symptoms normalised within 3 months. In some of the patients, substitution was not optimally adjusted to hormonal impairments.     

Evaluation of the pituitary-adrenal axis before, during and after pituitary adenomectomy. Is perioperative glucocorticoid therapy necessary?

Under the supposition that ACTH secretion will be compromised by surgical trauma, patients with pituitary adenomas undergoing transsphenoidal adenomectomy are frequently given corticoids, even though this therapy is controversial. We studied 10 patients with pituitary adenomas whose adrenocortical function was sufficient prior to surgery. The ACTH and cortisol levels rose significantly during surgery in all of these patients. Five patients completed a two-year postoperative follow-up period and their ACTH and cortisol values remained within normal limits. It may be that patients undergoing transsphenoidal surgery for pituitary adenomas do not need perioperative glucocorticoid treatment, since the hypophyseal-adrenal axis does retain its integrity.     

Efficacy and complications of neurosurgical treatment of acromegaly

The aim of the study was to evaluate the frequency of occurrence of pituitary failure following neurosurgery and the efficacy of transsphenoidal tumour resection in acromegalic patients. We retrospectively evaluated 85 patients (60 female and 25 male), of mean age 43.9 ± 13.2 years, treated by transsphenoidal neurosurgery. Macroadenoma and microadenoma of pituitary were found in 66 (77.6%) and 19 (22.4%) of these patients, respectively. Criteria of cure following neurosurgery were: basal GH < 2.5 μg/l, GH at 120 min in OGTT < 1.0 μg/l and serum concentration of IGF-1 within normal ranges for age and sex. After surgery 32 patients (37.6%) were cured and 53 patients (62.4%) required somatostatin analogue treatment. In patients cured by surgery, lower levels of basal GH (P < 0.05), IGF-1 (P < 0.001), GH at 120 min in OGTT and smaller size of pituitary tumour (P < 0.05) were found at diagnosis, as compared to patients in whom surgery was unsuccessful. Significant correlation between basal serum level of GH at diagnosis and size of pituitary tumour was found (P < 0.001). Invasive tumours were found in 45 of 53 (84.9%) patients not cured and in only 8 of 32 (25.0%) patients cured (P < 0.001). Impaired function of pituitary anterior lobe after surgery was observed in 30% and 4% of patients with macro- and microadenoma, respectively (P < 0.05). The efficacy of neurosurgery is affected by concentration of basal serum GH and IGF-1, GH at 120 min in OGTT, tumour size and invasiveness. Hypopituitarism after surgery is more frequent in patients with macroadenoma. Pituitary insufficiency, as a consequence of surgery, was found in 21% of patients with normal pituitary function prior to operation.     

Radiotherapy in paediatric Cushing’s disease: efficacy and long term follow up of pituitary function

Pituitary radiotherapy (RT) is an effective second-line treatment for paediatric Cushing’s disease (CD). We report long-term efficacy and anterior pituitary function in a cohort of paediatric CD patients treated with RT. Between 1988 and 2008, from our cohort of 48 paediatric CD patients, eight paediatric CD patients (5 males and 3 females) underwent second-line pituitary RT (45 Gy in 25 fractions), following unsuccessful transsphenoidal surgery. Out of eight whose long term follow up is available, four patients were cured by RT. Minimum follow up of 2 years is available for all patients. Four patients achieved cure after RT. Two patients were not cured even after follow up of 60 and 132 months, respectively. Out of four uncured patients, two of them had suppressible low dose dexamethasone cortisol with altered circadian rhythm suggesting possibility of response in near future with follow up of just 26 months. Five patients were hypogonadal and one patient was hypothyroid. All patients were below their target height at the time of last follow up. None of the patients had posterior pituitary dysfunction. This series of patients illustrates the efficacy and long-term follow up of pituitary function in children with CD treated with RT. This study also emphasizes the need of growth hormone statues assessment and timely intervention.     

The endoscopic versus the traditional approach in pituitary surgery

The transsphenoidal route is the most widely used technique for pituitary adenoma surgery due to its rapidity, good tolerance, effectiveness and low complication rate. These are the parameters we utilized in comparing endoscopic with microscopic transsphenoidal surgery. We reviewed the medical records of 418 patients affected by pituitary adenomas who underwent endoscopic transsphenoidal surgery between May 1998 and December 2004, and in this paper, we present the results of 381 patients who fulfilled the follow-up criteria after a minimum period of 15 months. Our experience confirms the previous data on the rapidity and satisfactory tolerance of the endoscopic procedure. We also confirm the low complication rate, specifying that complications characteristic of the approaching phase were certainly reduced; instead, complications characteristic of tumor removal still remained similar to those reported in the microsurgical literature. The results were comparable with those of the best microsurgical series regarding endosellar lesions, but tumor removal was notably superior when dealing with tumors having an extrasellar extension. The improvement may be explained by the excellent vision of the deep surgical fields due to the endoscope and by the extreme flexibility of the surgical trajectory, mainly due to the absence of the divaricator, giving access to the ramifications of the tumor, otherwise difficult to reach.     

Which patients benefit from provocative adrenal testing after transsphenoidal pituitary surgery?

OBJECTIVE Recent data suggest that recovery of anterior pituitary function promptly follows surgical decompression and that hypothalamic-pituitary-adrenal axis assessment need not be delayed following transsphenoidal pituitary surgery. We hypothesized that one protocol for both glucocorticoid supplementation and axis investigation prior to discharge may be applied to all transsphenoidal pituitary surgery patients. The protocol examined the merits of preoperative testing and of basal and hypoglycaemia-stimulated cortisol and ACTH measurements in post-operative axis evaluation. DESIGN Rapid tetracosactrin stimulation testing classified patients according to preoperative adrenal integrity. All patients received tapered doses of hydrocortisone beginning on the morning of surgery and discontinued after 48hours. PATIENTS Of 28 consecutive patients with various pituitary tumours, 19 completed all aspects of the protocol. All evaluable information from the other 9 was incorporated into the final conclusions and recommendations. MEASUREMENTS Morning serum cortisol was measured 24 hours after the last hydrocortisone dose. Plasma ACTH and serum cortisol were measured during insulin tolerance testing within 8 days after surgery. Patients received clinical evaluations and repeat testing as clinically indicated during 6–30 months of follow-up. RESULTS Both peak serum cortisol >550nmol/l and peak plasma ACTH of >4.4pmol/l during insulin tolerance testing were 100% sensitive and specific in predicting sustained hypothalamic-pituitary-adrenal axis integrity after surgery. For patients entering surgery with normal tetracosactrin tests, an initial morning serum cortisol >270nmol/l provided 100% specificity for preserved axis integrity, but a low cortisol did not indicate axis dysfunction. For patients entering surgery with cortisol deficiency, an initial morning cortisol <60nmol/l indicated sustained axis failure, but higher values proved inconclusive. However, the basal cortisol, but not ACTH, on the day of insulin tolerance testing conclusively defined axis status in 18 of 19 study patients (95%). CONCLUSIONS We conclude that (1) a 48-hour perioperative hydrocortisone reducing regimen may be used in all uncomplicated transsphenoidal pituitary surgery cases regardless of pituitary-adrenal axis status before surgery; (2) preoperative adrenal testing aids interpretation of the initial morning serum cortisol and may be used to direct further testing; (3) a single morning serum cortisol drawn 24 hours after glucocorticoid withdrawal suffices for pituitary-adrenal axis investigation if results suggest no change in axis function, as occurred in most study patients; (4) while insulin tolerance testing 5–8 days after surgery is 100% accurate in determining the need for sustained glucocorticoid replacement due to clinically significant hypopituitarism, repeat morning cortisol measurement obviates provocative testing in 95% of cases; and (5) basal and stimulated plasma ACTH values provide no information additional to serum cortisol measurements in post-operative axis evaluation.     

Management of aggressive pituitary adenomas: current treatment strategies

Aggressive pituitary adenomas are notoriously difficult to manage due to their size, invasiveness, speed of growth and high frequency of recurrence. Except for prolactinomas, surgery (usually transsphenoidal but sometimes transcranial) is the first-line option, but re-growth of aggressive tumors is almost inevitable and monitoring and repeat surgery is required to control symptoms. In prolactinomas, dopamine agonists are the first-line treatment and they normalize prolactin levels in most patients even with macroprolactinomas. Somatostatin analogues offer another pharmacotherapy for pituitary adenomas either for primary therapy, pre-operatively to reduce the tumor volume and make it more amenable to surgical removal, or post-surgery to control re-expansion. When surgery and pharmacotherapy fail, radiotherapy is a useful third-line strategy that reduces recurrence, while extreme pituitary adenomas with metastases may potentially be managed with chemotherapy (although more data are needed). A combination of these therapies will be required for aggressive pituitary adenomas and careful follow-up is essential.     

Spontaneous remission of functioning pituitary adenomas without hypopituitarism following infarctive apoplexy: two case reports

Functioning pituitary adenomas may exhibit spontaneous remission after pituitary apoplexy usually in association with hypopituitarism. We report two patients who presented with sudden headache and double vision, showed a ring-enhanced sellar tumor on MRI, underwent transsphenoidal surgery that revealed a coagulation necrotic adenoma without massive hemorrhage, and showed normal pituitary function after the surgery. Definitive diagnoses were made based on immunohistochemistry of the necrotic cells. The findings were consistent with the presence of selective infarct of a GH adenoma and a prolactinoma that had led to remission of acromegaly and menstrual disturbance, respectively, without pituitary insufficiency. In contrast to hemorrhagic apoplexy, infarctive apoplexy tends to affect only the tumor and thus presents with mild symptoms and lack pituitary deficiencies.     

Progressive improvement of impaired visual acuity during the first year after transsphenoidal surgery for non-functioning pituitary macroadenoma

Objective Improvement of visual field defects continues even years after the initial surgical treatment. Because this process of continuing improvement has not been documented for visual acuity, we audited our data to explore the pattern of recovery of visual acuity until 1 year after transsphenoidal surgery for non-functioning pituitary macroadenoma. Design Retrospective follow-up study. Patients Forty-three patients (mean age 56 ± 14 years), treated by transsphenoidal surgery for non-functioning pituitary macroadenoma, were included in this analysis. Results Visual acuity improved significantly within 3 months after transsphenoidal surgery. The mean visual acuity increased from 0.65 ± 0.37 to 0.75 ± 0.36 (P < 0.01) (right eye), and from 0.60 ± 0.32 to 0.82 ± 0.30 (P < 0.01) (left eye). Visual acuity was improved 1 year after transsphenoidal surgery compared to the 3 months postoperative values. The mean visual acuity increased from 0.75 ± 0.36 to 0.82 ± 0.34 (P < 0.05) (right eye), and from 0.82 ± 0.30 to 0.88 ± 0.27 (P < 0.05) (left eye). Conclusion Visual acuity improves progressively after surgical treatment for non-functioning pituitary macroadenomas, at least within the first year after transsphenoidal surgery.     

Repeat endoscopic transsphenoidal surgery for acromegaly: remission and complications

Reported biochemical remission rates following surgical intervention for acromegaly range from 38 to 83 %. In patients not achieving surgical remission, few options remain, mostly limited to medical management and radiation therapy. There is debate over whether or not to offer reoperation to patients in whom surgical remission is not achieved with initial resection. Retrospective chart review was undertaken to determine all patients having acromegaly with persistently elevated GH and/or IGF-1 levels after initial pituitary adenoma resection, and who underwent reoperation using endoscopic endonasal approach at a single institution. Biochemical remission was defined as a postoperative GH level <1 ng/mL and a normal postoperative IGF-1 level in the absence of any medical therapy. In total, 14 patients underwent repeat surgical intervention for acromegaly via endoscopic transsphenoidal approach. Of the 14 patients, 8 (57 %) achieved biochemical remission following repeat surgical intervention. Lower preoperative GH levels were associated with greater chance of biochemical remission (P = 0.048). New endocrinopathies were seen in 2 patients (14 %), and both were transient diabetes insipidus. Meningitis occurred in 2 patients (14 %); both were aseptic meningitis with no sequelae. No mortality was encountered. Repeat surgical intervention for acromegaly via endoscopic transsphenoidal approach appears safe and effective. With no mortality and minimal morbidity, repeat surgical intervention via endoscopic transsphenoidal approach appears a reasonable option for these hard-to-treat patients and should be considered for patients in whom surgical remission is not achieved with initial surgery.     

Treatment of pituitary-dependent Cushing's syndrome: long-term results of unilateral adrenalectomy followed by external pituitary irradiation compared to transsphenoidal pituitary surgery

BACKGROUND: The preferred treatment of Cushing's disease (CD) nowadays is transsphenoidal pituitary surgery (TPS). Prior to TPS, patients at the Leiden University Medical Centre were treated by unilateral adrenalectomy followed by external pituitary irradiation (UAPI). We report on long-term results of both UAPI and TPS and compare remission, relapse rates, and complications. PATIENTS AND METHODS: A retrospective study was carried out on 130 patients with CD. Patients with pituitary macroadenoma were excluded. Eighty-six and 44 patients underwent UAPI and TPS, respectively. Of these patients, 85 and 41 were evaluable for long-term results. RESULTS: Remission following UAPI and TPS was identical at 64% (54/85 and 27/41). Cumulative relapse was also comparable - 17% (9/54) and 22% (6/27), respectively, - for UAPI and TPS, although the mean follow-up periods were different - 21.4 years and 8.5 years, respectively. Cumulative disease-free survival curves after UAPI and TPS are identical until 5 years of follow-up, but diverge thereafter indicating more sustained remissions following UAPI (P = 0.17, Wilcoxon statistic). Pituitary dysfunction following UAPI (36%) and pituitary surgery (55%) likewise did not differ significantly. However, pituitary dysfunction was an immediate event after TPS, whereas it developed after a mean interval of 17.8 years following UAPI.Low-dose dexamethasone testing during follow-up had no value in predicting therapeutic outcome. CONCLUSIONS: The results of unilateral adrenalectomy followed by external pituitary irradiation do not justify that this therapy is totally abandoned in favour of transsphenoidal pituitary surgery. Unilateral adrenalectomy followed by external pituitary irradiation is a valid therapeutic modality for the treatment of Cushing's disease, and could be considered as alternative to bilateral adrenalectomy and under some circumstances to transsphenoidal pituitary surgery.     

Transsphenoidal pituitary surgery via the endoscopic technique: results in 35 consecutive patients with Cushing's disease

OBJECTIVE AND DESIGN: The endoscopic technique has been recently introduced in the field of transsphenoidal pituitary surgery. This technique allows inspection of sellar, supra- and parasellar structures and removal of the tumor under direct visualization, is minimally traumatic and permits easier reoperations. This is the first report on the results of endoscopic surgery for patients with Cushing's disease. Our aim was to retrospectively analyze the results of pituitary surgery in 35 consecutive patients with Cushing's disease operated in our hospital after the introduction of the endoscopic technique (1998-2004). METHODS: Remission was defined as suppression of plasma cortisol (< or =50 nmol/L) after 1 mg dexamethasone overnight determined in the first 3 months after surgery and disappearance of clinical signs and symptoms of hypercortisolism. The patients were followed for an average of 27 months (range 4 to 81 months, median 20 months). RESULTS: Pituitary MRI showed a macroadenoma in 6 patients, a microadenoma in 17 patients and no adenoma in 12 patients. After the initial surgery 27 patients (77%) were in remission. None of the patients had a relapse during follow-up. In the remaining 8 patients hypercortisolemia persisted after surgery. Three of them had a second endoscopic pituitary surgery resulting in remission in two patients. In one patient a second endoscopic pituitary surgery will soon follow. The remaining four patients were treated with radiotherapy postoperatively. Two of them were at the time of data collection in remission. One patient from the remission group had a serious epistaxis and three patients had cerebrospinal fluid leakage, one requiring an external lumbar drain, shortly after surgery. No complications were recorded in the failure group. Postoperatively 34% of all patients required substitution with levothyroxine, 40% required substitution with glucocorticoids, 17% received estrogens or testosterone and 6% still required desmopressin. CONCLUSIONS: Endoscopic transsphenoidal pituitary surgery resulted in our series of patients with Cushings disease in an excellent postoperative remission rate. A randomized clinical trial, comparing endoscopic and conventional pituitary surgery in patients with Cushings disease, is needed to determine the pros and cons of both techniques.