Transsphenoidal Selective Adenomectomy Research Articles

11C-methionine PET aids localization of microprolactinomas in patients with intolerance or resistance to dopamine agonist therapy

PurposeTo assess the potential for 11C-methionine PET (Met-PET) coregistered with volumetric magnetic resonance imaging (Met-PET/MRCR) to inform clinical decision making in patients with poorly visualized or occult microprolactinomas and dopamine agonist intolerance or resistance.Patients and methodsThirteen patients with pituitary microprolactinomas, and who were intolerant (n = 11) or resistant (n = 2) to dopamine agonist therapy, were referred to our specialist pituitary centre for Met-PET/MRCR between 2016 and 2020. All patients had persistent hyperprolactinemia and were being considered for surgical intervention, but standard clinical MRI had shown either no visible adenoma or equivocal appearances.ResultsIn all 13 patients Met-PET/MRCR demonstrated a single focus of avid tracer uptake. This was localized either to the right or left side of the sella in 12 subjects. In one patient, who had previously undergone surgery for a left-sided adenoma, recurrent tumor was unexpectedly identified in the left cavernous sinus. Five patients underwent endoscopic transsphenoidal selective adenomectomy, with subsequent complete remission of hyperprolactinaemia and normalization of other pituitary function; three patients are awaiting surgery. In the patient with inoperable cavernous sinus disease PET-guided stereotactic radiosurgery (SRS) was performed with subsequent near-normalization of serum prolactin. Two patients elected for a further trial of medical therapy, while two declined surgery or radiotherapy and chose to remain off medical treatment.ConclusionsIn patients with dopamine agonist intolerance or resistance, and indeterminate pituitary MRI, molecular (functional) imaging with Met-PET/MRCR can allow precise localization of a microprolactinoma to facilitate selective surgical adenomectomy or SRS.

Prognostic factors of biochemical remission after transsphenoidal surgery for acromegaly: a structured review.

Biochemical control is the main determinant of survival, clinical manifestations and comorbidities in acromegaly. Transsphenoidal selective adenomectomy (TSA) is the initial treatment of choice with reported biochemical remission rates varying between 32 and 85%. Understanding the limiting factors is essential for identification of patients who require medical treatment. We reviewed the English literature published in Medline/Pubmed until Dec 31, 2019 to identify eligible studies that described outcomes of TSA as primary therapy and performed analyses to determine the main predictors of remission. Most publications reported single-institution, retrospective studies. The following preoperative parameters were consistently associated with lower remission rates: cavernous sinus invasion by imaging, larger tumor size and higher GH levels. Young age and preoperative IGF-1 levels were predictive in some studies. When controlled for covariates, the best single preoperative predictor was cavernous sinus invasion, followed by preoperative GH levels. Conversely, low GH level in the first few days postoperatively was a robust predictor of durable remission. The influence of tumor histology (sparsely granular pattern, co-expression of prolactin and proliferation markers) on surgical remission remains to be established. Few studies developed predictive models that yielded much higher predictive values than individual parameters. Surgical outcome prognostication systems could be further generated by machine learning algorithms in order to support development and implementation of personalized care in patients with acromegaly.

Ex Vivo1H NMR study of pituitary adenomas to differentiate various immunohistochemical subtypes

Pituitary adenomas (PAs) are benign growths arising from epithelial cells in the adenohypophysis of the pituitary gland. To date, there has been no detailed metabolic characterization of PAs of various subtypes. In this study, we report nuclear magnetic resonance (NMR) based metabolomic analysis of surgically resected tumors from forty five pituitary tumor patients [gonadotropic (LH/FSH-secreting) = 17; prolactinomas (PRL-secreting) = 11, Cushing’s disease (ACTH-secreting) = 4, non-functional = 5, and mixed = 8] who underwent transsphenoidal selective adenomectomy. Compared to LH/FSH-secreting tumors, PRL-secreting tumors showed statistically significant decrease in the levels of N-acetylaspartate (NAA), myo-inositol (mI), scyllo-inositol (sI), glycine, taurine, phosphoethanolamine (PE) and increase in the levels of glutamine. When compared with LH/FSH-secreting tumors, ACTH-secreting tumors showed statistically significant decrease in the levels of sI, glycine, PE and increase in the levels of aspartate. Although lipid extracts of PAs showed the presence of many common lipid molecules, only glycerophosphoethanolamine (GPE) showed statistically significant decrease in PRL, ACTH and non-functional subtypes when compared to LH/FSH-secreting tumors. Changes observed in these metabolite concentrations among various subtypes of PAs reflect metabolic heterogeneity in these tumors and may pave the way towards the development of metabolic markers to distinguish various immunohistochemical subtypes of PAs.

Age- and Sex-Specific Differences as Predictors of Surgical Remission Among Patients With Acromegaly.

Sex and age are factors conferring resistance to medical treatment in patients with acromegaly. However, their impact on outcomes of transsphenoidal-selective adenomectomy (TSA) has not been evaluated. To analyze age- and sex-related differences concerning surgical outcomes of growth hormone (GH)-secreting pituitary adenomas. Retrospective. Single-center tertiary hospital. Patients with acromegaly (n = 463) who underwent TSA between January 2000 and July 2014. TSA. Tumor characteristics and surgical outcomes. Sex differences existed in the baseline insulinlike growth factor-1 levels and the mean tumor size. Overall, surgical remission rates were 89.7% and 76.5% in male and female patients, respectively (P < 0.001). Total tumor tissue resection was performed in 92.6% and 85.8% of male and female participants, respectively (P = 0.021). Premenopausal women had a higher proportion of pituitary adenoma with cavernous sinus invasion than did men aged <50 years (35.3% vs 21.7%, P = 0.007). In immediate postoperative, 75-g oral glucose tolerance tests, fewer premenopausal women reached <1 ng/dL nadir GH levels than did men aged <50 years (59.9% vs 87.7%, P < 0.001). Surgical results were similar in both sexes among older patients (≥50 years). However, premenopausal women had significantly lower long-term remission rates than did men aged <50 years (69.3% vs 88.0%, P < 0.001). Premenopausal women with acromegaly tend to have larger tumors, more aggressive tumor types, and lower remission rates than do men. However, further studies on the clinical implications are needed.

Acromegaly: the effect of somatostatin analogues on tumour volume shrinkage

Acromegaly is a rare disease, caused by growth hormone (GH) hypersecretion and secondarily elevated insulin-like growth hormone 1 (IGF-1) level. Nearly all patients with acromegaly suffer from somatotroph pituitary adenoma. The main goal of treatment is to normalise both GH and IGF-1 levels, which reduces symptoms, complications and mortality. Transsphenoidal selective adenomectomy performed by an experienced neurosurgeon is the first-line therapy of choice. Therapy with somatostatin analogues (SSA) is used as a neoadjuvant treatment prior to surgery and in a persistent disease following the surgery. The long-acting somatostatin analogues reduce serum GH/IGF-1 levels and tumour volume. In this clinical review, mechanisms and role of 1st and 2nd generation somatostatin analogues in the treatment of patients with acromegaly are presented, with particular emphasis on the effects on somatotroph pituitary adenoma volume reduction.

Intraoperative Identification of a Normal Pituitary Gland and an Adenoma Using Near-Infrared Fluorescence Imaging and Low-Dose Indocyanine Green.

The intraoperative distinction between normal and abnormal pituitary tissue is crucial during pituitary adenoma surgery to obtain a complete tumor resection while preserving endocrine function. Near-infrared (NIR) fluorescence imaging is a technique to intraoperatively visualize tumors by using indocyanine green (ICG), a contrast agent allowing visualization of differences in tissue vascularization. Although NIR fluorescence imaging has been described in pituitary surgery, it has, in contrast to other surgical areas, never become widely used. To evaluate NIR fluorescence imaging in pituitary surgery, both qualitatively and quantitatively, and to assess the additional value of resecting adenoma tissue under NIR fluorescence guidance. We included 10 patients planned to undergo transnasal transsphenoidal selective adenomectomy. Patients received multiple intravenous administrations of 5 mg ICG, up to a maximum of 15 mg per patient. Endoscopic NIR fluorescence imaging was performed at multiple points in time. The NIR fluorescent signal in both the adenoma and pituitary gland was obtained, and the fluorescence contrast ratio was assessed. Four patients had Cushing disease, 1 had acromegaly, and 1 had a prolactinoma. Four patients had a nonfunctioning macroadenoma. In 9 of 10 patients with a histologically proven pituitary adenoma, the normal pituitary gland showed a stronger fluorescent signal than the adenoma. A fluorescence contrast ratio of normal pituitary gland to adenoma of 1.5 ± 0.2 was obtained. In 2 patients; adenoma resection was actually performed under NIR fluorescence guidance instead of under white light. NIR fluorescence imaging can easily and safely be implemented in pituitary surgery. The timing of ICG administration is important for optimal results and warrants further study. It appears that injection of ICG can best be postponed until some part of the normal pituitary gland is identified. Subsequent repeated low-dose ICG administrations improved the distinction between adenoma and gland.

Surgical management of Cushing's disease.

Transsphenoidal selective adenomectomy is the first-line treatment for Cushing's disease. At experienced centers, early remission rates after transsphenoidal surgery range from 65 to 98%, however disease relapse frequently occurs with rates ranging from 2 to 35% at long-term follow up. This article discusses recently reported studies on the surgical outcomes from transsphenoidal surgery for Cushing's disease. One of the keys to a successful long-term surgical outcome is meticulous dissection using the adenoma's pseudocapsule as a surgical plane for complete resection. MRI-negative and invasive ACTH-secreting adenomas pose particular challenges for pituitary surgeons.

Cushing’s disease: current trends in treatment

SUMMARY Cushing’s disease (CD) is an uncommon endocrine disorder resulting from an adrenocorticotrophin-producing pituitary adenoma. Its clinical features and subsequent comorbidities are the consequence of hypercortisolism and may be life-threatening if untreated. Trans-sphenoidal selective adenomectomy or hypophysectomy remain recommended first-line treatments for CD and may be repeated if unsuccessful or following recurrence of the tumor. Pituitary radiotherapy, either conventional fractionated external beam or in the form of radiosurgery, is a second-line treatment option, but its effects are delayed for several years. Bilateral adrenalectomy is a valuable treatment option for acutely unwell patients or for those who are unable to take or tolerate medical therapy. Steroidogenesis inhibitors such as metyrapone, ketoconazole, etomidate and mitotane have their place at many stages in the management of CD and are usually very effective. Pituitary tumor-targeted agents, such as cabergoline or pasireotide, ...

The relationship between efficacy of surgical treatment of Cushing disease and pathological – immunohistochemical and ultrastructural – confirmation of corticotroph tumour presence

Background and purposeThe most common cause of Cushing disease (CD) is ACTH-secreting pituitary adenoma. Transsphenoidal selective adenomectomy is the treatment of choice. Frequency of remission varies from 60% to 90%, depending on the site and the surgeon's experience. This study aims to answer the question whether confirmation of corticotroph adenoma in pathological examinations increases the probability of surgical cure for CD. Material and methodsThe prospective study involved 36 patients with CD operated on with the transsphenoidal approach and followed up for at least 18 months. Following the surgical procedure, the specimen was examined by a pathologist. The study evaluated the significance of positive histological (immunohistochemical and ultrastructural) examination results for achieving surgical cure for CD. ResultsTwenty-three of 36 patients (63.9%) were regarded as being surgically cured of CD. Persistent CD was confirmed in 13 patients (36.1%). Pituitary insufficiency was found in 5 patients (13.9%), whereas 3 patients (8.3%) were diagnosed with diabetes insipidus. A significant difference was demonstrated between the cured and the non-cured group with reference to the results of pathological examination of surgical specimens. Pathomorphological confirmation of corticotroph adenoma was significantly more frequently observed in the cured group in comparison with the non-cured group (p = 0.028). ConclusionsPathological confirmation of corticotroph pituitary adenoma may be regarded as an important predictor of the surgical cure of CD.

Transsphenoidal microsurgery in 541 patients with Cushing's disease

Objective To analyze the transsphenoidal microsurgical effect of Cushing's disease. Method The clinical data of 541 Cushing's disease cases were analyzed retrospectively in this study from 1981 to 2007. Results CT/MRI revealed microadenoma in 358 cases (66.2％ ), macroadenoma in 76 ( 14.0％ ) ,huge adenoma in 3 ( 0.6％ ) and negative results in 104 ( 19. 2％ ). Pathological examination confirmed pituitary ACTH adenoma in 408 ( 75.4％ ), pituitary ACTH cell hyperplasia in 45 ( 8. 3％ ), no evidence of adenoma or hyperplasia in 88 ( 16. 3％ ). In our group, the cure rate were 85.0％ ( 347/408 ),24. 4％ (11/45) and 45.5％ (40/88) respectively in Cushing's disease patients with pituitary ACTH adenoma, pituitary ACTH cell hyperplasia and negative pathological results. The follow up period ranged from half year to 25 years( average 3.1 years). Recurrence rate was 13. 3％. Average recurrent time was 3.4 years (0.5 - 16.5 years ). Conclusions Transsphenoidal selective adenomectomy plus resection of parsadenomatous pituitary tissue is the first choice in the treatment of Cushing's disease. Repeated transsphenoidal pituitary surgery or pituitary radiotherapy could be underwent for patients after failed surgery of recurrenct cases. Key words: Cushing syndrome; Microsurgery; Transsphenoidal surgery

Diagnosis, management and therapeutic outcome in prepubertal Cushing's disease

Cushing's disease (CD) in prepubertal children is very rare and presents important diagnostic and therapeutic challenges. We report experience of the management of this subpopulation of CD patients. Retrospective patient case note review. Between 1985 and 2008, 17 prepubertal children (13M, 4F), aged 5.7-14.1 years presented to our centre for diagnosis and management of CD. All children had subnormal linear growth and excessive weight gain at presentation. A high proportion (85% of males, 75% of females) had evidence of excessive virilisation. Striae and hypertension were seen in 41% of patients. The investigation with highest sensitivity (100%) for CD was excessive increase of serum cortisol to i.v. CRH (mean increase 113%). Pituitary imaging performed in all the patients showed poor concordance with findings at surgery (31%). In contrast bilateral simultaneous inferior petrosal sinus sampling (BSIPSS), performed in 11/16 subjects showed a high correlation with surgical findings (91%). In 16 patients, transsphenoidal selective adenomectomy (TSS) achieved a cure rate of 44%. However, in the 11 patients who had pre-operative BSIPSS, the cure rate was 64%. Of the 16 patients, 9 patients who were not cured by TSS received external pituitary radiotherapy. Prepubertal CD had distinctive features with increased frequency in males, abnormal auxology and excessive virilisation. The cortisol response to i.v. CRH administration was particularly exuberant and contributed to diagnosis. BSIPSS was much more helpful than pituitary imaging in localisation of the microadenoma and was associated with improved cure rate by TSS.

Tratamiento de la enfermedad de Cushing con ketoconazol

Cushing's disease (CD), which is caused fundamentally by a pituitary microadenoma, is a rare endocrine disease in the paediatric age and which is associated with significant morbidity. The current treatment of choice for CD is trans-sphenoidal selective adenomectomy resulting in long-term remission rates. Pharmacological management of CD is directed at decreasing adrenal steroid secretion. Ketoconazole inhibits adrenal enzyme activity and decreases cortisol secretion. Our patient is a girl of 13 years and eight months of age with CD. The clinical manifestations were obesity, decrease in growth rate, Cushingoid phenotype, headache and arterial hypertension. The hormone determinations showed elevated values of UFC and ACTH. The circadian rhythm cortisol and ACTH and the short and long dexamethasone tests of provide definitive diagnosis of CD. The cranial MRI with gadolinium suggests the presence of microadenoma in the right pituitary lobe. The diagnosis is confirmed after performing a selective catheterisation of the inferior petrosal sinuses with CRH stimulus. While waiting for trans-sphenoidal surgery, the treatment with ketoconazole (200 mg/24 h) controlled the hypercortisolism. After the surgical procedure, the patient received replacement therapy with hydrocortisone for 1 month. At the present time, the patient, without fulfilling the post surgery cure criteria, has been 2 and a half years in clinical and hormonal remission.

Surgical Treatment of Recurrent Cushing's Disease

The aim of this study was to evaluate the role of transsphenoidal selective adenomectomy alone or in combination with adjuvant therapy in treatment of recurrent Cushing's disease. A total of 16 patients with recurrent Cushing's disease underwent reoperation, 15 via a transsphenoidal approach and one via a combined transsphenoidal/transcranial approach. Selective adenomectomies were performed in 13 patients and hemihypophysectomies were performed in three patients. Endocrinologically, recurrence was diagnosed by an overnight 2-mg dexamethasone suppression test. All patients underwent a 1.5-T magnetic resonance imaging scan, and eight patients underwent inferior petrosal sinus sampling. After selective adenomectomy, six of the 13 patients went into remission. Recurrence always occurred at the localization of the original tumor. In three patients without intraoperative tumor detection, hypophysectomy did not lead to remission. In 10 patients with persistent disease, adjuvant therapy (radiotherapy, adrenalectomy) led to normalization of basal cortisol levels in eight patients and clinical remission in one patient. One patient was lost to follow-up. In 10 patients, no evidence of an adenoma was visible on the preoperative magnetic resonance imaging scan. Inferior petrosal sinus sampling allowed correct prediction of the tumor localization in two of eight patients. By performing repeated selective adenomectomy, patients with recurrent Cushing's disease can be cured without the risk of endocrine deficits or major complications. Dynamic endocrine tests are of paramount importance for surgical decision making. Imaging and inferior petrosal sinus sampling are not helpful in locating the recurrent tumor. If normalization can not be achieved, adjuvant therapy is mandatory.

Long-term follow-up results of transsphenoidal surgery for Cushing's disease in a single centre using strict criteria for remission.

Transsphenoidal selective adenomectomy (TSA) is widely accepted as the treatment of choice for Cushing's disease but not all patients are cured by this procedure. The success of surgery depends on the skill and experience of the surgeon but the criteria used to define remission are highly variable. We have analysed the outcome following surgery in our centre using the stringent requirement of a postoperative serum cortisol of < 50 nmol/l as our definition of remission and assessed whether changes in surgical policy, including a greater emphasis on selective procedures and the move in recent years to a single surgeon undertaking all pituitary surgery, have improved complication and remission rates. The case notes, histology and pituitary imaging of 54 consecutive patients (42 females, mean age 41 years) with pituitary-dependent Cushing's syndrome who had undergone transsphenoidal surgery between January 1980 and November 2000 were reviewed. Follow-up was for a median of 6 years (range 6 months to 21 years). One patient died within 1 week of surgery (1.9%) and major morbidity occurred in eight patients (15%). Clinical and biochemical remission was achieved in 41 patients (77%) with only two recurrences (5%) to date. Success was related to tumour size with 37 (86%) of 43 intrasellar lesions successfully resected compared with only four (40%) of 10 extrasellar adenomas. Twenty-four (59%) of those in remission developed partial or complete hypopituitarism compared with four (33%) of those not in remission. The extent of surgical exploration predicted the development of hypopituitarism (88% total hypophysectomy, 33% hemihypophysectomy, 14% selective adenomectomy) but not remission (75% total hypophysectomy, 87% hemihypophysectomy, 71% selective adenomectomy). Among complications, an excess of venous thromboembolic disease was noted, with three patients (6%) developing deep venous thrombosis or pulmonary embolism postoperatively. Comparison of the data for individual surgeons revealed an improvement in outcome over time, with 100% remission of microadenomas, 29% hypopituitarism and 12% complications following the move to a single surgeon undertaking all pituitary surgery. Transsphenoidal surgery is a safe and effective treatment for Cushing's disease and our results compare favourably with those from published series, the majority of which comprise relatively small numbers. The presence of an intrasellar lesion and postoperative serum cortisol < 50 nmol/l are good predictors of remission in the long term but historically in our centre this can only be achieved in a significant number of patients at the expense of some degree of hypopituitarism. However, the surgical outcome for Cushing's disease, including a reduced frequency of hypopituitarism, can be improved if patients are operated on by a single pituitary surgeon, using selective adenomectomy as the preferred surgical approach wherever possible.

Transsphenoidal adenomectomy in cushing's disease via a lateral rhinotomy approach

Cushing's disease may be treated by surgical pituitary adenomectomy. We present a surgical approach to the pituitary gland that increases the possibilities of a selective adenomectomy, and compare our results with those of other studies. A retrospective study of patients with Cushing's disease undergoing transsphenoidal selective adenomectomy via a lateral rhinotomy at Sahlgrenska University Hospital from 1984-93 is presented. Thirty-one patients (26 women, five men; mean age: 44 years, range: 13-75 years) with Cushing's disease were followed for a median time of 4.5 years after operation (range: 1-10 years). Preoperative and postoperative urinary and serum cortisol, and circadian rhythm of serum cortisol were measured. We also measured serum TSH, T4, PRL, FSH, LH, and testosterone as well as urine and plasma osmolality. Our remission rate was 77% and the recurrence rate 3%. Hormonal insufficiency was rare. Hypothyroidism and hypogonadism were present in 3% of the patients, and diabetes insipidus occurred in 6% of the patients. Selective adenomectomy with its good opportunities for cure and improvement should be regarded as the treatment of choice for Cushing's disease. Using the lateral rhinotomy approach to the sphenoidal cavity results in good accessibility to the sella turcica and its pituitary adenomas, a low frequency of postoperative pituitary insufficiency, and a high remission rate.

Surgical outcome after repeated transsphenoidal surgery in acromegaly.

Transsphenoidal selective adenomectomy is the most efficient primary treatment for acromegaly. However, management of persistent or recurrent disease remains controversial. The objective of the present study was to evaluate the early and long-term efficacy and safety of a second transsphenoidal surgery performed in those cases. The results of a retrospective study of 16 patients undergoing reoperation by the senior author (J.H.) between 1970 and 1991 are reported. Reoperation was performed for persistent or progressive acromegaly in 11 patients, visual impairment in four, and disease recurrence in one. Normalization of growth hormone (GH) was defined as a basal GH level of less than 5 micrograms/L and suppression to less than 2 micrograms/L during the oral glucose tolerance test. Long-term follow-up data were available in 15 patients. The second transsphenoidal surgery induced a greater than 50% decrease of GH level in 11 patients. Three (19%) of 16 patients were cured according to the authors' criteria and remained so after 2, 7, and 20 years. Two more patients had a postoperative basal GH level of less than 5 micrograms/L but incomplete suppression during the oral glucose tolerance test. Thus, a total of five patients (31%) achieved a basal GH of less than 5 micrograms/L. One other patient who had no initial improvement after the second transphenoidal surgery had spontaneous normalization of his GH level after 13 years. The following complications of the second surgery occurred in three patients: one subarachnoid hemorrhage, two new visual field defects, one cranial nerve palsy, and one meningitis. Moreover, 10 patients (62.5%) developed one or more new pituitary hormone deficiencies. In conclusion, reoperation for persistent or recurrent acromegaly has low success and high complication rates. According to the authors' experience, this procedure should be reserved for patients unresponsive to other forms of therapy or with progressive visual impairment despite medical therapy.

Transsphenoidal selective adenomectomy is the treatment of choice in patients with Cushing's disease. Considerations concerning preoperative medical treatment and the long-term follow-up.

Cushing’s observation, that most patients with the disease named after him harbor small basophilic pituitary adenomas, has been confirmed by the success of transsphenoidal surgery in the majority of patients. Monoclonality of such tumors supports the concept of a primary pituitary origin of the disease, which indeed then should be cured after their selective removal. It has become evident that ACTH secretion by the normal corticotrophs surrounding these microadenomas is suppressed in most cases and that this suppression persists for many months after the selective removal of ACTH-secreting microadenomas before a gradual normalization occurs. This initial period after surgery is accompanied by clinically evident hypocortisolism to a degree that is seldom achieved more thoroughly after surgery on other types of pituitary tumors. A gradual return to normal of the diurnal rhythm of ACTH and cortisol, of the response to an insulin-induced hypoglycemia, of daily adrenal cortisol production, as well as a return to normal sensitivity of the restored hypothalamopituitary adrenal axis to low dose dexamethasone supports the concept of a real cure in these patients. Most series describing the results of selective removal of ACTH-secreting tumors by transsphenoidal surgery report an overall percentage of immediate remission of about 75%. Amongst the therapeutic failures a small group of patients can be identified in whom the diagnosis of pituitary-dependent Cushing’s disease was wrong after all. This group includes individuals with occult tumors secreting ACTH and/or CRH ectopically, patients with primary glucocorticoid receptor resistance, and patients with secondary autonomous adrenocortical lesions. The majority of therapeutic failures, however, are neurosurgical. Several categories can be recognized: patients in whom extensive pituitary exploration did not reveal an adenoma, patients in whom the tumor could not be completely removed (in many of these cases invasive tumor penetration of bone or surrounding tissue made selective removal technically impossible), and finally an undetermined number of patients with a seemingly discrete lesion that was, in retrospect at microscopical examination, surrounded by hyperplastic corticotrophs. There is no ideal therapy for patients with Cushing’s dis

Transsphenoidal selective adenomectomy is the treatment of choice in patients with Cushing's disease. Considerations concerning preoperative medical treatment and the long-term follow-up

Transsphenoidal selective adenomectomy is the treatment of choice in patients with Cushing's disease. Considerations concerning preoperative medical treatment and the long-term follow-up

TRH/GnRH Test in Acromegaly

We investigated the rate of recurrence in acromegaly in 20 patients who were found to have a TRH and GnRH induced GH response postoperatively after primarily successful transsphenoidal selective adenomectomy in a retrospective study. All operations had been carried out by the same neurosurgeon (R.F.). Successful therapy was defined as basal GH-levels < or = 2 ng/ml and no evidence of residual tumour in the postoperative neuroradiological examination. The follow-up period ranged from 5 to 14 years (mean 7.7 years). At the last follow-up visit an OGTT was performed and SmC measured. In spite of the long-follow-up period we did not find patients with recurrent acromegaly in this investigation. We conclude that, in contrast to previous studies, a stimulation of GH in the TRH/GnRH test does not necessarily predict likely recurrence of acromegaly in patients with an adequate suppression of GH during an OGTT following operative microsurgical treatment.

Transsphenoidal resection in Cushing's disease: undetectable serum cortisol as the definition of successful treatment.

We tested the hypothesis that in Cushing's disease, ACTH secretion from the normal pituitary surrounding an ACTH-secreting adenoma is inhibited and hence removal of the entire adenoma should result in an undetectable serum cortisol in the immediate post-operative period. A retrospective study of patients undergoing transsphenoidal selective adenomectomy, hemi-hypophysectomy or total hypophysectomy for Cushing's disease at St Bartholomew's Hospital between 1985 and 1990. Forty-eight consecutive patients (33 women, mean age 43, range 7-69 years) undergoing transsphenoidal hypophysectomy for Cushing's disease. Ten patients who underwent a second operation were re-evaluated; the patients were followed for a median time of 40 months after operation (range 15-70). Post-operatively, serum cortisol was measured daily at 0900 h. Serum TSH, T4, prolactin, LH, FSH, testosterone or oestradiol plus plasma and urine osmolality were measured. After initial surgery, post-operative serum cortisol was undetectable (< 50 nmol/l) in 20 out of 48 patients (42%) and < 300 nmol/l in 32 out of 48 patients (67%). Re-exploration of the pituitary fossa in 10 patients found undetectable cortisol levels in 25 (52%) and levels < 300 nmol/l in 39 (81%) patients. Cushing's syndrome has not recurred, clinically or biochemically, in any patient in whom the post-operative cortisol was < 50 nmol/l. Post-operatively, hypothyroidism was present in 40% of patients and hypogonadism in 53% of men and 30% of premenopausal women. Diabetes insipidus, persisting for at least six months, occurred in 46% of patients. Cushing's disease has not recurred in any patient with an undetectable serum cortisol (< 50 nmol/l) post-operatively. Serum cortisol should be regarded as a tumour marker in Cushing's disease and the aim of transsphenoidal hypophysectomy for Cushing's disease should be to render the immediate post-operative serum cortisol undetectable.