Recovery Of Pituitary Function Research Articles

RADIOLOGICAL ASPECTS OF HEMORRHAGE INTO PITUITARY ADENOMAS

Objective. To reveal the characteristic radiological features of pituitary apoplexy, which are able to influence its treatment policy. Material and methods. 82 patients with pituitary apoplexy were analyzed. Surgery was not performed in 37 cases and its need disappeared during medical treatment. 45 patients were operated on in different periods after the onset of hemorrhage. The characteristics of MR images of a pituitary apoplexy focus and the likelihood of complete tumor resorption were assessed. Results. Cystic cavities in the tumor stroma were more frequently found at 3 months after the onset of hemorrhage. Complete resorption occurred mainly in pituitary adenomas measuring < 40 mm in size. Tumor resorption occurred more often in diffuse infiltration of the tumor stroma. Conclusion. Medical therapy may be the mainstay of treatment for pituitary apoplexy in tumors < 40 mm with a hemorrhage duration of less than 3 months if cysts are absent in the stroma, regardless of a patient’s status. The probability of pituitary function recovery in this case was 87.5%.

Longitudinal behavior of autoimmune GH deficiency: from childhood to transition age

Some cases of apparently idiopathic GH deficiency (GHD) may be caused by pituitary autoimmunity. To study the variations in pituitary function and antipituitary antibodies (APA) from childhood to transition age in patients with apparently idiopathic GHD. We conducted a longitudinal study. Pituitary function and APA detection by immunofluorescence were investigated in 24 childhood patients with isolated GHD before starting recombinant GH therapy and after the stopping of this therapy in transition age. Sera of patients positive for APA were processed by double immunofluorescence to identify their pituitary target. At diagnosis, 16 out of 24 patients were APA positive targeting only somatotrophs (group 1), while the remaining eight were APA negative (group 2). When retested off therapy, 12 out of 16 patients in group 1 persisted being APA positive, while the remaining four became negative with recovery of pituitary function. All patients in group 2 persisted being APA negative but still showing GHD. Of the 12 patients persistently APA positive, eight with confirmed GHD showed APA still targeting somatotrophs, whereas four showed APA targeting only gonadotrophs associated with isolated hypogonadotropic hypogonadism (HH). Patients with APA at middle but not at high titer in childhood may show a remission of autoimmune GHD in childhood after GH replacement therapy. As APA may shift their target in transition period, an early characterization of APA by double immunofluorescence is advisable in APA positive GHD patients showing delayed puberty, to allow an early diagnosis and an appropriate therapy, thus preventing the progression toward HH.

A case of Sheehan’s syndrome in early postpartum period presenting partial recovery of pituitary function after immediate steroid replacement therapy

A case of Sheehan’s syndrome in early postpartum period presenting partial recovery of pituitary function after immediate steroid replacement therapy

Ipilimumab-induced hypophysitis: a detailed longitudinal analysis in a large cohort of patients with metastatic melanoma.

Ipilimumab (Ipi) is approved by the Food and Drug Administration for the treatment of unresectable or metastatic melanoma. Little is known about Ipi-induced hypophysitis (IH), an important treatment complication. The objectives of the study were as follows: 1) to examine the prevalence of IH, 2) to characterize the clinical course and treatment outcomes in IH, 3) to identify the risk factors for the development of IH, and 4) to determine optimal strategies for the management of IH. This was a retrospective review. The study was conducted at a tertiary referral center. One hundred fifty-four adult patients with metastatic melanoma were evaluated at Massachusetts General Hospital and were treated with Ipi between March 2008 and December 2013. The intervention included treatment with Ipi. Pituitary magnetic resonance imaging, pituitary hormone assessment, and patient survival were measured. IH was diagnosed in 17 patients (11%). Male gender (P = .02) and older age (P = .005), but not the cumulative dose of Ipi, were risk factors for IH. All patients with IH had anterior hypopituitarism (none had diabetes insipidus). Hypopituitarism was persistent in most individuals (76%). Diffuse pituitary enlargement was observed exclusively in all cases of IH and, upon retrospective review of magnetic resonance imaging scans, this finding preceded the clinical diagnosis of hypophysitis in eight patients. Pituitary enlargement resolved rapidly (within 40 d in seven of seven patients). Median survival in patients with IH was 19.4 vs 8.8 months (P = .05) in the remainder of the cohort. Male gender and older age are risk factors for IH. Pituitary enlargement is sensitive and specific for IH in the appropriate setting, can precede the clinical diagnosis, and resolves rapidly. Anterior pituitary function recovery is uncommon. The incidence of hypophysitis may positively predict survival in melanoma patients treated with Ipi.

Recovery of pituitary function following treatment of an unruptured giant cavernous carotid aneurysm using Surpass flow-diverting stents

Giant aneurysms arising from the cavernous internal carotid artery (ICA) can mimic pituitary adenomas and may cause pituitary dysfunction due to their mass effect on the pituitary gland. We report...

Anterior panhypopituitarism in diffuse large B-cell stage IV lymphoma

The most common presentation of metastases to the pituitary gland in systemic lymphoma is diabetes insipidus resulting from infiltration of the infundibulum/posterior lobe. We describe a 69-year-old man with diffuse large B-cell stage IV lymphoma who presented with anterior pituitary hypofunction, without features of posterior pituitary involvement. He presented with a few months of postural dizziness and hypotension, weight loss, fever, strabismus of right eye and a superficial abdominal wall mass. At this time he had no history of malignancy. Biochemically he had hypovolemic hyponatremia, secondary hypothyroidism and adrenal insufficiency. Further hormonal work-up revealed panhypopituitarism but no diabetes insipidus. Imaging of the brain, thorax and abdomen demonstrated diffuse intracranial pachymeningeal thickening and enhancement, multiple lymphadenopathies, a bulky right adrenal gland and a large left suprarenal mass, which were indicative of an infiltrative disease. Imaging of the pituitary showed heterogeneous enhancement of the anterior lobe with an unremarkable pituitary stalk and posterior lobe. Biopsy of the superficial abdominal wall mass revealed diffuse large B-cell lymphoma confirmed by bone marrow aspiration biopsy. Positron emission tomography (PET) scan confirmed diffuse systemic disease involving the right orbital apex, bilateral adrenal glands, bone and bone marrow, retroperitoneum and subcutaneous tissues; however, the pituitary gland, infundibulum and hypothalamus did not show any lesions on the PET scan. The patient was commenced on two cycles of chemotherapy but unfortunately died, thus recovery of pituitary function was not tested. Pure anterior pituitary hypofunction can uncommonly present in individuals with metastases to the pituitary gland, in contrast to the more common posterior pituitary/infundibulum involvement.

Pituitary abscess following expanding sphenoid sinus pyocele: Complication of endoscopic endonasal transsphenoidal surgery

Pituitary abscess is a rare but potentially life-threatening condition with an incidence of 0.2%–1.1% of operative pituitary lesions. Diagnosis can be challenging, because this disorder shares many similarities with other pituitary lesions in terms of signs and symptoms and radiographic findings. Most pituitary abscesses are categorized as secondary, arising from preexisting pituitary lesions or in conjunction with transsphenoidal surgery, sepsis, meningitis, or sinusitis. There have been only a few reports of primary pituitary abscess, which occurs without any of the aforementioned risk factors.We present a case of primary pituitary abscess in a 38-year-old woman with headaches, blurry vision, polyuria, and polydipsia who was found to have hypopituitarism. Brain magnetic resonance imaging showed a sellar/suprasellar mass, which was endoscopically resected via a transsphenoidal approach. Egress of yellow-greenish creamy fluid was noted on dural incision. The patient was treated with a 6-week course of antibiotic therapy postoperatively and had resolution of symptoms.A PubMed search was performed; all cases of pituitary abscess reported in the literature were screened, and 200 cases including our case were analyzed with a focus on outcomes. The most common presentations were headache, visual disturbance, and endocrine abnormalities. Approximately 66.1% of patients achieved partial or complete recovery of pituitary function; 75.7% with vision deficits recovered visual function. Treatment via a craniotomy had a recurrence rate of 17.2% compared with 9.7% via a transsphenoidal approach. To our knowledge, this is the first systematic review on the topic and the largest series reported.

Endocrinological outcomes of pure endoscopic transsphenoidal surgery: a Croatian Referral Pituitary Center experience

AimTo analyze early remission, complications, and pituitary function recovery after pure endoscopic endonasal transsphenoidal surgery (PEETS), a novel method in pituitary adenoma treatment.MethodsTesting of all basal hormone values and magnetic resonance imaging (MRI) were performed preoperatively and postoperatively (postoperative MRI only in nonfunctioning adenomas) in 117 consecutive patients who underwent PEETS in the period between 2007 and 2010. The series consisted of 21 somatotroph adenomas, 61 prolactinomas, and 4 corticotroph and 31 nonfunctioning adenomas. Sixty-three were macroadenomas and 54 were microadenomas. Remission was defined as hormonal excess normalization on the seventh postoperative day in functioning adenomas and as normal MRI findings approximately four months postoperatively in nonfunctioning adenomas. The presence of hypogonadism, growth hormone deficiency, and hypothyroidism was assessed on the seventh postoperative day. Hypocortisolism was assessed through necessity for replacement therapy within 18 months postoperatively.ResultsRemission was achieved in 84% of patients: in 100% of microadenoma and 70% of macroadenoma patients (P < 0.001, odds ratio [OR], 28.16, 95% confidence interval [CI], 1.61-491.36), respectively. Endocrinological complications occurred in 17.1% of patients: in 9% of microadenoma and 24% of macroadenoma patients (P = 0.049, OR, 3.06; 95% CI, 1.03-9.08). Duration of empirical hydrocortisone replacement therapy was significantly shorter in microadenoma patients (P < 0.001). Thirty-five percent of preoperatively present hormonal deficiencies improved after the surgery. Between tumor types there were no significant differences in remission, complications, and normal pituitary function recovery.ConclusionPatients with microadenomas had higher remission and lower complication rates following PEETS, emphasizing the necessity for early detection and treatment of pituitary adenomas. PEETS is a discussion-worthy method for microprolactinoma treatment.

Diffuse large B-cell non Hodgkin's lymphoma in a 65-year-old woman presenting with hypopituitarism and recovering after chemotherapy: a case report

IntroductionDiffuse large B-cell non Hodgkin's lymphoma may involve the pituitary either as a primary central nervous system lymphoma or, more frequently, as metastasis from systemic lymphoma leading to hypopituitarism. A partial recovery of pituitary function after treatment with chemotherapy has previously been described but complete recovery with cessation of all hormone supplements is excessively rare. We report a patient presenting with anterior hypopituitarism with subsequent complete and sustained recovery of pituitary function after successful treatment of the lymphoma.Case presentationA 65-year-old Caucasian woman with lethargy, loss of appetite and peripheral edema was found to have anterior hypopituitarism. Magnetic resonance imaging showed no mass lesions in the pituitary although a positron emission tomography scan showed abnormal pituitary activity. An abdominal computed tomography scan revealed multiple intra-abdominal lymph nodes, which on histology proved diagnostic of diffuse large B-cell non Hodgkin's lymphoma. She received six cycles of R-CHOP chemotherapy, after which she achieved a complete metabolic response at all known previous sites of the disease, confirmed by positron emission tomography scanning. Concomitant with the tumor response, there was full recovery of adrenal, thyroid and gonadal axes which has persisted at 10 months follow-up.ConclusionAlthough rare, it is important to recognize lymphomatous infiltration of the pituitary as a potentially reversible cause of hypopituitarism.

Recovery of pituitary function in the late-postoperative phase after pituitary surgery: results of dynamic testing in patients with pituitary disease by insulin tolerance test 3 and 12 months after surgery

The insulin tolerance test (ITT) is considered the gold standard for assessment of GH and ACTH reserve in patients with pituitary disease following pituitary surgery and is usually performed after 6-12 weeks. However, abnormal axes may not be completely recovered by then. The aim of this study was to evaluate dynamic testing 3 and 12 months after transsphenoidal pituitary surgery. Serial dynamic testing was performed in 36 patients (13 women, age 18-78) at 3 and 12 months after transsphenoidal surgery. Compared with 3-month results, median GH peak levels during ITT after 12 months increased by 38% (P<0.05). In patients initially classified as GH deficiency (GHD), median GH peak increased after 12 months by 23% (P<0.05). At 3 and 12 months, 36% (13/36) and 47% (17/36) were GH sufficient respectively. Median cortisol peak levels after 12 months increased by 17% (P<0.01) compared with 3-month ITT. In ACTH-insufficient (AI) patients, peak cortisol levels increased significantly by 12% (P<0.05) at 12 months, and in ACTH-sufficient patients, peak cortisol levels increased significantly by 13% (P<0.05). At 12 months, there was recovery from AI in 11% of the patients, and recovery from GHD in 11% of patients. Serial dynamic testing results in a change in classification by ITT results in a relevant proportion of patients. Dynamic testing should be repeated during follow-up.

Effect of long‐term cabergoline therapy on the immunological pattern and pituitary function of patients with idiopathic hyperprolactinaemia positive for antipituitary antibodies

The occurrence of antipituitary antibodies (APA) in patients with idiopathic hyperprolactinaemia (IH) and the effects of dopamine agonists on these antibodies and long-term pituitary function outcome have been so far not evaluated. This longitudinal study was aimed at investigating, in patients with IH the occurrence of APA and the effect of cabergoline on the pituitary function and behaviour of APA. Sixty-six patients with IH were studied. APA (by indirect immunofluorescence) and pituitary function were investigated every year for 3 years. Seventeen patients resulted APA positive (Group 1) and 49 APA negative (Group 2). Eight patients of Group 1 (Group 1a) and 24 of Group 2 (Group 2a) were asymptomatic and then not treated; instead, nine patients in Group 1 (Group 1b) and 25 in Group 2 (Group 2b), showing symptoms of hyperprolactinaemia, were treated with cabergoline for 2 years. Among the untreated patients, during the follow-up, those with APA positive (Group 1a) showed an increase of APA titres and PRL levels with partial pituitary impairment in some of them; instead those with APA negative (Group 2a) persisted negative with normal pituitary function despite persistent hyperprolactinaemia. Among the treated patients, those with APA positive (Group 1b) showed normalization of PRL levels, APA disappearance and recovery of pituitary function (when initially impaired) during cabergoline treatment, persisting also at last observation (off-therapy). Instead all patients of Group 2b persisted with APA negative during the follow-up with normalization of PRL levels and stable normal pituitary function during cabergoline therapy but showing a further increase of PRL at the last observation. The presence of APA in some patients with IH suggests a possible occurrence of autoimmune hypophysitis at potential/subclinical stage; an early and prolonged cabergoline therapy could interrupt the progression to an overt clinical stage of the disease. However, the small amount of patients investigated suggests caution against generalization of our assumption and prompts to further controlled studies on a more numerous population to verify these conclusions.

Suppression and Recovery of the Hypothalamic Function after High-Dose Corticosteroid Treatment in Preterm Infants

Background: High-dose systemic dexamethasone is effective in facilitating extubation of ventilated infants with bronchopulmonary dysplasia. Although the suppression and recovery of pituitary-adrenal response had been assessed after corticosteroid treatment in very low birth weight infants, its effect on hypothalamic function has not been longitudinally monitored. Aims: This study was designed to assess the longitudinal hypothalamic response before, during and 4 weeks after a 3-week dose-tapering course of systemic dexamethasone treatment. Patients and Methods: Twenty very low birth weight infants had blood collected for corticotropin-releasing hormone, ACTH and cortisol measurements immediately before starting dexamethasone (week 0), after receiving the maximum dose of treatment (week 1), at the end of the 3-week course (week 3) and 4 weeks after stopping corticosteroids (week 7). Results: All circulating hormone concentrations were significantly suppressed during the treatment period at week 1 and week 3 compared with pretreatment concentrations at week 0 (p < 0.001). The recovery of pituitary function started early soon after week 1, whereas that of hypothalamus and adrenal functions started after the end of the dexamethasone course. Plasma ACTH concentration at week 7 had returned to the pretreatment level, but plasma corticotropin-releasing hormone (p < 0.05) and serum cortisol (p < 0.001) concentrations remained significantly suppressed. Partial recovery of hypothalamic and adrenal function was observed at week 7 (62 vs. 36% of their pretreatment levels, respectively). Conclusion: Our findings suggest that the hypothalamic function is suppressed during systemic corticosteroid treatment but partial recovery occurs 4 weeks after stopping therapy. Even in preterm infants, the hypothalamic-pituitary-adrenal axis behaves in a similar manner as in adult subjects and the pituitary function recovers earlier than that of hypothalamus and adrenals.

Lymphocytic Hypophysitis Causing Hypopituitarism and Diabetes Insipidus, and Subsequent Association With Primary Autoimmune Hypothyroidism and Type 1 Diabetes Mellitus, in a Nonpregnant Female With Complete Recovery of Pituitary Function and Pregnancy

We describe a case of lymphocytic hypophysitis (LYH) in a 25-year-old nulliparous woman who presented with marked lethargy, profound tiredness, weight gain, postural hypotension, and visual disturbance. Endocrine investigations revealed low thyroid stimulating hormone, low T4, and high prolactin levels. Her CT scan revealed a macroadenoma with suprasellar extension, encroaching on the optic chiasm. In view of visual disturbance and clinical hypopituitarism, transphenoidal resection of the tumor was per- formed and normal-looking pituitary tissue was preserved. Histol- ogy revealed LYH. During postoperative period, she developed diabetes insipidus followed by type 1 diabetes mellitus and autoim- mune primary hypothyroidism. Over a period of 3 years, her pitu- itary function completely recovered. Subsequently she had 2 suc- cessful pregnancies. She has been followed for 10 years with no recurrence of LYH. The recovery of pituitary function in LYH and subsequent successful pregnancies as well as the association with diabetes insipidus and primary autoimmune thyroiditis are recog- nized. The association with type 1 diabetes mellitus, however, is unusual. This case highlights the importance of careful follow up because spontaneous remission of pituitary hormone deficiencies and the emergence of other autoimmune diseases can occur.

Effect of one month ketoconazole treatment on GH, cortisol and ACTH release after ghrelin, GHRP-6 and GHRH administration in patients with cushing’s disease

GH responses to ghrelin, GHRP-6, and GHRH in Cushing's disease (CD) are markedly blunted. There is no data about the effect of reduction of cortisol levels with steroidogenesis inhibitors, like ketoconazole, on GH secretion in CD. ACTH levels during ketoconazole treatment are controversial. The aims of this study were to compare the GH response to ghrelin, GHRP-6, and GHRH, and the ACTH and cortisol responses to ghrelin and GHRP-6 before and after one month of ketoconazole treatment in 6 untreated patients with CD. Before treatment peak GH (microg/L; mean +/- SEM) after ghrelin, GHRP-6, and GHRH administration was 10.0 +/- 4.5; 3.8 +/- 1.6, and 0.6 +/- 0.2, respectively. After one month of ketoconazole there was a significant decrease in urinary cortisol values (mean reduction: 75%), but GH responses did not change (7.0 +/- 2.0; 3.1 +/- 0.8; 0.9 +/- 0.2, respectively). After treatment, there was a significant reduction in cortisol (microg/dL) responses to ghrelin (before: 30.6 +/- 5.2; after: 24.2 +/- 5.1). No significant changes in ACTH (pg/mL) responses before (ghrelin: 210.9 +/- 69.9; GHRP-6: 199.8 +/- 88.8) and after treatment (ghrelin: 159.7 +/- 40.3; GHRP-6: 227 +/- 127.2) were observed. In conclusion, after short-term ketoconazole treatment there are no changes in GH or ACTH responses, despite a major decrease of cortisol levels. A longer period of treatment might be necessary for the recovery of pituitary function.

Advances in Pituitary Adenoma Surgery

Following a century of technical developments and refinements, a variety of standard approaches are available today for the surgical treatment of pituitary tumors. The vast majority of the lesions can be dealt with satisfactorily utilizing minimally invasive trans-sphenoidal approaches. The goal of surgical treatment is a complete resection of the tumor mass, decompression of visual pathways, and elimination of hormonal oversecretion, while preserving normal glandular function and avoiding potential surgical complications. The tumor's size, extension, configuration, and the magnitude of hormonal oversecretion, respectively, are the essential factors that decide whether all these goals can be reached. Another important factor is the individual skill and experience of the surgeon. Still, several lesions that develop mainly outside of the sella require transcranial approaches, of which the pterional and subfrontal routes are the most widely used. With microsurgical techniques and standard approaches, mortality is far below 1% and morbidity is remarkably low. The most favorable surgical results are obtained with microadenomas which are visible using MR. Only recently has the recovery of pituitary function following surgery been convincingly demonstrated. With the extended trans-sphenoidal approaches, lesions have become accessible which previously have been considered contraindications for trans-sphenoidal surgery. The introduction of new technical tools such as neuronavigation, endoscopy, and intraoperative imaging open new avenues and widens even more the spectrum of accessible lesions. Indications for surgery, the preoperative workup, surgical techniques, results, limitations, and new technical developments are briefly reviewed.

Lymphocytic hypophysitis in pregnancy with complete recovery of pituitary function after transsphenoidal surgery: A case report

Autoimmune hypophysitis during pregnancy is a rare inflammatory disease primarily affecting the pituitary gland. Rapid development of symptoms is one of the clinical characteristics. We herein report on a 34-year-old, extremly adipose (BMI 62.5) pregnant woman referred to us at the 34th week of gestation. Ten weeks earlier she had developed increasing headache, nausea and vertigo. At the 31th week of gestation the fetal development was small in respect to this stage. MRI showed a pituitary mass with suprasellar extension impinging on the optic chiasm. The perimetry showed bitemporal visual field defects. The patient developed polydipsia and polyuria. The clinical aspect and the biochemical evaluation revealed panhypopituitarism. Thus, after adaquate substitution, including desmopressin, because the risk of complication, consecutive cesarean section and endonasal transsphenoidal surgery with resection of the tumour mass was performed. The histopathological evaluation showed lymphoplasmacytic infiltration of pituitary tissue. Postoperatively, the substitution of pituitary function was continued with additional methylprednisolone therapy. At the first postoperative control the desmopressin substitution could be finished. Three years after the surgical intervention the development of the child was adequate and there was a complete restitution of the pituitary function of our patient. Postoperative MRI did not show residual tumour mass.

Advances in Pituitary Adenoma Surgery

Following a century of technical developments and refinements, a variety of standard approaches are available today for the surgical treatment of pituitary tumors. The vast majority of the lesions can be dealt with satisfactorily utilizing minimally invasive trans-sphenoidal approaches. The goal of surgical treatment is a complete resection of the tumor mass, decompression of visual pathways, and elimination of hormonal oversecretion, while preserving normal glandular function and avoiding potential surgical complications. The tumor's size, extension, configuration, and the magnitude of hormonal oversecretion, respectively, are the essential factors that decide whether all these goals can be reached. Another important factor is the individual skill and experience of the surgeon. Still, several lesions that develop mainly outside of the sella require transcranial approaches, of which the pterional and subfrontal routes are the most widely used. With microsurgical techniques and standard approaches, mortality is far below 1% and morbidity is remarkably low. The most favorable surgical results are obtained with microadenomas which are visible using MR. Only recently has the recovery of pituitary function following surgery been convincingly demonstrated. With the extended trans-sphenoidal approaches, lesions have become accessible which previously have been considered contraindications for trans-sphenoidal surgery. The introduction of new technical tools such as neuronavigation, endoscopy, and intraoperative imaging open new avenues and widens even more the spectrum of accessible lesions. Indications for surgery, the preoperative workup, surgical techniques, results, limitations, and new technical developments are briefly reviewed.

Spontaneous Pregnancy and Partial Recovery of Pituitary Function in a Patient with Sheehan's Syndrome

Sheehan's syndrome is caused by pregnancy-related hemorrhage leading to ischemic necrosis of the anterior pituitary gland and hypopituitarism. Spontaneous pregnancy in Sheehan's syndrome is very rare. We report the case of a patient with Sheehan's syndrome who suffered from anterior pituitary insufficiency, but with sparing of gonadotropic function. The patient became pregnant spontaneously and, after her second delivery, thyrotropic function recovered. However, the patient's growth hormone and cortisol levels remained unresponsive to an insulin-tolerance test. This case demonstrates that pituitary function may recover from less extensive pituitary ischemia. We emphasize the importance of early identification of pregnancy in such cases. It is crucial to institute adequate hormone-replacement therapy during pregnancy, since hypopituitarism is associated with high fetal and maternal morbidity and mortality.

Treatment of Pituitary Tumors: Surgery

Following a century of technical developments and refinements, a variety of standard operation techniques to date are available for the surgical treatment of pituitary tumors. The vast majority of the lesions can be dealt with satisfactorily utilizing transsphenoidal approaches. The goal of surgical treatment is rapid eradication of the tumor mass, decompression of visual pathways, and elimination of hormonal oversecretion while preserving the normal gland and avoiding potential surgical complications. The tumor's size, extension, and configuration and the magnitude of hormonal oversecretion, are the essential factors that decide whether all the goals can be reached. Another important factor is the individual skill and experience of the surgeon. Still, several lesions that are mainly developed outside of the sella require transcranial approaches, of which the pterional and subfrontal routes are the most widely used. With microsurgical techniques and standard approaches, mortality is far below 1% and morbidity is remarkably low. The most favorable surgical results are obtained with microadenomas, which in the MR image are depicted as distinct low intensity lesions. Only recently has the recovery of pituitary function following surgery been convincingly demonstrated. With the extended transsphenoidal approaches, lesions become accessible that previously have been considered contraindications for transsphenoidal surgery. The introduction of new technical gadgets such as neuronavigation, endoscopy, and intraoperative imaging open new avenues and, even more, widen the spectrum of accessible lesions. Indications for surgery, the preoperative workup, surgical techniques, results, limitations, and new technical developments are briefly reviewed in this article.

Use of antagonists in ovarian stimulation protocols

Gonadotrophin-releasing hormone (GnRH) antagonists have been introduced in IVF to prevent premature LH surge. They bind competitively to pituitary receptors and prevent endogenous GnRH from exerting any stimulus on pituitary cells, avoiding the initial 'flare-up' effect and decreasing gonadotrophin secretion within a few hours. Pituitary reserve and gonadotrophin synthesis are not affected; therefore, the recovery of pituitary function is rapid. Two different regimes have been described. The multiple-dose protocol involves the administration of 0.25 mg cetrorelix (or ganirelix) daily from day 6–7 of stimulation, or when the leading follicle is 14–15 mm, until human chorionic gonadotrophin (HCG) administration. The single-dose protocol involves the single administration of 3 mg cetrorelix on day 7–8 of stimulation. Both antagonists with either regimen seem to be equally effective in the prevention of the LH surge. Compared with a long luteal agonist protocol, the treatment is shorter and requires a smaller amount of gonadotrophins. Pregnancy rate seems to be lower, but a decrease in the incidence of severe ovarian hyperstimulation syndrome (OHSS) is reported by several studies. A promising aspect of antagonists may be the possibility of making treatment less aggressive. Finally, in antagonist cycles, ovulation triggering is possible by GnRH agonists, avoiding the deleterious effect of HCG and thus preventing OHSS.