Partial Hypophysectomy Research Articles

The recovery time of hypothalamic-pituitary-adrenal axis after curative surgery in Cushing's disease and its related factor.

Patients with Cushing's disease (CD) experienced transient central adrenal insufficiency (CAI) after successful surgery. However, the reported recovery time of hypothalamic-pituitary-adrenal (HPA) axis varied and the related factors which could affect recovery time of HPA axis had not been extensively studied. This study aimed to analyze the duration of CAI and explore the factors affecting HPA axis recovery in post-operative CD patients with biochemical remission. Medical records of diagnosis with CD in Huashan Hospital were reviewed between 2014 and 2020. 140 patients with biochemical remission and regular follow-up after surgery were enrolled in this retrospective cohort study according to the criteria. Demographic details, clinical and biochemical information at baseline and each follow-up (within 2 years) were collected and analyzed. Overall, 103 patients (73.6%) recovered from transient CAI within 2 years follow-up and the median recovery time was 12 months [95% confidence intervals (CI): 10-14]. The age was younger and midnight ACTH at baseline was significantly lower, while the TT3 and FT3 levels were significantly higher in patients with recovered HPA compared to patients with persistent CAI at 2-year follow-up (p < 0.05). In persistent CAI group, more patients underwent partial hypophysectomy. TT3 at diagnosis was an independent related factor of the recovery of HPA axis, even after adjusting for gender, age, duration, surgical history, maximum tumor diameter, surgical strategy, and postoperative nadir serum cortisol level (p = 0.04, OR: 6.03, 95% CI: 1.085, 22.508). Among patients with unrecovered HPA axis at 2-year follow-up, 23 CAI patients (62%) were accompanied by multiple pituitary axis dysfunction besides HPA axis, including hypothyroidism, hypogonadism, or central diabetes insipidus. HPA axis recovered in 73.6% of CD patients within 2 years after successful surgery, and the median recovery time was 12 months. TT3 level at diagnosis was an independent related factor of postoperative recovery of HPA axis in CD patients. Moreover, patients coexisted with other hypopituitarism at 2-year follow-up had a high probability of unrecovered HPA axis.

Surgical outcome of transsphenoidal surgery in Cushing's disease: a case series of 1106 patients from a single center over 30 years.

Transsphenoidal surgery (TSS) is the first-line treatment for patients with Cushing's disease (CD). However, the reported remission rates of patients who received TSS vary widely between different studies, and the predictors of surgical outcomes remain controversial. The present study analyzed the early outcome of TSS in a large population of patients with CD at a single center, and identified potential predictors of initial remission of TSS in patients with CD. The clinical features and surgical outcomes of CD patients who underwent TSS between 1988 and 2018 at Peking Union Medical College Hospital (PUMCH) were collected and analyzed from their medical records. Of the 1604 CD patients who underwent TSS at PUMCH between February 1988 and October 2018, 1106 patients had complete medical data and pathological results. After surgery, the overall postoperative initial remission rate was 72.5, and 27.5% of patients maintained persistent hypercortisolism. The initial remission rate of patients with preoperative noninvasive adenoma based on MRI (77.1%), intraoperative noninvasiveness (72.5%), microadenoma (74.3%), pathological confirmation (76.4%), and first TSS (73.9%) was significantly higher than that in patients with preoperative invasive adenoma (53.0%), intraoperative invasiveness (60.7%), macroadenomas (65.9%), pathologically negative (49.7%), and repeat TSS (56.0%), respectively (all P < 0.05). The initial remission rate in patients with pseudocapsule-based extracapsular resection (88.1%), MRI-visible adenoma (74.2%) was higher than that in patients without pseudocapsule-based extracapsular resection (77.1%), and with MRI-negative results (64.5%), respectively, but did not reach statistical significance (All P > 0.05). Striking, there was no significant differences in initial remission rates between patients who underwent selective adenomectomy and enlarged adenomectomy (P > 0.05). Whereas, the initial remission rates in patients who underwent partial hypophysectomy only was 51.0%, which was much lower than that in patients underwent selective adenomectomy and enlarged adenomectomy (P < 0.05). The TSS is a safe and effective procedure for the treatment of CD. Whereas, preoperative invasiveness based on MRI, intraoperative invasiveness, macroadenomas pathologically negative, and repeat TSS are related to lower initial remission rates.

Application of different variants of endoscopic transphenoidal removal of corticotropinomas in order to increase the frequency and duration of remission

Itsenko-Cushing’s disease is a severe neuroendocrine disease caused by chronic hyperproduction of adrenocorticotropic hormone by a corticotrophic pituitary tumor (corticotropinoma). Surgical tumor resection remains the gold standard in the treatment of Itsenko-Cushing’s disease and leads to remission in 65–95 % of cases. Despite the benign nature of the disease, even in specialized neurosurgical centers, the recurrence rate of the disease is 25–35 % of cases. This paper presents an analysis of the effectiveness of various options for endoscopic transnasal removal of corticotropinomas, the selection of which was based on the topographic and anatomical features of the tumors. It was found that each of the surgical treatment options provides comparable results in achieving remission (from 81,3 to 87,9 %), while the most optimal method of surgical treatment in terms of recurrence-free survival and postoperative endocrine disorders is partial hypophysectomy, which will increase the likelihood of long-term remission of the disease.

CMET-10. INTRACRANIAL SOLITARY PITUITARY METASTASIS: THE IMPLICATIONS FROM FIVE CASES

Abstract BACKGROUND Pituitary gland metastasis is a rare disease which represents only 1% of pituitary gland lesions. Intracranial solitary pituitary metastasis tends to be misdiagnosed as pituitary adenoma, resulting in a delayed anti-tumor treatment. METHODS Five cases of patients with pituitary gland metastasis recorded between 2014 and 2018 in our hospital were investigated with reference to patient demographics, symptoms at presentation, radiological and histological findings, management and outcomes. RESULTS Five patients (4 male and 1 female) were included and the median age was 48 years (range: 21 to 66). In those five cases, central nervous system related symptoms were the first sign of malignancy, including visual loss (5 in 5 patients), visual field defects (5 in 5 patients), apituitarism (5 in 5 patients), headache (4 in 5 patients), hypothroidism (4 in 5 patients) and diabetes insipidus (2 in 5 patients). All patients received total or partial hypophysectomy and pathologically revealed metastatic adenocarcinoma in 4 patients and metastatic squamous carcinoma in 1 patient. Further examinations by Computed Tomography (CT) or Positron Emission Computed Tomography (PET) indicated lung as primary site in five cases. EGFR mutation and ROS1 fusion were found in 3 and 1 adenocarcinoma patient, respectively, through gene detection of tissue. Postoperative radiotherapy (5 patients), target therapy (4 patients) and chemotherapy (1 patient) were given as subsequent treatment. During the follow-up, four patients died and the overall survival was 2, 8, 28 and 30 months, respectively. CONCLUSION We found that pituitary symptoms usually presented as the first sign of malignancy in intracranial solitary pituitary metastasis. Lung is the most frequently primary site, particularly in adenocarcinoma with driver gene mutation. Patients may benefit from multidiscipline treatment, including resection of pituitary metastasis combined with radiotherapy and targeted therapy.

Outcomes of three-Tesla magnetic resonance imaging for the identification of pituitary adenoma in patients with Cushing's disease.

Pituitary adenoma has been reported to be detectable in only 36-63% of Cushing's disease (CD) patients by magnetic resonance imaging (MRI). In this study, we investigate the outcomes and problems associated with tumor identification using 3-Tesla (3-T) MRI, which provides clearer images than ≤1.5-T MRI, in 115 patients who were initially diagnosed with CD. Before surgery, 31 macroadenomas (27%) and 54 microadenomas (47%) were identified by 3-T MRI, but pituitary adenoma was invisible on MRI in the remaining 30 cases (26%). The smallest tumor diameter amenable to a definitive diagnosis was 2 mm, and spoiled gradient-echo was the best sequence for diagnosing microadenomas. In 14 of 30 cases of MRI-invisible CD, the pituitary adenoma was identified during surgery. Nine of these 14 tumors that developed from outside the pituitary gland were retrospectively identified on MRI by comparison with surgical findings. The remaining 16 cases of MRI-invisible CD in which the pituitary adenoma was not identified during surgery involved partial hypophysectomy. Seven cases were hormonally remitted, but another nine cases experienced persistent disease after surgery. The sensitivity and specificity of the pituitary adenoma diagnosis in CD patients after the introduction of 3-T MRI were 80% and 100%, respectively. However, the sensitivity decreased to 72% when macroadenomas were excluded. Some adenomas associated with CD are still undetectable on 3-T MRI due to tumor size, location and intensity. However, sensitivity can be improved by monitoring tumors that develop outside the pituitary gland.

Transsphenoidal surgery in Cushing disease: The challenging microadenoma (Local experience)

Abstract Background: Cushing disease is uncommon challenging disease. The adenomas are usually small in size in most case making the disease diagnosis and management is sometimes difficult. In some cases, the tumor cannot be identified on imaging studies and in many cases the adenoma is eccentric in location adding more difficulties to the trans-sphenoid approach for excision of such tricky tumors. Object: to evaluate the challenge of diagnosis and trans-sphenoid surgery for ACTH pituitary microadenomas. Methods: 21 patients with ACTH secreting adenomas were involved in this retrospective study. All cases were operated up on via trans-sphenoid approach during the period from January 2009 till October 2015. All of them were microadenomas. All patients had obvious Cushing manifestations. In all cases magnetic resonance (MR) imaging and CT paranasal sinuses were performed. In this study: cases with macroadenomas and recurrent cases after previous trans-sphenoid approach or gamma knife radiosurgery were excluded. Results: Among the 21 patients; 14 were female and 7 weremale with age ranging from 21 to 44 years. The imaging study was positive for microadenoma in 18 patients while in 3 cases; no tumor was seen on the MRI imaging. All were operated via the trans-sphenoid approach (12 patients via the microscopic technique and other 9 patients via the endoscopic technique). The adenoma was successfully removed in 15 out of the 18 patients with evident adenoma on pre-operative MRI imaging while partial hypophysectomy were done in 5 cases without an evident adenoma on pre-operative MRI study or difficult adenoma identification. In one patient; the procedure was aborted because of sphenoid sinus abnormalities and the tumor was successfully removed via trans-cranial approach. Disease remission was achieved in 17 patients. In 4 patients; complete remission was not achieved and gamma knife radiosurgery was done after surgery. Disease progression occurred in two patients with initial remission and was treated gamma knife radiosurgery. 13 patients had an ACTH deficiency after surgery while other hormonal replacement therapy is needed in only 5 cases. CSF rhinorrhea occurred in 2 patients and was managed with transient lumbar drain without any subsequent morbidities. Transient diabetes insipidus occurred in 6 cases and was treated conservatively. Conclusions: The transsphenoidal approach ACTH secreting pituitary microadenomas is considered safe and effective for achieving disease remission despite the challenge of diagnosis and intra-operative tumor identification.

Analogs of Luteinizing Hormone-Releasing Hormone in the Treatment of Endometriosis

Agonists of luteinizing hormone-releasing hormone (LHRH) induce a reversible hypoestrogenic state through the down-regulation of LHRH receptors and desensitization of the pituitary. Since endometrial implants are estrogen sensitive, LHRH agonists have frequently been used for medical treatment of endometriosis. Nowadays, LHRH agonists can be considered in general as a second-line medical treatment for endometriosis-related symptoms, as oral therapy with dienogest is as effective and has fewer side effects. However, therapy with LHRH agonists for 3-6 months prior to in vitro fertilization remains the treatment of choice in patients with endometriosis, as it significantly increases pregnancy rates. LHRH agonists are used prior to surgery and as an adjuvant after an operation to prevent recurrence or prolong disease-free intervals. Adverse effects of LHRH agonists are due to hypoestrogenism and include hot flushes, vaginal dryness, loss of libido, sleep disturbances and a diminished bone density which limits the duration of their administration to 6 months. For long-term treatment, add-back of estrogen and/or progestin,/or progestin only with or without bisphosphonates, can be used, but existing studies only cover a 12-month period of treatment. LHRH antagonists competitively block the pituitary receptors for LHRH. Consequently, a partial pharmacological hypophysectomy with a reduction of the estrogen levels to a desired level is possible if LHRH antagonists are adequately dosed. As endometriotic implants require relatively high levels of estrogen, partially lower plasma levels of estrogens are sufficient to prevent the loss of bone density. A long-term treatment without add-back therapy is also possible.

Selective inferior petrosal sinus sampling without venous outflow diversion in the detection of a pituitary adenoma in Cushing’s syndrome

Conventional MRI may still be an inaccurate method for the non-invasive detection of a microadenoma in adrenocorticotropin (ACTH)-dependent Cushing's syndrome (CS). Bilateral inferior petrosal sinus sampling (BIPSS) with ovine corticotropin-releasing hormone (oCRH) stimulation is an invasive, but accurate, intervention in the diagnostic armamentarium surrounding CS. Until now, there is a continuous controversial debate regarding lateralization data in detecting a microadenoma. Using BIPSS, we evaluated whether a highly selective placement of microcatheters without diversion of venous outflow might improve detection of pituitary microadenoma. We performed BIPSS in 23 patients that met clinical and biochemical criteria of CS and with equivocal MRI findings. For BIPSS, the femoral veins were catheterized bilaterally with a 6-F catheter and the inferior petrosal sinus bilaterally with a 2.7-F microcatheter. A third catheter was placed in the right femoral vein. Blood samples were collected from each catheter to determine ACTH blood concentration before and after oCRH stimulation. In 21 patients, a central-to-peripheral ACTH gradient was found and the affected side determined. In 18 of 20 patients where transsphenoidal partial hypophysectomy was performed based on BIPSS findings, microadenoma was histologically confirmed. BIPSS had a sensitivity of 94% and a specificity of 67% after oCRH stimulation in detecting a microadenoma. Correct localization of the adenoma was achieved in all Cushing's disease patients. BIPSS remains the gold standard in the detection of a microadenoma in CS. Our findings show that the selective placement of microcatheters without venous outflow diversion might further enhance better recognition to localize the pituitary tumor.

Recurrent Cushing's Syndrome after Adrenal Autotransplantation

Adrenalectomy with adrenal autotransplantation used to be performed frequently for Cushing's disease in the past because of the limitations of conventional radiological techniques and the lack of adequate neurosurgical techniques. Today, however, bilateral adrenalectomy may be still required for selective patients with Cushing's syndrome when partial hypophysectomy has failed to control hypercortisolism or the source for ectopic ACTH syndrome could not be determined. Here, we report a case of recurrent Cushing's syndrome due to a pituitary adenoma, who was treated with bilateral adrenalectomy and autotransplantation for her Cushing's syndrome. Having determined pituitary adenoma as the cause of recurrent Cushing's syndrome after endocrinological investigations and imaging, we were able to treat the patient with transsphenoidal adenomectomy. We suggest that transsphenoidal resection of the adenoma rather than excision of the autotransplants and adrenal remnants should be the preferred treatment method for recurrent Cushing's disease.

Management of ACTH-secreting supradiaphragmatic adenomas

Supradiaphragmatic adrenocorticotropic hormone (ACTH) secreting pituitary adenomas are exceptionally encountered (14 cases previously described) and raise issues concerning their nosology and management. If surgery is the treatment of choice, the nature of surgical approach (craniotomy, transsphenoidal approach) remains controversial. To illustrate this issue, we presented two cases of supradiaphragmatic ACTH secreting pituitary adenomas successfully excised via a subfrontal approach. Both patients were female (20 and 41 years) and had a typical Cushing's syndrome. MRI revealed, in both cases, a suprasellar mass in contact with the pars tuberalis of the pituitary. In the first case, the patient underwent initially a transsphenoidal approach with negative exploration and subsequent partial hypophysectomy. One year later, the patient was operated on again via a subfrontal approach, allowing excision of a supradiaphragmatic adenoma and a complete cure of Cushing's disease. In the second case, the patient underwent initially a subfrontal approach and was definitely cured. In both cases, the diaphragma sellae was found to be intact and the pituitary stalk could be preserved. Postoperative MRI demonstrated a clearly visible intact pituitary stalk in conjunction with normal aspect of the pituitary. Supradiaphragmatic pituitary adenomas are most likely adenomas of the pituitary stalk with extra-axial development. Surgery remains the treatment of choice. Should the superior approach be preferred, the transsphenoidal-transtuberculum sellae approach may represent a viable alternative when performed by a well-trained surgical team. Surgery may be difficult, and drawbacks are non negligible, particularly in elderly patients. In these cases, stereotactic radiosurgery should receive more consideration.

Surgical Remission of Pituitary Adenomas Confined to the Neurohypophysis in Cushing’s Disease

Partial or total removal of the pituitary cures 60-80% of patients with Cushing's disease (CD) in whom an adenoma cannot be identified at surgery. Many patients who fail complete or partial hypophysectomy are cured by sellar and parasellar irradiation. As part of a series of prospective studies of CD, we identified 12 patients (34.5 +/- 19.9 yr; 11 females; four children) with tumors located completely within the neurohypophysis among 730 patients undergoing surgery for CD. The study was conducted at a tertiary referral center at a clinical research hospital. All 12 patients had clinical and biochemically defined CD. Tumor was visible at surgery in 11 patients; all 12 tumors were positive for ACTH by immunohistochemistry. Two tumors were excised at repeat surgery because of persistent hypercortisolism within 14 d of negative exploration of the adenohypophysis. There were no long-term complications. At follow-up of 71.9 +/- 34.2 months (range, 30-138 months), all patients are in remission of CD. Adult patients have had significant improvement in weight and body mass indices, with restoration of normal menses in all women. In the four pediatric patients, height, weight, and body mass indices have been restored toward normal by surgical remission of CD. Hypopituitarism or long-term neurohypophysial dysfunction has not occurred. We report a new subset of patients with CD, ACTH-secreting adenomas that arise wholly within the posterior lobe of the pituitary gland. In cases of CD in which an adenoma is not identified in the adenohypophysis and in patients with persistent hypercortisolism after complete or partial excision of the anterior lobe, tumor within the neurohypophysis should be considered; selective adenomectomy of a neurohypophyseal, ACTH-secreting tumor can produce long-term remission.

A risk-benefit assessment of octreotide in the treatment of acromegaly.

Acromegaly was the first pituitary disease to be recognised as a clinical entity, although initially it was not clear whether the eosinophilic adenomas causing pituitary enlargement were causative or just a manifestation of the syndrome itself. Following the documented clinical improvement of patients with acromegaly after partial hypophysectomy, it was proven that the pituitary adenomas were aetiological. The treatment of acromegaly has changed during the last decades; the introduction of the somatostatin (SMS) analogue octreotide has had major implications. Octreotide was the first SMS analogue to become available for clinical use. It is generally well tolerated, but is associated with the development of gallstones in 15 to 20% of patients. Other adverse effects include transient injection-site pain, abdominal, diarrhoea, gastritis (long term therapy) and loss of scalp hair. No long haematological or biochemical adverse effects have been reported. Desensitisation to the beneficial effects of octreotide therapy is highly unusual. A long-acting formulation of octreotide is being studied, and should be available by the end of 1997.

Failure of Partial Hypophysectomy as Definitive Treatment in Cushing's Disease Owing to Nodular Corticotrope Hyperplasia: Report of Four Cases.

Nodular corticotrope hyperplasia is a rare pathology causing Cushing's syndrome owing to a primary pituitary disease or ectopic CRH production. In this study, we evaluated the laboratory and pathological findings and results of transsphenoidal pituitary surgery in four patients with Cushing's disease. Dynamic tests of pituitary-adrenal function (dexamethasone suppression, metyrapone, CRH, and DDAVP tests) were done before and after transsphenoidal pituitary surgery. Plasma and total urinary cortisol, serum 11-deoxycortisol, and plasma ACTH were determined by RIA. Hormonal dynamic tests and radiologic studies were compatible with a pituitary ACTH source. The transsphenoidal surgery revealed the presence of corticotrope hyperplasia confirmed by immunoperoxidase stain and a preserved reticulum framework in the removed pituitary tissue of these four patients. The pituitary surgery led to a short period of improvement in two of the patients (1 and 4), a 3-yr remission in one patient (patient 2), and no improvement in one (patient 3). We conclude that although our patients appear to have inadequate suppression with high-dose dexamethasone, there is no way to diagnose this pathology presurgically, and that total hypophysectomy, bilateral adrenalectomy, and irradiation are the only alternatives for definitive treatment. A CRH-secreting ectopic tumor could not be found in our patients either before or after surgery in the follow-up period.

Pituitary-thyroid axis controls the final differentiation of the dorsal skeletal muscle in urodelan amphibians.

A histoenzymological study of the ATPase activity of myosin in the dorsal axis muscle (dorsalis trunci) was carried out on two species of urodelan amphibians: Pleurodeles waltlii, a euthyroid species with spontaneous metamorphosis and Ambystoma mexicanum, a neotenic hypothyroid species. P. waltlii and A. mexicanum underwent an operation after which cytological analysis of the remaining pituitary were carried out in parallel. The muscle phenotype of urodelan amphibians varies according to the thyroid status of the species. In euthyroid adults, IIA fibers are dominant whereas in hypothyroid adults, IIC fibers are dominant. The number of type IIB (fast) and type I fibers (slow) are similar in both species. Physiological or experimental modulation of the concentration of circulating thyroid hormones results in a modification of the muscle fiber type profile pertaining to the considered species. We found that pituitary (TSH) plays a dominant role in the maturation of type IIC fibers in both species. Moreover, it seems to modulate the development of IIA fibers in P. waltlii and that of IIB fibers in A. mexicanum. Its action is thus species specific. Through partial or total hypophysectomy experiments, we have been able to demonstrate the influence of the hypophysothyroidian axis on the appearance of the adult muscle phenotype during metamorphosis.

Early repeat surgery for persistent Cushing's disease.

The potential efficacy of early repeat transsphenoidal surgery for persistent Cushing's disease has not previously been examined. On 222 patients with no prior pituitary treatment and a preoperative diagnosis of Cushing's disease, 29 (13%) remained hypercortisolemic after an initial transsphenoidal pituitary exploration. Seventeen of these 29 patients underwent further surgery 7 to 46 days after the initial transsphenoidal approach in order to completely excise suspected residual tumor. Patients were followed for 4 to 84 months (mean +/- standard deviation, 34 +/- 25 months) to document sustained remission or recurrence of Cushing's disease (a urine free cortisol level > 90 micrograms/day was considered evidence of recurrence). Of the 17 patients with repeat surgery, 12 (71%) had resolution of hypercortisolism (morning plasma cortisol level < 5 micrograms/dl); however, in three of these 12, hypercortisolism recurred 5, 12, and 24 months later. In 14 patients a lesion that appeared to be a tumor was identified during the initial procedure or on histological examination. Of these, 12 had immediate resolution of hypercortisolism and nine are still in remission. Three patients, in whom no adenoma could be identified during the initial surgery or an examination of the partial hypophysectomy specimen from the initial surgery, had persistent Cushing's syndrome after the second operation. Seven (41%) of the 17 patients developed hypopituitarism requiring treatment with thyroid hormone, gonadal steroid, or vasopressin replacement. The low incidence of identification of an adenoma on computerized tomography or magnetic resonance images (three of 17 patients), the failure to find a corticotrophic adenoma during the initial surgery (10 of 17 patients), and the failure of these 17 patients to respond to the initial transsphenoidal surgery suggest that they may comprise a subset of patients who are more difficult to treat successfully with surgery than most patients with Cushing's disease. Despite that, early reoperation induced immediate remission of hypercortisolism in 71% of cases, but did so at the expense of a high risk of hypopituitarism. However, since the alternative treatments (such as radiation therapy, long-term drug therapy, or bilateral adrenalectomy) also have potential adverse effects, early reoperation deserves consideration for the management of persistent Cushing's disease, especially when an adrenocorticotrophic hormone-secreting adenoma was partially excised during the first surgery.

Preoperative Diagnosis of Lymphocytic Hypophysitis (Adenohypophysitis) Unresponsive to Short Course Dexamethasone

Lymphocytic hypophysitis (adenohypophysitis) is a rare lymphocytic infiltration of the pituitary gland that usually occurs during pregnancy. Because of its rarity, it has seldom been diagnosed preoperatively, and no trials of therapeutic treatment have been reported to date. We describe a 29-year-old woman with a pituitary mass and visual-field defects during pregnancy. The patient's pituitary profile revealed an abnormal thyroid axis and relatively low prolactin for her stage of pregnancy. This finding suggested adenohypophysitis, and the patient was given a trial course of dexamethasone. The progression of the visual-field defects, however, indicated that the steroids, both in dosage and duration, were not effective. Thus, the patient underwent a partial hypophysectomy for decompression. The pathology report confirmed adenohypophysitis, and steroids were continued for the remainder of the pregnancy, with slow resolution of the visual-field defects to normal. This report is the first case of adenohypophysitis where the diagnosis was suspected preoperatively, and a trial course of steroids was given. The steroids at the dosage and duration used were not effective. Further evaluation of the use of steroids in this disease is warranted.

Preoperative Diagnosis of Lymphocytic Hypophysitis (Adenohypophysitis) Unresponsive to Short Course Dexamethasone

Lymphocytic hypophysitis (adenohypophysitis) is a rare lymphocytic infiltration of the pituitary gland that usually occurs during pregnancy. Because of its rarity, it has seldom been diagnosed preoperatively, and no trials of therapeutic treatment have been reported to date. We describe a 29-year-old woman with a pituitary mass and visual-field defects during pregnancy. The patient's pituitary profile revealed an abnormal thyroid axis and relatively low prolactin for her stage of pregnancy. This finding suggested adenohypophysitis, and the patient was given a trial course of dexamethasone. The progression of the visual-field defects, however, indicated that the steroids, both in dosage and duration, were not effective. Thus, the patient underwent a partial hypophysectomy for decompression. The pathology report confirmed adenohypophysitis, and steroids were continued for the remainder of the pregnancy, with slow resolution of the visual-field defects to normal. This report is the first case of adenohypophysitis where the diagnosis was suspected preoperatively, and a trial course of steroids was given. The steroids at the dosage and duration used were not effective. Further evaluation of the use of steroids in this disease is warranted.

Low recurrence rate after partial hypophysectomy for prolactinoma: the predictive value of dynamic prolactin function tests.

To determine the factors influencing the outcome of transethmoidal partial hypophysectomy for suspected prolactinoma and the predictive value of pre and post-operative dynamic PRL function tests. A retrospective study of patients undergoing surgery for a suspected prolactinoma in Cardiff between 1979 and 1989. Eighty-two hyperprolactinaemic patients (75 women, seven men) diagnosed as having a prolactinoma on the basis of dynamic PRL function tests, radiological investigation and exclusion of other causes. TSH and PRL responses to domperidone (10 mg i.v.) and TRH (200 micrograms i.v.) measured preoperatively, 2 months post-operatively, and annually thereafter. CT scan performed preoperatively in 58 patients. Operative findings, including adenoma size, documented in each case. Forty-two patients (51%) had microadenomas (less than 10 mm), 37 (46%) had macroadenomas and in three no tumour was found at operation. Preoperatively, normal responses of both TSH (incremental rise less than 2.0 mU/l) and PRL (greater than 100% rise) to domperidone were observed in two patients only: both had an abnormal vascular supply to the pituitary rather than an adenoma. Serum PRL was normalized in the early post-operative period (less than 72 h; 'early cure') in 65 patients (79%). The highest early cure rate (96%, n = 26) was in patients with adenomas of 5-9 mm, lower rates being achieved for lesions of 10-19 mm (80%, n = 30), less than 5 mm (63%, n = 19) or greater than or equal to 20 mm (57%, n = 7). The early cure rate was strongly correlated with preoperative PRL, ranging from 100% in patients with PRL less than 1000 mU/l (n = 13) to zero in those with PRL greater than 10,000 mU/l. Dopamine agonist therapy of between 5 weeks and 4 years duration prior to surgery was associated with a significantly reduced early cure rate (60 vs 94%, P less than 0.02) in macroadenoma but not microadenoma patients. Recurrent hyperprolactinaemia during mean follow-up of 51.7 months occurred in eight patients (12%), in five cases within 2 months of surgery and in the others at 26, 48 and 50 months. Recurrence could not be predicted from any preoperative parameter, but a serum PRL greater than 150 mU/l 1-3 days following microadenomectomy was associated with early recurrence and probably indicates failed surgery. An abnormal response of TSH to domperidone was documented 2 months post-operatively in 11/60 patients with normal basal PRL, and preceded all three late recurrences. Of four patients with abnormal responses of both PRL and TSH at this time, two have relapsed to date. In carefully selected patients, partial hypophysectomy is an acceptable alternative to medical treatment for prolactinoma. Preoperatively, dynamic tests accurately identified those patients whose hyperprolactinaemia was non-adenomatous in origin and, post-operatively, identified a subgroup of patients at increased risk of late recurrence.

CASE OF BREAST CANCER ASSOCIATED WITH A PITUITARY ADENOMA

We report a case of breast cancer associated with a pituitary adenoma. The patient was a 44-year-old woman. She noticed signs of acromegaly about 22 years ago. At the age of 43, she found a painless mass of the left breast, and consulted our hospital. A diagnosis of breast cancer associated with acromegaly was made. After intra-arterial chemotherapy, extended radical mastectomy and partial hypophysectomy were performed sequentially. The breast cancer was in stage IIIb (T4bn0M0, scirrhous type), and was estrogen receptor positive. No recurrence was noted as of 2 years after surgery. The pituitary adenoma was eosinophilic.It is unknown if the development and growth of breast cancer is accelerated by human growth hormone. The incidence of breast cancer in persons with acromegaly may be more than expected.

Transsphenoidal microsurgery for Cushing disease. A report of 216 cases.

We report cumulative results of the transsphenoidal microsurgical treatment of Cushing disease in 221 patients: 173 patients had selective adenomectomy, 25 had total hypophysectomy, 6 had partial hypophysectomy, and 12 had exploration only. Five patients were excluded from analysis because intraoperative technical difficulties precluded exposure of the pituitary gland. The selection of candidates for transsphenoidal exploration was based on endocrinologic criteria. Magnetic resonance imaging was the preferred radiologic test. Selective venous sampling of adrenocorticotropic hormone further refined the diagnosis when endocrinologic and radiologic procedures were not definitive. Remission of disease was achieved in 164 of 216 (76%) patients analyzed (95% CI, 69 to 81). Among patients with histologic confirmation of adenomas, the percentage having remission was significantly higher (P less than 0.001) in patients with microadenomas than in patients with macroadenomas and in patients with intrasellar adenomas than in patients with extrasellar extension of their adenoma or perforation of the sellar floor by adenoma (P less than 0.001). Five patients had an ectopic source of adrenocorticotropic hormone secretion. Two patients had diffuse pituitary hyperplasia. Complications occurred in 9.3% of the patients, including two deaths that were apparently unrelated to surgery (CI, 5.4 to 13). The results indicate that transsphenoidal surgery is the preferred treatment for most patients with Cushing disease.