Changes in the Options for Management of Prolactin Secreting Pituitary Adenomas.

Objectives Initial therapy for the management of prolactinomas has long been maintained to be medical, consisting of a dopamine agonist. These therapies may have troublesome side effects, and some prolactinomas are resistant to medical therapy regarding lowering prolactin levels or shrinking the tumor. These issues have revived interest in surgery for prolactin-secreting adenomas as an early therapeutic option. We report our analysis of surgery for prolactin microadenomas in women, using the transsphenoidal endoscopic approach. Design We reviewed a contemporary series of 33 women (mean age = 31.8 years) with microprolactinomas who underwent early surgical intervention, which was a three-dimensional transnasal transsphenoidal endoscopic operation. Setting The study was conducted at a tertiary academic referral center for pituitary tumors. Main Outcome Measures Preoperative and postoperative prolactin. Results Overall, 28 patients had received preoperative dopamine agonists, 24 of these experienced a variety of drug-related side effects, and 4 had tumors that were resistant to lowering prolactin or tumor shrinkage. Preoperative prolactin levels averaged 90.3 ng/mL (range = 30.7-175.8 ng/mL). We observed a 94% normalization rate in postoperative prolactin (mean = 10.08 ng/mL, range = 0.3-63.1 ng/mL). During the follow-up (mean = 33.9 months), five patients had elevated prolactin; four required reinitiation of medical therapy, two had surgical reexploration, and none received radiation therapy. Complications included syndrome of inappropriate antidiuretic hormone secretion ( n = 3), transient diabetes insipidus ( n = 1), postoperative epistaxis ( n = 1), and fat graft site infection ( n = 1). Conclusion This review supports the consideration of transsphenoidal surgery as an early intervention for some women with prolactin-secreting microadenoma. Indications include significant side effects of medical therapy and tumors that do not respond to standard medical management.

Optimizing pre-, intra-, and postoperative management of patients with sellar pathology undergoing transsphenoidal surgery.

OBJECTIVE: Perioperative management of patients with sellar lesions is complex, requiring input from a multidisciplinary team of specialists for ongoing management of both endocrinological and neurosurgical issues. Here, the authors reviewed the experience of a single multidisciplinary center over 10 years to identify key postoperative practices that ensure positive outcomes for patients with sellar lesions who undergo transsphenoidal surgery. METHODS: The authors performed a retrospective review of all transsphenoidal operations carried out by the senior author at a single center from April 2008 through November 2018. They included only adult patients and recorded perioperative management. They also reviewed the evolution of clinical practices for perioperative care at their institution to identify strategies for ensuring positive patient outcomes, and they reviewed the literature on select related topics. RESULTS: In total, 1023 operations in 928 patients were reviewed. Of these, 712 operations were for pituitary adenomas (69.6%), and 122 were for Rathke cleft cysts (11.9%). The remainder included operations for craniopharyngiomas (3.6%), arachnoid cysts (1.7%), pituitary tumor apoplexy (1.0%), and other sellar pathologies (12.2%). Among the reviewed operations, the median hospital stay was 3 days (IQR 2-3). Patient management details during the pre-, intra-, and postoperative periods were identified, including both shared characteristics of all patients undergoing transsphenoidal surgery and unique characteristics that are specific to certain lesion types or patient populations. CONCLUSIONS: Patients with sellar lesions who undergo transsphenoidal surgery require complex, multidisciplinary perioperative care to monitor for common adverse events and to improve outcomes, but there is a dearth of high-quality evidence guiding most perioperative practices. Here, the authors reviewed practices at their institution across more than 1000 transsphenoidal operations that may help ensure successful patient outcomes.

Diabetes Insipidus After Endoscopic Transsphenoidal Surgery.

BACKGROUND: Diabetes insipidus (DI) is a recognized transient or permanent complication following transsphenoidal surgery (TSS) for pituitary tumors. OBJECTIVE: To describe significant experience with the incidence of DI after TSS, identifying predictive characteristics and describing our diagnosis and management of postoperative DI. METHODS: A retrospective analysis was performed of 700 patients who underwent endoscopic TSS for resection of pituitary adenoma (PA), Rathke cleft cyst (RCC), or craniopharyngioma. Inclusion criteria included at least 1 wk of follow-up for diagnosis of postoperative DI. Permanent DI was defined as DI symptoms and/or need for desmopressin more than 1 yr postoperatively. All patients with at least 1 yr of follow-up (n = 345) were included in analyses of permanent DI. Multivariable logistic regression models were constructed to identify predictors of transient or permanent postoperative DI. RESULTS: The overall rate of any postoperative DI was 14.7% (103/700). Permanent DI developed in 4.6% (16/345). The median follow-up was 10.7 mo (range: 0.2-136.6). Compared to patients with PA, patients with RCC (odds ratio [OR] = 2.2, 95% CI: 1.2-3.9; P = .009) and craniopharyngioma (OR = 7.0, 95% CI: 2.9-16.9; P ≤ .001) were more likely to develop postoperative DI. Furthermore, patients with RCC (OR = 6.1, 95% CI: 1.8-20.6; P = .004) or craniopharyngioma (OR = 18.8, 95% CI: 4.9-72.6; P ≤ .001) were more likely to develop permanent DI compared to those with PA. CONCLUSION: Although transient DI is a relatively common complication of endoscopic and microscopic TSS, permanent DI is much less frequent. The underlying pathology is an important predictor of both occurrence and permanency of postoperative DI.

Surgical and radiosurgical treatment strategies for Cushing's disease.

INTRODUCTION: Cushing's disease (CD) is rare disorder that should be adequately managed to optimize long-term prognosis. Treatment of CD is multidisciplinary and often includes surgical resection, adjuvant stereotactic radiosurgery (SRS), and medical treatment. Here we review surgical and radiosurgical treatment strategies for ACTH producing pituitary adenomas. METHODS: A comprehensive literature review was carried out to review remission and recurrence rates, and complications of surgical and SRS treatments of ACTH producing pituitary adenomas. RESULTS: Surgical resection plays a central role in the management of ACTH secreting pituitary adenomas and usually allows rapid endocrine remission that ranges from 69 to 90%. The most common complications after resection include some degree of new hypopituitarism, diabetes insipidus and CSF leak. Devastating complications, such as injury of vascular and neural structures, are very rare. Surgeon experience and adequate pre-operative imaging are important for safe and successful surgery. Endocrine recurrence rates after resection range from 9 to 30%. SRS is often employed for incompletely resected adenomas. Endocrine remission after SRS ranges from 35 to 72%. The most common complication of SRS is new anterior pituitary gland deficiency. Recurrence rates after GKRS range from 18 to 24%. CONCLUSIONS: Transsphenoidal resection of ACTH producing pituitary adenoma is a safe and highly effective procedure for CD in experienced hands. Radiosurgery is more frequently used as treatment of residual and recurrent adenoma and persistent CD. Long-term endocrine and imaging follow-up is important as delayed recurrences and hypopituitarism are not infrequent.

Prolactinomas and nonfunctioning adenomas: preoperative diagnosis of tumor type using serum prolactin and tumor size.

OBJECTIVE: Prolactinoma and nonfunctioning adenoma (NFA) are the most common sellar pathologies, and both can present with hyperprolactinemia. There are no definitive studies analyzing the relationship between the sizes of prolactinomas and NFAs and the serum prolactin level. Current guidelines for serum prolactin level cutoffs to distinguish between pathologies are suboptimal because they fail to consider the adenoma volume. In this study, the authors attempted to describe the relationship between serum prolactin level and prolactinoma volume. They also examined the predictive value that can be gained by considering tumor volume in differentiating prolactinoma from NFA and provide cutoff values based on a large sample of patients. METHODS: A retrospective analysis of consecutive patients with prolactinomas (n = 76) and NFAs (n = 217) was performed. Patients were divided into groups based on adenoma volume, and the two pathologies were compared. RESULTS: A strong correlation was found between prolactinoma volume and serum prolactin level (r = 0.831, p < 0.001). However, there was no significant correlation between NFA volume and serum prolactin level (r = -0.020, p = 0.773). Receiver operating characteristic curve analysis of three different adenoma volume groups was performed and resulted in different serum prolactin level cutoffs for each group. For group 1 (≤ 0.5 cm3), the most accurate cutoff was 43.65 µg/L (area under the curve [AUC] = 0.951); for group 2 (> 0.5 to 4 cm3), 60.05 µg/L (AUC = 0.949); and for group 3 (> 4 cm3), 248.15 µg/L (AUC = 1.0). CONCLUSIONS: Prolactinoma volume has a significant impact on serum prolactin level, whereas NFA volume does not. This finding indicates that the amount of prolactin-producing tissue is a more important factor regarding serum prolactin level than absolute adenoma volume. Hence, volume should be a determining factor to distinguish between prolactinoma and NFA prior to surgery. Current serum prolactin threshold level guidelines are suboptimal and cannot be generalized across all adenoma volumes.

Outcomes After Repeat Transsphenoidal Surgery for Recurrent Cushing Disease: Updated.

BACKGROUND: Transspheniodal surgery (TSS) for Cushing disease (CD) is considered the first-line treatment; however, reported recurrence rates are high. OBJECTIVE: To systemically review indications and outcomes for repeat TSS in recurrent CD. METHODS: Retrospective review of patients undergoing TSS from 2008 to 2018 was performed. Patients undergoing repeat TSS for clinical and/or biochemically recurrent CD with follow-up at least 12 mo postoperatively were included. These data were analyzed in our "current cohort" and combined with our previously published data in a "combined cohort." RESULTS: The current cohort of patients undergoing operations from 2008 to 2018 with repeat surgery following a prior operation included 15 patients. Pathology at the time of first operation was positive for adrenocortiotrophic hormone (ACTH) adenoma in 13/15 (86.7%) and 9/15 (60%) had evidence of recurrence after a previous surgical procedure on preoperative magnetic resonance imaging (MRI). Remission was achieved immediately postoperatively in 13/15 (86.7%). Over an average follow-up of 34.7 mo (range: 12-116), 11/15 (68.8%) achieved persistent remission. When combined with the historical cohort that underwent an operation during 1992-2006, 44/51 (86.3%) patients had a prior operation demonstrating ACTH adenoma and 35/51 (68.6%) had evidence of recurrent disease on preoperative MRI. Thirty-five (68.6%) patients went into remission immediately postoperatively. Thirty one (60.8%) had continued remission at most recent reported follow-up. CONCLUSION: Recurrent CD can be a therapeutic challenge; however, these data demonstrate that in many patients repeat surgery can be an effective and safe next step prior to radiation or medical therapy.

A practical method for prevention of readmission for symptomatic hyponatremia following transsphenoidal surgery.

INTRODUCTION: Patients undergoing transsphenoidal pituitary surgery (TSS) are at risk for several serious complications, including the syndrome of inappropriate antidiuretic hormone and subsequent hyponatremia. OBJECTIVE: In this study, we examined the effect of 1 week of post-discharge fluid restriction to 1.0 L daily on rates of post-operative readmission for hyponatremia. METHODS: We retrospectively analyzed all patients undergoing TSS from 2008 to 2014 and prospectively recorded patient data from 2015 to 2017. Patients were divided into a control cohort (2008-2014), who were discharged with instructions to drink to thirst; and an intervention cohort (2015-2017) who were instructed to drink less than 1.0 L daily for 1 week post-operatively. RESULTS: This study included 788 patients; 585 (74.2%) in the control cohort and 203 (25.8%) in the intervention cohort. Overall, 436 (55.3%) were women, the median age was 47 (range 15-89), and average BMI was 29.4 kg/m2 (range 17.7-101.7). Patients were relatively well matched. Of patients in the intervention group, none was readmitted for hyponatremia (0/203), compared to 3.41% (20/585) in the control group (p = 0.003). Patients in the intervention group also had significantly higher post-operative week one sodium levels (140.1 vs 137.5 mEq/L; p = 0.002). No fluid balance complications occurred in patients who followed this protocol. CONCLUSION: Hyponatremia can be a life-threatening complication of TSS, and prevention of readmission for hyponatremia can help improve patient safety and decrease costs. Mandatory post-discharge fluid restriction is a simple and inexpensive intervention associated with decreased rates of readmission for hyponatremia and normal post-operative sodium levels.

A Benchmark for Preservation of Normal Pituitary Function After Endoscopic Transsphenoidal Surgery for Pituitary Macroadenomas.

INTRODUCTION: We report a contemporary consecutive series of 80 patients operated on for benign pituitary macroadenomas, followed endocrinologically for at least 3 months postoperatively. These patients were systematically evaluated preoperatively by high-resolution magnetic resonance imaging designed to detect the position of normal gland relative to the lesion. The rate of preservation of normal pituitary was critically analyzed using this strategy combined with endoscopic transsphenoidal resection. METHODS: This is a retrospective review of 46 women and 34 men with mean postoperative follow-up of 14 months (range, 3-30 months). The lesions encountered consisted of 80 pituitary macroadenomas (55 nonfunctioning, 18 acromegaly, 5 prolactinoma, 1 Cushing, one thyroid-stimulating hormone). Pituitary endocrine status was determined preoperatively and at most recent follow-up, and categorized as normal or impaired, based on laboratory studies showing new hormone deficiency or the need for pituitary hormone replacement therapy. RESULTS: Fifty-three patients (66.3%) had normal endocrine function preoperatively; 3 (5.7%) had loss of function postoperatively (1 transient). Twenty-seven patients (33.8%) had impaired function preoperatively; postoperatively 20 (74.1%) were unchanged, and 5 (18.5%) were worse; 2 (7.4%) recovered lost pituitary function. Of 80 patients undergoing resection, 5 (6.3%) had worsened pituitary function postoperatively. Patients with recurrent lesions (n = 5, 6.3%) and those presenting with pituitary tumor apoplexy (n = 5, 6.3%) were more likely to become further impaired. Other endocrine sequelae included 2 patients with permanent postoperative diabetes insipidus and 3 with transient symptomatic syndrome of inappropriate secretion of antidiuretic hormone. CONCLUSIONS: The preservation and restoration of hormonal function are essential to assessing the outcome of surgery and to the patient's quality of life. Careful analysis of the anatomy of the pituitary lesions and their effect on the anatomy and physiology of the pituitary gland are crucial to success and allow modern technological advances to provide fewer complications of therapy and improved outcomes for our patients. The benchmarks provided in this article are a stimulus for even better results in the future as we take advantage of technical and conceptual advances and the benefits of multidisciplinary collaboration.

Headache in Patients With Pituitary Lesions: A Longitudinal Cohort Study.

BACKGROUND: Headache is a presenting feature in 37% to 70% of patients with pituitary tumor. Other pituitary lesions may also present with headache, and together these lesions account for about 20% of all primary brain lesions. Although pituitary lesions have been associated with headache, the exact nature of the relationship remains undefined. It is not always clear whether the presenting headache is an unrelated primary headache, a lesion-induced aggravation of a preexisting primary headache, or a separate secondary headache related to the lesion. OBJECTIVE: To characterize headache in patients referred to a multidisciplinary neuroendocrine clinic with suspected pituitary lesions and to assess changes in headache in those who underwent surgery. METHODS: We used a self-administered survey of headache characteristics completed by patients upon presentation and after any pituitary surgical procedure. RESULTS: One hundred thirty-three participants completed the preoperative questionnaire (response rate of 99%). The overall prevalence of headache was 63%. Compared to patients without headache, the group with headache was more likely to be female (P = .001), younger (P = .001), and to have had a prior headache diagnosis (P < .001). Seventy-two percent of patients reported headache localized to the anterior region of the head. Fifty-one patients with headache underwent transsphenoidal pituitary surgery. Headache was not associated with increased odds of having surgery (odds ratio, 0.90). At 3 months, 81% of surgically treated patients with headache who completed the postoperative questionnaire (21/26) reported improvement or resolution of headaches. No patient who completed the postoperative questionnaire (44/84) reported new or worsened headache. CONCLUSION: Frequent, disabling headaches are common in patients with pituitary lesions referred for neuroendocrine consultation, especially in younger females with a preexisting headache disorder. Surgery in this group was associated with headache improvement or resolution in the majority and was not found to cause or worsen headaches. Suggestions for revision of the International Classification of Headache Disorders diagnostic criteria pertaining to pituitary disorders are supported by these findings.

Post-operative Streptococcus pneumoniae meningoencephalitis complicating surgery for acromegaly in an identical twin.

This case report provides provocative and useful data regarding two aspects of acromegaly and its management. The patient, who is one of a pair of identical twins, has no known hereditary, genetic or otherwise potentially etiologic factors as compared to her unaffected sister. Secondly, transsphenoidal surgery, which was ultimately successful, was complicated by pneumococcal meningitis, an unusual event with only four previously reported patients, three of whom ended in death or major neurologic deficits. In this case, a 57-year-old woman gradually developed classical signs and symptoms of acromegaly while her identical twin sister remained normal with no evidence of endocrine disease. Endoscopic transsphenoidal surgery was complicated by the development of meningitis 25 days after surgery. This was controlled following a difficult hospital course. Streptococcus pneumoniae meningoencephalitis is a rare but life-threatening complication of transsphenoidal surgery. A high index of suspicion for incipient meningitis should be maintained when patients present with severe headache and increased intracranial pressure, even if they initially lack the typical symptoms and signs. Immediate and aggressive treatment is necessary to avoid significant neurologic deficit.

The current status of endoscopy in transsphenoidal surgery: an international survey.

OBJECTIVE: A survey-based study was designed to assess opinions related to transsphenoidal endoscopy, to evaluate the current global attitudes of neurosurgeons regarding the use of this procedure, and to solicit basic data from key institutions worldwide, with the advantage that large series of cases become available for analysis. METHODS: A web-based multi-item questionnaire was distributed to the surgical departments of 393 neurosurgical centers by means of an invitation e-mail. The questionnaire was composed of 2 sections: section 1 focused on the surgical technique for pituitary adenomas (standard technique), and section 2 concentrated on surgery for skull base tumors (extended technique). Each section was composed of 2 parts: multiple choice questions and free textual responses. RESULTS: From a total of 393 neurosurgical centers, from 23 countries, that received the questionnaire, 87 of them (22%) submitted complete or incomplete responses. The surgical procedure, in 60 cases had been performed by a neurosurgeon, in 53 cases by a neurosurgeon and an otolaryngologist, and in 4 cases by an otolaryngologist only. The endoscope (2- and 3-dimensional) was used in 85.2% of transsphenoidal procedures versus the microscope in 14.8% of cases. The endonasal route was used for approach in 93.2% versus the sublabial route in 6.8% of cases. Computer-guided navigation was used by survey population in 71 cases, micro-Doppler in 51 cases, and Cavitron Ultrasonic Surgical Aspirator in 43 cases. Several hundreds of extrasellar tumors were operated using the extended technique. CONCLUSIONS: Transsphenoidal endoscopy for pituitary and anterior skull base tumors has become established as a routine method of dealing with a variety of lesions. The level of interest in the neurosurgical surgery community is reflected by the geometric expansion of contributions to the literature on endoscopic surgery.

Recognizing the clinical manifestations of acromegaly: case studies.

PURPOSE: To present case studies of a 36-year-old woman and a 73-year-old man who presented with the syndrome of acromegaly, and to provide primary care nurse practitioners (NPs) with the understanding of the clinical and laboratory features needed for early recognition and treatment of this fascinating disease. DATA SOURCES: A comprehensive review of published literature on acromegaly is presented. The findings discussed include the history, physical examination, and diagnostic studies of two patients presenting in different ways. They both saw multiple healthcare providers, and had symptoms and signs eventually leading to the diagnosis of acromegaly. CONCLUSIONS: Acromegaly is the result of excessive amounts of growth hormone (GH) and insulin-like growth factor type 1 (IGF-1), almost always caused by a benign adenoma of the pituitary gland. This leads to coarse facial features, soft tissue swelling (including the tongue), enlargement of the hands and feet, respiratory problems, hypertension, diabetes mellitus, carpal tunnel syndrome, and osteoarthritis. Early recognition and appropriate referral can reverse some of the signs and symptoms over time, and lead to decreased mortality and a markedly improved quality of life. IMPLICATIONS FOR PRACTICE: These cases exemplify the challenges faced by NPs and other healthcare providers in diagnosing patients with acromegaly.

Early recognition of Cushing's disease: a case study.

PURPOSE: To present a case study of a 34-year-old woman with Cushing's disease and provide nurse practitioners (NPs) with the understanding of the clinical presentation needed for early recognition and treatment of the disease. DATA SOURCES: A comprehensive review of published literature on Cushing's disease. Findings from history, physical examination, and diagnostic studies of a woman presenting to primary care NPs, physicians and other healthcare providers with multiple symptoms of Cushing's disease. CONCLUSIONS: Cushing's disease is the result of the pituitary gland producing excess amounts of adrenocorticotropic hormone (ACTH) causing the overproduction of cortisol. The disease is fairly rare and is seen mostly in women. Common chief complaints include increased facial hair, weight gain, amenorrhea, changes in the face, neck, and abdomen, with muscle wasting of the lower extremities. Untreated, diabetes mellitus and hypertension can occur and increase the patient's morbidity and mortality. Early recognition and appropriate referral can reverse the signs and symptoms over time and lead to a significantly improved quality of life. IMPLICATIONS FOR PRACTICE: This case presented the challenges faced by NPs and physicians in diagnosing patients with Cushing's disease.

Management of pituitary tumors in pregnancy.

Successful pregnancy and delivery is dependent upon normal function of the pituitary gland. Benign tumors of the pituitary are relatively common and may interfere with normal pregnancy in a variety of ways. Symptoms related to pituitary tumors can include headache, fatigue, and visual loss. Some may present dramatically with pituitary tumor apoplexy, mimicking subarachnoid hemorrhage, meningitis, or myocardial infarction. In this article, the types of tumors likely to become symptomatic during pregnancy are reviewed. The various options of management are determined by the stage of pregnancy and whether there is visual loss or other signs of mass effect. Management options include close observation, medical therapy, or surgical removal of the tumor. Decision making for symptomatic adenomas during pregnancy is illustrated by two representative case reports.

The diagnosis and management of lymphocytic hypophysitis.

Although a relatively rare phenomenon, lymphocytic hypophysitis can represent a difficult diagnostic and therapeutic challenge. This condition was initially thought to be an autoimmune phenomenon occurring primarily in women in the postpartum state. It is now recognized as a disorder that can affect both men and women over a rather large age range, from young adults to the elderly, and may be linked to a number of autoimmune phenomena. We have reviewed the literature on lymphocytic hypophysitis, and added the detailed analysis of seven cases of presumed lymphocytic hypophysitis from our own experience. The case studies demonstrate the wide spectrum of manifestations of this disorder, the differential diagnosis and the rationale and the nuances of treatment. Diagnostic studies, including laboratory evaluation and the characteristic MRIs, are reviewed. The histopathology and results of special stains are also presented, emphasizing the characteristic pathologic findings in this spectrum of pituitary disease. Our experience and that of others demonstrates that this condition has a characteristic presentation - that is, headache, hypopituitarism and diabetes insipidus. When significant mass effect is present, suprasellar and parasellar extension may produce visual loss and/or diplopia. Treatment strategies and outcomes are given for each of the seven patients. Corticosteroids are recommended as first-line management, and are usually successful. Relapses requiring additional therapy, however, are not uncommon. In such cases, trans-sphenoidal surgery, other more aggressive forms of medical therapy and rarely, radiosurgery can also be employed. Lymphocytic hypophysitis is a challenging entity. With accurate diagnosis and sequential, expertly managed therapeutic measures, it can be controlled. Continued surveillance of the patients is essential, as relapses may occur.

Perioperative management of patients undergoing transsphenoidal pituitary surgery.

BACKGROUND: The sellar and parasellar region is a confluence of several critical anatomical structures from various physiological systems located in close proximity to one another. Patients with pathology in this critical region of the central nervous system therefore make up a unique subset of neurosurgical patients that require careful preoperative and postoperative attention to numerous management details involving neurological, visual, and neuroendocrine function. A thorough understanding of the underlying anatomical and physiological principles of each of these systems, as well as the medical and surgical nuances involved in each case, is required to provide optimized management for patients with pituitary pathology. In this review, we discuss the major preoperative and postoperative considerations in patients undergoing resection for pituitary lesions in the modern era of transsphenoidal surgery.