ABSTRACT
CONTEXT: Confirming a diagnosis of Cushing disease (CD) remains challenging, yet is critically important before recommending transsphenoidal surgery for adenoma resection. OBJECTIVE: To describe predictive performance of preoperative biochemical and imaging data relative to post-operative remission and clinical characteristics in patients with presumed CD. DESIGN, SETTING, PATIENTS, INTERVENTIONS: Patients (nâ =â 105; 86% female) who underwent surgery from 2007 through 2020 were classified into 3 groups: group A (nâ =â 84) pathology-proven ACTH adenoma; group B (nâ =â 6) pathology-unproven but with postoperative hypocortisolemia consistent with CD; and group C (nâ =â 15) pathology-unproven, without postoperative hypocortisolemia. Group A + B were combined as confirmed CD and group C as unconfirmed CD. MAIN OUTCOMES: Group A + B was compared with group C regarding predictive performance of preoperative 24-hour urinary free cortisol (UFC), late night salivary cortisol (LNSC), 1-mg dexamethasone suppression test (DST), plasma ACTH, and pituitary magnetic resonance imaging (MRI). RESULTS: All groups had a similar clinical phenotype. Compared with group C, group A + B had higher mean UFC (Pâ <â 0.001), LNSC (Pâ =â 0.003), DST (Pâ =â 0.06), and ACTH (Pâ =â 0.03) and larger MRI-defined lesions (Pâ <â 0.001). The highest accuracy thresholds were: UFC 72 µg/24 hours; LNSC 0.122 µg/dL, DST 2.70 µg/dL, and ACTH 39.1 pg/mL. Early (3-month) biochemical remission was achieved in 76/105 (72%) patients: 76/90(84%) and 0/15(0%) of group A + B vs group C, respectively, Pâ <â 0.0001. In group A + B, nonremission was strongly associated with adenoma cavernous sinus invasion. CONCLUSIONS: Use of strict biochemical thresholds may help avoid offering transsphenoidal surgery to presumed CD patients with equivocal data and improve surgical remission rates. Patients with Cushingoid phenotype but equivocal biochemical data warrant additional rigorous testing.
Subject(s)
Adrenocorticotropic Hormone/blood , Hydrocortisone/analysis , Hypophysectomy , Pituitary ACTH Hypersecretion/diagnosis , Pituitary Gland/pathology , Adrenocorticotropic Hormone/metabolism , Adult , Aged , Biopsy , Female , Humans , Hydrocortisone/metabolism , Magnetic Resonance Imaging , Male , Middle Aged , Pituitary ACTH Hypersecretion/blood , Pituitary ACTH Hypersecretion/surgery , Pituitary ACTH Hypersecretion/urine , Pituitary Gland/diagnostic imaging , Pituitary Gland/metabolism , Pituitary Gland/surgery , Predictive Value of Tests , Preoperative Period , Reference Values , Retrospective Studies , Saliva/chemistryABSTRACT
PURPOSE: To evaluate the impact of using consistent complication-avoidance protocols in patients undergoing endoscopic pituitary adenoma surgery including techniques for avoiding anosmia, epistaxis, carotid artery injury, hypopituitarism, cerebrospinal fluid leaks and meningitis. METHODS: All patients undergoing endoscopic adenoma resection from 2010 to 2020 were included. Primary outcomes included 90-day complication rates, gland function outcomes, reoperations, readmissions and length of stay. Secondary outcomes were extent of resection, short-term endocrine remission, vision recovery. RESULTS: Of 514 patients, (mean age 51 ± 16 years; 78% macroadenomas, 19% prior surgery) major complications occurred in 18(3.5%) patients, most commonly CSF leak (9, 1.7%) and meningitis (4, 0.8%). In 14 of 18 patients, complications were deemed preventable. Four (0.8%) had complications with permanent sequelae (3 before 2016): one unexplained mortality, one stroke, one oculomotor nerve palsy, one oculoparesis. There were no internal carotid artery injuries, permanent visual worsening or permanent anosmia. New hypopituitarism occurred in 23/485(4.7%). Partial or complete hypopituitarism resolution occurred in 102/193(52.8%) patients. Median LOS was 2 days; 98.3% of patients were discharged home. Comparing 18 patients with major complications versus 496 without, median LOS was 7 versus 2 days, respectively p < 0.001. Readmissions occurred in 6%(31/535), mostly for hyponatremia (18/31). Gross total resection was achieved in 214/312(69%) endocrine-inactive adenomas; biochemical remission was achieved in 148/209(71%) endocrine-active adenomas. Visual field or acuity defects improved in 126/138(91.3%) patients. CONCLUSION: This study suggests that conformance to established protocols for endoscopic pituitary surgery may minimize complications, re-admissions and LOS while enhancing the likelihood of preserving gland function, although there remains opportunity for further improvements.
Subject(s)
Adenoma , Hypopituitarism , Pituitary Neoplasms , Adenoma/surgery , Adult , Aged , Endoscopy , Humans , Middle Aged , Pituitary Neoplasms/surgery , Postoperative Complications , Retrospective Studies , Treatment OutcomeABSTRACT
INTRODUCTION: Longer lifespan and newer imaging protocols have led to more older adults being diagnosed with pituitary adenomas. Herein, we describe outcomes of patients ≥ 65 years undergoing endoscopic adenoma removal. To address selection criteria, we also assess a conservatively managed cohort. METHODS: A retrospective analysis of 90-day outcomes of patients undergoing endoscopic pituitary adenomectomy from 2010 to 2019 by a neurosurgical/ENT team was performed. Tumor subtype, cavernous sinus invasion, extent of resection/early remission, endocrinology outcomes, complications, re-operations and readmissions were analyzed. A comparator cohort ≥ 65 years undergoing clinical surveillance without surgery was also analyzed. RESULTS: Of 468 patients operated on for pituitary adenoma, 123 (26%) were ≥ 65 years (range 65-93 years); 106 (86.2%) had endocrine-inactive adenomas; 18 (14.6%) had prior surgery. Of 106 patients with endocrine-inactive adenomas, GTR was achieved in 70/106 (66%). Of 17 patients with endocrine-active adenomas, early biochemical remission was: Cushing's 6/8; acromegaly 1/4; prolactinomas 1/5. Gland function recovery occurred in 28/58 (48.3%) patients with various degrees of preoperative hypopituitarism. New anterior hypopituitarism occurred in 3/110 (2.4%) patients; permanent DI in none. Major complications in 123 patients were: CSF leak 2 (1.6%), meningitis 1 (0.8%), vision decline 1 (0.8%). There were no vascular injuries, operative hematomas, anosmia, deaths, MIs, or thromboembolic events. Median length of stay was 2 days. Readmissions occurred in 14/123 (11.3%) patients, 57% for delayed hyponatremia. Intra-cohort analysis by age (65-69, 70-74, 75-79, ≥ 80 years) revealed no outcome differences. Cavernous sinus invasion (OR 7.7, CI 1.37-44.8; p = 0.02) and redo-surgery (OR 8.5, CI 1.7-42.8; p = 0.009) were negative predictors for GTR/NTR. Of 105 patients evaluated for presumed pituitary adenoma beginning in 2015, 72 (69%) underwent surgery, 8 (7%) had prolactinomas treated with cabergoline and 25 (24%) continue clinical surveillance without surgery, including two on new hormone replacement. CONCLUSION: This study suggests that elderly patients carefully selected for endoscopic adenoma removal can have excellent short-term outcomes including high resection rates, low complication rates and short length of stay. Our experience supports a multidisciplinary approach and the concept of pituitary centers of excellence. Based on our observations, approximately 25% of elderly patients with pituitary adenomas referred for possible surgery can be monitored closely without surgery.
Subject(s)
Adenoma/surgery , Pituitary Neoplasms/surgery , Adenoma/physiopathology , Aged , Aged, 80 and over , Headache/physiopathology , Humans , Magnetic Resonance Imaging , Neurosurgical Procedures/methods , Pituitary Neoplasms/physiopathology , Retrospective Studies , Visual Acuity/physiologyABSTRACT
The original version of this article unfortunately contained errors in legend numbers of Figure 2 caption.
ABSTRACT
BACKGROUND: Parasellar meningiomas involving the cavernous sinus and Meckel's cave pose a management challenge because of invasion around neurovascular structures and the pituitary gland. The management options range from aggressive resection to focused radiotherapy alone. We present a strategy for these tumors that includes endonasal bony decompression, partial tumor removal, and stereotactic radiotherapy (SRT) in select cases. METHODS: The tumor location, previous treatments, cranial neuropathies, pituitary dysfunction, tumor control rates, use of stereotactic radiosurgery, SRT, and complications were retrospectively evaluated. RESULTS: Twenty patients (age range, 43-81 years; 65% women; 90% with World Health Organization grade I; median follow-up, 57 months; 14 without previous debulking and RT; 6 with previous debulking and RT) underwent endonasal bony decompression and partial tumor removal. The most common tumor locations were cavernous sinus (95%), Meckel's cave (95%), sella (75%), petroclival (60%), and optic canal/orbit (30%). Three patients with large meningiomas underwent staged transcranial and endonasal debulking. Of the 14 patients without previous debulking and RT, 11 had undergone postoperative SRT, with tumor shrinkage in 3 (27%). At the last follow-up examination, for these 14 patients and the 6 patients who had undergone previous surgery and RT, tumor control was 100% and 33% (P < 0.001) and the cranial neuropathies had improved in 57% and 33%, respectively. Major complications occurred in 2 patients: a permanent sixth cranial nerve palsy and cerebrospinal fluid leakage requiring reoperation. CONCLUSIONS: Endonasal bony decompression and selective tumor removal, followed by SRT, appears to be a reasonable treatment option for most previously untreated parasellar meningiomas. For patients who have undergone previous debulking and RT, new targeted treatment strategies are needed.
Subject(s)
Cavernous Sinus/surgery , Cytoreduction Surgical Procedures/methods , Decompression, Surgical/methods , Meningeal Neoplasms/surgery , Meningioma/surgery , Neuroendoscopy/methods , Skull Base Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Cavernous Sinus/diagnostic imaging , Cranial Nerve Diseases/etiology , Female , Humans , Male , Meningeal Neoplasms/complications , Meningeal Neoplasms/diagnostic imaging , Meningeal Neoplasms/radiotherapy , Meningioma/complications , Meningioma/diagnostic imaging , Meningioma/radiotherapy , Middle Aged , Nasal Cavity , Natural Orifice Endoscopic Surgery , Pituitary Diseases/etiology , Postoperative Complications/epidemiology , Radiosurgery , Retrospective Studies , Skull Base Neoplasms/complications , Skull Base Neoplasms/diagnostic imaging , Skull Base Neoplasms/radiotherapyABSTRACT
CONTEXT: Primary bilateral macronodular adrenal hyperplasia (BMAH) is a rare form of adrenal Cushing syndrome conventionally treated with adrenalectomy. Medical treatment is often reserved for patients not eligible for surgery. However, to date there have been few studies about the efficacy of mifepristone for the treatment of BMAH associated with hypercortisolism. OBJECTIVE: To describe a series of patients with hypercortisolism due to BMAH treated with mifepristone from multiple medical practices. DESIGN: We retrospectively assessed four patients treated with mifepristone for hypercortisolism due to BMAH who had either failed unilateral adrenalectomy, declined surgery, or were poor surgical candidates. RESULTS: Mifepristone induced clinical improvement and remission of the signs and symptoms of hypercortisolism in all described patients with BMAH. The median treatment duration at the time of efficacy response assessment was 5 months (range: 3 to 18 months). Improvement in cardiometabolic parameters was observed as early as 2 weeks after treatment was started. All patients achieved improvements in glycemic control and hypertension and had significant weight loss. The most common adverse event observed with mifepristone therapy was fatigue. Increases in TSH level occurred in two patients. CONCLUSION: Mifepristone can be an effective medical alternative to surgery in patients with hypercortisolism due to BMAH.
Subject(s)
Adrenal Hyperplasia, Congenital/drug therapy , Hormone Antagonists/therapeutic use , Mifepristone/therapeutic use , Adrenal Hyperplasia, Congenital/diagnostic imaging , Adrenal Hyperplasia, Congenital/pathology , Adult , Aged , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , PrognosisABSTRACT
BACKGROUND: Rathke's cleft cysts (RCCs) are common sellar lesions. Their management remains controversial, particularly when small or asymptomatic. Herein we review a consecutive series of RCC patients managed with surgery or observation. METHODS: All patients with a new diagnosis of presumed RCC, based on MRI, from February 2012-March 2018 were retrospectively divided into observational and surgical cohorts based on an intent-to-treat model. The cohorts were compared for clinical presentation, and cyst volume. The observational cohort was followed for change in cyst size. The surgical cohort was followed for changes in endocrinopathy, visual symptoms, headache and recurrence. RESULTS: Of 90 patients (mean age 36.7 ± 19.4 years; 68% female), 60% (n = 54) were in the observational cohort and 40% (n = 36) in the surgical cohort. Average follow-up was 13 ± 23 months in the observational cohort and 24 ± 19 months in the surgical group. In comparing the cohorts, mean ages were similar with more women in the surgical group (81% vs. 56%, p = 0.04). Most patients in the observational cohort had incidentally-discovered RCCs (n = 50, 88%) as opposed to the surgical cohort (n = 6, 17%). The surgical cohort had higher rates of headache (89% vs 26%, p < 0.001), endocrinopathy (36% vs 0%, p < 0.001), and visual dysfunction (19% vs 0%, p = 0.001). Mean cyst volume and maximal cyst dimensions were greater in the surgical cohort (0.94 ± 0.77 cm3 and 14.2 ± 4.1 mm), compared to the observational cohort (0.1 ± 0.14 cm3 and 6.4 ± 3 mm), (p < 0.001). Among the 53% (n = 30/54) of patients in the observational group with follow-up, 3 (10%) had spontaneous RCC shrinkage, 1 (3%) had modest asymptomatic growth (at 10 months from initial MRI), and 87% had stable cyst size. Of the 36 patients recommended to have surgery, 89% (n = 32) did so. Post-operatively, complete or partial resolution of headache, endocrinopathy and visual dysfunction were documented in 90% (n = 28/30), 75% (n = 10/12), and 100% (n = 7/7), respectively. On follow-up MRI, 8 (22%) patients had some cyst reaccumulation, of whom 3 (8%) were symptomatic and underwent uneventful reoperation. No major complications such as hematoma, CSF leak, new endocrinopathy or visual deficits occurred. CONCLUSION: From this consecutive series, a majority (60%) of RCCs do not appear to warrant surgical intervention and have a low risk of cyst progression. However, surgical cyst removal appears to be indicated and safe for patients with larger, symptomatic RCCs. Simple cyst drainage has a high rate of improvement in pituitary gland function, visual function and headache resolution with low complication rates and symptomatic recurrence risk. These findings stress the importance of careful case selection and potential utility of volumetric assessment for patients with RCCs.
Subject(s)
Central Nervous System Cysts/pathology , Central Nervous System Cysts/surgery , Adult , Central Nervous System Cysts/diagnostic imaging , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Pituitary Gland/diagnostic imaging , Pituitary Gland/physiology , Retrospective Studies , Young AdultABSTRACT
Tumors of hypothalamic neurons that produce vasopressin are rare. We retrieved all cases of vasopressin-positive tumors in the sellar region from the database of the Department of Pathology. Five cases fulfilled the selection criteria, representing the first series of such tumors. Clinical, radiologic, and pathologic features were reviewed. Four tumors classified as neurocytomas were identified in 3 females and 1 male patient; the ages at onset of symptoms ranged from 17 to 40 years. All were large sellar masses with suprasellar extension and/or invasion of the parasellar sinuses. Three patients had the syndrome of inappropriate antidiuresis; in one of these, a 6-year history was initially considered to be idiopathic. One patient died of progressive disease; 3 had incomplete resections and are being followed. In contrast to these patients with neurocytoma, a 65-year-old woman had Cushing disease and a 0.8 cm mass that was completely resected at transsphenoidal surgery; this tumor was a gangliocytoma producing vasopressin associated with corticotroph hyperplasia. We postulate that the small amount of vasopressin secreted by this mature gangliocytic tumor was locally bound to corticotrophs, resulting in hyperplasia and Cushing disease, without sufficient overproduction to cause systemic effects of vasopressin excess. Hypothalamic neurocytoma is a tumor that can mimic pituitary neuroendocrine tumors and olfactory neuroblastoma but is distinguished by positivity for neurofilaments, NeuN, and TTF-1 and negative staining for adenohypophysial biomarkers. Our cases illustrate that neurocytoma and gangliocytoma are 2 variants of tumors of hypothalamic neurons that can produce vasopressin. The morphologic and proliferative features of these 2 tumor types represent 2 ends of a spectrum; their function also can result in divergent clinical manifestations, one characterized by reduced urine output and the other by the more insidious features of glucocorticoid excess.
Subject(s)
Diuresis , Ganglioneuroma/pathology , Hypothalamic Neoplasms/pathology , Neurocytoma/pathology , Pituitary ACTH Hypersecretion/etiology , Adolescent , Adult , Aged , Female , Ganglioneuroma/complications , Humans , Hypothalamic Neoplasms/complications , Male , Neurocytoma/complications , Vasopressins/metabolismABSTRACT
PURPOSE: In most clinical series of Cushing's disease (CD), over 80% of patients are women, many of whom are of reproductive age. The year following pregnancy may be a common time to develop CD. We sought to establish the incidence of CD onset associated with pregnancy. METHODS: A retrospective review was conducted for patients with biochemically-proven CD. Demographics, clinical history, biochemistry, imaging, pathology, and outcomes were reviewed. Pregnancy-associated CD was defined as symptom onset within 1 year of childbirth. RESULTS: Over 10 years, 77 patients including 64 women (84%), with CD underwent endonasal surgery. Of the 64 women, 64% were of reproductive age (15-45 years) at the time of diagnosis, and 11 (27%) met criteria for pregnancy-associated CD. Of these 11 women, median number of pregnancies prior to onset of CD was 2 (range 1-4) compared to zero (range 0-7) for 30 other women with CD onset during reproductive age (p = 0.0024). With an average follow-up of 47 ± 34 months, sustained surgical remission rates for woman with pregnancy-associated CD, other women of reproductive age, and women not of reproductive age were 91%, 80% and 83%, respectively. The average lag-time from symptom onset to diagnosis for women with pregnancy-associated CD was 4 ± 2 years. CONCLUSIONS: In this exploratory study, over one quarter of women of reproductive age with CD appeared to have symptomatic disease onset within 1 year of childbirth. This relatively high rate of pregnancy-associated CD suggests a possible causal relationship related to the stress of pregnancy and pituitary corticotroph hyperactivity in the peripartum period. This possible association suggests a heightened degree of clinical suspicion and biochemical testing for CD may be warranted after childbirth. Further study of this possible link between pregnancy and CD is warranted.
Subject(s)
Pituitary ACTH Hypersecretion/metabolism , Adolescent , Adult , Corticotrophs/metabolism , Corticotrophs/pathology , Female , Humans , Middle Aged , Peripartum Period , Pituitary ACTH Hypersecretion/pathology , Pituitary Neoplasms/metabolism , Pituitary Neoplasms/pathology , Pregnancy , Pregnancy Complications , Retrospective Studies , Young AdultABSTRACT
Context. Transient secondary adrenal insufficiency (SAI) is an expected complication following successful adenomectomy of ACTH-secreting pituitary adenomas or unilateral adrenalectomy for cortisol-secreting adrenal adenomas. To date, no pharmacological therapy has been shown to hasten recovery of the hypothalamic-pituitary-adrenal (HPA) axis in this clinical scenario. Case Description. A 33-year-old woman underwent uncomplicated unilateral adrenalectomy for a 3.7 cm cortisol-secreting adrenal adenoma. Postoperatively, she developed SAI and was placed on hydrocortisone 15 mg/day, given in divided doses. In the ensuing six years, the patient's HPA axis failed to recover and she remained corticosteroid-dependent. Quarterly biochemical testing (after withholding hydrocortisone for 18 hours) consistently yielded undetectable serum cortisol and subnormal plasma ACTH levels. While she was on hydrocortisone 15 mg/day, mifepristone was initiated and gradually titrated to a maintenance dose of 600 mg/day after 5 months. Rapid recovery of the HPA axis was subsequently noted with ACTH rising into the supranormal range at 4 months followed by a subsequent rise in cortisol levels into the normal range. After 6 months, the dose of hydrocortisone and mifepristone was lowered and both were ultimately stopped after 8 months. The HPA axis remains normal after an additional 16 months of follow-up. Conclusion. Mifepristone successfully restored the HPA axis in a woman with prolonged secondary adrenal insufficiency (SAI) after adrenalectomy for Cushing's syndrome (CS).
ABSTRACT
OBJECTIVE: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are the most recently approved antihyperglycemic medications. We sought to describe their association with euglycemic diabetic ketoacidosis (euDKA) in hopes that it will enhance recognition of this potentially life-threatening complication. RESEARCH DESIGN AND METHODS: Cases identified incidentally are described. RESULTS: We identified 13 episodes of SGLT-2 inhibitor-associated euDKA or ketosis in nine individuals, seven with type 1 diabetes and two with type 2 diabetes, from various practices across the U.S. The absence of significant hyperglycemia in these patients delayed recognition of the emergent nature of the problem by patients and providers. CONCLUSIONS: SGLT-2 inhibitors seem to be associated with euglycemic DKA and ketosis, perhaps as a consequence of their noninsulin-dependent glucose clearance, hyperglucagonemia, and volume depletion. Patients with type 1 or type 2 diabetes who experience nausea, vomiting, or malaise or develop a metabolic acidosis in the setting of SGLT-2 inhibitor therapy should be promptly evaluated for the presence of urine and/or serum ketones. SGLT-2 inhibitors should only be used with great caution, extensive counseling, and close monitoring in the setting of type 1 diabetes.
Subject(s)
Benzhydryl Compounds/adverse effects , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Diabetic Ketoacidosis/chemically induced , Glucosides/adverse effects , Hypoglycemic Agents/adverse effects , Sodium-Glucose Transporter 2 Inhibitors , Adult , Aged , Benzhydryl Compounds/administration & dosage , Diabetic Ketoacidosis/prevention & control , Female , Glucosides/administration & dosage , Humans , Hypoglycemic Agents/administration & dosage , Male , Middle AgedABSTRACT
OBJECTIVE: Hyponatremia is a known but underrecognized presentation of sellar lesions. Herein, we present a series of patients who presented with single or multiple episodes of hyponatremia. METHODS: Over 5 years, patients undergoing endonasal surgery for a de novo sellar mass with hyponatremia as an initial presentation were included. Pathology, sodium levels, pituitary hormonal status, and treatment course were documented. RESULTS: Of 282 patients, 16 (5.7%) (9 males, 7 females, age 32 to 84 years) presented with severe hyponatremia, with a mean serum sodium level of 115 ± 6 mmol/L (range, 101 to 125 mmol/L), and 3 patients had 2 or more episodes. Severe hyponatremia was a presenting sign in 0, 4.1, 14.3, and 37.5% of patients with craniopharyngiomas (n = 10), pituitary adenomas (n = 243), Rathke's cleft cysts (RCCs) (n = 21), and sellar arachnoid cysts (n = 8), respectively (P<.01). Half of the patients presenting with hyponatremia, including 6 of 10 patients with adenomas and 2 of 3 patients with RCCs, had pituitary apoplexy or cyst rupture. All patients had anterior pituitary gland dysfunction, including 81% with hypoadrenalism and 69% with hypothyroidism. Following surgery, hormonal status was unchanged or improved in 15 patients (median follow-up, 14 months). No patient had tumor/cyst recurrence or recurrent hyponatremia. CONCLUSION: Severe hyponatremia was a presenting sign in 5.7% of patients with sellar pathology, most frequently in patients with arachnoid cysts, RCCs, and pituitary apoplexy. Patients with new-onset severe hyponatremia and no obvious pharmacologic or systemic cause should undergo pituitary hormonal evaluation and brain imaging. Surgical resection and correction of hormonal deficiencies are associated with resolution of recurrent hyponatremic episodes.
Subject(s)
Central Nervous System Cysts , Craniopharyngioma , Hyponatremia , Pituitary Neoplasms , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, LocalABSTRACT
Hypopituitarism is common after moderate and severe traumatic brain injury (TBI). Herein, we address the association between mild TBI (mTBI) and pituitary and metabolic function in retired football players. Retirees 30-65 years of age, with one or more years of National Football League (NFL) play and poor quality of life (QoL) based on Short Form 36 (SF-36) Mental Component Score (MCS) were prospectively enrolled. Pituitary hormonal and metabolic syndrome (MetS) testing was performed. Using a glucagon stimulation test, growth hormone deficiency (GHD) was defined with a standard cut point of 3 ng/mL and with a more stringent body mass index (BMI)-adjusted cut point. Subjects with and without hormonal deficiency (HD) were compared in terms of QoL, International Index of Erectile Function (IIEF) scores, metabolic parameters, and football career data. Of 74 subjects, 6 were excluded because of significant non-football-related TBIs. Of the remaining 68 subjects (mean age, 47.3±10.2 years; median NFL years, 5; median NFL concussions, 3; mean BMI, 33.8±6.0), 28 (41.2%) were GHD using a peak GH cutoff of <3 ng/mL. However, with a BMI-adjusted definition of GHD, 13 of 68 (19.1%) were GHD. Using this BMI-adjusted definition, overall HD was found in 16 (23.5%) subjects: 10 (14.7%) with isolated GHD; 3 (4.4%) with isolated hypogonadism; and 3 (4.4%) with both GHD and hypogonadism. Subjects with HD had lower mean scores on the IIEF survey (p=0.016) and trended toward lower scores on the SF-36 MCS (p=0.113). MetS was present in 50% of subjects, including 5 of 6 (83%) with hypogonadism, and 29 of 62 (46.8%) without hypogonadism (p=0.087). Age, BMI, median years in NFL, games played, number of concussions, and acknowledged use of performance-enhancing steroids were similar between HD and non-HD groups. In summary, in this cohort of retired NFL players with poor QoL, 23.5% had HD, including 19% with GHD (using a BMI-adjusted definition), 9% with hypogonadism, and 50% had MetS. Although the cause of HD is unclear, these results suggest that GHD and hypogonadism may contribute to poor QoL, erectile dysfunction, and MetS in this population. Further study of pituitary function is warranted in athletes sustaining repetitive mTBI.
Subject(s)
Athletes , Football , Hypopituitarism/epidemiology , Metabolic Syndrome/epidemiology , Quality of Life , Retirement , Adult , Aged , Athletes/psychology , Cohort Studies , Erectile Dysfunction/blood , Erectile Dysfunction/diagnosis , Erectile Dysfunction/epidemiology , Football/psychology , Health Surveys/methods , Humans , Hypopituitarism/diagnosis , Hypopituitarism/psychology , Male , Metabolic Syndrome/diagnosis , Metabolic Syndrome/psychology , Middle Aged , Prevalence , Prospective Studies , Quality of Life/psychology , Retirement/psychologyABSTRACT
OBJECTIVE: To review and evaluate medical therapies for Cushing's disease (CD), with an emphasis on recent clinical trial experience with pasireotide and mifepristone, and to discuss the therapeutic potential and appropriate selection of these compounds in this patient population. METHODS: Recently published Phase III trial data for each compound are reviewed and assessed, and relative benefits and risks are examined and compared where possible. RESULTS: Mifepristone and pasireotide are both potentially beneficial for CD patients but have greatly dissimilar mechanisms of action and adverse event (AE) profiles. Pasireotide acts at the level of the pituitary adenoma, reducing cortisol levels through inhibition of adrenocorticotropic hormone (ACTH) release. However, pasireotide reduces insulin secretion and incretin hormone response and is associated with significant risk for new or worsening hyperglycemia. Mifepristone ameliorates the signs and symptoms of hypercortisolemia via glucocorticoid receptor (GR2) blockade, but this approach raises serum cortisol levels and increases risk for adrenal insufficiency (AI), hypokalemia, and endometrial thickening. While response to pasireotide can be monitored via measurements of serum, urine, or late-night salivary cortisol, evaluation of response to mifepristone is solely based on changes in clinical parameters (e.g., hyperglycemia, hypertension, body weight/composition). CONCLUSION: Management of persistent CD is challenging, and the decision to initiate medical treatment hinges on many factors. Pasireotide may be a more attractive option for most patients due to its action at the underlying tumor and the ability to monitor biochemical responses. However, mifepristone may be more appropriate when it is necessary to avoid or minimize risk for hyperglycemia-related complications.
Subject(s)
Mifepristone/therapeutic use , Pituitary ACTH Hypersecretion/drug therapy , Somatostatin/analogs & derivatives , Adrenocorticotropic Hormone/antagonists & inhibitors , Adrenocorticotropic Hormone/metabolism , Humans , Mifepristone/pharmacology , Receptors, Glucocorticoid/antagonists & inhibitors , Somatostatin/pharmacology , Somatostatin/therapeutic useABSTRACT
OBJECTIVE: Patients undergoing pituitary adenoma or Rathke cleft cyst (RCC) removal are often administered perioperative glucocorticoids regardless of lesion size and preoperative adrenocorticotropic hormone/cortisol levels. To minimize unnecessary glucocorticoid therapy, we describe a protocol in which patients with normal preoperative serum cortisol and adrenocorticotropic hormone levels are given glucocorticoids only if postoperative day 1 or 2 (POD1 or POD2) cortisol levels decrease below normal. METHODS: A total of 207 consecutive patients undergoing endonasal surgery for an adenoma or RCC were considered for study. Of these, 68 patients with preoperative adrenal insufficiency or Cushing disease were excluded. Glucocorticoids were withheld unless POD1 or POD2 morning cortisol values were below normal (≤4 µg/dL). Subsequent adrenal status was assessed through follow-up biochemical and clinical evaluations. RESULTS: The 139 patients included 119 with macroadenomas, 14 microadenomas, and 6 RCCs (follow-up, 3-41 months; median, 10 months). Nine patients (6.5%), all with macroadenomas (mean diameter, 26 ± 10 mm) had low POD1 or POD2 cortisol values and received glucocorticoids; of these, five patients were weaned off within 3-28 weeks of surgery. Overall, 12 of 139 patients (8.6%) were treated for early (n = 9) or delayed (n = 3) adrenal insufficiency but only 5 patients (3.6%) remain on glucocorticoid replacement. No patient experienced an adrenal crisis. Using morning POD1 or POD2 cortisol values >4 µg/dL as a measure of adequate hypothalamic-pituitary-adrenal axis function, yields a sensitivity of 96%, a specificity of 57%, and a positive predictive value of 98%. CONCLUSIONS: In patients with normal preoperative cortisol levels undergoing endonasal removal of a pituitary adenoma or RCC, normal morning cortisol values on POD1 and POD2 reliably predicts adequate and safe adrenal function in 98% of patients. This simple protocol of withholding postoperative glucocorticoids avoids unnecessary steroid exposure and poses minimal risk to the well-informed closely monitored patient.
Subject(s)
Adenoma/surgery , Central Nervous System Cysts/surgery , Glucocorticoids/therapeutic use , Hydrocortisone/blood , Pituitary Neoplasms/surgery , Adenoma/blood , Adrenocorticotropic Hormone/blood , Adult , Aged , Biomarkers/blood , Central Nervous System Cysts/blood , Circadian Rhythm/physiology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Nose , Pituitary ACTH Hypersecretion/blood , Pituitary ACTH Hypersecretion/surgery , Pituitary Neoplasms/blood , Postoperative Period , Predictive Value of Tests , Sensitivity and Specificity , Sphenoid Bone/surgeryABSTRACT
OBJECT: Endoscopy as a visual aid (endoscope assisted) or as the sole visual method (fully endoscopic) is increasingly used in pituitary adenoma surgery. Authors of this study assessed the value of endoscopic visualization for finding and removing residual adenoma after initial microscopic removal. METHODS: Consecutive patients who underwent endoscope-assisted microsurgical removal of pituitary adenoma were included in this study. The utility of the endoscope in finding and removing residual adenoma not visualized by the microscope was noted intraoperatively. After maximal tumor removal under microscopic visualization, surgeries were categorized as to whether additional tumor was removed via endoscopy. Tumor removal and remission rates were also noted. Patients undergoing fully endoscopic tumor removal during this same period were excluded from the study. RESULTS: Over 3 years, 140 patients (41% women, mean age 50 years) underwent endoscope-assisted adenoma removal of 30 endocrine-active microadenomas and 110 macroadenomas (39 endocrine-active, 71 endocrine-inactive); 16% (23/140) of patients had prior surgery. After initial microscopic removal, endoscopy revealed residual tumor in 40% (56/140) of cases and the additional tumor was removed in 36% (50 cases) of these cases. Endoscopy facilitated additional tumor removal in 54% (36/67) of the adenomas measuring ≥ 2 cm in diameter and in 19% (14/73) of the adenomas smaller than 2 cm in diameter (p < 0.0001); additional tumor removal was achieved in 20% (6/30) of the microadenomas. Residual tumor was typically removed from the suprasellar extension and folds of the collapsed diaphragma sellae or along or within the medial cavernous sinus. Overall, 91% of endocrine-inactive tumors were gross-totally or near-totally removed, and 70% of endocrine-active adenomas had early remission. CONCLUSIONS: After microscope-based tumor removal, endoscopic visualization led to additional adenoma removal in over one-third of patients. The panoramic visualization of the endoscope appears to facilitate more complete tumor removal than is possible with the microscope alone. These findings further emphasize the utility of endoscopic visualization in pituitary adenoma surgery. Longer follow-ups and additional case series are needed to determine if endoscopic adenomectomy translates into higher long-term remission rates.
Subject(s)
Adenoma/diagnosis , Adenoma/surgery , Neoplasm, Residual/prevention & control , Neuroendoscopy , Nose , Pituitary Neoplasms/diagnosis , Pituitary Neoplasms/surgery , Sphenoid Sinus , Adenoma/complications , Adenoma/pathology , Adult , Aged , Aged, 80 and over , Diabetes Insipidus/etiology , Female , Follow-Up Studies , Humans , Hypopituitarism/etiology , Incidence , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Recurrence, Local/prevention & control , Neuroendoscopy/adverse effects , Neuroendoscopy/methods , Pituitary Neoplasms/complications , Pituitary Neoplasms/pathology , Radiotherapy, Adjuvant , Retrospective Studies , Risk Factors , Stroke/etiology , Treatment Outcome , Vision Disorders/etiologyABSTRACT
OBJECT: Symptomatic sellar arachnoid cysts (ACs) have typically been treated via the transsphenoidal route. After sellar cyst wall fenestration, some authors have advocated cyst wall resection and increasing communication between the AC and suprasellar subarachnoid space (SAS). This study is a report of the authors' experience using a simplified approach to reinforce a defective diaphragma sellae or unseen arachnoid diverticulum by deliberately not enlarging the AC-SAS communication and obliterating the cyst cavity with adipose tissue followed by skull base reconstruction. METHODS: A retrospective analysis was conducted of patients who underwent an endonasal transsphenoidal obliteration of symptomatic ACs with a fat graft and skull base repair. RESULTS: Between July 1998 and September 2010, 8 patients with a sellar AC were identified (6 women and 2 men, mean age 57 years). Clinical presentation included headache, pituitary dysfunction, and visual dysfunction (4 patients each group). Maximal cyst diameter averaged 22 mm (range 15-32 mm). In all cases the sellar communication to the SAS was deliberately not enlarged. The endoscope was used for visualization in 8 of 9 procedures. Postoperatively, headache improved in all 4 patients, vision in all 4 patients, and partial resolution of endocrine dysfunction (hyperprolactinemia and/or recurrent hyponatremia) occurred in 3 (75%) of 4 patients. No new endocrinopathy, CSF leak, meningitis, or neurological deficits occurred. Two patients experienced cyst reaccumulation: 1 symptomatic recurrence was treated with reoperation at 43 months postsurgery, and 1 asymptomatic partial recurrence continued to be monitored at 29 months postsurgery. CONCLUSIONS: Sellar ACs can be effectively treated using endonasal fenestration and obliteration with fat with resultant reversal of presenting symptoms in the majority of patients. This simplified technique of AC cavity obliteration without enlarging communication to the SAS has a low risk of CSF leakage, and in most cases appears to effectively disrupt cyst progression, although longer follow-up is required to monitor for cyst recurrence.
Subject(s)
Arachnoid Cysts/surgery , Endoscopy/methods , Sella Turcica/surgery , Adipose Tissue/transplantation , Adult , Aged , Aged, 80 and over , Arachnoid Cysts/diagnosis , Female , Humans , Male , Middle Aged , Pituitary Function Tests , Postoperative Complications/etiology , Postoperative Complications/surgery , Recurrence , Retrospective Studies , Subarachnoid SpaceABSTRACT
The complex pathophysiology of traumatic brain injury (TBI) involves not only the primary mechanical event but also secondary insults such as hypotension, hypoxia, raised intracranial pressure and changes in cerebral blood flow and metabolism. It is increasingly evident that these initial insults as well as transient events and treatments during the early injury phase can impact hypothalamic-pituitary function both acutely and chronically after injury. In turn, untreated pituitary hormonal dysfunction itself can further hinder recovery from brain injury. Secondary adrenal insufficiency, although typically reversible, occurs in up to 50% of intubated TBI victims and is associated with lower systemic blood pressure. Chronic anterior hypopituitarism, although reversible in some patients, persists in 25-40% of moderate and severe TBI survivors and likely contributes to long-term neurobehavioral and quality of life impairment. While the rates and risk factors of acute and chronic pituitary dysfunction have been documented for moderate and severe TBI victims in numerous recent studies, the pathophysiology remains ill-defined. Herein we discuss the hypotheses and available data concerning hypothalamic-pituitary vulnerability in the setting of head injury. Four possible pathophysiological mechanisms are considered: (1) the primary brain injury event, (2) secondary brain insults, (3) the stress of critical illness and (4) medication effects. Although each of these factors appears to be important in determining which hormonal axes are affected, the severity of dysfunction, their time course and possible reversibility, this process remains incompletely understood.
Subject(s)
Brain Injuries/complications , Brain Injuries/physiopathology , Hypopituitarism/etiology , Hypopituitarism/physiopathology , HumansABSTRACT
Hormonal dysfunction is a known consequence of moderate and severe traumatic brain injury (TBI). In this study we determined the incidence, time course, and clinical correlates of acute post-TBI gonadotroph and somatotroph dysfunction. Patients had daily measurement of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, estradiol, growth hormone, and insulin-like growth factor-1 (IGF-1) for up to 10 days post-injury. Values below the fifth percentile of a healthy cohort were considered abnormal, as were non-measurable growth hormone (GH) values. Outcome measures were frequency and time course of hormonal suppression, injury characteristics, and Glasgow Outcome Scale (GOS) score. The cohort consisted of 101 patients (82% males; mean age 35 years; Glasgow Coma Scale [GCS] score Subject(s)
Brain Injuries/complications
, Follicle Stimulating Hormone/blood
, Human Growth Hormone/blood
, Hypopituitarism/etiology
, Luteinizing Hormone/blood
, Adolescent
, Adult
, Age Factors
, Aged
, Aged, 80 and over
, Brain Injuries/metabolism
, Estradiol/blood
, Female
, Glasgow Outcome Scale
, Humans
, Hypopituitarism/blood
, Immunoassay
, Insulin-Like Growth Factor I/metabolism
, Male
, Middle Aged
, Multivariate Analysis
, Patient Selection
, Testosterone/blood
ABSTRACT
OBJECTIVE: Giant pituitary adenomas (> or =40 mm) pose a major management challenge. We describe the experience of a single surgeon and a dedicated neuro-endocrine team with multimodality treatment of these tumours in three specialized institutions. DESIGN: Retrospective data set analyses. PATIENTS: Fifty-one consecutive patients with a giant adenoma (39 endocrine-inactive, 12 endocrine-active; mean tumour diameter 45 mm) treated over 10 years by an endonasal transsphenoidal approach were included. All patients had surgical resection followed by radiotherapy and/or medical therapy as judged necessary. MEASUREMENTS: Hormonal and visual status, extent of resection, tumour control rates, complications and use of medical and radiotherapy were evaluated. RESULTS: Surgery resulted in gross total, near total and subtotal removal in21 (41%), 10 (20%) and 20 (39%) patients respectively. Complete tumour removal was associated with absence of cavernous sinus invasion (P < 0.001). Long-term endocrine function improved in 49% of patients and new endocrinopathy occurred in 14.6%; 76% required long-term hormone replacement therapy. Vision improved in 81.5% of the patients and there was no visual worsening. At the last follow up (median 30 months), tumour control was achieved in 96% of patients: 59% with surgery alone, 20% with surgery plus focussed radiotherapy, 18% with surgery and medical therapy and two with all three modalities. CONCLUSIONS: Endonasal surgery provides effective initial treatment for patients with giant adenomas. Multimodality therapy was needed in almost 50% of patients and this rate will likely increase with longer follow up. Close collaboration of neurosurgeons with endocrinologists and radiation oncologists is essential for optimal treatment of patients with these challenging tumours.