Nonfunctioning Adenomas Research Articles

A Case of Silent Corticotroph Adenoma

Background: Silent Corticotroph Adenomas (SCAs) are tumors with no biochemical or clinical features consistent with hypercortisolism but have positive immunostaining for ACTH. They account for approximately 1.1-6% of all pituitary adenomas and 5.5% of nonfunctioning adenomas. Clinical Case: A 49-year-old woman presented to clinic with a 6-month history of headache, vision changes, fatigue, hair thinning, brittle nails, lightheadedness, polydipsia, easy bruising, increased appetite, and weight gain of 178 pounds in 2 years. Labs obtained: morning cortisol 10 mcg/dl(7-25 mcg/dl), ACTH 59 pg/ml(7.2-63 pg/ml), IGF-1 96 ng/ml(52-328 ng/ml), LH 0.2 mIU/ml(1.9-12.5 mIU/ml), FSH 0.8 mIU/ml(2.5-10.2mIU/ml), alpha subunit <0.1 ng/ml(52-328 ng/ml), TSH 0.991 uIU/ml(0.358-3.74 uIU/ml), free T4 1.12 ng/dl(0.76-1.46 ng/dl), salivary cortisol 66 ng/dl(<100 ng/dl), 24-hour urine cortisol 10 mcg/24hr(3.5-45 mcg/24hr) and prolactin 64.3 ng/ml(2.8-29.2 ng/ml). No hook effect noted with serial dilution. MRI brain showed a 22 x 29 x 26 mm sellar mass extending into the suprasellar cistern displacing and compressing the optic nerves and chiasm superiorly with partial invasion into the right cavernous sinus. She had an endoscopic resection of the sellar mass. She developed diabetes insipidus post-operatively and required desmopressin transiently. In the immediate post-operative period, morning cortisol and ACTH were 16.9 ug/dl(6.2-19.4 ug/dL) 24.8 pg/ml(7.2-63.3 pg/ml) respectively. She was sent home without steroids. Pathology showed a staining pattern consistent with pituitary adenoma with positive staining for ACTH. One month after her surgery she was admitted with symptoms of orthostatic hypotension. Cortisol at 5pm was 3 ug/dl(2.3-11.9 ug/dl), ACTH 31.7 pg/ml(7.2-63.3pg/ml). She had a cosyntropin stimulation test done with peak cortisol of 19.3 ug/dl at 60 minutes. Due to her symptoms, she was started on oral hydrocortisone (HC) for secondary adrenal insufficiency (AI), but was eventually tapered off the steroids. Six months after her surgery, she developed worsening headaches. Repeat MRI obtained showed significant growth of the residual adenoma on the right side of the sella, invading the cavernous sinus. Morning cortisol level of 5.3 mcg/dl(4.3-22.4 mcg/dl) and ACTH level was 11 pg/ml(6-50 pg/ml). She had a repeat endoscopic resection of the pituitary tumor. Her post-surgery cortisol at 2 PM was 3 mcg/dl at which time patient reported symptoms of AI. She was discharged on HC. Pathology again showed a staining pattern consistent with pituitary adenoma with positive staining for ACTH. MIB-1 proliferative index was 5.6%. P53 immunostaining showed a moderate density of moderately intense nuclei in the adenoma. Conclusion: This case illustrates aggressive nature of SCAs with higher risk of recurrence compared to other non-functioning adenomas and therefore requires close follow up.

Clinical Outcomes in Patients With NFPAs Treated With Stereotactic Linear Accelerator Radiation Therapy

Abstract Background: Non-functioning pituitary adenoma (NFPAs) are benign tumors of the pituitary gland characterized by the absence of hormonal hypersecretion. Surgical treatment and fractionated stereotactic radiotherapy (FSRT) are necessary in majority of patients. NFPAs appear to cause higher mortality compared to the general population. Objective: To assess outcomes in patients with NFPAs treated with stereotactic linear accelerator radiation therapy. Material and Methods: Comparative, observational, longitudinal study, with prolective evaluation, from January 1987 to August 2019. Results: 264 patients (65.5% women and 34.5% men, mean age 43 ± 16 years) with a diagnosis of non-functional adenomas were evaluated. 30 patients received FSRT (14%), 93% were macroadenomas, and 80% of the cases were operated as a first line of treatment. The mean number of surgeries before radiotherapy was 1.2+-.847 (0-4). FSRT were used in 91.7% (n=21) because of post-surgical recurrence. Diabetes insipidus after surgery was transitory in 5.4%, and persistent in 4.0%. Hypopituitarism was identified in 59.4% before radiation (n=19), and in 13 patients (7.7%) after mean of 6.5+-5.5 years of FSRT. Dyslipidemia (62.0% vs. 45.9%), high blood pressure (16.5% vs. 23%), type 2 diabetes mellitus (10% vs. 77%) and heart failure (10% vs. 8.4%) were observed in the irradiated vs. non-irradiated groups, respectively (p&amp;lt;0.05). Conclusions: FSRT is a useful and safe strategy as an adjuvant treatment in patients with NFPA.

Desmopressin Test in Silent Corticothoph Pituitary Adenomas, a Preliminary Study - a Comparison With Cushing Disease

Introduction: Silent corticothop adenomas (SCAs) account for 9 to 19% of nonfunctioning pituitary adenomas and behave as the most agressive pituitary tumors with more invasiveness and high recurrence rate. The identification of these patients during the preoperative stage could predict better surgery results. Some authors refer to high basal ACTH level in the preoperative evaluation as the only marker but until this date, there are no clinical and hormonal markers that could predict its occurrence. The aim of this study is to evaluate the response to desmopressin test and the presence of silent corticothoph tumors. Patients and Methods: Among 496 patients underwent pituitary surgery, 425 were pituitary adenomas, (106 were acromegaly, 46 Cushing disease, 10 prolactinomas, 263 nonfunctioning adenomas). Twenty-three patients, 17 with Cushing disease, (CD), mean age: 31 y, 13 female and 4 male) and 6 patients with SCA (mean age: 47 y, 5 female and 1 male) had positive ACTH confirmed by immunohistochemical analysis. Clinical characteristics: in the CD group, 53% had hypertension (9/17), 42% diabetes (7/17), 100% dyslipidemia, BMI was 30.7 kg/m2. Among SCA group, 67% hypertension, 50% diabetes, 50% dyslipidemia, BMI was 28 kg/m2. All patients were evaluated with basal ACTH and DHEAS before surgery. Patients with SCA underwent desmopressin test and were compared to CD. Dexamethasone suppression test (DST 1 mg) and 24-hour free urinary test was performed in patients with CD and in two patients with SCA. Response to desmopressin test was considered positive when increase in cortisol was above 20% and in ACTH of 35% using chemiluminescence assay (Immulite 2000). Results: Among CD group, the median (med) basal ACTH was 75.9 pg/mL (30.9 to 211), the med basal cortisol was 22.5 µg/dL (14.5 to 43.5), the med DHEAS was 170 µg/dL (33 to 465), the med 24h urinary free cortisol of 454.5 µg/24 h (149 to 1673) and med basal cortisol after DST 1mg of 15.4 µg/dL (4.7 to 31.5). Among SCA, med basal ACTH was 19.4 pg/mL (9.5 to 65.5), the med basal cortisol was 9.5 µg/dL (7.8 to 16.4) and the med DHEAS was 104.5 µg/dL (82 to 127). Only 4 patients with CD had macroadenomas. All of them responded with ACTH increase (med increase of 98%, 31.6 to 377%), and only 4 did not respond to cortisol increase (med increase of 54.4%, 0 to 167%). All patients with SCA had macroadenomas. Only one patient did not respond to ACTH increase (med increase of 123.5%, 9.5 to 1522%, 9.5 to 1522%), and 3 patients did not respond to cortisol increase (med increase of 17.9%, 0 to 234%). Discussion: SCA are invasive tumors, with high recurrence and tests predicting their occurrence are missing. We hypothesized that as ACTH is present in the adenoma a response to desmopressin test could exist (like CRH). Conclusion:The desmopressin test can be a useful tool in the evaluation of SCA and can predict pathological phenotype in preoperative tumors.

Immunohistochemical Profile of Nonfunctioning Pituitary Adenomas

Background: Nonfunctioning pituitary adenomas (NFPAs) are neuro-endocrine tumors without clinical and laboratory signs of anterior pituitary hormonal hypersecretion. The recent World Health Organization classification is based on the adenohypophyseal cell lineages and requires immunohistochemical evaluation of adenohypophyseal hormones and pituitary transcription factors. There are few data regarding the age and sex prevalence of different cell-types nonfunctioning adenomas and clinical data correlations. Objective: To discover the immunohistochemical profile of large cohort of NFPAs. Materials and Methods: The study includes 100 consecutive cases of endoscopically transsphenoidally removed nonfunctional pituitary adenomas, immunohistochemically assessed for anterior pituitary hormones and transcription factors. Clinical presentation, imaging, laboratory hormonal data and immunohistochemical staining features have been analyzed. All patients (64 women and 36 men) have been divided into four age groups: 20-34 (A) years old, 35-44 (B) years old, 45-59 (C) years old, 60-70 (D) years old. Peculiarities of immunohistochemical profile have been statistically analyzed in those age groups. Results: Most tumors (97%) were macroadenomas with mass effect symptoms. In the groups of silent corticotroph and Pit-1 adenomas most of the patients had subclinical symptoms of hormonal hypersecretion. The proportions of silent gonadotroph adenomas have appeared to be increased with age with predominant prevalence in group D (60%) in women and group C (78, 6%) in men. The proportions of silent Pit-1 adenomas decreased with age with maximum rate in group A (77,8%) in women and in group A (50%) in men. The incidence of silent corticotroph adenomas was different: increasing with age in women with maximum (36,8%) in group C and decreasing from young age (30%-0%) in men age groups B-D respectively. Plurihormonal pituitary adenomas from different cell lineages were found only in women, with maximum incidence rate (17,6%) in group B. The incidence of “null cell” adenomas didn’t differ in men and women in group B and C but was much more higher in men in groups A and D (16,7% vs 0% and 33% vs 6,6% respectively). Conclusions: The different age and sex prevalence of NFPAs, revealed in our study, may be helpful in diagnosing and optimal treatment of NFPAs.

Impaired Muscle Strength and Performance in Patients With Mild Autonomous Cortisol Secretion

Background: Glucocorticoid-induced myopathy is well-recognized in overt Cushing syndrome (CS), but the impact of mild cortisol secretion on muscle is unclear. Recent data suggest that patients with mild autonomous cortisol secretion (MACS) are frailer and report more weakness than patients with non-functioning adrenal adenomas. We hypothesized that MACS is associated with 1) objective measures of impaired muscle strength and performance and 2) increased tissue accumulation of advanced glycation end products (AGEs), a measure of accelerated aging. Aim: To determine the effect of MACS on muscle mass, strength, performance, and tissue accumulation of AGEs. Methods: We conducted a cross-sectional analysis as part of an ongoing cohort study in patients with MACS compared to age and sex-matched referent subjects without cortisol excess. MACS was defined as serum cortisol >1.8 mcg/dL after the 1 mg overnight dexamethasone suppression test (DST), in the absence of overt signs and symptoms of CS. We measured hand grip strength with hand grip dynamometer and evaluated functional performance on the timed up and go test, 6 minute walk test, and gait speed assessment. Tissue accumulation of AGEs was measured with point-of-care AGE reader. Appendicular lean mass was calculated and adjusted for height in participants who underwent body composition scan. Results: A total of 23 patients with MACS and 23 age and sex-matched referent subjects without cortisol excess were enrolled. The median age of diagnosis was 63 years (range, 51–81), and 26 (56%) were women. In the MACS cohort, median cortisol following 1 mg DST was 2.6 µg/dL (range, 1.9–13.0), median DHEA-S 37 µg/dL (range, 5.0- 141.0), and median ACTH 8.5 pg/mL (range, 5.0–38.0). Patients with MACS had lower hand grip strength (median 29.3 vs. 32.5 kg, p=0.052), slower gait speed (median 1.1 vs. 1.4 m/s, p=0.001), covered less distance during the 6 minute walk test (median 453 vs. 510 m, p=0.001), and took longer to complete the timed up and go test (median 10.1 vs. 8.6 s, p=0.04) than referent subjects without cortisol excess. Accumulation of AGEs was higher in patients with MACS (median 2.9 vs. 2.4, p=0.01). No significant difference was observed in appendicular lean mass (n=19 pairs, 7.8 vs. 7.5 kg/m2, p=0.57). Conclusions: MACS is associated with decreased muscle strength and performance without a significant change in muscle mass, suggesting poor muscle quality. We also observed increased tissue accumulation of AGEs in MACS patients, consistent with our hypothesis of MACS-induced accelerated aging. These findings may help explain the increased frailty observed in MACS, and suggest muscle assessment be considered in all patients with autonomous cortisol secretion. Further studies should examine the impact of muscle and functional impairments on morbidity in MACS, and its possible reversal with either a structured exercise intervention or adrenalectomy.

Characterization of Gonadotroph Pituitary Adenomas Based on the Recent 2017 WHO Pituitary Tumor Classification

Abstract Introduction: More than 20% of pituitary adenomas are nonfunctional, the majority of which are of gonadotroph origin. Whereas previously, immunohistochemistry of pituitary hormones was used to classify adenoma subtypes, in 2017 the World Health Organization (WHO) reclassified pituitary adenomas using transcription factor expression in addition to immunohistochemistry. With this change, clinically nonfunctional gonadotroph adenomas can be distinguished among: (1) those staining for the transcription factor SF-1 and gonadotropins FSH and/or LH (FSH/LH+), (2) those that stain for SF-1 but not for FSH or LH (FSH/LH- SF1+), and (3) true null cell adenomas. It is unclear whether these three subgroups behave similarly clinically, or if they have distinct manifestations or outcomes. Our aim was to characterize these subgroups in regard to tumor size, recurrence and pituitary insufficiency. Methods: In a retrospective chart review, 71 patients from 2017-2020 who presented to the hospital for transsphenoidal resection of clinically nonfunctioning pituitary adenomas were reviewed. All patients with pituitary adenomas that stained positive for SF-1 and negative for T-PIT and PIT-1, and tumors that were negative for all three transcription factors were evaluated. Those lacking clinical data were excluded. Clinical characteristics examined include: demographics, tumor size, invasion of cavernous sinus, and hormone deficiencies. Results: Of the 71 pituitary tumors, 45% (n=32) stained positive for the beta subunit FSH and/or LH (FSH/LH+) and SF-1, 44% (n=31) stained for SF-1 with negative pituitary hormone stains (FSH/LH- SF1+), and 11% (n=8) were negative for all transcription factors and hormones (true null). All tumors were macroadenomas (&amp;gt;1 cm). While there were &amp;gt;50% males in the FSH/LH+ and FSH/LH- SF1+ groups, in the true null group only 25% of patients were male. Most patients were &amp;gt;50 years old in all 3 groups (81% FSH/LH+, 75% FSH/LH- SF1+, 88% true null). The prevalence of cavernous sinus involvement was 36% in both groups that stained for SF-1, but was 62% in the true null group. Both SF-1+ groups had similar tumor sizes and prevalence of panhypopituitarism (15-21%), but there were more episodes of recurrence since last known follow up in the FSH/LH- SF1+ group (20%), compared to FSH/LH+ tumors (7%). The true null group had ≥50% rates for both panhypopituitarism and recurrence. Conclusions: In this study, we highlighted the category of FSH/LH- SF1+ gonadotroph adenomas and compared these to FSH/LH+ and true null cell tumors. Based on clinical features, FSH/LH- SF1+ gonadotroph adenomas are similar to FSH/LH+ staining pituitary adenomas in regard to age, sex, size, and degree of cavernous sinus invasion, although there were more recurrences in the FSH/LH- SF1+ group. Though less common, our cohort suggests more aggressive tendencies in the true null group compared to SF-1 staining tumors.

Treatment of Postsurgical Clinically Nonfunctioning Pituitary Adenomas Remnants With Cabergoline

Background: The standard first-line therapy for clinically nonfunctioning adenomas (NFPA) is transsphenoidal surgery, however there is no consensus of the optimal postsurgical treatment for residual adenoma. Medical therapy, such as cabergoline (CAB), may be an alternative for preventing growth of postoperative pituitary tumor remnants. The moment of introduction dopamine agonist (DA) is still uncertain. Objective: To assess tumor behavior in patients who used CAB in the postoperative period. Design and methods: A retrospective cross-sectional study was performed with twenty one patients with NFPA treated surgically. All patients stayed with residual tumor and were divided in two groups: patients who received CAB early in postoperative period (Group A, n=6) and when tumor growth were detected during follow-up (Group B, n=15). CAB dosage was 1.5mg or 3.5mg per week. A change in tumor size was considered significant and recorded as such if a difference of at least 5 mm in major diameter was observed. MRI was performed four months after surgery and yearly thereafter in all patients. Subjects in treatment groups also underwent MRI 6 months following medical therapy. No patients were treated by irradiation before or during the follow-up. Statistical analysis was performed using the Fisher’s exact test. Results: From 21 patients, 11 were men and 10 women with similar mean age in two groups (p=0.651). MRI in group A showed stabilization of residual tumor in 50% (3/6) and tumor reduction in 50% (3/6) in group A. In group B, tumor shrinkage was observed in 47% (7/15), stabilization in 27% (4/15) and enlarged in 27% (4/15). No statistical difference between groups was obtained regarding tumor shrinkage and stabilization with the treatment (Group A n=6 versus Group B n=11, p=0.281). In contraste Batista et al., 2016, have already shown that CAB was effective alternative in residual tumor reduction in a study with 74 patients. Conclusion: A multicenter study is necessary to define the role of CAB in the treatment of residual tumor in postsurgical patients with NFPA.

Pituitary Diseases Registry Study in Latvia. Part 1

Background: Our registry study is designed to create a unified database of pituitary disease patients in Latvia. Methods: We collected 3 yrs data from medical records with pituitary diseases from one clinical university hospital and 4 outpatients clinics. Prospective cohort analysis was performed based on demographic data, MRI, laboratory data, data on medications and regimens used to treat pituitary diseases, information on co-morbidities and concomitant medications used in 355 patients with various pituitary diseases: prolactinomas, clinically nonfunctional adenomas (CNFA), acromegalies, empty sella syndrome, Cushing’s disease (CD), Ratke’s pocket cysts, meningiomas, craniopharyngoma, pituitary aplasia and hypoplasia, TSH-omas, germinoma, glioma, chondrosarcoma, pericytoma. Results: From July 2016 to July 2019, 355 people (71.7% women) with pituitary diseases were registered. The mean age in the cohort was 43.4 yrs (range 18–83 yrs). Prolactinomas were the most common adenomas (40.8%), followed by CNFA (28.5%), acromegaly (16.1%) and empty sella syndrome (5.1%), CD (2.3%), Ratchet pocket cysts (2.3%), meningiomas (1.4%), craniopharyngiomas (1.1%), pituitary aplasia and hypoplasia (0.8%), TSH-omas (0.6%), germinoma (0.3%), glioma (0.3%), chondrosarcoma (0.3%), pericitoma (0.3%). Female dominance was observed in patients with prolactinoma and CNFA, ​​empty sella syndrome, Ratke’s pocket cysts, CD, meningiomas, TSH-omas. Patients in the cohort most often received drug therapy with any type of medication alone (octreotide LAR, lanreotide, bromocriptine, cabergoline, pegvisomant) in 50.5% of cases; various types of combination therapy in 13% of cases. The majority of patients (81.7%) were treated with 1or more medication for co-morbidity. Thyroid disease was slightly more common than cardiovascular disease: 86.1% vs. 81.3%. In 10.1% of the cohort, cancer of various localities was detected. Both types of diabetes or other disorders of carbohydrate metabolism were found in 36.3% of cases. Conclusion: Based on the study of the pituitary disease register in Latvia, a unified database of pituitary disease patients has been created, which allows analyzing the population characteristics of the pituitary diseases, the applied treatment schemes for the treatment of pituitary diseases; types of neurosurgery, medication and radiation therapy. A state register may be set up in the future.

Clinical, Laboratory and Radiological Findings of Patients with Surrenal Mass; Single Center Experience

Amaç: Sürrenal insidentolamalar, başka nedenlerle yapılan görüntüleme testleri sırasında tesadüfen saptanan kitlelerdir. Günümüzde abdominal görüntüleme tekniklerinin yaygın olarak kullanılmaya başlanması ile birlikte sürrenal insidentaloma tanısının sıklığı artmıştır. Her adrenal insidentaloma, malign olup olmadığı ve hormonal işlevi olup olmadığı açısından değerlendirimelidir. Bu değerlendirme tedavi planlanması ve hastanın takibi için önemlidir.Materyal ve Metod: Toplam 68 sürrenal kitlesi olan vakanın klinik, radyolojik, hormonal ve labaratuvar takiplerini retrospektif değerlendirdik.Bulgular: Vakaların %58,8’i kadın (n:40), %41,2’si erkekti (n:28). Bu hastalardan 36’sı bilgisayarlı tomografi, 22’si bilgisayarlı tomografi ve manyetik rezonans görüntüleme, 10 tanesi de manyetik rezonans görüntüleme sonuçlarına göre değerlendirilmiştir. Adrenal insidentalomaların kitle çapı 4-95 mm idi. Adrenal insidentalomalı hastaların %42’si (n:29) opere edilmişti. Otuz beş hastada non-fonksiyone adenom(NFA) saptanırken, 33 hastada fonksiyonel adenom(FA) saptanmıştır. Klinikopatolojik değerlendirilmelerine göre surrenal kitlelerde 22 (%32,3) adet feokromositoma, 7 (%10,2) adet cushing sendromu ve 4(%1,4) adet conn sendromu saptanmıştır. Eşlik eden hastalıklar açısından değerlendirildiğinde; surrenal kitlesi olan hastalardan 15’inde (% 22,1) hipertansiyon ve diabetes mellitus, 26’sında (%38,2) diabetes mellitus, 27’sinde (%39,7) komorbidite olmadığı görüldü.Sonuç: Çalışmamızdaki adrenal insidentaloma vakalarının çoğu non-fonksiyone adenomdur. Fonksiyone adenomlar içinde klinik olarak en çok feokromositoma ve daha sonra ise cushing sendromu saptanmıştır. Adrenal kitlelerin cerrahiye gidişinde fonksiyonel olmaları ve boyutları belirleyicidir.

Spectrum of adrenal disorders in a referral hospital of Bangladesh

Background: Adrenal diseases are common and their presentations are variable. This study aimed to determine the frequency and presenting features of various adrenal diseases in a tertiary care hospital of Bangladesh.&#x0D; Methods: This retrospective descriptive study was carried out in Endocrinology in-patient department of BIRDEM General Hospital, Dhaka, Bangladesh, from October 2017 to December 2018. During this time, total 745 patients were screened; out of whom 91 had adrenal diseases.&#x0D; Results: Mean age of the study population was 39.6±11.5 years. Among them, 65.9% were male. Most (75.8%) cases had adrenal insufficiency, followed by endogenous Cushing’s syndrome (8.8%), Conn’s syndrome (6.6%), non-functioning adenoma (3.3%), congenital adrenal hyperplasia (CAH) (2.2%), pheochromocytoma (1%), myelolipoma (1%) and adrenal carcinoma (1%). According to functional status, most (75.8%) were hypofunctional. Of the patients with adrenal insufficiency, secondary adrenal insufficiency was the most common (78.3%). Among the secondary adrenal insufficiencies, 75.9% had iatrogenic adrenal insufficiency and 24.1% had pituitary diseases. Regarding the cases of primary adrenal insufficiency, 20% cases were due to adrenal tuberculosis, 6.6% were due to adrenal histoplasmosis and 73.3% were idiopathic. Most of the adrenal insufficiency patients presented with hypotension (66.7%), followed by gastrointestinal symptoms (76.8%), weight loss (55.1%), hyponatraemia (42%), pigmentation (13%) and hypoglycemia (10%). In this study, 9.9% patients had adrenal incidentaloma. Most of them (88.9%) were benign. Causes of Cushing’s syndrome among the study population were, iatrogenic (66.7%), adrenal (16.7%) and pituitary cause (16.7%). In this study, 16.5% patients had endocrine hypertension and the causes were endogenous Cushing’s syndrome (53.3%), Conn’s syndrome (40%) and pheochromocytoma (6.7%). Of the hypertensive patients, 60% had co-existing hypokalemia.&#x0D; Conclusion: Adrenal insufficiency was the most common adrenal disorder followed by endogenous Cushing’s syndrome, Conn’s syndrome, non-functioning adenoma and other adrenal disorders. Presentations of adrenal disorders are variable. Among the cause of adrenal insufficiency iatrogenic adrenal insufficiency was the most common.&#x0D; Birdem Med J 2021; 11(2): 103-107

The utility of dynamic MRI in differentiating the hormone-producing ability of pituitary adenomas

PurposeTo investigate the relationship between dynamic magnetic resonance imaging (MRI) findings and hormonal activity in pituitary adenomas.MethodsWe retrospectively evaluated the dynamic MRI findings in 244 patients with pathologically confirmed pituitary adenomas and a diagnosis of clinically active prolactin (PRL)-producing adenomas. Among the 244 pituitary adenomas, 55, 16, 6, and 4 produced growth hormone (GH), PRL, adrenocorticotropic hormone, and thyroid-stimulating hormone, respectively, while 163 were non-functioning (NF) adenomas. For each adenoma, we calculated the washout rate (WR) and early (EER) and delayed (DER) tumour-to-normal-tissue enhancement ratios.ResultsThe respective mean values of the WR, EER, and DER were 9.4%, 75.2%, and 64.5% for GH-producing adenomas; 6.2%, 117.1%, and 106.2% for PRL-producing adenomas; and 5.4%, 116.7%, and 108.7% for NF adenomas. GH-producing adenomas had significantly lower EER and DER values than PRL-producing (P < 0.001) and NF adenomas (P < 0.001). In ROC analysis of GH-producing and non-GH-producing adenomas, the areas under the curves of WR, EER, and DER were 0.593, 0.825, and 0.857, respectively.ConclusionThere are differences in dynamic MRI features between GH-producing and non-GH-producing adenomas, which suggests that EER and DER may be useful for diagnosing GH-producing adenomas.

Results of Endoscopic Surgery in Patients with Pituitary Adenomas : Association of Tumor Classification Grades with Resection, Remission, and Complication Rates.

ObjectiveThe endoscopic endonasal transsphenoidal approach is a widely-used method for the surgical treatment of pituitary adenomas. We aimed to evaluate the results of endoscopic surgery by comparing preoperative classification methods and investigating their relationship with postoperative resection and remission rates and complications. MethodsWe retrospectively reviewed the medical records of 236 patients (118 males) who underwent surgery for pituitary adenomas. Preoperative Knosp classification, tumor size (TS), suprasellar extension (SSE), postoperative resection and remission rates, and complications were evaluated. ResultsThe follow-up period was 3 months to 6 years. The patients’ ages ranged between 16 and 84 years. Endocrinologically, 114 patients (48.3%) had functional adenoma (FA), and 122 patients (51.7%) had non-functional adenoma (NFA). Among the FA group, 92 (80.7%) showed remission. A statistically significant difference was found between patients with and without remission in terms of the Knosp, TS, and SSE classifications (p<0.01). Knosp, TS, and SSE classification grades were found to be correlated with the resection rates (p<0.01). Meningitis was seen in seven patients (3.0%), diabetes insipidus in 16 (6.9%; permanently in two [0.9%]), and rhinorrhea in 19 (8.1%). Thirty-six patients (15.3%) developed pituitary insufficiency and received hormone replacement therapy. ConclusionThe resection categories and remission rates of FAs were directly proportional to the adenoma sizes and Knosp grades, while the degree of suprasellar growth further complicated resection and remission rates. Adenoma sizes less than 2 cm and SSEs less than 1 cm are associated with favorable remission and resection rates.

The frontal QRS-T angle in patients with incidentally discovered nonfunctional adrenal adenomas.

Few studies have used electrocardiography (ECG) to examine nonfunctional adrenal adenomas (NFAAs). No study has investigated the QRS-T angle in NFAA patients. We analyzed the frontal QRS-T angle of patients with incidentally discovered NFAAs. Adult patients with incidentally discovered NFAAs were included. Patients with chronic diseases other than hypertension or obesity were excluded. The overnight dexamethasone suppression test was performed. Levels of plasma renin and aldosterone, as well as metanephrine fractions in 24-h urine were measured. We performed abdominal magnetic resonance imaging and computed tomography to exclude hormonal hypersecretion and nonadenomas. The frontal QRS-T angle was calculated and verified based on surface ECG. Patients were grouped in terms of QRS-T angle as normal and abnormal, and the abnormal patients were divided into positive and negative subgroups. Of all patients (n=58), six (10.34%) had abnormal QRS-T angles. Hypertension increased the risk of an abnormal QRS-T angle six-fold (odds ratio 6.000; 95% confidence interval 0.982-36.652, p=0.034). The frequency of hypertension was similar between the normal, abnormally positive, and abnormally negative groups (p=0.086). The mean SV1+RV5 value was lower in the abnormal QRS-T angle group (p=0.012). Age, gender, obesity, antihypertensive medication use, prediabetes status, adenoma size or side, hyperlipidemia, and adrenal hormone levels were all not associated with the QRS-T angle. Our study is the first to analyze the association between an abnormal QRS-T angle and NFAA. An abnormal QRS-T angle was found in a significant proportion of patients and was associated with hypertension but seemingly, not with left ventricular hypertrophy. We recommend ECG and blood pressure measurement at the time of diagnosis of an NFAA and on follow-up.

Cardiovascular and metabolic consequences in patients with asymptomatic adrenal adenomas.

The incidence of adrenal tumors has increased over the past 20 years, most of which are incidentally discovered nonfunctioning adenomas (NFA) and tumors with mild autonomous cortisol secretion (MACS). This review aimed to summarize recent progress in understanding cardiometabolic risk in patients with NFA and MACS and to provide updates on the effect of treatment on improving outcomes in this population. NFA and MACS are associated with adverse cardiovascular risk factors and metabolic derangements, which are likely mediated by excessive glucocorticoid secretion. Recent studies showed significantly higher prevalence of hypertension, impaired glucose metabolism, obesity, and dyslipidemia in patients with NFA and MACS. Adrenalectomy may improve comorbidities in selected patients. Asymptomatic adrenal adenomas are common and are associated with adverse cardiometabolic changes. In selected patients, adrenalectomy may reduce cardiometabolic risk and improve clinical outcomes.

Contemporary Experience of Posterior Retroperitoneoscopic Adrenalectomy in the US

As the incidence of adrenalectomy increases steadily, so does the use of minimally invasive approaches like posterior retroperitoneoscopic adrenalectomy (PRA). To date, the largest studies of PRA have been from abroad, and we sought to provide a contemporary US update on the outcomes after PRA. A retrospective chart review was conducted on all PRAs performed at a single tertiary care institution between 2013 and 2020. Patient demographic characteristics, indication for operation, operative details, and postoperative course were abstracted. Outcomes of interest included 30-day mortality, conversion to open or transabdominal approach, postoperative complication, and 30-day readmission. A total of 249 PRAs were performed between 2013 and 2020. The population was 54.2% women and mean (SD) age was 54.1 (14.1) years. Most lesions (60.6%) were left-sided, and the most common diagnosis was nonfunctioning adenoma (39.4%), followed by pheochromocytoma (21.3%) and aldosteronoma (16.6%). Mean (SD) tumor size was 3.2 cm (range 0.5 to 9.4 cm). Median operative length was 110 minutes (range 30 to 319 minutes). Overall, the complication rate was 6.4%. Nine patients (3.6%) had a minor postoperative complication (Clavien-Dindo I to III) and 5 patients (2.0%) had a major postoperative complication (Clavien-Dindo IV to V), including 1 mortality (0.4%). There were 2 conversions of approach (0.8%). The majority of patients (58.2%) were discharged on postoperative day 1, and 92.0% were discharged by postoperative day 3. The 30-day readmission rate was 1.6%. Current practice demonstrates that PRA is an extremely safe approach, with a complication rate < 7% and mortality rate < 1%. In addition, the vast majority of patients are able to return home in an expedient manner.

Complication Rates after Endoscopic Transsphenoidal Surgery for ACTH-Secreting Pituitary Adenomas: A Comparative Analysis with GH and Nonfunctioning Adenomas.

Objectives Some complications have been more frequently reported after surgery for adrenocorticotropin hormone (ACTH)-secreting pituitary adenomas. We compared complication rates in patients with ACTH-secreting pituitary adenomas with those in patients with growth hormone secreting pituitary adenomas (growth hormone [GH] group) and nonfunctioning adenomas (nonfunctioning group). Design A comparative three-group analysis was performed for all patients who had endoscopic transsphenoidal surgery for pituitary adenomas at our center between January 2011 and May 2019. Variables included demographics, preoperative clinical and radiological characteristics, and postoperative radiological and endocrinological outcomes. Complications were divided into four categories: endocrinological, neurosurgical, medical, and ENT (ear-nose-throat)-related complications. Univariate and multivariate statistical analysis were performed. Results A total of 111 patients with pituitary adenomas and a mean age of 53.7 years were included (25 ACTH, 35 GH, and 51 nonfunctioning adenomas). Overall, 28 patients had microadenomas (25.2%) and 83 had macroadenomas (74.8%). Univariate statistical analysis for complications between groups showed no differences in neurosurgical and medical complications. Transient diabetes insipidus and postsurgical bacterial sinusitis were the only variables more frequently seen in the ACTH group ( p = 0.01 and 0.04, respectively). Multivariate analysis for transient diabetes insipidus showed no differences between groups ( p = 0.58). Conclusion Complication rates were similar in all three adenoma groups, particularly concerning major infections, thrombotic events, postoperative cerebrospinal fluid (CSF) leak, and transient diabetes insipidus. Transient diabetes insipidus was related with adenoma size and intraoperative CSF leak. Despite postoperative bacterial sinusitis was statistically higher in the ACTH group, this data should be interpreted with caution given the low number of patients with this complication.

Pituitary Hormonal Status after Endoscopic Endonasal Transphenoidal Removal of Nonfunctioning Pituitary Adenoma: 5 years' Experience in a Single Center.

Background:This study focuses on hormonal disorder and medical complications postoperative endoscopic endonasal transsphenoidal approach of nonfunctioning adenoma at Prasat Neurological Institute, Bangkok, between January 2013 and December 2017.Methods and Material:Baseline characteristics, clinical complications, and hormonal status data were collected from the patients' medical records and analyzed using the descriptive statistics.Results:There were four surgeons who operated 126 cases, 17 of them were reoperation. The average age of the patients was 49 years old. The average length of stay was 13 days, and average operating time was 134 min. Visual field defect was the most common presenting symptom. Almost all the tumors were classified as pituitary macroadenoma which invaded one or two sellar walls. Total or near total tumor removal was the most extend of resection. There were 61 cases developed early diabetes insipidus (DI), but only 12 cases continue to long-term DI. Seven cases were meningitis. Three cases were death. Out of 83 patients who had preoperative intact hypothalamic-pituitary-adrenal (HPA) axis and hypothalamic pituitary thyroidal (HPT) axis, 2 and 3 of them developed postoperative impair HPA and HPT axis in that order. In addition, among 45 patients who had preoperative impair HPA and HPT axis, 6 of them achieved postoperative endocrinological normalization.Conclusion:In preoperative intact pituitary hormone patients, the total or near total tumor removal of non functioning pituitary adenoma may have hypopituitarism during early postoperative period but gradually returned to normal during 4-6 month postoperative period.

Deployment of a bioabsorbable plate as the rigid buttress for skull base repair after endoscopic pituitary surgery.

Bioresorbable alloplastic implants have become desirable as a rigid buttress for reconstructing skull base defects. This study aimed to describe the use of a biodegradable plate (PolyMax RAPID) in skull base repair of endoscopic endonasal pituitary surgery and to investigate the clinical outcome and safety of this novel method. Between January 2019 and January 2020, 22 patients with pituitary adenomas who underwent endoscopic skull base repair with a Polymax RAPID plate were included. After endonasal transsphenoidal surgery, a trimmed bioresorbable plate was placed in the position between the dura and the bone of the skull base to reconstruct the sellar floor and buttress the pituitary gland and sellar packing. The patient demographics, radiologic imaging, and postoperative outcomes were carefully reviewed. All patients were followed up by a routine nasal endoscopic assessment and radiologic examinations. The present study comprised 10 (45.5%) males and 12 (54.4%) females with an average age of 51.9 years. There were 7 (31.8%) growth hormone (GH) secreting adenomas, 2 (9.1%) thyroid stimulating hormone (TSH) secreting adenomas, and 13 (59.1%) non-functioning adenomas. Enlarged sellar floor and paranasal sinusitis were seen in 13 (59.1%) and 11 (50.0%) cases shown by preoperative computed tomography (CT) or magnetic resonance imaging (MRI), respectively. There were 6 (27.3%) grade-1 and 16 (72.7%) grade-0 cases by intraoperative cerebrospinal fluid (CSF) leak grading. None of these patients received lumbar drains postoperatively and no postoperative CSF rhinorrhea was detected in our series. The PolyMax RAPID plates which could be clearly identified on postoperative CT or sagittal T1-weighted MRI were shown to provide an ideal rigid buttress for sellar repair. The Polymax RAPID plate can be an optimal implant to achieve rigid repair of sellar floor defects after endonasal transsphenoidal pituitary surgery.

Endoscopic endonasal approach for pituitary adenomas: Results from a multidisciplinary management

BackgroundEndoscopic endonasal approach (EEA) has gained increasing acceptance in the world; however, pituitary adenomas require multidisciplinary management for good outcomes. The aim of this study is to report the results of this management of a consecutive series of patients who underwent a purely endoscopic endonasal approach for pituitary adenomas resection in our hospital and compare them to other series. MethodsA retrospective review of clinical and radiographic records of 80 consecutive patients with pituitary adenomas who were operated on using an EEA between 2011 and 2019 was performed. The patientś clinical, ophthalmologic, endocrinologic and radiographic outcomes were evaluated. Results57% were women and 43% men. The age ranged from 10 to 79 years. 72 tumours (90%) were macroadenomas; in 19 patients (23.75%) the cavernous sinus was invaded. There were 58 non-functioning adenomas and 17 growth hormone secreting, 4 prolactin-secreting, and 1 thyroid-stimulating hormone-secreting adenomas. Gross total resection was achieved in 76.2% of tumours without cavernous sinus invasion. Of the 53 patients presenting with visual loss, 47 (88.6%) improved or normalized. The remission rates with EEA alone were 58% in the GH-secreting adenomas and 75% in the prolactinomas group. Complications included CSF leak in 12.5%, new hormonal deficit in 18.75%, epistaxis in 6.25%, sella hematoma in 3.75% and neuroinfection in 1 patient (1.25%). We did not have mortality. The follow-up was from 6 to 87 months. ConclusionsA multidisciplinary management is required for the adequate treatment of pituitary adenomas. With good surgical training, the EEA is safe and effective around the world. Our results are similar compared with those reported in previous series of microscopic or endoscopic approaches.

Early Experience of Endoscopic Endonasal Transphenoidal Surgery for Pituitary Adenoma: Preliminary Report of 56 Cases Operated in a West African Institution

Although endoscopic endonasal approach (EEA) has been popularized worldwide for pituitary adenoma surgery, in sub-Saharan Africa, neurosurgeons are still only starting their experience with it. This study was designed to assess the early results of EEA for pituitary adenoma from an under-equipped environment, namely, the Department of Neurosurgery of the Teaching Hospital of Yopougon Abidjan and Bouaké in Ivory Coast. The data of 56 cases of EEA for pituitary adenoma surgery performed between 2016 and March 2019 at the Teaching Hospital of Yopougon-Abidjan and Bouaké were retrospectively assessed. Pre- and postoperative neuro-ophthalmologic and hormonal status were analyzed. Moreover, the quality of tumor removal, and pre- and postoperative complications were also evaluated. In this study, there were nonfunctional adenomas (20), prolactinoma (18), Cushing disease (9), and acromegaly (3). A reduced visual acuity and/or visual field defect was observed in 49 cases. The mean operation time was 225 ± 94.7 minutes. The tumor removals were complete in 57.14%, subtotal in 35.71%, and partial in 7.14%. These led to a visual improvement in 69.64%. Postoperative complications were cerebrospinal fluid leaks (19.64%), diabetes insipidus (12.50%), visual worsening (7.14%), meningitis (3.57%), and carotid injury (3.57%) that led to death. This study represents the early surgical experience using EEA for treating pituitary adenoma in an under-equipped environment. Although the postoperative complication rate was relatively high, refinements of local surgeons' technique would lead to a better patient outcome.