The role of intervention timing and treatment modality in visual recovery following pituitary apoplexy: a systematic review and meta-analysis.

INTRODUCTION: Pituitary apoplexy has historically been considered an emergent condition that necessitates surgical intervention when there is acute symptomatic onset. This potentially serious condition often occurs in the setting of an underlying adenoma, cystic lesion, or other sellar mass. When these mass lesions hemorrhage within the confined space of the sella turcica, the pituitary gland is subjected to hemorrhagic ischemia. Furthermore, critical neurovasculature in close proximity to the sella can sustain collateral damage. In the present study, we investigate whether early versus delayed surgical intervention (in terms of three timelines: before versus after 48 h, 72 h, and 7 days, respectively) results in differences in visual outcomes for patients experiencing pituitary apoplexy with acute onset neurological and/or neuro-opthalmic symptoms. Furthermore, we compare the efficacy of surgical decompression versus expectant management of this condition. METHODS: Accordingly, we queried the PubMed, Scopus, and Embase databases in adherence to PRISMA guidelines. Quantitative meta-analysis was performed according to the Mantel-Haenszel method and forest plots were generated using Review Manager v5.4. P-values < 0.05 were defined as the threshold for statistical significance. RESULTS: Twenty-nine studies remained eligible for review following initial search and screen, including 16 studies describing the role of intervention timing and 15 studies comparing intervention modality. Most patients presented with a visual deficit, and all patients underwent surgery - most commonly via the endoscopic endonasal (EEA) approach. Two hundred and twenty patients were included in the sub-analysis for the 7-day cutoff point. Furthermore, 81 patients underwent surgical decompression of the sella prior to 48 h, and 32 patients underwent surgical decompression between 48-72 h following presentation. Almost all patients exhibited improved vision post-decompression, including 19/19 patients (100%) in the post-72-h cohort. On meta-analysis using the Mantel-Haenszel method, there was a significant difference in vision outcomes in favor of patients who underwent surgical decompression before 7 days as compared to after seven days (OR 5.88, 95% CI [1.77, 19.60], I2 = 0%, p < 0.01). In a separate sub-analysis, there was a total of 288 patients across 15 studies comparing surgical versus conservative management of pituitary apoplexy. These management options proved equivocal on meta-analysis (p > 0.05). CONCLUSION: In the present study, timing of surgical intervention for pituitary apoplexy was predictive of visual function recovery only at the 7-day timepoint, as has been reported by previous studies. Ultimately, this suggests that pituitary apoplexy involving severe visual deficits or altered mental status is best addressed within the first seven days post-presentation, and that both surgery and conservative management can offer similar outcomes. When apoplexy is suspected, IV corticosteroids should be administered independent of acuity or severity to prevent secondary adrenal crisis. Subsequently, for patients presenting without severe visual or other neurological deficits, expectant management is recommended. Management should be patient-specific and dependent upon the severity of symptoms present at onset.

Pituitary apoplexy score, toward standardized decision-making: a descriptive study.

Pituitary apoplexy (PA), a rare and life-threatening complication of pituitary adenomas, prompts urgent glucocorticoid administration. The optimal surgical approach is debated, and the Pituitary Apoplexy Score (PAS) aids decision-making. Our retrospective study (2003-2022) assesses variables in PA patient groups (surgical vs. non-surgical), applying PAS to establish a significant threshold for surgical decisions. Additionally, we aim to compare the rates of ophthalmological and endocrine deficit between both groups and identify any associated variables. PAS discrepancies were observed, with averages of 1.7 ± 1.7 (p < 0.0001) for conservative and 3.9 ± 1.7 (p < 0.0001) for surgical groups, confirmed by multivariate analysis (p = 0.009). A PAS threshold of 5, showing over 80% positive predictive value, was established. Patients with low prolactin levels (< 5 ng/ml) had higher corticotropic deficiency prevalence at 3-month and 1-year follow-ups (p = 0.017 and 0.027). Our study supports PAS as a valuable PA management tool, suggesting potential variable adjustments. Multicenter studies are crucial due to PA's low incidence.

Pituitary apoplexy: a comprehensive analysis of 93 cases across functioning and non-functioning pituitary adenomas from a single-center.

INTRODUCTION: Pituitary apoplexy (PA) is a rare clinical syndrome due to acute/subacute pituitary hemorrhage and/or infarction; data on PA in functioning pituitary adenoma (FPA) is scarce. METHODS: A retrospective record-review of details of PA in non-functioning (NFPA) and FPA managed at tertiary endocrine center. RESULTS: 93 patients [56 males; 33.3% FPA: 5 acromegaly, 14 prolactinoma, and 12 Cushing's Disease (CD)] diagnosed with PA were included. Median age was 40 years, with younger age of presentation in FPA. Type A (acute) [49.5%] and headache (78.5%) were the commonest presentations, with PA being the initial manifestation in 98.4% of NFPA. Median (range) Pituitary Apoplexy Score (PAS) was 2 (0-8). Median tumor diameter was 2.5 cm, with larger tumors in FPA (3.2 cm vs. 2.3 cm). 29 (46.7%) NFPA-PA and 14 (45.2%) FPA-PA patients [71% prolactinoma, 33% in CD, and none in acromegaly] were conservatively managed. In the NFPA cohort, those managed surgically had significantly higher PAS (4 vs. 1) and larger tumor size (2.6 vs. 1.8 cm); however, both arms had comparable recovery of neuro-visual, radiological, and hormonal outcomes. In FPA cohort, CD and acromegaly required definitive treatment, whereas prolactinomas were effectively managed (clinical and biochemical recovery) with oral cabergoline and glucocorticoids. Matching PAS cohorts (to overcome allocation bias for management approach) in macroadenomas (excluding prolactinoma) showed comparable neuro-deficit and hormonal recovery between surgical and conservative approaches. CONCLUSION: PA in FPA has distinct features and management issues. Carefully selected patients (PAS guided) in NFPA with PA for conservative management have comparable outcomes to surgery.

Pituitary and COVID-19 vaccination: a systematic review.

PURPOSE: This systematic review aims to examine the latest research findings and assess the impact of COVID-19 vaccination on the pituitary gland. METHOD: PubMed and Tripdatabase were searched from January 1st, 2020 to February 12th, 2024. Case reports, case series and reviews related to post COVID-19 vaccination pituitary disease were included. Eligible articles were tabulated and analysed in the attempt to provide an overview on the epidemiology, clinical presentation, imaging, treatment, outcomes and pathophysiological background of post COVID-19 vaccination pituitary disease. RESULTS: Among the 23 case reports included in this review, post COVID-19 vaccination hypophysitis was reported in 9 patients, pituitary apoplexy (PA) in 6 cases, SIADH in 5 cases and Isolated ACTH deficiency in 2 cases. Additionally, precipitating adrenal crisis was registered in 7 patients and pituitary tumor enlargement in 1 patient after receiving COVID-19 vaccination. CONCLUSION: Despite the rarity of these events, our research findings suggest an association between COVID-19 vaccination and the subsequent development of pituitary diseases. The most common manifestations include hypophysitis with ADH deficiency, PA and SIADH, with symptoms typically emerging shortly after vaccine administration. Potential pathogenetic mechanisms include molecular mimicry, vaccine adjuvants and vaccine-induced thrombotic thrombocytopenia (VITT), with the presence of ACE2 receptors in the hypothalamus-pituitary system contributing to the process. These findings can aid in diagnostic and treatment decisions for patients presenting with these syndromes. Nevertheless, given the rarity of these events, safety and efficacy of the currently available COVID-19 vaccines remain robust and we strongly advocate continuing pursuing vaccination efforts.

Pituitary apoplexy in cushing's disease: a single center study and systematic literature review.

INTRODUCTION: Pituitary apoplexy (PA) in Cushing's disease (CD) is rare with data limited to case reports/series. METHODS: We retrospectively reviewed case records of PA in CD managed at our center from 1987 to 2023 and performed a systematic literature review. RESULTS: We identified 58 patients (44 females), including twelve from our center (12/315 CD, yielding a PA prevalence in CD of 3.8%) and forty six from systematic review. The median age at PA diagnosis was 35 years. The most common presentation was type A (79.3%) and symptom was headache (89.6%), with a median Pituitary Apoplexy Score (PAS) of 2. Median cortisol and ACTH levels were 24.9 µg/dl and 94.1 pg/ml, respectively. Apoplexy was the first manifestation of underlying CD in 55.2% of cases, with 31.1% (14/45) presenting with hypocortisolemia (serum cortisol ≤ 5.0 µg/dl), underscoring the importance of recognizing clinical signs/symptoms of hypercortisolism. The median largest tumor dimension was 1.7 cm (53/58 were macroadenomas). PA was managed surgically in 57.8% of cases, with the remainder conservatively managed. All five PA cases in CD with microadenoma achieved remission through conservative management, though two later relapsed. Among treatment-naïve CD patients with macroadenoma, PA-related neuro-deficit improvement was comparable between surgical and conservative groups. However, a greater proportion of surgically managed patients remained in remission longer (70% vs. 38.5%; p = 0.07), for an average of 31 vs. 10.5 months. CONCLUSION: PA in CD is more commonly associated with macroadenomas, may present with hypocortisolemia, and surgical treatment tends towards higher and longer-lasting remission rates.

Pituitary apoplexy: a systematic review of non-gestational risk factors.

PURPOSE: Pregnancy is a known risk factor for Pituitary Apoplexy (PA) but there is a lack of consistency in the literature regarding non-gestational risk factors responsible for PA. METHODS: We did a systematic review following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to identify the non-gestational risk factors associated with the development of PA in adult patients with pituitary adenoma. Also, we discuss here a case of an elderly female with pituitary macroadenoma who was initially planned for pituitary resection electively but underwent emergency surgery after she developed PA. RESULTS: As per screening and eligibility criteria, seven studies with 4937 study participants were included in this systematic review out of which 490 (9.92%) patients had PA, including asymptomatic subclinical PA (SPA) and symptomatic clinical PA (CPA). The macroadenomas and negative staining of the tumor were found to be a significant risk factor consistently in multivariate analysis in three and two retrospective studies, respectively. However, the results were varied for any significant difference in the risk factors for apoplexy between SPA and CPA. Similarly, there was no consistency among the studies for risk factors significantly responsible for CPA or PA compared to controls. CONCLUSION: No single non-gestational risk factor is solely responsible for the development of PA in a pituitary adenoma compared to the control population. Tumor size (macroadenoma) and the non-functioning status of the adenoma are the only significant factors contributing independently toward an apoplectic event in most patients. Such patients can be prioritized for early pituitary tumor resection.

Pituitary Apoplexy: a re-appraisal of risk factors and best management strategies in the COVID-19 era.

Pituitary apoplexy (PA) is a clinical syndrome caused by acute hemorrhage and/or infarction of the pituitary gland, most commonly in the setting of a pituitary macroadenoma. PA generally presents with severe headache, nausea, vomiting, visual disturbance, and, in more severe cases, altered mental status. Many factors have been attributed to the risk of developing PA, including most recently, numerous reports showcasing an association with COVID-19 infection or vaccination. Initial management of PA includes evaluation and correction of deficient hormones and electrolytes and an assessment if surgical decompression to relieve pressure on optic nerves and other brain structures is needed. While prompt recognition and treatment are crucial to avoid morbidity and mortality, in the modern era, PA is less commonly considered a true neurosurgical emergency requiring immediate (< 24 h) surgical decompression. Traditionally, surgical decompression has been the standard of care for significant mass effects. However, several studies have shown similar outcomes in visual and hormonal recovery with either surgical decompression or conservative medical management. Unfortunately, most evidence on optimal management strategies is limited to retrospective case series, small prospective studies, and one multi-center observational study. This review aims to provide the most up-to-date evidence on the role of COVID-19 in PA and best management strategies.

Subarachnoid hemorrhage due to pituitary adenoma apoplexy-case report and review of the literature.

Pituitary apoplexy (PA) may be complicated by development of subarachnoid hemorrhage (SAH). We conducted a literature review to evaluate the rate of PA-associated tumor rupture and SAH. We conducted a systematic literature search (PubMed, Web of Science, Medline) for patients with PA-associated SAH and report a case SAH following PA. Suitable articles, case series, and case reports were selected based on predefined criteria following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). We reviewed included publications for clinical, radiological, surgical, and histopathological parameters.We present the case of a patient with PA developing extensive SAH whilst on the MRI who underwent delayed transsphenoidal resection. According to our literature review, we found 55 patients with a median age of 46 years; 18 (32.7%) were female. Factors associated with PA-related SAH were hypertension, diabetes mellitus, prior trauma, anticoagulant, and/or antiplatelet therapy. The most common presenting symptoms included severe headache, nausea and/or vomiting, impaired consciousness, and meningeal irritation. Acute onset was described in almost all patients. Twenty-two of the included patients underwent resection. In patients with available outcome, 45.1% had a favorable outcome, 10 (19.6%) had persisting focal neurological deficits, 7 developed cerebral vasospasms (12.7%), and 18 (35.3%) died. Mortality greatly differed between surgically (9.1%) and non-surgically (44.8%) treated patients. PA-associated SAH is a rare condition developing predominantly in males with previously unknown macroadenomas. Timely surgery often prevents aggravation or development of severe neuro-ophthalmological defects and improves clinical outcome.

Pituitary apoplexy in endocrinologically silent adenoma during somatostatin analog administration for pancreatic neuroendocrine tumor: A case report.

A dopamine agonist administered for prolactinoma treatment and pituitary stimulation tests are reported as risk factors for pituitary apoplexy. We report a case of an 82-year-old patient who suffered from pituitary apoplexy in an endocrinologically silent adenoma during lanreotide administration. The patient was diagnosed with a pancreatic neuroendocrine tumor with lymph node metastasis and treated with lanreotide for two years. An endoscopic endonasal transsphenoidal approach was used for tumor and hematoma removal. The specimen showed growth hormone and prolactin positivity and was diagnosed as pit1-lineage plurihormonal adenoma. The tumor also showed positivity for somatostatin receptor 2. Thus, lanreotide treatment is a risk factor for pituitary apoplexy even in silent adenoma.

Comparing neuroendocrine recovery between surgical and conservative management in pituitary apoplexy patients: a propensity score-matched analysis.

Pituitary apoplexy is a rare and potentially life-threatening clinical syndrome. Patients may present with severeneuro-ophthalmologic or endocrine symptoms. Current evidence is unclear whether conservative or surgicalmanagement leads to the best neuroendocrine outcomes. This study aimed to compare neuroendocrine outcomesbetween surgical and conservative treatments in a single center. Cases of patients with pituitary apoplexy whoreceived transsphenoidal surgery or conservative management in Songklanagarind Hospital between January 1,2005 and December 31, 2022 were retrospectively reviewed. A propensity score matching method was used toadjust bias from treatment selection (surgery or conservative treatment). Differences in visual field, visual acuity,cranial nerve, and endocrine outcomes between the surgical and conservative treatment groups were analyzedusing logistic regression analysis. This study included 127 patients, with 98 and 29 patients in the surgical and theconservative treatment group, respectively. The optimal matching method was used for propensity score matching.Compared to the conservative group, the surgically treated patients had a significantly higher rate of visual fieldrecovery (odds ratio (OR): 12.89, P = 0.007). However, there were no statistical differences in the recovery rate ofpreoperative visual acuity, cranial nerve, and endocrine deficits between the groups. Transsphenoidal surgery wasassociated with a higher rate of visual field recovery when compared to the conservative treatment for pituitaryapoplexy patients. Careful selection of appropriate treatment based on the patient's presentation andneuroendocrine status will result in the best outcomes while avoiding unnecessary surgical intervention.

Feasibility of Early Surgical Treatment for Adolescent Patients with Prolactinoma: A Case Report and Literature Review.

Background and Objectives: Prolactinomas are the most common pituitary adenomas, comprising 30-50% of such tumors. These adenomas cause hyperprolactinemia, leading to decreased fertility, reduced energy and libido, and galactorrhea. Diagnosing and treating prolactinomas in adolescents present unique challenges, as symptoms may be confused with age-related developmental variations. This case report explores the outcomes of early surgical intervention in an adolescent with a prolactinoma. Materials and Methods: A 14-year-old female presented delayed menarche and absent pubertal development. Initial evaluation revealed hyperprolactinemia (228.37 ng/mL) with normal estradiol levels. Initial management through observation was adopted, but persistent amenorrhea and severe headaches prompted further investigation. Magnetic resonance imaging revealed a cystic pituitary mass with apoplexy. Due to concerns regarding delayed puberty and the need for rapid normalization of prolactin levels, the patient underwent transsphenoidal surgery. Results: After operation, prolactin levels normalized, menarche occurred within three months, and secondary sexual characteristics developed within eight months. Pathology confirmed a pituitary adenoma with a high Ki-67 index (15%). Conclusions: Early surgical intervention for prolactinomas in adolescents can achieve successful biochemical remission and resolution of endocrine symptoms. Adolescents, particularly those with a high Ki-67 index and potential resistance to dopamine agonists, may benefit from prompt surgical management, resulting in improved clinical outcomes and complete tumor resection.

THE PLACE OF SURGERY IN THE MANAGEMENT OF PROLACTIN SECRETING ADENOMAS.

Introduction: Surgery has lost a lot of ground as the main therapy of most prolactinomas as it is clear from the current guidelines in most prolactin secreting adenomas, even in the setting of optic compression. However, we believe that surgery is still an important part in the treatment of this type of adenomas. This study is aimed to define what is the role of pituitary surgery in the current setup of prolactinoma management. Material and methods: In this retrospective, single-center study we analyzed 12 consecutive patients who underwent primary endoscopic transsphenoidal surgery for prolactinomas, between 2013 and 2022. Surgical indication, previous dopamine agonist (DA) treatment, remission rates, surgical complications, pituitary function and imagistic appearance are presented. Results: Of the 12 patients included, 4 had giant PRL and 8 macroadenomas, while 9 of them had previous DA treatment. The main surgical indication was pituitary apoplexy in 5 patients followed by CSF leak after DA treatment, 3 cases, and DA resistance in 3 cases. The main surgical complications were transitory diabetes insipidus in 7 cases. Normalization of prolactin levels was achieved in 2 patients. Conclusions: Surgical intervention should be strongly considered in all patients with neurologic symptoms referable to the lesion, resistance to medical therapy, other treatment failure or with complications after DA treatment. The endoscopic endonasal surgery offers good surgical outcomes with low rates of surgical complications and should remain an open option for specific cases.

Antiplatelet and anticoagulation therapy and the risk of pituitary apoplexy in pituitary adenoma patients.

PURPOSE: Pituitary apoplexy can be a life threatening and vision compromising event. Antiplatelet and anticoagulation use has been reported as a contributing factor in pituitary apoplexy (PA). Utilizing one of the largest cohorts in the literature, this study aims to determine the risk of PA in patients on antiplatelet/anticoagulation (AP/AC) therapy. METHODS: A single center, retrospective study was conducted on 342 pituitary adenoma patients, of which 77 patients presented with PA (23%). Several potential risk factors for PA were assessed, including: patient demographics, tumor characteristics, pre-operative hormone replacement, neurologic deficits, coagulation studies, platelet count, and AP/AC therapy. RESULTS: Comparing patients with and without apoplexy, there was no significant difference in the proportion of patients taking aspirin (45 no apoplexy vs. 10 apoplexy; p = 0.5), clopidogrel (10 no apoplexy vs. 4 apoplexy; p = 0.5), and anticoagulation (7 no apoplexy vs. 3 apoplexy; p = 0.7). However, male sex (p-value < 0.001) was a predictor for apoplexy while pre-operative hormone treatment was a protective factor from apoplexy (p-value < 0.001). A non-clinical difference in INR was also noted as a predictor for apoplexy (no apoplexy: 1.01 ± 0.09, apoplexy: 1.07 ± 0.15; p < 0.001). CONCLUSIONS: Although pituitary tumors have a high risk for spontaneous hemorrhage, the use of aspirin is not a risk for hemorrhage. Our study did not find an increased risk of apoplexy with clopidogrel or anticoagulation, but further investigation is needed with a larger cohort. Confirming other reports, male sex is associated with an increased risk for PA.

Differences in clinical, hormonal, and radiological presentation and in surgical outcomes in patients presenting with and without pituitary apoplexy. A multicenter study of 245 cases.

PURPOSE: To compare the clinical, hormonal, and radiological presentation and surgical outcomes of patients with macroadenomas presenting with pituitary apoplexy and patients not presenting pituitary apoplexy. METHODS: Multicentre retrospective study of patients presenting with macroadenomas and pituitary apoplexy in three Spanish tertiary hospitals between 2008 and 2022. We selected as control group (non-pituitary apoplexy), patients with pituitary macroadenomas without apoplexy who underwent pituitary surgery between 2008 and 2020. RESULTS: A total of 60 patients with apoplexy and 185 without apoplexy were enrolled. Patients with pituitary apoplexy were more frequently men (70% vs. 48.1%, p = 0.003), had higher prevalence of hypertension (43.3% vs. 26.0%, p = 0.011) and of obesity (23.3% vs. 9.7%, P = 0.007), were under treatment with anticoagulants more commonly (11.7% vs. 4.3%, P = 0.039) and had larger (27.5 ± 11.03 vs. 23.6 ± 12.55 mm, p = 0.035) and invasive pituitary macroadenomas more frequently (85.7% vs. 44.3%, P < 0.001) than those without apoplexy. Surgical remission was more frequent in patients with pituitary apoplexy than those without apoplexy (OR 4.55, P < 0.001), but they developed new pituitary deficits (OR 13.29, P < 0.001) and permanent diabetes insipidus (OR 3.40, P = 0.022) more commonly. However, visual improvement (OR 6.52, p < 0.001) and complete pituitary function recovery (OR 2.37, P < 0.001) was more common in patients without apoplexy. CONCLUSION: Surgical resection is more common in patients presenting with pituitary apoplexy than those without apoplexy; however, visual improvement and complete recovery of pituitary function is more common in patients without apoplexy. The risk of new pituitary deficits and permanent diabetes insipidus is higher in patients with apoplexy than in those without it.

Intrasellar hemorrhagic chordoma masquerading as pituitary apoplexy: case report and review of the literature.

BACKGROUND AND IMPORTANCE: Chordomas are centrally located, expansile soft tissue neoplasms that arise from the remnants of the embryological notochord. Hemorrhagic presentation is exceedingly rare and can resemble pituitary apoplexy. Moreover, a purely intrasellar location of a chordoma is extremely uncommon. We report a case of a hemorrhagic intrasellar chordoma in an adult male, which presented similarly to pituitary apoplexy and was resolved with surgical resection. CLINICAL PRESENTATION: A 69-year-old male presented with a 4 week history of acute onset headache and concurrent diplopia, with significantly reduced testosterone and slightly reduced cortisol. His left eye demonstrated a sixth cranial nerve palsy. Magnetic resonance imaging of the brain showed a large hemorrhagic mass in the pituitary region with significant compression of the left cavernous sinus and superior displacement of the pituitary gland. The patient underwent an endoscopic endonasal transsphenoidal approach for the resection of the lesion. Near total resection was achieved. Final pathology revealed chordoma with evidence of intratumoral hemorrhage, further confirmed by immunopositive stain for brachyury. Post-operatively, the patient had improved diplopia and was discharged home on low dose hydrocortisone. At 3-month follow-up, his diplopia was resolved and new MRI showed stable small residual disease. CONCLUSIONS: Apoplectic chordomas are uncommon given chordoma's characteristic lack of intralesional vascularity and represent a diagnostic challenge in the sellar region. Our unique case demonstrates that despite our initial impression of pituitary apoplexy, this was ultimately a case of apoplectic chordoma that responded well to endoscopic endonasal surgery.

Long-term oncological outcomes after haemorrhagic apoplexy in pituitary adenoma managed operatively and non-operatively.

INTRODUCTION: Depending on severity of presentation, pituitary apoplexy can be managed with acute surgery or non-operatively. We aim to assess long-term tumour control, visual and endocrinological outcomes following pituitary apoplexy with special emphasis on patients treated non-operatively. METHODS: Multicentre retrospective cohort study. All patients with symptomatic pituitary apoplexy were included. Patients were divided into 3 groups: group 1: surgery within 7 days; group 2: surgery 7 days-3 months; group 3: non-operative. Further intervention for oncological reasons during follow-up was the primary outcome. Secondary outcome measures included visual and endocrinological function at last follow-up. RESULTS: One hundred sixty patients were identified with mean follow-up of 48 months (n = 61 group 1; n = 34 group 2; n = 64 group 3). Factors influencing decision for surgical treatment included visual acuity loss (OR: 2.50; 95% CI: 1.02-6.10), oculomotor nerve palsy (OR: 2.80; 95% CI: 1.08-7.25) and compression of chiasm on imaging (OR: 9.50; 95% CI: 2.06-43.73). Treatment for tumour progression/recurrence was required in 17%, 37% and 24% in groups 1, 2 and 3, respectively (p = 0.07). Urgent surgery (OR: 0.16; 95% CI: 0.04-0.59) and tumour regression on follow-up (OR: 0.04; 95% CI: 0.04-0.36) were independently associated with long-term tumour control. Visual and endocrinological outcomes were comparable between groups. CONCLUSION: Urgent surgery is an independent predictor of long-term tumour control following pituitary apoplexy. However, 76% of patients who successfully complete 3 months of non-operative treatment may not require any intervention in the long term.

Pituitary apoplexy secondary to metastatic breast carcinoma into a gonadotroph cell adenoma of the pituitary.

A 65 year-old lady with metastatic breast cancer presented with pituitary apoplexy. Following surgery, histopathology confirmed metastatic breast carcinoma into a gonadotroph cell adenoma of the pituitary. Tumours that metastasise to a normal pituitary gland are unusual. More so, such neoplasm-to-neoplasm metastasis is extremely rare. This is, as far as we are aware, the first description of a metastasis into a gonadotroph cell pituitary adenoma presenting as apoplexy.

Outcomes of pituitary apoplexy: a comparison of microadenomas and macroadenomas.

PURPOSE: We aimed to assess clinical characteristics of apoplexy of pituitary microadenomas compared to macroadenomas. METHODS: We retrieved clinical records of patients > 18 years old, hospitalized in Rambam hospital between January 2001 and October 2017, with pituitary apoplexy and follow-up of at least one year. We compared clinical course and outcomes of apoplexy between patients with microadenomas and macroadenomas, and between patients who received conservative or surgical treatment. Statistical analysis was done using Fisher's exact and Mann-Whitney tests. RESULTS: Twenty-seven patients with pituitary apoplexy were included in the final analysis: mean age was 40.7 ± 12.5 years, 13(48%) were female, 7(26%) had microadenomas, and 21(78%) harbored clinically nonfunctioning pituitary adenomas. Upon admission, hyponatremia, random cortisol level of < 200 nmol/L, and secondary hypothyroidism, were evident in 6/20, 8/18, and 4/18 patients with macroadenoma and 1/5, 2/5, and 1/6 patients with microadenoma, respectively (P = 1.0). Hypogonadotropic hypogonadism was evident in 9/12 men with macroadenoma. In 12 macroadenoma patients, the tumor abutted the optic chiasm, of whom eight had visual field defects. Fifteen patients with macroadenoma and two with microadenoma underwent transsphenoidal surgery. Median follow-up was 3 years. At last follow-up visit, patients with microadenoma had lower rates of corticotropic deficiency or secondary hypothyroidism compared to macroadenoma patients (1/7 vs. 13/20 respectively, p = 0.033). Only two patients with macroadenomas had persistent visual field defects. Outcomes were comparable between conservative and surgical treatment groups. CONCLUSIONS: Long term pituitary hormone deficiencies are more common in pituitary apoplexy patients with macroadenomas. Apoplexy of pituitary microadenoma carries a more favorable prognosis.

GnRH agonist-associated pituitary apoplexy: a case series and review of the literature.

PURPOSE: To examine the clinical presentation and longitudinal outcome of Pituitary Apoplexy (PA) after gonadotropin-releasing hormone agonist (GnRHa) in a series of patients and compare to prior reports. METHODS: A retrospective chart review was performed on seven patients receiving GnRHa who developed PA. Prior reported cases were analyzed. RESULTS: Six men (median age 72 years) with prostate cancer and one woman (aged 22 years) undergoing oocyte donation presented with PA between 1990 and 2020. Most presented with within 24 h of the first dose, but two developed PA 1 to 5 months after GnRHa initiation. The main clinical manifestations were headache (100%), nausea and vomiting (86%). While no patients had a previously known pituitary tumor, all had imaging demonstrating sellar mass and/or hemorrhage at presentation. Among those surgically treated (5/7), 80% (4/5) of patients had pathologic specimens that stained positive for gonadotropins; the remaining patient's pathologic specimen was necrotic. At the time of PA, the most common pituitary dysfunction was hypocortisolism. Central adrenal insufficiency and central hypothyroidism were reversible in a subset. Pituitary imaging remained stable. CONCLUSIONS: This is the first report of a case series with PA after GnRHa administration with longitudinal follow-up. Although infrequent, PA can be life-threatening and should be suspected among patients receiving GnRHa, with or without a known pituitary adenoma, who develop acute headache, nausea and/or vomiting. Since hypopituitarism was reversible in a subset, ongoing pituitary function testing may be indicated.

COVID-19 and the pituitary.

BACKGROUND: Despite COVID-19 being identified as severe respiratory viral infection, progressively many relevant endocrine manifestations have been reported greatly contributing to the severity of the clinical presentation. Systemic involvement in COVID-19 is due to the ubiquitous expression of angiotensin-converting enzyme 2 (ACE2) receptor, responsible for the entry in the cells of SARS-CoV-2, Several reports in humans and animal models showed a significant ACE2 mRNA expression in hypothalamus and pituitary cells. Moreover, higher mortality and poorer outcomes have been widely described in COVID-19 patients with obesity, diabetes and vertebral fractures, which are all highly prevalent in subjects with pituitary dysfunctions. AIM: To review the main endocrine manifestations of COVID-19 with their possible implications for pituitary diseases, the possible direct and indirect involvement of the pituitary gland in COVID-19, the impact of COVID-19 on the management of established pituitary diseases which can be already at increased risk for worse outcomes and on neurosurgical activities as well as vaccination. CONCLUSIONS: Our review underlines that there could be a specific involvement of the pituitary gland which fits into a progressively shaping endocrine phenotype of COVID-19. Moreover, the care for pituitary diseases need to continue despite the restrictions due to the emergency. Several pituitary diseases, such as hypopituitarism and Cushing disease, or due to frequent comorbidities such as diabetes may be a risk factor for severe COVID-19 in affected patients. There is the urgent need to collect in international multicentric efforts data on all these aspects of the pituitary involvement in the pandemic in order to issue evidence driven recommendations for the management of pituitary patients in the persistent COVID-19 emergency.