Acromegaly complicated with fulminant pituitary apoplexy: clinical characteristic analysis and review of literature.

PURPOSE: To retrospectively summarize the clinical features of acromegaly complicated with fulminant pituitary apoplexy and analyze the prognostic factors to guide early identification and timely treatment of such patients. METHODS: A retrospective analysis was carried out to summarize the clinical manifestations, hormone changes, imaging, treatment and follow-up of ten patients with acromegaly complicated with fulminant pituitary apoplexy admitted to our hospital from February 2013 to September 2021. RESULTS: The mean age of the ten patients (five males and five females) at the time of pituitary apoplexy was 37.1 ± 13.4 years old. There were nine cases with sudden severe headaches and five cases with visual impairment. All patients had pituitary macroadenomas, of which six cases with Knosp grade ≥3. The level of GH/IGF-1 hormone after pituitary apoplexy was lower compared with pre-apoplexy, and 1 patient reached biochemical remission spontaneously. Seven patients underwent transsphenoidal pituitary surgery after apoplexy and one patient was treated with long-acting somatostatin analog. The biochemical remission rate was 37.5% in eight patients immediately after treatment and 50% at the last follow-up. Patients with Knosp grade ≥3 were less likely to achieve biochemical remission than those with Knosp grade <3 (16.7% vs. 100%, p = 0.048), and patients who achieved biochemical remission had a smaller maximum tumor diameter [20.1 (20.1,28.0) mm vs. 44.0 (44.0,60) mm, p = 0.016]. CONCLUSION: Acromegaly complicated with fulminant pituitary apoplexy remains a diagnostic and therapeutic challenge.

Surgery for Pituitary Tumor Apoplexy Is Associated with Rapid Headache and Cranial Nerve Improvement.

Pituitary tumor apoplexy (PTA) classically comprises sudden-onset headache, loss of vision, ophthalmoparesis, and decreased consciousness. It typically results from hemorrhage and/or infarction within a pituitary adenoma. Presentation is heterologous, and optimal management is debated. The time course of recovery of cranial nerve deficits (CNDs) and headaches is not well established. In this study, a retrospective series of consecutive patients with PTA managed at a single academic institution over a 22-year period is presented. Headaches at the time of surgery were more severe in the early and subacute surgical cohort and improved significantly within 72 h postoperatively (p < 0.01). At one year, 90% of CNDs affecting cranial nerves (CNs) 3, 4, and 6 had recovered, with no differences between early (<4 d), subacute (4−14 d), and delayed (>14 d) time-to-surgery cohorts. Remarkably, half recovered within three days. In total, 56% of CN2 deficits recovered, with the early surgery cohort including more severe deficits and recovering at a lower rate (p = 0.01). No correlation of time-to-surgery and rapidity of recovery of CNDs was observed (p = 0.65, 0.72). Surgery for PTA is associated with rapid recovery of CNDs in the early, subacute, and delayed time frames, and with rapid headache improvement in the early and subacute time frames in 50% or more of patients.

Endoscopic Endonasal Transsphenoidal Approach for the Surgical Treatment of Pituitary Apoplexy and Clinical Outcomes.

Purpose: This study investigated the clinical manifestations, surgical method, and treatment outcomes of patients with pituitary apoplexy and evaluated the safety and effectiveness of the endoscopic endonasal transsphenoidal approach in the treatment of pituitary adenomas. Patients and methods: In this retrospective study, were analyzed the data of patients with symptomatic pituitary apoplexy who received surgical treatment by endoscopic endonasal transsphenoidal approach from January 2017 to June 2020 at the Department of Neurosurgery of the First Affiliated Hospital of Bengbu Medical College. Patients were followed up through outpatient visits and telephone interviews. Results: Data for 24 patients including 13 males and 11 females with an average age of 46.46 years were analyzed. Headache (83.33%) and visual disturbances (75.00%) were the most common preoperative manifestations. In the 24 patients, 21 (87.50%) tumors were completely removed and 3 (12.50%) were partly removed. Intractable headache improved in all patients over a mean follow-up time of 25.16 months, and postoperative improvement in visual acuity was achieved in 17 of 18 patients (94.44%) with vision defects. Four patients (16.67%) experienced transient urinary collapse after the operation. No intracranial infection, carotid artery injury, or death occurred. Conclusion: The endoscopic endonasal transsphenoidal approach is a safe and effective method for the treatment of pituitary apoplexy.

Metastases to the Pituitary Gland: Histological Patterns of Spread and Review of the Literature.

Few studies have focused on histological patterns of metastatic spread to the pituitary gland. We review our experience and that in the literature, 1970-present. Departmental cases, 1998-2021, were assessed for anterior versus posterior gland and/or capsular involvement and cohesive tumor obliterating underlying pituitary architecture versus metastatic cells filling pituitary acini with relative acinar preservation. Eleven autopsy/15 surgical cases, including 2 metastases to pituitary adenomas, were identified. Cohesive/obliterative patterns predominated histologically in both surgical and autopsy cases, but acinar filling by metastatic cells was extensive in 3/26 cases, focal in 5/26, and had resulted in initial erroneous impressions of atypical pituitary adenoma/pituitary carcinoma in 1 case and pituitary adenoma with apoplexy in another, likely due to focusing on necrotic areas in the specimen where the acinar pattern had been broken down and not appreciating nearby areas with acinar filling by metastatic cells. Although most pituitary metastases produce readily identifiable cohesive/obliterative patterns, diagnostic challenges remain with the less frequently seen "acinar filling" pattern. A dichotomy exists between patients with symptomatic pituitary metastases occurring early in the disease course and requiring surgical excision versus patients in whom asymptomatic small pituitary metastases are found incidentally at autopsy, the latter almost invariably in late disease stages, with widely disseminated metastatic disease.

Isolated Third Cranial Nerve Palsy in Pituitary Apoplexy: Case Report and Systematic Review.

OBJECTIVES: To report a case of isolated third nerve palsy from pituitary apoplexy and perform a systematic literature review. MATERIALS AND METHODS: MEDLINE/EMBASE databases were searched up to September 2020. INCLUSION CRITERIA: Age≥18, isolated third nerve palsy from pituitary apoplexy. EXCLUSION CRITERIA: Age<18, presence of other neurological findings, no hemorrhage or infarction of pituitary. RESULTS: Case report: A 76-year-old woman presented with headache and right-sided ptosis. Right-eye exam revealed complete ptosis, absent pupillary constriction and accommodation, depressed and abducted eye on primary gaze, and -1 impaired depression, adduction, elevation, without other neurological findings. Brain MRI was suggestive of pituitary apoplexy. Pathology after transsphenoidal resection revealed an infarcted pituitary adenoma. Third nerve palsy resolved completely in 21 days. Systematic review: Twenty-three studies reporting 35 patients were selected from 182 abstracts. Twenty-nine (83%) had complete isolated third nerve palsy. Headache was reported in 31 (97%). Thirty-one had hemorrhage and 1 had infarction of pituitary. Cavernous sinus invasion occurred in 14 (50%). Twenty-eight were managed surgically (80%) and 7 medically (20%). Nerve palsy resolved completely in 27 (82%) and partially in 4 (11%). CONCLUSIONS: Pituitary apoplexy is an important differential diagnosis in patients with isolated third nerve palsy. Isolated third nerve palsy in apoplexy appears to have favorable prognosis.

Pituitary Apoplexy: A Retrospective Study of 33 Cases From a Single Center.

Purpose: Acute symptomatic pituitary apoplexy is a rare and potentially life-threatening condition. However, pituitary apoplexy can also present with milder symptoms and stable hemodynamics. Due to the rarity of this inhomogeneous condition, clinical studies are important to increase the knowledge. Methods: We retrospectively reviewed all consecutive cases of pituitary apoplexy being admitted between January 1st, 2005 and December 31st, 2019 at the Karolinska University Hospital, Stockholm, Sweden, for symptoms, results of magnetic resonance (MRI), biochemistry, management and mortality. Results: Thirty-three patients were identified with pituitary apoplexy, 18 were men (55%) and mean age was 46.5 (17.2) years. The incidence of symptomatic pituitary apoplexy was 1.6 patients/year (0.76 patients/1,000,000 inhabitants/year). The majority presented with headache (n=27, 82%) and hormonal deficiencies (n=18, 55%), which were most frequent in men. ACTH deficiency was present in nine patients (27% but 50% of those with hormonal deficiencies). All had the characteristic findings on MRI. Only three patients (9%) required acute pituitary surgery, while eight were operated after more than one week. Seven (21%) were on antithrombotic therapy. None of the patients died in the acute course. During follow-up (7.6 ± 4.3 years) none of the hormonal deficiencies regressed and 3 patients died from non-related causes. Conclusion: Our study confirmed the rarity and the symptoms of this condition. Surprisingly, only 3 patients needed acute neurosurgical intervention, perhaps due to milder cases and a general intensified treatment of precipitating factors. An early awareness and in severe cases decision on pituitary surgery is of utmost importance to avoid severe complications.

Asymptomatic pituitary apoplexy induced by corticotropin-releasing hormone in a 14 year-old girl with Cushing's disease.

OBJECTIVES: Pituitary apoplexy is a rare complication of Cushing's disease (CD), especially in the paediatric age and even more rarely it can occur following anterior pituitary stimulation tests. CASE PRESENTATION: We report a case of a 14-year-old girl who was admitted to our Hospital for evaluation of a possible Cushing's syndrome (CS). Her symptoms and initial laboratory tests were suggestive of CD. Magnetic resonance imaging (MRI) revealed a microadenoma of the pituitary gland. As part of her evaluation she was submitted to a corticotropin-releasing hormone (CRH) stimulation test. Two and a half months later the patient was re-evaluated and presented with both clinical improvement of CS, biochemical resolution of hypercortisolism and tumour size reduction in the MRI, also evidencing a haemorrhagic component favouring the diagnosis of pituitary apoplexy after CRH stimulation test. The patient denied any episodes of severe headache, nausea, vomiting or visual changes. CONCLUSIONS: To our knowledge, the authors report the first case of a pituitary apoplexy after a CRH stimulation test in the paediatric age.

Secondary Pituitary Abscess Inside Adenoma: A Case Report and Review of Literature.

BACKGROUND: Pituitary abscesses within pre-existing pituitary conditions, such as craniopharyngioma, pituitary adenoma, or Rathke cleft cyst, are quite rare. A case of pituitary abscess secondary to adenoma is presented, and the literature is reviewed. CASE DESCRIPTION: An 11-year-old boy presented with a 3-day history of sudden-onset headache and visual loss. Magnetic resonance imaging demonstrated a sellar region lesion with intralesional hemorrhage. Preoperative diagnosis was pituitary adenoma with apoplexy. An endoscopic transnasal transsphenoidal approach was used for emergent total tumor resection. Pathology confirmed the diagnosis of pituitary adenoma with apoplexy and inflammation, and microbiologic examination was positive for Staphylococcus aureus. CONCLUSIONS: Secondary pituitary abscess is a rare entity, and preoperative diagnosis is challenging. The treatment strategy includes prompt surgical resection and drainage of the abscess, followed by prolonged antibiotic therapy.

Significance of Elevated HMGB1 Expression in Pituitary Apoplexy.

BACKGROUND/AIM: High-mobility group box 1 (HMGB1) is a nuclear DNA-binding protein that exerts a range of proinflammatory actions when it is secreted extracellularly. We hypothesized that HMGB1 released from damaged cells in pituitary apoplexy would exacerbate the neurological symptoms due to acute inflammation. PATIENTS AND METHODS: All the patients included in this study suffered from non-functioning pituitary adenoma. Four patients with apoplexy and three patients without apoplexy were included in this study. They underwent endonasal transsphenoidal endoscopic surgery to resect the tumors. We conducted enzyme-linked immunosorbent assay (ELISA) to measure HMGB1 in the surgical specimens. RESULTS: Patients with apoplexy expressed HMGB1 at significantly higher levels than those in the non-apoplexy group (p=0.0478). CONCLUSION: HMGB1 may be involved in subacute inflammation of pituitary apoplexy. Further work is needed to elucidate the detailed biological significance of HMGB1 in this disease.

Coagulative necrotic pituitary adenoma apoplexy: A retrospective study of 21 cases from a large pituitary center in China.

PURPOSE: Coagulative necrotic pituitary apoplexy (CNPA) is a clinical entity with unique intraoperative and histopathological manifestations. We aimed to improve the knowledge of this rare disease through the largest case series published to date. METHODS: A retrospective review of 21 CNPA patients was performed from among 5095 patients who underwent surgery for pituitary adenomas at a single institution between January 2009 and June 2017. The demographic, clinical, endocrine, neuroimaging, intraoperative, and histopathological findings, management and prognosis were summarized. RESULTS: Headache was the most common symptom that was observed in 21 patients, followed by visual disturbances (17/21, 81.0%), nausea and vomiting (16/21, 76.2%), electrolyte disturbance (13/21, 61.9%), and oculomotor palsies (10/21, 47.6%). Hypopituitarism with at least one anterior pituitary deficiency, especially panhypopituitarism (10/21, 47.6%), was present in 81.0% of patients. Most patients (81.0%) showed typical MRI appearances. All 21 patients underwent transsphenoidal surgery (TSS), and 16 patients had total tumor resection demonstrated by postoperative MRI. Cottage cheese-like necrosis was observed in 16 patients (76.2%) intraoperatively. Histopathology showed large areas of pink, acellular, coagulative necrotic areas in the central zone, and a pseudocapsule in the border zone. After follow-up for 4.3 ± 2.3 years, only 28.6% of patients still suffered from corticotropic deficiency, and 9.5% of patients had gonadotropic deficiency. These patients were administered the appropriate corresponding hormones for life. CONCLUSIONS: CNPA can be correctly diagnosed preoperatively by typical clinical and MRI characteristics. Early surgery combined with hyperbaric oxygen therapy early postoperatively usually yields satisfactory endocrine and neuro-ophthalmic outcomes.

Post-Traumatic Pituitary Tumor Apoplexy After Closed Head Injury: Case Report and Review of the Literature.

BACKGROUND: Head trauma is a rare inciting factor of pituitary apoplexy (PA); however, there is a clear temporal relationship between trauma and apoplexy, and this is the first reported case of PA after an assault. CASE DESCRIPTION: We present a rare case of a 63-year-old man who developed PA after sustaining a closed head injury from assault with a metal pole. The patient had a known pituitary tumor for which he had previously declined surgical resection. On initial computed tomography scan, there was no traumatic intracerebral hemorrhage or subarachnoid hemorrhage. There was sellar expansion but no obvious sellar hemorrhage. Within 48 hours of admission, the patient was presumed septic after developing altered mental status, fevers, hypotension, and tachycardia. Magnetic resonance imaging of the brain with and without gadolinium revealed a poorly enhancing, necrotic, and hemorrhagic pituitary mass, consistent with pituitary tumor apoplexy. After administration of intravenous glucocorticoids, the patient underwent emergent endoscopic transsphenoidal resection of the pituitary tumor apoplexy. Postoperatively, the patient had neurologic improvement with stable vision. CONCLUSIONS: Early and accurate diagnosis is important to allow for timely neurosurgical intervention. Symptoms of fever, hypotension, and tachycardia in a patient with a known sellar mass should raise the suspicion of hypocortisolemia from pituitary tumor apoplexy.

Apoplexy in nonfunctioning pituitary adenomas.

Pituitary apoplexy is an uncommon event, occurring due to the infarction and/or haemorrhage usually of a previously unknown pituitary adenoma. It can occur in all adenoma subtypes but is more common in nonfunctioning pituitary adenomas. The physiopathology is not completely clear, and precipitating factors, such as major surgeries, anticoagulant use or pituitary dynamic tests, can be found in up to 40% of patients. The clinical presentation is characterized by a rapid onset with a headache as the main symptom, but visual disturbances can also be present as well as meningism and intracranial hypertension. The diagnosis is based on imaging evaluations, mainly using magnetic resonance imaging, which can show various patterns depending on the timeframe following the occurrence of the apoplectic event. Pituitary hormonal deficits are also common, and the evaluation of hormonal levels is mandatory. Pituitary apoplexy can be managed by surgery or conservative treatment, and a multidisciplinary team is essential for the decision-making process. The outcome is usually positive with both surgical and conservative approaches, but surveillance is needed due to the risk of re-bleeding or tumour recurrence.

An Unusual Presentation of Pituitary Gland Apoplexy With Noninfectious Meningitis.

Pituitary adenomas make up 10% of intracranial tumors, but because of their location, they may go undetected for long periods. In this article, we report the case of a 68-year-old white man found deceased in his residence, who died of acute pituitary tumor apoplexy. He was known to have severe symptoms including acute headache, vision loss, and altered behavior. When found, his home was in extreme disarray, mimicking a possible assault. At autopsy, the decedent had multiple superficial abrasions about the upper and lower extremities, as well as a 2.5 × 3-cm pituitary adenoma compressing the carotid arteries and optic nerves. Initial coroner and police investigators were strongly considering homicide with robbery as a motive, given the disarray present at the scene. This case highlights the importance of postmortem examination of the pituitary gland in all cases where neurological symptoms are reported prior to death.

Postoperative Neurologic Outcome in Patients with Pituitary Apoplexy After Transsphenoidal Surgery.

OBJECTIVE: Pituitary apoplexy can cause severe neuro-ophthalmologic or endocrinologic sequelae, requiring timely treatment. The present study was performed to evaluate postoperative neurologic outcomes and to identify their risk factors in patients who underwent transsphenoidal surgery for pituitary apoplexy. METHODS: Forty-one consecutive patients with pituitary apoplexy who underwent transsphenoidal surgery were reviewed retrospectively. The initial rates of visual acuity (VA) decrease, visual field (VF) defect, and ocular palsy were 34.1%, 46.3%, and 68.3%, respectively. The median maximal diameter and tumoral volume was 2.6 cm (range, 2.0-4.6 cm) and 5.3 cm3 (range, 2.4-38.8 cm3), respectively. Seventeen patients (41.5%) underwent surgery within 7 days. The median follow-up duration was 45 months (range, 12-196 months). RESULTS: At the last follow-up, 62.9% (22/35) of patients had made a full recovery from preoperative neurologic deficits, with partial recovery observed in the remaining patients. The rates of improvement and full recovery from VA decrease were 92.9% and 57.1%, respectively; those from VF defect were 94.7% and 36.8%, respectively; and those from ocular palsy were 100.0% and 96.4%, respectively. On multivariate analysis, initial visual impairment score (≥20) was the only significant risk factor for postoperative neurologic sequelae (P < 0.001; odds ratio, 40.8). Surgical timing was not associated with postoperative neurological recovery (P = 0.733). CONCLUSIONS: Ocular palsy was fully recovered in 96.4% patients with pituitary apoplexy after transsphenoidal surgery. Initial visual impairment status was found to be more strongly associated with postoperative neurologic recovery than surgical timing.

Sphenoid sinus mucosal thickening in the acute phase of pituitary apoplexy.

PURPOSE: In pituitary apoplexy (PA), there are preliminary reports on the appearance of sphenoid sinus mucosal thickening (SSMT). SSMT is otherwise uncommon with an incidence of up to 7% in asymptomatic individuals. The aim of this study was to evaluate the incidence and clinical significance of SSMT in patients with PA and a control group of surgically treated non-functioning pituitary adenomas (NFPAs). METHODS: Retrospective review of clinical and imaging variables in PA and NFPA patients. Sphenoid sinus mucosal thickness was measured on the presenting MRI scan by a blinded neuroradiologist. Pathological SSMT was defined as >1 mm adjacent to the pituitary fossa. Forward stepwise logistic regression was used to identify factors associated with SSMT. RESULTS: There were 50 NFPA and 47 PA patients. PA patients were managed conservatively (N = 11) or surgically (N = 36). The median sphenoid sinus mucosal thickness was greater in the PA than NFPA groups (2.0 vs. 0.5 mm; p < 0.001). In multivariate analysis of both the PA and NFPA groups, the presence of PA was the only factor associated with SSMT (OR 0.043, 95% CI 0.012-0.16; p < 0.001). In multivariate analysis of the PA group alone, a shorter time from symptom onset to presenting MRI scan (OR 0.12, 95% CI 0.026-0.54; p = 0.006) and a more severe grade of apoplexy (OR 7.29, 95% CI 1.10-48.40; p = 0.04), were associated with SSMT. CONCLUSION: The incidence of SSMT is higher in patients with PA, especially during the acute phase of PA. The aetiology of SSMT in PA is unclear and may reflect inflammatory and/or infective changes.

Spontaneous retroclival hematoma in pituitary apoplexy: case series.

OBJECT: Pituitary apoplexy is a rare and potentially life-threatening disorder that is most commonly characterized by a combination of sudden headache, visual disturbance, and hypothalamic/hormonal dysfunction. In many cases, there is hemorrhagic infarction of an underlying pituitary adenoma. The resulting clinical symptoms are due to compression of the remaining pituitary, cavernous sinuses, or cranial nerves. However, there are only 2 case reports in the literature describing spontaneous retroclival expansion of hemorrhage secondary to pituitary apoplexy. Ten cases of this entity with a review of the literature are presented here. METHODS: This is a single-institution retrospective review of 2598 patients with sellar and parasellar masses during the 10-year period between 1999 and 2009. The pituitary and brain MRI and MRI studies were reviewed by 2 neuroradiologists for evidence of apoplexy, with particular attention given to retroclival extension. RESULTS: Eighteen patients (13 men and 5 women; mean age 54 years) were identified with presenting symptoms of sudden onset of headache and ophthalmoplegia, and laboratory findings consistent with pituitary apoplexy. Ten of these patients (8 men and 2 women; mean age 55 years) had imaging findings consistent with retroclival hematoma. CONCLUSIONS: Retroclival hemorrhage was seen in the majority of cases of pituitary apoplexy (56%), suggesting that it is more common than previously thought.

Spontaneous remission of acromegaly and Cushing's disease following pituitary apoplexy: Two case reports.

In this double case report, we present two special cases of pituitary apoplexy. First, we describe a patient with growth hormone deficiency despite clinical suspicion of acromegaly. Imaging showed evidence of a recent pituitary apoplexy, which might have caused spontaneous remission of the acromegaly before presentation at our outpatient clinic. Second, we describe a patient who presented with spontaneous remission of Cushing's disease after pituitary apoplexy, followed by a spontaneous remission of a relapse of the Cushing's disease due to a second pituitary apoplexy. These cases show that patients in spontaneous remission of hormonally active pituitary adenomas should be suspected of a pituitary apoplexy. Furthermore, even after spontaneous remission following pituitary apoplexy, careful long-term follow-up of these patients is mandatory, as relapses of hormonal hypersecretion can occur.

An unexpected headache: pituitary apoplexy in a pregnant woman on anticoagulation.

Pituitary apoplexy is a rare event in which the pituitary gland undergoes infarction or haemorrhage, most commonly in the setting of an underlying tumour. We report on apoplexy of an undiagnosed pituitary adenoma precipitated both by physiological enlargement of the pituitary in pregnancy and prophylactic anticoagulation from a history of deep vein thrombosis. The haemorrhage was managed conservatively without significant complications.

Pituitary apoplexy presenting with anorexia and hyponatraemia.

Pituitary apoplexy, a syndrome caused by haemorrhage into the pituitary gland, typically manifests as sudden severe headache, visual symptoms and hypopituitarism, including adrenal insufficiency. We report a case of a 65-year-old man with adrenal insufficiency due to pituitary apoplexy presenting with anorexia following temporal headache and diagnosed through evaluation for hyponatraemia. MRI focusing on the pituitary gland helped to confirm the diagnosis. Our experience serves as a useful reminder of this atypical presentation of pituitary apoplexy, also known as 'subclinical pituitary apoplexy,' and underscores the importance of careful evaluation for hyponatraemia using serial urine osmolality, which is useful to distinguish hypovolaemic hyponatraemia from euvolaemic hyponatraemia. Clinicians should consider pituitary apoplexy as a differential diagnosis in cases of anorexia, loss of energy or hyponatraemia, following headache even when the patient is lacking classical symptoms such as severe headache or visual symptoms.