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.

Complete and Immediate Resolution of See-Saw Nystagmus Following Pituitary Macroadenoma Resection: Case Report and Review of the Literature.

See-saw nystagmus (SSN) is a rare form of nystagmus characterised by alternating elevation with incyclotorsion of one eye and concomitant depression with excyclotorsion of the other eye, often due to abnormalities involving the midbrain and parasellar region. Herein, we highlight a rare case of pendular SSN, which demonstrated complete resolution following resection of a pituitary macroadenoma. A patient in their 40s was identified to have SSN and was diagnosed with a pituitary macroadenoma. They underwent an endoscopic endonasal transsellar approach for resection of the pituitary adenoma. Their nystagmus resolved immediately after surgery. From a review of the literature, resolution and/or significant improvement in SSN occurred in 74% of cases following treatment, with 100%, 86% and 50% following treatment for medication-induced, neurological infarcts, and mass-effect aetiologies of SSN, respectively. SSN is a rare entity with a wide array of aetiologies. Identification of the causative aetiology and appropriate treatment can lead to significant improvement or resolution of the nystagmus in most cases.

Pituitary Adenoma Masquerading as Diabetic Third Nerve Palsy.

A 46-year-old uncontrolled diabetic female visited the ophthalmology outpatient department with a sudden onset of drooping of the upper lid and restriction of movements in adduction, depression, and elevation in the right eye, suggestive of third nerve palsy. Initially, it was thought to be due to a vasculogenic cause due to uncontrolled diabetes, but visual fields revealed bitemporal hemianopia, characteristic of a pituitary adenoma. The diagnosis was confirmed by a CT scan. The patient then underwent a trans-nasal endoscopic removal of the pituitary macroadenoma, followed by a partial recovery of vision.

An invasive nasopharyngeal carcinoma with extension to the pituitary gland mimicking an invasive pituitary macroadenoma: A case report.

Herein, we report a rare case of invasive nasopharyngeal carcinoma with extension to the pituitary gland misdiagnosed as a pituitary macroadenoma. A 50-year-old woman was referred to our department with a diagnosis of pituitary macroadenoma. She presented with headache, visual disturbances, weakness, nausea, vomiting, and hypoglycemia. Polyuria was not reported. On pituitary magnetic resonance imaging, a large mass was observed to extend from the sella turcica to the sphenoid sinus, optic chiasm, and nasopharynx, leading to the initial diagnosis of an invasive pituitary macroadenoma. Biochemical investigations revealed corticotropin deficiency, secondary hypothyroidism, hypogonadotropic hypogonadism, and moderate hyperprolactinemia. Hormone replacement therapy was initiated. After hydrocortisone initiation, diabetes insipidus was revealed. Subsequent magnetic resonance imaging showed an infiltration of the nasopharynx with an extension to the pituitary gland. An endoscopic biopsy confirmed the diagnosis of undifferentiated nasopharyngeal carcinoma. The patient was referred to the oncology department for chemo and radiotherapy. Invasive nasopharyngeal carcinoma presenting with pituitary extension is very rare. It should be considered in the differential diagnosis of pituitary macroadenoma with hypopituitarism. Proper management of such cases requires a multidisciplinary approach.

Giant Clinically Non-Functioning Pituitary Adenoma Presenting as New Onset Generalized Tonic‒Clonic Seizures: A Case Report.

Background: Giant Clinically Non-Functioning Pituitary Adenomas (GCNFPA) are pituitary neuroendocrine tumours spanning beyond 4 cm in diameter without clinically apparent secretory function. They elicit insidious growth pertaining to its asymptomatic nature and present at large sizes from mass effect. Certain clinical features such as headache and visual disturbances are common presentations of GCNFPAs owing to their size, while others such as seizures are extremely rare. Case Report: A 63-year-old woman presented with back-to-back generalized tonic clonic seizures to the A&E and was treated with Levetiracetam. Following initial normal blood investigations, a visual field analysis revealed a bitemporal upper quadrantanopia and further evaluation using MRI found a giant pituitary lesion with suprasellar extension through the third ventricle into the lateral ventricles with significant mass effect. She underwent neuro-navigation guided endonasal transsphenoidal subtotal resection 2 weeks later. The histological diagnosis of null cell adenoma with a Ki67 of 3% was made. At 3 months of follow-up, she is symptom free and monitored with serial MRIs. Conclusion: Seizures are an uncommon presentation of GCNFPAs limited to a few case reports. This illustrates the importance of careful evaluation of patient presentations to correctly diagnose pituitary neoplasms and prioritizing symptom relief in choosing surgical approaches.

Pituitary Macroadenoma: A Comprehensive Case Study of Surgical Intervention and Postoperative Management.

This case report presents a comprehensive analysis of a 48-year-old woman diagnosed with pituitary macroadenoma, detailing the clinical presentation, surgical intervention, and postoperative management. The patient exhibited a complex array of symptoms, including persistent headaches, insomnia, and anemia, with a history of trauma and blood transfusion. Magnetic Resonance Imaging (MRI) confirmed the presence of a large, lobulated pituitary macroadenoma, prompting a trans-nasal trans-sphenoidal endoscopic excision. The surgical procedure was successful, but postoperative complications, revealed by a CT scan, included hyperdense lesions and mixed-density collections. Incorporating antibiotics, analgesics, antacids, and anti-emetics, vigilant postoperative care addressed these complications. This case underscores the challenges and successes in managing pituitary macroadenomas, highlighting the importance of individualized care, multidisciplinary collaboration, and ongoing research for optimizing patient outcomes. The insights gained from this case contribute to the evolving understanding and refinement of strategies for addressing these complex tumors.

Medically responsive amyloidogenic giant sellar-parasellar prolactinoma.

Background: Giant prolactinomas are rare; among them, the amyloidogenic variant, prolactinomas with extensive spherical amyloid deposits, are rare, with only 30 cases reported with recommendations of surgical management contrary to the routine prolactinoma's medical management. Case Description: We report here a case of giant amyloidogenic prolactinoma in a 32-year-old male patient who had a very atypical presentation in terms of clinical, radiological, and pathological features and responded to dopamine agonist therapy like a normal prolactinoma. Conclusion: Amyloidogenic giant prolactinomas are rare. Contrary to usual belief, even they remain medically responsive; however, more literature is required to decide their ideal management.

The Role of Optical Coherence Tomography in the Early Detection of Chiasmal Compression: Hypophyseal Adenoma Presenting With Bitemporal Nerve Fiber Layer Thinning.

Hypophyseal adenomas can present with or without minimal visual disturbances. We present a case of a 40-year-old male with a hypophyseal adenoma, highlighting bitemporal peripapillary retinal nerve fiber layer (NFL) thinning on optical coherence tomography (OCT) as a major sign of chiasmal damage despite minimal asymmetrical nonspecific changes detected on initial visual field testing. The bitemporal NFL thinning prompted further evaluation with MRI, which confirmed the presence of a macroadenoma of the hypophysis. Despite the large adenoma, treatment with cabergoline led to regression, and the patient's visual field improved. This case underscores the importance of OCT in detecting subtle structural changes associated with pituitary tumors, as it can facilitate early diagnosis and prompt intervention for optimal visual outcomes.

Moyamoya Disease with Non-Functional Pituitary Macroadenoma: A Case Report of a Rare Presentation.

Moyamoya disease (MMD) is a rare neurological condition characterized by brain blood vessel narrowing, leading to collateral vessel formation. Diagnosis typically involves cerebral angiography and magnetic resonance angiography (MRA), with surgical revascularization often providing superior outcomes. Here, we present the case of a 55-year-old woman with hypertension, diabetes, and a history of ischemic stroke. She recently experienced a hemorrhagic stroke due to MMD, compounded by a non-functional pituitary macroadenoma. Recognizing signs of a hemorrhagic stroke is crucial to prevent future occurrences and ensure optimal outcomes. However, our understanding of the connection between MMD and pituitary macroadenoma remains incomplete. Further research is essential to refine diagnostic techniques and treatment strategies. Through continued research and awareness, we can strive for improved outcomes and an enhanced quality of life for individuals affected by MMD and its complications.

Successful medical management of a pituitary macroadenoma with features of resistant acromegaly and hyperprolactinemia using pasireotide.

BACKGROUND: The somatostatin analog, pasireotide, is used for the treatment of acromegaly after the failure of surgery and/or first-line medical treatment. CASE PRESENTATION: A 48-year-old male reported that during a workup for obesity in his home country, hyperprolactinemia was diagnosed and a 3.5 × 3.5 cm pituitary macroadenoma was identified on pituitary MRI. He received cabergoline for 6 months; then he was lost to follow-up. He presented at our Endocrine clinic 2 years later for treatment of obesity (BMI 49.5 kg/m2). Biochemical workup revealed that in addition to hyperprolactinemia (7,237 [normal: 85-323 mIU/L), he had acromegaly, evident by elevated insulin-like growth factor 1 (IGF-1) level (450 [normal: 88-210 µg/L]), and a positive growth hormone suppression test, secondary hypothyroidism, and secondary hypogonadism. Pituitary MRI showed that the adenoma encased parts of the left and right internal carotid arteries and encroached on the optic chiasm. Surgical excision was therefore not feasible. He was treated with cabergoline and later, long-acting release (LAR) octreotide. Prolactin levels were reduced with cabergoline, but IGF-1 levels did not respond to octreotide, and it was discontinued. The patient abandoned radiotherapy after two sessions. He was started on LAR pasireotide 40 mg every 4 weeks and continued on cabergoline 0.5 mg per week. His biochemical response was dramatic, with a near normalization of IGF-1 levels in 3 months. After 6 months from starting pasireotide, we increased cabergoline dose from 0.5 mg/week to 3 mg/week. Three months later, IGF-1 level was normalized. The patient developed type 2 diabetes as a side effect of pasireotide; however, this was well-controlled with medications. CONCLUSIONS: The case suggests that pasireotide can provide marked biochemical improvement in acromegaly after the failure of both cabergoline monotherapy and cabergoline plus octreotide. This further confirms a potentially efficacious treatment regimen in treatment-resistant acromegaly with hyperprolactinemia.

Machine Learning Analysis of Post-Operative Tumour Progression in Non-Functioning Pituitary Neuroendocrine Tumours: A Pilot Study.

Post-operative tumour progression in patients with non-functioning pituitary neuroendocrine tumours is variable. The aim of this study was to use machine learning (ML) models to improve the prediction of post-operative outcomes in patients with NF PitNET. We studied data from 383 patients who underwent surgery with or without radiotherapy, with a follow-up period between 6 months and 15 years. ML models, including k-nearest neighbour (KNN), support vector machine (SVM), and decision tree, showed superior performance in predicting tumour progression when compared with parametric statistical modelling using logistic regression, with SVM achieving the highest performance. The strongest predictor of tumour progression was the extent of surgical resection, with patient age, tumour volume, and the use of radiotherapy also showing influence. No features showed an association with tumour recurrence following a complete resection. In conclusion, this study demonstrates the potential of ML models in predicting post-operative outcomes for patients with NF PitNET. Future work should look to include additional, more granular, multicentre data, including incorporating imaging and operative video data.

Calcified Pituitary Adenoma Mimicking Craniopharyngioma: A Case Report.

A 60-year-old woman presented with a history of a previously diagnosed sellar mass and a recent onset of severe headache, vision loss, and dizziness. The patient was found to have a large mass with curvilinear calcification on imaging. Histopathology confirmed the presence of a pituitary adenoma with abnormal acini, consistent with adenoma, and moderate amounts of granular eosinophilic cytoplasm. A detailed analysis of the patterns of calcification and the radiological morphology is crucial to distinguishing between pituitary adenoma and craniopharyngioma. Recognition of these patterns can aid in distinguishing between these conditions, providing a more accurate diagnosis and an effective treatment plan.

Predicting the Consistency of Pituitary Macroadenomas: The Utility of Diffusion-Weighted Imaging and Apparent Diffusion Coefficient Measurements for Surgical Planning.

Understanding the consistency of pituitary macroadenomas is crucial for neurosurgeons planning surgery. This retrospective study aimed to evaluate the utility of diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) as non-invasive imaging modalities for predicting the consistency of pituitary macroadenomas. This could contribute to appropriate surgical planning and therefore reduce the likelihood of incomplete resections. The study included 45 patients with pathologically confirmed pituitary macroadenomas. Conventional MRI sequences, DWIs, ADC maps, and pre- and post-contrast MRIs were performed. Two neuroradiologists assessed all of the images. Neurosurgeons assessed the consistency of the tumor macroscopically, and histopathologists examined it microscopically. The MRI findings were compared with postoperative data. According to the operative data, macroadenomas were divided into the two following categories based on their consistency: aspirable (n = 27) and non-aspirable tumors (n = 18). A statistically significant difference in DWI findings was found when comparing macroadenomas of different consistencies (p < 0.001). Most aspirable macroadenomas (66.7%) were hyperintense according to DWI and hypointense on ADC maps, whereas most non-aspirable macroadenomas (83.3%) were hypointense for DWI and hyperintense on ADC maps. At a cut-off value of 0.63 × 10-3 mm2/s, the ADC showed a sensitivity of 85.7% and a specificity of 75% for the detection of non-aspirable macroadenomas (AUC, 0.946). The study concluded that DWI should be routinely performed in conjunction with ADC measurements in the preoperative evaluation of pituitary macroadenomas. This approach may aid in surgical planning, ensure that appropriate techniques are utilized, and reduce the risk of incomplete resection.

Pituitary Apoplexy Presenting with Isolated Third Nerve Palsy: A Rare Case Report.

A 46-year-old female came to neurosurgery outpatient department with sudden onset of drooping of RE upper eyelid and restriction of movements in adduction, depression and elevation in right eye. Patient was a known case of diabetes mellitus whose blood sugar levels were deranged. On examination, patient was diagnosed pituitary macroadenoma. Patient was treated for her uncontrolled diabetes mellitus following which she had underwent transsphenoidal pituitary macroadenoma removal. On treatment, patient's ptosis had subsided and restriction of movement has resolved.

Case report: Complete restoration of the HPA axis function in Cushing's disease with drug treatment.

This report describes a rare case of a 20-year-old man with an ACTH- and prolactin-secreting invasive pituitary macroadenoma causing hyperprolactinemia and Cushing's disease. He was later found to have an AIP mutation. Treatment with cabergoline (1.5 mg weekly) normalized prolactin concentrations and induced a major shrinkage of the adenoma. Not only was urinary free cortisol normalized for more than 14 years, but also the treatment induced normal hypothalamo-pituitary-adrenal (HPA) axis function as illustrated by the reappearance of a normal cortisol/ACTH circadian rhythm, cortisol suppression to dexamethasone, and disappearance of the excessive and aberrant responses to CRH and desmopressin, respectively. This case is the first description of complete restoration of the physiological characteristics of the HPA axis by a medication during the treatment of Cushing's disease. Although exceptional, it illustrates that drugs targeting the pituitary adenoma can bring true complete remission of Cushing's disease.

Secondary xanthogranulomatous hypophysitis mimicking a pituitary macroadenoma: a case report.

Hypophysitis is an extremely rare inflammatory disease that can mimic the clinical and radiological features of a pituitary adenoma. In this case report, we describe a 45-year-old woman with secondary xanthogranulomatous hypophysitis (XGH) who presented with signs of a pituitary macroadenoma. The patient complained of headaches, visual impairment, and amenorrhea-galactorrhea syndrome. Her physical examination was normal. Laboratory investigation revealed corticotropin, thyrotropin, and gonadotropin deficiencies. She also had low visual acuity in her right eye and an altered visual field. Pituitary magnetic resonance imaging revealed an intra and suprasellar mass measuring 13 × 11 × 16 mm, with hemorrhagic necrosis, that was having a discrete mass effect on the patient's optic chiasm and pituitary stalk. The patient was treated with hydrocortisone and levothyroxine, and then transferred to the Neurosurgery department for total transsphenoidal resection of the mass. Histological examination of the tumor permitted a diagnosis of XGH of a remodeled Rathke's pouch cyst to be made. Systemic conditions such as tuberculosis, sarcoidosis, and other granulomatous diseases were excluded. The etiopathogenesis of XGH remains poorly characterized, but it may be a progressive form of lymphocytic hypophysitis or a remodeled Rathke's pouch cyst. Screening for autoimmune pathology and systemic diseases is essential to guide appropriate management.

Pituitary Macroadenoma With Macronodular Adrenal Hyperplasia and Novel Armadillo Repeat-Containing Protein 5 (ARMC5) Mutation.

We present an unusual case of primary bilateral macronodular adrenal hyperplasia (PBMAH) in a 72-year-old African American man. The patient was found to harbor massively enlarged bilateral adrenal glands on imaging along with mild autonomous cortisol secretion. His workup for PBMAH included leukocyte analysis for the armadillo repeat-containing protein 5 (ARMC5) gene. The test revealed a novel heterozygous somatic ARMC5 mutation. The patient was initially managed conservatively. He subsequently presented with unprovoked bilateral pulmonary emboli. This was followed by the discovery of a nonsecreting pituitary macroadenoma, a hitherto unreported but putative association.

Is the OCT a predictive tool to assess visual impairment in optic chiasm compressing syndrome in pituitary macroadenoma? A prospective longitudinal study.

Visual dysfunction is a prevalent symptom in patients with non-functioning pituitary macroadenoma (NFPM); the role of OCT in such patients has not been yet determined. This is a prospective longitudinal observational study over a period of 6 years, on 20 patients presenting a radiological compression of the optic chiasma without visual acuity (VA) and visual field (VF) disturbances. The primary endpoint was to evaluate the impact of NFPA on neuro-axonal loss by measuring RNFL thickness using OCT at inclusion (T0), 12 months (T1), 24 months (T2), and 36 months (T3), respectively. The secondary endpoint was to monitor the evolution of OCT over time and assess any relationship between the degree of OCT alteration and the degree of radiological and clinical optic chiasm compression syndrome. Among the 20 patients included, eight (40%) showed an altered RNFL-OCT at diagnosis, while the remaining 12 (60%) showed a normal pattern. During a mean ophthalmologic follow-up of 60 months, 4 patients (20%) presented an asymptomatic reduction of RNFL-OCT thickness although all 20 had a VA/VF stable. To our knowledge, this study represents the first attempt to longitudinally evaluate the natural history and evolution of RNFL-OCT in patients with radiologically asymptomatic chiasmatic compression syndrome. The results do not clearly demonstrate the role of the OCT as an early prognostic factor for visual dysfunction.

Pituitary macroadenoma with panhypopituitarism masquerading as schizophrenia: a diagnostic dilemma managed conservatively.

Introduction and importance: Secretory pituitary macroadenoma also known as prolactinoma are benign neoplasm comprising very minimal cases of intracranial masses. Among the various presentation suggestive of panhypopituitarism, psychosis, and features of schizophrenia is very rarely seen. In the majority of cases, neurosurgical intervention for the excision of tumor is considered a standard treatment modality but conservative management with dopamine agonist and steroids have also been shown to provide an optimal level of care also improving the quality of level of patient. Case presentation: A 42-year-old Asian male presented with a history of talking to self, delusion of persecution, over talkativeness, hallucination, increased suspiciousness, and history of lost and found in the streets where he was working as a migrant worker. The patient was initially managed in line of schizophrenia with the antipsychotics drug of choice. On further assessment there was no improvement of psychiatric symptoms but they further deteriorated with additional neuropsychiatric symptoms; hence, MRI brain was carried out. Following which, the diagnosis of pituitary macroadenoma was confirmed and further more hormonal analysis was done, which showed findings suggestive of panhypopituitarism. The patient was then managed conservatively with dopamine agonist and steroids, which showed rapid improvement of psychiatric symptoms with a massive reduction in the size of the pituitary macroadenoma. Clinical discussion: With the incidence of 100 per million cases pituitary adenomas are considered locally invading with the characteristic compression of the surrounding structure, presenting as visual hallucinations, olfactory hallucinations, episodes of losing time, apathy, and features suggestive of adrenal insufficiency, hypogonadotrophic hypogonadism, and symptoms secondary to hormonal imbalance such as hypothyroidism. Psychiatric symptomatic presentations are considered a very rare presentation in cases of pituitary macroadenoma. Also, psychiatric features and symptoms of psychosis are associated with prolcatinomas through idiopathic mechanism and the basic casualty has not been established. Surgical intervention such as trans-sphenoidal resection of the mass can be undertaken in case where mass effects is present but long-term remission and prognosis is found not to be fruitful. Conservative treatment with dopamine agonist such as cabergoline and steroids also plays a meaningful role in abrupt management in such cases. Conclusion: Pituitary macroadenoma presenting as a patient of schizophrenia is noted very rarely in medical literature; hence, investigations in view of neurosurgical diagnosis in cases presenting as psychosis should be considered for ideal holistic management. Conservative management can also be a breakthrough treatment modality in complete recovery of pituitary macroadenoma.

An audit of the use of CT pituitary scans to exclude a pituitary macroadenoma.

BACKGROUND: Pituitary imaging is often required to exclude an adenoma suspected clinically or biochemically. Although magnetic resonance (MR) is the gold standard, computerised tomography (CT) is faster, cheaper and induces less claustrophobia. Our audit at Auckland City Hospital, New Zealand, investigated whether the use of CT of the pituitary as the first line imaging to assess for a pituitary macroadenoma reduces the need for MR. METHODS: We investigated the usefulness of CT pituitary imaging in the exclusion of pituitary macroadenoma between 2012 and 2020. A re-audit was then undertaken for a period of one year between March 2021 and March 2022 to assess outcomes once a departmental policy change was implemented. At Auckland City Hospital, 32 patients across eight years were eligible for this analysis, of which 31 had data available. In our re-audit, 29 patients were eligible for this analysis. We collected data on patient demographics, relevant hormone levels, indication for imaging and imaging results and subsequent management. RESULTS: After CT pituitary imaging, 28/31 (90%) of patients did not require further imaging because the clinical question had been addressed. One year after routine initial CT pituitary imaging was implemented by the Auckland City Hospital Endocrinology Department, 29 CT pituitary scans were performed to exclude a pituitary macroadenoma. Of these patients one required further imaging due to the finding of an expanded pituitary sella but not a pituitary macroadenoma. CONCLUSION: CT pituitary imaging to exclude a pituitary macroadenoma is a useful test that may reduce the need for MR pituitary scans. TRIAL REGISTRATION: Not applicable. This was an audit as defined by the New Zealand National Ethics Advisory Committee guidelines. Please see 'Declarations' section.