A Comprehensive Review of Empty Sella and Empty Sella Syndrome.

OBJECTIVE: Incidental radiographic findings of an empty sella are prevalent in up to 35% of the general population. While empty sella was initially considered clinically insignificant, a subset of patients exhibits endocrine or neuro-ophthalmologic manifestations which are diagnostic of empty sella syndrome (ESS). Recent studies suggest that more patients are affected by ESS than previously recognized, necessitating a deeper understanding of this condition. This comprehensive review describes a practical approach to evaluating and managing ESS. METHODS: Literature review was conducted on etiologies and risk factors associated with primary and secondary empty sella, the radiologic features that differentiate empty sella from other sellar lesions, and the role of clinical history and hormone testing in identifying patients with ESS, as well as treatment modalities. RESULTS: Pituitary function testing for somatotroph, lactotroph, gonadotroph, corticotroph, and thyrotroph abnormalities is necessary when suspecting ESS. While an isolated empty sella finding does not require treatment, ESS may require pharmacologic or surgical interventions to address hormone deficits or intracranial hypertension. Targeted hormone replacement as directed by the endocrinologist should align with guidelines and patient-specific needs. Treatment may involve a multidisciplinary collaboration with neurology, neurosurgery, or ophthalmology to address patient symptoms. CONCLUSION: This review underscores the evolving understanding of ESS, stressing the significance of accurate diagnosis and tailored management to mitigate potential neurologic and endocrine complications in affected individuals.

The 1 µg Synacthen stimulation test in the diagnosis of secondary adrenal insufficiency in patients with Rathke's cleft cyst and empty sella syndrome.

INTRODUCTION: Rathke's cleft cyst (RCC) and primary empty sella syndrome (PESS) are usually incidental findings on magnetic resonance imaging (MRI) scans. In most cases, these lesions do not cause mass effect symptoms and do not require surgical intervention. In patients with RCC or PESS, it is important to exclude secondary adrenal insufficiency (SAI), which may be a life-threatening condition. MATERIAL AND METHODS: The incidence of SAI was assessed in patients with RCC or PESS detected by MRI, using the 1 µg Synacthen stimulation test. A total of 38 patients were analysed. Test results were linked to clinical symptoms and the type of cystic lesion. RESULTS: Assuming that cortisol levels < 14.6 µg/dL in Synacthen test are the criterion of SAI diagnosis, SAI was diagnosed only in 2 patients (5%). Adopting the traditional criterion of cortisol levels < 18 µg/dL, SAI would be diagnosed in 7 patients (18.4 %). Dizziness (Chi2 = 3.89; p = 0.049) and apathy (Chi2 = 3.87; p = 0.049) were significantly more frequent in the PESS group than in the RCC group. CONCLUSIONS: The incidence of SAI in the general patient population with empty sella syndrome and Rathke's cleft cysts is low. The 1 µg Synacthen test seems to be a valuable tool in the diagnosis of SAI among patients with RCC and PESS. Further studies are necessary to determine the sensitivity and specificity of the 1 µg Synacthen test with the standardization of test protocol and considering the cortisol level at the 20-minute timepoint. PESS patients report dizziness and apathy more frequently than RCC patients, which does not result from the disturbance of the hypothalamic-pituitary-adrenal axis, but probably from the different pathogenesis of these cystic lesions.

Primary empty sella syndrome-caused rhabdomyolysis misdiagnosed as recurrent sepsis: a case report and literature review.

We reported a case of a 68-year-old man who presented with recurrent fever and multiorgan dysfunction. His significantly elevated procalcitonin and C-reactive protein levels indicated recurrent sepsis. However, no focus of infection and no pathogens were identified through a variety of examinations and tests. Although the increase of creatine kinase was less than five times the upper limit of normal value, the diagnosis of rhabdomyolysis secondary to adrenal insufficiency resulting from primary empty sella syndrome was finally made, as supported by serum myoglobin elevation, serum cortisol, and adrenocorticotropic hormone deficiency, bilateral adrenal atrophy on computed tomography, and empty sella on magnetic resonance imaging. After the glucocorticoid replacement treatment, the patient's myoglobin gradually returned to normal range, and his condition continued to improve. Rhabdomyolysis resulting from a rare cause may be misdiagnosed as sepsis in patients who present with increased procalcitonin levels.

Myopathic syndrome revealing a rare condition: Sheehan syndrome, a case-based review.

This report presents a case of a Sheehan syndrome diagnosed with a delay of 29 years after occurrence of first symptoms, following a laborious birth ended with dead fetus and massive hemorrhage. The 50-year-old patient, with early menopause from the age of 21, is referred to our rheumatology department to investigate the etiology of a myopathic syndrome, which started 2 months before and gradually worsened. The differential diagnosis took into consideration the autoimmune, infectious, paraneoplastic, endocrinological, and drug-induced myopathic syndrome. Paraclinical investigations revealed panhypopituitarism, and cerebral magnetic resonance imaging detected empty-sella. The etiology of a myopathic syndrome is often multifactorial; therefore, it is important to continue the investigations even after identifying one possible etiological factor, especially when it does not seem to fully explain the clinical-paraclinical picture. Usually, the multiple dimensions of panhypopituitarism bring the patient to various medical specialties depending on the dominant symptomatology. Given the rarity of the above-mentioned syndrome in the present, and the long gap between the initial event and the final diagnosis, its identification continues to be a challenge.

Analysis of clinical features of primary empty sella.

OBJECTIVE: A retrospective analysis of clinical data of 60 patients with primary empty sella (PES) was conducted to further improve the understanding of the disease. METHODS: The clinical data of 60 patients diagnosed with PES admitted to the Department of Endocrinology of Wuhan Union Hospital for different reasons from January 2000 to September 2018 were analyzed. RESULTS: The 60 cases comprised 22 (36.67%) male and 38 (63.33%) female patients, for a male-to-female ratio of 1:1.73. There was predominance of 50-59 year-olds and women with multiple pregnancies. Of the 60 patients, 41.67% showed fatigue, 26.67% dizziness and headache, 21.67% nausea and vomiting, 18.33% anorexia, and 6.67% visual impairment and other symptoms. Twenty-seven patients (45.0%) had normal pituitary function, and 33 (55.0%) had hypopituitarism. Complete PES was more prone to result in hypopituitarism than partial PES. Men with PES were more likely to have hypopituitarism than women. CONCLUSION: The incidence of PES was significantly higher in women than in men; PES was common in middle-aged and older women with multiple pregnancies. Symptoms were diverse and clinical manifestations may lack specificity compared to other diseases and need to be differentiated. About half of PES patients may develop hypopituitarism. Therefore, for patients with empty sella detected on magnetic resonance imaging (MRI) with or without clinical symptoms, the pituitary function should be thoroughly and promptly evaluated.

Successful Electroconvulsive Therapy in Idiopathic Intracranial Hypertension With Mood Disorder and Partial Empty Sella Syndrome.

ABSTRACT: Patients with idiopathic intracranial hypertension (IIH) often experience significant burden from psychiatric comorbidities. Mood disorders are present in up to half of all patients with IIH, and they are often refractory to treatment by psychopharmacologic agents. Electroconvulsive therapy (ECT) is the criterion standard for treatment of patients with the most severe psychiatric burden but has relative contraindications in those possessing pathologies that raise intracranial pressure (ICP). There is a growing body of literature that a multidisciplinary care model would allow for patients with elevated ICP to receive ECT safely. Despite the high prevalence of mood disorders in patients with IIH, there are only 2 published case reports describing ECT delivery to patients from this cohort. We report our own case of a patient with IIH and major depressive disorder who received 38 bitemporal treatments with a positive response and no change in baseline ICP. Her positive response, along with the absence of elevation of ICP, aligns with the prior reports; however, her IIH symptoms have not responded as reported in the 2 cases-despite receiving more than 4 times the amount of treatments. Moreover, our patient possessed unique imaging for a partial empty sella syndrome, which has recently been found to be the only significant finding in patients who had a mood disorder before IIH diagnosis, versus a mood disorder developing after IIH diagnosis. This case serves to provide evidence of the safety and success of ECT in patients with IIH, relying on multidisciplinary care from psychiatry, neurology, and neuro-ophthalmology.

Clinical course of primary empty sella in children: a singlecenter experience.

BACKGROUND: Various studies, mainly conducted in adults, have examined the hormonal axis in primary empty sella (PES), and reported various forms of pituitary deficiencies. We report our experience with PES in pediatric patients in terms of pituitary function, associated impairments, and responses to treatment. METHODS: We reviewed 10,560 cranial and 325 pituitary magnetic resonance imagings (MRIs) performed at our university hospital between January 2010 and December 2020 and identified patients with PES. Patients with additional abnormal MRI findings, a history of cranial surgery or radiotherapy, autoimmunity, long-term use of chemotherapeutic or immunosuppressive agents or incomplete diagnostic evaluation were excluded. Clinical, radiological and laboratory evaluations were recorded. RESULTS: The study included 17 patients [9 girls, 8 boys; median age 12.4 years (7.25, 4.3 - 17)]. The median size of the pituitary was 2 mm (0.7, 1.2 - 3). Based on age-dependent pituitary height measurements, fifteen (88%) patients had pituitary gland hypoplasia. Five patients presented with short stature, two had both pubertal delay and short stature, and one had pubertal delay. Nine patients presented with neurological symptoms such as headaches, tinnitus, tics, and dizziness. Five short patients had growth hormone deficiency. None of the patients had hyper- or hypoprolactinemia, adrenal insufficiency, hypothyroidism, or diabetes insipidus. There was statistically no significant association between the size of the pituitary gland and the severity of hypopituitarism (p = 0.42). CONCLUSIONS: The high incidence of pituitary dysfunctions ascertain that this entity should not be considered a normal variant but, should instead be carefully evaluated with appropriate basal and dynamic hormonal testing.

Bilateral Petrous Apex Cephalocele Associated with a Wide Sella.

ABSTRACT: Petrous apex cephalocele (PAC) is a rare type of cephalocele. It is usually asymptomatic. It can be unilateral or bilateral. Bilateral cases are less common. They are etiologically and clinically different entities from unilateral ones. A 56-year-old female patient presented to the hospital with the complaint of a severe nonspecific headache. She has been examined in ear nose throat, ophthalmology, and finally neurology clinics. Bilateral PAC was incidentally found in magnetic resonance imaging (MRi) examination. Headache was associated with PAC because no additional pathology could explain the clinical symptomatology. There is a proven relationship between empty sella and PAC. Regarding PAC less than 50 cases are known. Our paper aims to contribute to the literature by exhibiting etiologic and clinic differences between unilateral and bilateral PAC. It highlights the relationship between PAC and broad sella that is a different entity from empty sella and shows this remarkable radiological appearance. The authors presented our case accompanied by clinical and MRi findings.

Empty Sella Syndrome Associated with Growth Hormone Deficiency: the First Case Report of Weiss-Kruszka Syndrome.

Weiss-Kruszka syndrome (WSKA), caused by heterozygous loss-of-function variants in ZNF462 gene, is a recently described and extremely rare genetic disorder. The main phenotypes include characteristic craniofacial features, ptosis, dysgenesis of the corpus callosum, and neurodevelopmental impairment. We report the first Korean boy with molecularly confirmed WSKA presenting with an atypical manifestation. A 16-year-old boy with a history of bilateral ptosis surgery presented with short stature (-3.49 standard deviation score) and delayed puberty. The patient showed characteristic craniofacial features including an inverted triangular-shaped head, exaggerated Cupid's bow, arched eyebrows, down-slanting palpebral fissures, and poorly expressive face. He had a mild degree of intellectual disability and mild hypotonia. Endocrine studies in the patient demonstrated complete growth hormone deficiency (GHD) associated with empty sella syndrome (ESS), based on a magnetic resonance imaging study for the brain that showed a flattened pituitary gland and cerebrospinal fluid space herniated into the sella turcica. To identify the genetic cause, we performed whole exome sequencing (WES). Through WES, a novel de novo heterozygous nonsense variant, c.4185del; p.(Met1396Ter) in ZNF462 was identified. This is the first case of WSKA accompanied by primary ESS associated with GHD. More clinical and functional studies are needed to elucidate this association.

Primary empty sella: The risk factors and associations with the cerebral small vessel diseases-An observational study.

OBJECTIVE: To investigate the risk factors of primary empty sella (PES) and its associations with cerebral small vessel diseases (CSVD). METHODS: A total of 132 consecutive patients were recruited from Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University from December 2018 to January 2020, including 69 cases of PES, and age, gender-matched 63 subjects without PES. Demographics and clinical characteristics were recorded. Enlarged perivascular spaces (PVS) and white matter hyperintensities (WMH), which are image markers for CSVD, were assessed. Univariate logistic regression models and multivariate logistic regression models were performed to predict the independent risk factors of PES. RESULTS: There was a significant difference in baseline characteristics in terms of hypertension (p < 0.001) and pregnancy (p = 0.019) between PES and the control group; among markers of CSVD, whole WMH (p = 0.030) and periventricular hyperintensities (PVH) (p = 0.027) were significantly different; however, no significant differences concerning deep WMH, total PVS, basilar ganglia-PVS and centrum semiovale-PVS (p > 0.05). After adjusting relevant potential confounders, multivariate logistic regression revealed hypertension (OR=3.158, 95 %CI: 1.452∼6.865, p = 0.004) and pregnancy (OR=2.236, 95 %CI: 1.036-4.826, p = 0.040) were independent risk factors for PES. CONCLUSION: Hypertension and pregnancy are independent risk factors of PES. There is a possible correlation between PES and WMH, especially PVH, however, further studies are required to confirm these findings.

Variation in the MRI appearance of the canine pituitary gland.

A recent publication described pathological findings in the pituitary gland incidentally discovered during routine necropsies of the brain of dogs and cats; however, imaging characteristics of these lesions were not reported. Aims of this retrospective, observational study were to characterize MRI variants and incidental lesions in pituitary glands of dogs with no clinical signs of pituitary disease. Cranial MRIs from dogs with no suspicion of pituitary disease, based on history and presenting clinical signs, were retrieved from a veterinary teleradiology database during the period of January 2014 to January 2016. Images were reinterpreted by two observers and pituitary lesions were described based on consensus. A total of 580 scans were evaluated and pituitary lesions were detected in 78 dogs (13.44%). Pituitary cystic lesions were the most common finding and occurred in 31 dogs (5.34%). Of these 31 dogs, the majority (74%) were of toy or brachycephalic breed. Partial or total empty sella lesions were detected in 14 dogs (2.41%), and all of these were small or toy breeds. A significantly increased incidence of the partial empty sella lesion was found in male dogs (P = .034). Pituitary lesions greater than 1 cm occurred rarely (0.69%). There was a significant association between low-field (LF) MRI strength and detection of a partial or total empty sella lesion (P = .0112), and detection of a pituitary lesion greater than 1 cm (P = .0125). A significant difference was present between the MRI field strength (FS) that identified pituitary cysts and the FS that detected an empty sella (P = .0068), with the former being a high FS and the latter a LF strength. The findings from this study indicated that up to 13% of dogs with no presenting clinical signs of pituitary disease may have MRI pituitary lesions.

Chiasmapexy for secondary empty sella syndrome: diagnostic and therapeutic considerations.

PURPOSE: Secondary empty sella syndrome (SESS) following pituitary surgery remains a diagnostic and therapeutic challenge. The aim of this study was to specify the diagnostic criteria, surgical indications and results of chiasmapexy in the SESS. METHODS: Three cases from two experienced neurosurgical centers were collected and the available literature was reviewed. RESULTS: The 3 patients were operated for a giant non-functioning pituitary adenoma, a cystic macroprolactinoma, and an arachnoid cyst respectively. Postoperative visual outcome was initially improved, and then worsened progressively. At the time of SESS diagnosis, visual field defect was severe in all cases with optic nerve (ON) atrophy in 2 cases. Patients were operated via an endoscopic endonasal extradural approach. One patient was re-operated because of early fat reabsorption. Visual outcome improved in 1 case and stabilized in 2 cases. Statistical analyses performed on 24 cases from the literature review highlighted that patient age and severity of the preoperative visual defect were respectively significant and nearly significant prognostic factors for visual outcome, unlike the surgical technique. CONCLUSION: T2-weighted or CISS/FIESTA sequence MRI is mandatory to visualize adhesions, ON kinking and neurovascular conflict. TS approach is the most commonly used approach. The literature review could not conclude on the need for an intra or extradural approach suggesting case by case adapted strategy. Intrasellar packing with non-absorbable material such as bone should be considered. Severity of the visual loss clearly decreases the visual outcome suggesting early chiasmapexy. In case of severe and long standing symptoms before surgery, benefits and surgical risks should be carefully balanced.

Primary Empty Sella.

Primary empty sella (PES) syndrome is a misnomer as it is not a syndrome but a radiological finding with possible endocrine abnormalities. No specific headache type has been shown to be caused by PES. Endocrine screening may be considered for asymptomatic persons with PES.

Retinal nerve fibre and ganglion cell inner plexiform layer analysis by optical coherence tomography in asymptomatic empty sella patients.

Purpose: To investigate the clinical importance of the thicknesses of the retinal nerve fibre (RNFL) and ganglion cell and inner plexiform layer (GCL+) by spectral domain optic coherence tomography (SD-OCT) in asymptomatic empty sella (ES) patients.Materials and methods: In this cross-sectional, non-randomized prospective study, 44 ES patients and 74 age- and sex-matched healthy individuals were evaluated. All the patients and controls competed an automated 30-2 visual field (VF) test. The mean deviation (MD), pattern standard deviation (PSD), RNFL, and GCL + thickness values obtained with SD-OCT were compared statistically between the two groups.Results: No marked VF defects were found in either group, and there was no statistically significant between-group difference in MD or PSD values. In terms of RNFL thickness, the average and superior quadrant RNFL values of the ES patients were thinner than those of the controls, with statistical significance (p = 0.013 and p = 0.043, respectively). Although other measured RNFL quadrant thicknesses and foveal thickness (FT), macular volume (MV), and average macular thickness (AMT) values were reduced in the ES group, these differences were not statistically significant. The average GCL + value and GCL + values in six sectors in the patient group were significantly lower than those in the control group.Conclusions: Asymptomatic ES patients have a risk of primary ES syndrome and should be followed up using a multidisciplinary approach. Objective and quantitative RNFL and GCL + thickness measurements obtained with OCT can provide valuable data for monitoring these patients.

[Empty sella syndrome: a case report]. / Syndrome de la selle turcique vide: à propos d'un cas.

Empty sella syndrome is a condition in which the sella turcica is partially or totally filled with cerebrospinal fluid causing a displacement of the pituitary gland. We here report the case of a 49-year old obese patient with progressive headaches, physical asthenia and hypothyroidism. Brain scanner showed empty sella syndrome.

Sinus Bradycardia as a Rare and Unusual Presentation of Partial Empty Sella Syndrome: A Case Report.

BACKGROUND Empty sella syndrome (ESS) occurs when the pituitary gland becomes flattened or shrinks, which leads to filling of the sella turcica with cerebrospinal fluid. This causes the appearance of empty sella on imaging. ESS is often diagnosed after the workup of pituitary disorders, or as an incidental finding after brain imaging. To the best of our knowledge, this is the first case report in which ESS was diagnosed after an incidental finding of bradycardia pre-operatively. CASE REPORT We present the case of a 66-year-old man who was admitted electively to undergo a transforaminal lumbar interbody fusion at the level of L5-S1. He was found to be bradycardic pre-operatively. Upon further workup, he was found to have a thyroid-stimulating hormone (TSH) level of 0.358 uIU/ML (normal range, 0.465-4.680 uIU/ML) and a free thyroxine (FT4) level of 0.8 ng/dL (normal range, 0.8-2.2ng/dL). He also had a history of hypotestosteronemia. He was diagnosed with central hypothyroidism at the time of admission. Subsequently, a magnetic resonance imaging (MRI) scan of the brain was performed, and partial empty sella syndrome was diagnosed. CONCLUSIONS Bradycardia in the setting of empty sella syndrome is a rare condition. It is of utmost importance for clinicians to keep in mind a wide differential that includes other non-cardiac causes for common cardiac symptoms such as bradycardia.

Treatment of empty sella associated with visual impairment: a systematic review of chiasmapexy techniques.

PURPOSE: Chiasmapexy is a poorly described surgical procedure adopted to correct the downward displacement of suprasellar visual system (SVS) into an empty sella (ES) causing visual worsening. The aim of our study is to define the indications for extradural and intradural chiasmapexy. METHODS: A systematic literature review has been performed on MEDLINE database (US National Library of Medicine), including only articles that depicted cases of surgically treated patients affected by ES and progressive delayed visual worsening. Moreover, we have reported three cases of secondary ES syndrome (SESS) with visual worsening treated in our Department with transsphenoidal (TS) microsurgical intradural approach. Finally, we have compared the results of extradural and intradural chiasmapexy described in literature. RESULTS: The etiology of visual impairment is different in primary and secondary ESS. In primary ESS (PESS) the only predisposing factor is a dehiscence of diaphragma sellae, and the anatomical distortion caused by displacement of optic chiasm or traction of pituitary stalk and infundibulum may determine a direct injury of neural fibers and ischemic damage of SVS. In PESS the mechanical elevation of SVS performed through extradural approach is sufficient to resolve the main pathologic mechanism. In SESS, arachnoidal adhesions play an important role in addition to downward herniation of SVS. Consequently, the surgical technique should provide elevation of SVS combined to intradural release of scar tissue and arachnoidal adhesions. In treatment of SESS, the intradural approaches result to be more effective, guaranteeing the best visual outcomes with the lowest complications rates. CONCLUSIONS: The intradural chiasmapexy is indicated in treatment of SESS, instead the extradural approaches are suggested for surgical management of PESS.

Macroprolactinemia and Empty Sella Syndrome.

Macroprolactinemia is a polymeric form of prolactin-release, causing mildly symptomatic clinical pictures. The former can be isolated or associated with other causes of hyperprolactinemia. The association with an empty sella syndrome is rare. We report a case of a female patient discovered with this association. It's about a female patient 47 years old, followed up since the age of 31 years for bilateral galactorrhea and a spaniomenorrhea. There has been no associated drug intake. Her exploration has showed a serum prolactin level of 635 mIU/L. Thyroid test results were normal T4 = 10,2ng/L and TSH = 1.76 mIU/L. A brain scan has showed an empty sella turcica. Despite the unchanged levels of prolactinemia, the evolution under dopaminergic 5 mg /D has been marked by the occurrence of a pregnancy with persistent moderate hyperprolactinemia in the postpartum. Chromatography has showed a predominance of the macroprolactin form with: Prolactin monomer at 4.8%, Big Prolactin at 5% and Big Big Prolactin at 83%, thus stopping bromocriptine. Our observation suggests that macroprolactinemia can be associated with conventional etiologies of moderate hyperprolactinemia as the empty sella syndrome. Its detection would prevent the use of dopaminergic therapy which seems not useful.