Persisting Embryonal Infundibular Recess (PEIR): Two Case Reports and Systematic Literature Review

Persisting Embryonal Infundibular Recess (PEIR): Two Case Reports and Systematic Literature Review Abstract Context The persisting embryonal infundibular recess (PEIR) is a rare anomaly of the floor of the third ventricle with a debated pathogenesis. It can be a cause of misdiagnosis in the case of cystic lesions of the sellar and suprasellar area. Objective To describe two recently evaluated cases and provide a systematic literature review. Evidence Acquisition and Case Descriptions PEIR has been previously reported in six adult patients. Because in some cases it was associated with hydrocephalus and/or empty sella, a possible role of altered intracranial pressure in PEIR formation has been postulated. We evaluated two female patients, aged 34 and 50 years, referred to the Pituitary Surgery Clinic of the University of Brescia with the diagnosis of a sellar cyst and craniopharyngioma, respectively. Endocrine screening and visual field testing were normal. No signs of hydrocephalus or empty sella, as well as other indirect signs of intracranial hypertension, were visible on MRI scans. After a multidisciplinary reevaluation, diagnosis of PEIR was made in both cases. Both patients are followed but have not developed any disturbance related to the PEIR in the following 18 months. Conclusions PEIR is a rare condition, probably unrecognized and the result of dysembriogenesis, which should be included in the differential diagnosis of cystic sellar lesions. Imaging features (funnel pituitary stalk and cyst in the sella) appear pathognomonic. A normal endocrine evaluation might help in the diagnosis and warrants conservative treatment. The persisting embryonal infundibular recess (PEIR) is a rare anomaly involving the floor of the third ventricle, particularly the infundibular recess of the pituitary gland and the sellar region. The normal infundibular recess is a small funnel-shaped extension of the third ventricle inside the pituitary stalk (1, 2). It constitutes the remnant of the larger embryonal infundibular recess, which becomes obliterated during development (3). PEIR has been recently defined as the persistence of the embryonal morphology of the infundibular recess (4). Being relatively rare, this condition can be misinterpreted as a neoplastic, cystic lesion of the sellar and suprasellar area. Herein we report two new cases and provide a systematic review of the literature. Material and Methods Literature review A systematic review of the English literature was made on PubMed and SCOPUS databases. The following keywords were cross-matched: persistent, persisting, embryonal, infundibulum, infundibular, recess, third ventricle, dilated, dilation, and pituitary stalk. The results were analyzed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram (5). Case Descriptions Case 1 This 34-year-old woman experienced an episode of severe headache preceded by loss of concentration and transient left eye amaurosis. Her medical history included undefined connective tissue disorder, congenital strabismus, and temporary blindness due to retinal detachment 10 years before. Head CT scan documented a cystic-appearing space-occupying lesion in the sella turcica. The patient did not report any symptom due to pituitary or hypotalamic dysfunction. Her basal pituitary function was unremarkable: FT4, 0.88 ng/dL (0.7 to 1.77 ng/dL); TSH, 1 mcU/mL (0.4 to 3.4 mcU/mL); morning cortisol, 11.1 μg/dL (6.7 to 22.6 μg/dL); ACTH, 18 pg/mL (10 to 50 pg/mL); IGF-I, 165 ng/dL (70 to 251 ng/dL); prolactin, 11 ng/mL (2 to 25 ng/mL); LH (in luteal phase), 4.5 mcU/mL; FSH, 3.6 mcU/mL; and estradiol, 328 pg/mL. Ophthalmological assessment did not document papilledema or new visual defects. Brain MRI (Fig. 1A–1F) documented a dilated pituitary stalk, surrounding a tubular cavity with the same signal as cerebrospinal fluid (CSF). This cavity appeared to be in continuity with the third ventricle superiorly and showed a dilated inferior end inside the sella turcica, which was slightly enlarged. Hydrocephalus and empty sella were excluded. Figure 1. View largeDownload slide Case 1. MRI T1-weighted sequence before contrast administration, (A) sagittal and (B) coronal section. MRI T1-weighted sequence after contrast administration, (C) sagittal and (D) coronal section. (E, G, H) Magnetic resonance cisternography with three-dimensional balanced steady-state gradient echo sequence, reformatted following the pituitary stalk (E: sagittal section, G: axial at the level of the stalk; H: axial, at the level of the sella). (F) MRI T2-weighted sequence, coronal section. AH, adenohypophysis; IIIVen, third ventricle; OC, optic chiasm; PitS, pituitary stalk. Figure 1. View largeDownload slide Case 1. MRI T1-weighted sequence before contrast administration, (A) sagittal and (B) coronal section. MRI T1-weighted sequence after contrast administration, (C) sagittal and (D) coronal section. (E, G, H) Magnetic resonance cisternography with three-dimensional balanced steady-state gradient echo sequence, reformatted following the pituitary stalk (E: sagittal section, G: axial at the level of the stalk; H: axial, at the level of the sella). (F) MRI T2-weighted sequence, coronal section. AH, adenohypophysis; IIIVen, third ventricle; OC, optic chiasm; PitS, pituitary stalk. At the 18-month follow-up, the patient is clinically well and has decided to not undergo any biochemical and radiological study. Case 2 This 50-year-old woman underwent head CT scan after mild head trauma, which ruled out posttraumatic lesions and incidentally documented calcifications above the sella turcica, which were initially interpreted as a craniopharyngioma (Fig. 2A–2C). The patient did not report any symptom due to pituitary or hypothalamic dysfunction. Her basal pituitary function was unremarkable: FT4, 1 ng/dL (0.7 to 1.77 ng/dL); TSH, 0.67 mcU/mL (0.4 to 3.4 mcU/mL); morning cortisol, 9.1 μg/dL (6.7 to 22.6 μg/dL); ACTH, 12 pg/mL (10 to 50 pg/mL); IGF-I, 65 ng/dL (54 to 199 ng/dL); prolactin, 5 ng/mL (2 to 25 ng/mL); LH (in luteal phase), 19 mcU/mL; FSH, 7 mcU/mL; and estradiol, 337 pg/mL. Ophthalmological assessment excluded papilledema and visual deficits. Brain MRI excluded the diagnosis of craniopharyngioma, showing a cystic lesion of the sella turcica with similar features to the previous case (Fig. 2D–2F). An enlarged sella was documented; the calcifications documented on CT were then interpreted as remnants of the dorsum sellae, partly eroded by direct pulsations of CSF inside the sella turcica (Fig. 2A–2C). Hydrocephalus and empty sella were excluded, as well as other indirect signs of intracranial hypertension. Comparison with a brain MRI performed 4 years prior documented the same images, which had not been reported. Figure 2. View largeDownload slide Case 2. MRI T1-weighted sequence after contrast administration, (A) sagittal, (B) axial, and (C) coronal sections. (D–F) Magnetic resonance cisternography with three-dimensional balanced steady-state gradient echo sequence, reformatted following the pituitary stalk (D: sagittal, E: axial; F: coronal planes). (G–I) CT bone window in (G) sagittal, (H) axial, and (I) coronal sections. The white arrows point to the thinned dorsum sellae. The calcifications are consistent with residuals of the partially eroded dorsum sellae. IIIVEn, third ventricle; OC, optic chiasm; PitS, pituitary stalk. Figure 2. View largeDownload slide Case 2. MRI T1-weighted sequence after contrast administration, (A) sagittal, (B) axial, and (C) coronal sections. (D–F) Magnetic resonance cisternography with three-dimensional balanced steady-state gradient echo sequence, reformatted following the pituitary stalk (D: sagittal, E: axial; F: coronal planes). (G–I) CT bone window in (G) sagittal, (H) axial, and (I) coronal sections. The white arrows point to the thinned dorsum sellae. The calcifications are consistent with residuals of the partially eroded dorsum sellae. IIIVEn, third ventricle; OC, optic chiasm; PitS, pituitary stalk. At the 18-month follow-up, the patient is clinically well. Sellar region MRI and pituitary assessment were unchanged: FT4, 1.2 ng/dL (0.7 to 1.77 ng/dL); TSH, 1 mcU/mL (0.4 to 3.4 mcU/mL); morning cortisol, 9.1 μg/dL (6.7 to 22.6 μg/dL); ACTH, 15 pg/mL (10 to 50 pg/mL); IGF-I, 153 ng/dL (70 to 251 ng/dL); prolactin, 8.1 ng/mL (2 to 25 ng/mL); LH (in follicular phase), 10 mcU/mL; FSH, 8 mcU/mL; and estradiol, 130 pg/mL. Results of literature review Of the 160 articles we retrieved in the English literature, 143 articles were discarded during title and abstract analysis, whereas 17 articles were selected for full-text analysis. Of these, nine were excluded as they did not describe PEIR. After further detail analysis, two articles were discarded because the described condition was hypothetical for one patient (6) and not PEIR but rather enlargement of the infundibular recess associated with hydrocephalus (7) for two patients (Supplemental Fig. 1). A total of six papers, describing one case each, were then included in this review. Discussion To our knowledge, Šteňo et al. (4) were recently the first to use the term PEIR and provided a literature review together with the description of a new case (Table 1). In the earliest reported cases (8–10), which were studied with X-rays and ventriculography, PEIR was apparently associated with hydrocephalus or empty sella, but the reporting authors underlined the possibility of a mere coincidental association (9) and the peculiarity of the “empty sellalike” image that was associated with PEIR (10). Morota et al. (7) were the first, to our knowledge, to hypothesize a possible connection of the condition with hydrocephalus and empty sella; they described two cases of infundibular recess enlargement that have been included in other reviews of PEIR (4, 6). An in-detail analysis documented that these two cases are the only ones without any intrasellar component, leading to the possibility that they are not PEIR but rather an enlargement of the infundibular recess related to hydrocephalus (2). We then decided to discard their study in this review, including only PEIR with an intrasellar component and with suggestive radiological imaging. Table 1. Previously Described Cases of PEIR Together With the Two New Cases Author, Year Age, Y/Sex Presenting Symptoms Imaging Modality Hydrocephalus (Cause or Type)/Empty Sella Endocrine Status Treatment Outcome/Follow-Up Kühne and Schwartz, 1975 (8) 34/F Headache, weight gain, irregular menses X-ray, VG, CA Yes (midbrain mass)/no NA NA NA Cabanes, 1978 (9) 60/F Headache, blurring of vision, Hakim triad X-ray, VG, CA Yes (NPH)/no NA V-P shunt for NPH Improvement/4 years Schumacher and Gilsbach, 1979 (10) 47/F Signs of increased intracranial pressure X-ray, VG, CA Yes (cerebellar hemangioblastoma)/no NA Removal of cerebellar hemangioblastoma NA/NA Vallee et al., 1982 (11) 56/M Frontal headache, loss of vision in one eye, central retina artery thrombosis X-rays, CT, VG Yes (aqueductal stenosis)/no No deficit (after treatment) V-P shunt Unchanged/1 year Iplikcioglu et al., 2004 (12) 34/F Headache, dysmenorrhea, galactorrhea, bitemporal hemianopia CT, MRI Yes/yes Mild hyper-PRL (55 ng/mL) V-P shunt refused NA/NA Šteňo et al., 2009 (4) 24/M GH deficit, then hypogonadism, headaches MRI No/no GH and testosterone deficit Surgical exploration Well on replacement therapy, analgesics/8 years Present series 34/F Headache with transient visual loss CT, MRI No/no Normal Observation Unchanged at 18 months 50/F Incidental (head trauma) CT, MRI No/no Normal Observation Unchanged at 18 months Radiology unchanged at 5 years Author, Year Age, Y/Sex Presenting Symptoms Imaging Modality Hydrocephalus (Cause or Type)/Empty Sella Endocrine Status Treatment Outcome/Follow-Up Kühne and Schwartz, 1975 (8) 34/F Headache, weight gain, irregular menses X-ray, VG, CA Yes (midbrain mass)/no NA NA NA Cabanes, 1978 (9) 60/F Headache, blurring of vision, Hakim triad X-ray, VG, CA Yes (NPH)/no NA V-P shunt for NPH Improvement/4 years Schumacher and Gilsbach, 1979 (10) 47/F Signs of increased intracranial pressure X-ray, VG, CA Yes (cerebellar hemangioblastoma)/no NA Removal of cerebellar hemangioblastoma NA/NA Vallee et al., 1982 (11) 56/M Frontal headache, loss of vision in one eye, central retina artery thrombosis X-rays, CT, VG Yes (aqueductal stenosis)/no No deficit (after treatment) V-P shunt Unchanged/1 year Iplikcioglu et al., 2004 (12) 34/F Headache, dysmenorrhea, galactorrhea, bitemporal hemianopia CT, MRI Yes/yes Mild hyper-PRL (55 ng/mL) V-P shunt refused NA/NA Šteňo et al., 2009 (4) 24/M GH deficit, then hypogonadism, headaches MRI No/no GH and testosterone deficit Surgical exploration Well on replacement therapy, analgesics/8 years Present series 34/F Headache with transient visual loss CT, MRI No/no Normal Observation Unchanged at 18 months 50/F Incidental (head trauma) CT, MRI No/no Normal Observation Unchanged at 18 months Radiology unchanged at 5 years Abbreviations: CA, cerebral angiography; NA, not available; NPH, normal pressure hydrocephalus; PRL, prolactin; VG, ventriculography; V-P, ventriculo-peritoneal. View Large Table 1. Previously Described Cases of PEIR Together With the Two New Cases Author, Year Age, Y/Sex Presenting Symptoms Imaging Modality Hydrocephalus (Cause or Type)/Empty Sella Endocrine Status Treatment Outcome/Follow-Up Kühne and Schwartz, 1975 (8) 34/F Headache, weight gain, irregular menses X-ray, VG, CA Yes (midbrain mass)/no NA NA NA Cabanes, 1978 (9) 60/F Headache, blurring of vision, Hakim triad X-ray, VG, CA Yes (NPH)/no NA V-P shunt for NPH Improvement/4 years Schumacher and Gilsbach, 1979 (10) 47/F Signs of increased intracranial pressure X-ray, VG, CA Yes (cerebellar hemangioblastoma)/no NA Removal of cerebellar hemangioblastoma NA/NA Vallee et al., 1982 (11) 56/M Frontal headache, loss of vision in one eye, central retina artery thrombosis X-rays, CT, VG Yes (aqueductal stenosis)/no No deficit (after treatment) V-P shunt Unchanged/1 year Iplikcioglu et al., 2004 (12) 34/F Headache, dysmenorrhea, galactorrhea, bitemporal hemianopia CT, MRI Yes/yes Mild hyper-PRL (55 ng/mL) V-P shunt refused NA/NA Šteňo et al., 2009 (4) 24/M GH deficit, then hypogonadism, headaches MRI No/no GH and testosterone deficit Surgical exploration Well on replacement therapy, analgesics/8 years Present series 34/F Headache with transient visual loss CT, MRI No/no Normal Observation Unchanged at 18 months 50/F Incidental (head trauma) CT, MRI No/no Normal Observation Unchanged at 18 months Radiology unchanged at 5 years Author, Year Age, Y/Sex Presenting Symptoms Imaging Modality Hydrocephalus (Cause or Type)/Empty Sella Endocrine Status Treatment Outcome/Follow-Up Kühne and Schwartz, 1975 (8) 34/F Headache, weight gain, irregular menses X-ray, VG, CA Yes (midbrain mass)/no NA NA NA Cabanes, 1978 (9) 60/F Headache, blurring of vision, Hakim triad X-ray, VG, CA Yes (NPH)/no NA V-P shunt for NPH Improvement/4 years Schumacher and Gilsbach, 1979 (10) 47/F Signs of increased intracranial pressure X-ray, VG, CA Yes (cerebellar hemangioblastoma)/no NA Removal of cerebellar hemangioblastoma NA/NA Vallee et al., 1982 (11) 56/M Frontal headache, loss of vision in one eye, central retina artery thrombosis X-rays, CT, VG Yes (aqueductal stenosis)/no No deficit (after treatment) V-P shunt Unchanged/1 year Iplikcioglu et al., 2004 (12) 34/F Headache, dysmenorrhea, galactorrhea, bitemporal hemianopia CT, MRI Yes/yes Mild hyper-PRL (55 ng/mL) V-P shunt refused NA/NA Šteňo et al., 2009 (4) 24/M GH deficit, then hypogonadism, headaches MRI No/no GH and testosterone deficit Surgical exploration Well on replacement therapy, analgesics/8 years Present series 34/F Headache with transient visual loss CT, MRI No/no Normal Observation Unchanged at 18 months 50/F Incidental (head trauma) CT, MRI No/no Normal Observation Unchanged at 18 months Radiology unchanged at 5 years Abbreviations: CA, cerebral angiography; NA, not available; NPH, normal pressure hydrocephalus; PRL, prolactin; VG, ventriculography; V-P, ventriculo-peritoneal. View Large Embryogenesis During embryogenesis (Fig. 3), pituitary gland development begins at ∼22 days of gestation, when the hypophyseal placode, which will give origin to the adenohypophysis, becomes distinguishable. It corresponds to a small area of ectoderm, rostral to the buccopharyngeal membrane that is adherent to the overlying neuroectoderm, which, in turn, constitutes the neural plate (13). These two cell populations are located next to each other and contribute to form the pituitary gland as a single structure (13, 14). Figure 3. View largeDownload slide Normal embryogenesis and PEIR. (A) In the 22-day-old embryo, the hypophyseal placode can be distinguished. (B, C) In the 28-day-old embryo, the invagination of the Rathke pouch begins; after 37 days, the infundibular recess is formed. (D) Between 40 and 60 days, the rudimentary neurohypophysis is located posterior to the adenohypophysis. (E) In the 8-week-old embryo, the adenohypophysis is completely separated from the pharynx due to the partial obliteration of the Rathke cleft, which gives origin to the pharyngo-hypophyseal stalk. (F) In the 3-month-old embryo, the anatomical configuration is similar to the adult one. (G) In the adult, the pituitary stalk with an obliterated infundibular recess is normally present. (H) In the case of PEIR, the obliteration of the recess is missing and filled with CSF from the third ventricle. AH, adenohypophysis; AntL, anterior hypophyseal lobe; B-PM, buccopharyngeal membrane; Df, diencephalon floor; Ect, ectoderm; End, endoderm; HP, hypophyseal placode; Inf, infundibulum; InfR, infundibular recess; IntL, intermediate hypophyseal lobe; Mes, mesoderm; MesE, mesencephalon; NEct, neuroectoderm; NH, neurohypophysis; OC, optic chiasm; P-HS, pharyngo-hypophyseal stalk; PitS, pituitary stalk; PosL, posterior hypophyseal lobe; PrE, prosencephalon; PT, pars tuberalis of the adenohypophysis; RhE, rhombencephalon; RP, Rathke pouch; SphB, sphenoid bone; SphS, sphenoid sinus. Figure 3. View largeDownload slide Normal embryogenesis and PEIR. (A) In the 22-day-old embryo, the hypophyseal placode can be distinguished. (B, C) In the 28-day-old embryo, the invagination of the Rathke pouch begins; after 37 days, the infundibular recess is formed. (D) Between 40 and 60 days, the rudimentary neurohypophysis is located posterior to the adenohypophysis. (E) In the 8-week-old embryo, the adenohypophysis is completely separated from the pharynx due to the partial obliteration of the Rathke cleft, which gives origin to the pharyngo-hypophyseal stalk. (F) In the 3-month-old embryo, the anatomical configuration is similar to the adult one. (G) In the adult, the pituitary stalk with an obliterated infundibular recess is normally present. (H) In the case of PEIR, the obliteration of the recess is missing and filled with CSF from the third ventricle. AH, adenohypophysis; AntL, anterior hypophyseal lobe; B-PM, buccopharyngeal membrane; Df, diencephalon floor; Ect, ectoderm; End, endoderm; HP, hypophyseal placode; Inf, infundibulum; InfR, infundibular recess; IntL, intermediate hypophyseal lobe; Mes, mesoderm; MesE, mesencephalon; NEct, neuroectoderm; NH, neurohypophysis; OC, optic chiasm; P-HS, pharyngo-hypophyseal stalk; PitS, pituitary stalk; PosL, posterior hypophyseal lobe; PrE, prosencephalon; PT, pars tuberalis of the adenohypophysis; RhE, rhombencephalon; RP, Rathke pouch; SphB, sphenoid bone; SphS, sphenoid sinus. In the next stage, the neural crest mesenchyme extends between the prosencephalon and the surface ectoderm in front of the buccopharyngeal membrane, except for the region of the placode (14, 15). Thereafter, the saccular Rathke pouch, whose walls and roof are constituted by the placode, takes shape (13). Likewise, the primordium of the infundibular recess becomes visible on the floor of the third ventricle (13). After 37 days of gestation, the infundibular recess is formed and indicates the outgrowth of the neurohypophysis (13). During the next stages, the Rathke pouch is constricted by continued proliferation of the surrounding mesenchyme to form a closed vesicle but remains for a time connected to the ectoderm of the stomodeum by a solid cord of cells, which can be traced down the posterior edge of the nasal septum (13). The dorsal wall of the Rathke pouch remains thin and fuses with the adjoining part of the neurohypophysis as the pars intermedia (13). The growth of the neurohypophysis and of the pars tuberalis of the neurohypophysis around the infundibular recess leads to its obliteration except at its upper end, where it persists as the infundibular recess of the third ventricle (9, 11, 13). Etiology Different embryogenic theories were proposed to explain PEIR. The first theory proposed the mechanism of arrested proliferation of cells (8–11), but evidence of such process was missing. Therefore, other authors proposed a second theory, based on the presence of the hydrocephalus and consequent raised intraventricular pressure as primum movens of the PEIR (7). Nevertheless, Šteňo et al. (4), who did not find the hydrocephalus, proposed again a dysembryogenic theory, attributing to the hydrocephalus the role of unmasking the underlying anomaly. It is known that in some animals, the recessus infundibuli persists within the posterior pituitary lobe, but in humans, it normally ends above the plane of the diaphragma sellae (11). PEIR might then be the result of dysembryogenesis (Supplemental Fig. 1). Endocrinological data Strikingly, limited endocrinological data are available on PEIR (Table 1) and in some reports might be influenced by associated conditions, such as hydrocephalus. In both our patients, endocrine assessment did not document any evidence of hypopituitarism. Moreover, no symptoms or signs due to hypothalamic involvement, such as temperature dysregulation or disturbances in appetite and sleep, were evident. Radiology Brain MRI imaging can document the pathognomonic features of PEIR (Figs. 1 to 2 and Supplemental Fig. 1): a funnel-shaped, CSF-filled tunnel in the enlarged pituitary stalk is coupled with a cyst in the sellar area, located mainly posteriorly to the anterior lobe of the pituitary gland. Sellar enlargement is usually present. Natural history Data on the natural history of PEIR are extremely limited (Table 1). After surgical exploration, which confirmed the nonneoplastic nature of the lesion, Šteňo et al. (4) reported a stable condition after 8 years. There are no reports on radiological or clinical progression of this condition. Both our patients are stable at the latest follow-up (18 months) from a clinical and endocrine point of view. In one of our patients, no radiological progression of PEIR is evident even after 5 years. Treatment No treatment should be considered if PEIR is an isolated finding. Associated conditions, such as hydrocephalus, which might lead to a progression of PEIR image, should be treated accordingly. It is of paramount importance to correctly diagnose this condition to avoid unnecessary treatment. Conclusions PEIR is a rare, dysembriogenetic condition of the sellar and suprasellar region, probably underrecognized, which should be included in the differential diagnosis of cystic sellar lesions. Pituitary function is usually unaffected and remains stable over time, but further data have to be collected on the natural history of this condition. Abbreviations: Abbreviations: CSF cerebrospinal fluid PEIR persisting embryonal infundibular recess Acknowledgments Disclosure Summary: The authors have nothing to disclose. References 1. Rhoton AL . Anatomy of the pituitary gland and sellar region. In: Thapar K , Kovacs K , Scheithauer BW , Lloyd RV , eds. Diagnosis and Management of Pituitary Tumors . Totowa, NJ : Humana Press ; 2001 : 13 – 40 . 2. Tsutsumi S , Hori M , Ono H , Tabuchi T , Aoki S , Yasumoto Y . The infundibular recess passes through the entire pituitary stalk . Clin Neuroradiol . 2015 ; 26 ( 4 ): 465 – 469 . 3. Standring S , Borley NR , Collins P , Crossman AR , Gatzoulis MA , Wigley CB . Development of the nervous system. In: Standring S , ed. Gray’s Anatomy: The Anatomical Basis of Clinical Practice . Edinburgh : Churchill Livingstone/Elsevier ; 2008 : 319 – 353 . 4. Šteňo A , Popp AJ , Wolfsberger S , Belan V , Šteňo J . Persisting embryonal infundibular recess . J Neurosurg . 2009 ; 110 ( 2 ): 359 – 362 . 5. Moher D , Liberati A , Tetzlaff J , Altman DG , PRISMA Group . Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement . BMJ . 2009 ; 339 : b2535 . 6. Kuroiwa M , Kusano Y , Ogiwara T , Tanaka Y , Takemae T , Hongo K . A case of presumably Rathke’s cleft cyst associated with postoperative cerebrospinal fluid leakage through persisting embryonal infundibular recess . Neurol Med Chir (Tokyo) . 2014 ; 54 ( 7 ): 578 – 581 . 7. Morota N , Watabe T , Inukai T , Hongo K , Nakagawa H . Anatomical variants in the floor of the third ventricle; implications for endoscopic third ventriculostomy . J Neurol Neurosurg Psychiatry . 2000 ; 69 ( 4 ): 531 – 534 . 8. Kühne D , Schwartz RB . Persisting intrapituitary recessus infundibuli . Neuroradiology . 1975 ; 10 ( 3 ): 177 – 178 . 9. Cabanes J . Asymptomatic persistence of infundibularis recessus . J Neurosurg . 1978 ; 49 ( 5 ): 769 – 772 . 10. Schumacher M , Gilsbach J . A new variety of “empty sella” with cystic intrasellar dilatation of the recessus infundibuli . Br J Radiol . 1979 ; 52 ( 623 ): 862 – 864 . 11. Vallee B , Besson G , Person H , Mimassi N . Persisting recessus infundibuli and empty sella . J Neurosurg . 1982 ; 57 ( 3 ): 410 – 412 . 12. Iplikcioglu AC , Bek S , Gokduman CA , Dinc C , Cosar M . Primary empty sella syndrome associated with dilated infundibular recessus . J Neurol Sci Turish . 2004 ; 21 : 127 – 130 . 13. Kollias SS , Ball WS , Prenger EC . Review of the embryologic development of the pituitary gland and report of a case of hypophyseal duplication detected by MRI . Neuroradiology . 1995 ; 37 ( 1 ): 3 – 12 . 14. Musumeci G , Castorina S , Castrogiovanni P , Loreto C , Leonardi R , Aiello FC , Magro G , Imbesi R . A journey through the pituitary gland: development, structure and function, with emphasis on embryo-foetal and later development . Acta Histochem . 2015 ; 117 ( 4–5 ): 355 – 366 . 15. Kioussi C , Carrière C , Rosenfeld MG . A model for the development of the hypothalamic-pituitary axis: transcribing the hypophysis . Mech Dev . 1999 ; 81 ( 1–2 ): 23 – 35 . Copyright © 2018 Endocrine Society http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Clinical Endocrinology and Metabolism Oxford University Press

Persisting Embryonal Infundibular Recess (PEIR): Two Case Reports and Systematic Literature Review

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Abstract

Abstract Context The persisting embryonal infundibular recess (PEIR) is a rare anomaly of the floor of the third ventricle with a debated pathogenesis. It can be a cause of misdiagnosis in the case of cystic lesions of the sellar and suprasellar area. Objective To describe two recently evaluated cases and provide a systematic literature review. Evidence Acquisition and Case Descriptions PEIR has been previously reported in six adult patients. Because in some cases it was associated with hydrocephalus and/or empty sella, a possible role of altered intracranial pressure in PEIR formation has been postulated. We evaluated two female patients, aged 34 and 50 years, referred to the Pituitary Surgery Clinic of the University of Brescia with the diagnosis of a sellar cyst and craniopharyngioma, respectively. Endocrine screening and visual field testing were normal. No signs of hydrocephalus or empty sella, as well as other indirect signs of intracranial hypertension, were visible on MRI scans. After a multidisciplinary reevaluation, diagnosis of PEIR was made in both cases. Both patients are followed but have not developed any disturbance related to the PEIR in the following 18 months. Conclusions PEIR is a rare condition, probably unrecognized and the result of dysembriogenesis, which should be included in the differential diagnosis of cystic sellar lesions. Imaging features (funnel pituitary stalk and cyst in the sella) appear pathognomonic. A normal endocrine evaluation might help in the diagnosis and warrants conservative treatment. The persisting embryonal infundibular recess (PEIR) is a rare anomaly involving the floor of the third ventricle, particularly the infundibular recess of the pituitary gland and the sellar region. The normal infundibular recess is a small funnel-shaped extension of the third ventricle inside the pituitary stalk (1, 2). It constitutes the remnant of the larger embryonal infundibular recess, which becomes obliterated during development (3). PEIR has been recently defined as the persistence of the embryonal morphology of the infundibular recess (4). Being relatively rare, this condition can be misinterpreted as a neoplastic, cystic lesion of the sellar and suprasellar area. Herein we report two new cases and provide a systematic review of the literature. Material and Methods Literature review A systematic review of the English literature was made on PubMed and SCOPUS databases. The following keywords were cross-matched: persistent, persisting, embryonal, infundibulum, infundibular, recess, third ventricle, dilated, dilation, and pituitary stalk. The results were analyzed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram (5). Case Descriptions Case 1 This 34-year-old woman experienced an episode of severe headache preceded by loss of concentration and transient left eye amaurosis. Her medical history included undefined connective tissue disorder, congenital strabismus, and temporary blindness due to retinal detachment 10 years before. Head CT scan documented a cystic-appearing space-occupying lesion in the sella turcica. The patient did not report any symptom due to pituitary or hypotalamic dysfunction. Her basal pituitary function was unremarkable: FT4, 0.88 ng/dL (0.7 to 1.77 ng/dL); TSH, 1 mcU/mL (0.4 to 3.4 mcU/mL); morning cortisol, 11.1 μg/dL (6.7 to 22.6 μg/dL); ACTH, 18 pg/mL (10 to 50 pg/mL); IGF-I, 165 ng/dL (70 to 251 ng/dL); prolactin, 11 ng/mL (2 to 25 ng/mL); LH (in luteal phase), 4.5 mcU/mL; FSH, 3.6 mcU/mL; and estradiol, 328 pg/mL. Ophthalmological assessment did not document papilledema or new visual defects. Brain MRI (Fig. 1A–1F) documented a dilated pituitary stalk, surrounding a tubular cavity with the same signal as cerebrospinal fluid (CSF). This cavity appeared to be in continuity with the third ventricle superiorly and showed a dilated inferior end inside the sella turcica, which was slightly enlarged. Hydrocephalus and empty sella were excluded. Figure 1. View largeDownload slide Case 1. MRI T1-weighted sequence before contrast administration, (A) sagittal and (B) coronal section. MRI T1-weighted sequence after contrast administration, (C) sagittal and (D) coronal section. (E, G, H) Magnetic resonance cisternography with three-dimensional balanced steady-state gradient echo sequence, reformatted following the pituitary stalk (E: sagittal section, G: axial at the level of the stalk; H: axial, at the level of the sella). (F) MRI T2-weighted sequence, coronal section. AH, adenohypophysis; IIIVen, third ventricle; OC, optic chiasm; PitS, pituitary stalk. Figure 1. View largeDownload slide Case 1. MRI T1-weighted sequence before contrast administration, (A) sagittal and (B) coronal section. MRI T1-weighted sequence after contrast administration, (C) sagittal and (D) coronal section. (E, G, H) Magnetic resonance cisternography with three-dimensional balanced steady-state gradient echo sequence, reformatted following the pituitary stalk (E: sagittal section, G: axial at the level of the stalk; H: axial, at the level of the sella). (F) MRI T2-weighted sequence, coronal section. AH, adenohypophysis; IIIVen, third ventricle; OC, optic chiasm; PitS, pituitary stalk. At the 18-month follow-up, the patient is clinically well and has decided to not undergo any biochemical and radiological study. Case 2 This 50-year-old woman underwent head CT scan after mild head trauma, which ruled out posttraumatic lesions and incidentally documented calcifications above the sella turcica, which were initially interpreted as a craniopharyngioma (Fig. 2A–2C). The patient did not report any symptom due to pituitary or hypothalamic dysfunction. Her basal pituitary function was unremarkable: FT4, 1 ng/dL (0.7 to 1.77 ng/dL); TSH, 0.67 mcU/mL (0.4 to 3.4 mcU/mL); morning cortisol, 9.1 μg/dL (6.7 to 22.6 μg/dL); ACTH, 12 pg/mL (10 to 50 pg/mL); IGF-I, 65 ng/dL (54 to 199 ng/dL); prolactin, 5 ng/mL (2 to 25 ng/mL); LH (in luteal phase), 19 mcU/mL; FSH, 7 mcU/mL; and estradiol, 337 pg/mL. Ophthalmological assessment excluded papilledema and visual deficits. Brain MRI excluded the diagnosis of craniopharyngioma, showing a cystic lesion of the sella turcica with similar features to the previous case (Fig. 2D–2F). An enlarged sella was documented; the calcifications documented on CT were then interpreted as remnants of the dorsum sellae, partly eroded by direct pulsations of CSF inside the sella turcica (Fig. 2A–2C). Hydrocephalus and empty sella were excluded, as well as other indirect signs of intracranial hypertension. Comparison with a brain MRI performed 4 years prior documented the same images, which had not been reported. Figure 2. View largeDownload slide Case 2. MRI T1-weighted sequence after contrast administration, (A) sagittal, (B) axial, and (C) coronal sections. (D–F) Magnetic resonance cisternography with three-dimensional balanced steady-state gradient echo sequence, reformatted following the pituitary stalk (D: sagittal, E: axial; F: coronal planes). (G–I) CT bone window in (G) sagittal, (H) axial, and (I) coronal sections. The white arrows point to the thinned dorsum sellae. The calcifications are consistent with residuals of the partially eroded dorsum sellae. IIIVEn, third ventricle; OC, optic chiasm; PitS, pituitary stalk. Figure 2. View largeDownload slide Case 2. MRI T1-weighted sequence after contrast administration, (A) sagittal, (B) axial, and (C) coronal sections. (D–F) Magnetic resonance cisternography with three-dimensional balanced steady-state gradient echo sequence, reformatted following the pituitary stalk (D: sagittal, E: axial; F: coronal planes). (G–I) CT bone window in (G) sagittal, (H) axial, and (I) coronal sections. The white arrows point to the thinned dorsum sellae. The calcifications are consistent with residuals of the partially eroded dorsum sellae. IIIVEn, third ventricle; OC, optic chiasm; PitS, pituitary stalk. At the 18-month follow-up, the patient is clinically well. Sellar region MRI and pituitary assessment were unchanged: FT4, 1.2 ng/dL (0.7 to 1.77 ng/dL); TSH, 1 mcU/mL (0.4 to 3.4 mcU/mL); morning cortisol, 9.1 μg/dL (6.7 to 22.6 μg/dL); ACTH, 15 pg/mL (10 to 50 pg/mL); IGF-I, 153 ng/dL (70 to 251 ng/dL); prolactin, 8.1 ng/mL (2 to 25 ng/mL); LH (in follicular phase), 10 mcU/mL; FSH, 8 mcU/mL; and estradiol, 130 pg/mL. Results of literature review Of the 160 articles we retrieved in the English literature, 143 articles were discarded during title and abstract analysis, whereas 17 articles were selected for full-text analysis. Of these, nine were excluded as they did not describe PEIR. After further detail analysis, two articles were discarded because the described condition was hypothetical for one patient (6) and not PEIR but rather enlargement of the infundibular recess associated with hydrocephalus (7) for two patients (Supplemental Fig. 1). A total of six papers, describing one case each, were then included in this review. Discussion To our knowledge, Šteňo et al. (4) were recently the first to use the term PEIR and provided a literature review together with the description of a new case (Table 1). In the earliest reported cases (8–10), which were studied with X-rays and ventriculography, PEIR was apparently associated with hydrocephalus or empty sella, but the reporting authors underlined the possibility of a mere coincidental association (9) and the peculiarity of the “empty sellalike” image that was associated with PEIR (10). Morota et al. (7) were the first, to our knowledge, to hypothesize a possible connection of the condition with hydrocephalus and empty sella; they described two cases of infundibular recess enlargement that have been included in other reviews of PEIR (4, 6). An in-detail analysis documented that these two cases are the only ones without any intrasellar component, leading to the possibility that they are not PEIR but rather an enlargement of the infundibular recess related to hydrocephalus (2). We then decided to discard their study in this review, including only PEIR with an intrasellar component and with suggestive radiological imaging. Table 1. Previously Described Cases of PEIR Together With the Two New Cases Author, Year Age, Y/Sex Presenting Symptoms Imaging Modality Hydrocephalus (Cause or Type)/Empty Sella Endocrine Status Treatment Outcome/Follow-Up Kühne and Schwartz, 1975 (8) 34/F Headache, weight gain, irregular menses X-ray, VG, CA Yes (midbrain mass)/no NA NA NA Cabanes, 1978 (9) 60/F Headache, blurring of vision, Hakim triad X-ray, VG, CA Yes (NPH)/no NA V-P shunt for NPH Improvement/4 years Schumacher and Gilsbach, 1979 (10) 47/F Signs of increased intracranial pressure X-ray, VG, CA Yes (cerebellar hemangioblastoma)/no NA Removal of cerebellar hemangioblastoma NA/NA Vallee et al., 1982 (11) 56/M Frontal headache, loss of vision in one eye, central retina artery thrombosis X-rays, CT, VG Yes (aqueductal stenosis)/no No deficit (after treatment) V-P shunt Unchanged/1 year Iplikcioglu et al., 2004 (12) 34/F Headache, dysmenorrhea, galactorrhea, bitemporal hemianopia CT, MRI Yes/yes Mild hyper-PRL (55 ng/mL) V-P shunt refused NA/NA Šteňo et al., 2009 (4) 24/M GH deficit, then hypogonadism, headaches MRI No/no GH and testosterone deficit Surgical exploration Well on replacement therapy, analgesics/8 years Present series 34/F Headache with transient visual loss CT, MRI No/no Normal Observation Unchanged at 18 months 50/F Incidental (head trauma) CT, MRI No/no Normal Observation Unchanged at 18 months Radiology unchanged at 5 years Author, Year Age, Y/Sex Presenting Symptoms Imaging Modality Hydrocephalus (Cause or Type)/Empty Sella Endocrine Status Treatment Outcome/Follow-Up Kühne and Schwartz, 1975 (8) 34/F Headache, weight gain, irregular menses X-ray, VG, CA Yes (midbrain mass)/no NA NA NA Cabanes, 1978 (9) 60/F Headache, blurring of vision, Hakim triad X-ray, VG, CA Yes (NPH)/no NA V-P shunt for NPH Improvement/4 years Schumacher and Gilsbach, 1979 (10) 47/F Signs of increased intracranial pressure X-ray, VG, CA Yes (cerebellar hemangioblastoma)/no NA Removal of cerebellar hemangioblastoma NA/NA Vallee et al., 1982 (11) 56/M Frontal headache, loss of vision in one eye, central retina artery thrombosis X-rays, CT, VG Yes (aqueductal stenosis)/no No deficit (after treatment) V-P shunt Unchanged/1 year Iplikcioglu et al., 2004 (12) 34/F Headache, dysmenorrhea, galactorrhea, bitemporal hemianopia CT, MRI Yes/yes Mild hyper-PRL (55 ng/mL) V-P shunt refused NA/NA Šteňo et al., 2009 (4) 24/M GH deficit, then hypogonadism, headaches MRI No/no GH and testosterone deficit Surgical exploration Well on replacement therapy, analgesics/8 years Present series 34/F Headache with transient visual loss CT, MRI No/no Normal Observation Unchanged at 18 months 50/F Incidental (head trauma) CT, MRI No/no Normal Observation Unchanged at 18 months Radiology unchanged at 5 years Abbreviations: CA, cerebral angiography; NA, not available; NPH, normal pressure hydrocephalus; PRL, prolactin; VG, ventriculography; V-P, ventriculo-peritoneal. View Large Table 1. Previously Described Cases of PEIR Together With the Two New Cases Author, Year Age, Y/Sex Presenting Symptoms Imaging Modality Hydrocephalus (Cause or Type)/Empty Sella Endocrine Status Treatment Outcome/Follow-Up Kühne and Schwartz, 1975 (8) 34/F Headache, weight gain, irregular menses X-ray, VG, CA Yes (midbrain mass)/no NA NA NA Cabanes, 1978 (9) 60/F Headache, blurring of vision, Hakim triad X-ray, VG, CA Yes (NPH)/no NA V-P shunt for NPH Improvement/4 years Schumacher and Gilsbach, 1979 (10) 47/F Signs of increased intracranial pressure X-ray, VG, CA Yes (cerebellar hemangioblastoma)/no NA Removal of cerebellar hemangioblastoma NA/NA Vallee et al., 1982 (11) 56/M Frontal headache, loss of vision in one eye, central retina artery thrombosis X-rays, CT, VG Yes (aqueductal stenosis)/no No deficit (after treatment) V-P shunt Unchanged/1 year Iplikcioglu et al., 2004 (12) 34/F Headache, dysmenorrhea, galactorrhea, bitemporal hemianopia CT, MRI Yes/yes Mild hyper-PRL (55 ng/mL) V-P shunt refused NA/NA Šteňo et al., 2009 (4) 24/M GH deficit, then hypogonadism, headaches MRI No/no GH and testosterone deficit Surgical exploration Well on replacement therapy, analgesics/8 years Present series 34/F Headache with transient visual loss CT, MRI No/no Normal Observation Unchanged at 18 months 50/F Incidental (head trauma) CT, MRI No/no Normal Observation Unchanged at 18 months Radiology unchanged at 5 years Author, Year Age, Y/Sex Presenting Symptoms Imaging Modality Hydrocephalus (Cause or Type)/Empty Sella Endocrine Status Treatment Outcome/Follow-Up Kühne and Schwartz, 1975 (8) 34/F Headache, weight gain, irregular menses X-ray, VG, CA Yes (midbrain mass)/no NA NA NA Cabanes, 1978 (9) 60/F Headache, blurring of vision, Hakim triad X-ray, VG, CA Yes (NPH)/no NA V-P shunt for NPH Improvement/4 years Schumacher and Gilsbach, 1979 (10) 47/F Signs of increased intracranial pressure X-ray, VG, CA Yes (cerebellar hemangioblastoma)/no NA Removal of cerebellar hemangioblastoma NA/NA Vallee et al., 1982 (11) 56/M Frontal headache, loss of vision in one eye, central retina artery thrombosis X-rays, CT, VG Yes (aqueductal stenosis)/no No deficit (after treatment) V-P shunt Unchanged/1 year Iplikcioglu et al., 2004 (12) 34/F Headache, dysmenorrhea, galactorrhea, bitemporal hemianopia CT, MRI Yes/yes Mild hyper-PRL (55 ng/mL) V-P shunt refused NA/NA Šteňo et al., 2009 (4) 24/M GH deficit, then hypogonadism, headaches MRI No/no GH and testosterone deficit Surgical exploration Well on replacement therapy, analgesics/8 years Present series 34/F Headache with transient visual loss CT, MRI No/no Normal Observation Unchanged at 18 months 50/F Incidental (head trauma) CT, MRI No/no Normal Observation Unchanged at 18 months Radiology unchanged at 5 years Abbreviations: CA, cerebral angiography; NA, not available; NPH, normal pressure hydrocephalus; PRL, prolactin; VG, ventriculography; V-P, ventriculo-peritoneal. View Large Embryogenesis During embryogenesis (Fig. 3), pituitary gland development begins at ∼22 days of gestation, when the hypophyseal placode, which will give origin to the adenohypophysis, becomes distinguishable. It corresponds to a small area of ectoderm, rostral to the buccopharyngeal membrane that is adherent to the overlying neuroectoderm, which, in turn, constitutes the neural plate (13). These two cell populations are located next to each other and contribute to form the pituitary gland as a single structure (13, 14). Figure 3. View largeDownload slide Normal embryogenesis and PEIR. (A) In the 22-day-old embryo, the hypophyseal placode can be distinguished. (B, C) In the 28-day-old embryo, the invagination of the Rathke pouch begins; after 37 days, the infundibular recess is formed. (D) Between 40 and 60 days, the rudimentary neurohypophysis is located posterior to the adenohypophysis. (E) In the 8-week-old embryo, the adenohypophysis is completely separated from the pharynx due to the partial obliteration of the Rathke cleft, which gives origin to the pharyngo-hypophyseal stalk. (F) In the 3-month-old embryo, the anatomical configuration is similar to the adult one. (G) In the adult, the pituitary stalk with an obliterated infundibular recess is normally present. (H) In the case of PEIR, the obliteration of the recess is missing and filled with CSF from the third ventricle. AH, adenohypophysis; AntL, anterior hypophyseal lobe; B-PM, buccopharyngeal membrane; Df, diencephalon floor; Ect, ectoderm; End, endoderm; HP, hypophyseal placode; Inf, infundibulum; InfR, infundibular recess; IntL, intermediate hypophyseal lobe; Mes, mesoderm; MesE, mesencephalon; NEct, neuroectoderm; NH, neurohypophysis; OC, optic chiasm; P-HS, pharyngo-hypophyseal stalk; PitS, pituitary stalk; PosL, posterior hypophyseal lobe; PrE, prosencephalon; PT, pars tuberalis of the adenohypophysis; RhE, rhombencephalon; RP, Rathke pouch; SphB, sphenoid bone; SphS, sphenoid sinus. Figure 3. View largeDownload slide Normal embryogenesis and PEIR. (A) In the 22-day-old embryo, the hypophyseal placode can be distinguished. (B, C) In the 28-day-old embryo, the invagination of the Rathke pouch begins; after 37 days, the infundibular recess is formed. (D) Between 40 and 60 days, the rudimentary neurohypophysis is located posterior to the adenohypophysis. (E) In the 8-week-old embryo, the adenohypophysis is completely separated from the pharynx due to the partial obliteration of the Rathke cleft, which gives origin to the pharyngo-hypophyseal stalk. (F) In the 3-month-old embryo, the anatomical configuration is similar to the adult one. (G) In the adult, the pituitary stalk with an obliterated infundibular recess is normally present. (H) In the case of PEIR, the obliteration of the recess is missing and filled with CSF from the third ventricle. AH, adenohypophysis; AntL, anterior hypophyseal lobe; B-PM, buccopharyngeal membrane; Df, diencephalon floor; Ect, ectoderm; End, endoderm; HP, hypophyseal placode; Inf, infundibulum; InfR, infundibular recess; IntL, intermediate hypophyseal lobe; Mes, mesoderm; MesE, mesencephalon; NEct, neuroectoderm; NH, neurohypophysis; OC, optic chiasm; P-HS, pharyngo-hypophyseal stalk; PitS, pituitary stalk; PosL, posterior hypophyseal lobe; PrE, prosencephalon; PT, pars tuberalis of the adenohypophysis; RhE, rhombencephalon; RP, Rathke pouch; SphB, sphenoid bone; SphS, sphenoid sinus. In the next stage, the neural crest mesenchyme extends between the prosencephalon and the surface ectoderm in front of the buccopharyngeal membrane, except for the region of the placode (14, 15). Thereafter, the saccular Rathke pouch, whose walls and roof are constituted by the placode, takes shape (13). Likewise, the primordium of the infundibular recess becomes visible on the floor of the third ventricle (13). After 37 days of gestation, the infundibular recess is formed and indicates the outgrowth of the neurohypophysis (13). During the next stages, the Rathke pouch is constricted by continued proliferation of the surrounding mesenchyme to form a closed vesicle but remains for a time connected to the ectoderm of the stomodeum by a solid cord of cells, which can be traced down the posterior edge of the nasal septum (13). The dorsal wall of the Rathke pouch remains thin and fuses with the adjoining part of the neurohypophysis as the pars intermedia (13). The growth of the neurohypophysis and of the pars tuberalis of the neurohypophysis around the infundibular recess leads to its obliteration except at its upper end, where it persists as the infundibular recess of the third ventricle (9, 11, 13). Etiology Different embryogenic theories were proposed to explain PEIR. The first theory proposed the mechanism of arrested proliferation of cells (8–11), but evidence of such process was missing. Therefore, other authors proposed a second theory, based on the presence of the hydrocephalus and consequent raised intraventricular pressure as primum movens of the PEIR (7). Nevertheless, Šteňo et al. (4), who did not find the hydrocephalus, proposed again a dysembryogenic theory, attributing to the hydrocephalus the role of unmasking the underlying anomaly. It is known that in some animals, the recessus infundibuli persists within the posterior pituitary lobe, but in humans, it normally ends above the plane of the diaphragma sellae (11). PEIR might then be the result of dysembryogenesis (Supplemental Fig. 1). Endocrinological data Strikingly, limited endocrinological data are available on PEIR (Table 1) and in some reports might be influenced by associated conditions, such as hydrocephalus. In both our patients, endocrine assessment did not document any evidence of hypopituitarism. Moreover, no symptoms or signs due to hypothalamic involvement, such as temperature dysregulation or disturbances in appetite and sleep, were evident. Radiology Brain MRI imaging can document the pathognomonic features of PEIR (Figs. 1 to 2 and Supplemental Fig. 1): a funnel-shaped, CSF-filled tunnel in the enlarged pituitary stalk is coupled with a cyst in the sellar area, located mainly posteriorly to the anterior lobe of the pituitary gland. Sellar enlargement is usually present. Natural history Data on the natural history of PEIR are extremely limited (Table 1). After surgical exploration, which confirmed the nonneoplastic nature of the lesion, Šteňo et al. (4) reported a stable condition after 8 years. There are no reports on radiological or clinical progression of this condition. Both our patients are stable at the latest follow-up (18 months) from a clinical and endocrine point of view. In one of our patients, no radiological progression of PEIR is evident even after 5 years. Treatment No treatment should be considered if PEIR is an isolated finding. Associated conditions, such as hydrocephalus, which might lead to a progression of PEIR image, should be treated accordingly. It is of paramount importance to correctly diagnose this condition to avoid unnecessary treatment. Conclusions PEIR is a rare, dysembriogenetic condition of the sellar and suprasellar region, probably underrecognized, which should be included in the differential diagnosis of cystic sellar lesions. Pituitary function is usually unaffected and remains stable over time, but further data have to be collected on the natural history of this condition. Abbreviations: Abbreviations: CSF cerebrospinal fluid PEIR persisting embryonal infundibular recess Acknowledgments Disclosure Summary: The authors have nothing to disclose. References 1. Rhoton AL . Anatomy of the pituitary gland and sellar region. In: Thapar K , Kovacs K , Scheithauer BW , Lloyd RV , eds. Diagnosis and Management of Pituitary Tumors . Totowa, NJ : Humana Press ; 2001 : 13 – 40 . 2. Tsutsumi S , Hori M , Ono H , Tabuchi T , Aoki S , Yasumoto Y . The infundibular recess passes through the entire pituitary stalk . Clin Neuroradiol . 2015 ; 26 ( 4 ): 465 – 469 . 3. Standring S , Borley NR , Collins P , Crossman AR , Gatzoulis MA , Wigley CB . Development of the nervous system. In: Standring S , ed. Gray’s Anatomy: The Anatomical Basis of Clinical Practice . Edinburgh : Churchill Livingstone/Elsevier ; 2008 : 319 – 353 . 4. Šteňo A , Popp AJ , Wolfsberger S , Belan V , Šteňo J . Persisting embryonal infundibular recess . J Neurosurg . 2009 ; 110 ( 2 ): 359 – 362 . 5. Moher D , Liberati A , Tetzlaff J , Altman DG , PRISMA Group . Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement . BMJ . 2009 ; 339 : b2535 . 6. Kuroiwa M , Kusano Y , Ogiwara T , Tanaka Y , Takemae T , Hongo K . A case of presumably Rathke’s cleft cyst associated with postoperative cerebrospinal fluid leakage through persisting embryonal infundibular recess . Neurol Med Chir (Tokyo) . 2014 ; 54 ( 7 ): 578 – 581 . 7. Morota N , Watabe T , Inukai T , Hongo K , Nakagawa H . Anatomical variants in the floor of the third ventricle; implications for endoscopic third ventriculostomy . J Neurol Neurosurg Psychiatry . 2000 ; 69 ( 4 ): 531 – 534 . 8. Kühne D , Schwartz RB . Persisting intrapituitary recessus infundibuli . Neuroradiology . 1975 ; 10 ( 3 ): 177 – 178 . 9. Cabanes J . Asymptomatic persistence of infundibularis recessus . J Neurosurg . 1978 ; 49 ( 5 ): 769 – 772 . 10. Schumacher M , Gilsbach J . A new variety of “empty sella” with cystic intrasellar dilatation of the recessus infundibuli . Br J Radiol . 1979 ; 52 ( 623 ): 862 – 864 . 11. Vallee B , Besson G , Person H , Mimassi N . Persisting recessus infundibuli and empty sella . J Neurosurg . 1982 ; 57 ( 3 ): 410 – 412 . 12. Iplikcioglu AC , Bek S , Gokduman CA , Dinc C , Cosar M . Primary empty sella syndrome associated with dilated infundibular recessus . J Neurol Sci Turish . 2004 ; 21 : 127 – 130 . 13. Kollias SS , Ball WS , Prenger EC . Review of the embryologic development of the pituitary gland and report of a case of hypophyseal duplication detected by MRI . Neuroradiology . 1995 ; 37 ( 1 ): 3 – 12 . 14. Musumeci G , Castorina S , Castrogiovanni P , Loreto C , Leonardi R , Aiello FC , Magro G , Imbesi R . A journey through the pituitary gland: development, structure and function, with emphasis on embryo-foetal and later development . Acta Histochem . 2015 ; 117 ( 4–5 ): 355 – 366 . 15. Kioussi C , Carrière C , Rosenfeld MG . A model for the development of the hypothalamic-pituitary axis: transcribing the hypophysis . Mech Dev . 1999 ; 81 ( 1–2 ): 23 – 35 . Copyright © 2018 Endocrine Society

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Journal of Clinical Endocrinology and MetabolismOxford University Press

Published: May 16, 2018

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