Partial ectopic posterior pituitary: A rare imaging entity with literature review.

Abnormal development of the posterior pituitary gland can lead to an ectopic location of the neurohypophysis, commonly seen at the median eminence of the hypothalamus or along the infundibular stalk. A partial ectopic posterior pituitary (PEPP) is a very rare variant of the ectopic posterior pituitary, defined as the presence of a double bright spot of neurohypophysis seen in both orthotopic and ectopic locations. We report a two-year-old male toddler with bilateral optic nerve hypoplasia and severe visual impairment who presented to the endocrine outpatient clinic for hypopituitarism evaluation. Magnetic resonance imaging (MRI) of the brain revealed a hypoplastic pituitary gland and infundibulum with a double bright spot of neurohypophysis in the expected normal location and along the median eminence. Severe hypoplasia of both optic nerves and the optic chiasm was also seen. Septum pellucidum was present with no evidence of other brain malformations. The findings are in the septo-optic dysplasia spectrum associated with hypothalamic-pituitary dysfunction and a very rare entity called PEPP. To our knowledge, only a handful of reported cases of this rare entity exist in the literature.

Copy number variation in pituitary stalk interruption syndrome: A large case series of sporadic non-syndromic patients and literature review.

Abnormal hypothalamic/posterior pituitary development appears to be a major determinant of pituitary stalk interruption syndrome (PSIS). The observation of familial cases and associated congenital abnormalities suggests a genetic basis. Single-gene mutations explain less than 5% of the cases, and whole exome sequencing has shown heterogeneous results. The present study aimed to assess copy number variation (CNV) using array-based comparative genomic hybridization (aCGH) in patients with non-syndromic PSIS and comprehensively review data from the literature on CNV analysis in congenital hypopituitarism (CH) patients. Twenty-one patients with sporadic CH from our outpatient clinics presented with ectopic posterior pituitary (EPP) and no central nervous system abnormalities on magnetic resonance image (MRI) or any other malformations on physical examination at presentation were enrolled in the study. aCGH using a whole-genome customized 400K oligonucleotide platform was performed in our patients. For the literature review, we searched for case reports of patients with CH and CNV detected by either karyotype or aCGH reported in PubMed up to November 2021. Thirty-five distinct rare CNVs were observed in 18 patients (86%) and two of them (6%) were classified as pathogenic: one deletion of 1.8 Mb in chromosome 17 (17q12) and one deletion of 15 Mb in chromosome 18 (18p11.32p11.21), each one in a distinct patient. In the literature review, 67 pathogenic CNVs were published in 83 patients with CH, including the present study. Most of these patients had EPP (78% out of the 45 evaluated by sellar MRI) and were syndromic (70%). The most frequently affected chromosomes were X, 18, 20 and 1. Our study has found that CNV can be a mechanism of genetic abnormality in non-syndromic patients with CH and EPP. In future studies, one or more genes in those CNVs, both pathogenic and variant of uncertain significance, may be considered as good candidate genes.

Diagnostic value of magnetic resonance imaging ectopic posterior pituitary hyperintense signal in pituitary macroadenoma.

Objective: When the lesions in the sellar region are large, they can involve both the inside and outside the sella, which brings challenges to the differential diagnosis of pituitary macroadenoma and lesions other than macroadenoma. Therefore, this study explored the diagnostic value of an ectopic posterior pituitary hyperintense signal (EPPHS) in pituitary macroadenoma and its possible causes. Methods: The clinical and imaging data of 131 patients with sellar tumors or tumor-like lesions involving both intrasellar and extrasellar regions in the Affiliated Hospital of Guizhou Medical University from February 2011 to December 2021 were analyzed retrospectively. The diagnostic value of EPPHS in pituitary macroadenoma was analyzed. The differences in clinical and imaging indexes between the EPPHS-positive group and the EPPHS-negative group were compared. Results: These 131 cases of sellar tumors or tumor-like lesions involving both intrasellar and extrasellar regions included 91 cases of pituitary macroadenoma and 40 cases of lesions other than macroadenoma. The receiver operator characteristic (ROC) curve analysis suggested that EPPHS had a diagnostic value in diagnosing pituitary macroadenoma [area under the curve (AUC) = 0.857, P = 0.0001]. Compared with the EPPHS negative group, the median prolactin level in the EPPHS positive group was significantly higher (P < 0.05). Through ROC curve analysis, prolactin value was found to be of diagnostic value for EPPHS (AUC = 0.612, P = 0.0312). Conclusion: In sellar tumors or tumor-like lesions involving both intrasellar and extrasellar regions, the appearance of EPPHS is helpful in the diagnosis of pituitary macroadenoma. The formation of EPPHS may be related to injuries to the pituitary stalk.

Whole Exome Sequencing in Patients With Ectopic Posterior Pituitary.

Context: Ectopic posterior pituitary (EPP), a condition in which the posterior pituitary gland is displaced due to defective neuronal migration, is frequently associated with hypopituitarism. Genetic variants play a role, but many cases remain unexplained. Objective: A large EPP cohort was studied to explore the importance of genetic variants and how they correlate with clinical findings. Methods: Whole exome sequencing was performed on a discovery sample of 27 cases to identify rare variants. The variants that met the criteria for rarity and biological relevance, or that were previously associated with EPP (ROBO1 and HESX1), were then resequenced in the 27 cases plus a replication sample of 51 cases. Results: We identified 16 different variants in 12 genes in 15 of the 78 cases (19.2%). Complete anterior pituitary deficiency was twice as common in cases with variants of interest compared to cases without variants (9/15 [60%] vs 19/63 [30.1%], respectively; Z test, P = 0.06). Breech presentation was more frequent in the variant positive group (5/15 vs 1/63; Z test, P = 0.003). Four cases had variants in ROBO1 and 1 in HESX1, genes previously associated with EPP. The ROBO1 p.S18* variant has not been reported previously; ROBO1 p.Q1227H has not been associated with EPP previously. Conclusion: EPP cases with variants of interest identified in this study were more likely to present with severe clinical disease. Several variants were identified in genes not previously associated with EPP. Our findings confirm that EPP is a multigenic disorder. Future studies are needed to identify additional genes.

Pituitary stalk interruption syndrome: phenotype, predictors, and pathophysiology of perinatal events.

PURPOSE: There is limited data regarding Pituitary Stalk Interruption Syndrome (PSIS) from India. Moreover, the pathophysiological link between perinatal events and PSIS is unclear. We aim to elucidate the predictors of PSIS among patients with growth hormone deficiency (GHD) and perinatal events in PSIS by comparing cohorts of PSIS and genetically proven GHD without PSIS. METHODS: Among 179 GHD patients, 56 PSIS and 70 genetically positive GHD (52-GHRHR, 15-POU1F1, and 3-PROP1) patients were included. Perinatal events, clinical anomalies, pituitary hormone deficiency, and imaging findings were recorded. We compared PSIS-isolated GHD (PSIS-IGHD) subgroup with GHRHR-IGHD and PSIS-combined pituitary hormone deficiency (PSIS-CPHD) subgroup with POU1F1/PROP1-CPHD. RESULTS: PSIS patients (45 males, median age: 12.5 years) most commonly presented with short stature. At last follow-up (median age: 17.35 years), gonadal (during pubertal-age), thyroid and cortisol axes were affected in 81.6%, 62.5%, and 62.5%. 10/13 (77%) of PSIS children with initial IGHD diagnosis manifested hypogonadism during pubertal age. Male predominance, sporadic presentation, and clinical anomalies were significantly higher in both PSIS subgroups than in the respective genetic subgroups. Breech presentation was higher in PSIS-CPHD than POU1F1/PROP1-CPHD (44.4% vs 5.5%, p = 0.004). Neonatal hypoglycemia (22% vs. 0%, p = 0.05) and jaundice (42 vs. 5%, p = 0.004) were higher in PSIS-CPHD than PSIS-IGHD. CONCLUSION: Later age at presentation and frequent hypogonadism were observed in our PSIS cohort. Male sex, sporadic presentation, clinical anomalies, and breech presentation predicted PSIS at presentation. Breech presentation in PSIS is likely due to stalk interruption rather than hormonal deficiency.

Ectopic neurohypophisis in a boy: A case report and review.

Ectopic neurohypophysis is rare anomaly which is characterized by ectopic location of posterior pituitary lobe (neurohypophysis), pituitary stalk abnormalities and association with dysfunction of anterior lobe related with growth hormone or with multiple dysfunction of the same.We present a rare case of posterior ectopic pituitary and pituitary stalk hypoplasia isolated in 2 year-old male patient.

Utility of Constructive Interference in Steady-State Sequence in Detecting Thin Pituitary Stalk in Pituitary Stalk Interruption Syndrome.

Pituitary stalk interruption syndrome (PSIS) is a rare congenital anomaly, causing hypothalamic-pituitary malfunction. It is characterized by hypoplastic anterior pituitary, absent or thin infundibulum, and absent or ectopic posterior pituitary. Its early recognition is important in disease management. MRI plays a pivotal role in early diagnosis. We report a case of a 13-year-old male child, presenting with stunting of growth and discrepancy between chronological and bone age of four years. A subsequent MRI revealed a small anterior pituitary, hypoplastic pituitary stalk, and an absence of visualization of the bright pituitary gland signal in the sella. The posterior pituitary gland was present ectopically in the midline along the floor of the third ventricle near the median eminence.

Evidence That the Etiology of Congenital Hypopituitarism Has a Major Genetic Component but Is Infrequently Monogenic.

PURPOSE: Congenital hypopituitarism usually occurs sporadically. In most patients, the etiology remains unknown. METHODS: We studied 13 children with sporadic congenital hypopituitarism. Children with non-endocrine, non-familial idiopathic short stature (NFSS) (n = 19) served as a control group. Exome sequencing was performed in probands and both unaffected parents. A burden testing approach was used to compare the number of candidate variants in the two groups. RESULTS: First, we assessed the frequency of rare, predicted-pathogenic variants in 42 genes previously reported to be associated with pituitary gland development. The average number of variants per individual was greater in probands with congenital hypopituitarism than those with NFSS (1.1 vs. 0.21, mean variants/proband, P = 0.03). The number of probands with at least 1 variant in a pituitary-associated gene was greater in congenital hypopituitarism than in NFSS (62% vs. 21%, P = 0.03). Second, we assessed the frequency of rare, predicted-pathogenic variants in the exome (to capture undiscovered causes) that were inherited in a fashion that could explain the sporadic occurrence of the proband's condition with a monogenic etiology (de novo mutation, autosomal recessive, or X-linked recessive) with complete penetrance. There were fewer monogenic candidates in the probands with congenital hypopituitarism than those with NFSS (1.3 vs. 2.5 candidate variants/proband, P = 0.024). We did not find any candidate variants (0 of 13 probands) in genes previously reported to explain the phenotype in congenital hypopituitarism, unlike NFSS (8 of 19 probands, P = 0.01). CONCLUSION: Our findings provide evidence that the etiology of sporadic congenital hypopituitarism has a major genetic component but may be infrequently monogenic with full penetrance, suggesting a more complex etiology.

3D fat-suppressed T1-weighted volume isotropic turbo spin-echo acquisition (VISTA) imaging for the evaluation of the ectopic posterior pituitary gland.

OBJECTIVE: We evaluated the usefulness of fat-suppressed three-dimensional T1-weighted volume isotropic turbo spin-echo acquisition (FS 3D T1W-VISTA) imaging for the evaluation of the ectopic posterior pituitary gland (EPPG). MATERIALS AND METHODS: This retrospective study included 9 patients with EPPG due to causes other than tumor. All underwent sagittal two-dimensional (2D) T1W-, FS 3D T1W-VISTA- (VISTA), and 3D T2W-driven equilibrium radiofrequency reset pulse (DRIVE) imaging. Two radiologists independently reviewed the 2D T1W- and VISTA images for their image quality and for visualization of the EPPG and of pituitary stalk transection. DRIVE findings were used as the reference standard for pituitary stalk transection. Interobserver and intermodality agreements were evaluated with the kappa (κ) coefficient. The mean grade assigned to the 2D T1W- and the VISTA imaging technique for visualization of the EPPG was assessed by the Mann-Whitney U test. RESULTS: Interobserver agreement for visualization of the EPPG on 2D T1W- and VISTA images was excellent (κ = 0.82 and κ = 1.00, respectively). The mean grade for EPPG visualization was significantly higher for VISTA- than 2D T1W images (p = 0.0039). CONCLUSION: FS 3D T1W-VISTA imaging is useful for the evaluation of EPPG. Conventional MRI yields insufficient information for the evaluation of the ectopic posterior pituitary gland (EPPG). The visualization of the EPPG was significantly higher for fat-suppressed three-dimensional T1-weighted volume isotropic turbo spin-echo acquisition (FS 3D T1W-VISTA) than 2D T1W images. FS 3D T1W-VISTA imaging is useful for the evaluation of the EPPG.

Brain MRIs may be of low value in most children diagnosed with isolated growth hormone deficiency.

OBJECTIVES: Brain MRIs are considered essential in the evaluation of children diagnosed with growth hormone deficiency (GHD), but there is uncertainty about the appropriate cut-off for diagnosis of GHD and little data about the yield of significant abnormal findings in patients with peak growth hormone (GH) of 7-10 ng/mL. We aimed to assess the frequency of pathogenic MRIs and associated risk factors in relation to peak GH concentrations. METHODS: In this retrospective multicenter study, charts of patients diagnosed with GHD who subsequently had a brain MRI were reviewed. MRIs findings were categorized as normal, incidental, of uncertain significance, or pathogenic (pituitary hypoplasia, small stalk and/or ectopic posterior pituitary and tumors). Charges for brain MRIs and sedation were collected. RESULTS: In 499 patients, 68.1% had normal MRIs, 18.2% had incidental findings, 6.6% had uncertain findings, and 7.0% had pathogenic MRIs. Those with peak GH<3 ng/mL had the highest frequency of pathogenic MRIs (23%). Only three of 194 patients (1.5%) with peak GH 7-10 ng/mL had pathogenic MRIs, none of which altered management. Two patients (0.4%) with central hypothyroidism and peak GH<4 ng/mL had craniopharyngioma. CONCLUSIONS: Pathogenic MRIs were uncommon in patients diagnosed with GHD except in the group with peak GH<3 ng/mL. There was a high frequency of incidental findings which often resulted in referrals to neurosurgery and repeat MRIs. Given the high cost of brain MRIs, their routine use in patients diagnosed with isolated GHD, especially patients with peak GH of 7-10 ng/mL, should be reconsidered.

Coexistence of Ectopic Posterior Pituitary and Sellar/Suprasellar Arachnoid Cyst: A Case Report.

BACKGROUND: The ectopic posterior pituitary (EPP) is a rare condition characterized by the ectopic location of the posterior pituitary lobe associated with varying degrees of stalk anomalies. The arachnoid cysts (AC) are benign lesions of the arachnoid, which account for 1% of all intracranial space-occupying lesions. Sellar/suprasellar ACs account for approximately 1% of all ACs. This is the first case of coexistence EPP with sellar/suprasellar AC. CASE REPORT: A 67-year-old woman presented with 6 months history of fatigue. Her medical history was positive for irregular menstruation. Her endocrine examinations indicated low free thyroxine level with low TSH level, low oestradiol with low gonadotrophin level, slightly elevated prolactin level. Her Insulin-like growth factor-1 was below the normal levels. Dynamic contrast hypophysis MRI revealed a sellar cystic lesion with a dimension of 18 × 14 × 14 mm, extending from the suprasellar cistern, traversing the diaphragma sellae and reaching the level of the floor of the 3rd ventricle, consistent with sellar/suprasellar AC. There was no wall enhancement. The optic chiasm was compressed. The precontrast T1-weighted magnetic resonance images did not demonstrate the characteristic bright spot of posterior pituitary within the sella, which was higher in position, in the region of the median eminence. The pituitary stalk was not present. CONCLUSION: Although speculative, we have a hypothesis to explain how the EPP and sellar/- suprasellar AC coexist in this patient. Due to the absence of stalk, CSF may enter the sella tursica from the central aperture of the diaphragma sellae through which normally the stalk passes.

MRI of ectopic posterior pituitary gland with dysgenesis of pituitary stalk in a patient with hypogonadotropic hypogonadism.

The ectopic posterior pituitary is a rare condition which is characterized by the ectopic location of posterior lobe of pituitary, pituitary stalk abnormalities, and associated clinical manifestations of anterior lobe related growth hormone dysfunction or less commonly multiple anterior pituitary dysfunctions. We present a rare case of posterior ectopic pituitary and pituitary stalk hypoplasia with isolated hypogonadotropic hypogonadism in a 36-year-old female patient.

SCREENING OF PROP-1, LHX2 AND POU1F1 MUTATIONS IN PATIENTS WITH ECTOPIC POSTERIOR PITUITARY GLAND.

OBJECTIVE: Ectopic posterior pituitary gland (EPP) is usually characterized by an abnormal pituitary stalk and hypoplasia of the anterior hypophysis. The genetic mechanisms involved in the development of EPP remain uncertain. The aim of this study is to determine whether mutations in the three genes, PROP-1, LHX2, and POU1F1, are associated with the risk for and the characteristics of EPP. METHODS: In the Endocrinology Outpatient Clinic of "Dr. Behcet Uz" Children's Hospital, 27 patients with EPP were submitted to sequencing analyses of the PROP-1, LHX2, and POU1F1 genes. RESULTS: Growth hormone, thyrotropin, corticotropin, gonadotropin, and vasopressin deficiency were observed in 22 (81.5%), 23 (85.2%), 17 (63%), 14 (51.9%), and two (7.4%) patients. Thirteen patients (48.1%) presented with hyperprolactinemia. Fourteen patients (51%) had a history of birth dystocia, and 12 cases (42.1%) had a history of breech presentation. Central nervous system abnormalities included five cases with corpus callosum agenesis, one case with schizencephaly, and one case with Chiari type 1 malformation. We identified a homozygous p.S109* mutation in exon 2 in one male patient with EPP and two different PROP1 gene polymorphisms (A142T or c.109+3 G>A polymorphism) in thirteen patients. CONCLUSIONS: Our results suggest that PROP1 gene abnormalities might explain the genetic mechanisms involved in the development of EPP.

The Missing Link: A Case of Absent Pituitary Infundibulum and Ectopic Neurohypophysis in a Pediatric Patient with Heterotaxy Syndrome.

We report a case of absent pituitary infundibulum and ectopic neurohypophysis in a 4-year-old patient presenting clinically with hypopituitarism as well as heterotaxy syndrome complicated by global developmental delay and growth retardation. The clinical and laboratory workup of our patient suggested underlying hypopituitarism related to either congenital or acquired pathology, necessitating MRI to distinguish between them. We explain the various structural causes of hypopituitarism and detail how to predict the MRI findings and treatment, based on a fundamental understanding of the anatomy and pathophysiology of the hypothalamic pituitary axis and distinguishing anterior versus posterior pituitary hormone derangements. We also discuss two important theories widely acknowledged in the literature to explain congenital hypopituitarism: 1. Head trauma typically during birth resulting in a stretch injury to the infundibulum. 2. Congenital fetal maldevelopment of midline structures.

Hypopituitarism in children with cerebral palsy.

Poor growth and delayed puberty in children with cerebral palsy is frequently felt to be related to malnutrition. Although growth hormone deficiency is commonly described in these children, multiple pituitary hormone deficiency (MPHD) has not been previously reported. We present a series of four children with cerebral palsy who were born before 29 weeks gestation who were referred to the regional endocrinology service, three for delayed puberty and one for short stature, in whom investigations identified MPHD. All patients had a height well below -2 standard deviation score (2nd centile) at presentation and three who had MRI scans had an ectopic posterior pituitary gland. We therefore recommend that the possibility of MPHD should be considered in all children with cerebral palsy and poor growth or delayed puberty. Early diagnosis and treatment is essential to maximise growth and prevent associated morbidity and mortality.

Classical and non-classical causes of GH deficiency in the paediatric age.

Growth hormone deficiency (GHD) may result from a failure of hypothalamic GHRH production or release, from congenital disorders of pituitary development, or from central nervous system insults including tumors, surgery, trauma, radiation or infiltration from inflammatory diseases. Idiopathic, isolated GHD is the most common sporadic form of hypopituitarism. GHD may also occur in combination with other pituitary hormone deficiencies, and is often referred to as hypopituitarism, combined pituitary hormone deficiency (CPHD), multiple pituitary hormone deficiency (MPHD) or panhypopituitarism. Children without any identifiable cause of their GHD are commonly labeled as having idiopathic hypopituitarism. MRI imaging is the technique of choice in the diagnosis of children with hypopituitarism. Marked differences in MRI pituitary gland morphology suggest different etiologies of GHD and different prognoses. Pituitary stalk agenesis and ectopic posterior pituitary (EPP) are specific markers of permanent GHD, and patients with these MRI findings show a different clinical and endocrine outcome compared to those with normal pituitary anatomy or hypoplastic pituitary alone. Furthermore, the classic triad of ectopic posterior pituitary gland, pituitary stalk hypoplasia/agenesis, and anterior pituitary gland hypoplasia is generally associated with permanent GHD. T2 DRIVE images aid in the identification of pituitary stalk without the use of contrast medium administration. Future developments in imaging techniques will undoubtedly reveal additional insights. Mutations in a number of genes encoding transcription factors - such as HESX1, SOX2, SOX3, LHX3, LHX4, PROP1, POU1F1, PITX, GLI3, GLI2, OTX2, ARNT2, IGSF1, FGF8, FGFR1, PROKR2, PROK2, CHD7, WDR11, NFKB2, PAX6, TCF7L1, IFT72, GPR161 and CDON - have been associated with pituitary dysfunction and abnormal pituitary gland development; the correlation of genetic mutations to endocrine and MRI phenotypes has improved our knowledge of pituitary development and management of patients with hypopituitarism, both in terms of possible genetic counseling, and of early diagnosis of evolving anterior pituitary hormone deficiencies.

Two novel heterozygous missense variations within the GLI2 gene in two unrelated Argentine patients.

Several heterozygous GLI2 gene mutations have been reported in patients with isolated GH deficiency (IGHD) or multiple pituitary hormone deficiency (MPHD) with or without other malformations. The primary aim of this study was to analyze the presence of GLI2 gene alterations in a cohort of patients with IGHD or MPHD and ectopic/absent posterior pituitary. The coding sequence and flanking intronic regions of GLI2 gene were amplified and directly sequenced from gDNA of 18 affected subjects and relatives. In silico tools were applied to identify the functional impact of newly found variants (Polyphen2, SIFT, Mutation Taster). We identified two novel heterozygous missense variations in two unrelated patients, p.Arg231Gln and p.Arg226Leu, located in the repressor domain of the protein. Both variations affect highly conserved amino acids of the Gli2 protein and were not found in the available databases. In silico tools suggest that these variations might be disease causing. Our study suggests that the GLI2 gene may be one of the candidate genes to analyze when an association of pituitary hormone deficiency and developmental defects in posterior pituitary gland. The highly variable phenotype found suggests the presence of additional unknown factors that could contribute to the phenotype observed in these patients.

Two novel heterozygous missense variations within the GLI2 gene in two unrelated argentine patients / Two novel heterozygous missense variations within the GLI2 gene in two unrelated Argentine patients

Several heterozygous GLI2 gene mutations have been reported in patients with isolated GH deficiency (IGHD) or multiple pituitary hormone deficiency (MPHD) with or without other malformations. The primary aim of this study was to analyze the presence of GLI2 gene alterations in a cohort of patients with IGHD or MPHD and ectopic/absent posterior pituitary. The coding sequence and flanking intronic regions of GLI2 gene were amplified and directly sequenced from gDNA of 18 affected subjects and relatives. In silico tools were applied to identify the functional impact of newly found variants (Polyphen2, SIFT, Mutation Taster). We identified two novel heterozygous missense variations in two unrelated patients, p.Arg231Gln and p.Arg226Leu, located in the repressor domain of the protein. Both variations affect highly conserved amino acids of the Gli2 protein and were not found in the available databases. In silico tools suggest that these variations might be disease causing. Our study suggests that the GLI2 gene may be one of the candidate genes to analyze when an association of pituitary hormone deficiency and developmental defects in posterior pituitary gland. The highly variable phenotype found suggests the presence of additional unknown factors that could contribute to the phenotype observed in these patients.

Mutaciones heterocigotas en el gen GLI2 fueron previamente comunicadas como causa de déficit aislado de hormona de crecimiento (IGHD) o déficit múltiple de hormonas hipofisarias (MPHD), con o sin otras malformaciones. El objetivo del estudio fue analizar la presencia de alteraciones en el gen GLI2 en un grupo de pacientes con IGHD o MPHD acompañado de neurohipófisis ectópica o ausente. La secuencia codificante y las regiones intrónicas flanqueantes del gen GLI2 fueron amplificadas y secuenciadas de manera directa a partir de ADN genómico extraído de sangre periférica proveniente de 18 sujetos afectados y sus familiares. Se utilizaron herramientas informáticas para predecir el impacto funcional de las nuevas variantes encontradas (Polyphen2, SIFT, Mutation Taster). Identificamos dos nuevas variantes heterocigotas con pérdida de sentido en dos pacientes no relacionados, p.Arg231Gln y p.Arg226Leu, localizadas en el dominio represor de la proteína. Estas variantes afectan aminoácidos altamente conservados en la secuencia proteica de GLI2 y no se encuentran informadas en las bases de datos disponibles. Las herramientas informáticas utilizadas sugieren que estas variantes pueden ser la causa del desarrollo de la enfermedad. Nuestro resultados indican que el gen GLI2 es uno de los genes candidatos a estudiar cuando existe una asociación entre déficit de hormonas hipofisarias y alteraciones en el desarrollo de la neurohipófisis. Se sugiere la existencia de otros factores adicionales que podrían contribuir a la variabilidad del fenotipo observado.

Pituitary stalk interruption syndrome: Case report of three cases with review of literature.

Pickardt syndrome (Pickardt-Fahlbusch syndrome) is a rare congenital syndrome characterized by tertiary hypothyroidism caused by the interruption of the portal veins between hypothalamus and adenohypophysis. Typical features of this syndrome are tertiary hypothyroidism with low thyroid stimulating hormone, hyperprolactinemia and other pituitary hormone deficiencies. Pituitary stalk interruption syndrome is characterized by a triad of thin or interrupted pituitary stalk, aplasia or hypoplasia of the anterior pituitary and absent or ectopic posterior pituitary (EPP) seen on magnetic resonance imaging (MRI). It is a congenital anomaly of pituitary whose exact prevalence is unknown. In some cases, it is restricted to EPP or pituitary stalk interruption. We are presenting the case history along with MRI finding of three children's who presented with short stature and delayed puberty.

Pituitary stalk transection syndrome: Comparison of clinico-radiological features in adults and children with review of literature.

Hypo-pituitarism results from impaired production of one or more of anterior pituitary trophic hormones. A rare cause of hypo-pituitarism is pituitary stalk transection syndrome. The MRI features of this condition in children and its association with hormonal deficiencies have been reported earlier. Reports on adults with this disorder are scarce, with only one small case series published in the recent literature. We studied the hormonal deficiency pattern and MRI findings of 12 patients with pituitary stalk transection syndrome who presented to our department between 2004 and 2011. Six patients were children and six were adults (≥18 years). This article compares the adult clinico-radiological phenotype of pituitary transection syndrome with the pediatric group of patients with same condition.