Familial ROBO1 deletion associated with ectopic posterior pituitary, duplication of the pituitary stalk and anterior pituitary hypoplasia

2019 ◽  
Vol 32 (1) ◽  
pp. 95-99
Author(s):  
Marcello Scala ◽  
Andrea Accogli ◽  
Anna Maria Elsa Allegri ◽  
Elisa Tassano ◽  
Mariasavina Severino ◽  
...  
Keyword(s):  
Anterior Pituitary ◽  
Pituitary Stalk ◽  
Comparative Genomic ◽  
Posterior Pituitary ◽  
Loss Of Function ◽  
Human Pituitary ◽  
Developmental Abnormalities ◽  
Pituitary Development ◽  
Pituitary Hypoplasia ◽  
Ectopic Posterior Pituitary

Abstract Background The genetic causes of abnormal pituitary development have been extensively studied in the last few years. ROBO1 is involved in neurogenesis and axon guidance. Loss-of-function variants in ROBO1 have been associated with pituitary stalk interruption syndrome (PSIS), suggesting that its haploinsufficiency could impair the guidance of hypothalamic axons to the pituitary gland leading to developmental abnormalities. Case presentation We report a 4.5-year-old girl with anterior pituitary hypoplasia and pituitary stalk duplication in the ventral-dorsal direction. Her father had a similar pituitary phenotype, characterized by anterior pituitary hypoplasia combined with ectopic posterior pituitary. Comparative genomic hybridization (CGH) microarray analysis identified a 343.7 kb deletion of 3p12.3 encompassing ROBO1 in both individuals. Conclusions We report the first familial ROBO1 deletion in two individuals with peculiar pituitary anomalies, including the rare pituitary stalk duplication in the ventral-dorsal direction. These findings widen the spectrum of the phenotypes associated with ROBO1 haploinsufficiency and support its role in human pituitary development.

scholarly journals Pituitary Hypoplasia Is the Best MRI Predictor of the Severity and Type of Growth Hormone Deficiency in Children With Congenital Growth Hormone Deficiency

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A683-A683
Author(s):  
Himanshu Sharma ◽  
Anshul Kumar ◽  
Naincy Purwar ◽  
Nitish Mathur ◽  
Balram Sharma ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Pituitary Stalk ◽  
Hormone Deficiency ◽  
Common Finding ◽  
Pituitary Hormone ◽  
Posterior Pituitary ◽  
Mri Findings ◽  
Pituitary Hypoplasia ◽  
Ectopic Posterior Pituitary

Abstract Background and Objectives: Congenital idiopathic growth hormone deficiency(GHD) is associated with various MRI abnormalities, including both sellar anomalies such as pituitary hypoplasia, ectopic pituitary, empty sella and abnormalities of the pituitary stalk and extrasellar abnormalities such as Arnold Chiari malformation, corpus callosum agenesis, arachnoid cyst, septum pellucidum agenesis, enlarged ventricles, vermis dysplasia, and sphenoid cyst. However, it remains contentious whether MRI brain findings could provide an additional avenue for precisely predicting the differentiation of GHD based on severity(severe or partial) and type(isolated GHD or multiple pituitary hormone deficiency MPHD). This study aimed to ascertain the abnormality that is the best predictor of severe GHD and type of GHD amongst the different MRI findings. Methods: This was an analytical cross-sectional study conducted from 2018-2020. During the study period, we included a total of 100 subjects diagnosed to have idiopathic GHD after the exclusion of syndromic causes, system illness, presence of pituitary mass, and those with h/o cranial irradiation. Patients were divided into severe GHD and partial GHD based on peak stimulated GH of <5 ng/dl and ≥ 5 ng/dl respectively and into groups based on isolated GHD and MPHD. Patients were further divided into groups based on the presence of pituitary hypoplasia,extrasellar brain abnormalities (EBA), and presence of ectopic posterior pituitary and/or pituitary stalk abnormalities(EPP/PSA), respectively. Analyses were performed using SPSS version 24.0 software. Results: Amongst 100 subjects with idiopathic congenital GHD, 66 (66%) subjects had Isolated GHD while the remaining 34 (34%) had MPHD. 71 had severe GHD, and 29 had partial GHD. Amongst the MRI findings, pituitary hypoplasia was the most common finding observed in 53% of patients, while 23(23%) had EBA, and 25(25%) had EPP/PSA. Pituitary hypoplasia was observed to be the best predictor of severity of GHD with an odds ratio(OR) of 10.8 (95% CI 3.38-29.6) followed by ectopic posterior pituitary /pituitary stalk abnormalities (OR =2.8, 95% CI 1.5-9.5) while the presence of extrasellar abnormalities was the weakest predictor (OR =1.8, 95% CI 1.05-3.2). Pituitary hypoplasia was the only finding to significantly predict MPHD (OR=9.2). On ROC analysis, a Pituitary height SDS of -2.03 had a 73.2 % sensitivity and specificity of 79.3%(AUC =0.787,95% CI 0.7-0.873) for severe GHD and a sensitivity of 88.2 % and specificity of 66.7% (AUC =0.745, 95% CI 0.68-0.877) for MPHD. Conclusion: We observed Pituitary hypoplasia to be not only the most frequent MRI abnormality but also the best predictor of severe GHD and MPHD amongst various sellar and extrasellar abnormalities.

Ectopic posterior pituitary tissue and paracentric inversion of the short arm of chromosome 1 in twins

1995 ◽  
Vol 133 (1) ◽  
pp. 87-92 ◽  
Author(s):  
Selma F Siegel ◽  
Mamdouha Ahdab-Barmada ◽  
Silva Arslanian ◽  
Thomas P Foley
Keyword(s):  
Pituitary Gland ◽  
Causal Relationship ◽  
Median Eminence ◽  
Anterior Pituitary ◽  
Paracentric Inversion ◽  
Chromosome 1 ◽  
Pituitary Stalk ◽  
Posterior Pituitary ◽  
Pituitary Tissue ◽  
Ectopic Posterior Pituitary

Siegel SF, Ahdab-Barmada M, Arslanian S, Foley Jr TP. Ectopic posterior pituitary tissue and paracentric inversion of the short arm of chromosome 1 in twins. Eur J Endocrinol 1995;133:87–92. ISSN 0804–4643 Twin boys with hypopituitarism, hypoplasia of the anterior pituitary gland, ectopic posterior pituitary tissue and paracentric inversion of the short arm of chromosome 1 are described. The smooth appearance at the base of the median eminence and the absence of a pituitary stalk at autopsy in these boys implies that the hypopituitarism resulted from a developmental aberration. It remains to be determined if there is a causal relationship between the chromosome 1 anomaly and hypopituitarism. Selma F Siegel, Division of Endocrinology, Children's Hospital of Pittsburgh, 3705 Fifth Avenue, Pittsburgh, PA, 15213, USA

Extra pituitary midline structural abnormalities associated with ectopic posterior pituitary detected on a new rapid MR protocol (FAST1.2)

2021 ◽  
Author(s):  
Arthur Lyra ◽  
Daniel de Faria Guimarães ◽  
Altino Sá Meira ◽  
Arthur Castello Berchielli Nunes ◽  
Guilherme Vieira Peixoto ◽  
...  
Keyword(s):  
Sella Turcica ◽  
Pituitary Stalk ◽  
Control Group ◽  
Hypothalamic Hamartoma ◽  
Pars Intermedia ◽  
Posterior Pituitary ◽  
Pineal Cyst ◽  
Imaging Results ◽  
Structural Abnormalities ◽  
Ectopic Posterior Pituitary

Abstract Background Ectopic posterior pituitary (EPP) is a malformation of the hypothalamic-pituitary region. Our goal was to describe midline structural brain abnormalities in patients with EPP using a dedicated protocol (FAST1.2 protocol) of magnetic resonance imaging (MRI) to evaluate the hypothalamus and pituitary gland, highlighting their clinical-laboratory correlations. Methods A cross-sectional study of patients diagnosed with EPP, and a control group. All individuals were submitted to a dedicated MRI protocol called FAST1.2, which combines the FAST1 protocol developed by our group with 3D T2DRIVE imaging. Results We evaluated 36 individuals with EPP and 78 individuals as a control group. One patient had two posterior pituitary lobes, one inside the sella turcica and the other along the pituitary stalk; in five patients, the EPP was along the pituitary stalk; in 28 the EPP was at the infundibular recess of the third ventricle, and in two the EPP was hypothalamic. In the EPP group, eleven individuals had interhypothalamic adhesion (IHA), three septo-optic dysplasia, one a cerebellar malformation, and one a pineal cyst. We did not observe a higher frequency of severe hormonal deficiency or developmental delay in patients with IHA. In the control group, eleven patients had a pineal cyst, three pars intermedia cysts, one hydrocephalus, and one hypothalamic hamartoma. Conclusion FAST1.2 acquisition allows confident recognition of regional anatomy and recognition of midline structural abnormalities on T2DRIVE, particularly including the pituitary stalk and IHA, thereby making MRI acquisition faster with no need for intravenous contrast administration. We suggest that IHA could be associated with defects in neuronal migration, as might occur in patients with EPP.

Suckling-Induced Rise in Prolactin: Mediation by Prolactin-Releasing Factor From Posterior Pituitary

Physiology ◽  
1988 ◽  
Vol 3 (4) ◽  
pp. 172-175
Author(s):  
N Ben-Jonathan ◽  
JF Hyde ◽  
I Murai
Keyword(s):  
Anterior Pituitary ◽  
Pituitary Stalk ◽  
Pituitary Hormone ◽  
Posterior Pituitary ◽  
Small Peptide ◽  
Anterior Pituitary Hormone

The suckling-induced rise in prolactin, an anterior pituitary hormone that is essential for the maintenance of lactation, is mediated by the posterior pituitary. The posterior pituitary contains prolactin-releasing factor (PRF), a small peptide that is distinct from known prolactin secretagogues. The hypothalamus, the site of all known releasing hormones, has only little PRF activity. Pituitary stalk secretion abolishes the PRF activity in the posterior pituitary, indicating that it originates in the hypothalamus, perhaps as a biologically inactive precursor. The chemical identity of PRF is unknown but it appears to play an important role during lactation and might also be involved in the pathology of hyperprolactinea.

scholarly journals Diagnóstico tardío de síndrome de interrupción del tallo hipofisario

2017 ◽  
Vol 4 (3) ◽  
pp. 44-46
Author(s):  
Vanessa Garzón Graciano ◽  
Santiago González Narvaez ◽  
Jhon Alexander Alzate Piedrahita ◽  
Víctor Hugo Ruiz Granada ◽  
Santiago Vallejo González
Keyword(s):  
Anterior Pituitary ◽  
Clinical Presentation ◽  
Delayed Diagnosis ◽  
Pituitary Hormones ◽  
Pituitary Stalk ◽  
Neurologic Involvement ◽  
Pituitary Hypoplasia ◽  
Laboratory Examinations ◽  
Development Laboratory ◽  
Leg Fracture

El síndrome de interrupción del tallo hipofisario (PSIS, por sus siglas en inglés) es una anomalía congénita de probable origen genético causante de hipopituitarismo, que se caracteriza por hipoplasia de la adenohipófisis, neurohipófisis ectópica e interrupción del tallo hipofisario. Suele presentarse con baja estatura y deficiencia adenohipofisaria. El retraso en el diagnóstico se relaciona con alta morbimortalidad. Se reporta el caso de un hombre de 39 años con fractura de cadera por fragilidad y posterior compromiso neurológico secundario a hiponatremia severa, hipoglucemia e hipotensión arterial. Presentaba hábito eunucoide y ausencia de caracteres sexuales secundarios, con genitales infantiles. Los paraclínicos mostraron compromiso de todas las hormonas adenohipofisarias, sin afección neurohipofisaria. Una resonancia magnética nuclear mostró hallazgos consistentes con PSIS.   Abstract The pituitary stalk interruption syndrome (PSIS) is a congenital defect with a possible genetic origin which causes hypopituitarism. It consists of anterior pituitary hypoplasia, ectopic posterior pituitary and interruption of the pituitary stalk. Its clinical presentation consists mainly in short stature and anterior pituitary hormonal deficiencies. The delayed diagnosis may cause morbidity and mortality. We report the case of a 39 year old male who presented with a frailty leg fracture and neurologic involvement due to severe hyponatremia, hypoglycemia and hypotension. He lacked secondary sexual development. Laboratory examinations showed an inadequate secretion of all anterior pituitary hormones without diabetes insipidus. A magnetic resonance image showed findings consistent with PSIS.  

scholarly journals Pituitary stalk interruption syndrome is characterized by genetic heterogeneity

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0242358
Author(s):  
Raja Brauner ◽  
Joelle Bignon-Topalovic ◽  
Anu Bashamboo ◽  
Ken McElreavey
Keyword(s):  
Genetic Heterogeneity ◽  
Hypogonadotropic Hypogonadism ◽  
Gene Mutations ◽  
Pituitary Stalk ◽  
Specific Gene ◽  
Genetic Syndromes ◽  
Pituitary Development ◽  
Pediatric Endocrinologist ◽  
Novel Variants ◽  
Pituitary Hypoplasia

Pituitary stalk interruption syndrome is a rare disorder characterized by an absent or ectopic posterior pituitary, interrupted pituitary stalk and anterior pituitary hypoplasia, as well as in some cases, a range of heterogeneous somatic anomalies. A genetic cause is identified in only around 5% of all cases. Here, we define the genetic variants associated with PSIS followed by the same pediatric endocrinologist. Exome sequencing was performed in 52 (33 boys and 19 girls), including 2 familial cases single center pediatric cases, among them associated 36 (69.2%) had associated symptoms or syndromes. We identified rare and novel variants in genes (37 families with 39 individuals) known to be involved in one or more of the following—midline development and/or pituitary development or function (BMP4, CDON, GLI2, GLI3, HESX1, KIAA0556, LHX9, NKX2-1, PROP1, PTCH1, SHH, TBX19, TGIF1), syndromic and non-syndromic forms of hypogonadotropic hypogonadism (CCDC141, CHD7, FANCA, FANCC, FANCD2, FANCE, FANCG, IL17RD, KISS1R, NSMF, PMM2, SEMA3E, WDR11), syndromic forms of short stature (FGFR3, NBAS, PRMT7, RAF1, SLX4, SMARCA2, SOX11), cerebellum atrophy with optic anomalies (DNMT1, NBAS), axonal migration (ROBO1, SLIT2), and agenesis of the corpus callosum (ARID1B, CC2D2A, CEP120, CSPP1, DHCR7, INPP5E, VPS13B, ZNF423). Pituitary stalk interruption syndrome is characterized by a complex genetic heterogeneity, that reflects a complex phenotypic heterogeneity. Seizures, intellectual disability, micropenis or cryptorchidism, seen at presentation are usually considered as secondary to the pituitary deficiencies. However, this study shows that they are due to specific gene mutations. PSIS should therefore be considered as part of the phenotypic spectrum of other known genetic syndromes rather than as specific clinical entity.

scholarly journals ACQUIRED ECTOPIC POSTERIOR PITUITARY BRIGHT SPOT DUE TO VASCULOTOXIC SNAKEBITE

2020 ◽  
Vol 6 (5) ◽  
pp. e207-e211
Author(s):  
Liza Das ◽  
Anil Bhansali ◽  
Chirag Kamal Ahuja ◽  
Márta Korbonits ◽  
Pinaki Dutta
Keyword(s):  
Literature Review ◽  
Anterior Pituitary ◽  
Young Female ◽  
Bright Spot ◽  
Delayed Presentation ◽  
Posterior Pituitary ◽  
Secondary Amenorrhea ◽  
Male Predominance ◽  
Normal Stature ◽  
Ectopic Posterior Pituitary

Objective: Vasculotoxic envenomation is an uncommon cause of hypopituitarism. Most described cases have varying extent of anterior pituitary dysfunction, but posterior pituitary involvement is extremely rare. Methods: Clinical, biochemical, and radiologic evaluation of a young female who presented with secondary amenorrhea was performed. A brief literature review of envenomation-induced hypopituitarism is included. Results: A 26-year-old female presented with secondary amenorrhea since the age of 20 years. She had normal stature. Her past medical history was significant for a vasculotoxic snakebite 12 years back requiring hemodialysis, but no hormonal testing was done at that time. Current evaluation showed anterior hypopituitarism. An insulin-induced hypoglycemia test confirmed deficiencies of cortisol and growth hormone axes (peak values 348 nmol/L and 0.03 ng/mL). There was no diabetes insipidus. Magnetic resonance imaging revealed a hypoplastic anterior pituitary with an ectopic posterior pituitary. In view of normal stature and secondary amenorrhea, a diagnosis of envenomation-induced hypopituitarism with ectopic posterior pituitary (EPP) was made. A brief literature review of envenomation-induced hypopituitarism showed both acute and delayed presentation, male predominance, and variable lag period (weeks to years). Nearly half of all patients were asymptomatic. The most common axis involved in acute presentation was the cortisol axis, whereas the thyroid and gonadotroph axes were commonly involved in delayed hypopituitarism. Conclusion: Vasculotoxic envenomation is a rare cause of acquired hypopituitarism. EPP in the index case was probably due to the “axonal dieback” phenomenon and subsequent regeneration of the axons at a more caudal site. This case, being the first instance of acquired EPP following envenomation, expands the spectrum of envenomation-induced hypopituitarism.

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