scholarly journals DIAGNOSIS OF ENDOCRINE DISEASE: Pituitary stalk interruption syndrome: etiology and clinical manifestations

2019 ◽  
Vol 181 (5) ◽  
pp. R199-R209 ◽  
Author(s):  
Julia Vergier ◽  
Frederic Castinetti ◽  
Alexandru Saveanu ◽  
Nadine Girard ◽  
Thierry Brue ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Environmental Influence ◽  
Age At Onset ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Current Data ◽  
Pituitary Stalk ◽  
Pituitary Hormone ◽  
Developmental Defect ◽  
Posterior Lobe

Pituitary stalk interruption syndrome (PSIS) is a congenital pituitary anatomical defect. This syndrome is an antenatal developmental defect belonging to the holoprosencephaly phenotype spectrum. It is heterogeneous regarding clinical, biological and radiological presentation and is characterized by the following triad: thin (<1 mm) or interrupted pituitary stalk connecting the hypothalamus to the pituitary gland, no eutopic posterior lobe, and hypoplasia or aplasia of the anterior lobe. This review reports current knowledge about the composite pathogenesis, for which underlying mechanisms remain unclear. Current data suggest genetic origins involving early developmental gene mutations with complex inheritance patterns and environmental influence, placing PSIS at the crossroads between Mendelian and multifactorial diseases. The phenotype associated with PSIS is highly heterogeneous with a high incidence of various combinations of hormonal deficiencies, sometimes associated with extra-pituitary birth defects. The age at onset is variable, but typical presentation is evolutive combined anterior pituitary hormone deficiencies at pediatric age, which progress even during adulthood to panhypopituitarism. Therefore, patients’ follow-up throughout life is essential for adequate management.

scholarly journals Pituitary Stalk Interruption Syndrome and Isolated Pituitary Hypoplasia May Be Caused by Mutations in Holoprosencephaly-Related Genes

2013 ◽  
Vol 98 (4) ◽  
pp. E779-E784 ◽  
Author(s):  
Christina Tatsi ◽  
Amalia Sertedaki ◽  
Antonis Voutetakis ◽  
Eleni Valavani ◽  
Maria-Alexandra Magiakou ◽  
...  
Keyword(s):  
Phenotypic Variability ◽  
Gene Mutations ◽  
Pituitary Stalk ◽  
Hormone Deficiency ◽  
Molecular Defect ◽  
Pituitary Hormone ◽  
Developmental Defect ◽  
Central Incisor ◽  
Related Gene ◽  
Pituitary Hypoplasia

Context: Holoprosencephaly (HPE) is a developmental defect characterized by wide phenotypic variability, ranging from minor midline malformations (eg, single central incisor) to severe deformities. In 10–15% of HPE patients, mutations in specific genes have been identified (eg, SHH, TGIF, SIX3). Pituitary stalk interruption syndrome (PSIS) constitutes a distinct abnormality of unknown pathogenesis, whereas isolated pituitary hypoplasia (IPH) has been linked to various developmental genes. Objective: Three of our patients with PSIS had a single central incisor, a malformation encountered in some HPE cases. Based on this observation, we initiated a search for mutations in HPE-associated genes in 30 patients with PSIS or IPH. Design and Participants: The entire coding region of the TGIF, SHH, and SIX3 genes was sequenced in patients with combined pituitary hormone deficiency associated with either PSIS or IPH and in healthy controls. Results: Two novel mutations in the HPE-related genes were detected (ie, c.799 C&gt;T, p.Q267X in the TGIF gene, and c.1279G&gt;A, p.G427R in the SHH gene) in 2 of our patients. The overall incidence of HPE-related gene mutations in our nonsyndromic and nonchromosomal patients was 6.6%. No molecular defect in the SIX3 gene was detected in our cohort. Conclusions: The data suggest that HPE-related gene mutations are implicated in the etiology of isolated pituitary defects (PSIS or IPH). Alternatively, PSIS or IPH may constitute mild forms of an expanded HPE spectrum.

scholarly journals Contrasting clinical manifestations of SDHB and VHL associated chromaffin tumours

2009 ◽  
Vol 16 (2) ◽  
pp. 515-525 ◽  
Author(s):  
Umasuthan Srirangalingam ◽  
Bernard Khoo ◽  
Lisa Walker ◽  
Fiona MacDonald ◽  
Robert H Skelly ◽  
...  
Keyword(s):  
Malignant Disease ◽  
Tumour Size ◽  
Age At Onset ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Catecholamine Secretion ◽  
Renal Cell Carcinomas ◽  
Von Hippel Lindau ◽  
Increased Risk ◽  
Multifocal Disease

Mutations in succinate dehydrogense-B (SDHB) and the von Hippel-Lindau (VHL) genes result in an increased risk of developing chromaffin tumours via a common aetiological pathway. The aim of the present retrospective study was to compare the clinical phenotypes of disease in subjects developing chromaffin tumours as a result of SDHB mutations or VHL disease. Thirty-one subjects with chromaffin tumours were assessed; 16 subjects had SDHB gene mutations and 15 subjects had a diagnosis of VHL. VHL-related tumours were predominantly adrenal phaeochromocytomas (22/26; 84.6%), while SDHB-related tumours were predominantly extra-adrenal paragangliomas (19/25; 76%). Median age at onset of the first chromaffin tumour was similar in the two cohorts. Tumour size was significantly larger in the SDHB cohort in comparison with the VHL cohort (P=0.002). Multifocal disease was present in 9/15 (60%) of the VHL cohort (bilateral phaeochromocytomas) and only 3/16 (19%) of the SDHB cohort, while metastatic disease was found in 5/16 (31%) of the SDHB cohort but not in the VHL cohort to date. The frequency of symptoms, hypertension and the magnitude of catecholamine secretion appeared to be greater in the SDHB cohort. Renal cell carcinomas were a feature in 5/15 (33%) of the VHL cohort and 1/16 (6%) of the SDHB cohort. These data indicate that SDHB-related tumours are predominantly extra-adrenal in location and associated with higher catecholamine secretion and more malignant disease, in subjects who appear more symptomatic. VHL-related tumours tend to be adrenal phaeochromocytomas, frequently bilateral and associated with a milder phenotype.

scholarly journals Causes and Follow-Up of Central Diabetes Insipidus in Children

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Wendong Liu ◽  
Jing Hou ◽  
Xiuqin Liu ◽  
Limin Wang ◽  
Guimei Li
Keyword(s):  
Diabetes Insipidus ◽  
Signal Intensity ◽  
Central Diabetes Insipidus ◽  
Pituitary Stalk ◽  
Control Group ◽  
Pituitary Hormone ◽  
Posterior Lobe ◽  
Healthy Children ◽  
Posterior Pituitary ◽  
Urine Testing

Objective. To identify the causes of central diabetes insipidus (CDI) by evaluating the values of magnetic resonance imaging (MRI) in the diagnosis of pediatric CDI, providing evidence for the clinical diagnosis and treatment of CDI. Methods. Seventy-nine patients with CDI (CDI group) hospitalized from July 2012 to March 2017 and 43 healthy children (control group) were enrolled in this study. All cases underwent MRI examination including T1-weighted three-dimensional magnetization-prepared rapid gradient-echo (T1WI-3D-MP RAGE) imaging sequences. The pituitary volume, the signal intensity of posterior pituitary, and the morphology of pituitary stalk were measured between two groups. The medical history, urine testing, imaging of hypothalamic-pituitary region, and hormone levels were also recorded. Results. Age and gender were matched between the CDI and control groups. The height and BMI in the CDI group were less and the urine volume in 24 h was higher than those in the control group. The signal intensity of the posterior pituitary was higher in the control group, whereas the pituitary volume was smaller in the CDI group. In the CDI group, 44 cases presented with morphological changes of the pituitary stalk. Clinical symptoms mainly included polydipsia, polyuria, short stature, and vomiting. All patients were confirmed by water deprivation vasopressin test. Forty-four CDI children were associated with hypopituitarism, including 33 cases of PSIS with multiple pituitary hormone deficiencies (MPHD) and 11 cases of growth hormone deficiency (IGHD). The pituitary volume in the cases of pituitary stalk interruption syndrome (PSIS) with MPHD was smaller than that in the IGHD patients. Conclusions. The signal intensity ratio of the posterior lobe, pituitary volume, and the morphology of pituitary stalk on T1WI-3D-MP RAGE image contribute to the diagnosis of CDI.

scholarly journals A case of pituitary stalk interruption syndrome diagnosed in a 2-year-old child masquerading as syndrome of inappropriate antidiuretic hormone secretion

2021 ◽  
Vol 7 (6) ◽  
pp. 312
Author(s):  
Ali Kumble ◽  
Abhishek K. Phadke ◽  
Sapheliya Nazar
Keyword(s):  
Anterior Pituitary ◽  
Wide Spectrum ◽  
Hormone Replacement ◽  
Hormone Secretion ◽  
Clinical Manifestations ◽  
Pituitary Stalk ◽  
Serum Cortisol Level ◽  
Delayed Puberty ◽  
Pituitary Hormone ◽  
Inappropriate Antidiuretic Hormone Secretion

<p class="abstract">Pituitary stalk interruption syndrome (PSIS) is included under the spectrum of midline abnormalities and is considered as a part of the holoprosencephaly (HPE) wide spectrum. Genetic basis has been identified in few familial cases. PSIS have anterior pituitary hormone deficiencies and a wide spectrum of clinical presentation. The typical clinical manifestations of PSIS are growth retardation, hypoglycemia and delayed puberty. We report a case of PSIS with hyponatremic seizures as initial presentation. Two-year-old girl with growth and development appropriate for age, presented with acute respiratory infection and generalized tonic clonic seizures.  There was history of similar illness two weeks prior and was treated for hyponatremia. Child had euvolemic hyponatremia and symptomatic hypoglycemia.  Serum cortisol level was observed to be low and thyroid function test was abnormal. MRI brain showed hypoplastic anterior pituitary and ectopic posterior pituitary (hallmark of PSIS) and absent septum pellucidum. Child was treated with   hormone replacement therapy with hydrocortisone and thyroxine. Child improved and is on follow up. Clinical suspicion, early diagnosis and treatment prevent worsening of endocrine impairment, permanent short stature and associated morbidities with PSIS.</p>

scholarly journals CDON gene contributes to pituitary stalk interruption syndrome associated with unilateral facial and abducens nerve palsy

2021 ◽  
Author(s):  
Monika Obara-Moszyńska ◽  
Bartłomiej Budny ◽  
Małgorzata Kałużna ◽  
Katarzyna Zawadzka ◽  
Aleksander Jamsheer ◽  
...  
Keyword(s):  
Anterior Pituitary ◽  
Nerve Palsy ◽  
Abducens Nerve ◽  
Abducens Nerve Palsy ◽  
Pituitary Stalk ◽  
Hormone Deficiency ◽  
Congenital Defects ◽  
Pituitary Hormone ◽  
Incomplete Penetrance ◽  
Posterior Lobe

AbstractThe relationship between congenital defects of the brain and facial anomalies was proven. The Hedgehog signaling pathway plays a fundamental role in normal craniofacial development in humans. Mutations in the sonic hedgehog (SHH) signaling gene CDON have been recently reported in patients with holoprosencephaly and with pituitary stalk interruption syndrome (PSIS). This study’s aim was an elucidation of an 18-year-old patient presenting PSIS, multiple pituitary hormone deficiency, and congenital unilateral facial and abducens nerve palsy. Additionally, bilateral sensorineural hearing loss, dominating at the right site, was diagnosed. From the second year of life, growth deceleration was observed, and from the age of eight, anterior pituitary hormone deficiencies were gradually confirmed and substituted. At the MRI, characteristic triad for PSIS (anterior pituitary hypoplasia, interrupted pituitary stalk and ectopic posterior lobe) was diagnosed. We performed a comprehensive genomic screening, including microarrays for structural rearrangements and whole-exome sequencing for a monogenic defect. A novel heterozygous missense variant in the CDON gene (c.1814G > T; p.Gly605Val) was identified. The variant was inherited from the mother, who, besides short stature, did not show any disease symptoms. The variant was absent in control databases and 100 healthy subjects originating from the same population. We report a novel variant in the CDON gene associated with PSIS and congenital cranial nerve palsy. The variant revealed autosomal dominant inheritance with incomplete penetrance in concordance with previous studies reporting CDON defects.

Modern methods of treating rosacea

2019 ◽  
Vol 1 (7) ◽  
pp. 65-71
Author(s):  
O. A. Egorova ◽  
K. A. Novikov
Keyword(s):  
Clinical Manifestations ◽  
Treatment Method ◽  
Current Data ◽  
Trigger Factors ◽  
Laser Technology ◽  
Individual Approach ◽  
Modern Methods ◽  
Methods Of Treatment ◽  
Choice Of Therapy

Presented current data on the etiology of rosacea, the main aspects of pathogenesis, clinical forms of the disease. Reflects trigger factors leading to rosacea, as well as complicating its course. Modern methods of treatment are described, including the use of new safe preparations of ivermectin and brimonidine, providing a good, lasting effect of clinical manifestations of rosacea. The role of laser technology, actively occupying a leading place in the choice of physiotherapeutic treatment method, is noted. The need for an individual approach in the choice of therapy for each patient with rosacea is emphasized.

Adult systemic lupus erythematosus in Egypt: The nation-wide spectrum of 3661 patients and world-wide standpoint

Lupus ◽  
2021 ◽  
pp. 096120332110142
Author(s):  
Tamer A Gheita ◽  
Rasha Abdel Noor ◽  
Esam Abualfadl ◽  
Osama S Abousehly ◽  
Iman I El-Gazzar ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Age Of Onset ◽  
Wide Spectrum ◽  
Age At Onset ◽  
Disease Onset ◽  
Clinical Manifestations ◽  
Population Based ◽  
Systemic Lupus ◽  
Cross Sectional

Objective The aim of this study was to present the epidemiology, clinical manifestations and treatment pattern of systemic lupus erythematosus (SLE) in Egyptian patients over the country and compare the findings to large cohorts worldwide. Objectives were extended to focus on the age at onset and gender driven influence on the disease characteristics. Patients and method This population-based, multicenter, cross-sectional study included 3661 adult SLE patients from Egyptian rheumatology departments across the nation. Demographic, clinical, and therapeutic data were assessed for all patients. Results The study included 3661 patients; 3296 females and 365 males (9.03:1) and the median age was 30 years (17–79 years), disease duration 4 years (0–75 years) while the median age at disease onset was 25 years (4–75 years). The overall estimated prevalence of adult SLE in Egypt was 6.1/100,000 population (1.2/100,000 males and 11.3/100,000 females).There were 316 (8.6%) juvenile-onset (Jo-SLE) and 3345 adult-onset (Ao-SLE). Age at onset was highest in South and lowest in Cairo (p < 0.0001). Conclusion SLE in Egypt had a wide variety of clinical and immunological manifestations, with some similarities with that in other nations and differences within the same country. The clinical characteristics, autoantibodies and comorbidities are comparable between Ao-SLE and Jo-SLE. The frequency of various clinical and immunological manifestations varied between gender. Additional studies are needed to determine the underlying factors contributing to gender and age of onset differences.

scholarly journals Pan-American Lancehead Pit-Vipers: Coagulotoxic Venom Effects and Antivenom Neutralisation of Bothrops asper and B. atrox Geographical Variants

Toxins ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 78
Author(s):  
Lachlan A. Bourke ◽  
Christina N. Zdenek ◽  
Edgar Neri-Castro ◽  
Melisa Bénard-Valle ◽  
Alejandro Alagón ◽  
...  
Keyword(s):  
Evolutionary Biology ◽  
Current Knowledge ◽  
Clinical Manifestations ◽  
In Vivo Studies ◽  
Factor X ◽  
Clotting Factors ◽  
Bothrops Asper ◽  
Species Specific

The toxin composition of snake venoms and, thus, their functional activity, can vary between and within species. Intraspecific venom variation across a species’ geographic range is a major concern for antivenom treatment of envenomations, particularly for countries like French Guiana that lack a locally produced antivenom. Bothrops asper and Bothrops atrox are the most medically significant species of snakes in Latin America, both producing a variety of clinical manifestations, including systemic bleeding. These pathophysiological actions are due to the activation by the venom of the blood clotting factors Factor X and prothrombin, thereby causing severe consumptive coagulopathy. Both species are extremely wide-ranging, and previous studies have shown their venoms to exhibit regional venom variation. In this study, we investigate the differential coagulotoxic effects on human plasma of six venoms (four B. asper and two B. atrox samples) from different geographic locations, spanning from Mexico to Peru. We assessed how the venom variation of these venom samples affects neutralisation by five regionally available antivenoms: Antivipmyn, Antivipmyn-Tri, PoliVal-ICP, Bothrofav, and Soro Antibotrópico (SAB). The results revealed both inter- and intraspecific variations in the clotting activity of the venoms. These variations in turn resulted in significant variation in antivenom efficacy against the coagulotoxic effects of these venoms. Due to variations in the venoms used in the antivenom production process, antivenoms differed in their species-specific or geographical neutralisation capacity. Some antivenoms (PoliVal-ICP, Bothrofav, and SAB) showed species-specific patterns of neutralisation, while another antivenom (Antivipmyn) showed geographic-specific patterns of neutralisation. This study adds to current knowledge of Bothrops venoms and also illustrates the importance of considering evolutionary biology when developing antivenoms. Therefore, these results have tangible, real-world implications by aiding evidence-based design of antivenoms for treatment of the envenomed patient. We stress that these in vitro studies must be backed by future in vivo studies and clinical trials before therapeutic guidelines are issued regarding specific antivenom use in a clinical setting.

scholarly journals Novel missense mutation of SASH1 in a Chinese family with dyschromatosis universalis hereditaria

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Lu Cao ◽  
Ruixue Zhang ◽  
Liang Yong ◽  
Shirui Chen ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Sequence Alignment ◽  
Multiple Sequence Alignment ◽  
Molecular Genetic ◽  
Family Members ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Mendelian Inheritance ◽  
Chinese Family ◽  
Multiple Sequence

Abstract Background Dyschromatosis universalis hereditaria (DUH) is a pigmentary dermatosis characterized by generalized mottled macules with hypopigmention and hyperpigmention. ABCB6 and SASH1 are recently reported pathogenic genes related to DUH, and the aim of this study was to identify the causative mutations in a Chinese family with DUH. Methods Sanger sequencing was performed to investigate the clinical manifestation and molecular genetic basis of these familial cases of DUH, bioinformatics tools and multiple sequence alignment were used to analyse the pathogenicity of mutations. Results A novel missense mutation, c.1529G>A, in the SASH1 gene was identified, and this mutation was not found in the National Center for Biotechnology Information Database of Short Genetic Variation, Online Mendelian Inheritance in Man, ClinVar, or 1000 Genomes Project databases. All in silico predictors suggested that the observed substitution mutation was deleterious. Furthermore, multiple sequence alignment of SASH1 revealed that the p.S510N mutation was highly conserved during evolution. In addition, we reviewed the previously reported DUH-related gene mutations in SASH1 and ABCB6. Conclusion Although the affected family members had identical mutations, differences in the clinical manifestations of these family members were observed, which reveals the complexity of the phenotype-influencing factors in DUH. Our findings reveal the mutation responsible for DUH in this family and broaden the mutational spectrum of the SASH1 gene.

scholarly journals Allelic Variants in Established Hypopituitarism Genes Expand Our Knowledge of the Phenotypic Spectrum

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1128
Author(s):  
Marilena Nakaguma ◽  
Nathalia Garcia Bianchi Pereira Ferreira ◽  
Anna Flavia Figueredo Benedetti ◽  
Mariana Cotarelli Madi ◽  
Juliana Moreira Silva ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Male Patient ◽  
Missense Variant ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Incomplete Penetrance ◽  
Growth Hormone Gene ◽  
Posterior Lobe ◽  
Allelic Variants ◽  
Phenotypic Spectrum

We report four allelic variants (three novel) in three genes previously established as causal for hypopituitarism or related disorders. A novel homozygous variant in the growth hormone gene, GH1 c.171delT (p.Phe 57Leufs*43), was found in a male patient with severe isolated growth hormone deficiency (IGHD) born to consanguineous parents. A hemizygous SOX3 allelic variant (p.Met304Ile) was found in a male patient with IGHD and hypoplastic anterior pituitary. YASARA, a tool to evaluate protein stability, suggests that p.Met304Ile destabilizes the SOX3 protein (ΔΔG = 2.49 kcal/mol). A rare, heterozygous missense variant in the TALE homeobox protein gene, TGIF1 (c.268C>T:p.Arg90Cys) was found in a patient with combined pituitary hormone deficiency (CPHD), diabetes insipidus, and syndromic features of holoprosencephaly (HPE). This variant was previously reported in a patient with severe holoprosencephaly and shown to affect TGIF1 function. A novel heterozygous TGIF1 variant (c.82T>C:p.Ser28Pro) was identified in a patient with CPHD, pituitary aplasia and ectopic posterior lobe. Both TGIF1 variants have an autosomal dominant pattern of inheritance with incomplete penetrance. In conclusion, we have found allelic variants in three genes in hypopituitarism patients. We discuss these variants and associated patient phenotypes in relation to previously reported variants in these genes, expanding our knowledge of the phenotypic spectrum in patient populations.

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