scholarly journals Congenital Hypopituitarism During the Neonatal Period: Epidemiology, Pathogenesis, Therapeutic Options, and Outcome

2021 ◽  
Vol 8 ◽  
Author(s):  
Laura Bosch i Ara ◽  
Harshini Katugampola ◽  
Mehul T. Dattani
Keyword(s):  
Pituitary Gland ◽  
Developmental Disorders ◽  
Neonatal Period ◽  
Phenotypic Variability ◽  
Hormone Replacement ◽  
Clinical Manifestations ◽  
Pituitary Hormone ◽  
Mri Findings ◽  
Congenital Hypopituitarism ◽  
Stimulating Hormone

Introduction:Congenital hypopituitarism (CH) is characterized by a deficiency of one or more pituitary hormones. The pituitary gland is a central regulator of growth, metabolism, and reproduction. The anterior pituitary produces and secretes growth hormone (GH), adrenocorticotropic hormone, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, and prolactin. The posterior pituitary hormone secretes antidiuretic hormone and oxytocin.Epidemiology:The incidence is 1 in 4,000–1 in 10,000. The majority of CH cases are sporadic; however, a small number of familial cases have been identified. In the latter, a molecular basis has frequently been identified. Between 80–90% of CH cases remain unsolved in terms of molecular genetics.Pathogenesis:Several transcription factors and signaling molecules are involved in the development of the pituitary gland. Mutations in any of these genes may result in CH includingHESX1, PROP1, POU1F1, LHX3, LHX4, SOX2, SOX3, OTX2, PAX6, FGFR1, GLI2, andFGF8. Over the last 5 years, several novel genes have been identified in association with CH, but it is likely that many genes remain to be identified, as the majority of patients with CH do not have an identified mutation.Clinical manifestations:Genotype-phenotype correlations are difficult to establish. There is a high phenotypic variability associated with different genetic mutations. The clinical spectrum includes severe midline developmental disorders, hypopituitarism (in isolation or combined with other congenital abnormalities), and isolated hormone deficiencies.Diagnosis and treatment:Key investigations include MRI and baseline and dynamic pituitary function tests. However, dynamic tests of GH secretion cannot be performed in the neonatal period, and a diagnosis of GH deficiency may be based on auxology, MRI findings, and low growth factor concentrations. Once a hormone deficit is confirmed, hormone replacement should be started. If onset is acute with hypoglycaemia, cortisol deficiency should be excluded, and if identified this should be rapidly treated, as should TSH deficiency. This review aims to give an overview of CH including management of this complex condition.

scholarly journals SAT-241 Pituitary Stalk Interruption Syndrome Presenting as Neonatal Hypotonia

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Nordie Anne Bilbao
Keyword(s):  
Pituitary Gland ◽  
Neonatal Period ◽  
Hormone Replacement ◽  
Brain Mri ◽  
Rare Condition ◽  
Pituitary Stalk ◽  
Pituitary Hormone ◽  
Thyroid Function Tests ◽  
Acth Stimulation ◽  
Central Hypothyroidism

Abstract Pituitary stalk interruption syndrome (PSIS) is a rare condition that include congenital anatomic abnormalities of the pituitary gland and hypopituitarism. There is a wide variety of clinical presentation, with the age at presentation encompassing from neonatal period to adulthood and including one or more pituitary hormone deficiencies. In recent literature there is increasing recognition of PSIS presenting in the neonatal period, mostly involving hypoglycemia. Our patient is a full-term male infant who presented in the newborn period with hypotonia and hypothermia. He also had hypoglycemia, which was initially thought to be associated to hyperinsulinism in the context of gestational diabetes. Micropenis was noted on physical exam. As part of the study for hypotonia, serial thyroid function tests were obtained revealing central hypothyroidism. A low dose ACTH stimulation test was performed which revealed adrenal insufficiency. The patient was started on cortisol and thyroid hormone replacement. Brain MRI showed an ectopic neurohypophysis located along the floor of the hypothalamus, a small anterior pituitary gland, and a partially absent infundibulum, findings consistent with pituitary stalk interruption syndrome. The patient received testosterone injections for micropenis and is being followed for development of other pituitary hormone deficiencies. PSIS is a rare congenital condition that is increasingly recognized in neonates manifesting with signs of hypopituitarism.

scholarly journals Specific language impairment: linguistic and neurobiological aspects

2006 ◽  
Vol 64 (2a) ◽  
pp. 173-180 ◽  
Author(s):  
Simone Rocha de Vasconcelos Hage ◽  
Fernando Cendes ◽  
Maria Augusta Montenegro ◽  
Dagma V. Abramides ◽  
Catarina A. Guimarães ◽  
...  
Keyword(s):  
Clinical Manifestation ◽  
Language Impairment ◽  
Specific Language Impairment ◽  
Pervasive Developmental Disorders ◽  
Developmental Disorders ◽  
Standardized Test ◽  
Clinical Manifestations ◽  
Mri Findings ◽  
Specific Language ◽  
Cortical Involvement

Specific language impairment (SLI) occurs when children present language maturation, at least 12 months behind their chronological age in the absence of sensory or intellectual deficits, pervasive developmental disorders, evident cerebral damage, and adequate social and emotional conditions. The aim of this study was to classify a group of children according to the subtypes of SLI and to correlate clinical manifestations with cortical abnormalities. Seventeen children with SLI were evaluated. Language assessment was based on standardized test (Peabody) and a non-standardized protocol, which included phonological, syntactical, semantical, pragmatical and lexical aspects of language. All children, except one, had abnormal MRI. Thirteen children presented perisylvian polymicrogyria. The MRI findings in the remaining three patients were: right frontal polymicrogyria, bilateral fronto-parietal atrophy, and hypogenesis of corpus callosum with Chiari I. The data show that patients with posterior cortical involvement tended to present milder form of SLI (no sign of articulatory or bucofacial praxis disturbance), while diffuse polymicrogyric perisylvian cortex usually was seen in patients who presented severe clinical manifestation, mainly phonological-syntactic deficit. In conclusion, SLI may be associated with perisylvian polymicrogyria and clinical manifestation may vary according to the extent of cortical anomaly.

scholarly journals MOLECULAR GENETIC CHARACTERISTICS CHILDREN WITH GROWTHHORMONE DEFICIENCY

2017 ◽  
Vol 9 (4) ◽  
pp. 12-16
Author(s):  
O S Berseneva ◽  
A S Glotov ◽  
O S Glotov ◽  
E A Serebryakova ◽  
T E Ivashenko ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Genetic Studies ◽  
Genetic Characteristics ◽  
Therapeutic Algorithms ◽  
Congenital Hypopituitarism

Clinical manifestations of heterogeneity of growth hormone deficiency when definitive results of hormonal stimulus test determines the need to search for molecular genetic markers of the disease to form personalized therapeutic algorithms. Molecular genetic analysis in patients with congenital hypopituitarism was carried out by new-generation sequencing (NGS) with "Amplisek" technology. All patients with congenital hypopituitarism, who are in a special registry of Saint Petersburg, were included in this study. differences in the frequency of detection of mutations in patients with multiple anterior pituitary hormone deficiency and in patients with isolated growth hormone deficiency were found. The mutation frequency of diagnosis in genes responsible for congenital hypopituitarism in patients of St. Petersburg were studied.Mutations in genes associated with congenital hypopituitarism were identified in 16.3% of patients with pituitary dwarfism (16 of 98). The most commonly diagnosed mutations are changes in gene PROP1. In carrying out the molecular genetic studies of patients with congenital hypopituitarism is necessary to consider the likelihood of the presence of these rare pathologies such as loss of genes GHSR, ARNT2, BTK. Currently conducting molecular genetic studies in patients with congenital hypopituitarism further predicts development of the disease and, if necessary, adjust the ongoing replacement therapy.

scholarly journals SAT-067 Maternal Transmission of Pituitary Stalk Interruption Syndrome(PSIS)

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Snigdha Reddy Likki ◽  
Holley F Allen ◽  
Chelsea Gordner
Keyword(s):  
Pituitary Gland ◽  
Adrenal Insufficiency ◽  
Anterior Pituitary ◽  
Hormone Replacement ◽  
Growth Failure ◽  
Pituitary Stalk ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Z Score ◽  
Central Hypothyroidism

Abstract BACKGROUND: Pituitary stalk interruption syndrome (PSIS) is a rare entity characterized by thin or absent pituitary stalk, hypoplastic/aplastic anterior pituitary and ectopic posterior pituitary (EPP) on magnetic resonance imaging (MRI). PSIS can be associated with variable degrees of pituitary insufficiency 1. Most cases of combined pituitary hormone deficiency are sporadic, however in familial cases, there can be AD or AR inheritance with more than 30 genes identified in association with combined pituitary hormone deficiency (CPHD). We describe how diagnosis of 2 children with PSIS led to the discovery of the condition in their mother. Clinical Case: Child 1 presented at age 3yrs with growth failure in 2003 with ht z score -4.24 SD. Subsequent work up revealed low IGF-1 (< 25 ng /mL) and MRI showed EPP, small anterior pituitary gland and absent pituitary stalk. No GH stim test was performed. He was started on GH supplementation and later was diagnosed with central hypothyroidism, central adrenal insufficiency and hypogonadotropic hypogonadism and is doing well on multiple hormone replacement at age 19 yrs. Child 2, a half-brother to child 1 (same mother), presented at age 1yr with growth failure in 2017 with ht z score -2.06. GH stimulation test with glucagon was abnormal and resulted in a very low GH response (peak GH 0.52 ng/mL). MRI showed EPP with small anterior pituitary gland and interruption of the stalk. Later he was found to have central hypothyroidism and mild central adrenal insufficiency. He is receiving standard hormone replacement at 3 yrs of age. Mother of above 2 patients presented 6 mos postpartum in 2017 after her 7th and last pregnancy with fatigue and amenorrhea. Laboratory evaluation revealed central hypothyroidism (FT4 0.76 ng/dL) and she was prescribed levothyroxine followed by resumption of her menses. She was unable to breastfeed her children due to lack of supply. There were no concerns for DI, amenorrhea or infertility. She was referred to Endocrinology in 2019 for persistent fatigue with a question of GH deficiency. IGF-1 level was normal 114 ng/mL(z score -0.39) and GH stimulation test (clonidine + glucagon) was abnormal with peak GH 1.85 ng/ml. MRI showed EPP with hypoplastic pituitary stalk. Genetic testing was done for CPHD Sequencing Panel at Prevention Genetics which includes GL12, HESX1, LHX3, LHX4, OTX2, POU1F1, PROP1F1, PROP1, SOX2, SOX3 genes and results were negative. She has 4 other children (21, 12, 11, 10yrs) who are currently being investigated for hormone deficiencies. One child died at 3 months of age due to SIDS. Conclusion: We present 3 family members with PSIS. This family highlights the variable clinical phenotype of PSIS and importance of careful family history when evaluating children with congenital pituitary abnormalities and supports the need for more extensive gene panels for evaluation of CPHD. Reference:. Acta Endocrinologica, 2017. 13(1):96–105

scholarly journals Functional Restoration of Pituitary after Pituitary Allotransplantation into Hypophysectomized Rats

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 267
Author(s):  
Jai Ho Choi ◽  
Jung Eun Lee ◽  
Hong-Lim Kim ◽  
Seung Hyun Ko ◽  
Se Hoon Kim ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Weight Change ◽  
Morphological Changes ◽  
Hormone Replacement ◽  
Functional Restoration ◽  
Pituitary Hormone ◽  
Post Transplantation ◽  
Electron Microscopic ◽  
Rapid Weight Gain ◽  
Hypophysectomized Rats

Long-term hormone replacement therapy due to panhypopituitarism can lead to serious complications and thus, pituitary transplantation is considered a more desirable. We investigated functional restoration after allotransplatation of the pituitary gland. We transplanted extracted pituitary gland into the omentum of an hypophysectomized rat. Two experiments were performed: (1) to confirm the hypophysectomy was successful and (2) to assess functional restoration after pituitary transplantation. Pituitary hormone level and weight change were consecutively assessed. Electron microscopic (EM) examinations were performed to identify morphological changes at 3 days after transplantation. We confirmed that pituitary gland was properly extracted from 6 rats after sacrifice. The findings showed (1) a weight loss of more than 3% or (2) a weight change of less than 2% along with a decreased growth hormone (GH) level by more than 80% at 2 weeks post-hypophysectomy. A further four rats underwent pituitary transplantation after hypophysectomy and were compared with the previously hypophysectomized rats. All showed rapid weight gain during the two weeks after transplantation. The thyroid-stimulating hormone, prolactin, and GH levels were restored at one week post-transplantation and maintained for 10 weeks. Hypophyseal tissue architecture was maintained at 3 days after transplantation, as indicated by EM. These data suggest that a transplanted pituitary gland can survive in the omentum with concomitant partial restoration of anterior pituitary hormones.

scholarly journals Disrupted Hypothalamo-Pituitary Axis in Association With Reduced SHH Underlies the Pathogenesis of NOTCH-Deficiency

2020 ◽  
Vol 105 (9) ◽  
pp. e3183-e3196
Author(s):  
Houda Hamdi-Rozé ◽  
Michelle Ware ◽  
Hélène Guyodo ◽  
Aurélie Rizzo ◽  
Leslie Ratié ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Notch Signaling ◽  
Molecular Mechanisms ◽  
Phenotypic Variability ◽  
Sella Turcica ◽  
Notch Signaling Pathway ◽  
Incomplete Penetrance ◽  
Chemical Inhibition ◽  
Congenital Hypopituitarism ◽  
The Relationship

Abstract Context In human, Sonic hedgehog (SHH) haploinsufficiency is the predominant cause of holoprosencephaly, a structural malformation of the forebrain midline characterized by phenotypic heterogeneity and incomplete penetrance. The NOTCH signaling pathway has recently been associated with holoprosencephaly in humans, but the precise mechanism involving NOTCH signaling during early brain development remains unknown. Objective The aim of this study was to evaluate the relationship between SHH and NOTCH signaling to determine the mechanism by which NOTCH dysfunction could cause midline malformations of the forebrain. Design In this study, we have used a chemical inhibition approach in the chick model and a genetic approach in the mouse model. We also reported results obtained from the clinical diagnosis of a cohort composed of 141 holoprosencephaly patients. Results We demonstrated that inhibition of NOTCH signaling in chick embryos as well as in mouse embryos induced a specific downregulation of SHH in the anterior hypothalamus. Our data in the mouse also revealed that the pituitary gland was the most sensitive tissue to Shh insufficiency and that haploinsufficiency of the SHH and NOTCH signaling pathways synergized to produce a malformed pituitary gland. Analysis of a large holoprosencephaly cohort revealed that some patients possessed multiple heterozygous mutations in several regulators of both pathways. Conclusions These results provided new insights into molecular mechanisms underlying the extreme phenotypic variability observed in human holoprosencephaly. They showed how haploinsufficiency of the SHH and NOTCH activity could contribute to specific congenital hypopituitarism that was associated with a sella turcica defect.

The Pituitary Gland: Embryology, Physiology, and Pathophysiology

2000 ◽  
Vol 19 (2) ◽  
pp. 9-17 ◽  
Author(s):  
Angela Dorton
Keyword(s):  
Pituitary Gland ◽  
Anterior Pituitary ◽  
Pituitary Hormones ◽  
Thyroid Stimulating Hormone ◽  
The Body ◽  
Pars Intermedia ◽  
Pituitary Hormone ◽  
Pars Tuberalis ◽  
Pars Distalis ◽  
Stimulating Hormone

The pituitary gland, the “master gland” of the body, is composed of endocrine cells, which secrete hormones essential for homeostasis. The gland consists of the adenohypophysis (anterior pituitary) and the neurohypophysis (posterior pituitary), two unique structures that differ anatomically and functionally.The neurohypophysis is innervated by nerve cells in the hypothalamus and forms the connection between it and the pituitary gland. The hypothalamus stimulates release and inhibition of pituitary hormones. The neurohypophysis secretes oxytocin and antidiuretic hormone.The adenohypophysis is composed of three structures: the pars distalis, the pars intermedia, and the pars tuberalis. The anterior pituitary (pars distalis) is responsible for the release of hormones that include growth hormone, prolactin, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, adrenocorticotropic hormone, and melanocyte-stimulating hormone.Disorders of the pituitary are predominately those of insufficient hormone release and may have profound effects on the neonate. The potential causes of and clinical symptomatology that may accompany pituitary hormone insufficiency in the neonatal period are explored.

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 X-linked congenital adrenal hypoplasia: a case presentation

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hong Ouyang ◽  
Bo Chen ◽  
Na Wu ◽  
Ling Li ◽  
Runyu Du ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Hormone Replacement ◽  
Slipped Capital Femoral Epiphysis ◽  
Clinical Manifestations ◽  
Addison’S Disease ◽  
Addison's Disease ◽  
Case Presentation ◽  
Early Symptoms ◽  
Congenital Adrenal Hypoplasia ◽  
Adrenal Hypoplasia

Abstract Background Most patients with congenital adrenal hypoplasia (AHC) develop symptoms during infantile and juvenile periods, with varying clinical manifestations. AHC is a disease that is easily misdiagnosed as Addison’s disease or congenital adrenal hyperplasia (CAH). There was also a significant time difference between the age at which patients developed symptoms and the age at which they were diagnosed with AHC. Most patients showed early symptoms during infantile and juvenile periods, but were diagnosed with AHC many years later. Case presentation We are currently reporting a male patient who developed systemic pigmentation at age 2 and was initially diagnosed with Addison’s disease. At 22 years of age, he experienced a slipped capital femoral epiphysis (SCFE), a disease mostly seen in adolescents aged 8–15 years, an important cause of which is endocrine disorder. Testes evaluated using color Doppler Ultrasonography suggested microcalcifications. Further genetic testing and auxiliary examinations revealed that the patient had hypogonadotropic hypogonadism (HH) and DAX-1 gene disorders, at which time he was diagnosed with AHC complicated by HH. He was given hormone replacement therapy, followed by regular outpatient review to adjust the medication. Conclusions The typical early symptoms of AHC are hyperpigmentation and ion disturbance during infantile and juvenile periods, while few patients with AHC develop puberty disorders as early symptoms. AHC is prone to being misdiagnosed as Addison’s disease, and then gradually develops the symptoms of HH in adolescence. The definitive diagnosis of AHC ultimately is based on the patient’s clinical presentation, laboratory results and genetic testing results.

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