scholarly journals Three Japanese patients with congenital pituitary hormone deficiency and ophthalmological anomalies

2011 ◽  
Vol 3 (3) ◽  
pp. 20 ◽  
Author(s):  
Kuniko Takanashi ◽  
Yashuto Suzuki ◽  
Ayumu Noro ◽  
MInako Sugiyama ◽  
Masanori Nakanishi ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Growth Failure ◽  
Japanese Patients ◽  
Optic Nerve Hypoplasia ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Impaired Liver Function ◽  
Pituitary Hormone Deficiency ◽  
Impaired Liver ◽  
Congenital Hypopituitarism

The clinical phenotype of congenital pituitary hormone deficiency is variable and can be associated with a number of structural abnormalities of the central nervous system. We report three Japanese patients with congenital pituitary hormone deficiency and ophthalmological anomalies. Two of the patients initially showed strabismus and unilateral optic nerve hypoplasia. Thereafter, growth failure became evident, leading to the diagnosis of pituitary hormone deficiency. The other patient had severe congenital hypopituitarism with respiratory distress and hypoglycemia from the first day of life. In addition, he had prolonged jaundice and impaired liver function with bilateral optic nerve hypoplasia. Neuroimaging of the pituitary region in all three patients demonstrated a small anterior pituitary lobe and no pituitary stalk. Our findings indicate that clinical variability of congenital hypopituitarism must be considered. In a patient with ophthalmological symptoms, endocrine evaluation and neuroimaging of the CNS including the pituitary region should be considered.

High prevalence of pituitary hormone deficiency in both unilateral and bilateral optic nerve hypoplasia

2019 ◽  
Vol 108 (9) ◽  
pp. 1677-1685 ◽  
Author(s):  
Sara Dahl ◽  
Maria Kristoffersen Wiberg ◽  
Kristina Teär Fahnehjelm ◽  
Lars Sävendahl ◽  
Ronny Wickström
Keyword(s):  
Optic Nerve ◽  
Optic Nerve Hypoplasia ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Pituitary Hormone Deficiency ◽  
High Prevalence

scholarly journals Evolving pituitary hormone deficits in primarily isolated GHD: a review and experts’ consensus

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Gerhard Binder ◽  
Dirk Schnabel ◽  
Thomas Reinehr ◽  
Roland Pfäffle ◽  
Helmuth-Günther Dörr ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Current Knowledge ◽  
Serum Insulin ◽  
Growth Failure ◽  
Endocrine Function ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Hypothalamic Region ◽  
Pituitary Hormone Deficiency ◽  
Combined Pituitary Hormone Deficiency

Abstract Isolated growth hormone deficiency (GHD) is defined by growth failure in combination with retarded bone age, low serum insulin-like growth factor-1, and insufficient GH peaks in two independent GH stimulation tests. Congenital GHD can present at any age and can be associated with significant malformations of the pituitary-hypothalamic region or the midline of the brain. In rare instances, genetic analysis reveals germline mutations of transcription factors involved in embryogenesis of the pituitary gland and the hypothalamus. Acquired GHD is caused by radiation, inflammation, or tumor growth. In contrast to organic GHD, idiopathic forms are more frequent and remain unexplained. There is a risk of progression from isolated GHD to combined pituitary hormone deficiency (> 5% for the total group), which is clearly increased in children with organic GHD, especially with significant malformation of the pituitary gland. Therefore, it is prudent to exclude additional pituitary hormone deficiencies in the follow-up of children with isolated GHD by clinical and radiological observations and endocrine baseline tests. In contrast to primary disorders of endocrine glands, secondary deficiency is frequently milder in its clinical manifestation. The pituitary hormone deficiencies can develop over time from mild insufficiency to severe deficiency. This review summarizes the current knowledge on diagnostics and therapy of additional pituitary hormone deficits occurring during rhGH treatment in children initially diagnosed with isolated GHD. Although risk factors are known, there are no absolute criteria enabling exclusion of children without any risk of progress to combined pituitary hormone deficiency. Lifelong monitoring of the endocrine function of the pituitary gland is recommended in humans with organic GHD. This paper is the essence of a workshop of pediatric endocrinologists who screened the literature for evidence with respect to evolving pituitary deficits in initially isolated GHD, their diagnosis and treatment.

scholarly journals A novel OTX2 mutation in a patient with combined pituitary hormone deficiency, pituitary malformation, and an underdeveloped left optic nerve

2012 ◽  
Vol 167 (3) ◽  
pp. 441-452 ◽  
Author(s):  
Darya Gorbenko Del Blanco ◽  
Christopher J Romero ◽  
Daniel Diaczok ◽  
Laura C G de Graaff ◽  
Sally Radovick ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Mutation Screening ◽  
Genetic Alterations ◽  
Dominant Negative ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Pituitary Hormone Deficiency ◽  
Combined Pituitary Hormone Deficiency ◽  
Coding Regions ◽  
Dominant Negative Inhibitor

Orthodenticle homolog 2 (OTX2) is a homeobox family transcription factor required for brain and eye formation. Various genetic alterations in OTX2 have been described, mostly in patients with severe ocular malformations. In order to expand the knowledge of the spectrum of OTX2 mutation, we performed OTX2 mutation screening in 92 patients with combined pituitary hormone deficiency (CPHD). We directly sequenced the coding regions and exon–intron boundaries of OTX2 in 92 CPHD patients from the Dutch HYPOPIT study in whom mutations in the classical CPHD genes PROP1, POU1F1, HESX1, LHX3, and LHX4 had been ruled out. Among 92 CPHD patients, we identified a novel heterozygous missense mutation c.401C>G (p.Pro134Arg) in a patient with CPHD, pituitary malformation, and an underdeveloped left optic nerve. Binding of both the wild-type and mutant OTX2 proteins to bicoid binding sites was equivalent; however, the mutant OTX2 exhibited decreased transactivation. We describe a novel missense heterozygous OTX2 mutation that acts as a dominant negative inhibitor of target gene expression in a patient with CPHD, pituitary malformation, and optic nerve hypoplasia. We provide an overview of all OTX2 mutations described till date, which show that OTX2 is a promising candidate gene for genetic screening of patients with CPHD or isolated GH deficiency (IGHD). As the majority of the OTX2 mutations found in patients with CPHD, IGHD, or short stature have been found in exon 5, we recommend starting mutational screening in those patients in exon 5 of the gene.

scholarly journals Endocrine Status in Patients with Optic Nerve Hypoplasia: Relationship to Midline Central Nervous System Abnormalities and Appearance of the Hypothalamic-Pituitary Axis on Magnetic Resonance Imaging

2003 ◽  
Vol 88 (11) ◽  
pp. 5281-5286 ◽  
Author(s):  
N. H. Birkebæk ◽  
L. Patel ◽  
N. B. Wright ◽  
J. R. Grigg ◽  
S. Sinha ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Optic Nerve ◽  
Magnetic Resonance ◽  
Optic Nerve Hypoplasia ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Endocrine Dysfunction ◽  
Resonance Imaging ◽  
Hypothalamic Pituitary Axis ◽  
Group 2

Abstract We here: 1) describe the phenotypic spectrum, including magnetic resonance imaging (MRI) appearances of the pituitary stalk and anterior and posterior pituitary [H-P (hypothalamic-pituitary) axis], in children with optic nerve hypoplasia (ONH) with or without an abnormal septum pellucidum (SP); and 2) define endocrine dysfunction according to the MRI findings. Medical records of 55 children with ONH who had been assessed by ophthalmology and endocrine services were reviewed. All had MRI of the brain and H-P axis. Forty-nine percent of the ONH patients had an abnormal SP on MRI, and 64% had a H-P axis abnormality. Twenty-seven patients (49%) had endocrine dysfunction, and 23 of these had H-P axis abnormality. The frequency of endocrinopathy was higher in patients with an abnormal SP (56%) than a normal SP (39%). Patients were divided into four groups based on SP and H-P axis appearance: 1) both normal; 2) abnormal SP and normal H-P axis; 3) normal SP and abnormal H-P axis; and 4) both abnormal. The frequency of multiple pituitary hormone deficiency was highest (56%) in group 4, lower (35%) in group 3, and even lower (22%) in group 2. Precocious puberty was most common in group 2. None of the patients in group 1 had endocrine dysfunction. Thus, SP and H-P axis appearances on MRI can be used to predict the likely spectrum of endocrinopathy.

scholarly journals Hypoglycemia as a manifestation of congenital multiple pituitary hormone deficiency in patients without growth retardation: a clinical series

2017 ◽  
Vol 63 (3) ◽  
pp. 182-188
Author(s):  
Maria A. Kareva ◽  
Elizaveta M. Orlova ◽  
Maria A. Melikyan ◽  
Alexandr V. Vorontsov ◽  
Victoria P. Vladimirova ◽  
...  
Keyword(s):  
Growth Retardation ◽  
Limit Of Detection ◽  
Growth Failure ◽  
Pituitary Stalk ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Ketotic Hypoglycemia ◽  
Secondary Hypothyroidism ◽  
Clinical Series ◽  
Congenital Hypopituitarism

Congenital hypopituitarism is usually diagnosed in children with growth retardation. Severe life-threatening hypoglycemia and cholestasis can be early manifestations of hypopituitarism in neonates. The pituitary stalk interruption syndrome revealed by MRI confirms the diagnosis of congenital hypopituitarism. We report six cases of children admitted with recurrent ketotic hypoglycemia since early age. The median age of the first clinical presentation of hypoglycemia was 16 months. The median age at primary endocrinological examination was 45 months. At the first examination none of the patients had growth failure. Neonatal jaundice was noticed in four patients. Free T4 levels were decreased in all the patients (median level, 8.6 pmol/l; the lower limit of normal being 10 pmol/l), while the TSH level was normal or moderately increased, suggesting secondary hypothyroidism. Cortisol levels were low (median 92 nmol/L; range, 37—130 nmol/l). IGF-1 level was below the limit of detection (<25 ng/ml) in all patients and reached the normal values in none of patients. All children had elevated prolactin levels: 540—1778 mU/l (normal level, 90—540 mU/l). MRI of the brain revealed similar abnormalities in the chiasmal sellar region in all the patients: anterior pituitary hypoplasia, thin or interrupted pituitary stalk, ectopic neurohypophysis into the chiasm and the hypothalamic structures. Ketotic hypoglycemia can be the first manifestation of congenital hypopituitarism before the growth failure. Hormonal results showing secondary hypothyroidism, secondary adrenal failure, low IGF-1 and pituitary stalk interruption syndrome detected by MRI are sufficient for making the diagnosis of congenital combined pituitary deficiency in children with hypoglycemia; GH-stimulation tests could be avoided in these cases.

Sign in / Sign up

Export Citation Format

Share Document