Clinical and imaging characteristics and treatment follow-up of pituitary stalk interruption syndrome in children / 中华实用儿科临床杂志

Pituitary stalk interruption syndrome (PSIS) is associated with low viability and growth retardation of children and adolescents.Because of complex and variable clinical features,PSIS is often misdiagnosed.Now,the features of clinical manifestations and delineation of pituitary structure in magnetic resonance imaging are summarized,which can help the doctors to make more refined diagnosis,and to also make suggestions for hormone replacement therapy and focus of follow-up.

Clinical features of pituitary stalk interruption syndrome in neonates and infants / 中华实用儿科临床杂志

Pituitary stalk interruption syndrome (PSIS) is characterized by a thin or absent pituitary stalk,hypoplasia of the adenohypophysis,and ectopic neurohypophysis.The occurrence of PSIS is associated with perinatal abnormalities and congenital gene mutations.PSIS manifestations include a wide spectrum of clinical phenotypes and pituitary hormone deficiencies of variable degree and timing of onset.The phenotype in children and adolescents includes short stature and abnormal sexual development.However,the manifestations of PSIS in neonates and infants are not specific.The phenotype in the neonatal period includes hypoglycemia,hyponatremia,micropenis,cryptorchidism,malformations,jaundice,constipation and poor appetite.Great importance should be attached to the prognostic value of magnetic resonance imaging (MRI) in pituitary region,and the pituitary characteristics indicated by MRI are closely associated with the clinical phenotypes of PSIS.Once PSIS is diagnosed,hormone replacement therapy should be performed in early stage and subsequent long-term follow-up is demanded.

Research advances in etiology of pituitary stalk interruption syndrome / 中华实用儿科临床杂志

Pituitary stalk interruption syndrome (PSIS) is characterized by a thin or absent pituitary stalk,hypoplasia of the adenohypophysis,and ectopic neurohypophysis.PSIS manifestations include a wide spectrum of clinical phenotypes and pituitary hormone deficiencies of variable degree and timing of onset.To date,the underlying mechanisms involved in PSIS ontogenesis have remained unclear.Perinatal injury and abnormal pituitary development during the embryonic period have more recently been proposed.Thus far,10 genes mutations,chromosome micro deletions and micro duplications are proved to have been associated with PSIS.Now,the research advances of etiology of PSIS ave reviewed.

Síndrome de interrupción del tallo pituitario: Relaciones clínicas, bioquímicas y neurorradiológicas / Pituitary stalk interruption syndrome: Clinical, biochemical and neuroradiological relationships

El síndrome de interrupción del tallo pituitario (PSIS) se caracteriza por la demostración neurorradiológica de un tallo pituitario ausente, interrumpido o hipoplásico, adenohipófisis aplásica/hipoplásica o neurohipófisis ectópica. Este síndrome se ha relacionado con formas severas de hipopituitarismo congénito (HPC), asociado a múltiples deficiencias de hormonas pituitarias (MPHD). Evaluamos a pacientes con HPC y PSIS, analizando los signos y los síntomas neonatales al diagnóstico, relacionándolos con las deficiencias hormonales pituitarias y signos neurorradiológicos presentes. Estudiamos retrospectivamente a 80 pacientes asistidos en el Hospital de Niños de Córdoba, con diagnóstico de HPC, de los cuales 42 (52%) presentaron PSIS; 22 mujeres y 20 varones, EC: 5 días-9,5 años. El 62% presentó MPHD y el 38% insuficiencia somatotrófica aislada (IGHD). El análisis de las variables perinatales demostró antecedentes de parto natural en el 52% (11/21) de las MPHD vs. 13% (2/15) de las IGHD. Cuatro pacientes, 2 con MPHD y 2 con IGHD presentaban antecedentes obstétricos consistentes en presentación podálica y transversa respectivamente, todos ellos resueltos mediante operación cesárea. Los signos y los síntomas perinatales fueron hipo- glucemia: 61% en MPHD vs. 19% en IGHD, p: 0,0105; ictericia: 38% en MPHD vs. 25% en IGHD; micropene: 77% en MPHD y colestasis: 19% en MPHD. Convulsiones neonatales se presentaron en el 75% de los niños con MPHD e hipoglucemia. EC media de consulta: 2,1 años en MPHD (30% en el período neonatal, 70% antes de 2 años) y 3,6 años en IGHD (44% en menores de 2 años). Los pacientes con MPHD presentaban: tallo no visible 81% (n: 21/26) vs. tallo hipoplásico: 19% (n: 5/26), p: 0,0001; en IGHD 56% (n: 9/16) vs. 44% (n: 7/16), p: 0,5067, respectivamente. El 100% de los neonatos con HPC tenían tallo pituitario ausente. Concluimos que la demostración de PSIS en niños con HPC proporciona información valiosa como predictor de la severidad fenotípica, la presencia de MPHD y de la respuesta al tratamiento. La baja frecuencia de antecedentes obstétricos posicionales potencialmente distócicos, como parte de los mecanismos fisiopatogénicos responsables de PSIS, indicaría la necesidad de analizar la importancia de posibles factores genéticos y epigenéticos involucrados. El diagnóstico precoz de HPC debe sospecharse en presencia de signos y síntomas clínicos, tales como hipoglucemia, colestasis, micropene y defectos asociados en la línea media facial. La resonancia magnética cerebral debe formar parte de los estudios complementarios en pacientes con esta presunción diagnóstica, especialmente a edades tempranas. El reconocimiento tardío de esta entidad puede aumentar la morbilidad y la mortalidad con efectos potenciales deletéreos y permanentes.

Pituitary stalk interruption syndrome (PSIS) is characterised by the combination of an interrupted or thin pituitary stalk, absent or ectopic posterior pituitary, and anterior pituitary hypoplasia. It is manifested as isolated (IGHD) or combined pituitary hormone deficiencies (CPHD) of variable degrees and timing of onset, with a wide spectrum of clinical phenotypes. PSIS may be an isolated morphological abnormality or be part of a syndrome. A retrospective evaluation is presented of clinical signs and symptoms present at early life stages, as well as an analysis of their relationship with hormone laboratory tests and diagnostic imaging in children with congenital hypopituitarism (CHP), and PSIS. This study was performed in a single centre on a sample of 42 children out of a total of 80 CHP patients, with a chronological age range between 5 days and 9.5 years from a database analysed over a period of 26 years. The study included 26/42 (62%) with CPHD and 16/42 (38%) with IGHD. The analysis of perinatal variables showed a natural delivery in 52% (11/21) of CPHD vs 13% (2/15) of IGHD. Four patients, two with CPHD and two IGHD had breech and transverse presentation respectively. All of them were resolved by caesarean section. The perinatal histories showed hypoglycaemia (61% CPHD vs 19% IGHD, P=.0105), jaundice (38% CPHDvs25% IGHD), micropenis (75%CPHD), hypoglycaemic seizures (75% CPHD), and cholestasis (19% CPHD). The mean CA of consulting for CPHD patients was 2.1 years, 30% in neonatal period and 70% before 2 years. The mean chronical age (CA) was 3.6 years in IGHD patients, with 44% of them less than 2 years. MRI showed that 81% of CPHD patients had absence of pituitary stalk vs 19% with thin pituitary stalk (P=.0001); Patients with IGHD presented 56% absence of pituitary stalk vs 44% with thin pituitary stalk (P=.5067). All (100%) of the patients diagnosed in the neonatal stage had absent pituitary stalk. The characterisation of GH deficient patients by presence and type of hypothalamic-pituitary imaging abnormality provides valuable information as a predictor of phenotypic severity, treatment response, and the potential to develop additional hormonal deficiencies. We conclude that demonstrating PSIS in children with HPC provides valuable information as a predictor of phenotypic severity, presence of MPHD, and response to treatment. The low frequency of potentially dysfunctional positional obstetric history, as part of the pathophysiological mechanisms responsible for PSIS, would indicate the need to analyse the importance of possible genetic and epigenetic factors involved. Early diagnosis of HPC should be suspected in the presence of clinical signs and symptoms, such as hypoglycaemia, cholestasis, micropenis, and associated facial midline defects. MRI should be part of complementary studies in patients with this diagnostic suspicion, especially at an early age. Late recognition of this entity may increase morbidity and mortality with potential permanent deleterious effects.

From the perspective of embryonic development on genetic pathogenic factors of pituitary stalk interruption syndrome / 中华内分泌代谢杂志

Pituitary stalk interruption syndrome (PSIS) is a newly discovered rare endocrinological syndrome characterized by structrual defect of pituitary and multiple deficiencies of a series of hypothalamic hormones, and thus leading to a cluster of clinical symptoms. This review will illustrate the genetic pathogenic factors influence on embryonic development, and briefly introduce the current studies of Whole-Exome Sequencing on PSIS.

Pituitary stalk interruption syndrome: Clinical features and progress in etiology / 中华内分泌代谢杂志

Pituitary stalk interruption syndrome(PSIS), as a rare congenital defect manifesting with varying degrees of pituitary hormone deficiency, its diagnosis is frequently delayed in clinical practice for the signs and symptoms during the neonatal period and infancy are often overlooked. The typical features of PSIS can be detected by magnetic resonance imaging. Several genes in Wnt, Notch, and Shh signaling pathways that related to hypothalamic-pituitary development, have been found to be associated with this rare syndrome. Nevertheless, the etiology in the majority of cases still remains unknown.In this review, we provide an overview of clinical features of PSIS and summarize our current understanding of its etiology. Furthermore, we propose future research directions for it. This manuscript is a Chinese translation version of review article entitled Pituitary stalk interruption syndrome: from clinical findings and pathogenesis in Journal of Neuroendocrinlogy[Journal of Neuroendocrinology,2017,29(1):DOI : 10.1111/jne.12451]. The authors have attained permissions from Journal of Neuroendocrinology and John Wiley and Sons Ltd.

The diagnostic value of enhanced MRI of pituitary for pituitary stalk interruption syndrome and a correlation analysis between enhanced MRI and pituitary target gland function damage / 中国医学装备

Objective:To observe and research the diagnostic value of enhanced MRI of pituitary for pituitary stalk interruption syndrome (PSIS) and explore the correlation between enhanced MRI and pituitary target gland function damage.Methods: 80 patients with PSIS were divided into part of pituitary stalk interruption group (38cases) and complete pituitary stalk interruption group (42cases). And 80 healthy people were divided into control group. The relative hormonal level of three groups were detected, and the correlation between appearance of MRI and insufficient hormonal type, amount and severity degree were analyzed.Results: In part of pituitary stalk interruption group, the heights of anterior pituitary gland were less than 3mm in 10 cases, and they were between 3-5mm in 23 cases and they were more than 5mm in 5 cases. And in them, there were 4 cases were posterior pituitary deficiency, 15 cases were heterotopia, 11 cases were volume diminished. In complete pituitary stalk interruption group, the heights of anterior pituitary gland were less than 3mm in 23 cases, and they were between 3-5mm in 16 cases and they were more than 5mm in 3 cases. And in them, there were 8 cases were posterior pituitary deficiency, 32 cases were heterotopia, 1 cases were volume diminished. All of the hormonal levels included growth hormone, insulin-like growth factor, free thyroxine, serum thyroid stimulating hormone (TSH), cortisol and adrenocorticotrophic hormone (ACTH) in complete pituitary stalk interruption group were significantly lower than that in part of pituitary stalk interruption group and control group (F=224.92,F=2571.80, F=369.50,F=67.73,F=2677.94,F=24.17,P<0.05), respectively. The differences of growth hormone, TSH, cortisol and ACTH, excepted insulin-like growth factor and free thyroxine, between part of pituitary stalk interruption group and control group were not significant. And pituitary-gonadal hormones level of part of pituitary stalk interruption group was significantly lower than that of control group (F=354.94,F=247.00, F=247.83,F=655.05,F=48.10,P<0.05). Besides, the differences of follicle-stimulating hormone, luteinizing hormone, estradiol, testosterone and prolactin levels between part of pituitary stalk interruption group and complete pituitary stalk interruption group were no significant.Conclusion: Enhanced MRI of pituitary can effectively diagnose pituitary stalk interruption syndrome and damage degree of pituitary target gland function.

Delayed diagnosis of pituitary stalk interruption syndrome with severe recurrent hyponatremia caused by adrenal insufficiency

Pituitary stalk interruption syndrome (PSIS) involves the occurrence of a thin or absent pituitary stalk, hypoplasia of the adenohypophysis, and ectopic neurohypophysis. Diagnosis is confirmed using magnetic resonance imaging. Patients with PSIS have a variable degree of pituitary hormone deficiency and a wide spectrum of clinical manifestations. The clinical course of the disease in our patient is similar to that of a syndrome of inappropriate antidiuretic hormone secretion. This is thought to be caused by failure in the suppression of vasopressin secretion due to hypocortisolism. To the best of our knowledge, there is no case report of a patient with PSIS presenting with hyponatremia as the first symptom in Korean children. Herein, we report a patient with PSIS presenting severe recurrent hyponatremia as the first symptom, during adolescence and explain the pathophysiology of hyponatremia with secondary adrenal insufficiency.

Growth without growth hormone in combined pituitary hormone deficiency caused by pituitary stalk interruption syndrome

Growth hormone (GH) is an essential element for normal growth. However, reports of normal growth without GH have been made in patients who have undergone brain surgery for craniopharyngioma. Normal growth without GH can be explained by hyperinsulinemia, hyperprolactinemia, elevated leptin levels, and GH variants; however, its exact mechanism has not been elucidated yet. We diagnosed a female patient aged 13 with combined pituitary hormone deficiency (CPHD) caused by pituitary stalk interruption syndrome (PSIS). The patient has experienced recurrent hypoglycemic seizures since birth, but reached the height of 160 cm at the age of 13, showing normal growth. She grew another 8 cm for 3 years after the diagnosis, and she reached her final adult height of 168 cm which was greater than the midparental height, at the age of 16. The patient's blood GH and insulin-like growth factor-I levels were consistently subnormal, although her insulin levels were normal. Her physical examination conducted at the age of 15 showed truncal obesity, dyslipidemia, and osteoporosis, which are metabolic features of GH deficiency (GHD). Herein, we report a case in which a PSIS-induced CPHD patient attained her final height above mid parental height despite a severe GHD.

Advance in genetic study of pituitary stalk interruption syndrome / 中华内分泌代谢杂志

Pituitary stalk interruption syndrome(PSIS) is a developmental defect,characterized by a thin or absent pituitary stalk. PSIS is a rare disease with combined pituitary hormone deficiencies, the pathogenesis of which is related to genetic mutations and environmental factors. It is also a genetically and clinically heterogeneous disease. Nine genes were found to be related to PSIS,including HESX1,LHX4,OTX2,SOX3,CDON,GPR161, PROKR2,TGIF and Wnt,Notch,SHH signalling pathways. In recent years,the intensive genetic studies show that four novel genes(CDON,GPR161,PROKR2,TGIF)and SHH pathway are related to PSIS,which provides a brand-new etiopathogenesis of PSIS.

Clinical analyses of 11 cases with pituitary stalk interruption syndrome / 中华全科医师杂志

Eleven male patients with pituitary stalk interruption syndrome (PSIS) at our hospital were retrospectively analyzed with respects to clinical features,endocrine status and imaging characteristics.The clinical manifestations included growth retardation and delayed puberty.All of them were deficient in growth hormone and pituitary gonadotropin secretion.Secondary hypothyroidism and hypocortisolism occurred in 8 patients and one had concurrent central diabetes insipidus.MRI with gadolinium contrast revealed no pituitary stalk or slim and anterior pituitary hypoplasia with ectopic posterior pituitary.The clinical characteristics of PSIS are growth retardation and delayed puberty,partial or complete adenohypophyseal dysfunction.The detection of hypothalamic pituitary region by MRI is an important diagnostic tool.

The influencing factors on the height of patients with pituitary stalk interruption syndrome / 中华内分泌代谢杂志

Thirty cases of pituitary stalk interruption syndrome were divided into normal height (group 1) and short stature (group 2).There was no significant difference in growth hormone or insulin-like growth factor-Ⅰ levels between two groups(P＞0.05).Expected height and body mass index in group 1 were higher than those in group 2,while testosterone,cortisol,and FT4 were lower.Height were positively correlated with age,expected height,birth weight,and body mass index.The height of patients with pituitary stalk interruption syndrome depended on both genetic factors and the hormones from pituitary-target gland.

Advance in diagnosis and therapy of pituitary stalk interruption syndrome / 中华内分泌代谢杂志

Pituitary stalk interruption syndrome(PSIS) is a rare disease characterized by different degrees of anterior pituitary hormone deficiency.The typical imaging finding is a thin or absent pituitary stalk,often associated with an ectopic posterior pituitary and a hypoplastic anterior pituitary.The cause is still unkown.Dynamic contrastenhanced MRI helps to confirm the diagnosis.Replacement of multiple anterior pituitary hormones is the key of the treatment.Doctors should have a thorough understanding of the disease and give patients efficacious treatment and a better prognosis would be obtained.

Clinical analysis of 5 cases of pituitary stalk interruption syndrome and literature review / 中华内分泌代谢杂志

Objective To analyze the clinical characteristics of the patients with pituitary stalk interruption syndrome (PSIS) in our hospital in the past seven years, and to achieve better comprehension of this kind of disease. Methods Five patients with PSIS (4 males, 1 female) in our hospital were retrospectively analyzed, regarding clinical manifestation, laboratory and imaging data. Results The clinical features of 5 cases of PSIS were as follows: (1) growth retardation; (2) high incidence of breech delivery; (3) 159-165 cm in body height; (4) retarded bone age; (5) average intelligence; (6) adenohypophyseal dysfunction in clinical and laboratory examinations; (7) normal posterior pituitary function; (8) MRI with gadolinium contrast revealed no pituitary stalk and anterior pituitary hypoplasia with ectopic posterior pituitary. The pathogenesis of PSIS is not clear. Appropriate hormonal replacement therapy is the only effective way. Conclusion PSIS is rarely seen and its clinical feature is different from pituitary dwarfism and hypogonadotropic hypogonadism. The realization for this syndrome should be emphasized and early therapy is essential.

Clinical diagnosis of 5 cases of pituitary stalk interruption syndrome / 中华内分泌代谢杂志

Objective To raise the level of clinical diagnosis for the patients with pituitary stalk interruption syndrome (PSIS). Methods Five patients (4 males) with PSIS were retrospectively analyzed with respects to the clinical features, endocrine status and image characteristics. Magnetic resonance imaging (MRI) scan was performed at hypothalamic-pituitary region. Results The clinical manifestations of all patients consisted of growth retardation and delayed puberty without polyuria. Deficiency of multiple anterior pituitary hormones was revealed in all patients by the evaluation of endocrine status. The features of MRI included a lack of visible pituitary stalk, absence of posterior lobe hypersignal in the sella turcica and a hyperintense spot in the region of the thalamus opticus. Conclusion The clinical characteristics of patients with PSIS are growth retardation and delayed puberty. The evaluation of anterior pituitary function is necessary. The detection of an anatomical abnormality around hypothalamic-pituitary region by MRI is important diagnostic evidence.

MR Imaging Diagnosis of Pituitary Stalk Interruption Syndrome / 实用放射学杂志

Objective To study MRI features of pituitary stalk interruption syndrome(PSIS).Methods 10 cases in 42 with growth retardation patients diagnosed as PSIS by MRI,all of them were male,age ranged from 5 to 18 with average 13.6 years.Results The anterior-pituitary superior border was depressed,anterior-pituitary volume decreased(average height 2.1 mm,average width 7.8 mm),ectopic posterior-pituitary lobe located at infundibulum stem and pituitary stalk was absent in all cases.The blood hormorne test showed the growth hormone deficiency and multiple growth hormone deficienty.Conclusion PSIS often see in men,MRI findings of PSIS are characteristic.

Imaging Diagnosis of Pituitary Stalk Interruption Syndrome / 实用放射学杂志

Objective To analyze the CT and MRI features of pituitary stalk interruption syndrome, so that to improve the diagnostic knowledge of this disease.Methods The imaging and clinical data of 4 patients with pituitary stalk interruption syndrome were retrospectively analyzed. Results In all of the 4 cases, the pituitary stalk were not shown by CT in 2 and by MRI in 4,the high signal intensity of the posterior lobe disappeared on T1WI,while a small nodule in infundibulum with high signal intensity on T1WI was found. Conclusion MRI is the most valuable imaging modality for the diagnosis of pituitary stalk interruption syndrome.