Pituitary Stalk Interruption Syndrome Research Articles

Distinct pituitary hormone levels of 184 Chinese children and adolescents with multiple pituitary hormone deficiency: a single-centre study

BackgroundPituitary tumors and/or their treatment are associated with multiple pituitary hormone deficiency (MPHD) in adults, but the distinct pituitary hormone profile of MPHD in Chinese children and adolescents remains unclear.MethodsPatients with MPHD were divided into four groups according to their MRI results: 1) pituitary stalk interruption syndrome (PSIS); 2) hypoplasia; 3) normal; and 4) tumor survivor.ResultsAmong the 184 patients, 93 patients (50.5%) were with PSIS, 24 (13.0%) had hypoplastic pituitary gland, 10 (5.4%) patients were normal, and 57 (31.0%) were tumor survivors. There was an association between abnormal fetal position and PSIS (P ≤ 0.001). The CA/BA in PSIS, hypoplasia, normal, tumor survivor groups were 2.27 ± 1.05, 1.48 ± 0.39, 1.38 ± 0.57, 1.49 ± 0.33, and HtSDS were − 3.94 ± 1.39, − 2.89 ± 1.09, − 2.50 ± 1.05, − 1.38 ± 1.63. Patients in PSIS group had the largest CA/BA (P ≤ 0.001 vs. hypoplasia group, P = 0.009 vs. normal group, P ≤ 0.001 vs. tumor survivors) and lowest HtSDS (P ≤ 0.001 vs. hypoplasia group, P = 0.003 vs. normal group, P ≤ 0.001 vs. tumor survivors). The levels of TSH in the PSIS, hypoplasia, normal, and tumor survivor groups were 1.03 ± 1.08 (P = 0.149 vs. tumor survivors), 1.38 ± 1.47 (P = 0.045 vs. tumor survivors), 2.49 ± 1.53 (P < 0.001 vs. tumor survivors), and 0.76 ± 1.15 μIU/ml. The levels of GH peak in PSIS, hypoplasia, normal, tumor survivor groups were 1.37 ± 1.78, 1.27 ± 1.52, 3.36 ± 1.79, 0.53 ± 0.52 ng/ml and ACTH were 27.50 ± 20.72, 25.05 ± 14.64, 34.61 ± 59.35, 7.19 ± 8.63 ng/ml. Tumor survivors had the lowest levels of GH peak (P ≤ 0.001 vs. PSIS group, P = 0.002 vs. hypoplasia group, P ≤ 0.001 vs. normal group) and ACTH (all the P ≤ 0.001 vs. the other three groups).ConclusionThe frequency of PSIS is high among children and adolescents with MPHD. The severity of hormone deficiencies in patients with MPHD was more important in the tumor survivor group compared with the other groups.

Delayed diagnosis of congenital hypopituitarism associated with low socio-economic status and/or migration.

The clinical presentation of combined pituitary hormone deficiency (CPHD) is variable. Some patients present with hypoglycemia during the neonatal period or during the first few years of life. Others present later in childhood with growth failure. We report on 7 patients with very late diagnosed severe hypopituitarism with pituitary stalk interruption syndrome. Five out of the 7 patients had recently migrated to Belgium and the 2 other patients were from low socio-economic status families. All of them presented to our clinic for short stature and some also complained of lack of pubertal development. Four out of the 7 patients reached final height which was within their target height, despite very delayed treatment.Conclusion: We illustrate the overall good outcome of these children with delayed diagnosed severe hypopituitarism. Adverse life conditions and social deprivation are thought to be the cause of their late diagnosis. In the current global socio-politic context, pediatricians in high-income countries should stay aware that migration and poor socio-economic status can be associated with specific clinical presentations.What is Known:• The clinical presentation of combined pituitary hormone deficiency (CPHD) is variable. Some patients present with hypoglycemia during the neonatal period or during the first few years of life. Others present later in childhood with growth failure.• A few case reports are published with very late diagnosis of congenital hypopituitarism.What is New:• We report on the largest series of delayed diagnosis of congenital hypopituitarism and illustrate the survival of these children with overall good prognosis.• Migration and social deprivation are thought to be the main cause of this late diagnosis.

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

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.

Pituitary stalk interruption syndrome: MRI findings in a case of pituitary hypogonadism

Pituitary stalk interruption syndrome: MRI findings in a case of pituitary hypogonadism

Clinical features of anterior pituitary hypofunction

Objective To investigate the common etiology, clinical manifestations and abnormal hormone levels of anterior pituitary hypofunction (APH). Methods A retrospective analysis was performed on 140 patients diagnosed with APH at Department of Endocrine & Metabolic Diseases, Fujian Provincial Hospital from January 2013 to January 2017. Basic clinical data were collected to analyze the common causes of APH, main clinical manifestations and laboratory examination results of the patients. Results Among all 140 patients, 30 (21.4%) were pituitary adenoma patients, 28 (20.0%) were postoperative pituitary adenoma patients, 18 (12.9%) suffered from pituitary hypofunction caused by craniocerebral radiotherapy, 16 (11.4%) developed pituitary stalk interruption syndrome, and 15 (10.7%) had with Sheehan syndrome. There were 67 (94.4%) cases of growth hormone deficiency (growth hormone function measured in only 71 of 140 subjects), 114 (81.4%) cases of gonadal hormone deficiency, 113 (80.7%) cases of thyroid hormone deficiency and 107 (76.4%) cases of adrenocortical hypofunction. Fatigue in 40 (28.6%) cases and delayed growth in 13 (9.3%) cases were the most common complaints, headache in 11 (7.9%) and visual impairment in 10 (7.1%) were the most common symptoms. In male patients, hormonal abnormalities included growth hormone deficiency (94.6%, 53/56), gonadal hormone deficiency (85.0%, 68/80), thyroid hormone deficiency (81.3%, 65/80), and adrenocortical hormone deficiency (78.8%, 63/80). In femal patients, hormonal abnormalities included growth hormone deficiency (93.3%, 14/15), thyroid hormone deficiency (80.0%, 48/60), gonadal hormone deficiency (76.7%, 46/60), and adrenocortical hormone deficiency (73.3%, 44/60). Conclusions The most common reason leading to APH is pituitary adenoma, followed by pituitary adenoma after surgery. The most common complaint is fatigue. The most important hormone abnormalities are? growth hormone and gonadal hormone. There are differences in hormone abnormality caused by APH in different genders. Key words: Hypopituitarism; Clinical features; Pituitary hormones; Etiology

Pituitary stalk interruption syndrome with late revelation: about 5 cases

Pituitary stalk interruption syndrome with late revelation: about 5 cases

Pituitary stalk interruption syndrome: about 9 case report

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Pituitary stalk interruption syndrome: an uncommon presentation

Pituitary stalk interruption syndrome: an uncommon presentation

Short stature and undescended testis in pituitary stalk interruption syndrome

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

MR Imaging Findings of Pituitary Stalk Interruption Syndrome: Report of Three Cases

Hipofiz sapı kesilme sendromu (HSKS), hipofiz glandının nadir bir konjenital anomalisidir. HSKS pituiter stalk yokluğu veya ince olması, ektopik posterior hipofiz glandı ve hipoplastik veya aplastik anterior hipofiz glandı triadı ile karakterize bir antitedir. Klinik olarak ortaya çıkışı hormonal eksikliklerin derecesine bağlıdır ve semptomlar yaşa bağlı olarak değişiklik göstermektedir. Bu izole büyüme hormonu eksikliği olabileceği gibi multipl ön hipofiz hormon yetmezliği olarak da karşımıza çıkabilmektedir. Bu sendrom hipofizer yetmezlik olan çocukların değerlendirilmesinde manyetik rezonans görüntülemenin yaygın kulanımı sonrası tanımlanmıştır. Manyetik rezonans görüntülemenin kullanımı ile hastalığın erken tanısı kolaylaşmıştır. Erken tanı ve tedavi ile bu nadir hastalığın boy kısalığı gibi kalıcı etkileri önlenebilir. Bu yazıda, boy kısalığı ve gecikmiş puberte şikayeti olan üç olgu, manyetik rezonans görüntüleme (MRG) bulguları ile birlikte sunulmuştur.

OR06-6 Whole-Exome Sequencing of Patients with Pituitary Stalk Interruption Syndrome (PSIS) Reveals Probably Pathogenic Variants in Novel Candidate Genes.

Background: Pituitary Stalk Interruption Syndrome (PSIS) is characterized by the presence of a thin or absent pituitary stalk, usually associated with an ectopic posterior pituitary, hypoplasia of the anterior pituitary and pituitary hormone deficiencies. The identification of pathogenic variants in novel genes has clinical implications for the management of the patients and genetic counseling. Objective: to identify pathogenic variants in patients with PSIS using whole-exome sequencing (WES) (trio approach). Method: We performed whole exome sequencing in eleven patients (trio approach) with PSIS using Agilent Sure Select and Illumina NextSeq technology. The patients had been screened for genes previously associated to hypopituitarism by Sanger or Target gene panel. We searched for pathogenic variants considering de novo, homozygous, compound heterozygous and X- linked inheritance. Results: We identified 116 rare allelic variants (excluding synonymous) located in exons or splice sites: 47 de novo, 20 homozygous, 48 compound heterozygous and 1 X-linked. All variants were expressed in pituitary and/or hypothalamus. Of these, 11 variants were highlighted because the genes had correlation to malformations of central nervous system, midline defects or hormonal deficiencies: LCMT1, PCDHB14, ATXN1, ATXN7, KRT18, SYNE1, WDR27, CC2D2A, HAUS5, IFT140 and ELF4. Among them, five were de novo: two were found in genes associated to cleft palate (LCMT1 and KRT18), two in genes previously associated to neurological phenotype (ATXN7 and ATXN1), one in a gene related to organization of neural cadherin-like cell adhesion (PCDHB14).ELF4 was X-linked and was previously associated with isolated growth hormone deficiency. Conclusion: The WES identified 11 potentially pathogenic variants in new candidate genes for PSIS.

SUN-244 Birth and Perinatal Characteristics of Children with Congenital GH Deficiency (GHD) Due to Abnormal Pituitary Development: Data from a Prospective, Multinational Observational Study

Perinatal characteristics of children with non-acquired GHD are highly variable. Children with structural hypothalamic-pituitary abnormalities such as ectopic posterior pituitary (EPP) with/without pituitary stalk interruption syndrome, septo-optic dysplasia (SOD), or isolated anterior pituitary aplasia/hypoplasia (AP/HP) usually display more severe GHD than those with normal hypothalamic-pituitary magnetic resonance imaging (MRI) findings, and a higher prevalence of multiple pituitary hormone deficiencies (MPHD). Birth and perinatal characteristics in patients with structural hypothalamic-pituitary findings were assessed using data from the Genetics and Neuroendocrinology of Short Stature International study (GeNeSIS). Patients were grouped according to investigator-provided diagnoses: 1) EPP (N=396; including interrupted pituitary stalk; reported MPHD 57%); 2) SOD (N=202; MPHD 78%); 3) AP/HP (N=509; MPHD 36%); and 4) Other GHD (N=10470; non-acquired, non-pituitary abnormality associated; MPHD 9%). Birth/perinatal characteristics for EPP were compared to other diagnoses by ANOVA (all other diagnoses) and pairwise using Dunnett adjustment for continuous variables, and Chi-Square (all other diagnoses) and Fisher’s exact test (pairwise) for categorical variables. Gestation duration was ≈39 weeks for all diagnoses. Mean birth weight standard deviation scores (SDS) were 0.02 for EPP, -0.11 for SOD (p value for difference from EPP=0.651), -0.26 for AP/HP (p=0.020), and -0.38 for Other (p<0.001), while birth length SDS were -0.44, -0.17 (p=0.257), -0.60 (p=0.370) and -0.74 (p=0.003) respectively. Breech presentation was reported for 15% in the EPP group vs 3% SOD, 7% AP/HP and 5% Other (p<0.001 pairwise from EPP for all), with higher rates of reported Caesarean section for EPP (21%) vs SOD (17% [p=0.280]), AP/HP (17% [p=0.104]), and Other (14% [p<0.001]) or instrument assisted delivery (5%, 2% [p=0.167], 2% [p=0.033], and 2% [p=0.001] respectively). Perinatal asphyxia, then pregnancy, delivery, and neonatal complications were most prevalent for EPP and/or SOD, with values for EPP vs Other of 10% vs 3%, 18% vs 8%, 11% vs 4%, 35% vs 8%, respectively (p<0.001 for all) and 13% (p=0.027), 10% (p=0.911), 8% (p=0.249), 20% (p<0.001) respectively for AP/HP. In conclusion, among children with GHD, those with structural hypothalamic-pituitary abnormalities had delivery and perinatal complications more frequently than those without such MRI findings, but had birth weight and length SDS closer to the general population average. These findings from a large cohort of children with GHD reinforce previous smaller series suggesting that patients with congenital CNS midline defects and ultimately GHD or MPHD were more likely to have had complications during pregnancy and delivery, although causality is not established.

SUN-457 Congenital Growth Hormone Deficiency Associated with Hip Disorders in Children and Adolescents

Growth hormone deficiency (GHD) is the commonest pituitary hormone deficiency and may require treatment with recombinant human GH (rhGH) for a variable period, ranging from a few years to lifelong. In this respect, surveillance for the long-term side-effects of rhGH treatment is important. Orthopedic complications may occur with rhGH, but some patients may develop hip disorders before rhGH is started, suggesting that untreated GHD/hypopituitarism may be associated with hip pathology. We aimed to: 1. describe clinical data of patients with congenital GHD receiving rhGH associated with hip dysplasia or Legg-Calve-Perthes disease (LCPD) 2. identify those patients with GHD who presented with hip dysplasia before rhGH was initiated in an attempt to determine whether GHD and hip dysplasia occur coincidentally, or if the hip dysplasia could be a manifestation of the underlying neurodevelopmental disorder; 3. determine whether patients receiving rhGH develop LCPD as an adverse effect or not. We performed a retrospective study of pediatric and adolescent patients seen between 1992 to 2017 with congenital GHD and hip disorders. Data were collected through a review of the patients’ medical records. From over 300 eligible patients with congenital GHD followed-up by a single physician in a single tertiary center, 12 patients were included in this study. Ten patients had septo-optic dysplasia (SOD) and 2 had multiple pituitary deficiencies with pituitary stalk interruption syndrome. Hip dysplasia was present in 9 patients and was diagnosed at a mean age of 5.52 years (range 0.86-13.54). These patients had no traumatic births. Five (56%) patients had acetabular dysplasia, 1 (11%) patient had subluxated hips and 3 (33%) had dislocated hips. rhGH was started at an average age of 5.60 years (range 1.94-13.16). Four patients (44%) had developed hip dysplasia on average 4.53 years (0.53-10.15) prior to initiating rhGH treatment. All 4 had bilateral hip dysplasia and isolated GHD. LCPD was present in 3 patients (25%) and was diagnosed at 3, 15 and 18 years old. rhGH was started at age 4, 10 and 14 years, respectively. One patient had developed LCPD one year before rhGH was commenced and did not progress. In 2 patients, LCPD was diagnosed after rhGH was started and did temporarily progress in one of them, but rhGH was not discontinued because LCPD did not seem to be related to rhGH treatment. In conclusion, this study suggests that hip dysplasia could be a manifestation of an underlying GH deficiency, either isolated or in combination with other pituitary hormone deficiencies and complex midline disorders. Additionally, rhGH may not necessarily be causative in patients with hip dysplasia or LCPD receiving rhGH. Nevertheless, we recommend monitoring for development of hip dysplasia in children on rhGH treatment.

Abstract #516 Short Stature and Undescended Testis in Pituitary Stalk Interruption Syndrome

Abstract #516 Short Stature and Undescended Testis in Pituitary Stalk Interruption Syndrome

Causes and Follow-Up of Central Diabetes Insipidus in Children.

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.

Importance of Magnetic Resonance Imaging in Pituitary Stalk Interruption Syndrome

Importance of Magnetic Resonance Imaging in Pituitary Stalk Interruption Syndrome

Farklı Klinik Bulgularla Tanı Alan Hipofiz Sapı Kesilme Sendromu: İki Olgu Raporu

Farklı Klinik Bulgularla Tanı Alan Hipofiz Sapı Kesilme Sendromu: İki Olgu Raporu

Ectopia of the pituitary

The adenohypophysis has alarge intrasellar part and two small parts at the pituitary stalk and the pharynx. Near this extrasellar pituitary tissue, and also in sinus sphenoidalis and sinus cavernosus, ectopic pituitary adenomas can develop. They are indistinguishable in structure and function from usual intrasellar adenomas. The neurohypophysis can show dystopias within complex malformations. In so-called pituitary stalk interruption syndrome, areal ectopia of the neurohypophysis is found at the eminentia mediana of the hypothalamus. Ectopic tissue in the pituitary is extremely rare: foci of ganglionic cells were found in the neurohypophysis and adrenocortical tissue in the adenohypophysis. Focal squamous epithelia in the anterior pituitary are acommon finding but they are rather metaplastic from parenchymal cells than ectopic tissue. Small foci of ectopic salivary gland tissue are not rare in the intermediate zone.

Pituitary Stalk Interruption Syndrome: Presentation of a Rare Case

AbstractPituitary stalk interruption syndrome is a congenital anomaly characterized by interrupted or thin pituitary stalk, hypoplastic or absent anterior pituitary, and an absent or ectopic posterior pituitary gland. The exact incidence rate of this syndrome is not known. However, the estimated incidence rate is 0.5/1,000,000 births. In this case report, we wanted to present a case of interrupted pituitary stalk syndrome, which presented with seizures and thyroid hormone deficiency. A 5-year-old female patient was admitted to our emergency department with vomiting, fever, and seizures with new onset. She had a twin who was ex-utero intrapartum in taken history. She was diagnosed with hypothyroidism and started on levothyroxine. Her height was in 25 to 50th percentile and her weight was in 10 to 25th percentile. She had mild mental retardation. On contrast-enhanced cranial magnetic resonance imaging scan, the pituitary stalk was absent, posterior pituitary was ectopic, and anterior pituitary was hypoplastic. The patient was diagnosed with interrupted pituitary stalk syndrome. After the symptoms were relieved, patient started on carbamazepine for epileptic seizures and hormone replacement therapy with levothyroxine and hydrocortisone. She was routinely followed up after the proper diagnosis. Leuprolide (gonadotropin-releasing hormone) and Norditropin (biosynthetic growth hormone) were added to medical therapy. Her height and weight were in 25th percentile after the long-term follow-up of approximately 10 years. On neurological examination, situation of mild mental retardation persisted. Pituitary stalk interruption syndrome is a very rare entity. However, radiologists should keep this syndrome in mind for patients who present with hypoglycemia, seizures, jaundice, cryptorchidism, and hypothyroidism in neonatal period and growth retardation with pituitary hormone deficiencies in childhood.

Clinical features of pituitary stalk interruption syndrome in neonates and infants

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. Key words: Pituitary stalk interruption syndrome; Infant, newborn; Infant; Clinical characteristics; Diagnosis; Therapy