Congenital bilateral perisylvian syndrome with pituitary hypoplasia and ectopic neurohypophysis

Congenital bilateral perisylvian syndrome (CBPS) is a congenital neurological syndrome characterized by pseudobulbar palsy, cognitive deficits and bilateral perisylvian abnormalities observed on imaging. The described abnormality in CBPS is polymicrogyria located in the frontal, parietal, and/or occipital lobes. A few syndromes or abnormalities associated with this syndrome have been documented. Pituitary abnormalities are rare disorders. Association of CBPS with pituitary abnormalities has not been reported previously. In this case, a combination of bilateral perisylvian polymicrogyria with pituitary hypoplasia and ectopic neurohypophysis, caused by a possible single common insult, is presented.     

Agenesis of the internal carotid artery and congenital pituitary hypoplasia: proposal of a cause of congenital hypopituitarism

We describe a patient with microphallus without pigmentation and multiple pituitary hormone deficiencies. The left internal carotid artery and carotid canal were absent and the pituitary gland and sella turcica showed hypoplasia on MRI and magnetic resonance angiography. The internal carotid artery develops in the 4th embryonic week, while the pituitary primordium develops in the 3rd to 4th week. This suggests a possible relationship between internal carotid artery and congenital hypopituitarism. However, there is bilateral blood supply to the hypophysis via the superior and inferior hypophysial arteries, so it is unknown why pituitary hypoplasia may arise from blocking the unilateral blood supply. Conclusion:disruption of internal carotid artery perfusion may lead to pituitary hypoplasia with congenital hypopituitarism as a new disease entity in humans.Abbreviations AICA agenesis of the internal carotid artery - CNPAS congenital nasal pyriform aperture stenosis - CPH congenital pituitary hypoplasia - SMCI solitary maxillary central incisor     

Pituitary function in a patient with septo-optic dysplasia and pituitary dwarfism (Kaplan-Grumbach-Hoyt syndrome)

The case of a seventeen-year-old female patient with septo-optic dysplasia and pituitary dwarfism is presented. Mental retardation and epilepsy, in addition to absence of the septum pellucidum, point to a widespread lesion of the central nervous system. There is unilateral hypoplasia of the optic nerve. She is of small stature. The dynamic pituitary tests point to deficiency of GH, TSH and ACTH, and an adequate reserve of prolactin, gonadotrophins and vasopressin. TSH insufficiency is probably of primary pituitary origin.     

Imperforate anus,bilateral hydronephrosis,bilateral undescended testes and pituitary hypoplasia: a variant of Hall-Pallister syndrome or a new syndrome?

A patient with multiple congenital malformations, including imperforate anus, bilateral cryptorchidism and microphallus, is described. At 4 months of age the infant had generalized convulsions and hypoglycaemia. Bilateral hydronephrosis was diagnosed at 8 months of age. At 10 months he was diagnosed as having panhypopituitarism secondary to anterior pituitary hypoplasia, shown on CT and MRI scans. This clinical picture partially resembles that of Hall-Pallister syndrome. However, the absence of some typical features such as craniofacial and limb abnormalities and, above all, hypothalamic hamartoblastoma, would also suggest the possibility of a new, previously unreported, syndrome.     

Subhypothalamic high-intensity signals identified by magnetic resonance imaging in children with idiopathic anterior hypopituitarism. Evidence suggestive of an 'ectopic' posterior pituitary gland

Magnetic resonance imaging in two children with idiopathic hypopituitarism demonstrated a signal of high intensity near the optic tract that was consistent with the signal produced by posterior pituitary tissue. Patient 1 was a 15-year-old girl with panhypopituitarism but intact posterior pituitary function. Computed tomography disclosed widening of the superior aspect of the pituitary stalk and a partially empty sella. Magnetic resonance imaging disclosed a 3-mm high-intensity signal abutting the optic tract in the midline just above the sella. The pituitary stalk was not clearly defined, the pituitary gland was small, and the sella was filled with cerebrospinal fluid. Patient 2 was a 12-year-old boy with isolated deficiency of growth hormone secretion. Findings from magnetic resonance imaging and computed tomography were similar to those in patient 1. These data suggest that the high-intensity magnetic resonance imaging findings represent a displaced or "ectopic" posterior pituitary gland, and that the hypopituitary state is due to an insult to the pituitary stalk.     

生长激素缺乏并垂体柄中断13例临床分析

目的 分析垂体柄中断综合征(PSIS)患者的临床特点,提高对该类疾病的认识.方法 回顾分析对2008年1月至2009年6月间浙江大学医学院附属儿童医院内分泌科收治的13例PSIS患者的临床表现、实验室检查和影像学表现.结果 PSIS患儿13例,男性9例,女性4例.均以生长迟缓为主诉,身高81.5～135.0cm,均低于同年龄、同性别正常儿童平均身高的2个标准差以下,生长激素激发试验峰值均低于5μg/L;其中1例合并性发育迟缓,1例合并中枢性尿崩症;1例伴垂体性甲低,1例伴垂体性肾上腺皮质功能减退.结论 PSIS以生长迟缓为主要临床表现,部分性或完全性垂体前叶功能减退,磁共振检查特点为垂体小,垂体柄缺如,垂体后叶异位.     

Congenital hypopituitarism with hypoplasia of the anterior pituitary gland and a normal posterior pituitary lobe

We report a female infant with congenital hypopituitarism. All anterior pituitary hormones were deficient, and the anterior pituitary gland was undetectable on magnetic resonance images. Antidiuretic hormone secretion was appropriate, and the posterior lobe was localized at the end of the stalk, in the sella. These observations suggest that the posterior pituitary gland may develop independently of the anterior lobe. Congenital hypopituitarism, hypoplasia of the anterior pituitary gland     

Early-onset of septo-optic dysplasia. A case report with follow-up

The case of a nine-month'old girl with septo-optic dysplasia is reported. The patient suffered in neonatal life from severe hypoglycemia, conjugated hyperbilirubinemia and nystagmus. At the age of 2 months ophthalmological examination revealed bilateral optic nerve hypoplasia; at the age of 9 months endocrinological investigations showed GH and ACTH deficiency and substitutive hormone therapy was started. MRI scans demonstrated dilatation of ventricles and pituitary ectopia. At the age of 27 months hypothyroidism due to TSH deficiency developed. The auxological and neurological follow-up is reported. The importance of direct ophthalmoscopy of the optic nerve in neonatal age is stressed: an early diagnosis can favourably influence the outcome of the disease.     

Perisylvian polymicrogyria,infantile spasms and arthrogryposis: The severe end of the spectrum of congenital bilateral perisylvian polymicrogyria

Congenital bilateral perisylvian polymicrogyria (CBPP) is the most frequent type of polymicrogyria in children. A 3-month-old male patient is described here with the combination of CBPP, infantile spasms and arthrogryposis. Only four patients have been reported earlier in the literature with this combination. Three of them had epilepsy. These patients represent the more severe phenotype of CBPP, characterized by early onset of symptoms, epilepsy, mental retardation, pseudobulbar palsy and arthrogryposis.     

以新生儿胆汁淤积症为首要表现的垂体柄阻断综合征4例

目的：探讨以新生儿胆汁淤积症为首要表现的垂体柄阻断综合征（PSIS）的临床特点,提高对PSIS的认识。方法：对4例以新生儿胆汁淤积症起病的PSIS患儿的临床特点、实验室检查、肝脏组织病理检查、影像学表现及预后进行回顾性分析。结果：男3例,女1例,均以新生儿胆汁淤积症为首要表现,诊断年龄2～3月龄。4例均表现为胆汁淤积、低血糖和生长发育迟缓。隐睾和小阴茎各1例。4例总胆红素均升高,以直接胆红素升高为主,丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）均升高,以AST升高更明显,γ-谷氨酰转移酶均正常,总胆汁酸均升高;4例均存在肾上腺皮质功能减退,3例生长激素缺乏,2例中枢性甲状腺功能减退。2例行肝组织活检,肝脏病理提示肝细胞气球样变并相互融合形成多核巨细胞,肝细胞内胆汁淤积,毛细胆管内胆栓形成,免疫组化胆盐输出泵在1例无表达,1例部分表达。4例垂体MRI均未显示垂体柄、垂体后叶异位,3例垂体前叶发育不良。4例均予氢化可的松口服治疗,2例甲状腺功能减退的患儿予左甲状腺素钠口服替代治疗。随访4～19个月,4例患儿肝功能正常,甲状腺激素水平、皮质醇水平正常,未出现严重感染,生长发育水平较正常同年龄同性别儿童落后。结论：新生儿期表现为胆汁淤积症、低血糖的患儿应警惕PSIS,垂体MRI有助于明确诊断;早期诊断和治疗可改善PSIS的预后。     

Familial syndrome with panhypopituitarism,hypoplasia of the hypophysis,and poorly developed sella turcica.

Two sisters who died at the age of 2.5 years and 5 weeks are described. Both showed signs of panhypopituitarism. At necropsy, no hypophysis could be found in the first child and a rudimentary and partly ectopic hypophysis was found in the other. Both children had a flat, poorly developed sella turcica, and the sellar anomaly could be seen in skull x-rays. These patients represent a hereditary syndrome characterised by neonatal panhypopituitarism, hypoplasia of the pituitary gland, and flat sella turcica.     

Clinico-radiological correlation in childhood hypopituitarism

Non-tumor etiology constitutes a major group of childhood hypopituitarism. Magnetic resonance imaging has enormously complimented hormonal assessment in these patients. We describe clinico-radiological correlates in thirtyone children (23 boys), aged 1–17 years with a peak GH (growth hormone) levels <7 ng/mL after pharmacological stimuli. Hypoplastic pituitary gland was the most frequent abnormality in children with isolated growth hormone deficiency (IGHD) as compared to stalk abnormalities in children with multiple pituitary hormone deficiencies. MRI tetrad (hypoplastic/absent pituitary, hypoplastic stalk, absent/ectopic posterior pituitary bright spot and empty sella) was more prevalent in IGHD. MRI abnormalities correlated with the severity of growth hormone deficiency.     

Empty sella syndrome, panhypopituitarism, and diabetes insipidus

We present an 18-month-old girl with short stature, obesity, panhypopituitarism, diabetes insipidus, and visual defects. Postmortem examination revealed brain atrophy due to a diffuse encephalopathy, numerous calcified neurons in cerebral cortex, deep telencephalic and diencephalic nuclei, diffuse neuronal necrosis in hypothalamic nuclei, moderate atrophy of optic nerves, very thin hypophyseal stalk, and empty sella with the hypophysis compressed to the dorsal aspect of the concavity. Our hypothesis is that the presence of an empty sella in a child with hypophyseal-hypothalamic abnormalities should alert physicians to the existence of hypothalamic lesions secondary to a perinatal insult. We discuss the possible pathogenesis of these findings as well as lines of evidence available in the literature.     

Empty sella in short children with and without hypothalamic-pituitary abnormalities

A study was conducted on growth hormone (GH) response to oral clonidine (0.15 mg/m²), GH and cortisol responses to i.m. glucagon (0.1 mg/kg), and glucose response to an oral load of glucose (1.75 g/kg). Measurements were made on the circulating concentrations of free thyroxine (FT4), thyroid stimulating hormone (TSH) and different growth parameters and CT sellar images in 25 GH deficient children (Peak GH response to clonidine and glucagon<7 ug/ml), 15 growth retarded children (Ht<5th percentile for age and gender) with sickle cell disease (SCD) and GH deficiency, 30 randomly selected children with normal variant short stature (NVSS) (HtSDS 2SD below the mean for age and gender with normal GH response to stimulation (>10 ug/ml) and 20 age-matched normal children were evaluated. Out of the 25 children with GH deficiency, five had multiple pituitary hormonal deficiency (GH<TSH and/or ACTH. deficiencies), and 20 had isolated GH deficiency. Empty sella, either complete or partial, was detected in 9 out the 20 children with isolated GH deficiency (45%), 4 out of the 5 children with multiple pituitary deficiency (80%), all the children with SCD and GH deficiency (100%), 3 out of the 30 children with NVSS (10%) and in none of the normal children. The insulin-like growth factor-1 (IGF-I) concentrations were significantly lower in the two groups of children with GH deficiency compared to those with NVSS. The height standard deviation scores (HTSDS) were significantly lower and the annual growth velocity was slower in children with idiopathic GH deficiency and empty sella compared to those with NVSS and those with empty sella associated with SCD. The bone age delay (yr) did not differ among the 3 groups of children with short stature. All children with isolated GH deficiency associated with empty sella had normal body mass indices (BMI), while all the children with SCD and empty sella had BMI below the 5th percentile for the corresponding age and gender. None of the children had glucose intolerance. In conclusion, children with growth retardation and abnormal hypothalamic pituitary functions have high incidence of empty sella. However, empty sella is detected in considerable number (10%) of short children with normal hypothalamic pituitary function.     

Hypothalamic-pituitary dysfunction in primary empty sella syndrome in childhood

In a series of 37 consecutive CT scans performed in children referred to our pediatric endocrine unit, an empty (eight) or partially empty (one) sella turcica was found in nine (24%) patients with short stature or delay in sexual maturation, precocious puberty, or hypoparathyroidism. The size and contour of the sella were abnormal in only three patients. Five of the nine children had evidence of decreased growth hormone secretion as determined by subnormal GH secretory responses to provocative tests (peak GH concentration less than 7 ng/ml) or assessment of endogenous 24-hour GH secretion (mean 24-hour GH concentration less than 3 ng/ml). Two children had multiple pituitary hormone deficiencies. Although primary empty sella syndrome was often associated with hypothalamic-pituitary dysfunction in this series, the prevalence of an empty sella in normal children is unknown. Further identification and evaluation of children with empty sella may provide new information regarding the cause of pituitary dysfunction in childhood.     

Auxological, clinical and MRI findings in Taiwanese children with growth hormone deficiency

Growth hormone deficiency (GHD) may be classified into partial isolated GHD (partial IGHD), severe IGHD or multiple pituitary hormone deficiency (MPHD) by the severity of GHD or associated with deficiency of one or more other anterior pituitary hormones during provocative tests. Morphological alterations on magnetic resonance imaging (MRI) in patients with GHD include pituitary hypoplasia, absence or interruption of pituitary stalk, and absence or ectopic posterior lobe. This study investigated the auxological, clinical severity, and anatomical characteristics of the pituitary hypothalamic region by MRI and correlated their relationships. We evaluated these parameters in 45 Taiwanese children with GHD (31 males and 14 females), aged from 3.13 to 17.91 years (10.5+/-2.5), who were divided into diagnostic subgroups of partial IGHD (18 patients), severe IGHD (13 patients), and MPHD (14 patients). We found that BA-CA, peak GH, IGF-I, IGF-I SDS, and height SDS were significantly different among these three groups. The partial IGHD group had significantly higher IGF-I than the MPHD group. There was no significant difference in prematurity, cesarean delivery, birth order, neonatal jaundice, and target height among these three groups. On MRI, patients with MPHD had significantly smaller pituitary height (PHt) SDS (p = 0.0012) and higher frequency of pituitary hypoplasia, pituitary stalk interruption, and ectopic posterior lobe (p = 0.026, 0.008, 0.005, respectively) than the other two groups. Furthermore, PHt SDS was correlated not only with peak GH (r = 0.40, p = 0.0058), but also with basal IGF-I SDS (r = 0.49, p = 0.0007) and body height SDS (r = 0.44, p = 0.025). In conclusion, morphological alterations on MRI of the hypothalamic-pituitary area are correlated with the severity of hypopituitarism. Meticulous evaluation of auxological, clinical and MRI findings can help evaluation of the severity of hypopituitarism and facilitate appropriate treatment in children with GHD.     

Endocrine disorders in septo-optic dysplasia (De Morsier syndrome) — evaluation and follow up of 18 patients

Septo-optic dysplasia (SOD) is characterized by hypoplasia of the optic nerve, various types of forebrain defects and hormonal deficiencies. We have studied the clinical and endocrinological characteristics of 18 such patients retrospectively to: (1) better define the endocrine abnormalities in children with SOD; and (2) to find approaches for the interdisciplinary long-term care of children with SOD. The children were seen at the Children's Hospital of the University of Munich from 1976 to 1992 (8 boys, 10 girls; age at initial presentation: 1 day–13 years of age, mean 1.9 years). Unilateral hypoplasia of the optic nerve was found in 7 cases, bilateral hypoplasia in 11. Sonographic, CCT or MRI yielded the following results: 4 of the patients had a cavum septum pellucidum, 3 patients had hypoplasia of the cerebellum, 1 aplasia of the corpus callosum and 1 aplasia of the fornix. An empty sella with or without an ectopic pituitary was seen in 4 cases. Height standard deviation score (SDS) at time of diagnosis was –4.0 to +0.4, mean –2.92. Endocrine deficiencies were present in all 11 patients who had undergone endocrinological investigations. Seven patients suffered from isolated growth hormone (GH) deficiency or multiple hypopituitarism. One had diabetes insipidus centralis, 2 had hypogonadotropic hypogonadism, 1 had hypothyroidism and 2 adrenal insufficiency. Hypothalamic testing was performed only in a subset of patients: in 5 of 11 children tested a thyrotropin releasing hormone (TRH test), in two out of nine a gonadotropin releasing hormone (GnRH) test, and in three out of six GH releasing hormone (GHRH) test yielded abnormal results. High prolactin levels were measured in two out of five patients.Conclusion SOD is characterized by optic nerve hypoplasia and a variety of endocrine deficiencies. In addition, forebrain malformations are present in most SOD patients. Hormonal disorders are present in some SOD patients which may be of hypothalamic origin and need to be investigated systematically.     

Congenital corectopia (eccentric pupils): a marker for chromosomal and central nervous system abnormality.

We present a case series of five children with congenital corectopia without any associated ocular cause: three had chromosomal abnormalities; one a probable prenatal diplegia, and one bilateral perisylvian dysplasia with vermian and midbrain hypoplasia. Bilateral congenital corectopia is an ophthalmic sign that merits chromosomal analysis and neuro-developmental assessment.     

Growth hormone deficiency in children: Role of magnetic resonance imaging in assessing aetiopathogenesis and prognosis in idiopathic hypopituitarism

To search for the presence of morphostructural abnormalities of the hypothalamus-pituitary region in growth hormone deficient (GHD) children magnetic resonance imaging (MRI) was performed in 30 GHD patients (age 10.09±3.5 years) and in 15 healthy agematched controls. MRI demonstrated a significantly small sella and pituitary volume compared to controls and normal literatures values. In 20 patients the structures were extremely small and an abnormal development of the pituitary stalk was observed, and in 18 of these patients the bright spot indicating the neurohypophysis was dislocated to the distal part of the mal-developed stalk, although these children had a normal fluid balance. From a functional point of view hypothalamus and pituitary defects were equally distributed between the two morphological groups. The patients with multiple endocrine defects had the smallest pituitary volume and abnormal stalk. A possible pathogenetic role of perinatal trauma or dysembriogenic events are discussed. A careful follow up of patients with isolated GHD presenting MRI abnormalities of the pituitary is suggested for the possible evolution in panhypopituitarism.