Clinical Consultation Guide on Imaging in Male Infertility and Sexual dysfunction.

Imaging can benefit clinicians in evaluating men with infertility or sexual dysfunction by giving an overview of a patient's overall clinical condition before undertaking an invasive procedure. An understanding of the limitations and advantages of image modalities used in clinical practice will ensure that clinicians can optimize patient care with imaging when necessary. PATIENT SUMMARY: The objective of this article was to review the current literature on imaging modalities used for the diagnosis and management of male infertility and sexual dysfunction. An understanding of the advantages and limitations of these imaging modalities will ensure that clinicians can optimize patient care with imaging when necessary.

NELF knockout is associated with impaired pubertal development and subfertility.

Puberty and reproduction require proper signaling of the hypothalamic-pituitary-gonadal axis controlled by gonadotropin-releasing hormone (GnRH) neurons, which arise in the olfactory placode region and migrate along olfactory axons to the hypothalamus. Factors adversely affecting GnRH neuron specification, migration, and function lead to delayed puberty and infertility. Nasal embryonic luteinizing hormone-releasing factor (NELF) is a predominantly nuclear protein. NELF mutations have been demonstrated in patients with hypogonadotropic hypogonadism, but biallelic mutations are rare and heterozygous NELF mutations typically co-exist with mutations in another gene. Our previous studies in immortalized GnRH neurons supported a role for NELF in GnRH neuron migration. To better understand the physiology of NELF, a homozygous Nelf knockout (KO) mouse model was generated. Our findings indicate that female Nelf KO mice have delayed vaginal opening but no delay in time to first estrus, decreased uterine weight, and reduced GnRH neuron number. In contrast, male mice were normal at puberty. Both sexes of mice had impaired fertility manifested as reduced mean litter size. These data support that NELF has important reproductive functions. The milder than expected phenotype of KO mice also recapitulates the human phenotype since heterozygous NELF mutations usually require an additional mutation in a second gene to result in hypogonadotropic hypogonadism.

SOX3 deletion in mouse and human is associated with persistence of the craniopharyngeal canal.

CONTEXT: SOX3 is an early developmental transcription factor involved in pituitary development. In humans, over- and underdosage of SOX3 is associated with X-linked hypopituitarism with variable phenotypes ranging from isolated GH deficiency (GHD) to panhypopituitarism, with or without mental retardation and, in most cases, with reported pituitary imaging, an ectopic/undescended posterior pituitary. PATIENT: We present a young patient with hemophilia B and developmental delay who had a 2.31-Mb deletion on Xq27 including SOX3, F9, and eight other contiguous genes. He developed GH and gonadotropin deficiency, whilst his thyroid function was in the low normal range. Magnetic resonance imaging revealed a eutopic posterior pituitary and the unusual finding of a persistent craniopharyngeal canal that has not previously been described in patients with congenital hypopituitarism. OBJECTIVE AND METHODS: To establish whether loss of SOX3 can account for the human phenotype, we examined in detail the hypothalamo-pituitary region of neonatal Sox3 null mice. RESULTS: Consistent with the patient's phenotype, Sox3 null mice exhibit a ventral extension of the anterior pituitary that penetrates, and generates a mass beneath, the sphenoid bone. This suggests that the defect results from abnormal induction of Rathke's pouch, leading to a persistent connection between Rathke's pouch and the oral ectoderm. CONCLUSIONS: Our observations expand the spectrum of phenotypes observed in association with altered SOX3 dosage and may affect the approach to genetic screening. Screening for SOX3 should be advised not only for hypopituitary patients with an ectopic posterior pituitary, but also for those with a structurally normal pituitary and additional findings, including clefts and a persistent craniopharyngeal canal, with or without mental retardation.

[The frequency of structural abnormalities in the hypothalamo-pituitary region and their clinical significance in patients with growth hormone deficiency]. / Wystepowanie zmian strukturalnych w okolicy podwzgórzowo-przysadkowej i ich znaczenie kliniczne u pacjentów z somatotropinowa niedoczynnoscia przysadki.

INTRODUCTION: In children with confirmed growth hormone deficiency (GHD) the most common diagnosis is idiopathic isolated GHD. Nevertheless, it cannot be ignored, that the GHD might also be caused by structural malformations or tumours in hypothalamo-pituitary region. The aim of the study was to evaluate the frequency of structural malformations in the hypothalamo-pituitary region in children with growth hormone deficiency and its correlation with clinical parameters. MATERIAL AND METHODS: 99 patients with growth hormone deficiency were examined (30 girls and 69 boys). Mean age of the patients was 10±3.4 years. The diagnosis of growth hormone deficiency was based on standard criteria: growth hormone level below 10 ng/ml in two stimulatory tests and auxological data. Magnetic resonance imaging was performed in pituitary protocol: (SE, TSE in T1- and T2-weighted pictures). Patients were divided into two groups: with malformations (ZM) of hypothalamo-pituitary region and without the malformations (BM). In the course of analysis, the ZM group was divided into the following subgroups: with a severe malformation (Mw) and with mild malformations (Mmn). The results of growth hormone stimulatory tests, IGF-1 level, additional hormonal disorders and auxological parameters were compared between the groups. RESULTS: In the examined group structural malformations of hypothalamo-pituitary region were found in 42% (n=42) of patients. The most common finding was pituitary hypoplasia and ectopy of the posterior lobe. The groups did not differ by age, mean height deficiency (in SDS) and mean height of parents. The mean IGF-1 level was statistically significantly lower in ZM group than in BM group (p <0.04). Similarly the maximal growth hormone secretion in stimulatory tests was lower in ZM patients. The age of diagnosis was statistically significantly younger in the Mw subgroup, and multihormonal hypopituitarism was diagnosed only in patients with a severe structural malformation of hypothalamo-pituitary region. CONCLUSIONS: 1. The structural malformations of hypothalamo-pituitary region were found in 42% of patients. 2. The diagnosis of multihormonal hypopituitarism in a patient is connected with an increased risk of the presence of severe structural abnormalities in hypothalamo-pituitary region. 3. IGF-1 level and maximal GH secretion are negatively correlated with the presence of malformations of the hypothalamo-pituitary region.

Displasia septo-optica. Evaluación clínica, endocrinológica y neuro-radiológica. Seguimiento de 46 pacientes pediátricos / Septo-optic dysplasia. Clinical, endocrinological, and neuroradiological evaluation. Follow-up of 46 pediatric patients

La displasia septo-óptica (DSO) es una condición rara y altamente heterogénea, definida por la combinación de hipoplasia del nervio óptico (HNO), malformaciones cerebrales de la línea media, tales como aplasia/hipoplasia de septum pellucidum y cuerpo calloso, e insuficiencia hipotálamo-hipofisaria de grado variable. Se realizó un trabajo que tuvo como objetivo caracterizar la población de pacientes con diagnóstico de DSO seguidos en nuestro Hospital durante 7 años. Se incluyeron 46 pacientes (18 mujeres) que fueron divididos en 2 grupos, según tuviesen o no insuficiencia hipotálamo-hipofisaria (IHH). El 58.7% (n=27) presentó IHH de algún tipo, mientras que el 41.3% (n=19) no la presentó. En aquellos 19 pacientes con IHH se diagnosticaron deficiencia de GH y TSH (85.1%) y de ACTH (48.1%). La longitud corporal (mediana) del grupo con IHH fue más baja (p = 0,01) que la del grupo sin IHH, a pesar de que la edad fue menor a 2 años en todos los casos. Los pacientes fueron seguidos 1,3-8,3 años. Se observaron incidencias similares de agenesia del cuerpo calloso, del septum pellucidum, y ventriculomegalia, pero las alteraciones del desarrollo cortical se observaron con mayor frecuencia en los pacientes sin IHH. La ictericia neonatal, convulsiones y/o hipoglucemia, y micropene en neonatos y lactantes con DSO se presentaron en el subgrupo con IHH. El 58,7% de los pacientes con DSO presentaron algún grado de insuficiencia hipotálamo-hipofisaria. En la mayoría de los casos el diagnóstico de IHH no se realizó en el momento de aparición de los síntomas, sino más tardíamente en su seguimiento. En el 45% de los pacientes se evaluaron alteraciones radiológicas del SNC, específicamente en la región hipofisaria. Una fracción importante de las deficiencias de TSH/T4 (36,4%), GH (50%) y ACTH (23%) aparecieron mas tardíamente en el curso de la evolución. En 10 niños con déficit de hormona de crecimiento (2 tests farmacológicos sin respuesta) se realizó el tratamiento sustitutivo con rhGH (durante un periodo de 4±3 años), observándose una mejoría promedio de + 1,5 SDS en la talla de estos pacientes. En conclusión, la hipoplasia neonatal de nervios ópticos, asociada o no a ictericia e hipoglucemia, debe ser un signo de alarma para el diagnóstico de DSO, con riesgo de insuficiencia suprarrenal, shock y muerte, y puede requerir, por lo tanto, urgente tratamiento. Las deficiencias pueden aparecer en el curso de la evolución, a pesar del carácter congénito de la anomalía. Finalmente, se deben sustituir las deficiencias hormonales y tener presente que el tratamiento con rhGH puede mejorar la talla final en estos pacientes (AU)

Septo-optic dysplasia (SOD) is a rare and highly heterogeneous condition consisting of a combination of optic nerve hypoplasia (ONH), midline brain abnormalities, such as aplasia/hypoplasia of the septum pellucidum (ASP) and corpus callosum; and variable degree of hypoyalamo-pituitary insufficiency. The aim of this study was to characterize a population of SOD patients diagnosed and followed at the Garrahan Pediatric Hospital, from 1989 to 2006. We included 46 patients (18 females), that were divided into two groups according to the presence or absence of hypothalamic-pituitary insufficiency (IHH). Fifty nine% of SOD patients presented with IHH. GH and TSH deficiencies were diagnosed in 85.1% of IHH patients, while ACTH deficiency was found in 48.1%. Height (median) for the IHH group was shorter (p = 0,01) than for the group without IHH. Patients were followed for 1.3-8.3 years. Similar incidence of corpus callosum and/or septum pellucidum agenesis and ventriculomegaly were found in the two groups, but we observed more association with cortical developmental disorders in patients without IHH. In newborns, the association of ophthalmologic disorders and jaundice, seizures and/or hypoglycemia and micropene should frequently lead to the diagnosis of SOD and IHH. While 58,7% of DSO patients presented with hypothalamic-pituitary deficiency, only 45% of them showed sellar radiological abnormalities. Although SOD is a congenital disease, hormonal deficiencies may appear during follow-up. In 10 children with SOD and GH deficiency, rhGh treatment (for 4±3 years) improved height in 1.5 SDSs. In conclusion: in newborns with nerve optic hypoplasia, associated or not with jaundice, seizures and hypoglycaemia, the diagnosis of SOD and IHH should be considered. Treatment could be an emergency need because of risk of adrenal insufficiency and hypoglycemia (AU)

[Biological mechanisms and genes involved in puberty]. / Mécanismes biologiques et gènes impliqués dans le développement de la puberté.

Puberty is an important step in human development. Onset of puberty, including neurobiological mechanisms important for the increase of hypothalamic GnRH pulses remains a mystery. After birth, GnRH secretion remains elevated and then decreases during childhood regardless of any steroid gonadal feedback. This period of quiescence of the gonadotropic axis during childhood is linked to a central inhibition of GnRH secretion which is replaced by an activator tone at puberty. The study of the pathology of the pubertal timing, including delayed puberty led to the discovery of new genes involved in the migration of GnRH neurons and genes involved in the neuroendocrine regulation of the gonadotropic axis. Recently, the emphasis on the importance of the kiss/GPR54 system in modulating control of the gonadotropic axis at puberty has recently emerged from Human genetics studies.

Circadian pattern of prolactin secretion in children with growth hormone deficiency and congenital organic lesions in the hypothalamic-pituitary region.

OBJECTIVES: Prolactin (Prl) secretion in children manifests circadian rhythm. The aim of the study was to assess circadian Prl pattern in children with growth hormone deficiency (GHD) and congenital organic disorders in the hypothalamic-pituitary region (HPR). MATERIAL AND METHODS: The analysis comprised 47 children (aged: 11.05+/-3.5 years) with GHD, divided (based on MRI) into subgroups: NORM (no disturbances in HPR); HP (pituitary hypoplasia) and PSIS (pituitary stalk interruption syndrome). The profile of circadian Prl secretion was determined, based on Prl measurements in serum every 3 hours during 24 hours. The macroscopic analysis of circadian Prl rhythm in particular groups was performed. The comparison group consists of 41 children (aged: 11.45+/-3.20 years) with idiopathic short stature (ISS). RESULTS: In GHD-HP, diurnal and nocturnal Prl concentrations were low but with the dispersion between them and with normal rhythm in most of cases. In GHD-PSIS, diurnal and nocturnal Prl concentrations were on the same level and the rhythm was not observed in most of cases. No significant differences were found in Prl secretions and Prl rhythm between GHD-NORM and ISS. The rhythm of Prl secretion was disturbed in: 72.7% of children with GHD-PSIS, 23.5% - with GHD-HP, 10.5% with GHD-NORM and 7.3% with ISS, only. CONCLUSIONS: Congenital organic lesions of HPR are associated with quantitative disorders and changes of the circadian pattern of Prl secretion. In children with GHD without organic lesions of HPR, the circadian rhythm of Prl secretion was not different from that with ISS.

GH response to ghrelin in subjects with congenital GH deficiency: evidence that ghrelin action requires hypothalamic-pituitary connections.

OBJECTIVES: Evaluation of GH response to ghrelin in patients with GH deficiency (GHD) may help to elucidate the site and mechanism of action of ghrelin. We aimed to investigate the GH-releasing effect of ghrelin in children and young adults with childhood-onset GHD. DESIGN: All subjects underwent ghrelin testing and neuro-imaging examination. Magnetic resonance imaging evidenced the presence of a vascular pituitary stalk (VPS) or its complete absence (PSA). PATIENTS AND METHODS: Seventeen prepubertal children and nine adult patients with childhood-onset GHD were selected for the study. The children were enrolled at a median age of 5.8 years. The adult subjects were included at a median age of 23.3 years. The diagnosis of GHD in the adult patients had been established at a median age of 8.5 years. Ghrelin was administered at a dose of 1 microg/kg body weight, i.v. at time zero, and blood for GH determination was obtained at 0, 15, 30, 45, 60, 75, 90, 105 and 120 min. RESULTS: Median GH response after ghrelin was similar between children and adults. Median peak GH response to ghrelin (7.45 microg/l, IQR: 3.9-11.3 microg/l) was significantly higher in patients with VPS (10.9 microg/l, IQR: 2.4-15.1 mcirog/l) than in those with PSA (IQR: 2.3-6.7 microg/l; P=0.001). It was significantly higher in subjects with isolated GHD (12.5 microg/l, IQR: 10.8-15.5 microg/l) than in those with multiple pituitary hormone deficiencies (5.15 microg/l, IQR: 2.4-9.0 microg/l; P=0.003). No correlation was found between the GH peak after ghrelin and body mass index. CONCLUSION: The GH response to ghrelin in patients with congenital hypopituitarism depends on the degree of the anatomical abnormalities and lends further support to the assumption that the main action of the peptide is exerted at the hypothalamic level and requires the integrity of hypothalamic-pituitary connections.

High proportion of pituitary abnormalities and other congenital defects in children with congenital nasal pyriform aperture stenosis.

We aimed to determine the occurrence of pituitary dysfunction and additional malformations in patients with congenital nasal pyriform aperture stenosis (CNPAS) and to predict which patients are at risk of pituitary dysfunction. Among the 40 studied patients, hypothalamo-pituitary (HP) axis abnormalities were found in 16 patients (40%), with endocrine dysfunction (n = 9) and/or abnormal HP MRI findings (n = 15). A normal HP axis on MRI was highly predictive of normal endocrine function. Of the 40 patients, 31 had additional abnormalities in the cranio-facial area (n = 26), the brain (n = 12), the vertebrae (n = 5), the limbs (n = 4), the heart (n = 7) and the kidney (n = 3). Six patients had syndromic associations: VACTERL (n = 4), CHARGE (n = 1) and RHYNS (n = 1) syndromes. Craniofacial and brain malformations were more common in patients with HP axis abnormalities than in patients with normal HP axis. Familial history of midline defects and/or consanguinity were found in 30% of patients. In conclusion, HP axis abnormalities are frequent in patients with CNPAS and justify MRI of the brain early in life and clinical evaluation to screen for patients with pituitary insufficiency. CNPAS may be a genetically heterogeneous condition with a large phenotypic variability that shares common etiological mechanisms with the various forms of the holoprosencephaly phenotype.

Final height and growth hormone secretion after completion of growth hormone therapy in patients with idiopathic growth hormone deficiency and with abnormalities of the hypothalamic-pituitary region.

AIMS: The aim of the study was an evaluation of final height and growth hormone (GH) secretion after completion of GH therapy (retesting) in patients with GH deficiency (GHD). PATIENTS AND METHODS: The analysis comprised 53 patients (43 boys, 10 girls) with childhood-onset GHD, who completed GH therapy and reached final height. Magnetic resonance imaging (MRI), performed in all the patients, led to the following groups: pituitary stalk interruption syndrome (PSIS), pituitary hypoplasia (HP), craniopharyngioma (CP) -- patients after tumour excision, patients with normal hypothalamic-pituitary region (NP). RESULTS: In 51 patients, final height was normal. The height gain was significantly (p<0.05) greater in PSIS than in that other groups. In retesting, GH secretion was significantly (p<0.005) lower in PSIS and CP than in HP and in NP and also (p<0.05) in HP than in NP. Permanent severe GHD was confirmed in all the patients with PSIS and CP and in some patients with HP (37.5%), while it was excluded in all the patients with normal pituitary in MRI. CONCLUSIONS: It seems that in patients with PSIS and CP, the confirmation of persistent character of GHD needs no retesting, while in patients with normal MRI results, GHD diagnosis should be established with special attention.

[Neuroradiological investigation in patients with idiopathic growth hormone deficiency]. / Investigação neurorradiológica de pacientes com deficiência idiopática de hormônio do crescimento.

OBJECTIVE: The aim of this study was to analyze the type and frequency of cranial computed tomography and magnetic resonance imaging anomalies in patients with idiopathic growth hormone deficiency, and also to investigate the possible relationship between neuroradiological images and the presence of isolated growth hormone or multiple pituitary hormone deficiency. METHODS: Magnetic resonance and computed tomography images were obtained for 37 patients with idiopathic growth hormone deficiency. The patients were divided into two groups: patients with isolated growth hormone (group A) and patients with multiple pituitary hormone deficiencies (group B). RESULTS: Computed tomography was normal in 25 (68%), and abnormal in 12 (32%) patients. We observed empty sella in 50%, partially empty sella in 17% and anterior pituitary hypoplasia in 33% patients. MRI studies revealed normal findings in the hypothalamus-pituitary area in 17 (46%) and abnormal in 20 (54%) patients. We did not observed differences in the frequency of computed tomography alterations when groups A and B were compared (p = 0.55). With magnetic resonance imaging we observed, empty sella in 10%, partially empty sella in 15% and anterior pituitary hypoplasia in 75% patients. Among those patients whose magnetic resonance images were altered, the posterior lobe of the pituitary gland was identified in an abnormal position in 70%, and the hypophyseal stalk was thin or interrupted in 60%. The patients from group B presented a higher frequency of magnetic resonance imaging anomalies (90%) when compared to group A (10%), p = 0.03. There was disagreement between the two methods in 43% of cases, but we didn't observe a difference in the frequency of alterations when computed tomography was compared with magnetic resonance imaging (p = 0.06). CONCLUSIONS: The most frequent defects observed using magnetic resonance imaging are anterior pituitary hypoplasia and ectopic posterior pituitary lobe. The association of glandular hypoplasia with other magnetic resonance imaging abnormalities can suggest the presence of multiple anterior pituitary deficiencies.

Investigação neurorradiológica de pacientes com deficiência idiopática de hormônio do crescimento / Neuroradiological investigation in patients with idiopathic growth hormone deficiency

OBJETIVO: Avaliar a freqüência e os tipos de alterações observadas à tomografia computadorizada e ressonância magnética em pacientes com deficiência aparentemente idiopática de hormônio do crescimento e investigar a possível relação entre imagem neurorradiológica e presença de deficiência isolada e múltipla de hormônio do crescimento. MÉTODOS: Realizamos tomografia computadorizada e ressonância magnética da região hipotálamo-hipofisária em 37 pacientes com deficiência de hormônio do crescimento. Os pacientes foram divididos em deficiência isolada de hormônio do crescimento (Grupo A) e deficiência múltipla de hormônio do crescimento (Grupo B). RESULTADOS: A tomografia computadorizada foi normal em 25 (68 por cento) e alterada em 12 (32 por cento) pacientes. Observamos sela vazia em 50 por cento dos pacientes, parcialmente vazia em 17 por cento e hipoplasia hipofisária em 33 por cento. Não observamos diferença entre o percentual de alterações à tomografia computadorizada entre os Grupos A e B (p = 0,55). A ressonância magnética foi normal em 17 (46 por cento) e alterada em 20 (54 por cento) pacientes. A ressonância magnética, observamos sela vazia em 10 por cento, parcialmente vazia em 15 por cento e hipoplasia hipofisária em 75 por cento dos pacientes. Entre os pacientes com ressonância magnética alterada, 70 por cento apresentavam neuro-hipófise ectópica, e em 60 por cento a haste hipofisária estava afilada ou ausente. Os pacientes do Grupo B apresentaram maior percentual de alterações à ressonância magnética quando comparados aos do Grupo A (p = 0,03). Houve discordância entre tomografia computadorizada e ressonância magnética em 43 por cento; entretanto, não observamos diferença no percentual de anormalidades quando comparamos tomografia computadorizada e ressonância magnética (p = 0,06). CONCLUSAO: A hipoplasia hipofisária e a neuro-hipófise ectópica são as alterações mais encontradas em pacientes com deficiência de hormônio do crescimento. A associação de hipoplasia hipofisária com outras anormalidades observadas à ressonância magnética pode sugerir a presença de deficiência múltipla de hormônio do crescimento.

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.

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.

Obesidad: estimulación hipotalámica y regulación endócrina, metabólica y nutricional / Obesity: hypothalamic stimulation and endocrine, metabolic and nutritional regulation

Presenta una nueva metodología para mediciones del eje hipotálamo hiposófico adrenal(HHA), y sus diferentes reacciones al estrés en humanos. Esta técnica pone por primera vez estas mediciones en relación a variables de salud y enfermedad en algunos sistemas somáticos, en una población base; y sus resultados indican que el eje HHA no solo regula la secreción de cortisol y otras hormonas sino que es seguido por consecuencias para la salud y la enfermedad. También queda relevado el impacto del strés sobre variables endócrinas, antropométricas, metabólicas y hemodinámicas

Neuroendocrine dysplasia in mice lacking protein tyrosine phosphatase sigma.

Protein tyrosine phosphatase sigma (PTP-sigma, encoded by the Ptprs gene) is a member of the LAR subfamily of receptor-like protein tyrosine phosphatases that is highly expressed during mammalian embryonic development in the germinal cell layer lining the lateral ventricles of the developing brain, dorsal root ganglia, Rathke's pouch, olfactory epithelium, retina and developing lung and heart. On the basis of its expression and homology with the Drosophila melanogasterorthologues DPTP99 and DPTP100A (refs 5,6), which have roles in the targeting of axonal growth cones, we hypothesized that PTP-sigma may also have a modulating function in cell-cell interactions, as well as in axon guidance during mammalian embryogenesis. To investigate its function in vivo, we generated Ptprs-deficient mice. The resulting Ptprs-/-animals display retarded growth, increased neonatal mortality, hyposmia and hypofecundity. Anatomical and histological analyses showed a decrease in overall brain size with a severe depletion of luteinizing hormone-releasing hormone (LHRH)-immunoreactive cells in Ptprs-/- hypothalamus. Ptprs-/- mice have an enlarged intermediate pituitary lobe, but smaller anterior and posterior lobes. These results suggest that tyrosine phosphorylation-dependent signalling pathways regulated by PTP-sigma influence the proliferation and/or adhesiveness of various cell types in the developing hypothalamo-pituitary axis.

[Diabetes insipidus with a hypothalamo-hypophyseal morphologic anomaly during a pregnancy]. / Diabète insipide avec anomalie morphologique hypothalamo-hypophysaire au cours d'une grossesse.

BACKGROUND: Diabetes insipidus is uncommon in pregnancy. Despite physiological modifications in hydroelectrolytic balance during normal pregnancy, the capacity of the kidney to concentrate urine is preserved, partially due to lower vasopressin secretion. CASE REPORT: A young woman developed diabetes insipidus during the third trimester of normal pregnancy. The disease regressed totally after delivery. However, magnetic resonance imaging revealed a persistent expansive intrasellar image with a high-intensity signal. DISCUSSION: Onset of diabetes insipidus is usually rapidly progressive in pregnancy. Occurring generally during the third trimester in normal pregnancies, diabetes insipidus is generally well tolerated and responds to dDAVP, usually without pituitary abnormally, and regresses after delivery. Two types are distinguished: partially latent diabetes insipidus occurring during pregnancy and due to a central rather than nephrogenic origin; and excessive vasopressinase activity leading to diabetes insipidus usually associated with liver anomalies and high frequency of pre-eclampsia. During normal pregnancy, the size of the anterior pituitary increases and the normal high-intensity signal in the posterior pituitary seen on MRI usually regresses or disappears. In diabetes insipidus, the posterior pituitary hypersignal image generally disappears, reflecting reduced vasopressin storage. Few observations of diabetes insipidus occurring during pregnancy have been reported with morphological explorations. Most have described a "normal" aspect of the pituitary, specifically in the post partum period. In our patient, the weak vasopressin response to the end of water restriction at post partum when the diabetes insipidus symptoms had disappeared would suggest partial central diabetes insipidus revealed by pregnancy. Other pathologies involving this region could also be involved due to the unusual and persistent sellar image, with an expansive process showing a high intensity signal on MRI. An asymptomatic craniopharyngioma cyst was hypothesized and would be more compatible with the observed symptoms.

Ectrodactyly-ectodermal dysplasia-clefting syndrome and hypothalamo-pituitary insufficiency.

We report on 2 brothers with ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome and hypothalamo-pituitary insufficiency. Both had hypogonadotropic hypogonadism. One brother had partial TSH and prolactin deficiency, and the other had mild primary hypothyroidism, due most probably to irradiation therapy which he had undergone a few years earlier because of Hodgkin disease. The association of hypogonadotropic hypogonadism with EEC was reported once previously. Hypothalamopituitary dysfunction could be considered as yet another manifestation of EEC syndrome. This report reconfirms that EEC syndrome is a pleiotropic trait with reduced penetrance. Alternatively, we may be dealing with a (new) autosomal or X-linked recessive condition.

Hypothalamic-hypophyseal dysgenesis as a neuroimaging correlate of pituitary hormone deficiency in anophthalmia.

PURPOSE: To document the association of neurohypophyseal dysgenesis with hypopituitarism in a child with primary bilateral anophthalmia. METHODS: An infant with bilateral anophthalmia underwent magnetic resonance imaging and endocrinologic evaluation. RESULTS: Magnetic resonance imaging showed dysgenesis confined to the hypothalamus and hypophyseal stalk. Endocrinologic testing showed low serum cortisol and pituitary gonadotropin levels. CONCLUSION: Magnetic resonance imaging can help predict which children with anophthalmia will have endocrinologic deficiencies.

[Hypopituitarism caused by pituitary stalk transsection syndrome. Pathogenic hypotheses apropos of 7 cases]. / Hypopituitarisme par syndrome d'interruption de la tige infundibulaire. Hypothèses pathogéniques à propos de sept observations.

Magnetic resonance imaging (MRI) of the hypothalamic hypophyseal area was performed in seven children with multiple hypophyseal deficiency including growth hormone deficiency. In all cases stalk transection syndrome was found. In four cases MRI showed cranial or cerebral malformations. Perinatal asphyxia was found in only one child, and congenital hypopituitarism was present in two cases. The discussion focuses on the mechanisms that might be responsible for this syndrome. The malformation theory, while not taking into account all situations, seems to be the most appropriate, the reasons being the MRI finding and the patients' case histories.