Diagnosing and treating anterior pituitary hormone deficiency in pediatric patients.

Hypopituitarism, or the failure to secrete hormones produced by the anterior pituitary (adenohypophysis) and/or to release hormones from the posterior pituitary (neurohypophysis), can be congenital or acquired. When more than one pituitary hormone axis is impaired, the condition is known as combined pituitary hormone deficiency (CPHD). The deficiency may be primarily due to a hypothalamic or to a pituitary disorder, or concomitantly both, and has a negative impact on target organ function. This review focuses on the pathophysiology, diagnosis and management of anterior pituitary hormone deficiency in the pediatric age. Congenital hypopituitarism is generally due to genetic disorders and requires early medical attention. Exposure to toxicants or intrauterine infections should also be considered as potential etiologies. The molecular mechanisms underlying the fetal development of the hypothalamus and the pituitary are well characterized, and variants in the genes involved therein may explain the pathophysiology of congenital hypopituitarism: mutations in the genes expressed in the earliest stages are usually associated with syndromic forms whereas variants in genes involved in later stages of pituitary development result in non-syndromic forms with more specific hormone deficiencies. Tumors or lesions of the (peri)sellar region, cranial radiation therapy, traumatic brain injury and, more rarely, other inflammatory or infectious lesions represent the etiologies of acquired hypopituitarism. Hormone replacement is the general strategy, with critical periods of postnatal life requiring specific attention.

[A Pediatric Case of Xanthogranuloma in the Suprasellar Region Detected by a Severe Short Stature after 6 Years Growth Failure].

Here we report a case of a 12-year-old girl who was referred to our department because of marked short stature of more than -5 SD below the median. Although her growth failure began suddenly at 6 years of age, she never had an examination because she had no other symptoms. Brain MRI examination suggested a tumor in the suprasellar region, and endocrine examination revealed combined pituitery hormone deficiency due to the tumor. Before surgery, the supplementation with hydrocortisone and levothyroxine was initiated. The pathological diagnosis of the surgically removed tumor was xanthogranuloma. The pattern of her growth curve showed a growth failure with sudden onset, which is a typical pattern of short stature secondary to pituitary disfunction including growth hormone deficiency associated with brain tumors. This case suggests that growth failure could be the only symptom in pediatric cases with brain tumors. Improved awareness regarding the association of growth failure with brain tumors is needed for earlier diagnosis and treatment. Furthermore, the growth curves should be carefully evaluated in regular health examinations at school.

Alteration of ghrelin/obestatin ratio in adolescence with polycystic ovarian syndrome.

Ghrelin, an endoggenous for the growth hormone secretagogue receptor, has been shown to participate in the regulation of energy homeostasis and pituitary hormone secretion. Obestatin, encoded by the same gene as ghrelin, is described as a physiological opponent of ghrelin. Ghrelin and obestatin are altered in polycystic ovary syndrome (PCOS), which is characterized by insulin resistance and pituitary hormone secretion disorder. The aim of this study was to evaluate ghrelin/obestatin imbalance in relation to insulin resistance and pituitary hormone in adolescence with PCOS. This restrospective case-control study included 33 adolescence with PCOS and 38 control adolescence. Ghrelin and obestatin concentrations in serum were determined by RIA, and the serum fasting glucose and Insulin were determined by the glucose oxidase color method and INS-EASIA. The serum LH and FSH were measured by highly specific hemiluminescence immunoassays. We found that the serum ghrelin levels and ghrelin/obestatin ratio were significant lower in PCOS group than in control group, and the serum obestatin levels were significant higher in PCOS group than in control group. The ghrelin/obestatin ratios were negatively correlation with LH/FSH ratio and insulin resistant index in PCOS group. The findings of this study suggest that ghrelin/obestatin imbalance may play a role in pathogenesis of adolescent PCOS.

[Clinical characteristics of central diabetes insipidus: a retrospective analysis of 230 cases].

Objective: To evaluate the clinical characteristics and etiologies of central diabetes insipidus (CDI). Methods: The clinical data of 230 patients with CDI in the Department of Endocrinology of Chinese PLA General Hospital from 2008 June to 2014 December were collected and analyzed retrospectively. Results: The three most common causes of CDI were idiopathic CDI, lymphocytic hypophysitis and intracranial germ cell tumors. Among all the CDI, the idiopathic CDI accounted for 37.48%. There were significant differences in age onset and gender distribution among the different causes of CDI. The patients with intracranial germ cell tumors [age of onset(19.2±10.2) years] were younger than the other types of CDI. Germ cell tumors patients were more common in male, and lymphocytic hypophysitis patients were more common in female. The most frequent abnormality of anterior pituitary in patients with CDI was growth hormone deficiency, followed by hypogonadism, adrenal insufficiency and hypothyroidism. The dysfunction of thyroid axis and adrenal axis in patients with germ cell tumor was more common than those in patients with idiopathic and lymphocytic hypophysitis. Conclusions: The most common causes of central diabetes insipidus were idiopathic CDI, lymphocytic hypophysitis and intracranial germ cell tumors. There were differences in age of onset, gender distribution and abnormal production of anterior pituitary hormones among all causes of CDI patients.

Hypopituitarism.

Hypopituitarism refers to deficiency of one or more hormones produced by the anterior pituitary or released from the posterior pituitary. Hypopituitarism is associated with excess mortality, a key risk factor being cortisol deficiency due to adrenocorticotropic hormone (ACTH) deficiency. Onset can be acute or insidious, and the most common cause in adulthood is a pituitary adenoma, or treatment with pituitary surgery or radiotherapy. Hypopituitarism is diagnosed based on baseline blood sampling for thyroid stimulating hormone, gonadotropin, and prolactin deficiencies, whereas for ACTH, growth hormone, and antidiuretic hormone deficiency dynamic stimulation tests are usually needed. Repeated pituitary function assessment at regular intervals is needed for diagnosis of the predictable but slowly evolving forms of hypopituitarism. Replacement treatment exists in the form of thyroxine, hydrocortisone, sex steroids, growth hormone, and desmopressin. If onset is acute, cortisol deficiency should be replaced first. Modifications in replacement treatment are needed during the transition from paediatric to adult endocrine care, and during pregnancy.

The incidence of anterior pituitary hormone deficiencies in patients with microprolactinoma and idiopathic hyperprolactinaemia.

INTRODUCTION: Patients with microprolactinoma and idiopathic hyperprolactinaemia are not generally considered to be at risk of hypopituitarism and are therefore not routinely screened for this abnormality. In our clinical practice, we have observed a number of patients with nonmacroadenomatous hyperprolactinaemia to have anterior pituitary hormone deficits. AIMS: We aimed to establish the frequency and clinical significance of anterior pituitary hormone deficiencies, comparing patients with radiologically proven microprolactinomas and patients with idiopathic hyperprolactinaemia. STUDY DESIGN: We retrospectively examined the casenotes of 206 patients with hyperprolactinaemia from our centre. Patients who did not fit the profile of surgically naïve microprolactinoma or idiopathic hyperprolactinaemia or who had incomplete data were excluded, resulting in a study group of 56 patients. RESULTS: A total of 35 patients with MRI evidence of microprolactinoma were identified, three (8.57%) of whom had one or more anterior pituitary hormone deficiencies. A total of 21 patients with MRI-negative idiopathic hyperprolactinaemia were identified, nine (42%) of whom had one or more anterior pituitary hormone deficiencies (P<.01). Only one patient in the MRI-positive group had deficiency that required hormone replacement, in contrast six patients in the MRI-negative group had deficiencies that were of clinical significance and which required hormone replacement. SUMMARY: This study shows a clinically significant incidence of anterior pituitary hormone deficiency in patients with idiopathic hyperprolactinaemia. The authors recommend that dynamic pituitary assessment should be considered routinely in this patient group. A prospective study would be required to assess the underlying cause for these abnormalities, as they suggest a nontumour pan-pituitary process.

Clinical presentation and outcome of children with central diabetes insipidus associated with a self-limited or transient pituitary stalk thickening, diagnosed as infundibuloneurohypophysitis.

OBJECTIVE: Despite lymphocytic or autoimmune infundibuloneurohypophysitis (INH) is an increasingly recognized aetiology in children with central diabetes insipidus (CDI); clinical data on epidemiology (clinical evolution, predisposing factors, complications), diagnosis and management of this entity are limited and mostly based on published case reports. The aim of this study was to gain a broader insight in the natural history of this disease by analysing the clinical presentation, radiological pituitary stalk changes, associated autoimmunity and hormonal deficiencies in children with CDI and a self-limiting or transient stalk thickening (ST), diagnosed as autoimmune infundibuloneurohypophysitis, during the last 15 years in four Belgian university hospitals. DESIGN AND PATIENTS: The medical files of nine CDI patients with a ST at initial presentation and no signs of Langerhans cell histiocytosis or germinoma at presentation and/or during follow-up of more than 1.5 years were reviewed. RESULTS: Age at presentation ranged from 3 to 14 years. Two patients had a positive family history of autoimmunity. Three children presented with associated growth failure, two with nausea and one with long-standing headache. Median maximal diameter of the stalk was 4.6 mm (2.7-10 mm). Four patients had extra-pituitary brain anomalies, such as cysts. One patient had central hypothyroidism, and another had a partial growth hormone deficiency at diagnosis. Within a mean follow-up of 5.4 (1.5-15) years, stalk thickening remained unchanged in two patients, regressed in one and normalized in six children. CDI remained in all, while additional pituitary hormone deficiencies developed in only one patient. CONCLUSIONS: In this series of children INH with CDI as initial presentation, CDI was permanent and infrequently associated with anterior pituitary hormone deficiencies, despite a frequent association with nonstalk cerebral lesions.

Primary lymphocytic hypophysitis: Clinical characteristics and treatment of 50 cases in a single centre in China over 18 years.

OBJECTIVE: Primary lymphocytic hypophysitis (LYH) is rare, and it is often evaluated in a small case series. This study aimed to describe the diagnosis and treatment of primary LYH in a larger cohort. DESIGN: A retrospective study of the diagnosis and treatment of primary LYH was conducted at Peking Union Medical College Hospital from 1999 to 2016. PATIENTS: Fifty patients (28 histologically diagnosed and 22 clinically-diagnosed) were eligible for inclusion. MEASUREMENTS: Clinical, endocrine, pathological and imaging findings; therapies and outcomes were assessed. Ordinal logistic regression analysis was used to evaluate the association between the clinical parameters and outcomes (eg, improvements in pituitary function, regression of lesion size on MRI and disease recurrence). RESULTS: Central diabetes insipidus (CDI) (72.0%) was the most common endocrine dysfunction. Hypogonadotropic hypogonadism was the most frequently observed (60.0%) manifestation of anterior pituitary dysfunction; adrenal insufficiency was the third most common (26.0%) manifestation; and IGF-1 axis defects were the least frequent (22.0%). Thickening of the pituitary stalk was the most frequent (96.0%) imaging finding, and 78.0% of the patients exhibited both intrasellar and suprasellar expansion. Pharmacological dose of glucocorticoids was identified to be significantly associated with increased odds of anterior pituitary function improvement. No observed covariates were significantly associated with improvement of CDI and recurrence. CONCLUSION: The sequence of anterior pituitary deficiencies in Chinese primary LYH patients was atypical (LH/FSH>TSH>ACTH>IGF-1 axis deficiency). A pharmacological dose of glucocorticoids was significantly associated with the improved anterior pituitary insufficiency.

Relationship of each anterior pituitary hormone deficiency to the size of non-functioning pituitary adenoma in the hospitalized patients.

Non-functioning pituitary adenoma (NFPA) is often associated with hypopituitarism. Diagnosis of hypopituitarism is important because of its poor prognosis and low quality of life. Among hypopituitarism, it is difficult to diagnose secondary adrenocortical insufficiency and GH deficiency without hormone stimulation test. Therefore, the aim of our study was to identify patients with NFPA who require more careful endocrinological examination. We examined the relationship between NFPA size and the prevalence of each hypopituitarism or the response of each anterior pituitary hormone by insulin tolerance test, LHRH test and TRH test. We studied 63 patients with NFPA admitted for evaluation of pituitary function and surgical indication. They were classified three groups by tumor diameter. The prevalence of GH deficiency, male secondary hypogonadism, secondary hypothyroidism and PRL deficiency were higher in the group of larger tumor diameter (p<0.0001, p<0.05, p<0.05 and p<0.05, respectively). However, that of secondary adrenocortical insufficiency only tended to be higher (p=0.07). In the group with small NFPA (less than 20 mm), the prevalence of secondary adrenocortical insufficiency was 38% although those of GH deficiency, male secondary hypogonadism, secondary hypothyroidism and PRL deficiency were 0%, 0% and 8% and 9%, respectively. Anterior pituitary hormone responses except TSH had significantly negative correlation with tumor diameter (ACTH: r=-0.40, GH: r=-0.57, LH: r=-0.69, FSH: r=-0.46, PRL: r=-0.36). The results suggested physicians should proactively suspect GH deficiency, male secondary hypogonadism and secondary hypothyroidism in patients with larger NFPA. On the other hand, adrenocortical function should be examined even in patients with small NFPA.

Relationship between pituitary stalk (PS) visibility and the severity of hormone deficiencies: PS interruption syndrome revisited.

CONTEXT: Pituitary stalk interruption syndrome (PSIS) is a rare cause of combined pituitary hormone deficiency characterized by a triad shown in pituitary imaging, yet it has never been evaluated due to the visibility of pituitary stalk (PS) in imaging findings. OBJECTIVE: The major objective of the study was to systematically describe the disease including clinical presentations, imaging findings and to estimate the severity of anterior pituitary hormone deficiency based on the visibility of the PS. METHODS: This was a retrospective study including 74 adult patients with PSIS in Shanghai Clinical Center for Endocrine and Metabolic Diseases between January 2010 and June 2014. Sixty had invisible PS according to the findings on MRI, while the rest had a thin or intersected PS. Basic characteristics and hormonal status were compared. RESULTS: Of the 74 patients with PSIS, age at diagnosis was 25 (22-28) years. Absent pubertal development (97·3%) was the most common presenting symptom, followed by short stature. Insulin tolerance test (ITT) and gonadotrophin-releasing hormone (GnRH) stimulation test were used to evaluate the function of anterior pituitary. The prevalence of isolated deficiency in growth hormone (GH), gonadotrophins, corticotrophin and thyrotrophin were 100%, 97·2%, 88·2% and 70·3%, respectively. Although the ratio of each deficiency did not vary between patients with invisible PS and with visible PS, panhypopituitarism occurred significantly more frequent in patients with invisible PS. Patients with invisible PS had significantly lower levels of luteinizing hormone (LH), follicle stimulation hormone (FSH) and hormones from targeted glands including morning cortisol, 24-h urine free cortisol, free triiodothyronine (FT3), free thyroxine (FT4) and testosterone (T) in male than patients with visible PS. Moreover, patients with invisible PS had lower peak LH and FSH in GnRH stimulation test, and higher peak cortisol in ITT while peak GH remained unchanged between two groups. CONCLUSIONS: The prevalence of multiple anterior pituitary hormone deficiency was high in adult patients with PSIS. And more importantly, we found the visibility of PS shown on MRI might be an indication of the severity of PSIS.

Mutations in NFKB2 and potential genetic heterogeneity in patients with DAVID syndrome, having variable endocrine and immune deficiencies.

BACKGROUND: DAVID syndrome is a rare condition combining anterior pituitary hormone deficiency with common variable immunodeficiency. NFKB2 mutations have recently been identified in patients with ACTH and variable immunodeficiency. A similar mutation was previously found in Nfkb2 in the immunodeficient Lym1 mouse strain, but the effect of the mutation on endocrine function was not evaluated. METHODS: We ascertained six unrelated DAVID syndrome families. We performed whole exome and traditional Sanger sequencing to search for causal genes. Lym1 mice were examined for endocrine developmental anomalies. RESULTS: Mutations in the NFKB2 gene were identified in three of our families through whole exome sequencing, and in a fourth by direct Sanger sequencing. De novo origin of the mutations could be demonstrated in three of the families. All mutations lie near the C-terminus of the protein-coding region, near signals required for processing of NFΚB2 protein by the alternative pathway. Two of the probands had anatomical pituitary anomalies, and one had growth and thyroid hormone as well as ACTH deficiency; these findings have not been previously reported. Two children of one of the probands carried the mutation and have to date exhibited only an immune phenotype. No mutations were found near the C-terminus of NFKB2 in the remaining two probands; whole exome sequencing has been performed for one of these. Lym1 mice, carrying a similar Nfkb2 C-terminal mutation, showed normal pituitary anatomy and expression of proopiomelanocortin (POMC). CONCLUSIONS: We confirm previous findings that mutations near the C-terminus of NFKB2 cause combined endocrine and immunodeficiencies. De novo status of the mutations was confirmed in all cases for which both parents were available. The mutations are consistent with a dominant gain-of-function effect, generating an unprocessed NFKB2 super-repressor protein. We expand the potential phenotype of such NFKB2 mutations to include additional pituitary hormone deficiencies as well as anatomical pituitary anomalies. The lack of an observable endocrine phenotype in Lym1 mice suggests that the endocrine component of DAVID syndrome is either not due to a direct role of NFKB pathways on pituitary development, or else that human and mouse pituitary development differ in its requirements for NFKB pathway function.

A novel hook-shaped enhancement on contrast-enhanced sagittal magnetic resonance image in acute Sheehan's syndrome: a case report.

We report characteristic magnetic resonance (MR) image findings in a case of Sheehan's syndrome. A 37-year-old woman experienced complications of retained placenta and massive bleeding (3600 g) during delivery of a full-term baby. A pituitary function test demonstrated panhypopituitarism. MR image of the pituitary gland on postpartum day 10 revealed swelling of the anterior lobe. A hook-shaped enhancement was demonstrated on a sagittal image. The pituitary stalk, majority of the marginal zone of the anterior lobe, the anterior lobe just in front of the posterior lobe, and posterior lobe were well enhanced. In contrast, the central portion and the superior margin, just in front of the stalk insertion of the anterior lobe, were not enhanced. Anatomically, blood supply to these unenhanced portions of the anterior lobe was via the hypophyseal long portal vein and trabecular artery, which are tributaries of the superior hypophyseal artery that originate far from the internal carotid artery. Based on clinical history and MR image findings, the patient was diagnosed with Sheehan's syndrome and treated with hydrocortisone and levothyroxine. Follow-up MR image revealed marked atrophy of the anterior lobe. The characteristic hook-shaped enhancement in Sheehan's syndrome well reflected the vulnerability to massive bleeding based on the complex pituitary vasculature, which has not been reported previously. MR image with contrast enhancement is useful in the diagnosis of the acute phase of Sheehan's syndrome and in evaluating infarction of the anterior lobe.

Clinical characteristics of central diabetes insipidus in Taiwanese children.

BACKGROUND/PURPOSE: Data on the clinical features of children with central diabetes insipidus (CDI) are lacking in Taiwan. This study investigated the clinical manifestations and etiology of CDI in Taiwanese children. METHODS: From 1983 to 2012, 62 children with permanent diabetes insipidus were enrolled in the study. They were diagnosed at the Department of Pediatrics of National Taiwan University Hospital. Their medical records were thoroughly reviewed and their clinical symptoms and signs, laboratory data, and etiologies were analyzed. RESULTS: The patients' median age at diagnosis was 10 years and the median interval between initial manifestations and diagnosis was 0.5 years. The most common symptoms and signs were polyuria, polydipsia, nocturia, and growth retardation. Most patients had low urine osmolality and elevated plasma osmolality on diagnosis. Absence of a posterior pituitary hyperintense signal and thickening of the pituitary stalk were common findings on magnetic resonance imaging. Approximately 80% of the patients had anterior pituitary hormone deficiency and all patients had growth hormone deficiency. Approximately 60% of patients had intracranial lesions, the most common causes of which were germ cell tumor and Langerhans cell histiocytosis. Two patients were initially believed to have idiopathic CDI but intracranial lesions were detected during the follow-up period. CONCLUSION: Because a delayed diagnosis of CDI is common in Taiwanese children, a high index of suspicion is important. The underlying etiology of CDI in children may not initially be obvious. Long-term surveillance is therefore necessary, especially for the early detection of evolving treatable intracranial lesions.

Mutations in LHX3 result in a new syndrome revealed by combined pituitary hormone deficiency.

Combined pituitary hormone deficiency (CPHD) has been linked with rare abnormalities in genes encoding transcription factors necessary for pituitary development. We have isolated LHX3, a gene involved in a new syndrome, using a candidate-gene approach developed on the basis of documented pituitary abnormalities of a recessive lethal mutation in mice generated by targeted disruption of Lhx3 (ref. 2). LHX3, encoding a member of the LIM class of homeodomain proteins, consists of at least six exons located at 9q34. We identified a homozygous LHX3 defect in patients of two unrelated consanguineous families displaying a complete deficit in all but one (adrenocorticotropin) anterior pituitary hormone and a rigid cervical spine leading to limited head rotation. Two of these patients also displayed a severe pituitary hypoplasia, whereas one patient presented secondarily with an enlarged anterior pituitary. These LHX3 mutations consist of a missense mutation (Y116C) in the LIM2 domain at a phylogenetically conserved residue and an intragenic deletion predicting a severely truncated protein lacking the entire homeodomain. These data are consistent with function of LHX3 in the proper development of all anterior pituitary cell types, except corticotropes, and extrapituitary structures.

Deficient anterior pituitary with common variable immune deficiency (DAVID syndrome): a new case and literature reports.

Deficient anterior pituitary with common variable immune deficiency (DAVID) syndrome is a rare condition characterized by adrenocorticotropic hormone (ACTH) deficiency and primary hypogammaglobulinemia. It is due to heterozygous mutations of the nuclear factor kappa-B subunit 2 (NFKB2) gene. Only a few isolated cases have been reported since its first description by our team. Through the international multicenter GENHYPOPIT network, we identified a new case of DAVID syndrome. We then conducted an extensive review of the DAVID syndrome cases published from 2012 to 2022. A 7-year-old boy was diagnosed with symptomatic hypoglycemia revealing ACTH deficiency. Laboratory tests showed asymptomatic hypogammaglobulinemia. He harbored a heterozygous point mutation in NFKB2 gene (c.2600C > T, p.Ala867Val). His management included hydrocortisone replacement treatment, and he also received subcutaneous immunoglobulins during the Covid-19 pandemic. We analyzed 28 cases of DAVID syndrome with ACTH deficiency. ACTH deficiency was the only hormone deficiency in 79% of patients, but some patients harbored growth hormone (GH) and thyroid stimulating hormone (TSH) deficiencies. The first presenting symptoms were sinus/pulmonary infections (82%, mean age of 3 years) and alopecia (mean age of 4.7 years). ACTH deficiency was the third presenting condition (mean age at diagnosis of 8.6 years). All patients had hypogammaglobulinemia (decreased IgA and IgM levels), and 57% of patients had at least one autoimmune manifestation. Heterozygous mutations at the 3'end of the NFKB2 gene, coding for the C-terminal domain of the protein, were identified in all cases. Better knowledge of DAVID syndrome will help clinicians make an early diagnosis to avoid life-threatening complications.

Anterior hypopituitarism is rare and autoimmune disease is common in adults with idiopathic central diabetes insipidus.

OBJECTIVE: Central diabetes insipidus is a rare clinical condition with a heterogenous aetiology. Up to 40% of cases are classified as idiopathic, although many of these are thought to have an autoimmune basis. Published data have suggested that anterior hypopituitarism is common in childhood-onset idiopathic diabetes insipidus. We aimed to assess the incidence of anterior hypopituitarism in a cohort of adult patients with idiopathic diabetes insipidus. DESIGN AND PATIENTS: We performed a retrospective review of the databases of two pituitary investigation units. This identified 39 patients with idiopathic diabetes insipidus. All had undergone magnetic resonance imaging scanning and dynamic pituitary testing (either insulin tolerance testing or GHRH/arginine and short synacthen testing) to assess anterior pituitary function. RESULTS: One patient had partial growth hormone deficiency; no other anterior pituitary hormonal deficits were found. Thirty-three percent had at least one autoimmune disease in addition to central diabetes insipidus. CONCLUSIONS: Our data suggest that anterior hypopituitarism is rare in adult idiopathic diabetes insipidus. Routine screening of these patients for anterior hypopituitarism may not, therefore, be indicated. The significant prevalence of autoimmune disease in this cohort supports the hypothesis that idiopathic diabetes insipidus may have an autoimmune aetiology.

Long-term outcome of hypothalamic pituitary tumors in Langerhans cell histiocytosis.

BACKGROUND: Hypothalamic-pituitary (HP) disease is the most common CNS manifestation of Langerhans cell histiocytosis (LCH) frequently leading to diabetes insipidus (DI) and anterior pituitary hormone deficiencies (APD). On MRI, loss of the normal posterior pituitary signal and thickening of the pituitary stalk have been described, as well as neurodegenerative signal changes associated with neuropsychological disabilities in some patients. The influence of therapy on the long-term course of HP tumors and neurodegeneration (ND) is not well-understood. PROCEDURE: In this retrospective survey we focused on patients with LCH and HP disease with clinical and MRI data available at diagnosis of HP disease and at least three follow up investigations. We collected clinical and MRI follow-up information for central review and analysis. RESULTS: We identified 22 patients with HP tumors (HPT) registered at the LCH study center. Many different treatment regimens were applied for variable periods, with more than one regimen in most patients. Regression of the tumor was seen in the majority, but all patients had APD or ND on MRI at last follow up. In none of the patients APD and ND regressed or resolved. A deterioration of radiological ND was noted in 17 patients leading to overt clinical neuropsychological impairment in five. CONCLUSIONS: Patients with HPT appear to be at high risk to develop permanent neuroendocrine consequences. Coordinated studies for patients with LCH and HP disease including thorough MRI monitoring and neuropsychological tests are needed.

Oral manifestation associated with multiple pituitary hormone deficiency and ectopic neurohypophysis.

Multiple pituitary hormone deficiency (MPHD) is the diminished secretion of all the hormones produced in the anterior lobe of the pituitary gland. The oral manifestation of this condition includes delayed eruption and prolonged retention of primary teeth, delayed formation and eruption of permanent teeth, delay in development and growth of the jaws, tendency towards development of deep bite and enamel disturbances. This paper reports the case of an adolescent patient with MPHD. Clinical examination revealed partial ankylosis and prolonged retention ofprimary second molars, primary maxillary canines and deep bite. Dental treatment included extraction of all molars with prolonged retention preceded by the necessary medical care with clinical and radiographic follow-up afterwards. The patient was also referred to an orthodontist for orthodontic treatment. Patients' medical condition should always be investigated by clinicians when faced with cases of delayed tooth eruption and bone development.

Anterior pituitary dysfunction in moderate-to-severe chronic traumatic brain injury patients and the influence on functional outcome.

OBJECTIVE: The objective of this study is to determine the prevalence of anterior pituitary dysfunction in moderate-to-severe chronic traumatic brain injury (TBI) patients. The investigation of a relationship between pituitary hormonal status and body mass index (BMI) in TBI patients by observing changes in BMI was conducted as well as an assessment of whether there is a difference in functional outcome related to anterior pituitary dysfunction in TBI patients. METHODS: Forty-five TBI patients and 30 normal controls underwent a series of standard endocrine tests for anterior pituitary hormone function. It was studied whether changes in BMI correlated with anterior pituitary hormone levels. This study also compared changes in mini-mental state examination (K-MMSE) and functional independence measure (FIM) scores between patients in the hormone-sufficient and -deficient groups. RESULTS: Anterior pituitary dysfunction was found in 31.1% of TBI patients. Changes in BMI statistically correlated with IGF-1 and basal cortisol levels. A meaningful difference was found between the hormone-sufficient and -deficient groups in light of the K-MMSE and FIM score gains. CONCLUSIONS: These findings strongly suggest that patients who suffer head trauma should be routinely tested for anterior pituitary hormone deficiency.