Surgery versus conservative care for Rathke's cleft cyst.

BACKGROUND: Rathke's cleft cysts are benign cystic lesions of the sellar region, which may cause headache, pituitary deficiencies and visual disturbances from mass effect. Their management is not standardized yet. This study is about establishing a consensus for medical care of RCC. MATERIAL AND METHODS: We performed a retrospective observational study of all patients that were diagnosed or followed for RCC between 2008 and 2018 (11 years), in the neurosurgical and the adult endocrine departments of our institution. The study's average time length of follow-up is 72.9 months (from 2 to 385 months). RESULTS: The 57 included patients were divided into 2 groups: group A, which included 39 patients that were conservatively managed and group B, which included 18 surgically treated patients. Group A showed either an improvement or a spontaneous resolution of headaches in 56.1% of the cases (P<0.01); a resolution of hyperprolactinemia in 70% of the cases (P=0.21); and of hypogonadism, ACTH deficiency, growth hormone deficiency in 100% of the cases. There was no spontaneous improvement of visual disturbances (P<0.01) or diabetes insipidus (P=0.29) during follow-up. Regarding group B, surgery allowed improvement or complete resolution of headaches in 60% of the cases; visual troubles in 100% of the cases (P<0.01); and hyperprolactinemia in 100% of the cases. Pituitary deficiencies were not improved by surgery. CONCLUSIONS: This study offers guidance in decision-making regarding the management of RCC patients. Surgery is particularly suitable for treating visual disturbances caused by RCC. Regular follow-up is more appropriate than surgery concerning headaches, hyperprolactinemia, endocrine disruptions and diabetes insipidus.

Diabetes insipidus and syndrome of inappropriate antidiuresis (SIADH) after pituitary surgery: incidence and risk factors.

Electrolyte disorders are relatively frequent and potentially serious complications after pituitary surgery. Both DI (diabetes insipidus) and SIADH (syndrome of inappropriate antidiuresis) can complicate and prolong hospital and intensive care unit stay, and the latter may even be preventable. We aim to assess the incidence of both electrolyte disorders and their risk factors. From a prospective registry of patients who underwent endoscopic transnasal transsphenoidal surgery (TSS) for pituitary adenoma, patients with postoperative DI and SIADH were identified. Univariable and multivariable statistics were carried out to identify factors independently associated with the occurrence of either DI or SIADH. A total of 174 patients were included, of which 73 (42%) were female. Mean age was 54 years (range 20-88). During postoperative hospital stay, 13 (7.5%) patients presenting with DI and 11 (6.3%) with SIADH were identified. Patients who developed DI after surgery had significantly longer hospital stays (p = 0.022), as did those who developed SIADH (p = 0.002). Four (2.3%) patients were discharged with a diagnosis of persistent DI, and 2 (1.1%) with the diagnosis of SIADH. At the last follow-up, 5 (2.9%) patients presented with persistent DI, while none of the patients suffered from SIADH. Younger age (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.94-1.01, p = 0.166) and pituitary apoplexy (OR 2.69, 95% CI 0.53-10.65, p = 0.184) were weakly associated with the occurrence of DI. We identified younger age (OR 0.96, 95% CI 0.92-0.99, p = 0.045) and lower preoperative serum sodium (OR 0.83, 95% CI 0.71-0.95, p = 0.008) as independent risk factors for SIADH. Although we found a weak association among age, pituitary apoplexy, and the occurrence of DI, no independent predictor was identified for DI. For postoperative SIADH however, lower age and preoperative serum sodium were identified as significant predictors. None of these findings were sufficiently supported by preexisting literature. Both electrolyte disorders are exquisitely hard to predict preoperatively, and further research into their early detection and prevention is warranted.

Langerhans Cell Histiocytosis Involving Second Cervical Vertebra and the Hypothalamus and Pituitary in an Adult.

BACKGROUND: Adult-onset Langerhans cell histiocytosis (LCH) with simultaneous involvement of the high cervical spine and the hypothalamus is rare. CASE DESCRIPTION: We have reported a case of adult-onset LCH in the second cervical vertebra with bony destruction and subsequent diabetes insipidus due to simultaneous involvement of the hypothalamus and pituitary stalk. Magnetic resonance imaging of the hypothalamus and pituitary lesion and immunohistochemistry of the cervical lesion revealed LCH. Posterior fusion of the cervical spine (first, third, and fourth cervical vertebrae) was performed, followed by systemic chemotherapy. The cervical fusion was well maintained, and the patient achieved clinical remission. No new LCH lesion was found during the follow-up of >2 years. CONCLUSIONS: Patients with known LCH of the spine showing new symptoms of diabetes insipidus should be examined for infiltrating lesions of the pituitary stalk or hypothalamus. In cases of severe instability of the spine, surgical treatment should be performed. If multiple and systemic LCH lesions are found, systemic chemotherapy should be administered.

Truncating RAX Mutations: Anophthalmia, Hypopituitarism, Diabetes Insipidus, and Cleft Palate in Mice and Men.

CONTEXT: The transcription factor RAX is a paired-type homeoprotein that plays a critical role in eye and forebrain development of vertebrate species. RAX knockout mice have anophthalmia, cleft palate, and an abnormal hypothalamus and display perinatal lethality. In humans, homozygous or compound heterozygous RAX mutations have been reported to cause bilateral microphthalmia or anophthalmia without consistent associated features. Congenital hypopituitarism can be associated with various eye or craniofacial anomalies; however, the co-occurrence of congenital hypopituitarism, anophthalmia, cleft palate, and diabetes insipidus has been very rare. RESULTS: We report the case of a child with anophthalmia, congenital hypopituitarism, diabetes insipidus, and bilateral cleft lip and palate who had a homozygous frameshift truncating mutation c.266delC (p.Pro89Argfs*114) in exon 1 of the RAX gene. Rax knockout mice show loss of ventral forebrain structures, pituitary, and basosphenoid bone and palate and a misplaced anterior pituitary gland along the roof of the oral cavity. CONCLUSIONS: Our patient's phenotype was more severe than that reported in other patients. Although most of the previously reported patients with RAX mutations showed either a missense or some less severe mutation in at least one of their RAX alleles, our patient was homozygous for truncating mutations that would yield a severe, null protein phenotype. The severity of the genetic defect, the precise match between the knockout mouse and the patient's endocrine phenotypes, and the prominent roles of RAX in eye and pituitary development and diencephalic patterning suggest that the RAX null mutations could fully account for the observed phenotype.

Juvenile-onset gout and adipsic diabetes insipidus: A case report and literature review.

The prevalence of juvenile-onset gout has been increasing. Hereditary factors and secondary diseases should be considered in these patients. Adipsic diabetes insipidus (ADI) is characterized by arginine vasopressin (AVP) deficiency, which results in hypotonic polyuria, and dysfunction of thirst osmoreceptors, which results in failure to generate a thirst sensation in response to hypernatremia. We herein report a case of a boy with gouty arthritis, refractory hyperuricemia, prominent hypernatremia, a high creatinine concentration, and a history of surgery for a hypothalamic hamartoma. The patient was diagnosed with central diabetes insipidus after endocrine evaluation. Because he never had symptoms of thirst, the final diagnosis was corrected to ADI. This is the first report of gout due to chronic ADI in an adolescent. Volume contraction due to ADI might be one cause of hyperuricemia and renal impairment in such patients. Moreover, AVP deficiency might directly lead to low urate clearance due to the lack of vasopressin receptor 1 stimulation. Lack of polydipsia and polyuria may delay the diagnosis of ADI and lead to severe complications of a chronic hyperosmolar status. Sufficient and effective establishment of normovolemia is critical for these patients.

The Relationship Between Posterior Pituitary Bright Spot on Magnetic Resonance Imaging (MRI) and Postoperative Diabetes Insipidus for Pituitary Adenoma Patients.

BACKGROUND This study is to investigate the predictive value of posterior pituitary bright spot (PPBS) on magnetic resonance imaging (MRI) for postoperative diabetes insipidus (DI) in patients with pituitary adenoma. MATERIAL AND METHODS This was a retrospective study. In total, 65 patients with pituitary adenoma who underwent transsphenoidal surgery were enrolled. Before surgery, all patients had MRI examinations. The length of pituitary stalk and position of PPBS in T1WI sagittal and coronal sections were analyzed. The volume and height of the tumor was calculated in enhanced T1WI. Urine volume was monitored to analyze the clinical factors contributing to DI. RESULTS Among the 65 cases of pituitary adenoma, there were 54 cases of positive PPBS and 11 cases of negative PPBS. There were 32 cases of transient DI, and among these, 22 cases were positive PPBS and 10 cases were negative PPBS. However, there were 33 cases without DI, and among these, 32 cases were positive PPBS and one case was negative PPBS. The negative PPBS was significantly higher in cases with DI, compared with positive PPBS (P<0.05). Logistic regression showed that preoperative negative PPBS was an important predictor for postoperative DI (P<0.05). CONCLUSIONS Postoperative DI should be considered when there is negative preoperative PPBS on MRI. Also, severe pituitary stalk compression indicates higher risk of postoperative DI.

Delayed Occurrence of Diabetes Insipidus After Transsphenoidal Surgery with Radiologic Evaluation of the Pituitary Stalk on Magnetic Resonance Imaging.

BACKGROUND: Diabetes insipidus (DI) is a major complication of transsphenoidal surgery (TSS). DI usually occurs within a couple of days after TSS. Delayed occurrence of postoperative DI is rarely observed and its developing mechanisms remain unknown. METHODS: Six patients were identified as having postoperative delayed DI, which was defined as DI that first occurred 2 or more weeks after TSS. They consisted of 1 male and 5 females, and their mean age was 38.3 years (range, 10-76 years). Five patients were histologically diagnosed with Rathke cleft cyst (RCC), and one had RCC coexisting with prolactin-secreting adenoma. Sequential T1-weighted magnetic resonance imaging was evaluated for hyperintensity (HI) in the pituitary stalk and the posterior lobe, indicating the location of antidiuretic hormone. RESULTS: No patients had any DI before TSS. Delayed DI occurred 2 weeks to 3 months after TSS and persisted for 2 weeks to 5 months. T1-weighted magnetic resonance imaging showed that the HI in the posterior lobe became faint but did not disappear after DI occurrence, and their intensities increased with recovery from DI. In contrast, the HI in the pituitary stalk was found faintly preoperatively and turned clear postoperatively and decreased with recovery from DI. The morphologic patterns were dependent on DI duration. CONCLUSIONS: In the delayed occurrence of DI, it was suggested that preoperative antidiuretic hormone transport was mildly congested yet not completely blocked when DI manifested postoperatively. Gradual spreading of inflammation to the infundibulum after RCC removal was considered as 1 possible mechanism of this delayed DI development.

Diabetes insipidus is an unfavorable prognostic factor for response to glucocorticoids in patients with autoimmune hypophysitis.

INTRODUCTION: Autoimmune hypophysitis (AH) has a variable clinical presentation and natural history; likewise, its response to glucocorticoid therapy is often unpredictable. OBJECTIVE: To identify clinical and radiological findings associated with response to glucocorticoids. DESIGN AND METHODS: 12 consecutive patients with AH, evaluated from 2008 to 2016. AH was the exclusion diagnosis after ruling out other pituitary masses and secondary causes of hypophysitis. Mean follow-up time was 30 ± 27 months (range 12-96 months). RESULTS: MRI identified two main patterns of presentation: global enlargement of the pituitary gland or panhypophysitis (n = 4, PH), and pituitary stalk abnormality only, or infundibulo-neuro-hypophysitis (n = 8, INH). Multiple tropin defects were more common in PH (100%) than those in INH (28% P = 0.014), whereas diabetes insipidus was more common in INH (100%) than that in PH (50%; P = 0.028). All 4 PH and 4 out of 8 INH were treated with glucocorticoids. Pituitary volume significantly reduced in all PH patients (P = 0.012), defective anterior pituitary function recovered only in the two patients without diabetes insipidus (50%) and panhypopituitarism persisted, along with diabetes insipidus, in the remaining 2 (50%). In all INH patients, either treated or untreated, pituitary stalk diameter reduced (P = 0.008) but diabetes insipidus persisted in all. CONCLUSIONS: Glucocorticoid therapy may improve anterior pituitary function in a subset of patients but has no effect on restoring posterior pituitary function. Diabetes insipidus appears as a negative prognostic factor for response to glucocorticoids.

Spontaneous intermittent MRI changes of a pituitary stalk lesion causing diabetes insipidus and amenorrhea.

Lymphocytic infundibulo-neurohypophysitis is a rare disorder. We report the case of a 29 year-old woman with diabetes insipidus and amenorrhea, in whom the magnetic resonance imaging demonstration of a pituitary stalk lesion was intermittent. We suggest that, in patients with endocrine dysfunction and positivity of circulating antipituitary antibodies at high title, magnetic resonance imaging should be repeated after few months, if negative.

Prediction of postoperative diabetes insipidus using morphological hyperintensity patterns in the pituitary stalk on magnetic resonance imaging after transsphenoidal surgery for sellar tumors.

PURPOSE: Diabetes insipidus (DI) remains a complication of transsphenoidal surgery (TSS) for sellar and parasellar tumors. Antidiuretic hormone (ADH) appears as hyper intensity (HI) in the pituitary stalk and the posterior lobe of the pituitary gland on T1-weighted magnetic resonance (MR) imaging. Its disappearance from the posterior lobe occurs with DI, indicating a lack of ADH. The appearance of HI in the pituitary stalk indicates disturbances in ADH transport. METHODS: This retrospective study included 172 patients undergoing TSS for sellar tumors at our institute from 2006 to 2014. Sequential T1-weighted MR images without enhancement were evaluated for HI in the pituitary stalk and the posterior lobe to assess the localization of ADH before and at intervals after TSS. DI was assessed pre- and postoperatively. HI in the pituitary stalk showed the following morphology: (1) ovoid in the distal end of the pituitary stalk (group A), (2) linear in the distal part of the pituitary stalk (group B), (3) linear in the whole pituitary stalk (group C). RESULTS: Preoperative DI occurred in 6 patients (3.5 %) with no HI observed in the posterior lobe. Postoperative DI was transient in 82 patients (47.7 %), and permanent in 11 (6.4 %). One week after surgery, HI was absent in the posterior lobe in 74 patients (43.0 %), and present in the pituitary stalk in 99 patients (57.6 %); both were significantly correlated with postoperative DI (p < 0.001). The absence of HI in the posterior lobe (A, 48.9 %; B, 68.3 %; C, 92.3 %), persistence of DI (A, 3.7 days; B, 45.9 days; C, 20.5 months), and duration until HI recovery in the posterior lobe (A, 3.6 months; B, 6.8 months; C, 22.9 months) were greatest in group C, followed by group B, and then group A. Fourteen group A patients did not have postoperative DI despite having HI in the pituitary stalk and the posterior lobe. Four group C patients developed permanent DI with persistence HI in the pituitary stalk. CONCLUSION: HI in the pituitary stalk and its absence in the posterior lobe indicated postoperative DI, which was transient if HI was detected in the pituitary stalk. DI duration could be predicted by the length of HI in the pituitary stalk, which corresponded to the degree of ADH transport obstruction.

Pituitary stalk thickening: the role of an innovative MRI imaging analysis which may assist in determining clinical management.

CONTEXT: Disease processes that affect the pituitary stalk are broad; the diagnosis and management of these lesions remains unclear. OBJECTIVE: The aim was to assess the clinical, biochemical and histopathological characteristics of pituitary stalk lesions and their association with specific MRI features in order to provide diagnostic and prognostic guidance. DESIGN AND METHODS: Retrospective observational study of 36 patients (mean age 37years, range: 4-83) with pituitary stalk thickening evaluated at a university hospital in Oxford, UK, 2007-2015. We reviewed morphology, signal intensity, enhancement and texture appearance at MRI (evaluated with the ImageJ programme), along with clinical, biochemical, histopathological and long-term follow-up data. RESULTS: Diagnosis was considered certain for 22 patients: 46% neoplastic, 32% inflammatory and 22% congenital lesions. In the remaining 14 patients, a diagnosis of a non-neoplastic disorder was assumed on the basis of long-term follow-up (mean 41.3months, range: 12-84). Diabetes insipidus and headache were common features in 47 and 42% at presentation, with secondary hypogonadism the most frequent anterior pituitary defect. Neoplasia was suggested on size criteria or progression with 30% sensitivity. However, textural analysis of MRI scans revealed a significant correlation between the tumour pathology and pituitary stalk heterogeneity in pre- and post-gadolinium T1-weighted images (sensitivity: 88.9%, specificity: 91.7%). CONCLUSIONS: New techniques of MRI imaging analysis may identify clinically significant neoplastic lesions, thus directing future therapy. We propose possible textural heterogeneity criteria of the pituitary stalk on pre- and post-gadolinium T1 images with the aim of differentiating between neoplastic and non-neoplastic lesions with a high degree of accuracy.

A very rare entity of diabetes insipidus associated with Edwards syndrome.

Edwards syndrome is the second most commonly seen trisomy. It was first described by John Hamilton Edwards in 1960. Although most cases result in termination or foetal loss, live births have been documented in 5%. Edwards syndrome is characterized by multisystem anomalies, of which holoprosencephaly (HPE) is observed in 4-8% of cases. The clinical findings correspond to the degree of HPE malformation. Convulsions and endocrinopathies are among the severe clinical findings. The most common endocrinopathies are central diabetes insipidus (DI), hypothyroidism, hypocortisolism and growth hormone deficiency. The coexistence of holoproencephaly and DI in Edwards syndrome was discussed under the light of literature.

Predictors of neoplastic disease in children with isolated pituitary stalk thickening.

BACKGROUND: The significance of pituitary stalk thickening (PST) on magnetic resonance imaging (MRI) is often unclear. We evaluated presenting symptoms, MRI findings, clinical course, and outcome predictors of patients with PST. PROCEDURE: We used a computerized search of the medical record from 1995 to 2008 to identify patients with PST without pituitary mass on MRI. Baseline and follow-up MRIs were reviewed in a blinded fashion. Relevant clinical data were abstracted. RESULTS: 69 patients with reported PST and adequate imaging for review were identified; 42 met study criteria. Median age at first abnormal MRI was 13.6 years (range: 0.8-19.7); 43% were male. Median follow-up was 3.4 years (range 0-12.8). Patients with diabetes insipidus (DI) were significantly more likely to have a neoplastic process than those without (P = 0.0008). Of 16 patients with DI, 8 (50%) had a neoplastic process, including germ cell tumor (n = 4), Langerhans cell histiocytosis (n = 3), and lymphoma (n = 1). Among patients with DI, 7 (44%) also developed anterior pituitary hormone dysfunction (APD), either at presentation or on pre-biopsy follow-up, including 6/8 patients with stalk neoplasm and only 1/8 patients with non-neoplastic PST (P = 0.04). Twenty-six patients presented without DI; none was found to have neoplasm of the stalk except one patient with craniopharyngioma. Progression of PST on follow-up imaging was significantly associated with a subsequent neoplastic diagnosis (P = 0.04). CONCLUSION: Patients with PST without DI are unlikely to have a neoplastic process. Among patients with DI, APD or progressive stalk increase over time are predictive of neoplasia.

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.

Altered cerebral glucose metabolism in an animal model of diabetes insipidus: a micro-PET study.

The Brattleboro rat is an animal model of genetically induced central diabetes insipidus. These rats show cognitive and behavioral disorders, but no neurodegenerative disease has been observed. We studied brain glucose uptake, a marker of neuronal activity, in 6 Brattleboro rats, in comparison with 6 matched Long-Evans (LE) control rats. A group of 3 Brattleboro rats and 3 Long-Evans rats was studied in vivo and another group of animals was studied ex vivo. In vivo studies were performed using fluorodeoxyglucose labeled with fluorine 18 ((18)F-FDG) and a dedicated small-animal PET device. At 30 min and 60 min p.i., (18)F-FDG uptake was significantly higher in the frontal cortex, striatum, thalamus and cerebellum of Brattleboro rats than in LE rats when measured by PET in vivo (p<0.05), but only a trend towards higher values was found ex vivo. Our results show for the first time that brain glucose metabolism is modified in Brattleboro rats. This altered brain glucose metabolism in Brattleboro rats may be related to the observed cognitive and behavioral disorders. Functional analyses of brain metabolism are promising to investigate cognitive behavioral disturbances observed in Brattleboro rats and their link to diabetes insipidus.

Vector analysis correlating bullet trajectory to outcome after civilian through-and-through gunshot wound to the head: using imaging cues to predict fatal outcome.

OBJECTIVE: We identify radiographic imaging similarities found on head computed tomographic (CT) scans of patients with through-and-through gunshot wounds to the head with fatal outcomes. METHODS: A retrospective analysis was conducted over an 18-month period from June 2001 through December 2002. Two hundred seventeen gunshot wound patients were evaluated. Exclusion criteria included any patient with cardiopulmonary injury and instability, airway compromise, or extracranial injuries affecting prognosis. Thirty-seven patients with isolated gunshot wounds to the head were included, 10 of which were fatal. Vital signs, examination results, Glasgow coma scale (GCS) score, intracranial pressure monitoring, surgical data, days in the intensive care unit, and CT scan appearance were collected. A Cartesian xyz coordinate system was created centered on the dorsum sella. Bullet pathways on CT scans were plotted and graphed onto a standardized magnetic resonance imaging scan. RESULTS: Ten patients progressed to brain death. GCS score and pupil irregularity were associated with fatal outcome (P < 0.0001). CT scans showed that brain shift was more common in survivors. Seventy percent of nonsurvivors had minimal brain shift. A tram-track sign on CT scans correlated with fatal outcome (P = 0.005). Vector analysis of nonsurvivors showed an area of the brain approximately 4 cm above the dorsum sella that, when penetrated through the midline, led to brain death (P = 0.0006). This zone was coined the zona fatalis. CONCLUSION: We confirm that GCS score and diabetes insipidus correlated with fatal outcome. In the setting of low-velocity gunshot wounds, fatal outcome and low GCS score were associated with a tram-track sign on CT scans. Bullet passage through a particular supra-dorsum sellar transventricular zone was associated with fatal outcome.