Endocrinological aspects of Langerhans cell histiocytosis complicated with diabetes insipidus

Langerhans cell histiocytosis (LCH) is a rare disorder and may be complicated with hypopituitarism and diabetes insipidus (DI) due to invasion of the hypothalamic-pituitary area. In this study, 10 patients with complete (4) and partial (6) type central DI were found among 125 LCH patients in our hospital records. The water deprivation test, followed by the pitressin test, was performed to confirm DI. Hypothalamic-pituitary endocrine function tests were carried out on these 10 patients at the initial diagnosis and during follow-up. All patients revealed growth hormone insufficiency in the insulin hypoglycemic tolerance test. Four patients had impairment of cortisol secretion, demonstrated by insulin hypoglycemic stimulating test results. Two patients had poor response in the thyrotropin releasing hormone stimulating test. Two patients had only partial responses in the luteinizing hormone releasing hormone test. Four patients had hyperprolactinemia. All patients underwent surgical treatment followed by chemotherapy and/or radiotherapy. One patient completely recovered from the endocrine disorder, 3 patients required smaller doses of desmopressin, and one patient had normal adrenal, thyroid, and gonadal function. Hypothalamic-pituitary disorders in LCH should not be neglected. Treatment of LCH can partially or completely reverse associated endocrine disorders. Therefore, endocrine studies and hormone replacement should be mandatory for patients with LCH.     

CNS sequelae in Langerhans cell histiocytosis: progressive spinocerebellar degeneration as a late manifestation of the disease

Central nervous system involvement in Langerhans cell histiocytosis (LCH), formerly known as histiocytosis X, is manifested mainly by diabetes insipidus reflecting local infiltration of Langerhans cells into the posterior pituitary or hypothalamus. We describe two patients with progressive spinocerebellar degeneration appearing 4 and 6 years after the initial diagnosis of LCH. No correlation was found between the clinical course of the disease or its treatment and the neurological impairment. An extensive search for metabolic, toxic, neoplastic, and hereditary etiologies for progressive cerebellar degeneration was negative.     

Central nervous system disease in Langerhans cell histiocytosis

Central nervous system (CNS) disease in Langerhans cell histiocytosis (LCH) is a poorly understood complication of yet unknown frequency. By far the most common manifestation is in the hypothalamic-pituitary system with diabetes insipidus as the leading sign, followed by other endocrinopathies and hypothalamic dysfunction. However, essentially all other parts of the CNS may be involved. On the one hand, space-occupying histiocytic infiltrates may lead to size- and site-depending symptoms, extending from adjacent bone lesions or arising from the meninges or choroid plexus. On the other hand, a progressive neurological deterioration can occur with mainly cerebellar-pontine symptoms. In this article, these clinical patterns are described in correlation with the morphology on MR imaging and histopathology. Further, the therapeutic strategies are reviewed critically, and guidelines for the management of patients with LCH-related CNS disease are presented.     

Persistent high MR signal of the posterior pituitary gland in central diabetes insipidus

We describe three cases of central diabetes insipidus, each with a different pathogenesis, in which unexpected hyperintensity of the posterior pituitary gland was seen on T1-weighted MR images obtained at the time of presentation. In the first case (idiopathic), the posterior pituitary signal persisted more than 10 years; in the second case (Langerhans cell histiocytosis), the signal disappeared within 3 months, despite early specific chemotherapy with etoposide; and in the third case (transient), the posterior signal disappeared within 1 year, but it was documented at the time of spontaneous reversal of polyuria and polydipsia.     

Effect of contrast concentration on abdominal enhancement in the rabbit: spiral computed tomography evaluation

BACKGROUND: Langerhans' cell histiocytosis (LCH) is an uncommon, poorly understood granulomatous disease, characterized by the idiopathic proliferation of Langerhan's cells or their marrow precursors. In 1985, the Philadelphia Work-shop adopted the term "Langerhans' cell histiocytosis" (LCH) to differentiate it from reactive and neoplastic causes of histiocytosis. METHODS: This study includes 73 pediatric patients diagnosed with this condition in Dublin, Ireland, and Nottingham, England, during a 34-year period (1959 to 1993). These patients are reviewed with respect to clinical presentation, difficulty with making a histological diagnosis, their management, and outcome. RESULTS: A total of 49 patients (67%) had head and neck involvement. Bony involvement was the most frequent sign, most frequently located in the skull. There were 11 deaths (15%) in this series, all associated with multisystem disease, and nine of these deaths were in children younger than 2 years of age. CONCLUSIONS: The role of otolaryngologists is important in the early and accurate evaluation, staging, and diagnosis of LCH. It may mimic more common diseases, such as otitis externa, acute mastoiditis, skin rash, gingivitis, or cervical lymphadenopathy. Patients with multisystem disease may be so ill at presentation that the head and neck lesions may be overlooked. The current management of LCH has become increasingly conservative, and in the 1990s, fewer cases are given chemotherapy or radiotherapy. The prognosis is very good for single-system disease and poor for multisystem disseminated disease with early onset.     

Pulmonary Wegener's granulomatosis: changes at follow-up CT

The objective of this study was to assess the reversibility of pulmonary lesions in Wegener's granulomatosis using serial CT. We reviewed the follow-up CT scans of ten treated patients with confirmed Wegener's granulomatosis. The delay between the first evaluation before treatment and the second, on patients in clinical and biological remission, ranged from 6 to 54 months (mean 20.5 months). Follow-up CT showed a decrease in the extent of disease in all cases. Lesions disappeared completely, without scarring, in 4 of 4 ground-glass opacities, 25 of 36 nodules, and 4 of 9 pulmonary consolidations; they disappeared with residual scarring in 8 of 8 masses, 3 of 9 pulmonary consolidations, and 2 of 36 nodules. The majority of lesions disappear without scarring. Residual fibrosis may follow the occurence of masses and pulmonary consolidation. Computed tomography permits assessment of cicatricial lesions.     

Bronchocentric granulomatosis and central diabetes insipidus successfully treated with corticosteroids

Bronchocentric granulomatosis (BCG) is a rare chronic granulomatous lung disease that leads to destruction of the airway walls. It has been observed in association with various conditions, but never, so far, been reported to involve the central nervous system. We report a case of histologically confirmed pulmonary bronchocentric granulomatosis temporally associated with a partial central diabetes insipidus (CDI). Although the pathological basis of the posterior pituitary gland involvement was not ascertained, the temporal association of bronchocentric granulomatosis and central diabetes insipidus, as well as the fact that corticosteroid treatment provided stable remission of both conditions after a 10 month follow-up, strongly suggest that central diabetes insipidus was aetiologically related to bronchocentric granulomatosis in this patient.     

Magnetic resonance imaging changes after stereotactic radiation therapy for childhood low grade astrocytoma

BACKGROUND: Stereotactic radiotherapy (SRT) is fractionated radiotherapy delivered under stereotactic guidance to produce highly focal and precise therapy. We studied the incidence of imaging changes that can mimic tumor progression after completion of SRT for childhood low grade astrocytoma. METHODS: Between June 1992 and September 1994, we prospectively treated 28 children with low grade astrocytomas with SRT. The patients ranged in age from 2 to 22 years (median: 10 yrs) and none had received prior radiation therapy or radiosurgery. Routine fractionation was employed (180-200 centigray[cGy]) to a total dose of 5220-6000 cGy over 5 to 6 weeks. All of the patients underwent initial and follow-up magnetic resonance imaging (MRI) according to protocol. RESULTS: Median clinical follow-up for the 28 patients was 24 months (range, 5-32 mos) with a median radiographic follow-up of 15 months (range, 3-26 mos). Fifteen patients had reduction in tumor size, one patient had stable disease. Twelve patients (43%) developed increased size of the lesion, increased signal intensity or enhancement, cysts or cavitations, and an increase in edema or mass effect on follow-up MRI. Most of these changes occurred between 9 and 12 months after the start of SRT and resolved or decreased by 15 to 21 months. All but one patient had normal or stable neurologic examinations. CONCLUSIONS: Treatment-related MRI changes are common after conventionally fractionated schedules using stereotactic radiation techniques for patients with low grade astrocytomas. These changes can be distinguished from tumor progression by their transient nature as well as the general absence of clinical symptoms.     

Prolonged response of multicentric reticulohistiocytosis to low dose methotrexate

We describe a case of multicentric reticulohistiocytosis complicated by central retinal vein thrombosis and trigeminal neuropathy. A variety of treatment modalities were tried in this patient. Both skin disease and arthritis responded to low dose methotrexate over 8 years of followup. Graduated compression gloves produced an excellent cosmetic improvement in the disfiguring skin lesions.     

Lumbar intervertebral disc herniation in children less than 16 years of age. Long-term follow-up study of surgically managed cases

STUDY DESIGN: In this retrospective study, the long-term clinical results of lumbar intervertebral disc herniation in children less than 16 years of age were reviewed. OBJECTIVES: To evaluate the effectiveness of surgical treatment including posterior discectomy, extraperitoneal anterolateral discectomy, and anterior interbody fusion for lumbar intervertebral disc herniation in children less than 16 years of age. SUMMARY OF BACKGROUND DATA: Although previous follow-up studies on surgically managed lumbar intervertebral disc herniation in children and adolescents generally reveal good outcomes, few reports have focused on the time course of clinical findings and the long-term results. METHODS: The outcome of subjective symptoms, clinical signs, and time-related change of the intervertebral disc space in 11 patients were evaluated with an average follow-up period of 9 years (range, 5-12 years). RESULTS: The posterior discectomy procedure relieved clinical symptoms quickly. In the case of central herniation with or without intervertebral instability, extraperitoneal anterolateral discectomy or anterior interbody fusion led to favorable long-term results. Clinical symptoms (lower back pain, leg pain) and neurologic disturbance disappeared within 3 months after surgery. Recovery of normal straight leg raising test results (tight hamstrings), however, required much more time than recovery of other symptoms. Narrowing of the intervertebral disc space progressed up to 3-6 months after discectomy, but then disc space widening occurred. CONCLUSIONS: Satisfactory long-term clinical results and early return to school life were obtained with each surgical procedure. It is important to aim toward an early return to school via surgical treatment.     

Aggressive fibrous dysplasia of the maxillary sinus

Fibrous dysplasia is usually a slowly progressive, benign disease that develops over several years and presents with deformity or mild symptomatology. Five of 34 patients (ages 4-21 years), who were subsequently diagnosed histologically as having fibrous dysplasia of the maxillary sinus, rapidly developed soft tissue masses of the malar region over a period of less than 4 months with accompanying pain (2 patients) and nasal obstruction and exophthalmos (2 patients). Each was clinically suspected of having a sarcoma; two had been thought to have an "osteofibrosarcoma" on initial biopsy at outside hospitals. After resection, all lesions developed regrowth. At histopathologic examination, both initial and recurrent masses proved to be typical fibrous dysplasia with spicules of woven bone in cellular, sometimes vascular, fibrous tissue. No malignant degeneration was found. On conventional radiography, aggressive fibrous dysplasia produced opacification and expansion of the maxillary sinus and apparent disruption of its wall with an associated soft tissue mass. Computed tomography (CT) demonstrated voluminous heterogeneous masses with "ground glass appearance", calcifications, areas of enhancement, low attenuation, cystic areas, and a thinned, sometimes interrupted, maxillary wall. Despite the aggressive clinical course for both initial and recurrent lesions, the CT findings of a "ground glass" mass with calcifications surrounded by a maxillary sinus wall, even if incomplete, can suggest the diagnosis of aggressive fibrous dysplasia.     

Localized eosinophilic granuloma (Langerhans' cell histiocytosis) of the orbital frontal bone

Four patients (aged 5, 8, 14, and 51 years at initial manifestation) with isolated eosinophilic granulomas of the orbital frontal bone displayed short symptomatic periods (two weeks to three months) and some combination of erythema of the lids, a soft, palpable anterior orbital mass, periorbital pain, and osteolytic bone lesions on roentgenography. The bone lesions roentgenographically exhibited irregular, serrated, and sclerotic margins, distinguishing them from the more oval appearance of dermoid cysts. Electron microscopy performed in one case disclosed the presence of Langerhans' granules in the cytoplasm of the histiocytes, indicating that the orbital disease is a mild form of "histiocytosis X" and a benign proliferation of a specific kind of histiocyte--the Langerhans' cell. On follow-up (two to 20 years), after incomplete curettage of two lesions coupled with low doses of postoperative radiotherapy, there was reconstitution of the bone defects, whereas more extensive surgery performed on the other two patients resulted in permanent but subclinical bone defects.     

The work of the epidemiological health laboratory of the Black Sea Fleet in World War II

Between October 1983 and December 1991, 14 patients (mean age 48.1 [range 38 to 68] years) presented with single, clear, cystic-appearing juxtafoveal lesions beneath the retina, with discrete borders measuring approximately 2 mm in diameter. All patients had vision of 6/7.5 or better, which did not deteriorate over a follow-up period of 3 to 91 (mean 18.1) months. Angiographically, the lesions showed relative homogeneous hyperfluorescence with very discrete margins, the angiographic appearance of serous retinal pigment epithelial detachment. We describe the clinical and angiographic appearance on presentation and in follow-up and discuss the probable relationship of these lesions to central serous choroidopathy.     

Radiological features of focal nodular hyperplasia of the liver in children

BACKGROUND: Focal nodular hyperplasia (FNH) is an unusual hepatic tumour in children and should be distinguished from other hepatic lesions. OBJECTIVE: To describe the imaging characteristics of FNH in children. MATERIALS AND METHODS: We examined five patients (three boys and two girls, mean age 9.4 years) with pathologically confirmed FNH. The diagnosis was obtained by tumour resection (n = 4) and percutaneous needle biopsy (n = 1). One patient with multiple FNHs showed recurrent lesions after tumour resection. All patients were studied with US (including colour and power Doppler US [n = 3]) and CT. Dynamic enhanced CT scans were available in three patients. MRI (n = 2) or coeliac angiography (n = 1) was performed in three patients. RESULTS: Seven of eight FNH lesions in five patients were demonstrated by imaging. The average size of the lesions was 6.5 cm. Six lesions detected on US showed variable echogenicity with a central hyperechoic scar (n = 2). On Doppler examination, central or peripheral hypervascular areas were seen (n = 3). Six lesions detected on contrast-enhanced CT showed high attenuation (n = 4) or iso-attenuation (n = 2). On early phase scans, all the lesions (n = 3) showed high attenuation. Irregular linear or ovoid central scars were detected in two patients on CT. MR demonstrated three lesions in two patients, one of which had not been detected by US or CT. A central low signal intensity scar (n = 1) was seen on T2-weighted MRI. Coeliac angiography performed in one patient showed a hypervascular mass with homogeneous staining. CONCLUSION: FNH in children shows a wide spectrum of imaging findings on various radiological examinations and the typical central scar was not always seen on imaging studies. Dynamic enhanced CT obtained in the early phase and colour Doppler studies may be helpful in the diagnosis of FNH by allowing characterisation of tumour vascularity. FNH should be included in the differential diagnosis of liver mass in children.     

Lymphocutaneous infection due to Scedosporium apiospermum

Lymphocytic hypophysitis is a rare disorder predominantly affecting females during the antepartum or postpartum period. It is characterized by destruction and lymphocytic infiltration of the pituitary gland, probably by an autoimmune process, leading to a pituitary mass lesion and/or various degrees of hypopituitarism. The lesion is usually confined to the adenohypophysis. Posterior pituitary gland or stalk involvement is rare, although patients presenting with diabetes insipidus have been reported. We describe a girl aged 13 years 9 months with lymphocytic hypophysitis who presented with diabetes insipidus and secondary amenorrhea. MRI of the brain revealed a 1 cm enhancing mass in the pituitary stalk. A biopsy of the mass by right pterional craniotomy showed lymphocytic infiltration without neoplastic cells or granuloma formation. To our knowledge, this is the youngest reported patient with a diagnosis of lymphocytic hypophysitis. In this case report, her clinical presentation is discussed along with a review of the literature. CONCLUSION: We present the first childhood case of lymphocytic hypophysitis which is an autoimmune inflammatory disorder of the pituitary gland. Although this is a rare condition in adults, it also needs to be considered in the pediatric population. Conservative management is preferred unless there are signs of increased intracranial pressure. Most importantly, close monitoring for multiple hormone deficiencies is indicated in this condition.     

Refractory angina despite patent coronary artery bypass grafts: treatment with transmyocardial laser revascularization and scintigraphic evidence of improved myocardial perfusion

Erdheim-Chester disease is a rare sporadic systemic histiocytic disease of unknown aetiology that affects multiple organ systems. The case records of all patients with Erdheim-Chester disease who had been seen at the Mayo Clinic between 1975 and 1996 were reviewed to assess the neurological manifestations of the disease. Two of 10 patients had neurological involvement. A 42 year old woman developed central diabetes insipidus and a progressive cerebellar syndrome. Brain MRI showed a lesion in the left pons with patchy gadolinium enhancement and T2 weighted signal abnormalities extending into both cerebellar peduncles and the medulla. Biopsy of the brainstem mass showed a xanthogranulomatous lesion. The second patient was a 53 year old man with retroperitoneal fibrosis secondary to xanthogranulomatous infiltration. Although he had no neurological symptoms and a normal neurological examination, MRI of the head showed multiple uniformly enhancing extra-axial masses along the dura of both convexities and the falx, and a mass in the left orbital apex. Both patients had the characteristic radiographic and bone scan findings of Erdheim-Chester disease. Review of the literature disclosed a wide variety of neurological manifestations in Erdheim-Chester disease. The most frequent CNS manifestations are diabetes insipidus, cerebellar syndromes, orbital lesions, and extra-axial masses involving the dura.     

Molecular biological studies on patients with nephrogenic diabetes insipidus]

Nephrogenic diabetes insipidus is a rare, mostly X-linked recessive disorder characterised by renal tubular resistance to the antidiuretic effect of arginine vasopressin. The gene responsible for the X-linked nephrogenic diabetes insipidus, the G-protein-coupled vasopressin V2-receptor, has been localised on the Xq28 region. In this study four patients were investigated with molecular genetic methods. Diagnosis was based on clinical symptoms and lack of increase of urinary osmolality after administration of the arginine vasopressin, or the synthetic vasopressin analogue DDAVP. Three different mutations (C112R, N317K, W323S) were found in three patients, while no mutation was detected in the fourth patient. Since earlier histiocytosis X has been diagnosed in this patient, this patient has probably central diabetes insipidus. Although the main symptoms of the disease can be found in all patients, there are significant differences in the seriousness of the symptoms as well as in some other symptoms. The explanations might be the different mutations in the V2-receptor gene and the various other genetic and environmental factors; these findings provide further evidence that X-linked nephrogen diabetes insipidus results from defects in the V2-receptor gene.     

Malignant prolactinoma: case report and review of the literature

BACKGROUND: Malignant prolactinomas are rare events. To date, only 14 patients with metastases in- or outside the central nervous system have been reported. CASE DESCRIPTION: We present a patient who developed a metastasis to the cauda equina, which is the first case documented with MRI. A giant prolactinoma in this 51-year-old man was partially removed by a transcranial approach. After radiotherapy and treatment with bromocriptine, the patient had a remission for 3 years. Thereafter, a sacral intraspinal tumor was diagnosed. Because of increasing prolactin levels not responding to bromocriptine and a radiologically suspected intrasellar tumor, we operated transsphenoidally first and found only fibrous tissue. We performed a sacral laminectomy and almost totally removed an intradural tumor. Histopathology and immunohistochemistry confirmed the diagnosis of a prolactinoma metastasis. The patient received radiotherapy and bromocriptine and has no evidence of recurrent tumor or metastases after a follow-up of 38 months, thus being the second reported patient with long-term remission of the disease. DISCUSSION: We review the literature on this topic and try to establish common features of the course of this rare malignant disease and the efficacy of therapy in the cases reported hitherto.     

Sertraline in the treatment of premature ejaculation: a double-blind placebo controlled study

Twelve children with obstetric paralysis were diagnosed as having a posterior dislocation of the humeral head. The diagnosis was suspected on clinical grounds and confirmed by computed tomography (CT) scans in all cases. All 12 patients were treated with open reduction via an anterior approach. The age range at the time of surgery was from 7 months to 7 years (average, 2 years and 3 months). All patients were immobilized in a shoulder spica for 6 weeks and a further 6 weeks in an orthosis. All patients were examined by CT scans in the postoperative period, which confirmed a satisfactory reduction in all cases. With a minimal follow-up of 12 months, there have been no redislocations. This article demonstrates that dislocation of the shoulder in association with obstetric paralysis is not rare, as previously described, and shows that once diagnosed, the dislocation can be satisfactorily treated by a single anterior open reduction of the shoulder.     

Rapid development of the new ambulances. From emergency transports to mobile emergency care

The role of chemotherapy (CHT) in the management of low-grade astrocytoma (LGA) is still unclear. Nineteen children with nonresectable symptomatic LGA were treated with carboplatin (CBDCA) and etoposide (E). There were 15 newly diagnosed cases and 4 were relapses; 6 of the children were under 5 years old. In all children radiological evaluation by CT scan and/or MRI was performed after four courses of CHT. We observed complete response (CR)+ minor response (MR) in 37% of these cases and an improvement in neurological symptoms in 63%. Radiological evaluation performed in 6 patients who received CHT for longer periods (8-12 courses) showed major responses (CR+PR) in 67%. Local radiotherapy (40 Gy) was administered after CHT in 14 cases, but in 3 of these radiotherapy was delayed for 2 years. Five patients did not receive radiotherapy. The overall survival was 58% after an average follow-up of 60 months. All patients with brain stem tumors died of progressive disease even though 3 of these had shown clinical improvement after chemotherapy. In conclusion, in the treatment of nonresectable symptomatic LGA, CHT with CBDCA associated with E can be used to postpone radiotherapy in young children and even to avoid radiotherapy in some cases.