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diabetes insipidus [keywords]
- Adipsic diabetes insipidus and venous thromboembolism (VTE): recommendations for addressing its hypercoagulability. [JOURNAL ARTICLE]
- Hormones (Athens) 2014 Jul; 13(3):420-423.
Adipsic diabetes insipidus (ADI) is a rare disorder. It can occur after transcranial surgery for craniopharyngeoma, suprasellar pituitary adenoma and anterior communicating artery aneurysm but also with head injury, toluene exposure and developmental disorders. It is often associated with significant hypothalamic dysfunction and complications like obesity, sleep apnea, thermoregulatory disorders, seizures and venous thromboembolism (VTE). Morbidity and mortality data have been reported as single case reports with only one large series suggesting increased risk for VTE in patients with ADI. Here we report a mini-series of four patients with ADI and VTE. Post-surgery immobilization, obesity, infection, with prolonged hospitalization, hemoconcentration and changes in coagulation which might be induced by inadequate hormone treatment in the postoperative period (high doses of glucocorticoids, sex steroids and DDAVP replacement) may all contribute to the pathogenesis of VTE. Thromboprophylactic treatment after pituitary surgery and during episodes of hypernatremia is therefore warranted.
- Ipilimumab-induced Hypophysitis: A Detailed Longitudinal Analysis in a Large Cohort of Patients with Metastatic Melanoma. [JOURNAL ARTICLE]
- J Clin Endocrinol Metab 2014 Jul 31.:jc20142306.
Context: Ipilimumab (Ipi) is approved by the FDA for treatment of unresectable or metastatic melanoma. Little is known about ipilimumab-induced hypophysitis (IH), an important treatment complication. Objective: To (i) examine the prevalence of IH, (ii) characterize the clinical course and treatment outcomes in IH, (iii) identify risk factors for the development of IH, and (iv) determine optimal strategies for the management of IH. Design: Retrospective review Setting: Tertiary referral center Subjects: 154 adult patients with metastatic melanoma evaluated at Massachusetts General Hospital (MGH) and treated with Ipi between March 2008 and December 2013. Intervention(s): Treatment with Ipi Main Outcome Measure(s): Pituitary magnetic resonance imaging (MRI), pituitary hormone assessment, patient survival. Results: IH was diagnosed in 17 patients (11%). Male gender (p = 0.02) and older age (p = 0.005), but not the cumulative dose of Ipi, were risk factors for IH. All patients with IH had anterior hypopituitarism (none had diabetes insipidus). Hypopituitarism was persistent in most individuals (76%). Diffuse pituitary enlargement was observed exclusively in all cases of IH and, upon retrospective review of MRI's, this finding preceded the clinical diagnosis of hypophysitis in 8 patients. Pituitary enlargement resolved rapidly (within 40 days in 7/7 patients). Median survival in patients with IH was 19.4 vs 8.8 months (p = 0.05) in the remainder of the cohort. Conclusions: Male gender and older age are risk factors for IH. Pituitary enlargement is sensitive and specific for IH in the appropriate setting, can precede the clinical diagnosis, and resolves rapidly. Anterior pituitary function recovery is uncommon. The incidence of hypophysitis may positively predict survival in melanoma patients treated with Ipi.
- Pituitary Dysfunction in Granulomatosis with Polyangiitis: The Mayo Clinic Experience. [JOURNAL ARTICLE]
- J Clin Endocrinol Metab 2014 Jul 31.:jc20141962.
Context: Pituitary involvement of granulomatosis with polyangiitis (GPA) has been described in case reports. The aim of this study was to describe the clinical presentation and outcomes of pituitary disease in patients with GPA evaluated at a tertiary referral center. Setting: Retrospective review of patients with GPA-related pituitary disease seen at Mayo Clinic, Rochester, MN. Patients: Six hundred thirty-seven patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis were followed at our institution from 1996 through 2011. Eight patients (1.3%) with clinically confirmed pituitary involvement formed the basis of this study. Interventions: None Measurements: Pituitary function was assessed with hormonal testing including TSH, free T4, cortisol, ACTH, prolactin, FSH, LH, estradiol, testosterone, IGF-1, and simultaneous serum and urine osmolalities. Results: Secondary hypogonadism and diabetes insipidus (DI) were the predominant manifestations of pituitary disease (87.5% and 75% of patients, respectively). All patients had abnormal pituitary imaging. A sellar mass with central cystic change and peripheral enhancement was the commonest imaging finding. Pituitary disease was managed with glucocorticoids in combination with cyclophosphamide or rituximab, achieving disease remission in all but one patient. However, permanent anterior pituitary dysfunction was noted in 63% of the patients. DI was more often reversible, with resolution in 66.7% of the patients. Conclusions: Pituitary involvement in GPA is rare, but it needs to be recognized to avoid unnecessary biopsies of sellar lesions encountered in the context of GPA and to minimize the risk of irreversible pituitary function loss by prompt implementation of definitive medical therapy for the vasculitis.
- Risk factors for polyuria in a cross-section of community psychiatric lithium-treated patients. [JOURNAL ARTICLE]
- Bipolar Disord 2014 Jul 29.
Polyuria increases the risk of dehydration and lithium toxicity in lithium-treated patients. Risk factors have been inconsistently described and the variance of this adverse effect remains poorly understood. This study aimed to establish independent risk factors for polyuria in a community, secondary-level lithium-treated sample of patients.This was a cross-sectional study of the lithium-treated patients attending a general adult and an old age psychiatry service. Participants completed a 24-hour urine collection. Urine volume and the presence of polyuria were the outcomes of interest. The relationship between outcome and the participant's demographic and clinical characteristics was explored with univariable and multivariable analysis.A total of 122 participants were included in the analysis, with 38% being diagnosed with polyuria. Female gender and increased body weight independently predicted the presence of polyuria (standardized regression coefficient 1.01 and 0.94, respectively; p = 0.002 and p = 0.003, respectively). Female gender and increased body weight, lithium dose, and duration of lithium treatment independently predicted higher 24-hour urine volumes (standardized regression coefficients 0.693, p < 0.0005; 0.791, p < 0.0005; 0.276, p = 0.043; 0.181, p = 0.034, respectively). Of three different weight metrics, lean body weight was the most predictive.Female gender and increased body weight explain part of the variance of this adverse effect. Both risk factors offer fresh insights into the pathophysiology of this potentially reversible and dangerous adverse effect of lithium treatment. Future research should focus on understanding the differences between the genders and between different body compositions in terms of lithium pharmacokinetics and pharmacodynamics.
- Sonic hedgehog mutations are not a common cause of congenital hypopituitarism in the absence of complex midline cerebral defects. [JOURNAL ARTICLE]
- Clin Endocrinol (Oxf) 2014 Jul 23.
Sonic Hedgehog (SHH) and GLI2, an obligatory mediator of SHH signal transduction, are holoprosencephaly (HPE)-associated genes essential in pituitary formation. GLI2 variants have been found in patients with congenital hypopituitarism without complex midline cerebral defects (MCD). However, data on the occurrence of SHH mutations in these patients are limited. We screened for SHH and GLI2 mutations or copy number variations (CNV) in patients with congenital hypopituitarism without MCD or with variable degrees of MCD.Detailed data on clinical, laboratory and neuroimaging findings of 115 patients presenting with congenital hypopituitarism without MCD, septo-optic dysplasia or HPE were analyzed. The SHH and GLI2 genes were directly sequenced and the presence of gene CNV was analyzed by multiplex ligation-dependent probe amplification (MLPA).Anterior pituitary deficiency was found in 74% and 53% of patients with SOD or HPE, respectively. Diabetes insipidus was common in patients with HPE (47%) but infrequent in patients with congenital hypopituitarism or SOD (7% and 8%, respectively). A single heterozygous nonsense SHH mutation (p.Tyr175Ter) was found in a patient presenting with hypopituitarism and alobar HPE. No other SHH mutations or CNV were found. Nine GLI2 variations (8 missense and 1 frameshift) including a homozygous and a compound heterozygous variation were found in patients with congenital hypopituitarism or SOD but not in HPE patients. No GLI2 CNV were found.SHH mutations or CNV are not a common cause of congenital hypopituitarism in patients without complex MCD. GLI2 variants are found in some patients with congenital hypopituitarism without complex MCD or SOD. However, functional analyses of these variants are needed to strengthen genotype-phenotype relationship. This article is protected by copyright. All rights reserved.
- A novel CISD2 intragenic deletion, optic neuropathy and platelet aggregation defect in Wolfram syndrome type 2. [JOURNAL ARTICLE]
- BMC Med Genet 2014 Jul 24; 15(1):88.
Wolfram Syndrome type 2 (WFS2) is considered a phenotypic and genotypic variant of WFS, whose minimal criteria for diagnosis are diabetes mellitus and optic atrophy. The disease gene for WFS2 is CISD2. The clinical phenotype of WFS2 differs from WFS1 for the absence of diabetes insipidus and psychiatric disorders, and for the presence of bleeding upper intestinal ulcers and defective platelet aggregation. After the first report of consanguineous Jordanian patients, no further cases of WFS2 have been reported worldwide. We describe the first Caucasian patient affected by WFS2.The proband was a 17 year-old girl. She presented diabetes mellitus, optic neuropathy, intestinal ulcers, sensorineural hearing loss, and defective platelet aggregation to ADP. Genetic testing showed a novel homozygous intragenic deletion of CISD2 in the proband. Her brother and parents carried the heterozygous mutation and were apparently healthy, although they showed subclinical defective platelet aggregation. Long runs of homozygosity analysis from SNP-array data did not show any degree of parental relationship, but the microsatellite analysis confirmed the hypothesis of a common ancestor.Our patient does not show optic atrophy, one of the main diagnostic criteria for WFS, but optic neuropathy. Since the "asymptomatic" optic atrophy described in Jordanian patients is not completely supported, we could suppose that the ocular pathology in Jordanian patients was probably optic neuropathy and not optic atrophy. Therefore, as optic atrophy is required as main diagnostic criteria of WFS, it might be that the so-called WFS2 could not be a subtype of WFS. In addition, we found an impaired aggregation to ADP and not to collagen as previously reported, thus it is possible that different experimental conditions or inter-patient variability can explain different results in platelet aggregation. Further clinical reports are necessary to better define the clinical spectrum of this syndrome and to re-evaluate its classification.
- A 23-year-old female with a mixed germ cell tumor of the pituitary infundibulum: the challenge of differentiating neoplasm from lymphocytic infundibuloneurohypophysitis-a case report and literature review. [Journal Article]
- Case Rep Endocrinol 2014.:129471.
The pathologic spectrum of diseases that infiltrate the pituitary infundibulum includes a broad variety of clinical entities. There are significant differences in the prevalence of these etiologies depending on the age of presentation. Lymphocytic infundibuloneurohypophysitis (LINH) predominates over other causes of infundibular disease in adults over age 21. Differentiating LINH from other causes of infundibular disease can be difficult because the various etiologies often have similar clinical presentations and radiologic imaging characteristics. We report the first case in an adult of a mixed germ cell tumor comprised of germinoma and embryonal cell carcinoma infiltrating the pituitary infundibulum. In our case, a 23-year-old female was initially misdiagnosed as having LINH. She presented with panhypopituitarism and diabetes insipidus, which is the most common initial presentation in both entities. The two diagnoses are difficult to distinguish based on MRI imaging, CSF findings, and histopathological examination. Our case demonstrates the need for close follow-up of patients with isolated lesions of the pituitary infundibulum and reinforces the need for biopsy of an infundibular lesion when progression of disease is demonstrated. In our case, biopsy with comprehensive immunohistochemical staining was the sole means of making a definitive diagnosis.
- Burkitt's lymphoma presenting with hypopituitarism: a case report and review of literature. [Journal Article]
- Endocrinol Diabetes Metab Case Rep 2014.:140029.
Hypopituitarism is a rare presentation of Burkitt's lymphoma (BL). The purpose of this report is to present a case of BL presenting with panhypopituitarism and to review other case reports of lymphoma presenting with pituitary dysfunction to highlight the distinguishing features of these cases from other benign aetiologies of pituitary dysfunction such as non-functioning pituitary adenomas. We reviewed a total of 11 cases of lymphoma presenting with pituitary dysfunction published from 1998 to 2013 including the present case. The demographics, clinical presentations, laboratory features, radiological findings, histological diagnosis, treatment administered and outcomes were described. Of the total number of patients, 45.5% of the cases had diffuse large B-cell lymphoma while 27.3% had BL. Anterior pituitary dysfunction was more common than posterior pituitary dysfunction at presentation. The other common associated presenting symptoms were painful ophthalmoplegia, cranial nerve palsies and constitutional symptoms. Hypothalamic-pituitary abnormalities were often demonstrated radiologically to be associated with cavernous sinus and/or stalk involvement. All patients who completed immunochemotherapy responded haematologically. Pituitary dysfunction also improved in most cases although the recovery tended to be partial. In conclusion, a high index of suspicion of underlying malignancy, such as lymphoma, should be present in patients presenting with acute pituitary dysfunction associated with painful ophthalmoplegia, rapidly evolving neurological features, radiological features atypical of a pituitary adenoma and constitutional symptoms. An early diagnosis is essential as prompt initiation of definitive therapy will induce disease remission and recovery of pituitary dysfunction.Hypopituitarism may be the presenting symptom of lymphoma in the absence of associated overt symptoms or signs of a haematological malignancy resulting in delay in diagnosis and institution of treatment.Pituitary dysfunction due to tumour infiltration has a greater tendency to involve the posterior pituitary and infundibulum resulting in diabetes insipidus and hyperprolactinaemia compared with a non-functioning pituitary adenoma.The common associated symptoms of hypopituitarism due to lymphoma infiltration of the hypothalamic-pituitary system include painful ophthalmoplegia, cranial nerve palsies and constitutional symptoms.Radiological abnormalities of the hypothalamic-pituitary region are usually present and often associated with cavernous sinus or stalk involvement.With early institution of definitive treatment, both haematological response and improvement of pituitary dysfunction are expected although the reversal of hypopituitarism tends to be partial and delayed.A high index of suspicion of underlying malignancy such as lymphoma should be present in patients presenting with acute pituitary dysfunction associated with painful ophthalmoplegia, radiological features atypical of pituitary adenomas and constitutional symptoms to enable early diagnosis and prompt initiation of definitive therapy.
- The role of Ki-67 in women with a resistant prolactinoma: A retrospective analysis in 199 hospitalized patients over a period of 5 years. [Journal Article]
- Pak J Pharm Sci 2014 Jul; 27(4 Suppl):1075-81.
Proliferation-associated antigen Ki-67 is used for the histological evaluation of different tumors. Few studies have been conducted on women with a resistant prolactinoma. To better define the characteristics and to evaluate the differences between patients with different Ki-67 labeling index (LI), a retrospective study was designed to recruit 199 females with a resistant prolactinoma. The patients were divided into two groups, patients with Ki-67 LI≥3% and patients with Ki-67 LI<3%. Tumors in the LI>3% group were also larger (p=0.043), had a higher rate of invasion (p=0.014), and were associated with more frequent polyuria and polydipsia (p=0.008) compared to the LI<3% group. The pre- and post-operative PRL levels in the LI>3% group remained significantly higher compared to patients with LI<3% (p<0.05). The incidences of transient diabetes insipidus and hyponatremia in the LI>3% group were also significantly higher (p=0.037, p=0.041). Additionally, the postoperative PRL normalization rate was lower in patients with LI>3% compared with patients with LI<3% (p=0.028). The recurrence rate in the LI>3% and LI<3% groups were 27.27% and 8.47%, respectively. In conclusion, high Ki-67 LI is predictive sign of a poor prognosis in women with resistant prolactinoma.