Cushing’s Disease and Pregnancy: Case Report and Literature Review

ObjectiveTo describe a patient with untreated Cushing’s disease who had 2 spontaneous pregnancies that resulted in healthy babies on both occasions.MethodsWe present a case report with clinical, laboratory, and imaging data and discuss the literature pertaining to pregnancy in patients with Cushing’s syndrome.ResultsA 28-year-old woman came to our endocrinology clinic with a 1-year history of symptoms and signs of Cushing’s syndrome. An elevated 24-hour urinary cortisol excretion and an unsuppressed 1-mg overnight dexamethasone test confirmed the diagnosis. On her next visit, she reported a confirmed pregnancy, which ultimately resulted in the birth of a normal child. Further work-up subsequently showed 2 elevated 24-hour urinary cortisol values, loss of diurnal variation, and an elevated corticotropin level. There was lack of suppression on low-dose and high-dose overnight dexamethasone suppression tests. Magnetic resonance imaging of the pituitary showed normal findings. Inferior petrosal sinus sampling was recommended, but she declined the procedure. The patient returned 3 years later for reevaluation, at which time she reported the birth of another healthy child by cesarean delivery 10 months previously. There were no reported maternal or fetal complications. Examination at this visit revealed buccal pigmentation and proximal myopathy. Investigations showed increased 24-hour urinary cortisol excretion and serum corticotropin levels. Repeated magnetic resonance imaging disclosed a microadenoma on the right side of the pituitary. Unstimulated inferior petrosal sinus sampling showed a gradient to the right; thus, the presence of pituitary-dependent Cushing’s disease was confirmed.ConclusionOur case demonstrates that patients with pituitary-dependent Cushing’s disease are more likely to have spontaneous pregnancies with favorable outcomes than are patients with Cushing’s syndrome due to other causes. Our patient, despite having Cushing’s disease for more than 7 years, had 2 uneventful pregnancies that produced normal healthy children, without exacerbation of her disease during pregnancy. (Endocr Pract. 2007;13: 296-299)     

Graves’ Disease and Stiff-Person (Stiff-Man) Syndrome: Case Report and Literature Review

ObjectiveTo report an association between two autoimmune conditions, Graves’ disease and stiff-person (stiff-man) syndrome, and discuss the relevant literature.MethodsWe present a case of a 52-year-old white woman with stiff-person syndrome who also had Graves’ disease, discuss her management, and review the related literature. Pertinent published reports from 1950 through 2004 were researched with use of MEDLINE and PubMed, and cross-references to other articles were reviewed.ResultsA 52-year-old white woman presented with symptoms of hyperthyroidism due to Graves’ disease. Laboratory data were as follows: thyrotropin < 0.005 μIU/mL, thyroxine 11.1 μg/dL, free thyroxine index (FTI) 10.7, and triiodothyronine 170 ng/dL. Thyroid-stimulating immunoglobulins (TSI) and thyrotropin-binding inhibitory immunoglobulins (TBII) were positive at 1,986% and 82.5 U/L, respectively. The hyperthyroidism was treated with propranolol. She had a long-standing history of musculoskeletal complaints and was ultimately diagnosed with stiff-person syndrome. During her thyroid evaluation, she had severe neurologic deterioration that necessitated hospitalization and treatment with clonazepam, baclofen, intravenous immunoglobulin, and subsequently prednisone and azathioprine for appreciable symptomatic relief. The aggressive immunosuppression had a profound effect on her symptoms of hyperthyroidism, results of thyroid function tests, and thyrotropin receptor antibodies (TRABs). Thyrotropin was 0.52 μIU/mL, thyroxine was 6.9 μg/dL, and FTI was 5.7. The TSI decreased from 1,986% to 248%, and her TBII normalized from 82.5 U/L to < 5 U/L. She was clinically and biochemically euthyroid at last follow-up in May 2004.ConclusionThis case illustrates the association between TRAB-positive Graves’ disease and stiff-person syndrome and the improvement of Graves’ disease with immunosuppressive therapy. (Endocr Pract. 2005;11: 259-264)     

Unusual Clinical Course of Graves’ Thyrotoxicosis and Concomitant Sarcoidosis: Case Report and Review of Literature

ObjectiveTo report a case of Graves’ disease with concomitant sarcoidosis involving the thyroid gland.MethodsWe present the clinical, laboratory, imaging, and pathologic findings and describe the clinical course of a patient with Graves’ disease and sarcoidosis, who was unresponsive to propylthiouracil and radioiodine treatment.ResultsA 23-year-old woman presented with thyrotoxicosis and a large goiter. Laboratory studies and findings on thyroid uptake and scan were consistent with Graves’ disease. She was also found to have hilar lymph-adenopathy and hepatosplenomegaly. Despite treatment with antithyroid drugs and radioiodine therapy, her hyperthyroidism persisted. Surgical resection of the thyroid gland and 2 lymph nodes disclosed noncaseating granulomas, consistent with sarcoid.ConclusionAutoimmune endocrinopathies and, less commonly, thyroid autoimmune disease have been reported in patients with sarcoidosis. Similarities exist in the pathogenesis of these two conditions. Concomitant sarcoidosis in the thyroid gland in patients with Graves’ disease may contribute to the resistance to antithyroid drugs and radioiodine therapy. (Endocr Pract. 2007;13:159-163)     

Rotigotine Transdermal Patch in Parkinson’s Disease: A Systematic Review and Meta-Analysis

Background and Methods

The efficacy and safety of rotigotine transdermal patch in Parkinson’s disease (PD) were studied in some clinical trials. We performed a systematic review and meta-analysis of randomized controlled trials to evaluate the efficacy, tolerability, and safety of rotigotine transdermal patch versus placebo in PD.

Results

Six randomized controlled trials (1789 patients) were included in this meta-analysis. As compared with placebo, the use of rotigotine resulted in greater improvements in Unified Parkinson’s Disease Rating Scale activities of daily living score (weighted mean difference [WMD] –1.69, 95% confidence interval [CI] –2.18 to –1.19), motor score (WMD –3.86, 95% CI –4.86 to –2.86), and the activities of daily living and motor subtotal score (WMD –4.52, 95% CI –5.86 to –3.17). Rotigotine was associated with a significantly higher rate of withdrawals due to adverse events (relative risk [RR] 1.82, 95% CI 1.29–2.59), and higher rates of application site reactions (RR 2.92, 95% CI 2.29–3.72), vomiting (RR 5.18, 95% CI 2.25–11.93), and dyskinesia (RR 2.52, 95% CI 1.47–4.32) compared with placebo. No differences were found in the relative risks of headache, constipation, back pain, diarrhea, or serious adverse events.

Conclusions

Our meta-analysis showed that the use of rotigotine can reduce the symptoms of PD. However, rotigotine was also associated with a higher incidence of adverse events, especially application site reactions, compared with placebo.     

Disseminated Cryptococcosis in a Non-Hodgkin’s Lymphoma Patient with Late-Onset Neutropenia Following Rituximab-CHOP Chemotherapy: A Case Report and Literature Review

Rituximab-related late-onset neutropenia (R-LON) is an adverse event associated with rituximab. A 65-year-old woman presented with diffuse large B-cell lymphoma of the kidney without bone marrow involvement. She was treated with 4 cycles of CHOP chemotherapy consisting of doxorubicin, cyclophosphamide, vincristine, and prednisolone at 4-week intervals. Rituximab was also administrated of the second, third, fourth CHOP cycles. She developed a high fever of 38°C, nausea, and severe neutropenia following the four cycles of R-CHOP chemotherapy. Her leukocyte count was 160/μl without neutrophils. Initially, a blood and pleural fluid and cerebrospinal fluid cultures were positive for Cryptococcus neoformans. Once she became asymptomatic following treatment with fluconazole and neutropenia was recovered with lenograstim, she had neck stiffness and admitted soon. Cerebro-spinal fluid (CSF) culture was positive for Cryptococcus neoformans. Treatment with amphotericin B(AMPH-B) and flucytosine(5-FC) was initiated as diagnosis of cryptococcus meningitis. Lenograstim was administrated for 9 months, and amount of dose was 9,750 μg. Cryptococcosis with malignant lymphoma is rare disease, and previously 17 cases were reported. Of note, mortality of disseminated cryptococcosis with malignant lymphoma is 54%. The more and more rituximab is widely used; the cases of severe infection in R-LON may increase.     

Changes in Olfactory Bulb Volume in Parkinson’s Disease: A Systematic Review and Meta-Analysis

Objective

The changes in olfactory bulb (OB) volume in Parkinson’s disease (PD) patients have not yet been comprehensively evaluated. The purpose of this meta-analysis was to explore whether the OB volume was significantly different between PD patients and healthy controls.

Methods

PubMed and Embase were searched up to March 6, 2015 with no language restrictions. Two independent reviewers screened eligible studies and extracted data on study characteristics and OB volume. Additionally, a systematic review and meta-analysis using a random-effects model were conducted. Publication bias was determined by using funnel plots and Begg’s and Egger’s tests. Subgroup analyses were performed to assess possible sources of heterogeneity.

Results

Six original case-control studies of 216 PD patients and 175 healthy controls were analyzed. The pooled weighted mean difference (WMD) in the OB volume between the PD patients and the healthy participants was -8.071 for the right OB and -10.124 for the left OB; these values indicated a significant difference among PD patients compared with healthy controls. In addition, a significant difference in the lateralized OB volume was observed in PD patients, with a pooled WMD of 1.618; these results indicated a larger right OB volume than left OB volume in PD patients. In contrast, no difference in the lateralized OB volume was found in healthy controls. No statistical evidence of publication bias among studies was found based on Egger’s or Begg’s tests. Sensitivity analyses revealed that the results were consistent and robust.

Conclusions

Overall, both the left and the right OB volume were significantly smaller in PD patients than in healthy controls. However, significant heterogeneity and an insufficient number of studies underscore the need for further observational research.     

Epidemiology of Dengue Disease in Malaysia (2000–2012): A Systematic Literature Review

A literature survey and analysis was conducted to describe the epidemiology of dengue disease in Malaysia between 2000 and 2012. Published literature was searched for epidemiological studies of dengue disease, using specific search strategies for each electronic database; 237 relevant data sources were identified, 28 of which fulfilled the inclusion criteria. The epidemiology of dengue disease in Malaysia was characterized by a non-linear increase in the number of reported cases from 7,103 in 2000 to 46,171 in 2010, and a shift in the age range predominance from children toward adults. The overall increase in dengue disease was accompanied by a rise in the number, but not the proportion, of severe cases. The dominant circulating dengue virus serotypes changed continually over the decade and differed between states. Several gaps in epidemiological knowledge were identified; in particular, studies of regional differences, age-stratified seroprevalence, and hospital admissions.

Protocol registration

PROSPERO #CRD42012002293

Author summary

Dengue disease is a tropical and subtropical mosquito-borne viral illness, and is a major health concern in Malaysia. We conducted this literature analysis and review to describe the epidemiology of dengue disease in Malaysia between 2000 and 2012, to determine the impact of dengue disease on the Malaysian population, and to identify future research priorities. We used well-defined methods to search and identify relevant research, and data were selected according to predetermined inclusion criteria. This long-term review highlights the changing epidemiology of dengue fever in Malaysia. Although the overall incidence has stabilized in recent years, dengue disease remains a public health burden. Our review demonstrates an increased incidence of all forms of dengue disease and a predominantly adult age distribution. Changes in circulating dengue virus serotypes may have implications for the incidence and severity of dengue disease. Increasing levels of rainfall, humidity, temperature, and urbanization have been identified as risk factors for dengue disease outbreak. We believe that the recent improvements to the surveillance system in Malaysia should, if pursued over the next few years, greatly improve our understanding of the burden of dengue fever and enable us to monitor the impact of disease control measures in the future.     

Cognitive Functions and Stereopsis in Patients with Parkinson’s Disease and Alzheimer’s Disease Using 3-Dimensional Television: A Case Controlled Trial

Stereopsis or depth perception is an awareness of the distances of objects from the observer, and binocular disparity is a necessary component of recognizing objects through stereopsis. In the past studies, patients with neurodegenerative disease (Alzheimer dementia, AD; Parkinson’s disease IPD) have problems of stereopsis but they did not have actual stimulation of stereopsis. Therefore in this study, we used a 3-dimensional (3D) movie on 3D television (TV) for actual stereopsis stimulation. We propose research through analyzing differences between the three groups (AD, IPD, and Controls), and identified relations between the results from the Titmus Stereo Fly Test, and the 3D TV test. The study also looked into factors that affect the 3D TV test. Before allowing the patients to watch TV, we examined Titmus stereo Fly Test and cognitive test. We used the 3D version of a movie, of 17 minutes 1 second duration, and carried out a questionnaire about stereopsis. The scores of the stereopsis questionnaire were decreased in AD patients, compared with in IPD and controls, although they did not have any difference of Titmus Stereo Fly Test scores. In IPD patients, cognitive function (Montreal cognitive assessment, MoCA) scores were correlated with the scores of the stereopsis questionnaire. We could conclude that Titmus fly test could not distinguish between the three groups and cognitive dysfunction contributes to actual stereopsis perception in IPD patients. Therefore the 3D TV test of AD and IPD patients was more effective than Titmus fly test.     

Lipid Integration in Neurodegeneration: An Overview of Alzheimer’s Disease

Various types of lipids and their metabolic products associated with the biological membrane play a crucial role in signal transduction, modulation, and activation of receptors and as precursors of bioactive lipid mediators. Dysfunction in the lipid homeostasis in the brain could be a risk factor for the many types of neurodegenerative disorders, including Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. These neurodegenerative disorders are marked by extensive neuronal apoptosis, gliosis, and alteration in the differentiation, proliferation, and development of neurons. Sphingomyelin, a constituent of plasma membrane, as well as its primary metabolite ceramide acts as a potential lipid second messenger molecule linked with the modulation of various cellular signaling pathways. Excessive production of reactive oxygen species associated with enhanced oxidative stress has been implicated with these molecules and involved in the regulation of a variety of different neurodegenerative and neuroinflammatory disorders. Studies have shown that alterations in the levels of plasma lipid/cholesterol concentration may result to neurodegenerative diseases. Alteration in the levels of inflammatory cytokines and mediators in the brain has also been found to be implicated in the pathophysiology of neurodegenerative diseases. Although several mechanisms involved in neuronal apoptosis have been described, the molecular mechanisms underlying the correlation between lipid metabolism and the neurological deficits are not clearly understood. In the present review, an attempt has been made to provide detailed information about the association of lipids in neurodegeneration especially in Alzheimer’s disease.     

Memantine Monotherapy for Alzheimer’s Disease: A Systematic Review and Meta-Analysis

Background

We performed an updated meta-analysis of randomized placebo-controlled trials testing memantine monotherapy for patients with Alzheimer’s disease (AD).

Methods

The meta-analysis included randomized controlled trials of memantine monotherapy for AD, omitting those in which patients were also administered a cholinesterase inhibitor. Cognitive function, activities of daily living, behavioral disturbances, global function, stage of dementia, drug discontinuation rate, and individual side effects were compared between memantine monotherapy and placebo groups. The primary outcomes were cognitive function and behavioral disturbances; the others were secondary outcomes.

Results

Nine studies including 2433 patients that met the study’s inclusion criteria were identified. Memantine monotherapy significantly improved cognitive function [standardized mean difference (SMD)=−0.27, 95% confidence interval (CI)=−0.39 to −0.14, p=0.0001], behavioral disturbances (SMD=−0.12, 95% CI=−0.22 to −0.01, p=0.03), activities of daily living (SMD=−0.09, 95% CI=−0.19 to −0.00, p=0.05), global function assessment (SMD=−0.18, 95% CI=−0.27 to −0.09, p=0.0001), and stage of dementia (SMD=−0.23, 95% CI=−0.33 to −0.12, p=0.0001) scores. Memantine was superior to placebo in terms of discontinuation because of inefficacy [risk ratio (RR)=0.36, 95% CI=0.17¬ to 0.74, p=0.006, number needed to harm (NNH)=non significant]. Moreover, memantine was associated with less agitation compared with placebo (RR=0.68, 95% CI=0.49 to 0.94, p=0.02, NNH=non significant). There were no significant differences in the rate of discontinuation because of all causes, all adverse events, and individual side effects other than agitation between the memantine monotherapy and placebo groups.

Conclusions

Memantine monotherapy improved cognition, behavior, activities of daily living, global function, and stage of dementia and was well-tolerated by AD patients. However, the effect size in terms of efficacy outcomes was small and thus there is limited evidence of clinical benefit.     

Combined Hepatocellular–Cholangiocarcinoma with Fever of Unknown Origin: A Case Report and Review of Literature

Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC–CC) is a rare form of primary liver cancer (PLC). It is difficult to make a correct preoperative diagnosis of cHCC–CC because of the lack of special features of the disease. We here present a case of a 68-year-old man who presented with fluctuant fever, chills, and sweating and was eventually diagnosed as cHCC–CC after surgery. The tumor was 6.0 cm in diameter with distinct borders and no satellite lesions or lymph nodes were observed during macroscopic examination of the resection specimen. The fever resolved in the postoperative period till the 28th day after surgery, when the patient developed extensive abdominal metastases and died shortly after. More attention should be paid to the patient with PLC showing abnormal features such as FUO, normal range of tumor markers, atypical imaging, and less cirrhosis. Hepatic resection is the treatment of choice although with short-term outcomes.     

Gibberellin Biosynthesis in Plants and Fungi: A Case of Convergent Evolution?

As well as being phytohormones, gibberellins (GAs) are present in some fungi and bacteria. Indeed, GAs were first discovered in the fungus Gibberella fujikuroi, from which gibberellic acid (GA3) and other GAs are produced commercially. Although higher plants and the fungus produce structurally identical GAs, there are important differences in the pathways and enzymes involved. This has become particularly apparent with the identification of almost all of the genes for GA-biosynthesis in Arabidopsis thaliana and G. fujikuroi, following the sequencing of the Arabidopsis genome and the detection of a GA-biosynthesis gene cluster in the fungus. For example, 3b-hydroxylation occurs early in the pathway in G. fujikuroi and is catalyzed by a cytochrome P450 monooxygenase, whereas it is usually the final step in plants and is catalyzed by 2-oxoglutarate-dependent dioxygenases. Similarly, 20-oxidation is catalyzed by dioxygenases in plants and a cytochrome P450 in the fungus. Even where cytochrome P450s have equivalent functions in plants and Gibberella, they are unrelated in terms of amino acid sequence. These profound differences indicate that higher plants and fungi have evolved their complex biosynthetic pathways to GAs independently and not by horizontal gene transfer.     

Epidemiology of Dengue Disease in the Philippines (2000–2011): A Systematic Literature Review

This literature analysis describes the available dengue epidemiology data in the Philippines between 2000 and 2011. Of 253 relevant data sources identified, 34, including additional epidemiology data provided by the National Epidemiology Center, Department of Health, Philippines, were reviewed. There were 14 publications in peer reviewed journals, and 17 surveillance reports/sources, which provided variable information from the passive reporting system and show broad trends in dengue incidence, including age group predominance and disease severity. The peer reviewed studies focused on clinical severity of cases, some revealed data on circulating serotypes and genotypes and on the seroepidemiology of dengue including incidence rates for infection and apparent disease. Gaps in the data were identified, and include the absence incidence rates stratified by age, dengue serotype and genotype distribution, disease severity data, sex distribution data, and seroprevalence data.

Protocol registration

PROSPERO CRD42012002292     

PSYCHOSIS AND SYSTEMIC LUPUS ERYTHEMATOSUS—A Review of the Literature and Case Reports

In a review of the literature of the last 60 years concerning the association between psychosis and systemic lupus erythematosus, reports of 227 cases of this association were found. The average incidence of psychosis in the various series of systemic lupus erythematosus that were reviewed was 22 per cent. In only 25 per cent of the cases in which the information was given was the psychosis associated with steroid therapy.The psychiatric manifestations are variable and may be associated with a neurological disorder. Psychosis may antedate by many years other features of lupus. The psychosis due to lupus may respond to steroid therapy. Since systemic lupus erythematosus sometimes may be an important differential diagnosis of functional psychosis, appropriate diagnostic studies should be carried out in psychotic patients who have an accelerated sedimentation rate or positive serological test for syphilis without apparent reason.