Gynecomastia as a presenting symptom of Graves' disease in a 49-year-old man.

SUMMARY: Gynecomastia is a symptom with a potential high disease burden. It has a variety of underlying causes, such as malignant, drug-related or hormonal. The presence of gynecomastia can be explained in thyrotoxicosis due to a concomitant disbalance of sex hormones. Interestingly, it rarely is the presenting symptom of Graves' disease. A 49-year-old man presented to our outpatient clinic with right-sided gynecomastia. After thorough history taking, more symptoms of thyrotoxicosis were present. Treatment was started with thiamazole and later levothyroxine. Three months after this treatment the gynecomastia and other symptoms resolved completely. A disbalance of sex hormones due to an increased expression of the protein sex hormone-binding globulin (SHBG) caused by thyrotoxicosis could result in gynecomastia. In vitro and in vivo research in mice suggest that the pathophysiology of thyrotoxicosis-associated gynecomastia is due to upregulation of hepatocyte nuclear factor-4α (HNF4A) in liver cells. Subsequent increase of SHBG results in a decrease of free testosterone levels. LEARNING POINTS: Gynecomastia is a common finding (up to almost 40%) on physical examination in patients with hyperthyroidism. In gynecomastia, thyroid function tests should be examined on initial presentation because of the relative simple treatment. The pathophysiology of thyrotoxicosis-associated gynecomastia is well understood by a sex-hormonal disbalance due to an increased expression of SHBG. Due to the well explainable pathophysiology, reduction of symptoms can be expected after treatment. The underlying mechanism of an increased expression of SHBG is not well understood. However, in vitro and in vivo research in mice suggests that thyrotoxicosis causes an increased expression of HNF4A in liver cells. Thus, upregulating the expression of SHBG. Interestingly, HNF4A is suspected to play an important role in MODY. Future research will clarify the importance of this gene and might open up new insights for therapy.

Cytomegalovirus-associated thrombosis.

Cytomegalovirus (CMV) infections are often asymptomatic, but symptoms can range from a mononucleosis-like syndrome to a severe, disseminated infection in immunocompromised patients. We present two cases of immunocompetent patients with acute CMV infection directly followed by portal vein thrombosis in one and pulmonary embolism in the other patient. Thromboembolism may be a severe complication of acute CMV infection, with possible therapeutic implications.

Shared decision-making and providing information among newly diagnosed patients with hematological malignancies and their informal caregivers: Not "one-size-fits-all".

OBJECTIVE: To optimize personalized medicine for patients with hematological malignancies (HM), we find that knowledge on patient preferences with regard to information provision and shared decision-making (SDM) is of the utmost importance. The aim of this study was to investigate the SDM preference and the satisfaction with and need for information among newly diagnosed HM patients and their informal caregivers, in relation to sociodemographic and clinical factors, cognitive coping style, and health related quality of life. METHODS: Newly diagnosed patients and their caregivers were asked to complete the Hematology Information Needs Questionnaire, the Information Satisfaction Questionnaire, and the Threatening Medical Situations Inventory. Medical records were consulted to retrieve sociodemographic and clinical factors and comorbidity by means of the ACE-27. RESULTS: Questionnaires were completed by 138 patients and 95 caregivers. Shared decision-making was preferred by the majority of patients (75%) and caregivers (88%), especially patients treated with curative intent (OR = 2.7, P = .041), and patients (OR = 1.2, P < .001) and caregivers (OR = 1.2, P = .001) with a higher monitoring cognitive coping style (MCCS). Among patients, total need for information was related to MCCS (P = .012), and need for specific information was related to MCCS and several clinical factors. Importantly, dissatisfaction with the information they received was reported by a third of the patients and caregivers, especially patients who wanted SDM (χ2  = 7.3, P = .007), and patients with a higher MCCS (OR = 0.94, P = .038). CONCLUSION: The majority of HM patients want to be involved in SDM, but the received information is not sufficient. Patient-tailored information is urgently needed, to improve SDM.

Effect of vitamin D supplementation on health status in non-vitamin D deficient people with type 2 diabetes mellitus.

OBJECTIVE: Increased levels of depressive symptoms, fatigue or pain (all dimensions of reduced health-related quality of life (HRQOL)) are common in people with type 2 diabetes mellitus (DM). Earlier studies have reported associations between low vitamin D status and fatigue and depressive symptoms. The aim of the present study was to examine the effects of vitamin D supplementation on dimensions of HRQOL in people with type 2 DM. DESIGN: Randomised, double-blind, placebo-controlled trial. METHODS: The effect of monthly cholecalciferol 50,000 IU vs placebo on HRQOL was assessed in 275 adults with type 2 DM derived from general practices. HRQOL at baseline and after six months using the Short Form 36 Health Survey (SF-36) was collected. Linear regression analyses were used to compare the change in HRQOL over time between the vitamin D and placebo group. RESULTS: 187/275 (68%) completed baseline and follow-up SF-36 and were included in the analysis. Median serum 25-hydroxyvitamin D almost doubled in the intervention group compared to that in the placebo group (58.5-106.0 nmol/L vs 60.0-61.5 nmol/L, respectively). A small significant difference (adjusted B: -8.90; 95% CI: -17.16 to -0.65) between both groups was seen concerning the SF-36 domain role limitations due to physical problems in disadvantage of the vitamin D group. CONCLUSIONS: Six months of vitamin D supplementation did not improve HRQOL in non-vitamin D-deficient people with type 2 DM managed on oral antidiabetic therapy.

Vitamin D status and health-related quality of life in patients with Type 2 diabetes.

AIMS: To test whether vitamin D status was associated with health-related quality of life in people with Type 2 diabetes mellitus. METHODS: Demographic and clinical characteristics, including health-related quality of life scores, were obtained from 241 adult patients with Type 2 diabetes managed with oral hypoglycaemic agents. Health-related quality of life was assessed using the Short-Form 36 Health Survey. Multiple logistic regression analysis was used to investigate the association between vitamin D status and health-related quality of life, with adjustment for confounders. RESULTS: The mean age of the patients included in the study was 67 ± 8 years. Their mean HbA1c concentration was 52 ± 8 mmol/mol (6.9 ± 0.7%) and their mean serum 25-hydroxyvitamin D concentration was 59 ± 23 nmol/l. Vitamin D deficiency (serum 25-hydroxyvitamin D < 50 nmol/l) was present in 38% of patients. No significant associations were found between vitamin D status and health-related quality of life. CONCLUSIONS: Vitamin D status was not associated with health-related quality of life in patients with Type 2 diabetes. This could be explained by the relatively high serum 25-hydroxyvitamin D concentration, good glycaemic control and relatively good health-related quality of life of all patients. A prospective study among patients with vitamin D deficiency and poor glycaemic control would be interesting for future research.

Vitamin D status is associated with skin autofluorescence in patients with type 2 diabetes mellitus: a preliminary report.

BACKGROUND: Skin autofluorescence is a non-invasive measurement of advanced glycation end products (AGE), which are suggested to be one of the major agents in the pathogenesis and progression of diabetes related cardiovascular complications. Recently, low vitamin D status has been linked to the progression of type 2 diabetes mellitus (T2DM) and cardiovascular disease. The aim of this study is to investigate the association between vitamin D status and skin autofluorescence in patients with T2DM. METHODS: In this preliminary report skin autofluorescence was measured non-invasively with an AGE-reader in 245 patients with T2DM treated with lifestyle advice, metformin and/or sulphonylurea-derivatives. All patients were randomly assigned to receive either vitamin D 50,000 IU/month or placebo for 6 months. RESULTS: Skin autofluorescence was significantly higher in patients with a serum 25(OH)D < 50 nmol/l compared to patients with a serum 25(OH)D > 75 nmol/l (2.81 versus 2.41; p < 0.001). Mean serum 25(OH)D was 60.3 ± 23.4 nmol/l and was independently associated with skin autofluorescence (ß -0.006; p < 0.001). Mean vitamin D increased from 60.8 to 103.6 nmol/l in the intervention group, however no effect was seen on accumulation of skin AGEs after 6 months compared to placebo. CONCLUSIONS: Vitamin D status is independently associated with skin auto fluorescence in patients with well-controlled T2DM. No effect was seen on the amount of skin AGEs after a short period of 6 months vitamin D supplementation. Further research with longer follow-up and measurement of circulating advanced glycation end products is needed to elucidate the causality of the association.

Ain't No Sunshine When She's Gone: Pseudohypoparathyroidism Discovered in an Adult.

An 18-year-old negroid woman presented with progressive cramps in both hands. She was Jamaican and had moved to The Netherlands 8 months before. On physical examination Trousseau's sign was positive. Laboratory analysis showed severe hypocalcaemia (1.17 mmol/L) and hyperphosphatemia (2.0 mmol/L). Urinary excretion of both calcium (0.8 mmol/day) and phosphate (5 mmol/day) was low, as is seen in hypoparathyroidism. However, the PTH level was increased (22.1 pmol/L), whereas 25-(OH)-vitamin D was low (31 nmol/L). An Ellsworth-Howard test showed only a fivefold increase in urinary phosphate excretion after administration of synthetic PTH, supporting the diagnosis pseudohypoparathyroidism. Upon treatment with calcium supplementation and alfacalcidol, her symptoms disappeared. Pseudohypoparathyroidism (PHP) is a rare hereditary disorder resembling hypoparathyroidism, although plasma PTH levels are elevated. PHP is caused by alterations in the PTH receptor, inducing target tissue resistance to PTH. This results in hypocalcaemia and hyperphosphatemia, while PTH levels are elevated. The diagnosis is confirmed by the Ellsworth-Howard test, which will show a 100-fold increase in phosphate excretion if the PTH receptor functions properly. Treatment is lifelong supplementation of calcium and alfacalcidol. In our patient, symptoms were probably evoked by the lack of sunlight in Dutch winter, decreasing vitamin D levels and thereby aggravating hypocalcaemia.

Vitamin D and gestational diabetes: a systematic review and meta-analysis.

BACKGROUND: Conflicting results currently exists on the association between vitamin D and glucose metabolism. The role of maternal vitamin D status in gestational diabetes mellitus (GDM) is not clear. This meta-analysis aimed to examine this role in women with GDM compared with normal glucose tolerance (NGT). METHODS: We performed a systematic review and meta-analysis by searching MEDLINE database, the Cochrane library and Uptodate® Online for English-language literature up to September 2011. Summary odds ratios were calculated using a random-effects model meta-analysis. RESULTS: Seven observational studies were eligible for the meta-analysis, including 2146 participants of whom 433 were diagnosed with GDM. Four studies reported a high incidence of vitamin D deficiency in pregnant women (>50%). Overall vitamin D deficiency (serum 25-hydroxyvitamin D (25OHD)<50 nmol/l) in pregnancy was significantly related to the incidence of GDM with an odds ratio of 1.61 (95% CI 1.19-2.17; p=0.002). Serum 25OHD was significant lower in participants with GDM than in those with NGT (-5.33 nmol/l (95% CI -9.73 to -0.93; p=0.018). CONCLUSIONS: This meta-analysis indicates a significant inverse relation of serum 25OHD and the incidence of GDM. However, it remains unclear whether this association is causal due to the observational study design of the studies. Clinical trials are needed to examine whether vitamin D supplementation will improve glycemic control in women with GDM.

Intensive management of hyperglycaemia in acute coronary syndromes. Study design and rationale of the BIOMArCS 2 glucose trial.

BACKGROUND: Elevated admission plasma glucose is associated with increased mortality in patients who are admitted with an acute coronary syndrome. This may be mediated by increased inflammation, apoptosis and coagulation, and by a disturbed endothelial function that can be found in hyperglycaemic patients. Insulin has several characteristics that may potentially counteract these mechanisms. METHODS: The BIOMArCS programme is a multi-centre initiative and currently consists of three different studies. The effects of acute coronary syndrome on acute biomarkers washout are studied in the BIOMArCS pilot and the value of biomarkers in predicting upcoming acute coronary syndrome events is studied in BIOMArCS 1. The third study (BIOMArCS 2 glucose), which will be presented here, investigates the effectiveness and safety of intensive glucose level control compared with conventional glucose management in patients with acute coronary syndrome and an admission plasma glucose of 7.8-16 mmol/l. In BIOMArCS 2 glucose, a total of 300 patients without insulin-treated diabetes mellitus will be randomized in a 1:1 ratio to either intensive or conventional glucose management on top of standard medical care. The primary endpoint is infarct size as expressed by the cardiac troponin T level 72 h after admission. To study the metabolic effects of insulin administration, we will investigate biomarker washout patterns of various metabolic mechanisms up to 7 days after admission. These markers will address inflammation, oxidative stress, hypercoagulability, endothelial activation and vasodilatation. IMPLICATIONS: Current acute coronary syndrome guidelines lack a clear strategy for hyperglycaemia treatment. This study will extend our knowledge on this matter as it may clarify mechanisms and generate hypotheses of if and how myocardial infarct size may be limited by glucose management at admission.

[Variable presentation of antiglomerular basement membrane (anti-GBM) disease: rapid recognition vitally important]. / Wisselende presentatie van antiglomerulaire-basaalmembraanziekte: snelle herkenning van vitaal belang.

The classic clinical presentation of anti-GBM disease, or Goodpasture's disease, is pulmonary haemorrhage in combination with rapidly progressive glomerulonephritis. However, presenting symptoms vary considerably. To illustrate this, this article describes 3 male patients with anti-GBM disease, aged 25, 27 and 25 years respectively. The first patient presented with massive haemoptysis without glomerulonephritis, the second patient presented with a microcytic anaemia, caused by subclinical alveolar bleeding, and the third patient presented with rapidly progressive glomerulonephritis in combination with respiratory failure. All 3 patients required mechanical ventilation but did survive. Two patients progressed to end-stage renal disease (ESRD). Earlier recognition might prevent respiratory failure and ESRD. Therefore, despite heterogeneous clinical presentation, immediate recognition of anti-GBM disease is vitally important in view of the potentially lethal consequences if left untreated.

Epididymo-orchitis due to brucellosis: not only to be considered in endemic areas. Two cases for the price of three patients.

We report 2 patients with epididymo-orchitis, caused by Brucella melitensis, accompanied by severe delay of diagnosis. In 1 patient the correct diagnosis was only suspected after his wife had been diagnosed with brucellosis. Our cases illustrate that diagnosing brucellosis can be difficult in nonendemic areas, especially when physicians are unfamiliar with it. Important clues pointing to brucellosis as cause of epididymo-orchitis are a travel history to endemic areas, unresponsiveness to empiric antibiotic treatment, and a preceding period of episodic subfebrile temperature, night sweats and fatigue. Serology is the diagnostic test of choice because it is faster and more sensitive than blood cultures. Delay of diagnosis may lead to serious complications. Therefore, alertness for brucellosis is warranted, also, if not especially, in nonendemic areas.

Nodular fasciitis: an unexpected finding on computed tomography and positron emission tomography.

Nodular fasciitis is an uncommon lesion that is also designated as a pseudosarcomatous, self-limiting reactive process. We describe a 40-year-old woman with a nodular fasciitis that was detected by computed tomography (CT), positron emission tomography (PET) with 18F-fluorodeoxyglucose (18-FDG), and histology while she was being examined for upper abdominal pain.

Multidisciplinary structured lifestyle intervention reduces the estimated risk of cardiovascular morbidity and mortality.

BACKGROUND: Current guidelines for prevention and treatment of cardiovascular disease (CVD) emphasise the importance of a healthy lifestyle. However, successful lifestyle intervention is proving to be a challenge for healthcare professionals. OBJECTIVES: Evaluation of the effect of lifestyle intervention on cardiovascular risk factors, on reaching treatment targets and on the estimated risk of cardiovascular morbidity and mortality. METHODS: The effect of a six-month multidisciplinary structured lifestyle intervention programme was assessed in 186 patients with and without a history of CVD. RESULTS: Multidisciplinary structured lifestyle intervention reduced the estimated ten-year risk of cardiovascular morbidity and mortality. The relative risk reduction was similar in patients with and without a history of CVD, the absolute risk reduction was higher in patients with a history of CVD. In both groups blood pressure and body weight decreased, and the maximal work rate and maximal oxygen uptake increased significantly. Blood levels of total cholesterol and cholesterol/HDL ratio decreased significantly in patients with a history of CVD. In addition, target levels for blood pressure and physical fitness were more frequently reached in both patient groups. CONCLUSION: Multidisciplinary structured lifestyle intervention had beneficial effects on cardiovascular risk factors. Relative risk reduction was similar in patients with and without evidence of cardiovascular disease. Follow-up is needed to see how well these effects can be maintained.