Mitochondrial energetics and contents evaluated by flow cytometry in human maternal and umbilical cord blood.

Background: Mitochondrial dysfunction may relate to metabolic disorders. The relation between maternal and fetal mitochondrial function needs attention due to heritage.Objectives: To evaluate the use of the staining methods TetraMethylRhodamine Methyl Ester (TMRM) and Mitotracker Green (MTG) for flow cytometric measurements of umbilical cord blood mitochondrial function. Methods: 53 euthyroid at-term pregnant women and their offspring were included by blood collections. The offspring had blood drawn from the clamped umbilical cord. Flow cytometry with MTG, TMRM and Propidium Iodide were performed the following day. A cell count (antibody coating and flow cytometry) was performed for 9 maternal and cord samples. As a quality control, blood of 32 healthy donors was evaluated by flow cytometric analyzes same day as sampling and the following day to test stability of the measurements.Results: Cord mitochondrial measurements were lower than maternal. Maternal and cord mitochondrial function were positively correlated, especially reflected by MTG fluorescence-intensity (FI). Samples stored presented with very changed fluorescence patterns. However, the fluorescence intensity ratios MTG/TMRM of stained white blood cells were related within same day measurements, depicting an extensive and common bioenergetic cellular change.Conclusion: Cord blood flow cytometry by MTG- and TMRM- staining is possible with fluorescence intensity positively correlated to maternal fluorescence intensity. Storage of blood triggers mitochondrial dynamics. The methods are applicable with certain reservations, and they benefit from their non-invasive character compared to mitochondrial evaluation by muscle-biopsies.

Reduced Gene Expression of Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1α in Whole Blood in Euthyroid Patients One Year After Hemithyroidectomy for Benign Euthyroid Goiter.

We have previously reported decreased thyroid function within the laboratory reference range and changes in mitochondrial function after hemithyroidectomy. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and coactivator-1ß (PGC-1ß) are key regulators of mitochondrial biogenesis and function. The aim was to examine the influence of hemithyroidectomy on the longitudinal change in mRNA expression of these genes. In addition, we measured longitudinal changes in mRNA expressions of the mitochoncrial-related genes nuclear factor erythroid-derived 2-like 2 (NFE2L2), mitochondrial transcription factor A (TFAM), and sodium dismutase 2 (SOD2). Twenty-eight patients were examined before and 1, 3, 6, and 12 months after hemithyroidectomy for benign euthyroid goiter. Thyroid stimulating hormone (TSH) and thyroid hormones were measured, and whole blood gene expression of PGC-1α, PGC-1ß, NFE2L2, TFAM, and SOD2 was examined by reverse transcription quantitative Polymerase Chain Reaction. We used mixed effect regression models to investigate changes in gene expression with time. Averaged over all follow-up visits, TSH increased (p=0.001), tT3 declined (p=0.01), and fT4/tT3 ratio increased (p=0.03) over one-year follow-up, but fT4 remained unchanged. Averaged over all follow-up visits, whole blood PGC-1α levels (p<0.001) and SOD2 (p=0.009) levels declined, but PGC-1ß, TFAM, and NFE2L2 did not change over one-year follow-up. The study demonstrates significant downregulation of whole blood PGC-1α and SOD2 gene expressions in hemithyroidectomized patients with a concomitant increase in TSH concentration within the reference range. Thus, hemithyroidectomized patients may likely have impaired mitochondrial function.

Rapidly progressing HELLP syndrome and massive liver destruction in a 22-year-old female pregnant with monochorionic diamniotic gemelli.

Haemolysis Elevated Liver parameters and Low Platelets (HELLP) syndrome can present with abdominal pain as the only symptom. It can be rapid with failure of multiple organs and is a cause of maternal death. A 22-year-old female pregnant with twins contacted her local hospital due to abdominal pain. Within 20 hours of the debut of the abdominal pain, a caesarean section was performed, the patient was re-operated due to the suspicion of abdominal bleeding. Bescause she was hypotensive and blood tests showed signs of liver destruction and acidosis, she was transferred to the intensive care unit (ICU). During an admission of 40 days, the patient received 5 plasmapheresis treatments and 10 courses of haemodialysis. CT scans showed massive liver haematomas intraparenchymal and subcapsular. The CT scan images are very interesting and included in the case report.This case presents a good prognosis after a rapid progression of HELLP in spite of a dramatic clinical presentation. This topic is of great interest to a wide spectre of clinicians, as an early multidisciplinary approach is necessary.

Corrigendum to "Impaired Fertility Associated with Subclinical Hypothyroidism and Thyroid Autoimmunity: The Danish General Suburban Population Study".

[This corrects the article DOI: 10.1155/2015/132718.].

Impaired Fertility Associated with Subclinical Hypothyroidism and Thyroid Autoimmunity: The Danish General Suburban Population Study.

INTRODUCTION: The aim of this study was to estimate the significance of TSH, thyroid peroxidase antibody (TPOAb), and mild (subclinical) hypothyroidism in women from The Danish General Suburban Population Study (GESUS) on the number of children born, the number of pregnancies, and the number of spontaneous abortions. METHODS: Retrospective cross sectional study of 11254 women participating in GESUS. Data included biochemical measurements and a self-administrated questionnaire. RESULTS: 6.7% had mild (subclinical) hypothyroidism and 9.4% prevalent hypothyroidism. In women with mild hypothyroidism TPOAb was significantly elevated and age at first child was older compared to controls. TSH and TPOAb were negatively linearly associated with the number of children born and the number of pregnancies in the full cohort in age-adjusted and multiadjusted models. TSH or TPOAb was not associated with spontaneous abortions. Mild (subclinical) hypothyroidism was associated with a risk of not having children and a risk of not getting pregnant in age-adjusted and multiadjusted models. Prevalent hypothyroidism was not associated with the number of children born, the number of pregnancies, or spontaneous abortions. CONCLUSION: Impaired fertility is associated with TSH, TPOAb, and mild (subclinical) hypothyroidism in a Danish population of women.

Pregnancy-induced alterations in mitochondrial function in euthyroid pregnant women and pregnant women with subclinical hypothyroidism; relation to adverse outcome.

BACKGROUND: It is well documented that overt hypothyroidism is associated with adverse pregnancy outcomes, but studies of subclinical hypothyroidism have demonstrated conflicting results. OBJECTIVE: Thyroid hormones are known to regulate mitochondrial function, and the aim of this study was to examine the possible relationship of subclinical hypothyroidism and mitochondrial dysfunction to adverse pregnancy outcomes in pregnant women. METHODS: Women in their third trimester of pregnancy (n = 113) who did not receive thyroid medication were included in this cross-sectional study. All participants were interviewed, and their thyroid status was determined. All participants had concentrations of thyroid hormones (fT4 and tT3) within the reference range. In addition to thyroid status, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were measured by flow cytometry. To establish a reference range of MMP and ROS, a group of euthyroid, nonpregnant women were used as euthyroid controls. Adverse pregnancy outcome was defined as preterm delivery, preeclampsia, placental abruption, Apgar score <7 points 1 minute after birth, or postpartum hemorrhage. RESULTS: The prevalence of subclinical hypothyroidism among pregnant women was 17% (n = 19), and the number of overall adverse pregnancy outcomes was increased (p = 0.02) compared with that in euthyroid pregnant women. Preeclampsia, poor Apgar score, and postpartum hemorrhage were more frequent in the subclinical hypothyroidism group than in the euthyroid group (p = 0.04, p = 0.001 and p = 0.03, respectively), and more women showed prolonged gestation and gave birth later than 41 weeks of gestation than in the euthyroid group (p = 0.04). Compared with euthyroid, nonpregnant controls, a physiological upregulation of mitochondrial function was observed in euthyroid pregnant women. This was impaired in pregnant women with subclinical hypothyroidism. Compared with euthyroid, nonpregnant controls, pregnant women had increased ROS regardless of their thyroid status. CONCLUSION: We speculate that the unfavorable effects on mitochondrial function in women with subclinical hypothyroidism may be associated with higher prevalence of adverse pregnancy outcomes.

Weight Gain and Serum TSH Increase within the Reference Range after Hemithyroidectomy Indicate Lowered Thyroid Function.

Background. Weight gain is frequently reported after hemithyroidectomy but the significance is recently discussed. Therefore, the aim of the study was to examine changes in body weight of hemithyroidectomized patients and to evaluate if TSH increase within the reference range could be related to weight gain. Methods. In a controlled follow-up study, two years after hemithyroidectomy for benign euthyroid goiter, postoperative TSH and body weight of 28 patients were compared to preoperative values and further compared to the results in 47 matched control persons, after a comparable follow-up period. Results. Two years after hemithyroidectomy, median serum TSH was increased over preoperative levels (1.23 versus 2.08 mIU/L, P < 0.01) and patients had gained weight (75.0 versus 77.3 kg, P = 0.02). Matched healthy controls had unchanged median serum TSH (1.70 versus 1.60 mIU/L, P = 0.13) and weight (69.3 versus 69.3 kg, P = 0.71). Patients on thyroxin treatment did not gain weight. TSH increase was significantly correlated with weight gain (r = 0.43, P < 0.01). Conclusion. Two years after hemithyroidectomy for benign euthyroid goiter, thyroid function is lowered within the laboratory reference range. Weight gain of patients who are biochemically euthyroid after hemithyroidectomy may be a clinical manifestation of a permanently decreased metabolic rate.

Persistent cellular metabolic changes after hemithyroidectomy for benign euthyroid goiter.

BACKGROUND: The significance of perturbations of thyroid-stimulating hormone (TSH) and thyroid hormones within the laboratory reference ranges after hemithyroidectomy is unknown. Our aim was to examine changes in TSH and thyroid hormones after hemithyroidectomy for benign euthyroid goiter, focusing on tissue response by examining the mitochondrial membrane potential (MMP) of peripheral blood mononuclear cells (PBMCs) and basal oxygen consumption (V˙O2). MATERIALS AND METHODS: In a prospective study on 28 patients and controls, we examined serum TSH and thyroid hormones before hemithyroidectomy and 1, 3, 6 and 12 months after hemithyroidectomy for benign euthyroid goiter. In the hemithyroidectomy group, flow cytometry was used to measure the MMP of tetramethylrhodamine methyl ester (TMRM)- and MitoTracker Green (MTG)-stained PBMCs, and V˙O2 was measured by an Oxycon Pro apparatus. RESULTS: One year after hemithyroidectomy, TSH had increased from a median of 0.97 mIU/l (interquartile range, IQR: 0.69-1.50 mIU/l) to 2.10 mIU/l (IQR: 1.90-3.00 mIU/l; p < 0.001); free thyroxine (fT4) had decreased from a median of 16.0 pmol/l (IQR: 14.9-17.0 pmol/l) to 14.8 pmol/l (IQR: 14.1-16.4 pmol/l; p = 0.009), whereas total triiodothyronine variations did not differ from those in controls. Concomitantly, the MMP of TMRM- and MTG-stained PBMCs was increased by 58% (p < 0.001) and 22% (p = 0.008), respectively. V˙O2 was increased by 14% (p = 0.01). CONCLUSION: Hemithyroidectomy for benign euthyroid goiter induced persistently increased TSH and decreased fT4, sustained mitochondrial hyperpolarization and increased V˙O2. Our results demonstrate a decrease after hemithyroidectomy of the metabolic state to which the individual is adapted, with persistent cellular metabolic changes in a hemithyroidectomized patient group which is normally considered clinically and biochemically euthyroid.