Gestation-suppressed serum TSH levels during early pregnancy are not associated with altered maternal and neonatal outcomes.

Objective: The aim of the study was to investigate the impact of suppressed serum TSH levels (sTSH) during early pregnancy on maternal and neonatal outcomes. Methods: In this single-centre, retrospective cohort study 1081 women were screened at 11.8 ± 2.4 weeks of pregnancy for TSH, free T4 (FT4) and TPOAb. Exclusion criteria were twin- and assisted- reproduction pregnancies, women with TSH levels >3.74 mIU/L, severe hyperthyroidism, treated for thyroid dysfunction before or after screening and gestational blood sampling <6 or >16 weeks of pregnancy. The prevalence of adverse pregnancy outcomes was compared between the study group sTSH (TSH: < 0.06 mIU/L; n = 36) and euthyroid controls (TSH: 0.06-3.74 mIU/L; n = 1045), and the impact of sTSH on pregnancy outcomes verified in logistic regression analyses. Results: Median (IQR) serum TSH level in women with sTSH was 0.03 (0.03-0.03) vs 1.25 (0.81-1.82) mIU/L in controls and FT4 levels 18.0 (14.4-20.3) vs 14.2 (12.9-15.4) pmol/L; both P < 0.001. None of the women with sTSH had thyrotropin receptor antibodies. Compared with controls, the prevalence of TPOAb positivity (TAI) was comparable between groups (5.6% vs 6.6%; P = 0.803). The prevalence of maternal and neonatal pregnancy outcomes was comparable between the study and control group. The logistic regression analyses with corrections for TAI, FT4 and demographic parameters confirmed the absence of an association between sTSH, and the following outcomes: iron deficient anaemia (aORs (95% CI)): 1.41 (0.64-2.99); P = 0.385, gestational diabetes: 1.19 (0.44-2.88); P = 0.713, preterm birth: 1.57 (0.23-6.22);P = 0.574 and low Apgar-1' score: 0.71 (0.11-2.67); P = 0.657. Conclusions: Suppressed serum TSH levels during the first to early second trimester of pregnancy were not associated with altered maternal or neonatal outcomes.

Impact of thyroid hormone treatment on maternal pregnancy outcomes in women with subclinical hypothyroidism without TPOAb: a retrospective cross-sectional study.

BACKGROUND: Evidence on the impact of thyroid hormone treatment (LT4) on maternal pregnancy outcomes in women with subclinical hypothyroidism (SCH) without thyroid peroxidase antibodies (TPOAb) positivity is scarce. METHODS: Single centre, cross-sectional study in 1460 women screened for TSH, free T4 and TPOAb at median 13 (11-17) weeks of gestation during the period 2013-2014. Exclusion criteria were twin- and assisted reproduction pregnancies, TPO positivity, overt thyroid dysfunction, and treatment with LT4 before screening. The impact of LT4 on maternal pregnancy outcomes was investigated in a group of 53 women with SCH (TSH > 3.74 mIU/L) in which LT4 was initiated at median 13 (10-22) weeks (treated group). The control group included 18 women with SCH (TSH > 3.74 mIU/L). The prevalence of pregnancy complications in these two groups was compared with that in a euthyroid reference (REF) group of 1389 women (TSH ≤ 3.74 mIU/L). RESULTS: The prevalence of pre-eclampsia and gestational diabetes (GDM) was higher in the control group vs the REF group (16.7% vs 5.0% and 27.8% vs 18.9%; p = 0.017 and p = 0.016, respectively), but comparable in the treated group vs the REF group (7.6% vs 5.0% and 22.6% vs 18.9%; p = 0.918 and 0.676, respectively). The prevalence of iron-deficiency anaemia was lower in the treated vs the REF group (17.0% vs 32.5%; p = 0.017). CONCLUSION: Pregnant women with untreated SCH and without TPOAb positivity had a higher prevalence of pre-eclampsia and GDM compared with euthyroid women, while this was not the case in women with treated SCH, even when it was initiated after the first trimester.

An Unusual Case of Primary Hyperparathyroidism: Case Report of a Bifocal Intrathyroidal Parathyroid Carcinoma.

Intrathyroidal parathyroid carcinoma is an extremely rare cause of primary hyperparathyroidism. We reported a 51-year old woman who presented symptoms of hypercalcemia. 99mTc sestamibi single-photon emission computed tomography/computed tomography (CT) revealed a large hypermetabolic nodule in the left thyroid lobe suggestive of hyperfunctioning parathyroid tissue. 11C-methionine positron emission tomography/computed tomography (PET/CT) and 18F-fluorocholine PET/CT confirmed the nodule in the left thyroid lobe and also revealed a hypermetabolic activity on the posterior surface of the lower left pole. The patient underwent a total thyroidectomy and parathyroidectomy, and a diagnosis of bifocal intrathyroidal parathyroid carcinoma was confirmed. We present the first reported case of bifocal intrathyroidal carcinoma and discuss the discordant imaging results.

Endocrine disorders in obstructive sleep apnoea syndrome: A bidirectional relationship.

Obstructive sleep apnoea (OSA) is a common disorder characterized by recurrent episodes of apnoea or hypopnea due to total or partial pharyngeal collapse and temporary upper airway obstruction during sleep. The prevalence of OSA is increasing and currently affects about 30% of men and 13% of women in Europe. Intermittent hypoxia, oxidative stress, systemic inflammation, and sleep fragmentation resulting from OSA can provoke subsequent cardiometabolic disorders. The relationships between endocrine disorders and OSA are complex and bidirectional. Indeed, several endocrine disorders are risk factors for OSA. Compared with the general population, the prevalence of OSA is increased in patients with obesity, hypothyroidism, acromegaly, Cushing syndrome, and type 1 and 2 diabetes. In some cases, treatment of the underlying endocrine disorder can improve, and occasionally cure, OSA. On the other hand, OSA can also induce endocrine disorders, particularly glucose metabolism abnormalities. Whether continuous positive airway pressure (CPAP) treatment for OSA can improve these endocrine disturbances remains unclear due to the presence of several confounding factors. In this review, we discuss the current state-of-the-art based on the review of the current medical literature for key articles focusing on the bidirectional relationship between endocrine disorders and OSA and the effects of treatment. Screening of OSA in endocrine patients is also discussed, as it remains a subject of debate.

Obstructive sleep apnea is not associated with diabetic retinopathy in diabetes: a prospective case-control study.

PURPOSE: Diabetic retinopathy (DR) is the most common ocular complication of type 2 diabetes mellitus (T2D) and is associated with diabetes duration, glycemic control, and hypertension (HTN). Obstructive sleep apnea (OSA) is frequent in T2D and is associated with poor glycemic control. However, it is unclear if there is an association between OSA and DR. This study aimed to assess whether or not the presence of OSA in patients with T2D was associated with DR. METHODS: In this prospective case-control study, consecutive patients with DM attending the ophthalmology clinics were recruited to include patients with DR (cases) and without DR (controls). OSA was diagnosed by attended polysomnography (PSG). Blood pressure and a fasting morning blood sample, including glycosylated hemoglobin (HbA1c), were recorded. Patients were matched for age, body mass index (BMI), gender, and T2D duration. RESULTS: Thirty diabetic patients with DR were matched with 30 controls. In all patients, the prevalence of moderate-to-severe OSA was 57%. In the logistic regression analysis, DR was associated with increased HbA1c (OR 2.63, 95% CI 1.35-5.16, p = 0.004) but not with any PSG parameter. In the DR group, PSG parameters were not associated with the severity of ocular disease (non-proliferative, proliferative, presence/absence of macular edema). The proliferative aspect of DR was correlated with age (p = 0.017). DR occurred more frequently in uncontrolled diabetes compared to well-controlled diabetes (80% vs 38%, p = 0.029). CONCLUSIONS: In patients with T2D, the presence of DR is not associated with OSA, but with poorly controlled T2D.

Association between thyroid autoimmunity and gestational diabetes mellitus in euthyroid women.

Objective: Pregnant women with autoimmune (subclinical) hypothyroidism have an increased risk of developing gestational diabetes mellitus (GDM). However, this association remains controversial in euthyroid women with thyroid autoimmunity (TAI). Therefore, the aim of the study was to determine the association between TAI and GDM in euthyroid women in a logistic regression analysis with adjustments for baseline/demographic parameters. Methods: Cross-sectional study in 1447 euthyroid women who performed their entire clinical/biological workup and oral glucose tolerance test (OGTT) in our center. At median 13 (11-17) weeks of gestation, thyroid-stimulating hormone, free T4, and thyroid peroxidase antibodies (TPOAb) were measured, baseline characteristics were recorded, and an OGTT was performed between 24 and 28 weeks of pregnancy. Exclusion criteria were pre-pregnancy diabetes, assisted pregnancies, and women with (treated) thyroid dysfunction before or after screening. The diagnosis of GDM was based on 2013 World Health Organization criteria, and TAI was defined as TPOAb levels ≥60 kIU/L. Results: Two hundred eighty women were diagnosed with GDM (19.4%), 26.1% in women with TAI, and 18.9% in women without TAI (P = 0.096). In the logistic regression analysis, TAI was associated with GDM in women older than 30 years (adjusted odds ratio 1.68 (95% CI, 1.01-2.78); P = 0.048). Maternal age >30 years, pre-pregnancy BMI ≥30 kg/m2, and other than Caucasian background were also associated with GDM; aOR 1.93 (95% CI, 1.46-2.56); P < 0.001, 2.03 (95% CI, 1.46-2.81); P < 0.001 and 1.46 (95% CI, 1.03-2.06); P = 0.034, respectively. Conclusions: In older pregnant women, the presence of TAI in euthyroid women was associated with GDM. In line with the literature data, (higher) age and BMI were strongly associated with GDM. Future investigations should focus on treatments that might prevent the development of GDM in euthyroid women with TAI.

Does foetal gender influence maternal thyroid parameters in pregnancy?

Objective: It is unknown if foetal gender influences maternal thyroid function during pregnancy. We therefore investigated the prevalence of thyroid disorders and determined first-trimester TSH reference ranges according to gender. Methods: A cross-sectional study involving 1663 women with an ongoing pregnancy was conducted. Twin and assisted pregnancies and l-thyroxine or antithyroid treatment before pregnancy were exclusion criteria. Serum TSH, free T4 (FT4) and thyroid peroxidase antibodies (TPOAb) were measured at median (interquartile range; IQR) 13 (11-17) weeks of gestation. Subclinical hypothyroidism (SCH) was present when serum TSH levels were >3.74 mIU/L with normal FT4 levels (10.29-18.02 pmol/L), and thyroid autoimmunity (TAI) was present when TPOAb were ≥60 kIU/L. Results: Eight hundred and forty-seven women were pregnant with a female foetus (FF) and 816 with a male foetus (MF). In women without TAI and during the gestational age period between 9 and 13 weeks (with presumed high-serum hCG levels), median (IQR range) serum TSH in the FF group was lower than that in the MF group: 1.13 (0.72-1.74) vs 1.24 (0.71-1.98) mIU/L; P = 0.021. First-trimester gender-specific TSH reference range was 0.03-3.53 mIU/L in the FF group and 0.03-3.89 mIU/L in the MF group. The prevalence of SCH and TAI was comparable between the FF and MF group: 4.4% vs 5.4%; P = 0.345 and 4.9% vs 7.5%; P = 0.079, respectively. Conclusions: Women pregnant with an MF have slightly but significantly higher TSH levels and a higher upper limit of the first-trimester TSH reference range, compared with pregnancies with a FF. We hypothesise that this difference may be related to higher hCG levels in women pregnant with a FF, although we were unable to measure hCG in this study. Further studies are required to investigate if this difference has any clinical relevance.

Thyroid Disorders and In Vitro Outcomes of Assisted Reproductive Technology: An Unfortunate Combination?

Background: The impact of thyroid disorders on in vitro outcomes of assisted reproductive technology (ART) remains controversial. Therefore, the aim of our study was to investigate whether thyroid peroxidase antibodies (TPO-Abs)/thyroid autoimmunity (TAI) or thyroid function (serum thyrotropin [TSH])/subclinical hypothyroidism are associated with an altered number of oocyte retrieval (NOR), fertilization rate (FR), and embryo quality (EQ). Methods: Cross-sectional study in 279 women in a single center, comprising 297 cycles and 1168 embryos. In vitro data (NOR, FR, and EQ) were documented in two groups; one according to thyroid function in women without TAI (TSH ≤2.5 and >2.5 mIU/L) and one according to the presence/absence of TAI (determined by TPO-Abs). EQ was evaluated according to international criteria and classified as excellent/good and poor. Women treated with levothyroxine (LT4) were excluded. Furthermore, the impact of thyroid parameters on outcomes, normal NOR (>6 or 8) and high FR (>60%), was verified in a multivariable logistic regression model. Results: In women without TAI, 27% had TSH levels >2.5 mIU/L, the prevalence of TAI was 8%, and overall, 6% of women had TSH levels >4.2 mIU/L. NOR, FR, and EQ were comparable between study groups. In the regression analysis, women aged ≥30 years and receiving a high ovarian stimulation dosage (>2300 IU/cycle) had lower rates of normal NOR (odds ratio [OR] 0.18 [95% confidence interval, CI 0.04-0.72]; p = 0.016 and OR 0.17 [CI 0.06-0.48]; p < 0.001, respectively). Conclusions: Our results do not suggest an impact of thyroid antibodies/autoimmunity and (dys)function on ART in vitro outcomes.

The Impact of Thyroid Disorders on Clinical Pregnancy Outcomes in a Real-World Study Setting.

Background: Subclinical hypothyroidism (SCH) and thyroid autoimmunity (TAI) have been associated with poor clinical pregnancy outcomes. However, these outcomes also depend on a number of demographic and obstetric variables. Therefore, the aim of this study was to investigate the impact of thyroid disorders on these outcomes, after adjustment for associated demographic and obstetrical parameters. Methods: This is cross-sectional study including 1521 pregnant women who underwent work-up and follow-up in the Centre Hospitalier Universitaire (CHU) Saint-Pierre, Brussels, and had ongoing pregnancies. Thyroid function (thyrotropin [TSH], free thyroxine [fT4]) and TAI (thyroid peroxidase antibodies) was determined at median (Q1-Q3) 13 (11-17) weeks. Baseline parameters and the prevalence of poor clinical pregnancy outcomes were compared between controls (no TAI and TSH <2.51 mIU/L) and three study groups (isolated TAI [TSH <2.51 mIU/L], SCH1 [TSH 2.51-3.7 mIU/L], SCH2 [TSH >3.7 mIU/L]). The impact of the different thyroid groups and demographic/obstetric independent variables on six poor clinical pregnancy outcomes (preeclampsia, intrauterine growth restriction [IUGR], preterm birth, neonatal intensive care unit [NICU] admission, low birth weight, and macrosomia) was investigated in a logistic regression model. Treatment with thyroid hormone before and during pregnancy and assisted and multiple pregnancies were exclusion criteria. Results: In total, 79 preeclampsias (5.2%), 40 IUGRs (2.6%), 79 preterm births (5.2%), 10 admissions to NICU (0.66%), 74 low birth weights (4.9%), and 94 babies with macrosomia (6.2%) were documented. TAI was independently associated with NICU admission (adjusted odds ratio [aOR] 16.92 confidence interval [CI 3.36-85.29]; p < 0.001) and TSH, as a continuous variable in the whole range, with preeclampsia (aOR 1.97 [CI 1.18-3.31]; p = 0.010). Trends were present for an association between SCH2 and preeclampsia (aOR 16.73 [CI 1.43-196.42]; p = 0.025), and for SCH1with NICU admission and low birth weight (aOR 19.36 [CI 1.18-316.97]; p = 0.038 and 21.38 [CI 1.29-353.39]; p = 0.032, respectively). Conclusions: Pregnant women with TAI had a significantly higher risk of an admission of the baby to the NICU, and SCH tended to be associated with a higher risk of preeclampsia and low birth weight. Other poor clinical pregnancy outcomes were not associated with thyroid disorders, but with demographic and obstetric parameters.

Prevalence of undiagnosed glucose intolerance and type 2 diabetes in patients with moderate-to-severe obstructive sleep apnea syndrome.

PURPOSE: Overweight and obesity are major causal factors for obstructive sleep apnea syndrome (OSAS), providing insight into why one third of patients with OSAS suffer from diabetes mellitus and another third from glucose intolerance. However, a significant proportion of the general population remains undiagnosed for glucose metabolism disorders. The primary aim of this study was to establish the prevalence of known and newly diagnosed glucose metabolism disorders in patients with moderate and severe OSAS referred to the sleep lab for continuous positive airway pressure (CPAP) therapy. METHODS: We prospectively included consecutive patients with moderate or severe OSAS referred for CPAP therapy. A fasting blood sample was collected to determine glycosylated hemoglobin (HbA1c), glucose, and homeostatic model assessment (HOMA) index. Baseline demographic data and medication intake were recorded. RESULTS: Of 280 consecutive patients (70% men, mean ± SD body mass index 33 ± 7 kg/m2, apnea-hypopnea index 49 ± 25), 22% exhibited diabetes and 44% glucose intolerance. Undiagnosed diabetes and glucose intolerance was found in 79 of 280 patients (28%). Insulin resistance was associated with OSAS severity in multivariate linear regression analysis (regression coefficient 2.40 [95% CI 0.07-4.72]; p = 0.04). CONCLUSION: In this population of overweight and obese patients with moderate and severe OSAS, 66% of patients had diabetes or glucose intolerance and 28% were newly diagnosed. Diabetes and glucose intolerance were not related to OSAS severity, contrary to insulin resistance. These data suggest that there is value in systematic screening for glucose metabolism disorders in all patients with moderate and severe OSAS.

Screening for Thyroid Dysfunction in Pregnancy With Targeted High-Risk Case Finding: Can It Be Improved?

CONTEXT AND OBJECTIVE: Targeted screening is proposed for the detection of thyroid dysfunction in pregnant women rather than universal screening (US). We aimed to determine the detection rate of subclinical hypothyroidism (SCH) and overt hypothyroidism (OH) based on American Thyroid Association guidelines (ATA-GL) and whether it could be improved. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of 1832 pregnant women in a single center. Thyroid function (TSH and free T4) and iron status were determined. The high-risk group (HRG) included women with one or more ATA-GL risk factors and the low-risk group (LRG) included women without. Participants with other risk factors [body mass index (BMI) 30 to 39.9 kg/m2, Caucasian background] were classified as HRG+ and those with iron deficiency as HRG++. RESULTS: The HRG included 64% of women and the LRG included 36% (P < 0.001). Of all participants, 4.5% had SCH and 0.5% OH. The detection rate of SCH and OH was comparable between the LRG and HRG (46% vs 54% and 25% vs 75%; P = 0.560 and 0.157, respectively). In the HRG, the detection rate of SCH was lower than that of US (54% vs 100%; P < 0.001), but that of OH was comparable (75%; P = 0.596). The detection rate of SCH in the HRG+ and HRG++ was comparable to that in the US group (81% and 88% vs 100%; P = 0.220 and 0.439, respectively). CONCLUSIONS: Targeted high-risk case finding screening was not effective for the detection of SCH but performed better for OH. When obesity in the range BMI 30 to 39.9 kg/m2 and a Caucasian background were included as risk factors, the detection rate of SCH became comparable with that of US.

Thyroid autoimmunity and intracytoplasmic sperm injection outcome: a systematic review and meta-analysis.

BACKGROUND: Since 2010, three meta-analyses have been published on the impact of thyroid autoimmunity (TAI) on pregnancy outcomes in infertile women treated with assisted reproductive technology (ART). The initially observed high risk of miscarriage became very low in the most recent meta-analysis published in 2016. OBJECTIVE: To investigate whether the lower risk of miscarriage in the latest meta-analysis was associated with the increased use of intracytoplasmic sperm injection (ICSI) in recent studies. DATA SOURCE: MEDLINE was searched from January, 1990, to May, 2017. STUDY SELECTION: Data from case-control and cohort studies, on ART (IVF/ICSI) pregnancy outcomes in women with and without TAI. Only studies were included in which women were treated with ICSI. DATA EXTRACTION AND SYNTHESIS: Four studies were retained including 1855 ICSI cycles (290 with and 1565 without TAI). In women with a clinical pregnancy (114 ICSI cycles with TAI and 651 without), there was no difference in miscarriage or live birth rates: respective combined OR 0.95 (95% CI, 0.48 to 1.87) and 1.12 (95% CI, 0.62 to 2.03). There was no difference in age in women with and without TAI: combined mean difference of 0.13 years (95% CI, -0.51 to 0.76), but serum TSH was higher in women with TAI: combined mean difference of 0.20 mIU/L (95% CI, 0.07 to 0.33). CONCLUSION: Infertile women with TAI treated with ICSI had no increased risk of a first trimester miscarriage compared with women without TAI.

Pregnancy outcomes are not altered by variation in thyroid function within the normal range in women free of thyroid disease.

OBJECTIVE: In the recently revised guidelines on the management of thyroid dysfunction during pregnancy, treatment with thyroid hormone (LT4) is not recommended in women without thyroid autoimmunity (TAI) and TSH levels in the range 2.5-4.0 mIU/L, and in a recent study in that particular group of pregnant women, more complications were observed when a treatment with LT4 was given. The objective of the study was therefore to investigate whether variation in thyroid function within the normal (non-pregnant) range in women free of thyroid disease was associated with altered pregnancy outcomes? DESIGN: Cross-sectional data analysis of 1321 pregnant women nested within an ongoing prospective collection of pregnant women's data in a single centre in Brussels, Belgium. METHODS: Thyroid peroxidase antibodies (TPO-abs), thyroid-stimulating hormone (TSH), free T4 (FT4) and ferritin levels were measured and baseline characteristics were recorded. Women taking LT4, with TAI and thyroid function outside the normal non-pregnant range were excluded. Pregnancy outcomes and baseline characteristics were correlated with all TSH and FT4 levels within the normal range and compared between two groups (TSH cut-off < and ≥2.5 mIU/L). RESULTS: Tobacco use was associated with higher serum TSH levels (OR: 1.38; CI 95%: 1.08-1.74); P = 0.009. FT4 levels were inversely correlated with age and BMI (rho = -0.096 and -0.089; P < 0.001 and 0.001 respectively) and positively correlated with ferritin levels (rho = 0.097; P < 0.001). Postpartum haemorrhage (>500 mL) was inversely associated with serum FT4 levels (OR: 0.35; CI 95%: 0.13-0.96); P = 0.040. Also 10% of women free of thyroid disease had serum TSH levels ≥2.5 mIU/L. CONCLUSIONS: Variation in thyroid function during the first trimester within the normal (non-pregnant) range in women free of thyroid disease was not associated with altered pregnancy outcomes. These results add evidence to the recommendation against LT4 treatment in pregnant women with high normal TSH levels and without TPO antibodies.

Maternal thyroid parameters in pregnant women with different ethnic backgrounds: Do ethnicity-specific reference ranges improve the diagnosis of subclinical hypothyroidism?

OBJECTIVE: Guidelines on the management of thyroid dysfunction during pregnancy have recently been updated and, for the diagnosis of subclinical hypothyroidism (SCH), a thyroid-stimulating hormone (TSH) upper reference limit (cut-off) of 4.0 mIU/L has been proposed when no institutional values are available. It is also suggested that serum TSH and thyroid autoimmunity (TAI) may be different according to the ethnic background of the women. We therefore determined the prevalence of TAI and SCH in pregnant women with different ethnic backgrounds and, to define SCH, we used different first trimester TSH upper reference cut-offs (institutional, ethnicity-specific, 2.5 mIU/L [Endocrine Society] and 4.0 mIU/L [American Thyroid Association]). DESIGN: Cross-sectional data analysis of 1683 pregnant women nested within an ongoing prospective database of pregnant women. METHOD: The study was performed in a single centre in Brussels, Belgium. During the first antenatal visit, thyroid peroxidase antibodies (TPO-abs), TSH and free T4 (FT4) were measured and baseline characteristics recorded. Data from 481 women with sub-Saharan (SaBg; 28.6%), 754 North African (NaBg; 44.8%) and 448 Caucasian (CaBg; 26.6%) backgrounds were analysed. For the calculation of TSH reference ranges, women with TAI, outliers, twin and assisted pregnancies were excluded. RESULTS: The prevalence of TAI was significantly lower in the SaBg group than in NaBg and CaBg groups (3.3% vs 8.6% and 11.1%; P<.001, respectively). Median TSH was significantly lower in SaBg and NaBg groups as compared with the CaBg group (1.3 and 1.4 vs 1.5 mIU/L; P=.006 and .014, respectively). The prevalence of women with SCH was comparable between all groups when 2.5 mIU/L was used as cut-off, but when 4.0 mIU/L or the institutional cut-off (3.74 mIU/L) was used, it was significantly higher in the CaBg group vs the NaBg group (5.4% vs 2.1% and 7.1% vs 3.3%, P=.008 and .013, respectively). The use of ethnicity-specific cut-offs did not change the prevalence of SCH as compared to the use of institutional cut-offs. However, when these cut-offs were used, the prevalence of SCH reduced by >70% (4.5% instead of 16.7%; P<.001) relative to the 2.5 mIU/L cut-off. CONCLUSIONS: Pregnant women with a sub-Saharan African background had a lower prevalence of TAI and TSH levels as compared with women from other backgrounds. The use of ethnicity-specific TSH cut-offs in early pregnancy was not more specific for the diagnosis of SCH as compared to the use of the institutional cut-off.

Prevalence of thyroid dysfunction and autoimmunity in the older population and implications of age-specific reference ranges.

OBJECTIVE: To investigate the prevalence of thyroid dysfunction and autoimmunity (TAI) and to determine age-specific reference ranges in individuals <60 and ≥60-year-old. Furthermore we investigated the impact of the age-specific reference ranges on the prevalence of thyroid dysfunction. DESIGN: Retrospective analysis of laboratory data collected over six months in 2015, mainly from individuals consulting the outpatient clinic. METHOD: Data from 676 individuals were withheld, after having applied strict exclusion criteria to avoid confounders. After exclusion of individuals with TAI (TPO-abs >60kIU/L) and/or outliers, data of 547 individuals were used to determine age-specific reference ranges. The prevalence of subclinical hypothyroidism (SCH) and subclinical hyperthyroidism (sch) was determined according to the reference ranges from the commercial assay and also according to the calculated age-specific reference ranges. From our study population. RESULTS: From the 676 individuals included, 559 (83%) were <60year-old and 117 (17%) ≥60year-old. The prevalence of sch and TAI was comparable between both groups (8.6% vs. 13.7% and 15.4% vs. 20.5% respectively). The prevalence of SCH was significantly higher in individuals ≥60years, compared to that in individuals <60years (14.5% vs. 5.4%; p<0.001). The calculated 2.5 and 97.5 percentile for the age-specific TSH range was 0.24 and 4.4 mIU/L in individuals <60years and 0.15 and 8.2mIU/L in individuals ≥60years. When these the prevalence of sch and SCH was then determined on the basis of the age-specific reference ranges, the prevalence of SCH significantly decreased in individuals ≥60years (14.5% to 5%; p=0.027) and it then became comparable with that in individuals <60years (5% vs. 3%). CONCLUSIONS: The prevalence of SCH was higher in individuals ≥60years, compared to that in individuals <60years, but when age-specific TSH reference ranges were used, it was comparable between both study groups. In order to avoid misclassification in older individuals, it is important to use age-specific reference ranges in daily clinical practice.

Prevalence of thyroid autoimmunity and dysfunction in women with iron deficiency during early pregnancy: is it altered?

OBJECTIVE: Thyroid disorders and iron deficiency (ID) are associated with obstetrical and fetal complications. Iron is essential for the normal functioning of thyroid peroxidase (TPO-abs) and ID is frequent during pregnancy. The aim of this study was to compare the prevalence of thyroid autoimmunity (TAI) and dysfunction during the first trimester of pregnancy in women with and without ID. DESIGN: Cross-sectional data analysis of 1900 pregnant women nested within an ongoing prospective collection of pregnant women's data. METHOD: The study was performed in a single, tertiary referral center. During the first antenatal visit, ferritin, TPO-abs, thyroid-stimulating hormone (TSH) and free T4 (FT4) were measured and age and BMI were recorded. ID was defined as ferritin <15µg/L, TAI when TPO-abs was >60kIU/L, and subclinical hypothyroidism (SCH) when TSH was >2.5mIU/L. RESULTS: ID was present in 35% of women. Age and BMI were comparable between both groups. In the ID group, the prevalence of TAI and SCH was significantly higher, compared with that in the non-ID group (10% vs 6% and 20% vs 16%; P=0.011 and 0.049 respectively). Ferritin was inversely correlated with serum TSH (ρ=-0.076; P=0.001) and positive with FT4 levels (ρ=0.112; P<0.001). In the logistic regression model, ID remained associated with TAI after correction for confounding factors (P=0.017). The association with SCH was absent after correction for the confounders in the logistic regression model (P=0.082), but remained present in the linear regression model (P=0.035). CONCLUSIONS: ID was frequent during the first trimester of pregnancy and was associated with a higher prevalence of TAI, higher serum TSH, and lower FT4 levels.

Hypophosphatemia related to paraneoplastic Cushing syndrome in prostate cancer: cure after bilateral adrenalectomy.

We report the case of a 71-year-old man with progressive metastatic prostate cancer in whom simultaneous occurrence of paraneoplastic Cushing syndrome (CS) and tumor-induced osteomalacia (TIO) initially was suspected. However, the evolution of biochemical markers of phosphate metabolism during disease course and after bilateral adrenalectomy argued against the diagnosis of TIO. Despite the persistence of progressive prostate cancer, CS and hypophosphatemia resolved in parallel after bilateral adrenalectomy. Thus, these data suggest that paraneoplastic CS per se was involved in the pathogenesis of hypophosphatemia. Calcitriol and intact fibroblast growth factor 23 (FGF23) levels were within the reference range at onset, which is inappropriate in the setting of severe hypophosphatemia. All parameters of phosphate metabolism normalized after resolution of hypercortisolism. Based on the known suppressive effect of glucocorticoids (GCs) on bone remodeling and the inverse relationship between bone turnover rate and circulating FGF23 levels, we postulate that GCs interfere indirectly with phosphate homeostasis by inducing inappropriate FGF23 production and release. This mechanism could further aggravate the hypophosphatemia resulting from GC-induced inhibition of intestinal phosphate absorption. Studies directed at the identification of the molecular pathways in bone mediating the interference of GCs with phosphate metabolism are warranted.

A delayed fatal metastatic Hürthle cell carcinoma.

Hürthle (oxyphilic or oncocytic) cell carcinoma is a variant of follicular cell carcinoma of thyroid. Although this entity of thyroid cancer is well known, its occurrence in young patients has scarcely been reported. We report a case of a 26 year-old male patient, at the time of diagnosis, of Turkish origin, who developed a tracheal, pulmonary and mediastinal metastatic Hürthle cell carcinoma with bilateral cervical and mediastinal lymphadenopathies. This case illustrates an aggressive and metastatic cancer at the time of diagnosis and resistant to all treatment options including surgery, chemotherapy and radioactive iodine.