Reference intervals for thyroid-stimulating hormone, free thyroxine, and free triiodothyronine in elderly Chinese persons.

Background Thyroid hormone levels are essential for diagnosing and monitoring thyroid diseases. However, their reference intervals (RIs) in elderly Chinese individuals remain unclear. We aimed to identify factors affecting thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) levels using clinical "big data" to establish hormone level RIs for elderly Chinese individuals. Methods We examined 6781, 6772, and 6524 subjects aged ≥65 years who underwent FT3, FT4, and TSH tests, respectively, at the Peking Union Medical College Hospital between September 1, 2013, and August 31, 2016. Hormones were measured using an automated immunoassay analyzer (ADVIA Centaur XP). RIs were established using the Clinical Laboratory Standards Institute document C28-A3 guidelines. Results The median TSH was significantly higher in women than in men; the opposite was true for median FT3 and FT4 levels. No differences were observed in TSH or FT4 by age in either sex or overall; FT3 levels significantly decreased with age. Seasonal differences were observed in TSH and FT3 levels but not FT4 levels; the median TSH was the highest in winter and lowest in summer, whereas the median FT3 was the lowest in summer (albeit not significantly). RIs for TSH were 0.53-5.24 and 0.335-5.73 mIU/L for men and women, respectively; those for FT3 were 3.76-5.71, 3.60-5.42, and 3.36-5.27 pmol/L in 64- to 74-, 75- to 84-, and 85- to 96-year-old subjects, respectively. The RI for FT4 was 11.70-20.28 pmol/L. Conclusions RIs for TSH in elderly individuals were sex specific, whereas those for FT3 were age specific.

[Thyroid function for Chinese pregnant women in 2010-2012].

OBJECTIVE: To evaluate thyroid function and iodine nutritional status for pregnant women from various regions of China by determining plasma levels of thyrotrophin( TSH), free triiodothyronine( FT3), and free thyroxine( FT4). METHODS: Plasma samples were obtained from pregnant women that participated in the 2010-2012 China National Nutrition and Health Survey. Plasma levels of TSH, FT3, and FT4 were determined by using an automated chemiluminescence immunoassay analyzer. Thyroid function was evaluated according to the determined levels. RESULTS: A total of 877 plasma samples collected from pregnant women residing in different regions of China wereanalyzed for levels of TSH, FT3, and FT4. The median TSH levels detected in the first, second, and third trimesters of pregnancy were 1. 56, 1. 84, and 1. 89 m IU/L, respectively. The median FT4 levels were 17. 21, 16. 29 and 16. 35 pmol/L, respectively. The median FT3 levels were 4. 70, 4. 39 and 4. 18 pmol/L, respectively. The rate of normal thyroid function for this cohort was 78. 1%, and for the pregnant women that resided in large cities the rate was 71. 2%. The most common type of abnormal thyroid function that was detected was subclinical hypothyroidism. It had an overall incidence of10. 5%, and those residing in regions of rural poverty had the highest rate( 14. 5%). The normal rate of thyroid function for adult pregnant women at the end of the trimester( 28-40 weeks) during pregnancy was significantly lower than that of the pregnant women in the first and second trimester. CONCLUSION: The rate of normal thyroid function in pregnant women is low( less than 80%). Subclinical hypothyroidism is the main type of thyroid dysfunction during pregnancy. It should be continued to pay attention to the relationship between the high incidence of subclinical hypothyroidism and iodine nutritional status of pregnant women, especially subclinical hypothyroidism caused by insufficient iodine intake.

Data mining: Seasonal and temperature fluctuations in thyroid-stimulating hormone.

BACKGROUND: Thyroid-stimulating hormone (TSH) plays a key role in maintaining normal thyroid function. Here, we used "big data" to analyze the effects of seasonality and temperature on TSH concentrations to understand factors affecting the reference interval. METHODS: Information from 339,985 patients at Peking Union Medical College Hospital was collected from September 1st, 2013, to August 31st, 2016, and retrospectively analyzed. A statistical method was used to exclude outliers, with data from 206,486 patients included in the final analysis. The research period was divided into four seasons according to the National Weather Service. Correlations between TSH concentrations and season and temperature were determined. RESULTS: Median TSH levels during spring, summer, autumn, and winter were 1.88, 1.86, 1.87, and 1.96 mIU/L [corrected], respectively. TSH fluctuation was larger in winter (±0.128) than in summer (±0.125). After normalizing the data from each year to the lowest TSH median value (summer), TSH appeared to peak in winter and trough in summer, showing a negative correlation with temperature. Pearson correlation analysis indicated that the monthly median TSH values were negatively correlated with temperature (r = -0.663, p < .001). CONCLUSIONS: This study showed significant seasonal- and temperature-dependent variation in TSH concentrations. Thus, these might be important factors to consider when diagnosing thyroid function disorders.

Melanin-concentrating hormone is necessary for olanzapine-inhibited locomotor activity in male mice.

Olanzapine (OLZ), an atypical antipsychotic, can be effective in treating patients with restricting type anorexia nervosa who exercise excessively. Clinical improvements include weight gain and reduced pathological hyperactivity. However the neuronal populations and mechanisms underlying OLZ actions are not known. We studied the effects of OLZ on hyperactivity using male mice lacking the hypothalamic neuropeptide melanin-concentrating hormone (MCHKO) that are lean and hyperactive. We compared the in vivo effects of systemic or intra-accumbens nucleus (Acb) OLZ administration on locomotor activity in WT and MCHKO littermates. Acute systemic OLZ treatment in WT mice significantly reduced locomotor activity, an effect that is substantially attenuated in MCHKO mice. Furthermore, OLZ infusion directly into the Acb of WT mice reduced locomotor activity, but not in MCHKO mice. To identify contributing neuronal mechanisms, we assessed the effect of OLZ treatment on Acb synaptic transmission ex vivo and in vitro. Intraperitoneal OLZ treatment reduced Acb GABAergic activity in WT but not MCHKO neurons. This effect was also seen in vitro by applying OLZ to acute brain slices. OLZ reduced the frequency and amplitude of GABAergic activity that was more robust in WT than MCHKO Acb. These findings indicate that OLZ reduced Acb GABAergic transmission and that MCH is necessary for the hypolocomotor effects of OLZ.

[Clinical values of triptorelin stimulating test in assessing hypothalamus-pituitary-gonad axis function in male patients with hypothalamus-pituitary-gonad axis disorders].

OBJECTIVE: To investigate the clinical values of luteinizing hormone-releasing hormone (LHRH) α (triptorelin) stimulating test in the differential diagnoses of hypothalamus-pituitary-gonad axis (HPGA) disorders. METHODS: A total of 229 male patients with various HPGA disorders were recruited for triptorelin stimulating test. And all patients were followed up for 12 - 48 months until a definite diagnosis was made. The values of triptorelin stimulating test in the differential diagnoses of HPGA disorders were assessed by examining the close relationship between LHmax and the final clinical diagnosis. RESULTS: (1) LH levels rose steady after an intramuscular injection of triptorelin 100 µg and the time of LHmax appeared at 45 - 60 min. (2) LHmax < 4 U/L indicated the function of HPGA was not activated. LHmax in the range of 4 - 12 U/L indicated the patients might have constitutional delayed puberty development. LHmax > 12 U/L indicated the fulfilled puberty development. CONCLUSION: Triptorelin stimulating test can precisely evaluate the functions of HPGA in various HPGA disorders and provide valuable information for the differential diagnoses in constitutional delayed puberty development, hypogonadotropic hypogonadism, central and peripheral precocious puberty disorders.

Five novel mutations of SRD5A2 found in eight Chinese patients with 46,XY disorders of sex development.

Individuals with male karyotype (46,XY) affected by 5α-reductase type 2 deficiency, a rare autosomal recessive inherited disorder, can have an almost female phenotype or partially virilized external genitalia. Mutations in the steroid-5-α-reductase (SRD5A2) gene, leading to functional impairment of 5α-reductase type 2, are responsible for this disorder. Our present study analyzed SRD5A2 gene mutations in eight unrelated 46,XY Chinese patients with disorders of sex development. Direct sequencing of genomic DNA for SRD5A2 gene revealed the presence of one homozygous (p.Q6X) and seven compound heterozygous mutations (p.G203S/R227Q, p.L20P/R227Q, p.Q6X/p.A228V, p.C222Ffs232X/p.R246Q, p.W140X/F219Sfs278X, p.Q71X/L185Tfs192X and p.Q6X/p.N193S) in our patients. Among them, p.C222Ffs232X, p.A228V, p.Q71X, L185Tfs192X and p.W140X mutations have not been previously reported. These novel mutations may provide us new insights into the molecular mechanism of 5α-reductase type 2 deficiency. Seven out of eight patients had at least one variant in exon 4, and 8 of 12 (66.7%) mutations were located in exon 4. The expanded mutation database of the SRD5A2 gene should benefit patients in the diagnosis and treatment of this disease.

[Clinical values of single or repeated triptorelin stimulating test in the differential diagnosis between idiopathic hypogonadotropic hypogonadism and constitutional delayed puberty].

OBJECTIVE: To investigate the values of single or repeated luteinizing hormone (LH) releasing hormone analogue (triptorelin) stimulating test in the differential diagnosis between idiopathic hypogonadotropic hypogonadism (IHH) and constitutional delayed puberty (CDP). METHODS: Male patients (n = 133) without puberty onset after the age of 14 were recruited for triptorelin stimulating test and were followed up for 24 - 48 months until the diagnosis were confirmed: 86 were IHH and the other 47 were CDP. Repeated triptorelin stimulating tests were conducted in 9 IHH patients and 13 CDP patients one year after the first stimulating tests with an attempt to evaluate the dynamic change of hypothalamus-pituitary-testis axis function. The relationship between the final diagnosis and the peak LH value (LH(max)), and the changes of repeated LH(max) were investigated. RESULTS: In the single triptorelin stimulating test, LH(max) was (1.9 +/- 1.2) U/L in IHH group, which was significantly lower than that in CDP group [(13.7 +/- 8.3) U/L] (P < 0.01); 75 IHH patients (87.2%) had a LH(max) lower than 4 U/L, while only 2 CDP patients (4.3%) had a LH(max) lower than 4 U/L. When LH(max) < 4U/L was used as a criteria for the diagnosis of IHH, the single triptorelin stimulating test had a sensitivity of 87.2%, a specificity of 95.7%, and a positive predictive value of 97.4%. The repeated triptorelin stimulating tests performed one year later showed that the LH(max) in the 9 IHH patients increased from (4.7 +/- 2.5) U/L to (5.1 +/- 3.3) U/L (P = 0.78), while that in the 13 CDP patients increased from (10.7 +/- 3.3) U/L to (24.5 +/- 5.7) U/L (P < 0.05). CONCLUSIONS: A single triptorelin stimulating test is highly effective in differentiating IHH from CDP. For some patients without definitive diagnosis, a repeated triptorelin stimulating test performed one year later may provide more valuable information on the dynamic change of the hypothalamus-pituitary-testis axis function.

Mutational analysis of androgen receptor gene in four Chinese patients with male pseudohermaphroditism.

OBJECTIVE: To show mutational analysis for androgen insensitivity syndrome (AIS)-associated male pseudohermaphroditism (MPH). DESIGN: Case report. SETTING: Key laboratory of endocrinology at a university hospital. PATIENT(S): Four unrelated Chinese patients with MPH referred to our clinic were investigated in this study. INTERVENTION(S): Genomic DNA was extracted from peripheral blood leukocytes, and coding sequence abnormalities of androgen receptor (AR) gene were assessed by polymerase chain reaction and direct sequencing analysis. MAIN OUTCOME MEASURE(S): Molecular characterization of the AR gene. RESULT(S): Four mutations (p.P913R, p.D732 N, p.N848 K, fs879X, and p.R608 K) in the AR gene were identified in our study. The p.P913R mutation in the AR gene has not been described previously. CONCLUSION(S): Our study identified a novel mutation in the AR gene that may provide us new insights into the molecular mechanisms of AIS. The expanded database of these mutations should benefit patients in the diagnosis and treatment of this syndrome.

[A report of familial male-limited precocious puberty caused by a germ-line heterozygous mutation (M398T) in luteinizing hormone receptor gene].

OBJECTIVE: To clarify the possible gene mutations in luteinizing hormone(LH) receptor gene in a boy with LH independent precocious puberty and probe the mechanism the of diseases caused by LH receptor activating mutations. METHODS: (1) Describe the clinical manifestations and laboratory data in a 5-year-old boy with LH independent precocious puberty. (2) Peripheral leukocytes were collected from the proband, his parents and other 20 normal puberty developed males. PCR and direct DNA sequence of 11 exons in LH receptors gene were conducted. RESULTS: (1) The proband was diagnosed to have LH independent precocious puberty according to the clinical symptoms and the laboratory tests. (2) A germ-line heterozygous point mutation in the 11 exon of LH receptor gene was found in the proband and his mother: c1193 T-->C leading to amino acid change with M398T, which causes consecutively an activation of the LH receptor. (3) Other nucleotide changes in the proband and other normal males include c935 A-->G (N312S) and c1065 -->C (same sense mutation). CONCLUSIONS: (1) A germ-line heterozygous point mutation in the LH receptor gene with M398T leads to consecutively activation of the LH receptor and LH independent precocious puberty. (2) The same point mutation does not have any influence on the puberty development, menstruation and productive functions of the proband's mother. (3) The LH receptor gene has possible polymorphism in the Han ethnic population.

Testosterone replacement therapy improves insulin sensitivity and decreases high sensitivity C-reactive protein levels in hypogonadotropic hypogonadal young male patients.

BACKGROUND: Many clinical studies suggest the inverse relationship between testosterone levels and insulin sensitivity in men, however the causative relationship of these two events is still not determined. The purpose of this study was to investigate the effects of testosterone replacement therapy (TRT) on insulin sensitivity, body composition, serum lipid profiles and high sensitivity C-reactive protein (hsCRP) in hypogonadotropic hypogonadal (HH) puberty undeveloped male patients. METHODS: In this prospectively designed study, we compared homeostasis model assessment of insulin resistance (HOMA-IR), insulin areas under the curves (AUC) of 3-hour oral glucose tolerance test (OGTT) and other metabolic parameters between 26 HH patients and 26 healthy men. The patients' HOMA-IR, insulin AUC, body composition, lipid profiles, hsCRP and other parameters were compared before and after nine-month TRT. RESULTS: The average levels of total testosterone (TT) in HH and healthy group were (0.9 +/- 0.6) nmol/L and (18.8 +/- 3.4) nmol/L, respectively. HOMA-IR in HH group was significantly higher than the healthy group (5.14 +/- 5.16 vs 2.00 +/- 1.38, P < 0.005). Insulin AUC in 3-hour OGTT in HH group was significantly higher than the healthy group (698.6 +/- 414.7 vs 414.2 +/- 267.5, P < 0.01). Fasting glucose level in HH group was significantly higher than control group ((5.1 +/- 0.6) mmol/L vs (4.7 +/- 0.3) mmol/l, P < 0.005). Height, weight and grasp strength of the patients were significantly increased after 9-month TRT. Significant reductions in HOMA-IR (from 5.14 +/- 5.16 to 2.97 +/- 2.16, P < 0.01), insulin AUC (from 698.6 +/- 414.7 to 511.7 +/- 253.9, P < 0.01) and hsCRP (from (1.49 +/- 1.18) mg/L to (0.70 +/- 0.56) mg/L, P < 0.05) were found after TRT. Serum total cholesterol, LDL-C, HDL-C and triglyceride were all decreased, albeit with no significant difference compared to the level prior to TRT. CONCLUSIONS: HOMA-IR, insulin AUC and fasting glucose level in HH young male patients were significantly higher than those of the control group, which suggests that low level of testosterone in male adolescents might be a risk factor for insulin resistance. TRT can significantly improve patients' insulin sensitivity and suppress serum hsCRP, which in return suggests that TRT may prevent the HH patients from developing diabetes mellitus and cardiovascular diseases (CVD) in future.

[Testosterone replacement in hypogonadotropic hypogonadal young male improves insulin sensitivity].

OBJECTIVE: To evaluate the effect of testosterone replacement therapy in patients with hypogonadotrophic hypogonadism (HH) on insulin sensitivity and high sensitivity C reactive protein (hsCRP). METHODS: 21 males with HH, aged 15 - 30, and 18 age, and BMI-matched healthy males underwent detection of homeostasis model assessment insulin resistance index (HOMA-IR). Second, the values of weight, abdominal circumstance, grips strength, body composition, total testosterone (TT), fast blood glucose and insulin, serum lipid profile, and hsCRP were compared before and after 9-month testosterone replacement therapy in the HH patient group. RESULTS: (1) Before treatment the TT level of the HH patients WAS (0.9 +/- 0.6) nmol/L, significantly lower than that of the healthy control group (18.8 +/- 3.2) nmol/L. The fast insulin level of the HH patients was (16.0 +/- 9.8) mIU/L, significantly higher than that of the control group [(8.4 +/- 3.3) mIU/L, P = 0.018]. The HOMA-IR of the HH patient was 3.7 +/- 2.4, not significantly different from that of the control group (1.8 +/- 0.7, P = 0.021). (2) After testosterone therapy, the fast insulin level of the HH patients decreased from (16.0 +/- 9.8) mIU/L to (12.1 +/- 7.4) mIU/L (P = 0.03); the HOMA-IR decreased from (3.7 +/- 2.4) to (2.7 +/- 1.7) (P = 0.045); and the total cholesterol, LDL-c, HDL-c, and Triglyceride all decreased, but not significantly (all P > 0.05). The hsCRP decreased from (1.49 +/- 1.18) mg/L to (0.70 +/- 0.56) mg/L (P = 0.025). CONCLUSION: Short period of testosterone replacement therapy in young HH male patients significantly improves the insulin sensitivity and decreases the risk of cardiovascular disease.

[The survey of puberty timing in healthy boys in Daqing city in northern China].

OBJECTIVE: To investigate the puberty timing in healthy adolescent boys in Daqing city in northern China. METHODS: A cross-sectional and longitudinal combined survey was performed. On 150 male students aged 6-15. Follow up was conducted for 4 years. The serum levels of luteinizing hormone (LH), Follicular Stimulating Hormone (FSH) and total testosterone (TT) were measured. The puberty timing and anthropometry including the body height, weight, and genital development according to Tanner's stages were all recorded. RESULTS: The mean age of puberty onset in healthy adolescent boys is (12.0+/-1.6) years. The growth velocity in the first year after puberty onset is (6.9+/-0.4) cm/year. The level of plasma TT at the time of puberty onset is (1.0+/-0.3) nmol/L. CONCLUSION: The puberty timing of boys in the Daqing city, northern China is in the range from 8 to 14 years.

[Puberty development of the healthy adolescent girls of Daqing city, Heilongjiang province].

OBJECTIVE: To investigate the process of puberty development of healthy adolescent girls in Northern China. METHODS: 288 adolescent girls of Daqing city, Heilongjiang province, aged 5 to 16, were studied and followed up yearly for four years. The height, weight, fat percentage, second sex characteristics, and the blood levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E(2)) were examined. RESULTS: The mean age of puberty onset of these healthy adolescent girls was 8.5 years +/- 1.1 years. The blood levels of FSH, LH and E(2) were 0.2 mIU/L, 1.1 mIU/L and 0.06 nmol/L respectively (the 95 percentiles were 2.5 mIU/L, 2.3 mIU/L and 0.12 nmol/L respectively). Their mean age of menarche was 12.4 years +/- 1.2 years. The mean age of breast development was 8.8 years +/- 1.1 years. CONCLUSION: The girls in Northern China begin their puberty development at younger ages than reported before.