bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low Thyrotropin Levels Are Not Associated with Bone Loss in Older Women: A Prospective Study*
Authors: Bauer Douglas C. , Nevitt Michael C. , Ettinger Bruce , Stone Katie 
Published: January 2014

Abstract
The relationship between excess thyroid hormone and bone loss is controversial. To determine whether low TSH levels, indicating excessive thyroid hormone, are associated with low bone mass or accelerated bone loss in older women, we performed a prospective cohort study of 458 women over age 65 yr participating in the multicenter Study of Osteoporotic Fractures.
Three hundred and twenty-three women were randomly selected from the entire cohort of 9704; an additional 135 randomly selected thyroid hormone users were studied. Medical history, medication use, and calcaneal bone mineral density (BMD) were assessed at the baseline visit. Serum was collected and stored at −190 C. Hip and spine BMD were measured approximately 2 yr later, and follow-up calcaneal and hip BMD measurements were obtained after mean follow-up periods of 5.7 and 3.5 yr, respectively. TSH levels were determined in baseline serum samples using a third generation chemiluminescent assay.
After adjustment for age, weight, previous hyperthyroidism, and use of estrogen, bone loss over 4–6 yr was similar in women with low, normal, or high TSH. For example, femoral neck bone loss was −0.3%/yr (95% confidence interval, −0.8%, 0.3%) among women with low TSH (≤0.1 mU/L) and −0.5%/yr (95% confidence interval, −0.7%, −0.3%) in those with normal TSH (0.1–5.5 mU/L). There were no statistically significant differences in baseline bone mass of the calcaneus, spine, or femoral neck or trochanteric hip subregions. Baseline total hip BMD was 6% lower (P = 0.01) in women with low TSH. Similar results were obtained in analyses confined to women not taking estrogens.
We found no consistent evidence that low TSH, a sensitive biochemical marker of excess thyroid hormone, was associated with low BMD or accelerated bone loss in older ambulatory women.
A Randomized, Cross-Over Trial of Once-Daily Versus Twice-Daily Parathyroid Hormone 1–34 in Treatment of Hypoparathyroidism
Authors: Winer Karen K. , Yanovski Jack A. , Sarani Babak , Cutler Jr. Gordon B. 
Published: January 2014

Once-daily sc injection of PTH 1–34 can normalize mean serum and urine calcium levels in patients with hypoparathyroidism; however, once-daily PTH has diminishing effects on serum calcium after 12 h, such that serum calcium levels fall below the normal range in some patients. Once-daily PTH also causes a marked increase in bone turnover, with persistent increases in markers of bone formation and resorption. To test the hypothesis that a twice-daily PTH regimen can produce more physiological control than a once-daily regimen, we performed a randomized cross-over trial, lasting 28 weeks, in 17 adult subjects with hypoparathyroidism. Each 14-week study arm was divided into a 2-week inpatient dose-adjustment phase and a 12-week outpatient phase. The PTH dose (given sc once daily at 0900 h or twice daily with one dose at 0900 h and the other at 2100 h) was adjusted to maintain both serum and urine calcium within, or close to, the normal range.During the second half of the day (12–24 h), twice-daily PTH increased serum calcium and magnesium levels more effectively than once-daily PTH. In patients with calcium receptor mutations (CaR), once-daily PTH normalized urine calcium, provided that serum calcium was maintained at levels below normal range. However, twice-daily PTH treatment produced higher mean serum calcium in patients with CaR with no significant rise in urine calcium excretion, and with no significant differences in either serum or urine calcium levels between CaR and patients with acquired or idiopathic hypoparathyroidism. Thus, treatment with twice-daily PTH is the better regimen for patients with CaR to overcome their tendency to hypercalciuria while producing near-normal levels of serum calcium. The total daily PTH dose was markedly reduced with the twice-daily regimen (twice daily 46 ± 52 vs. once daily 97 ± 60 μg/day, P &lt; 0.001). We conclude that a twice-daily PTH regimen provides effective treatment of hypoparathyroidism and reduces the variation in serum calcium levels at a lower total daily PTH dose.
Ineffective Cardiorespiratory Function in Hyperthyroidism1
Authors: Kahaly George J. , Nieswandt Jana , Wagner Stefan , Schlegel Jens , Mohr-Kahaly Susanne , Hommel Gerhard 
Published: January 2014

Dyspnea on exertion is a common complaint in hyperthyroidism, and this thyroid dysfunction has been implicated as a primary cause of impaired effort tolerance. Using spirometry and spiroergometry, 42 patients with untreated hyperthyroidism were examined, and the condition was controlled 7 days later under propranolol monotherapy, as well as after 6 months in euthyroidism.
While hyperthyroid, reduced forced vital capacity and tidal volume at the anaerobic threshold (AT) were observed in comparison to euthyroidism. Decreased oxygen (O2) pulse at AT (7 ± 0.4 vs. 9.1 ± 0.4 mL/beat, P = 0.0012) and at maximal exercise was noted in hyperthyroidism and was enhanced under propranolol (8.9 ± 0.4 mL/beat, P = 0.0001). During exercise, the increment of minute ventilation (16.1 ± 0.7 vs. 20.2 ± 1.0 L/min, P = 0.0015), O2 uptake (9 ± 0.5 vs. 11.4 ± 0.5 mL/min/kg, P = 0.0022), O2 pulse (4.0 ± 0.3 vs. 5.6 ± 0.3 mL/beat, P = 0.0001), and heart rate (53 ± 2 vs. 65 ± 3 beat/min, P = 0.0004) was markedly lower in hyper- vs. euthyroidism. Work rate at AT and at maximum was reduced in hyper- vs. euthyroidism (107.4 ± 3 vs. 141.1 ± 4 watt, P= 0.0001). Negative correlations between free T3 and O2 pulse at AT (r = −0.59, P = 0.0005), delta O2 uptake (r = −0.54, P = 0.0007), delta minute ventilation (r = −0.48, P = 0.0007), and maximal work rate (r = −0.62, P = 0.0001) were noted.
In hyperthyroidism, analysis of respiratory gas exchange showed low efficiency of cardiopulmonary function, respiratory muscle weakness, and impaired exercise capacity, which were reversible in euthyroidism.
The Effect of Gonadotropin-Releasing Hormone Agonist on Type I Collagen C-Telopeptide and N-Telopeptide: the Predictive Value of Biochemical Markers of Bone Turnover
Authors: Amama Ernest A. , Taga Michiyoshi , Minaguchi Hiroshi 
Published: January 2014

To evaluate the clinical utility of recently developed biochemical markers in the assessment of bone metabolism during GnRH agonist (GnRHa) treatment, we compared five bone resorption markers[ C-telopeptide (CTX) and N-telopeptide (NTX) of type I collagen, hydroxyproline (Hpr), pyridinoline (Pyr), and deoxypyridinoline (Dpyr)] and two bone formation markers [total alkaline phosphatase (Alp) and osteocalcin (OC)]. Sixty-eight normally menstruating women were injected with a long-acting GnRHa once a month for 24 weeks for the treatment of endometriosis or leiomyoma.
The mean percentage bone loss at the lumbar spine was 3.79% at the end of treatment. Although levels of all markers increased significantly as the treatment progressed, CTX and NTX exhibited the highest correlation coefficients between bone loss at 24 weeks and the seven markers measured at 0, 4, 12, 16, and 24 weeks of treatment. Serum estradiol levels were similarly suppressed during the treatment in both fast losers (whose bone loss was more than the mean) and slow losers (whose bone loss was less than the mean). However, significantly higher z-scores of bone resorption markers, but not of bone formation markers, were observed in the fast losers at 24 weeks of treatment, suggesting a more accelerated bone resorption in this group. Whereas the three highest z-scores at 24 weeks of treatment were CTX, NTX, and Dpyr (in that order), the highest z-score (P &lt; 0.05) was observed for CTX in the fast losers. The subjects in the highest quartile of CTX, the highest, and second highest quartiles of NTX at 24 weeks of treatment experienced 2.1, 2.2, and 1.7 times more bone loss (P &lt; 0.001), respectively, than those in the lowest quartiles. Furthermore, the subjects in the highest quartile of both CTX and NTX experienced 3.6 times more bone loss (P &lt; 0.001) than those in the lowest quartile of both markers. These results indicate that both CTX and NTX are useful and sensitive markers for bone resorption in a hypoestrogenic state induced by GnRHa.
Iodine Intake and the Pattern of Thyroid Disorders: A Comparative Epidemiological Study of Thyroid Abnormalities in the Elderly in Iceland and in Jutland, Denmark
Authors: Laurberg Peter , Pedersen Klaus M. , Hreidarsson Astradur , Sigfusson Nikulas , Iversen Eigil , Knudsen Preben R. 
Published: January 2014

Thyroid abnormalities are common in all populations, but it is difficult to compare results of epidemiological studies, because different methods have been used for evaluation. We studied the importance of the population iodine intake level for the prevalence rate of various thyroid abnormalities in elderly subjects.Random samples of elderly subjects (68 yr) were selected from the central person registers in Jutland, Denmark, with low (n = 423) and, in Iceland, with longstanding relatively high (n = 100) iodine intake.Females from Jutland had a high prevalence of goiter or previous goiter surgery (12.2%), compared with males from Jutland (3.2%) and females (1.9%) and males (2.2%) from Iceland. Abnormal thyroid function was very common in both areas, with serum TSH outside the reference range in 13.5% of subjects from Jutland and 19% of those from Iceland. In Jutland, it was mainly thyroid hyperfunction (9.7% had low, 3.8% had high serum TSH), whereas in Iceland, it was impaired thyroid function (1% had low, 18% had high serum TSH). All subjects with serum TSH more than 10 mU/L had autoantibodies in serum, but antibodies were, in general, more common in Jutland than in Iceland.Thus, thyroid abnormalities in populations with low iodine intake and those with high iodine intake develop in opposite directions: goiter and thyroid hyperfunction when iodine intake is relatively low, and impaired thyroid function when iodine intake is relatively high. Probably, mild iodine deficiency partly protects against autoimmune thyroid disease. Thyroid autoantibodies may be markers of an autoimmune process in the thyroid or secondary to the development of goiter.
Serum Lipids, Lipoproteins, and Lipid Metabolizing Enzymes in Identical Twins Discordant for Obesity
Authors: Rönnemaa Tapani , Marniemi Jukka , Savolainen Markku J. , Kesäniemi Y. Antero , Ehnholm Christian , Bouchard Claude , Koskenvuo Markku 
Published: January 2014

abstractObesity is associated with adverse changes in plasma lipoprotein metabolism, but it is not known completely how this association is modified by genetic factors. We assessed the contribution of obesity to serum lipid and lipoprotein levels and lipid metabolizing enzyme activities by examining 23 identical twin pairs (9 male, 14 female) who had, on the average, an 18-kg intrapair difference in BW. Compared with lean co-twins, obese co-twins had approximately 20% higher low-density lipoprotein (LDL) cholesterol (P &lt; 0.01), 20% lower high-density lipoprotein2 cholesterol (P = 0.010), and 90% (men) or 35% (women) higher (P ≤ 0.06) total, very-low-density lipoprotein and LDL triglycerides. The pairs were divided into subgroups by the gender-specific median value of abdominal visceral fat (AVF) area in the obese co-twin and by apolipoprotein E 4 phenotype. The intrapair differences in serum cholesterol fractions were similar in twin pairs with high or low AVF, whereas only high AVF pairs showed significant differences in triglyceride fractions. The greatest intrapair differences in total, very-low-density lipoprotein and LDL triglycerides were observed in apolipoprotein E 4-positive pairs expressing high AVF. Compared with lean co-twins, lecithin cholesterol acyltransferase activity was 18% higher (P &lt; 0.001) and hepatic lipase activity was 38% higher (P = 0.016) in obese co-twins with high AVF. When genetic factors are identical, obesity is associated with an atherogenic lipid profile, especially in subjects with high visceral fat accumulation.
Gene Transcription of Receptors for Growth Hormone-Releasing Peptide and Somatostatin in Human Pituitary Adenomas1
Authors: Nielsen Steen , Mellemkjær Søren , Rasmussen Lars M. , Ledet Thomas , Astrup Jens , Weeke Jørgen , Jørgensen Jens O. L. 
Published: January 2014

abstract
Growth hormone (GH)-releasing peptides (GHRP) or secretagogs (GHS) constitute a family of synthetic compounds with potent and specific GH releasing activity. The receptor (GHS-R) has recently been cloned even though the endogenous ligand remains to be identified. GHRPs act both at the hypothalamic and the pituitary level through mechanisms involving amplification of GH-releasing hormone activity and functional somatostatin antagonism. In the present study we examined the co-expression of messenger RNA (mRNA) for GHS-R and all 5 somatostatin receptor subtypes (sstr 1–5) in 28 human pituitary tumors by RT-PCR. GHS-R transcription was detected in 11 out of 12 somatotroph adenomas and in 2 out of 2 prolactinomas, whereas GHS-R expression was detected in only 2 out of 14 clinically nonfunctioning adenomas (NFPA), and no expression was seen in the only ACTH secreting adenoma. Almost all tumors expressed sstr 2 mRNA (n = 24), whereas only 1 tumor expressed sstr 4 mRNA. The expression of sstr 3 mRNA was inversely associated with GHS-R expression (P &lt; 0.001), which could be attributed to a high prevalence of sstr 3 expression in NFPA.
This study suggests that GHS-R expression is predominantly observed in somatotroph adenomas and much less so in NFPA. Moreover, the presence of a distinct pattern of somatostatin receptor subtype co-expression is suggested, which may provide a molecular basis for the complex interaction between GHRPs and somatostatin.
Steroid Regulation of Prostaglandin Dehydrogenase Activity and Expression in Human Term Placenta and Chorio-Decidua in Relation to Labor1
Authors: Patel Falguni A. , Clifton Vicki L. , Chwalisz K. , Challis John R. G. 
Published: January 2014

NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (PGDH) is the key catabolic enzyme controlling levels of biologically active PGs. PGDH is localized to syncytiotrophoblast in placenta, and to trophoblast cells in chorion. To examine the regulation of PGDH by steroids and to determine any changes with labor, we obtained placenta and chorion from term elective cesarean section or spontaneous delivery and isolated trophoblast cells using a Percoll density gradient. Cells were treated with varying concentrations of cortisol, progesterone, the synthetic progestins R5020, and medroxyprogesterone acetate with or without RU486 or the specific progesterone receptor antagonist, onapristone, and the 3β-hydroxysteroid dehydrogenase inhibitor, trilostane. The activity of PGDH was assessed by measurement of 13,14-dihydro-15-keto-PGF2α. PGDH messenger ribonucleic acid was quantified by in situ hybridization and computerized image analysis.The basal output of 13,14-dihydro-15-keto-PGF2α was lower in placenta or chorion collected at spontaneous labor than in that obtained at elective cesarean section. Cortisol had a significant dose-dependent inhibitory effect on PGDH activity in both placental and chorion trophoblast cells and significantly decreased levels of PGDH messenger ribonucleic acid. Responses were similar between tissues from laboring and nonlaboring women. PGDH activity was increased by R5020 and medroxyprogesterone acetate and was inhibited by RU486, onapristone, and trilostane. We conclude that cortisol inhibits PGDH activity and expression and that progestagens increase PGDH activity in human chorion and placenta.
Serum Free Insulin-Like Growth Factor I (IGF-I), Total IGF-I, and IGF-Binding Protein-3 Concentrations in Normal Children and Children with Growth Hormone Deficiency1
Authors: Kawai Nobuyasu , Kanzaki Susumu , Takano-Watou Syouko , Tada Chiaki , Yamanaka Yoshitaka , Miyata Tsuyoshi , Oka Masanori , Seino Yoshiki 
Published: January 2014

To evaluate the role of serum free or unbound insulin-like growth factor I (IGF-I) on bone growth, we measured serum free IGF-I levels in 354 healthy children and adults (193 males and 161 females, aged 0–40 yr) and in 21 prepubertal GH-deficient (GHD) children (complete GHD, n = 5; partial GHD, n = 16) using a recently developed immunoradiometric assay.
We obtained the following results. 1) In the normal children, the serum free IGF-I levels were low in infancy (&lt;1 yr of age; males, 0.71± 0.26 μg/L, mean ± sd; females, 1.05 ± 0.49μ g/L), increased during puberty (males, 5.84 ± 2.18 μg/L; females, 5.80 ± 1.49 μg/L), and declined thereafter. 2) Free IGF-I in the serum occupied about 0.95–2.02% of the total IGF-I values, with the highest ratio occurring in infancy (males, 1.77± 0.60%; females, 2.02 ± 0.87%). 3) The sd scores of serum free IGF-I in the 21 GHD children ranged from −3.30 to 0.30, and the 5 complete GHD children had free IGF-I values more than −2 sd below those of age-matched normal subjects. 4) There was a significant correlation between the sd scores of free IGF-I and those of total IGF-I (r = 0.715; P&lt; 0.0005) in the GHD children. 5) In the 16 partial GHD children receiving GH treatment, the serum free IGF-I levels were elevated to 209% of pretreatment levels after 1 month of GH treatment and remained high during GH therapy. The GH-induced increase in the serum free IGF-I levels was significantly higher than those of the total IGF-I and IGF binding protein-3 levels. 6) The percent increase in the serum free IGF-I level after 1 month of GH treatment showed a significant positive correlation with that of the GH-induced improvement in the percent increase in the height velocity during 1 yr of GH therapy (r = 0.526; P &lt; 0.05).
These results show that free IGF-I in the serum has an essential role in bone formation because the higher free IGF-I levels were observed when the growth rate accelerated. The measurement of serum free IGF-I may become a useful tool for both diagnosing GH deficiency and predicting growth responses to long term GH therapy.
Lack of Effect of GnRH Agonists on Final Height in Girls with Advanced Puberty: A Randomized Long-Term Pilot Study
Authors: Bouvattier C. , Coste J. , Rodrigue D. , Teinturier C. , Carel J. C. , Chaussain J. L. , Bougnères P. F. 
Published: January 2014

Abstract
GnRH agonists improve final height in girls with “true” precocious puberty. To test if a comparable effect can be obtained in older girls, we performed a long-term controlled study in 30 caucasian girls whose puberty started between 8.4 and 10 yr (9.4 ± 0.1 yr), a variant of normal called “advanced” puberty. At entry into trial, these girls had clinical, biological, and sonographic manifestations of puberty and a bone age greater than 10.9 yr. They were randomized 2:1 to receive 3.75 mg triptorelin im every 4 weeks for 2 yr (n = 20, group I) or no treatment (n = 10, group II). Mean height at inclusion was 135.2 ± 4.3 cm (+0.6 sds) in group I, 136.1 ± 4.2 cm (+0.8 sds ) in group II, with target height 157.6 ± 4.3 cm (group I) and 157.8 ± 4.7 cm (group II), and predicted height (Bayley-Pinneau) 154.1 ± 3.9 cm and 155.2 ± 3.7 cm. Although GnRH agonists transiently delayed sexual maturation as well as bone age and growth rate, they had no clear-cut long-standing effect, and final height was comparable in treated (157.6 ± 4.0 cm) and untreated girls (156.1 ± 5.3 cm) (NS).
A Frame-Shift Mutation in the Type I Parathyroid Hormone (PTH)/PTH-Related Peptide Receptor Causing Blomstrand Lethal Osteochondrodysplasia
Authors: Karperien Marcel , van der Harten Hans J. , van Schooten Ron , Farih-Sips Hetty , den Hollander Nicolette S. , Kneppers Sander L. J. , Nijweide Peter , Papapoulos Socrates E. , Löwik Clemens W. G. M. 
Published: January 2014

AbstractBlomstrand osteochondrodysplasia (BOCD) is a rare lethal skeletal dysplasia characterized by accelerated endochondral and intramembranous ossification. Comparison of the characteristics of BOCD with type I PTH/PTH-related peptide (PTHrP) receptor-ablated mice reveals striking similarities that are most prominent in the growth plate. In both cases, the growth plate is reduced in size due to a strongly diminished zone of resting cartilage and the near absence of columnar arrangement of proliferating chondrocytes. This overall similarity suggested that an inactivating mutation of the PTH/PTHrP receptor might be the underlying genetic defect causing BOCD. Indeed, inactivating mutations of the PTH/PTHrP receptor have been recently identified in two cases of BOCD.We describe here a novel inactivating mutation in the PTH/PTHrP receptor. Sequence analysis of all coding exons of the type I PTH/PTHrP receptor gene and complementary DNA of a case with BOCD identified a homozygous point mutation in exon EL2 in which one nucleotide (G at position 1122) was absent. The mutation was inherited from both parents, supporting the autosomal recessive nature of the disease. The missense mutation resulted in a shift in the open reading frame, leading to a truncated protein that completely diverged from the wild-type sequence after amino acid 364. The mutant receptor, therefore, lacked transmembrane domains 5, 6, and 7; the connecting intra- and extracellular loops; and the cytoplasmic tail. Functional analysis of the mutant receptor in COS-7 cells and of dermal fibroblasts obtained from the case proved that the mutation was indeed inactivating. Neither the transiently transfected COS-7 cells nor the dermal fibroblasts responded to a challenge with PTH or PTHrP with a rise in intracellular cAMP levels, in sharp contrast to control cells. Our results provide further evidence that BOCD is caused by inactivating mutations of the type I PTH/PTHrP receptor and underscore the importance of this receptor in mammalian skeletal development
Cerebrospinal Fluid and Plasma Leptin Measurements: Covariability with Dopamine and Cortisol in Fasting Humans*
Authors: Hagan Mary M. , Havel Peter J. , Seeley Randy J. , Woods Stephen C. , Ekhator Nosa N. , Baker Dewleen G. , Hill Kelly K. , Wortman Matthew D. , Miller Andrew H. , Gingerich Ronald L. , Geracioti Thomas D. 
Published: January 2014

Abstract
Leptin (OB protein) is an important signal in the regulation of energy balance. Leptin levels correlate with adiposity, but also decrease acutely with caloric restriction and increase with refeeding. The brain is an established critical site of leptin function, yet little is known about leptin concentrations in the central nervous system relative to plasma levels, psychiatric diagnoses, and other endocrine parameters. Therefore, using a novel ultrasensitive leptin assay, we explored relationships of human plasma and cerebrospinal fluid (CSF) leptin levels to body mass index, smoking, posttraumatic stress disorder diagnosis, and levels of dopamine, monoamine metabolites,β -lipotropin, glucocorticoid, and thyroid and cytokine hormones. A strong linear relation between CSF and plasma leptin levels in the am (r = 0.63; P &lt; 0.002) and afternoon (r = 0.90; P &lt; 0.0001) was revealed. CSF and plasma leptin concentrations decreased during a 12- to 20-h period of fasting. A strong association was found between plasma leptin and CSF dopamine levels (r = 0.74; P &lt; 0.01) as well as between CSF leptin levels and urinary free cortisol (r = 0.73; P &lt; 0.01). Both of these parameters covaried with leptin independently of adiposity, as estimated by body mass index. Implications for leptin transport, regulation, and its potential role in therapeutic strategies for obesity and diabetes are discussed.