bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Thyroid Dysfunction on High-Density Lipoprotein Subfraction Metabolism: Roles of Hepatic Lipase and Cholesteryl Ester Transfer Protein1
Authors: Tan K. C. B. , Shiu S. W. M. , Kung. A. W. C. 
Published: January 2014

abstractTo investigate the effect of thyroid dysfunction on high-density lipoprotein (HDL) metabolism, we measured HDL subfractions, apolipoprotein A-I containing particles (LpA-I and LpA-I:A-II), and the activities of enzymes involved in the remodeling and metabolism of HDL[ namely hepatic lipase (HL), lipoprotein lipase, and cholesteryl ester transfer protein (CETP)] in 18 hyperthyroid and 17 hypothyroid patients before and after treatment. HDL was subfractionated by density gradient ultracentrifugation, and LpA-I was analyzed by electroimmunodiffusion. The major changes were found in the HDL2 subfraction and in LpA-I particles. HDL2-C and LpA-I were reduced in hyperthyroidism (P &lt; 0.01, P &lt; 0.05, respectively) and increased in hypothyroidism (both P &lt; 0.05) compared with their respective euthyroid matched controls. Changes in HDL2-cholesterol were reversed after treatment in both hyper- and hypothyroid patients, and LpA-I also decreased in the hypothyroid patients after treatment. HL (P &lt; 0.05) and CETP activities (P &lt; 0.05) were elevated in hyperthyroidism and reduced in hypothyroidism (P &lt; 0.05, P &lt; 0.01 respectively) and both were related to free T4 levels. The changes in HDL2-C and LpA-I correlated significantly with changes in HL after treatment but not with CETP or lipoprotein lipase. In summary, HDL metabolism was altered in thyroid dysfunction, and the effect of thyroid hormone on HDL was mediated mainly via its effect on HL activity.
Thresholds for Surgery and Surgical Outcomes for Patients with Primary Hyperparathyroidism: A National Survey of Endocrine Surgeons
Authors: Sosa Julie Ann , Powe Neil R. , Levine Michael A. , Udelsman Robert , Zeiger Martha A. 
Published: January 2014

abstract
A 1991 NIH Consensus Development Conference statement provided recommendations for the management of patients with asymptomatic and minimally symptomatic primary hyperparathyroidism (1° HPT), but adherence to these guidelines has not been documented. We conducted a cross-sectional survey of North American members of the American Association of Endocrine Surgeons inquiring about surgeon and 1° HPT patient characteristics, thresholds for surgery, and clinical outcomes. Multivariate regression was used to assess the relationship of physician characteristics to practice patterns and outcomes.
Of 190 surgeons surveyed, 147 (77%) responded; 109 provided complete responses (57%). These surgeons spend 66% of their time in patient care and perform an average of 33 (range, 1–130) parathyroidectomies/yr. More than 72% of 1° HPT patients who underwent surgery were asymptomatic or minimally symptomatic. High volume surgeons (&gt;50 cases/yr) had significantly lower thresholds for surgery with respect to abnormalities in preoperative creatinine clearance, bone densitometry changes, and levels of intact PTH and urinary calcium compared to their low volume colleagues (1–15 cases/yr). Overall reported surgical cure rates were 95.2% after primary operation and 82.7% after reoperation. Compared to high volume surgeons, low volume endocrine surgeons had significantly higher complication rates after primary operation (1.9% vs. 1.0% respectively; P &lt; 0.01) and reoperation (3.8% vs. 1.5%; P &lt; 0.001) as well as higher in-hospital mortality rates (1.0% vs. 0.04%; P &lt; 0.05).
Endocrine surgeons operate on a large number of asymptomatic or minimally symptomatic 1° HPT patients. Even among a group of highly experienced surgeons who typically see patients after referral from endocrinologists, clinical outcomes and criteria for surgery vary widely and appear to be associated with surgeon experience. Their criteria for surgery diverge from NIH guidelines. These results implore the endocrine community to examine the evidential basis for decisions made in the management of 1° HPT.
Adrenocortical Overexpression of Gastric Inhibitory Polypeptide Receptor Underlies Food-Dependent Cushing’s Syndrome1
Authors: N’Diaye Nina , Tremblay Johanne , Hamet Pavel , De Herder Wouter W. , Lacroix André 
Published: January 2014

abstract
Abnormal responsiveness of adrenocortical cells to gastric inhibitory polypeptide (GIP) in food-dependent Cushing’s syndrome suggested that adrenal expression of ectopic, overexpressed, or mutated GIP receptor (GIPR) underlies this syndrome. The expression of GIPR was studied by RT-PCR in human adrenal tissues from two patients with GIP-dependent Cushing’s syndrome (adenoma, bilateral hyperplasia), five fetal or adult controls, one patient with Cushing’s disease, and four patients with non-food-dependent cortisol-secreting adenomas or bilateral hyperplasias and compared to that in normal pancreas. Hybridization of the RT-PCR-amplified ribonucleic acids with the human GIPR complementary DNA showed an overexpression of GIPR in the adrenals of the two GIP-dependent Cushing’s syndrome patients compared to that in normal adrenal tissues (2–3 orders of magnitude) or pancreas (10-fold); no signal could be seen in adrenal adenomas or macronodular hyperplasia from cases of non-food-dependent Cushing’s syndrome. No mutation of the GIPR was identified by sequencing the full-length receptor in GIP-dependent adrenal tissue. New alternative spliced isoforms of the GIPR were found, but are identical in GIP-dependent and normal adrenal tissues. Incubation of adrenal cells with GIP stimulates cortisol secretion in GIP-dependent, but not in normal fetal, adult, or non-food-dependent Cushing’s syndrome, adrenals. We conclude that the GIPR overexpression and its coupling to steroidogenesis underlie GIP-dependent Cushing’s syndrome.
Deleterious Missense Mutations and Silent Polymorphism in the Human 17β-Hydroxysteroid Dehydrogenase 3 Gene (HSD17B3)1
Authors: Moghrabi Nabil , Hughes Ieuan A. , Dunaif Andrea , Andersson Stefan 
Published: January 2014

abstractIsozymes of 17β-hydroxysteroid dehydrogenase (17βHSD) regulate levels of bioactive androgens and estrogens in a variety of tissues. For example, the 17βHSD type 3 isozyme catalyzes the conversion of the inactive C19-steroid androstenedione to the biologically active androgen, testosterone, in the testis. Testosterone is essential for the correct development of male internal and external genitalia; hence, deleterious mutations in the HSD17B3 gene give rise to a rare form of male pseudohermaphroditism termed 17βHSD deficiency. Here, 2 additional missense mutations in the HSD17B3 gene in subjects with 17βHSD deficiency are described. One mutation (A56T) impairs enzyme function by affecting NADPH cofactor binding. A second mutation (N130S) led to complete loss of enzyme activity. Also, a single base pair polymorphism in exon 11 of the HSD17B3 gene is described. The polymorphic A allele encodes a protein with a serine rather than a glycine at position 289 (GGT → AGT). The frequency of the G allele (Gly) was 0.94, and that of the A allele (Ser) was 0.06. No difference in the frequencies of the G and A alleles was detected in 32 apparently normal women and 46 women with polycystic ovary syndrome. Enzymes bearing either glycine or serine at this position have similar substrate specificities and kinetic constants. The current findings boost to 16 the number of mutations in the HSD17B3 gene that impair testosterone synthesis and cause male pseudohermaphroditism, and add 1 apparently silent polymorphism to this tally.
Analysis of Meiosis in Intratesticular Germ Cells from Subjects Affected by Classic Klinefelter’s Syndrome
Authors: Foresta Carlo , Galeazzi Carlo , Bettella Andrea , Marin Paola , Rossato Marco , Garolla Andrea , Ferlin Alberto 
Published: January 2014

Abstract
Azoospermic subjects affected by Klinefelter’s syndrome may occasionally show the presence of intratesticular residual foci of spermatogenesis, and the retrieval of mature spermatozoa from the testis may permit fertility and paternity by means of intracytoplasmic sperm injection.
Previous studies have demonstrated that these subjects show the presence of an increased incidence of hyperaploid spermatozoa. Here we analyzed, by fluorescence in situ hybridization using specific probes for chromosomes 8, X, and Y, the spermatogenic process and the meiotic progression of 47,XXY germ cells retrieved by fine needle aspiration of the testis in ten azoospermic patients affected by classic Klinefelter’s syndrome. All patients had lower testicular volume, higher gonadotropins, and lower testosterone plasma levels compared with control subjects. Cytological analysis of the testicular cells retrieved by fine needle aspiration showed the presence of Sertoli cells only in eight subjects, while germ cells were observed in two patients. In each patient Sertoli cells showed a 47,XXY karyotype, and the same chromosome pattern was observed in spermatogonia and primary spermatocytes of patients presenting a residual spermatogenesis. Secondary spermatocytes, spermatids, and mature spermatozoa showed different sex chromosome patterns, reflecting their origin from 47,XXY spermatogonia.
In conclusion, this study demonstrated that, in subjects affected by Klinefelter’s syndrome, residual germ cells may be present in the testis and that 47,XXY spermatogonia are able to undergo and complete the spermatogenic process leading to mature spermatozoa. These data further suggest the need to evaluate the sex chromosome status of sperm from patients affected by Klinefelter’s syndrome undergoing assisted reproductive techniques.
Ethnicity and Migration as Determinants of Human Prostate Size*
Authors: Jin B. , Turner L. , Zhou Z. , Zhou E. L. , Handelsman D. J. 
Published: January 2014

Abstract
The roles of ethnicity and migration in determining the size of human prostate zones during midlife were explored. Prostate size was measured by planimetric ultrasound in 163 men residing in Sydney who were either Australian non-Chinese (AR; n = 116) or Chinese migrants (ACM; n = 47) and had lived in Australia for a median of 7.3 yr (range, 0.2–25 yr). These were compared with Chinese men residing in China (CR; n = 210). Central and total prostate volumes were estimated by a single observer using the same equipment at both sites. After adjustment for age, central and total prostate volumes were significantly smaller, and plasma prostate-specific antigen and 5α-dihydrotestosterone (DHT) concentrations and International Prostate Syndrome Scores were significantly lower, in CR compared with either ACM or AR, whereas the scores of the latter two groups were similar. Almost all of the population difference in total prostate volumes could be accounted for by differences in central prostate volumes. The strongest correlates of age-adjusted prostate volume were prostate-specific antigen and DHT, the latter presumably reflecting the quantitative importance of prostatic stromal type II 5α-reductase activity to circulating DHT concentrations. Sex hormone-binding globulin concentrations were significantly higher in CR and significantly lower in ACM compared with those in AR, but the significance of these observations is unclear. These findings highlight the importance of the central zone of the prostate as well as provide evidence for an environmental factor influencing prostate growth. This factor operates over a relatively short time period compared with the evolution of prostate disease. Hence, this study provides evidence that ethnicity and geographical factors, such as migration, can influence the growth of the normal human prostate during midlife and may facilitate future studies of the origins and pathogenesis of human prostate disease.
Endogenous Sex Hormones and Cognitive Function in Older Men*
Authors: Barrett-Connor Elizabeth , Goodman-Gruen Deborah , Patay Brad 
Published: January 2014

AbstractThe objective of this study was to determine whether endogenous sex hormone levels predict cognitive function in older men. Our study design was an exploratory analysis in a population-based cohort in Rancho Bernardo, California. The study participants were 547 community-dwelling men 59–89 yr of age at baseline who were not using testosterone or estrogen therapy. Between 1984 and 1987, sera were collected for measurement of endogenous total and bioavailable testosterone and estradiol levels. Between 1988 and 1991, 12 standard neuropsychological instruments were administered, including two items from the Blessed Information-Memory-Concentration (BIMC) Test, three measures of retrieval from the Buschke-Fuld Selective Reminding Test, a category fluency test, immediate and delayed recall from the Visual Reproduction Test, the Mini-Mental State Examination with individual analysis of the Serial Sevens and the “World” Backwards components, and the Trail-Making Test Part B. In age- and education-adjusted analyses, men with higher levels of total and bioavailable estradiol had poorer scores on the BIMC Test and Mini-Mental State Examination. Men with higher levels of bioavailable testosterone had better scores on the BIMC Test and the Selective Reminding Test (long-term storage). Five associations were U-shaped: total testosterone and total and bioavailable estradiol with the BIMC Test; bioavailable testosterone with the “World” test; and total estradiol with the Trail-Making Test. All associations were relatively weak but independent of age, education, body mass index, alcohol use, cigarette smoking and depression. In these older men, low estradiol and high testosterone levels predicted better performance on several tests of cognitive function. Linear and nonlinear associations were also found, suggesting that an optimal level of sex hormones may exist for some cognitive functions.
Modulation of 11β-Hydroxysteroid Dehydrogenase Isozymes by Growth Hormone and Insulin-Like Growth Factor: In Vivo and In Vitro Studies1
Authors: Moore J. S. , Monson J. P. , Kaltsas G. , Putignano P. , Wood P. J. , Sheppard M. C. , Besser G. M. , Taylor N. F. , Stewart P. M. 
Published: January 2014

The interconversion of hormonally active cortisol (F) and inactive cortisone (E) is catalyzed by two isozymes of 11β-hydroxysteroid dehydrogenase (11βHSD), an oxo-reductase converting E to F (11βHSD1) and a dehydrogenase (11βHSD2) converting F to E. 11βHSD1 is important in mediating glucocorticoid-regulated glucose homeostasis and regional adipocyte differentiation. Earlier studies conducted with GH-deficient subjects treated with replacement GH suggested that GH may modulate 11βHSD1 activity.In 7 acromegalic subjects withdrawing from medical therapy (Sandostatin-LAR; 20–40 mg/month for at least 12 months), GH rose from 7.1 ± 1.5 to 17.5 ± 4.3 mU/L (mean ± se), and insulin-like growth factor I (IGF-I) rose from 43.0 ± 8.8 to 82.1 ± 13.7 nmol/L (both P &lt; 0.05) 4 months after treatment. There was a significant alteration in the normal set-point of F to E interconversion toward E. The fall in the urinary tetrahydrocortisols/tetrahydocortisone ratio (THF+allo-THF/THE; 0.82 ± 0.06 to 0.60 ± 0.06; P &lt; 0.02) but unaltered urinary free F/urinary free E ratio (a marker for 11βHSD2 activity) suggested that this was due to inhibition of 11βHSD1 activity. An inverse correlation between GH and the THF+allo-THF/THE ratio was observed (r = −0.422; P &lt; 0.05). Conversely, in 12 acromegalic patients treated by transsphenoidal surgery (GH falling from 124 ± 49.2 to 29.3 ± 15.4 mU/L; P &lt; 0.01), the THF+allo-THF/THE ratio rose from 0.53 ± 0.06 to 0.63 ± 0.07 (P &lt; 0.05). Patients from either group who failed to demonstrate a change in GH levels showed no change in the THF+allo-THF/THE ratio.In vitro studies conducted on cells stably transfected with either the human 11βHSD1 or 11βHSD2 complementary DNA and primary cultures of human omental adipose stromal cells expressing only the 11βHSD1 isozyme indicated a dose-dependent inhibition of 11βHSD1 oxo-reductase activity with IGF-I, but not GH. Neither IGF-I nor GH had any effect on 11βHSD2 activity.GH, through an IGF-I-mediated effect, inhibits 11βHSD1 activity. This reduction in E to F conversion will increase the MCR of F, and care should be taken to monitor the adequacy of function of the hypothalamo-pituitary-adrenal axis in acromegalic subjects and in GH-deficient, hypopituitary patients commencing replacement GH therapy. Conversely, enhanced E to F conversion occurs with a reduction in GH levels; in liver and adipose tissue this would result in increased hepatic glucose output and visceral adiposity, suggesting that part of the phenotype currently attributable to adult GH deficiency may be an indirect consequence of its effect on tissue F metabolism via 11βHSD1 expression.
Tension Pneumocranium, a Rare Complication of Transsphenoidal Pituitary Surgery: Mayo Clinic Experience 1976–1998
Authors: Sawka Anna M. , Aniszewski Jaroslaw P. , Young William F. , Nippoldt Todd B. , Yanez Paulino , Ebersold Michael J. 
Published: January 2014

We describe four cases of symptomatic pneumocranium, a rare, potentially life-threatening complication of transsphenoidal pituitary surgery. Symptomatic pneumocranium manifested as impaired mental status, headaches, and grand mal seizures, early in the postoperative course after transsphenoidal pituitary surgery. Furthermore, a Cushing response, including systemic hypertension and bradycardia (secondary to intracranial hypertension) was seen, which has not been previously described in association with symptomatic pneumocranium. We describe a previously unreported risk factor for tension pneumocranium, untreated obstructive sleep apnea. Other factors predisposing to tension pneumocranium in our patients included: cerebrospinal fluid leaks, postoperative positive-pressure mask ventilation, large pituitary tumors, and intraoperative lumbar drainage catheters. Surgical drainage of the pneumocranium and repair of any coexistent cerebrospinal fluid leak markedly improved neurologic status.
Symptomatic pneumocranium occurring early in the postoperative course after transsphenoidal pituitary surgery is rare, but prompt recognition and treatment of this condition can be life-saving.
Serum Cytokines in Thyrotoxicosis1
Authors: Siddiqi A. , Monson J. P. , Wood D. F. , Besser G. M. , Burrin J. M. 
Published: January 2014

Overproduction of thyroid hormones promotes bone resorption in vivo and in vitro, and we have evaluated whether mediators of such effects could include the osteotropic cytokines. Previous studies have demonstrated raised serum interleukin (IL)-6 in thyrotoxic patients, but differentiating the contribution of the elevated thyroid hormones from that of the autoimmune inflammation present in Graves’ disease (GD) has been difficult. We undertook a longitudinal study of 34 patients (19–45 yr old) with GD, toxic nodular goiter (TNG), or a history of thyroid carcinoma but no evidence of disease recurrence, receiving sufficient T4 to suppress TSH. Controls were 12 euthyroid females. The following measurements were made basally and for 6 months after carbimazole treatment: serum free T4, T3, bone-specific alkaline phosphatase (b-ALP), IL-6, IL-8, IL-1β, tumor necrosis factor-α, IL-11, and urinary deoxypyridinoline (Udpd). Compared with controls (IL-6, 1.1 ± 0.3 ng/L; IL-8, 3.2 ± 0.8 ng/L), untreated patients with GD and TNG had elevated IL-6 (GD, 7.11 ± 0.88 ng/L; TNG, 7.30 ± 0.77 ng/L; P &lt; 0.001) and IL-8 (GD, 10.3 ± 1.23 ng/L; TNG, 9.81 ± 1.27 ng/L; P &lt; 0.001). These levels fell after treatment and were then indistinguishable from those in control subjects. Thyroid carcinoma patients on TSH suppressive therapy also had significantly raised levels of IL-6 (2.5 ± 0.42 ng/L) and IL-8 (4.4 ± 0.63 ng/L). When data from all the patients were pooled, the levels of IL-6 and IL-8 correlated with serum T3 and free T4 but not with Udpd or b-ALP. IL-1β, IL-11, and tumor necrosis factor-α were not raised in any patient.The elevations in serum IL-6 and -8 that occur in hyperthyroidism seem to result from the chronic effects of thyroid hormone excess rather than the accompanying autoimmune inflammatory condition produced by Graves’ thyroid or eye disease. The site of the presumed increased production of IL-6 and -8 is most likely from bone osteoblasts, despite the inability of bone markers (such as Udpd and b-ALP) to correlate with acute changes in thyroid hormone status produced by antithyroid therapy.
Success Rate of Radioiodine Therapy in Graves’ Disease: The Influence of Thyrostatic Medication
Authors: Sabri Osama , Zimny Michael , Schulz Gernot , Schreckenberger Mathias , Reinartz Patrick , Willmes Klaus , Buell Udalrich 
Published: January 2014

There is controversy whether simultaneous thyrostatic medication influences the outcome of radioiodine (131I) therapy in Graves’ disease by reducing the absorbed energy dose of 131I when delivering a standard dose. We therefore sought to ascertain whether the outcome of ablative 131I therapy is in any way affected by simultaneous thyrostasis (carbimazole) by aiming for a constant absorbed dose of 200–250 Gy. We prospectively studied 207 patients with Graves’ disease (106 with and 101 without simultaneous carbimazole at the time of 131I therapy). All patients were reexamined 3, 6, and 12 months after 131I therapy. The 101 nonthyrostatic patients showed a highly significantly greater success rate (93%) than the 106 thyrostatic patients (49%). Stepwise logistic regression demonstrated that failure was related to the administration of carbimazole during 131I therapy (P &lt; 0.00005) and the absorbed dose (P &lt; 0.025), but was not related to free T3, free T4, TSH receptor antibodies, or thyroid volume. The success rate was 100% in 93 nonthyrostatic patients with absorbed doses of 200 Gy or more, but was only 12.5% (1 of 8) for absorbed doses less than 200 Gy. Correlation between success and absorbed dose was significantly higher for nonthyrostatic than for thyrostatic patients (r = 0.93 vs. r = 0.24). Sixteen patients who discontinued thyrostasis 1–3 days before 131I therapy showed 94% successes.
Simultaneous thyrostasis is the decisive factor against a successful 131I therapy even if the significantly reduced 131I uptake/half-life values under thyrostasis are compensated with a higher delivered dose to ensure a comparable absorbed dose, possibly due to the additionally effective radioprotective properties of carbimazole. Therefore, if clinically feasible, we recommend discontinuing thyrostasis at least 1 day before beginning 131I therapy, because even in hyperthyroid nonthyrostatic patients the success rate was 100%.