外源性睾酮对去睾丸家兔性激素以及血脂和载脂蛋白水平的影响

目的 :探讨不同剂量的外源性睾酮对去势 (双侧睾丸切除 )雄性家兔性激素以及血脂和载脂蛋白水平的影响。方法 :成熟雄性新西兰白兔 40只 ,随机分成 5组 (n =8) :对照组、单纯去势组、低睾酮血症组 [去势后肌注十一酸睾酮 (TU) ,3mg/kg ,每 2周一次 ]、生理水平组 (去势后肌注TU ,6mg/kg ,每 2周一次 )及高睾酮血症组 (去势后肌注TU ,1 2mg/kg ,每 2周一次 )。 8周后测量血清总睾酮 (TT)、雌二醇 (E2 )、脱氢表雄酮 (DHEA)及总胆固醇 (TC)、高密度脂蛋白胆固醇 (HDL C) ,低密度脂蛋白胆固醇 (LDL C) ,甘油三酯 (TG) ,载脂蛋白A1 (ApoA1 ) ,载脂蛋白B(ApoB)。结果 :雄兔血清TT水平在去势后明显下降至极低水平 ,明显低于对照组 (P <0 .0 1 ) ,3mg/kgTU补充后轻度升高 ,仍明显低于对照组 (P <0 .0 1 ) ,形成低睾酮血症 ,6mg/kgTU补充后与对照组相比无显著差异 (P >0 .0 5) ,接近生理水平 ,1 2mg/kgTU补充后明显高于对照组和低睾酮血症组 (P均 <0 .0 1 ) ,形成高睾酮血症。血清E2 水平在对照组和生理水平组相近并且最低 ,单纯去势组和低睾血症组相近 ,高睾酮血症组最高。E2 /TT比值在对照组和生理水平组相近并且最小 ,在单纯去势组最大 ,低睾酮血症组大于高睾酮血症组。单纯去势组、低睾酮血症组和高睾酮血症     

Accuracy of serum luteinizing hormone and serum testosterone measurements to assess the efficacy of medical castration in prostate cancer patients

Background

Luteinizing hormone-releasing hormone (LH-RH) agonists are the standard for androgen deprivation therapy (ADT) in prostate cancer (PCa) patients. Current guidelines recommend serum testosterone measurement to assess the efficacy of ADT and to define castration resistance. However, serum testosterone does not reflect the exclusive effect of castration due to its extratesticular production. The aim of this study is to analyze if serum LH reflects better than serum testosterone the activity of LH-RH agonists.

Methods

Serum LH and serum testosterone were measured with chemiluminescent immunoassay (CLIA) in a cohort study of 1091 participants: 488 PCa patients “on LH-RH agonists”, 303 “off LH-RH agonist” in whom LH-RH agonists were withdrawn, and 350 men with PCa suspicion “no LH-RH agonist” who never received LH-RH agonists. In a validation cohort of 147 PCa patients, 124 on “LH-RH agonists” and 19 “off LH-RH agonists”, serum testosterone was also measured with liquid chromatography and tandem mass spectrometry (LC MSMS).

Results

The area under the curve (AUC) to distinguish patients “on versus off LH-RH agonists” was 0.997 for serum LH and 0.740 for serum testosterone, P < 0.001. The 97.5 percentile of serum LH in patients “on LH-RH agonists” was 0.97 U/L, been the most efficient threshold 1.1 U/L. The AUCs for serum LH, testosterone measured with CLIA and with LC MSMS, in the validation cohort, were respectively 1.000, 0.646 and 0.814, P < 0.001. The efficacy to distinguish patients “on versus off LH-RH agonists” was 98.6%, 78.3%, and 89.5% respectively, using 1.1 U/L as threshold for serum LH and 50 ng/dL for serum testosterone regardless the method.

Conclusions

Serum LH is more accurate than serum testosterone regardless the method, to distinguish patients “on versus off LH-RH agonists”. The castrate level of serum LH is 1.1 U/l. These findings suggest that assessment of LH-RH agonist efficacy and castration resistance definition should be reviewed.

     

慢性应激状态下大鼠睾酮水平测定

目的通过对于慢性应激模型和运动疲劳模型大鼠的血清睾酮水平的对比研究,探讨慢性应激过程中睾酮水平变化规律及其与发生疲劳的关系。方法建立大鼠慢性不可预测性应激模型及运动性疲劳模型;应用大鼠轨迹追踪系统对不同应激时间大鼠进行活动量观测,应用放射性免疫法对各组大鼠进行血清总睾酮和游离睾酮进行测定。结果与正常组比较,慢性应激大鼠第1周组活动量(运动轨迹长度,下同)增加(P0.01),第2周组活动量下降(P0.01)。各实验组大鼠游离睾酮与总睾酮之间均存在线性相关。慢性应激各组随应激时间延长,其游离睾酮与总睾酮比值呈逐渐下降趋势,并且能够达到运动疲劳组水平。结论慢性应激条件可以明显引起大鼠睾酮水平下降。提示分层检测慢性疲劳综合征人群血清总睾酮及游离睾酮的水平以及进行动态性研究可能为本病症的诊断提供生化指标。以游离睾酮与总睾酮比值为指标检测雄性激素水平,能够更好地反映干预因素对动物生理上的影响。     

Association of Thyroid Function with Posttraumatic Stress Disorder: a Systematic Review and Meta-Analysis

Objective: To conduct a systematic review and meta-analysis describing the association of thyroid function with posttraumatic stress disorder (PTSD) in adults.Methods: The authors conducted a comprehensive search from databases’ inception to July 20, 2018. The meta-analysis included studies that reported mean values and standard deviation (SD) of thyroid hormone levels (thyroid-stimulating hormone &lsqb;TSH], free thyroxine &lsqb;FT4], free triiodothyronine &lsqb;FT3], total T4 &lsqb;TT4], and total T3 &lsqb;TT3]) in patients with PTSD compared with controls. Five reviewers worked independently, in duplicate, to determine study inclusion, extract data, and assess risk of bias. The mean value and SD of the thyroid function tests were used to calculate the mean difference for each variable. Random-effects models for meta-analyses were applied.Results: The meta-analysis included 10 observational studies at low-to-moderate risk of bias. Studies included 674 adults (373 PTSD, 301 controls). The meta-analytic estimates showed higher levels of FT3 (+0.28 pg/mL; P = .001) and TT3 (+18.90 ng/dL; P = .005) in patients with PTSD compared to controls. There were no differences in TSH, FT4, or TT4 levels between groups. In the subgroup analysis, patients with combat-related PTSD still had higher FT3 (+0.36 pg/mL; P = .0004) and higher TT3 (+31.62 ng/dL; P<.00001) compared with controls. Conversely, patients with non–combat-related PTSD did not have differences in FT3 or TT3 levels compared with controls.Conclusion: There is scarce evidence regarding the association of thyroid disorders with PTSD. These findings add to the growing literature suggesting that thyroid function changes may be associated with PTSD.     

Effective Testosterone Suppression for Prostate Cancer: Is There a Best Castration Therapy?

Achieving and maintaining effective suppression of serum testosterone levels in men treated with androgen ablation is one of the essential strategies in the management of prostate cancer. Historically, a serum testosterone below 50 ng/dL was considered to be the castrate level. Current data suggest that the new target for either surgical or chemical castration is a serum testosterone level of lower than 20 ng/dL in an attempt to maximize therapeutic outcomes. Testosterone breakthrough and the acute-on-chronic effects of administration of a luteinizing hormone-releasing hormone analogue may cause testosterone levels to periodically rise, sometimes to noncastrate levels. The goal of androgen ablation is to identify those agents that will most consistently achieve and maintain the lowest testosterone levels possible.Key words: Prostate cancer, Androgen ablation, LHRH analogues, LHRH antagonists, TestosteroneThe cornerstone of understanding the basic biology of prostate cancer relies upon the important discovery that prostate cancer is a hormonally responsive tumor. The current use of androgen ablation therapy in prostate cancer includes treatment based on serum prostate-specific antigen (PSA) only or local recurrence; neoadjuvant or adjuvant treatment of high-risk disease, usually in combination with radiation therapy; and treatment of patients with metastatic disease regardless of symptoms. The American Society of Clinical Oncology (ASCO) 2007 guidelines and National Comprehensive Cancer Network (NCCN) 2009 guidelines recommend either luteinizing hormone-releasing hormone (LHRH) agonists or bilateral orchiectomy as first-line therapy for men with advanced prostate cancer.^1,2Medical or chemical castration is almost exclusively performed by the use of injectable LHRH analogues, with a minor role for estrogen and limited experience with LHRH antagonists. Surgical castration through bilateral orchiectomy is infrequently used today.Intermittent hormonal therapy (IHT) is being investigated as an alternative to continuous hormonal therapy with a potential for reduced morbidity and a delay of the progression to hormone-refractory disease.³ Although intermittent therapy may rely upon restoring a normal testosterone level, it is believed that the testosterone level should be as low as possible when the patient is on treatment, thus generating the lowest serum PSA level possible and likely improving outcome.⁴ Although the data on IHT are promising, trials reported thus far are relatively small and somewhat underpowered, and it is likely that its use will increase in the future as trials mature.There is growing recognition that many men may not achieve acceptable levels of testosterone using androgen ablation. This has led to a renewed interest in the significance of the testosterone level in the modern era of prostate cancer management. Can we define the best castration therapy for prostate cancer? Is this the therapy that provides the lowest and most consistent levels of testosterone suppression? To quote Dr. Claude Schulman in a recent editorial: “less is more.”⁵     

Calcium,Parathyroid Hormone,and Vitamin D in Patients with Primary Hyperparathyroidism: Normograms Developed from 10000 Cases

ObjectiveTo better define the typical and atypical biochemical profiles of patients with surgically proven primary hyperparathyroidism.MethodsIn this single-center, prospectively conducted study of consecutive patients with surgically proven primary hyperparathyroidism over a 7-year period, we analyzed serum calcium, parathyroid hormone, and 25-hydroxyvitamin D concentrations.ResultsA total of 10 000 patients were included, and more than 210 000 calcium, parathyroid hormone, and 25-hydroxyvitamin D values were evaluated. Both calcium and parathyroid hormone levels demonstrated a Gaussian distribution with the average calcium concentration being 10.9 ± 0.6 mg/dL and the average parathyroid hormone concentration being 105.8 ± 48 pg/mL. The average highest calcium and parathyroid hormone concentrations were 11.4 ± 0.7 mg/dL and 115.3 ± 50 pg/mL, respectively. At least 1 calcium value of 11.0 mg/dL was seen in 87% of patients, but only 21% had 1 or more calcium value above 11.5 mg/dL. Only 7% had a single serum calcium level reaching 12.0 mg/dL. Normocalcemic hyperparathyroidism was seen in just under 3% of patients who had identical findings at surgery. An average parathyroid hormone concentration less than 65 pg/mL was seen in 16%, with 10% of patients who had no high parathyroid hormone values. The average 25-hydroxyvitamin D concentration was 22.4 ± 9 ng/mL, with levels decreasing as calcium levels increased (P < .001); 36% had 25-hydroxyvitamin D levels below 20 ng/mL.ConclusionsPatients with PHPT present with a number of distinct biochemical profiles, but as a group, they present with a near-normal Gaussian distribution of both calcium and parathyroid hormone levels. Either serum calcium or parathyroid hormone remained normal in 13% of patients, yet the findings at surgery are similar to those of patients with elevated calcium or parathyroid hormone. Low 25-hydroxyvitamin D is an expected finding in patients with PHPT, decreasing as serum calcium levels increase. (Endocr Pract. 2011;17:384-394)     

Methylprednisolone increases plasma leptin levels in Graves' hyperthyroidism patients with active Graves' ophthalmopathy.

Whether leptin, a product of the ob gene, can be stimulated by glucocorticoid administration has been an issue of controversy. We investigated the effect of intravenous administration of methylprednisolone (500 mg/day x 3 days) on plasma levels of leptin in 16 patients (female/male = 11/5) with Graves' hyperthyroidism and active ophthalmopathy who received pulse therapy. Significant elevation of plasma leptin levels started at the eighth hour (13.9+/-1.8 ng/mL, p=0.042) and lasted until the 72nd hour (21.2+/-5.0 ng/mL, p=0.009), as compared with basal levels (8.8+/-1.2 ng/mL). When methylprednisolone was replaced with oral prednisolone (10 mg three times per day x 2 weeks), no difference in plasma leptin levels was noted compared with basal measurement. Under methylprednisolone administration, a significant suppression of tumor necrosis factor-alpha began at the 24th hour (8.1+/-1.3 pg/mL, p=0.004) and lasted until the 48th hour (8.1+/-1.0 pg/mL, p=0.008), as compared with basal measurement (12.5+/-1.5 pg/mL). Compared with basal levels (93+/-2 mg/dL), significant elevation in the plasma glucose level started at the third hour (135+/-10 mg/dL, p=0.000) and lasted until the 72nd hour (110+/-4 mg/dL, p=0.019). The timing of serum insulin elevation approximated that of plasma glucose (3 hours: 14+/-3 microU/mL, p=0.006) and lasted until the end of prednisolone administration (2 weeks: 12+/-2 microU/mL, p=0.044), when compared with basal levels (14+/-3 microU/mL). We concluded that the parental administration of pharmacological doses of methylprednisolone to patients with Graves' hyperthyroidism could acutely raise their plasma level of leptin.     

Virilizing Adrenal Ganglioneuroma in a Woman with Subclinical Cushing Syndrome

ObjectiveTo describe a patient with a virilizing adrenal ganglioneuroma and subclinical Cushing syndrome.MethodsDetailed clinical, laboratory, radiologic, and pathologic findings are presented, and the pertinent literature is reviewed.ResultsA 56-year-old postmenopausal woman was referred for evaluation of a 3.6- by 3.0-cm right adrenal mass, which had been diagnosed during a work-up for hirsutism. A bilateral oophorectomy done 2 months before the presentation failed to correct the elevated testosterone levels. On examination, she had severe hirsutism on her face, chest, back, and extremities, as well as male pattern baldness and clitoromegaly. Biochemical evaluation showed elevated total and free serum testosterone levels of 319 ng/dL (reference range, 20 to 70) and 78 pg/mL (reference range, 1 to 9), respectively, values in the adult male range. The serum dehydroepiandrosterone sulfate level was 117 μ/dL (reference range, 10 to 152), and the urine free cortisol was 10.4 μg/24 h (reference range, < 45). A laparoscopic adrenalectomy revealed a 5.0-cm adrenal ganglioneuroma containing nests of adrenocortical cells. On the first day postoperatively, the serum cortisol level was < 1.0 μg/dL. At 1 month after adrenalectomy, the total and free testosterone levels had declined to 16 ng/dL and 3.1 pg/mL, respectively. At 2 months postoperatively, normal results of a cosyntropin stimulation test (basal and peak cortisol levels of 13.6 and 20.0 μg/dL, respectively) indicated recovery of the hypothalamic-pituitary-adrenal axis.ConclusionTo our knowledge, this is the first case report of a virilizing adrenal ganglioneuroma with this unique pathologic finding and concomitant subclinical Cushing syndrome. (Endocr Pract. 2008;14:584-587)     

Hypothyroidism as A Cause of Hyponatremia: Fact or Fiction?

ObjectiveTo illustrate that severe primary hypothyroidism alone may not be enough to cause hyponatremia in the otherwise healthy ambulatory patient.Methods:A retrospective chart review was conducted using an academic health center enterprise-wide electronic health record to identify 10 patients with primary hypo thyroidism and same-day serum thyroid-stimulating hormone (TSH), sodium, creatinine, and calculated glomerular filtration rate (GFR). Same-day free triiodothyronine or free thyroxine was also recorded if tested. Patients were included in our case series if they met the following inclusion criteria: TSH level > 100 μU/mL and same-day sodium and creatinine levels. All laboratory tests were collected on an outpatient basis.ResultsThe 10 subjects (2 men and 8 women) were ages 19 to 97 years (median, 51.5 years). Median TSH was 193 μU/mL (range, 104.2 to 515.6 μU/mL; normal, 0.40 to 5.50 μU/mL) with median sodium of 138 mmol/L (range, 136 to 142 mmol/L; normal, 135 to 146 mmol/L). The lowest sodium was 136 mmol/L with concurrent TSH of 469.7 μU/mL, free triiodothyronine of 1.0 pg/mL (normal, 1.8 to 4.6 pg/mL), and free thyroxine of 0.2 ng/ dL (normal, 0.7 to 1.8 ng/dL). Median GFR was 67.5 mL/ min/1.73 m² (range, 44 to 114 mL/min/1.73 m²; normal, 90 to 120 mL/min/1.73 m²).ConclusionIn our small series of patients with extreme TSH elevations, none had a serum sodium level below normal (< 135 mmol/L), even in the presence of a reduced GFR. Hyponatremia can be a common occurrence in hospitalized and/or chronically ill patients; however, in an otherwise relatively healthy ambulatory patient, hypothyroidism, even when severely undertreated, may be a less clinically relevant cause of hyponatremia. (Endocr Pract. 2012;18:894-897)     

Calcium Challenge to Confirm Secondary Hyperparathyroidism Caused by Decreased Calcium Intake

ObjectiveSecondary hyperparathyroidism commonly occurs in the setting of mid-to low-normal serum calcium levels, often in the setting of chronic kidney disease, phosphate loading, vitamin D deficiency, or insufficient calcium intake or absorption. In this article, we report 9 patients who had adequate kidney function (estimated glomerular filtration rate >60 mL/min/1.73 m²) and normal 25-hydroxy vitamin D level (≥30 ng/dL) and whose secondary hyperparathyroidism resolved after starting adequate oral calcium intake.MethodsOur retrospective case series included 8 women and 1 man; the mean age was 69.0 ± 12.2 years (mean ± standard deviation). The initial intact parathyroid hormone (iPTH) level was 80.6 ± 13.4 pg/mL (reference range [ref], 10-65 pg/mL), corrected serum calcium level was 9.2 ± 0.2 mg/dL (ref, 8.5-10.5 mg/dL), serum phosphate level was 3.6 ± 0.4 mg/dL (ref, 2.5-4.9 mg/dL), 25-hydroxy vitamin D level was 42.2 ± 10.5 mg/dL (ref, 20-50 ng/mL), and estimated glomerular filtration rate was 72.6 ± 14.4 mL/min/1.73 m². Patients were treated clinically with oral calcium 600 mg twice a day.ResultsiPTH was retested after a mean duration of 17.6 ± 12.7 days of calcium supplementation; the iPTH level decreased to 51.0 ± 10.6 pg/mL, with all patients achieving iPTH in the normal range with normocalcemia, consistent with hyperparathyroidism being because of insufficient calcium intake or absorption. All patients were normocalcemic after supplementation.ConclusionSecondary hyperparathyroidism can result from insufficient oral calcium intake. Calcium challenge is an efficacious and cost-effective tool for confirming and treating secondary hyperparathyroidism in the setting of normal vitamin D levels and kidney function.     

Virilizing Ovarian Leydig Cell Tumor in A Woman with Subclinical Cushing Syndrome

ObjectiveTo report the case of a patient with a virilizing ovarian Leydig cell tumor and subclinical Cushing syndrome attributable to an adrenal adenoma.MethodsDetailed clinical, laboratory, radiologic, and pathologic findings are presented, and the pertinent literature is reviewed.ResultsA 49-year-old woman was referred for evaluation of a left adrenal mass (3.0 by 2.4 cm), which had been diagnosed by computed tomographic scan 4 years previously during a work-up for hirsutism. On examination, she had central obesity, facial hirsutism, and male pattern baldness. Work-up showed elevated total and free testosterone levels of 196 ng/dL (reference range, 20 to 70) and 24 pg/mL (1 to 9), respectively. Other results (and reference ranges) were as follows: dehydroepiandrosterone sulfate, 7.5 μg/dL (10 to 221); corticotropin, 12 pg/mL (5 to 50); morning cortisol, 1.4 μg/dL after a 1-mg overnight dexamethasone suppression test; and urine free cortisol, 48.8 μg/24 h (20 to 100). The testosterone level decreased by 14% after a 2-day low-dose dexamethasone suppression test. Findings on transvaginal ovarian ultrasonography and a computed tomographic scan of the pelvis were normal. A laparoscopic adrenalectomy revealed an adrenal adenoma. On the first day postoperatively, the cortisol level was less than 1.0 μg/dL; however, the testosterone level remained elevated. At 6 months postoperatively, a normal result of a cosyntropin stimulation test indicated recovery of the hypothalamic-pituitaryadrenal axis. Bilateral oophorectomy revealed a 1.3-cm right ovarian Leydig cell tumor. Postoperatively, the testosterone level declined to less than 20 ng/dL.ConclusionTo our knowledge, this is the first case report of a virilizing ovarian Leydig cell tumor in a patient with subclinical Cushing syndrome. (Endocr Pract. 2008;14:358-361)     

Are There Variances Of Calculated Free Testosterone Attributed To Variations In Albumin And Sex Hormone-Binding Globulin Concentrations In Men?

ObjectiveCalculated free testosterone (cFT) is determined from total testosterone (TT), sex hormone binding globulin (SHBG), and albumin (Alb) levels using mathematical formulae. Variations in cFT due to changes in SHBG or Alb have not been investigated. We evaluated potential cFT variances determined with fixed Alb (4.3 g/dL) and measured Alb, and the point at which low SHBG and Alb combinations produced significant cFT variance.MethodWe analyzed 11,176 data points from 5,797 men. cFT values with fixed versus actual Alb values were evaluated and compared. cFT levels were theoretically determined for all possible combinations of TT, SHBG, and Alb (8,343,552 combinations). Agreement between the 2 measures was assessed with Lin’s concordance coefficient.ResultsMean Alb was 4.06 ± 0.32 g/dL. Mean SHBG was 39.0 ± 23.6 nmol/L. A fixed Alb of 4.3 g/dL did not produce significant variance for most cFT evaluations. Accuracy decreased when Alb was ≤3.5 g/dL in combination with SHBG ≤30 nmol/L, and this occurred in 1.2% of all data points.ConclusionA fixed Alb of 4.3 g/dL is acceptable for most clinical evaluations. If Alb is <3.5 g/dL and SHBG is <30 nmol/L, the variance increases, and a free testosterone (FT) measurement by equilibrium dialysis is warranted for better accuracy. (Endocr Pract. 2013;19:236-242)     

Selective targeting of bioengineered platelets to prostate cancer vasculature: new paradigm for therapeutic modalities

Androgen deprivation therapy (ADT) provides palliation for most patients with advanced prostate cancer (CaP); however, greater than 80% subsequently fail ADT. ADT has been indicated to induce an acute but transient destabilization of the prostate vasculature in animal models and humans. Human re‐hydrated lyophilized platelets (hRL‐P) were investigated as a prototype for therapeutic agents designed to target selectively the tumour‐associated vasculature in CaP. The ability of hRL‐P to bind the perturbed endothelial cells was tested using thrombin‐ and ADP‐activated human umbilical vein endothelial cells (HUVEC), as well as primary xenografts of human prostate tissue undergoing acute vascular involution in response to ADT. hRL‐P adhered to activated HUVEC in a dose‐responsive manner. Systemically administered hRL‐P, and hRL‐P loaded with super‐paramagnetic iron oxide (SPIO) nanoparticles, selectively targeted the ADT‐damaged human microvasculature in primary xenografts of human prostate tissue. This study demonstrated that hRL‐P pre‐loaded with chemo‐therapeutics or nanoparticles could provide a new paradigm for therapeutic modalities to prevent the rebound/increase in prostate vasculature after ADT, inhibiting the transition to castration‐recurrent growth.     

Serum Hormone Concentrations in Transgender Individuals Receiving Gender-Affirming Hormone Therapy: A Longitudinal Retrospective Cohort Study

ObjectiveTo examine the association of various gender-affirming hormone therapy regimens with blood sex hormone concentrations in transgender individuals.MethodsThis retrospective study included transgender people receiving gender-affirming hormone therapy between January 2000 and September 2018. Data on patient demographics, laboratory values, and hormone dose and frequency were collected. Nonparametric tests and linear regression analyses were used to identify factors associated with serum hormone concentrations.ResultsOverall, 196 subjects (134 transgender women and 62 transgender men), with a total of 941 clinical visits, were included in this study. Transgender men receiving transdermal testosterone had a significantly lower median concentration of serum total testosterone when compared with those receiving injectable preparations (326.0 ng/dL vs 524.5 ng/dL, respectively, P = .018). Serum total estradiol concentrations in the transgender women were higher in those receiving intramuscular estrogen compared with those receiving oral and transdermal estrogen (366.0 pg/mL vs 102.0 pg/mL vs 70.8 pg/mL, respectively, P < .001). A dose-dependent increase in the hormone levels was observed for oral estradiol (P < .001) and injectable testosterone (P = .018) but not for intramuscular and transdermal estradiol. Older age and a history of gonadectomy in both the transgender men and women were associated with significantly higher concentrations of serum gender-affirming sex hormones.ConclusionIn the transgender men, all routes and formulations of testosterone appeared to be equally effective in achieving concentrations in the male range. The intramuscular injections of estradiol resulted in the highest serum concentrations of estradiol, whereas transdermal estradiol resulted in the lowest concentration. There was positive relationship between both oral estradiol and injectable testosterone dose and serum sex hormone concentrations in transgender people receiving GAHT.     

Serum melatonin levels and insomnia in patients with Machado-Joseph Disease

We previously reported a patient with Machado-Joseph Disease (MJD) who had severe insomnia and a low serum melatonin (MLT) level, and whose insomnia was alleviated by oral MLT replacement therapy. The aims of this study were to examine whether patients with MJD are likely to have insomnia, and whether there is a relationship between the degree of insomnia and the serum MLT level among patients with MJD. This study included 8 patients with MJD. A 58-year-old-patient with cervical spondylosis was also included in this study to check the condition of the test room for sleeping. All patients filled out the Japanese version of Pittsburgh Sleep Quality Index (PSQI-J) questionnaire. We obtained blood samples at 12:00 and 24:00 hours to measure the MLT level. We checked the sleep condition of the patient once an hour and recorded the grade in sleep-logs: the grades of sleep condition were asleep, sleepy, or awake. Statistical analyses were performed to search for correlations between the PSQI score and the serum MLT level or actual sleep time using Spearman’s rank correlation coefficient. Seven of the 8 MJD patients had a total PSQI score of above 5.5 (cut-off level). The daytime MLT level (at 12:00 hours) was below 2.8 pg/mL in all 8 patients, whereas the mean night-time MLT level (at 24:00 hours) of the MJD patients (23.6 ± 17.5 pg/mL) was lower than that of the control patient (43.0 pg/mL) and also lower than the reported cut-off level among healthy people aged 30–50 years (55.5 pg/mL). There was a negative correlation between the total PSQI score and the serum MLT level among the MJD patients (P < 0.05). Our results show that a low serum MLT level may contribute to insomnia in patients with MJD.

     

Estrogenic side effects of androgen deprivation therapy

Androgen deprivation therapy (ADT) is part of standard therapy for locally advanced or metastatic prostate cancer and is frequently used in men with a rising prostate-specific antigen following radical prostatectomy or radiation therapy. In some men, ADT may be administered for years or even decades. The intended therapeutic effect of ADT is testosterone deficiency. Because estrogen is a normal metabolite of testosterone, ADT also results in estrogen deficiency. ADT has a variety of adverse effects, many of which are primarily related to estrogen deficiency. Bone mineral density may decrease by 4% to 13% per year in men receiving ADT. The fracture rate for patients on ADT averages 5% to 8% per year of therapy. Hot flashes, gynecomastia, and breast tenderness are common side effects associated with ADT. In the clinic, minimum baseline testing should include weight measurement, blood pressure reading, and fasting lipid panel and serum glucose tests. Currently, there are no large outcome trials in men on ADT testing the available therapies for adverse effects. No therapies are specifically approved for treatment of adverse effects in men on ADT. Although some therapies can be used for a single indication (based upon small studies), there is currently no agent to treat the multiple estrogenic side effects of ADT.     

LH secretion and testosterone concentrations are blunted after resistance exercise in men.

This study examined the hypothesis that exercise-induced changes in circulating testosterone would be centrally mediated via hypothalamic-pituitary release of luteinizing hormone (LH). We tested this hypothesis by examining overnight LH, total and free testosterone (TT and FT), and cortisol (C) concentrations in 10 young healthy men (21 +/- 1 yr) during two experimental sessions: a control and an acute heavy-resistance exercise bout (50 total sets consisting of squats, bench press, leg press, and latissimus dorsi pull-down). Exercise was performed from 1500 to 1700, and blood sampling began at 1700 and continued until 0600 the next morning. Blood was sampled every 10 min for LH and every hour for TT, FT, and C. Hormonal concentrations were determined via RIA, and the secretion characteristics of LH were analyzed with deconvolution analysis. When overnight postexercise concentrations were compared with control concentrations, no statistically significant (P < or = 0.05) differences were observed for LH half-life, LH pulse frequency, interpulse interval, pulse amplitude, or pulse mass. Significant differences were observed for LH production rate (13.6 +/- 4 and 17.9 +/- 5 IU. l distribution volume(-1) x day(-1) for exercise and control, respectively, a 24% reduction). For the ANOVA marginal main effect means due to condition, C was significantly elevated (5.9 +/- 0.7 vs. 4.0 +/- 0.4 microg/dl), while TT (464 +/- 23 vs. 529 +/- 32 ng/dl) and FT (15.6 +/- 0.7 vs. 18.3 +/- 0.9 pg/ml) were significantly decreased for the exercise condition. These data demonstrate that the decline in overnight testosterone concentrations after acute heavy-resistance exercise is accompanied by a blunted LH production rate and elevated C concentrations.     

Addison’S Disease in Evolution: An Illustrative Case and Literature Review

ObjectiveTo present a case of symptomatic autoimmune adrenal insufficiency with initially normal serum cortisol and to caution about limitations of the current diagnostic algorithm for adrenal insufficiency, which does not reflect the pathophysiology of early disease.MethodsWe describe the clinical presentation and relevant investigations of a patient ultimately found to have Addison’s disease, which is followed by a focused review of the literature.ResultsA 41-year-old Caucasian woman with autoimmune hypothyroidism, premature ovarian failure, and microscopic colitis presented with nausea, salt craving, increased skin pigmentation, and postural hypotension. Initial bloodwork revealed a normal morning cortisol of level of 19.2 μg/dL (normal, 7.2 to 25 μg/dL) but an adrenocorticotropic hormone (ACTH) level 10 times normal, at 513.6 pg/mL (normal, < 52.5 pg/mL). Her potassium was normal, but her aldosterone level was 4.12 ng/dL (normal, 12.3 to 62.5 ng/dL) and her renin activity was increased (23.0 mg/dL/hour; normal, < 6.0 mg/dL/hour). Six weeks after initial presentation, she was found to have anti-adrenal antibodies. It was not until 10 weeks after her initial symptomatic presentation that her morning cortisol level was found to be subnormal and a formal diagnosis of adrenal insufficiency was made.ConclusionThe present case and literature review reveal that common diagnostic approaches will miss patients with (possibly symptomatic) early adrenal insufficiency. We suggest that serum ACTH level testing or tests of mineralocorticoid function be included in the initial step of investigation for suspected primary adrenal insufficiency. (Endocr Pract. 2014;20:e176-e179)     

46,XX SRY-Positive Male Syndrome Presenting with Primary Hypogonadism in the Setting of Scleroderma

ObjectiveTo describe a case of SRY gene translocation in a man with scleroderma presenting with primary hypogonadism.MethodsWe present the clinical, physical, laboratory, and pathologic findings of the study patient and discuss the cytogenetic analysis and the cause of the sexual dysfunction. Relevant literature is reviewed.ResultsA 35-year-old man with a recent diagnosis of diffuse cutaneous sclerosis was referred by his rheumatologist because of a low testosterone level. His medical history was notable for right cryptorchidism corrected after birth. He had no history of sexual activity, but reported normal erectile function before his current presentation. Physical examination findings were remarkable for a height of 157.5 cm; weight of 72.7 kg; extensive, diffuse thickening of the skin; mild gynecomastia; little axillary and pubic hair; and soft testes (1-2 mL bilaterally). Initial laboratory testing revealed the following values: follicle-stimulating hormone, 22.1 mIU/mL (reference range, 1.4-18.1 mIU/mL); luteinizing hormone, 19.7 mIU/mL (reference range, 1.5-9.3 mIU/mL); total testosterone, 25 ng/dL (reference range, 241-827 ng/dL); and free direct testosterone, 0.8 pg/mL (reference range, 8.7-25.1 pg/mL). Laboratory test results were consistent with primary hypogonadism. A urologist performed testicular biopsy, which showed severe testicular atrophy with absent spermatogenesis. Primary hypogonadism due to Klinefelter syndrome or testicular fibrosis secondary to scleroderma was suspected. Karyotype analysis showed a 46,XX karyotype, and fluorescence in situ hybridization was consistent with a 46,XX,Xp22.3(SRY +) gene translocation. After a normal prostate-specific antigen level was documented, testosterone replacement therapy was initiated, and he was referred for genetic counseling.ConclusionsThe 46,XX SRY-positive male syndrome is rare. Adult diagnosis can be challenging because of normal sexual development. Scleroderma, which rarely can occur in Klinefelter-type syndromes, further complicated the diagnosis in this case. (Endocr Pract. 2011;17:95-98)