Mean Serum Sex Hormone-binding Globulin Research Articles

Longitudinal changes over three years in sex steroid hormone levels in women aged 70years and over.

Sex steroid levels in women vary with increasing age from the age of 70years (70+). Whether this reflects change within individuals with age or a survival advantage is not known. This study aimed to determine the stability of circulating sex steroids and SHBG over time in individual women aged 70+. A prospective cohort study. 400 women, aged 70+ not using any sex steroid, anti-androgen/oestrogen or glucocorticoid therapy. Sex steroid concentrations, measured by liquid chromatography-tandem mass spectrometry and sex hormone-binding globulin (SHBG) by immunoassay, in paired blood samples drawn 3years apart and analysed together. 400 women, median (IQR) age 78.0 (8.6)years, were included in the analysis. Mean testosterone concentrations were statistically significantly higher in follow-up samples compared with baseline. The change was modest (mean change 31pmol/L, 95% confidence interval (CI) 2.4-59.8; p=.034), and an increase was not observed in all women. There was a statistically significant decline in mean body mass index (mean change -0.4kg/m2 , 95% CI 0.6 to -0.3; p<.001) and a significant increase in the mean serum SHBG concentration (mean change 4.0 nmol/L, 95% CI 2.7-5.4; p<.001). The change observed in testosterone was not explained by the observed change in SHBG. There was no significant change in the mean oestrone or dehydroepiandrosterone concentration. Testosterone concentrations in women aged 70+ were more likely to increase than decrease. Whether increasing testosterone concentrations in older women confer a survival advantage needs investigation.

Serum Sex Hormone Binding Globulin (SHBG) Relation with Different Components of Metabolic Syndrome in Men with Type 2 Diabetes.

Sex hormone binding globulin (SHBG) is demonstrated to be decreased in subjects with metabolic syndrome (MetS). The aim of the present study was to investigate the association of SHBG in relation to MetS components among men with type 2 diabetes (T2D). This cross-sectional study was carried out among 429 Saudi T2D male patients aged >30 years. Metabolic syndrome was defined using International Diabetes Federation (IDF) criteria. Fasting blood glucose (FBG), HbA1c, albumin, and lipid parameter were measured. Gonadal hormones, namely total testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and SHBG were determined using ELISA. The SHBG levels of the MetS group was significantly lower than non-MetS group 47.25±31.03 nmol/l vs. 56.55±37.84 nmol/l; p=0.013. As the MetS score increases, SHBG and HDL levels decrease while weight, BMI, waist circumference, SBP, DBP, FBG, HbA1c, TC, and TG levels increase. SHBG correlated with age, BMI, TG, HDL, TT, free testosterone, and bio-available testosterone. This is the first study that provides detailed analyses of SHBG with MetS components in male diabetic subjects. The mean serum SHBG levels gradually declined with the addition of MetS components in T2D men. TT, free testosterone, and bio-available testosterone remained independently associated with SHBG by multivariable regression analysis.

Sex Hormone - Binding Globulin in Obese Type 2 Diabetics

Background: Obesity is one of risk factors for type 2 diabetes because of its association with insulin resistance and poor glycemic control. Sex hormone–binding globulin (SHBG) and adipose tissue hormones have a role in development of insulin resistance, hyperlipidemia and type 2 diabetes. Serum SHBG has a role in glucose homeostasis and low levels are associated with development of diabetes, cardiovascular diseases, insulin resistance and hyperinsulinemia. Aim of work: to study the relationship between serum SHBG, obesity, and metabolic parameters in type 2 diabetes in both sex. Patients and Methods: forty obese type 2 diabetic patients and ten obese non-diabetic as controls were included in this study. Blood was taking from all subjects for estimation of glucose, Lipid profile, insulin and SHBG. Results: there was highly significant decrease in mean serum SHBG concentration in diabetic group compared with control non diabetic group. There were significant negative associations between serum SHBG and age, disease duration, BMI and glucose. On the other hand, there were non significant correlations between SHBG and waist circumference, fasting insulin, HOMA-IR, cholesterol and triglyceride levels. Conclusion: Low serum SHBG is associated with hyperglycemia in both sexes, independent of insulinemia

Association of serum bisphenol-A concentration and male reproductive function among exposed workers.

Bisphenol-A (BPA) can alter endocrine function in animals, yet the relationship between human exposure to BPA and male reproductive function is not well understood. We collected serum samples from 281 male workers exposed to BPA and 278 controls. Serum BPA concentrations were analyzed by gas chromatography-mass spectrometry after derivatization. The serum levels of sex hormone-binding globulin (SHBG) and total testosterone (TT) were detected by radioimmunoassay and levels of inhibin B (INB) and androstenedione (AD) by enzyme-linked immunosorbent assay. We examined the association of BPA exposure and male sex hormone levels by multivariable linear regression. Both serum BPA concentrations and detection rates were greater in males exposed than those not exposed to BPA, but the two groups did not differ in levels of SHBG, TT, INB, or AD. Compared with exposure for ≤5 years, exposure for >5 years was associated with increased serum BPA and SHBG 1evels and decreased AD levels. Compared with undetectable BPA and BPA ≤ 18.75 ng/mL, BPA level >18.75 ng/mL was associated with low AD and high SHBG levels (P < 0.05). On adjusted multivariable regression, increased serum BPA level was associated with decreased mean serum AD level (0.18 ng/mL; 95% confidence interval CI -0.22 to -0.13) and increased mean serum SHBG level (2.79 nmol/L; 95% CI 2.11-3.46). Serum BPA levels were increased after occupational exposure. BPA exposure was negatively associated with serum AD level but positively associated with serum SHBG level.

Sex Hormone-binding Globulin: A Novel Marker for Nodal Metastases Prediction in Prostate Cancer Patients Undergoing Extended Pelvic Lymph Node Dissection

To examine the association between sex hormone-binding globulin (SHBG) and lymph node invasion (LNI) in patients treated with radical retropubic prostatectomy and extended pelvic lymph node dissection (ePLND). The preoperative serum SHBG level was measured in a cohort of 168 consecutive patients (mean age 63.9 years, range 48-77) who underwent radical retropubic prostatectomy with ePLND for clinically localized prostate cancer. Logistic regression models tested the association between the predictors (including prostate-specific antigen, clinical stage, primary and secondary biopsy Gleason grades, and SHBG) and LNI. Logistic regression coefficients were used to calculate the predictive accuracy, which was subjected to 200 bootstrap resamples to reduce overfit bias. Thirteen patients (7.7%) had LNI. The mean serum SHBG level was significantly greater in the patients with LNI than in those without LNI (50.0 vs 35.1 nmol/L, respectively; P < .001). Univariate analysis indicated that preoperative SHBG was the single most informative predictor of LNI (77.8% vs 71.7% for prostate-specific antigen, 63.9% for clinical stage, and 63.1% and 54.2% for primary and secondary Gleason grade, respectively). On multivariate analysis, preoperative SHBG was still significantly associated with LNI (P < .001), after accounting for the other variables. The addition of preoperative SHBG increased the predictive accuracy of the base model using clinically established predictors from 72.7% to 82.8% (10.1% gain; P < .001). The results of this study provide novel evidence that SHBG might serve as a significant multivariate predictor of LNI in patients with prostate cancer undergoing ePLND. The use of preoperative serum SHBG could help to identify patients at risk of LNI who should undergo ePLND.

Associations of Serum Sex Hormone Binding Globulin (SHBG) Levels with SHBG Gene Polymorphisms in the CARDIA Male Hormone Study

In the sex hormone binding globulin (SHBG) gene, a pentanucleotide-repeat polymorphism [(TAAAA)(n)] and a single nucleotide polymorphism (D327N) have been associated with circulating SHBG concentrations in women. Only one study, limited to Scandinavians, has examined these associations in men. Using data from the Coronary Artery Risk Development in Young Adults (CARDIA) Male Hormone Study, the authors assessed associations of SHBG polymorphisms with serum SHBG levels in 511 Black men and 698 White men who had SHBG measured in multiple serum samples collected over an 8-year period from 1987 to 1996 and were aged 20-34 years at the time of the first SHBG measurement. Multivariable repeated-measures analyses were used to assess associations of (TAAAA)(n) and D327N polymorphisms with SHBG concentrations. Results showed statistically significant differences in mean SHBG concentrations for White men with genotypes of (TAAAA) 6/6 (35.1 nmol/liter), 6/x (30.8 nmol/liter), and x/x (29.6 nmol/liter), where x represents a repeat length greater than 6 (p = 0.001). For Black men, the pattern of association was similar, albeit not statistically significant (p = 0.35). There was no relation between D327N genotype and SHBG levels. These results suggest that the (TAAAA)(n) repeat length in the SHBG gene, but not the D327N variant, might contribute to the interindividual variability in serum SHBG levels.

Serum concentrations of sex hormone binding globulin are elevated in kwashiorkor and anorexia nervosa but not in marasmus , ,

Customary blood protein markers for malnutrition are of limited value in the diagnosis of protein-energy malnutrition or anorexia nervosa in children and in the follow-up to refeeding in such children. For these diseases, we compared the diagnostic value of sex hormone binding globulin (SHBG) with that of albumin, transferrin, transthyretin, and retinal binding protein and determined the relations between concentrations of insulin, insulin-like growth factor I, and SHBG. SHBG was assayed in children with protein-energy malnutrition (29 children with kwashiorkor and 28 with marasmus), in 29 anorectic girls (before and after refeeding), and in age- and sex-matched control subjects. Mean (+/-SE) serum SHBG concentrations were higher in the children with kwashiorkor (0.18 +/- 0.07 micromol/L) than in the children with marasmus (0.11 +/- 0.05 micromol/L, P < 0.0001) or the control subjects (0.11 +/- 0.03 micromol/L, P < 0.0005). In the children with anorexia nervosa before weight gain, serum SHBG concentrations were significantly higher (0.10 +/- 0.04 micromol/L) than in the age-matched control subjects (0.06 +/- 0.03 micromol/L, P < 0.001) and decreased significantly after 30 d of refeeding (0.04 +/- 0.01 micromol/L, P < 0.0001). This decrease was negatively correlated with insulin-like growth factor I but not with insulin. Mean serum SHBG concentrations were influenced neither by inflammation, as indicated when C-reactive protein was used as a marker (0.27 +/- 0.27, 0.34 +/- 0.42, and <0.04 micromol/L in the children with marasmus, kwashiorkor, and anorexia nervosa, respectively), nor by glomerular filtration, as indicated when cystatin-C was used as a marker (68.46 +/- 23.08, 66.90 +/- 43.08, and 49.23 +/- 7.69 micromol/L, respectively). The high SHBG concentration observed in anorexia nervosa and kwashiorkor seems to be of multifactorial origin. For these 2 diseases, SHBG is a reliable marker of nutritional status, is unrelated to either C-reactive protein or cystatin-C, and may be helpful in distinguishing kwashiorkor from marasmus and as a follow-up marker after refeeding.

Role of androgens in female-pattern androgenetic alopecia, either alone or associated with other symptoms of hyperandrogenism.

The roles of androgen hypersecretion, in situ enzyme activity, and androgen receptors in androgenetic alopecia in women are still a matter of debate. We studied 187 women with alopecia, which we graded I, II, or III, according to Ludwig's classification, and 21 healthy control women. All participants were subjected to full basal and 1 h post-beta-1-24 corticotropin stimulation endocrine profiles. Abnormal hormone profiles were observed in 67% of the patients with alopecia alone (group A, n = 110) and in 84% of the patients with alopecia plus other symptoms of hyperandrogenism including acne, hirsutism, and menstrual cycle disturbances (group B, n = 77). Mean serum 5alpha-androstane-3alpha,17beta-diol glucuronide (3alpha-AdiolG) levels in all three patient groups (6.50+/-4.10, 8.90+/-5.80, and 14.70+/-8.90 nmol/l, respectively) correlated with the grade of alopecia (I-III) and were significantly higher than in the control group (4.80+/-2.05 nmol/l, P < 0.005). Mean serum sex hormone-binding globulin (SHBG) levels were inversely correlated with the grade of alopecia (I-III) and were significantly lower in all three patient groups (50.55+/-23.50, 40.00+/-17.65, and 38.80+/-14.10 nmol/l, respectively) than in the control group (61.15+/-17.65 nmol/l, P < 0.05). Mean serum levels of delta4-androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and 3alpha-AdiolG were higher in group B than in group A, and higher in group A than in the control group. The significant correlations found between adrenal secretion - either positive (with 3alpha-AdiolG levels and the body mass index) or negative (with SHBG levels) - might reflect the important contribution of secretory and metabolic components in the development of alopecia, the severity of which has been shown to be very closely related to observed levels of two of these parameters (3alpha-AdiolG and SHBG).

A prospective longitudinal study of serum testosterone, dehydroepiandrosterone sulfate, and sex hormone-binding globulin levels through the menopause transition.

The aims of this study were to describe, in relation to date of final menses, the average androgen levels of women in the years before and after this date, and to determine the extent to which these average levels were dependent on age and body mass index (BMI) and the degree of tracking in residual androgen levels, or the extent to which individuals above (below) the mean for their age or time relative to final menstrual period (FMP) and BMI remain above (below) the mean as time progresses. Serial levels of serum sex hormone-binding globulin (SHBG), testosterone (T), and dehydroepiandrosterone sulfate (DHEAS) were measured annually in 172 women from the Melbourne Women's Midlife Health Project who experienced a natural menopause during 7 yr of follow-up. Fasting blood samples were drawn between days 4-8 if women were still menstruating or after 3 months of amenorrhea. The free androgen index (FAI) was calculated as the ratio ofT to SHBG x 100. Means of the log-transformed androgen levels were analyzed as a double logistic function of time relative to FMP as well as age and BMI, and correlations between repeated androgen levels were measured. Mean SHBG levels decreased by 43% from 4 yr before to 2 yr after the FMP. The time of most change was 2 yr before FMP [95% confidence interval (CI), 0.8-3.2]. SHBG levels were, on the average, 5% lower for each halving of estradiol (E2) levels and 4% lower for each kilogram per m2 of BMI (P < 0.0001). About one third of the decline in SHBG was explained by E2 and BMI. After adjusting for all variables, SHBG showed strong tracking. Mean T levels did not vary with time relative to FMP and were independent of age and BMI. Residual values of T showed weak tracking. The FAI increased by 80% from 4 yr before FMP to 2 yr after FMP, and changed maximally 2.2 yr before FMP (95% CI, 1.2-3.2). The FAI was not related to age or E2, but was, on the average, 4% higher for each kilogram per m2 of BMI (P < 0.0001). Residual values of FAI showed moderate tracking. Mean DHEAS levels were not related to the FMP, but were 1.5% lower for each year of age (P < 0.01) and 3.8% lower for each kilogram per m2 of BMI (P < 0.0001). Residual values of DHEAS showed strong tracking. It is concluded that SHBG and FAI levels change at the time of the menopause, at least partially due to the decline in E2. DHEAS decreases as a function of age, not time relative to FMP, and T remains unchanged during the menopausal years. SHBG and DHEAS show a high degree of stability within an individual over time.

Increased prevalence of type 2 diabetes mellitus and impaired glucose tolerance in first-degree relatives of girls with a history of precocious pubarche.

To assess whether abnormal responses to an oral glucose load, dyslipidaemia and hyperandrogenaemia, which are commonly found in girls with a history of precocious pubarche, can also be detected in first-degree relatives of these patients. Sixty first-degree relatives (age, 41.4 +/- 4.4 years; BMI, 26.9 +/- 3.3 kg/m2) of girls diagnosed with precocious pubarche were studied. The prevalence of gestational diabetes mellitus and the hirsutism score were assessed in the females. The study was performed during the early follicular phase of the menstrual cycle in females and at random in males. All subjects underwent a standard 75 g 2-h oral glucose tolerance test (OGTT). Serum lipids and lipoproteins were measured in baseline blood samples in all subjects, while serum testosterone, sex hormone-binding globulin (SHBG) levels and the free androgen indices were determined only in females. Impaired glucose tolerance (IGT) and type 2 diabetes mellitus were diagnosed according to the criteria of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Seven subjects (11.6%) had type 2 diabetes while a further 14 (23.3%) had IGT; prevalences significantly higher than those reported for the present population of the same age (type 2 diabetes, 2.5% and IGT, 7. 5%; P < 0.001 and P < 0.001, respectively). BMIs were similar in patients with either normal or abnormal glucose tolerance. Abnormal levels of at least two lipid parameters were found in 40% of subjects. Four out of 10 hirsute women and six non-hirsute women reported gestational diabetes. Mean serum SHBG levels were lower in female relatives compared with population controls (P < 0.0005). First-degree relatives of girls with precocious pubarche are at a higher risk of impaired glucose tolerance and type 2 diabetes which, in most cases, is accompanied by an unfavourable lipid profile. Hyperandrogenism and an increased prevalence of gestational diabetes mellitus are frequent among females. These data may prove useful in identifying a specific subset of the population at increased risk of developing metabolic disturbances known to predispose to cardiovascular disease.

Changes in androgens during treatment with four low-dose contractptives

The aim of the present study was to compare changes in the endogenous androgen environment in healthy women while on low-dose oral contraceptives (OCs). One-hundred healthy women were randomized to receive one of four OCs during six months: 21 tablets of Cilest ®, Femodeen ®, Marvelon ®, or Mercilon ®. During the luteal phase of the pretreatment cycle, body weight and blood pressure were recorded and the following parameters were measured: sex hormone-binding globulin (SHBG), corticosteroid-binding globulin (CBG), testosterone (T), free testosterone (FT), 5α-dihydrotestosterone (DHT), androstenedione (A), dehydroepiandrosterone-sulphate (DHEA-S) and 17α-hydroxy-progesterone (17OHP) while also the free androgen index (FAI) was calculated. Measurements were repeated during the 3rd week of pill intake in the 4th and the 6th pill month. There were no differences on body mass and blood pressure with the use of the four OCs. The mean serum DHEA-S decreased significantly in all groups though less in the Mercilon ® group when compared to Cilest ® and Marvelon ® (approximately 20% vs 45%). Mean serum SHBG and CBG increased significantly in all four groups approximately 250% and 100%, respectively. In each group CBG also increased significantly but less in women taking Mercilon ® (−75%) as compared to the others (−100%). Current low-dose OCs were found to have similar impact on the endogenous androgen metabolism with significant decreases of serum testosterone, DHT, A, and DHEA-S. They may be equally beneficial in women with androgen related syndromes such as acne and hirsutism.

Effects of different doses of norethisterone on ovarian function, serum sex hormone binding globulin and high density lipoprotein-cholesterol

The ovarian effects of different doses of norethisterone (NET) were compared in 45 normally menstruating women in order to find the lowest effective dose of the Chinese NET “visiting pill”. Subjects were randomly divided into 3 groups. Each subject in each group was taking 0.5, 1.5 or 3.0 mg per day from days 5 to day 18 of the cycle. Blood samples were taken on days 5, 8, 11, 14, 17, 20, 23, 26 and 29 of the cycle. Serum oestradiol (E 2), progesterone (P), sex hormone binding globulin (SHBG), high density-lipoprotein cholesterol (HDL-C), and NET concentrations were measured. Ovulation, delayed ovulation, ovulation inhibition and follicular activity were classified by the analysis of the peripheral serum levels of sex hormones. Ovulation occurred in 7 women in the 0.5 mg group, in 2 women in the 1.5 mg group and in none of the 3.0 mg group. Mean serum SHBG levels were reduced progressively by 6.6% (Group 0.5), 15.5% (Group 1.5) and 23.4% (Group 3.0). There were no significant changes in HDL-C levels in any group. There was a significant correlation of mean serum NET concentrations with dose. The lack of complete inhibition of ovulation in most women in the 1.5 mg and 0.5 mg groups might suggest that the dose of NET required when used as a visiting pill could not be reduced below 3.0 mg.

Serum SHBG levels during normal menstrual cycle and after insertion of levonorgestrel-releasing IUD

Daily serum sex hormone binding globulin (SHBG) levels were measured during normal ovulatory menstrual cycles in ten women between the ages of 23 and 34 by the method of precipitation with ammonium sulfate. The results showed that the mean SHBG levels in a cycle were quite different among individuals, but that the SHBG levels were constant during a certain menstrual cycle. Neither SHBG peaks on day LH-0 (52.64 +/- 19.89 nmol/L) (x +/- SD) nor the mean SHBG levels between the follicular phase (57.10 +/- 17.64 nmol/L) and luteal phase (64.75 +/- 23.42 nmol/L) show any significant differences. The correlations between the mean SHBG levels and the mean concentrations of progesterone (P), estradiol (E2) and androstenedione during the menstrual cycles were insignificant, whereas the mean SHBG levels during the follicular and luteal phase and on LH-0 day were significantly correlated with the mean concentrations of testosterone (t = 0.474; p less than 0.05). In ten women between the ages of 25 and 34, serum SHBG, E2, P, and levonorgestrel (LNG) levels were measured once on day 20-21 of the pretreatment cycle and 3 times/week during the 1st, and 2 times/week during the 6th treatment cycle after insertion of a levonorgestrel-releasing IUD (LNG-IUD). The mean value of SHBG in the pretreatment blood samples (62.09 +/- 23.09 nmol/L) was higher than that after insertion of the LNG-IUD (41.82 +/- 20.50 nmol/L), though the difference was not significant (p greater than 0.05). The correlation between LNG and SHBG was highly significant (r = 0.89, p less than 0.01). The significance of this correlation and the degree of suppression of ovarian function are discussed.

Serum Sex Hormone-Binding Globulin and Serum Nonsex Hormone-Binding Globulin-Bound Testosterone Fractions in Prepubertal Boys with Chronic Renal Failure

We had previously reported that serum sex hormone binding-globulin (SHBG) decreases and serum non-SHBG-bound testosterone (T) and free T increase significantly from infancy to late prepuberty in normal prepubertal children of both sexes. We had also shown an age-related delay in these changes in hypopituitary boys, which was reversed by GH treatment. Stunted growth and delayed puberty are conspicuous features of chronic renal failure (CRF). As another model of delay of growth and development, serum SHBG and serum T fractions were determined in 13 boys with CRF on chronic dialysis. In CRF, mean serum SHBG was significantly higher (99.1 +/- 68.9 nmol/L; P less than 0.05) than in 31 control (C) children of similar ages (66.2 +/- 34.9 nmol/L), while serum non-SHBG-bound T and free T were significantly lower (0.16 +/- 0.12 in CRF vs. 0.24 +/- 0.12 in C and 0.010 +/- 0.005 in CRF vs. 0.016 +/- 0.01 in C, respectively). On the other hand, serum total T (1.31 +/- 0.88 in CRF vs. 1.08 +/- 0.56 in C) and serum insulin-like growth factor-I (IGF-I; 1.06 +/- 0.74 in CRF vs. 1.35 +/- 1.70 in C) were not significantly different. A significant negative correlation between serum SHBG and chronological age as well as a significant positive correlation between serum non-SHBG-bound T and chronological age were found. For a given age, serum SHBG was higher, while serum non-SHBG-bound T was lower in patients with CRF (by analysis of covariance, P less than 0.01). It is postulated that, as has been proposed for hypopituitary boys, this delayed increment in serum T fractions could be responsible for the delay in the onset of puberty reported in CRF. It is known that GH decreases serum SHBG, acting on hepatic cells either directly or through the action of IGF-I. Since it has been suggested that patients with CRF have peripheral resistance to GH or IGF-I, the high levels of SHBG that we have detected in prepubertal boys with CRF could be taken as an additional evidence of this biological resistance.

Nocturnal Serum Thyrotropin (TSH) Surge and the TSH Response to TSH-Releasing Hormone: Dissociated Behavior in Untreated Depressives*

TSH secretion, with particular regard to the nocturnal surge of the hormone, was evaluated in 15 women (age range, 35-66 yr; mean, 50 yr) with untreated major endogenous depression and 15 healthy women (age range, 32-67 yr; mean, 53 yr) using an ultrasensitive assay. Mean morning (0830 h) TSH values did not differ in the 2 groups (1.3 +/- 02 mU/L in depressives and 1.4 +/- 0.1 mU/L in controls), whereas mean nighttime (2400-0200 h) values were significantly reduced in depressives (1.5 +/- 0.3 vs. 3.1 +/- 0.3 mU/L; P less than 0.0005). At variance with the control group, morning and nighttime TSH values did not differ in the depressives. The nocturnal serum TSH surge was abolished in 14 of 15 depressed patients. The mean peak TSH value after TRH was slightly yet significantly lower in the depressives. Patients with subnormal (less than 0.4 mU/L) TSH values in the morning had a serum TSH increase after TRH less than 2 mU/L in 5 of 6 cases and a lack of the nocturnal TSH surge in 6 of 6. Among the 9 patients with normal TSH values in the morning, the nocturnal serum TSH surge was lost in 8 of 9, whereas the response to TRH was normal in all. The depressives, at variance with other reports, showed significantly lower values of total and free thyroid hormones. Mean serum sex hormone-binding globulin (SHBG) and ferritin were also significantly reduced. In conclusion, major endogenous depression is associated with a major impairment of TSH secretion, which baseline TSH measurements in the morning and the evaluation of the TSH response to TRH may not reveal. In this regard, the loss of the nocturnal serum TSH rise would appear to be a more sensitive indicator of hypothalamus-pituitary-thyroid axis alterations in depressives than the TRH test, which is commonly used in the evaluation of these patients. The lack of the nocturnal TSH surge may be responsible for the reduced thyroid hormone secretion and supports the case for some degree of central hypothyroidism in endogenous depression.

High serum sex hormone-binding globulin (SHBG) and low serum non-SHBG-bound testosterone in boys with idiopathic hypopituitarism: effect of recombinant human growth hormone treatment.

We measured serum sex hormone-binding globulin (SHBG), total testosterone (T), non-SHBG-bound T, albumin-bound T, free T, and SHBG-bound T in 19 prepubertal boys with hypopituitarism. Serum SHBG decreased with age with a slope similar to that in 91 normal prepubertal boys at higher level, and therefore, it reached similar values at a later age. Serum SHBG was significantly higher in hypopituitary prepubertal boys [mean, 123 +/- 12 (+/- SE) nmol/L] than in normal prepubertal boys (76 +/- 4; P less than 0.001) despite the fact that their mean age was also higher (10.0 +/- 4 vs. 7.1 +/- 4.1 yr; P less than 0.001). In 4 boys with isolated hypogonadotropic hypogonadism (Kallman's syndrome), aged 15.6 +/- 1.5 yr, serum SHBG was 21 +/- 14 nmol/L, a value below the 95% confidence limit of the regression line in GH-deficient boys. The affinity constants of association of the SHBG-DHT complex were similar in hypopituitary and normal boys. Eleven of the 19 hypopituitary boys (mean chronological age, 8.3 +/- 2.5 yr; mean bone age, 4.1 +/- 2.1 yr) were treated with recombinant hGH (0.5 U/kg BW.week) for 1 yr. Their mean serum SHBG level before treatment was 154 +/- 14 nmol/L, and it decreased gradually to 106 +/- 5 nmol/L (P less than 0.01) after 12 months of treatment. The tendency toward normalization of serum SHBG during treatment suggested that GH deficiency was responsible for the high serum SHBG levels. Serum SHBG correlated negatively with age in both treated hypopituitary and normal boys, but the slope of the regression line was significantly steeper in treated hypopituitary boys (P less than 0.01). On the other hand, the mean serum non-SHBG-bound T level was 0.10 +/- 0.02 (+/- SE) nmol/L in hypopituitary boys, significantly lower than that in normal boys (0.21 +/- 0.02 nmol/L; P less than 0.02). Since serum total T concentrations were similar in the two groups, the higher serum SHBG concentration resulted in lower serum bioavailable T levels in the hypopituitary boys. These changes might explain the poor response to T treatment reported in GH-deficient patients. The lower serum non-SHBG-bound T concentrations in the GH-deficient boys suggest there may be delayed exposure of central nervous system structures to increased levels of sex hormones, which, in turn, may slow body maturation. This mechanism might play a role in the delay of puberty that occurs in patients with isolated GH deficiency.

Serum Sex Hormone—Binding Globulin in Amiodarone-Treated Patients

The lodinated antiarrhythmic drug amiodarone frequently causes an elevation of the serum thyroxine (T4) level in patients who remain clinically euthyroid. Less frequently, true iodine-induced hyperthyroidism may occur. The clinical and laboratory distinction between these two conditions is often difficult. Since the serum sex hormone-binding globulin (SHBG) concentration is elevated in hyperthyroidism, this study was carried out to evaluate the serum SHBG concentration as a possible marker of hyperthyroidism in patients receiving amiodarone. Patients treated with amiodarone were divided into three groups: clinically euthyroid with normal serum T4 and triiodothyronine (T3) concentrations, clinically euthyroid with elevated serum T4 and normal T3 concentrations, and clinically hyperthyroid with elevated serum T4 and T3 concentrations. The mean serum SHBG concentration was significantly elevated in amiodarone-induced hyperthyroid patients, while it was normal in euthyroid patients treated with amiodarone who had normal or elevated serum T4 concentrations. The results suggest that the hyperthyroxinemia induced by amiodarone is not associated with excess thyroid hormone action in the liver unless the serum T3 concentration is also elevated.

A method for the determination of sex hormone binding globulin in human serum

A simple and rapid method for serum sex hormone binding globulin (SHBG) was developed. Sera from pregnant women were pooled and the SHBG concentration was measured by Rosner's method. This pool was diluted with charcoal-treated and heated serum to give standards ranging in concentrations from 26.8-0.8 micrograms/L. Two sets of tubes containing dihydrotestosterone (DHT), assay and control tubes, were prepared. Diluted standards and unknowns were added to assay and control tubes along with tritiated DHT. Following incubation, cold saturated ammonium sulfate was added to each tube, mixed, centrifuged and the supernatant counted. Mean SHBG concentration (microgram/L +/- SEM) in normal men was 3.6 +/- 0.4, normal women 11.4 +/- 2.2, pregnant women 58 +/- 2.6, obese women 3.3 +/- 1.0, hirsute women 2.9 +/- 0.2, hypothyroid women 7.3 +/- 1.0, and hyperthyroid women 26.0 +/- 1.6. These results correlate well with previous reports. This method is fast, convenient, and up to 40 samples can be analyzed in one assay.

Estrogen-androgen imbalance in patients with hirsutism and amenorrhea.

The serum concentration of estradiol (E2), testosterone (T), dihydrotestosterone (DHT) of 12 patients with hirsutism and amenorrhea were measured by radioimmunoassay, percent unbound E2 and T by equilibrium dialysis and concentration of sex hormone binding globulin (SHBG) by competitive ligand-binding assay. These were compared with values of 10 normal men and with values obtained throughout the follicular phase of 5 normal women. Only 4 of the 12 patients with hirsutism and amenorrhea had elevated serum T concentrations, the mean serum T concentration of this group being only 35% higher than the normals (p < 0.05). The mean serum E2 concentration (41.8 ± 6.0 pg/ml) was only 35% that of normal follicular phase E2 levels. The mean serum SHBG concentration of hirsute patients was 40% that of normal women and their mean unbound unconjugated E2 and T were 130% and 160%, respectively, of normal. Despite the high unbound fraction, the mean plasma unbound unconjugated E2 concentration was one-half the mean follicular phase levels. Nine of 12 patients with hirsutism had higher than normal concentrations of unbound unconjugated T resulting in a mean two times that of normal women. Because the ratio of unbound E2/T was abnormally low in 11 of 12 patients, it is suggested that the relative and absolute hypoestrogenism which is common in these patients may contribute to the hirsutism by potentiating the effect of T on hair growth. Similarly, subnormal serum SHBG concentrations in patients with hirsutism may also be a reflection of low serum unbound E2/T ratio.