Surgical stress induces a marked and sustained increase of adrenal androgen secretion in postmenopausal women.

We analyzed the secretion of adrenal androgens in response to surgical stress in eight (8) postmenopausal women. ACTH, cortisol (F) and adrenal androgens, such as dehydroepiandrosterone (DHEA), delta 4-androstendione (delta 4-A), dehydroepiandrosterone sulfate (DHEA-S) and testosterone (T) were measured at 08:00 and 20:00 hr the day before and for three consecutive days after operation, as well as at 0, 15, 30, 60, 120 minutes during cholocystectomy. Basal levels of ACTH, F, DHEA, delta 4-A, DHEA-S and T were found within the normal range for this age group before surgery. During surgery the ACTH was significantly increased, reaching a peak value at 30 min after surgery initiation. F, DHEA and delta 4-A were significantly increased during and after surgery, returning to pre-surgery levels by the third day post-surgery. DHEA-S levels did not increase during surgery but was found significantly increased the day after surgery, returning to presurgical levels two days later. We conclude that surgical stress can induce adrenal androgen hypersecretion during and within the early days post-surgery. Because the adrenal androgens levels are declining and respond suboptimally to exogenous corticotropin releasing hormone (CRH) or ACTH bolus injection in aging women, it is conceivable that this remarkable response of adrenal androgens to surgical stress is probably of biological significance and conceivably mediated by a CRH/ACTH-independent mechanism.

The influence of smoking habits on thyroid gland volume: an ultrasonic approach.

The effects of smoking habits on thyroid function, echo-texture (nodules and/or cysts) and thyroid gland volume were determined by using ultrasound and measuring serum Thyroxin (T4), Triiodothyronine (T3), Thyrotropin (TSH) and TPO antibodies (ab-TPO) in 189 healthy smokers and non-smokers, randomly selected (111 females and 78 males) among the employees of our hospital and their relatives. When the entire group of subjects was considered the mean ratio of thyroid gland volume/body weight was found to be significantly higher in male (P < 0.05) and female (P < 0.05) smokers compared with non-smokers. In female smokers, mean serum thyroid-stimulating hormone (TSH) was lower (P < 0.05) and the degree of smoking was positively correlated with the ratio of thyroid gland volume/body weight (P < 0.05). However, when the subjects with a family history of goitre in first degree relatives were excluded from our study (14 females and 9 males), no significant differences in mean ratio of thyroid volume/weight or TSH between the remaining smokers and non-smokers were detected. In both sexes, the correlation between the degree of smoking and thyroid volume, although positive, did not reach statistical significance. No difference in prevalence of abnormal echogenicity and echo-texture (nodules and cysts) between smokers and non-smokers was detected. It is concluded that smoking habits present a goitrogenic effect only in subjects with a family history of goitre but have no influence on thyroid gland texture.

Corticotropin-releasing-hormone levels in pregnancy-induced hypertension.

UNLABELLED: High levels of corticotropin-releasing hormone (CRH) circulate in the plasma of pregnant women especially during the third trimester and even higher levels have been reported in abnormal pregnancies of various etiologies. One of these etiologies is pregnancy-induced hypertension (PIH). OBJECTIVE: To measure CRH blood levels with a sensitive method in a large number of pregnant women with PIH, starting from very early stages of gestation, and to compare them with those in normal controls. STUDY DESIGN: Venous blood was withdrawn from, (a) 10 healthy women aged 20-35 years, (b) 62 pregnant women with PIH (109 samples), mean age 29.1 years and (c) 75 healthy pregnant women (81 samples), mean age 28.5 years, used as matched controls. In pregnant women, blood collection started at the 10th week of gestation. In 14 women from group b and in 22 from group c blood was withdrawn during labor as well. CRH was assayed by RIA. RESULTS: Levels in non-pregnant women were between 19.0-40.6 pg/ml (28.37 +/- 2.53 pg/ml, mean +/- S.E.M.). In both groups of pregnant women there was a progressive increase in plasma CRH levels becoming quite sharp towards the end of gestation. Between 10 and 20 weeks, CRH (mean +/- S.E.M.) in PIH group was 69.3 +/- 3.2 pg/ml versus 41.6 +/- 2.4 pg/ml in matched controls, at 21-25 weeks 168.0 +/- 12.8 pg/ml versus 58.5 +/- 3.8 pg/ml, at 32-35 weeks 1378.5 +/- 61.4 pg/ml versus 298.3 +/- 16.9 pg/ml and at 38 weeks 2800.0 +/- 114.1 pg/ml versus 825.0 +/- 59.8 pg/ml. At term, CRH levels were 3784.0 +/- 197.3 pg/ml in PIH, versus 1386.0 +/- 101.8 pg/ml in normal pregnancy. Statistically, at every stage of gestation, CRH levels were highly significantly different in the PIH group (P < 0.0005). One hour postpartum there was a c. 60% decrease in plasma CRH levels in both b and c groups. In three women with pre-eclampsia who underwent premature labor due to a dead fetus around the 30th week, very high levels were noticed in sequential blood samples for 4-5 weeks prior to labor. CONCLUSIONS: (a) CRH levels in women with PIH are significantly higher compared to healthy pregnant women at any stage of gestation starting from week 10; (b) very high levels during pregnancy might be predictive of premature labor or fetal loss; and (c) CRH measurement might prove to be a helpful diagnostic tool in women with pregnancy-induced hypertension.

24-hour secretion of growth hormone (GH), insulin-like growth factors-I and -II (IGF-I, -II), prolactin (PRL) and thyrotropin (TSH) in young adults of normal and tall stature.

Studies of the growth hormone (GH) secretory dynamics of children with normal and idiopathic short stature (ISS) have revealed that the regulation of the GH-somatomedin (GHS) axis can differ significantly among normal individuals. Information on the GH secretion in idiopathic tall stature (ITS) is scarce. We previously showed that the GH response to stimulation with GH-releasing hormone (GHRH) in male, late adolescents and young adults with ITS is significantly greater than that of their sex and age-matched controls of average height. In the present study, we studied the 24-hour (hr) GH, insulin-like growth factor-I and -II (IGF-I and -II), prolactin (PRL) and thyroid-stimulating hormone (TSH) secretion by every 30 minutes (min) sampling in 12 young, healthy male Greek army recruits. Group I [n = 6, age 22 + 1.4 years (y.), mean + standard deviation (SD)] had a height of 198.5 + 4.2cm, at least 3 SD's above the mean of the Greek male population. Group II (n = 6, age 20.5 + 1.05 y.) had a height of 169.2 + 3.4cm, within 2SD's of the normal mean. Serum IGF-I levels were determined in both unextracted and extracted samples. Our results indicated that the number of secretory bursts and the circadian panel of GH, IGF-I and -II, PRL and TSH were similar in the two groups. Both the amplitude of the secretory GH peaks (5.08 + 3.07 vs. 3.3 + 0.8 ng/ml, p = 0.19,) and the area under the curve (AUC) of the 24-hour GH secretion (9.8 + 5.5 vs. 6.6 + 1.3 ng/ml/hr, p = 0.2) were higher in group I than in group II, but the difference was not significant. A significant nocturnal increase of both IGF-I and -II levels was found only in extracted human plasma (p < 0.001), whereas measurements of IGF-I in unextracted samples failed to reveal circadian variation (p < 0.1). We conclude that no significant differences were found in this pilot study of the neurosecretory regulation of the GHS axis between individuals of tall and normal stature. A tendency for greater amount of GH secretion per secretory peak was found in persons with tall stature; however, this finding needs to be confirmed in a larger study. IGF-I and -II levels had a significant circadian variation with a large nocturnal surge, when measured in extracted plasma. The latter, might be explained by circadian variation of the circulating IGF-binding proteins and its detection appears to be method of extraction-dependent.

Incidence of gynaecomastia in 954 young males and its relationship to somatometric parameters.

The incidence of gynaecomastia was evaluated in 954 healthy young men aged 18-26 years, and was correlated with several somatometric parameters (height, weight, testes size, eye colour, scalp hair colour, scalp hair density, acne, density and extent of body hair). Gynaecomastia (> 2 cm breast tissue) was found in 40.5% (bilateral 85%, left 7.8%, right 7.2%) of the subjects. Highly statistically significant differences were found between subjects with or without gynaecomastia in their weight (79.7 +/- 10.7 kg versus 69.1 +/- 7.8 kg respectively; p < 0.001) and in their body hair (subjects with gynaecomastia had more dense and extensive body hair than those without; p < 0.001). When the density and extent of body hair was analysed separately for each age, it was found that subjects with gynaecomastia had completed the development of body hair earlier, since 80% of them had completed their body hair by the age of 23 years versus only 45% of those without gynaecomastia. This observation leads to the assumption that obesity and/or an earlier maturation of the subjects with gynaecomastia may play a role in the development of breast tissue, although the possibility of an increased tissue sensitivity to hormonal action cannot be excluded.

Menstrual disturbances in thyrotoxicosis.

OBJECTIVES: In thyroid textbooks it is stated that hyperthyroidism in women may be associated in almost 50% of the cases with hypomenorrhoea, oligomenorrhoea or amenorrhoea and perhaps with reduced fertility. Our experience at a busy thyroid clinic has given a picture which differs from that described in the literature. Most of our female thyrotoxic patients had normal menstruation. This study was performed to define the menstrual abnormalities in hyperthyroidism. DESIGN AND PATIENTS: We investigated the menstrual history, starting 6 months before the discovery of the disease, the smoking habits and the body mass index (BMI), in 214 female, premenopausal thyrotoxic patients and a similar number of normal controls matched for age and weight. MEASUREMENTS: TT4 and TT3 were measured by radioimmunoassay, while BMI was calculated from the ratio of body weight in kg to height in m2. RESULTS: Of the 214 patients, 168 (78.5%) had regular menstrual cycles and 46 (21.5%) irregular cycles. No difference in BMI was found between the patients with or without menstrual abnormalities. Out of the 46 patients with irregular periods, 23 (50%) were smokers, while only 32 out of the 168 patients (19%) with normal periods were smokers (P < 0.001). TT4 levels were higher as a group in patients with menstrual disturbances (mean +/- SD 267.7 +/- 66.9 nmol/l) than in those with normal periods (240.6 +/- 47.6 nmol/l) (P < 0.05). The 23 smokers with irregular periods had higher TT4 levels (280.5 +/- 51.8 nmol/l) than the remaining non-smokers from the same group (241.9 +/- 43.7 nmol/l) (P < 0.01). No such differences were found for TT3 levels. Out of 214 normal controls, matched for age and weight, 196 (91.6%) had normal menstruation and 18 (8.4%) irregular cycles. The latter group included mainly women with oligomenorrhoea. Out of 18 normal controls with irregular periods, 6 (33.3%) were smokers, while 57 (29.1%) out of 196 with normal periods were smokers. CONCLUSIONS: These data demonstrate that hyperthyroidism in women is less frequently associated with menstrual abnormalities than was previously believed. Furthermore, no patient presented with amenorrhoea. Smoking and TT4 levels are strongly associated with the occurrence of menstrual disturbances in thyrotoxicosis.

Contribution to the problem of hyperprolactinaemia: experience with 4,199 prolactin assays and 117 prolactinomas.

OBJECTIVE: To help define the normal and pathological serum prolactin concentration ranges in adult females. PATIENTS AND METHODS: Serum prolactin was assayed in a mixed population of 4,199 women divided into five groups: (A) 753 with normal menses consulting for infertility (control group); (B) 2,523 with menstrual disorders; (C) 519 with hirsutism and normal cycles; (D) 201 with galactorrhoea and normal cycles; (E) 203 with galactorrhoea and menstrual disorders. RESULTS: In each group, a separate subset (2%, 3%, 1%, 15%, and 42.3%, respectively) was distinguished, with scattered prolactin values above 30 ng/mL, in which 117 prolactinomas were found, with an incidence ranging from 11 to 57% in cases with prolactin of 31-49 ng/mL and from 65 to 87.5% in those with prolactin > or = 50 ng/mL. The frequency distribution of values from 1 to 30 ng/mL was strikingly similar in the 753 subjects of group A and the 2,523 patients of group B: 91% and 92.6%, respectively, between 1 and 15 ng/mL, and 5.5% and 4.7% from 16 to 20 ng/mL. Values > 20 ng/mL were found in 4.4% of the subjects in group A, 5.5% in group B, 5.1% in group C, 21.8% in group D, and 18.7% in group E. CONCLUSIONS: (a) Normal prolactin values can be considered to include 1-15 ng/mL and 16-20 ng/mL, the former corresponding to the vast majority of normal subjects or patients, and the latter being the extreme limit of normal, for which from a clinical point of view repetition of the assay and a follow-up is advocated. (b) Values between 21 and 30 are rare and could be considered as hyperprolactinemia necessitating further investigation. (c) Values between 31 and 49 are suspect, and values > or = 50 ng/mL are suggestive of the presence of a prolactinoma, warranting thorough investigation.

Are adrenal and testicular androgen levels correlated?

To investigate the reported correlation between adrenal and testicular serum androgen levels, testosterone, DHEAS and androstenedione were measured in the serum of 92 healthy young males. Testosterone and androstenedione were found to have a weak but statistically significant correlation, while no correlation existed between testosterone and DHEAS, or DHEAS and androstenedione. These results indicate that although common steroidogenic pathways lead to androgen synthesis in both adrenals and testes, the regulation of steroid production in these glands is influenced by different factors. The correlation of testosterone with androstenedione can be attributed to their peripheral interconversion as well as to the fact that half of androstenedione is of testicular origin. Various other aspects of the androgen regulation mechanism such as ACTH stimulation and the role of aging, are presented and discussed.

Incidence and characteristics of microprolactinomas (3-5 mm) in 4199 women assayed for prolactin.

Difficulties and controversies still exist in the diagnosis of small (3-5 mm) prolactinomas (micro-PRL-omas). In the present study serum prolactin (PRL) was assayed in 4199 women aged 14-43 years belonging to 4 groups: A: 753 women with normal cycles (NC) and infertility (control group), B: 2523 with menstrual disorders, C: 519 with NC and hirsutism, D: 404 with galactorrhoea. The distribution of PRL values from 1 to 30 ng/ml was almost similar in the subjects of group A, B and C. Within this range the vast majority of subjects (91%, 92.2% and 88% respectively in these 3 groups and 83% in group D) had PRL levels from 1 to 15 ng/ml and together with the proportion of subjects with PRL values 16 to 20 ng/ml they included 96.7% of the entire mixed population. A proportion of scattered outlying PRL values above 30 ng/ml was found in each group (A = 2%, B = 3%, C = 1% and D = 28.7%) and in this subset 117 prolactinomas (PRL-omas) were found, 19 (23%) in the 83 subjects with PRL levels 31-49 ng/ml and 98 (75.3%) in the 130 subjects with PRL values greater than or equal to 50 ng/ml. Of the 117 PRL-omas 9 were bigger than 10 mm and 4 had a size from 6 to 9 mm. In the remaining 104 the size was presumed from direct or indirect radiological evidence to be 3-5 mm.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal hyperresponsiveness to ACTH stimulation in women with polycystic ovary syndrome: an adrenarchal type of response.

Adrenal responsiveness to ACTH stimulation (1 mg, i.m.) was assessed by measuring cortisol (Cort) and 17-hydroxyprogesterone (17OHP) at 0, 30, 60, and 90 minutes and progesterone (P), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), delta 4-androstenedione (delta 4A), and testosterone (T) at 0, 60, and 90 minutes post-ACTH in 30 women with polycystic ovary syndrome (PCO). The results were compared with those from 12 normally menstruating women. Three distinct patterns of responses of the adrenal steroids were observed in PCO patients, while cortisol response was similar to that of normal controls: (a) normal responders (n = 9, 30% of PCO patients), in whom a delta max response similar to that of normals was observed, although basal delta 4A and T levels were found to be elevated; (b) 21-OH dysfunction group (n = 6, 16.6%), in whom delta max 17OHP levels and delta max 17OHP to delta max Cort ratio were significantly higher than those of normals and the other PCO groups, indicating a dysfunction at the 21-hydroxylase level; (c) adrenarchal type of response group (n = 16, 53%), in whom statistically significant (P less than .0001) hyperresponsiveness of DHEA and, in 11 of them, of delta 4A, with high delta max delta 4A to delta max DHEA to delta max Cort ratios were found, indicative of a selective overproduction of the steroids during steroidogenesis. Moreover, the significantly higher delta max delta 4A to delta max 17OHP ratio found in group c is a further indication of increased 17,20-lyase efficiency, as is encountered during adrenarche.(ABSTRACT TRUNCATED AT 250 WORDS)

Paradoxical growth hormone response following thyroid-stimulating hormone administration in the polycystic ovary syndrome.

Growth hormone (GH) and prolactin (PRL) responses after TRH administration were studied in 31 women presenting with the clinical, biochemical and ultrasonographic characteristics of the polycystic ovarian (PCO) syndrome; their results were compared with those of 20 normally menstruating women investigated during the early follicular phase of the cycle. Based on the GH responses two PCO subgroups were observed: (a) nonresponders (n = 16) who showed delta max GH responses (0.7 +/- 0.27 ng/ml, x +/- SE) similar to those of the normals (0.97 +/- 0.20 ng/ml), and (b) responders (n = 15), 48.4% of the PCO patients who showed a paradoxical increase in GH levels (delta max GH, 18.0 +/- 1.96 ng/ml) following thyrotropin-releasing hormone (TRH) administration significantly higher than those observed either in nonresponder PCO patients or in normals. Furthermore, basal GH levels were found to be significantly higher in the responder PCO subgroup (5.65 +/- 0.75 ng/ml) compared to either nonresponders (1.58 +/- 0.21 ng/ml) or normals (1.8 +/- 0.18 ng/ml). However, no correlation was found between basal GH levels and delta max GH responses observed. Additionally, basal PRL and delta max PRL levels following TRH administration did not differ either between the two PCO subgroups or those observed in normal controls. delta 4A, T and E2 levels were similar between the two PCO subgroups. No correlation was found between the delta max GH responses to delta max PRL or the post-luteinizing hormone-releasing hormone stimulation test delta max luteinizing hormone:follicle-stimulating hormone ratio observed or to steroid levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased GH response to GHRH in normal tall men.

The importance of growth hormone secretion to the growth of an individual raises the question of the role that the secretory capacity of this hormone may play in defining the variations of height within the population. To investigate this problem we studied the response of GH to GHRH in 20 normal tall (mean +/- SD height 190.8 +/- 2.4 cm, range 187-196 cm) adult males of the third decade and in 17 age-matched controls of average height (mean +/- SD height 173.8 +/- 1.6 cm, range 171-177 cm). Synthetic GHRH (1-29) NH2 (Kabi, Vitrum, Sweden) was administered at 0800 h after an overnight fast and blood was drawn for GH assay. In the tall subjects basal GH concentrations at -15 and 0 min were not significantly different from those of the controls. However, the tendency to higher basal GH levels and spontaneous peaks was evident in tall individuals. Only three basal GH values were below 1 micrograms/l (0.8-0.9 micrograms/l; 1 microgram/l = 2mU/l) in the tall individuals while 24 of 33 basal GH values in the controls ranged between 0.25 and 0.87 micrograms/l. At +15 and +30 min after GHRH the rise in GH was significantly greater in the tall subjects. Moreover, the integrated area under the response curves was significantly greater in the tall subjects than the controls (P less than 0.01). No differences in the mean serum testosterone and prolactin levels were found in the two groups. It is postulated that if this enhanced pituitary responsiveness is constant and chronic in tall individuals a definite relation of their stature to the GH secretion is to be anticipated.

Vaginal cytology in endocrinopathies.

In order to evaluate the diagnostic significance of vaginal smears in endocrinopathies associated with menstrual disorders, the cytologic pattern of vaginal smears was examined in 703 patients who had a well-established diagnosis of the disorder's origin. The patients were classified into four groups according to their menstrual disorders: primary amenorrhea (159 patients), secondary amenorrhea (116 patients), primary oligomenorrhea (214 patients) and secondary oligomenorrhea (214 patients). Using the maturation index and the maturation value, three cytologic patterns of vaginal smears were distinguished: parabasal cell pattern, intermediate cell pattern and superficial cell pattern. The frequency with which the cytologic patterns occurred in the groups of patients and their subdivisions are presented. As a whole, the 703 patients showed 25.2% with a parabasal cell pattern, 58.3% with an intermediate cell pattern and 16.5% with a superficial cell pattern. Although the cytohormonal pattern of vaginal smears in endocrinopathies with associated menstrual disorders is not diagnostic of a specific endocrinopathy, the cellular patterns may prove helpful in suggesting a range of diagnoses or in excluding some possibilities.

Postmenopausal vaginal cytohormonal pattern in 597 healthy women and 301 patients with genital cancer.

Cytohormonal evaluation was made on vaginal smears of three groups of women, all over 50 years of age and menopausal for at least one year. The first group consisted of 597 control healthy women, and the second and the third groups consisted of 134 patients with squamous cervical cancer and 167 patients with endometrial adenocarcinoma, respectively. It was found that 4% of the 597 healthy women had vaginal smears with an unequivocal estrogenic effect as compared with a 6% incidence in patients with squamous carcinoma of the cervix and a 12% incidence in patients with endometrial adenocarcinoma. It is concluded that increased estrogenic activity in a woman more than one year after menopause should lead to a thorough clinical investigation to exclude an asymptomatic carcinoma of the cervix or endometrium.

Pituitary function in 8 patients with familial pituitary dwarfism.

Pituitary function was evaluated in four pairs of familial pituitary dwarfs (two sisters, 28 and 20 years old, two brothers 15 and 10 years old, one girl 19 years old and her brother 7 years old, and one girl 9 years old and her brother 3 6/12 years old), who all proved to have multiple pituitary hormone deficiency (MPHD), in order to find out whether a distinct intrafamilial or interfamilial pattern of deficiency existed. The response of FSH and LH to LRH, of TSH to TRH, of growth hormone (GH) to L-dopa, and of prolactin to sulpiride administration was studied. Basal levels of ACTH and cortisol (F) were also measured on two consecutive days. Basal FSH, LH and GH concentrations were below the sensitivity of the assay in all patients (except one who had measurable levels of LH) and showed no change after the appropriate stimulation. Basal TSH was normal in 6 patients and slightly increased in two members of the same family. Both these patients presented an exaggerated response to TRH. Three of the remainder patients showed a small and the other three no response to TRH. Basal prolactin values ranged within the normal limits, but prolactin was not increased during the sulpiride provocative rest. Mean basal ACTH was normal in 5 and low in 3 patients. Mean cortisol levels were normal in 5, near the lower normal limit in 2, and low in one patient. This patient had also a low ACTH concentration. It is concluded that the lack of a common pattern of hormone deficiency in all families indicates a variability in the expression of the hypothalamo-pituitary defect, which suggests that the familial MPHD dwarfism constitutes a genetically and pathogenetically heterogenous group.