D. Bernasconi

The impact of obesity on hormonal parameters in hirsute and nonhirsute women.

The influence of obesity on sex hormone-binding globulin (SHBG) and androgen concentrations in hirsute and nonhirsute women has been evaluated. The study was performed in 226 hirsute women (88 obese and 138 non-obese) classified as being affected by polycystic ovarian syndrome (PCOS) or by idiopathic hirsutism (IH) and in 100 nonhirsute control women ([C] 60 lean and 40 obese). SHBG, free testosterone (fT), androstenedione (A), estradiol (E2), dehydroepiandrosterone sulfate (DHEAS), and gonadotropin levels were measured during the first week of the menstrual cycle by radioimmunoassay (RIA). A significant negative correlation between SHBG and body mass index (BMI) was observed in PCOS, IH, and C women. In obese women--whether PCOS, IH, or C-fT levels were significantly higher and, conversely, SHBG levels were lower than in non-obese women. A negative correlation between SHBG and fT was evidenced in each group. Upper-body obesity was associated with lower SHBG and higher fT levels than lower-body obesity. In conclusion, obesity, particularly upper-body obesity, is associated with a reduction in SHBG and an increase in fT in both nonhirsute and hirsute women.

Estrogen and Progesterone Receptors in Uterine Leiomyomas

The purpose of our study was to evaluate the contrasting data between estrogen receptors (ER) and progesterone receptors (PgR) in uterine leiomyomas, endo‐metrium and myometrium. Uteri were obtained from 30 women undergoing hysterectomy for uterine leiomyomas (24 premenopausal and 6 postmenopausal patients). Cytosolic and nuclear ER and PgR were analysed in uterine tissues by the method of single saturation point assay at a final concentration 5 nM of [3H‐17P]estradiol and [3H]ORG‐2058. Our results confirm that leiomyomas undergo changes similar to those observed in other uterine tissues during the menstrual cycle. The ER levels show decreased values during the postovulatory phase. After subdividing leiomyomas according to their topographic criteria, as submucous or subserosal, we observed that ER and PgR are significantly more numerous in submucous than in subserosal myomas, both in proliferative and in the secretive phase of the cycle. These results agree with the hypothesis that leiomyomas have a different etiology and may explain why some myomas decrease after progestin therapy (submucous), while others (subserosal) remain unchanged.

Endocrine Evaluation in Patients Treated with Interferon-Alpha for Chronic Hepatitis C

The aim of our study was to evaluate the hormonal profile in a group of 31 subjects who underwent recombinant interferon-alpha therapy for chronic active hepatitis C. Hormonal determinations were performed before treatment began and at the end of the 3rd and 6th months of therapy. Free-T4 concentrations, though remaining in the normal range, showed a significant reduction (p < 0.05) after 3 and 6 months of therapy compared with pretreatment levels. A lesser decrease in free-T3 levels was also seen. TSH basal values did not show any variation, while an increased secretory response to TRH stimulation was observed at the end of the 6th month. Thyroglobulin and calcitonin levels remained normal, while an increase in antithyroglobulin and antithyreoperoxidase antibody levels was observed in 4 patients (12.9%). No modifications in the other pituitary hormones or in adrenal and sex steroid concentrations were noticed. A significant increase in IGF-I concentrations (p < 0.05) was observed during treatment, and an inverse correlation was seen between IGF-I and alanine aminotransferase levels (p < 0.01). This study supports the view that interferon treatment can influence thyroid function. The increase in IGF-I concentration observed during therapy may reflect an improvement in patients with hepatic disease, but a direct stimulatory effect of interferon on IGF-I secretion cannot be excluded.

The use of flutamide in the management of hirsutism

The aim of our study was to evaluate the clinical efficacy of flutamide (Flu), when used alone, on the course of hirsutism and to assess its effect on hormonal secretion. Thirty-six hirsute women [11 patients were affected by polycystic ovarian syndrome (PCOs), and 25 were classified as having idiopathic hirsutism (IH)] were treated with Flu, 375 mg daily for a 4-month period. We found a marked clinical improvement in the degree of hirsutism in all patients. Testosterone and free testosterone fell significantly in both groups, while SHBG concentrations showed an increase in PCOs. In these patients, a reduction in androstenedione levels was also evident. Basal DHEAS concentrations showed a significant decrease only in PCO women. No significant modifications in gonadotropin response to LHRH nor in adrenal steroid response to ACTH stimulation were observed in 12 of the IH women before therapy and after the first month. Although the main action of flutamide is attributed to its peripheral antiandrogenic properties, the decrease in circulating androgen levels observed during treatment suggests that it can also modulate androgen production and /or metabolism.

TSH-secreting adenomas: rare pituitary tumors with multifaceted clinical and biological features.

TSH-secreting pituitary adenomas (TSH-omas) are a rare cause of hyperthyroidism in clinical practice. As their diagnosis is often delayed, these tumors are mostly diagnosed as macroadenomas, preventing an effective and radical cure and leading to serious local and systemic comorbidities. In addition to neurosurgery, medical therapy with the effective and tolerable SS analogs is a fundamental tool for the treatment of TSH-omas. We report 3 cases of TSH-macroadenomas which displayed different clinical presentations. All patients showed increased free-thyroid hormone levels with inappropriately normal (2 patients) or high (1 patient) TSH levels. Magnetic resonance imaging (MRI)/computed tomography (CT) evidenced a pituitary macroadenoma and octreoscan was positive in all patients. In the 2 patients who underwent neurosurgery, hormonal hypersecretion by the tumor normalized. Histology showed nuclear pleomorphism and fibrosis, whereas immunohistochemistry showed positivity for TSH and, in a lesser amount, for FSH. In one of these patient (case 1), however, the presence of a tumor remnant inside the left cavernous sinus prompted us, in accordance with the patient, to start therapy with octreotide-long-acting release. As the third patient had a cardiac comorbidity which contraindicated neurosurgery, he underwent satisfactory treatment with long-acting SS analogs alone which normalized thyroid hormone levels. In this case, previous treatment with amiodarone confused and delayed the correct diagnosis of TSH-oma. As a result of improved laboratory and morphological techniques, TSH-omas should currently be diagnosed in early stages, thus enabling most patients to be managed satisfactorily through a combined approach.

Use of an artificial neural network to predict Graves' disease outcome within 2 years of drug withdrawal.

Background  Graves’ disease (GD) is an autoimmune disorder characterized by hyperthyroidism, which can relapse in many patients after antithyroid drug treatment withdrawal. Several studies have been performed to predict the clinical course of GD in patients treated with antithyroid drugs, without conclusive results. The aim of this study was to define a set of easily achievable variables able to predict, as early as possible, the clinical outcome of GD after antithyroid therapy.

ANDROGEN RECEPTORS IN NORMAL AND PATHOLOGICAL THYROIDS

The purpose of this study was to determine the presence of cytosolic and nuclear androgen receptors (AR) in both normal and nodular thyroid tissues from twelve women and six men. Samples of benign thyroid nodules and corresponding surrounding normal tissue were processed by the single saturation point assay, using [3H] R1881 ([3H] Methyltrienolone) at final concentration of 5 nM. The results show the presence of AR (cytosolic and/or nuclear) in all examined tissue samples. The nuclear AR content was higher (p < 0.01) in normal rather than in nodular thyroid tissues. The same pattern was observed when nuclear AR were analyzed according to the sex. In addition, nuclear AR content was significantly (p < 0.05) higher in normal thyroid tissue from men than from women. Our data suggest an androgen influence on thyroid tissue. If androgens are supposed to exert an antagonist role on estrogen actions also in thyroid tissue, the presence of higher nuclear AR concentration in the male rather than in the female normal thyroid may justify the lower incidence of thyroid diseases in men. Moreover, the lower AR levels found in male as well as in female nodular and goitrous tissues support the hypothesis that androgens may act with an antagonist mechanism on thyroid growth.

Thyroid and steroid receptors

Estradiol and progesterone receptor proteins (ER, PgR) have been demonstrated in neoplastic and non-neoplastic human thyroid. The aim of this study was to determine the sexual steroid receptor content of pathological non-malignant thyroid (solitary adenoma, simple nontoxic goiter), and the adjacent normal tissue of the thyroid. The results show the presence of ER and PgR (cytosolic and/or nuclear) in most of examined tissues both pathological and normal. Low levels of steroid receptors are found in the cytosol fraction, whereas the receptor content is higher in the nuclear fraction. No correlation could be found between receptor levels and patients’ age, menstrual state in females, and sexual steroid circulating hormones. A significant difference has been observed between adenomas and simple goiters (p < 0.001) in the nuclear ER, and between normal tissue surrounding adenoma and normal tissue in goiters (p < 0.05). This result suggests that estradiol and progesterone receptors are present in thyroid tissue and may have a physiological function.

Estradiol and progesterone receptors in normal and pathologic colonic mucosa in humans

The presence of estradiol (E) and progesterone (Pg) receptors (R) has been demonstrated also in normal and neoplastic tissues known to be hormone-independent and in particular in primitive colonic cancer, and, possibly, in healthy colonic mucosa. In this study endoscopic and surgical colonic mucosa specimens from 55 subjects were analyzed and divided as follows: 21 samples from healthy subjects, 12 normal mucosa samples from subjects affected with colonic cancer, 8 adenomatous polyps specimens, 5 samples from ulcerative colitis drawn on areas showing macroscopic lesions and 9 colonic cancer specimens. In the control group we have observed 6 cases positive for ER (28.6%) and 2 positive for PgR (14, 3%). Six normal mucosa specimens from subjects affected with colonic cancer were found to be positive for ER (50%) and 2 for PgR (16.7%). Five colonic cancers resulted ER positive (55.5%) and 4 PgR positive (44.4%). Four polyps were ER positive (50%) and 3 PgR positive (37.5%); in this group only one subject showed positive binding in the surrounding normal tissue. These data confirm the presence of ER and PgR in colonic cancer and colonic adenomas (so-called precancerous disease); in these subjects the finding of steroid receptors also in normal mucosa suggests that the presence of steroid binding could be considered as a marker of a precancerous condition.

Cytosolic and nuclear androgen receptor activity in the cancer of the larynx

It is well known that the larynx is a target organ for androgens and the cancer of larynx is more frequent in male subjects. We have evaluated the androgen receptors (AR) in the cytosol (ACR) and in salt extractable (ANR) and salt resistant nuclear fraction (AMR) in a group of 24 male patients with cancer of the larynx surgically removed. In addition specimens obtained from the normal mucosa of the same subjects were analyzed. In 5 patients estrogen (ER) and progesterone (PgR) receptors were also assayed. In all subjects blood samples were taken before surgery for the assay of the following hormones: LH, FSH, estradiol, testosterone, dihydrotestosterone, Δ 4-androstenedione, dehydroepiandrosterone sulfate, Cortisol. The results observed showed that 18 out of 24 normal larynx mucosa specimens and 17 out of 24 larynx cancer specimens were positive for ACR or ANR or AMR. The 5 samples of normal and cancer tissues analyzed for ER and PgR were negative. In conclusion there is no significant correlation between AR positivity from one size, histology, degree of differentiation and invasivity of the cancer, age of patients and hormonal blood levels from the other. The high ANR and AMR positivity (normal hormonal translocation and binding on DNA acceptors) confirm that the normal and cancer larynx are target tissue for androgens and establish the hormone dependence of this cancer. Hormonal therapy could be envisaged as an alternative or a complementary therapy for this type of cancer at least in the cases in which the analysis of hormone receptors will prove to be positive.