Resistin levels are normal in hypothyroidism and remain unchanged after attainment of euthyroidism: relationship with insulin levels and anthropometric parameters.

The aim of this controlled prospective study was to investigate resistin levels in hypothyroidism before and after restoration of euthyroidism and correlate the results with body weight (BW), body fat (BF), waist circumference (WC), body mass index (BMI) and serum insulin levels. Fifty-three hypothyroid patients with Hashimoto's disease (6 males, 47 females) and 30 controls matched for age, BMI and BF were investigated. Anthropometric parameters, resistin and insulin levels were measured. All patients were started on levothyroxine treatment and 4 to 5 months after initiation of treatment the investigations were repeated. Hypothyroid patients exhibited normal resistin values, which were no different from controls (mean+/-SD 7.4+/-4.0 vs 5.1+/-3.5 ng/ml, p=0.063). Normalization of circulating thyroid hormone levels produced no significant change in resistin levels (7.4+/-4.0 vs 6.8+/-4.2 ng/ml, p=ns) and post-treatment resistin levels did not differ from euthyroid controls. Furthermore, no gender difference was demonstrated in resistin levels either before (6.4+/-3.7 for males vs 7.6+/-4.1 ng/ml for females, p=ns) or after therapy (7.9+/-4.3 vs 6.7+/-4.3 ng/ml, for males and females respectively, p=ns), nor was there a difference in resistin levels in either sex induced by treatment of hypothyroidism (6.4+/-3.7 vs 7.9+/-4.3 ng/ml for males, p=ns, and 7.6+/-4.1 vs 6.7+/-4.3 ng/ml for females, p=ns). However, a small but significant difference in resistin levels was found between female patients and female controls (7.6+/-4.1 vs 5.0+/-4.0 ng/ml, p=0.047). Insulin levels and homeostasis model assessment insulin resistance (HOMA-IR) index did not differ before and after treatment in hypothyroid patients (13.0+/-10.2 vs 12.6+/-11.8 microU/ml, 22.7+/-1.4 vs 21.8+/-1.3, respectively, p=ns for both) or between patients and controls. In conclusion, our results demonstrate that resistin levels are normal in hypothyroidism and remain within normal range after attainment of euthyroidism. Resistin is not associated with serum insulin and HOMA-IR index, as well as BMI, BF, WC and BW.

Gonadal effect of radiation from 131I in male patients with thyroid carcinoma.

The role of iodine-131 therapy in the management of differentiated thyroid carcinoma is well established. Because the spermatogonia are very sensitive to radiation, there is concern that large doses of the latter could result in azoospermia and permanent infertility. For patients treated with a single ablation dose, testicular function recovers within months and the risk of infertility is diminished. Gonadal damage may be cumulative in those requiring multiple administrations. In all young male patients, but especially in those with metastatic or pelvic disease or both, the long-term storage of semen should be addressed prior to therapy. Sperm banking should be considered in patients likely to be given cumulative doses greater than 14 GBq of 131I. However, the patient's threshold for sperm banking might be even lower than that.

Free and total insulin-like growth factor (IGF)-I, -II, and IGF binding protein-1, -2, and -3 serum levels in patients with active thyroid eye disease.

To determine whether serum levels of total (T) and free (F) IGF-I and -II and IGF binding protein (IGFBP),-1, -2, and -3 are normal in euthyroid patients with Graves' disease and active thyroid ophthalmopathy, we investigated the above-mentioned parameters in 21 patients (11 male, 10 female) aged 50.8 +/- 11.8 yr (range 35-70) and 19 healthy individuals matched for age, gender, and body mass index. All patients had active thyroid eye disease (TED) with clinical activity scores > or = 4 and positive orbital octreoscan in both eyes. Serum T and F IGF-I and IGF-II were determined using noncompetitive time-resolved monoclonal immunofluorometric assays, IGFBP-1 was determined by an in-house RIA, IGFBP-2 by a novel in-house time-resolved immunofluorometric assay, whereas IGFBP-3 by an immunoradiometric assay. All data are expressed as mean +/- SD. Our results show that T and F IGF-I, -II, and IGFBP-1, -2, and -3 levels in patients were similar to controls and did not show any significant difference. Specifically, mean T IGF-I for patients group was 131 (61), F IGF-I was 0.47 (0.16), T IGF-II was 1056 (300), F IGF-II was 1.45 (0.54), IGFBP-1 was 33 (14), IGFBP-2 was 848 (377), and finally IGFBP-3 was 3953 (1422). For controls, mean T IGF-I was 146 (51), F IGF-I was 0.85 (0.43), T IGF-II was 939 (197), F IGF-II was 1.53 (0.53), IGFBP-1 was 44 (24), IGFBP-2 was 764 (316) and finally IGFBP-3 was 3721 (1017). Furthermore, no statistically differences emerged in the ratio between molar weights of T IGF-I/IGFBP-3 and T IGF-II/IGFBP-3, as well as to the F/T IGF-I and F/T IGF-II. Finally, no relationship was found between the levels of the above-mentioned parameters and clinical activity scores, octreoscan scores, and thyroid hormones. Our data demonstrate for the first time that serum levels of IGFs (including free fractions) and IGFBPs are not increased in euthyroid Graves' patients with active TED. The increased IGF levels in retrobulbar tissues previously described, appear to be independent of serum IGFs concentration and probably represent autocrine and/or paracrine activity.

A prospective controlled study of the impact of hyperthyroidism on reproductive function in males.

The aim of this prospective controlled study was to ascertain the effect of hyperthyroidism on sperm quality and composition. We studied 23 thyrotoxic male patients, aged 43.8 +/- 2.4 yr (mean +/- SEM), and 15 healthy male controls of approximately the same age (42.2 +/- 2.2 yr). Two semen analyses at intervals of 2-3 wk were obtained before and about 5 months after euthyroidism was achieved either by methimazole alone (14 patients) or (131)I plus methimazole (9 patients). Total fructose, zinc (Zn), and magnesium (Mg) were also measured in seminal plasma in 16 patients, because 7 had semen volume less than 2 ml. In the control group semen analysis was performed only once. Mean (+/-SEM) semen volume was within normal range both in patients (3.3 +/- 0.2 ml) and controls (3.5 +/- 0.4 ml; P = NS). Mean sperm density was lower in patients, although the difference compared with controls did not reach statistical significance (35.7 +/- 5.3 vs. 51.5 +/- 6.1 x 10(6)/ml; P = 0.062). The same was found with sperm morphology (68 +/- 7% vs. 78 +/- 8%; P = NS). Finally, mean motility was lower in thyrotoxic males than in controls (28 +/- 8% vs. 57 +/- 7%; P < 0.01). After treatment, sperm density and motility improved [35.7 +/- 5.3 vs. 43.3 +/- 6.5 x 10(6)/ml (P = NS) and 28 +/- 8% vs. 45 +/- 7% (P < 0.05), respectively], but sperm morphology did not change (68 +/- 7% vs. 70 +/- 6%; P = NS). Mean values for fructose, Zn, and Mg did not differ between controls and patients either before or after achievement of euthyroidism [9.2 +/- 0.7, 3.0 +/- 0.5, and 4.2 +/- 0.7 nmol/liter vs. 8.6 +/- 0.9, 3.0 +/- 0.5, and 4.7 +/- 0.8 nmol/liter (patients before) and 9.1 +/- 0.7, 3.1 +/- 0.6, and 4.5 +/- 0.9 nmol/liter (patients after treatment) for fructose, Zn, and Mg, respectively]. Moreover, according to the treatment given, no statistically significant differences were found before or after treatment. Finally, seminal plasma fructose, Zn, and Mg levels did not correlate with sperm parameters or with pretreatment thyroid hormone levels. In conclusion, the results of our study indicate that male patients with hyperthyroidism have abnormalities in seminal parameters, mainly sperm motility. These abnormalities improve or normalize when the patients become euthyroid. Restoration of sperm parameters was independent of the treatment provided for the hyperthyroid syndrome. Moreover, seminal plasma elements, such as fructose, Zn, and Mg, did not correlate with sperm density, motility, or morphology.

Serum levels of tumor necrosis factor-alpha, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and soluble interleukin-1 receptor antagonist in patients with thyroid eye disease undergoing treatment with somatostatin analogues.

The aim of this prospective, randomized study was to investigate the serum levels of tumor necrosis factor-alpha (TNF-alpha), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble interleukin-1 receptor antagonist (sIL-1RA) in patients with thyroid eye disease (TED) before and 1 and 3 months after treatment with somatostatin analogues (SM-a). Thirty patients, all with signs and symptoms of TED, were studied. Twenty-two patients (13 females) had active eye disease with a clinical activity score (CAS) > or = 4 (patients with active disease [PA]) and 8 patients (5 females) had inactive TED with CAS < or = 3 (patients with inactive disease [PI]). All PA patients had a positive orbital octreoscan, whereas PI patients had a negative one. Fifteen patients from the PA group were selected randomly and received SM-a (PA-S subgroup), while the remaining 7 patients were used as control subgroup (PA-C), received neither therapy, nor placebo. From the 15 patients who received SM-a (PA-S), 6 received octreotide (OCT) and 9 lanreotide (LRT). TED was reevaluated using the CAS 1 and 3 months after the initiation of SM-a treatment. Ten healthy individuals (6 females) were used as controls (group C). We found an increase in the basal levels of TNF-alpha (14.2 +/- 7.1 pg/mL), sICAM-1 (809.1 +/- 167.0 ng/mL), and sIL-1RA (542.1 +/- 259.0 pg/mL) in PA patients as a total group compared with the PI (1.6 +/- 1.9, 676.8 +/- 73.4, 267.6 +/- 152.8, respectively) group and C (1.9 +/- 1.4, 598.0 +/- 126.2, 258.6 +/- 155.1, respectively). The basal levels of TNF-alpha (13.3 +/- 8.3 pg/mL) and sIL-1RA (533.7 +/- 308.9 pg/mL) in PA-S as well as in PA-C (16.0 +/- 2.9, 560.2 +/- 107.3, respectively) subgroups were also increased compared with PI patients and C (1.9 +/- 1.4 and 258.6 +/- 155.1, respectively). The same was true for sICAM-1 when baseline levels compared with C (817.1 +/- 187.3 and 791.9 +/- 123.5, respectively vs. 598.0 +/- 126.2 ng/mL). After SM-a, serum levels of sICAM-1 and sVCAM-1 were decreased significantly 1 (781.2 +/- 205.9, 1,193.5 +/- 511.8 ng/mL) and 3 months (786.8 +/- 199.6, 1,122.1 +/- 225.3 ng/mL) after the initiation of treatment. In conclusion, serum levels of TNF-a, sICAM-1, and sIL-1RA were elevated in patients with active TED compared to controls. Furthermore, sICAM-1 and sVICAM-1 levels declined during the treatment with SM-a in patients with active TED.

Cabergoline as a first-line treatment in newly diagnosed macroprolactinomas.

There are few long-term studies of cabergoline (CAB) administration in patients with macroprolactinomas. All of these studies included different type of patients, such as patients with idiopathic hyperprolactinemia, microprolactinomas and previously treated or untreated macroprolactinomas. We report a study of CAB treatment conducted exclusively in patients with newly diagnosed, untreated, macroprolactinomas. Twelve patients (6 M, 6 F) with macropolactinomas were investigated prospectively for 12 months to determine the effects of prolonged treatment with CAB on serum PRL levels, tumor size, visual fields and prevalence of side effects. Nine of these patients continued therapy and follow-up for 6 or more additional months of CAB administration. Our results demonstrated that CAB decreased the volume of the tumor in all patients investigated 3 months after the initiation of treatment. Specifically, mean tumor volume was 11,327 +/- 25,187 mm3 before the study and decreased to 4281 +/- 8465 mm3 and 1544 +/- 2118 mm3 in the second and last measurement, respectively. However, these changes were not statistically significant, most probably due to the very high SD. As far as the maximum diameter is concerned, mean values was 22.8 +/- 16.9 mm before the study and decreased to 16.6 +/- 10.9 mm and 13.4 +/- 7.5 mm in the 3 months and last examination, respectively. These changes were statistically significant (p = 0.005 and p = 0.007). The mean percentage decrease of the tumor volume and maximum tumor diameter was 42.4 +/- 14.0% and 24.7 +/- 4.8% respectively in the third month and 67.2 +/- 17.3% and 35.9 +/- 11.8% in the last estimation. These differences were statistically significant, (p < 0.01 and p < 0.001, respectively). The same was also true for PRL levels, the mean of which was 14,719 +/- 20,616 before treatment and became normal in the third month (153.3 +/- 63.4) and continued to be throughout the study. Four patients had visual field defects, which improved or even completely resolved during the treatment period. Finally, the CAB doses used were particularly small, i.e., 0.5-2 mg per week. All the patients recovered from their clinical problems and symptoms. This remarkable improvement was associated with an excellent tolerability of the long-term treatment due to the low incidence of side effects. In conclusion, the results of the present study demonstrated that CAB produced tumor shrinkage and normalized PRL levels in all the patients studied. Also, clinical symptoms disappeared and visual fields improved. These beneficial effects were associated with a very high compliance rate and minimal side effects. Thus, CAB can be considered a first-line pharmacological treatment of macroprolactinomas.

Growth hormone response to thyrotrophin releasing hormone in women with polycystic ovarian syndrome.

Recent clinical studies have suggested that women with polycystic ovarian syndrome (PCOS) may have disturbances of growth hormone (GH) kinetics and the GH/insulin-like growth factor (IGF)-I system. The knowledge that in various metabolic abnormalities there is a paradoxical sensitivity of pituitary somatotrophs to thyrotrophin releasing hormone (TRH) administration led to this investigation of the GH secretory response to TRH in women with PCOS. Twenty-four women with PCOS and 18 control women were studied. TRH was given as a single i.v. injection (time 0) and blood samples for GH measurements were obtained at -15, 0, 15, 30, 60 and 90 min. The GH responses were expressed as the area under the curve (AUC) or the differences from the basal value (Deltamax). The GH response to TRH (mean +/- SEM) was greater in women with PCOS (Deltamax 2.47 +/- 1. 73 versus 0.47 +/- 0.06 ng/ml, P < 0.05 and GH AUC 8.05 +/- 2.10 versus 2.58 +/- 0.18 ng/ml/90 min, P < 0.05). According to GH response to TRH, two PCOS subgroups were identified: (i) normal responders (n = 14) who showed Deltamax GH response (0.36 +/- 0.06 ng/ml)and GH AUC (1.93 +/- 0.64 ng/ml/90 min) similar to that in the controls and (ii) over-responders (n +/- 10) who showed a paradoxical increase in GH concentrations in response to TRH (Deltamax GH response 5.43 +/- 1.27 ng/ml and GH AUC 16.62 +/- 3.51 ng/ml per 90 min) that was significantly higher than in normally responding PCOS patients (P < 0.0001) or in controls (P < 0.0001). These data demonstrate an enhanced GH response to TRH administration in a subgroup of women with PCOS.

Disturbances of menstruation in hypothyroidism.

OBJECTIVES: Most thyroid textbooks describe hypothyroidism resulting in changes in the length of the menstrual cycle and in the amount of bleeding. Our experience at a busy thyroid clinic had given a picture which differs from that presented in the literature. The aim of this study was to determine the frequency and type of menstrual irregularities in premenopausal hypothyroid patients. DESIGN AND PATIENTS: We investigated the menstrual history, starting 6 months before the discovery of the disease, in 171 female premenopausal hypothyroid patients and 214 normal controls, with similar age and body mass index (BMI). MEASUREMENTS: TSH, TT4, TT3 and thyroid antibodies were measured by radioimmunoassay, while BMI was calculated from the ratio of body weight in kg to height in m2. RESULTS: Of the 171 hypothyroid patients, 131 (76.6%) had regular cycles and 40 (23.4%) irregular periods. Oligomenorrhoea and menorrhagia were the most common features in the latter group. No difference in BMI was found between the patients with or without menstrual abnormalities, or between patients and controls. TSH, TT4 and TT3 levels did not differ between patients with normal and abnormal menstruation. Forty-six (26.9%) out of 171 patients had subclinical hypothyroidism (group A), 42 (24.6%) mild hypothyroidism (group B) and 83 (48.5%) severe hypothyroidism (group C). Thirty-seven from group A (80.4%), 32 from group B (76.2%) and 62 from group C (74.7%) had normal periods. These differences were not statistically significant. Eighty-eight (88.9%) out of 99 patients in whom thyroid antibodies were measured had positive titres. Nineteen (21.6%) of the patients with positive thyroid antibodies had menstrual irregularities. This percentage did not differ from that found in the whole group of patients (23.4%). Out of 214 normal controls, 196 (91.6%) had normal menstruation and 19 (8.4%) irregular cycles. The latter group included mainly women with oligomenorrhoea. CONCLUSIONS: These data demonstrate that hypothyroidism in women is less frequently associated with menstrual disturbance than was previously described. Also, menstrual irregularities tend to be more frequent in sever hypothyroidism in comparison with mild cases, although this finding was not statistically significant. Oligomenorrhoea and menorrhagia are the most common menstrual disturbances.

Somatostatin receptor scintigraphy before and after treatment with somatostatin analogues in patients with thyroid eye disease.

Octreotide, a potent synthetic long-acting somatostatin analogue, has been shown to have a beneficial effect in thyroid eye disease (TED). Orbital scintigraphy using ocetreoscan-111 is a useful study, which can be used to visualize somatostatin-receptor-bearing cells and also to select patients who might benefit from octreotide therapy. One major limitation of this therapy is that the drug must be administered parenterally and used several times daily. Lanreotide, a new somatostatin analogue, has a much longer duration of action in comparison with octreotide, and has recently been found to have a beneficial effect in the treatment of thyroid eye disease. The aim of this study was to investigate the orbital Indium-111-pentetreotide activity after treatment with octreotide and lanreotide in patients with thyroid ophthalmopathy. Fourteen patients were studied. 12 with bilateral and 2 with unilateral thyroid eye disease, (10 females and 4 males) and all with moderately severe symptoms of ophthalmopathy. All were treated with antithyroid drugs and were euthyroid at the time of the study. All patients were investigated with orbital scintigraphy using octreoscan-111 and selected for study on the basis of a positive octreoscan. Five patients received 30 mg lanreotide intramuscularly once every 2 weeks over a period of 3 months, and 5 patients received octreotide 100 microg subcutaneously thrice daily for 3 months. Four patients served as controls and received no treatment. The octreoscan-111 scintigraphy was repeated in all patients 3 months after the first examination. The NOSPECS classification and the clinical activity score (CAS) of thyroid ophthalmopathy were also evaluated before and 3 months after the initiation of treatment. All patients who received treatment had a negative follow-up octreoscan while controls had a positive octreoscan. NOSPECS score and CAS were improved with treatment, but unchanged in control patients. The reduced uptake of octreoscan may be the result of blocking of somatostatin receptors, or reduction in receptor-expressing tissues, downregulation of somatostatin receptors in target tissues, or a combination of these factors.

Giant prolactinoma presented as unilateral exophthalmos in a prepubertal boy: response to cabergoline.

We report the case of a giant prolactinoma in a 7-year-old boy, which was complicated by unilateral exophthalmos. The initial levels of prolactin (PRL) were about 80,000 microU/ml. Treatment with cabergoline (CAB) resulted in rapid normalization of serum PRL (6 weeks after initiation of treatment) and reduction of tumor size. In particular, magnetic resonance imaging (MRI), which was done 2.5 months after the patient was put on CAB, revealed tremendous improvement with a decrease in the size of the tumor which now showed no extrasellar extension. Subsequent MRI studies demonstrated further improvement. Exophthalmos, anisocoria and visual fields improved. In summary, this patient represents the first report of the therapeutic use of CAB as the primary mode of treatment in a 7-year-old boy with infiltrative giant prolactinoma complicated by unilateral exophthalmos. It is a noninvasive treatment that can preserve and restore vision, as well as pituitary function, and is preferable to surgery or radiation in the treatment of prolactin-secreting macroadenoma in childhood and adolescence.

Leptin levels in women with polycystic ovary syndrome before and after treatment with diazoxide.

Leptin, a product of the ob gene, is a 16 kDa protein which is produced by adipocytes. In humans, obesity is a common finding in women with polycystic ovary syndrome (PCOS). The role, however, of leptin in PCOS is not clear. Some studies have reported increased levels of leptin in PCOS, while others report that they are normal. Also, insulin resistance is a common finding in PCOS. The aim of this study was to investigate further the role of insulin in leptin secretion in patients with PCOS by treating them for 10 days with diazoxide, an insulin-reducing compound. Eight women with PCOS, mean age 22.1 +/- 2.7 years, with mean body mass index (BMI) 28.4 +/- 5.7kg/m2, were studied. An oral glucose tolerance test (OGTT) was performed in all women and blood samples were taken before and at 30, 60, 90, 120 and 150 min after the administration of glucose. Glucose, insulin, leptin, free testosterone, delta4 androstenedione, sex hormone binding globulin (SHBG), LH, FSH, IGF-I and insulin-like growth factor-binding protein-3 (IGFBP-3) were measured in the sera taken before the administration of glucose, while glucose and insulin levels were measured in all samples which were collected after the administration of glucose. Diazoxide 300 mg daily was given to all women starting after the end of the OGTT for 10 days. A second OGTT was performed the day after the discontinuation of the diazoxide treatment. The same hormonal and biochemical parameters were also measured in all patients during the second OGTT. After the administration of diazoxide a reduction in sum insulin (262 +/- 147 vs 679 +/- 341 microU/ml. P<().01), leptin (18.5 +/- 10.6 vs 24.2 +/- 10.2 ng/ml, P<0.01), free testosterone (3.0 +/- 1.9 vs 5.1 +/- 1.9 pg/ml, P<0.01), delta4 androstenedione (3.8 +/- 1.9 vs 5.7 +/- 2.0 ng/ml, P<0.01) and IGF-I (219.5 +/- 69.2 vs 314.5 +/- 82.3 ng/ml, P<0.01) levels was observed. Serum SHBG (38.8 +/- 16.8 vs 27.8 +/- 12.1 nmol/l, P<0.01) and sum glucose levels (994.1 +/- 252.7 vs 711.1 +/- 166.1 mg/dl, P<0.05) were increased while IGFBP-3 (3.96 +/- 2.49 vs 3.75 +/- 2.24mg/l), FSH (6.2 +/- 1.8 vs 6.0 +/- 2.5 mU/l) and LH (18.9 +/- 6.7 vs 21.4 +/- 6.7 mU/l) concentrations did not change significantly. A significant positive correlation was found between serum leptin and BMI values before and after administration of diazoxide as well as between leptin, insulin and IGFBP-3 values. Also, sum insulin values correlated significantly with BMI. However, when multiple regression analysis was used this correlation was eliminated except that between leptin and BMI. This was most probably due to the small number of cases. The mechanism of the reduction of leptin levels is unclear. However, it is suggested that the concomitant decrease of insulin levels may play a role.

Effect of gonadotrophin-releasing hormone agonist treatment on growth hormone secretion in women with polycystic ovarian syndrome.

The suppression of the pituitary-gonadal axis by the administration of gonadotrophin-releasing hormone agonists (GnRH-a) is used occasionally as an adjunct therapy with gonadotrophins for ovulation induction in women with polycystic ovarian syndrome (PCOS). A number of recent clinical studies have suggested that women with polycystic ovaries (PCO) may have disturbances of normal growth hormone (GH) kinetics and alterations in the GH/insulin-like growth factor (IGF)-I system. The purpose of this study was to determine the effect of GnRH-a administration on GH-releasing hormone (GHRH)-stimulated GH release in women with PCOS. Eight women with PCO and six control women were studied before and after 2 months of treatment with the long acting GnRH-a triptoreline (3.75 mg monthly injections). GHRH was given as a single i.v. injection and blood samples for GH measurements were obtained at -15, 0, 30, 60, 90 and 120 min. The GH responses were expressed as the area under the curve (AUC) or the differences from the basal value (delta(max)). The GH response to GHRH (mean +/- SEM) was lower in women with PCO (AUC 114.9 +/- 43.1 versus 206.2 +/- 28.7 ng/ml/120 min, P < 0.05 and delta(max) 31.6 +/- 8.2 versus 49.4 +/- 5.8 ng/ml, P < 0.05). After treatment with the GnRH-a, the GH response to GHRH was significantly smaller than before treatment in both groups (PCO AUC 34.6 +/- 9.0 ng/ml/120 min and delta(max) 12.4 +/- 3.1 ng/ml; controls AUC 148.8 +/- 28.4 ng/ml/120 min and delta(max) 31.2 +/- 6.1 ng/ml), but the PCO group had a significantly smaller response. These data demonstrate that women with PCO have a reduced GH response to GHRH compared with normal controls and that GnRH-a administration causes a further GH reduction in both groups. Women with PCO have a greater suppression of GH response to GHRH during treatment with GnRH-a. This suggests that a different level of sensitivity in the somatotrophic axis exists in PCOS.

Lanreotide in the treatment of patients with thyroid eye disease.

Octreotide, a potent synthetic somatostatin (SM) analogue, was recently evaluated and found to have a beneficial effect in thyroid eye disease (TED), mostly in those patients with a positive Octreoscan-111. Lanreotide (LRT; Somatuline-Ipsen), a new SM long-acting analogue, is more active than natural SM and shows a much longer duration of action. The aim of the present preliminary study was to evaluate the therapeutic effect of LRT in the treatment of TED. Five patients, three males and two females, mean age 50.6 +/- 7.6 S.D. (45-64) years, all with severe symptoms of TED were studied. A similar number of patients, matched for age, sex and severity of ophthalmopathy served as controls. All the patients and controls were investigated with orbital scintigraphy using 111 In DTPA-D-Phe1-octreotide (Octreoscan-111) and selected on the basis of positive octreoscan. The NOSPECS system, as adapted by Donaldson et al. (Journal of Clinical Endocrinology and Metabolism 1973 37 276-285) and a disease activity score, as proposed recently by an International Workshop, have been followed in this study in order to evaluate the response to treatment. The five patients who comprised the treatment group received 0.04 g LRT i.m. once every 2 weeks over a period of 3 months, after which the Octreoscan-111 was repeated. The control patients were given an injection of water i.m., also once every 2 weeks for 3 months, after which they were evaluated clinically. No Octreoscan-111 was performed in the controls. All patients and controls were evaluated by the same physician, who was unaware of the type of treatment used. A decrease in the NOSPECS score and the clinical activity score was regarded as a positive response, while no change or an increase in the NOSPECS score along with no clinical improvement was regarded as a negative response. After 3 months of treatment with LRT, four patients showed a statistically significant improvement in ophthalmopathy in both eyes and one in one eye. Three of the control patients with TED did not show any change, one showed a minor improvement in one eye and no change in the other and one showed deterioration in both eyes. An interesting finding was that orbital Octreoscan-111 activity was absent in all the patients after LRT treatment. In conclusion, these preliminary results show that LRT has a beneficial effect on patients with TED, and that since it has to be given only once every 2 weeks, it is probably superior to any other form of SM treatment. However, as the number of patients was small, further studies are needed to confirm our results.

Somatostatin receptor scintigraphy and octreotide treatment in patients with thyroid eye disease.

OBJECTIVE: Octreotide, a potent long-acting synthetic somatostatin analogue, has been reported to have a beneficial effect in thyroid eye disease (TED), but the precise mechanism of action remains unexplained. 111In-DTPA-D-Phe1-octreotide (Octreoscan-111) has been used to localize a number of endocrine tumours and visualize somatostatin receptors in the retrobulbar tissue of patients with TED. Furthermore, this technique can predict the inhibitory effect of octreotide on hormone secretion by endocrine tumours, as there is a close relation between the clinically observed inhibition and visualization of the tumour using Octreoscan-111. The aims of the present study were to confirm the beneficial effect of octreotide in patients with TED, to investigate the presence of somatostatin receptors in the orbital area and also, if possible, to ascertain whether this technique could select those patients with TED who might benefit from treatment with octreotide. DESIGN: A prospective study. SETTING: An endocrine clinic of a national hospital. PATIENTS: Twenty treated thyrotoxic patients with TED, 5 treated thyrotoxic patients without TED and 5 normal individuals were studied. In 12 patients with TED, 5 without TED and 5 normal individuals, Octreoscan-111 scintigraphy of the orbits was performed. The remaining 8 patients with ophthalmopathy served as controls. In patients with TED who were investigated with Octreoscan-111, 300 micrograms octreotide daily was given for 12 weeks. RESULTS: Six patients in both eyes and one patient in one eye showed an improvement in ocular manifestations as assessed by clinical criteria and changes in the NOSPECS score, while the rest showed no improvement. The patients who showed an improvement had a high number of somatostatin receptors and positive orbital scans, while with one exception the patients who did not respond had a low number of receptors and negative orbital scans (P < 0.02). None of the 5 patients without TED nor the normal individuals had a positive orbital scan. Seven out of 8 control patients with TED showed no change in the disease during the trial, while 1 deteriorated. CONCLUSIONS: We conclude that octreotide has a beneficial effect in thyroid eye disease and that Octreoscan-111 could predict those patients with thyroid eye disease who might benefit from this treatment.

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.