Predictors of morbidity and mortality in acromegaly: an Italian survey.

OBJECTIVE: To describe demographic and hormonal characteristics, comorbidities (diabetes mellitus and hypertension), therapeutic procedures and their effectiveness, as well as predictors of morbidity and mortality in a nationwide survey of Italian acromegalic patients. DESIGN: Retrospective multicenter epidemiological study endorsed by the Italian Society of Endocrinology and performed in 24 tertiary referral Italian centers. The mean follow-up time was 120 months. RESULTS: A total of 1512 patients, 41% male, mean age: 45±13 years, mean GH: 31±37 µg/l, IGF1: 744±318 ng/ml, were included. Diabetes mellitus was reported in 16% of cases and hypertension in 33%. Older age and higher IGF1 levels at diagnosis were significant predictors of diabetes and hypertension. At the last follow-up, 65% of patients had a controlled disease, of whom 55% were off medical therapy. Observed deaths were 61, with a standardized mortality ratio of 1.13 95% (confidence interval (CI): 0.87-1.46). Mortality was significantly higher in the patients with persistently active disease (1.93; 95% CI: 1.34-2.70). Main causes of death were vascular diseases and malignancies with similar prevalence. A multivariate analysis showed that older age, higher GH at the last follow-up, higher IGF1 levels at diagnosis, malignancy, and radiotherapy were independent predictors of mortality. CONCLUSIONS: Pretreatment IGF1 levels are important predictors of morbidity and mortality in acromegaly. The full hormonal control of the disease, nowadays reached in the majority of patients with modern management, reduces greatly the disease-related mortality.

Efficacy of the new long-acting formulation of lanreotide (lanreotide Autogel) in somatostatin analogue-naive patients with acromegaly.

OBJECTIVE: To evaluate efficacy and safety of lanreotide autogel (ATG) 120 mg injections every 4-8 weeks in somatostatin analogue-naïve patients with acromegaly. DESIGN: Open, non-comparative, phase III, multicenter clinical study. METHODS: Fifty-one patients (28 women, aged 19-78 yr): 39 newly diagnosed (de novo) and 12 who had previously undergone unsuccessful surgery (post-op, 11 macro and 1 micro) were studied. ATG 120 mg was initially given every 8 weeks for 24 weeks and subsequently changed according to GH levels: if 5 microg/l every 4 weeks (group C, 19 patients). Treatment duration was 48-52 weeks. The primary objective was to control GH and IGF-I levels (GH

Clinical presentation and outcome of pituitary adenomas in teenagers.

OBJECTIVE: Pituitary adenomas rarely occur in childhood and adolescence, but their mass effect and endocrine abnormalities can compromise both quality and length of life. In this study we evaluated the symptoms at onset and the long-term consequences induced in teenagers by functioning or nonfunctioning pituitary adenomas. DESIGN AND PATIENTS: Clinical, biochemical and neuroradiological data of 44 young patients (12 males and 32 females, aged 16.3 +/- 1.9 years at diagnosis) with pituitary adenomas were evaluated retrospectively at baseline and after therapy. Patients underwent surgery, radiotherapy and/or medical treatment depending on clinical history and endocrine secretion of the tumour. Follow-up ranged from 8 to 252 months (median 55 months). MEASUREMENTS: Baseline and dynamic pituitary function were evaluated in all cases at diagnosis and after treatments. Magnetic resonance imaging (MRI) or computed tomography (CT) scan were performed before therapy and during follow-up. Hormone levels were measured using commercial radioimmunologic or immunoradiometric methods. RESULTS: Pituitary macroadenomas (group 1) or microadenomas (group 2) were found in 61% and 39% of cases, respectively. Overall, 68% were PRL-secreting, 7% GH-secreting, 5% ACTH-secreting and 20% nonfunctioning. The most frequent symptoms at onset were oligoamenorrhoea (62%) and galactorrhoea (59%) in the girls, and headache (58%) in the boys. Pubertal development was delayed in 12/27 (44%) cases with macroadenoma. Growth failure was observed in 4/44 (9%) patients (3 in group 1 and 1 in group 2). At diagnosis, hypopituitarism was detected in 10/27 (37%) patients with macroadenoma. Surgery alone cured 4/18 (22%) and 4/9 (44%) patients in group 1 and group 2, respectively. Adjuvant therapies (second surgery and/or radiotherapy and/or medical treatment) cured the disease in 2/13 (15%) patients with macroadenoma and allowed a persistent normalization in other 4/13 (31%) and 2/4 (50%) cases in group 1 and group 2, respectively. Medical treatment alone cured 2/9 (22%) patients with PRL-secreting macroadenoma and normalized PRL levels in another six (66%) with macroprolactinoma and in 2/7 (28%) patients with microprolactinoma. CONCLUSION: Delay of growth was rarely observed in teenagers with pituitary adenomas. At the onset of the disease, many girls complained of oligoamenorrhoea and galactorrhoea, while headache and delay of pubertal development were the symptoms more frequently referred by boys. Surgery alone was effective in a minority of patients and adjuvant therapies were helpful to obtain the remission of the disease in many cases. In patients with PRL-secreting pituitary adenoma, medical treatment, both as first choice or as adjuvant therapy, normalizes serum PRL levels in 14/27 (52%) cases.

Longitudinal study on goiter prevalence and goitrogen factors in northeastern Sicily.

A longitudinal study was carried out in an area of endemic goiter of north-eastern Sicily. Three different surveys (in 1977, 1983 and 1994) evaluated the epidemiological prevalence of goiter in schoolchildren of the endemic area (towns of Bronte, Troina and Maniaci) in comparison to an iodine sufficient control area (Catania). Biochemical studies were also performed on urinary iodine and thiocyanate (SCN) excretion and 131I thyroid uptake. In the town of Troina an experimental program of active iodine prophylaxis was carried out from 1979 to 1987 by iodinating the municipal water supply. The aim of this study was to evaluate the effect of an active iodine prophylaxis program in comparison to the "silent iodoprophylaxis" due to improved economic conditions and widespread introduction of industrially produced food. In the 1977-94 period a significant decrease of goiter prevalence in schoolchildren was observed in all areas where no active iodoprophylaxis had been introduced. An abnormal prevalence of goiter, however, was still present in Bronte (12.1%) and Maniaci (25.9%) schoolchildren in respect to Catania (0.7%). In Troina, goiter prevalence decreased from 52.2 to 6.1% after only five years of active iodine prophylaxis (1983). It increased to 8.4% seven years after the program was discontinued (1994). In all areas studied average urinary iodine excretion increased by 70-100 micrograms/day except in the more rural area at Maniaci. During the same period urinary SCN values decreased by 30-40% and were lower in Troina (non volcanic soil) than in other towns studied. The balance between iodine and SCN intake appears a relevant factor in the etiology of endemic goiter in these areas and the iodine/SCN ratio inversely correlated with goiter prevalence. The persistence of endemic goiter in spite of the important changes in life style and socio-economic conditions if compared to the dramatic amelioration obtained by an active iodine prophylaxis program, confirms the inadequacy of the silent iodine prophylaxis, and further supports the need of an immediate introduction of active iodine prophylaxis in the areas of endemic goiter in Sicily.

Clinical features and hormonal characteristics in a case of ovarian arrhenoblastoma.

We report a case of a 34-year-old woman affected with ovarian arrhenoblastoma characterized by very high testosterone (T) levels (34.0-60.0 ng/ml; n.v.0.2-0.9) and suppressed gonadotropin levels. The physical examination revealed: severe hirsutism, acne, amenorrhea and other virilization signs. Basal hormonal evaluation also showed a markedly elevated 17-hydroxyprogesterone (17-OHP) and a mild delta 4 Androstenedione (A) and dehydroepiandrosterone sulfate (DHEAs) increase. ACTH test induced only slight changes in androgen secretion. By contrast, dexamethasone test greatly decreased A and DHEAs whereas T levels were only partially suppressed. Moreover, hCG test was clearly stimulatory for T and A. Suppressed gonadotropin levels did not respond to LHRH stimulation. The removal of the neoplasia was followed by normalization of T levels and increase of serum gonadotropins with subsequent restoration of a normal responsiveness to LHRH and resumption of an ovulatory menstrual cycle. This observation suggests that the high T levels played a primary role in the pathogenesis of the gonadotropin suppression and anovulation. Recovery of acne was complete whereas hirsutism score was reduced but still elevated after one year. This may be due to postoperative A and DHEAs levels slightly above the normal range, indicating the presence of adrenal hyperandrogenism.

Pubarche induction with testosterone treatment in women with panhypopituitarism.

OBJECTIVE: To evaluate the efficacy and safety of T therapy in the induction of pubic hair growth in women with congenital panhypopituitarism. DESIGN: Prospective clinical study. SETTING: Patients followed at the University Endocrinology Clinic. PATIENTS: Four women with congenital panhypopituitarism, showing no pubic hair development, currently treated with substitutive therapy with L-thyroxine, cortisone acetate, and estrogen-progestin combination. INTERVENTIONS: A long-acting T preparation (25 to 50 mg) was given IM each month; serum T levels were determined before and after 12 and 24 months of therapy. MAIN OUTCOME MEASURE: Evaluation of pubarche stages (according to Tanner classification of stages). RESULTS: Patients developed pubarche (Tanner stage 3 to 5) after 3 to 18 months of T therapy. Testosterone levels were within the normal range during treatment. No hirsutism or other side effects were recorded. CONCLUSION: A cautious T treatment represents an effective and safe approach to the problem of pubarche induction in women with congenital panhypopituitarism.

Hypergonadotropinemia not associated to ovarian failure and induced by factors interfering in radioimmunoassay.

Unexpectedly high LH and FSH serum levels, measured by conventional RIA methods employing a rabbit antibody, were observed in eight women 18 to 34 years of age who came to our observation for acne and/or hirsutism and with no sign of premature ovarian failure. Reinvestigation of patient histories revealed that all of them had previously received multiple injections of a multimicrobial vaccine containing rabbit proteins. Luteinizing hormone and FSH were remeasured by IRMA and ELISA. These techniques revealed that serum levels of both gonadotropins were within the normal range in all subjects. We believe that falsely elevated gonadotropin levels were induced by the presence of heterophilic antibodies against rabbit serum interfering in the conventional RIA.

Ovulation monitored by serum 17 beta-estradiol and ultrasound: differential ovarian response to human gonadotropins in various anovulatory states.

Ovulation induction with human gonadotropins (hMG or pFSH and hCG) was simultaneously monitored with daily serum 17 beta-estradiol measurements and ultrasound in 38 infertile women. They were subgrouped as follows: A, hypogonadotropic hypogonadism (n. 7); B, polycystic ovary syndrome (n. 13); C, non-PCO chronic anovulation (n. 6); D, unexplained infertility (n. 12). The dose of hMG and the duration of therapy were assessed individually depending on the results of the monitoring when serum estradiol concentration was 500-1500 pg/ml and/or ultrasound showed of a follicle of at least 18 mm, hMG was stopped and hCG was administered 36 hours later. Ovulation was obtained in 61 cases and pregnancy occurred in 12 women out of 64 monitored cycles. The highest pregnancy rate was observed in hypogonadotropic hypogonadism; this group also required the greatest total dose of hMG to obtain ovulation. We confirm that women with PCOS are at increased risk with this therapy, since 5 subjects in our series showed signs of ovarian hyperstimulation in spite of the lowest total dose of FSH administered to this group. We conclude that anovulatory states of various origin are associated with different ovarian sensitivity.

Influence of abstinence length on ejaculate characteristics.

In order to study the influence of sexual abstinence on sperm concentration and semen volume, we have evaluated 195 semen samples of healthy individuals, grouped as follows according to abstinence length: A) 2-4 days; B) 5-7 days; C) more than 7 days. Differences between semen samples collected at home or at the laboratory were also studied. Semen volume was smaller in group A than in group B and C (p less than 0.01), while no significant difference was found in sperm concentration among the three groups. The place of collection did not affect semen characteristics. These results suggest that while a shorter abstinence is associated with a smaller semen volume the length of abstinence does not affect sperm concentration.