OBJECTIVE: To evaluate the effect of a 6-month treatment with slow-release lanreotide (LAN) on cardiovascular risk and atherosclerosis in 24 normotensive patients with active acromegaly (GH=67.4 +/- 12.6 mU/l, IGF--I=866.0 +/- 55.8 microg/l) and 24 healthy subjects sex-, age- and body mass index-matched with the patients (as controls). DESIGN: Open, prospective, multicenter. METHODS: The following were measured before and after 6 months of LAN treatment (dose 60-90 mg/month): fasting GH, IGF-I, LDL, HDL and total cholesterol, triglyceride, glucose, glycosylated hemoglobin, insulin and fibrinogen levels, intima-media thickness (IMT) and blood systolic and diastolic peak velocity (SPV and DPV respectively) in both common carotids. RESULTS: At study entry, insulin, total and LDL cholesterol, triglyceride and fibrinogen levels were higher while HDL cholesterol levels were lower in patients than in controls. At the right (0.88 +/- 0.04 vs 0.77 +/- 0.03 mm, P=0.05) and left (0.93 +/- 0.03 vs 0.78 +/- 0.02 mm, P=0.01) common carotid IMT was significantly higher in patients than in controls; 12 patients and two controls showed an IMT of > or = 1 mm (chi(2)=8.2, P=0.004). After 6 months of LAN treatment, disease control was achieved in 15 patients (62.5%). Insulin, triglyceride and fibrinogen levels were significantly decreased, and a trend toward a decrease of IMT in the right (from 0.90 +/- 0.05 to 0.78 +/- 0.04 mm, P=0.06) and left (from 0.95 +/- 0.04 to 0.84 +/- 0.04 mm, P=0.06) common carotid arteries was observed only in patients with disease control, while SPV and DPV did not change. CONCLUSIONS: LAN treatment for 6 months significantly lowered GH, IGF-I, insulin and fibrinogen levels and reduced IMT of both common carotid arteries in normotensive patients with acromegaly.
M. Minozzi, M. Faggiano, G. P. Jori and G. Lombardi
Laparoscopy, allowing visualization of the pelvic organs, represents a valuable method for the study of several syndromes connected with the pathology of internal genitalia. The use of this technique in the gynecologic field has been completely reviewed by Palmer (1960, 1963), Albano & Cittadini (1962), Thoyer-Rozat (1962, 1965), Tenti et al. (1963), Steptoe (1967) and Cohen (1970).
We mean to consider the use of laparoscopy only in some endocrine and genetic syndromes connected with gonadal pathology. The use of laparoscopy in amenorrhea and in the infertile female is both of gynecologic and endocrinologic interest, and its diagnostic value has been recently reviewed by Cohen (1970). However, for a more selected genetic and endocrinologic interest, we will consider here only the amenorrhea due to uterus agenesis, inasmuch as it includes a particular form of male pseudohermaphroditism: "testicular feminization syndrome" – with female external genitalia and phenotype. Moreover, beside cytogenetic data fundamental
G. Lombardi, Ch. Oliver, G. Lupoli and M. Minozzi
In 15 patients with congenital adrenal hyperplasia, the corticotrophic and melanotrophic functions were evaluated by plasma ACTH and β-MSH radioimmunoassay. Evaluation of the corticotrophic and melanotrophic functions was also performed in 3 subjects after provocative tests (insulin-induced hypoglycaemia, metyrapone) and in 5 subjects after infusion of synthetic MIF (MSH-release inhibiting factor).
The results indicate a significant increase in plasma ACTH and β-MSH in CAH. In addition, we found that although in most cases there was a significant positive correlation between the plasma ACTH and β-MSH levels, in some only the plasma ACTH values were high and β-MSH values normal. No other anomalies of the corticotrophic and melanotrophic functions occurred in CAH as shown by the results of the provocative tests. Lastly, it must be emphasized that no modifications of plasma β-MSH after synthetic MIF infusion were found in subject with normal or high plasma β-MSH. These findings induce us to consider it unlikely that synthetic MIF is active in man.
G Palmieri, G Lotrecchiano, G Ricci, R Spiezia, G Lombardi, AR Bianco and G Torino
Palmieri G, Lotrecchiano G, Ricci G, Spiezia R, Lombardi G, Bianco AR, Torino G. Gonadal function after multimodality treatment in men with testicular germ cell cancer. Eur J Endocrinol 1996;134:431–6. ISSN 0804–4643
We evaluated gonadal function in 63 patients with testicular cancer both within 1 month of unilateral orchiectomy before further treatment (pretreatment) and 3 years after treatment discontinuation (post-treatment). Sixteen patients underwent orchiectomy alone (group 1), nine patients underwent infradiaphragmatic radiotherapy (group 2) and 28 patients received four cycles (group 3) and 10 patients received six cycles (group 4) of cisplatin-based chemotherapy (cisplatin, vinblastine and bleomycin—PVB, or cisplatin, etoposide and bleomycin—PEB), Pretreatment semen analyses showed reduced sperm cell density, motility and impaired morphology of spermatozoa in all four groups (p>0.05). At the same time elevated estradiol and decreased serum follicle-stimulating hormone (FSH) levels in 28.5% of subjects were correlated with high serum beta human chorionic gonadotropin concentrations. Semen analyses revealed the lowest values for all parameters after infradiaphragmatic radiotherapy. Sperm cell count, motility and morphology were significantly better in patients treated with orchiectomy alone or with a conventional dose of chemotherapy than in the groups that received radiotherapy or high doses of chemotherapy (p < 0.05). We also observed a correlation between serum FSH values and sperm cell density for both pretreatment and post-treatment in every group of patients (p<0.05). Persistent subclinical Leydig cell dysfunction in groups treated with radiotherapy or high doses of chemotherapy was expressed by increased basal luteinizing hormone levels (78% of patients in group 2 vs 60% of patients in group 4) (p < 0.05) and by normal testosterone serum values (89% of patients in group 2 vs 80% of patients in group 4). Spermatogenesis and Leydig cell function are, therefore, persistently impaired in the majority of testicular cancer patients treated with radiotherapy or with more intensive chemotherapy.
G Palmieri, Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Facoltà di Medicina e Chirurgia, Università "Federico II", Via S Pansini 5, 80131 Napoli, Italy
G. Lombardi, N. Panza, S. Cei, F. Cosimato and M. Minozzi
Plasma TRH was determined by radioimmunoassay in normal and abnormal thyroid state. In euthyroid adult subjects, the plasma TRH level were 31.9 ± 11 pg/ml (mean ± sd). No significant differences were observed with regard to sex, pregnancy or age, except for the acute increase in newborn infants. The plasma TRH levels evaluated in abnormal thyroid states were found significantly (P < 0.001) increased in hyperthyroidism (49.1 ± 14 pg/ml) and decreased in hypothyroidism (22.1 ± 6 pg/ml). Nor were any significant differences observed in simple goitre, pituitary adenoma and empty sella. Lastly, plasma TRH and TSH levels were also evaluated after acute administration of L-dopa, 2-Br-α-ergocriptine and chlorpromazine in normal and hypothyroid subjects. Contemporaneous modifications of plasma TRH and TSH levels (decreased after L-dopa and 2-Br-α-ergocriptine, increased after chlorpromazine) were observed in hypothyroidism.
The results indicate that plasma TSH modifications at birth as well as under catecholaminergic influences are at least partially mediated by variations of TRH secretion. Moreover, the inverse plasma TRH and TSH modifications in abnormal thyroid states agree with different feedback effects at the hypothalamic (positive) and pituitary (negative) level. It is possible that the significance of the positive feedback at the hypothalamic levels can be interpreted when taking into account the extra-pituitary effects of TRH.
EA Palmieri, S Fazio, V Palmieri, G Lombardi and B Biondi
OBJECTIVES: To ascertain whether myocardial contractility and total arterial stiffness are significantly altered in human thyrotoxicosis, and to what extent they are affected by acute beta(1)-adrenergic blockade. METHODS: Doppler-echocardiography was used to assess left ventricular (LV) structure and function, hemodynamics and total arterial stiffness in untreated overt hyperthyroid patients before and 2 h after 5 mg bisoprolol given orally compared with age- and sex-matched healthy euthyroid controls. RESULTS: Compared with controls, untreated patients (n=20) had a higher heart rate (HR) and LV stroke index (SI), which were associated with higher pulse pressure (PP), larger LV end-diastolic volume index (EDVI, an index of preload,+11%, P<0.05), marginally increased stress-corrected LV midwall fractional shortening (MWS, an index of myocardial contractility,+5%; P=0.066), and shorter isovolumic relaxation time (IVRT). These changes resulted in a higher cardiac index (CI) and a lower systemic vascular resistance (SVR), which were associated with fairly normal mean blood pressure (BP) but higher PP/stroke volume (an index of total arterial stiffness,+29%; P<0.01). After bisoprolol, compared with controls, the randomly treated patients (n=10) had comparable HR but additionally increased SI; PP remained enhanced, EDVI was further enlarged (+26%, P<0.001), stress-corrected MWS was substantially unchanged, and IVRT remained shorter. Overall, these effects attenuated the high-output state, which was associated with normalization of PP/stroke volume without changes of mean BP. CONCLUSIONS: In human overt hyperthyroidism, myocardial contractility does not play a major role in increasing LV performance, which is instead predominantly sustained by increased preload with enhanced LV diastolic function. In addition, human thyrotoxicosis is associated with increased total arterial stiffness despite fairly normal mean BP. In this scenario, acute beta(1)-adrenergic blockade blunts the cardiovascular hyperkinesia predominantly by slowing HR - a process that is associated with normalization of total arterial stiffness.
E. Calabresi, G. Fiorelli, G. Forti, G. Lombardi, M. Pazzagli, E. Dell'Acqua and M. Serio
Androstenedione (Δ), oestradiol-17β (Oe2), 5α-dihydrotestosterone (DHT), progesterone (P) and testosterone (T) concentrations have been measured by radioimmunoassay in ovarian and peripheral venous blood from 15 women in the luteal phase of the cycle.
The ovarian blood samples were obtained during surgical intervention from 15 ovaries containing the corpus luteum and from 5 contralateral ovaries.
The mean concentration of DHT in ovarian venous blood was not higher than that found in the cubital vein.
However in some cases with high concentrations of testosterone in ovarian venous blood, a small but significant DHT gradient was found.
E. Martino, S. Grasso, G. Bambini, G. Pardo, P. Vitti, F. Aghini-Lombardi and A. Pinchera
Abstract. The ontogeny of thyrotropin-releasing hormone (TRH) in pancreata of human foetuses from 15–36 weeks of gestation and of infants has been studied. TRH was detectable in the pancreas of a 15 week old foetus; a progressive increase of pancreatic TRH content was observed until the 34th week of gestation, whereas a progressive decrease was found in the late period of pregnancy and in 1 year old infants. In contrast, the pancreatic insulin content showed a progressive increase during the entire pregnancy and in the first year after birth. These data indicate that TRH and insulin have different ontogenetic patterns in the human pancreas.
A Colao, G Vitale, R Pivonello, A Ciccarelli, C Di Somma and G Lombardi
Several experimental and clinical studies have indicate that the heart is an end-organ of GH action. Patients with either childhood- or adulthood-onset GH deficiency (GHD) have abnormalities of cardiac structure and function, such as reduced cardiac mass, impaired diastolic filling and reduced left ventricular response at peak exercise. These cardiovascular abnormalities can be reversed, at least partially, after GH replacement therapy. On the other hand, the chronic overproduction of GH and IGF-I in acromegaly leads to the development of a specific cardiomyopathy. Concentric cardiac hypertrophy occurs in more than two-thirds of patients at diagnosis and is commonly associated with diastolic dysfunction. In later stages, impaired systolic function ending in heart failure can occur if GH/IGF-I excess is not controlled. Additionally, acromegalic cardiomyopathy is complicated by abnormalities of cardiac rhythm and cardiac valves. Successful control of acromegaly is accompanied by a decrease of the left ventricular mass and improvement of cardiac function. These beneficial effects appear earlier in young patients with short disease duration than in elderly patients. In conclusion, GH and IGF-I play a main role in the regulation of cardiac development and performance.