Final height and endocrine function in thalassaemia intermedia.

We present data of a detailed study of endocrine function in 50 patients (21 males, 29 females) with thalassaemia intermedia, 15-46 years old (mean age 28.7 yr), with raised serum ferritin levels (mean 1540 micrograms/l). Mean haemoglobin concentration was 8.1 g/dl. Half of them had had more than 50 transfusions in their life and had received irregular intramuscular or subcutaneous chelation therapy. Delayed puberty was one of the most frequent (36%) clinical endocrine abnormalities found in our patients. Primary amenorrhea was observed in two patients and secondary amenorrhea in four patients. Two males, aged 19 and 36 years, had hypogonadism. A poor response to GnRH, found in three females and in both males tested, suggested that pituitary dysfunction was wholly or partially responsible for hypogonadism. Gonadal function was normal in all patients studied. Glucose intolerance and primary hypothyroidism were less frequent (24 and 5.7%, respectively) and milder than in thalassaemia major patients. Two patients had low T3 and T4 and normal basal and stimulated response of TSH to TRH. This condition has been found in euthyroid sick syndrome and it is likely that it represents an adaptive response by the body to minimize catabolism when undergoing major stress. As a consequence, we believe that periodic endocrine evaluation should be carried out in subjects with beta-thalassaemia intermedia, particularly in those over 14 years old, in order to detect and to treat endocrine dysfunction.

Hypoparathyroidism in chronic alcohol intoxication: a preliminary report.

It is well known that osteoporosis is more common in chronic alcoholists than in age-matched controls. Possible aetiological factors could be: malabsorption of calcium and vitamin D, liver disease, abnormal parathyroid function. With this study, the authors investigated parathyroid hormone (PTH) behaviour in thirteen selected patients with alcohol abuse, free from any clinical or humoral sign of hepatopathy, and in ten healthy subjects as a control group. In alcohol abusers a significant reduction of plasmatic PTH, compared to normal calcium levels were found. A possible direct interaction effect between ethyl alcohol and PTH may be suggested, even if further studies are required.

Loss of nocturnal increase in plasma concentration of atrial natriuretic peptide in hypertensive chronic renal failure.

Diurnal change of plasma atrial natriuretic peptide (ANP) concentration was investigated in 12 patients with hypertension due to chronic renal failure (CRF) and in 12 patients with essential hypertension (EH) of comparable degree. Blood pressure (BP) monitoring was performed at 15-min intervals, while peripheral blood samples were obtained at 4-hour intervals starting from 8.00 h. The mean 24-hour plasma levels (+/- SEM) of ANP were 24.3 +/- 1.8 pmol/l in EH and 23.4 +/- 1.2 pmol/l in CRF. In EH, plasma ANP concentration was highest at 4.00 h (33.5 +/- 0.8 pmol/l) and lowest at 16.00 h (15.5 +/- 0.6 pmol/l). In CRF, no significant circadian change was present (22.2 +/- 3.1 and 20.4 +/- 3.6 pmol/l, respectively), and the nocturnal fall in BP was lost. Our data demonstrate that in CRF the loss and possible reversal of the nocturnal decline in BP is associated with the disappearance of any significant circadian variation in the circulating concentrations of ANP. These findings suggest a role for ANP in the alteration of BP variability of CRF, possibly mediated by autonomic dysfunction, and are further evidence for the existence of a relation between the circadian rhythms of ANP and BP.

[Normal ranges of bone mineral content of the distal radius determined with single photon absorptiometry. Study of 1521 cases]. / Intervalli di normalità del contenuto minerale osseo del radio distale determinato con l'assorbiometria a fotone singolo. Studio di 1521 casi.

The normal ranges and mathematical equations of bone mineral content (BMC), normalized to radial width (BMC/W) vs. age at the distal radius, were obtained by single photon absorptiometry (SPA), and compared in two different normal populations, one of postmenopausal females and the other of control males. The female population included 1359 postmenopausal women, aged 35 to 75 years; normal control males were 162, of the same age. The results obtained in the two groups of patients show a statistically significant (p less than 0.001) correlation between age and BMC/W, expressed in a polinomial third-degree regression. The slope of the regression curves is quite different between males and females: the mean decrement, evaluated from regression polinomial fits, results 0.5% per year for normal females, and 0.3% per year for normal males. The maximum decrement (1% per year) is observed at the mean age of 51 years, which is the average age of peri-menopausal women in our province (Ferrara). The authors believe SPA to be a simple and reliable technique in measuring peripheral bone loss rate. SPA may be useful in the diagnosis and treatment of postmenopausal women, but is not recommended in the short-term follow-up of osteoporosis.

Plasma levels of atrial natriuretic peptide are increased in normotensive postmenopausal women as a function of age.

The aim of this study was to assess the changes in atrial natriuretic peptide (ANP) levels before and after menopause and to test whether they depend on age or are an integral part of the hormonal changes in menopause. We measured plasma ANP, plasma renin activity (PRA), plasma aldosterone, serum estradiol-17 beta and progesterone concentrations in 103 normotensive women, either in premenopause (n = 35; mean age: 24 years), in physiological menopause (n = 34; mean age: 43 years) or surgically induced menopause (n = 34; mean age: 55 years). The last two groups were matched for duration of menopause and were comparable in their estrogen and progesterone status. PRA and plasma aldosterone concentrations decreased in postmenopausal women, whereas systolic blood pressure and ANP increased. These results were not confirmed after adjustment for age by covariance analysis. In all of the groups, plasma ANP concentrations were not significantly correlated with systolic or diastolic blood pressure, nor with plasma aldosterone, estrogen and progesterone concentrations. These correlations were not improved by correction for age. Plasma ANP concentrations were consistently correlated with age. These data suggest that the increase in plasma ANP levels found in postmenopausal women is related with age and that ANP does not play a direct role in the physiological hormonal changes of menopause.

Serum thymidine kinase in diagnosis and follow-up of the small cell carcinoma of the lung.

Serum thymidine-kinase (sTK) was assayed in 48 males affected by small cell carcinoma of the lung (SCCL) at the time of diagnosis. On the same drawing carcinoembryonic antigen (CEA) and beta 2microglobulin (beta 2 microG) were assayed in 19 of these subjects. For staging, the criterion of limited (LD) and extensive (ED) disease was used. Mean sTK and CEA values were above normal range in both the LD and ED groups, while mean beta 2 microG value remained below normal range. Thirty-two patients were subsequently submitted to therapy; sTK was assayed at the end of each treatment cycle. Mean sTK concentrations differed depending on response to therapy. From the data obtained it is concluded that sTK assay is helpful for diagnosis of SCCL; CEA to a lesser extent, above all in association with sTK, and beta microG not at all. sTK assay can also be useful for prognosis and follow-up.

Consistent changes in the circadian rhythms of blood pressure and atrial natriuretic peptide in congestive heart failure.

We demonstrated in previous works that the circadian rhythms of blood pressure (BP) and atrial natriuretic peptide (ANP) are antiphasic in normal subjects and in essential hypertension. The aim of the present study was to assess the circadian rhythms of BP and ANP in 20 patients with stable congestive heart failure (CHF), divided into two groups of 10 according to their New York Heart Association functional class. A matched control group of 10 normal volunteers was also studied. Noninvasive BP monitoring at 15-min intervals was performed for 24 h. Peripheral blood samples were also obtained at 4-h intervals starting from 08:00 h. The mean (+/- SEM) circadian mesors of ANP plasma levels were 13.4 +/- 1.7 pmol/L in the control group, 28.6 +/- 2.4 pmol/L in the group of 10 patients in class II, and 81.5 +/- 12 pmol/L in the group of 10 patients in class III-IV. In normal subjects, plasma ANP concentration was highest at 04:00 h (21.5 +/- 2.7 pmol/L) and lowest at 16:00 h (8.8 +/- 2.4 pmol/L; p less than 0.01). Both groups of patients with CHF showed no significant circadian change in the plasma levels of ANP and also a significantly blunted circadian rhythm of BP. Cosinor analysis confirmed the loss of the circadian rhythms of ANP and BP in CHF patients. Our findings support the existence of a causal relationship between the circadian rhythms of ANP and BP.

Atrial strain is the main determinant of release of atrial natriuretic peptide.

We studied the response of atrial natriuretic peptide to the hemodynamic and renin-aldosterone variations occurring in four patients who developed cardiac tamponade, either occurring in idiopathic fashion in one or secondary to metastatic involvement of the pericardium in three. Right atrial pressure, heart rate and arterial blood pressure were monitored and serial blood samples were taken before and over three hours after pericardiocentesis. During cardiac tamponade, normal levels of atrial natriuretic peptide (mean +/- SEM: 54 +/- 7.4 pg/ml) were observed in the plasma despite increased right atrial pressure (23 +/- 3.8 cm H2O) and heart rates (98 +/- 4.4). Removal of pericardial fluid (540 to 1160 ml) was associated at first with a 200% increase in plasma concentrations of atrial natriuretic peptide (108 +/- 8.8 pg/ml; P less than 0.001), then with a gradual decline toward normal levels, simultaneous with the normalization of right atrial pressure and heart rate. Activity of renin and concentrations of aldosterone in the plasma were increased during tamponade and returned gradually to normal after pericardiocentesis (3.8 +/- 0.9 to 1.2 +/- 0.3 ng/ml/h and 20 +/- 4.2 to 9 +/- 3.2 ng/dl, respectively; P less than 0.01). These data confirm that atrial strain, not intracavitary pressure in itself nor heart rate, is the main determinant of the acute release of atrial natriuretic peptide, which is associated with a suppressing effect on the renin-aldosterone system. In addition, our data indicate that secretion of atrial natriuretic peptide during cardiac tamponade is not stimulated by secondary hyperaldosteronism.

SHBG, testosterone, androstenedione, 17-OH-Progesterone plasma levels in PCO affected women treated with a triphasic oral contraceptive.

A triphasic oral contraceptive Trigynon (Schering) or Triphasil (Wyeth) was administered to 13 anovulatory women with hyperandrogenism, enlarged polycystic ovaries and reversal of LH/FSH ratio. After three months of treatment total Testosterone, Androstenedione and 17-OH-Progesterone levels significantly decreased while SHBG significantly increased. Reduction of hair growth and improvement of acne were noted. Side effects were minimal.

PIP: A trial of a triphasic oral contraceptive in 13 women with polycystic- ovary syndrome is presented, backed up with data on levels of sex hormone binding globulin (SHBG), testosterone, androstenedione, 17-OH-progesterone and other hormones. This illness is really a hyperandrogenic response of the ovary secondary to high gonadotropin levels and unopposed estrogens with low SHBG. Only mediocre results have been reported with low-dose oral contraceptive treatment, compared to earlier high-dose pills. The pills used here contained 50 mcg levonorgestrel (LNG) with 30 mcg ethinyl estradiol (EE) for 6 days, 75 mcg LNG and 40 mcg EE for 5 days, and 125 mcg LNG with 30 mcg EE for 10 days. After 3 months of treatment LH levels fell from 29.7 to 3.6 mIU/m1; FSH fell from 12.3 to 2.6 mIU/m1, and the LH/FSH ratio decreased from 2.34 to 1.38. All androgens declined significantly (p0.01), into the normal range. Serum cortisol rose significantly from 16.9-36.7 mcg/100 ml. SHBG rose from 1.67-3.0 mcg/100 ml, the high limit of normal. Hirsutism and acne improved in all but 1 patient. 1 woman dropped out because of weight gain, and another because of nausea and headache. These results suggest that triphasic oral contraceptives may be safe and effective for chronic anovulatory syndrome.

Prolactinemia during the menstrual cycle. A possible role for prolactin in the regulation of ovarian function.

We measured the concentration of circulating prolactin (PRL) in the serum during ovulatory and anovulatory cycles of normoprolactinemic menstruating women. The results demonstrate that during the luteal phase of ovulatory cycles a significant increase of PRL is observed together with that of progesterone. On the contrary, in menstruating women with anovulatory cycles we could not detect these increases. These data, analyzed together with the concomitant changes of gonadotrophins secretion, suggest a possible luteotrophic action of PRL in humans during the menstrual cycle.

Effect of the hormonal contraception on serum reverse triiodothyronine levels.

Thyroid hormones and the thyroxine-binding globulin are increased during hormonal treatment with oral contraceptives without changes in the thyroidal economy. Now we report that even reverse triiodothyronine, the main peripheral catabolite of thyroxine, is significantly increased during therapy with oral contraceptives.

Blood prolactin levels: influence of age, menstrual cycle and oral contraceptives.

The relationships between the serum levels of estradiol, progesterone and prolactin have been analysed in normal women in relation to age, to menstrual cycle, and in oral contraceptives users. We have been able to detect significant differences between the prolactinemia values during the cycle in different age groups as well as following oral contraceptives. A word of caution is presented for the evaluation of the prolactin blood level which should always be related to the physiological phase of the cycle and to the age of the subjects.

Folic acid deficiency in beta-thalassaemia heterozygotes.

Plasma and red cell folate mean contents have been found to be significantly lower in 41 symptom-free beta-thalassaemia heterozygotes than in 21 controls. Such decreases must be considered as effects of an increased folate utilization caused by the enhanced total, both effective and ineffective, erythropoiesis. Since no close correlation has been found between packed cell volume and plasma or red blood cell folate levels, it seems that in 'healthy' beta-thalassaemia subjects, the degree of anaemia is not influenced by folate body reserves. However, the frequent finding of reduced red cell folate contents suggests that further folate imbalance might lead to clinically significant degrees of folate deficiency.

Endocrine assessment of hypogonadism in patients affected by thalassaemia major.

Gonadotrophin releasing hormone (GRH) was administered to 54 patients (39 prepubertal and 15 pubertal) with beta-thalassaemia major to assess pituitary gonadotrophin secretory reserve. Human chorionic gonadotrophin (HCG) was also administered to 10 of the prepubertal boys to assess gonadal endocrine function. Many patients, some with and some without pubertal changes and including prepubertal children aged from 7 to 12 years, had evidence of pituitary hypofunction. A normal pituitary response to GRH stimulation, with decreased gonadal hormone response to the HCG test, found in 3 subjects, demonstrated that gonadal endocrine failure may also occur.