Serum concentrations of insulin-like growth factor-I (IGF-I) in patients with liver cirrhosis.

BACKGROUND/AIMS: Insulin-like growth factor-I is an important anabolic polypeptide with various effects. The circulating insulin-like growth factor-I is mainly liver derived. The aim of this study was to determine insulin-like growth factor-I serum levels in patients with cirrhosis and to clarify their association with patients' clinical condition and the etiology of cirrhosis. METHODOLOGY: Forty patients with liver cirrhosis were enrolled. Cirrhosis was in 22 cases induced by virus, in 10 due to primary biliary cause and in the rest 8 of alcoholic origin. The Child score index was found as A (n = 26), B (n = 9), C (n = 5). Twenty, age-matched healthy subjects, were used as a control group. Serum insulin-like growth factor-I was measured by an immunoradiometric assay in all subjects. RESULTS: Serum insulin-like growth factor-I levels in liver cirrhosis were found very significantly lower than in healthy individuals (57.4 +/- 7.0 ng/mL vs. 198.8 +/- 16.3 ng/mL, p = 0.0000001). In liver cirrhosis insulin-like growth factor-I was negatively correlated with spleen enlargement (r = -0.46, p = 0.0031). Child B and C patients showed significantly reduced insulin-like growth factor-I levels in comparison to patients staged as Child A (28.9 +/- 3.0 ng/mL vs. 72.8 +/- 9.3 ng/mL, p = 0.0016). The comparison of 12 patients with viral induced cirrhosis (Child A) to 14 patients with non-viral cirrhosis, of the same clinical stage, showed non-significant difference (84.2 +/- 16 ng/mL vs. 63.1 +/- 10.3 ng/mL, p = 0.27). CONCLUSIONS: Insulin-like growth factor-I synthesis is disturbed in liver cirrhosis and reflects the severity of the clinical stage. It represents a good marker of hepatic function. The etiology of cirrhosis does not seem to influence its levels.

Frequency of HLA antigens in Graves' hyperthyroidism and mitral valve prolapse.

BACKGROUND AND AIMS OF THE STUDY: An association between Graves' hyperthyroidism (G) and mitral valve prolapse (MVP) has been reported, but possible genetic linkage between the two disorders has not. METHODS: One hundred and five patients (pts) with G were studied after therapy, in a euthyroid state. MVP (auscultatory plus echocardiographic findings) was present in 33 pts (31%). Frequency of human lymphocyte antigens (HLA) in pts with G and in pts with G plus MVP was compared to 170 normal subjects (NL). There was no difference in HLA-A antigens among the three groups. RESULTS: The frequency of HLA B-15 was greater in pts with G plus MVP (18.9%) compared to NL (3%) and to G without MVP (4.2), p < 0.01. The frequency of HLA-B39 was greater in G without MVP (13.8%) compared to NL (4.1%), p < 0.01. The HLA DRB1*1601-2 was more frequent in G with (30.3%) or without (29.2%) MVP compared to NL (13.5%), p < 0.01. The frequency of HLA DRB1*1401-10 and DQA1*0104 were greater in NL (16.5%) compared to G with (3.0%) or without (4.2%) MVP, p < 0.01. CONCLUSIONS: The data confirmed previous observations that the frequency of MVP is high in pts with G. Further, the data indicated a possible genetic linkage between the two abnormalities.

Free urinary cortisol immunoreactive levels in premature and full term infants.

Urinary free immunoreactive cortisol excretion was measured in 20 full term, 20 premature and 20 premature newborns of mothers who had been treated with 12 mg betamethasone 48 hours before delivery. In 10 full term newborns delivered normally, values were 40 +/- 20 nmol/mmol creatinine on the first, 23 +/- 8 on the second and 21 +/- 6 on the third day of life. In 10 full term newborns with stressful delivery, the corresponding values were 63 +/- 39, 44 +/- 33 and 32 +/- 17 nmol/mmol creatinine in the first three days of life. The levels of urinary free immunoreactive cortisol of 10 premature newborns delivered without stress were 170 +/- 116, 91 +/- 75 and 70 +/- 61 nmol/mmol creatinine respectively, on days one, two and three of life. Ten premature infants with respiratory distress syndrome had values of 471 +/- 187, 526 +/- 465 and 636 +/- 906 nmol/mmol creatinine, respectively. The 10 premature newborns whose mothers had received betamethasone, had urinary free immunoreactive cortisol levels of 109 +/- 120, 55 +/- 42 and 66 +/- 84 nmol/mmol creatinine, lower than the other premature infants. This difference, however, was not statistically significant. We conclude that premature infants regardless of stress or normal labor have high urinary free immunoreactive cortisol excretion, suggesting that prematurity per se is a potent stress.

Fine needle aspiration biopsy cytology in the diagnosis of thyroid cancer: comparative study of 213 operated patients.

Between 1982 and 1984, fine needle aspiration biopsy cytology (ABC) was performed in 1100 patients (aged 14-80, 993 women), with nodular goitre, who had either a solitary cold nodule or dominant hypofunctioning nodule(s) within a multinodular or diffusely enlarged gland. Surgery was performed in 213 patients based on clinical and cytological criteria, and the histology of the surgical specimens was correlated with the cytological findings. ABC specimens were sufficient for cytological diagnosis in 190 patients and were classified as malignant (positive), suspicious or benign. In 37 patients who had a final histological diagnosis of malignancy, cytology was positive or suspicious in 33 and benign in 4. In the remaining 153 patients with benign histology there were 7 positive or suspicious aspirates, and 146 benign. The 37 malignancies included papillary carcinomas in 26 patients (24 positive or suspicious and 2 benign on cytology), Hürthle-cell tumours in 6 (6 positive), follicular carcinoma in 1 (negative), anaplastic carcinoma in 1 (suspicious), medullary carcinoma in 2 (1 positive, 1 negative), and lymphoma in 1 (positive). Our results indicate that the overall sensitivity rate of the ABC method for cancer was 89.2 per cent, the diagnostic specificity 95.4 per cent, the false-positive rate 17.5 per cent and the false negative rate 2.6 per cent. The overall accuracy of the method was 94.2 per cent. It is concluded that papillary and Hürthle-cell carcinomas can be diagnosed accurately with ABC but we recommend that the method be used in conjunction with clinical information and other conventional diagnostic procedures.

Changes of sympathetic activity during tooth extraction.

Urinary VMA excretion was studied in 3 groups of young and healthy subjects, before and 2 h after a standard tooth extraction. Local anaesthesia was either a solution of lignocaine 2% (1st group, n = 17) or a mixture of lignocaine 2% with noradrenaline bitartrate, 1250 micrograms/100 ml, (2nd group, n = 13) or lignocaine 2% with adrenaline hydrochloride 1250 micrograms/100 ml (3rd group, n = 10). Mean VMA excretion rose from 3.6 +/- 2.8 to 6.7 +/- 4.6 mg/g creatinine, in the first group. In the 2nd group, the mean VMA excretion was 2.3 +/- 1.2 and rose to 6.2 +/- 2.8, whereas in the 3rd it rose from 2.3 +/- 0.92 to 8.3 +/- 7.6 mg/g creatinine. The increase of VMA excretion after the tooth extraction was of the same order in the 3 groups studied and was not affected by the addition of noradrenaline and adrenaline in the anaesthetic solution.

Infusions of hFSH and hLH in normal men. I. Kinetics of human follicle stimulating hormone.

Serial serum assays of immunoreactive FSH before, during and after a 4 h intravenous infusion of human follicle stimulating hormone (hFSH) in five healthy men revealed two disappearance rate constants with corresponding mean half-lives of 2.9 and 50.6 h. The mean distribution spaces calculated for the fast and slow component were 4.36 1 and 75.9 1 respectively. The average value for the metabolic clearance rate was 17.2 ml/min and for the endogenous production rate 50.9 mU/min. Two of the subjects had human luteinizing hormone (hLH) added in the infusions without the FSH kinetics changing.

Infusions of hFSH and hLH in normal men. II. Serum testosterone response to infused hLH and hFSH.

Standardized 4 h intravenous infusions of human follicle stimulating hormone (hFSH) and/or human luteinizing hormone (hLH) were given either separately or combined to 7 normal male volunteers. The infusions raised the serum gonadotrophin levels at least 10 (FSH) and 18 (LH) times above the basal ones. Serum testosterone (T) levels were measured serially before, during and after the infusions and, in 4 subjects, during a corresponding period of another normal day. During a normal or basal 24 h period fluctuations were seen and also a circadian rhythm with lower levels in the evening. The infusion of hFSH alone (3 subjects) did not alter the serum T levels. The infusion of hLH alone in 2 subjects raised serum T levels by 17% and 55% over those of the basal day. The combined FSH/LH infusion caused a significant rise (35-68%) in 4 subjects and greater rise in 2 of them than after infusion of the hLH alone. The serum T responses were gradual, reaching a maximum 7-8 h after the end of the infusion.

Hormonal responses to a first course of clomiphene citrate in women with amenorrhoea.

The hormonal criteria of a "normal" or "ovulatory" response, and three grades of subnormal anovulatory responses, were defined during a first course of treatment with clomiphene citrate in twenty patients with amenorrhoea for which no organic cause could be found. The hormonal responses were estimated by frequent serum measurements and by the menstrual response. Seven patients had a normal or ovulatory response with a late rise of serum progesterone and subsequent menses. Their serum luteinizing hormone (LH) and oestradiol (E2) responses were greater than in spontaneous menstrual cycles. Five patients gave only partial responses, with menstruation and no prior rise of progesterone, Their serum LH and E2 responses were generally lower than in the normal group but had the same pattern except for an absence of the luteal phase rise in E2. Five patients who did not menstruate showed smaller and more variable responses. The remaining five showed no hormonal responses. The second and third groups had ovulatory responses on subsequent clomiphene courses, whereas no improvement was shown by the last group. The serum E2 responses offered the most sensitive index of the responsiveness to clomiphene. Response values in our normal group suggested that higher progesterone levels need to be reached after clomiphene administration than in spontaneous cycles for ovulation to be inferred. The serum prolactin showed no consistent response during the clomiphene test; three patients with moderately raised basal prolactin levels had "normal" responses.

The effect of yttrium-90 implantation on endocrine function and visual fields in patients with "functionless" pituitary tumors, with biopsy and radiological findings.

Thirty patients with symptoms from "functionless" pituitary tumours were treated by yttrium-90 implants, and we report here the effects on symptoms, pituitary function and visual fields. On biopsy, about a third of the tumours showed some hormone granules. In the sixteen fully assessed at 1 year, pituitary function was improved in 25%, unchanged in 62-5%, and reduced in 12-5%. Improvement was confined to those in whom gonadotrophin secretion was the only function impaired pre-implant. Visual field defects were present pre-implant in ten patients (twenty eyes); at 1 year post-implant these defects had lessened in 80% and deteriorated in only 5% of eyes. Subsequently, within 5 years of the implant the field defects had worsened or recurred in four patients, all with initially extensive suprasellar projection; further treatment was then given. Remineralization of the sella was seen after implantation in seven cases, with reduction in fossa size in five. Thus pituitary implantation appears to be a practicable and reasonably simple procedure suitable for the treatment of most cases of "functionless" pituitary tumour. The "supressive" doses of irradiation used are adequate to shrink most tumours without loss of pituitary function.

Gel filtration of human urinary immunoreactive luteinizing hormone.

In human urinary concentrates and also in a urinary gonadotrophin standard (2nd IRP-HMG), gel-filtration analysis revealed three main peaks of immunoassayable luteinizing hormone (LH). A similar analysis of LH extracted from human pituitaries showed most of the activity in a peak of larger molecular weight, and only minor fractions in the positions of the urinary peaks. In an extract of normal human serum, analyss showed only one similar peak of large molecular weight, which also emerged before the urinary peaks. During an i.v. infusion of pituitary LH into normal men, the urinary LH activity increased but was still found only in the same three peaks on gel filtration, and all were of a molecular weight smaller than that of the infused material; but a higher proportion of the urinary LH was found in the earliest of these peaks compared with that found before infusion. Conversely, 20-35 h after the i.v. infusion, there was a slightly higher proportion of LH activity in the third peak of smallest molecular weight. These findings suggest that the urinary immunoassayable LH, which is found in three peaks of different molecular weights, is derived from the pituitary or serum LH of higher molecular weight. The changes in the proportions of larger or smaller molecular weight fractions in the urine during and after LH infusion suggest that the earliest peak may be disaggregated serum LH, while the last or smallest molecular weight peak may comprise metabolites of LH.

Thyroid function in patients treated with radioactive iodine for thyrotoxicosis.

A series of 105 patients treated at least two years earlier with radioactive iodine for thyrotoxicosis have been surveyed. Eighty-five patients (81%) were euthyroid clinically and on the basis of routine thyroid function tests. Of the euthyroid patients 46 (54%) had normal thyroid-stimulating hormone (TSH) levels and 39 (46%) had raised TSH levels. There was no difference in serum triiodothyronine levels between these two groups but the serum protein bound iodine and serum thyroxine, though still well within the normal range, were significantly lower in the group with raised TSH levels. The serum cholesterol was also significantly higher in this latter group.Most of the euthyroid patients were seen again a year later. None had become hypothyroid and neither those with normal nor those with raised TSH levels showed any evidence of a decline in the level of serum thyroxine.It is concluded that raised serum TSH levels in patients treated with iodine-131 are not necessarily indicative of hypothyroidism. There is no indication that patients who have this abnormality become overtly hypothyroid over a 12-month follow up.

Combined test for assessment of anterior pituitary function.

A combined test consisting of the simultaneous administration of insulin, thyrotrophin-releasing hormone (TRH), and luteinizing hormone and follicle stimulating hormone-releasing hormone (LH/FSH-RH) was performed in 24 people. Eleven of these also had the three individual tests performed separately, and the remaining 13 had a separate test of either LH/FSH-RH and TRH together or singly at a later date. In both normal people and patients, whether the tests were performed alone or in combination, no difference was found between the hormone responses (growth hormone, cortisol, LH, FSH, thyroid-stimulating hormone) seen to these stimuli.It is proposed that combined administration of insulin and the hypothalamic releasing hormones may be used as a single test for the assessment of anterior pituitary function. The test is convenient and time saving, and with care can be performed in outpatients.