The assessment of the dopaminergic tonus by urinary determinations of homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC) in normal, obese and GH-deficient short children.

In order to assess the dopaminergic tonus, urinary determinations of HVA and DOPAC and also of noradrenaline (NA), adrenaline (A), and methoxyhydroxyphenylglycol (MHPG) were performed in 86 obese children, 11 growth hormone (GH)-deficient short children and also in 40 control children. Part of the obese patients were subjected to a low carbohydrate, low calorie diet and also to short-term (9-14 days) courses of diethylpropion (DEP) 50 mg/day, meclofenoxate (MEC) 100 mg/day and thyroid extract (THE) 1-2 mg/kg/day. The GH-deficient patients received only THE in substitutive (5-10 mg/kg/day) doses. Significative correlations between DOPAC and age, weight and height were found in controls. In the obese group a significantly increased mean level of HVA was found (1.45 +/- 0.09 mg/24 h vs 1.15 +/- 0.10 in controls). The excretion of DOPAC was slightly greater but far from significance. There was also a significant decrease of HVA but not DOPAC in the DEP-treated obese. The rest of the drugs and the diet alone were not effective in any way. Normal levels in all metabolites except NA and A were found in GH-deficient short children. The therapy with thyroid extract did not alter the excretion levels. These findings indicate that in infantile obesity the dopaminergic tonus is somewhat increased but its pathophysiological significance is doubtful. In GH-deficient short children of standard appearance the dopaminergic tonus seems to be undistinguishable from normal.

Serum-to-saliva transfer of the immunoreactive insulin (IRI) in children with obesity associated with insulin-resistance.

Assuming that the serum-to-saliva transfer of insulin reflects internalization and re-cycling of the hormone in the membrane-located binding sites of salivary epithelial cells and that these cells have in obesity a'marked decrease in insulin receptor content, it has been postulated that insulin resistance in infantile obesity can be detected by the changes in the salivary immunoreactive insulin during the oral glucose tolerance test (OGTT). The study included 31 obese children and adolescents of both sexes, subjected to OGTT. Samples of blood and saliva were collected at 30, 60, 120, 180 and 240 minutes for determinations of glucose and IRI. The blood glucose values were generally normal whereas IRI was excessively high. The dynamics of salivary IRI was similar (easy peak followed by slow descent) with the mean serum values but lower by about two-thirds, and the peak was 30-60 minutes delayed. The serum IRI values correlated significantly with the saliva ones at all time-intervals except for the 30-minute ones. The serum IRI values were significantly lower at the 30-minute time interval, whereas the salivary IRI were the lowest (and of borderline significance) at the 60-min. time interval. The mean glucose/kg doses given orally were not significantly different in the two groups. It was concluded that a hormonal activity detectable by IRI assay through the PEG separation method does exist, with a concomitant variation of serum-to-saliva transfer as shown by the OGTT test. It was also concluded that since the salivary values are lower, the direction of the flow is from serum to saliva and not the reverse. Finally, on the basis of our data, an "in situ" synthesis of insulin (hormonogenic exocrinism) can not be ruled out.

Studies concerning the effects of a pineal peptide extract on collagen metabolism.

The effects of Crinofizin (Cfz), cortisone, triiodothyronine (T3) and methylthiouracil (MTU), alone or in association with one another, on collagen metabolism of impuberal and adult rabbits were tested. These effects were assessed by the hydroxyprolinuria (Hyp) assay corroborated with observations regarding mortality, body weight, diuresis and excretion of nitrogenous substances. Cfz given alone stimulated weight gain and did not alter characteristically the Hyp. Cortisone and T3 given in various doses and ways without Cfz induced general phenomena of the antianabolic or catabolic type, affecting characteristically the Hyp, which was low after administration of cortisone and increased after T3; association of Cfz to both cortisone and T3 had general protecting and corrective effects and brought Hyp towards or at normal values. Chronic administration of MTU with or without Cfz did not have significant effects. The corrective value of Cfz by anabolic and anti-catabolic actions on collagen metabolism disturbed by cortisone or T3 in excess is discussed.

Peptide hormones in saliva. I. Insulin in saliva during the oral glucose tolerance test in female patients.

The radioimmunoassay (RIA) of insulin was performed in the serum and saliva of 27 female patients during the oral glucose tolerance test (OGTT). The patients were divided into two groups: 19 non-diabetic patients and 8 patients diagnosed as impaired glucose tolerance (IGT) disease. In one patient in each group, the OGTT was performed twice at intervals of 3-5 days. The results show that immunoreactive insulin (IRI) is present in saliva and its concentration increases during the glucose stimulation test from 6.48 +/- 1.13 microU/ml (means +/- SEM) in basal conditions at peak values of 45.46 +/- 10.14 microU/ml at 2 hrs after glucose intake. In patients with IGT salivary IRI increases from 5.18 +/- 1.39 microU/ml in basal conditions to peak values of 83.34 +/- 25.85 microU/ml at 3 hrs after glucose administration. Great response variations were observed either inter-individual or intraindividual in both groups of patients. Some patients had unusual high salivary IRI concentration especially in those with gastrointestinal troubles. Further, some hypotheses and experimental models, are advanced, considered useful for the explanation of the physiologic significance of the salivary IRI or of the IRI-like material.

Primary hyperparathyroidism. Report of a clinical case without bone lesions.

A 26-year-old woman was admitted to the Institute of Endocrinology in Bucharest for evaluation of primary hyperparathyroidism (P-HPT). Anamnesis revealed a 10-year history of nephrolithiasis; peptic ulcer, chronic pancreatitis, cholelithiasis. Eight months previously, she had given birth to a child who had neonatal hypocalcaemic tetany. Investigations revealed the presence of moderate hypercalcaemia, hypercalciuria, hypo-phosphoremia; serum chloride level was above 100 mEq/1, and the chloride phosphate ratio was greater than 33. X-ray films of the abdomen revealed the presence of nephrolithiasis and right nephrocalcinosis. Selenium methyonine scanning, ultrasonography and computerized tomography were negative. On surgical exploration a 2-3 cm parathyroid adenoma was removed from between the trachea and the esophagus.

Growth deficiency with high circulating growth hormone levels: the insulin stimulation test in 39 children.

Thirty nine patients with abnormal high basal hGH levels were selected and analysed as a part of a retrospective study of the results of 1,500 insulin stimulation tests (IST), applied in children and adolescents with growth deficiency. Their height, weight, and bone age were lower than their corresponding chronological age. Both in girls and in boys groups, responders and nonresponders subgroups were detected as judging by the results of the secretagogue action of insulin on hGH. The hGH basal levels were 43.88 +/- 18.27 microU/ml (X +/- SD) in boys (no = 22) and 56.61 +/- 35.21 microU/ml in girls (no = 17). It is to be noted that the hGH nonresponder group had deeper hypoglycemia at 30 minutes post-insulin injection than the responder group: 53.6 +/- 13.0 mg/100 ml (X +/- SD) vs 66.0 +/- 11.5 mg/100 ml respectively (p less than 0.01). Two siblings, a girl and a boy, had the highest basal and stimulated hGH, either during the IST or starvation. One of them, the boy, during the starvation test, had a paradoxical fall of about two orders of magnitude of the serum hGH 4 hr after basal sample collection. These two siblings are similar to the familial Laron type dwarfism. The possible mechanisms of growth deficiency in children with constant high but variable hGH values are discussed, as well as the aspects concerning the therapeutic ways to improve their linear growth.

The dyslipemic syndrome in acromegaly.

The clinico-hormonal course of acromegaly and the presence of the hyperlipemic syndrome were studied in relation to age, sex, associated hypothyroidism, diabetes, obesity and cardiovascular and atherosclerotic complications in 43 acromegalic patients (18 males and 25 females) of which 6 had received no treatment and 37 had been submitted 2 - 13 years to conventional roentgentherapy (31 cases), 90Y (5 cases) and hypophysectomy (1 case). Hyperlipemia (HLP), present in 24 acromegalic patients (55.8% of the cases) unrelated to age, was more frequent in women (64% as against 44% in males) and correlated with the clinico-hormonal evolution (GH greater than 20 mg) (60% of the cases), and associated hypothyroidism (79%), obesity (42%) and diabetes (25%). Of the hyperlipemic acromegalic patients, 62% had cardiovascular and atherosclerotic complications. The results of the study point to the need for a hypoglucidic, hypolipidic and associated treatment for hypothyroidism, diabetes and obesity in the prophylaxis of acromegalic atherosclerosis.

The role of the renin-angiotensin system in arterial hypertension in hypercorticism.

The authors have studied on 25 cases of hypercorticism, one of the mechanisms of producing arterial hypertension, the renin-angiotensin system. The study showed that in only 20% of the cases plasma renin activity was high whereas in the remaining 80% other mechanisms were responsible for the hypertension. In the cases in which the plasma activity of renin was high, by studying the changes in the value of electrolytes we were able to derive some understanding of the mechanism of action of the RA2A system. Thus, the literature data show that sometimes the excess of glucocorticoids causes hypertension by activating directly the RA2A system and concomitently inhibiting the renin-kalikrein system (RKKS) and PgS; at other times, the excess of glucocorticoids is exerted on the same renin-angiotensin system, but via ACTH and ADH, the electrolytes values being those that demonstrate the borrowed mechanism.