There is sound clinical evidence that many benign breast conditions, especially pain, nodularity, and cysts, are likely to have their pathogenesis in hormonal events during reproductive life. Yet the classical theories of persisting hyperestrogenism and luteal progestogen deficiency have not stood up to detailed investigation. Recent work has demonstrated the importance of dynamic hormonal changes and of chronobiological rhythms--daily, menstrual, and seasonal. Recent developments and findings are reviewed to point to the directions in which the basic etiology of these conditions is likely to be discovered.

Breast Diseases↗

PubMedDate not supplied

Increased plasma corticosteroid-binding globulin in insulin-dependent pubertal diabetics: relationships with other glycoproteins, growth hormone and prolactin.

A selected group of 13 juvenile-onset insulin-dependent diabetics in mid-late puberty (stages 3-4) and under comparable conditions of metabolic control was studied in order to evaluate the plasma levels of corticosteroid-binding globulin (CBG, transcortin: expressed as the binding capacity for cortisol) in relation to the levels of other glycoproteins and to growth hormone (GH) and prolactin (PRL) responsiveness to provocative tests (arginine infusion and TRH injection, respectively). Further evidence was provided that juvenile-onset diabetics show most frequently enhanced plasma CBG binding capacity; statistical significance with p-values less than 0.01 was attained in comparison to 25 age-matched controls. Among other variables examined, only hemoglobin A1c amd alpha 2-macroglobulin were significantly raised in the diabetic group (p less than 0.01 and less than 0.02, respectively). In our patients growth hormone response to arginine infusion was in the normal range, whereas PRL response to TRH was slightly but significantly supranormal in terms of maximum value and maximum increment above baseline value. No correlation was found between CBG binding capacity and other variables examined. We conclude that raised levels of CBG may occur as an additional alteration of the plasma glycoprotein pattern in juvenile-onset insulin-dependent diabetics. Specific regulatory factors conceivably subserve plasma concentrations of different glycoproteins.

Adolescent↗

PubMedDate not supplied

Plasma bile pigment conjugation modalities in icterus syndromes of various origin.

Plasma azopigments derived from conjugated bilirubin were analyzed by thin-layer chromatography according to HEIRWEGH et al. in 14 cases of obstructive jaundice and in 11 of acute hepatitis. The chromatographic patterns were compared with those obtained from azopigments derived from 8 normal bile samples. The plasma pigment patterns did not differ from those of the bile in number and chromatographic mobility of the spots. However, the quantitative percentages of the plasma azopigments were significantly modified: the alpha 0 fraction (free azodipyrrolic pigment) increased in both icteric syndromes, while the delta fraction (mainly glucuronide azopigment) decreased. Moreover, the behavior of two closed components of the delta group showed significant differences in both icteric syndromes. It can be postulated that the synthesis of bilirubin diconjugates decreases both in hepatocellular and cholestatic jaundice, while monoglucuronidated as well as saccharide and glucoside conjugates increase. In cholestatic jaundice the conjugation with glucuronic acid mainly takes place in the normal way, whereas compounds with different features are formed in hepatitis.

Bile↗

PubMedDate not supplied

Temporal aspects of glucocorticoid action and clinical implications.

Administration of glucocorticoids is effective and necessary in various diseases, but the appearance of side effects may compromise its results. Timing as well as dosing designed to obtain, for the highest number of patients, maximal beneficial effects with minimal undesired effects, is particularly pertinent to long-term corticosteroid therapy, in view of the rhythms exhibited by the endogenous secretion of adrenal cortical and coordinating hormones, primarily ACTH. In experimental animals, properly-timed circadian treatment can be preferred to alternate-day treatment for avoiding certain side effects. To secure the desired effect each day rather than only on alternate days, a chronobiologically correct corticosteroid therapy seeks the best compromise between timing for most of the desired and least of the undesired effects. This was the aim in the design of a chronopluricorticoid drug, with the time specification on its label. The clinical use of this preparation allowed the inferential statistical demonstration of a rhythmic circadian organization maintained during therapy, while the pharmacological results gained were similar to those obtained by the conventional administration of larger doses of corticoids.

Adrenal Cortex↗

PubMedDate not supplied

Peptide hormone analogues and novel clinical applications.

Clinical application of peptide hormone analogues is rapidly expanding. Peculiar aminoacid residues, conformational turns and the degree of molecular flexibility may represent critical keys for differential interaction with the receptor sites, hence for specific biological effects. Broadly different biological responses may be elicited as a function of dose and timing of administration. The clinical use of the heptadecapeptide analogue ACTH 1-17 (Synchrodyn 1-17) has provided new diagnostic information about subtle alterations of the adrenal function and has been valuable to presenting the rhythmic ordering of several functions, especially of those which are more dependent on the glucocorticoid modulation. In this sense, the use of a synthetic hormone analogue presenting a wide range of programmable effects appears essential for a better medicine. A large body of evidence indicates that the same concept applies to most actions of the gonadotropin-releasing hormone (LH-RH) related analogues. The availability of small computerized instruments for data collection and analysis of the endogenous rhythmicities, on the one hand, and for programmable administration of the analogues, on the other hand, is already providing new approaches to heretofore unsuccessful therapies.

Adrenocorticotropic Hormone↗