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It is well known that the immune reactivity is modulated by gender. In fact, women show a more effective immune response as well as a more frequent development of autoimmune diseases. In particular, 17 beta-estradiol (E2) in patients with systemic inflammatory diseases leads to an higher production of IgG and IgM in peripheral blood mononucleated cells (PBMC) and the secretion of metalloproteinases and IL-6 by synovial fibroblasts. The effect of E2 seems to be partially related to its concentration. In fact, at the physiological concentration, E2 seems to exert a pro-inflammatory effect, while at pharmacological concentrations shows anti-inflammatory effects. Steroid hormones can be converted in downstream hormones along defined pathways. The conversion of dehydroepiandrosterone (DHEA) in peripheral macrophages leads to the androgen production. Subsequently the enzyme aromatase converts androgens in estrogens, and its activity is increased by some inflammatory cytokines such as IL-1beta, IL-6 and TNF-alpha. In the synovial fluids of rheumatoid arthritis (RA) patients the levels of estrogens result significantly increased compared with controls, showing the consequence of this unbalanced steroid metabolism. Furthermore, the metabolism of estrogens leads to some downstream hydroxylated metabolites, that are not waste products, but still active molecules in the inflammatory response. In fact, it has been found that synovial fluids of RA patients present a different ratio of 16-hydroxylated estrogen metabolites/ 2-hydroxylated metabolites, confirming that also the unbalanced metabolism of estrogens and not only the estrogen concentration seems to be related to the development and worsening of rheumatoid arthritis.

Tryptophan hydroilase in brain, normally is not saturated by its substrate; therefore the rate of tryptophan hydroxilation in brain is controlled by the concentration of tryptophan. In the other hand, brain tryptophan content is controlled by the ratio of the concentration of free tryptophan (i.e. not bound to serum proteins) to that of the other circulating amino acids, wich compete for the same transport mechanism from blood to brain. The administration of an amino acid mixture, containing all essential amino acids but not tryptophan, caused a parallel depletion of total and free serum tryptophan and of tryptophan and serotonin in brain. The mechanism of the observed fall in serum tryptophan is a rapid removed of endogenous tryptophan from circulation, secondary to an increased incorporation of tryptophan into proteins by the liver. These results suggest the hypothesis that brain serotonin synthesis is controlled by a perpherical mechanism.

The literature on primary and secondary hyperparathyroidism is surveyed in the presentation of an account of the present positon. Reference is also made to personal clinical experience, particularly in secondary cases. The physiopathology of parathormone, calcitonin and vitamin D is described; the last, in fact, has proved useful in the treatment of secondary forms. The usual symptomatological tests of performance are explained, together with their diagnostic value. The clinical symptoms and their physiopathological significance are also illustrated. Stress is laid on the importance of conservative management in secondary forms. Good results now enable parathyroidectomy to be avoided or delayed in many cases.