The endocrine system is so intimately tied to elementary body functions that malfunctions within the endocrine system are pathogenic and potentially life threatening. To understand human endocrinology, the elucidation of defects is even more required because from the defects the healthy, normal situation might be inferred. If, for example, an enzyme defect inhibits steroid hormone biosynthesis and results in major, fatal imbalances of water homeostasis, we recognize the central role of steroidogenic enzymes for the control of renal functions. Since aromatase mutations not only cause sex reversal, but also lead to growth failures, we perceive the action of estrogen for chondrocyte maturation (see Sect. 11.​6.​3). Experiments in humans, for example, to knock out target genes by molecular biological means which in mice have given stunning and astonishing results are generally forbidden; therefore, endocrinologists depend on the analysis of genetic variations, even though this may be very difficult in certain situations. Information on genes defects in endocrine diseases will complete the discussion of the endocrine system and its elements, especially with respect to an extended description of genes and their products.

We describe different forms of malfunctions: In the endocrine system, release of hormones might be too high or too low. An untimely release of a hormone might occur and disturb homeostasis. The most frequent faults are oversecretion or undersecretion or tumors of endocrine active cells. Other failures involve autoimmune diseases where the immune systems rejects endocrine cells as “foreign” and destroys them, with the consequence of major endocrine dysfunctions. And there are genetic defects: either inherited or individually acquired. These might result in disturbances of the endocrine circuits presented so far. Some genetic defects give rise to infertility and are not handed down.

Many defects involve the fetus in utero. If elementary functions are blocked, fetal death occurs. In these instances, the analysis of the causes is most often impossible. If maternal hormones, however, can substitute for the lacking fetal ones, the child may survive until parturition. Once the umbilical cord has been cut, the newborn is in mortal danger in congenital adrenal hyperplasia, for example, since no cortisol is provided by the adrenal glands. The lack of aldosterone biosynthesis is as dangerous for the newborn. If identified early, such diseases can be controlled.

Other malfunctions become apparent after several weeks or much later. A growth hormone (GH) deficit is not life threatening but may lead to much reduced growth. When the defect is related to the biosynthesis of GH, recombinant GH can be used as a substitute, and its use may lead to relatively normal growth. The individual is, however, resistant to GH therapy if the GH receptor is defective either by mutations or by deletions of the receptor gene. Here the therapy is inefficient. There are, for example, two murine strains with inherited obesity: In the ob/ob mouse, the leptin gene is mutated. Here obesity is controlled by administration of leptin, and adipose tissue already acquired is removed. In the db/db mouse, however, the leptin receptor is mutated and administered leptin does not change adiposity. In human society adiposity, however, is rarely caused genetically. Not enough exercise or activity and an extremely lipid-rich diet are causal for most of the adiposeness.

Since many genetic defects of the endocrine systems involve the CNS, they might be reflected in mental development of a child.