Since H63D syndrome was first described, the authors of this paper systematically investigated for the first time to what extent the adrenal glands, as an integral part of the HPA and SAM axes, are also affected by damage caused by non-transferrin bound iron (NTBI), a hallmark of H63D syndrome. Due to the rarity of the H63D syndrome, the representatives of a number of institutions that regularly deal with the topic in the context of their clinical and research activities have come together for this purpose. Thus, a small but significant amount of patient data could be collected worldwide, analyzed and evaluated, with surprisingly clear pathological results. A secondary aspect is that after reviewing the currently available literature, the team of authors came to the conclusion that the issue of HPA and SAM axes dysfunctions and adrenal synthesis activity seems to be also more frequent in other iron metabolic disorders than it is addressed to in everyday’s clinical practice. The result of this work is a warning call to closely monitor the catecholamine balance, the synthesis and control of all "stress hormones", the condition of the adrenal glands as well as other axis structures very early in the course of the H63D syndrome, in order to make unnecessary organ damages at least a little less likely, if not to prevent it to a large extent if detected early.