PMC9248759_01
(A, B). Every preovulation or premenstrual period, during concomitant estrogen peaks, patient's TED signs and symptoms would become dramatically worse. Typically, this started on cycle day 10. Her cycles were short when the TED started (13 days total, indicating a possible lack of progesterone). When menses came and estrogen levels dropped to near zero (Figure 5), periorbital congestion and edema also dropped dramatically. This is evident in the one-day change photographed in the 2nd and 3rd panels. This was not edema-specific, it also occurred in the eyelid retraction, even after bilateral orbital decompression (not shown here). The lids retracted 1-2mm above the iris from cycle days 9 - 13, and then lowered to the level of the iris from cycle days 1 - 4.
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Regrettably, as I am not an oculoplastic surgeon, I do not have CAS scores for her disease, but we have the below visual diary (  Figures 3A, B  ).
Estrogen and ERalpha exert genomic and non-genomic effects on IGF-1R, IGF, and other growth factors. Given the increase in E2 in GD and HD, is there a concomitant increase in ERalpha and IGF-1R, via the mechanisms posited here? If so, it is plausible that estrogen is a disease driver in TED. (Adapted with open access creative commons permission from).
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ERalpha which binds to promoter of target genes, and upregulates IGF-1, IGF-1R ( Figure 4 ). Estrogen also stimulates cytosolic ER to interact with adaptor proteins, such as Shc or the p85 subunit of PI3K.
The ebb and flow of steroid hormones in a typical menstrual cycle. Several autoimmune disease symptoms are exacerbated by the rises in estrogen seen in both the first (follicular) and second (luteal) phases of the cycle. In GD and HD, these effects could be more profound due to the lack of steroid hormone homeostasis. Estrogen at periovulatory and premenstrual levels significantly increases IGF-1R, IGF, and GH. (Image copied with permission from).
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Consequently, at periovulatory levels in GD of HD, the GH/IGF-1 increase during periovulatory days may be considerable (  Figure 5  ).