When Hormones Fail To Act

In this issue, Brucker-Davis and colleagues [1] give us a better definition of resistance to thyroid hormone. Most of the patients in their study had the attention-deficit hyperactivity disorder, and many had an IQ that was lower than expected. All had elevated serum thyroid hormone levels, although the variation was wide. Interestingly, most had serum thyroid-stimulating hormone concentrations within the normal range; furthermore, pulse and basal metabolic rates were about the same in patients and controls. Few patients were overtly hypothyroid or hyperthyroid, but most had some features of these states.

How did diseases with poorly acting hormones come to be recognized in the first place? And what do these uncommon disorders mean for practitioners?

The idea of a hormone-resistant disease is usually traced to 1942 and Fuller Albright of the Massachusetts General Hospital. In that year, Albright wrote an article titled “Pseudo-hypoparathyroidism—an example of ‘Seabright-Bantam Syndrome.’ Report of three cases” (2; see facsimile reprint in 3). The disease was called “pseudo” because it resembled a known disease—hypoparathyroidism—but the injection of parathyroid hormone into one patient did not produce the expected increases in serum calcium concentration or urinary phosphate excretion.

Albright's report was seen as the first to show the failure of an end-organ response to a hormone. Albright was, in fact, more cautious. He was certainly looking for such a failure and wrote, but only speculatively, that there might be “a deficiency in or interference with some hypothetical substance with which parathyroid hormone reacts.” But he also noted that there could be “blood antibodies (‘antihormones’) to the parathyroid hormone” and that “there are probably further possibilities.” Perhaps his insight was to regard these patients as fundamentally different from those who did indeed lack hormones.

Albright's 1942 report was not a “bolt from the blue.” He had been mulling over …