Robert I. Gregerman, MD (1930-2021). An Editorial Reminiscence.

Abstract

Robert I. Gregerman, MD, a luminary in endocrine research and a pioneering investigator of the metabolic aspects of aging, died October 6, 2021, in San Antonio, Texas, at age 91 years. At the time of his death, following a protracted illness, he was at home, with family and hospice care members by his side. Dr. Gregerman leaves behind a distinguished legacy of academic accomplishment embodied in 60 years of innovative contributions to the medical literature and in generations of trainees who have themselves become leaders in the fields of endocrinology and biomedical gerontology. Robert (Bob) Gregerman (Figure 1) will be remembered as among the inaugural group of gifted scientists presciently recruited by Nathan W. Shock, PhD (1907– 1989), to “grow” the first inter-disciplinary program on aging research at the National Institutes of Health (NIH). In 1956, as a newly minted commissioned officer in the United States Public Health Service (USPHS), Bob arrived at Dr. Shock’s brainchild, then known as the Gerontology Branch of the National Heart Institute and a uniquely creative hybrid of a research enterprise–operating administratively as a unit within the NIH, housed on the grounds of the Baltimore City Hospitals (BCH) and affiliated academically with the Johns Hopkins University School of Medicine several miles away. By 1961, Bob had become the founding chief of the Endocrine Section within the Gerontology Branch, which in 1968 moved into its own NIH-financed building, designated the Gerontology Research Center (GRC), on the BCH campus, and subsequently matured into the intramural research program of the National Institute on Aging (NIA) established in 1974. Bob Gregerman’s laboratory at the GRC remained at the forefront of investigations into the endocrinology of aging for another two decades, during which time he was promoted to Professor of Medicine at Johns Hopkins. Then, in 1994, following retirement from the USPHS he moved with his wife Marjorie to San Antonio, Texas (Figure 2), to direct the research programs of the San Antonio Geriatric Research, Education and Clinical Center (GRECC) at the Audie L. Murphy Memorial Veterans Hospital, and with an appointment as Professor of Medicine at the affiliated University of Texas Health Science Center at San Antonio (UTHSCSA). In San Antonio, he extended the research inquiries he had long pursued in Baltimore, until formal retirement in 2011 afforded him time and opportunity for his favored activities, namely, visiting the UTHSCSA medical library to keep abreast of the literature and conferring with former trainees and colleagues over advances in the biology and endocrinology of aging. Many years earlier, he had written, “my field always serves as a reminder of the finiteness of time.” In the last years of his life (Figure 3), then, when his scientific endeavors, and his delight in pursuing them, did recede under the assaults of time, it likely came to him with regret but as no great surprise. For those who admired Bob Gregerman and considered his influence a constant in their lives, there remains the science, the work, the striving for a kind of benevolent truth. The substance of his scientific contributions represents a progression of illuminating discoveries anticipating, and in many cases directly generating, research trends in endocrinology and aging. Over many years, for example, his research focus on thyroid physiology introduced findings that continue to inform concepts of thyroid hormone metabolism during aging and illness. In early collaboration with Nathan Shock, Bob conducted kinetic studies of thyroxine (T4) turnover in healthy men, demonstrating a 50% decrease of T4 degradation over the adult age span of 20–80 years. He reasoned that this finding, together with earlier observations of generally stable T4 blood levels yet reduced thyroid accumulation of radioiodide with age, in turn implied that levothyroxine replacement dosage requirement for hypothyroidism should be decreased in older individuals – an hypothesis subsequently confirmed in multiple clinical studies and discussed under current guidelines for the treatment of hypothyroidism in the elderly. In later work, Bob extended his studies of thyroid hormone metabolism in humans to states of nonthyroidal illness, showing that, unlike the case with aging, peripheral disposal of T4 is accelerated (if not invariably so) during the course of acute infectious illnesses. The same studies revealed infection-related increases in circulating concentrations of free T4 (FT4) unassociated with changes in concentrations of thyroid hormone-