Division of Endocrinology & Diabetes

Milestones in Thyroid Research at Einstein and Montefiore: 1920-2011

History and Personal Reflections


Martin J. Surks, MD
Martin J. Surks, MD, MACP
Program Director, Division of Endocrinology and Metabolism
Professor of Medicine (Endocrinology) and Pathology

  1. Introduction 
  2. David Marine: 1920-1945 
  3. The Medical Physics Laboratory: early 1940s-~1960 
  4. Jack H. Oppenheimer: 1959 - 1976 
  5. Martin I. Surks: 1966 - 
  6. References 

As a senior member of the faculty of the Division of Endocrinology and Metabolism and Department of Medicine at Montefiore Medical Center and Albert Einstein College of Medicine, whose research and clinical interests have been focused on thyroid physiology and pathophysiology, I am in a unique position to comment on the pioneering thyroid research published by clinicians and scientists who have worked here, beginning in 1920. Findings from this body of research have benefited the health of hundreds of millions of people around the world.

Introduction

Martin J. Surks, MD, MACP
Professor of Medicine (Endocrinology) and Pathology

I have spent most of my career at Montefiore Medical Center and the Albert Einstein College of Medicine, with offices and laboratories located at Montefiore Medical Center. As a senior member of the faculty of the Division of Endocrinology and Metabolism and Department of Medicine whose research and clinical interests have been focused on thyroid physiology and pathophysiology  I am in a unique position to comment on the pioneering thyroid research published by clinicians and scientists who have worked here beginning in 1920. Findings from this body of research have benefited the health of hundreds of millions of people around the world.

Founded in 1884 by leaders of the Jewish community in New York, Montefiore was a hospital designated to care for patients with tuberculosis and other chronic illnesses. How a hospital established for patients with chronic diseases evolved into a major academic institution that valued research as well as clinical care is not clear. The transition occurred, at least in part, by recruitment of staff for clinical duties, who had research interests as well, and were productive both in the research and clinical arenas. Such was the case for Dr. David Marine, recruited as Chairman of Pathology and Director of Research Laboratories in 1920, and some of his successors. Marine remained in that position until retirement in 1945. Marine’s work, as well as others, was supported mainly by Montefiore Hospital under the leadership of E.M Bluestone and Martin Cherkasky.

The e-published Montefiore Milestones provides a list of many "firsts" and signal achievements, but none related to thyroid disease. My objective here is simply to preserve what I can of the historical record of thyroid research at Montefiore Medical Center, as has been done for important achievements in other fields. I accumulated primary documents dating back to the mid-1940s from people who were there, many of whom were my distinguished teachers and colleagues, and friends. They are preserved electronically in the reference section. Since I am not a historian, I hope that this paper and accompanying primary sources may stimulate others to explore areas of interest in a more rigorous manner.

David Marine, MD

Background and Sources 

The most prevalent thyroid disease in the world in the early 20th century was to be recognized later as an iodine deficiency disorder. It included endemic goiter, probable hypothyroidism and endemic cretinism. Its cause was unknown. We now know that iodine deficiency and hypothyroidism not only impairs quality of life but also adversely affects brain development and intellectual function, often permanently. Some estimates by the World Health Organization suggest an average 10 - 20% decrease in economic productivity in affected populations.

Hypothyroidism results from a decrease in secretion of thyroid hormone, l- thyroxine, by the thyroid gland. Iodine is an important component of l- thyroxine, 4 atoms per molecule, reported by EC Kendall in 1915. The iodine content was correct but his proposed chemical structure (an indole) was not. Its structure, synthesis and biological activity in man was reported by Harrington and colleagues in 1925. Kendall went on to determine the structure of cortisone in the mid-1940s, and, with Hench, showed its profound anti-inflammatory effects in patients with rheumatoid arthritis, leading to a Nobel Prize in 1950 for them and T. Reichstein.

Iodine is a trace element and is distributed unevenly in the earth’s crust, being relatively abundant in coastal areas and progressively more and more scarce inland. Since most of the world’s population lived inland, hundreds of millions of people were affected by iodine deficiency. It was David Marine who established in laboratory investigations an association between iodine deficiency and thyroid hyperplasia and goiter. He proposed that endemic goiter was due to iodine deficiency, could be reversed and /or prevented by iodine supplementation and carried out the clinical studies to confirm these hypotheses.

O.P. Kimball, who worked and published with Marine on the epidemiological studies, summarized the classic studies and subsequent history of iodine supplementation in salt, up to 1961. According to Kimball, "The prevention of endemic goiter in man, as it is known today throughout the world, is based entirely on the findings and teachings of David Marine."

I met Josef Matovinovic at my first meeting of the American Thyroid Association in 1969. Learning that I was at Montefiore, he shared with me Marine’s seminal accomplishments. Subsequently, he sent me his publication, which is both a homage to and summary of Marine’s work, replete with Marine’s personal reflections of his research, obtained during interviews.

The Research 

Marine graduated from Johns Hopkins Medical School in 1905, became the first pathologist interested in thyroid disease, initially working in Cleveland, Ohio, an epicenter of endemic goiter both in man and animals. He came to Montefiore Hospital as Chairman of Pathology and Director of Research Laboratories in 1920. His seminal epidemiologic study, reported in 1920, showed that 56% of schoolgirls in Akron, Ohio had goiter, which regressed in 66% of children who took twice yearly iodine supplementation. Separately, while less than 1% of children without goiter developed goiter when treated similarly with iodine, about 20% of girls not taking iodine developed goiter in a 2 ½ year observation period. The studies were the first to show that endemic goiter resulted from iodine deficiency, and could be both treated as well as prevented with iodine supplementation.

His studies were widely confirmed and stimulated introduction of iodine supplementation of salt, addition to water supplies, annual injections of iodinated oils, or other approaches suitable to geographic, cultural, political and religious practices in different populations. Successful iodine supplementation resulted in elimination of iodine deficiency diseases, including endemic cretinism, in those areas which were rendered iodine sufficient.

Subsequent studies by Marine and colleagues and others focused on how to supplement iodine in populations, iodized salt in North America, in order to prevent endemic goiter and cretinism. These studies continue even today, principally in Asia, Africa and South America . Josef Matovinovic told me that Marine was nominated but did not receive the Nobel Prize for this work, but he did not document that in his paper. I was not able to find a listing of nominees for the Nobel Prize in order to confirm this contention.

Other Important Contributions 

  1. Iodine is necessary for normal thyroid function.
  2. Preoperative treatment with iodine decreases the incidence of "thyroid storm" in Graves' patients treated by thyroidectomy.
  3. Iodine uptake in thyroid cancer tissue is much lower than in adjacent normal thyroid (concept of the "cold nodule").

The Medical Physics Laboratory

Background and Sources 

A second major chapter in thyroid research at Montefiore Medical Center was the development of the Medical Physics Laboratory, immediately at the end of World War II. This unit, along with only a few others in the United States, studied the uses of radioactive iodine (I-131) in investigations of thyroid physiology and treatment of thyroid diseases. The leader of this research at Montefiore Medical Center was Samuel M. Seidlin, a practicing endocrinologist, Chief of Endocrinology and part-time investigator.

Samuel M. Seidlin, MD

SAMUEL SEIDLIN.jpgDr. Samuel Seidlin’s pioneering work using radioiodine for diagnosis and therapy of thyroid cancer during the early1940s, published widely in the medical literature and lay press, e.g. LIFE Magazine, made Montefiore known around the world. Observations by Seidlin and colleagues remain the basis for treatment of thyroid cancer and some other thyroid disorders even to this day.

I obtained most of the details concerning this period from a published historical vignette of the beginning of radioiodine therapy of thyroid cancer, and memoir of Samuel M Seidlin by Edward Siegel, PhD, who was Physicist-in-Charge of the Medical Physics Laboratory and Radiation Protection Officer at Montefiore Hospital between 1948 and 1962. Dr. Siegel generously provided me his curriculum vita, listing important publications from the laboratory. Also, at my request, he gave me an unpublished document he prepared for the Montefiore Archives in 1984, on the occasion of the hospital’s 100th Anniversary, describing his personal recollections of his tenure at Montefiore Hospital.

Additional details were provided to me by Bernard A. Sachs, MD (see curriculum vita), who was my friend and one of my teachers. He became a member of the Radioisotope Board in 1952, which still meets weekly, and was its Chairman between 1963 and 1976. Bernie was a practicing endocrinologist, who was Chief of the Endocrine Clinic (1955-1968), which still meets weekly, Head of the Endocrine Service (1960-1968), and Senior Endocrinologist (1968-1976). Bernie established an Endocrine Training Program, which combined with the training program of the Albert Einstein College of Medicine, in 1988. The Division of Endocrinology and Metabolism is headed by Norman Fleischer, MD, and I remain the Program Director of the training program, which has evolved into one of the premier programs in the country. Dr. Sachs also founded and directed the Lipid Metabolism Laboratory (1952 - 1976) and was a Director of the Coronary Drug Project, a multicenter trial to compare effects of estrogen, clofibrate, and D- thyroxine on lowering of blood lipids.

Finally, I had hundreds of interactions with a number of voluntary Attending Physicians who were there, participating in the weekly meetings of the Isotope Board and, variably, in the research that emanated from the Unit. They include Joseph Krakauer, Arthur Bauman, Frank A. Graig, Theodore Spaet, Stanley Kass and Kenneth Rosenheck. They were my teachers and friends, some for decades. In fact, I still use daily in my practice, a Hertel Exophthalmometer, given to me by Frank Graig when he retired from endocrine practice to become Chief of Medicine at Grasslands Hospital, now Westchester Medical Center.

The continuing transformation of Montefiore Hospital from a chronic disease facility to a comprehensive medical center that stressed both general clinical care and clinical investigation was accelerated by the appointment of Dr. Louis Leiter as Chairman of Medicine. Dr. Leiter had published important studies on kidney disease and was an elected member of the prestigious academic societies, the American Society of Clinical Investigation (nickname, "the Young Turks"), and the Association of American Physicians (nickname, "the Old Turks"). He was my Chairman during Internal Medicine training and became a good friend and strong supporter. Samuel Seidlin was one of his first clinical appointments.

Soon after arriving at Montefiore, Seidlin discovered a patient (BB) with severe thyrotoxicosis living on the wards of the hospital. BB had metastatic thyroid cancer, and had a thyroidectomy nearly 20 years earlier. Since his thyroid gland was removed, Seidlin considered the possibility that his known metastases were functional, i.e., producing thyroid hormone in excess, causing thyrotoxicosis. With physicist, L.D Marinelli, he obtained radioiodine made in the cyclotron at MIT-Harvard and administered some to BB. Scanning BB with a hand-held Geiger counter gave startling results. All known metastases were highly functional, and an additional skull metastasis was discovered by scanning the area at BB’s request because of pain in his skull that "was not a headache". Dr. David Marine was there and commented that he had seen many thyroid metastases over the years but this was the first time he heard metastases "talk" (the audible clicks of the Geiger counter). Seidlin’s group treated BB in 1943, and then repeatedly with radioiodine, until the metastatic lesions no longer accumulated the isotope (1949). His pain disappeared, thyrotoxicosis remitted and he regained his body weight. No new lesions appeared and some completely disappeared over a period of nearly 10 years. BB died in 1952 with autopsy proven anaplastic carcinoma, thought to be due to the large amounts of radioiodine he had received.


From left: B.B. before treatment (1943), B.B. after treatment (1949)
Over the years, more than 30 patients with metastatic thyroid cancer were studied, and 16 with functioning metastases were treated with radioiodine. All had total thyroidectomy before treatment so that normal thyroid tissue did not compete with the metastases for the administered isotope.

At the time of the first treatment of BB, there were only 2 other laboratories in the United States that were studying radioiodine in man, and none had treated a comparable patient. The success of the treatment in this patient was widely publicized in the medical literature (5, 7) and the lay press (Life Magazine). Major figures from all over the world came to Montefiore to learn from this experience and for advice on setting up their own isotope facilities (7) .

After Seidlin’s death in 1955, the Medical Physics Laboratory continued to make important contributions to the diagnosis and management of thyroid disease. A long list of publications emanated from the laboratory (5, 7). Particularly notable was the finding that technetium localized to but was not retained by the thyroid, and that agent is still used today. Also, Montefiore contributed 603 carefully followed patients, who had been treated with radioiodine for hyperthyroidism, to a national cooperative study to determine the safety of this therapeutic approach. The long term incidence of thyroid cancer after radioiodine treatment of hyperthyroidism was lower than that of patients treated with antithyroid drugs. Thus, both the effectiveness and safety of the first treatment of a non-malignant disease with radioisotopes was established.

The Medical Physics Laboratory was so active in patient management and research that, in the 1950s, it was the largest consumer of radioiodine in the world (per Dr. Abersold, Atomic Energy Commission (5, 7)). The laboratory gradually evolved into the Department of Nuclear Medicine.

Vignette Concerning the Medical Physics Laboratory and Rosalyn S. Yalow, PhD, Nobel Laureate

Question: Did Dr Rosalyn Yalow cross paths with Dr Seidlin and colleagues at the Medical Physics Laboratory at Montefiore, before establishing the isotope laboratory at the VA Hospital, Bronx, NY?

Aaron Yalow and Rosalyn Sussman, 2 young physicists met during postdoctoral training in the Midwest . After they married and returned to New York , Aaron took a position with the Medical Physics Laboratory at Montefiore and for many years participated in the research efforts of the group. He is coauthor of papers published from the laboratory, and continued as a consultant both to the laboratory and to other laboratories using radioisotopes, including those of Jack H. Oppenheimer and Martin J. Surks.

Rosalyn S. Yalow, PhD 

Dr. Rosalyn (now) Yalow was recruited by the Veterans Administration Hospital, Bronx , NY to develop an isotope unit. She was quickly joined by Solomon A. Berson, MD. Their joint investigations first in thyroid disease and then on the metabolism of radioactively labeled proteins, including albumin and insulin, led to important findings that resulted in development of the radioimmunoassay, a new type of measurement that quickly revolutionized biology and medicine. Their new technology enabled measurements of biological substances, including hormones, at picomolar concentrations. Their classic paper on insulin binding to globulins was initially rejected by the Journal of Clinical Investigation. Their work eventually resulted in a Nobel Prize to Dr Yalow. Unfortunately, Sol Berson met an untimely early death and could not share the prize, which is not awarded posthumously.
 

Solomon A. Berson, MD 

Since the VA Hospital was only several miles away from Montefiore Hospital , and since her husband was working in the Medical Physics Laboratory; it would be no surprise if Rosalyn Yalow obtained some experience in that laboratory that may have helped her develop the new isotope facility at the VA. I recalled hearing that this was the case in a talk by David V. Becker, MD, Chief Division of Nuclear Medicine at New York Hospital , in his Presidential Lecture to the American Thyroid Association in 1983. He mentioned that Ros had spent some time at the Medical Physics Laboratory at Montefiore Hospital . However, I was unable to find documentation for this in her biography, autobiography, the Internet or from discussions with Jesse Roth, MD Jesse, s friend of long duration, was a Fellow at the VA in 1961-3, when I was a medical resident there (Sol Berson was my Attending in Medicine for 4 months). Jesse and Shimon Glick, his co-Fellow, developed a radioimmunoassay for Growth Hormone and demonstrated the dependence of growth hormone secretion on blood glucose.
 

Through the courtesy of a distinguished colleague and friend, James Hurley, MD, now Emeritus Associate Professor of Medicine, who was a long time colleague and close friend of David Becker, I obtained a copy of David Becker’s presidential address to the members of the American Thyroid Association, given on October 7, 1983. He related a personal communication to him from Ros that mentioned her association with the Medical Physics Laboratory at Montefiore before she worked at the VA Hospital.

David’s address was extensively documented and includes a copy of a footnote on page 843 from the classic 1946 JAMA paper of Seidlin et al. The footnote states: "Dr. E. J. Baumann, Chemistry Department, Montefiore Hospital , developed a procedure for extracting iodine from the urine so that it could be refed to the patient in the form of sodium iodide. This technique was utilized whenever the amount of I* involved warranted it. The efficiency of recovery was consistently high, 80 to 95%."

Later in David’s talk: "To maximize the effect from the expensive isotope. Emil J Baumann who ran the chemistry laboratory at Montefiore Hospital and who had collaborated with David Marine on many thyroid studies extracted the radioiodine from the patient's urine so it could be re-administered. A young volunteer was assigned the task of purifying the urine. Her name was Roslyn Sussman and she had recently married Aaron Yalow, a physicist on their team. She tells me that it was her first clinical exposure to radioiodine"

It is interesting to conjecture that this cross-fertilization may have contributed to the fact that the initial published studies of Berson and Yalow, with another friend, Dr. Arthur J. Bauman, from the new VA Laboratory focused on the thyroid.

Jack H. Oppenheimer, MD

The third chapter, which overlapped the second, began with the recruitment of my mentor and friend, Dr Jack H. Oppenheimer, who established the Endocrine Research Laboratory at Montefiore in 1960. His laboratory became famous throughout the world for a series of important research findings on thyroid physiology, pathophysiology, disease and mechanisms of action of thyroid hormones.

Jack’s initial interest was neuroendocrinology and, to that end, during Fellowship in Endocrinology at Columbia College of Physicians and Surgeons. He did a study of thyroid levels (measured as protein-bound iodine) in patients with seizures, most treated with phenytoin (Dilantin). The neurology residents tried to dissuade him, telling him that thyroid levels were always low in these patients, a finding that had never been reported. Jack’s study confirmed their impression and showed that the fall in thyroid levels occurred within a few days after treatment with Dilantin started.

Jack’s extraordinary talent was always to jump forward from even simple clinical observations made in man or animals to work out their mechanism. In this case, now at Montefiore, he showed that Dilantin competed with thyroxine for binding sites on the specific proteins that transported thyroid hormone in blood to tissues throughout the body, and in a further study that structural analogues of Dilantin, interacted in a manner consistent with their degree of homology with the hormone (11). His studies with thyroid binding proteins, above, stimulated him to develop the first practical method for measurement of free thyroid hormones, thought to be the biologically active form of the hormone. His findings in this area are the basis for Free T4 measurement used widely around the world today.

He then isolated a third binding protein, thyroxine-binding prealbumin, now called transthyretin, and studied its metabolism in man. Jack was the first experimental subject to receive this isotopically labeled protein and I was the second. He put these findings together in a classic study of the effect of nonthyroidal disease on free T4 and the binding proteins that still forms the basis of how we think about influence of illness and other catabolic states on the thyroid system. This is usually called either the euthyroid sick or low T3 syndrome. When methods became available for T3 measurement, he and colleagues showed that nonthyroidal disease or any catabolic state, including restriction of calories alone, was associated with a decrease in serum T3 and Free T3.

His next years at Montefiore focused on two lines of research. First were quantitative studies of T4 and T3 metabolism, which established the extent of T4 conversion toT3, and showed that the effect of propylthiouracil on lowering T3 in blood was due to inhibition of the conversion reaction, coming to the remarkable conclusion that T3, not T4, was the principal thyroid hormone. Metabolic studies in man, in which both of us were again subjects, suggested that the dose of thyroxine used for treatment of hypothyroidism, 300 ug per day at that time, was much too large. Using the newly developed assay for thyrotropin ( TSH ), he and colleagues showed that the average replacement dose was actually about 150 ug per day, a finding that had enormous impact on patient care around the world.

The second line of research was on the consequences of rate of entry of thyroid hormones from plasma to tissues. Prevailing concepts were that thyroid hormone in blood enters tissues slowly, accounting for the relatively slow biological effects of the hormone. He showed that the opposite was true, that thyroid hormones in blood rapidly exchanged with thyroid hormones in tissues, and that the exchange rates could be manipulated by the use of certain drugs, such as Phenobarbital. Although thyroid hormone was bound to all subcellular fractions, only the nucleus had a limited number of binding sites, which, when characterized, had all attributes of hormone receptors ; i.e. binding sites that were directly linked to biological effects of the hormone. That conclusion was proven correct with the subsequent cloning of the thyroid hormone receptors some years later.

At Montefiore, he moved quickly up the ranks to Professor of Medicine, and Head of the Division of Endocrinology, succeeding Dr Bernard Sachs. He moved to the University of Minnesota in 1976 to be Director of the Division of Endocrinology and Metabolism, and the Thyroid Research Unit, and was Professor of Medicine, Cell Biology and Neuroscience.

Along with many Fellows and colleagues, he continued to be very productive studying the regulation by thyroid receptors of various gene products. His laboratory reported a series of papers on molecular mechanisms underlying thyroid hormone-stimulated lipogenesis, another series on identification of the S14 gene as a primary target for rapid thyroid hormone action and model for studies of the molecular mechanisms of thyroid-stimulated lipid synthesis and, a new area, involving the molecular mechanisms underlying hormone-dependent brain development. Still concerned with clinical thyroidology, he reported on regulation of TSH by T4 and T3, and on the dosage of thyroxine required for management of thyroid cancer. His curriculum vita lists nearly 270 peer-reviewed research papers.

Jack Oppenheimer was widely recognized as one of the most productive and original clinical investigators in the world. He was elected to prestigious academic societies, the American Society of Clinical Investigation and the Association of American Physicians, served on Editorial Boards of prestigious Journals, and on the Endocrine Study Section of the National Institute of Health. He was very active in the American Thyroid Association, chairing many committees, serving on its Council, and was elected its President (1985). He received the Van Meter Award for outstanding research by a young investigator, (1965) and its Distinguished Service Award (1992). He was widely sought after as Visiting Professor both in the United States and internationally. He trained nearly 75 endocrine fellows and graduate students. Beginning at Montefiore, Jack was considered to be one of the most outstanding clinical scientists of his time.

Martin I. Surks, MD, MACP

The fourth and still ongoing chapter describes the contributions of Dr. Martin I. Surks, who trained in Internal Medicine at Montefiore (Dr. Louis Leiter) and at the Bronx VA Hospital (Drs. Julius Wolf and Solomon Berson), then in Endocrinology with Dr. Jack Oppenheimer. He came to Montefiore to train in general medicine because all PGY-1 positions required training in surgery and pediatrics as well as medicine. Although his goal was to practice medicine, he was also impressed that the hospital supported a metabolic ward for research.

A career changing chance meeting with Jack Oppenheimer redirected him to endocrinology. He admitted a 55-year old with a mild urinary tract infection. The patient seemed to have low intelligence, doing menial work for the New York City Parks Department. Examination revealed a left Babinski sign. Surks remembers being in the X-ray reading room trying to interpret the patient’s clearly abnormal skull X-ray, when a voice behind him said, “I see you have a case of hypoparathyroidism here.” Of course, it was Jack. He helped Surks and his resident, David Levenson, evaluate and treat the patient. Serum calcium, which took several days to measure, was very low and phosphorus was high. Since history was negative for primary causes, Jack suggested we do a workup for pseudohypoparathyroidism, only 45 cases previously reported in the literature. Surks and David Levenson were controls for the Ellsworth-Howard tests then employed to determine whether the PTH extract was bioactive. The findings showed that the crude parathyroid extract, then available, was active, but the patient did not respond to it. Nor did he raise serum calcium after repeated PTH injections. Both findings supported the diagnosis of pseudohypoparathyroidism. A published report with David Levenson was Dr. Surks’ first paper, and stimulated him to spend time in Jack’s laboratory.

After a productive NIH-sponsored Fellowship under Jack, he obtained a research position in the US Army, stationed at the Medical Research and Nutrition Laboratory at Fitzsimons General Hospital, Denver, CO. Assigned to study the effects of high altitude exposure on human performance, he published a number of studies focused on thyroid hormone and protein metabolism at high altitude, Pike’s Peak, CO, 14,010 feet. The most important was a demonstration of marked loss of water from the plasma and extracellular compartment, without decrease in total body water. The shift in body water from the extracellular to the intracellular compartment likely contributes to the frequently disabling high altitude headache, a finding supported by recent studies that employed MRI techniques.

He returned to Montefiore and continued to work on high altitude effects on cellular metabolism and also worked closely with Jack Oppenheimer on studies of thyroid hormone turnover and absorption. He developed reagents to set up radioimmunoassays for T4 and T3, and a TSH assay with reagents from the National Pituitary Agency, NIH. These assays formed the basis of the Endocrine Diagnostic Laboratory at Montefiore, which still prospers today. He studied patterns of serum T4 and T3 concentrations after patients ingested various thyroid hormone preparations then available for hormone replacement, and on a major revision of dosage of levothyroxine in hypothyroid patients.

When Jack Oppenheimer moved to Minnesota in 1976, Dr. Surks was appointed his successor, and in 1978, Professor of Medicine. In addition to developing the endocrine training program and endocrine division and providing voluntary service to the endocrine community, his laboratory pursued several lines of research, funded by the National Institutes of Health. With a number of colleagues, particularly Dr.Charles DeFesi, he developed methods for determining the number of pituitary cells in rat pituitary, particularly thyrotrophs ( TSH secreting) and somatotrophs (GH secreting), and their dependence on thyroid state. In contrast to the then prevailing concept that pituitary progenitor cells could evolve into specific cell lines, they showed unique thyroid hormone regulated rates of replication and degradation of the individual cell populations.

He further studied animal models of nonthyroidal disease, the tumor bearing rat, and effect of tumor on regulation of T3 receptors and response to T3. In cultured GC (GH-producing), his group reported dependence of cell replication and amino acid uptake on T3, that the effect occurred early in the G1 phase of the cell cycle, that the S phase (DNA synthesis) was associated with a doubling of T3 receptors in parallel with DNA, and that, in rats, T3 increased the secretion of GH and GH mRNA, and decreased TSH secretion and B-TSH mRNA.

Another line of research focused on development of method for measurement of Free T4, in undiluted serum, at physiologic temperature and pH. Those studies in collaboration with Drs. Kenneth Hupart and Charles DeFesi showed that Free T4 was unchanged even in severe nonthyroidal disease and also led to an understanding of the mechanism of the Dilantin-induced decrease in serum T4 and Free T4 that was described first by Jack Oppenheimer (see above). The laboratory showed that the Dilantin effect was only a laboratory artifact since Free T4 was unchanged in Dilantin-treated patients when measured in undiluted serum.

During the last decade, Surks has been a key contributor to the debate on the TSH reference range and subclinical hypothyroidism. He chaired the evidence-based consensus development conference on subclinical hypothyroidism, and with colleagues argued against the abrupt recommendation to decrease the upper reference limit for TSH to 2.5 mIU/L, a recommendation that still remains unsupported by new data.

Since the prevalence of subclinical hypothyroidism is nearly 15% in apparently thyroid disease-free older people, Surks and Joseph G. Hollowell studied that group intensely. They demonstrated that older people, as a population, shift their TSH distribution to higher values, and that about 50% of older people thought to have subclinical hypothyroidism based on a minimal increase in TSH , have values within their age-specific reference limit. Thus, the prevalence of subclinical hypothyroidism appears significantly overestimated, a finding that influences the categorization of millions of older people with or without thyroid disease. Further studies with Laura Boucai confirmed the observations and also showed specificity of TSH distribution in different race and ethnic groups. These very recent studies argue strongly for development of age- and race/ethnic-specific reference limits for TSH in order to minimize misclassification of people with thyroid disease, particularly older people, Finally, studies done in collaboration with colleagues at the Ageing Institute at Albert Einstein College of Medicine, Gil Atzmon, Ilan Gabriely and Nir Barzilai showed that the age-related shift in TSH distribution to higher values with age was genetically determined and associated with 2 SNPs in the TSH receptor that may contribute to longevity.

Dr. Surks was recognized for his contributions to thyroid research by election to prestigious scientific academic societies, the American Society for Clinical Investigation, the Association of American Physicians, and the Interurban Clinical Club. He received a Mastership from the American College of Physicians. His Curriculum Vitae lists 210 publications. He served on Editorial Boards of Endocrinology and the Journal of Clinical Endocrinology and Metabolism and on grant review boards for the Veterans Administration and the National Institute of Health. He was a member of the Endocrine Section of the American Board of Internal Medicine and its Chairman for 4 years. He was a founder of both the Endocrine Self Assessment Program and its Editor-in-Chief and of the Association of Program Directors of Endocrinology and Metabolism and served as its President. He was very active in the American Thyroid Association, serving as its Secretary, (COO) for 5 years and its President. Dr. Surks was given its Van Meter Award for research and its Distinguished Service Award. He was also awarded d the Sidney H. Ingbar Distinguished Service Award by the Endocrine Society for service to the field. He has trained 70 Fellows and continues as Program Director of the endocrine training program at Albert Einstein College of Medicine.

References

  1. Montefiore Milestones  
  2. Kimball OP 1961. Prevention of Endemic Goiter in Man; Archives of Internal Medicine; 107: 190-204. (PDF)
  3. Matovinovic J 1978. David Marine (1880-1976); Nestor of Thyroidology; Perspectives in Biology and Medicine; Summer Issue: 566 - 589 (PDF)
  4. Marine D, Kimball OP 1920. The Prevention of Simple Goiter in Man; Archives of Internal Medicine; 661-672. (PDF)
  5. Seidlin SM, Marinelli LD, Oshry E 1946. Radioactive Iodine Therapy Effect on Functioning Metastases of Adenocarcinoma of the Thyroid. JAMA 132; 838-847. (PDF)
  6. Siegel E 1999. The Beginnings of Radioiodine Therapy of Metastatic Thyroid Cancer: A Memoir of Samuel M. Seidlin, MD (1895- 1955) and His Celebrated Patient. Cancer Biotherapy & Radiopharmaceuticals; 14: 71- 79. (PDF)
  7. Curriculum Vitae: Edward Siegel, PhD (PDF)
  8. Siegel E May 25, 1984, Corrected September, 2003. Some Recollections of my Tenure at Montefiore Hospital: A Half-Life with Radioiodine and the Thyroid Gland. (to the author’s knowledge, unpublished) (PDF)
  9. Curriculum Vitae: Bernard A. Sachs, MD (PDF)
  10. Becker DV; Presidential Address to the American Thyroid Association, October 7, 1983. (PDF)
  11. Curriculum Vitae: Jack H. Oppenheimer, MD (PDF)
  12. Curriculum Vitae: Martin I. Surks, MD, MACP (PDF)
 

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