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| Physicians Against Obesity |
| PHYSICIANS AGAINST OBESITY AUTHOR: CALVIN EZRIN, M.D., F.A.C.P, F.R.C.P.C. The rising incidence of obesity has continued in the face of the best efforts of physicians to control it. All authorities agree that our genes cannot change in such a short time, therefore, environmental factors must be largely responsible. Fast foods and inadequate exercise have been blamed. Public health policies are now directed to encourage healthier lifestyles. These measures are praiseworthy and give promise of considerable benefit in the fullness of time. I am writing to offer my colleagues a novel concept of control of overweight that has been remarkably successful in my office practice of endocrinology. It is based on the control of two principle chemicals, namely insulin and serotonin. Selective insulin resistance to its hypoglycemic effect is common in obesity with resultant compensatory hyperinsulinism. However, because insulin is the dominant fat-building and fat-storing hormone of the body, functions that are not impaired in the insulin resistant state, hyperinsulinism contributes to further weight gain. Also, adipokines, resistin, IL-6, and TNF" produced in fat contribute significantly to the accompanying insulin resistance, setting up a vicious cycle of fat begetting more fat. An initial weight gain of as little as 15 to 20 pounds from a variety of possible causes, e.g., depression, pregnancy, smoking cessation, steroids, or inactivity, sets in motion a progressive process that no longer requires that the inciting cause be present. Initially most of the added fat is deposited in the abdomen where insulin resistant adipokines are produced. Insulin also appears to be appetite stimulating, contributing to further weight gain. Ultimately, when enough weight has been gained, adding to the insulin resistance, the compensatory over-production of insulin becomes insufficient to maintain normoglycemia and PHYSICIANS AGAINST OBESITY Page 2 type 2 diabetes results. However, if weight can be lost the diabetes can be reversed. If insulin is reduced by a low-calorie, low-carbohydrate diet aided by aerobic exercise, fat is released from storage and becomes available as a major source of energy. Weight loss is enhanced by sufficient insulin reduction to produce a mild beneficial ketosis which results in decreased appetite and a mild naturesis. Testing urine ketones morning and night helps to regulate carbohydrate intake which should be reduced sufficiently to maintain a steady, light positivity. Supplementary multivitamins and calcium should be added to compensate for the reduced nutrients normally produced by fruits and vegetables. There is no need for extra protein or fat on this regimen. So far, the program outlined seemed destined for success, but like every other low-calorie regimen, after initial promising results, it ultimately fails. Serotonin deficiency is behind the futility of calorie-restricted diets. Serotonin is the principle neurotransmitter that determines the fate of the other 39 by regulating the quality of sleep. It is depleted by chronic stress and also by dieting, especially low-carbohydrate programs. Since cerebral serotonin is confined to the brain by the blood-brain barrier, it is not measurable by blood tests. The chief clinically relevant symptoms of serotonin deficiency are: 1. Sleep disturbances, e.g. insomnia, middle-of-the-night awakening, snoring, sleep apnea, and daytime fatigue. 2. Carbohydrate cravings which temporarily provide a brief burst of serotonin via an insulin-mediated increased transfer of tryptophane (the precursor of serotonin) across the blood-brain barrier. Although the comfort produced by the surge of serotonin is short-lived, the calories consumed to produce it are more lasting. This desperate search for serotonin from carbohydrate-containing comfort foods accounts for the inability of PHYSICIANS AGAINST OBESITY Page 3 dieters, after initial success, to continue to lose. Ultimately, they regain weight, often to more than they lost. Because long-term success on calorie-restricted diets is so rare, physicians have generally lost interest in dietary approaches to resistant overweight. Commercial programs have taken up the task with no greater success in the long run. Physicians can recapture their proper influence in obesity management by adopting the serotonin-deficiency model and the means to correct it. Serotonin can be replenished only by repeated deep sleep. Normally, under the influence of sufficient serotonin, sleep progresses from a shallow dream-ridden state, in which the eyes track the dreams on a mental screen (R.E.M. or rapid eye movement sleep), to a deeper level of non-R.E.M. sleep which is dreamless and associated with the multiplication of all 40 neurotransmitters. The main function of sleep appears to be the replenishment of neurotransmitters depleted during the day. When serotonin is deficient, sleep does not progress sufficiently beyond the REM level and, even after several hours of light sleep, the individual awakens tired and has diminished energy in the day that follows. The patients cannot sleep deeply because they lack sufficient serotonin; but they lack serotonin because they cannot sleep deeply. How can serotonin be replenished from an external source to initiate deep restorative sleep? To answer this question requires understanding of the mechanisms of action of known serotonin-related agents, namely, trazodone, the SSRI’s, and fenfluramine. For sleep enhancement, trazodone, an early weak antidepressant, is the most suitable source of serotonin. It is a serotonin modulator, capable of temporarily increasing minimal amounts of cerebral serotonin to provide a “jump-start” for the process of sleep, allowing it to descend to the deeper restorative level that otherwise could not be achieved. At the end of the night the initial PHYSICIANS AGAINST OBESITY Page 4 level of serotonin will have been multiplied to produce beneficial effects in the day to follow. These are increased energy and mental function, curbing of carbohydrate cravings, and a gradual refilling of a depleted serotonin reservoir. After many nights of good sleep, sufficient serotonin will have been replenished to allow the gradual withdrawal of the trazodone. If sleep disturbances or carbohydrate cravings reappear, then the withdrawal should be postponed unless a less stressful period is available. Thus, rather than being addictive, ultimately trazodone makes itself unnecessary. Trazodone is very well tolerated with minimal side effects, the most spectacular, though rare, being priapism. This sustained erection can easily be treated by an ephedrine-containing cold remedy, e.g., Sudafed. Selective serotonin re-uptake inhibitors (SSRI’s) are better antidepressants than trazodone but their mode of action does not favor sleep. They inhibit the inactivation of serotonin by blocking its re-uptake and thereby recycle it without actually increasing it. Therefore, they do not add to the depleted store of serotonin. Fenfluramine, the serotonin-related component of phen-fen, increased the release of pre-formed systemic serotonin to produce toxic cardiac and pulmonary effects which led to its withdrawal. In practice, a new patient complaining of resistant obesity should be informed about the important roles of insulin excess and serotonin deficiency. These are described in lay terms in my book “Your Fat Can Make You Thin.” Since there are no laboratory tests for serotonin deficiency, trazodone in a small, initial dose (e.g. 25 to 100 mg) should be prescribed immediately along with a low-calorie, low-fat, low-carbohydrate, normal protein diet, plus appropriate multivitamin and calcium supplements. Exercise suggestions as described in my book help to round out the program. Testing for ketones in the urine, a.m. and p.m. with Ketostix, should begin within two days to PHYSICIANS AGAINST OBESITY Page 5 determine that insulin has been adequately reduced to permit excessive fat to be used as a major source of energy. Ketosis testing involves the patient as the managing partner of the weight-loss enterprise. If ketones become negative, the cause can usually be easily identified by the patient and corrected promptly. Serotonin status can be determined by symptoms of carbohydrate cravings or sleep disturbance. However, the presence of ketosis is objective evidence of adequate serotonin, which, if deficient, would have produced carbohydrate cravings and a resultant rise of insulin with its antilipolytic and antiketotic effects. Ketosis is associated with naturesis, which is more evident in the early weeks of treatment. In women with initial fluid retention, rapid water-weight loss can produce postural hypotension and the risk of fainting. Salt should not be restricted at this time; at least 5 gm (1 teaspoons) or equivalent in salty foods, (e.g. pickles) should be prescribed, otherwise there are no significant complications. Diabetes should come under better control because of the low-carbohydrate diet and, ultimately, because of the loss of fat and its insulin-resisting adipokines. With sufficient weight loss and adequate insulin reserve, diabetes has often been reversed. There is no fixed dose of trazodone that is suitable for everyone. Therefore, until carbohydrate cravings and sleep disturbances are controlled, the dose should be gradually increased at intervals of one to two weeks. A maximum dose of 600 mg was proposed when it was first used as an antidepressant, but it is unusual to require that amount in this weight-loss program. The “Insulin Resistance Syndrome” has blossomed into a collection of wide-ranging disorders, beginning with cardiovascular disease, some malignancies, infertility, and diabetes. Resistance to the hypoglycemic effect of insulin is common to these conditions. An important, but not necessarily the only cause, of this resistance is excess adipose tissue. Reversal of adiposity is the logical first step in the management of these disorders. Lifestyle PHYSICIANS AGAINST OBESITY Page 6 changes leading to weight loss have proven superior to medication in the prevention of diabetes. What is missing from medical practice is a simple, effective program of permanent weight loss that could be employed with confidence by doctors confronted by these hitherto discouraging patients. With the temporary aid of serotonin-enhancing trazodone, and the effective utilization of the beneficial effects of insulin reduction, we can achieve permanent control of overweight. The details of stabilization and maintenance of the desired weight are contained in my book which also presents a useful approximation of the presumed pathophysiologic process that lends itself to a practical solution. It has worked well in my practice and it should also work for you. PHYSICIANS AGAINST OBESITY AUTHOR: CALVIN EZRIN, M.D., F.A.C.P, F.R.C.P.C. The rising incidence of obesity has continued in the face of the best efforts of physicians to control it. All authorities agree that our genes cannot change in such a short time, therefore, environmental factors must be largely responsible. Fast foods and inadequate exercise have been blamed. Public health policies are now directed to encourage healthier lifestyles. These measures are praiseworthy and give promise of considerable benefit in the fullness of time. I am writing to offer my colleagues a novel concept of control of overweight that has been remarkably successful in my office practice of endocrinology. It is based on the control of two principle chemicals, namely insulin and serotonin. Selective insulin resistance to its hypoglycemic effect is common in obesity with resultant compensatory hyperinsulinism. However, because insulin is the dominant fat-building and fat-storing hormone of the body, functions that are not impaired in the insulin resistant state, hyperinsulinism contributes to further weight gain. Also, adipokines, resistin, IL-6, and TNF" produced in fat contribute significantly to the accompanying insulin resistance, setting up a vicious cycle of fat begetting more fat. An initial weight gain of as little as 15 to 20 pounds from a variety of possible causes, e.g., depression, pregnancy, smoking cessation, steroids, or inactivity, sets in motion a progressive process that no longer requires that the inciting cause be present. Initially most of the added fat is deposited in the abdomen where insulin resistant adipokines are produced. Insulin also appears to be appetite stimulating, contributing to further weight gain. Ultimately, when enough weight has been gained, adding to the insulin resistance, the compensatory over-production of insulin becomes insufficient to maintain normoglycemia and PHYSICIANS AGAINST OBESITY Page 2 type 2 diabetes results. However, if weight can be lost the diabetes can be reversed. If insulin is reduced by a low-calorie, low-carbohydrate diet aided by aerobic exercise, fat is released from storage and becomes available as a major source of energy. Weight loss is enhanced by sufficient insulin reduction to produce a mild beneficial ketosis which results in decreased appetite and a mild naturesis. Testing urine ketones morning and night helps to regulate carbohydrate intake which should be reduced sufficiently to maintain a steady, light positivity. Supplementary multivitamins and calcium should be added to compensate for the reduced nutrients normally produced by fruits and vegetables. There is no need for extra protein or fat on this regimen. So far, the program outlined seemed destined for success, but like every other low-calorie regimen, after initial promising results, it ultimately fails. Serotonin deficiency is behind the futility of calorie-restricted diets. Serotonin is the principle neurotransmitter that determines the fate of the other 39 by regulating the quality of sleep. It is depleted by chronic stress and also by dieting, especially low-carbohydrate programs. Since cerebral serotonin is confined to the brain by the blood-brain barrier, it is not measurable by blood tests. The chief clinically relevant symptoms of serotonin deficiency are: 1. Sleep disturbances, e.g. insomnia, middle-of-the-night awakening, snoring, sleep apnea, and daytime fatigue. 2. Carbohydrate cravings which temporarily provide a brief burst of serotonin via an insulin-mediated increased transfer of tryptophane (the precursor of serotonin) across the blood-brain barrier. Although the comfort produced by the surge of serotonin is short-lived, the calories consumed to produce it are more lasting. This desperate search for serotonin from carbohydrate-containing comfort foods accounts for the inability of PHYSICIANS AGAINST OBESITY Page 3 dieters, after initial success, to continue to lose. Ultimately, they regain weight, often to more than they lost. Because long-term success on calorie-restricted diets is so rare, physicians have generally lost interest in dietary approaches to resistant overweight. Commercial programs have taken up the task with no greater success in the long run. Physicians can recapture their proper influence in obesity management by adopting the serotonin-deficiency model and the means to correct it. Serotonin can be replenished only by repeated deep sleep. Normally, under the influence of sufficient serotonin, sleep progresses from a shallow dream-ridden state, in which the eyes track the dreams on a mental screen (R.E.M. or rapid eye movement sleep), to a deeper level of non-R.E.M. sleep which is dreamless and associated with the multiplication of all 40 neurotransmitters. The main function of sleep appears to be the replenishment of neurotransmitters depleted during the day. When serotonin is deficient, sleep does not progress sufficiently beyond the REM level and, even after several hours of light sleep, the individual awakens tired and has diminished energy in the day that follows. The patients cannot sleep deeply because they lack sufficient serotonin; but they lack serotonin because they cannot sleep deeply. How can serotonin be replenished from an external source to initiate deep restorative sleep? To answer this question requires understanding of the mechanisms of action of known serotonin-related agents, namely, trazodone, the SSRI’s, and fenfluramine. For sleep enhancement, trazodone, an early weak antidepressant, is the most suitable source of serotonin. It is a serotonin modulator, capable of temporarily increasing minimal amounts of cerebral serotonin to provide a “jump-start” for the process of sleep, allowing it to descend to the deeper restorative level that otherwise could not be achieved. At the end of the night the initial PHYSICIANS AGAINST OBESITY Page 4 level of serotonin will have been multiplied to produce beneficial effects in the day to follow. These are increased energy and mental function, curbing of carbohydrate cravings, and a gradual refilling of a depleted serotonin reservoir. After many nights of good sleep, sufficient serotonin will have been replenished to allow the gradual withdrawal of the trazodone. If sleep disturbances or carbohydrate cravings reappear, then the withdrawal should be postponed unless a less stressful period is available. Thus, rather than being addictive, ultimately trazodone makes itself unnecessary. Trazodone is very well tolerated with minimal side effects, the most spectacular, though rare, being priapism. This sustained erection can easily be treated by an ephedrine-containing cold remedy, e.g., Sudafed. Selective serotonin re-uptake inhibitors (SSRI’s) are better antidepressants than trazodone but their mode of action does not favor sleep. They inhibit the inactivation of serotonin by blocking its re-uptake and thereby recycle it without actually increasing it. Therefore, they do not add to the depleted store of serotonin. Fenfluramine, the serotonin-related component of phen-fen, increased the release of pre-formed systemic serotonin to produce toxic cardiac and pulmonary effects which led to its withdrawal. In practice, a new patient complaining of resistant obesity should be informed about the important roles of insulin excess and serotonin deficiency. These are described in lay terms in my book “Your Fat Can Make You Thin.” Since there are no laboratory tests for serotonin deficiency, trazodone in a small, initial dose (e.g. 25 to 100 mg) should be prescribed immediately along with a low-calorie, low-fat, low-carbohydrate, normal protein diet, plus appropriate multivitamin and calcium supplements. Exercise suggestions as described in my book help to round out the program. Testing for ketones in the urine, a.m. and p.m. with Ketostix, should begin within two days to PHYSICIANS AGAINST OBESITY Page 5 determine that insulin has been adequately reduced to permit excessive fat to be used as a major source of energy. Ketosis testing involves the patient as the managing partner of the weight-loss enterprise. If ketones become negative, the cause can usually be easily identified by the patient and corrected promptly. Serotonin status can be determined by symptoms of carbohydrate cravings or sleep disturbance. However, the presence of ketosis is objective evidence of adequate serotonin, which, if deficient, would have produced carbohydrate cravings and a resultant rise of insulin with its antilipolytic and antiketotic effects. Ketosis is associated with naturesis, which is more evident in the early weeks of treatment. In women with initial fluid retention, rapid water-weight loss can produce postural hypotension and the risk of fainting. Salt should not be restricted at this time; at least 5 gm (1 teaspoons) or equivalent in salty foods, (e.g. pickles) should be prescribed, otherwise there are no significant complications. Diabetes should come under better control because of the low-carbohydrate diet and, ultimately, because of the loss of fat and its insulin-resisting adipokines. With sufficient weight loss and adequate insulin reserve, diabetes has often been reversed. There is no fixed dose of trazodone that is suitable for everyone. Therefore, until carbohydrate cravings and sleep disturbances are controlled, the dose should be gradually increased at intervals of one to two weeks. A maximum dose of 600 mg was proposed when it was first used as an antidepressant, but it is unusual to require that amount in this weight-loss program. The “Insulin Resistance Syndrome” has blossomed into a collection of wide-ranging disorders, beginning with cardiovascular disease, some malignancies, infertility, and diabetes. Resistance to the hypoglycemic effect of insulin is common to these conditions. An important, but not necessarily the only cause, of this resistance is excess adipose tissue. Reversal of adiposity is the logical first step in the management of these disorders. Lifestyle PHYSICIANS AGAINST OBESITY Page 6 changes leading to weight loss have proven superior to medication in the prevention of diabetes. What is missing from medical practice is a simple, effective program of permanent weight loss that could be employed with confidence by doctors confronted by these hitherto discouraging patients. With the temporary aid of serotonin-enhancing trazodone, and the effective utilization of the beneficial effects of insulin reduction, we can achieve permanent control of overweight. The details of stabilization and maintenance of the desired weight are contained in my book which also presents a useful approximation of the presumed pathophysiologic process that lends itself to a practical solution. It has worked well in my practice and it should also work for you.
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| Publications by Dr. Ezrin |
1. Childhood Diabetes. University of Toronto Medical Journal, 26:233, 1949
2. Prothrombin Consumption in Haemophiliac Kindred. Journal of Clinical Pathology, 4:460, 1949
3. Three Types of Chromophil Cells of the Adenohypophysis. American Journal of Pathology, 30:391, 1954
4. The Delta Cell of the Human Adenohypophysis: Its Response to Acute and Chronic Illness. Journal of Clinical Endocrinology, 18:917, 1956 (with H.E. Swanson, J.C. Humphrey, J.W. Dawson and W.D. Wilson)
5. The Clinical and Metabolic Effects of Glucagon, Canadian Medical Association Journal, 78:96, 1958 (with J.M. Salter, W.A. Ogryzlo and C.H. Best)
6. Resistance to Insulin Due to Neutralizing Antibodies. Journal of Clinical Endocrinology, 19:1055, 1959 (with P.J. Moloney)
7. Beta and Delta Cells of the Human Adenohypophysis: Their Response to Adrenocortical Disorders. Journal of Clinical Endocrinology, 19:621, 1959 (with H.W. Swanson, J.C. Humphrey, J.W. Dawson and F.M. Hill)
8. Cells of the Human Adenohypophysis in Thyroid Disorders. Journal of Clinical Endocrinology, 19:958, 1959 (with H.E. Swanson, J.C. Humphrey, J.W. Dawson and F.M. Hill)
9. Metabolic Effects of Glucagon in Human Subjects. Metabolism, 9:753, 1960 (with J.M. Salter, J.C. Laidlaw and A.C. Gornall)
10. The Natural History of the Delta Cell of the Human Adenohypophysis: In Childhood, Adulthood and Pregnancy. Journal of Clinical Endocrinology, 20:952, 1960 (with H.W. Swanson)
11. A "Diurnal Pattern" in the Rate of Disappearance of L-Thyroxine Labeled with Radio-Active Iodine (T4-I131) from the Serum. Journal of Clinical Endocrinology, 21:582, 1961 (with P.C. Walfish, A. Britton and P. Melville)
12. Experience with an In Vitro Test of Thyroid Function (The Erythrocyte Uptake of T3-I131). Canadian Medical Association Journal, 84:637, 1961 (with P.G. Walfish, A. Britton and R. Volpe)
13. Radioactive Iodine in the Treatment of Hyperthyroidism, Parts I, II and III. Canadian Medical Association Journal, 83:1407, 1960; 84:37, 1961; 84:84, 1961 (with R. Volpe, D.L. Schatz, J.A. Peller, J. Vale and M.W. Johnston)
14. The Metabolic Rate and Serum Protein-bound Iodine of Adrenalectomized Rabbits Maintained on Reduced Cortisone Therapy. Endocrinology, 68:559, 1961 (with J. Broder, B. Langer and W.J. Horsey)
15. Psychosexual Identification (Psychogender) in the Intersexed. Canadian Psychology Association Journal, 4:49, 1959 (with D. Cappon and P. Lynes)
16. Histology of the Human Pituitary In Relation to Thyrotropin Secretion. Proceedings of Conference on Throtropin, sponsored by NIH, held at Harriman, N.Y., 1961, Ed. S. Werner, publisher Chas. C. Thomas Co., p 129-137
17. A Probable Partial Deletion of the Y Chromosomes In an Intersex Patient. The Lancet, 294, 1961 (with P.E. Conen, J.D. Bailey, W.H. Allemang and D.W. Thompson)
18. "Iodide Myxoedema" in Patients with Chronic Chest Disease. Canadian Medical Association Journal, 85:847, 1961 (with J. MacLachlan, E.P. Walter and R. Volpe)
19. Diarrhea Caused by Pancreatic Islet Cell Tumours. Canadian Medical Association Journal, 86:847, 1962 (with J.C. Edmeads, R.E. Mathews and N.P. McPhedran)
20. Diuretic Effect of Oxytocin in a Patient with Reversed Diurnal Rhythm of Water and Electrolyte Excretion. Canadian Medical Association Journal, 87:673, 1962 (with L.W. Loach and T.F. Nicholson)
21. Physiologic Effects of Extracts of a Diarrhea-Producing Nonbeta Islet Cell Tumour of the Pancreas. Surgery, Gynocology and Obstetrics, 115:490, 1962 (with R.E. Matthews, H.D. Brett, J.C. Edmeads and N.T. McPhedran)
22. Acromegaly: A Review of 100 Cases, Canadian Medical Association Journal, 87:1106, 1962 (with D.A. Gordon, F.M. Hill)
23. Genetic Factors in Hashimoto's Struma. Canadian Medical Association Journal, 88:915, 1963 (with R. Volpe, M.W. Johnston and J.W. Steiner)
24. Resistance and Allergy to Insulin. Applied Therapeutics, 5:680, 1963
25. Panhypopituitarism Caused by Hand-Schuller-Christian Disease. Canadian Medical Association Journal, 89:1290, 1963 (with R. Chaikoff and H. Hoffman)
26. The Cells of the Human Adenohypophysis in Pregnancy, Thyroid Disease and Adrenal Cortical Disorders. In "Cytologie de 1 Adenohypophyse," Editors J. Benoit and C. DaLage, Editions 1963, 183-200 (with S. Murray)
27. The Pituitary Gland. Ciba Clinical Symposia, Vol. 15, No. 3, 1963
28. Anabolic Agents. Canadian Medical Association Journal, 92:529, 1965
29. Studies of Iodine Metabolism in Hashimoto's Thyroiditis. Journal of Clinical Endocrinology, 25:593, 1965 (with R. Volpe, V.V. Row, B.R. Webser and M.W. Johnston)
30. Abnormal Thyroid metabolism in Two Patients with Non-Toxic Nodular Goiters. Acta Endocrinology Kobenhavn, 46:665 (with V. Row, M.W. Johnston and R. Volpe)
31. The Association of I131-Labeled Thyroxine and Triiodothyronine with Serum Proteins After Starch Gel Electrophoresis. Canadian Journal of Biochemistry, 43:1477, 1965 (with A. Britton, B.R. Webster and R. Volpe)
32. The Pituitary Gland. In Ciba Collection of Medical Illustrations, Endocrine sysem and Selected Metabolic Diseases, Vol. IV, Editor F. Netter, 1965, 3:35
33. 1271-Iodotyrosine-Like Compounds in Normal Human Serum. Clinical Chemistry Acta, 13:666, 1966 (with V.V. Row and R. Volpe)
34. Effects of Graves Disease on the "Thyrotroph" of the Adenohysis. Journal of Clinical Endocrinology, 26:287, 1966 (with S. Murray)
35. Embryology of the Thyrotroph. Journal of Clinical Endocrinology, 26:1343, 1966 (with F. Rosen)
36. Iodide Metabolism in Ontario. Acta Endocrinology Kobenhavn, 54:604, 1967 (with F. Rosen and R. Volpe)
37. Further Studies on the Rate of Disappearance of Labeled T4 from the Intravascular Compartment. Acta Endocrinology Kobenhavn, 55:497, 1967 (with B.R. Webster and R. Volpe)
38. The Endocrine Aspects of Transsphenoidal Hypophysectomy. Canadian Medical Association Journal, 97:72, 1967 (with T.D.R. Briant, F. Rosen and G. Firestone)
39. Uptake of Radioactive Thyroid Hormones by the Normal and Diseased Human Liver. Acta Endocrinology Kobenhavn, 60:411, 1969 (with A. Zaninovich and R. Volpe)
40. Effect of Pregnancy on the Somatotroph and the Prolactin Cell of the Human Adenohyypophysis. Journal of Clinical Endocrinological Metabolism, 29:1533-1533, 1969 (with L.C. Goluboff)
41. Immunofluorescent Localization of the LH cell of the Human Adenohypophysis. Journal of Clinical Endocrinology, 30:181-184, 1970 (with J. Bain)
42. Autoradiography of Tritiated Thymidine Labeled Anterior Pituitary Cells in Propylthiouracil Treated Rats. Endocrinology, 87 (No. 6): 1113, 1970 (with I.E. Stratmann and E.A. Sellers)
43. Embryology and Anatomy of the Thyrotropin-Secreting Cell (Thyrotroph). In "The Thyroid," Editors S.C. Werner and S.H. Ingbar, Harper and Row, N.Y., 1971, p. 131-136
44. The Origin of Thyroidectomy Cells as Revealed by High Resolution Radioautography. Endocrinology, 90:728-734, 1972 (with I.E. Stratmann, E.A. Sellers and G.T. Simon)
45. Systematic Endrinology, Editors C. Ezrin, J.O. Godden, R. Volpe and R. Wilson. Harper and Row, Hagerstown, 1973--Ezrin contributed Introduction and first three chapters on neuroendocrinology, adenohypophysis and neurohypophysis, p. 1-53
46. Effect of TRH (Thyrotropin-Releasing Hormone) on the Fine Structure and Replication of TSH and Prolactin Cells in the Rat. Z. Zellforsch., 145:23-37, 1973 (with I.E. Stratmann, K, Kovacs and E.A. Sellers)
47. L-Thyroxine in the Treatment of Obesity Without Increase in Loss of Lean Body Mass. Metabolism, 22:No. 4 (April), 617-622, 1973 (with L. Lamki, I. Koven and G. Steiner)
48. Hypothyroidism and Hyperparathyroidism Associated with Lithium. Lancet, 2:231, 1973 (with P.E. Garfinkel and H.C. Stancer)
49. Cytoplasmic Microfilaments in Human Adenohypophysical Cells. Abstract No. 206, 9th Acta Endocinologica Congress. Acta Endocrinologica Kovenhavn, Suppl. 177:206, 1973 (with K. Kovacs, E. Horvath and I.E. Stratmann)
50. Origin, Possible Function and Fate of "Follicular Cells" in the Anterior Lobe of the Human Pituitary. American Journal of Pathology, 77:199-212, 1974 (with E. Horvath, K. Kovacs and G. Penz)
51. Estrogen-Induced Transformation of Somatotrophs Into Mammotrophs in the Rat. Cellular Tissue Res., 152-229-238. 1974 (with I.E. Strattman and E.A. Sellers)
52. Diagnosis of Mild Hypothyroidism in the Face of Equivocal Test Results. Answer to Question in "Questions and Answers," J.A.M.A., 228-1658, 1974
53. Two Distinct Types of Microfilaments in the Cytoplasm of Human Adenohypophysical Cells. In "Electron Microscopic Concepts of Secretion: Ultrastructure of Endocrinological and Reproductive Organs." Editor M. Hess, J. Wiley & Sons, Inc., 1975 (with E. Horvath, K, Kovacs and I.E. Stratmann)
54. Cytoplasmic Microfilaments in the Anterior Lobe of the Human Pituitary Gland. Acta Anatomica, 87:414-426, 1974 (with K. Kovacs, E. Horvath and I.E. Strattman)
55. Pituitary Chromophobe Adenomas consisting of Prolactin Cells: A Histologic Immunocytological and Electron Microscopic Study. Virchows Arch. Pathol. Anat., 366(2):113-123, 1975 (with K. Kovas, E. Horvath, B. Corenblum, A.M.T. Sirek and G. Penz)
56. Effect of Starvation on Pituitary Growth Hormone (GH) and Blood GH Levels in Rats. Federation of American Societies for Experimental Biology Meeting. 1975 (with A.M.T. Sirek, E. Horvath and K. Kovacs)
57. A New Look at Pituitary Adenomas: Structure Elucidating Function. Canadian Medical Association Journal 114:225, 1976 (with A.M.T. Sirek, B. Corenblum, E. Horvath, N.B. Rewcastle and K. Kovacs)
58. Localization of Prolactin in Chromophobe Pituitary Adenomas: Study of Human Necropsy Material by Immunoperoxidase Technique. Journal of Clinical Pathology, 29:250-258, 1976 (with K. Kovacs, B. Corenblum, A.M.T. Sirek and G. Penz)
59. Clinical Endocrinology: A Survey of Current Practice. C. Ezrin, J.O. Godden and P. Walfish. Published by Appleton-Century-Crofts, 1977
60. Acidophil Stem Cell Adenoma of the Human Pituitary. Arch. Path. Lab. Med., 101-594-99, 1977 (with E. Horvath and K. Kovacs)
61. Effects of Hypothroidism on Somatotrophs and Lactotrophs of Rat Pituitary: Molecular. Cell Endocrinology, 7:195-202, 1977 (with B. Corenblum, K. Kovacs and G. Penz)
62. Pituitary Adenomas Associated with Elevated Blood Follicle Stimulating Hormone Levels. A Histologic, Immunocytologic and Electron Microscopic Study of Two Cases. Fertility and Sterility, 29:622-627, 1977 (with K. Kovacs, E. Horvath, G.R. Van Loon, N.B. Rewcastle and A.A. Rosenbloom)
63. Psychiatric Aspects of Endocrine and Metabolic Disorders. In "Psychosomatic Medicine," Editors E.D. Wittkower and H. Warnes. Harper and Row, N.Y., 1977 p. 2800-2950
64. Clinical Pituitary Disorders. Bull. Los Angeles Neurological Societies, 42:81-91, 1977
65. Abundance of Prolactin Cells in the Non-Tumorous Parts of Pituitary Gland Harbouring Prolactinomas. Ann. Royal College of Physicians & Surgeons of Canada, January 1978, p. 47 (with K. Kovacs, N. Ryan, E. Horvath and W. Singer)
66. Pituitary Hyperthyroidism. Case Report and Review of the Literature. American Journal of Medicine, 64:177-181, 1978 (with G. Tolis, C. Bird and C. Bertrand)
67. A Functional Anatomy of the Endocrine Hypothalamus and Hypophysis. Medical Clinician of North America, 62:229-233, 1978 (with K. Kovacs and E. Horvath)
68. Hyperprolactinemia. Morphologic and Clinical Considerations. medical Clinician of North America, 62:393-408, 1978 (with K. Kovacs and E. Horvath)
69. Silent Corticotroph Cell Adenoma with Lysosomal Accumulation and Crinophagy. A Distinct Clinicopatholigic Entity. American Journal of Medicine, 64;492-499, 1978 (with K. Kovacs, T.A. Bayler and S.T. Hassaram)
70. Prolactin Cells in the Nontumourous Portions of the Anterior Lobe. Horm. Metab. Res., 10:409-412, 1978 (with K. Kovacs, N. Ryan, E. Horvath and G. Penz)
71. Hypothalamic Hypopituitarism Presenting as Galactorrhea-Amenorrhea. J.A.M.A. 239(17):1783-1785, 1978 (with D. Streja and B. Corenblum)
72. Regression of a Pituitary Tumor, a Possible Effect of Bromergocryptine. American Journal of Medicine, 66:697-702, 1979 (with S.R. George, G.N. Burrow and B. Zinman)
73. Systematic Endocrinology, Second Edition. Harper and Row, Hagerstown, 1979 (with J.O. Godden and R. Volpe)
74. Cushing's Syndrome and Autoimmunity. Arch. Path. Lab. Med. 103:244-8, 1979 (with A.J. And, E.C. Andrada and F.T. Murray)
75. Anatomy and Cytology of the Normal and Abnormal Pituitary Gland. In "Endocrinology," Vol. 1, Edited by DeGroot, L.J. Grune & Stratton, N.Y., p. 103-122, 1979 (with E. Horvath and K. Kovacs)
76. Thyrotrophs in Old Age. An Immunocytologic Study of Human Pituitary Glands. Endocrinologie, 73:191-198, 1979 (with N. Ryan and K. Kovacs)
77. Subcellular Immunohistochemistry of the Human Pituitary. Proc. 37th Ann. Meet. Electron Microscopy Society of America, 37:226-227, 1979 (with E. Horvath, N. Ryan, D.J. McComb and K. Kovacs)
78. Correlative Ultrastructural Morphometry of Sparsely Granulated Prolactin Cell Adenomas of the Human Pituitary. Proc. 37h Ann. Meet. Electron Microscopy Society of America, 37:228-229. 1979 (with D.J. McComb, K. Kovacs and E. Horvath)
79. Thyrotroph Cell Adenoma of the Human Pituitary Gland Associated With Primary Hypothyroidism. Clinical and Morphologic Features. Acta Endocrinology (kbn) 95:41-48, 1980 (with Ms. Katz, R.E. Gregerman, E. Horvath and K. Kovacs)
80. Gonadotroph Cell Adenoma of the Pituitary in a Woman With Longstanding Hypogonadism. Arch. Gynecol. 229:57-65, 1980 (with K. Kovacs, E. Horvath and N.B. Rewcastle)
81. Null Cell Adenoma of he Human Pituitary. Virchows Arch. A. Pathol. Anat. Histol., 387:165-174, 1980 (with K. Kovacs, E. Horvath and N. Ryan)
82. Correlative Ultrastructural Morphometry of Human Prolactin Producing Adenomas. Acta Neurchir., 53:217-224, 1980 (with D.J. McComb, K. Kovacs, E. Horvath, W. Singer, D.W. Killinger, H.S. Smyth and M.H. Weiss)
83. Immunoelectron Microscopic Evidence of Prolactin Release in Prolactin Producing Pituitary Adenomas During Misplaced Exocytosis. IRCS Med., Sci. 8:121, 1980 (with N. Ryan, D.J. McComb, E. Horvath and K. Kovacs)
84. Pituitary Adenomas in Old Age. J. Gerontology, 35:16-22, 1980 (with K. Kovacs, N. Ryan, E. Horvath and W. Singer)
85. The Effects of Estrogen on prolactin Cells of the Male Rat Pituitary. An Immunocytologic and Autoradiographic Study. Endocrine Res. Comm., 7:37-144, 1980 (with B. Corenblum, K. Kovacs and G. Penz)
86. Mammosomatroph Cell Adenoma of the Human Pituitary. Proc. 38th Ann. Meet. Electron Microscopy Society of America, 726-727, 1980 (with E. Horvath, K. Kovacs, D.W. Killinger, H.S. Smyth, M.E. Platts and M.S. Weiss)
87. Clinical Pituitary Disorders. In "Pituitary Diseases," CRC Press, Boca Raton, FL p. 1-83, 1980 (Editors E. Horvath, K. Kovacs, B. Kaufman, M.H. Weiss)
88. Acidophil Stem Cell Adenoma of the Human Pituitary. Clinical-Pathological Analysis of 15 Cases. Cancer, 47-791, 1981 (with E. Horvath, K. Kovacs, W. Singer, H.S. Smyth, D.W. Killinger and M.H. Weiss)
89. Pathology of the Adenohypophysis. In "Bloodworth," JMB Jr. (ed.) 1982 Endocrine Pathology, Williams & Wilkins, Baltimore (with K. Kovacs and E. Horvath)
90. Adenoma of the Human Pituitary Producing Growth Hormone and Thyrotopism. A Histologic, Immunocytologic and Fine Structural Study. Virchows Arch. Path. Anat., 394-59, 1982 (with K. Kovacs, E. Horvath and M.H. Weiss)
91. Pathophysiology of Acromegaly. Endocrine Reviews, 4;271-290, 1983 (with S. Melmed, G.D. Braunstein, E. Horvath and K. Kovacs)
92. Sellar Glomangioma. Ultrastructure Pathology, 7:49-54, 1984 (with S.L. Asa, K. Kovacs, E. Horvath and M.H. Weiss)
93. Cytology of Normal Pituitary and Pituitary Tumors. In "Pituitary Tumors," Edited by W.D. Odell and D.H. Nelson, 71-143, 1984 Futura Publishing Co. (with S.L. Asa, E. Horvath and K. Kovacs)
94. Centrioles and Cilia in Non-Tumorous Anterior Lobe and Adenomas of the Human Pituitary. Path. Europ. Vol. 1:81-86, 1985 (with E. Horvath and K. Kovacs)
95. Acromegaly Due to Secretion of Growth Hormone by an Ectopic Pancreatic Islet Cell Tumor. New England Journal of Medicine, 312:917, 1985 (with S. Melmed, K. Kovacs, R. Goodman and L.A. Forman)
96. Effects of Caloric Restriction and Exercise on Insulin Receptors in Obesity Association with Changes in Membrane Lipids. Metabolism, 35:80-87, 1986 (with N. Neufeld, L. Corbo, D. Long and M.A. Bush)
97. Anatomy and Pathology of the Thyrotroph. In "The Thyroid," Editors S.H. Ingbar and L.E. Braverman, 5th Edition, J.B. Lippincott, Philadelphia, 1986, p. 36-42
98. Rhabdomyosarcoma in the Region of the Sella Turcica. Acts Neurochir (wien) (1987), 88:142-146 (with S. Jalslah, K. Kovacs, E. Horvath, et al)
99. Pathology of Acromegaly. In "Acromegaly-A Century of Scientific and Clinical Progress." 1987 (Editors R.J. Robbins and S. Melmed) Plenum Press (with K. Kovacs)
100. Metastatic Carcinoma to Pituitary Adenomas: A Report of Two Cases. Exp. Clinical Endocrinology, 92(1):69-76, 1988 (with J.A. Ramsay, K, Kovacs, B.W. Scheithauer and M.H. Weiss)
101. Anatomy and Histology of the Normal and Abnormal Pituitary Gland. In "Endocrinology 2nd Edition, Vol 1," Edited by L.J. DeGroot, Saunders, Philadelphia, 1989
102. Hypothalamic and Pituitary Disorders, p. 1116-1126. In "Internal Medicine for Dentistry," Edited by L.F. Ross and D. Kaye, Mosby, 2nd Edition, 1990
103. Neuroendocrinology, book chapter. In "Neurological Surgery," Edited by Julian Youmans, 23rd Edition, 1990 p. 741-751 (with M.H. Weiss)
104. The Endocrine Control Diet, 256 pp. Harper and Row, N.Y., 1990 (with R.E. Kowalski)
105. O Regime Do Controle Endocrino, Agencia Siciliano de Livros, Jornais e Revistas ltda. Sao Paulo Brasil, Capa, Carlos Perrone, 1990 (with R.E. Kowalski)
106. Hereditary Diabetes Insipidus: An Immunchistochemical Study of the Hypothalamus and Pituitary Gland. Acta Neuropathol. 81:345-348, 1991 (with C. Bergeron, K. Kovacs and C. Mizzen)
107. Sustained Pulsatile Insulin Secretion From Adenomatous Human Beta Cells; Synchronous Cycling of Insulin, C-Peptide and Proinsulin. Diabetes, 401453-1458, 1991 (with H. Chou, E. Ipp, R.R. Boshwer, et al)
108. Die Stoffwechsel-Revolution. ECON Verlag, GmbH, Dusseldorf, Wien, New York and Moskau, 1992 (with R.E. Kowalski)
109. Recurrent Acromegaly Resulting From Ectopic Growth Hormone Gene Expression by a Metastatic Pancreatic Tumor. Cancer, 71:66-70, 1993 (with S. Ezzat, S. Yamashita and S. Melmed)
110. The Type 2 Diabetes Diet Book (Revised Third Edition). 320 pp. Lowell House, Los Angeles, 1999 (with R.E. Kowalski)
111. Your Fat Can Make You Thin. 236 pp. Lowell House/McGraw-Hill, Los Angeles, Chicago, 2000 (with K.L. Caron)
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