John W. Gofman, M.D., Ph.D., Spring 1993
- Part 1 -- Introduction
- Part 2 -- What Are the Consequences of Hypothyroidism?
- Part 3 -- How Much Radio-Iodine Is Required to Produce Hypo-Thyroidism?
- Part 4 -- Summary on Radiation-Induced Hypo-Thyroidism
There may be an interesting explanation for some of the mysterious health problems reported, in Belarus and Ukraine, within three years after the Chernobyl accident of 1986.
In 1989, a group of radiation experts who were sent to the Chernobyl area by the World Health Organization (WHO) denied that any of the health problems were related to radiation. In May 1991, a report by the International Atomic Energy Agency (IAEA) produced the same denial. Neither report denied health problems. Rather, the reports denied any connection between the problems and radiation. Both sets of experts claimed that the Chernobyl populations which they visited suffered from exaggerated fears about their radiation exposures.
We think that the explanation for some of the health problems may be radiation-induced hypo-thyroidism from radio-iodine --- rather than "radio-phobia." This essay explains why.
If this idea is right, then development of Chernobyl-induced hypo-thyroidism is far from complete in 1993. When hypo-thyroidism is induced by thyroid irradiation, it can become clinically evident within one year for some people, but can take up to 14 years (or longer) for some other people. We know of no studies which establish what is the longest possible delay.
The "Hanford Downwinders"
The induction of hypo-thyroidism by radio-iodine is necessarily a concern not only for Chernobyl populations and the early clean-up workers there, but also for "the Hanford Downwinders."
Some very large releases of radio-iodine were made from the Hanford Nuclear Reservation in Washington state during the 1940s (especially 1944-47) and up to 1957. The people were not warned and were not told. Starting in 1986, pressure from the Hanford Education Action League and other citizen-groups has caused revelations about what happened. The US Government is sponsoring retroactive estimates now of the probable radiation doses to the thyroid at various times in various regions of Washington, Oregon, and Idaho.
What about the Future?
We added "and Beyond" to the title because, so long as large scale nuclear fission enterprises exist, a part of humanity's health is inevitably tied to the element, iodine, specifically to its short-lived radionuclides:
Iodine-131, half-life of 8.04 days.
Iodine-132, half-life of 2.28 hours.
Iodine-133, half-life of 20.90 hours.
Iodine-135, half-life of 6.70 hours.
In a sense, nature has been unkind on this issue. These radio-iodines are all produced in high abundance in the course of nuclear fission. Moreover, in elemental form, iodine very easily becomes airborne. Because it converts readily to the gaseous state, if abnormally high temperature occurs in a nuclear reactor and if the fuel-cladding ruptures, melts, or is destroyed by explosion, the radio-iodines can escape from the fuel and will be eager candidates for escape from the building too, if possible. No one denies that "enough" radio-iodine reaching the thyroid gland can induce hypo-thyroidism (see Part 3).
2 What Are the Consequences of Hypothyroidism?
Hypo-thyroidism is the medical state caused by a deficient supply of thyroid hormones in the cells of various body organs. Severe hypo-thyroidism is called myxedema. For tissues in general, thyroid hormones increase oxygen consumption and heat production, increase the metabolic rate of carbohydrates, fats, and proteins, increase cardiac output, and increase sensitivity of the nervous system. In early life, these hormones condition the system for differentiation and growth. They are essential for normal brain development in-utero and up to age 2 years.
When hypo-thyroidism develops after infancy, it produces a great variety of signs (verifiable by others) and symptoms (knowable only by the patient). Different individuals develop various features in various sequences and at various speeds. No one develops all the possible consequences.
A partial listing of some common features of hypo-thyroidism is provided on the left side of Table A (next page). On the right side is a listing of health problems reported by Chernobyl populations, anecdotally (without systematic study). There is a great deal of correspondence.
Many of the features of hypo-thyroidism can result from several other causes, too. No single feature guarantees that the cause is hypo-thyroidism. It can be "a diagnostic challenge," and correct diagnosis is quite often missed for years after hypo-thyroidism is present. Without treatment, hypo-thyroidism is slowly progressive, so the unhappy victims keep seeking help until finally a physician does make the correct diagnosis. Alert physicians who include hypo-thyroidism in their differential diagnosis will ask key questions, and will notice a constellation of signs and symptoms. Often (but not always) hypo-thyroidism can be confirmed by laboratory findings.
Treatment is usually simple and --- in adults and most children --- the consequences are reversible.
This is extremely fortunate, since some of the consequences of hypo-thyroidism in Table A can make life miserable or nearly impossible. Indeed, untreated hypo-thyroidism can advance with increasing loss of mental function and physical energy, and can even culminate in coma and death. Tragically, if hypo-thyroidism occurs in the first two years of life without prompt treatment, the afflicted child can develop irreversible brain-damage.
Some features of primary hypo-thyroidism.
From Leslie J. DeGroot et al, 1984,
The Thyroid and Its Diseases (5th edition).
Features reported anecdotally from the Chernobyl-affected
Compiled in the CNR essay, fall 1991.
|A) Retardation in rate of healing of wounds and of ulcerations, such as leg ulcers.||Slow recovery from illnesses and surgery. Incurable skin diseases.|
|B) The hair, both of the head and elsewhere, is dry, brittle, and sparse and lacks shine . . . Its growth is retarded and it falls out readily.||Hair-loss is reported.|
|C) Myxedematous patients are more subject to respiratory infections.||
Fevers abnormally often.
"Immune system weakening" (presumably this describes poor resistance to infections.)
Bronchitis. Lung diseases. Tuberculosis.
|D) Night blindness is not uncommon.||Vision-loss is reported.|
|E) Two-thirds of patients complain of dizziness, vertigo, or ringing in the ears.||Dizziness occurs with abnormal frequency.|
|F) Fatigue and lethargy are prominent. More time is spent sleeping.||
Fatigue at abnormal levels.
Sickliness (unspecified) in children.
|G) Measurement of the Basal Metabolic Rate gives values from 30 to 45 % below normal (reduced oxygen consumption).||"Metabolic changes."|
|H) Anorexia (loss of appetite). Weight-gain, if present, is due to fluid, not to obesity.||Appetite loss.|
|I) For childhood hypo-thyroidism: "During the entire time that a state of mild hypo-thyroidism exists, growth is slowed."||Weight gain is abnormally slow for children.|
|J) Headache is a common complaint.||Headaches are common.|
|K) In both sexes, libido is usually, but not invariably, decreased. Testicles . . . show tubular involution if onset was after puberty.||Reports from Chernobyl decontamination workers include abnormalities of sexual organs and their function.|
|L) Excessive menstrual bleeding in pre-menopausal women, sometimes with hypochromic anemia as a result of the bleeding. Also in some dental patients, excessive bleeding after tooth extraction.||
Nose-bleeds are commonly reported.
The "pink handkerchief" syndrome reported by mothers. Elevated rates of anemia (a non-anecdotal report from the Belarussian government, 1990).
|M) Anemias of several types have been reported commonly in hypo-thyroidism, ranging from pernicious anemia to microcytic hypochromic anemia. While some of the microcytic anemias may be secondary to blood loss, the pernicious anemia may be due to inadequate absorption of Vitamin B-12. Thyroid treatment cures this anemia in hypo-thyroid patients.||
Elevated rates of anemia.
"Anemias of unusual types."
|We have not seen features N through T reported for the Chernobyl regions (yet), but the reporting is haphazard and anecdotal (except for anemia), not rigorous or comprehensive.|
|N) A common characteristic is edema, with effusions of fluid in the pericardial, pleural, and peritoneal spaces. Puffy face and eyelids may occur. Peripheral non-pitting edema is an almost conclusive sign of advanced hypo-thyroidism according to DeGroot et al.|
|O) A classic consequence of hypo-thyroidism is "cold intolerance". As the metabolic rate begins to fall, "the first symptoms may be a decrease in sweating and dislike of cold."|
|P) Enlarged tongue and hoarse voice. Sometimes a slow rate of speech.|
|Q) Muscle weakness, muscle cramps and stiffness. Difficult breathing. Reflex relaxation-time is markedly prolonged --- often a useful diagnostic sign according to DeGroot et al.|
|R) Skin is notably dry, coarse, pale, and cold.|
|S) Memory is impaired and mentation is slow.|
|T) "Deafness is a very characteristic and troublesome symptom of hypo-thyroidism."|
3 How Much Radio-Iodine Is Required to Produce Hypo-Thyroidism?
A functioning thyroid gland concentrates iodide ion from a person's blood, oxidizes it, and finally combines the element, iodine, with other substances to produce the thyroid hormones (T4 and T3). When people ingest or inhale radio-iodine, the thyroid gland concentrates it out of the blood just as if it were not radioactive.
From "fallout," the most common source of serious exposure is ingestion of milk from cows which ingested radio-iodine on contaminated pasture. Children are at greater risk than adults because they often drink more milk and because their smaller glands receive a bigger dose per unit of ingested radio-iodine. This is not in dispute. For example, a newborn child's thyroid dose is about 16 times higher than an adult's dose, per ingested micro-curie of iodine-131.
A micro-curie is one millionth of one curie. A curie is the amount of a radioactive species which produces 37 billion radioactive decays per second. In contrast to a curie, a rad is a measure of dose --- the energy deposited per gram of tissue due to radioactive decays. For radio-iodine, rad and rem are the same.
Time between Dose and Diagnosis
The overwhelming proof of induction of hypo-thyroidism by iodine-131 (I-131) comes from the therapy of hyper-thyroidism with I-131 used specifically to inactivate or kill thyroid cells. Doses commonly range from 3,000 to about 25,000 thyroid-rems. There is no doubt that relief of hyper-thyroidism is commonly achieved, but a high proportion of these patients go on to develop hypo-thyroidism in subsequent years. The Nuclear Regulatory Commission (NRC) acknowledges that:
"The prevalence of late-onset hypo-thyroidism increases in all I-131 treatment groups. As an example, in patients receiving iodine-131 therapy doses (3,000 to 50,000 rads), the prevalence of permanent hypo-thyroidism was 11.5 percent in the first year. At the end of the sixth, ninth, and eleventh years, the prevalence was 32.7 percent, 47.3 percent, and 72.7 percent respectively" (p.II-60 in the 1989 NRC report: Health Effects Models for Nuclear Power Plant Accident Consequence Analysis, Low LET Radiation. Nureg/CR-4214, Revision 1, May 1989. The principal author of the thyroid section is Harry R. Maxon.). The NRC report assumes that new cases stop appearing 15 years after exposure.
A Claim That Doses up to 1.000-Rads May Be Safe
The same NRC report proposes that there is a threshold dose below which no risk of hypo-thyroidism occurs. For exposure by external radiation (gamma or X-rays), the NRC proposes a 200-rad threshold, but for exposure by radio-iodine, the NRC report proposes that all doses below 1,000 thyroid-rads may be safe.
We emphatically do not accept NRC's assumption of a high threshold dose. We are unaware of any appropriate study (meeting the basic Rules of Research) which would support it.
In providing risk-estimates in 1989 for the NRC, Maxon treats his own 1977 paper as still valid. So we examined it directly (Amer. Journal of Medicine, Vol.63), and used it. Maxon 1977 finds that incidence of hypo-thyroidism is proportional to dose (the linear dose-response) in a 1971 study of 6,000 radio-iodine patients who received between 2,500 and 20,000 thyroid-rems. The risk-value is 4.4 cases of hypo-thyroidism per million patients, per rem of dose, per year of follow-up. At five years post-treatment, in the lowest dose-group (2,500 thyroid-rems), approximately one out of every 8 patients had already developed hypo-thyroidism.
Maxon 1977 also discusses a very small study by Hamilton in 1975 of only 443 patients who received diagnostic doses (which are often in the range of 15 to 100 rads). Preliminary results showed 8 cases of hypo-thyroidism at 14 years of follow-up. Maxon 1977 (p.972) reaches a conclusion of great relevance: "The risk does not appear to be different from the risk of 4.4 [see above] which was estimated from the data on patients treated at dose levels of more than 2,500 rems." For the 1989 NRC report, Maxon does not discuss the small 1975 study --- or any other low-dose study which either supports or contradicts it.
In the absence of reliable low-dose human data, we think the responsible position is to assume, tentatively, that the linear dose-response of 4.4 is valid at all dose-ranges (no threshold), for the first 14 years. Our Table B (next page) takes this position. It is a prudent position --- instead of denying disease-induction when there is no good evidence for such denial.
Estimated Risks Starting at 10 Rems
Our Table B provides estimated risks per individual and per million exposed people in the dose-range of 10 to 3,000 thyroid-rems. This is the range of greatest relevance for Hanford Downwinders and Chernobyl populations.
For example, if cows stayed on pasture during the Chernobyl accident, and if people drank a liter of their milk per day, there may be millions of people in Belarus and Ukraine at risk of hypo-thyroidism in degrees ranging from mild to severe, developing at times from 1987 onward.
Table B suggests that for thyroid doses of 200 rems or more, we should expect at least one case of radiation-induced hypo-thyroidism, within 14 years, for every hundred people whose thyroids received such doses. The table shows how to calculate expectations for other time-periods after exposure.
As indicated by Table A, undiagnosed and untreated hypo-thyroidism can make life miserable. People at risk deserve careful, frequent, lifetime examinations --- not the callous assumption that they suffer from radio-phobia.
Prevention and Control of Papillary Thyroid Cancer
There is another reason for a determined effort to find and treat all cases of hypo-thyroidism. People rendered hypo-thyroid by iodine-131 have also experienced a potent producer of thyroid cancer.
Thyroid cell-proliferation, uptake of iodine, and output of thyroid hormones are all stimulated by thyroid stimulating hormone (TSH), delivered from the anterior pituitary gland. If thyroid hormone production is low due to primary hypo-thyroidism, there will be an elevation of TSH levels in blood over what they normally would be for that individual.
Col. A Col. B Col. C Col.D Full 14 years Later: Risk of Radiation Dose Cumulative Cases of Percent of Radiation-Induced to Thyroid Radiation-Induced Exposed with Hypo-Thyroidism from Iodine-131 Hypo-Thyroidism per with Hypo for an (rems) Million Exposed Thyroidism Exposed Individual 10 616 0.06% 1 chance in 1623 25 1540 0.15% 1 chance in 649 50 3080 0.31% 1 chance in 325 75 4620 0.46% 1 chance in 216 100 6160 0.62% 1 chance in 162 200 12320 1.23% 1 chance in 81 300 18480 1.85% 1 chance in 54 400 24640 2.46% 1 chance in 41 500 30800 3.08% 1 chance in 32 600 36960 3.70% 1 chance in 27 700 43120 4.31% 1 chance in 23 800 49280 4.93% 1 chance in 20 900 55400 5.54% 1 chance in 18 1000 61600 6.16% 1 chance in 16 2000 123200 12.32% 1 chance in 8 3000 184800 18.48% 1 chance in 5Table B uses the value from Maxon 1977 of 4.4 cases per million exposed, per rem, per year of follow-up (see our text). Column B is (Col.A) x (4.4) x (14), because we are arbitrarily showing a 14-year follow-up period. Readers can also adapt Col. B for fewer years. We do not know if new cases stop appearing after 14 years, or what the appropriate value would be per year after 14 years.
A sustained elevation in TSH level is exactly what is not a good idea for people who are also at risk for thyroid cancer, or may be already incubating a pre-clinical case. There exists widespread agreement that elevated TSH level is an important agent either in starting or stimulating development of thyroid cancers. For cases arising from well-differentiated papillary tissue, a common part of therapy is suppression of TSH by administration of thyroid hormone. Indeed, George Crile, Jr. (1966), demonstrated long ago that some of these thyroid cancers which have metastasized can be controlled for long periods (and even reversed) with administration of thyroid hormone.
A dedicated effort to identify and monitor people at risk for I-131-induced hypo-thyroidism could also have the potential benefit of preventing some thyroid cancers via hormone replacement.
4 Summary on Radiation-Induced Hypo-Thyroidism
We certainly do not rule out the possibility of some dose-level which kills or inactivates so few thyroid cells that a person never develops hypo-thyroidism to a bothersome degree. We would welcome such a finding. But right now, no one knows if it exists, or at what dose.
This is one of many important questions which could be studied by IPHECA (which is WHO's International Program on Health Effects of the Chernobyl Accident). There is an urgent need to establish an independent Watchdog Authority within IPHECA, to verify that studies of this question (and many others) are done objectively, with scrupulous obedience to the Rules of Research. One of those rules is: No Pre-Judgments.
The unsupported presumption of a 1,000-rad threshold for hypo-thyroidism from radio-iodine may be convenient for various governments and other interests, but it may be very harmful to the Hanford and Chernobyl populations.
# # # # #
The issues in this essay are treated in greater detail by Chapters 2 and 8 in CNR's 1993 book, Radiation and Chernobyl: This Generation and Beyond. Previous books by Dr. Gofman on ionizing radiation are (1981) Radiation and Human Health, (1985) X-Rays: Health Effects of Common Exams, and (1990) Radiation-Induced Cancer from Low-Dose Exposure: An Independent Analysis.
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