Hyperparathyroidism Following the Atomic Bombing in Nagasaki

Tsukasa TSUNODA, Nobuo MOCHINAGA, Toshifumi ETO and Harunobu MAEDA

ABSTRACT: Forty-three patients with hyperparathyroidism (HPT), includ- ing 20 atomic bomb survivors (46.5 per cent) were treated surgically in our institute during the last 19 years. The mean age of the patients at the time of atomic bomb exposure (AB*E) was 17.6 + 1.5 years. The mean latent interval between atomic bomb exposure and detection of HPT was 39,1 • 1.1 years. We compared the 20 AB*E patients with 23 patients who had a history of nei ther atomic bomb exposure nor therapeutic irradiation to the neck region (non-AB*E patients). It was determined that females were more prominently affected by HPT than males among AB*E patients. The parathyroid lesions in AB*E patients consisted of adenoma in 16 patients and hyperplasia in 4. A similar proport ion of pathological lesions was also observed in n0n-AB*E-patients. Thyroid lesions accompanied by HPT, however, were more often revealed in AB*E patients than in non-AB*E patients. The two most common lesions in AB*E patients were papillary carcinoma in 3 patients (15 per cent) and adenoma in 3 (15 per cent). These findings suggest that atomic bomb survivors may be at a greater risk of developing HPT with a high incidence of accompanying thyroid disease.

KEY WORDS: primary hyperparathyroidism, atomic bomb, thyroid diseases

INTRODUCTION

The relationship between hyperparathy- roidism (HPT) and external radiation was first suggested by Rosen in 1975,1 and since then it h~s b e e n demonstrated by several investigators. "-s AS a result of the atomic bombing of Nagasaki on August 9, 1945, Nagasaki University has encountered many patients who suffered from the effects of the bombing.

The purpose of this paper is to review the m

The Second Department of Surgery, Nagasaki Uni- versity School of Medicine, Nagasaki, Japan

Reprint requests to: Tsukasa Tsunoda, MD, The Second Department o f Surgery, Nagasaki University School of Medicine, 7-1 Sakamoto, Nagasaki City, Nagasaki 852, Japan

clinical features of our HPT patients, while paying special attention to the differences between atomic bomb exposure (AB*E) pa- tients and non-atomic bomb exposure (non- AB*E) patients.

PATIENTS AND METHODS

Between May 1971 and June 1990, 43 patients with HPT were treated surgically in our institute. The diagnosis of HPT was verified in all patients by histological exami- nations, which were made according to Rosai 9 and Kay. TM HPT was suspected after the detection of hypercalcemia in all patients except for one, whose parathyroid adenoma was found coincidentally after undergoing a total thyroidectomy for thyroid cancer. In 7 out of the 11 AB*E patients, who were

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discovered a f t e r December 1987, the hyper- calcemia was pointed out during the regular check-ups for atomic bomb survivors con- ducted by t h e Radiation Effects Research Foundat ion in Nagasaki. The measurement of parathyroid hormones began in our in- stitute in 1979. Abnormal ly high levels o f parathyroid h o r m o n e were revealed in all 33 H P T patients thereafter. The records of these patients were reviewed with special reference to the age at the time o f atomic b o m b exposure, sex, latent interval f rom atomic bomb exposure to detection of H P T and diseases of the parathyroid and thyroid. Student's' t-test and Chi-squared test were used for the statistical analysis of the data.

RESULTS

Twenty of 43 patients (46.5 per cent) in our series h a d a history of atomic bomb expo- sure. One pat ient also h a d a history of external irradiation to the neck for Graves' disease 3 years after the atomic b o m b expo- sure. Table 1 shows the age and sex distribu- tion o f patients at the time of exposure to the atomic bomb. Ninety per cent of the patients were younger than 30 years of age. T h e mean (__+S.E.) age was 17.6 _ 1.5 years, rang ing from 8 to 35. Female patients com- prised 75 per cent o f the AB*E patients. The re was no significant difference in age at the time of atomic b o m b exposure between males and females. The mean (• latent interval o f the disease between atomic b o m b exposure and detection o f hyperparathy- roidism was 39.1 • 1.1 years, ranging f rom 27 years 11 months to 44 years 7 months (Table 2). The re was no significan t differ- ence in the latent interval between males and females.

A comparison of the sex and age at the time of operat ion for AB*E patients and non-AB*E patients with H P T is shown in Table 3. Females were found to be the most p redominant ly affected by HPT o f both groups. There was no significant difference in m e a n age at operat ion between the two

Table 1. Age and Sex at the Time of Atomic Bomb Exposure

Age (yrs) No. of Pts Males Females

8to 9 1 0 1 10 to 19 14 (1) 4 l0 (1) 20 to 29 3 0 3 30 to 35 2 1 !

Total 20 5 15

No. of Pts: Number of patients ( ): Patient with additional external irradia- tion therapy for Graves' disease

Table 2. Interval between Atomic Bomb Exposure and Detection of Hyper- parathyroidism

Interval (yrs) No. of Pts Males Females

27 to 29 1 0 1 30 to 39 10 4 6 40 to 45 9 1 8

Total 20 5 15

No. of Pts: number of patients

Table 31 Comparison of Age and Sex in AB*E and Non-AB*E patients with Hyperparathyroidism

AB*E Pts Non-AB*E Pts

Total No. of Pts 20 23 Male : Female 5 : 15 8 : 15 Age at op (yrs) 57.4:hl.8 52.1•

AB*E Pts: Atomic bomb exposure patients Age at op (yrs): Age at operation (years) Mean • SE

groups. A histological examinat ion of the resected

parathyroid glands showed that two lesions in our series were adenoma and hyperplasia (Table 4). The mean maximum d i a m e t e r o f the resected parathyroid glands was 16.2 • 1.2 m m in the AB*E patients and 21.0 • 2.1 m m in the non-AB*E patients. The re was no s ign i f ican t d i f f e r ence b e t w e e n the two groups.

Thyroid disease developed more often in AB*E patients than in non-AB*E patients, a l though there was no statistical significance

510 Tsunoda et al. sJPn. J. tember Su9rff )

Table 4. Histological Diagnosis of the Parathyroid Glands and Size of Diseas- ed Glands in AB*E and non-AB*E Pts with Hyperparathyroidism

AB*E Pts Non-AB*E Pts (n=20) (n=23)

Diagnosis Adenoma 16 (80%) 16 (70%) Hyperplasia 4 (20%) 7 (30%)

Size - 9mm 1 3

10-1~ mm 14 8 20-29 mm 5 7 30- mm 0 5 mean+__ SE 16.2___1.2 mm 21.0+2.1 mm

AB*E Pts: Atomic bomb exposure patients n: number of patients

Table 5. Accompanying Thyroid Dis- eases in AB*E and Non-AB*E Pts with Hyperparathyroidism

AB*E Pts Non-AB*E Pts (n=20) (n=23)

Papillary Carcinoma 3 (15%) 1 (4%) Adenoma 3 (15%) 2 (9%) Adenomatous Goiter 2 (10%) 2 (9%)

Chronic Thyroiditis 1 (5%) 0 (0%) Graves' Disease 1 (5%) 0 (0%)

AB*E Pts: Atomic bomb exposure patients n: number of patients

between the two groups (Table 5). In AB*E patients, 10 abnormal thyroid pathologies were found in 8 patients (40 per cent o f the patients), including 3 papillary carcinomas and 3 adenomas. In non-AB*E patients, 5 abnormal thyroid pathologies were found in 5 patients (22 per cent), including 1 papillary carcinoma and 2 adenomas.

DISCUSSION

In the reported HPT series, 14-30 per cent o f patients had a history of radiation therapy to the n e c k region, leading investigators to suspect that previous irradiation was a causa- tive factor for HPT?,S,s, 6 In our series, a large

port ion (46.5 per cent) o f patients with HPT had a history of exposure to the atomic bombing of August 9, 1945. Furthermore, the port ion was higher than that of atomic bomb survivors in the total popula t ion of Nagasaki city (16-20 per cent) during 1970 to 1985. The number of the survivors was estimated from the possessors of Atomic Bomb sur- vivor 's h a n d b o o k , which was issued by Japanese Government. The radiation dose by atomic bomb was estimated between 20 and 600 rad in H P T patients. T M Therapeut ic radiation doses, which may also correlate with the development of HPT, have been reported to range between 60 and 4,570 rad? -5a,8 Fujiwara et al repor ted a statistically significant correlation between the dose of atomic b o m b radiation and the probability of developing HPT f rom the analysis o f data in the Hiroshima district, is These facts suggest that people who suffered exposure to the atomic bombing run a high risk of develo p- ing HPT, especially when the radiation dose was large.

The mean age at the time of exposure to the atomic bombing was 17.6 years, which is almost the same as that reported in previous studies on therapeut ic external irradia- tion. 4,B-s The mean latent interval between atomic bomb exposure and detection of hyperparathyroidism was 39.1 years, which again is similar to that in previous reports? -s In other words, exposure to i r radia t ion-- including therapeutic irradiation to the neck region ei ther in childhood, adolescence or young adu l thood- -may cause hyperparathy- roidism approximately 40 years after irradia- tion.

In our HPT series, females were the most predominant ly affected by HPT, especially among AB*E patients. It is also well known that HPT occurs more frequently in females than in males. Tisell et al reported that females are often affected by HPT in both irradiated and non-irradiated patients5

It is generally recognized that adenoma of the parathyroid gland is p redominant among irradiated HPT patients. No carcinoma of the

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parathyroid gland was observed in our series. Christmas et al, however, has reported that parathyroid carcinoma was found in 3 of 7 externally irradiated patients (43 per cent)?

The incidence of thyroid disease in AB*E patients was determined to be about twice of that in non-AB*E patients in this study. The thyroid and parathyroid seemed to have undergone similar exposure to irradiation because of their anatomic proximity at the time o f irradiation to the neck region. Tisell et al reported that all but one of the 50 HPT patients from whom tissue was available for investigation had abnormal thyroid glands. 7 We found thyroid abnormalities in 40 per cent of the irradiated patients, which is considered to be a relatively low incidence. This low incidence might be explained by an insufficient evaluation of the thyroid gland before and during operat ion due to a lack o f understanding regarding accompanying thy- roid diseases. Papillary carcinoma of the thyroid gland was found in 15 per cent of AB*E patients in our series. In the report by Tisell, carcinoma was found in 8 of 50 histologically verified thyroid specimens ac- companied by HPT (16.0 per cent). 7

It is therefore concluded that atomic bomb survivors may be at a greater risk of develop- ing H P T d n conjunct ion with a high inci- dence of accompanying thyroid disease.

(Received for publication on Sep. 1, 1990)

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