Addison’s Disease Secondary to Adrenocortical Destruction by Metastatic Carcinoma of the Breast’
JOHN A. GALLOWAY, A.B., M.D. and WILLIAM H. PERLOFF, M.D. Philadelphia, Pennsylvania
A FORTY-SIX year old white woman (M. R.) was admitted to the hospital in August 1956 because of a lump in the breast. A radical mastectomy was performed and followed by local roentgen rays, radon seed and radiocobalt radiation therapy. The pathologist reported, “Carcinoma, inflammatory type.” The patient’s blood pressure before discharge was 142 mm. Hg systolic, 86 mm. Hg diastolic. Her weight was 154 pounds. When seen again in January 1958 the blood pressure was 108 systolic over 64 dias- tolic and her weight was 148 pounds. Her skin showed areas of grey-brown pigmentation, par- ticularly in the creases of the hands and knuckles. Her complaints were chronic unremitting fatigue, pain in the lower part of her back and right hip, and persistent cough. Roentgeno- graphic examination revealed a “cannon-ball” mass in the right side of the mid-thorax and a destructive lesion in the right ileum. One week later bilateral adrenalectomy was performed. The glands were approximately two times normal size; the left gland weighed 19.7 gm. and the right gland weighed 14.6 gm. Approxi- mately 95 per cent of the glands were replaced by opaque, pinkish grey tumor tissue. The in- tact cortex was bright yellow. The patient was treated with cortisone and her condition tem- porarily improved. The blood pressure remained at levels of 118 to 130 mm. Hg systolic, 78 to 82 diastolic. The downhill course was relentless, however, and she died on April 28, 1958. A post- mortem examination was not made. Despite the absence of laboratory evidence, the clinical findings strongly suggested the presence of Addison’s disease, secondary to adrenocortical replacement by neoplastic tissue prior to surgery.
In the light of this case, a literature review was
undertaken of reports and statistics on the fre- quency of metastasis of epithelial tumors to the adrenal glands. The incidence of adrenal in- sufficiency from metastatic destruction of the cortex was also studied.
Metastasis of carcinomas to the adrenal glands is a common finding at autopsy. Glomset [1] in 1938 found adrenal metastases in 13 per cent of 821 patients with malignant tumors. Burke [2] in 1934 reported that adrenal metas- tases were present in 49 (13 per cent) of 371 pa- tients with tumors. He found metastases from primary tumors of the esophagus, stomach, testicle, penis, prostate, uterus, thyroid, tongue, bladder and pancreas in either one or both adrenals. In 1948 [3] a patient with adrenal metastasis from carcinoma of the gallbladder was described.
Metastasis of carcinoma of the breast to the adrenals occurs with a frequency that is equaled or exceeded only by bronchogenic carcinoma. Saphir and Parker [4] reviewed the literature in 1941, including a series compiled in 1880. (Table I.) In their own study of forty-three in- stances of carcinoma of the breast they found adrenal involvement in nineteen cases, in thir- teen of which the tumor was recognized on gross examination. In seven instances both adrenals were involved. They concluded that the adrenal gland was the third most common metastatic site for carcinoma of the breast, following the lung (twenty-eight cases) and the liver (twenty-four patients). Burke [2] reported nine cases of adrenal involvement in thirty-five women with carcinoma of the breast and Willis [5] in 1941 described forty-five women with car- cinoma of the breast, 9 of whom showed adrenal metastases. Clark and Rowntree [6] stated in
* From the Departments of Medicine and Endocrinology, Temple University School of Medicine and Medical Center, Philadelphia, Pennsylvania.
| Series from | Year | Total Cases | Adrenal Metas- tases | Per cent |
|---|---|---|---|---|
| von Torok and Wittel- shofer | 1880 | 336 | 6 | 1.8 |
| Gross | 1888 | 114 | 1 | 0.9 |
| Paget | 1889 | 735 | 30 | 3.8 |
| Williams | 1894 | 44 | 2 | 4.5 |
| Campiche and Lazarus- Barlow | 1904 | 470 | 35 | 9.7 |
| Warren and Whitham. | 1933 | 160 | 50 | 31.2 |
| Glomset | 1938 | 43 | 25 | 58.2 |
| Saphir and Parker | 1941 | 43 | 19 | 44.2 |
1934 that cancer of the breast produced adrenal metastases more frequently than any other type of tumor.
More recent statistical surveys of adrenal tumor metastases compare the incidence of car- cinoma of the lung and breast. (Table II.) In 1950 Abrams, Spiro and Goldstein [7] found the in- cidence to be 35.6 per cent for cancer of the lung and 53.9 per cent for cancer of the breast, Bul- lock and Hirst [8] reported 28.7 per cent for lung and 12.8 per cent for breast and Sahagian- Edwards and Holland [9], reporting in 1954, found 42 per cent for lung and 34 per cent for breast.
Except for one case, admittedly questionable, which was reported by Thomas Addison [10] in 1849, we have found no reported instance of adrenal insufficiency from carcinoma of the breast. In 1952 Butterly et al. [11] reported three and possibly four cases of Addison’s dis- ease resulting from destruction of the adrenal glands secondary to bronchogenic carcinoma. In a review of the literature they could find only seven cases reported in fifty years; four from bronchogenic carcinoma, one from gastric car- cinoma, and two cases in which the type of tumor was not mentioned. In 1952 Wallach and Scharfman [12] reported an additional case and the most recent reports of Sahagian-Edwards and Holland [9] cited four more cases in 1954.
It is not quite clear why adrenocortical in- sufficiency does not develop more frequently in such patients. A possible explanation is that the course of cancer of the breast is terminated JANUARY, 1960
| Series from | Bronchus | Breast | ||||
|---|---|---|---|---|---|---|
| No. Cases | Ad- renals | Per cent | No. Cases | Ad- renals | Per cent | |
| Abrams, Spiro and Goldstein | 160 | 57 | 35.6 | 167 | 90 | 53.9 |
| Bullock and Hirst | 397 | 114 | 28.7 | 186 | 24 | 12.8 |
| Sahagian-Edwards and Holland | 283 | 119 | 42 | 178 | 61 | 34 |
before sufficient adrenal cortex is compromised. Wells [13] stated in 1930 that 90 per cent of patients with Addison’s disease show complete destruction of the adrenal gland. Guttman [14] in the same year reported that bilateral meta- static tumors seldom give rise to Addison’s disease. He noted that although little adrenal tissue is recognized on gross examination, “one finds abundant nests of surviving parenchyma microscopically.” He concluded that “the in- complete destruction of the suprarenal glands may account for the absence of symptoms of Addison’s disease.” Whatever the mechanism, it would appear that the rapid death of some patients with cancer of the breast may be hastened by occult Addison’s disease.
SUMMARY
A case of carcinoma of the breast with meta- static destruction of the adrenal glands, produc- ing clinical evidence of Addison’s disease, is presented. An analysis of the literature indicates a high incidence of metastasis of cancer of the breast to the adrenals, of the same order of fre- quency as bronchogenic carcinoma, but the inci- dence of Addison’s disease is low.
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