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Adrenal tumor

Adrenal tumor

Epidemiology:

Adrenal tumors represent a heterogeneous group of diseases characterized by varying clinical behaviors, with their incidence reported at approximately 3-4 cases per 100,000 population annually. Among these tumors, spontaneous remission (SR) is exceptionally rare, particularly in malignant forms such as adrenocortical carcinoma and pheochromocytoma, wherein documented cases suggest that SR constitutes less than 1% of related incidences 1,2. While sporadic cases have been reported concerning spontaneous remission associated with adverse events like hemorrhage or pharmacological interventions, substantial clinical research is needed to elucidate the mechanisms underlying such occurrences 3,4.

Clinical Characteristics:

To date, there have been eight reported cases of SR of either primary or metastatic adrenal tumors. There are several clinical trends that may be observed among these cases. The patients’ age at the time of remission ranges from newborn to 72 years. Females showed slightly higher rates of SR of adrenal tumors. See table 1 below for further information.

Histological Characteristics:

Of the cases analyzed, the histology of the tumors was primarily reported as originating from the adrenal gland, with most identified as adrenal cortical or glandular lesions. Instances of non-adrenal malignancies, such as renal or other extraglandular tumor types, were excluded from this data collection to maintain diagnostic consistency.

Proposed Contributing Mechanisms:

Among the reported cases, proposed mechanisms varied considerably. In two cases, tumor remission was associated with drug withdrawal, while one report proposed an apoptotic mechanism as a possible cause. Another case suggested alterations in DNA ploidy pattern as a contributing factor to remission. The remaining cases did not report any specific therapeutic or mechanistic associations. Collectively, these findings highlight that drug withdrawal, cellular apoptosis, and genetic alterations may play contributory roles in the spontaneous remission of adrenal tumors.

Site and Extent of Remission:

Among the reported cases, most showed complete remission of the primary adrenal tumor, while a few demonstrated remissions at metastatic sites such as the skin and CNS. One patient maintained remission for over two years, indicating durable disease control. Although follow-up data are limited, these findings suggest that spontaneous remission in adrenal tumors can occasionally result in sustained remission.

Table 1: Adrenal Tumor SR Cases and Clinical Characteristics

Author–year

Age/sex

Primary site

Remission site

Proposed mechanisms

Follow-up

Pasqualini & Gurevich, 19565

21/F

Adrenal cortex

Endocrine glands

Not reported

Not reported

Saracco et al., 19886

Newborn / Not reported

Adrenal gland

Skin, CNS

DNA ploidy pattern

1 year

Huston, 19887

20/F

Adrenal gland

Adrenal gland

Not reported

Not reported

Fujiwara et al., 20018

72/M

Adrenal gland

Adrenal gland

Apoptotic mechanism

26 months

Takeshita et al., 20189

45/M

Adrenal gland

Adrenal gland

Not reported

190 days

Hanai et al., 202110

72/F

Adrenal gland

Adrenal gland

Drug withdrawal

6 months

Pangc et al., 201511

86 -year-old female

Left side nose

Clinical remission at 8 weeks

IHC T/B cell infiltration. Tcell mediated immune reaction

Clinical remission at 8 weeks

Kara, 200012

38 years old woman. Operated of appendicitis at the age of 5. At 26 right oophorectomy. At 37 ovarian cystectomy. Patient had smoked one pack of cigarettes daily for 20 years.

Kidney/Adrenal glands bilateral

After 6 months from the first admission her abdominal CT and USG revealed total regression of surreal haematoma.

After 6 months from the first admission her abdominal CT and USG revealed total regression of surreal haematoma.

Kirikorian et al., 198013

42 -year-old male

right submandibular, right epitrochlear, left axillary, right inguinal and right femoral regions

2 months following his lymphogram, peripheral lymphadenopathy was noted to regress 4 months following his lymphogram, he had no evidence of disease on physical exam and the previously abnormal lymph nodes observed on the abdominal lymphogram and chest roentgenogram had regressed showing equivocal abnormalities but no definite evidence of lymphoma he has continued asymptomatic and without evidence of disease 5 years since his initial diagnsis

host immunity, local host or environment factors, diagnostic tools may affect the course of the disease

2 months following his lymphogram, peripheral lymphadenopathy was noted to regress 4 months following his lymphogram, he had no evidence of disease on physical exam and the previously abnormal lymph nodes observed on the abdominal lymphogram and chest roentgenogram had regressed showing equivocal abnormalities but no definite evidence of lymphoma he has continued asymptomatic and without evidence of disease 5 years since his initial diagnsis

Kirikorian et al., 198013

68 -year-old female

right posterior cervical, right posterior auricular, right submandiibular, bilateral axillary

3 months later, it was noted that her peripheral lymphadenopathy had regressed the left hilar mass on chest roentgenogram resolved and the abdominal lymphogram demonstrated marked reduction in the size of the involved lymph nodes she continues asymptomatic without therapy and without clinical evidence of disease 2 years after her visit

host immunity, local host or environment factors, diagnostic tools may affect the course of the disease

3 months later, it was noted that her peripheral lymphadenopathy had regressed the left hilar mass on chest roentgenogram resolved and the abdominal lymphogram demonstrated marked reduction in the size of the involved lymph nodes she continues asymptomatic without therapy and without clinical evidence of disease 2 years after her visit

Kirikorian et al., 198013

43 -year-old female

bilateral cervical, supraclavicular, axillary, and inguinal, and right iliac mass

4 months later, her peripheral lymphadenopathy was noted to regress chest roentgenogram demonstrated reduction of the hiar and paratracheal lymphadenopathy and lymphogram showed reduction in the size of the opacified lymph nodes partial regression of her lymphadenopathy continued for 14 months subsequently, her generalized lymphadenopathy began to enlarge slowly 32 months following her initial visit, she has not yet required therapy

host immunity, local host or environment factors, diagnostic tools may affect the course of the disease

4 months later, her peripheral lymphadenopathy was noted to regress chest roentgenogram demonstrated reduction of the hiar and paratracheal lymphadenopathy and lymphogram showed reduction in the size of the opacified lymph nodes partial regression of her lymphadenopathy continued for 14 months subsequently, her generalized lymphadenopathy began to enlarge slowly 32 months following her initial visit, she has not yet required therapy

Uslu, 201914

18-year-old man. Smoker. History of lichen planus

muscle

While further investigations were in progress, the patient recovered spontaneously without treatment.

None reported

While further investigations were in progress, the patient recovered spontaneously without treatment.

Gutierrez et al., 198015

72-year-old woman, T.T.G., general symptoms of discomfort, anorexia, asthenia and loss of weight, UCL and diabetes, a large decubitis ulcer of 6 centimeters in diameter is in the sacral region

Notable decrease of the large pulmonary metastasis, most of the pulmonary metastases were diminished in size and others had disappeared

Spontaneous reversion

Notable decrease of the large pulmonary metastasis, most of the pulmonary metastases were diminished in size and others had disappeared

Kessel & Tynes et al., 198116

A forty-two-year-old black woman

A repeat IVP showed findings of papillary necrosis but no evidence of a cystic lesion. A selective right renal arteriogram proved that the lesion was no longer present

A repeat IVP showed findings of papillary necrosis but no evidence of a cystic lesion. A selective right renal arteriogram proved that the lesion was no longer present

Kessel & Tynes et al., 198116

A sixty-four-year-old white woman

a repeat IVP with nephrotomograms showed bilateral irregular renal outlines but failed to demonstrate the large mass. Repeat renal angiography showed only bilateral multiple small cysts

a repeat IVP with nephrotomograms showed bilateral irregular renal outlines but failed to demonstrate the large mass. Repeat renal angiography showed only bilateral multiple small cysts

Yoneda et al., 201217

Loh et al.18

Marti et al.19

Bittencourt et al.20

Motayagheni et al.21

References:

  1. Loh K., Gupta R., & Shlossberg A. Spontaneous remission of ectopic cushing's syndrome due to pheochromocytoma: a case report. Acta Endocrinologica. 1996;135(4):440-443. doi:10.1530/eje.0.1350440
  2. Marti J., Millet J., Sosa J., Roman S., Carling T., & Udelsman R. Spontaneous adrenal hemorrhage with associated masses: etiology and management in 6 cases and a review of 133 reported cases. World j. surg.. 2011;36(1):75-82. doi:10.1007/s00268-011-1338-6
  3. Bittencourt J., Averbeck M., & Schmitz H. Hemorrhagic shock due to spontaneous rupture of adrenal pheochromocytoma. Int. braz j urol.. 2003;29(5):428-430. doi:10.1590/s1677-55382003000500007
  4. Motayagheni N., Azhough R., Barband A., Niafar M., & Pourfathi H. Spontaneous rupture of adrenal pheochromocytoma in a patient with von recklinghausen′s disease. Indian Journal of Critical Care Medicine. 2009;13(2):94-95. doi:10.4103/0972-5229.56056
  5. Pasqualini RQ, Gurevich N. Spontaneous remission in a case of Cushing’s syndrome. J Clin Endocrinol Metab. 1956;16:406–410.
  6. Saracco S, Abramowsky C, Taylor S, Silverman RA, Berman BW. Spontaneously regressing adrenocortical carcinoma in a newborn: a case report with DNA ploidy analysis. Cancer. 1988;62(3):507–511. doi:10.1002/1097-Q
  7. Huston N. Spontaneous remission of phaeochromocytoma. N Z Med J. 1988;101(845):248.
  8. Fujiwara T, Kawamura M, Sasaki A, Asahi H, Sasou S, Itoh S, Hiramori K. Transient spontaneous regression of aggressive non-Hodgkin’s lymphoma confined to the adrenal glands. Ann Hematol. 2001;80(9):561–564. doi:10.1007/s002770100335
  9. Takeshita Y, Teramura C, Takamura T. Vanishing of ruptured adrenal mass with takotsubo cardiomyopathy. Endocr J. 2018;65(12):1155–1159. doi:10.1507/endocrj.EJ18-0119
  10. Hanai S, Kobayashi K, Kawashima I, Ichijo M, Nakagomi D. Disappearance of bilateral adrenal tumours: immunodeficiency-associated lymphoproliferative disorder in a patient with rheumatoid arthritis. Rheumatology (Oxford). 2021;60(7):e255–e257. doi:10.1093/rheumatology/keab138
  11. Pang, C., Sharma, D., & Sankar, T. (2015). spontaneous regression of Merkel cell carcinoma: A case report and review of the literature. International journal of surgery case reports, 7C, 104–108. https://doi.org/10.1016/j.ijscr.2014.11.027
  12. Kara, & Paydaş, S. (2000). spontaneous regression of bilateral surrenal haematoma and subclinical hypoaldosteronism in a patient with renal amyloidosis secondary to Familial Mediterranean Fever. International urology and nephrology, 32(2), 291–292. https://doi.org/10.1023/a:1007196926394
  13. Krikorian, J. G., Porightlock, C. S., Cooney, P., & Rosenberg, S. A. (1980). spontaneous regression of non-Hodgkin's lymphoma: a report of nine cases. Cancer, 46(9), 2093–2099. https://doi.org/10.1002/1097-0142(19801101)46:9<2093::aid-cncr2820460931>3.0.co;2-4
  14. Uslu, S., Yüce İnel, T., Karakaş, A., & Önen, F. (2019). Spontaneous Remission of Isaacs’ Syndrome. Balkan medical journal, 36(4), 251–252. https://doi.org/10.4274/balkanmedj.galenos.2019.2019.2.53
  15. Gutierrez et al., 1980. Spontaneous Regression of the Metastasis of Renal Carcinoma. Revista Clinica Espanola 158(3-4): Aug 15-31 1980; 163-166
  16. Kessel & Tynes, 1981. Spontaneous Regression of Renal Cysts. Urology 17(4): April 1981; 356-357
  17. Yoneda, T., Demura, M., Takata, H., Kometani, M., Karashima, S., Yamagishi, M., & Takeda, Y. (2012). Unilateral primary aldosteronism with spontaneous remission after long-term spironolactone therapy. The Journal of Clinical Endocrinology and Metabolism, 97(4), 1109-1113. doi:10.1210/jc.2011-2563
  18. Loh K., Gupta R., & Shlossberg A. Spontaneous remission of ectopic cushing's syndrome due to pheochromocytoma: a case report. Acta Endocrinologica. 1996;135(4):440-443
  19. Marti J., Millet J., Sosa J., Roman S., Carling T., & Udelsman R. Spontaneous adrenal hemorrhage with associated masses: etiology and management in 6 cases and a review of 133 reported cases. World j.
  20. Bittencourt J., Averbeck M., & Schmitz H. Hemorrhagic shock due to spontaneous rupture of adrenal pheochromocytoma. Int. braz j urol.. 2003;29(5):428-430
  21. Motayagheni N., Azhough R., Barband A., Niafar M., & Pourfathi H. Spontaneous rupture of adrenal pheochromocytoma in a patient with von recklinghausen′s disease. Indian Journal of Critical Care Medici