CASE REPORT
Normal delivery following resection of an androgen-secreting adrenal carcinoma
Toshiyasu Amano · Tetsuya Imao · Masaya Seki ·
Katsurou Takemae . Keishi Yamauchi . Satoru Hata
Received: 9 September 2010/Accepted: 2 November 2010/Published online: 26 November 2010 @ Japan Society for Reproductive Medicine 2010
Abstract A 31-year-old female presented to a gyneco- logical clinic complaining of amenorrhea and virilism over a 2-month period. Blood tests revealed high serum total testosterone and free testosterone levels. A left adrenal tumor was identified following computed tomography and she was referred to our clinic where a laparoscopic left adrenalectomy was performed. The tumor weighed 98 g and the pathological diagnosis according to Weiss’ criteria was adrenocortical carcinoma. The post-operative course was uneventful; her serum free testosterone level normal- ized and regular menstruation was observed 1 month post- operatively. The patient became pregnant 1 year later, resulting in the normal delivery of a girl.
Keywords Adrenal cancer . Androgen-secreting . Pregnancy · Delivery
Introduction
Androgen-secreting adrenal tumors are extremely rare; moreover, many of these tumors are diagnosed as malig- nant disease [1]. In general, adrenocortical carcinoma is
T. Amano ☒ · T. Imao · M. Seki · K. Takemae Department of Urology, Nagano Red Cross Hospital, Wakasato 5-22-1, Nagano 380-8582, Japan e-mail: amanot@nagano-med.jrc.or.jp
K. Yamauchi Department of Metabolic and Endocrinology, Nagano Red Cross Hospital, Nagano, Japan
S. Hata Department of Clinical Laboratory, Nagano Red Cross Hospital, Nagano, Japan
characterized by a high malignant potential and a poor prognosis, e.g., mean survival times vary between 2.1 years for Stage I to 1.1 years for Stage IV [2]. How- ever, the prognosis of androgen-secreting adrenal carci- nomas is not grim in cases demonstrating the absence of invasion or metastasis, for example, in a study by Cordera et al., only one of five androgen-secreting adrenal cancer patients died after 29 months and the other four were still alive with no evidence of disease for 29-387 months [1].
We report the case of a 31-year-old female who expe- rienced the normal delivery of a healthy child following the removal of an androgen-secreting adrenal carcinoma.
Case report
A 31-year-old female presented to a regional gynecological clinic complaining of amenorrhea and virilism over a 2-month period. Blood tests revealed low serum adreno- corticotropic hormone (ACTH) and high serum total tes- tosterone and free testosterone levels. Consequently, she was referred to the Department of Metabolic and Endo- crinology in our hospital for more detailed evaluation. Although elevated hemoglobin (15.9 g/dL) was detected, the results of additional blood tests were unremarkable (Table 1).
Computed tomography (CT) disclosed a left adrenal tumor (6.0 × 6.0 × 5.5 cm) (Fig. 1). 131I-aldosterol scin- tigram SPECT (single-photon emission CT) identified high uptake of radioisotope by the left adrenal tumor (Fig. 2). Positron emission tomography (PET) demonstrated no abnormal accumulations with the exception of the left adrenal region (Fig. 3).
Based on these data, the patient was diagnosed with a left androgen-secreting adrenal tumor. She was referred to
| WBC | 35.6 (102/LL) | |
| RBC | 501 (104/LL) | H |
| Hb | 15.9 (g/dL) | H |
| Ht | 48.8 (%) | H |
| Plats | 22.5 (104/LL) | |
| AST(GOT) | 13 (IU/L) | |
| ALT(GPT) | 9 (IU/L) | |
| LDH | 162 (IU/L) | |
| ALP | 199 (IU/L) | |
| T Prot | 7.7 (g/dL) | |
| BUN | 9.8 (mg/dL) | |
| Cr | 0.69 (mg/dL) | |
| UA | 5.1 (mg/dL) | |
| Na | 141 (mEq/L) | |
| K | 4.1 (mEq/L) | |
| Cl | 103 (mEq/L) | |
| FBS | 98 (mg/dL) | |
| CRP | 0.01 (mg/dL) | |
| LH | 1.16 (mIU/mL) | |
| FSH | 5.11 (mIU/mL) | |
| Total testosterone | 4.36 (ng/ml) | H |
| Free testosterone | 15.1 (pg/mL) | H |
| ACTH | 2.0 (pg/mL) | L |
| PRL | 14.21 (ng/ml) | |
| Adrenaline | 56 (pg/mL) | |
| Dopamine | 16 (pg/mL) | |
| Cortisol | 9.9 (µg/dL) | |
| Aldosterone | 320 (pg/mL) |
Low serum ACTH and high serum total testosterone, free testosterone and hemoglobin levels were detected
H Higher than normal range level, L lower than normal range level
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our clinic for surgical treatment and underwent a laparo- scopic left adrenalectomy. The tumor adhered slightly to the surrounding tissue; however, resection of the tumor with sparing of the left adrenal grand was uncomplicated. Operative time was 180 min and blood loss during the procedure was 30 mL. The total weight of the specimen was 98 g (tumor 86 g, adrenal gland + fat 12 g) (Fig. 4). Microscopical findings disclosed a tumor characterized by: (1) high nuclear grade, (2) clear cells comprising 0-25% of the neoplasm, (3) necrosis, (4) invasion of venous struc- tures, and (5) invasion of the tumor capsule. Thus, the pathological diagnosis per Weiss’ criteria was adrenocor- tical carcinoma (5 of 9 criteria were positive) [3, 4] (Fig. 5).
The post-operative course was uneventful; her serum free testosterone level normalized (<0.6 pg/mL) and reg- ular menstruation was evident 1 month post-surgery. CT, ultrasonography (USG) and PET findings were unre- markable. She became pregnant 1 year after the proce- dure. She was followed up by USG during her pregnancy 5] ; neither recurrence nor metastasis was observed. She gave birth to a girl (weight 3,516 g) at 40 weeks via normal delivery.
Discussion
Adrenocortical carcinoma is a rare tumor; its incidence has been reported as approximately 0.5-2 cases per million
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people per year [6]. Clinical investigations of the endo- crinological aspects of adrenocortical carcinoma revealed that Cushing’s syndrome and endocrinological non-
function tumors are most common; however, only 14-18% of these tumors are androgen-secreting [6-8].
The distinction between benign and malignant adreno- cortical tumors is rather unclear. The diagnosis is some- times rendered following consideration of a combination of clinical and pathological findings. In these situations, Weiss’ criteria are widely accepted for the pathological diagnosis of adrenocortical carcinoma [3, 4]; nine micro- scopic features including: (1) nuclear grade III or IV, (2) mitotic rate greater than 5/50 high-power fields, (3) atyp- ical mitoses, (4) clear cells comprising 25% or less of the tumor, (5) diffuse architecture, (6) necrosis, (7) invasion of venous structures, (8) invasion of sinusoidal structures, and (9) invasion of the tumor capsule have been described. When three or more of the nine criteria are evident in a specific tumor, the diagnosis of adrenocortical carcinoma is viable. The specificity and sensitivity of the Weiss system have been reported as 96 and 100%, respectively [9]. Thus, Weiss’ criteria are quite reliable. In the current case, five of the nine criteria were observed. Accordingly, the patho- logical diagnosis was adrenocortical carcinoma.
Overall 5-year survival rates of 35-38% have been doc- umented; however, 5-year survival rates in cases involving aggressive surgical intervention were higher (48.2-55%) [10-12]. Our patient presented to a local clinic at an early stage of the disease. As neither invasion nor metastasis was observed, we were able to perform radical resection of the left adrenal tumor. Fortunately, the adrenal carcinoma in this case secreted androgen, which induced male characteristic symptoms. Pure androgen-producing tumors are extremely rare; moreover, surgical resection affords an excellent treatment option in the absence of metastasis at the time of diagnosis [1]. Most adrenal cortical carcinomas, however, are detected too late for curative resection; consequently, treatment of metastatic disease with mitotane has met with limited success [2]. Thus, the early detection of adrenal tumors is essential with regard to effective treatment of this carcinoma. Accordingly, health screening including USG might be recommended for everybody.
No recurrence or metastasis was apparent at 1 year post- surgery based on CT, USG and PET. Subsequently, the patient became pregnant and was closely followed up by USG for recurrence or metastasis; however, the patient gave birth to a girl (weight 3,516 g) at 40 weeks via normal delivery. To the best of our knowledge, this case is only the second example involving a live birth following surgery for an androgen-secreting adrenal tumor in the English lan- guage literature [1]. In general, women characterized by severe hypertension, previous myocardial infarction, venous thromboembolism or cerebrovascular stroke, are at significant risk of complications during pregnancy [13]. In the current case, the aforementioned complications and recurrence were not observed; as a result, USG follow-up
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was continued. During pregnancy, major hormonal changes include elevation of estrogen, progesterone and prolactin levels, and it is possible that these hormonal increases may promote colorectal cancer progression [14]. The presence of androgen-secreting adrenal carcinoma may not be a restriction for gestation and delivery if the tumor is located and the patient has curative surgery.
Conclusion
We reported a case involving a 31-year-old female diag- nosed with a left androgen-secreting adrenal carcinoma without metastasis. Laparoscopic surgery was performed successfully; subsequently, her symptoms abated and her hormonal levels normalized. One year post-operatively, she became pregnant, which resulted in the normal delivery of a healthy girl. Early diagnosis and treatment are of the utmost importance for androgen-secreting carcinomas.
References
1. Cordera F, Grant C, van Heerden J, Thompson G, Young W. Androgen-secreting adrenal tumors. Surgery. 2003;134:874-80.
2. Wooten MD, King DK. Adrenal cortical carcinoma. Epidemiol- ogy and treatment with mitotane and a review of the literature. Cancer. 1993;72:3145-55.
3. Weiss LM. Comparable histologic study of 43 metastasizing and non-metastasizing adrenocortical tumors. Am J Surg Pathol. 1984;8:163-9.
4. Weiss LM, Medeiros LJ, Vickery AL Jr. Pathologic features of prognostic significance in adrenocortical carcinoma. Am J Surg Pathol. 1989;13:202-6.
5. Torloni MR, Vedmedovska N, Merialdi M, Betran AP, Allen T, Gonzalez R, et al. Safety of ultrasonography in pregnancy: WHO systematic review of the literature and meta-analysis. Ultrasound Obstet Gynecol. 2009;33:599-603.
6. Langer P, Bartsch D, Moebius E, Rothmund M, Nies C. Adre- nocortical carcinoma-our experience with 11 cases. Langen- beck’s Arch Surg. 2000;385:393-7.
7. Lipsett MB, Hertz R, Ross GT. Clinical and pathologic aspects of adrenocortical carcinoma. Am J Med. 1963;35:374-83.
8. Zakoji H, Tsuchida M, Kawaguchi M, Mikami Y, Kayanuma K, Nomura T, et al. Treatment of adrenocortical carcinoma: results in a consecutive series of 7 patients. Rinsho Hinyokika. 2009;63:603-7. (in Japanese).
9. Aubert S, Wacrenier A, Leroy X, Devos P, Carnaille B, Proye C, et al. Weiss system revisited: a clinicopathologic and immuno- histochemical study of 49 adrenocortical tumors. Am J Surg Pathol. 2002;26:1612-9.
10. Crucitti F, Bellantone R, Ferrante A, Ferrante A, Boscherini M, Crucitti P. The Italian registry for adrenal cortical carcinoma: analysis of a multi-institutional series of 129 patients. Surgery. 1996;119:161-70.
11. Schulick R, Brennan MF. Long-term survival after complete resection and repeat resection in patients with adrenocortical carcinoma. Ann Surg Oncol. 1999;6:719-26.
12. Icard P, Goudet P, Charpenay C, Charpenay C, Andreassian B, Carnaille B, et al. Adrenocortical carcinomas: surgical trends and results of a 253-patient series from the French association of endocrine surgeons study group. World J Surg. 2001;25:891-7.
13. Fraser S. Contraceptive choice for women with ‘risk factors’. Drug Saf. 1993;8:271-9.
14. Spanos CP, Mamopoulos A, Tsapas A, Syrakos T, Kiskinis D. Female fertility and colorectal cancer. Int J Colorectal Dis. 2008;23:735-43.