Case Repor
J Fam Med. 2014;1(2): 4.
No he Usual Suspecs: Challenges of Deecing Nonfuncioning Adrenal Corical Carcinoma – A Case Repor
Sivoravong J, Ly TM, Nejek VA* and Talari D
Deparmen of Family Medicine, Universiy of Norh Texas Healh Science Cener, USA
Absrac
Adrenal Corical Carcinomas (ACC) are rare affecing abou 1 ou of 1,000,000 persons in he general populaion wih he median age of 46 years old a he ime of diagnosis [1,2]. A umor of he adrenal corex may be funcioning or nonfuncioning. A funcioning adrenocorical umor may produce excessive corisol, aldoserone, esoserone, or esrogen ha can be used o help clarify a diagnosis. Here, we repor a case of nonfuncional adrenal corical carcinoma in a middle-aged paien seeking reamen for severe low back pain. The paien had no documened pas medical hisory, was no on any prescripion medicaions, and had no abnormal screening laboraory values. An abdominal ulrasound showed an enlarged solid isoechoic mass in he upper medial pole of he lef kidney. The workup found a Sage IV nonfuncioning ACC ha had measasized o he lumbar spine. This case is especially helpful in reminding family physicians o consider looking beyond ypical ACC hormone dysfuncion and consider invesigaing nonfuncioning ACC in he differenial for inracable low horacic and/or lumbar back pain.
Case Presenaion
Physical findings
A 58-year old Caucasian male presened o he Emergency Room (ER) complaining of progressively severe lef flank pain during he previous week. The pain radiaed from his lef flank across in a band like fashion o he anerior par of his abdomen. The paien had no documened pas medical hisory, was no aking any prescripion medicaions, had no fever or obvious signs of infecion, no exernal injuries or muscle rauma. The paien denied headache, recen weigh changes, ches pain, join siffness, swelling, nausea, and vomiing, neurologic or psychiaric difficulies.
The paien was iniially reaed wih Inravenous (IV) saline fluids, IV dexamehasone 6 mg every six hours, and IV morphine drip were given for pain conrol. Break-hrough pain was managed using 60 mg of hydrocodone biarrae wih aceaminophen as needed every four hours. The paien also received 4 mg of oral ondanseron as needed every four hours for nausea and ducosae sodium 100 mg wice daily for opioid-induced consipaion. For Deep Venous Thrombosis (DVT) prophylaxis, he paien received a daily 40 mg subcuaneous injecion of enoxaparin. A sudden onse of hyperension (presumably due o increasing pain) was conrolled wih 10 mg of Lisinopril and 25 mg of meoprolol XL. Subsequen urinary reenion secondary o obsrucive uropahy required caheerizaion and he addiion of 50 mg of oral behanechol plus 0.4 mg of amsulosin hydrochloride (Table 1).
Theme
Subheme
Illusraive Quoaion
Perceived conrol a conracepive iniiaion Pressure from a family member
My mom pu me on Depo when I was 14, I wasn’ even having sex. Bu i was like forced on me, even if I didn’ know abou he oher mehods, i was &quo;you go and ge ha&quo; and ha’s i, ‘cause I couldn’ even consen if I waned i or no.
My mom […] I feel like my mom pushed i on me as an embarrassmen. Or no even an embarrassmen, bu she didn’ approve of i, bu she was like if you’re going o keep doing i, I wan you o go o he docor’s…
Gender difference in auonomy
And I hink i’s differen beween boys and girls. I sill brough my mom, when I was ha age. And hen, like, bu my broher, he never had my mom and suff in he room.
Influence on daugher’s decision-making
And ha’s wha I go my daugher, my oldes wo kids on now. Because my daugher jus had a se of wins. I was her firs pregnancy, so I hink Depo is he bes one.
Prior encouners wih healh care providers Lack of knowledge among providers
I don' hink hey know much abou birh conrol.
Necessiy for openness
I wan all he facs. Don’ sugar coa, I need o know every possibiliy of everyhing. ‘Cause when I go his Implanon, he only hing she old me was “Oh you’re gonna have irregular periods,” whaever, whaever, bu she didn’ ell me all his oher suff ha could go wrong.
I’m leing you know everyhing, because I wan you o feel like you’re here, so you know wha’s going on. So I wan you o speak o me openly.
Providers dismissive of side effecs
I alked o he docor recenly abou birh conrol, like how I hink Depo made i no easy for me o have kids, and so she’s elling me, “well you only been married for like six monhs, so you shouldn’ worry abou no having kids, like, you jus sared rying.” I been having sex since I was 16! And I ain’ go pregnan ever! So she hinks she doesn’ wan o alk abou he whole conversaion. So she jus brushed me off like, “well you don’ need o go o anoher docor, you don’ need o see an OB/GYN so he can check you down here.” ‘Cause I’m like, here migh be somehing wrong down here! You don’ know.
Provider willingness o assis wih reurn o feriliy
I don’ have conrol over family planning, because, like I said, even hough I did ake he birh conrol pill and he sho, when I was ready o ge off of i, and I’ve been off of i, i was like, hey were here o help me ge he birh conrol, bu hey’re no here o help me figure ou how I can have a baby.
Aiude regarding safey and side effecs Side effecs as he primary conracepive concern
Tha would be he mos imporan hing ha you wanna ell he paien is he side effecs.
Negaive percepions of Depo Provera
Well I ried he Depo sho and I gained a lo of weigh and my hair fell ou. And I didn’ have a mensrual for like wo or hree monhs, and hen i came back again and hen I jus compleely sopped having hem. So I don’ like he Depo.
Safey concerns abou new mehods
Well hey had ha commercial on TV abou he Yaz one, and I was jus hinking abou how maybe hey came ou wih i oo fas and now i’s being recalled.
Concern abou lasing effecs on feriliy
And afer you sar i, you can’ ge pregnan for a long ime. I didn’ ge pregnan for years afer I go one sho. I hink you could ake i only like once a year and no ge pregnan.
Table 1: Admiing Vial Signs and Laboraory Tes Resuls.
Laboraory resuls, imaging sudies, differenial diagnosis
Table 1 shows hospial admission laboraory resuls. Table 2 illusraes addiional chemisry and endocrine sudies conduced on days 1-7 of inpaien say. Plasma meanephrine, normeanephrine, and dexamehasone suppression ess ruled ou pheochromocyoma and Cushing’s syndrome [3,4]. Radiographs showed lower spine degeneraive disc disease (no shown). Ulrasound of he abdomen showed an enlarged solid isoechoic mass slighly anerior o he upper medial pole of he lef kidney which provided physicians enough diagnosic jusificaion o order addiional imaging ess. Nonconras Magneic Resonance Imaging (MRI) of he lumbar spine showed arhrosis, moderaely severe neural foramina narrowing, spondylosis, arhropahy, canal senosis, broad-based Lumbar (L) and Sacral (S) disc bulges from L1, 2, L5 - S1 and a large mass involving L2 and L3. Abdominal Compued Tomography (CT) scan wihou conras showed a large adrenal mass which was confirmed on MRI (Figure 1) and suggesed measasis o he lumbar spine. A CT-guided needle biopsy iniially suggesed ACC and he respeced issues from he subsequen adrenoecomy confirmed he ACC diagnosis (Figure 1 and 2).
Figure 1: T2 weighed magneic resonance image of ACC mass.
Chemisry
Reference Unis
Collecion Dae
Collecion Time
Acual Unis
Day 1
9-28
2025
Calcium Ioniz 1.12-1.32 mmol/L
“
“
1.10
Anion Gap 5.0-19.0 mmol/L
“
“
18.0
Glucose 70-110 mg/dL
“
“
106.0
BUN 7-18 mg/dL
“
“
15
Creainine 0.8-1.3 mg/dL
“
“
1.1
Day 2
9-30
0527
CRP &l;0.29 mg/dL
0.88
Days 3 -4
Corisol undefined ug/dL
10-02
1804
7.18
10-03
0928
0.78
Day 5
10-05
1223
Plasma
Normetanephrine
0-145 pg/mL
“
“
83.0
Metanephrine
0-62 pg/mL
“
“
31.0
Day 6
10-08
0436
Prealbumin
20.0-40.0 mg/dL
23.4
Venus Blood Gases
mmHg
PH
7.350-7.45
“
1413
7.357
PCO2
44.0-48.0
“
“
51.4
PO2
38.0-42.0
“
“
27.9
HCO2
20-30 mmol/L
“
“
28.9
BASE EXCE
- 2 to +2
“
“
2.4
O2 SAT
60.0-80.0 %
“
“
48.5
Total CO2
21-31 mmol/L
“
“
30.4
Day 7
10-09
1523
Urine
ug/L
Metanephrine
undefined
“
“
44
Metanephrine Catecholamine
45-290 / 24 hr
“
“
81
Normetanephrine
Undefined
“
“
203
Normetanephrine Catecholamine
82-500 / 24 hr
“
“
376
Table 2: Additional Chemistry and Endocrine Study Results on Inpatient Days 1-7.
Confirmatory diagnosis and patient course
The patient underwent adrenoectomy. The tumor was 13.5 cm in length, and weighed 236 grams and obliterated the left adrenal gland and has areas of vascular invasion. Tissue immunostain studies were negative for renal cell carcinoma Ag, chromogranin A, S-100 Ag, and leukocyte common antigen, but were positive for inhibin-a, melan A, synaptophysin, pan keratin and calretinin. Histological report revealed nested, trabecular, and thick columns of elongated or ovoid cells divided by a delicate vascular network with diffuse growth patterns indicative of ACC (Figure 2). Based on overall morphology, clinical presentation and immunostaining pattern, the pathologist classified this highly malignant neoplasm as a poorly differentiated adrenal cortical carcinoma. The invasion of the L2-3 lumbar spine and the size of the mass suggested the patient had stage IV metastatic cancer (McFarlane/Sullivan classification) [5]. After the adrenoectomy, the patient received follow-up treatment with oral mitotane (adrenal-specific pharmacotherapy) using a dosing strategy similar to Terzolo et al [6] and was given prednisone for prevention of hypocortisolism.
Figure 2: Histology shows diffuse growth patterns indicative of ACC.
The patient was discharged to home with instructions to followup with the general surgeon and a hematology/oncology specialist in 2-weeks and a neurosurgeon within 1-week. Other discharge medications included oral 5 mg of hydrocodone bitartrate and 325 mg acetaminophen and oral 50 mg of morphine sulfate controlledrelease taken as needed for pain plus 100 mg of ducosate taken twice daily for opioid-induced constipation. The prognosis for this patient is considered very poor. In line with the literature [3,7,8], this patient has an estimated post-surgery survival rate of about 14-months.
Discussion
Observable versus non-apparent risks
Nonfunctional ACC is difficult to diagnose compare to functioning adrenal mass due to the lack of pathological hormonal presentation [3,8-10]. The differential diagnosis of the adrenal mass in this case includes adenoma, myelolipoma, cyst, lipoma, pheochromocytoma, adrenal cancer, metastatic cancer, hyperplasia, and tuberculosis [3,8-10]. Generally, about 50% of ACC are identified late in the disease process with distant metastasis in the lungs, liver, peritoneum, lymph nodes, and/or bones arising from other sources such as bronchogenic carcinoma, renal cell carcinoma or melanoma [2-4,8,9]. Although the patient presented here may represent less than one-third of all ACC cases, these dismal statistics suggest that many more nonfunctioning ACC cases potentially go unrecognized and untreated. Kapoor et al report the forensic prevalence of nonfunctioning ACC is as high as 8% discovered during autopsy [11].
One reason why earlier detection was obscured in this particular patient may be that the lower back pain may have been considered common given his age, as risks for nonfunctioning ACC may increase with age [11]. Another possible reason is that this patient did not present with endocrine abnormalities or the usual symptoms associated with functioning ACC. Thus, in the absence of these warning signs patients of any age are unlikely to seek medical treatment for back pain unless the pain has a sudden onset or is severe and intractable. These diagnostic difficulties suggest the need for heightened awareness of the risks and atypical clinical symptoms that may point towards ACC.
The mean age of diagnosis, in adults, is 45 years and men with adrenocortical carcinoma tend to have non-functional tumors after the age of 40 years [12]. The majority of adrenal cortical cancers are sporadic but up to 15% are linked to genetic defects especially when seen in children. Genetic syndrome that have been linked to adrenal cancer are Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, Multiple Endocrine Neoplasia (MEN1), Familial Adenomatous Polyposis (FAP), and Hereditary Nonpolyposis Colorectal Cancer (HNPCC) also called Lynch Syndrome (https://www.cancer.org/acs/ groups/cid/documents/webcontent/003081-pdf.pdf). Physicians should be aware of the possible link between nonfunctional ACC and radiating back pain due to the anatomical placement of an adrenal mass impinging on adjacent spinal nerves as in this case report. In terms of gender risks, Ng and Libertino (2003) [9] reported that in four out of seven studies (n=602), nonfunctional ACC was predominantly found in 62% of the women examined.
Suggested screening strategies
Currently, there are no clearly defined outpatients screening protocols to help identify nonfunctioning ACC. Here, we recommend adding a three-step preliminary differential screening protocol to help detect early stage nonfunctioning ACC in the outpatient setting: (1) consider age, sex, and presence of high risk genetic syndrome, (2) be suspicious with unexplained radiating and/or intractable low thoracic or lumbar back pain proximal to the adrenal gland area, (3) conduct ultrasonography tests as a screening method when patients meet criteria for #1 and #2. Thus, a potential change in examination and screening strategies in outpatient settings may be warranted in addition to becoming aware of the risk factors and unusual symptoms of nonfunctioning ACC. Due to the morbidity of late stage ACC, it is important for physicians to be vigilant in their examinations and thorough with the laboratory workup in ‘at-risk’ yet asymptomatic patients. This case serves to remind clinicians to look beyond the usual suspects and consider investigating an adrenal mass as nonfunctioning ACC may present only with intractable thoracic or lumbar back pain.
References
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- Allolio B, Fassnacht M. Clinical review: Adrenocortical carcinoma: clinical update. J Clin Endocrinol Metab. 2006; 91: 2027-2037.
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- Abiven G, Coste J, Groussin L, Anract P, Tissier F, Legmann P, et al. Clinical and biological features in the prognosis of adrenocortical cancer: Poor outcome of cortisol-secreting tumors from a series of 202 consecutive patients. J Clin Endocrinol Metab. 2006; 91: 2650–2655.
- Luton JP, Martinez M, Coste J, Bertherat J. Outcome in patients with adrenal incidentaloma selected for surgery: an analysis of 88 cases investigated in a single clinical center. Eur J Endocrinol. 2002; 143: 111–117.
- Ng L, Libertino JM. Adrenocortical carcinoma: diagnosis, evaluation and treatment. J Urol. 2003; 169: 5-11.
- Cook DM. Adrenal mass. Endocrinol Metab Clin North Am. 1997; 26: 829-852.
- Kapoor A, Morris T, Rebello R. Guidelines for the management of the incidentally discovered adrenal mass. Can Urol Assoc J. 2011; 5: 241-247.
- Benassai G, Desiato V, Benassai G, Bianco T, Sivero L, Compagna R, et al. Adrenocortical carcinoma: What the surgeon needs to know. Case report and literature review. Int J Surg. 2014; 12: 22-28.
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