THE AMERICAN JOURNAL of MEDICINE ®
A Man with a Clot on his Platelets: Adrenal Carcinoma and Dynamic Right Ventricular Inflow Obstruction
Anissa F McClelland, BSc, MBBS,a Amit K J Mandal, FRCP (Edin), FRCP,ª Fady Zakharious, MBBS, MRCP,a Constantinos G Missouris, MD, FRCpa,b,*
“Wexham Park Hospital, Frimley Health NHS Foundation Trust, Slough, UK; bUniversity of Cyprus Medical School, Nicosia, Cyprus.
KEYWORDS: Adrenocortical carcinoma; Caval; Right ventricular inflow; Thrombus
PRESENTATION
Adrenocortical carcinoma is a rare aggressive neoplasm that is often clinically silent until late in the disease process. A previously fit 82-year-old man presented to our service with a 4-week history of unintentional weight loss, worsen- ing exertional dyspnea, and right-sided pleuritic chest pain. His past medical history included polymyalgia rheumatica, for which he was taking a maintenance dose of predniso- lone 5 mg daily. He was a lifelong teetotaler and an ex- smoker of 30 pack-years up to the age of 50 years.
ASSESSMENT
Clinical inspection revealed an underweight icteric male. Secondary sexual characteristics were normal. Heart rate was 100 beats per minute and in sinus rhythm. Supine blood pressure was 124/60 mm Hg. On abdominal examination there was right upper quadrant tenderness and fullness, with pitting edema of the legs. The venous pressure was elevated, with jugular distension and prominent a-waves during both phases of respiration. Pulse oximeter oxygen saturations dropped from 98% on room air at rest when supine to 89% on sitting up. The resting 12-lead electrocar- diogram demonstrated sinus tachycardia with multifocal atrial ectopics.
Laboratory investigations were notable for D-dimer 10,765 umol/L (<500), alanine aminotransferase 1293 IU/L (4-59), alkaline phosphatase 152 IU/L (35-129), gamma-
glutamyl transferase 90 U/L (8-61), serum bilirubin 279 umol/L (<21), prothrombin time 29.4 seconds (12.5- 17.0), and serum albumin of 25 g/L (35-51). The full blood count, calcium chemistry, and markers of renal function were unremarkable. Functional tests of the adrenal gland, urinary steroid, and sex hormone profiles were within normal limits.
Computed tomography pulmonary angiography demon- strated a massive thrombus extending from the liver and inferior vena cava through to, and occupying, the right atrium. Computed tomography of the abdomen and pelvis further characterized a heterogeneous, complex, lobulated 10 × 16 × 5-cm mass posterior and superior to the right kidney arising from the adrenal gland. This was inseparable from a similar-sized liver deposit that invaded and throm- bosed the hepatic venous network and inferior vena cava, extending into the right atrium (Figures 1A-C).
DIAGNOSIS
These findings were consistent with metastatic nonfunction- ing adrenal cortical carcinoma.
Transthoracic echocardiography confirmed a 7.1 × 3.5- cm inhomogeneous echogenic mass in the right atrium pro- lapsing through the tricuspid valve, causing dynamic right ventricular inflow tract obstruction and near obliteration of the tricuspid valve during diastole (Figures 2A-C). There was preserved biventricular function.
Adrenocortical carcinoma is a rare and aggressive malig- nancy of the adrenal cortex with an annual incidence around 0.5-2.0 cases per million individuals. Unless identified early and surgically excised, it carries a poor prognosis. It has a bimodal distribution with a first peak at childhood (up to 6 years) and the second peak in the fourth to fifth decade of life.2,3
In 80% of cases it remains clinically dormant, with first presentation relating to effects of disseminated disease to
Funding: None.
Conflict of Interest: There are no conflicts of interest for all authors. Authorship: All authors had access to the data and a role in writing the manuscript.
Requests for reprints should be addressed to Constantinos G. Missou- ris, MD, Departments of Medicine and Cardiology, Wexham Park Hospi-
tal, Frimley Health NHS Foundation Trust, Wexham Street, Slough, UK. E-mail address: dinos.missouris@nhs.net
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lung, lymph nodes, liver, and bone. Protean clinical mani- festations associated with functional or secreting tumors (60% of cases), such as virilization, heterosexual pseudo- precocious puberty, and Cushing’s syndrome, perhaps con- vey a better prognosis because of earlier pick-up rates. Right-sided adrenocortical carcinoma is more often associ- ated with thrombosis to the right heart through direct drain- age of the right adrenal vein into the inferior vena cava (the left adrenal vein empties into the left renal vein). Associ- ated thrombotic hepatic venous occlusion leads to the clini- cal features of Budd-Chiari syndrome and portosystemic
shunting with peripheral edema, ascites, and fulminant hep- ato-renal failure.
MANAGEMENT
The patient was anticoagulated with treatment dose low- molecular-weight heparin (dalteparin 15,000 units subcuta- neously). Over the next week, there was rapid general decline with consumption coagulopathy, thrombocytopenia (platelets 10-20 × 109/L), encephalopathy, and progressive hepato-renal failure. Family discussions decided on best
ARTICLE IN PRESS
supportive and end-of-life care. The patient died 21 days after presentation.
Adrenocortical carcinoma is a rare and aggressive neoplasm, usually presenting in an advanced stage due to metastatic disease. Emphasis is therefore laid upon the need to exercise a high level of suspicion, for this often-dormant clinical entity, particularly among patients with late onset of symptoms related to steroid and hor- monal excess. Radical surgical excision remains the
treatment of choice for adrenocortical cancers that have not spread to other organs and where long-term cure may be achieved.4 Five-year survival with stage IV met- astatic disease is <10%, with a recurrence rate >90% (American Association of Endocrine Surgeons). Adju- vant chemotherapy has very little to add in the treatment of this cancer.
There are but a handful of reports thus far documenting the phenomenon of adrenocortical carcinoma with venous
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Figure 2 Continued.
tumor thrombus to the inferior vena cava and extending to the right heart. The only definitive management of atrial thrombus extension is complete surgical removal of the pri- mary tumor and cavoatrial mass under hypothermic cardio- pulmonary bypass, but with variable success. There is no credible beneficial role for peripheral thrombolysis with the inherent risks of clot fragmentation or thrombotic shower resulting in right ventricular outflow tract obstruction and fatal pulmonary embolus. Anticoagulation, on balance (there is still potential of conversion to a free-floating clot in the right ventricular inflow/outflow tract), is recom- mended to retard clot propagation during this thrombogenic state. Although, as in this case, disseminated intravascular coagulopathy and thrombocytopenia related to carcinoma- tosis and clot consumption can make the decision precari- ous. To our knowledge, this is the first documentation of adrenocortical carcinoma-associated dynamic right
ventricular inflow obstruction with diastolic tricuspid valve near occlusion that was compatible with life, albeit for a short period.
References
1. Kerkhofs TMA, Verhoeven RHA, van der Zwan JM, et al. Adrenocorti- cal carcinoma: a population-based study on incidence and survival in the Netherlands since 1993. Eur J Cancer 2013;49(11):2579-86.
2. Ng L, Libertino JM. Adrenocortical carcinoma: diagnosis, evaluation and treatment. J Urol 2003;169(1):5-11.
3. Wajchenberg BL, Albergaria Pereira MA, Medonca BB, et al. Adreno- cortical carcinoma: clinical and laboratory observations. Cancer 2000;88(4):711-36.
4. Icard P, Goudet P, Charpenay C, Andreassian B, Carnaille B, Chapuis Y. 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(7):891-7.