JRSM >
Volume 99, Number 3 >
Pp. 153-155
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1 Clinical Lecturer, Department of Nuclear Medicine, Addenbrooke's Hospital,
Cambridge CB2 2QQ, UK
2 Research Associate, Department of Nuclear Medicine, Addenbrooke's Hospital,
Cambridge CB2 2QQ, UK
3 Professor of Clinical Pharmacology, Clinical Pharmacology Unit, Department of
Nuclear Medicine, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
4 Senior Radiographer, Wolfson Brain Imaging Centre; Department of Nuclear
Medicine, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
5 Specialist Registrar, Department of Nuclear Medicine, Addenbrooke's Hospital,
Cambridge CB2 2QQ, UK
Correspondence to: Dr Isla S Mackenzie E-mail: ism22{at}cam.ac.uk
Adrenal masses vary in importance from being incidental findings of no clinical significance to having sinister consequences through malignancy. The importance in integrating the clinical history, biochemical findings and results of modern imaging techniques is illustrated in this case.
CASE HISTORY
A man of 70 presented to his general practitioner with a 2-month history of weight loss, anorexia, nausea and abdominal pains. Past medical history included pharyngeal pouch and excision of a malignant melanoma from his left shoulder 7 years previously. The previous melanoma was a 1 cm maximum diameter superficial spreading type of malignant melanoma showing invasion of the epidermis and superficial dermis with a maximum depth of 0.6 mm. The resection margins were clear. The patient had shown no clinical evidence of local recurrence or axillary lymphadenopathy at 6-monthly reviews and was discharged after 5 years of follow-up according to the prevalent protocol.
Physical examination was unremarkable except for a scar on his shoulder. Routine blood tests and chest radiograph were normal. He was referred to his local hospital where he was seen a month later and was found to be hypertensive, with a blood pressure of 190/96 mmHg, for which he was commenced on lisinopril. Abdominal ultrasound and subsequent computerized tomography scanning (Figure 1) revealed enlargement of both adrenal glands, reported as `probably benign'. In view of the hypertension and adrenal masses, urinary catecholamines were measured. 24-hour urinary noradrenaline (254 nmol/24 h) and adrenaline (21 nmol/24 h) excretion were normal, but 24-hour urinary dopamine was grossly elevated at 18 783 nmol (normal 53194 nmol). He was referred to the tertiary centre (3 months after his initial presentation to his general practitioner) for further investigation of possible bilateral dopamine secreting phaeochromocytoma.
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He was seen the next day. By now he was generally unwell with nausea and vomiting, and had lost 20 kg in weight since the start of his illness. He had no palpitations, sweats or fainting. He looked cachectic and tanned. There was no palpable lymphadenopathy. Blood pressure was 159/85 mmHg. Large masses were palpable in both abdominal flanks. Adrenal insufficiency was suspected and after performance of a short Synacthen test (baseline cortisol 296 nmol/L, 30-min cortisol 268 nmol/L) he was started on hydrocortisone. His symptoms improved dramatically with increases in appetite and weight, and rapid resolution of the nausea and vomiting.
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Although curative resection for isolated adrenal metastases is well described,1,2 this option was excluded by the discovery of other metastases. Repeat computerized tomography scanning confirmed enlarged left axillary lymph nodes together with further enlargement of the adrenals and loss of clear tissue planes.
Despite replacement steroids and a course of palliative dacarbazine chemotherapy, the patient died 9 months after first detection of the adrenal masses.
DISCUSSION
This case illustrates the potential for diagnostic confusion between dopamine-secreting phaeochromocytoma and metastatic malignant melanoma and demonstrates how knowledge of the metabolic pathways of catecholamines facilitates correct diagnosis (see below). The very late presentation of clinically significant hypoadrenalism several years after the excision of a primary low-grade malignant melanoma is unusual. Other interesting features of the case include the use of FDG-PET scanning and the less common technique of F-DOPA PET scanning to help to confirm the diagnosis and avoid the need for biopsy.
Explanation for elevated urinary dopamine
Adrenal masses associated with several-fold elevation of urinary dopamine
may at first sight seem diagnostic of dopamine-secreting phaeochromocytoma.
However, pure dopamine secreting phaeochromocytomas in adults are very rare
and tend to present with symptoms of hypotension, vomiting, diarrhoea and
collapse. Plasma dopamine levels are typically several-fold elevated. This
patient's plasma dopamine was only slightly elevated while, in contrast, the
urinary dopamine levels were extremely high. DOPA is an intermediary in the
synthesis of melanin from tyrosine, with the same enzyme—tyrosine
hydroxylase—catalysing both the initial synthesis of DOPA and its
subsequent conversion to dopaquinone, the precursor of the melanins
(Figure 4). Induction of
tyrosine hydroxylase in melanoma tissue leads to the formation of excessive
amounts of DOPA, melanogens and melanins. High circulating levels of DOPA are
converted to dopamine by the enzyme DOPA decarboxylase during renal excretion.
DOPA decarboxylase is mainly located in the kidneys, which explains the
greatly elevated dopamine levels found in this patient's
urine.3
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PET scanning in the diagnosis of adrenal masses
Adrenal masses often present a diagnostic problem. Fine needle biopsy may
be useful, but is not recommended for possible phaeochromocytoma. PET scanning
complements computerized tomography and magnetic resonance scanning by
providing more functional information about the adrenal masses. FDG-PET
scanning is frequently used to locate tumours or metastases in patients with
known primaries, including melanomas. F-DOPA PET scanning has mainly been used
as a research tool in studies of the brain, and more recently in the imaging
of phaeochromocytoma, and is less widely available than FDG. Whereas any
metabolically active tissue will accumulate FDG, a follow-up scan with F-DOPA,
as in our patient, may help confirm the origin of FDG hotspots and increases
sensitivity for detecting metastases in
melanoma.6
Hypoadrenalism and metastatic malignant melanoma
Adrenal metastases may present several years after the initial presentation
of melanoma and usually occur in patients in whom the original lesion was
judged as locally advanced. However, the only previous reports of such
patients developing clinically significant hypoadrenalism have been at or
shortly after initial presentation of the
melanoma2. Over 90%
of the adrenal cortices must be destroyed before there is significant loss of
function. Adrenal dysfunction may either develop gradually due to replacement
of adrenal tissue with tumour, or suddenly due to acute adrenal haemorrhage.
It has been suggested that prophylactic steroids should be given to any
patient with known adrenal metastases to avoid the risk of hypoadrenal crisis
due to adrenal
haemorrhage.7 There
are reports of successful outcomes following adrenalectomy for patients with
metastatic melanoma isolated to the adrenal
glands.1,2
However, the prognosis is significantly poorer if only incomplete resection of
disease can be
achieved.8
In summary, this case of a patient with malignant melanoma with hypoadrenalism and excess urinary dopamine excretion illustrates the importance of asking about any history of tumours when diagnosing adrenal masses, and highlights the value of integrating the history into the diagnostic process and of linking clinical features with knowledge of biochemical pathways.
Footnotes
Acknowledgments PET scanning at Addenbrooke's Hospital is supported by a Medical Research Council Wolfson Brain Imaging Centre Cooperative Group Grant. IM is supported by a British Heart Foundation Clnical PhD Studentship and a Sackler Award.
Competing interests None declared.
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