Diagnosis and Treatment > Signs and Symptoms
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Paediatric Endocrinology, Southern District Health Board, Dunedin, New Zealand
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Summary
Phaeochromocytomas are a rare clinical entity, with dual hormone-secreting lesions particularly uncommon, seen in <1%. ACTH is the most common hormone co-produced, and is potentially lethal if not diagnosed. We present the case of a previously well 10-year-old boy, who presented acutely with a hypertensive crisis and was found to have a unilateral, non-syndromic phaeochromocytoma. Medical stabilization of his hypertension was challenging, and took 3 weeks to achieve, before proceeding to unilateral adrenalectomy. Post-operatively the child experienced severe fatigue and was subsequently confirmed to have adrenal insufficiency. He improved markedly with hydrocortisone replacement therapy, which is ongoing 6 months post-operatively. In retrospect this likely represents unrecognized, sub-clinical ACTH-dependent Cushing's syndrome secondary to an ACTH/or precursor dual-hormone secreting phaeochromocytoma. At follow-up, his hypertension had resolved, there was no biochemical evidence of recurrence of the phaeochromocytoma, and genetic analysis was indicative of a sporadic lesion.
Learning points
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Dual hormone secreting phaeochromocytomas with ACTH/or a precursor may cause secondary adrenal insufficiency following surgical removal.
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The concurrent features of Cushing's syndrome can be mild and easily overlooked presenting diagnostic and management pitfalls.
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As concomitant syndromes of hormone excess are rare in phaeochromocytomas; the diagnosis requires a high index of suspicion.
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Serial/diurnal cortisol levels, ACTH measurement +/− low dose dexamethasone suppression (when clinically stable, appropriate adrenergic blockade in place, and well supervised), can all be considered as needed.
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Summary
Ipilimumab, a novel therapy for metastatic melanoma, inhibits cytotoxic T-lymphocyte apoptosis, causing both antitumor activity and significant autoimmunity, including autoimmune thyroiditis. Steroids are frequently used in treatment of immune-related adverse events; however, a concern regarding the property of steroids to reduce therapeutic antitumor response exists. This study describes the first reported case of ipilimumab-associated thyroid storm and implicates iopanoic acid as an alternative therapy for immune-mediated adverse effects. An 88-year-old woman with metastatic melanoma presented with fatigue, anorexia, decreased functional status, and intermittent diarrhea for several months, shortly after initiation of ipilimumab – a recombinant human monoclonal antibody to the cytotoxic T-lymphocyte-associated antigen 4 (CTLA4). On arrival, she was febrile, tachycardic, and hypertensive with a wide pulse pressure, yet non-toxic appearing. She had diffuse, non-tender thyromegaly. An electrocardiogram (EKG) revealed supraventricular tachycardia. Blood, urine, and stool cultures were collected, and empiric antibiotics were started. A computed tomography (CT) angiogram of the chest was negative for pulmonary embolism or pneumonia, but confirmed a diffusely enlarged thyroid gland, which prompted thyroid function testing. TSH was decreased at 0.16 μIU/ml (normal 0.3–4.7); free tri-iodothyronine (T3) was markedly elevated at 1031 pg/dl (normal 249–405), as was free thyroxine (T4) at 5.6 ng/dl (normal 0.8–1.6). With iopanoic acid and methimazole therapy, she markedly improved within 48 h, which could be attributed to lowering of serum T3 with iopanoic acid rather than to any effect of the methimazole. Ipilimumab is a cause of overt thyrotoxicosis and its immune-mediated adverse effects can be treated with iopanoic acid, a potent inhibitor of T4-to-T3 conversion.
Learning points
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While ipilimumab more commonly causes autoimmune thyroiditis, it can also cause thyroid storm and clinicians should include thyroid storm in their differential diagnosis for patients who present with systemic inflammatory response syndrome.
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Immune-related adverse reactions usually occur after 1–3 months of ipilimumab and baseline thyroid function testing should be completed before initiation with ipilimumab.
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Conflicting data exist on the use of prednisone for treatment of CTLA4 adverse effects and its attenuation of ipilimumab's antitumor effect. Iopanoic acid may be considered as an alternative therapy in this setting.
