A case study recently published in Endokrynologia Polska—the Polish Journal of Endocrinology—describes a patient whose systemic mastocytosis (SM) symptoms mimicked those of carcinoid syndrome (CS), highlighting the importance of differential diagnoses.
The case study described a 44-year-old woman who was admitted to the Endocrinology Department in the Military Institute of Medicine, National Research Institute, Warsaw, Poland, because of suspected CS. Two months prior to her hospitalization, the patient experienced a significant local reaction following a hornet sting. After being stung, she reported the periodic occurrence of headaches and facial flushing.
Following this, the patient experienced sudden cardiac arrest (SCA), which necessitated the use of brief cardiopulmonary resuscitation. Cardiac and neurologic causes of SCA were dismissed, as were organic pathologies and infections. She was referred for an endocrinological evaluation because of a possible neuroendocrine neoplasm being responsible for CS.
The patient’s condition continued to be serious, as she reported daily morning episodes of facial flushing, sudden headaches, conjunctival redness and nasal congestion, along with hypotension, drowsiness and desaturation. She exhibited slight improvement from treatment with a short-acting somatostatin analogue and glucocorticoid infusions. Based on the results of comprehensive diagnostic evaluations, however, the diagnosis of CS was largely ruled out.
The nature of her attacks, which involved episodes of conjunctival redness and nasal stuffiness, created mounting suspicion with respect to excessive histamine release and MC activation disorders. According to genetic testing, in which an activating point mutation in codon 816 of the KIT gene (D816V) was detected, a diagnosis of SM was ultimately rendered. The patient underwent treatment with glucocorticoids, antihistamines and a tyrosine kinase inhibitor, which led to clinical improvement.
The similarities between SM and CS
Clinical manifestations of SM include fatigue, fever, skin lesions, weight loss and musculoskeletal symptoms, along with mast cell (MC)–mediated symptoms such as flushing, syncope, headache, tachycardia, hypotension and gastrointestinal distress. Similarly, in patients with CS, episodic flushing, hypotension, tachycardia and dyspnea frequently are reported.
Among patients with CS, symptoms develop from the uncontrolled release of biogenic amines—primarily serotonin from a neuroendocrine tumor (NET). The patient in the case history experienced several classic manifestations of CS—namely, tachycardia, episodic flushing, dyspnea and hypotension. Negative testing for the presence of an NET prompted the consideration of other diagnoses. Thus, the patient underwent additional diagnostic procedures, which ultimately led to her fulfilling the World Health Organization criteria for an SM diagnosis.
MCs release mediators which can induce CS-related symptoms, including flushing, tachycardia and hypotension. Further, people with SM are susceptible to severe allergic reactions, particularly following Hymenoptera stings, as occurred in this patient after she was stung by a hornet.
Additionally, the bone changes seen on imaging studies are consistent with the occurrence of increased bone turnover, which is a symptom of SM. Cytokines released by MCs affect osteoclasts and osteoblasts, which is known to contribute to bone remodeling.
“Considering SM in the differential diagnosis of flushing episodes is essential, positioning it at the intersection of endocrinology due to the hormonal nature of the released mediators,” the authors stated. “Early diagnosis of SM offers the opportunity for targeted treatment with midostaurin, a tyrosine inhibitor, leading to improved prognosis.”
