Received: 7 September 2018
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LETTER TO THE EDITOR
WILEY
Pediatric Blood & Cancer
SOCIÉTÉ INTERNATIONALE D’ONCOLOGIE PÉDIATRIQUE SKOP INTERNATIONAL SOCIETY OF PAEDIATRIC ONCOLOGY
aspho The American Society of Pediatric Hematology/Oncology
Erythrocytosis as the first manifestation of adrenal carcinoma
The term “erythrocytosis” refers to the increase of circulating red cells, hemoglobin (Hb), and hematocrit (HCT).1 Severe hyperandrogenism is a cause of polycythemia, frequently misdiagnosed.2-5 A very rare cause of hyperandrogenism is testosterone-secreting adrenal cancer, espe- cially in children.
Case description. A 14-year-old female was referred to our pedi- atric unit for hirsutism and polycythemia. Increased concentration of Hb (17.3 g/dL) was incidentally demonstrated one year before, but severe hirsutism and deepening of the voice appeared during the last six months. During the physical examination, body mass index was 24.7 kg/m2, Tanner stage was III for breasts and V for pubic hair, and Ferriman-Gallwey evaluation scored 16. In addition, muscle hyper- trophy and clitoromegaly were evident. Nevertheless, Cushingoid fea- tures were absent. Blood pressure was normal. Biochemistry showed high Hb concentration (18.2 g/dL) and red blood cell count (5.94 million cells/uL). Hormonal evaluation, shown in Table 1, demonstrated a dra- matic increase of adrenal androgens. A wide solid lesion (14 x 11 cm) in the right adrenal gland was detected by ultrasonography and con- firmed by computerized tomography (CT). After unilateral adrenalec- tomy, pathology examination showed a capsulated Non-homogeneous mass, 14 cm of maximum diameter and 500 g of weight. Weiss score was six out of nine points, and Ki67 index was 5.8%. Adrenal cortical carcinoma (ACC) removal was suddenly followed by testosterone lev- els’ normalization, Hb reduction, and dramatic improvement of viril- ization. CT total body, performed after surgery, did not show remnant lesions, so adjuvant therapy was not prescribed. Eighteen months after surgery, hormone profile and Hb levels were normal, and tumor recur- rence was not evident. Written informed consent for publication of case history and images was given by the patient’s parents.
Discussion. ACC is extremely rare in children and teenagers.6,7 In many cases, it is characterized by aggressive behavior and bad prog- nosis, and only 16% to 47% of patients are still alive after five years.8 Cortisol or testosterone hypersecretion occurs in 50% and 15% of the cases, respectively.9 In females, severe hyperandrogenism causes vir- ilization and hirsutism. In both sexes, it induces pseudopuberty and growth accelerations followed by growth arrest, muscle hypertrophy, deepening of the voice, and polycythemia.10-12 Data in the literature about the association between severe hyperandrogenism and erythro- cytosis are scanty overall, and completely lacking in children.12 Previ- ous studies suggested that testosterone stimulates hematopoiesis in bone marrow stem cells and increases iron absorption at the intestinal level and its incorporation into erythrocytes.2,13-16
In our patient, polycythemia was detected several months before hirsutism appearance, but the diagnosis of ACC was delayed, increas-
| Basal | 2 months after adrenalec- tomy | adrenalec- 6 months after tomy | adrenalec- 12 months after tomy | Normal range | |
|---|---|---|---|---|---|
| Red blood cells (million cells/uL) | 5.94 | 4.97 | 4.94 | 4.59 | 4.00-4.50 |
| Hb (g/dL) | 18.2 | 14.8 | 14.6 | 13.9 | 12-14 |
| HCT (%) | 53 | 44 | 43 | 40 | 38-46 |
| Total testos- terone (ng/dL) | 268.2 | 45.9 | 29.1 | 12.8 | 5.0-75.0 |
| DHEAS (µg/dL) | 1874.0 | 160 | 191.8 | 185.0 | 18-391 |
| OH-Pg (ng/ml) | 6.4 | 1.0 | 1.4 | 0.50 | <2.9 |
| 21.0 Androstenedione (ng/ml) | 1.9 | 1.5 | 0.80 | <2.83 | |
| Cortisol (µg/dL) | 8.0 | 8.85 | 8.41 | 10.4 | 6.7-22.6 |
| UFC (µg/24h) | 124.8 | 168.56 | 139.70 | 103.1 | 58-403 |
| ACTH (pg/mL) | 13.4 | 6.95 | 9.2 | 0.0-50.0 | |
Abbreviations: ACTH, adrenocorticotropin; androstenedione, delta- 4 androstenedione; DHEAS, dehydroepiandrosterone-solfate; Hb, hemoglobin; HCT, hematocrit; OH-Pg, 17OH-progesterone; UFC, urinary- free cortisol.
ing the risk of tumor progression. Normalization of polycythemia following adrenalectomy confirms that appropriate diagnosis is mandatory for a resolution of erythrocytosis caused by hyper- androgenism, as also previously reported in some adults with testosterone-secreting testis or ovary tumors.12,17
In conclusion, our case highlights the role of polycythemia and Hb levels as markers of testosterone-secreting masses also in young patients. In these cases, the correct diagnostic and therapeutic management is mandatory for improving the outcome of the disease.
ORCID
Laura Cannavò ID https://orcid.org/0000-0002-4464-9421
Laura Cannavò 1 İD Giuseppina Zirilli1 Mario Lima2 Graziella Iaria3 Filippo De Luca1 Mariella Valenzise1
Abbreviations: Hb, hemoglobin; HCT, hematocrit; DHEAS, dehydroepiandrosterone-solfate; OH-Pg, 17-hydrossiprogesterone; CT, computerized tomography; ACC, adrenocortical carcinoma
1G. Martino Hospital, Pediatric Unit, Department of Adulthood and Childhood Human Pathology, University of Messina, Messina, Italy
2 Sant’Orsola Hospital, Department of Pediatric Surgery, University of Bologna, Bologna, Italy
3 Grande Ospedale Metropolitano Bianchi Melacrino Morelli, Reggio Calabria, Italy Correspondence
Laura Cannavò, Department of Human Pathology of Adulthood and Childhood, University of Messina, Messina, UOC di Pediatria, Pad. NI, 3º piano, AOU Policlinico Gaetano Martino, Via Consolare Valeria, 1, 98125 Messina, Italy.
Email: laura_cannavo@hotmail.it
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