Case 3: A 28-month-old with esotropia and acute lymphoblastic leukemia

A previously healthy 28-month-old girl presented to the emergency department with a one-month history of pallor and bruising, and a new petechial rash. An ophthalmology consult was pending for the onset of left eye esotropia four months previously. On examination, the child was pale and irritable, although without signs of acute distress. Her height, which had always been a parental concern, was 81 cm (<3rd percentile) and her weight 11.8 kg (50% percentile). Her respiratory and cardiovascular examinations were unremarkable. Her abdomen was soft and tender, with obvious hepatosplenomegaly. Cervical and inguinal lymphadenopathy was noted. The central nervous system (CNS) examination confirmed left eye esotropia, with no other neurological findings. The initial blood work revealed a white blood cell count of 129×109/L with peripheral blasts (104.49×109/L), hemoglobin level of 99 g/L and a platelet count of 13×109/L. Flow cytometry and a bone marrow aspiration confirmed a diagnosis of precursor B lymphoblastic leukemia. Further investigations revealed a second diagnosis. Brain magnetic resonance imaging with contrast performed to rule out mass lesions associated with CNS leukemia revealed an incidental finding of an ectopic and hypoplastic posterior pituitary measuring <2 mm in diameter (Figure 1). No cause for the ophthalmic symptoms was found and subsequent lumbar puncture revealed no evidence of CNS leukemia. Sagittal T1-weighted magnetic resonance imaging revealing an ectopic posterior pituitary bright spot (long arrow) and hypoplastic pituitary gland (short arrow) Routine biochemistry was within normal limits, with the exception of an elevated lactate dehydrogenase level, consistent with her diagnosis of leukemia. An endocrine consult was obtained along with a full pituitary hormone profile (Table 1). The adreno-corticotropic hormone (ACTH) stimulation test performed three months later was abnormal (99 nm/L to 434nm/L at 60 min after ACTH administration). Her thyroid-stimulating hormone level had also dropped. She was started on physiological dosing of hydrocortisone and low-dose thyroxine. Together with her low insulin-like growth factor-1 (IGF-1) level and abnormal growth curves, a diagnosis of growth hormone (GH) deficiency and evolving panhypopituitarism was made. Hormone profile Bold type indicates abnormal values Hormone profile Bold type indicates abnormal values The present case highlights the concurrent presentation of two rare paediatric diseases: congenital hypopituitarism (incidence <3/1,000,000) and precursor B cell acute lymphoblastic leukemia (B-ALL [incidence 44/1,000,000]). The presence of each influences the management of the other. Standard leukemia protocols require frequent procedures under sedation, including bone marrow aspirates and lumbar punctures with intrathecal chemotherapy. For our patient, this necessitates a care plan for the management of minor stress for such procedures with parental and team education around hydrocortisone dosing. Patients undergoing chemotherapy may experience unanticipated admissions for complications of therapy, such as fever and neutropenia, and require minor or major stress dosing of hydrocortisone. Again, education is key to preventing life-threatening presentations in these situations. Paediatric leukemia survivors are at increased risk for endocrine disorders compared with the general population, historically related to the use of CNS radiation. Close clinical and/or biochemical monitoring of the hypothalamic-pituitary axis is warranted in these patients to prevent additional morbidity related to, for example, hypothyroidism or delayed puberty. This is particularly relevant in our patient with evolving panhypopituitarism and leukemia therapy. Recombinant human GH has been effective in childhood cancer patients with GH deficiency due to radiation therapy to achieve their final height. However, GH and IGFs have mitogenic and proliferative properties, and there is controversy with regard to the relationship between GH treatment and the development of second neoplasms (SNs). The Childhood Cancer Survivor Study suggested a two-to threefold increased risk for SNs in GH-treated children; this risk decreased with increasing length of follow-up (1). Another study reported leukemia as the primary malignancy most commonly associated with the development of as SN after GH therapy (2). All SNs were solid tumours. We have opted to defer initiation of GH therapy for our patient until after completion of her intensive phase of chemotherapy. The present report describes the presentation of a young child with coexisting and previously unrecognized hypopituitarism and precursor B-ALL. Despite the rarity of the former, it is an important determinant in the management of the latter. Appropriate management of hypopituitarism is important for the physical and hormonal development of the child, weighing the risks and benefits of the timing of GH treatment in at-risk leukemia patients. Children with leukemia can present in many ways, and although it is satisfying to find a unifying diagnosis for a constellation of symptoms, one must always consider the possibility of an undiagnosed comorbid disease. Hypopituitarism poses unique challenges in the care of children presenting with leukemia. There is a potential risk for SN when giving GH to at-risk children, suggesting the need for careful and ongoing surveillance.

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