| Summary: | Endocrine deficits can occur as a result of target organ damage to the thyroid, gonad or adrenal gland by both radiotherapy and chemotherapy, as well as damage to the hypothalamo-pituitary (HP) axis. While most endocrine deficit can be pre-empted by regular surveillance, the detection of secondary adrenocortical insufficiency (SAI) poses a particular problem. The symptoms of SAI (tiredness, lethargy, etc.) are non-specific, and are very similar to those experienced from anti-cancer therapy. Moreover, existing tests of adrenal function are difficult to interpret, and may not be diagnostic in children with mild to moderate degrees of SAI. It is in the child’s interest for SAI to be promptly diagnosed and steroid replacement instigated. Correct diagnosis is essential as steroid therapy can have an adverse effect on growth and may cause weight gain. This study attempts to address the challenge of diagnosing SAI in long-term survivors of childhood cancer. Sensitive assays of steroids in saliva (cortisol, 17-hydroxyprogesterone, and adrostenedione) have been developed using radioimmunoassays with microencapsulated antibody. A reference range of these steroids in saliva has been derived from a control population of 147 schoolchildren (77 girls, 70 boys), aged 5 to 15 years, enabling salivary steroid profiles to be used in the assessment and monitoring of adrenocortical function in survivors of childhood cancer. These results have been compared with standard tests of adrenocortical function. The study group included 43 patients of whom 36 patients (15 girls, 21 boys) provided salivary profiles. Their average age was 12.9 years (range 7.0 to 19.8 years). These patients had received either radiotherapy for brain tumours, total body irradiation as part of conditioning treatment for bone marrow transplantation, or were patients with leukaemia who had relapsed and had received cranial irradiation in addition to the standard radiotherapy for prophylactic treatment. This thesis has shown that the use of salivary steroid profiles can be useful in both the diagnosis and in screening of SAI. We have also shown that SAI is not as prevalent as has been reported in previous studies.
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