Growth of a progesterone receptor-positive meningioma in a female patient with congenital adrenal hyperplasia

Meningioma growth has been previously described in patients receiving oestrogen/progestogen therapy. We describe the clinical, radiological, biochemical and pathologic findings in a 45-year-old woman with congenital adrenal hyperplasia secondary to a defect in the 21-hydroxylase enzyme who had chronic poor adherence to glucocorticoid therapy with consequent virilisation. The patient presented with a frontal headache and marked right-sided proptosis. Laboratory findings demonstrated androgen excess with a testosterone of 18.1 nmol/L (0–1.5 nmol) and 17-Hydroxyprogesterone >180 nmol/L (<6.5 nmol/L). CT abdomen was performed as the patient complained of rapid-onset increasing abdominal girth and revealed bilateral large adrenal myelolipomata. MRI brain revealed a large meningioma involving the right sphenoid wing with anterior displacement of the right eye and associated bony destruction. Surgical debulking of the meningioma was performed and histology demonstrated a meningioma, which stained positive for the progesterone receptor. Growth of meningioma has been described in postmenopausal women receiving hormone replacement therapy, in women receiving contraceptive therapy and in transsexual patients undergoing therapy with high-dose oestrogen and progestogens. Progesterone receptor positivity has been described previously in meningiomas. 17-Hydroxyprogesterone is elevated in CAH and has affinity and biological activity at the progesterone receptor. Therefore, we hypothesise that patients who have long-standing increased adrenal androgen precursor concentrations may be at risk of meningioma growth. Learning points: Patients with long-standing CAH (particularly if not optimally controlled) may present with other complications, which may be related to long-standing elevated androgen or decreased glucocorticoid levels. Chronic poor control of CAH is associated with adrenal myelolipoma and adrenal rest tissue tumours. Meningiomas are sensitive to endocrine stimuli including progesterone, oestrogen and androgens as they express the relevant receptors. Background Congenital adrenal hyperplasia (CAH) is the most common adrenal disorder diagnosed in children and is secondary to a defect in the 21-hydroxylase enzyme in more than 95% of cases. Virilisation of affected female children occurs in both the salt-losing and simple virilising forms of CAH. In normal adrenal steroidogenesis, ACTH promotes the production of pregnenolone from cholesterol, which is then converted to progesterone and 17-hydroxyprogesterone (17OHP) and cortisol. In the absence of 21-hydroxylase enzyme activity, production of cortisol (and to a varying extent aldosterone) is reduced, leading to increased ACTH secretion due to a decrease in negative feedback by cortisol at the level of the pituitary and hypothalamus. In 21 hydroxylase deficiency, steroid precursors are diverted into androgen synthesis pathways leading to testosterone, androstenedione and 17OHP excess. The major treatment goals in adults with CAH include avoidance of adrenal crisis, prevention of adrenal and gonadal hyperplasia and neoplasia, the prevention of long-term consequences of adrenal replacement therapies and optimisation of fertility (if required). Meningiomas are the most common primary brain tumours in adults (1). The higher prevalence of meningiomas in women suggests a link between sex steroids and meningiomas (1). Meningiomas commonly express the progesterone receptor (PR) and less commonly, oestrogen and androgen receptors (1).