Pituitary siderosis: the dark side of the pituitary

Abstract

A 23-year-old woman with persistent secondary amenorrhoea, 2 years after completion of non-ovarian toxic chemotherapy for osteosarcoma, was referred from the oncologist for investigation. She had severe sicklecell disease, diagnosed at age 18 months, requiring frequent red blood cells, exchange transfusion treatments, and a splenectomy. Despite oral chelation treatment, ferritin and transferrin saturation levels were raised (7000 μg/L and 121%, respectively). Pituitary investigations showed anterior hypopituitarism with several pituitary defi ciencies, including low concentrations of luteinising hormone (0·2 IU/L [normal range 0·8–10·4 IU/L]), follicle-stimulating hormone (0·8 IU/L [normal range 1·8–9·4 IU/L]), and oestradiol (<13 pmol/L [normal range 92–367 pmol/L]); normal concentrations of thyroid-stimulating hormone (2 mIU/L [normal range 0·17–4·05 mIU/L]); low free thyroxine (9·6 pmol/L [normal range 11·5–23·0 pmol/L]); and low morning cortisol concentrations on two successive days (133 nmol/L and 174 nmol/L [normal range 263–724 nmol/L]). An insulin tolerance test was contraindicated by the renal insuffi ciency secondary to chemotherapy. On MRI examination, coronal and sagittal T1-weighted sequences showed a normal pituitary and stalk, without evidence of pituitary tumour or infl ammation that could account for pituitary insuffi ciency (fi gure A, B). Coronal and sagittal T2-weighted sequences showed a normal posterior pituitary signal and a mainly homogeneous hypointense signal from the anterior pituitary, which was pathognomonic of pituitary siderosis (fi gure C, D). Haemosiderin deposition secondary to pituitary tumour apoplexy was excluded by the absence of clinical symptoms or indirect MRI signs of pituitary adenoma (eg, sella turcica deformation, pituitary stalk deviation, and pituitary mass). The MRI fi ndings led us to conclude that the patient had a rare hypopituitarism secondary to iron overload, caused by sickle-cell disease transfusion therapy. In severe thalassaemia requiring repeated transfusions, pituitary hypointense T2-weighted signal has been shown to be independently predictive of hypogonadism. Although such cases are rare, we suggest that pituitary MRI should be done in patients with sickle-cell disease who require frequent transfusions to assess the potential risk of hypopituitarism.