Hypopituitarism after radiotherapy for primary brain tumour: is radiotherapy the cause?†

R Mallik, U Aziz, K Madhavan, JA Ahlquist, Southend Hospital.

Case summary: A 67 year old lady was admitted with lethargy and drowsiness for 3 weeks.† She also complained of headache, polyuria and polydipsia.† She had a history of frontal lobe glioblastoma (WHO grade IV); in 2007 she had undergone surgical excision followed by radiotherapy and concurrent temozolomide.† Radiotherapy was delivered by intensity modulated radiotherapy (IMRT) in 30 fractions over 6 weeks, total dose 60 Gy.† She remained well until July 2015 when she presented with tumour recurrence at the original site and underwent re-excision.†

She was postmenopausal, had type 2 diabetes mellitus and also had a history of Gravesí disease not currently requiring treatment.† She was taking dexamethasone 4 mg twice daily and metformin 500 mg twice daily.† On examination she was Cushingoid.† Plasma glucose was 28.9 mmol/L, serum cortisol 4 nmol/L, TSH 0.07 mU/L, fT4 7.4 pmol/L, fT3 1.6 pmol/L, LH <0.1 U/L, FSH 1.2 U/L, prolactin 130 mU/L.† There was no evidence of diabetes insipidus.† MRI pituitary revealed a small pituitary gland, with no focal abnormality.† These findings indicated hypopituitarism 8 years after her first tumour removal and radiotherapy.† She was treated with glucocorticoid replacement and thyroxine, and also with gliclazide.

Discussion: Radiotherapy for primary brain tumours is known to cause hypopituitarism.† A recent study1 found that 47.7% of 107 such patients had multiple pituitary hormone deficiencies.† Hypopituitarism has been attributed to the hypothalamus and pituitary gland being in the field of radiation.† However in this case the pituitary gland was not in the field of radiation.† A dosimetric review confirmed that the dose of total radiation to the hypothalamus and pituitary gland was negligible, being around 4% of the total dose; we believe that this would not account for the development of hypopituitarism.†

The mechanism of hypopituitarism after radiotherapy for primary brain tumour is not clear.† IMRT allows accurate targeting of the radiotherapy.† It is possible that a very low dose of radiation to the pituitary gland, outside the primary target volume, may lead to loss of pituitary function, though this seems unlikely.† We suggest that other indirect mechanisms may be implicated in the development of hypopituitarism after radiotherapy for primary brain tumour.†

1) Kyriakakis N, Lynch J, Orme SM, Gerrard G, Hatfield P, Loughrey C, Short SC and Murray RD (2015).† Pituitary dysfunction following cranial radiotherapy for adult-onset non-pituitary brain tumours.† Clinical Endocrinology (in press) doi:10.1111/cen.12969