Endocrine Abstracts

Case history: A 42-year old female was urgently referred to the endocrinology clinic. Symptomatology included worsening lethargy, polydipsia, poor appetite, postural dizziness and hypogalactia. Relevant background included the delivery of a healthy baby at term four weeks prior (Emergency caesarean section, 1000 ml blood loss documented). She had undergone an MRI at 39 weeks gestation following a 10-day history of persistent headaches with associated photophobia and dizziness (pre-eclampsia excluded). Her MRI brain was initially reported as normal (antenatal course otherwise uncomplicated). Her GP had identified a secondary hypothyroidism and provided her with steroid cover.

Investigations: Further pituitary axis assessment by the endocrine team demonstrated the following: Na 146 mmol/l, TSH 0.06 (0.3–4.2 mu/l), Free T4 8.0 (9–23 pmol/l), Free T3 5.2 (2.5–5.7 pmol/l), Prolactin 207 (100–500 milliunit/l), IGF-1 18.2 (7.5–35 nmol/l), Oestradiol 207 pmol/l, FSH 3.2I U/l, LH 1123 IU/l, ESR 46. Short synacthen test (SST): 0 min = 212 nmol/l, 30 mins = 418 11 nmol/l, 60 mins = 523 nmol/l.

Results and treatment: Steroid supplementation had increased the severity of her thirst, nocturia and polyuria. A 24hour urinary collection yielded 3799 ml. A subsequent water deprivation test demonstrated an inability to concentrate urine, with a partial response to desmopressin (peak serum osmolality – 307 mOsmol/kg, peak urine osmolality pre-and post-desmopressin were 401 mOsmol/kg, and 592 mOsmol/kg respectively). She was commenced on desmopressin and her ACTH axis was further interrogated. The insulin stress test showed an impaired cortisol response to hypoglycaemia (plasma glucose 1.8 mmol/l, peak cortisol response 322 nmol/l, growth hormone axis preserved). A retrospective review of her initial MRI at 38 weeks gestation demonstrated an enlarged pituitary beyond that expected in pregnancy with diffuse T1 signal reduction raising the possibility of autoimmune hypophysitis or pituitary infarction. Her postpartum MRI demonstrated an enlarged pituitary stalk but no further features consistent with hypophysitis. Following investigation, she has been established on long-term levothyroxine, hydrocortisone and desmopressin with good symptomatic response, and has plans for further pregnancies. Eighteen months later, she has needed to continue her supplementation: re-interrogation of her axis has not suggested recovery.

Conclusions and point: Our case demonstrates a significant clinical and biochemical improvement in a patient with a grade III ACTH-secreting lung neuroendocrine tumour (NET) following metyrapone therapy. There is sparse data on the effectiveness and tolerability of metyrapone therapy in managing ectopic ACTH syndrome (especially secondary to NETs). This case serves to highlight that in tumours unsuitable for surgery, metyrapone provides an effective means to manage EAS.

Discussion Points: 1. Pitfalls of SST in context of pituitary disease 2. Impact of steroid deficiency on ADH axis 3. Differentiating between Sheehan’s syndrome and autoimmune hypophysitis