Case history/Investigations/Results and treatment: A previously healthy 36 year old female was admitted to a local intensive care unit with psychosis and intractable hypokalaemia. She had delivered a live preterm baby girl at 33 weeks gestation ten days previously. The hypokalaemia led to an endocrine consultation which revealed onset of symptoms in the third trimester, with no symptoms present pre-conception. Serum cortisol was 2,258 nmol/l with a nadir K+ of 2.2 mmol/l. She was transferred to our ITU to commence an etomidate infusion, and required sedation with olanzepine and propofol. Serum cortisol levels dropped to 300 nmol/l and over the following week octreotide, metyrapone, and ketoconazole were added. An octreotide test had suggested a partial response with ACTH falling from 4200 ng/l to 1800 ng/l at 300 minutes. Cross-sectional imaging revealed a 7.3−4.8 cm anterior mediastinal mass (presumed thymic primary) with widespread mediastinal and axillary lymphadenopathy, bilateral breast masses, and diffusely enlarged adrenal glands (all of which were DOTATATE-avid). An axillary node core biopsy revealed neuroendocrine carcinoma, with Ki-67 hotspots of 40%. Her recovery was complicated by Staphylococcus aureus bacteraemia and Candida albicans fungaemia. A bilateral adrenalectomy was performed due to ongoing hypercortisolaemia, unstable mental state, and hypertension with hypokalaemia despite maximal oral anti-adrenal therapy. This strategy was also felt to simplify future glucocorticoid management when treating the NET. Histology revealed a metastasis within the hyperplastic adrenal tissue, with Ki67 of 20%. All symptoms resolved post-operatively and she was commenced on monthly Lanreotide. Two-weeks post-operatively, plasma ACTH levels were 145 ng/l (pre-hydrocortisone) and 151 ng/l (120 m post-hydrocortisone). CT-scan suggested stable disease. We advised a conservative approach. Repeat scan at 6-months showed mild volumetric reduction in the presumed primary mediastinal primary tumour to 6.4−3.4 cm and at other involved sites.
Conclusions and points for discussion: We discuss how the physiology of pregnancy provided protection from cortisol excess, thus leading to the fulminant presentation. We hypothesise that hCG may have been a driver during pregnancy, stimulating rapid growth and high-grade activity of a previously quiescent NET. We consider whether this provides other therapeutic manoeuvres. We discuss the importance of basing treatment options not solely on markers such as Ki-67, but on the overall clinical picture and presentation. Finally we discuss the regression of the disease which we believe is unlikely due to Lanreotide alone but also removal of a pregnancy stimulus. This opens up discussion on how best to manage the NET in the future.