ESA-SRB-AOTA 2019

A prodigious presentation in a previously well indigenous woman (#575)

Matthew Balcerek 1 , Thomas Dover 2
  1. Sunshine Coast University Hospital, Birtinya, QLD, Australia
  2. Ipswich General Hospital, Ipswich, Queensland, Australia

Case

A 54-year-old indigenous female presented with polydipsia, peripheral oedema and generalised weakness of two-weeks duration. She was hypertensive (155/80mmHg), hyperglycaemic (19mmol/L), and hypokalaemic (2.4mmol/L). She was known to Endocrinology who were managing her T2DM (HbA1c 6.9%) and toxic multinodular goiter (euthyroid post radioactive iodine ablation).

She appeared overtly Cushingoid and biochemistry was consistent with ACTH-dependent Cushing’s syndrome, likely ectopic source (Fig-1). Peripheral CRH stimulation was not consistent with Cushing’s disease (Fig-2), and CT Pituitary did not visualise an adenoma. Metyrapone was commenced with daily cortisol monitoring.

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CT chest revealed a locally invasive right upper lobe lesion. Endobronchial biopsy confirmed malignant small cell neuroendocrine carcinoma and cytotoxic chemotherapy was commenced.

She was admitted post cycle-1 chemotherapy with hypotension (BP 60/40mmHg) and received 100mg IV hydrocortisone, achieving rapid haemodynamic stability. We hypothesise her presentation was related to acute adrenal insufficiency from chemotherapy induced tumour-lysis, resulting in marked reduction in plasma ACTH (66% decrease), and concomitant cortisol blockade (metyrapone).

Re-staging CT three months later showed disease progression which correlated clinically with a worsening of her Cushing’s syndrome and multiple infective complications. At the time of writing, plasma cortisol remains >2000 nmol/L despite metyraprone, ketoconazole and mitotane triple therapy. Chemotherapy has been withdrawn with provision of best supportive cares.

 

Discussion

Ectopic Cushing's syndrome (ECS) accounts for 10–15% of Cushing's syndrome cases1. It is caused by a variety of extrapituitary tumours, usually malignant. Onset of clinical features is usually abrupt and prodigious hypercortisolism, hypokalaemia and markedly elevated plasma ACTH concentrations should raise clinical suspicion.

SCLC and ECS carry a poor prognosis due to poor chemotherapy responsivity, severe infectious complications and high VTE risk. Care should be taken post chemotherapy if patients are adequately blocked with steroidogenesis inhibitors, as tumour-lysis may lead to rapid reductions in ACTH secretion and clinical manifestations of secondary adrenal insufficiency.

  1. Ilias I, et al. Cushing's syndrome due to ectopic corticotropin secretion: twenty years' experience at the National Institutes of Health. J Clin Endocrinol Metab. 2005 Aug; 90(8):4955-62.