Identifying ACTH sources

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This is a 52 year old woman with Cushing's Syndrome
  • 52-year-old woman
  • Presented at metabolic bone clinic
  • 18-month history of irritability
  • Central weight gain
  • Oligomenorrhoea
  • Recent non-traumatic, vertebral fracture
  • Appeared possibly Cushingoid
  • Radiology scans revealed a series of crush and wedge fractures of her vertebrae and her bone density showed severe spinal osteoporosis.
  • Her 24-hour urinary free cortisol (UFC) was three times the upper limit of normal on two occasions and she was referred to the endocrinology department.

What would you do next to diagnose this patient?

  1. Repeat 24-hour UFC
  2. Perform plasma midnight cortisol test
  3. Perform the corticotrophin-releasing hormone test
  • The patient was admitted to the endocrinology department and a plasma midnight cortisol test was performed over 48 hours.
  • The patient’s midnight sleeping cortisol levels were revealed to be 352 nmol/L and 435 nmol/L on successive days, and a 09:00 plasma ACTH measurement was 78 ng/L.
  • A pituitary MRI showed a suspicion of a 3 mm lesion on the left of the fossa and the patient was initiated on low-molecular weight heparin.

 

  • The patient was diagnosed with ACTH-dependent Cushing’s Syndrome.
  • With uncertainty over the pituitary lesion, BIPSS was performed and revealed a central:peripheral ratio of 1.4, five minutes after CRH administration.

What would you do next?

  1. Perform transsphenoidal surgery of the suspected pituitary tumour
  2. Undertake a CT scan of the chest, abdomen and pelvis
  3. Provide radiosurgery to the suspected pituitary tumour
  • With a BIPSS ratio that is not clearly indicative of Cushing’s Disease, a CT scan of the patient’s chest, abdomen and pelvis was performed revealing a 1 cm subcarinal node and bilateral adrenal hypertrophy.
  • A 68Ga-PET-DOTATATE scan showed that the subcarinal node was highly positive, but no other lesions were identified.
  • Endoscopic bronchial ultrasound and transbronchial fine-needle aspiration of the node showed neuroendocrine tumour (NET) cells with a low Ki-67 proliferation index.

What would you do next?

  1. Use a medical therapy to address her cortisol levels and then perform video-assisted thoracoscopic surgery (VATS)
  2. Perform VATS immediately
  3. Initiate chemotherapy for the NET
  • The patient was treated with metyrapone for three weeks to normalise her serum cortisol levels followed by VATS.
  • Surgical pathology confirmed a grade 1 NET, but no obvious primary tumour.
  • Post-surgery, the patient’s serum cortisol was <50 nmol/L. 
  • Following surgery, the patient was placed on hydrocortisone replacement therapy, which was titrated down over 6 months, and a subsequent Synacthen test revealed normal cortisol reserve.
  • Three years post-surgery, the patient remains free of treatment, with no clinical evidence of CS and steadily improving bone density.

Conclusion

The possibility of an ectopic source should always be considered when diagnosing ACTH-dependent CS, with the majority being bronchial carcinoids. The primary tumour can be very small, but even with lymph node metastases, long-term recurrence is not inevitable following surgery.

 

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