Endocrine Abstracts

Case history: A 37 year old mother of two was referred to DGH by the GP for possible PCOS in 2019. She had an 18 months of weight gain, hirsuitism, oligomenorrhoea, abdominal distension, back pain and fatigue. Medical history included asthma and she worked as a teacher. On Endocrine clinic review, she was noted to be floridly Cushingoid. Urgent referral to tertiary Endocrinology in Edinburgh was auctioned and a diagnosis of Cushing’s Disease was made alongside multiple resulting sequelae. Trans-sphenoidal surgery (TSS) undertaken, with further surgery a probability.

Investigations: Investigations showed a raised urinary cortisol of 1768nmol/24hr and plasma ACTH 122ng/L. A 10mm “asymmetry” of the pituitary with no obvious adenoma was reported on MRI. CT chest/abdo/pelvis revealed no extra-pituitary source of ACTH, plus new T7/8 fragility fractures. CRH stimulation test gave a flat response of 132ng/l to 148ng/L. Inferior petrosal sinus sampling (IPSS) was undertaken under GA as the patient could not lie flat due to pain. IPSS showed peripheral ACTH levels between 46 -109 rising to 1265-1560 in the petrosal sinus, consistent with a pituitary source. Again, a relatively flat ACTH and cortisol response during IPSS was noted, while prolactin levels indicated good cannulation of petrosal sinuses.

Results/treatment: A “Block and replace” regimen of Metyrapone / Hydrocortisone was initiated. Treatment of multiple sequelae of Cushing’s was undertaken, including anti-hypertensives, glucose monitoring, thromboprophylaxis, bisphosphonates, analgesics and diuretics was commenced while awaiting IPSS. The left side of the gland was debulked and post-operatively a transient AVP deficiency spontaneously resolved. Day 3 morning cortisol level was 139nmol/l indicating cure was unlikely. She was discharged on hydrocortisone. Since surgery, abdominal girth, weight and peripheral oedema have reduced but central obesity remains challenging. Blood pressure is controlled. The patient is undergoing serial dexamethasone suppression testing and MRI, with further TSS likely in future.

Conclusions/points for discussion: Cushing’s Disease is diagnostically challenging for non-specialty doctors and Endocrinologists alike, and there is often a significant delay in diagnosis. Medical management with Metyrapone was challenging due to a paradoxical worsening of hypokalaemia and hypertension, necessitating additional therapies and monitoring. Regular long term follow up of patients with treated Cushing’s is paramount in ensuring any recurrence of disease is identified promptly and early second surgery considered. This case highlights significant long term impact on patient morbidity and cardiovascular risk which can be worsened by clinical and pandemic-related delays.