Case summary: A 55 year-old lady was referred by ophthalmology following diagnosis of bilateral central serous retinopathy, an accumulation of sub-retinal fluid at the fundus associated with Cushings syndrome. She also had proximal myopathy, bruising, centripetal weight gain and hypertension. Cushings was confirmed by 1 mg overnight DST (cortisol 581 nmol/L) and 48 hr-LDDST (407 nmol/L). 24 hr UFC was raised at 2666 nmol/L (12486). The initial ACTH was low at 5 ng/L, but CT adrenals was normal. When re-measured five months later, ACTH was raised at 27.6 and 40.4 ng/L. Pituitary MRI showed a possible 2.5 mm microadenoma and CT chest was normal. Later inferior petrosal sinus sampling (IPSS) showed a central:peripheral ACTH gradient and was interpreted to exclude an ectopic source of ACTH. She underwent transsphenoidal hypophysectomy on two occasions, but histology showed no evidence of corticotroph adenoma. After the second surgery there was normal response to dexamethasone suppression. However postoperative imaging confirmed residual pituitary tissue and, besides persistent diabetes insipidus, other pituitary hormone secretion was intact. Four months later, 1 mg dexamethasone suppression was again abnormal (cortisol 211 nmol/L), but after only three weeks cortisol suppressed on 48 hr-LDDST (<30 nmol/L), and ACTH was again low (4 ng/L). With Cyclical Cushings likely, weekly 24 hr UFC was measured and showed cycling from 42 nmol/24H to 6,147 nmol/24H over 4 weeks. ACTH cycled from 3 ng/L to 12 ng/L. During the inactive phase, the patient complained of severe fatigue suggesting transient secondary adrenal insufficiency.
Discussion: Central serous retinopathy is a known ophthalmological presentation of Cushings. The diagnosis of cyclical Cushings explains the variation in ACTH measurements at presentation. Cyclical Cushings presents special challenges; if ACTH is low when cycling out of hypersecretion, ACTH-independent Cushings may be mistakenly diagnosed, or IPSS may be misinterpreted to exclude an ectopic ACTH source (normal pituitary will have central-peripheral gradient). It will be necessary to repeat the IPSS when we know the Cushings syndrome is active.