Endocrine Abstracts

Case History: A 56-year-old woman initially sought evaluation at an endocrine clinic in 2018 due to the discovery of an adrenal incidentaloma (AI). She complained of chest pain and underwent coronary computed tomography angiography, which revealed no significant coronary artery disease but incidentally detected a lung nodule. Subsequent interval assessment of the lung nodule via HRCT unveiled a well-defined 25 × 20 mm left adrenal mass. Further examination indicated a 30 Hounsfield unit (HU) density and 75% washout, consistent with a benign adrenal adenoma. The patient had well-controlled, relatively recent onset hypertension, weight gain (BMI 38) and easy bruising, but no proximal myopathy or pathognomonic striae.

Investigations: Additional assessments of the adrenal incidentaloma revealed normal 24-hour urine metanephrines and serum renin: aldosterone ratio. However, she exhibited elevated 24-hour urinary free cortisol levels on 3 occasions (189, 175 and 246 nmol/24 hours -normal range: 0-165), increased midnight salivary cortisol on 2 occasions (suggesting loss of circadian rhythm of cortisol secretion -9.4 and 6.7 nmol/l, normal: <2 nmol/l). There was failure to suppress cortisol during two overnight dexamethasone suppression tests (cortisol 397 and 385 nmol/l, <50 is considered normal), and during a low-dose dexamethasone suppression test (Cortisol 371, <50 is considered normal with low adrenocorticotropic hormone (ACTH) level (<5 ng/l). These findings were in summary strongly suggestive of Cushing’s syndrome stemming from the Left adrenal gland.

Treatment and Follow-up Outcome: Following multidisciplinary discussion, she underwent laparoscopic left adrenalectomy with peri-operative steroid cover in October 2019. Histopathological analysis of the resected adrenal gland revealed fibro-fatty tissue consistent with an encapsulated adrenocortical adenoma. Her 24-hour urinary cortisol levels normalized postoperatively; she lost all excess weight gained in the years prior to the diagnosis; her hypertension resolved indicating recovery from Cushing’s disease. However, despite more than four years since the operation, her remaining adrenal gland has repeatedly failed to adequately produce cortisol, in keeping with profound adrenal insufficiency. Subsequent stimulation tests performed in February, July, and December 2020, as well as yearly thereafter, consistently demonstrated inadequate cortisol production. However, her pituitary hormone levels, including insulin-like growth factor 1 (IGF-1), thyroid function tests (thyroid-stimulating hormone [TSH] and free thyroxine [FT4]), prolactin, and sex hormones, remained within normal ranges. She is currently receiving hydrocortisone replacement therapy and had a couple of hypoadrenal crises requiring medical intervention.Conclusion and points for discussionAdrenal hypercortisolism is independent of ACTH regulation and results in Hypothalamic-pituitary-adrenal axis suppression, with varying degrees of severity. Surgical removal of the culprit adrenal mass often leads to post-operative adrenal insufficiency, necessitating glucocorticoid replacement therapy perioperatively and for a variable period thereafter which in turn depends on the duration and severity of hypercortisolism and tumour size. A longer follow-up of these patients is often necessary to ensure resolution of Cushing’s syndrome and to assess recovery of the contralateral adrenal gland.