Endocrine Abstracts

A 73 year old female presented with a 5-year history of fatigue, anorexia and weight loss of 15 kg. Her primary care physician recorded a 09:00 h cortisol of 163 nmol/l. Previous medical history was one of abdominal diffuse B-cell lymphoma 9 years earlier treated with 6 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin and prednisolone) followed by CT-guided radiotherapy. Medications were transcutaneous buprenorphine 20 mg/hour, aspirin 75 mg od and omeprazole 20 mg od. Examination confirmed a weight of 40.8 kg (55 kg 5 years earlier), signs of weight loss and supine blood pressure 180/90 mmHg with no postural drop. Pigmentation was absent. The initial impression was one of opiate-induced hypoadrenalism. Investigations at 09:00 h confirmed cortisol 268 nmol/l, ACTH 149.6 ng/l, fT4 11.0 pmol/l, fT3 5.2 pmol/l, TSH 1.75 mU/l, FSH 88.6 IU/l, LH 21.5 IU/l, prolactin 251 mU/l, IGF-1 9.5 nmol/l, sodium 136 mmol/l, potassium 4.1 mmol/l, creatinine 39 mmol/l and eGFR >90 ml/min suggesting a diagnosis of primary hypoadrenalism but adrenal antibodies were negative. Further investigations at 09:00 h confirmed cortisol 244 mmol/l, ACTH 273.3 ng/l, DHEAS <0.3 umol/l, androstenedione <0.4 nmol/l, testosterone <0.4 nmol/l, plasma renin activity 0.2 nmol/l/hour, aldosterone 337 pmol/l, followed by a Short Synacthen test with cortisol levels 404 nmol/l and 419 nmol/l at 30 and 60 minutes respectively. Review of previous imaging identified 12 CT scans (3 pre-treatment and 9 post-treatment) which confirmed a decreased adrenal size latterly. Treatment with replacement dose of hydrocortisone resulted in resolution of symptoms and weight gain of 7.4 kg over 2 months. Repeat plasma renin activity and aldosterone respectively on treatment were 0.7 nmol/l/hour and 99 pmol/l supine and 0.7 nmol/l/hour and 144 pmol/l standing. We interpret the results as indicating decreased cortisol synthesis (in the zona fasciculata) and DHEAS, androstenedione and testosterone (in the zona reticularis) with preservation of aldosterone synthesis (in the zona glomerulosa) of the adrenals. The zona fasciculata and reticularis cells comprise 75% and 10% of the volume of the adrenal cortex and their loss would explain the decreased adrenal size and impaired steroid synthesis pattern. Acute effects of therapeutic radiation on the appearance and function of the adrenal glands have been reported but not so chronic. We postulate that the combination of therapeutic radiation with superimposed imaging radiation caused the loss of adrenal cell mass and the steroid synthesis abnormities recorded and possible mechanisms of such.