Endocrine Abstracts

Background: Isolated ACTH deficiency (IAD) is a rare cause of secondary adrenal insufficiency. Unlike Addison’s disease, classical features such as hyperpigmentation and marked electrolyte imbalance are absent, often leading to delayed recognition. Patients typically present with nonspecific symptoms such as fatigue, anorexia, and weight loss, which may progress to adrenal crisis if untreated.

Case Presentation: We report a 75-year-old gentleman with no significant past medical history aside from ischaemic heart disease and osteoarthritis, who experienced progressive decline over several months. He presented initially with fatigue, recurrent chest infections, anorexia, weight loss, and generalized weakness. Despite extensive investigations—including CT thorax/abdomen/pelvis, bronchoscopy, bone marrow biopsy, MRI brain and spine, and PET scanning—no underlying pathology was identified. His course was complicated by refractory hypercalcemia, hyponatremia, and acute kidney injury. Over four months, he deteriorated from being fully independent to bedbound, with severe muscle wasting, unsafe swallow necessitating nasogastric feeding, and recurrent hospital admissions. Neurological causes, including motor neuron disease, were strongly considered, but investigations remained unrevealing. Eventually, endocrinology assessment revealed low cortisol with inappropriately low ACTH, and a short Synacthen test confirmed inadequate cortisol response. Other pituitary hormones were preserved, and MRI pituitary was normal. A diagnosis of isolated ACTH deficiency was made. Hydrocortisone replacement therapy resulted in rapid clinical improvement, with resolution of hypercalcemia and restoration of mobility, strength, and independence within weeks. He remains stable on follow-up.

Discussion: This case highlights the diagnostic challenge of IAD due to its nonspecific presentation and absence of hallmark features of primary adrenal failure. Delay in diagnosis can lead to profound deconditioning and misdirected investigations, even raising consideration of palliative care. Hypercalcemia, though uncommon, may be a clue, occurring in up to 8% of patients with ACTH deficiency. Greater clinical awareness is essential, as many cases are initially overlooked or misattributed to infection, malignancy, or neurodegenerative disease. Early dynamic testing could prevent unnecessary invasive investigations, reduce hospital admissions, and markedly improve patient outcomes. Etiologies of IAD include autoimmune processes, gene mutations, trauma, and iatrogenic causes like drugs or immune checkpoint inhibitors. In this patient, no secondary cause was identified.

Conclusion: Isolated ACTH deficiency, though rare, should be considered in patients with unexplained systemic decline, recurrent hospitalizations, and refractory biochemical abnormalities. Early recognition and prompt glucocorticoid replacement can dramatically alter outcomes—even reversing near-terminal deconditioning. Clinicians should maintain a high index of suspicion to prevent missed diagnoses and avoid unnecessary invasive investigations.