GHRP-2 load test helps diagnose isolated ACTH deficiency in a patient with only epigastric discomfort
Background
Isolated adrenocorticotropic hormone (ACTH) deficiency is a form of hypopituitarism often linked to autoimmune disorders or hypophysitis. This condition typically presents with severe and recognizable symptoms such as severe hypoglycemia, hypotensive shock, and disturbances of consciousness, which prompt immediate and specific endocrine investigation. However, when patients present with non-specific, mild symptoms like general malaise or gastrointestinal discomfort, the diagnosis can be easily missed. This often leads to misdiagnosis, such as functional dyspepsia or depression, delaying appropriate treatment and posing a risk of adrenal crisis if the underlying deficiency is not identified.
Study Design
This case report details the diagnostic process for a 65-year-old Japanese man with persistent mild epigastric discomfort and general malaise. His initial symptoms led to a months-long misdiagnosis of functional dyspepsia and depression. Diagnostic workup included infection marker and antibody screens, an abdominal computed tomography (CT) scan, and contrast magnetic resonance imaging (MRI) of the brain. Key endocrine function tests were performed, including a corticotropin-releasing hormone (CRH) load test and a growth hormone-releasing peptide 2 (GHRP-2) load test to assess pituitary hormone responses.
Results
Initial imaging was unremarkable; adrenal CT showed no mass and pituitary MRI revealed normal size and structure without dyeing delay or deficits. Infection markers and autoimmune antibodies were all negative. The crucial findings came from dynamic pituitary function testing. The CRH load test demonstrated a poor response of both adrenocorticotropic hormone (ACTH) and cortisol after CRH administration. Complementing this, the GHRP-2 load test also showed a poor ACTH response.
These combined test results strongly suggested the presence of isolated ACTH deficiency, despite the atypical, non-hypoglycemic clinical presentation.
Based on this definitive endocrine evidence, the patient was diagnosed with idiopathic and isolated ACTH deficiency. A treatment regimen with hydrocortisone was initiated, which resulted in the rapid mitigation of his epigastric discomfort and general malaise, confirming the diagnosis.
Key Findings
- A 65-year-old man with isolated ACTH deficiency presented only with epigastric discomfort and general malaise, lacking typical symptoms like hypoglycemia.
- The patient was initially misdiagnosed with functional dyspepsia and depression for several months.
- A corticotropin-releasing hormone (CRH) load test showed a poor response of both ACTH and cortisol.
- A growth hormone-releasing peptide 2 (GHRP-2) load test confirmed poor ACTH response, aiding the diagnosis.
- Treatment with hydrocortisone quickly resolved the patient's symptoms, confirming the diagnosis.
Why It Matters
This case highlights that serious endocrine disorders like isolated ACTH deficiency can manifest with vague, non-classical symptoms such as stomach discomfort, which are commonly attributed to more benign conditions. Clinicians and individuals should consider endocrine dysfunction in the differential diagnosis for persistent, unexplained malaise or dyspepsia, even without hallmark signs like hypoglycemia. The use of provocative tests, including the GHRP-2 load test, is critical for uncovering pituitary insufficiencies that standard imaging might miss. For individuals using peptides or investigating HPA axis function, this underscores the importance of comprehensive diagnostic testing when vague but persistent symptoms arise, rather than assuming they are unrelated to endocrine health. This approach can prevent dangerous delays in life-saving treatments like glucocorticoid replacement.
