2026 ECNP Congress

EP01-1048

Secondary adrenal insufficiency mimicking treatment-resistant depression in an elderly patient: a case of a pituitary macroadenoma

Laia Laguna Sopena — S. Gomes da Costa, S. Casals Galard, E. del Amo Cardeñosa · Fundació Vidal i Barraquer, CSMA Sant Andreu, Barcelona, Spain

2026 ECNP Congress

Background

Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is a well-established biological marker in depressive disorders, usually associated with hypercortisolemia. However, emerging evidence suggests that low cortisol states, such as adrenal insufficiency (AI), can present with clinical features that mimic primary psychiatric depression. Epidemiological data indicate that individuals with AI have approximately a two-fold higher rate of affective and depressive disorders compared to the general population [1]. Consequently, unexplained or treatment-resistant depression (TRD) warrants endocrine evaluation to identify reversible medical mimics, as untreated HPA abnormalities are associated with higher rates of relapse [2].

Case Description A 74-year-old woman was admitted following a high-lethality autolytic attempt via drug overdose involving 50 mg of lorazepam and 100 mg of doxylamine. No prior psychiatric history. Over the previous year, she experienced progressive low mood, apathy, loss of motivation, and significant functional deterioration in executive tasks and household management. Previous antidepressant trials with citalopram (20 mg/day) and trazodone (100 mg/day) had been unsuccessful, leading to a diagnosis of severe major depressive disorder. During the current admission, organic screening was expanded, revealing a pituitary macroadenoma (22 x 11 x 13 mm) with extension into the left cavernous sinus. Endocrine testing confirmed a serum cortisol of 19.32 µg/dL and an ACTH of 12.2 pg/mL. Clinical evaluation concluded a diagnosis of secondary adrenal insufficiency (hypocortisolism) due to the macroadenoma. Pharmacological treatment was initiated with hydrocortisone (10 mg-5 mg-5 mg/day) alongside escitalopram and trazodone. Following the initiation of hydrocortisone replacement, the patient showed a rapid and dramatic improvement in energy levels, spontaneity of speech, and emotional reactivity. Recovery was sustained over time, with the patient regaining functional independence and showing high adherence at discharge.

Discussion

This case highlights the diagnostic challenge of differentiating primary psychiatric disorders from endocrine pathologies. Research indicates that correcting AI through glucocorticoid replacement significantly improves mood and well-being. Randomized trials demonstrate that appropriate hydrocortisone dosing leads to significantly fewer depressive symptoms, less fatigue, and better general health [3]. Furthermore, physiological replacement therapy has been shown to improve fatigue by better mimicking endogenous circadian rhythms [4]. In this patient, rapid symptom resolution suggests hypocortisolism was a major contributor to her depressive phenotype. Identifying such mimics is crucial for clinical outcomes in geriatric psychiatry [5].

Conclusions

Adrenal insufficiency is a significant risk factor and medical mimic for severe depressive disorders in elderly patients. While systematic screening for TRD is not yet standard practice, this case demonstrates that endocrine evaluation can identify reversible causes where replacement therapy leads to rapid clinical improvement. Therefore, clinicians should maintain a high suspicion for adrenal pathology in late-onset TRD accompanied by neurological or systemic features. Ultimately, this case underscores the clinical necessity of ruling out HPA axis dysfunction in patients with atypical features or a complicated course; identifying such reversible mimics is essential, as addressing underlying endocrine dysfunction can directly resolve apparent antidepressant resistance.

References

References

  1. Thomsen, A., Kvist, T., Andersen, P., Kessing, L., 2006. The risk of affective disorders in patients with adrenocortical insufficiency. Psychoneuroendocrinology 31 (5), 614-622.
  2. Halaris, A., Sohl, E., Whitham, E., 2021. Treatment-Resistant Depression Revisited: A Glimmer of Hope. J. Pers. Med. 11 (2), 155.
  3. Buning, J., Brummelman, P., Koerts, J., et al., 2015. Hydrocortisone Dose Influences Pain, Depressive Symptoms and Perceived Health in Adrenal Insufficiency: A Randomized Controlled Trial. Neuroendocrinology 103 (1), 771-778.
  4. Russell, G., Kalafatakis, K., Durant, C., et al., 2023. Ultradian hydrocortisone replacement alters neuronal processing, emotional ambiguity, affect and fatigue in adrenal insufficiency: The PULSES trial. J. Intern. Med. 295 (1), 51-67.
  5. Bykova, A., Bykov, Y., Bekker, R., 2021. Overcoming treatment resistance of depression in an advanced age female patient with Addison disease: a literature review with clinical case presentation. Siberian J. Life Sci. Agric. 13 (4), 316-351.