False Sense of Security: ACTH Stimulation Testing in Secondary Adrenal Insufficiency

Introduction:
In euvolemic hyponatremia, endocrinopathies such as hypothyroidism and adrenal insufficiency are possible etiologies. Secondary adrenal insufficiency (SAI) can cause hyponatremia due to impaired free water excretion. Panhypopituitarism is a possible etiology of gradual onset where gonadotropins (FSH, LH) lose production followed by TSH and ACTH. We present a case where an ACTH stimulation test misled the diagnostic workup.

Case Description:
A 69-year-old woman was admitted to our hospital with dizziness, weakness, nausea and vomiting. MRI revealed a 1.8 cm pituitary cyst. She had history of meningioma surgery several years prior. Sodium was 121 mEq/L, serum osmolarity 250 mOsm/Kg, potassium 4.3 mEq/L, uric acid 2.3 mg/dL, urine osmolarity 466 mOsm/Kg, urine sodium 80 mEq/L, TSH 3.01 uIU/mL, Free T4 0.62 ng/dL and cortisol 3.2 ug/dL. ACTH stimulation was performed with baseline cortisol of 2.2 ug/dL, 30 minutes 13 ug/dL, and 60 minutes 20.3 ug/dL. Patient was treated as SIADH but did not improve clinically or chemically. ACTH was soon reported as undetectable with negligible gonadotropins (FSH 1.6 mIU/ml and LH 0.2 mIU/ml). Two years prior FSH was 38.7 mIU/ml, LH 13.0 mIU/ml.  One year prior, FSH was 6 mIU/ml, LH 1.9 mIU/ml, and ACTH 17.3 pg/ml. Subsequently, patient was treated with steroids and rapidly improved clinically and chemically.

Discussion:
Diagnosing SAI can be challenging. SAI can be insidious in onset and difficult to recognize despite close laboratory monitoring. In our patient, there was a sharp falloff of gonadotropins one year prior which should have prompted further pituitary evaluation for SAI. Cortisol secretion is pulsatile and sometimes hard to interpret in this setting. Insulin tolerance testing is the gold standard but is rarely performed. ACTH 1 microgram testing has sensitivity of 83% but high dose 250 microgram is only 64%. An abnormal stimulation test has high specificity for SAI. In this case, delayed diagnosis of hypopituitarism, particularly SAI, could have disastrous consequences. False reassurance from an ACTH stimulation has to be guarded against.