The Value of 25 mcg Cortrosyn Stimulation Test to Assess Adult HPA Axis

The study consisted of two groups of adult patients 18 to 65 years of age. The first group (G1, n=10) included patients with hypothalamic/pituitary disease with at least one pituitary axis deficiency other than ACTH deficiency. The patients had the following diagnoses: acromegaly (n=1), prolactinoma (n=2), non-secreting pituitary macroadenomas (n=3), pituitary cholesterol granuloma (1), uncharacterized pituitary stalk lesion(1),recurrent null cell adenoma(1) and craniopharyngioma (n=1). The second group (G2, n=12) comprised healthy volunteers. The three CSTs and ITT were done in random order and separated by a median of 22 days (range, 2 - 64 days) from each other. Cortisol levels were measured at 30 and 60 minute (min) during CSTs. A peak cortisol cut-off of 18 μg/dl was used as the pass criterion during ITT. The result of total cortisol levels during ITT were used to determine free cortisol cut-offs during CSTs and ITT. None of the patients had pituitary surgery within six weeks prior to enrollment and none of the women were on estrogen.

Patients in G1 had to be on at least 3 months of stable hormone replacement for hormone deficiencies. All control subjects (G2) had normal TSH, free T4 and prolactin levels. All premenopausal women in the control group had a history of regular, age appropriate menses and none took birth control pills within 3 months of study entry. Postmenopausal subjects had appropriately elevated FSH concentration. All men in the control group had normal FSH and total testosterone levels.

Exclusion criteria included: inability of subject to give an informed consent, pregnancy, patients with diabetes mellitus type 1 and type 2, any pituitary insult such as pituitary surgery in the past 6 weeks, elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) more than 3 times the upper limit of normal, renal failure (defined as serum creatinine more than 2 mg/dl), history of malignancy in the last 5 years, severe acute illness and patients on opioid (fentanyl, oxycodone, hydrocodone, acetaminophen/hydrocodone) treatment. In addition, patients with a history of coronary artery disease, cerebrovascular disease, congestive heart failure, arrhythmias, or seizure disorder, were excluded due to the potential risk during ITT.

Study procedures: Patients with HPA axis disorders and control subjects interested in the study were contacted by the research team for a screening interview. A complete medical history was obtained for each study participant. For female participants, a reproductive history was taken. All women in reproductive age group had a negative urine pregnancy test.

All study participants were instructed to fast overnight for 12 hours prior to testing. Six patients were on glucocorticoid replacement and were instructed to hold their medication for 24 hours prior to their dynamic testing. All the tests were conducted at the Clinical Research Unit on site at the Cleveland Clinic. The study was approved by the Cleveland Clinic Institutional Review Board. All subjects signed an informed consent.