Background: It is recognised that there is cross-talk between the thyroid and hypothalamo-pituitaryadrenal (HPA) axes. The few available studies suggest that cortisol levels may be low and cortisol metabolism altered in some patients with thyrotoxicosis.
Aim: To compare HPA axis variables in the thyrotoxic state (TT) and euthyroid state (EU).
Materials and methods: Short synacthen testing (250 μg tetracosactide) was conducted on eight adults subjects with Graves disease when thyrotoxic (elevated free thyroid hormones and TSH <0.01 mU/l) and subsequently repeated after achievement of EU (normal range TSH). At each assessment measurements included: total plasma cortisol and salivary free cortisol at 0, 30, and 60 min following a 0900 h Synacthen; plasma ACTH and cortisol binding globulin (CBG) were measured at t=0, and a 24 h urine free cortisol collected.
Results: In TT, total basal plasma cortisol was significantly lower compared to patients in EU (241.0±49.4 vs 415.0±60.7 nmol/l, TT vs EU, P<0.01). Similarly, peak response to synacthen was reduced (688.6±55.6 vs 899.4±88.4 nmol/l, TT vs EU, P<0.01). ACTH values were similar in both states but baseline salivary free cortisol was lower in TT (5.2±0.8 vs 16.4±1.4 nmol/l, TT vs EU, P< 0.05), but not peak salivary free cortisol post Synacthen (48.0±3.9 vs 45.6±6.4 nmol/l, TT vs EU, P=0.4). CBG was lower in TT (39.7±5.4 vs 56.6±14.4 mg/l, TT vs EU, P=0.093). There was no significant difference in urinary free cortisol between TT and EU.
Discussion: In this small study, basal and stimulated levels of total cortisol were reduced in the TT state, which may be explained by a reduction in CBG levels. However, basal salivary cortisol was significantly reduced in TT with preservation of stimulated response. Further studies are required to determine the clinical consequences of these changes and understand whether cortisol production and utilisation are altered in TT.