Endocrine Abstracts

Context: Chronic hypercortisolism is known to impact the hypothalamus-pituitary-thyroid (HPT) axis, through a disruption of both thyrotropin-releasing-hormone and thyroid-stimulating hormone (TSH) release. These changes, in turn, are responsible for reduced triiodothyronine (T3) and thyroxine (T4) synthesis and secretion, eventually resulting in central hypothyroidism (C-Hypo). However, data on magnitude and timing of recovery of the above abnormalities are still controversial.

Objective: To evaluate:i)the frequency of C-Hypo at diagnosis in patients with ACTH-dependent hypercortisolism;ii)short- and mid-term dynamic changes of thyroid function parameters following implementation of appropriate surgical and/or medical therapy.

Methods: We retrospectively reviewed records from consecutive patients affected with hypercortisolism due to ACTH-secreting pituitary adenoma and ectopic ACTH syndrome (EAS). Included were patients with no known primary thyroid dysfunction, who had been serially tested for thyroid function parameters (TSH, free-T4 [FT4], free-T3 [FT3]) upon hypercortisolism confirmation (T₀), and at 3 (T₁), 6-9 (T₂), and 12-15 (T₃) months after surgery/medical therapy had been performed/started.

Results: Forty-five patients (35 females,10 males, median age 41yrs, range 12-74) affected with ACTH-secreting pituitary adenoma (n =41; microadenoma 92.7%) and EAS (n =4) were included in the study. C-Hypo was diagnosed at T₀ in 8/45 (17.8%) patients (FT4 10.5±1.6 pmol/l; FT3 4.0±0.7 pmol/l; TSH: M±SD 0.9±0.6 mU/l). Compared to C-Hypo patients, patients without C-Hypo had higher FT4 levels (15.3±2.6 pmol/l, P < 0.001) at T₀, whereas both TSH and FT3 concentrations were similar (TSH 1.3±1.1 mU/l, P = 0.56; FT3 4.5±1.0 pmol/l, P = 0.45). At T₁, 33/45 (73.3%) patients achieved remission of hypercortisolism and 12/45 (26.7%) were persistently hypercortisolemic. TSH concentrations increased significantly between T₀ and T₁ in cured patients (1.11±0.63 vs 2.05±1.35 mU/l, P < 0.001) but not in not-cured patients (1.89±1.63 vs 1.84±1.10 mU/l, P = 0.78). Similarly, FT3 significantly increased in cured patients only (4.31±0.99 vs 5.47±0.91 pmol/l, P = 0.001). No changes in FT4 concentrations were found between T₀ and T₁ in both cured and not-cured patients. Finally, a significant reduction in FT4/FT3 ratio was observed in cured patients (3.53±0.81 vs 2.57±0.72 pmol/l, P = 0.002). No significant changes were observed in thyroid function parameters in the further follow up in either cured (T₂ n =36; T₃ n =40) and not-cured patients (T₂ n =9;T₃ n =5).

Conclusions: Our data are consistent with an inverse correlation between hypercortisolism and thyroid function parameters before and after therapeutic control. The observed different behavior in FT3 and FT4 levels following remission of hypercortisolism may be related to recovery of the inhibitory effect of hypercortisolism on deiodinase activity.