Comparison of ACTH Secretion in Cushing's Adenoma and Clinically Silent Corticotroph Adenoma by Cell Immunoblot Assay.

Abstract

Immunocytochemical staining and cell immunoblot assay (CIBA) were performed in adenoma tissue from five patients with Cushing's disease and three patients with clinically silent corticotroph adenomas. All five patients with Cushing's disease showed hypersecretion of ACTH (130, 190, 331, 120, and 130 pg/ml), high levels of serum cortisol (26.6-44.0 micrograms/dl), and symptoms of Cushing's disease. All three patients with silent corticotroph adenoma showed hypersecretion of ACTH (110, 140, and 160 pg/ml) and normal levels of serum cortisol (11.4-26.8 micrograms/dl). The size of the pituitary adenoma on magnetic resonance imaging was smaller in patients with Cushing's disease (mean 8.2 mm) than in patients with silent corticotroph adenoma (mean 26.7 mm) (p = 0.001). Transsphenoidal surgery was performed to totally resect the adenoma tissue. Immunostaining for ACTH showed diffuse ACTH-immunopositive cells in all eight adenomas. CIBA technique showed a good correlation between percentage of ACTH-immunopositive cells and level of plasma ACTH in patients with Cushing's disease but no correlation between the two parameters in patients with silent corticotroph adenoma. The percentage of ACTH-secreting cells and the amount of hormone secreted by a single cell are too low in silent corticotroph adenomas to cause an increase in plasma ACTH level corresponding to the large tumor size.

Silent Corticotroph Adenoma Transformed in Secreting Adenoma with Severe Cushing's Disease after Two Pituitary Surgeries

“…Cystic and hemorrhagic changes inside the adenoma are also consistent with SCA as cited by other authors (18)(19)(20).…”

An Aberrant ACTH-producing Ectopic Pituitary Adenoma in the Sphenoid Sinus

“…Based on this finding, the present case [7.25 to 12.1] and the other three [8.08, 12.0 and 8.0] out of 16 EAPA cases documented (see Table 1) were shown to have relatively high ratios of ACTH (pg/ml) to cortisol (mg/dl) com- pared to common Cushing's diseases, although these three cases, unlike our case, were reported to have completely overt Cushingoid features including moon face, truncal obesity, skin striae, pigmentation and atrophy, cervicodorsal hump, hypertension and diabetes mellitus [4,13,15]. Although the discrepancy of clinical symptoms and endocrine profile could be related to the individual sensitivity to cortisol, it is also possible that an aberrant less-active ACTH molecule exists in the plasma of these EAPA patients [31]. In the present case, the existence of big ACTH molecules may be associated with the less pronounced Cushingoid features.…”

Silent corticotroph adenomas

“…In CD, plasma ACTH levels correlate with abundance of ACTHimmunopositive cells but not in SCAs [24]. Individual corticotroph cells in SCAs may secrete insufficient, or bio-inactive, ACTH molecules [24].…”

“…In CD, plasma ACTH levels correlate with abundance of ACTHimmunopositive cells but not in SCAs [24]. Individual corticotroph cells in SCAs may secrete insufficient, or bio-inactive, ACTH molecules [24]. SCAs potentially derive from POMC producing cells in the vestigial pars intermedia of the human pituitary [17], and the clinical silence may be due to dysregulated POMC processing [37].…”