FSH-producing macroadenoma associated in a patient with Cushing's disease.

OBJECTIVE AND IMPORTANCE: We encountered a Cushing's disease patient whose surgically removed pituitary macroadenoma was not an ACTH-producing, but rather a gonadotroph adenoma. Cure was obtained only after a tiny microadenoma, overlooked on preoperative studies, was removed by a 2nd operation from a compressed thin normal anterior pituitary gland. CLINICAL PRESENTATION: This 45-year-old woman with Cushing syndrome presented with diabetes mellitus and steroid psychosis. Endocrinological examinations suggested Cushing's disease and MRI disclosed an invasive macroadenoma (22 mm in diameter) with suprasellar extension. INTERVENTION: Despite total removal of the invasive macroadenoma by transsphenoidal surgery, her elevated serum cortisol- and ACTH levels failed to decrease. Histologic study of the surgical specimen disclosed that the tumor was a silent FSH-producing, rather than an ACTH-producing adenoma. Detailed re-evaluation of pre- and postoperative MRI suggested the presence of a 3-mm microadenoma on the left side of a thin compressed normal gland. Venous sampling of the cavernous sinus confirmed this suspicion. In a 2nd operation an ACTH-producing microadenoma was removed from inside the thin remaining compressed normal pituitary gland and endocrinological cure of Cushing's disease was achieved. CONCLUSION: Although double adenomas, being a non-ACTH producing macroadenoma associated with an ACTH producing tiny microadenoma, are extremely rare in patients with Cushing's disease, detailed preoperative MRI evaluation is necessary to avoid missing tiny adenomas hidden in a compressed normal pituitary gland which is the cause of Cushing's disease, especially when a macroadenoma is found in patient with Cushing's disease.

Sex difference and possible relationship to microvascular complications of serum prorenin levels in type 2 diabetic patients, measured by a novel antibody-activating direct enzyme kinetic assay.

Prorenin, a precursor of renin, was measured in sera from normal subjects and type 2 diabetic patients, using a newly developed antibody-activating direct enzyme kinetic assay. Levels of prorenin were examined in relationship to diabetic microangiopathies. The levels of antibody-activating direct prorenin (AAD-PR) were approximately 1.5-fold higher than levels of prorenin measured by a conventional enzyme-activating method. AAD-PR levels were significantly higher in males than in females and in diabetic patients than in normal subjects. Moreover, AAD-PR levels were higher in diabetic patients with microalbuminuria and even higher in those with macroalbuminuria. In normoalbuminuric diabetic patients, AAD-PR levels were higher in those with retinopathy. Furthermore, a significant positive correlation was seen between the AAD-PR levels and HbA(lc) in normoalbuminuric diabetic subjects without retinopathy. Thus, the determination of circulating serum prorenin measured as AAD-PR is related to glycemia and in type 2 diabetic patients may be a risk marker of diabetic microangiopathy. More studies are necessary to determine whether AAD-PR may actually predict the development of microangiopathy.