We describe a 64-year-old woman with a cystic pituitary mass presenting with
central diabetes insipidus. Brain magnetic resonance imaging (MRI) with enhancement showed enlargement of the pituitary gland with cystic portions and thickening of the pituitary stalk with homogeneous enhancement. Combined anterior pituitary stimulation test and
insulin-induced
hypoglycemic test confirmed the diagnosis of
panhypopituitarism, including adrenocortical insufficiency due to pituitary and hypothalamic dysfunction by stalk compression. Interestingly, the response of serum
cortisol to CRH was low and delayed, in contrast to the marked increase in plasma
ACTH. Molecular analysis of her plasma
ACTH by
Sephadex G75 gel exclusion chromatography coupled with radioimmunoassay (RIA) indicated a peak for high molecular weight
ACTH, i.e., proACTH, in addition to that for
1-39 ACTH. Three years later, enlargement of the pituitary gland with cystic portions and thickening of the pituitary stalk disappeared completely, followed by the decrease in plasma proACTH level. By the results of endocrinological study and the change of pituitary MRI findings,
lymphocytic hypophysitis was suggested. Synthesis of immature
ACTH is generally thought to be due to impaired processing of the precursor
proopiomelanocortin (
POMC) through activation of
prohormone convertase (PC)-1 by CRH. It is possible that the immature
ACTH in this case was produced by impaired processing of the precursor
POMC due to decreased CRH, dysfunction of corticotrophs in the anterior pituitary by compression of the normal pituitary, or
antibodies targeting hypothalamic and/or pituitary cells. This report suggested that impaired processing of
POMC may unusually play a role in adrenocortical insufficiency exhibited in
lymphocytic hypophysitis.