The cytoplasmic secretory granules of corticotrophs in the anterior pituitary are basophil in trichrome stains and
periodic acid-Schiff positive in the histochemical
stain for
glycoprotein due to their content of the glycosylated 16 000 N-terminal fragment of the precursor
protein proopiomelanocorticotrophin (POC). The granules show a positive immunocytochemical reaction to
antibodies raised against
ACTH,
beta-endorphin and N-terminal fragments of POC. A small subset of corticotrophs contains immunoreactive
alpha MSH in addition. Immunocytochemistry shows the corticotrophs to constitute about 15-20% of the anterior pituitary cells arranged both singly and in clumps. They are distributed in the median wedge and anteriorly, laterally and posteriorly adjacent to the pars nervosa which is often 'invaded' by corticotroph basophils. The
alpha MSH subset is prominent in the rudimentary intermediate lobe and is scattered anteriorly in the pituitary of the human fetus. Crooke cell hyalinization is associated with pathologically maintained hypercortisolaemia and with glucosteroid
therapy. The hyalinization is demonstrated in ultrastructure to be due to massive accumulation of intermediate cytoplasmic filaments 7-8 nm in diameter that are normally present in only small number. The change is associated with a varying degree of loss of secretory granules. In untreated
Addison's disease there is a marked increase in the number of corticotrophs, many of which are arranged in distended alveoli to form micronodules. The vast majority of cases of pituitary-dependent
Cushing's disease and all cases of Nelson's syndrome are associated with a basophil or
chromophobe adenoma. These give a positive immunocytochemical reaction with anti-
ACTH,
beta-endorphin and N-terminal POC. In ultrastructure the cells of the
chromophobe adenomas are seen to contain sparse secretory granules that are usually smaller than those in the chromophil
adenomas. There are only very few reports of pituitary-dependent
Cushing's disease found to be due to immunocytochemically confirmed corticotroph
hyperplasia with or without a
corticotroph adenoma. A few cases have been described in which the
adenoma cells show Crooke's hyalinization, associated in one example with secretion of a big
ACTH found more typically in ectopic
ACTH-secreting tumours. A group of cases due to
corticotroph adenoma has been reported whose excessive
ACTH secretion is reduced by treatment with the
dopamine agonist bromocriptine, in which it is suggested that the tumour cells arise from a subset of corticotrophs of pars intermedia origin.(ABSTRACT TRUNCATED AT 400 WORDS)