Insulin sensitivity was increased in untreated patients with aldosterone producing adenoma. Enhanced insulin receptor binding may contribute to this increased insulin sensitivity.

The balance of the conversion between DHEA-S and DHEA in the hyperthyroid state favoured DHEA-S. Similar to cortisol, the DHEA response in the CRH test in hyperthyroidism seemed to be insufficiently compensated for by increased ACTH, although the DHEA response to low-dose ACTH was similar in the hyperthyroid and euthyroid states. Increased DHEA-S might play some role in the pathological states in many organs in hyperthyroidism.

Abstract. In an attempt to investigate the clinical significance of anti-pituitary antibodies in patients with hypopituitarism, anti-pituitary antibody in plasma was examined in 10 such patients (7 cases of isolated ACTH deficiency, 1 of partial hypopituitarism, and 2 of Sheehan's syndrome), on two or three occasions with an interval of more than 6 months (longitudinal study). In a total of 16 relatives of these 4 patients (2 cases of Sheehan's syndrome, one in each of partial hypopituitarism and isolated ACTH deficiency) and one patient not involved in the longitudinal study, anti-pituitary antibodies were also examined (family study). Anti-pituitary antibodies reacting with rat pituitary cytoplasmic antigens (pituitary cell antibodies: PCA) and pituitary cell surface antibodies (PCSA) reacting with GH3 cells and/or AtT-20 cells were measured with indirect immunofluorescence. The longitudinal study revealed the disappearance of antibodies in 3 patients, 2 PCA positive and one both PCA and PCSA positive. In 3 patients, altered antibody titers or a newly appearing antibody were found during the follow-up period.

Wereport a male Japanese with corticotropin (ACTH)-independent macronodular adrenocortical hyperplasia (AIMAH)associated with multiple colon adenomas/carcinomas. The plasma cortisol level was elevated with no diurnal rhythm and was not suppressed with dexamethasone. Basal plasma ACTHwas unmeasurable but subnormally increased after administration of metyrapone or corticotropin releasing hormone. Both adrenals were resected and weighed 90g; the histopathologic findings were similar to those ofAIMAHas previously reported. At least 21 colon lesions which were adenomasor carcinomas, were resected endoscopically or surgically. This is the second reported case of the association ofAIMAHwith multiple colon polyps. An APCgene point mutation was detected in the colon cancer tissue by polymerase chain reaction (PCR)-single strand conformation polymorphism(SSCP)/direct sequencing analysis at the putative splice acceptor site consensus sequence. However, no abnormality ofAPCgene was detected in the adrenocortical hyperplastic tissue. The possible etiological coexistence of these two diseases is discussed.

A 46-year-old womanwith incidentally discovered thyrotropin (TSH)-producing pituitary adenoma showed endocrine data which was consistent with TSH-producing pituitary tumor. However,she showed only slight hyperthyroidism and the oversecretion and autonomoussecretion of TSH from the tumor seemed to be limited from the results of several endocrine examinations. Immunohistochemical examination revealed that not only TSH-p and TSH-a but also prolactin and growth hormone synthesizing cells were present in the tumor tissue. Pituitary-transcription activator 1 (Pit-1) immunoreactivity was also detected in the adenoma cell nuclei. It was conceivable that the presented TSH-producing adenoma clinically located close to the nonfunctioning adenoma and Pit-1 may have played an important role in the multidirectional differentiation or development of this tumor.

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Abstract.A 57-yr-old female with corticotropinoma showing no Cushingoid stigmata is reported. Basal plasma levels of ACTH measured with immunoradiometric assay and jl-endorphin were high, 12.6-15.9 pmol/l and 3.5 pmol/l, respectively. Plasma cortisol level and urinary free cortisol excretion were normal, 303-359 nmol/l and 171-226 nmol/day, respectively. Plasma ACTH markedly increased to 70.5 pmol/l with intravenous administration of 100 jig CRH. Diurnal rhythm of plasma ACTH was seen, but its level in the night was still high. Plasma ACTH suppression with dexamethasone was insufficient.CRH stimulation after dexamethasone suppression increased plasma ACTH level from 4.4 to 13.7 pmol/l. Intravenous administration of 4 ig desmopressin increased plasma ACTH from 15.6 to 19.6 pmol/l.Oral administration of 16 mg lepramide insufficiently decreased plasma ACTH from 7.3 to 5.3 pmol/l.However, plasma cortisol responses in these conditions were normal. Postoperative pathological study revealed subtype 1 corticotropinoma immunohistochemically and electron-microscopically. Postoperative basal plasma ACTH decreased to 3.9 pmol/l, although plasma cortisol did not change. Diurnal rhythm and dexamethasone suppressibility of plasma ACTH became normal. Plasma sample was chromatographed on a Sephadex G-75 column. The elution profile showed two peaks of ACTH, one of which was compatible with 1-39 ACTH and another with higher molecular weight ACTH which was probably secreted from corticotropinoma. Anomaly in processing of proopiomelanocortin was suspected.

Abstract.A 15-year-old girl with Cushing's disease exhibited adrenal insufficiency following incomplete transsphenoidal resection of a large pituitary corticotropinoma, approximately 35 mm in diameter. Within two weeks following surgery, her plasma ACTH level decreased from 42 to 13 pmol/1, while, her plasma cortisol levels and urinary excretion of free cortisol decreased from 607 nmol/l and 1112 nmol/day to 94 nmol/l and 55 nmol/day, respectively. Immunoreactive ACTH was characterized in plasma using Sephadex G-75 column chromatography and measuring ACTH with immunoradiometric assay (IRMA) and radioimmunoassay (RIA) to determine additional peaks, other than the one demonstrated for 1-39 ACTH.In particular, when measured with RIA, a broad peak including the high molecular weight ACTH was detected as well as 1-39 ACTH.The bioactivity of the high molecular weight ACTH in patient plasma was lower than the reference range of 1-39 ACTH, which is determined by the ability of dispersed rat adrenocortical cells to secrete corticosterone.The large pituitary corticotropinoma found in this patient secreted not only 1-39 ACTH but also high molecular weight proopiomelanocortin (POMC)-derived peptides, which could be detected by measuring with IRMA and RIA for ACTH.Based on the results of biological activity and molecular ratios, no positive evidence could be found to support the hypothesis that the high molecular weight ACTH induced any postoperative adrenal insufficiency in this patient. However, based on this study, the possibility of adrenal insufficiency should be carefully monitored, even when post-operative remnant tumor tissue is clearly present in patients with Cushing's disease, accompanied by macrocorticotropinoma.