Age-related changes in plasma growth hormone response to growth hormone-releasing factor in man.

The response of plasma growth hormone to synthetic growth hormone-releasing factor (hpGRF-44) administered intravenously was examined in normal men of various ages ranging from 20 to 75 years. Most of the subjects who were over forty years old had either no or much lower response of plasma growth hormone to hpGRF-44. In contrast plasma growth hormone increased markedly after hpGRF-44 injection in all men in their twenties and thirties. The mean peak level of plasma GH following hpGRF-44 administration was 29.6 +/- 20.4 (SD) ng/ml in men in their twenties, 30.2 +/- 26.5 ng/ml in their thirties, 9.7 +/- 5.2 ng/ml in their forties, 10.9 +/- 5.4 ng/ml in their fifties, 8.4 +/- 4.8 ng/ml in their sixties and 8.1 +/- 7.5 ng/ml in their seventies. These results suggest that somatotroph cells become less sensitive to growth hormone-releasing factor with aging.

Plasma pituitary hormone responses to the synthetic enkephalin analog (FK 33-824) in normal subjects and patients with pituitary diseases.

D-Ala, Mephe, Met, enkephalin (Sandoz FK 33-824) is a stable long acting analog of methionine-enkephalin. FK 33-824 (0.5 or 1.0 mg), elicited plasma GH and PRL responses in normal subjects. In 23 patients with pituitary dwarfism, the response of plasma GH was markedly impaired, while PRL responded to a variable degree. In patients with acromegaly, there was little or no increase in GH and PRL after FK 33-824. Plasma GH increased to a variable degree after FK 33-824 in patients with hyperprolactinemia, with little change in plasma PRL. FK 33-824 decreased plasma cortisol in normal subjects and patients with pituitary disease. These results show that patients with acromegaly and hyperprolactinemia due to pituitary adenomas and patients with pituitary dwarfism do not respond well to FK 33-824, presumably because of hypothalamic or pituitary derangement.

Anterior pituitary hormones in plasma and pituitaries from patients with Cushing's disease.

Pituitary adenomas were obtained from eight of nine patients with Cushing's disease, and the surrounding tissues as well were obtained from six of nine patients. ACTH, beta-lipotropin (beta-LPH), beta-endorphin, GH, TSH, LH, and PRL concentrations in these tissues were determined by RIA. Immunoreactive ACTH and beta-endorphin (beta-endorphin + beta-LPH) were present in high concentrations in all adenomas, and low concentrations were found in the surrounding tissues, except for one patient. As compared to levels seen in normal pituitary tissue, the GH concentration in the surrounding tissues was suppressed in five of six cases. TSH and LH concentrations were suppressed in four and three cases, respectively. The PRL concentration was not suppressed in any of the six patients studied. These four hormones were not detected in any adenoma. Plasma GH, TSH, and LH responses to various stimuli which were suppressed preoperatively returned to normal in most of the patients after adenomectomy. Basal plasma cortisol concentrations were normal or subnormal and were suppressed by the administration of 1 mg dexamethasone after adenomectomy, in contrast to the lack of such suppression preoperatively. ACTH and beta-endorphin secretion were stimulated by lysine-8-vasopressin and suppressed by dexamethasone and cyproheptadine in vitro.

The significance of alpha-subunit as a tumor marker for gonadotropin-producing pituitary adenomas.

We studied gonadotropin hormone alpha-subunit and gonadotropin secretion in four patients with gonadotropin-producing pituitary adenomas. All four patients had elevated plasma alpha-subunit levels, ranging from 2.8-8.5 ng/ml (normal, less than 0.5 ng/ml). alpha-Subunit responses to LHRH were less than those in seven patients with primary gonadal failure. The relative proportions of the gonadotropin and alpha-subunit peaks in one patient were the same before and after LHRH administration, based on gel filtration studies of plasma. The alpha-subunit levels decreased little during testosterone treatment in the two adenoma patients so treated. Immunohistochemical study of the adenomas from two patients demonstrated definite staining with alpha-subunit and gonadotropin antisera. Elevated plasma levels of alpha-subunit and its relative unresponsiveness to LHRH stimulation or testosterone suppression suggest that the alpha-subunit originated in tumor tissue and that its measurement is useful for the diagnosis of a gonadotropin-producing tumor in patients with elevated plasma levels of LH and/or FSH.

The effect of free fatty acids on growth hormone (GH)-releasing hormone-mediated GH secretion in man.

The effect of FFA on GH-releasing hormone (GHRH)-mediated secretion of GH was examined in six normal young men. Three of the men were infused with 250 ml of a lipid-heparin solution at 1.67 ml/min for 150 min, and the other three were given an equivalent volume of saline in the same manner. Thirty minutes after the start of infusion, 100 micrograms GHRH (the 44-amino acid form) were injected iv, and plasma GH and FFA were measured. One week later, the same men participated in an identical experiment, but the ones who had received lipid-heparin previously were given saline and vice versa. In both experiments, plasma FFA increased to 2.25 +/- 0.16 meq/liter (mean +/- SEM) 60 min after the start of lipid-heparin infusion, whereas FFA levels did not change significantly in the saline-treated group. Mean plasma GH levels reached peak concentrations in both groups 30 min after GHRH treatment. However, the peak GH response when lipid-heparin was given was significantly diminished (8.4 +/- 1.7 ng/ml), compared with the peak response when saline was given (28.9 +/- 7.1 ng/ml). These data suggest that plasma FFA elevations induced by lipid-heparin infusion inhibit GH secretion induced by GHRH.

The effect of glucose on growth hormone (GH)-releasing hormone-mediated GH secretion in man.

The effect of glucose on GH-releasing hormone (GHRH)-mediated GH secretion was examined in six normal young men. In two paired experiments, the six men drank a 75-g glucose solution or an equal volume of water 30 min before receiving, iv, 100 micrograms of the 44-amino acid form of human pancreatic GHRH (hGHRH-44). One week later, the same men underwent an identical experimental protocol in a cross-over trial. Basal plasma GH concentrations before hGHRH-44 administration were not statistically different in the two experiments [glucose experiment, 2.1 +/- 0.1 (+/- SE) ng/ml; water experiment, 2.6 +/- 0.6 ng/ml]. The mean peak plasma GH level occurred 30 min after hGHRH-44 administration in both experiments. However, the mean GH response was significantly diminished when the men received glucose (8.12 +/- 1.12 ng/ml) compared to that when they received only water (23.70 +/- 8.46 ng/ml; P less than 0.01). Thus, hyperglycemia may exert an inhibitory effect on the plasma GH response to hGHRH-44.

Endocrine characterization of the adrenal adenomas in a case of primary aldosteronism.

A 48-year-old man with typical clinical and biochemical features of primary aldosteronism was revealed on operation to have two adrenocortical adenomas in the left gland. An ACTH-dependent pattern of aldosterone secretion was demonstrated in terms of the parallel circadian rhythm of aldosterone with cortisol and the exaggerated response to ACTH but not to angiotensin II. Aldosterone and cyclic AMP release in vitro was studied using collagenase-dispersed cells of each adenoma. Not only the large adenoma but the small one showed basal and ACTH-stimulated releases of aldosterone greater than those by the adjacent tissue. In response to angiotensin II and potassium, the small adenoma showed a larger maximum increment of aldosterone than the large adenoma. This difference in endocrine features of the two adenomas suggests a possible transformation in their nature during development. An exaggerated cyclic AMP release by the adenomas in response to ACTH in vitro suggested the possible role of increased adenylate-cyclase activity in the hyperresponse of aldosterone to ACTH in this case.

[Radioimmunoassay of synthetic steroid hormones].

The problem and recent progress of radioimmunoassay for various kinds of synthetic steroid hormones are reviewed. The specificity and sensitivity depend mostly on the position of synthetic antigen (hemisuccinate or oxime). Using good antibodies, a direct radioimmunoassay without extraction procedures of samples is available. A simplified method is required for the monitoring of synthetic steroids to know the effects and side effects.

A receptor-immunoassay for the determination of the specificity of anti-HCG-beta sera.

In the receptor-immunoassay, the binding of anti-HCG-beta sera to 125I-HCG and 125I-HLH is measured in the presence of bovine corpus luteum "receptor". Anti-sera specific for HCG show little binding with 125I-HLH. The receptor-immunoassay permits an evaluation of specificity, affinity and the ability of anti-HCG-beta sera to compete with the "receptor" for binding to 125I-HCG.

Restoration of fertility with gonadotropin and bromocriptine in a hypogonadal man after removal of macroprolactinoma.

A case of male hypogonadism after removal of macroprolactinoma was successfully treated with gonadotropin. A 35-year-old man treated surgically for pituitary adenoma had elevated plasma prolactin and impaired pituitary function after the operation. He was on replacement of hydrocortisone, levothyroxine and testosterone depot along with bromocriptine. Normal plasma testosterone levels were achieved with HCG, 3,000 IU three times a week. The addition of 75 IU of FSH daily restored spermatogenesis and the sperm count reached the fertile range at the 11th month. Doses of HCG and FSH were cut in half at the 10th month without affecting the plasma testosterone levels. His wife was impregnated at the 12th month and gave birth to a normal baby girl.

[A study of the clinical usefulness of the CA15-3 radioimmunoassay kit].

We have studied the clinical usefulness of the CA15-3 radioimmunoassay (RIA) kit that has been developed with two monoclonal antibodies (115D 8 and DF 3). Serum levels of CA15-3 exceeding the normal level were found in a high percentage of patients with ovarian cancer (80%), lung cancer (62.5%) and breast cancer (29.3%). In patients with breast cancer, the mean concentrations of CA15-3 before operation were higher than those after operation. Further, the levels of CA15-3 showed a good correlation with the extent and the stage of the breast cancer. These results suggest that CA15-3 levels can provide monitoring information in the follow-up management of patients with breast cancer.

[Clinical evaluation of various tumor markers in pleural effusion and in the serum].

Various tumor markers and enzymes in the pleural effusion and serum have been measured in 47 patients with carcinoma and in 43 patients with benign disease, by means of a radioimmunoassay and biochemical methods. CEA in the pleural effusion showed a high specificity and sensitivity for the detection of the malignancy. In patients with a lung cancer, measurement of the NSE in the serum was more useful than in the pleural effusion. Further, both CA19-9 and SCC in the pleural effusion showed a high specificity in a differential diagnosis of cancer and benign diseases. On the other hand, CA 125, TPA and IAP in the pleural effusion and in the serum showed a high sensitivity, but a low specificity for diagnosing the malignancy. The levels of ADA were significantly higher in tuberculous pleural effusions than in carcinomatous effusions. Therefore, this suggests that measurement of the various tumor markers in both the pleural effusion and in the serum is useful in achieving a differential diagnosis of malignant and benign diseases.

Puberty due to ectopic HCG production in a girl with suprasellar ectopic pinealoma associated with panhypopituitarism.

A 13.5-year-old girl who developed puberty due to HCG production by suprasellar ectopic pinealoma was reported. This girl appeared to be in a state of precocious puberty at the age of 5 when ectopic pinealoma was first diagnosed. Her breasts started to develop at 13 years of age in spite of hypopituitarism. Plasma LH was found to increase for several months and gave rise to suspicion of the recurrence of the tumor, which was confirmed by the detection of HCG in plasma and CSF. Precocious puberty or puberty can be a characteristic endocrinological manifestation of an HCG producing tumor not only in boys but also in girls. The measurement of plasma HCG (or LH) can be a useful tumor marker in following the clinical course of an HCG producing tumor.

[Carcinoembryonic antigen in serum and the tissue of patients with colon cancer].

Carcinoembryonic antigen (CEA) levels in the serum and colon tissue were evaluated in 83 patients with colon cancer. The mean concentration of serum CEA increased in parallel with Dukes' stages. CEA concentrations in the cancerous and normal colon overlapped. In the same patient, however, CEA of cancerous colon tissue was always higher than that of normal colon tissue. There was no difference in CEA concentrations in colon cancer between Dukes' A and B. However, in patients with Dukes' C stage, the concentration was higher than in those with Dukes' A and B. The detection of tissue CEA concentration as well as serum CEA is a useful marker for monitoring patients with colon cancer.