Inhibition of L-dopa-induced growth hormone stimulation by pyridoxine and chlorpromazine.

One gram of L-dopa was administered orally to 12 male control subjects and induced an increase of growth hormone (GH) secretion. The L-dopa-induced GH response was inhibited by an intravenous infusion of pyridoxine, but pyridoxine did not inhibit the GH response to hypoglycemia. Chlorpromazine also inhibited L-dopa-induced GH stimulation. Glucose concentrations were unaffected by L-dopa, chlorpromazine, and pyridoxine administration in these subjects. The mechanism of the suppressed L-dopa-induced GH response by pyridoxine appears to be mediated by peripheral accleration of the conversion of L-dopa to dopamine, while that of chlorpromazine appears to be mediated through hypothalamic centers. Pyridoxine and chlorpromazine should be added to the list of other factors affecting the response to L-dopa-induced GH stimulation

Physician house calls: a complement to hospital-based medical care.

A physician-oriented, hospital-based Home Care Program (HCP) is described. The staff includes a director, resident physicians, nurses, social workers, and clerical personnel. House calls are made by resident physicians during off-duty hours, but patients, their families, and other health professionals may help with their care. Drugs, equipment and supplies are available through the hospital and contract vendors. The most common medical diseases are cardiac and cerebrovascular disorders, arthritis, diabetes mellitus, chronic pulmonary disorders and hypertension. Of 513 patients evaluated in one year, 337 were admitted to the HCP. Two-thirds were women. Ages ranged from 18 to 106 (median, 68 years). Under the HCP there was significant improvement and control of the medical problems, and a decrease in hospital and emergency room admissions, and clinic visits; 207 of the 337 patients were discharged. The HCP cost less than other outpatient and inpatient services. It proved to be a rewarding, economical and effective means of improving medical care for a metropolitan population dependent upon hospital-based physicians for medical services.

Pituitary function and growth hormone dynamics in acromegaloidism.

Acromegaloidism is a condition which resembles acromegaly by its clinical manifestations but is not due to pituitary or hypothalamic dysfunction. Twenty patients were diagnosed as having this disorder and the results from studying growth hormone (GH) responses in 15 patients (11 women and four men) were included in this report. Clinical manifestations closely resembled those of acromegalics, including history of progressive changes, acral enlargement, visual disturbances, abnormal visual fields in four patients, and sella turcica enlargement in two patients. The glucose tolerance test (GTT) was abnormal in 12/15 patients, 13/15 were > 10 percent obese, 8/15 had hypertension, 7/15 had large-statured relatives, but lactorrhea was absent in all patients. The mean serum GH concentration was 2.2 ng/ml, which suppressed to 0.6 ng/ml during the GTT; increased to 24 ng/ml during hypoglycemia; and increased to 10.3 ng/ml after L-dopa ingestion. Other pituitary hormones (LH, FSH, TSH, prolactin), the metyrapone test, 24-hour random and nocturnal sleeping GH concentrations were normal. These GH values and responses helped to differentiate acromegaloidism from treated and untreated acromegaly. The pathogenesis of acromegaloidism was not determined, but somatomedin studies may prove helpful in further defining this disorder.

Suppression of the hypothalamic-pituitary-adrenal axis after subcutaneous cortisone acetate administration in rats.

Groups of female rats were injected daily for 14 days with 10 mg of cortisone acetate subcutaneously, to study the mechanisms of glucocorticoid suppression on the hypothalamic-pituitary-adrenal axis. Pituitary adrenocorticotropic hormone (ACTH) content, plasma ACTH, adrenal venous corticosterone, adrenal weights, and the catabolic effects on body weight were studied simultaneously (under stressful and non-stressful conditions) before, during, and up to six weeks after cortisone. This study confirmed the results of other investigators that cortisone acetate caused catabolic weight loss and adrenal atrophy, but it was noted to persist up to six weeks after the injections. Glucocorticoid acetate was more effective in causing ACTH-axis suppression than succinate or phosphate preparations, and the effects were dose and time related. Significant depletion of pituitary ACTH content, suppression of plasma ACTH, and corticosterone secretion occurred five to seven days after beginning cortisone acetate (p=<0.001); it was continuous throughout the injection schedule (p=<0.001); it remained for two to four weeks after the cortisone was discontinued (p=<0.001). The animals showed minimum plasma ACTH responsiveness to severe acute stress during this two to four-week suppression phase, but rapid recovery occurred thereafter. Plasma ACTH was undetectable up to six weeks post-cortisone when the animals were not under stress. This may be related to residual cortisone acetate found at the injection sites, or to an altered or different ACTH-axis control mechanism. The sequence of events during recovery from cortisone suppression appeared to be (1) repletion of corticotrophin-releasing hormone (by inference), (2) repletion of pituitary ACTH content, (3) secretion of plasma ACTH, (4) reversal of adrenal atrophy, and (5) subsequent secretion of corticosterone.

Suppression of the hypothalamic-pituitary-adrenal axis after oral hydrocortisone succinate ingestion in rats.

Groups of Holtzman female rats were fed 10 mg/day of hydrocortisone succinate orally to study the responsiveness of the hypothalamic-pituitary-adrenal axis to acute stress. Pituitary ACTH content, plasma ACTH, adrenal venous corticosterone, and adrenal weights were studied simultaneously in experimental and control rats before, during, and up to two weeks after oral hydrocortisone administration. There was a significant decrease in pituitary ACTH content (p=<0.001), suppression of plasma ACTH and corticosterone in response to acute stress (p=<0.001), and adrenal atrophy during and following oral hydrocortisone administration. After discontinuing the hydrocortisone it required three to five days for the rats to respond adequately to acute stress. However, it was seven to ten days post-hydrocortisone before plasma ACTH and corticosterone responses to acute stress had returned to basal values, but decreased pituitary ACTH content and partial adrenal atrophy continued throughout the ten-day post-hydrocortisone study interval. Recovering from the suppressive effects of oral hydrocortisone was more rapid than following parenteral hydrocortisone. However, oral hydrocortisone causes identical but less sustained suppression of the hypothalamic-pituitary-adrenal axis as observed in animals treated with parenteral glucocorticoid preparations.

Endocrine function in a patient with asymmetrical acral hypertrophy and giantism: a possible variant of the Kippel-Trenaunay syndrome.

Endocrine function was evaluated in a 38-year-old man who had patchy asymmetrical acral hypertrophy and giantism. The history and clinical manifestations were consistent with previously described cases of the Klippel-Trenaunay syndrome. Pituitary and peripheral hormone concentrations were generally elevated, but his endocrine status appeared normal by clinical evaluation. Of particular interest were elevated growth hormone and somatomedin-A concentrations and responses to provocative tests. These findings suggest that this patient had abnormal cell receptor pathophysiology as the cause of the asymmetrical acral hypertrophy and giantism, which often occurred in the same anatomical site.

Plasma ACTH in rats following medical adrenalectomy.

We have previously reported that surgically adrenalectomized nonstressed rats showed delayed secretion of the expected increase in plasma ACTH concentrations following adrenalectomy.(1) However, increased plasma ACTH concentrations were always detected when these animals were subjected to severe stress, and their responsiveness increased again seven days or more following surgical adrenalectomy. We are now reporting similar results which were obtained following prolonged systemic glucocorticoid administration (medical adrenalectomy) in similar groups of rats.

Failure of selective pituitary adenomectomy to cure acromegaly.

Complete selective pituitary adenomectomy for acromegaly may fail to cure the underlying endocrinopathy. A 40-year-old man who had acromegaly of ten-years duration was initially treated with pituitary irradiation eight years prior to surgery. Three years after irradiation his mean GH concentration decreased from 53 to 9.0 ng/ml, then subsequently increased, and was associated with development of severe hyperglycemia. A transsphenoidal microdissection was performed, and a discrete pituitary adenoma was visualized and totally removed at surgery. GH concentrations decreased from 46 to 5.0 ng/ml one week after surgery and to 3.0 ng/ml 10 months after surgery. Despite improvement postoperatively, the patient still demonstrated abnormal GH dynamics and responses to the GTT, abnormal nocturnal and random GH sampling, and abnormal responses to the L-dopa, apomorphine, and TRH stimulation tests. Acromegaly could be caused by either hypothalamic hyperfunction, an autonomous pituitary tumor, or both; but the latter would not explain the results obtained in this patient. This suggests that reduction of GH to normal concentrations following selective pituitary adenomectomy is not synonomous with curing acromegaly.

Adverse effects of intravenous cannabis tea.

Adverse effects occurred in four youths after intravenous injection of an aqueous cannabis-seed tea, which was prepared by boiling the seeds. The effects were immediate and included nausea, vomiting, abdominal pain, watery diarrhea, chills, fever, hypovolemic shock, hypotension, and non-oligemic transitory renal failure. Other manifestations included persistent hypoglycemia, tachycardia, gastrointestinal bleeding, conjunctival hemorrhage, injury, jaundice, splenomegaly, leucocytosis, myalgia, arthralgia, motor weakness, and prostration. Ischemia was noted on electrocardiogram (EKG). All manifestations appeared to reverse within weeks, but these effects had been potentially fatal.

Hypoglobulinemia in acromegaly.

We have observed an apparent hypoglobulinemia in 17 of 35 patients (48.6%) with acromegaly. This unexpected finding was persistent and reproducible up to six years for five acromegalic patients, and more than one year for nine other patients. Serum globulin was analyzed by three different methods, and the deficiency was most noticeable in the alpha globulin fraction (alpha1 greater than alpha2). When hypoglobulinemia occurred in control hospital in-patients (11%) it was associated with chronic or severe illnesses, and limited nutritional intake, but similar medical problems were absent in the acromegalic patients. There was no correlation of the hypoglobulinemia in the 35 acromegalic patients to their growth hormone (GH) concentration (r = 0.07), ages, sex, treatment status, or to the seriousness or duration of the acromegaly. The pathophysiology of the apparent hypoglobulinemia in acromegaly is unknown, but may be related to transport and/or disposal of excess growth hormone, or a defect in protein synthesis.