George Tolis

Prolactin secretion in sixty-five patients with galactorrhea

Pituitary prolactin (PRL) secretion was evaluated in 65 galactorrheic individuals with nonfunctioning hypothalamic-pituitary tumors, acromegaly, prolactin-secreting tumors, Chiari-Frommel syndrome, Argonz-del Castillo syndrome, history of phenothiazine or α-methyldopa intake, primary hypothyroidism, use of contraceptive medications, and in patients with idiopathic galactorrhea. Mean serum prolactin concentrations in patients with prolactin-secreting pituitary tumors were significantly higher than those in other groups but over all there was no correlation between the serum prolactin levels and the grade of galactorrhea. Neither a single elevated serum prolactin level nor the degree of suppressibility after L-dopa administration was diagnostic of a pituitary tumor. However, a history of consistently high serum prolactin concentrations was highly indicative of a prolactin-secreting tumor.

Failure of naloxone to influence physiological growth hormone and prolactin secretion.

Morphine and the opioid peptides, fl-endorphin, [MetZ]enkephalin and [LeuZ]enkephalin are reported to stimulate growth hormone (GH) and prolactin (PRL) secretion in the rat2-5,7, 9,14. Hormone release has been demonstrated after both systemic [intravenous (IV), intraperitoneal (IP) or subcutaneous (SC)] and intracerebral ventricular (ICV) injections; the amounts given have, in general, been large (1-100 mg systemic or 1-100 #g ICV) and anesthetized rats have commonly been used. Shaar et al. is reported that enkephalin analogs administered SC in doses of 10 mg/kg also elicited GH and PRL release in the female rat. The site and mechanism of action of these effects has not been determined. A hypothalamic or other brain locus is suggested by the fact that the substances fail to elicit hormone release from pituitary glands in vitro 1. Martin et al. 1° showed that large hypothalamic lesions failed to completely block morphine-induced GH release and postulated that the effects were mediated at the level of the median eminence. Both enkephalin and fl-endorphin containing cell perikarya occur in the hypothalamus with axons that terminate in the median eminence ~,s. The role of endogenous opioids in the regulation of physiologic GH and PRL secretion is controversial. Previous reports in which single samples of blood were obtained by decapitation suggested a suppression of baseline G H and PRL levels after administration of naloxone, an opioid antagonist 2,7. Stress and suckling-induced PRL responses are also reported to be inhibited by prior administration of opioid antagonists 7. The objective of the present studies was to investigate the effects of naloxone on GH and PRL secretion in unanesthetized rats and in human subjects during sleep. Experiments in our laboratory have documented that physiologic GH secretion in unanesthetized, freely behaving rats is episodic with abrupt surges of secretion occurring at intervals of 3-4 h12, ~9. Basal PRL secretion in such rats is low (less than 10 ng/ml) with infrequent small secretory surges. Sleep-associated changes in GH and PRL secretion are well documented in man, a surge of GH occurring within 2 h of sleep

THE USE OF BROMOCRIPTINE IN THE GALACTORRHOEA-AMENORRHOEA SYNDROMES: THE CANADIAN COOPERATIVE STUDY

Treatment of patients with galactorrhoea and amenorrhoea due to hyperprolactinaemia is , determined by the nature of the primary disorder (Toiis e t al., 1974). In those patients in whom secondary causes such as hypothyroidism, drugs, excessive breast stimulation, etc., can be identified, treatment is directed at the underlying cause. In patients with prolactin secreting pituitary tumours complete removal of the lesion results in disappearance of the symptoms as the serum prolactin concentrations return to normal (Hardy, 1973; Vezina & Sutton, 1974). Two agents, L-dopa and bromocriptine (CB-I54), have been reported to decrease serum prolactin concentrations and to cause a return of menses and a cessation of galactorrhoea (Turkington, 1972; Besser et al., 1972; del Pozo et al., 1974). CB-154 appeared to be particularly promising agent because of its longer duration of action and fewer side effects and as a result of these encouraging reports a cooperative study of the agent bromocriptine (CB-154) was undertaken in a number of Canadian centres.

Hypoparathyroidism in transfusion-dependent patients with β-thalassemia

Hypoparathyroidism is thought to be a rare consequence of iron overload seen in β-thalassemic transfused patients. This study was conducted to determine the prevalence of hypoparathyroidism in a large number of β-thalassemic patients, and its potential correlation with the presence of other endocrinopathies caused by iron overload. Serum and urine biochemical parameters were measured in 243 thalassemic patients (136 females and 107 males) in order to determine the prevalence of hypoparathyroidism and evaluate bone turnover. The patients were divided into two groups according to the presence of hypoparathyroidism. We compared the prevalence of other endocrinopathies and disease complications in the two groups. Hypoparathyroidism was detected in 13.5% of the patients (33 subjects; 17 males and 16 females). Serum-intact parathyroid hormone, and total and ionized calcium were significantly lower, while phosphorus was significantly higher in thalassemic patients with hypoparathyroidism. The reduction in BMD was more prominent in normal thalassemic patients (Z score = −2.246 ± 0.97) compared with those with hypoparathyroidism (Z score = −1.975 ± 0.89), although the difference was not statistically significant. Disturbed glucose metabolism was more common in patients with hypoparathyroidism (P < 0.05). In addition, heart dysfunction was statistically more frequent in this group (odds ratio = 2.51, P < 0.05). Hypoparathyroidism is a not infrequently observed complication in thalassemic patients. Since the concentration of ferritin is not a valuable tool in the prediction of the development of hypoparathyroidism, parathyroid function should be tested periodically, particularly when other iron overload-associated complications occur.

Pregnancy in hyperprolactinemic women

Pregnancy achieved in women who receive treatment to correct the secretory dysfunction of nontumoral HPRL or microprolactinomas requires close prenatal care, but generally its course does not vary from normal. When a macroprolactinoma is present, consequences of pregnancy are insignificant, provided the tumor has been previously treated or bromocriptine is given continuously during the pregnancy. On those rare occasions when symptoms of tumor growth appear during pregnancy, bromocriptine and dexamethasone effectively control such manifestations. Breast-feeding of the infant can be allowed, and a second pregnancy within a short term is not contraindicated. When a new pregnancy is not desired, nonhormonal contraceptive methods are advised. Patients with nontumoral HPRL and microadenomas require periodic checkups. Macroadenomas may be surgically excised, but longterm bromocriptine treatment also achieves good results and is highly recommended.

Induction of menstruation with bromocryptine in patients with euprolactinemic amenorrhea

Three nulliparous women presented with secondary amenorrhea with no evidence of endocrinopathy and normal skull x-ray. Pulsatile gonadotropin secretion was reduced, but an adequate pituitary gonadotropin reserve was demonstrable with luteinizing hormone-release factor provocation. The administration of bromocryptine was associated with amplification of pulsatile secretion of gonadotropins and was followed, in two of the three, by ovulatory menstruation. It is suggested that bromocryptine should be considered for induction of menstruation in euprolactinemic secondary amenorrhea.

Osteoporosis in HFE2 juvenile hemochromatosis. A case report and review of the literature

Juvenile hemochromatosis (JH) is a severe form of hemochromatosis, which involves rapid iron overload and leads to organ damage, typically before the age of 30. We report a single case of a 25-year-old man suffering from juvenile hemochromatosis, with aggressive clinical manifestations, typically characterized by transaminasemia and progressive erectile dysfunction, due to hypogonadotropic hypogonadism. The clinical case appears interesting, as the patient also had secondary osteoporosis accompanied by increased bone resorption, which prevalently affected trabecular bone. Approximately 6xa0months after normalization of serum ferritin levels was achieved by frequent phlebotomies, he became eugonadal and bone mineral density of the lumbar spine increased. Our observations suggest that osteoporosis might occur in the state of JH even at a young age, mainly due to the deprivation of sex steroids and the direct tissue toxicity of iron.

Suppression of testicular steroidogenesis by the GnRH agonistic analogue Buserelin (HOE-766) in patients with prostatic cancer: studies in relation to dose and route of administration.

Forty-six patients with prostatic carcinoma received the gonadotropin releasing hormone agonistic analogue (GnRH-A) Buserelin at doses ranging from 0.05 to 1.5 mg subcutaneously and/or 0.4 to 1.2 mg intranasally (i.n.) daily for 12-120 weeks. An increase in plasma testosterone (T) was seen in 19% of patients on day 7 of therapy; with continuation of treatment plasma T as well as DHT and E2 levels fell by more than 50% within 2-4 weeks in those patients receiving greater than or equal to 50 micrograms s.c. and/or greater than or equal to 1 mg in daily dose. Persistently low plasma T levels (less than 1 ng/ml) were reached in 60% of patients receiving 50 micrograms s.c. in 89% of those treated with 1.2 mg i.n. and in 100% of patients who received initially 1.5 mg s.c. X 7 days followed by 1.2 mg i.n. daily. The above data indicate the importance of dose and route of administration in achieving significant suppression of plasma sex steroids in patients with prostate cancer in whom Buserelin can be used as an alternative to castration or estrogens.

Endocrine Pancreatic Insufficiency in Chronic Pancreatitis

Chronic pancreatitis (CP) is considered to be a rare cause of diabetes mellitus. However, in both the developed and developing world, there is an increasing number of patients suffering from pancreatitis probably due to lifestyle changes, which is partially associated with both social factors and the poor health status of immigrants. Owing to these circumstances, CP has evolved with one of the possible causes of diabetes in a selected group of patients and should be included in the differential diagnosis of diabetes. Several studies have shown that the long-term rate of diabetic complications in patients with CP and insulin-dependent diabetes is similar to that in patients with type 1 diabetes of equal duration. The hypothesis that early diagnosis of CP should result in better prognosis is not validated and may complicate the issue, since the risk of diabetes has been shown to increase significantly only once pancreatic calcification has developed. Accumulative evidence suggests that the risk of diabetes is not influenced by elective pancreatic surgical procedures other than distal pancreatectomy. The lack of contemporary data points to the urgent need for large prospective studies in order to accurately evaluate the special characteristics of disorders in glucose homeostasis in patients with CP.

Failure to interrupt established pregnancy in humans by D-tryptophan-6-luteinizing hormone-releasing hormone.

Four women 5 to 8 weeks into pregnancy, scheduled for therapeutic abortions, were given an analog of gonadotropin-releasing hormone, D-tryptophan-6-LHRH, in an effort to interrupt pregnancy. The treatment consisted of 100-micrograms injections, given twice daily for 5 to 10 days. No decline in serum beta-hCG or progesterone was noted, and menstrual extraction was needed in all women for pregnancy interruption. These data indicate that D-Trp-6-LHRH is not effective as an abortifacient in established pregnancy.