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Biomedical subjects

G Tolis

Publications and source records attributed to G Tolis.

At least 55 records · Page 3Linked to original sources

Sheehan's syndrome: in vivo diagnosis with the use of computerized axial tomography and pituitary provocative testing.

Postpartum amenorrhea associated with other symptoms and signs of hypopituitarism, such as inability to lactate, weakness, easy fatigability, sexual-hair loss, and clinical evidence of hypothyroidism, were found in two female patients with the antecedent of postpartum hemorrhage. The baseline values of the gonadal, thyroid, and glucocorticoid hormones were all consistently lower than normal. The serum levels of the pituitary hormones were low, and the responses to standard stimulatory tests were either insignificant or blunted. Plane skull films and conventional sella tomography did not reveal any abnormality in the sella turcica. CAT identified hypodensity in the area of the hypophysis with preservation of the pituitary stalk. The combination of the failure of provocative stimuli to affect anterior pituitary hormone release with the radiologic picture compatible with pituitary infarction readily makes the diagnosis of Sheehan's syndrome in vivo and should be used in patients where this syndrome is suspected.

Adrenocorticotropic Hormone↗

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.

Adenoma↗

Gonadotropin-releasing hormone agonistic analogues in the treatment of advanced prostatic carcinoma.

Orchiectomy or chronic administration of the gonadotropin releasing hormone agonistic analogue D, Ser (TBU)6, des Gly-NH2(10) ethylamide (HOE 766) were employed as therapeutic maneuvers in 25 patients with advanced prostatic carcinoma. HOE 766 administration effectively suppressed plasma testosterone to castrate levels that persisted for as long as treatment continued. Surgical and medical castration resulted in a significant decrease in prostatic size; this became evident earlier for surgically than medically treated patients (P less than .05), but no difference existed after the third month of treatment. Symptoms and signs of prostatism improved in practically all the patients. Among patients with stage D2 disease, there was an improvement in five as far as bone radiological assessment was concerned. Alkaline phosphatase levels did not show appreciable changes in patients showing objective stable disease or partial response according to National Prostatic Cancer Project criteria. Radioimmunoassayable prostatic acid phosphatase levels became normal in two of two stage C, five of five stage D1, and eight of seventeen patients with stage D2 disease, a rise in prostatic acid phosphatase (PAP), in alkaline phosphatase, and deterioration in bone radiology were associated with clinical evidence of relapse; this occurred despite persistently low levels of plasma testosterone. Serum thyroxine, cortisol, and prolactin levels remained unchanged following orchiectomy or chronic administration of HOE 766. Practically all patients complained of hot flashes and experienced a decrease in libido and potency, but none developed gynecomastia or thromboembolic episodes. The data indicate that HOE 766 can be used safely as an alternative to castration or estrogens for the treatment of patients with androgen-dependent prostatic cancer.

Acid Phosphatase↗

Transabdominal ultrasonography in the evaluation of patients with advanced prostatic carcinoma: effects of castration and of chronic administration of a gonadotropin releasing hormone agonistic analogue.

Twenty-two patients with advanced prostatic carcinoma were subjected either to orchiectomy (group I, n = 5) or to chronic administration of a gonadotropin releasing hormone agonistic analogue D, Ser (TBU)6, des Gly-NH2(10) LHRH nonapeptide (HOE 766) (group 2, n = 17). Plasma testosterone was similar in both groups prior to treatment (group 1: 636 +/- 129.29, group 2: 580.85 +/- 37.57; X +/- SE). The levels attained in group I were significantly lower (P less than .05) than those of group 2 through eight weeks of follow-up but were similar by the third month. Prostatic size (cm2) as estimated by transabdominal ultrasonography did not differ between the two groups prior to treatment (group 1: 23.6 +/- 3.35, group 2: 21.4 +/- 1.97; X +/- SE). Both therapies resulted in a decrease of prostatic size that was significantly more pronounced (P less than .05) in group I compared with group 2 by the first and third month; by the six month, there was no statistical difference in the prostatic size attained with either therapeutic modality. Persistent suppression of prostatic size was documented in all patients of group 2 chronically (up to 24 months) treated with HOE 766 even when there was evidence of uninhibited or progressive bony metastases. The above data 1) indicate the efficacy of the HOE 766 in inducing medical castration and prostatic shrinkage in advanced carcinoma of the prostate, 2) document the usefulness of transabdominal ultrasound in the follow-up of such patients, and 3) suggest a relationship between the rapidity of tumor shrinkage and Leydig cell suppression.

Buserelin↗

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.

Aged↗

Gonadotropins and estradiol responses to single intranasal or subcutaneous administration of a luteinizing hormone-releasing hormone agonist in the early follicular phase.

Single increasing intranasal and subcutaneous doses of a potent luteinizing hormone-releasing hormone (LH-RH) agonistic analog (D-Ser[TBU]6-des-Gly-NH2(10))LH-RH ethylamide (Buserelin) were administered on day 2 or 3 of the follicular phase in 59 normal women. Groups of five or six volunteers received intranasal doses ranging from 50 to 1300 micrograms and subcutaneous doses varying between 0.3 and 30 micrograms of the LH-RH agonist. Maximal amplitude of the serum gonadotropin response is observed at 6 hours. A sixfold increase is obtained for luteinizing hormone (LH) at a 200 micrograms intranasal dose, whereas maximal follicle-stimulating hormone (FSH) stimulation (threefold) is reached at a lower dose (100 micrograms). A 1000-micrograms dose elicits a more prolonged stimulation, levels of FSH and LH being two and five times above control levels at 11 hours. Similar response curves are obtained by the subcutaneous route, a maximal stimulation being reached at 3 micrograms for FSH and at 10 micrograms for LH. Serum estradiol levels are maximally increased at 11 hours after administration of 10 and 200 micrograms of the analog by the respective subcutaneous and intranasal routes. Twenty-four-hour response curves of gonadotropins indicate that the efficacy of the intranasal route is approximately 3% to 5% of the subcutaneous route. These observations should provide information useful in the investigation of the antifertility effects and medical treatments using an intranasal LH-RH agonist in the human being.

Administration, Intranasal↗

Depression: biological and neuroendocrine aspects.

Distorted biorhythms and altered neuroendocrine function may accompany depressive disorders. Restoration of the above derangements occurs with effective therapy, whereas persistence of the biological abnormalities is found in patients incompletely cured and may be predictive of early relapse. The commonest hormonal abnormalities are: decreased suppressibility of the ACTH-cortisol axis to dexamethasone, subnormal thyrotropin response to TRH and growth hormone release to hypoglycemia; attenuated gonadotropin production and abnormal light-dark entrained melatonin secretion. The observed hormonal derangements seem to be epiphenomena of the primary disorder. The reversibility of the disordered neuroendocrine control with treatment of the depressive syndrome suggests that the hormonal abnormalities represent a state rather than trait disorders. Finally, the lack of similar neuroendocrine derangements in schizophrenia or secondary exogenous depression suggests that different neurochemical alterations underlie these disorders.

Biological Clocks↗

Effect of morphine on the hypothalamic-pituitary axis in postmenopausal women.

In this study, 10 postmenopausal women were given 5 mg of morphine intravenously; and the serum level of prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and growth hormone (GH) were measured before and after morphine injection. A significant increase in serum prolactin as well as a significant decrease in LH were observed following the administration of morphine. It is suggested that morphine may affect a common neurotransmitter that controls both prolactin and LH secretion. It is also of interest that the increase in serum prolactin following morphine injection is of similar magnitude as observed in premenopausal patients.

Female↗

Pituitary responses to a neuroactive tripeptide (TRH) in Friedreich's ataxia families.

Oral glucose tolerance, thyroid function tests, as well as thyrotropin, prolactin and growth hormone release after administration of thyrotropin releasing hormone, were evaluated in patients with Friedreich's ataxia and unaffected family members. Impaired glucose tolerance was found in the majority of family members, affected or not. Thyroid hormone levels and PRL and TSH responses to TRH, were similar in all and normal. However, GH responses to TRH were abnormal in half of the patients, but in none of the unaffected family members. Paradoxical responses to neuropeptides may characterize some Friedreich's ataxia patients, and may predict the possibility of therapeutic maneuvers with such peptides in these patients.

Adolescent↗

Tumor growth inhibition in patients with prostatic carcinoma treated with luteinizing hormone-releasing hormone agonists.

Ten patients with prostatic carcinoma--six with stage C and four with stage D disease--were treated for 6 weeks to 12 months with agonistic analogues of luteinizing hormone-releasing hormone (LH-RH). [D-Trp6]LH-RH was given subcutaneously once daily at a dose of 100 microgram and [D-Ser(But)6]des-GlyNH2(10)-LH-RH ethylamide (HOE 766) was given subcutaneously (50 microgram once daily) or intranasally (500 microgram twice daily). In all patients, mean plasma testosterone levels showed a 75% suppression by the third week of treatment and remained low thereafter. This was followed by a decrease or normalization of plasma acid phosphatase levels by the second month of treatment and a 47% decrease in serum alkaline phosphatase by the 10th week of treatment in all but one patient. In patients with stage C disease presenting with prostatism or urinary outflow obstruction, there was a noticeable clinical improvement. In two such patients, a decrease in the size of the prostate was confirmed by ultrasonography. In patients with stage D disease manifested by diffuse bone metastases, there was relief of bone pain, and in one patient treated for greater than 12 months the improvement was documented by radioisotope bone imaging. It is concluded that superactive agonistic LH-RH analogues hold promise as therapeutic agents in patients with androgen-sensitive prostatic adenocarcinoma. Furthermore, the analogous of LH-RH may be used to assess the responsiveness of patients to surgical castration. Long-term administration of LH-RH analogues could become an alternative to surgical castration and estrogen therapy for the treatment of hormone-dependent prostatic carcinoma.

Buserelin↗

LH-RH-endocrine manipulation in cancer of the prostate.

The treatment of advanced stage D, cancer of the prostate is palliative, and based mainly on endocrine manipulations: orchiectomy or estrogen administration. Both attempt to achieve objective and subjective patient response by reducing either the amount or the action of circulating testosterone levels. This review discusses the history and rationale of these endocrine treatments. Two long term clinical studies completed during the 1950's and 1960's have shown the beneficial effects of estrogen use on patient survival. Despite several design errors, these studies indicated favorable results obtained by the combined use of orchiectomy and estrogens in producing long-term remissions. Recently, advances made in the use of hormone-receptor analysis have been applied to the selection of patients who may benefit from various forms of endocrine treatment. The application of these techniques stems from the encouraging results obtained with the use of receptor analysis in the management of advanced carcinomas of the breast, also a hormone-responsive tumor. Preliminary reports are encouraging as patient selection may be accomplished more rationally, while sparing potential non-responders the side-effects of long-term estrogen administration. The role of the recently available luteinizing hormone releasing hormone (LHRH) analogues as diagnostic and therapeutic tools in the treatment of advanced prostatic carcinoma is also discussed.

Gonadotropin-Releasing Hormone↗

Pseudocyesis: pituitary function before and after resolution of symptoms.

Pseudocyesis was clinically established in a 39-year-old woman. Pituitary function was assessed with the use of hypothalamic peptides and dopamine receptor agonists. Basal serum concentrations of anterior pituitary and ovarian hormones were normal. An exaggerated rise in luteinizing hormone (LH) and prolactin levels was seen following the administration of luteinizing hormone-release hormone and thyrotropin-releasing hormone (TRH), respectively. A paradoxic rise in growth hormone (GH) levels followed TRH administration, whereas the response to dopamine receptor agonists was normal. Pituitary hormone secretion after deflation remained similar to that before deflation, although a normal response of GH to apomorphine was reestablished. These data indicate that the amenorrhea of pseudocyesis is associated with normoprolactinemia and a readily releasable pituitary LH pool, which suggests a suprahypophyseal etiology of the amenorrhea. The abnormalities in GH secretion may also support this contention.

Adult↗

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.

Abortion, Therapeutic↗

Effect of clonidine on growth hormone and glucagon secretion.

The effect of clonidine (0.15 mg i.v.) on circulating GH, glucagon and glucose concentrations was measured in six normal subjects. GH and glucose increased but glucagon secretion remained unchanged. These data indicate that in man clonidine-induced GH secretion is not mediated by a stimulatory effect of clonidine on glucagon secretion and that alpha-adrenergic mechanisms have little role in the regulation of basal glucagon secretion.

Adult↗