Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aromatase inhibitor, 'pyridoglutethimide' (PyG), has been shown previously to suppress serum oestrogen levels in postmenopausal breast cancer patients and to achieve clinical responses at a dose of 500 mg twice daily (b.d.). This report gives the results of a detailed pharmacokinetic and endocrine study of PyG in ten patients. Four doses were tested at intervals of 2 weeks in the following order: 200 mg b.d., 400 mg b.d., 800 mg b.d., 1200 mg b.d. Concentration-time profiles of serum levels of PyG were curvilinear in all patients probably reflecting a saturation of metabolic enzymes. During repeat-dosing metabolism was enhanced approximately 2-fold. Plasma levels of oestradiol were significantly suppressed by the lowest dose of PyG. Although higher doses appeared to achieve greater suppression this was not statistically significant in this small group of patients. There were no significant effects at any dose on the serum levels of cortisol, aldosterone, luteinising hormone, follicle stimulating hormone, prolactin, sex hormone binding globulin or thyroid stimulating hormone. There was a dose-related increase in 17 alpha-hydroxyprogesterone levels and a dose-related decrease in levels of dehydroepiandrosterone sulphate (DHAS). The androgens DHA, testosterone and androstenedione also were significantly suppressed with at least one of the doses of PyG. Synacthen tests did not support these changes being a result of inhibition of 17,20 lyase. It is possible that they are due to enhanced clearance of DHAS. Two patients experienced no toxicity throughout the study, whilst a total of four patients were withdrawn because of side-effects: one at 400 mg b.d., two at 800 mg b.d., and one at 1200 mg b.d. The most frequent side-effects were nausea and lethargy. One patient showed an objective response to treatment.
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PMID:Endocrine, pharmacokinetic and clinical studies of the aromatase inhibitor 3-ethyl-3-(4-pyridyl)piperidine-2,6-dione ('pyridoglutethimide') in postmenopausal breast cancer patients. 193 11

The essentiality of zinc for humans was recognized in the early 1960s. The causes of zinc deficiency include malnutrition, alcoholism, malabsorption, extensive burns, chronic debilitating disorders, chronic renal disease, certain diuretics, the use of chelating agents such as penicillamine for Wilson's disease, and genetic disorders such as acrodermatitis enteropathica and sickle cell disease. The requirement of zinc is increased in pregnancy and during the growing age period. The clinical manifestations in severe cases of zinc deficiency included bullous-pustular dermatitis, alopecia, diarrhoea, emotional disorder, weight loss, intercurrent infections, hypogonadism in males and it is fatal if untreated. A moderate deficiency of zinc is characterized by growth retardation and delayed puberty in adolescents, hypogonadism in males, rough skin, poor appetite, mental lethargy, delayed wound healing, taste abnormalities and abnormal dark adaptation. In mild cases of zinc deficiency in human subjects, we have observed oligospermia, slight weight loss and hyperammonaemia. Zinc is a growth factor. As a result of its deficiency, growth is affected adversely in many animal species and in man. Inasmuch as zinc is needed for protein and DNA synthesis and cell division, it is believed that the growth effect of zinc is related to its effect on protein synthesis. Testicular functions are affected adversely as a result of zinc deficiency in both humans and experimental animals. This effect of zinc is at the end organ level and the hypothalamic--pituitary axis is intact in zinc-deficient subjects. Inasmuch as zinc is intimately involved in a cell division, its deficiency may adversely affect testicular size and thus its function. In mice, the incidence of degenerate oocytes, and hypohaploidy and hyperhaploidy in metaphase II oocytes were increased due to zinc deficiency. Zinc at physiological concentrations reduced prolactin secretion from the pituitary in vitro and it has been suggested that this trace element may have a role in the in vivo regulation of prolactin release. Thymopoietin, a hormone needed for T-cell maturation, has also been shown to be zinc dependent. It is clear that zinc may have several roles in biochemical and hormonal functions of various endocrine organs. Future research in this area is very much needed.
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PMID:Clinical, endocrinological and biochemical effects of zinc deficiency. 390 80

The requirement of zinc for humans was recognized in the early 1960s. The causes of zinc deficiency include malnutrition, alcoholism, malabsorption, extensive burns, chronic debilitating disorders, and chronic renal diseases; use of certain drugs such as penicillamine and, in some cases, diuretics; and genetic disorders such as acrodermatitis enteropathica and sickle cell disease. The requirement of zinc is increased in pregnancy and during growth. The clinical manifestations of severe zinc deficiency include bullous-pustular dermatitis, alopecia, diarrhea, emotional disorder, weight loss, intercurrent infections, and hypogonadism in males; zinc deficiency can be fatal if unrecognized and untreated. A moderate deficiency of zinc is characterized by growth retardation and delayed puberty in adolescents, hypogonadism in males, rough skin, poor appetite, mental lethargy, delayed wound healing, taste abnormalities, and abnormal dark adaptation. In mild cases of zinc deficiency in human subjects, we have observed oligospermia, slight weight loss, and hyperammonemia. Zinc is a growth factor. As a result of its deficiency, growth is affected adversely in many animal species and humans, probably because zinc is needed for protein and DNA synthesis and cell division. The effects of zinc and growth hormone on growth appear to be independent of each other in experimental animals. Whether zinc is required for the metabolism of somatomedin needs further investigation. Thyroid and adrenal functions do not appear to change as a result of zinc deficiency. Glucocorticoids may have an effect on zinc metabolism, although the clinical relevance of this effect is not known at present. In contrast, testicular function is affected adversely as a result of zinc deficiency in both humans and experimental animals. The effect appears to be a direct one since the hypothalamic-pituitary axis is intact, and may relate to the reduction in testicular size as a result of the need for zinc in cell division. In addition, zinc is required for the function of several testicular enzymes, although a specific role in steroidogenesis has not been identified. Zinc appears to have a role in the modulation of prolactin secretion, in the secretion and action of insulin, and in the production and biologic effects of thymic hormones. It is clear that the endocrine consequences of zinc deficiency are multiple, and that continued investigation should provide additional pathophysiologic and therapeutic insights.
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PMID:Clinical, endocrinologic, and biochemical effects of zinc deficiency. 391 98

Reported herein is the possible interaction between two drugs used to treat a man with a large prolactin-secreting pituitary adenoma. The patient had a long history of schizophrenia that was treated with many different medications, including phenothiazines. Evaluation of progressive lethargy led to the discovery of a large parasellar tumor and a prolactin level of 7,981 ng/ml. His serum prolactin level fell to the 400 ng/ml range during bromocriptine therapy but rose whenever the antipsychotic thioridazine was added to his regimen. A marked deterioration of his visual fields was noted after 3 months' therapy with both drugs, and this abnormality resolved five days after the thioridazine was stopped. The use of dopamine antagonists such as thioridazine in patients with prolactinoma may interfere with bromocriptine's action, resulting in potentially serious complications.
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PMID:Interactions between thioridazine and bromocriptine in a patient with a prolactin-secreting pituitary adenoma. 672 Jul 32

Ten women ages 22 to 39 years were treated with a single injection of Delestrogen on day 19 of the menstrual cycle and increasing doses of Parlodel on days 19 to 23. This treatment resulted in a shortening of the luteal phase and a decrease in the production of progesterone and had no effect on serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), or prolactin levels. Side effects reported with this therapy included lethargy, dizziness, nausea, vomiting, hot flashes, depression, and nasal congestion. These preliminary clinical data suggest a combination of estrogen and bromocriptine regimen is luteolytic and may be useful as an interceptive abortifacient preparation in the human being.
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PMID:Evaluation of Delestrogen and Parlodel as a luteolytic agent in humans. 706 Jul 69

A case of hypothalamic dysfunction in a girl with a twelve-year follow-up is reported. Onset occurred at the age of three with severe obesity, hypothermia, hypersomnia, and lethargy. Somatotropic, gonadotropic, and thyrotropic hormones were low, whereas prolactin was increased. Imaging techniques failed to disclose any lesion of the hypothalamus or pituitary. Clomipramine improved the vegetative disorders. The literature on clinical and hormonal disorders of hypothalamic dysfunction is reviewed.
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PMID:[Hypothalamic syndromes. Review of clinical and endocrinal semiology]. 823

A 34-year-old woman was hospitalised with hypotension, lethargy and ventricular tachycardia, five months after an uneventful pregnancy and delivery. Laboratory values were compatible with anterior (abnormal concentrations of adrenocorticotropin hormone, thyroid stimulating hormone, prolactin) and posterior (diabetes insipidus) pituitary gland insufficiency. An MRI scan revealed that there was no pituitary enlargement and that the pituitary stalk was normal. The prompt recognition of hypophysitis as a potentially fatal condition is important, as a life-saving treatment is available.
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PMID:[Clinical thinking and decision making in practice. A patient with postpartum malaise, anorexia, and ventricular tachycardia]. 1177 Feb 65

Symptomatic metastases to the pituitary (MP) from renal cell carcinoma (RCC) are rare. In this largest case series reported, we describe the clinical features, treatment and outcome of 5 patients. Over a 6-year period (2000-2006), we treated 5 patients (3 males; mean age 61 years) with large sellar masses and RCC. Four patients had a history of RCC, while in one, RCC was diagnosed after surgery. RCC was diagnosed a median of 11 years prior to diagnosis of MP (range 0-27 years). Four patients had previously developed distant metastases. Clinical presentation included bitemporal hemianopia (3 patients), lethargy (3), headaches (2) and diabetes insipidus (DI) (2). Panhypopituitarism was present in 3 patients and the other two had deficiency of at least ACTH and gonadotropin axes. Elevated prolactin was seen in 3 patients. MRI showed an enhancing sellar mass with suprasellar extension and chiasmal compression in all; prominent vascular flow voids were seen in 2. Three patients underwent transsphenoidal surgery and radiation, while 2 underwent radiotherapy alone. Four patients are alive (follow up 6-46 months); 1 patient died due to systemic metastases at 12 months. Metastases to the pituitary from RCC cause more severe hypopituitarism and visual dysfunction compared to those from other primaries, whereas DI is less common. MRI shows contrast enhancement, stalk involvement, sclerosis and/or erosion of sella and presence of vascular flow voids. Combined treatment using decompressive surgery and stereotactic radiotherapy may result in better outcomes.
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PMID:Symptomatic pituitary metastases from renal cell carcinoma. 1754 48

A case of ductal carcinoma in-situ (DCIS) associated with prolactinoma in a male patient is described. A 56-year-old gentleman presented with lethargy and loss of libido. His prolactin at presentation was 3680 mU/l and an MRI scan of the head revealed a pituitary tumour suggestive of prolactinoma. Following 18 months of treatment with cabergoline, the prolactin level reduced to 914 mU/l. However, 3 years later he presented with blood stained nipple discharge, the cytology of which was negative for cancer. Ultrasound scan of his right breast revealed a single dilated mammary duct. Microdochectomy was performed. The histology revealed incompletely excised DCIS. There is increasing evidence of prolactinoma associated with breast cancer with or without DCIS in females. A review of the literature reveals only one previous case report of this association in males. This is the first case of pure DCIS preceded by prolactinoma in a male patient.
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PMID:A rare case of male breast ductal carcinoma in-situ associated with prolactinoma. 2267 41

Aripiprazole is an atypical antipsychotic medication that is a partial dopamine D(2) and serotonin 5-hydroxytryptamine (1A) receptor agonist and 5-hydroxytryptamine (2A) receptor antagonist. It has a safer profile compared to other antipsychotic medications with regard to its effect on weight, glucose tolerance, prolactin level, and cardiac conduction. The common neurological adverse effects include headache, agitation, insomnia, sleepiness, and extrapyramidal symptoms. Seizures have not been reported in the pediatric population and only twice in adult patients. Here, we report a case of a healthy 3-year-old child who experienced prolonged lethargy, dystonia, and 2 witnessed seizures after incidental ingestion of 30 mg of aripiprazole. To our knowledge, this is the first reported case of aripiprazole-induced seizures in a child.
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PMID:Aripiprazole-induced seizure in a 3-year-old child: a case report and literature review. 2333 73


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