Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 36-year-old man with depression, Cushingoid features and hypogonadism was found to have simultaneous pituitary-dependent Cushing's disease and marked elevation of serum prolactin (PRL). CT-scan revealed a macroadenoma with suprasellar extension. Transphenoidal surgery cured the patient's Cushing's disease, but failed to correct his hyperprolactinemia, which was controlled by subsequent bromocriptine therapy. Immunostaining of the pituitary tumor was positive for PRL as well as for ACTH, and ACTH-related peptides beta-lipotropin and beta-endorphin in two distinct tumor cell lines. This pituitary tumor is one of the few mixed PRL- and ACTH-secreting tumors documented by immunostaining. It is the second reported in a macroadenoma, in which PRL-secreting tumoral cells are much more abundant than ACTH-secreting cells.
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PMID:Cushing's disease and hyperprolactinemia due to a mixed ACTH- and prolactin-secreting pituitary macroadenoma. 165 8

Some patients with major depressive disorder (MDD) have elevated plasma cortisol concentrations and show failure to suppress cortisol secretion upon administration of dexamethasone (DEX), yet they do not have Cushingoid features. To study whether this represents glucocorticoid (GC) resistance, [3H]-DEX-binding assays were used to measure, in vitro, the GC receptor affinity (1/Kd) and number (Bmax) in mononuclear leukocytes of 11 MDD patients and 15 control subjects. No receptor abnormalities were detected in the MDD group; thus any cellular defect leading to a lack of responsiveness to GC in the MDD patients, if present, probably lies beyond the initial receptor binding. DEX (1.0 mg orally) was administered to study in vivo GC receptor down-regulation. Compared to the control group, fewer depressed subjects down-regulated Bmax after DEX. By paired t-test, Bmax decreased significantly in the control group but not in the depressed group. Receptor number on the control day did not correlate significantly with the degree of receptor down-regulation, severity of depression or cortisol concentrations across all the subjects. These results do not lend support to previous reports suggesting that GC resistance in MDD results from a GC receptor-binding abnormality, and they emphasize the importance of considering receptor studies in the context of GC-mediated cell processes in order to identify the exact cellular defect(s) leading to GC resistance.
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PMID:Mononuclear leukocyte glucocorticoid receptor binding characteristics and down-regulation in major depression. 236 16

A 57-year-old woman who presented with depression and hypertension for which she had received anti hypertensive therapy including diuretics was found to have Cushingoid features. All medication was stopped and subsequent investigation demonstrated markedly elevated urinary free cortisol (UFC) levels. An increase in UFC occurred in response to the low dose dexamethasone suppression test and a further increase was noted during the high dose test. Plasma cortisol levels did not change significantly. Detailed examination of the data revealed that over the 6-day testing period the plasma creatinine had fallen from 1.4 mg/dl to 0.7 mg/dl while the creatinine clearance had doubled--presumably due to withdrawal of the diuretic. When the UFC was expressed per 100 ml of plasma filtered, there was no difference between any of the daily excretions. We conclude that a concurrent increase in glomerular filtration rate is one mechanism by which a 'paradoxical' increase in UFC in response to dexamethasone suppression may occur.
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PMID:A rise in the glomerular filtration rate as the cause of a 'paradoxical' increase in urinary free cortisol during dexamethasone suppression in a patient with an adrenal adenoma: a case report. 730 83

A 32-year-old woman was bedridden for a year because of chronic pain and headaches. She had insomnia, depression, suicidal thoughts and a severe chemical allergy. She had been on steroid therapy for two years and became Cushingoid with striae in the arm pits, groins and abdomen. However, she had no hypertension, nor the buffalo fat and hirsutism. She was very edematous, with a weight gain from 112 to 180 lbs. The fluid retention did not conform to the syndrome of inappropriate antidiuretic hormone. Studies revealed abnormal scalp EEG discharges and high-voltage seizure discharges in the posterior thalamus. Electrothalamic stimulation suppressed the thalamic discharges and relieved the patient's pelvic pain and headaches. After one month of several thalamic stimulations per day, she was able to get out of bed and ambulate. In addition, the patient no longer was edematous and was tolerating perfumes and floor detergents. Steroids were progressively reduced without complications of withdrawal. She went from a completely steroid dependent state to independent during the first 1-1/2 yrs of thalamic stimulation. With continued thalamic stimulation she has done well for 8-1/2 yrs, weighs 112 lbs, keeps house and drives a car. It's speculated the illness is a chronic pain multiple syndrome predominantly due to mesothalamic discharges and body infirmities. The mesothalamic discharge implicated neural networks, which represent biologic systems, i.e. pain, sleep, fluid retention, etc. Therapeutic stimulation attenuates the discharges and the neural networks return to their normal set points of homeostasis.
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PMID:Mesothalamic discharge in a chronic pain, allergy and fluid retention syndrome (case report). 766 2

Abnormalities of hypothalamus-pituitary-adrenal axis regulation are common in the elderly and excess glucocorticoids have been implicated in the loss of neural function in aging. In the current study, we examined cell signaling mediated through adenylyl cyclase in brain regions, heart and liver of young and aged rats given continuous infusions of dexamethasone (10 or 50 micrograms/kg/day) for 26 days. Aged control animals showed significant deficits in total adenylyl cyclase activity (assessed with forskolin-Mn++) in the brain regions and the heart; superimposed on this change, the striatum and the heart displayed interference with the response mediated either at the level of G-protein coupling to cyclase (striatum) or neurotransmitter receptor coupling to G-proteins (heart). Administration of dexamethasone to young rats did not reproduce the effects of aging on any of the measures of adenylyl cyclase, despite the fact that the higher dose produced Cushingoid effects. The same dexamethasone regimens given to aged rats produced alterations in G-protein coupling mechanisms in the cortex and in serotonergic-mediated cyclase responses in the striatum, and also decreased basal enzyme activity in the heart. In contrast to the brain regions and the heart, the liver showed unique effects of aging and dexamethasone. Total adenylyl cyclase activity, the enzymatic response to beta adrenergic stimulation and the number of beta adrenergic receptors were all elevated in aged animals as compared to the younger cohort. Dexamethasone decreased both hepatic beta receptor numbers and isoproterenol responsiveness in young animals, but increased receptor binding in aged animals. These data indicate that the defects associated with aging in the central nervous system and the cardiac cell signaling mediated through adenylyl cyclase are not a result of glucocorticoid excess; however, central and peripheral tissues respond differently to glucocorticoids in aged vs. young animals. Given the high incidence of hypothalamus-pituitary-adrenal axis dysregulation in the elderly, and particularly in elderly depression, effects of glucocorticoids on cell signaling may contribute to disruption of cell function and to hypo- or hyper-reactivity to drugs, such as antidepressants, that act by altering synaptic transmission.
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PMID:Aging and glucocorticoids: effects on cell signaling mediated through adenylyl cyclase. 893 Jan 49

Glucocorticoids are usually given for management of Graves' ophthalmopathy (GO) for their anti-inflammatory and immunosuppressive effects. The overall rate of favorable response for moderately severe and active GO is 77% in patients treated with methylprednisolone iv pulse therapy. When radioiodine therapy is indicated for hyperthyroidism in Graves' patients with high risk factors, the use of glucocorticoid with small doses and short periods is recommended to prevent the development or progression of GO. Cushingoid features, glucose intolerance, gastritis, hypertension, hepatitis, and depression are major adverse effects of glucocorticoids. Fatal liver failure after high dose of pulse therapy (9-12g) was observed in 0.8%. Limiting the cumulative dose to 4.5-6g, assessment of liver virus markers and monitoring liver function before, during and after i.v. treatment are warranted.
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PMID:[Steroid therapy for Graves' ophthalmopathy]. 1715 92