A ‘smart’ type of Cushing's syndrome

Abstract

Cushing's syndrome results from lengthy and inappropriate exposure to excessive concentrations of either endogenous or exogenous glucocorticoids. This case report describes a patient with a novel type of Cushing's syndrome due to the use of party drugs. A 35-year-old woman had gained 8 kg body weight in 5 months and complained of anxiety. She showed a Cushing-like appearance and mild hypertension (blood pressure, BP 150/95 mmHg). She reported daily use of increasing doses of g-hydroxybutyric acid (GHB), a popular party drug. ACTH plasma levels were in the upper normal range (41 ng/l), with normal plasma cortisol (0.36 mmol/l). She showed an abnormal overnight 1 mg dexamethasone suppression test (cortisol 0.38 mmol/l). The urinary excretion of free cortisol in 24 h was also increased (0.47 mmol/24 h). CT scanning of the abdomen showed normal adrenals. After stopping GHB intake she lost 7 kg body weight and her BP normalized (BP 135/80 mmHg). GHB is a popular party drug in the Netherlands, but it is also used as a narcotic and for the treatment of narcolepsy. We hypothesize that GHB may bind to the pituitary gland g-aminobutyric acid-B receptors leading to ACTH overproduction. European Journal of Endocrinology 157 779-781

Breaking the Taboo: Illicit Drug Use among Adolescents with Type 1 Diabetes Mellitus

“…Androgenic-anabolic steroids (AS), taken orally or by injection at doses much higher than would be prescribed, increase the risk of early heart attacks, strokes, liver tumors, kidney failure, serious psychiatric problems, and long-term effects [ 25 ]. Regular use of GHB may lead to Cushing's syndrome [ 26 , 27 ]. The health-related harms of cannabinoids use differ from those of other drugs in that they contribute little to mortality.…”

Reconsidering GHB: orphan drug or new model antidepressant?

“…Under resting conditions GHB induces a stimulation of cortisol secretion in animals and humans (Oyama et al, 1969; Van Cauter et al, 1997; Meerlo et al, 2004). One case of hypercortisolism was reported following chronic illicit use of GHB (Razenberg et al, 2007). In contrast, GHB showed a lasting suppression of withdrawal associated hypercortisolism in alcoholic patients (Nava et al, 2007).…”

Drugs and HPA axis

“…Fenofibrate, a lipid-lowering agent, also interferes with cortisol measurement at HPLC and a double HPLC-MS/MS is required for precise measurement [138]. As regards direct drug effects on UFC excretion, an increase in UFC has been observed in subjects on fenfluramine (180 mg/daily) [139] or chronic use of the narcotic chydroxybutyric acid [140] while a reduction is apparent in patients taking benzodiazepines [141,142] or mirtazapine [106,143]. Unlike serum cortisol, UFC measurements seem unaffected by estrogen replacement [144] or oral contraceptive administration [145].…”

“…Of note, false positive results occur mostly with the low dose dexamethasone suppression tests (1 mg or 2 mg overnight) whereas the suppressibility by high dose dexamethasone appears to be maintained in patients with Cushing's disease [155]. Other drugs which may lead to falsely high post-dexamethasone cortisol values are cholinergic agents such as physostigmine and the muscarinic agonist arecoline [156,157], serotonergic agonists, e.g., buspirone [158], citalopram [159], the GABAergic c-hydroxybutyric acid [140] and the lithiumtricyclic antidepressant association [160]. Of note, this effect by lithium could mask recovery of cortisol suppressibility by low doses of dexamethsasone, an index of favorable outcome in depressed patients treated with antidepressants [161].…”