scholarly journals Hepatic safety of ketoconazole in Cushing’s syndrome: results of a Compassionate Use Programme in France

2018 ◽  
Vol 178 (5) ◽  
pp. 447-458 ◽  
Author(s):  
Jacques Young ◽  
Jérôme Bertherat ◽  
Marie Christine Vantyghem ◽  
Olivier Chabre ◽  
Salima Senoussi ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Function ◽  
Cushing’S Syndrome ◽  
Total Bilirubin ◽  
Liver Enzymes ◽  
Cushing's Syndrome ◽  
Close Monitoring ◽  
Compassionate Use ◽  
Severe Hepatotoxicity ◽  
French Cohort

ObjectiveKetoconazole (KTZ) is one of few available treatments for Cushing’s syndrome (CS). Although KTZ has been associated with severe hepatotoxicity, little information is available about hepatic safety in CS. The aim of this study was to document changes in liver function in patients with CS treated with KTZ.DesignAn observational prospective French cohort study (Compassionate Use Programme (CUP)).MethodsEnrolled patients were stratified into a KTZ-naive cohort and a cohort already treated by another formulation of ketoconazole (KTZ-switch cohort). Liver function markers (alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, γ-glutamyltransferase and bilirubin) were monitored at regular intervals. Patients with ALT > 3 × ULN (upper limit of normal), total bilirubin > 2 × ULN or both ALP > 2 × ULN and ALT > ULN were considered to have liver injury.ResultsOverall, 108 patients were analysed (47 KTZ-naïve; 61 KTZ-switch). The median KTZ dose was 600 mg/day. Most abnormalities observed were asymptomatic mild increases of liver enzymes. Four patients in the KTZ-naïve cohort (8.5%) and two in the KTZ-switch cohort (3.3%) developed liver injury, considered related to KTZ in three cases (all KTZ-naïve in the first month of treatment). Five patients had mild liver function abnormalities at baseline and two had proven liver metastases. Two patients recovered on discontinuation of KTZ and the remaining patient died of unrelated causes.ConclusionsThese findings highlight the need for close monitoring of liver enzymes especially during the first six months of treatment. Liver enzyme abnormalities usually occurred within four weeks were asymptomatic and could be reversed on timely discontinuation of KTZ.

Hydralazine-induced liver injury: a review and discussion

2021 ◽  
Vol 14 (8) ◽  
pp. e243278 ◽  
Author(s):  
Meeta Bhardwaj ◽  
Nakul Jay Bhardwaj ◽  
Kendra Cueto ◽  
T Colin Killeen
Keyword(s):  
Side Effects ◽  
Liver Injury ◽  
Antihypertensive Agent ◽  
Adverse Reactions ◽  
Liver Enzymes ◽  
Injury Pattern ◽  
Hypertension Management ◽  
Close Monitoring ◽  
Hepatocellular Injury ◽  
Specific Symptoms

Hydralazine is a commonly prescribed antihypertensive agent. Some of its labelled adverse reactions include lupus-like syndrome, tachycardia, headache and fever. Despite its well-known side effects, little is known about hydralazine’s hepatotoxic effects. We report the case of a 54-year-old female patient who was started on hydralazine for hypertension management but later presented with hydralazine-induced liver injury. Her initial presentation consisted of non-specific symptoms and a hepatocellular injury pattern. Liver biopsy revealed hepatic steatosis. Three weeks after discontinuation of hydralazine, the patient’s liver enzymes normalised, and her symptoms resolved. Few studies have examined the incidence and mechanism by which hydralazine induces a liver injury pattern. With this case, we review the literature, the pathogenesis involved and the eventual management of hydralazine-induced liver injury. We propose close monitoring of liver enzymes for patients on hydralazine throughout their treatment course.

scholarly journals Methimazole induced hepatotoxicity: A rare adverse reaction

2019 ◽  
Vol 6 (3) ◽  
pp. 1
Author(s):  
Kevin C. Kohm ◽  
Lauren Pioppo ◽  
Jack Xu ◽  
Preston Keiffer ◽  
Eric Pagan ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Function ◽  
Side Effect ◽  
Hepatic Injury ◽  
Total Bilirubin ◽  
Liver Function Tests ◽  
Side Effect Profile ◽  
Function Tests ◽  
Painless Jaundice ◽  
Graves Orbitopathy

Methimazole (MMI) is a commonly used medication in the treatment of hyperthyroidism. The side effect profile is extensive and includes the rare but serious side effect of drug associated liver injury. We report the case of a 51-year-old female who presented with painless jaundice several weeks after initiating MMI therapy for treatment of hyperthyroidism complicated by Graves’ orbitopathy. Liver function tests on presentation showed alanine aminotransferase (ALT) 1366 IU/L, aspartate aminotransferase (AST) 853 IU/L, total bilirubin 26.2 mg/dl, alkaline phosphatase 954 IU/L. Workup of structural, infectious, and autoimmune causes of hepatic injury was negative. The patient was therefore found to have MMI associated liver injury. MMI was discontinued and the patient was started on ursodiol, resulting in resolution of her jaundice and improvement of her liver function tests.

scholarly journals COVID-19 associated variations in liver function parameters: a retrospective study

2020 ◽  
pp. postgradmedj-2020-138930
Author(s):  
Ram Krishan Saini ◽  
Neha Saini ◽  
Sant Ram ◽  
Shiv Lal Soni ◽  
Vikas Suri ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Function ◽  
Liver Enzyme ◽  
Inflammatory Markers ◽  
Liver Enzymes ◽  
Tertiary Care ◽  
Abnormal Liver Function ◽  
Gamma Glutamyl Transferase ◽  
Number Of Patients ◽  
Glutamyl Transferase

BackgroundCharacteristics of laboratory findings of COVID-19 patients are of great significance for diagnosis and treatment. Studies that have analysed the variations in hepatic profile in correlation with the inflammatory markers in SARS-CoV-2 are limited.MethodsWe retrospectively analysed liver function tests and inflammatory markers of 170 admitted patients with confirmed COVID-19 in the tertiary care centre, Post Graduate Institute of Medical Education and Research (PGIMER), India, using Roche Cobas Autoanalyzer.ResultsNumber of patients with normal liver enzyme levels were 63 (41.5%), while with raised levels of any of the liver enzymes were 89 (58.5%), out of which 43 (48.31%) had liver injury which manifested as increased severity in terms of intensive care unit (ICU) requirement (p=0.0005). Significantly raised levels of liver enzymes and liver injury were observed with age (p<0.0001) and in males (p=0.004). Significantly decreased levels of albumin and total proteins and increased levels of total bilirubin (p<0.0001) were seen in patients with abnormal liver enzyme levels and liver injury as compared to patients with normal levels. Significant increase in the levels of alanine transaminase and gamma-glutamyl transferase was seen on the 7th day, CRP and ferritin (p<0.0001) peaks were observed on 2nd and 3rd day respectively. A significant positive correlation was found between the levels of these inflammatory markers and liver function parameters.ConclusionsMore than half of patients admitted to the hospital with SARS-CoV-2 infection had an abnormal liver function which was found to be associated with raised levels of inflammatory markers. Significantly higher proportions of patients with abnormal liver function were elderly and males and were at higher risk of progressing to severe disease.

scholarly journals Merits and pitfalls of mifepristone in Cushing's syndrome

2009 ◽  
Vol 160 (6) ◽  
pp. 1003-1010 ◽  
Author(s):  
F Castinetti ◽  
M Fassnacht ◽  
S Johanssen ◽  
M Terzolo ◽  
P Bouchard ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Adrenal Insufficiency ◽  
Cushing’S Syndrome ◽  
Psychiatric Symptoms ◽  
Clinical Signs ◽  
Cushing's Syndrome ◽  
Close Monitoring ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion ◽  
Glucose Levels

ObjectiveMifepristone is the only available glucocorticoid receptor antagonist. Only few adult patients with hypercortisolism were treated to date by this drug. Our objective was to determine effectiveness and tolerability of mifepristone in Cushing's syndrome (CS).DesignRetrospective study of patients treated in seven European centers.MethodsTwenty patients with malignant (n=15, 12 with adrenocortical carcinoma, three with ectopic ACTH secretion) or benign (n=5, four with Cushing's disease, one with bilateral adrenal hyperplasia) CS were treated with mifepristone. Mifepristone was initiated with a median starting dose of 400 mg/day (200–1000). Median treatment duration was 2 months (0.25–21) for malignant CS, and 6 months (0.5–24) for benign CS. Clinical (signs of hypercortisolism, blood pressure, signs of adrenal insufficiency), and biochemical parameters (serum potassium and glucose) were evaluated.ResultsTreatment was stopped in one patient after 1 week due to severe uncontrolled hypokalemia. Improvement of clinical signs was observed in 11/15 patients with malignant CS (73%), and 4/5 patients with benign CS (80%). Psychiatric symptoms improved in 4/5 patients within the first week. Blood glucose levels improved in 4/7 patients. Signs of adrenal insufficiency were observed in 3/20 patients. Moderate to severe hypokalemia was observed in 11/20 patients and increased blood pressure levels in 3/20 patients.ConclusionMifepristone is a rapidly effective treatment of hypercortisolism, but requires close monitoring of potentially severe hypokalemia, hypertension, and clinical signs of adrenal insufficiency. Mifepristone provides a valuable treatment option in patients with severe CS when surgery is unsuccessful or impossible.

Iatrogenic Cushing's syndrome and steroid hepatopathy in a cat

1999 ◽  
Vol 35 (1) ◽  
pp. 48-51 ◽  
Author(s):  
M Schaer ◽  
PE Ginn
Keyword(s):  
Diabetes Mellitus ◽  
Cushing’S Syndrome ◽  
Liver Enzymes ◽  
Periodic Acid ◽  
Cushing's Syndrome ◽  
Periodic Acid Schiff ◽  
Glycogen Accumulation ◽  
Elevated Liver Enzymes ◽  
High Incidence ◽  
Iatrogenic Cushing’S Syndrome

The distinguishing clinical features of Cushing's syndrome in the cat include very friable skin, a high incidence of diabetes mellitus, and the general absence of steroid hepatopathy. This case report describes a nine-year-old, spayed female domestic shorthair with triamcinolone-induced Cushing's syndrome. Unique to this cat were markedly elevated liver enzymes which prompted an expanded clinical evaluation. An ultrasonographic-guided liver biopsy demonstrated diffuse hepatocellular vacuolation that stained periodic acid-Schiff (PAS) positive and was removed subsequently with diastase application, indicating glycogen accumulation. These findings are compatible with the rarely seen syndrome of steroid hepatopathy in the cat.

Acute Cholestatic Hepatitis Probably Associated with Risperidone

2005 ◽  
Vol 35 (2) ◽  
pp. 199-205 ◽  
Author(s):  
Francisca Llinares Tello ◽  
Carmen Hernández Prats ◽  
Nuria Bosacoma Ros ◽  
Enrique Pérez Martínez ◽  
Eduardo Climent Grana ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Function ◽  
Adverse Effects ◽  
Liver Enzymes ◽  
Liver Function Tests ◽  
Cholestatic Hepatitis ◽  
Neuroleptic Drug ◽  
Days Of Therapy ◽  
Vulnerable Patient ◽  
Toxic Liver Injury

Objective: Risperidone is an atypical neuroleptic drug widely used due to the lower incidence and severity of hepatic adverse effects in comparison to phenothiazines. Although idiosyncratic reversible hepatotoxicity may occur in association with risperidone, the interaction with fluoxetine might increase the risk of toxic liver injury in a vulnerable patient. Methods and Results: We present a case of acute cholestatic hepatitis probably associated with the use of risperidone after only a few days of therapy in a patient also treated with fluoxetine. The patient, a 64-year-old male, developed a rapid increase in liver enzymes after starting treatment with only four doses of risperidone 2 mg/day. Conclusions: We recommend obtaining baseline liver function tests before starting risperidone and regular monitoring to screen patients for liver damage during therapy whenever a patient is also receiving fluoxetine.

scholarly journals Recurrence and Severe Worsening of Hepatotoxicity After Reintroduction of Atorvastatin in Combination With Ezetimibe

2017 ◽  
Vol 10 ◽  
pp. 117954761773137 ◽  
Author(s):  
Silje Bergland Ellingsen ◽  
Elisabet Nordmo ◽  
Knut Tore Lappegård
Keyword(s):  
Liver Injury ◽  
Liver Enzymes ◽  
Current Data ◽  
Class Effect ◽  
Drug Induced ◽  
Good Tolerance ◽  
Drug Induced Liver Injury ◽  
Severe Hepatotoxicity ◽  
Elevated Liver Enzymes ◽  
History Of

Severe hepatotoxicity is a rare but well-known adverse reaction to statins. However, despite the widespread use of statins, only a few cases describing statin reexposure or switch to another statin after liver injury have been published. The literature on hepatotoxicity with ezetimibe alone or in combination with statins is also scarce. We report a case where a patient with a history of elevated liver enzymes while using atorvastatin, but prior and subsequent good tolerance to simvastatin and pravastatin, developed drug-induced liver injury on reexposure to a combination of atorvastatin and ezetimibe. The hepatotoxicity in our patient was most likely caused by reexposure to atorvastatin, although we cannot exclude ezetimibe as a contributing factor. This case highlights the risk of hepatotoxicity recurrence on rechallenge with the same statin. The tolerance to other statins in this case also strengthens the suspicion that statin-induced liver injury may not be a class effect, although the current data are too scarce to draw any definite conclusions.

scholarly journals Should we avoid using ketoconazole in patients with severe Cushing’s syndrome and increased levels of liver enzymes?

2018 ◽  
Vol 179 (5) ◽  
pp. L1-L2 ◽  
Author(s):  
Marine Ollivier ◽  
Magalie Haissaguerre ◽  
Amandine Ferriere ◽  
Antoine Tabarin
Keyword(s):  
Cushing’S Syndrome ◽  
Liver Enzymes ◽  
Cushing's Syndrome

scholarly journals Favorable outcome of pheochromocytoma in a dog with atypical Cushing’s syndrome and diabetes mellitus following medical treatment: a case report

2020 ◽  
Vol 16 (1) ◽  
Author(s):  
Ga-Won Lee ◽  
Cho-Rong Yoo ◽  
Dan Lee ◽  
Hee-Myung Park
Keyword(s):  
Case Report ◽  
Cushing’S Syndrome ◽  
Adrenal Mass ◽  
Liver Enzymes ◽  
Glycosylated Hemoglobin ◽  
Vena Cava ◽  
Clinical Signs ◽  
Cushing's Syndrome ◽  
Elevated Liver Enzymes

Abstract Background Pheochromocytoma (PCC) has poor prognosis and adrenalectomy is hard to be performed, in case of caudal vena cava invasion. The long-term administration of phenoxybenzamine in PCC has not been reported in dogs. Case presentation A 14-year-old castrated male Poodle dog presented with an abdominal mass. On physical examination, hypertension, increased lens opacity, calcinosis cutis, generalized alopecia, and systolic murmur were observed. Serum chemistry and urinalysis profiles revealed hyperglycemia, hypercholesterolemia, elevated liver enzymes, and glucosuria. Abdominal ultrasonography showed a right adrenal mass with invasion of the caudal vena cava, which was cytologically diagnosed as suspected PCC. An adrenal mass (width × height × length, 28 × 26 × 48 mm3) was found on computed tomography and diagnosed as PCC with increased plasma metanephrines and normetanephrines. An adrenocorticotropin hormone stimulation test showed elevated adrenal hormones (androstenedione, estradiol, progesterone, and 17-OH progesterone) with normal cortisol, compatible with atypical Cushing’s syndrome. The dog was managed with trilostane, phenoxybenzamine, and insulin therapy. Glycosylated hemoglobin and fructosamine levels gradually decreased, and hypertension resolved. In the 10-month follow-up period, the liver enzymes levels gradually decreased, and the clinical signs of the dog were well-controlled without deterioration. Conclusions This case report describes long-term medical management without adrenalectomy of PCC complicated with atypical Cushing’s syndrome and DM.

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