isotretinoin and Hypertriglyceridemia

Monitoring of triglycerides for patients on isotretinoin is practised primarily to avoid hypertriglyceridaemia-associated pancreatitis. The aim of this study was to describe clinically the published cases of hypertriglyceride-associated pancreatitis. A comprehensive search strategy using MEDLINE, Embase and grey literature was conducted (1960 to January 2016) to identify all case reports of isotretinoin-associated pancreatitis and all relevant studies of isotretinoin and triglycerides for any indication (≥ 20 patients). Terms related to isotretinoin, triglycerides and pancreatitis were searched with all available synonyms. Any studies that used isotretinoin and mentioned triglycerides or pancreatitis were searched in full text, where available, for cases of pancreatitis. Studies from all countries and published in any language were included, but Korean and Turkish studies could not be analysed. Two authors independently reviewed the publications to determine eligibility, and for data extraction. In total, 125 papers fulfilled the inclusion criteria and were searched for cases of pancreatitis. Eleven papers with 25 cases of pancreatitis associated with isotretinoin were identified; four of these cases were likely due to hypertriglyceridaemia. Three patients had elevated baseline triglycerides, but no monitoring. Pancreatitis occurred 6 and 7 weeks, and 6 months after initiation of therapy. For the fourth patient who was treated for glioblastoma and died, no detailed clinical information was available. Idiosyncratic pancreatitis associated with isotretinoin is the most frequent pancreatitis on isotretinoin, and patients should be warned about it. Hypertriglyceride-associated pancreatitis is an exceedingly rare adverse event of isotretinoin therapy. Our data cannot give a frequency or risk for either adverse event. Based on the clinical information of the patients available, we conclude that for patients without elevated baseline triglycerides, or risk thereof, monitoring of triglycerides during therapy is of little value.

Topics: Adolescent; Adult; Aged; Biomarkers; Female; Humans; Hypertriglyceridemia; Isotretinoin; Male; Pancreatitis; Triglycerides

Patients with severe recalcitrant nodular acne that is unresponsive to conventional therapy (including topical and systemic antibiotics) have few alternative effective treatment modalities other than the use of oral isotretinoin (Accutane). The cause of acne vulgaris is multifactorial, but the pathogenesis of this disorder of the pilosebaceous follicles arises mainly from endogenous factors. It is usually, but not always, associated with the onset of puberty. Severe acne, defined by the prevalence of facial and truncal inflammatory lesions, is a disfiguring disease that can often result in significant permanent scarring after the healing of deep inflammatory lesions and other disorders, such as systemic bacterial infections. Topical treatments are considered as the first line of therapy for less severe forms of acne, although systemic treatments such as antibiotics or antiandrogen agents are effective for either mild or moderate forms and sometimes effective for severe acne. However, in many patients with large numbers of nodules, longer treatment periods with these agents are required to reduce the count of inflammatory lesions. It has become increasingly evident that (because topical agents and antibiotic or antiandrogenic therapy have a slow onset of action) even mild or moderate acne that is treated in this way can result in scarring. In addition, the excessive use of systemic antibiotics has led to the detection of increasing numbers of antibiotic-resistant bacteria on the skin of patients with acne.(1) Therefore, because of its relatively rapid onset of action and its high efficacy with reducing more than 90% of the most severe inflammatory lesions, Accutane has a role as an effective treatment in patients with severe acne that is recalcitrant to other therapies.

Topics: Acne Vulgaris; Adolescent; Adult; Chemical and Drug Induced Liver Injury; Clinical Trials as Topic; Female; Humans; Hypertriglyceridemia; Isotretinoin; Male; Mental Disorders; Mucous Membrane; Patient Education as Topic; Product Labeling; Stomatitis; Vision Disorders

Topics: Acne Vulgaris; Administration, Oral; Adult; Blepharitis; Cheilitis; Conjunctivitis; Dermatologic Agents; Drug Eruptions; Drug Monitoring; Epistaxis; Female; Humans; Hypertriglyceridemia; Ichthyosis; Isotretinoin; Keratolytic Agents; Male; Pain; Pruritus; Severity of Illness Index; Treatment Outcome; Xerostomia

Combined biological therapy with 13-cis-retinoic acid (13-cRA) and interferon alpha-2a (IFN alpha-2a) was reported to be highly effective in squamous cell carcinoma of the cervix and skin. Squamous cell carcinoma of the penis is rare in the United States, accounting for less than 1/2% of all male malignancies. Because of the association of infection with human papillomavirus with both carcinomas of the cervix and penis and their shared squamous cell histology, we carried out a phase II study of 13-cRA and IFN alpha-2a in carcinoma of the penis.. Eighteen ambulatory patients with surgically unresectable, recurrent, and/or metastatic squamous cell carcinoma of the penis were treated with IFN alpha-2a, 3MU/day administered subcutaneously and 13-cRA, 1 mg/kg orally daily for at least eight weeks, unless intolerable toxicity occurred.. One patient was ineligible; one patient withdrew prior to treatment. Among the 16 eligible, treated patients, there was one complete response. Fourteen patients had progressive disease as their only treatment effect. Two patients were unevaluable for tumor response because they had no follow-up tumor measurements. No unexpected treatment-related toxicities were found on study. The only common form of grade 3 toxicity was hypertriglyceridemia found in eight of the 17 patients (47%). No toxicities above grade 3 were observed.. In contrast to its benefit in squamous cell carcinomas of the cervix and skin, the combination of 13-cRA and IFN alpha-2a has low efficacy in advanced carcinoma of the penis.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Disease Progression; Fatigue; Fever; Humans; Hypertriglyceridemia; Interferon alpha-2; Interferon-alpha; Isotretinoin; Life Tables; Male; Middle Aged; Penile Neoplasms; Recombinant Proteins; Survival Analysis; Treatment Failure

Interferon-alpha (IFN-alpha) has been safely given concurrently with radiation therapy (RT) in treating gliomas. As single agents, both IFN-alpha and cis-retinoic acid (CRA) have produced objective tumor regressions in patients with recurrent gliomas. In vitro, IFN-alpha2a and CRA enhance radiation therapy effects on glioblastoma cells more than either agent alone. This trial was conducted to determine the clinical effects of IFN-alpha2a and CRA when given concurrently with radiation therapy to patients with high-grade glioma. Newly diagnosed patients with high-grade glioma received IFN-alpha2a at a dosage of 3 to 6 million IU s.c. 4 times a day for 3 days per week and 1 mg/kg CRA by mouth 4 times a day for 5 days per week during the delivery of partial brain radiation therapy at 180 cGy x 33 fractions for 5 days per week for a total of 59.4 Gy during the 7-week period. Use of the antiepileptic phenytoin was prohibited after observing that the combination of IFN-alpha2a, CRA, and phenytoin was associated with a high rate of dermatologic toxicity not seen in a previous study with concurrent IFN-alpha2a and radiation therapy. Forty patients (26 men and 14 women) with a median age of 60 (range, 19 to 81 years) were enrolled between August 1996 and October 1998. Histopathologic diagnoses were glioblastoma multiforme or grade 4 anaplastic astrocytoma in 36 patients, and grade 3 anaplastic astrocytoma in 4 patients. Only 4 patients (10%) underwent a gross total resection of tumor prior to this therapy; 50% were asymptomatic when treatment was initiated. The planned 7-week course of concurrent therapy was completed by 75% of patients; 30% completed the 16-week course of IFN-alpha and CRA alone. At a median follow-up of 36 months, there were 37 deaths, with a median overall survival of 9.3 months and a 1-year survival rate of 42%. There was no improvement in survival compared with a similar group of 19 patients treated with concurrent IFN-alpha2a and radiation therapy in a previous trial. In the high-risk group of patients in the present study, concurrent treatment with IFN-alpha2a, CRA, and RT was feasible, but was not associated with a better outcome compared with a similar patient population treated with radiation therapy and IFN-alpha2a, or compared with radiation therapy alone in other trials.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Brain Neoplasms; Chemotherapy, Adjuvant; Combined Modality Therapy; Contraindications; Craniotomy; Drug Eruptions; Female; Glioblastoma; Humans; Hypertriglyceridemia; Immunologic Factors; Interferon alpha-2; Interferon-alpha; Isotretinoin; Life Tables; Male; Middle Aged; Phenytoin; Radiation Injuries; Radioisotope Teletherapy; Recombinant Proteins; Survival Analysis; Treatment Failure

Hypertriglyceridemia is a metabolic complication of retinoid therapy. In this study, we analyzed whether retinoids increase the expression of apo C-III, an antagonist of plasma triglyceride catabolism. In men, isotretinoin treatment (80 mg/d; 5 d) resulted in elevated plasma apo C-III, but not apo E concentrations. In human hepatoma HepG2 cells, retinoids increased apo C-III mRNA and protein production. Transient transfection experiments indicated that retinoids increase apo C-III expression at the transcriptional level. This increased apo C-III transcription is mediated by the retinoid X receptor (RXR), since LG1069 (4-[1-(5,6,7,8-tetrahydro-3,5,5,8, 8-pentamethyl-2-naphtalenyl)ethenyl]benzoic acid), a RXR-specific agonist, but not TTNPB ((E)- 4-[2-(5,6,7,8-tetrahydro-5,5,8, 8-tetramethyl-2-naphtalenyl)propenyl]benzoic acid), a retinoic acid receptor (RAR)-specific agonist, induced apo C-III mRNA in HepG2 cells and primary human hepatocytes. Mutagenesis experiments localized the retinoid responsiveness to a cis-element consisting of two imperfect AGGTCA sequences spaced by one oligonucleotide (DR-1), within the previously identified C3P footprint site. Cotransfection assays showed that RXR, but not RAR, activates apo C-III transcription through this element either as a homo- or as a heterodimer with the peroxisome proliferator-activated receptor. Thus, apo C-III is a target gene for retinoids acting via RXR. Increased apo C-III expression may contribute to the hypertriglyceridemia and atherogenic lipoprotein profile observed after retinoid therapy.

Topics: Adult; Apolipoprotein C-III; Apolipoproteins C; Benzoates; Bexarotene; Carcinoma, Hepatocellular; Cells, Cultured; Dimerization; Double-Blind Method; Gene Expression Regulation; HeLa Cells; Humans; Hypertriglyceridemia; Isotretinoin; Liver; Liver Neoplasms; Male; Mutagenesis, Site-Directed; Promoter Regions, Genetic; Receptors, Cytoplasmic and Nuclear; Receptors, Retinoic Acid; Recombinant Fusion Proteins; Regulatory Sequences, Nucleic Acid; Retinoid X Receptors; Retinoids; Tetrahydronaphthalenes; Transcription Factors; Transcription, Genetic; Transfection; Tumor Cells, Cultured

Retinoids are under intensive study for the treatment and prevention of cancer. Substantial dose-related toxicities of retinoids are a major obstacle to this work. In a recent retrospective analysis of combined 13-cis-retinoic acid (13cRA) and alpha-tocopherol (AT) in myelodysplasia, 13cRA toxicity was reduced significantly and 13cRA activity was enhanced. These results suggested the need for prospective testing of this new combination. This trial tested the hypotheses that At can reduce toxicity of high-dose 13cRA and does not interfere with 13cRA absorption/activity as reflected by reduced 13cRA serum levels.. This was a phase I trial design in which patients received fixed-dose 13cRA (100 mg/m2/d) plus escalating-dose AT (beginning at 800 IU/d, increased 400 IU/d each month until 2000 IU/d). We collected toxicity data every four weeks from self-report forms, clinical examinations and laboratory studies. AT effects on 13cRA toxicity were determined by comparing maximum toxicity at lowest AT dose with that at highest AT dose. We also measured serum levels of both agents every four weeks.. Of the 45 patients registered, 36 had cancer (active or prior history), 9 had premalignant lesions. Thirty-nine patients could be evaluated for initial-course toxicity; 31 for final course toxicity. Median time on treatment (all patients) was four months (range, 1-9 months); a total of 223 month-long courses of treatment were given. Eighteen percent of patients (7/39) developed grade 3 or 4 toxicity in the initial course. The rates of increase and decrease in 13cRA toxicity associated with increasing AT doses were similar: 36% decreased (11/31), 32% increased (10/31) (P = 0.84). At did not reduce 13cRA serum levels. After initial increases of mean AT plasma levels (17.9 micrograms/ ml at baseline to 45.4 micrograms/ml after first four-week course), subsequent AT plasma increases (< 2-fold) did not keep pace with increased AT doses (2-3-fold). No major activity occurred in the 21 patients with active refractory cancer. The complete response rate in patients with premalignant head-and-neck or lung lesions was 77.8% (7/9), which included two patients previously refractory to 13cRA alone.. Although escalating doses of AT did not reduce 13cRA toxicity, the rate of initial-course (including 800 IU/d of AT) high-grade toxicity was substantially lower than that typical of high-dose 13cRA-alone and similar to that typical of low-dose 13cRA-alone. Indeed, a trial of 13cRA-alone followed by 13cRA plus AT may have detected a significant toxicity difference. We did not design such a trial out of ethical concern for known side effects of high-dose 13cRA. The increase in AT serum levels was not proportional with increasing doses of AT, which may explain the lack of a dose-response effect of AT on 13cRA toxicity. Previous trials have established that 13cRA has an approximate 10% complete response rate in oral premalignancy. Our small trial's 77.8% complete response rate in premalignant lesions suggests that AT may enhance 13cRA clinical activity. Future trials of 13cRA plus AT are needed to define this combinations toxicity profile, clinical activity and pharmacokinetics.

Topics: Adult; Aged; Alanine Transaminase; Alkaline Phosphatase; Anticarcinogenic Agents; Antineoplastic Agents; Biomarkers; Cheilitis; Chemical and Drug Induced Liver Injury; Conjunctivitis; Drug Eruptions; Female; Humans; Hypertriglyceridemia; Isotretinoin; Leukoplakia, Oral; Lung Diseases; Male; Middle Aged; Neoplasms; Pain; Precancerous Conditions; Treatment Outcome; Vitamin E

Oral isotretinoin remains the most effective treatment for acne. The aim of this retrospective single-center cohort study was to estimate the prevalence of adverse events with the different oral isotretinoin brands used in acne treatment. The population consisted of all patients who consulted for acne between January 2015 and January 2020. The inclusion criterion was the initiation of treatment with oral isotretinoin. The exclusion criteria were the use of two or more brands during the same course of treatment and previous treatment with oral isotretinoin. Statistical analysis was carried out using Chi-square and Mann-Whitney tests. We analyzed 468 patients of whom 68.6% were female. The median age was 21 years. The median weight was 65 kg. The treatment was Roaccutane

Topics: Acne Vulgaris; Administration, Oral; Adult; Cohort Studies; Dermatologic Agents; Female; Humans; Hypercholesterolemia; Hypertriglyceridemia; Isotretinoin; Male; Prevalence; Retrospective Studies; Young Adult

Laboratory monitoring for adverse effects to isotretinoin occurs with variability. Standardization of laboratory monitoring practices represents an opportunity to improve quality of care.. We sought to develop an evidence-based approach to laboratory monitoring of patients receiving isotretinoin therapy for acne.. We reviewed laboratory data from 515 patients with acne undergoing 574 courses of isotretinoin from March 2003 to July 2011. Frequency, timing, and severity of abnormalities were determined.. Clinically insignificant leukopenia or thrombocytopenia occurred in 1.4% and 0.9% of patients, respectively. Elevated liver transaminases were detected infrequently and not significantly increased compared with baseline detection rates (1.9% vs 1.6% at baseline). Significant elevations occurred with triglyceride (19.3%) and cholesterol (22.8%) levels. The most severe abnormalities were grade 2 (moderate). Mean duration of treatment before abnormalities were detected was 56.3 days for hypertriglyceridemia, 61.9 days for alanine transaminitis, and 50.1 days for hypercholesterolemia.. This was a single-center experience examining variable isotretinoin laboratory monitoring practices.. In healthy patients with normal baseline lipid panel and liver function test results, repeated studies should be performed after 2 months of isotretinoin therapy. If findings are normal, no further testing may be required. Routine complete blood cell count monitoring is not recommended.

Topics: Acne Vulgaris; Adolescent; Adult; Alanine Transaminase; Child; Dermatologic Agents; Female; Humans; Hypercholesterolemia; Hypertriglyceridemia; Isotretinoin; Leukopenia; Liver; Liver Function Tests; Male; Middle Aged; Thrombocytopenia; Young Adult

Systemic isotretinoin effectively treats all forms of acne vulgaris. However, it has many side-effects, some potentially serious, that warrant limiting its use to serious cases of acne. Inappropriate use in large numbers of patients puts prescribers at risk of malpractice litigation should serious side-effects occur where safer alternative treatments were available. Doctors also risk losing access to the drug should authorities limit its use to reduce the occurrence of side-effects.

Topics: Acne Vulgaris; Administration, Oral; Attitude of Health Personnel; Chemical and Drug Induced Liver Injury; Dermatologic Agents; Humans; Hypertriglyceridemia; Isotretinoin; Mental Disorders; Practice Guidelines as Topic; Professional-Patient Relations; South Africa; Stomatitis; Vision Disorders

Multiple cutaneous osteomas are a rare complication of chronic inflammatory acne that often goes unrecognized. We report a case concerning a 35-year-old woman.. A 35-year-old woman had been treated for acne since the age of 22 years, as part of which she received two courses of oral isotretinoin. We noted the secondary appearance of several microcysts on the face for which the excision was very difficult. Curiously, these small formations did not contain keratin but were very callous. Histological examination revealed foci of osseous metaplasia, probably of postinflammatory origin. Treatment consisted solely of excision of the lesions.. Osteoma cutis comprises two distinct groups (primary and secondary). In our case, there were multiple cutaneous osteomas of the face resulting from chronic acne. The differential diagnosis was idiopathic miliary osteomatosis of the face, but this was ruled out by the young age of the patient, the improvement of the acneiform lesions under isotretinoin (confirming the initial diagnosis of acne) and the subsequent appearance of microcysts. Although there are as yet no codified treatments, excision appears to yield good results.

Topics: Acne Vulgaris; Adult; Anti-Bacterial Agents; Dermatologic Agents; Durapatite; Female; Fenofibrate; Humans; Hypertriglyceridemia; Hypolipidemic Agents; Isotretinoin; Minocycline; Neoplasms, Multiple Primary; Osteoma; Skin Neoplasms

Topics: Acne Vulgaris; Adolescent; Anticholesteremic Agents; Atorvastatin; Dermatologic Agents; Female; Heptanoic Acids; Humans; Hypertriglyceridemia; Isotretinoin; Pyrroles

The mechanism underlying hypertriglyceridemia-associated insulin resistance in humans remains poorly understood. It has been proposed that hypertriglyceridemia only produces insulin resistance when associated with an increased lipid delivery to muscle. Accordingly, hypertriglyceridemia secondary to a decreased clearance of triglyceride-rich particles should not cause insulin resistance. To verify this hypothesis, we assessed whole body and adipose tissue insulin sensitivity in 15 healthy male volunteers before and after a 5-day administration of isotretinoin (1 mg/kg/d), a vitamin A derivative that decreases the clearance of triglyceride-rich particles. Whole body insulin-mediated glucose disposal (6,6 (2)H(2)glucose), glucose oxidation (indirect calorimetry), lipolysis ((2)H(5) glycerol), and subcutaneous adipose lipolysis (microdialysis) were evaluated during a 3-step hyperinsulinemic euglycemic clamp. Isotretinoin increased plasma triglyceride from 0.97 +/- 0.15 to 1.30 +/- 0.22 mmol/L (P <.02), but did not change whole body insulin-mediated glucose disposal and lipolysis. These observations are consistent with an isotretinoin-induced inhibition of very-low-density lipoprotein (VLDL)-triglyceride clearance. The suppression of endogenous glucose production and the reduction in subcutaneous adipose glycerol concentrations by insulin remained equally unaffected after isotretinoin administration. We conclude that the impaired clearance of triglyceride-rich particles secondary to a 5-day isotretinoin administration does not impair insulin-mediated antilipolysis or glucose disposal. The data support the concept that hypertriglyceridemia-associated insulin resistance develops primarily when triglyceride production is increased.

Topics: Adipose Tissue; Adult; Blood Glucose; Calorimetry, Indirect; Deuterium; Epinephrine; Fasting; Glucose Clamp Technique; Glycerol; Humans; Hypertriglyceridemia; Insulin; Insulin Resistance; Isotretinoin; Kinetics; Lipolysis; Lipoproteins, VLDL; Male; Microdialysis; Oxidation-Reduction; Triglycerides

To investigate the effect of transcription-modulating drugs, fenofibrate and isotretinoin, on metabolic profile, insulin sensitivity of adipose and muscle tissues and gene expression in a genetic model of insulin resistance syndrome, polydactylous rat strain (PD/Cub).. Administration of fenofibrate (100 mg/kg/day), isotretinoin (30 mg/kg/day) or vehicle to adult male PD/Cub rats fed standard laboratory chow for 15 days.. Parameters of lipid and carbohydrate metabolism-oral glucose tolerance test, serum concentrations of insulin, triglycerides (TG), free fatty acids (FFA), glycerol, total cholesterol (CH); morphometric variables, in vitro insulin sensitivity of adipose and muscle tissues, catecholamine-stimulated lipolysis and the expression of ApoC-III and Hnf-4 genes in liver.. Both experimental groups displayed an increase in adiposity with contrasting effects on TG (lowered by fenofibrate and increased by isotretinoin) and gene expression (no change in fibrate-treated rats and increased expression of ApoC-III and Hnf-4 in isotretinoin-treated group). Fenofibrate-treated rats also showed decreased concentrations of FFA and CH with concomitant decrease of catecholamine-induced lipolysis in adipocytes, but also hyperinsulinemia and the highest insulin/glucose ratio. Isotretinoin increased glycerol concentrations and decreased the insulin sensitivity of peripheral tissues.. The PD/Cub rat showed a distinct pharmacogenetic reaction to fenofibrate and isotretinoin administration. Several lines of evidence now implicate specific variant(s) of ApoC-III and/or ApoA-V alleles as responsible for the dyslipidemia observed in this genetic model. The PD/Cub strain may also serve as a pharmacogenetic model for dissection of the retinoid-induced hypertriglyceridemia.

Topics: Adipose Tissue; Animals; Apolipoprotein C-III; Apolipoproteins C; Disease Models, Animal; DNA-Binding Proteins; Fenofibrate; Gene Expression Regulation; Glucose Tolerance Test; Hepatocyte Nuclear Factor 4; Hypertriglyceridemia; Hypolipidemic Agents; Insulin; Insulin Resistance; Isotretinoin; Lipids; Lipolysis; Male; Muscle, Skeletal; Obesity; Organ Size; Phosphoproteins; Rats; Rats, Inbred Strains; Transcription Factors

Topics: Acne Vulgaris; Case-Control Studies; Confounding Factors, Epidemiologic; Dermatologic Agents; Humans; Hypertriglyceridemia; Isotretinoin; Metabolic Syndrome

The ability of soy protein isolate to reduce the severity of 13-cis retinoic acid (13cRA)-induced hypertriglyceridemia was assessed in an animal model of this condition (rats fed a 13cRA-containing, casein-based diet). Male Fischer 344 rats (N = 7/group) were fed purified diets containing either casein or soy protein isolate and having either no 13cRA or retinoid at a level of 100 mg/kg diet-designated as Groups C, S, C + R, and S + R, respectively. Diet had no effect on either food intake or final body weight, and the serum levels of 13cRA were not significantly different for Groups C + R and S + R. Groups fed diets having 13cRA had significantly (p < 0.05) higher serum triglyceride levels than ones fed the corresponding retinoid-free diets, but the serum triglyceride level for Group S + R was significantly lower than for Group C + R, being 2.99 vs. 6.97 mM (265 vs. 617 mg/dl). Thus, soy protein isolate can reduce the severity of 13cRA-induced hypertriglyceridemia without affecting serum retinoid level.

Topics: Animals; Chemoprevention; Hypertriglyceridemia; Isotretinoin; Male; Rats; Rats, Inbred F344; Soybean Proteins

Previous research carried out in an animal model of retinoid-induced hypertriglyceridemia - rats fet a 13-cis retinoic acid (13cRA)-containing diet having casein as the protein source - has demonstrated that the complete replacement of dietary casein with soy protein isolate (SPI) can decrease the severity of this condition. In this study, the effect of partially replacing dietary casein with SPI was investigated. Five groups of male Fischer 344 rats were used in a 14-day study, with two groups being fed diets having casein as the protein source, without or with 13cRA (groups A and B, respectively), and three groups being fed 13cRA-containing diets in which SPI was used to bring about the isonitrogenous replacement of 25, 50, or 100% of the casein in the formula for the diet used for group B (groups C-E, respectively). Serum triglyceride concentration for group B was significantly different (p < 0.05) from that of groups A, D, and E (5.41 vs 2.62, 4.04, and 2.66 mmol/l, respectively). Serum cholesterol concentrations for groups D and E were significantly lower (p < 0.05) than for groups A and B (1.63 and 1.60 vs 2.00 and 2.14 mmol/l, respectively). Thus, the isonitrogenous replacement of 50% of dietary casein with SPI can reduce the severity of retinoid-induced hypertriglyceridemia while decreasing the serum concentration of cholesterol.

Topics: Animals; Caseins; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Dietary Proteins; Hypertriglyceridemia; Isotretinoin; Male; Rats; Rats, Inbred F344; Soybean Proteins

Retinoids in clinical use today are known to induce hypertriglyceridemia as one of their major side effects. The purpose of the present study was to determine, in an appropriate animal model, if retinoid-induced hypertriglyceridemia is mediated by retinoic acid receptors (RARs) and/or by retinoid X receptors (RXRs). Oral gavage of male Fischer rats with 13-cis-retinoic acid for 6 days caused a rapid and sustained increase in serum triglycerides that was reversible within 4 days posttreatment. In subsequent experiments, rats were treated by gavage once daily for 3 days with various retinoids, and serum triglyceride levels were determined 24 hr after the last treatment without fasting. All-trans- and 13-cis-retinoic acid, which can be converted to both RAR and RXR agonists, and 9-cis-retinoic acid, an RAR/RXR pan-agonist, caused dose-dependent increases in serum triglycerides at doses that did not cause weight loss or mucocutaneous toxicity. Ro 13-6298 and AGN 190121, two RAR-specific agonists, caused dose-dependent increases in serum triglycerides, although Ro 13-6298 only induced hypertriglyceridemia at weight-suppressive doses. Two RXR-selective agonists, LG100268 and AGN 191701, failed to induce hypertriglyceridemia or weight loss up to the highest doses tested. A structural isomer of AGN 190121 that does not activate RARs or RXRs, AGN 190727, did not induce hypertriglyceridemia. Hypertriglyceridemia induced by AGN 190121 was significantly inhibited by cotreatment with an RAR-selective antagonist, AGN 193109. Taken together, these data provide strong evidence that retinoid-induced hypertriglyceridemia is mediated, at least in part, by RARs. These data also suggest that RXR-specific agonists may have reduced potential to induce hypertriglyceridemia relative to RAR-active retinoids.

Topics: Animals; Fasting; Hypertriglyceridemia; Isotretinoin; Male; Naphthalenes; Rats; Rats, Inbred F344; Receptors, Retinoic Acid; Retinoids

Hypertriglyceridemia is frequently noted as a side effect when retinoids (e.g., 13-cis-retinoic acid) are used in human chemoprevention trials. Dietary oilseed proteins (e.g., cottonseed and soy protein) are known to reduce the severity of diet-induced hypertriglyceridemia, but their influence on drug-induced hypertriglyceridemia has not been studied previously. In the present study, the ability of dietary cottonseed protein (as cottonseed flour) to prevent drug-induced hypertriglyceridemia was investigated by feeding male Fischer 344 rats diets having casein or cottonseed protein flour with or without 13-cis-retinoic acid. Animals were fed diets for 2 weeks. Retinoid administration was associated with the induction of hypertriglyceridemia and with changes in serum fatty acid profile, the most noticeable being lowered levels of arachidonic acid. Levels of this fatty acid were 35 and 54% of control levels for retinoid-treated animals fed casein and cottonseed flour, respectively. Animals fed cottonseed flour had lower serum triglyceride levels than ones fed casein for both retinoid-containing and control diets. Dietary cottonseed flour had no effect on food intake or body weight and did not affect serum drug levels. Thus, dietary cottonseed protein can reduce the severity of retinoid-induced hypertriglyceridemia without having adverse effects on food intake or growth; in addition, because levels of 13-cis-retinoic are unaffected by cottonseed protein, it is unlikely that the chemopreventive effectiveness of the drug will be compromised by the inclusion of this protein in the diet.

Topics: Animals; Cottonseed Oil; Dietary Proteins; Fatty Acids; Hypertriglyceridemia; Isotretinoin; Male; Rats; Rats, Inbred F344

This is a case report of four patients of the same family with pachyderma. Their clinical findings are discussed in regard of a review of the literature. Also, because there are few data on effective treatment, their dramatic improvement with isotretinoin is of significant interest.

Topics: Adult; Aged; Female; Humans; Hypertension; Hypertriglyceridemia; Isotretinoin; Male; Osteoarthropathy, Primary Hypertrophic; Pedigree; Scalp Dermatoses; Skin Diseases

Systemic retinoids are used in the management of chronic cutaneous conditions and life-threatening dermatoses. Unfortunately, drug-induced hypertriglyceridemia may necessitate either dose reduction or discontinuation of therapy. The purpose of this article is to describe the successful management of isotretinoin-induced hypertriglyceridemia with gemfibrozil in a leukemia patient. Sequential serum chemistries were performed prior to, during, and following treatment with a systemic retinoid and a lipid-regulating agent. A prompt and sustained normalization of fasting triglycerides occurred following the initiation of gemfibrozil in a patient with isotretinoin-induced hypertriglyceridemia. When retinoids are being used in the management of serious conditions, the initiation of therapy with gemfibrozil to reduce the elevated triglycerides may be appropriate in those patients with retinoid-induced hypertriglyceridemia.

Topics: Acne Vulgaris; Adult; Combined Modality Therapy; Cytarabine; Gemfibrozil; Humans; Hydroxyurea; Hypertriglyceridemia; Immunologic Factors; Incidence; Isotretinoin; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male

Isotretinoin, a retinoid derivative, is in wide use as a treatment for severe acne and other dermatologic conditions. Its effects on serum lipids, most notably the induction of hypertriglyceridemia, have been well documented. We present a case of a young woman with a previous history of gestational hyperlipidemia who developed hypertriglyceridemia and pancreatitis after initiation of isotretinoin therapy. A history of gestational hyperlipidemia may serve as a marker to help identify patients who are at increased risk for developing severe hypertriglyceridemia while receiving isotretinoin. Her case emphasizes the need to consider the possibility of pancreatitis in patients who develop abdominal pain while receiving this drug.

Topics: Abdominal Pain; Acne Vulgaris; Adult; Female; Humans; Hypertriglyceridemia; Isotretinoin; Pancreatitis

Topics: Adolescent; Female; Granulomatous Disease, Chronic; Humans; Hypertriglyceridemia; Isotretinoin