Anabolic Steroids & Liver [GI]

[Michael Scally MD]

[OA] Drug-Induced Liver Injury by Selective Androgenic Receptor Modulators

Selective androgenic receptor modulators (SARMs) have not been approved by the U.S. Food and Drug Administration but they are heavily promoted as alternatives to androgenic anabolic steroids. We present two cases of liver injury associated with SARMs.

In both cases, the supplements were sent for toxicologic analysis and were screened by ultra‐high performance liquid chromatography/photodiode array and gas chromatography–mass spectrometry. The presence of SARM in both cases (Ligandrol in case 1 and RAD‐140 in case 2) was confirmed, and no other contaminants were identified.

Case 1

A previously healthy 24‐year‐old man presented with a 5‐week history of jaundice, anorexia, nausea, lethargy, and weight loss of 5 kg. He had used a gym supplement (LGD‐4033 LIGANDROL capsules) for 9 weeks, and his symptoms developed a week after its cessation. He had a history of binge drinking once a month. He was not on any regular medications and gave no previous history of liver disease. …

Case 2

A 49‐year‐old man presented with jaundice and itching of 5 weeks duration. His only regular medication was an antidepressant (venlafaxine) for 11 months. Four months prior to presentation, he reported using a SARM (RAD‐140) for 4 weeks and intermittent use thereafter. Investigations showed the following: bilirubin, 291 umol/L; ALT, 54 U/L; AST, 59 U/L; ALP, 327 U/L; GGT, 60 U/L; albumin, 40 g/L; globulin, 28 g/L; creatinine, 120 μmol/L (peaking at 132 μmol/L); INR, 1.2; platelets, 347 × 109/L; and R ratio of 5.0 (indicating mixed hepatocellular–cholestatic liver injury). …

Flores JE, Chitturi S, Walker S. Drug-Induced Liver Injury by Selective Androgenic Receptor Modulators. Hepatol Commun. 2020;4(3):450–452. Published 2020 Jan 3. doi:10.1002/hep4.1456 Error - Cookies Turned Off

 

[Michael Scally MD]

Elevated Testosterone Increases Risk of Hepatocellular Carcinoma in Men with Chronic Hepatitis B and Diabetes Mellitus

Background and aim: Male sex is a risk factor for hepatocellular carcinoma (HCC). Diabetes mellitus (DM) is associated with a doubled risk of HCC in patients with chronic hepatitis B (CHB). We examined the relationship between serum total testosterone and HCC risk in male CHB patients with DM.

Methods: We performed a retrospective cohort study of male CHB patients with DM between 2000 and 2017 using a territory-wide electronic healthcare database in Hong Kong. DM was defined by use of anti-diabetic medications, hemoglobin A1c ≥6.5%, and/or fasting glucose ≥7mmol/L in two measurements or ≥11.1mmol/L in one measurement.

Results: Of 928 male CHB patients with DM, 83 (8.9%) developed HCC at a median (interquartile range) of 10.7 (6.1-14.6) years.

Higher testosterone was associated with an elevated risk of HCC (adjusted hazard ratio [aHR] per 1 SD increase 1.23, 95% confidence interval [CI] 1.03-1.46; P=0.024). Upper tertile of testosterone (aHR 1.86, 95% CI 1.02-3.39, P=0.043), but not middle tertile (aHR 0.84, 95% CI 0.41-1.69 P=0.620), was associated with a higher risk of HCC than lower tertile.

The cumulative incidence (95% CI) of HCC at 5, 10 and 15 years were 4.4% (2.5%-7.2%), 12.4% (8.7%-16.7%) and 19.1% (14.2%-24.5%), respectively, in patients in upper tertile of testosterone.

By subgroup analysis, the association between testosterone and HCC was stronger in patients aged ≥50 years and those not receiving antiviral therapy.

Conclusions: Higher serum testosterone is associated with a higher incidence of HCC in male CHB patients with DM.

Yip TC, Wong GL, Chan HL, et al. Elevated testosterone increases risk of hepatocellular carcinoma in men with chronic hepatitis B and diabetes mellitus [published online ahead of print, 2020 Apr 28]. J Gastroenterol Hepatol. 2020;10.1111/jgh.15079. doi:10.1111/jgh.15079 Error - Cookies Turned Off

 

[Michael Scally MD]

[OA] Transient Jejuno-Jejunal Intussusception In An Anabolic Steroid User

Highlights
· Adult intussusception is a rare cause of abdominal pain with the majority of presentations being localised to the small bowel.
· Transient jejunal intussusception is usually diagnosed on CT with diagnostic laparoscopy performed to confirm resolution and exclude malignant causes.
· Polycythaemia was noted on the patient’s blood results which has been previously associated with anabolic steroid use and has been associated with intussusception in the literature.
· Laparoscopic and endoscopic examination demonstrated nil malignant or structural cause for intussusception in the presented patient.
· Anabolic steroid use may play a role in the development of intussusception in the adult population.

Introduction: Adult intussusception (AI) is both a challenging and rare diagnosis, with predisposing factors including malignancy, surgery and infection to name a few. Transient jejunal intussusception is a subset of AI which is usually diagnosed radiologically, with diagnostic laparoscopy utilised to determine whether a malignant cause is identifiable and subsequently treatable.

Presenting case: We present the case of a previously healthy 36-year-old male diagnosed with transient jejunal intussusception on computed tomography after presenting with abdominal pain. Blood tests on admission were normal apart from polycythaemia. His only significant history was that of chronic anabolic steroid use. He had a subsequent normal gastroscopy and colonoscopy with diagnostic laparoscopy demonstrating thickening of the small bowel. Histopathological analysis of the intraoperative specimen was normal. The patient improved and was discharged with no further complications.

Conclusion: This case highlights the potential association between anabolic steroid use resulting in polycythaemia, and AI or transient jejunal intussusception, along with further validating a conservative approach in the management of AI in patients deemed to be low risk of malignancy on pre-operative evaluation.

De Robles MS, O'Neill RS, Young CJ. Transient jejuno-jejunal intussusception in an anabolic steroid user-A case report [published online ahead of print, 2020 May 8]. Int J Surg Case Rep. 2020;70:126‐129. doi:10.1016/j.ijscr.2020.04.010 Transient jejuno-jejunal intussusception in an anabolic steroid user—A case report - ScienceDirect

 

[Michael Scally MD]

Drug-Induced Liver Injury Due To Mesterolone: A Case Report

Mesterolone is an anabolic steroid with an acceptable indication only in very specific medical situations. However, its illicit use is growing exponentially, usually in young men who frequent gyms. It is relatively easy to skirt health regulations and acquire these often-imported compounds. Frivolous use of anabolic steroids for purposes of improving one’s bodily appearance or athletic performance may have serious health consequences of which the medical community must be aware.

Report

A 43-year-old man, an amateur bodybuilder with no prior history of note, was admitted to our centre due to jaundice which had started one week beforehand. He did not have a rash, adenomegaly or fever. Following thorough questioning, he admitted to having used Proviron®25 mg/12 h as a muscle enhancer for 12 days and up to three weeks beforehand. …

Pérez Palacios D, Giráldez Gallego Á, Carballo Rubio V, Solà Fernández A, Pascasio Acevedo JM. Drug-induced liver injury due to mesterolone: A case report. Daño hepático inducido por mesterolona: a propósito de un caso. Gastroenterol Hepatol. 2019;42(10):629‐630. doi:10.1016/j.gastrohep.2019.06.001 https://www.sciencedirect.com/science/article/abs/pii/S021057051930158X?via%3Dihub

 

[Silentlemon1011]

Drug-Induced Liver Injury Due To Mesterolone: A Case Report

Mesterolone is an anabolic steroid with an acceptable indication only in very specific medical situations. However, its illicit use is growing exponentially, usually in young men who frequent gyms. It is relatively easy to skirt health regulations and acquire these often-imported compounds. Frivolous use of anabolic steroids for purposes of improving one’s bodily appearance or athletic performance may have serious health consequences of which the medical community must be aware.

Report

A 43-year-old man, an amateur bodybuilder with no prior history of note, was admitted to our centre due to jaundice which had started one week beforehand. He did not have a rash, adenomegaly or fever. Following thorough questioning, he admitted to having used Proviron®25 mg/12 h as a muscle enhancer for 12 days and up to three weeks beforehand. …

Pérez Palacios D, Giráldez Gallego Á, Carballo Rubio V, Solà Fernández A, Pascasio Acevedo JM. Drug-induced liver injury due to mesterolone: A case report. Daño hepático inducido por mesterolona: a propósito de un caso. Gastroenterol Hepatol. 2019;42(10):629‐630. doi:10.1016/j.gastrohep.2019.06.001 https://www.sciencedirect.com/science/article/abs/pii/S021057051930158X?via%3Dihub

Wow
Just from some Proviron.

That's really intriguing

 

[Michael Scally MD]

[OA] Body Building and Aminotransferase Elevations: A Review

In addition to liver injury, elevation of aminotransferases can be caused by strenuous exercise and use of muscle-building and weight-loss supplements. The purpose of this review is to discuss the various mechanisms of elevation of aminotransferases related to body building. A literature review was performed on clinical trials and case reports involving exercise or supplement use and their effects on aminotransferases.

Normal aminotransferase levels varied according to gender, age, body mass index, and comorbidities. Strenuous exercise and weight lifting, especially in the unaccustomed, can cause elevated aminotransferases in the absence of liver damage. Supplements such as anabolic steroids, ephedra, and LipoKinetix, amongst others, have also been associated with aminotransferase elevations. The pattern of elevation of aminotransferases is not helpful in distinguishing liver from muscle injury. Other associated muscle enzymes can be useful in making that distinction.

To prevent aminotransferase elevations, subjects not accustomed to moderate-high intensity workouts, are recommended to undertake gradual increase in intensity. When causes of liver injury have been ruled out, investigation into bodybuilding, extreme exercise, and supplement use is warranted.

Kim JV, Wu GY. Body Building and Aminotransferase Elevations: A Review. J Clin Transl Hepatol. Published online: Jun 3, 2020. doi: 10.14218/JCTH.2020.00005. Body Building and Aminotransferase Elevations: A Review

 

[Michael Scally MD]

Bodybuilding Supplements Leading to Copper Toxicity, Encephalopathy, Fulminant Hepatic Failure and Rhabdomyolysis

Millions of people worldwide use nutritional and dietary supplements, such as vitamins and minerals. These and other performance-enhancing substances are also used by high school, college, and professional athletes, bodybuilders, and amateur sports enthusiasts. The constituents of these supplements and their metabolites may be harmful and not listed on the product label.

We present a case report of a 32-year-old bodybuilder using myriad nutritional, performance-enhancing, and weight-loss supplements with life-threatening encephalopathy, hepatic failure, rhabdomyolysis, and copper toxicity mimicking Wilson's disease.

Emergency physicians and nurses should be aware of these potential deleterious effects and inquire about supplement use by patients with unexplained multiorgan failure. Family, friends, or acquaintances should be asked to bring the actual products to the hospital for analysis.

Richards JR, Scheerlinck PH, Owen KP, Colby DK. Bodybuilding supplements leading to copper toxicity, encephalopathy, fulminant hepatic failure and rhabdomyolysis [published online ahead of print, 2020 Jun 2]. Am J Emerg Med. 2020;S0735-6757(20)30460-5. doi:10.1016/j.ajem.2020.05.096 https://www.ajemjournal.com/article/S0735-6757(20)30460-5/pdf

 

[Millard]

We present a case report of a 32-year-old bodybuilder using myriad nutritional, performance-enhancing, and weight-loss supplements with life-threatening encephalopathy, hepatic failure, rhabdomyolysis, and copper toxicity mimicking Wilson's disease.

Quite a lot of OTC supplements. clenbuterol, growth hormone, insulin, SARMS but no anabolic steroids for a 300-lb bodybuilder "with minimal bodyfat"

 

[PissedOfIAsuperClient]

Yeah definitely stay away from almost all forms of hormonal orals for the sake of your liver. I have found from extensive experimentation that Live-52 DS is the most therapeutic supplement for liver health. Thorne also make something called "Liver Detox" which is pretty good also, it actual slows stage II detoxification and ramps up Phase I, which leeds to enhanced detoxification.

 

[Michael Scally MD]

 

[Michael Scally MD]

Ligandrol (LGD-4033)-Induced Liver Injury

We described a 32-year-old man who developed severe drug-induced liver injury after using Ligandrol (LGD-4033). The diagnosis was confirmed by a liver biopsy that showed cholestatic hepatitis with a mild portal, periportal, and perisinusoidal fibrosis. Ligandrol is a selective androgen receptor modulator that is available over the counter and via the internet.

Barbara M, Dhingra S, Mindikoglu AL. Ligandrol (LGD-4033)-Induced Liver Injury. ACG Case Rep J. 2020;7(6):e00370. Published 2020 Jun 11. doi:10.14309/crj.0000000000000370 Ligandrol (LGD-4033)-Induced Liver Injury : ACG Case Reports Journal

 

[Michael Scally MD]

[OA] Multiple Hepatocellular Adenomas Associated with Long-Term Administration of Androgenic Steroids for Aplastic Anemia: A Case Report and Literature Review

Introduction: Anabolic steroids are widely administered to patients with aplastic anemia (AA) and are associated with numerous medical complications. To assist with future diagnoses, we report about a young boy with multiple hepatocellular adenomas (HAs) induced by long-term use of anabolic androgenic steroids (AAS) for AA and present a related literature review.

Patient concern: A 15-year-old boy who was diagnosed with AA in 2011 had been treated with stanozolol (6 mg per day) and ciclosporin A (120-150 mg per day) for almost 4 years. He presented with epigastric pain and fever, and abdominal computed tomography showed a lesion of heterogenous density measuring 13.5 × 13.0 × 8.0 cm in the left hepatic lobe, which was initially misdiagnosed as a liver abscess.

Diagnosis: The patient went into hemorrhagic shock twice after invasive manipulation that aimed at diagnosis and was finally diagnosed with HA using fine needle aspiration.

Interventions: The patient discontinued AAS and only reserved ciclosporin A for AA treatment.

Outcomes: Follow-up abdominal computed tomography performed 4 years after AAS discontinuation showed obvious regression of the hepatic lesions.

Conclusion: It is of great importance for hematologists to completely understand that the long-term use of AAS may cause HA, which carries a great risk of hemorrhage and malignant transformation.

Wang L, Wang C, Li W, et al. Multiple hepatocellular adenomas associated with long-term administration of androgenic steroids for aplastic anemia: A case report and literature review. Medicine (Baltimore). 2020;99(28):e20829. doi:10.1097/MD.0000000000020829 Multiple hepatocellular adenomas associated with long-term... : Medicine

 

[Michael Scally MD]

[OA] Body Building and Aminotransferase Elevations

In addition to liver injury, elevation of aminotransferases can be caused by strenuous exercise and use of muscle-building and weight-loss supplements. The purpose of this review is to discuss the various mechanisms of elevation of aminotransferases related to body building.

A literature review was performed on clinical trials and case reports involving exercise or supplement use and their effects on aminotransferases. Normal aminotransferase levels varied according to gender, age, body mass index, and comorbidities.

Strenuous exercise and weight lifting, especially in the unaccustomed, can cause elevated aminotransferases in the absence of liver damage. Supplements such as anabolic steroids, ephedra, and LipoKinetix, amongst others, have also been associated with aminotransferase elevations.

The pattern of elevation of aminotransferases is not helpful in distinguishing liver from muscle injury. Other associated muscle enzymes can be useful in making that distinction.

To prevent aminotransferase elevations, subjects not accustomed to moderate-high intensity workouts, are recommended to undertake gradual increase in intensity. When causes of liver injury have been ruled out, investigation into bodybuilding, extreme exercise, and supplement use is warranted.

Villavicencio Kim J, Wu GY. Body Building and Aminotransferase Elevations: A Review. J Clin Transl Hepatol. 2020;8(2):161-167. doi:10.14218/JCTH.2020.00005 Body Building and Aminotransferase Elevations: A Review

 

[Michael Scally MD]

Nonalcoholic Fatty Liver Disease in Males with Low Testosterone Concentrations

Highlights
· Hepatic steatosis index was higher in low- compared with high-testosterone group.
· Triglyceride-to-HDL-C ratio was higher in low- compared with high-testosterone group.
· Hepatic steatosis index was inversely, independently associated with testosterone levels.
· Non-invasive indices of hepatic fibrosis were similar between groups.

Aims: There are limited clinical data on the association between serum testosterone concentrations and nonalcoholic fatty liver disease (NAFLD) in men. The main aim of this study was to evaluate the association between testosterone concentrations and NAFLD in adult men, in terms of noninvasive indices of NAFLD and hepatic fibrosis.

Methods: In this cross-sectional study, 98 men were recruited on an outpatient basis and were divided into low-testosterone (<12 nmol/l or <346 ng/dl, n = 37) or high-testosterone groups (≥12 nmol/l or ≥346 ng/dl, n = 61). Serum testosterone concentrations were measured by immuno-chemiluminescence. Hepatic steatosis index (HSI) and Triglyceride-to-HDL-C ratio (THR), as non-invasive indices of NAFLD, as well as AST-to-Platelet Ratio Index (APRI), fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS), as non-invasive indices of hepatic fibrosis, were calculated based on standard formulas.

Results: Both the non-invasive indices of NAFLD (HSI and THR) were higher in low-testosterone compared with high-testosterone group (HSI: 47.5 ± 2.9 vs. 38.4 ± 1.0, p = 0.005; THR: 1.70 ± 0.16 vs. 0.98 ± 0.07, p < 0.001). On the contrary, none of the non-invasive indices of hepatic fibrosis was different between groups. HSI (p = 0.038), but not THR, remained inversely independently associated with serum testosterone, after adjustment for potential confounders, including sex hormone-binding globulin.

Conclusions: Men with low testosterone concentrations have higher non-invasive indices of NAFLD (HSI and THR), but not of hepatic fibrosis (APRI, FIB-4, NFS), compared with counterparts of high testosterone concentrations. HSI was inversely and independently associated with testosterone concentrations.

Polyzos SA, Mousiolis A, Mintziori G, Goulis DG. Nonalcoholic fatty liver disease in males with low testosterone concentrations. Diabetes Metab Syndr. 2020;14(5):1571-1577. doi:10.1016/j.dsx.2020.07.049 https://www.sciencedirect.com/science/article/abs/pii/S1871402120302976?via%3Dihub

 

[Michael Scally MD]

[OA] Drug-Induced Liver Injury Associated With Alpha Bolic (RAD-140) and Alpha Elite (RAD-140 and LGD-4033)

We report a 52-year-old man who developed drug-induced liver injury after taking Alpha Bolic (contains RAD-140) and Alpha Elite (contains both RAD-140 and LGD-4033) supplements.

Liver biopsy demonstrated diffuse centrilobular canalicular cholestasis, prominent ductular reaction, and mild lobular inflammation with rare non-necrotizing epithelioid granuloma suggestive of drug-induced liver injury.

Liver enzymes returned to normal levels approximately 3 months after the patient stopped both supplements. We present the mechanism of drug-induced liver injury associated with 2 selective androgen receptor modulators, including RAD-140 and LGD 4033.

Barbara M, Dhingra S, Mindikoglu AL. Drug-Induced Liver Injury Associated With Alpha Bolic (RAD-140) and Alpha Elite (RAD-140 and LGD-4033). ACG Case Rep J. 2020 Jun 18;7(6):e00409. doi: 10.14309/crj.0000000000000409. PMID: 33062783; PMCID: PMC7535764. Drug-Induced Liver Injury Associated With Alpha Bolic... : ACG Case Reports Journal

 

[Michael Scally MD]

[OA] Low Testosterone Levels Predict Increasing Severity and Worse Outcomes of Hepatitis B Virus-related Acute-on-chronic Liver Failure

Background - Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is more prevalent among males than females and has a high rate of short-term mortality, and low serum testosterone has been prevalent in critical illness such as acute respiratory failure and cirrhosis, we investigated the association between testosterone level and severity of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) in males remains unknown.

Methods - This single-center observational study involved patients with HBV-ACLF planned to undergo treatment with an artificial liver support system. Morning blood samples were collected and androgen levels analyzed by chemi-bioluminescent immunoassay. Time to death or liver transplantation within 90 days comprised the primary composite outcome. We assessed the relationships between androgen levels, stage (early, middle, or late, categorized according to clinical manifestation), severity scores, and clinical outcomes of HBV-ACLF.

Results - Among 160 male subjects, 32 had early stage HBV-ACLF, 61 middle stage, and 67 end stage. Serum levels of total testosterone (TT), free testosterone index (FTI), dehydroepiandrosterone sulfate and cortisol were significantly lower among subjects than chronic hepatitis B patients and healthy controls, while androstenedione was higher.

Low TT, SHBG, FTI and high androstenedione were associated with increased stage (of HBV-ACLF, ascites, and hepatic encephalopathy) and severity scores (Model for End-stage Liver Disease and Chinese Group on the Study of Severe Hepatitis B-ACLF scores). Low TT (<142.39 ng/dL) was a risk factor for both the composite outcome and for death alone within 90 days. Multivariate analysis revealed TT to be a predictor for the composite outcome independent of age, BMI, SHBG, FTI, cortisol, and androstenedione.

Conclusion - Low serum testosterone is common among male patients with HBV-ACLF and predictive of increased severity and worse outcome of the disease.

Huang Y, Yan D, Zhang H, et al. Low Testosterone Levels Predict Increasing Severity and Worse Outcomes of Hepatitis B Virus-related Acute-on-chronic Liver Failure in Males. Virology Journal. Low Testosterone Levels Predict Increasing Severity and Worse Outcomes of Hepatitis B Virus-related Acute-on-chronic Liver Failure in Males

 

[Michael Scally MD]

[OA] [Updated] Anabolic Steroid Toxicity

Androgenic-anabolic steroids (AAS) are widely missed worldwide as performance-enhancing agents. The use of AAS started in competitive sports and spread to non-competitive athletes. The World Anti-Doping Agency banned AAS since the 1950s and has continued adding new methods and new variations of AAS. Currently, the CDC estimates that the majority of AAS users are adolescent males.

The hypothalamus is the integrating center for the reproductive axis (HPG). It receives signals from the amygdala, olfactory, and visual cortex. Gonadotropin-releasing hormone (GnRH) then gets released into a venous portal system that carries it to adenohypophysis of the pituitary gland. In addition to signals from the CNS, humoral factors from the testes also play a role in modulating the release of GnRH. Gonadotropin-releasing hormone release is pulsatile, seasonal, and circadian. Levels of GnRH are highest during spring and in the morning with peaks occurring every 90 to 120 minutes.

Once released, GnRH acts on the pituitary gland and promotes the production and release of luteinizing hormone (LH) and to a lesser extent, follicle-stimulating hormone (FSH). Luteinizing hormone, in turn, acts on Leydig cells in the testes, which are the site of production of most of the endogenous androgens. Androgen production also occurs in the adrenal cortex and the conversion of androstenedione peripherally. Testosterone, in turn, inhibits the production of GnRH in the hypothalamus. Testosterone is a 19-carbon steroid and is the most potent endogenous androgen. As such, it is the basis of most AAS.

Addition of various functional groups to this basic 19-carbon structure changes androgenic, anabolic, and toxicity profiles of AAS. Testosterone and other AAS act to increase muscle hypertrophy through modulating androgen receptor and its interaction with co-activators. It also increased muscle hypertrophy through modulation of receptor expression through intercellular metabolism, an anti-catabolic effect, by interfering with glucocorticoid receptor expression and various genomic and non-genomic pathways that act on the central nervous system.



Studies of long term AAS users showed an increase in muscle fiber hypertrophy. Both Type I and Type II had significant hypertrophy. Even though Type II muscle fibers compose the majority of muscle mass in power-lifters, it was Type I fibers that enlarged the most with a 33% increase in size. Additionally, Type II fibers require a lesser dose of testosterone 300 mg vs. 600 mg for Type I to exhibit hypertrophy. One of the critical mechanisms by which AAS induces muscle hypertrophy is by increasing the synthesis of contractile proteins.

Injections (IM) of 200 mg of testosterone enanthate increased synthesis two-fold by increasing the rate at which amino acids underwent reuse, while protein turnover rate was unchanged. Each muscle fiber contains multiple myonuclei that can support a certain level of protein synthesis. With resistance training, these myonuclei increase in size and can support an increase in protein synthesis and cross-sectional area of a muscle fiber. On average, this increase is no more than 26% for Type II muscle fiber, which is termed “ceiling theory,” however, with AAS supplementation, researchers observed a significant increase of 36%. This effect is even higher for Type I muscle fibers.

Short term administration of androgenic-anabolic steroids (300 mg per week for 20 weeks) increases the number of muscle satellite cells; this is thought to be because testosterone promotes satellite cell proliferation and entry into the cell cycle. As these cells enter the cell cycle, some daughter cells don’t differentiate and become quiescent cells. Other satellite cells while dividing may become new myonuclei or proceed to form new myotubules. While the exact mechanism remains unclear, murine models showed that testosterone-treated C3H 10T1/2 pluripotent mesenchymal cells showed increases in MyoD and myosin heavy chains.

Testosterone supplementation is a potent regulator of lipolysis via influencing catecholamine signal transduction. Testosterone also inhibits adipocyte precursor cells from differentiation. Finally, there may be an androgen receptor-independent pathway through which testosterone may act. AAS may work on G-protein coupled receptor at the plasma membrane, which would increase Ca2+ concentration and activate ERK1/2 kinases, which then would phosphorylate transcription factors.

Middlebrook I, Schoener B. Anabolic Steroid Toxicity. 2020 Oct 16. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan–. PMID: 31334979. Anabolic Steroid Toxicity - StatPearls - NCBI Bookshelf

 

[Michael Scally MD]

[OA] Androgenic Anabolic Steroid-Induced Liver Injury

Background: Anabolic androgenic steroids (AAS) usage is widespread and increasing. AAS drug-induced liver injury (DILI) is recognised but its clinical course and management is poorly described. We report 2 cases of AAS DILI with associated renal dysfunction, managed successfully with oral corticosteroids.

Methods: A comprehensive review identified 50 further cases to characterise the clinical and biochemical course. Causality grading was calculated using the updated Roussel Uclaf Causality Assessment Method (RUCAM) score. Data are presented as median values

Results: The most common AAS taken was methyldrostanolone. Patients commonly present with jaundice and pruritus but may exhibit other constitutional symptoms. Patients presented 56 days after starting, and bilirubin peaked 28 days after stopping, AAS.

Causality assessment was 'unlikely' in 1 (2%), 'possible' in 31 (60%) and 'probable' in 20 (38%).

Peak values were: bilirubin 705 μmol/L, alanine transaminase 125 U/L, aspartate transaminase 71 U/L, alkaline phosphatase 262 U/L, gamma-glutamyl transferase 52 U/L, international normalised ratio 1.1. Liver biopsies showed 'bland' canalicular cholestasis. 43% of patients developed kidney injury (peak creatinine 225 μmol/L).

Therapies included antipruritics, ursodeoxycholic acid and corticosteroids. No patients died or required liver transplantation.

Conclusions: Physicians are likely to encounter AAS DILI. Causality assessment using the updated RUCAM should be performed but defining indications and proving efficacy for therapies remains challenging.

Abeles RD, Foxton M, Khan S, et al. Androgenic anabolic steroid-induced liver injury: two case reports assessed for causality by the updated Roussel Uclaf Causality Assessment Method (RUCAM) score and a comprehensive review of the literature. BMJ Open Gastroenterol. 2020 Nov;7(1):e000549. doi: 10.1136/bmjgast-2020-000549. PMID: 33214235. Androgenic anabolic steroid-induced liver injury: two case reports assessed for causality by the updated Roussel Uclaf Causality Assessment Method (RUCAM) score and a comprehensive review of the literature | BMJ Open Gastroenterology

 

[Millard]

The most common AAS taken was methyldrostanolone.

18 of 52 published cases reviewed involved Superdrol

 

[Jerry5000]

What’s a concerning liver enzyme level ?