Gerstmann syndrome complicating polycythemia secondary to anabolic steroid use

Abstract

Anabolic steroid use is prevalent among athletes and bodybuilders. There are known cardiovascular, reproductive, musculoskeletal and neuropsychiatric risks associated with their prolonged use. Although there have been very few documented cases of strokes associated with anabolic steroid use, cardiomyopathy and secondary erythropoiesis can increase the risk of strokes in users with no other risk factors. We present a 49-year-old man with left parietal ischaemic stroke with haemorrhagic conversion resulting in Gerstmann syndrome secondary to a hypercoagulable state from chronic anabolic steroid use.

Background

Exogenous anabolic androgenic steroids (AAS) are taken at supraphysiological doses by athletes and bodybuilders to increase muscle mass and strength. A typical cycle of use can last between 4 and 16 weeks depending on the individual’s goals and the combination of substances used. Most commonly used substances are exogenous testosterone (over 30 natural and synthetic derivatives), synthetic steroidal androgens (such as oxandrolone and trenbolone acetate) and androgen precursors.¹

Users often take these substances in ‘stacks’ with other drugs to counter the side effects. Examples include using growth hormone for additional anabolic effect, human chorionic gonadotropin to counteract the reduction in testicular size, aromatase inhibitors to counteract gynecomastia, 5α reductase inhibitors to prevent balding and acne, and diuretics for water loss.²

Physiological changes associated with prolonged use include increased blood pressure, increased low-density lipoprotein (LDL), decreased high-density lipoprotein (HDL) and increased erythropoiesis. These effects can increase the risk of strokes in users who do not have other risk factors such as diabetes mellitus, hypertension, obesity and tobacco or alcohol use.³

Since 1988, there have been few documented cases of strokes related to prolonged AAS use. The causes were suggested to be secondary to hypercoagulopathy.^4–6 We present the first case of AAS-induced stroke with Gerstmann syndrome.

Case presentation

We present a 49-year-old man who presented with aphasia, ataxia and right-sided weakness that began on waking in the night. He was in hypertensive urgency on arrival to hospital (220/130 mm Hg). Previous medical history was significant for a reported stroke in his 20s, panic attacks and rhabdomyolysis. He denied a history of chronic obstructive pulmonary disease, obstructive sleep apnea, chronic kidney disease, diabetes, hypertension, hyperlipidemia, trauma, medication changes or recent procedures. He works as a personal trainer and trains 5–6 days/week (2–3 hours/day). The patient participated in bodybuilding competitions in his teens during which he used multiple types of anabolic steroids for prolonged periods of time and continue to use them intermittently. The patient was reluctant to disclose the exact substances used and his drug regimen, but we suspect he had monthly use of testosterone and other commonly used synthetic androgens such as trenbolone acetate and oxandrolone.

Investigations

Pertinent lab results: haemoglobin and haematocrit were elevated at 182 g/L and 55.2 g/dL, respectively. Creatinine was elevated at 1.6 mg/dL. Triglyceride was 234 mg/dL, LDL elevated at 192 mg/dL and HDL low at 27 mg/dL. Total and free testosterone were elevated at 993 ng/dL (264–916), 26.5 pg/mL (6.8–21.5). Janus Kinase 2 (JAK-2) was negative and erythropoietin (EPO) level within the normal range.

CT initially showed an ischaemic changes in the left posterior parietal area. There was mild surrounding hypoattenuation and small foci of surrounding haemorrhage consistent with acute ischaemia; in addition, there was a chronic infarct in the left inferior parietal area (figure 1). Repeat imaging showed a haemorrhagic transformation with a haematoma measuring 1.1×2.1×2.8 cm. MRI demonstrated left parietal parenchymal haematoma (figure 2). Transthoracic echocardiography with bubble study showed normal ejection fraction with moderately increased left ventricular wall thickness. CT angiography of head and neck revealed no arterial occlusion and a stable haematoma with surrounding subarachnoid haemorrhage.

Figure 1.

CT showed acute left posterior parietal haematoma measuring 1.1×2.1×2.8 cm. Mild surrounding hypoattenuation and small foci of surrounding haemorrhage consistent with acute ischaemia; chronic infarct in left inferior parietal area.

Figure 2.

MRI demonstrated a left parietal parenchymal haematoma.

The patient had no signs of arrhythmia in telemetry, no inflammatory markers for vasculitis, no markers of connective tissue disease and no signs of hypercoagulable disorders.

Treatment

Medical management for left parietal intracerebral haemorrhage, hyperlipidemia, hypertensive urgency, acute kidney injury and secondary polycythemia included blood pressure control with nicardipine drip followed by labetalol as well as levetiracetam for seizure prophylaxis. He received therapeutic phlebotomy of ~1000 cc with the improvement of symptoms.

Outcome and follow-up

His stroke symptoms improved after 2 days but he developed dysgraphia, dyscalculia, finger agnosia and left–right disorientation consistent with Gerstmann syndrome. Dysgraphia and left–right disorientation resolved but dyscalculia and finger agnosia remained on discharge.

Discussion

Gerstmann syndrome is a neurological disorder characterised by four primary symptoms: dyscalculia, dysgraphia, finger agnosia and left–right disorientation due to a stroke in the left parietal region of the angular gyrus.⁴ The cause of this patient’s stroke and subsequent presentation was suspected to be due to a hypercoagulable state from increased erythropoiesis. It is also likely that uncontrolled hypertension can be a secondary factor for the development of his presentation since he had both acute and chronic manifestations of the uncontrolled hypertension (acute kidney injury and left ventricular hypertrophy). Anabolic steroids have been shown to increase erythropoiesis causing secondary polycythemia.⁷ To our knowledge, this case is the first documented report of an AAS-induced stroke with symptoms of Gerstmann syndrome, although other areas of stroke might have been reported.

Other serious side effects with prolonged anabolic steroid use include a decrease in HDL levels, increase LDL/cholesterol levels and changes to blood pressure.⁷ These effects consequentially increase the risk of cardiomyopathy, myocardial infarctions, liver and kidney disease and strokes in chronic users. Stergiopoulos et al presented a 44-year-old recreational weightlifter with no prior cardiac history who had an acute inferior wall myocardial infarction. He presented with an extremely elevated blood pressure and polycythemia which are physiological changes associated with a history of using high-dose intramuscular testosterone and sildenafil.⁸

One of the first known cases of anabolic steroids induced stroke was reported in 1988. Frankle et al reported a 34-year-old bodybuilder who developed right hemiparesis and dysarthria a few days prior to his bodybuilding contest after using AAS for 4 years.⁵ Santamarina et al reported a 26-year-old amateur athlete who developed an ischaemic stroke after using stanozolol, a synthetic AAS. Similar to our case, the young athlete had positive imaging findings on his cerebral MRI for multiple strokes but had negative angiography and transesophageal echocardiography results.⁶

Shamloul et al demonstrated a unique and complicated case of a 37-year-old man who presented with acute right-sided weakness and altered mental status. He had a subacute left temporoparietal infarction that was confirmed by brain CT and MRI. This patient also had dilated cardiomyopathy and multiple thrombi in the left ventricle on echocardiography. He passed away eventually.⁹

The patient in our case had no other previous risk factors for strokes besides the chronic use of AAS. Other causes of secondary polycythemia such as chronic hypoxia, chronic kidney disease and obstructive sleep apnea were investigated and determined to not be the cause of polycythemia. Primary polycythemia vera was also unlikely given the normal EPO value and negative JAK-2. The JAK-2 mutation is found to be present in over 90% of patients with polycythemia vera.¹⁰ The patient’s previous stroke in his 20s can only be explained by his continuous, although occasionally interrupted, use of AAS.

It was also noted that the patient’s testosterone levels were not as elevated when comparing to patients who are on testosterone replacement therapy (TRT). This could be explained in several ways. Use of multiple substances and stacks could have altered the real measurement. Many synthetic compounds do not always appear in bloodwork and are undetectable. Short half-life is another reason. Testosterone cypionate, one of the most commonly used exogenous derivatives, has a half-life of 8 hours; therefore, elevated levels do not always appear in blood work. Other commonly used synthetic steroidal androgens such as trenbolone acetate and oxandrolone have half-lives of 48–72 and 10.5 hours, respectively. These data indicate that there is still much more research to be done on efficient ways to detect these synthetic compounds in chronic AAS users.

There are studies that have refuted association of TRT and risk of stroke in males. A systematic review of seven cohorts showed that in two cohorts there was a significant decrease in risk of ischaemic stroke (HR 0.64; 95% CI 0.52 to 0.80) (HR of 0.64; 95% CI 0.43 to 0.96).¹¹ The other five cohorts did not show any independent association between TRT and stroke. Eight randomised controlled trials were also analysed and a low frequency of stroke was observed in both control and testosterone supplement groups which prevented reaching any conclusions. Therefore, the authors concluded that the association between TRT and stroke is unclear and requires further studies for clarification.^{11 12}

Nevertheless, these studies evaluated a controlled TRT plan under medical professionals’ supervision and are different from self-administering athletes and bodybuilders who most likely take much higher doses of medication with more frequency and with no supervision. Therefore, the risk of stroke seems to be a real one for them as shown by this case.

Patient’s perspective.

After going through a really tough personal and professional time, I came to realise that using steroids and enhancing drugs was never worth it. The price I paid and will be paying after this is far greater than any benefit that I got out of using them. Too much cost, effort and complications for no real meaningful benefit.

Learning points.

• Exogenous anabolic androgenic steroids (AAS) are used among athletes and bodybuilders who want to build muscle mass and improve performance.

• The adverse side effects have been researched and documented for years.

• Many of the cases focused on the associated cardiovascular effects; however, there have been few cases reporting strokes induced by the effects of AAS.

• This case is a rare and complex presentation of an acute ischaemic turned haemorrhagic stroke with symptoms of Gerstmann syndrome due to secondary polycythemia from chronic AAS use.