healthmedicinet

Our 64 year old caucasian patient had a history of prostate cancer, diagnosed in 2001
[cT3, cN2, M0, G3, Gleason 9; prostate-specific antigen (PSA) 151 µg/l]. He was successfully
treated with local radiotherapy combined with chemical castration for 1 year (complete
remission, PSA nadir 0.01 µg/l). In 2006 a biochemical relapse occurred that was treated
by androgen ablation. In 2011 Cholin-Pet CT showed local relapse as well as suspect
lymph nodes. PSA was increased to 28.9 µg/l. The patient was enrolled into a clinical
trial of ipilimumab for asymptomatic castration refractory prostate cancer (CA184095;
NCT01057810) at the National Center for Tumor Diseases (NCT), Heidelberg. Starting
in August 2011 he received four infusions of ipilimumab (10 mg/kg) at 3-week-intervals
followed by three infusions at 3-month-intervals. Ipilimumab treatment was effective
as PSA dropped and CT showed tumor regression, but the patient also experienced severe
adverse effects: he had epigastric pain and pruritus, followed by heavy diarrhea,
one episode leading to exsiccosis and prerenal failure. In November 2011 hypophysitis
was diagnosed by decreased thyroid-stimulating hormone (TSH) levels and low thyroxine
levels, an abnormal thyrotropin-releasing hormone test, and low cortisone blood levels.
Thyroid volume was normal (24 ml) with presence of a small nodule (0.5 ml). Anti-thyroid
antibodies (anti-TPO and anti-TG) were elevated (Table 1). The patient was started on L-thyroxine at 50 µg/days and gradually increased to 100 µg once a day. He also received
Prednisolone 50 mg once daily, which was gradually reduced and switched to hydrocortisone
20 mg/days in January 2012. Following a normal Metopirone test in June 2012, hydrocortisone
was tapered and stopped in July 2012. Therapy with L-thyroxine 100 µg/days was continued. The study medication was continued within the
maintenance phase until July 2012.

Table 1. Laboratory findings

In August 2012, following surgery of an epigastric hernia the patient had severe postoperative
intraabdominal bleeding leading to hypovolemic shock followed by sepsis. He physically
recovered within 3 weeks, but slight personality changes remained. He slowly deteriorated
suffering from adynamia, memory disturbances, and fluctuating disorientation. When
the patient was admitted to our hospital in November 2012 he was bedridden, somnolent
and disoriented. He had episodes of agitation and hallucinations, and showed myocloni
and intermittent focal seizures of his right arm. Deep tendon reflexes were normal,
but Babinski’s sign was intermittently positive. He had no paresis. Cranial CT scan
was normal. Electroencephalography (EEG) showed generalized slowing with prevailing
of slow theta and delta waves. CSF cell count, glucose, and lactate were normal; protein
was 85.2 mg/dl (normal 50). Serum C-reactive protein was 76 mg/l (normal 5), erythrocyte
sedimentation rate 86 mm/h. Leukocyte count was 10.2/µl, erythrocyte count 4.08/ng,
haemoglobin 11.4 g/dl. Renal and liver functions were normal. Anti-thyroid antibodies
(anti-TPO and anti-TG) in serum were markedly elevated (Table 1). Antibodies associated with vasculitis proved negative. Anti-NMDA-, VGKC- or onconeural-antibodies
were neither determined in serum nor in CSF. Cranial MRI scan showed mild microangiopathic
changes, an old lacunar infarction in the right thalamus, and a normal pituitary gland.
CT-Scan of the abdomen and thorax showed stable disease at the primary site, and no
metastasis. PSA was 0.004 µg/l.

Levetiracetam 1,000 mg bid stopped focal seizures, but myoclonus and all other symptoms
and signs remained. The clinical and laboratory settings lead us to assume SREAT.
On the 3rd day after admission we started treatment with 1,000 mg methylprednisolone
intravenously for 3 days. On the 6th day we continued with Prednisolon 100 mg orally
and tapered to 60 mg once a day within a week. Episodes of hallucinations and anxious
agitation were treated with haloperidol 2 mg and lorazepam 0.5 mg tid. On the 3rd
day of steroid treatment the patient began to improve. On the 5th day he was able
to communicate coherently. The psychiatric symptoms disappeared, and the respective
medication was discontinued. The patient was still temporally disorientated and had
slowed psychomotor functions, but gradually improved. The EEG improved. Fifteen days
after the start of steroids the patient was discharged. Prednisolone was tapered by
10 mg every 4 weeks.

The patient’s condition further improved. At follow-up in June 2013 he only had subtle
memory deficits and was slightly temporally disoriented but was fully aware of this
and capable of coping in his daily living. The anti-TPO concentration was back to
normal (Table 1). Ipilimumab therapy was not resumed and the patient received no other treatment
for his prostate cancer after these complications. He remained in complete remission
with normal PSA values until the last follow-up so far in July 2014.