Three women were consecutively admitted to our medical intensive care unit for thyrotoxicosis after the ingestion of dietary pills accidentally containing high levels of thyroxin. These cases were observed during an outbreak in the Paris area. Despite similar blood levels of thyroid hormones, their clinical presentation and outcome were very different. One patient developed febrile confusion and died from malignant hyperthermia. The second one had progressive confusion requiring mechanical plasma exchange therapy and had a favorable outcome. The third one had very moderate symptoms. These exceptional observations raise several issues concerning diagnosis, physiopathology and treatment of thyrotoxicosis factitia.

A 57-year-old woman was admitted to our Medical Intensive Care Unit (MICU) for shock, coma and high fever. She had no relevant medical history but was taking spironolactone, metformin, doxylamine and “homeopathic pills”. Her weight was 77 kg and height 176 cm. Ten days before admission, the patient reported headache. Three days before admission in our MICU, she became confused. Next day, she was referred to the emergency department of another hospital (hour 0, H0). She was disorientated and agitated without neurological abnormalities. Blood pressure was 190/90 mmHg, pulse, 146 beats per minute and temperature, 38 °C. Brain CT scan and CSF analysis were normal. She was given 100 mg of intravenous loxipamine (H2), aciclovir, ceftriaxone and amoxicillin and was admitted to the medical ward. As cultures of blood, urine and CSF were negative, and the C-reactive protein value was normal, anti-infective therapies were discontinued. However, the temperature remained high (39.2 °C, H24) despite acetaminophen. Because of increasing agitation she was given 100 mg of intravenous tiapride at H14 and H32. Her consciousness afterwards deteriorated (Glasgow Coma Scale GCS = 4) and she became hypotensive. She received fluid loading (normal saline), norepinephrine, and the trachea was intubated. Whole body CT scan showed no abnormalities. The patient was then referred to our MICU (H40). She had severe circulatory failure, with diffuse mottling, oliguria and a mean blood pressure of 70 mmHg while receiving 1.5 μg/kg/min norepinephrine. Central body temperature was 40.9 °C (Figure 1). Room temperature was 20 °C. Transthoracic echocardiography showed a hyperkinetic heart but no other abnormality. On admission, blood test results were: sodium: 154 mmol/L, bicarbonates: 16 mmol/L, chloride: 125 mmol/L, lactates: 3 mmol/L, creatine kinase: 588 IU/L, creatininaemia 76 μmol/L. Blood gas analysis showed pH: 7.33, PaO₂: 229 mmHg while under a 75% inspired fraction of oxygen and PaCO2: 32 mmHg. Total blood count was normal, prothrombin time, 47%, coagulation factor V, 62% and fibrinogen, 6.2 g/L. Serum toxic screening with mass spectrography was negative. Hydrocortisone (100 mg 3 times a day) was started (a later report showed that cortisol level was normal). Although there was no documented bacterial infection, vancomycin, cefotaxime and gentamicin were started. Because the patient’s body temperature rose to 42.3 °C at H48 despite external cooling, hemodialysis was performed with a dialysate temperature of 33 °C. There was no muscular rigidity. The patient’s temperature went down to 38.2 °C by the end of dialysis (H56). However, circulatory failure worsened and epinephrine was administered because of left ventricle hypokinesia (H62). Hemodialysis was again started because of symptomatic hyperkaliemia (8 mmol/L, H66) related to massive rhabdomyolysis. The patient died of refractory shock, 43 hours after MICU admission (H84). Two days later, the French health authorities issued a message warning against the toxicity of “dietary pills”, which had been manually prepared in one particular pharmacy and contained huge amount of thyroxin. It turned out that these “dietary pills” were the “homeopathic pills” taken by our patient. Analysis of blood drawn on MICU admission confirmed hyperthyroidism (Table 1).

A 71-year-old previously healthy woman was admitted to our MICU 5 days after admission of Patient one for severe thyrotoxicosis. She had a history of depression and had been treated for 1 year with similar “dietary pills”. Her free T4 and TSH levels were normal in 6 months before. One week before admission, she reported fatigue, headache, myalgia, palpitations and fever. She stopped the dietary pills. The day of admission, mild confusion occurred. The patient was contacted by health authorities as a patient who had been prescribed the suspectedly toxic “dietary pills”. She was referred to our institution (day 0, D0) because of high levels of serum thyroid hormone (Table 1). The patient was awake but severely confused. She had no chills, sweating, jaundice or neck rigidity. Blood pressure was 130/60 and body temperature was 37 °C. Except for tachyarrhythmia, cardio-pulmonary examination was normal. ECG revealed atrial fibrillation. The patient was given 40 mg oral propranolol 4 times a day, 100 mg hydrocortisone 3 times a day, cholestyramine 3 times a day, and was given 4 tablets of propylthiouracyl 4 times a day for 24 hours and subcutaneous heparin. On D3, she was unable to speak and severely agitated. No muscular rigidity was observed. Because of clinical degradation and high plasma thyroid hormone levels, plasma exchange (PE) therapy was performed on D3 with 1.5l of 4% albumin and 1.5 L of hydroxy-ethyl-amidon, and repeated on D4 with the addition of 1L fresh frozen plasma (Figure 2). After a second PE, the patient was placed on a ventilator because of impaired consciousness (GCS: 7). An EEG did not reveal any features of epilepsy. A CT scan of the head was normal. The thyroid hormone levels slowly returned to close to normal, the patient’s consciousness gradually improved. She was extubated on D10. She experienced a perfect cognitive recovery but exhibited flaccid tetraparesia. An electromyogram confirmed myoneurogen abnormalities. On D25 she was referred to a rehabilitation facility for persistent inability to stand up and walk alone.

A 40-year-old woman was admitted to our MICU 5 days after the admission of Patient two (day 0, D0) for thyrotoxicosis. Her medical history was uneventful. She had been overweight (94 kg, 165 cm), and had taken the “dietary pills”, since 2004. Three weeks before admission, she started complaining of asthenia, myalgia, headache, sweating, tremor of the lower limbs and dyspnea. She spontaneously stopped the pills 6 days before admission. She heard about the toxicity of the pills through the media and went to the emergency department of our hospital. On admission, physical examination was normal except sinusal tachycardia (113 beats/min). Echocardiography and EEG were unremarkable. She was admitted to the MICU for monitoring and was treated with 40 mg oral propranolol 4 times a day, cholestyramine 3 times a day and 100 mg intravenous hydrocortisone 3 times a day. The thyroid hormone levels measured at D1 showed hyperthyroidism (Table 1). On the same day the patient was agitated and was given 100 mg oral clorazepate. She improved and was referred to the endocrinology department on D4. She had then an uneventful follow-up. At D10, her thyroid hormone levels were still high : TSH = 0.03 mIU/L (0.15–3.7), total T4 = 264 pmol/L (80–160), free T4 = 66.5 pmol/L (7.5–21.1) and free T3 = 9 pmol/L (3.6–7).

Written informed consent to publication of the present reports was obtained from each patient or from their closest relatives. Thyroid tests were performed using the following methods: TSH, Access US hTSH (Beckman Coulter), normal range : 0.15–3.7 mIU/L; Unbound tri-iodothyronine, Access Free T3 (Beckman Coulter), normal range : 3.6–7.0 pmol/L; Unbound Thyroxin, Access Free T4 (Beckman Coulter), normal range: 7.5–21.0 pmol/L; Total Thyroxin, Access total T4 (Beckman Coulter) normal range: 75–160 mol/L; Thyroid-Binding Globulin, RIA-gnost TBG (CISbio International), normal range (non-pregnant adults): 10–42 mg/L.