Faculty of Medicine

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    Nephrotic Syndrome Induced by Tiopronin in a Male Patient with Cystinuria.
    (Macedonian Academy of Sciences and Arts, 2025-06)
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    Severova Stojanoska, Ana
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    Gjorgjievska, Julija
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    Cystinuria is a rare, lifelong, autosomal recessive disorder characterized by high urine cystine excretion, leading to chronic and recurrent kidney stone formation. This inherited metabolic disorder occurs due to defective cystine, lysine, ornithine, and arginine reabsorption in the brush border membrane of the proximal renal tubule (S3 segment) and the gastrointestinal epithelial cells. Tiopronin is a thiol agent used in the treatment of severe homozygous cystinuria in patients who are resistant to conservative measures. We report an 18-year-old male with cystinuria confirmed by genetic testing, who was treated with conservative measures such as high fluid intake, low sodium diet, and oral potassium citrate since the diagnosis was made at four years of age. However, due to the recurrence of several calculi in both kidneys, tiopronin treatment was initiated at the dose of 250 mg three times a day. After three months of therapy, the patient developed nephrotic syndrome with proteinuria of 6.6 g/l, hypoproteinemia, hyperlipidemia, and edema. Considering the adverse effect of tiopronin, the drug was immediately withdrawn and the patient was managed with human albumin substitution, diuretics, and angiotensin receptor blocker, without corticosteroids. Complete clinical and biochemical remission was achieved within 7 days. Clinicians should be aware of this rare but serious adverse effect of tiopronin, and monitor patients receiving tiopronin carefully for the possible occurrence of edema, proteinuria, with the aim of timely intervention and tiopronin discontinuation.
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    Medication-induced Serotonin Syndrome
    (Macedonian Association of Internal Medicine, 2022-05)
    The increased prevalence of depression worldwide was amplified with COVID-19 pandemic which triggered 25% increase in prevalence of anxiety and depression (WHO 2022), with consequential increased use of antidepressants, associated with adverse reactions such as serotonin syndrome (SS) and their use in acute poisonings. Increased prescription of serotonin re-uptake inhibitors was registered in North Macedonia during last four years. SS is a potentially life-threatening clinical condition associated with increased serotonergic activity in the central nervous system. It is induced by certain herbs, medications in therapeutic doses and unintentional drug interactions as well as with psychoactive substances and self-poisoning. Clinically is presented as a triad of changes in mental status, autonomic hyperactivity and neuromuscular abnormalities, with prognosis ranging from benign to lethal. The diagnosis is based on medical history and clinical presentation. The signs appear within 24 hours, usually within the first 6 hours of initiating therapy. Typical clinical signs are tachycardia and hypertension, but in severe cases hyperthermia and dramatic changes in pulse, blood pressure, mental status, neuromuscular aberrations and DIC may develop. Diagnosis is made using Hunter's criteria for serotonin toxicity. Differential diagnoses of SS include ischemic brain events, meningoencephalitis, neuroleptic malignant or anticholinergic syndrome, malignant hyperthermia, intoxication by sympathomimetic agents, benzodiazepine withdrawal syndrome. The treatment of serotonin toxicity depends on the severity of the clinical presentation (mild, moderate, severe) and ranges from symptomatic to administration of 5-HT2 receptor antagonists (Cyproheptadine) and artificial ventilation. Thinking of SS helps us to avoid the inability to recognize the syndrome, misdiagnosis and late treatment considering the fast rate of SS progression.