Unmasking of Gitelman Syndrome during Pregnancy in an Adolescent with Thyrotoxic Crisis

Background. Gitelman syndrome (GS) is an inherited salt-losing renal tubulopathy characterized by hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria. Patients can be asymptomatic until late adolescence or adulthood, and hence may be discovered incidentally during presentation with other illnesses. GS has been described in association with thyroid disorders and should be considered in patients with hyperthyroidism and persistent hypokalemia, especially in those with associated hypomagnesemia and hypocalciuria. Case summary. In this report, we describe an 18-year-old female who presented with hyperemesis gravidarum and thyrotoxicosis, and was incidentally found to have GS, confirmed by the sequence analysis of SLC12A3. Conclusions. Thyroid dysfunctions, such as hypothyroidism, thyrotoxicosis, and thyroid nodules, may develop during pregnancy. A structural homology between the beta-human chorionic gonadotropin and thyroid stimulating hormone molecules, as well as their receptors is probably the basis for the transient thyrotoxicosis crisis during pregnancy. Since hyperemesis in pregnancy can also lead to hypokalemia and alkalosis, a high index of suspicion for GS during pregnancy is required for timely diagnosis and management.

Plasmapheresis as First Line Therapy for Thyrotoxicosis in a Critically Ill Patient

Introduction: The role of plasmapheresis (TPE) in thyrotoxicosis management is not well established. Its use may be determined on an individualized basis (1). We report a case of a critically ill patient where TPE was utilized as first-line therapy for refractory thyrotoxicosis. Clinical Case: A 33-year-old woman with Graves’ disease complicated by medication non-adherence presented with rapidly ascending paralysis and bulbar weakness. Primary work up was consistent with acute inflammatory demyelinating polyneuropathy (AIDP) based on EMG findings of motor fiber polyneuropathy with demyelinating features. Laboratory evaluation revealed uncontrolled hyperthyroidism (TSH <0.05 uU/mL, N 0.3-4.2 uU/mL; fT4 3.9 ng/dL, N 0.6-1.5 ng/dL; tT3 318, N 60-160 ng/dL). Initially, there was low concern for thyrotoxicosis based on a Burch-Wartofsky score of 15 (2). Standard dose methimazole and aggressive beta-blockade were initiated. Hospital course was complicated by hypoxic respiratory failure due to progressive paralysis requiring intubation and septic shock from Klebsiella pneumonia requiring initiation of pressors and broad-spectrum antibiotics. Biochemical evaluation showed increasing fT4 (3.8 ng/dL) and tT3 (419 ng/dL) levels. Burch-Wartofsky score increased to 55, consistent with a thyrotoxic crisis. Due to the patient’s critical condition, TPE was rapidly initiated along with standard therapy for thyrotoxic crisis (high dose methimazole, esmolol drip, stress dose corticosteroids, cholestyramine, and potassium iodide) as a bridge to definitive management with thyroidectomy. Rapid clinical improvement with a decline in fT4 levels (3.8 to 2.1 ng/dL) was noted after initiation of TPE with normalization in fT4 (1.5 ng/dL) and tT3 (54 ng/dL) after three sessions. Thyroidectomy was pursued after clinical stabilization. Surgical pathology showed diffuse papillary hyperplasia consistent with Graves’ disease. Due to persistent respiratory failure, the patient underwent tracheostomy placement. Repeat EMG revealed severe myopathic dysfunction without demyelinating features favoring a diagnosis of acute thyrotoxic myopathy over AIDP. Patient was ultimately discharged to a long term acute care facility due to slow neurological recovery. Conclusion: TPE should be considered as first line management in conjunction with conventional medical therapy in critically ill patients with thyrotoxicosis as a bridge to thyroidectomy due to rapid time to effect and patient stabilization. References: (1) Padmanabhan A, et al. J Clin Apher. 2019 Jun;34(3):171-354. (2) Bahn Chair RS, et al. Thyroid. 2011 Jun;21(6):593-646.

Plasmapheresis as an Effective Treatment for Thyroid Storm in Critical Patients: Case Reports and Systematic Literature Review

Background: Thyrotoxic crisis is a rare, multisystemic and lethal condition, especially when its reversal is delayed. The Burch Wartofsky score establishes severity and predicts the indication of plasmapheresis, but once there is organ dysfunction this therapy should be considered despite of the score. When it is added to conventional treatments it is really effective because of the quick clinical compensation of critically ill patients regardless of the main trigger factor of this emergency. Clinical Cases: 5 patients with thyrotoxic crisis, 1 man and 4 women that had Graves’disease (4 cases) or TSH-secreting tumor (1 case). The precipitating factors were: 1 case due to orchitis, 2 due to poor adhesion, 1 due to antithyroid drugs hepatoxicity and 1 due to ketoacidosis. All them had elevated free T4 ranging from 3.38 to >7.77 ng/dL. All them had high Burch Wartofsky scores (55 to 70) and severe organ dysfunctions: 4 cases with hepatopathy (hepatosplenomegaly, jaundice and coagulopathy) and cardiopathy (diastolic dysfunction and pulmonary hypertension) and 1 case with severe diabetic ketoacidosis. Plasmapheresis (2 to 3 sessions were performed) were indicated for clinical compensation and so subsequent definitive treatment: 3 cases received radioiodine therapy and 1 case had total thyroidectomy. All of them progressed well. The patient who died had already severe prior comorbidities. We performed a systematic survey on PubMed of English articles (case reports and reviews) in humans and we analyzed our 5 cases along with the 108 articles about the use of plasmapheresis in thyroid storm from 1970 to 2020 and we compare them to 394 ones of conventional treatments in past 10 years. Our objective was to evidence plasmapheresis is not related to a higher mortality of patients who underwent to it. We found 7% of mortality in both groups. The chi square test showed an Odds Ratio of (CI 95%) = 1,091 reinforcing there is no relation between number of deaths and treatment type. Conclusion: Plasmapheresis is a therapeutic option with few reports in the literature and without clear guidelines about indication criteria or better timing to initiate it. The statistical analysis showed that 3 or more organ dysfunctions in thyroid storm are related to higher death rates. Its early employment within 24 hours of the initial symptoms and the prompt normalization of free T4 are related to lower mortality. It is a safe and effective therapy that allows thyroid storm patients to be compensated to receive definitive treatment with lower chances of death. Reference: Ono Y, Ono S, Yasunaga H, Matsui H, Fushimi K, Tanaka Y. Factors Associated With Mortality of Thyroid Storm: Analysis Using a National Inpatient Database in Japan. Medicine (Baltimore). 2016;95(7):e2848.

Thyrotoxicosis. Clinical guidelines for diagnosis and treatment. Part ІІ

Background. Recently they have reported an increased rate of thyrotoxicosis, which is characterized by polyetiology, a variety of clinical manifestations and potential treatment. Appropriate treatment requires an accurate diagnosis and depends on the comorbidities and preferences of the patient. Purpose. To highlight the key points of clinical guidelines for diagnosis and treatment of thyrotpxicosis provided by the American Thyroid Association and the American Association of Clinical Endocrinologists, US Endocrine Society dealing with diagnosis and treatment of thyroid diseases as well as the local clinical protocols of SO «Grigoriev Institute for Medical Radiology and Oncology of the National Academy of Medical Sciences of Ukraine». Materials and methods. Based on the search of contributions in the electronic databases over the last 5 years, which are included in the Cochrane Library, PUBMED and MEDLINE databases. Clinical guidelines are based on expert consensus and assessing the significance according to the international guidelines for thyrotoxicosis. Results and discussion. The paper deals with up-to-date guidelines on diagnosis, management and treatment of patients with different forms of thyrotoxicosis. It presents a detailed strategy for those patients depending on etiology of the disease. The therapeutic approaches to treating Graves’ disease, autoimmune ophthalmopathy, thyrotoxic crisis, gravidae as well as the peculiarities of treating patients with subclinical hyperthyroidism and iodine-induced thyrotoxicosis have been substantiated. Conclusions. The treatment of thyrotoxicosis remains a challenging issue of modern internal medicine. Despite the existing numerous clinically proven protocols for the treatment of this pathology, the comorbid background of patients complicates following them. The implementation of the provided protocol elements will make it possible to introduce the principles of a customized approach in thyrotoxicosis patients.

Medicine

This chapter in the Oxford Handbook of Emergency Medicine encompasses all medicine practised in the emergency department (ED). It explores electrocardiogram interpretation, chest pain, cardiac ischaemia, acute coronary syndrome, ST segment elevation MI (STEMI), myocardial infarction, acute pericarditis, bradyarrhythmia, tachycardia, broad complex and regular narrow complex tachyarrhythmia, atrial fibrillation, hypertensive problems, implantable cardiac devices, and aortic dissection. It examines haemoptysis and administering oxygen, the dyspnoeic patient, hyperventilation, blood gas, pulmonary oedema, pleural effusion, asthma, chronic obstructive pulmonary disease (COPD), pneumonia, pulmonary aspiration, and spontaneous pneumothorax. It discusses deep venous thrombosis and pulmonary embolism, gastrointestinal bleeding, gastrostomy, and refeeding syndrome. Jaundice is explored, alongside ascites and liver failure. It discusses headache, subarachnoid haemorrhage, migraine, giant cell arteritis, space-occupying lesions, acute confusional state (delirium), transient global amnesia, and the unconscious patient. Falls in the elderly are examined, along with collapse and syncope, acute generalized weakness, stroke, intracerebral haemorrhage, transient ischaemic attacks, seizures, and status epilepticus. It explores hypoglycaemia, hyperglycaemic crises, sodium derangements, Addisonian crisis, and thyrotoxic crisis. It discusses acute kidney injury, chronic kidney disease, urinary tract infection, hyperkalaemia, and hypokalaemia. It ends with an exploration of porphyria, bleeding disorders, anticoagulants, blood transfusion, and sickle-cell disease.

Rapid control of thyrotoxicosis for urgent thyroidectomy

<p>Surgery for Grave’s disease is one possible option for definitive treatment. Thyroidectomy is performed after achieving a euthyroid state. Pre-operative preparation of the hyperthyroid patient is essential to avoid peri- and post-operative serious complications due to thyrotoxicosis mainly thyrotoxic crisis and death. The mainstay of preparation is the administration of anti-thyroid drugs. Occasionally rapid pre-operative optimization is required for special reasons (intolerance or side effects to anti-thyroid drugs or an aggravated serious disease with thyrotoxicosis). Various regimens for this aim were suggested with protocols composing various combination iodine (as a Lugol’s solution, or iopanoic acid, or ipodat sodium), steroids, usually dexamethasone and beta blockers, alternatively other options are plasmapheresis, lithium and exchange ionic resin. The restoration of hyperthyroid Grave’s disease to euthyroidism in our patient was rapidly accomplished with iodine, dexamethasone and beta blockers (at seventh day without complications). We propose a possible treatment protocol for these cases.</p>