Unexpected outcome ( positive or negative) including adverse drug reactions
CASE REPORT
Complete recovery after severe myxoedema coma complicated by status epilepticus Jesper Fjølner,1 Esben Søndergaard,2 Ulla Kampmann,2 Søren Nielsen2 1
Department of Anaesthesiology and Intensive Care, Aarhus University Hospital, Aarhus C, Denmark 2 Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus C, Denmark Correspondence to Dr Jesper Fjølner, [email protected] Accepted 19 February 2015
SUMMARY We report a case of life-threatening myxoedema presenting with hypothermia, hypotension, bradycardia, pericardial effusion and deep coma. The condition was complicated by prolonged status epilepticus. The optimal treatment strategy has been debated over the years and the literature is briefly reviewed. Treatment with L-thyroxine (LT4) monotherapy without initial loading dose and with no L-triiodothyronine (LT3) treatment was successful with full recovery after hospitalisation for more than a month. Myxoedema coma is a rare, reversible condition with a high mortality and should be considered as a differential diagnosis in medical emergencies.
BACKGROUND This manuscript describes a case of deep myxoedema coma (MC). This rare endocrine emergency may pose a diagnostic challenge as the symptoms overlap with other more common critical conditions. The patient surprisingly survived despite complicating status epilepticus, which is usually a grave prognostic sign. The treatment for this condition is debated. We describe an intentionally cautious but successful treatment and review the literature.
CASE PRESENTATION
To cite: Fjølner J, Søndergaard E, Kampmann U, et al. BMJ Case Rep Published online: [please include Day Month Year] doi:10.1136/bcr-2014209071
A 72-year-old woman was found in her home in a comatose state. She had a Glasgow Coma Scale (GCS) Score of 3, one pupil was dilated and a cerebral haemorrhage was suspected. Owing to hypoventilation, she was endotracheally intubated and brought to the emergency room. She had not been hospitalised over the past 10 years and took no prescription medicine. Alcohol overuse was initially suspected and later confirmed. Vital signs on arrival were a core temperature of 30°C (86°F), hypotension (65/40 mm Hg) and fluctuating oxygen saturation. Physical examination revealed generalised and facial non-pitting oedema, periorbital oedema, coarse hair and desquamation of the skin. An ECG showed low voltage, sinus bradycardia, long QT-interval and a first degree AV-block (figure 1). Arterial blood gas analysis was normal apart from p-lactate of 2.8 mmol/L and haemoglobin of 4.2 mmol/L. P-Sodium was 154 mmol/L, probably due to an initial administration of hypertonic saline. CT of the head and truncus revealed no brain pathology but showed a large pericardial effusion as the only abnormal finding (figure 2). In the intensive care unit (ICU) the patient was placed on mechanical ventilation. Circulation was
dependent on vasopressor support with norepinephrine, and rewarming was initiated with an inflatable air cover (‘Bair-Hugger’, Arizant Healthcare, 3M, USA) along with empirical antibiotic treatment. A pericardial effusion of 900 mL was evacuated, but the need for vasopressor support to maintain a mean arterial pressure above 60 mm Hg was unchanged. After ICU admission, myoclonia and seizures were noticed, and an EEG showed status epilepticus, which was treated with a valproate loading dose followed by maintenance infusion. Thyroid status revealed thyroid-stimulating hormone of 52.45 mIU/L (range 0.3–4.5), total triiodothyronine (T3) of 75 mg/day) were both associated with increased mortality, especially in elderly patients. The study also suggested better survival with low-dose LT4 treatment but concluded that low-dose LT4 or LT3 is safe and recommendable. Several authors recommend intravenous LT4 monotherapy23 24 but some reviews also suggest addition of LT3 in selected patients.20 25 Thus for elderly, fragile or cardiac unstable patients the use of intravenous LT4 as monotherapy is recommended. Some authors recommend administration of a loading bolus of intravenous LT4 of 200–500 mg, as this seems safe, bringing up circulating levels of T4 quickly and boosting peripheral T3-conversion. In one prospective study, this appeared to reduce mortality.3 In the present case, no LT3 and no bolus of LT4 was given because of the fragility of the patient, and due to the risk of cardiac complications. We administered 100 mg intravenous LT4 daily. As daily replacement dose for primary hypothyroidism is about 75–150 mg,23 26 our treatment regimen was intentionally conservative. This report describes a case of severe MC complicated with status epilepticus. Previously, there have been very few reports describing a favourable outcome. After 1.5 months of LT4 monotherapy treatment, in combination with supportive measures, the patient was discharged with no sequelae. MC with status epilepticus is a serious and rare combination that should be recognised by healthcare providers to ensure prompt diagnosis and treatment.
REFERENCES 1 2
3
4 5 6 7 8 9 10
11 12 13 14
15 16 17
Learning points ▸ Myxoedema coma is a rare but treatable endocrine emergency and must be considered as a differential diagnosis, when relevant, as symptoms overlap with other more common critical conditions. ▸ Treatment may be successful with intravenous L-thyroxine monotherapy. ▸ There are extremely few previous reports of myxoedema coma with complicating status epilepticus describing a favourable outcome.
18 19 20 21
22 23
24
Competing interests None. Patient consent Not obtained. Provenance and peer review Not commissioned; externally peer reviewed.
25 26
Wartofsky L. Myxedema coma. Endocrinol Metab Clin North Am 2006;35: 687–98. Yamamoto T, Fukuyama J, Fujiyoshi A. Factors associated with mortality of myxedema coma: report of eight cases and literature survey. Thyroid 1999;9:1167–74. Rodríguez I, Fluiters E, Pérez-Méndez LF, et al. Factors associated with mortality of patients with myxoedema coma: prospective study in 11 cases treated in a single institution. J Endocrinol 2004;180:347–50. Dutta P, Bhansali A, Masoodi SR, et al. Predictors of outcome in myxoedema coma: a study from a tertiary care centre. Crit Care 2008;12:R1. Beynon J, Akhtar S, Kearney T. Predictors of outcome in myxoedema coma. Crit Care 2008;12:111. Blum M. Myxedema coma. Am J Med Sci 1972;264:432–43. Kwaku MP, Burman KD. Myxedema coma. J Intensive Care Med 2013;22:224–31. Sanders V. Neurologic manifestations of myxedema. N Engl J Med 1962;266:599–603. Heinrich TW, Grahm G. Hypothyroidism presenting as psychosis: myxedema madness revisited. Prim Care Companion J Clin Psychiatry 2003;5:260–6. Constant EL, de Volder AG, Ivanoiu A, et al. Cerebral blood flow and glucose metabolism in hypothyroidism: a positron emission tomography study. J Clin Endocrinol Metab 2001;86:3864–70. Jansen HJ, Doebé SRO, Louwerse ES, et al. Status epilepticus caused by a myxoedema coma. Neth J Med 2006;64:202–5. Woods KL, Holmes GK. Myxoedema coma presenting in status epilepticus. Postgrad Med J 1977;53:46–8. Schenck J, Rizvi A, Lin T. Severe primary hypothyroidism presenting with torsades de pointes. Am J Med Sci 2006;331:154–6. Yamanaka S, Kumon Y, Matsumura Y, et al. Link between pericardial effusion and attenuation of QRS voltage in patients with hypothyroidism. Cardiology 2010;116:32–6. Nyrop M. [Cardiovascular manifestations of hypothyroidism]. Ugeskr Læger 1991;26:1849–51. Polikar R, Kennedy B. Decreased adrenergic sensitivity in patients with hypothyroidism. J Am Coll Cardiol 1990;15:1–2. Polikar R, Kennedy B, Ziegler M, et al. Plasma norepinephrine kinetics, dopamine-beta-hydroxylase, and chromogranin-A, in hypothyroid patients before and following replacement therapy. J Clin Endocrinol Metab 1990;70:277–81. Dyson A, Wood M. Treatment of myxoedema coma. Lancet 1956;:768–9. Sarlis NJ, Gourgiotis L. Thyroid emergencies. Rev Endocr Metab Disord 2003;4:129–36. Mathew V, Misgar RA, Ghosh S, et al. Myxedema coma: a new look into an old crisis. J Thyroid Res 2011;2011:493462. Chernow B, Burman K, McGuire R, et al. T3 may be a better agent than T4 in the critically ill hypothyroid patient—evaluation of transport across the blood-brain barrier in a primate model. Crit Care Med 1983;11:99–104. Hylander B, Rosenqvist U. Treatment of myxoedema coma factors associated with fatal outcome. Eur J Endocrinol 1985;108:65–71. Arlot S, Debussche X, Lalau JD, et al. Myxoedema coma: response of thyroid hormones with oral and intravenous high-dose L-thyroxine treatment. Intensive Care Med 1991;17:16–18. Jordan R. Myxedema coma. Pathophysiology, therapy, and factors affecting prognosis. Med Clin North Am 1995;79:185–94. Klubo-Gwiezdzinska J, Wartofsky L. Thyroid emergencies. Med Clin North Am 2012;96:385–403. Wall C. Myxoedema coma diagnosis and treatment. Am Fam Physician 2000;62:2485–90.
Copyright 2015 BMJ Publishing Group. All rights reserved. For permission to reuse any of this content visit http://group.bmj.com/group/rights-licensing/permissions. BMJ Case Report Fellows may re-use this article for personal use and teaching without any further permission. Become a Fellow of BMJ Case Reports today and you can: ▸ Submit as many cases as you like ▸ Enjoy fast sympathetic peer review and rapid publication of accepted articles ▸ Access all the published articles ▸ Re-use any of the published material for personal use and teaching without further permission For information on Institutional Fellowships contact [email protected] Visit casereports.bmj.com for more articles like this and to become a Fellow
Fjølner J, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2014-209071
3
CASE REPORT
Complete recovery after severe myxoedema coma complicated by status epilepticus Jesper Fjølner,1 Esben Søndergaard,2 Ulla Kampmann,2 Søren Nielsen2 1
Department of Anaesthesiology and Intensive Care, Aarhus University Hospital, Aarhus C, Denmark 2 Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus C, Denmark Correspondence to Dr Jesper Fjølner, [email protected] Accepted 19 February 2015
SUMMARY We report a case of life-threatening myxoedema presenting with hypothermia, hypotension, bradycardia, pericardial effusion and deep coma. The condition was complicated by prolonged status epilepticus. The optimal treatment strategy has been debated over the years and the literature is briefly reviewed. Treatment with L-thyroxine (LT4) monotherapy without initial loading dose and with no L-triiodothyronine (LT3) treatment was successful with full recovery after hospitalisation for more than a month. Myxoedema coma is a rare, reversible condition with a high mortality and should be considered as a differential diagnosis in medical emergencies.
BACKGROUND This manuscript describes a case of deep myxoedema coma (MC). This rare endocrine emergency may pose a diagnostic challenge as the symptoms overlap with other more common critical conditions. The patient surprisingly survived despite complicating status epilepticus, which is usually a grave prognostic sign. The treatment for this condition is debated. We describe an intentionally cautious but successful treatment and review the literature.
CASE PRESENTATION
To cite: Fjølner J, Søndergaard E, Kampmann U, et al. BMJ Case Rep Published online: [please include Day Month Year] doi:10.1136/bcr-2014209071
A 72-year-old woman was found in her home in a comatose state. She had a Glasgow Coma Scale (GCS) Score of 3, one pupil was dilated and a cerebral haemorrhage was suspected. Owing to hypoventilation, she was endotracheally intubated and brought to the emergency room. She had not been hospitalised over the past 10 years and took no prescription medicine. Alcohol overuse was initially suspected and later confirmed. Vital signs on arrival were a core temperature of 30°C (86°F), hypotension (65/40 mm Hg) and fluctuating oxygen saturation. Physical examination revealed generalised and facial non-pitting oedema, periorbital oedema, coarse hair and desquamation of the skin. An ECG showed low voltage, sinus bradycardia, long QT-interval and a first degree AV-block (figure 1). Arterial blood gas analysis was normal apart from p-lactate of 2.8 mmol/L and haemoglobin of 4.2 mmol/L. P-Sodium was 154 mmol/L, probably due to an initial administration of hypertonic saline. CT of the head and truncus revealed no brain pathology but showed a large pericardial effusion as the only abnormal finding (figure 2). In the intensive care unit (ICU) the patient was placed on mechanical ventilation. Circulation was
dependent on vasopressor support with norepinephrine, and rewarming was initiated with an inflatable air cover (‘Bair-Hugger’, Arizant Healthcare, 3M, USA) along with empirical antibiotic treatment. A pericardial effusion of 900 mL was evacuated, but the need for vasopressor support to maintain a mean arterial pressure above 60 mm Hg was unchanged. After ICU admission, myoclonia and seizures were noticed, and an EEG showed status epilepticus, which was treated with a valproate loading dose followed by maintenance infusion. Thyroid status revealed thyroid-stimulating hormone of 52.45 mIU/L (range 0.3–4.5), total triiodothyronine (T3) of 75 mg/day) were both associated with increased mortality, especially in elderly patients. The study also suggested better survival with low-dose LT4 treatment but concluded that low-dose LT4 or LT3 is safe and recommendable. Several authors recommend intravenous LT4 monotherapy23 24 but some reviews also suggest addition of LT3 in selected patients.20 25 Thus for elderly, fragile or cardiac unstable patients the use of intravenous LT4 as monotherapy is recommended. Some authors recommend administration of a loading bolus of intravenous LT4 of 200–500 mg, as this seems safe, bringing up circulating levels of T4 quickly and boosting peripheral T3-conversion. In one prospective study, this appeared to reduce mortality.3 In the present case, no LT3 and no bolus of LT4 was given because of the fragility of the patient, and due to the risk of cardiac complications. We administered 100 mg intravenous LT4 daily. As daily replacement dose for primary hypothyroidism is about 75–150 mg,23 26 our treatment regimen was intentionally conservative. This report describes a case of severe MC complicated with status epilepticus. Previously, there have been very few reports describing a favourable outcome. After 1.5 months of LT4 monotherapy treatment, in combination with supportive measures, the patient was discharged with no sequelae. MC with status epilepticus is a serious and rare combination that should be recognised by healthcare providers to ensure prompt diagnosis and treatment.
REFERENCES 1 2
3
4 5 6 7 8 9 10
11 12 13 14
15 16 17
Learning points ▸ Myxoedema coma is a rare but treatable endocrine emergency and must be considered as a differential diagnosis, when relevant, as symptoms overlap with other more common critical conditions. ▸ Treatment may be successful with intravenous L-thyroxine monotherapy. ▸ There are extremely few previous reports of myxoedema coma with complicating status epilepticus describing a favourable outcome.
18 19 20 21
22 23
24
Competing interests None. Patient consent Not obtained. Provenance and peer review Not commissioned; externally peer reviewed.
25 26
Wartofsky L. Myxedema coma. Endocrinol Metab Clin North Am 2006;35: 687–98. Yamamoto T, Fukuyama J, Fujiyoshi A. Factors associated with mortality of myxedema coma: report of eight cases and literature survey. Thyroid 1999;9:1167–74. Rodríguez I, Fluiters E, Pérez-Méndez LF, et al. Factors associated with mortality of patients with myxoedema coma: prospective study in 11 cases treated in a single institution. J Endocrinol 2004;180:347–50. Dutta P, Bhansali A, Masoodi SR, et al. Predictors of outcome in myxoedema coma: a study from a tertiary care centre. Crit Care 2008;12:R1. Beynon J, Akhtar S, Kearney T. Predictors of outcome in myxoedema coma. Crit Care 2008;12:111. Blum M. Myxedema coma. Am J Med Sci 1972;264:432–43. Kwaku MP, Burman KD. Myxedema coma. J Intensive Care Med 2013;22:224–31. Sanders V. Neurologic manifestations of myxedema. N Engl J Med 1962;266:599–603. Heinrich TW, Grahm G. Hypothyroidism presenting as psychosis: myxedema madness revisited. Prim Care Companion J Clin Psychiatry 2003;5:260–6. Constant EL, de Volder AG, Ivanoiu A, et al. Cerebral blood flow and glucose metabolism in hypothyroidism: a positron emission tomography study. J Clin Endocrinol Metab 2001;86:3864–70. Jansen HJ, Doebé SRO, Louwerse ES, et al. Status epilepticus caused by a myxoedema coma. Neth J Med 2006;64:202–5. Woods KL, Holmes GK. Myxoedema coma presenting in status epilepticus. Postgrad Med J 1977;53:46–8. Schenck J, Rizvi A, Lin T. Severe primary hypothyroidism presenting with torsades de pointes. Am J Med Sci 2006;331:154–6. Yamanaka S, Kumon Y, Matsumura Y, et al. Link between pericardial effusion and attenuation of QRS voltage in patients with hypothyroidism. Cardiology 2010;116:32–6. Nyrop M. [Cardiovascular manifestations of hypothyroidism]. Ugeskr Læger 1991;26:1849–51. Polikar R, Kennedy B. Decreased adrenergic sensitivity in patients with hypothyroidism. J Am Coll Cardiol 1990;15:1–2. Polikar R, Kennedy B, Ziegler M, et al. Plasma norepinephrine kinetics, dopamine-beta-hydroxylase, and chromogranin-A, in hypothyroid patients before and following replacement therapy. J Clin Endocrinol Metab 1990;70:277–81. Dyson A, Wood M. Treatment of myxoedema coma. Lancet 1956;:768–9. Sarlis NJ, Gourgiotis L. Thyroid emergencies. Rev Endocr Metab Disord 2003;4:129–36. Mathew V, Misgar RA, Ghosh S, et al. Myxedema coma: a new look into an old crisis. J Thyroid Res 2011;2011:493462. Chernow B, Burman K, McGuire R, et al. T3 may be a better agent than T4 in the critically ill hypothyroid patient—evaluation of transport across the blood-brain barrier in a primate model. Crit Care Med 1983;11:99–104. Hylander B, Rosenqvist U. Treatment of myxoedema coma factors associated with fatal outcome. Eur J Endocrinol 1985;108:65–71. Arlot S, Debussche X, Lalau JD, et al. Myxoedema coma: response of thyroid hormones with oral and intravenous high-dose L-thyroxine treatment. Intensive Care Med 1991;17:16–18. Jordan R. Myxedema coma. Pathophysiology, therapy, and factors affecting prognosis. Med Clin North Am 1995;79:185–94. Klubo-Gwiezdzinska J, Wartofsky L. Thyroid emergencies. Med Clin North Am 2012;96:385–403. Wall C. Myxoedema coma diagnosis and treatment. Am Fam Physician 2000;62:2485–90.
Copyright 2015 BMJ Publishing Group. All rights reserved. For permission to reuse any of this content visit http://group.bmj.com/group/rights-licensing/permissions. BMJ Case Report Fellows may re-use this article for personal use and teaching without any further permission. Become a Fellow of BMJ Case Reports today and you can: ▸ Submit as many cases as you like ▸ Enjoy fast sympathetic peer review and rapid publication of accepted articles ▸ Access all the published articles ▸ Re-use any of the published material for personal use and teaching without further permission For information on Institutional Fellowships contact [email protected] Visit casereports.bmj.com for more articles like this and to become a Fellow
Fjølner J, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2014-209071
3
