Myxoedema coma - Clinicals, Diagnosis, and Management

Emergency Medicine

Clinicals - History

Fact Explanation
Previous hypothyroidism. The myxoedema coma or hypothyroid coma is a rare but life threatening complication of hypothyroidism. It is the most severe presentation of profound hypothyroidism and is often fatal in spite of therapy. Some patients may have been treated for hypothyroidism but the crisis has been precipitated by a stress factor (as follows) or some of them may have been ignoring the treatments. Still, some patients present with a crisis for the first time. Previous hypothyroidism.
The myxoedema coma or hypothyroid coma is a rare but life threatening complication of hypothyroidism. It is the most severe presentation of profound hypothyroidism and is often fatal in spite of therapy. Some patients may have been treated for hypothyroidism but the crisis has been precipitated by a stress factor (as follows) or some of them may have been ignoring the treatments. Still, some patients present with a crisis for the first time.
A precipitating factor In patients with hypothyroidism, a stress factor can precipitate a myxoedema coma. The known stress factors are infections, burns, hypoglycemia, hypothermia, surgery, trauma and some drugs like Lithium. Treatment defaulters have been reported to present with more severe illness. A precipitating factor
In patients with hypothyroidism, a stress factor can precipitate a myxoedema coma. The known stress factors are infections, burns, hypoglycemia, hypothermia, surgery, trauma and some drugs like Lithium. Treatment defaulters have been reported to present with more severe illness.
A varying degree of altered consciousness The patients with hypothyroid coma can present with any degree of clouded consciousness ranging from mild to a severe psychotic state. Long-standing altered consciousness could be due to untreated hypothyroidism. Some cases may represent stroke syndromes. It's called "myxoedema madness" But the other more common causes of altered consciousness should be evaluated and excluded. i.e. hepatic encephalopathy. A varying degree of altered consciousness
The patients with hypothyroid coma can present with any degree of clouded consciousness ranging from mild to a severe psychotic state. Long-standing altered consciousness could be due to untreated hypothyroidism. Some cases may represent stroke syndromes. It's called "myxoedema madness" But the other more common causes of altered consciousness should be evaluated and excluded. i.e. hepatic encephalopathy.
Swelling of ankles Edema of ankles or generalized edema is a common presentation severe hypothyroidism. Laryngeal edema is a potential mortality factor. Swelling of ankles
Edema of ankles or generalized edema is a common presentation severe hypothyroidism. Laryngeal edema is a potential mortality factor.
Generalized weakness Muscle weakness and fatigue are very common features of hypothyroidism. It can affect various muscle groups. i.e. the diaphragm. Generalized weakness
Muscle weakness and fatigue are very common features of hypothyroidism. It can affect various muscle groups. i.e. the diaphragm.
Acute constipation Due to the paralytic ileus in acute severe hypothyroidism. Thyroxine is an essential hormone to maintain the bowel movements. Acute constipation
Due to the paralytic ileus in acute severe hypothyroidism. Thyroxine is an essential hormone to maintain the bowel movements.
Fainting They can present with acute myocardial fibrillations, causing syncope. Fainting
They can present with acute myocardial fibrillations, causing syncope.
Sudden death Sudden death has been reported in profound hypothyroidism. The thermoregulation, cardiac dysfunction may be causative factors. Sudden death
Sudden death has been reported in profound hypothyroidism. The thermoregulation, cardiac dysfunction may be causative factors.

Clinicals - Examination

Fact Explanation
Hypothermia Thyroxine is important in thermoregulation mechanisms. In hypothyroidism, the temperature set point is lowered. Hypothermia is a common feature in severe hypothyroidism. Hypothermia
Thyroxine is important in thermoregulation mechanisms. In hypothyroidism, the temperature set point is lowered. Hypothermia is a common feature in severe hypothyroidism.
Skin changes In addition to features of autoimmune diseases like vitiligo , chronic dermatosis has been found in higher incidences in thyroid disorders. Myxedema refers to the skin condition caused by increased glycosaminoglycan deposition in the skin. Generalized myxedema is still the classic cutaneous sign of hypothyroidism. The most notable content of these edematous parts are hyaluronic acid. Apart from those, coarse skin, thick skin, yellow coloration, dry skin and reduced sweating have been reported commonly. Skin changes
In addition to features of autoimmune diseases like vitiligo , chronic dermatosis has been found in higher incidences in thyroid disorders. Myxedema refers to the skin condition caused by increased glycosaminoglycan deposition in the skin. Generalized myxedema is still the classic cutaneous sign of hypothyroidism. The most notable content of these edematous parts are hyaluronic acid. Apart from those, coarse skin, thick skin, yellow coloration, dry skin and reduced sweating have been reported commonly.
Peripheral edema The edema is due to mucopolysaccharide deposition, as mentioned above. As a result the skin does not pit with pressure. Peripheral edema
The edema is due to mucopolysaccharide deposition, as mentioned above. As a result the skin does not pit with pressure.
Low blood pressure Hypotension is one of the common symptoms of hypothyroidism. It's also a factor determining the mortality in hypothyroid coma. Postural drop of blood pressure has also been reported in hypothyroid patients. Low blood pressure
Hypotension is one of the common symptoms of hypothyroidism. It's also a factor determining the mortality in hypothyroid coma. Postural drop of blood pressure has also been reported in hypothyroid patients.
A neck lump A neck lump confirming a goiter is suggestive of a thyroid disorder. A neck lump
A neck lump confirming a goiter is suggestive of a thyroid disorder.
Features of autoimmune conditions In instances where hypothyroidism is due to autoimmune thyroiditis. The common findings are vitiligo, alopecia and rheumatoid features. Features of autoimmune conditions
In instances where hypothyroidism is due to autoimmune thyroiditis. The common findings are vitiligo, alopecia and rheumatoid features.
Features of tarnsudative fluid collections in body spaces. i.e. Pericardial effusions, pleural effusion and ascites In profound hypothyroidism, there is a fluid transudation in body cavities. To exclude that, examining for dullness in chest and abdomen is necessary. Features of tarnsudative fluid collections in body spaces. i.e. Pericardial effusions, pleural effusion and ascites
In profound hypothyroidism, there is a fluid transudation in body cavities. To exclude that, examining for dullness in chest and abdomen is necessary.
Altered consciuosness Glasgow coma scale, Mini-Mental score and Mental State Examination are important, given there is adequate time. Patients can have a varying altered consciousness that probably might even progress to acute psychotic state, also known as "myxoedema madness" Altered consciuosness
Glasgow coma scale, Mini-Mental score and Mental State Examination are important, given there is adequate time. Patients can have a varying altered consciousness that probably might even progress to acute psychotic state, also known as "myxoedema madness"

Investigations - Diagnosis

Fact Explanation
Complete blood count Leucocyte count and differential count are important in diagnosing whether there is an infection present. Complete blood count
Leucocyte count and differential count are important in diagnosing whether there is an infection present.
Free T3 and T4 assay Free thyroid hormones are very low or even undetectable in hypothyroid crisis. Free T3 and T4 assay
Free thyroid hormones are very low or even undetectable in hypothyroid crisis.
TSH level TSH level can be elevated, and those instances it describes a primary thyroid disorder. TSH level
TSH level can be elevated, and those instances it describes a primary thyroid disorder.
Serum electrolytes Hypothyroidism is a cause for hyponatremia. Serum electrolytes
Hypothyroidism is a cause for hyponatremia.
Chest x-ray Radiological findings are pericardial and pleural effusions, cardiomegaly and in case of large goiters, tracheal compression and retrosternal extension. Chest x-ray
Radiological findings are pericardial and pleural effusions, cardiomegaly and in case of large goiters, tracheal compression and retrosternal extension.
12 lead chest ECG Usual recordings are prolonged QT segment, right bundle branch block (RBBB), flat or inverted T wave, QRS prolongation and sinus bradycardia. It reflects cardiac malfunction due to hypothyroidism. 12 lead chest ECG
Usual recordings are prolonged QT segment, right bundle branch block (RBBB), flat or inverted T wave, QRS prolongation and sinus bradycardia. It reflects cardiac malfunction due to hypothyroidism.

Investigations - Management

Fact Explanation
T3 , T4 hormone assays and TSH (Thyorid profile) To assess the response to treatments, and look out for complications. T3 , T4 hormone assays and TSH (Thyorid profile)
To assess the response to treatments, and look out for complications.

Management - Supportive

Fact Explanation
Maintaining the airway and securing the breathing It's the utmost priority since the patients either may present with respiratory failure or progress into it. Artificial airway management i.e. intubation may be essential in some cases but may be difficult. Maintaining the airway and securing the breathing
It's the utmost priority since the patients either may present with respiratory failure or progress into it. Artificial airway management i.e. intubation may be essential in some cases but may be difficult.
Fluid management A difficult decision, fluid supplementation is necessary in hypotension, and fluid restriction is necessary in hyponatremia. Fluid management should depend on the severity of each complication. In patients who have hyponatremia should be given hypertonic saline (i.e. 3%) and when hypotension is more prominet, 5%dextrose should be given. Fluid management
A difficult decision, fluid supplementation is necessary in hypotension, and fluid restriction is necessary in hyponatremia. Fluid management should depend on the severity of each complication. In patients who have hyponatremia should be given hypertonic saline (i.e. 3%) and when hypotension is more prominet, 5%dextrose should be given.
Warming Managing the hypothermia by external warming, but the accompanying vasodilatation may precipitate hypotension. Active re-warming can be life saving. Warming
Managing the hypothermia by external warming, but the accompanying vasodilatation may precipitate hypotension. Active re-warming can be life saving.
Continuous monitoring Respiratory and heart rates, systolic BP, temperature, urine output, conscious level, oxygen saturation, capillary blood sugar and volume status should be monitored frequently, the frequency depending on the severity of the presentation. Continuous monitoring
Respiratory and heart rates, systolic BP, temperature, urine output, conscious level, oxygen saturation, capillary blood sugar and volume status should be monitored frequently, the frequency depending on the severity of the presentation.
Patient education The patient should be de-briefed about the crisis he/she had to undergo, and how to be adherent to the medication to avoid future episodes. The drug interactions, how to look for drug adverse effects also should be added, with how to store medicine, when and how to take them and when to get the next thyroid profile done. Patient education
The patient should be de-briefed about the crisis he/she had to undergo, and how to be adherent to the medication to avoid future episodes. The drug interactions, how to look for drug adverse effects also should be added, with how to store medicine, when and how to take them and when to get the next thyroid profile done.

Management - Specific

Fact Explanation
Thyroid hormone supplementation T3 (triiodothyronine) is the active hormone in the body. Since in severe illnesses there can be a reduced conversion of T4 to T3, it's not very effective to give T4 (thyroxine) as the treatment option in emergency setting. T3 when given in intraveous form has a shorter half-life, so needs to give in loading dose followed by regular infusions. Triiodothyronine may not be widely available in the ER setting, and also because of it's potent action can increase the incidence of myocardial infarction or heart failure thus mortality. Some reports show adequate recovery with oral T3. Intravenous T4 is also recognized as a form of management. Once the patient is stabilized, conversion to oral T4 can be achieved. Thyroid hormone supplementation
T3 (triiodothyronine) is the active hormone in the body. Since in severe illnesses there can be a reduced conversion of T4 to T3, it's not very effective to give T4 (thyroxine) as the treatment option in emergency setting. T3 when given in intraveous form has a shorter half-life, so needs to give in loading dose followed by regular infusions. Triiodothyronine may not be widely available in the ER setting, and also because of it's potent action can increase the incidence of myocardial infarction or heart failure thus mortality. Some reports show adequate recovery with oral T3. Intravenous T4 is also recognized as a form of management. Once the patient is stabilized, conversion to oral T4 can be achieved.
Intravenous steroids Hypoadrenalism can be masked by hypothyroidism in a crisis. When thyroid hormones are replaced, hypoadrenalism becomes obvious. In emergency settings, to prevent associated mortality, intravenous setroids, preferably hydrocortisone is given. Intravenous steroids
Hypoadrenalism can be masked by hypothyroidism in a crisis. When thyroid hormones are replaced, hypoadrenalism becomes obvious. In emergency settings, to prevent associated mortality, intravenous setroids, preferably hydrocortisone is given.
Maintenance with oral thyroxine Daily thyroxine supplementation with oral tablets. The dose is to be stated small and gradually increased according to the TSH response as checked monthly. Once TSH reaches the desired level, yearly follow-up with thyroid profile is desirable. Maintenance with oral thyroxine
Daily thyroxine supplementation with oral tablets. The dose is to be stated small and gradually increased according to the TSH response as checked monthly. Once TSH reaches the desired level, yearly follow-up with thyroid profile is desirable.
Management of the precipitating factor i.e. Antibiotics for the infection. To remove the risk factor. Management of the precipitating factor
i.e. Antibiotics for the infection. To remove the risk factor.

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  1. ADAMS CRAWFORD W.. Electrocardiographic Changes in Hypothyroidism. CHEST [online] 1964 July [viewed 08 June 2014] Available from: doi:10.1378/chest.46.1.87
  2. AHN JI YUN, KWON HYUK-SOOL, AHN HEE CHOL, SOHN YOU DONG. A Case of Myxedema Coma Presenting as a Brain Stem Infarct in a 74-Year-Old Korean Woman. J Korean Med Sci [online] 2010 December [viewed 01 June 2014] Available from: doi:10.3346/jkms.2010.25.9.1394
  3. ALBASHIR S., OLANSKY L., SASIDHAR M.. Progressive muscle weakness: More there than meets the eye. Cleveland Clinic Journal of Medicine [online] December, 78(6):385-391 [viewed 01 June 2014] Available from: doi:10.3949/ccjm.78a.10116
  4. ANGEL JH, SASH L. Hypothermic coma in myxoedema. Br Med J [online] 1960 Jun 18, 1(5189):1855-9 [viewed 01 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/13793663
  5. ARTANTAş ŞöLEN, GüL ÜLKER, KıLıç ARZU, GüLER SERDAR. Skin findings in thyroid diseases. European Journal of Internal Medicine [online] 2009 March, 20(2):158-161 [viewed 01 June 2014] Available from: doi:10.1016/j.ejim.2007.09.021
  6. ASAMI TADASHI, SUZUKI HIROSHI, YAZAKI SATOSHI, SATO SEIICHI, UCHIYAMA MAKOTO. Effects of Thyroid Hormone Deficiency on Electrocardiogram Findings of Congenitally Hypothyroid Neonates. Thyroid [online] 2001 August, 11(8):765-768 [viewed 08 June 2014] Available from: doi:10.1089/10507250152484600
  7. ASIIMWE STEPHEN B., OKELLO SAMSON, MOORE CHRISTOPHER C., SALLUH JORGE I. F.. Frequency of Vital Signs Monitoring and its Association with Mortality among Adults with Severe Sepsis Admitted to a General Medical Ward in Uganda. PLoS ONE [online] 2014 February [viewed 09 June 2014] Available from: doi:10.1371/journal.pone.0089879
  8. BADUNI N, SINHA SK, SANWAL MK. Perioperative management of a patient with myxedema coma and septicemic shock Indian J Crit Care Med [online] 2012, 16(4):228-230 [viewed 09 June 2014] Available from: doi:10.4103/0972-5229.106510
  9. BENNETT WILLIAM E., HEUCKEROTH ROBERT O.. Hypothyroidism Is a Rare Cause of Isolated Constipation. Journal of Pediatric Gastroenterology and Nutrition [online] 2012 February, 54(2):285-287 [viewed 01 June 2014] Available from: doi:10.1097/MPG.0b013e318239714f
  10. BENTLEY RJ, BROWNE RJ. Paralytic ileus and dementia in a case of myxoedema. Postgrad Med J [online] 1969 Dec, 45(530):779-781 [viewed 01 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2466932
  11. BEYNON JENNIFER, AKHTAR SIMEEN, KEARNEY TARA. Predictors of outcome in myxoedema coma. Array [online] 2008 December [viewed 01 June 2014] Available from: doi:10.1186/cc6218
  12. BLUMENREICH MS. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition [web]; Chapter 153, The White Blood Cell and Differential Count. [viewed 08 June 2014] Available at http://www.ncbi.nlm.nih.gov/books/NBK261/
  13. BRAVERMAN LE, VAGENAKIS A, DOWNS P, FOSTER AE, STERLING K, INGBAR SH. Effects of Replacement Doses of Sodium-L-Thyroxine on the Peripheral Metabolism of Thyroxine and Triiodothyronine in Man J Clin Invest [online] 1973 May, 52(5):1010-1017 [viewed 09 June 2014] Available from: doi:10.1172/JCI107265
  14. BUCKLE RM, GARFIELD J. Myxedema coma complicated by respiratory failure. Proc R Soc Med [online] 1969 Jan, 62(1):38 [viewed 08 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2279074
  15. BURMAN KENNETH D., MCKINLEY-GRANT LYNN. Dermatologic aspects of thyroid disease. Clinics in Dermatology [online] 2006 July, 24(4):247-255 [viewed 06 June 2014] Available from: doi:10.1016/j.clindermatol.2006.04.010
  16. CATUREGLI PATRIZIO, KIMURA HIROAKI, ROCCHI ROBERTO, ROSE NOEL R. Autoimmune thyroid diseases. Current Opinion in Rheumatology [online] 2007 January, 19(1):44-48 [viewed 06 June 2014] Available from: doi:10.1097/BOR.0b013e3280113d1a
  17. CHINNASAMY ESWARI, RODIN ANDREW. A case of severe hypothyroidism presenting with multi-organ failure. EJEA [online] 2014 March [viewed 07 June 2014] Available from: doi:10.1530/endoabs.34.P416
  18. CRILLY M, ESMAIL A. Randomised controlled trial of a hypothyroid educational booklet to improve thyroxine adherence Br J Gen Pract [online] 2005 May 1, 55(514):362-368 [viewed 09 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1463159
  19. DANESHPAZHOOH M, MOSTOFIZADEH G M, BEHJATI J, AKHYANI M, ROBATI RM. Anti-thyroid peroxidase antibody and vitiligo: a controlled study. BMC Dermatol [online] 2006 Mar 10:3 [viewed 01 June 2014] Available from: doi:10.1186/1471-5945-6-3
  20. DUTTA P, BHANSALI A, MASOODI SR, BHADADA S, SHARMA N, RAJPUT R. Predictors of outcome in myxoedema coma: a study from a tertiary care centre Crit Care [online] 2008, 12(1):R1 [viewed 08 June 2014] Available from: doi:10.1186/cc6211
  21. FADEYEV VV, MORGUNOVA TB, SYTCH JP, MELNICHENKO GA. TSH and thyroid hormones concentrations in patients with hypothyroidism receiving replacement therapy with L-thyroxine alone or in combination with L-triiodothyronine. Hormones (Athens) [online] 2005 Apr-Jun, 4(2):101-7 [viewed 08 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/16613812
  22. FARLING P. A.. Thyroid disease. [online] 2000 July, 85(1):15-28 [viewed 08 June 2014] Available from: doi:10.1093/bja/85.1.15
  23. FELDKAMP J. [Autoimmune thyroiditis: diagnosis and treatment]. Dtsch med Wochenschr [online] December, 134(49):2504-2509 [viewed 06 June 2014] Available from: doi:10.1055/s-0029-1243053
  24. FIGUEIREDO MD, CARDOSO LC, FERREIRA AC, CAMPOS DV, DA CRUZ DOMINGOS M, CORBO R, NASCIUTTI LE, VAISMAN M, CARVALHO DP. Goiter and hypothyroidism in two siblings due to impaired Ca(+2)/NAD(P)H-dependent H(2)O(2)-generating activity. J Clin Endocrinol Metab [online] 2001 Oct, 86(10):4843-8 [viewed 06 June 2014] Available from: doi:10.1210/jcem.86.10.7934
  25. FRITSCH N., TRAN-VAN D., DARDARE E., GENTILE A., DEROUDILHE G., FONTAINE B.. [The myxoedema coma exists, we met it]. Annales Françaises d'Anesthésie et de Réanimation [online] 2007 September, 26(9):795-798 [viewed 01 June 2014] Available from: doi:10.1016/j.annfar.2007.03.009
  26. GORDON CHRISTOPHER J. Behavioral and Autonomic Thermoregulation in the Rat Following Propylthiouracil-induced Hypothyroidism1. Pharmacology Biochemistry and Behavior [online] 1997 September, 58(1):231-236 [viewed 01 June 2014] Available from: doi:10.1016/S0091-3057(97)00014-2
  27. GUPTA Y, AMMINI AC. Vitiligo, hypothyroidism and cardiomyopathy Indian J Endocrinol Metab [online] 2012, 16(3):463-465 [viewed 08 June 2014] Available from: doi:10.4103/2230-8210.95715
  28. HASSAN AI, AREF GH, KASSEM AS. Congenital iodide-induced goitre with hypothyroidism. Arch Dis Child [online] 1968 Dec, 43(232):702-704 [viewed 06 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2020155
  29. HAYNES RB, ACKLOO E, SAHOTA N, MCDONALD HP, YAO X. Interventions for enhancing medication adherence. Cochrane Database Syst Rev [online] 2008 Apr 16:CD000011 [viewed 09 June 2014] Available from: doi:10.1002/14651858.CD000011.pub3
  30. HAYS MARGUERITE T., MCGUIRE ROBERT A.. Distribution of Subcutaneous Thyroxine, Triiodothyronine, and Albumin in Man: Comparison with Intravenous Administration Using a Kinetic Model*. The Journal of Clinical Endocrinology & Metabolism [online] 1980 November, 51(5):1112-1117 [viewed 09 June 2014] Available from: doi:10.1210/jcem-51-5-1112
  31. HEINRICH TW, GRAHM G. Hypothyroidism Presenting as Psychosis: Myxedema Madness Revisited Prim Care Companion J Clin Psychiatry [online] 2003, 5(6):260-266 [viewed 01 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC419396
  32. HYLANDER B., ROSENQVIST U.. Treatment of myxoedema coma factors associated with fatal outcome. European Journal of Endocrinology [online] 1985 January, 108(1):65-71 [viewed 09 June 2014] Available from: doi:10.1530/acta.0.1080065
  33. IIDA KEIJI, HINO YASUHISA, OHARA TAKESHI, CHIHARA KAZUO. A case of myxedema coma caused by isolated thyrotropin stimulating hormone deficiency and Hashimoto’s thyroiditis. Endocr J [online] 2011 December, 58(2):143-148 [viewed 08 June 2014] Available from: doi:10.1507/endocrj.K10E-329
  34. JAMES R., JAMES J., VIJ A. S., VIJ K. K.. Postoperative myxoedema coma. Case Reports [online] December, 2014(feb13 1):bcr2013010066-bcr2013010066 [viewed 01 June 2014] Available from: doi:10.1136/bcr-2013-010066
  35. KABADI UDAYA M.. Optimal Daily Levothyroxine Dose in Primary Hypothyroidism. Arch Intern Med [online] 1989 October [viewed 09 June 2014] Available from: doi:10.1001/archinte.1989.00390100045012
  36. KANDUKURI RAJEEV C., KHAN MEHNAZ A., SOLTYS STEPHEN M.. Nonadherence to Medication in Hypothyroidism. Prim. Care Companion J. Clin. Psychiatry [online] 2010 May [viewed 01 June 2014] Available from: doi:10.4088/PCC.09m00863gre
  37. KARGILI A, TURGUT FH, KARAKURT F, KASAPOGLU B, KANBAY M, AKCAY A. A forgotten but important risk factor for severe hyponatremia: myxedema coma Clinics (Sao Paulo) [online] 2010 Apr, 65(4):447-448 [viewed 08 June 2014] Available from: doi:10.1590/S1807-59322010000400015
  38. KEHOE WA JR, DONG BJ, GREENSPAN FS. Maintenance Requirements of L-Thyroxine in the Treatment of Hypothyroidism West J Med [online] 1984 Jun, 140(6):907-909 [viewed 09 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1011127
  39. KOLLMAR R., SCHELLINGER PD., BARDUTZKY J., MEISEL F., SCHWANINGER M.. [Myxedema coma as a rare differential diagnosis of severe consciousness disturbance]. Der Nervenarzt [online] 2002 December, 73(12):1183-1185 [viewed 07 June 2014] Available from: doi:10.1007/s00115-002-1393-1
  40. KYRIACOS UNA, JELSMA JENNIFER, JAMES MICHAEL, JORDAN SUE, SALLUH JORGE I. F.. Monitoring Vital Signs: Development of a Modified Early Warning Scoring (Mews) System for General Wards in a Developing Country. PLoS ONE [online] 2014 January [viewed 09 June 2014] Available from: doi:10.1371/journal.pone.0087073
  41. LANIER JB, MOTE MB and CLAY EC. Evaluation and Management of Orthostatic Hypotension. Am Fam Physician. [online] 2011 Sep 1;84(5):527-536. [viewed 6th June 2014] Available on http://www.aafp.org/afp/2011/0901/p527.html
  42. LE MARQUAND HS, HAUSMANN W, HEMSTED EH. Death in Myxoedema Coma Br Med J [online] 1955 Sep 24, 2(4942):773 [viewed 01 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1980928
  43. LEBOFF MERYL S., KAPLAN MICHAEL M., SILVA J.ENRIQUE, LARSEN P.REED. Bioavailability of thyroid hormones from oral replacement preparations. Metabolism [online] 1982 September, 31(9):900-905 [viewed 09 June 2014] Available from: doi:10.1016/0026-0495(82)90179-2
  44. LEE CHRISTOPHER H., WIRA CHARLES R.. Severe angioedema in myxedema coma: a difficult airway in a rare endocrine emergency. The American Journal of Emergency Medicine [online] 2009 October, 27(8):1021.e1-1021.e2 [viewed 08 June 2014] Available from: doi:10.1016/j.ajem.2008.12.027
  45. LIEWENDAHL K., HELENIUS T., LAMBERG B.-A., MAHONEN H., WAGAR G.. Free thyroxine, free triiodothyronine, and thyrotropin concentrations in hypothyroid and thyroid carcinoma patients receiving thyroxine therapy. European Journal of Endocrinology [online] 1987 November, 116(3):418-424 [viewed 08 June 2014] Available from: doi:10.1530/acta.0.1160418
  46. LITTLE GJ. Thyroid morphology and function and its role in thermoregulation in the newborn southern elephant seal (Mirounga leonina) at Macquarie Island. J Anat [online] 1991 Jun:55-69 [viewed 01 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1260313
  47. LKLOUK . Myxoedema Coma: A Very Rare Presentation of Severe Hypothyroidism. J Med Cases [online] 2013 December [viewed 09 June 2014] Available from: doi:10.4021/jmc1503w
  48. MACAULAY MB, SHEPHERD RJ. Syncope in myxoedema due to transient ventricular fibrillation. Postgrad Med J [online] 1971 Jun, 47(548):361-363 [viewed 01 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2466917
  49. MACDONALD DW. Hypothermic Myxoedema Coma Br Med J [online] 1958 Nov 8, 2(5105):1144-1146 [viewed 01 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2026709
  50. MALDEN M. Hypothermic coma in myxoedema. Br Med J [online] 1955 Sep 24, 2(4942):764-6 [viewed 01 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/13250211
  51. MASOODI SHARIQRASHID, BASHIR MIRIFTIKHAR, AHMAD NADEEM, MIR SHAHNAZAHMAD, WANI ARSHADIQBAL. Lithium toxicity and myxedema crisis in an elderly patient. Indian J Endocr Metab [online] 2013 December [viewed 08 June 2014] Available from: doi:10.4103/2230-8210.123558
  52. MATHEW V, MISGAR RA, GHOSH S, MUKHOPADHYAY P, ROYCHOWDHURY P, PANDIT K, MUKHOPADHYAY S, CHOWDHURY S. Myxedema Coma: A New Look into an Old Crisis J Thyroid Res [online] 2011:493462 [viewed 08 June 2014] Available from: doi:10.4061/2011/493462
  53. MELISH JS. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition; Chapter 135: Thyroid Disease. [web] [viewed 01 June 2014] Available at http://www.ncbi.nlm.nih.gov/books/NBK241/
  54. OZKAN B, OLGUN H, CEVIZ N, POLAT P, TAYSI S, ORBAK Z, KOşAN C. Assessment of goiter prevalence, iodine status and thyroid functions in school-age children of rural Yusufeli district in eastern Turkey. Turk J Pediatr [online] 2004 Jan-Mar, 46(1):16-21 [viewed 06 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/15074369
  55. PUNZI LEONARDO, BETTERLE CORRADO. Chronic autoimmune thyroiditis and rheumatic manifestations. Joint Bone Spine [online] 2004 July, 71(4):275-283 [viewed 06 June 2014] Available from: doi:10.1016/j.jbspin.2003.06.005
  56. RODRIGO C, GAMAKARANAGE CS, EPA DS, GNANATHASAN A, RAJAPAKSE S. Hypothyroidism causing paralytic ileus and acute kidney injury - case report Thyroid Res [online] :7 [viewed 01 June 2014] Available from: doi:10.1186/1756-6614-4-7
  57. SAFER JD. Thyroid hormone action on skin Dermatoendocrinol [online] 2011, 3(3):211-215 [viewed 01 June 2014] Available from: doi:10.4161/derm.3.3.17027
  58. SCHUTT-AINE JC. Hypothyroid Myxedema and Hyponatremia in an Eight-Year-Old Child: A Case Report J Natl Med Assoc [online] 1980 Jul, 72(7):705-708 [viewed 08 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2552507
  59. SHAPIRO MARTIN F.. Diagnostic Decision: The Complete Blood Count and Leukocyte Differential Count: An Approach to Their Rational Application. Ann Intern Med [online] 1987 January [viewed 08 June 2014] Available from: doi:10.7326/0003-4819-106-1-65
  60. SIMMONS SUSAN. Myxedema coma. Nursing [online] 2010 June [viewed 09 June 2014] Available from: doi:10.1097/01.NURSE.0000376307.36712.6a
  61. STINSON JM, CUMMINGS CL. Acute Respiratory Failure and Hypothyroidism J Natl Med Assoc [online] 1980 Jan, 72(1):53-54 [viewed 08 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2537396
  62. TOMER YARON, HUBER AMANDA. The etiology of autoimmune thyroid disease: A story of genes and environment. Journal of Autoimmunity [online] 2009 May, 32(3-4):231-239 [viewed 06 June 2014] Available from: doi:10.1016/j.jaut.2009.02.007
  63. UNCU SIBEL, YAYLı SAVAş, BAHADıR SEVGI, ÖKTEN AYşENUR, ALPAY KöKSAL. Relevance of autoimmune thyroiditis in children and adolescents with vitiligo. [online] December, 50(2):175-179 [viewed 06 June 2014] Available from: doi:10.1111/j.1365-4632.2010.04665.x
  64. VAIDYA B., PEARCE S. H S. Management of hypothyroidism in adults. BMJ [online] 2008 July, 337(jul28 1):a801-a801 [viewed 09 June 2014] Available from: doi:10.1136/bmj.a801
  65. VERBALIS JOSEPH G., GOLDSMITH STEPHEN R., GREENBERG ARTHUR, SCHRIER ROBERT W., STERNS RICHARD H.. Hyponatremia Treatment Guidelines 2007: Expert Panel Recommendations. The American Journal of Medicine [online] 2007 November, 120(11):S1-S21 [viewed 08 June 2014] Available from: doi:10.1016/j.amjmed.2007.09.001
  66. WALL CR. Myxedema Coma: Diagnosis and Treatment. Am Fam Physician. [online] 2000 Dec 1;62(11):2485-2490 [viewed 09 June 2014] Available from: http://www.aafp.org/afp/2000/1201/p2485.html
  67. WALL CR. Myxedema coma: diagnosis and treatment. Am Fam Physician [online] 2000 Dec 1, 62(11):2485-90 [viewed 01 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/11130234
  68. WARTOFSKY LEONARD, BURMAN KENNETH D.. Alterations in Thyroid Function in Patients with Systemic Illness: The “Euthyroid Sick Syndrome”*. Endocrine Reviews [online] 1982 January, 3(2):164-217 [viewed 09 June 2014] Available from: doi:10.1210/edrv-3-2-164
  69. WARTOFSKY LEONARD. Myxedema Coma. Endocrinology and Metabolism Clinics of North America [online] 2006 December, 35(4):687-698 [viewed 09 June 2014] Available from: doi:10.1016/j.ecl.2006.09.003
  70. ZALETEL KATJA, GABERSCEK SIMONA. Hashimoto's Thyroiditis: From Genes to the Disease. Curr Genomics [online] 2011 December, 12(8):576-588 [viewed 06 June 2014] Available from: doi:10.2174/138920211798120763
  71. ZHANG YIYI, POST WENDY S., CHENG ALAN, BLASCO-COLMENARES ELENA, TOMASELLI GORDON F., GUALLAR ELISEO, HERNANDEZ ADRIAN V.. Thyroid Hormones and Electrocardiographic Parameters: Findings from the Third National Health and Nutrition Examination Survey. PLoS ONE [online] 2013 April [viewed 08 June 2014] Available from: doi:10.1371/journal.pone.0059489