HYPOTHYROIDISM.& MYXEDEMA CRISIS
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1) A 38-year-old lady presented with generalized weakness, joint pain, cold intolerance, and occasional vomiting. Laboratory tests showed mild anemia and elevated uric acid and CPK levels. 2) A 65-year-old woman was found confused by police and unable to answer questions. On examination, she had hypothermia, bradycardia, and low blood pressure. 3) Both patients likely have hypothyroidism, with the second presenting with myxedema crisis, a life-threatening complication of severe, untreated hypothyroidism precipitated by an illness or event.
![How common is it in India???....
• Hypothyroidism :
INDIA : 3.9% [Usha menon,A.G.Unnikrishnan,ijem july 2011]
WORLDWIDE :2 %
• Congenital hypothyroidism:
INDIA: 1:2640
WORLDWIDE :1 :3800 (vaidya & Pearce,2008)
• Subclinical :9.4%
M:F=6.2% :11.6%](https://image.slidesharecdn.com/sajidshypoth-myxedema-copy-130512005205-phpapp01/85/HYPOTHYROIDISM-MYXEDEMA-CRISIS-17-320.jpg)
![Do you need to treat Subclinical hypothyroidism
• 5-8% indivisual have SCH.
• 4.3 % progressed to overt hypothyroidism
• Treat at all ages if:
• Consider treatment, if:
2012 European Thyroid AssociationPublished by S. Karger AG, Basel
TSH >10.0 mU/l
Pregnancy (or pre-pregnancy)
Age <65 years
Symptoms or signs of hypothyroidism
High vascular risk IHD/DM/DL/SMOKER]
Positive thyroid peroxidase antibodies
Goitre](https://image.slidesharecdn.com/sajidshypoth-myxedema-copy-130512005205-phpapp01/85/HYPOTHYROIDISM-MYXEDEMA-CRISIS-33-320.jpg)
HYPOTHYROIDISM.& MYXEDEMA CRISIS
- 2. 2CASES…………!!!!!!!! 1)A 38 yr /old lady with generalised paresthesias,pain in diff.joints,generalised weakness, occasional vomiting; cough, she developed symptoms of tremor, irritability ,& she feels cold even in normal day. Seen by PCP & investigated: CBC-@ Normal,except than Hb-9.5gm/dl, uric acid-7.2mg/dl (N-≤6) ;CPK- 300, 2) 65 yoF with confusion brought in by police, Unable to answer questions 95F HR 50 BP 90/70 RR 20 02 85% EKG: low voltage, sinus bradycardia
- 3. THINK THYROID VAGUE SYMPTOMS MULTIPLE SYMPTOMS OLD AGE POSTPARTUM PERIOD COLD /HEAT INTOLERANCE DIMENTIA FORGETFULNESS MILD ANEMIA MILD HYPERURICEMIA ALTERED LIPID PROFILE ELEVT.CPK
- 4. HYPOTHYROIDISM & MYXEDEMA CRISIS Dr.Sajid Nomani MEM (PGT) Peerless Hospital & B.K.Roy Research Center Kolkata
- 5. Goals of Discussion….. • THYROID -quick review • HYPOTHYROIDISM Definition Clinical symptoms Treatment • MYXEDEMA CRISIS
- 6. The Thyroid Gland……. Vercelloni 1711: “a bag of worms ” whose eggs pass into the esophagus for digestive purposes Parry 1825: “a vascular shunt to cushion the brain from sudden increases in blood flow
- 7. Introduction…… • Largest endocrine gland • 20 grams in adult • Each lobe • 2-2.5cm in width and thickness • 4cm in height • Isthmus • 0.5cm thick • 2cm height and width
- 8. Introduction…… • Two principal hormones. • Thyroxine (T4 ) and triiodothyronine (T3). • Required for homeostasis of all cells. • Influence cell differentiation, growth, and metabolism • Considered the major metabolic hormones because they target virtually every tissue
- 9. In the Thyroid Gland…… 5 steps in the hormonogenesis 1. Trapping of inorganic Iodine from dietary Iodides 2. Activation of Iodine to high valance I2 3. Incorporation of I2 into Tyrosine of Thyroid Globulin 4. Coupling of formed MIT and DIT to form T4 & T3 5. Proteolysis of Thyroglobulin to release T4 & T3
- 11. Thyroid gland normally releases 100-125 mcg of thyroxine (T4) daily and small amounts of T3 Tri Iodo Thyronine – T3 10% is from thyroid gland 90% derived from conversion of T4 to T3 half life 6 hours 99.5% protein bound to TBG, TPA, TA Tetra Iodo Thyronine – T4 Is exclusively from thyroid gland half life 7 days 99.9% protein bound to TBG, TPA, TA From the thyroid gland - 80% of hormone secreted is T4 - 20% of hormone secreted is T3 POTENCY—T3:T4=4:1
- 12. Normal…….. • TSH :0.5-5.0 mIU/ L……….(Soon -TSH---2.5) • T4 (T) :4.5 - 12.5 µg/dl (F) :0.8 - 1.8 ng/L T4 is 99.9% protein bound to TBG, TPA, TA • T3 (T) :80 -200 ng/dl ( F) :2.3- 4.2 pg/ml T3 is 99.5% protein bound to TBG, TPA, TA Bound hormones are inactive – should not be measured Only Free T4 and Free T3 are metabolically active
- 13. Thyroid Function Tests • TSH • Free T4 • Free T3 • Anti-Thyroid Antibodies • Nuclear Scintigraphy • FNAC of nodule
- 14. What tests should I order ? As per the Guidelines of the AACE and ATA, ITS • TSH alone if Hypothyroidism is suspected • TSH and Free T4 only if Hyperthyroidism suspected • Free T3 if T3 toxicosis is suspected • For follow-up of treatment only TSH • Don’t order for Total T4 or Total T3 • Never order RIU in pregnancy or lactation
- 16. Introduction…. • This is the most common pathological hormone deficiency • Results in a slowing down of metabolic processes. • Prevalence 2-3% in the general population • Mean age at diagnosis is mid-40s • Male: Female 1:20
- 17. How common is it in India???.... • Hypothyroidism : INDIA : 3.9% [Usha menon,A.G.Unnikrishnan,ijem july 2011] WORLDWIDE :2 % • Congenital hypothyroidism: INDIA: 1:2640 WORLDWIDE :1 :3800 (vaidya & Pearce,2008) • Subclinical :9.4% M:F=6.2% :11.6%
- 18. Introduction….. • Classification: Time of onset: Congenital or acquired Severity: Clinical or subclinical Site of dysfunction: Primary or secondary/tertiary
- 20. Interpration…..!!!!!!!!!! LOWNORMALHIGH LOW NORMAL HIGH FREETHYROXINEorFT4 THYROID STIMULATING HORMONE - TSH PRIMARY HYPOTHYROID SECONDARY HYPOTHYROID SUB-CLINICAL HYPOTHYROID SECONDARY HYPERTHYROID EUTHYROID NON THYROID ILLNESS - NTI SUB-CLINICAL HYPERTHYROID PRIMARY HYPERTHYROID NTI or Pt. on ELTROXIN
- 21. Sign & symptoms….. Everything from the brain to the skin is affected by the hormone made by the thyroid gland. Hypothyroidism "It slows you down,It makes you lethargic and fatigued Your hair becomes brittle, and your skin becomes dry. You become cold much easier than the average person.
- 22. Sign & symptoms….. • Depends on degree of hormone deficiency (overt, subclinical) • Depends on speed of development of hormone deficiency (gradual, better tolerated)
- 23. General • Lethargy, Somnalence • Weight gain, Goitre • Cold Intolerence Cardiovascular • Bradycardia, Angina • CHF, Pericardial Effusion • HyperlipIdemia, Xanthelsma Haematological • Iron def. Anaemia, • Normo cytic /chromic Anaemia Reproductive system • Infertility, Menorrhagia • Impotence, Inc. Prolactin Neuromuscular • Aches and pains • Muscle stiffness • Carpel tunnel syndrome • Deafness, Hoarseness • Cerebellar ataxia • Delayed DTR, Myotonia • Depression, Psychosis Gastro-intestinal • Constipation, Ileus, Ascites Dermatological • Dry flaky skin and hair • Myxoedema, Malar flushes • Vitiligo, Carotenimia, Alop ecia Sign&symptoms…..
- 24. Clinical Signs of Hypothyroidism Coarse Hair; Dry cool and pale skin Goitre (not in all cases), Hoarseness of voice Non-pitting oedema (myxoedema) Puffiness of eyes and face Delayed relaxation of DTR Slow hoarse speech and slow movements Thinning of lateral 1/3 of eye brows Bradycardia, pericardial effusion
- 25. Management…… GOAL---keep TSH ,half of upper ref .range. L-Thyroxine 1.6mcg/kg/day in otherwise healthy patients in patients age>60 or if CAD present, 0.5- 1.0mcg/day and slowly increase T3-controversial recheck levels in 6 weeks
- 26. coming back…to our case 1 1)A 38 yr /old lady with generalised paresthesias,pain in diff.joints,generalised weakness ,& low mood. cold intolerance, occasional vomiting; cough WHAT FURTHER TO LOOK….. • History • CO-EXISTING FACTORS • Comorbidities • Age • Severity of hypothyroidism • Coexisting drugs
- 27. Additional Info generated…. • Family H/O hypothyroidism • Delivered 6 mo. back & Brest feeding • Taking Iron & Calcium tabs. • O/P—Small firm goiter • TSH—30 U/ml • FT4--- 0.4ng/ml • FURTHER TESTING ???? DIAGNOSIS Primary Hypothyroidism Postpartum Thyroiditis Anti TPO antibody(thy.peroxidase) Anti Tg(thyroglobulin)antibody USG FNAC
- 28. • Started---75mcg /day empty stomach • Called back after 6 weeks. Pt. reports good compliance TSH—20 u/l ↑ Doses—100mcg Called back after 6 week TSH---15u/l ???…… NOT CONTROLLED WHAT ARE CAUSES FOR HIGH DOSES REQUIRMENT??? IS THYROXINE TREATMENT DURING BREASTFEED SAFE TO BABY???
- 29. HIGH DOSES REQUIRMENT OF LEVOTHYROXINE • MALABSORPTION • Celiac disease • Small bowel surgery • MEDICATION • Estrogen • Amaidrone • Lithium prepration • Ferrous sulfate • Calcium • PPI • Carbamazepine • Phenytoin • Lovastatin • Bulk laxative • Magnesium prepration • Alumunium hydroxide
- 30. High doses requirment of lEVOTHYROXINE MALABSORPTION /↑EXCRETION OF T4 Gastrointestinal disorders, Impaired acid secretion Celiac disease Small bowel surgery MEDICATION Increase catabolism of T4: Rifampin Carbamazepine Phenytoin Phenobarbitol Drugs interfere T4absorption: Cholestyramine orcolestipol, Sucralfate Ferrous sulfate, Calcium Carbonate Aluminum hydroxide gels, Sertraline Raloxifene, Omeprazole
- 31. What to do??? • Space out thyroxine from other offending drugs. • Can be converted in night doses. • No adjustment for Renal / Hepatic diseases. • Safe in Breastfeeding. Our patient Spacing done between medication Cont.same doses; TSH reduced to—2.8 Called backed after 3 month for evaluation; TSH—0.1 REVERSIBLE HYPOTHYROIDISM 20%Autoimmune found to be reversible Spontaneous disappearance of blocking agent
- 32. Maternal Hypothyroidism • AACE recommendations • Carry out TSH assay routinely before pregnancy or during the first trimester to rule out thyroid disorder • Avoid complications by administering thyroid hormone replacement therapy • Both mild as well as overt hypothyroidism are managed by administering levothyroxine therapy which can be safely administered during pregnancy • Assess TSH levels every 6 weeks . • Increase the dose of thyroid hormone in pregnant women with moderate to severe hypothyroidism
- 33. Do you need to treat Subclinical hypothyroidism • 5-8% indivisual have SCH. • 4.3 % progressed to overt hypothyroidism • Treat at all ages if: • Consider treatment, if: 2012 European Thyroid AssociationPublished by S. Karger AG, Basel TSH >10.0 mU/l Pregnancy (or pre-pregnancy) Age <65 years Symptoms or signs of hypothyroidism High vascular risk IHD/DM/DL/SMOKER] Positive thyroid peroxidase antibodies Goitre
- 35. In the emerge ncy room MYXEDEMA CRISIS Life-threatening severe hypothyroidism • 80% -100 % mortality rate • Reduced to 15-20% with aggressively managment
- 36. MYXEDEMA CRISIS A rare clinical state of insidious onset, in an individual with pre-existing hypothyroidism End-stage of untreated hypothyroidism. Precipitated by intercurrent illness such as infection, stroke or CNS depressants
- 38. Our 2nd patient 65 yoF with confusion brought in by police, Unable to answer questions 95F HR 50 BP 95/75 RR 20 02 85% EKG: low voltage, sinus bradycardia… CT-WNL, Chest Xray---Pleural effusion • Found wandering in the street • Unable to answer questions • Skin is coarse and waxy • Tranverse surgical scar on neck • Generalized weakness and prolonged DTR
- 39. Myxedema Coma: Clinical • OFTEN ELDERLY (but not always!!) • History of hypothyroidism • Levothyroxine replacement, thyroid cancer, • surgery, RAIA • Physical exam • Comatose or decreased mental status • Hypothyroid signs: Cool/dry skin, delayed reflexes, • lid lag, thin hair, hypothermia, ileus, effusions Myxedema (not always easy to detect)
- 40. Myxedema Coma: Risk factor • Cold weather • Elderly women • Undiagnosed or under treated hypothyroidism • Precipitating event
- 41. Myxedema Coma: Precipitants • Discontinued thyroid hormone replacement • CVA or MI • Infection (UTI, URI) • Hemorrhage • Narcotics, diarrhea, comorbid illness
- 42. Myxedema Coma :Findings Decrease mental status – from baseline Hypothermia/ Hypoglycemia/ Hyponatremia Bradycardia Hypoventillation Peri-orbital edema Non-pitting Edema Delayed Tendon Reflex
- 43. Myxedema Coma :Findings Cardiac Bradycardia / hypotension CHF Cardiomegaly Pericardial effusion Low voltage EKG
- 44. Myxedema Coma :Findings Neck Thyroidectomy scar Goiter (uncommon) Dermatologic Dry, scaly, yellow skin Loss of lateral 3rd of eyebrows Non-pitting waxy edema of face / extremities
- 46. Diagnosis • Diagnosis is clinical • Thyroid panel reflects chronic state
- 47. Myxedema Coma: Workup • Basic lab tests and radiology • FT4, TSH • CBC (anemia), electrolytes (hyponatremic), • renal function (increased Cr) • EKG (bradycardia), CXR (effusions) • Evaluate for pituitary disorders • Cortisol, cosyntropin stimulation test • FSH, LH
- 48. Managment Supportive care ABCs Rewarming Treat precipitating causes
- 49. Treatment ::Myxedema Coma Rewarming : 0.5celcius/h.,passive rewarming Thyroid hormone Levothyroxine (T4) @4mcg/kg 300 - 500mcg IV Hydrocortisone 100mg IV q8 possible unrecognized adrenal or pituitary insufficiency Antibiotics & other supports
- 50. RECOMENDATION • The American Thyroid Association recommends screening at age 35 years and every 5 years thereafter, with closer attention to patients who are at high risk (eg, pregnant women, women >60 y, patients with type 1 diabetes or other autoimmune disease, patients with history of neck irradiation). • The American College of Physicians recommends screening all women older than 50 years who have one or more clinical features of disease. • The American Association of Clinical Endocrinologists recommends TSH measurements of all women of childbearing age before pregnancy or during the first trimester. • The US Preventive Task Force concludes that the evidence is insufficient to recommend for or against routine screening for thyroid disease in adults (Grade I recommendation).
Editor's Notes
- #52: Extensive fungal infection of the finger and toenails (onychomycosis) is often associated with hypothyroidism, a consequence of compromised cardiac contractility, leading to decreased blood flow to the extremities. The resulting low-oxygen state at the tips of the fingers and toes promotes fungal overgrowth.B. Slow capillary refilling, demonstrable by applying firm finger pressure to areas of thin skin, is a manifestation of reduced cardiac inotropy. As thyroid levels decline, cardiac contractility decreases. The worse this condition is, the closer to the heart it will manifest. It usually begins in the extremities, and patient will experience cold hands and feet. By the time it manifests above the knee, the patient has quite serious circulatory compromise.C. Poor capillary refilling, reflective of weak inotropy in the heart, leads to poor circulation at the extremities and facilitates fungal overgrowth in the nails. These signs are typical of longstanding hypothyroidism.D. Fluid leakage into extracellular spaces, a result of reduced glycoaminoglycan production also results in a characteristic swollen, scalloped tongue, which is very common in hypothyroid people.E. Conversion of beta-carotene to vitamin A is dependent on thyroid hormone. Thyroid deficiency will manifest as a yellowish buildup of carotene in the skin of the palms and soles. Poor circulation, also associated with hypothyroidism, facilitates fungal overgrowth between toes.F. Thyroid hormone drives production of glycoaminoglycans, responsible for keeping water inside cells. In hypothyroidism, water tends to leak into extracellular spaces causing significant edema, easily recognized around the legs and ankles.