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

10. The negative feedback…..

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

15. Hypothyroidism
The Underactive Thyroid

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

45. Myxedema Coma :Findings

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).