1. Thyroid disease
Dr . Bandar ghazal

3. Normal mass of thyroid about 30 g
Highly vascularized , receive about ml blood / min .

6. Follicular cells secret :
Thyroxine (tetraiodothyronine ) T4
Contains 4 ions of iodine
Tri iodothyronine T3
Contains 3 ions of iodine .
it also produce thyroglobulin
Parafollicular cells secret :
calcitonin
Thyroid gland secret and store thyroxin up to days supply .
Thyroglobulin essential for production (iodination by thyroperoxidase )and storage of hormone into colloids
With stimulation , release hormone and thyroglobulin .

7. Stimulators of thyroid gland :
Thyrotropine releasing hormone . TRH
Thyroid stimulating hormone . TSH
T4 is longer half life than T3 (which is 3 – 4 times more potent )
Released in the blood approximately 14:1 .
T4 is converted into T3 within cells .

8. Function
Regulate oxygen consumption , basal metabolism , growth and development
Regulate protein , fat and carbohydrate metabolism
Increase sensitivity to catecholamine's
Neural maturation .
Heat generation

9. Hyperthyroidism and thyrotoxicosis
Exposure of tissues to high level of circulating thyroid hormones from any cause
Hyperthyroidism :
thyrotoxicosis caused by excessive endogenous production of thyroid Hormones .
Primary : thyroid gland is the anatomical site of dysfunction
Secondary : increased secretion of TSH is a rare secondary cause of hyperthyroidism .

10. Clinical manifestations
General : Fatigue , weight loss , heat intolerance
Neuropsychiatric : Anxiety , insomnia , decreased concentration
Hyperreflexia , tremor , lid lag (, due to high adrenergic tone )
Cardiovascular :Palplitation , tachycardia , high systolic BP , high output heart failure
Gastrointestinal : Hyperphagia , increased frequency of bowel movement , loose stool , diarrhea
Genitourinary :Oligomenorrhea , amenorrhea
Musculoskeletal :Muscle weakness
Cutaneous :Hair loss , increased sweating
Increased oil production , acne , periorbital edema

11. Lid lag

12. Investigation TSH , F T4 , T T3 . CBC , KFT , LFT , CPK , RAIU :
High in hyperthyroidism
Low in other causes of thyrotoxicosis .
In case of pregnancy , lactation , amiodarone , lithium intake ????
TSI (thyroid stimulating immunoglobulin )
TRAP thyrotropin receptor antibodies
In case of suspected Graves disease .
U/S : to assess vascularity

13. Causes Graves disease Common (presence of autoantibodies )
Toxic multinodular goiter
common
Toxic adenoma
Thyroiditis ( acute , sub acute , chronic )
Common , thyroid inflammation causing release of stored hormones
Medication induced
Amiodarone , lithium , interferon alpha , tyrosine kinase inhibitor
Thyrotoxicosis factitia
Common ( thyroxine abuse , contaminated beef )
Struma ovarii
Rare (autonomous function thyroid tissue in ovarian teratoma )
Thyrotrope adenoma
Rare , TSH secreting pituitary adenoma

14. GRAVES DISEASE Most common cause of thyrotoxicosis .
Autoimmune disorder affecting thyroid gland , increasing synthesis and production of thyroid hormones .
F: M 8:1
Onset : 20– 60 years
Thyroid gland is typically hyperplastic and enlarged
Maybe associated with other pernicious anemia , myasthenia gravis , DM , celiac disease .
It has a familial tendency maybe accompanied by graves opthalmopathy , dermopathy .

15. Pathogenesis
T lymphocytes become sensitized to thyroid antigen and stimulate B lymphocyte to produce antibodies against TSH receptor
TSI thyroid stimulating immunoglobulin .
TRAB thyrotropin receptor antibodies .
Thyroid hormone production increase
Gland is diffusely enlarge
May have bruit , firm with smooth texture on examination .
Cervical lymphadenopathy can occur .

16. Graves opthalmopathy Graves opthalmopathy affects 25 % of PT .
Smoking is a risk factor .
Periorbital edema
Chemosis
Proptosis
Diplopia ( oculomotor paresis )
Vision loss
This condition does not respond to treatment of hyperthyroidism , and often needs steroids therapy and surgery

18. Pretibial myxedema
Rare infiltrative dermopathy of graves disease affecting % of pt
Non pitting edema
Indurated with peau d orange appearance typically on shins

21. Toxic adenoma Single Multiple (plummers disease )
Usually affect old age ,as prevalence of thyroid nodule increase with age .
Synthesis and secretion of hormone is independent of TSH
Not accompanied by opthalmopathy or dermopathy
AntI thyroid antibodies usually absent .
Exposure to contrast media or very high iodine intake may convert non toxic adenoma into toxic adenoma

22. Subacute thyroiditis Moderately enlarged tender gland
Thought to be due to viral infection
Maybe not tender called silent thyroiditis
Thyrotoxicosis result from released stored hormone resulting from destruction of follicles
Thyrotoxicosis followed by hypothyroidism then into euthyroid .
First 2 phases may last up to 3 months
During thyrotoxicosis there is low grade of thyroid uptake
Increased risk of recurrence

23. Thyrotoxicosis factitia
Due to ingestion of excessive amounts of exogenous thyroid hormone whether as form or replacement or abuse .
Consumption of contaminated beef

24. Struma ovarii
Thyroid tissue is contained in about 3 % of ovarian dermoid tumor and teratoma .

25. Pituitary tumor Rare No opthalmopathy seen Antibodies are normal
TSH is high or in normal range
Secondary hyperthyroidism
Due to pituitary adenoma , neoplasm or hyperplasia .

26. Management B –blocker : Atenelol , metoprolol , propranolol
To reduce sympathetic symptoms
Propranolol non selective , decrease peripheral conversion of T4 to T3
But requires to be administered 2 – 3 times a day
cardio selective such as atenelol , metoprolol is daily one dose , better adherence by PT

27. Thioamides : ( inhibit thyroperoxidase )
Methimazole
Propylthiouracil
In graves :
50 % will have spontaneous remission within 24 months .
Recurrence of hyperthyroidism is likely when TRAB is high at time of drug discontinuation . So if occur ablation or surgery
Radioactive iodine ablative therapy :
Pregnancy should be avoided 6 – 12 months after therapy
First line for toxic adenoma and multinodular
Thyroidectomy :
Choice of therapy depends on pt status age and preference and the cause of thyrotoxicosis
For example pt above 65 years with cardiovascular and other comorbidities , we start short term thioamide to normalize thyroid function then RAIT or surgery .
First line for toxic adenoma , multinodular and malignancy

28. In PT with graves opthalmopathy there is an escalation of antibodies following RAIT That may exacerbate the ocular symptoms So pretreatment is required by steroids And thyroid surgery is better than RAIT . For destructive thyroiditis : B blocker NSAIDS High dose of Steroids

29. Thyroid storm Rare High mortality 30 % sever form of thyrotoxicosis
Presence of hemodynamic decompensating ( shock ) .
Clinical status > lab value of T4 . 3
Higher risk pt with Graves disease .
high fever
Tachycardia
Altered mental status
Cardiac and hepatic dysfunctions
Abdominal pain , nausea , vomiting , diarrhea .
ICU
Supportive measure , b blocker
Propythiouracil then switch to methimazole .
Steroids ,
Plasmapheresis , surgery

30. Subclinical hyperthyroidism
It’s a condition where TSH LOW with normal T4, 3
25 % of PT will return to normal TSH value after 6 weeks .
1-7 % of PT will progress to hyperthyroidism / year
Persistent subclinical status may predispose pt to AFIB , cardiovascular complications , hip fracture

31. Treat
Observe
IF PERSISTENT TSH <0.1 MU/L and with symptoms or
cardiac risk factors
osteoporosis
If TSH >0.1 TO 0.5 .
IF TSH < 0.1
Without symptoms or risk factors .

32. Hypothyroidism Insufficient synthesis of thyroid hormones
Female : .male is 10 : 1

33. Causes Hashimoto thyroiditis Autoimmune associated with TPO antibody
Post thyroidectomy
Ex. Surgery due to cancer , Graves disease , goiter
Occur in all PT post thyrodectomy
In 20% after lobectomy
Post radioactive iodine therapy
Treatment of Graves disease , toxic adenoma .
Occur in 90 % of graves disease after (RAIT ) within one year .
Occur in 60 % in toxic multinodular goiter with onset delayed to many years .
Radiation to neck
Head and neck malignancy , hodgkin lymphoma
Thyroiditis (acute , subacute , suppurative )
Transient hypothyroidism ,
Central hypothyroidism
TSH deficiency due to hypothalmus or pituitary disease , TSH should not be used to assess therapy with thyroxine
Congenital hypothyroidism
Iodine deficiency
Common in developing countries
Drug induced
Amiodarone ,lithium , interferon alpha
Iodine thionamide ,
Tyrosine kinase inhibitor (sunitinib )

36. Sensitivity to heat / cold
Fatigue
Hypoglycemia
Increased cholesterol level

37. HASHIMOTOS THYROIDITIS
Primary condition of hypothyroidism
Autoimmune disorder characterized by diffuse infiltration of the thyroid gland by lymphocyte and plasma cells resulting in follicular atrophy and scarring
More common in pt with other autoimmune disorder and positive family history of thyroid autoimmunity .
Diffuse goiter can be seen most commonly in younger pt
90 % of pt have positive TPO antibody (thyroid peroxidase antibody )
Described by Hakaru Hshimoto

38. TSH , T3 , T4 levels
TPO antibodies ( Thyroid peroxidase )
Positive ANA

39. Levothyroxine
To normalize TSH
And to resolve signs symptoms of hypothyroidism
1.6 mcg / kg
Except for elderly pt and pt with cardiac disease
25 – 50 mcg / day
Absorbed in jejenum and ileium , taken 1 hour before breakfast or coffee
Absorption of thyroxine is about 70 – 80 %
Repeat TSH after 6 weeks .
Helps in both hypothyroidism and shrinkage of goiter

40. CRETINISM Hypothyroidism dating from birth
Thyroxine is essential for growth and development of brain during first 3 years
Earlier onset greater brain damage
Causes :
Radio iodine
Post radiation
Iodine deficiency
Drug induced
Hashimotos throiditis
Congenital developmental defects

41. Delayed dentation
Mental retardation
Large posterior fontanelle
Hypotonia
Same other features of hypothyrodism
Umbilical hernia

43. Investigation : cord blood T4 , Tsh
Serum t4 , tsh
RAIU
Xray of knee , foot and skull
Treatment :
Levothyroxine
15mcg /kg / d
Iodine rich food
Flollow up

44. MYXOEDEMA Common in women Two varient :
Hyperthyrois myxoedema (pretibia myxoedma )
Hypothyroid myxoedema
Causes : increases deposition of glycosamine glycan
Hasimotos thyroiditis

45. Myxoedema coma
Life threatening form of untreated sever hypothyroid with hemodynamic compromise .
Occur in pt with long standing hypothyroidism
Mortality is high
Risk factors :
Advanced age
cold exposure ,
Female gender
Events in undiagnosed pt such as ( infection , drug therapy , myocardial ischemia , trauma , stroke
ICU care is required

46. Lethargy stupor delirium
Psychosis
Hypotension
Convulsion
Hypoglycemia
Bradycardia ,Hyponatremia
Hypoventilation , hypoxemia , hypercapnia
Coma
Hypothermia ( temperature below c ) most common clinical manifestation

47. Examine the neck for scar
Tsh , ft4 , t3
Serum osmolaity, electrolytes
Creatinine
Glucose
CBC
Pan cultures for sepsis
Cortisol level to assess for adrenal insufficiency

48. Hemodynamics : Iv fluids , vasopressor
Hyperventilation if respiratory acidosis is significant
Passive warming rather than active warming to avoid vasodilatation
Thyoxine I/V
Loading dose 200 – 400 mcg followed by 1.6mcg/kg oral daily dose , dose is reduced to 75 % if given I/V.
Lower dose of thyroxine in elderly and in cardiac pt
Stress dose Hydrocortisone 100 mg every 8 hours
If random cortisol level > 18 mg / dl it can be stopped
Treatment of infection
Correction of hyponatremia with saline
Correction of hypoglycemia with iv dextrose

49. Goal of therapy is
Improve mental status
Metabolic parameters
Cardiopulmonary functions
When pt is stable start oral dose of thyroxine

50. Subclinical hypothyroidism
Typically asymptomatic
Diagnosed by elevated TSH and normal T4
Affect % of population
Repeat TSH in 2 months , bz it might be transient
progression rate from subclinical to hypothyroidsm is % / year
One third revert to normal thyroid function

51. Normal TSH level increase with age , up to 10 mu/l for person 80 years of age
Subclinical hypothyroidism with TSH above 10mu/l maybe at risk for CAD . HF
There is no evidence of treating subclinical hypothyroidism will improve quality of life
BP , weight , cognitive function .. But in pt with high LDL level normalization of TSH will lower LDL Llevel

52. TSH > 10 mu/l should be treated
mcg / d