hyperthyroidism

1. Zelalem
semegnew

2. Outline
Physiology of thyroid gland
Causes of thyrotoxicosis
Clinical features of hyperthyroidism
Diagnosis
Management
Thyroid storm
References

3. Thyroid gland
 Wt 20-25g
 parts
 Pyramidal lobe in 50%
 Rt &Lt. lobe
 Isthmus
 Blood supply
 aa Sup. thyroid aa
Inf. thyroid aa (thyrocervical trunk)
Ima aa in 3%
 veins Sup. thyroid vv
Middle thyroid vv
Inf. thyroid vv

4. Thyroid hormone
 Characteristics
Anabolic hormone
Secreted in two forms : T3 and T4
Ratio to T4 to T3 : 20 to 1
T3 is more active than T4

5. Thyroid hormone synthesis
 Begins with iodide
 Iodide enters the thyroid follicular cells by
active transport
 Thyroperoxidase catalyzes oxidation of iodide to
iodine
 Peroxidase catalyzes iodination of thyroglobulin
 Iodination of thyroglobulin ‘s tyrosine residue
yields 2 products
 Monoiodotyrosine (MIT)
 Diiodotyrosine (DIT)
 Peroxidase also catalyzes coupling
 2 DIT molecules= =T4
 MIT +DIT + T3

6. Thyroid hormone regulation
 Steps
Hypothalamus secretes TRH in to the
portal system
Pituitary thyrotrophs secrete TSH
Thyroid gland secretes T4 and T3
Thyroid hormones act as a negative
feedback to inhibit further secretion of
TRH and TSH

7. Thyroid hormone
 Thyroid hormone function ( 4 B’s)
Brain maturation
Bone growth
Beta adrenergic effects
BMR

8. Hyperthyroidism
Thyrotoxicosis
symptom complex due to raised levels of thyroid
hormones
 Hyperthyroidism
Reserved for disorders that result from sustained
overproduction and release of hormone by the thyroid
itself.
8/22/2015managment of hyperthyroidism

9. Causes of Thyrotoxicosis

10. Graves Disease (Basedow’s disease)
 Characteristics
The most common cause of thyrotoxicosis (60-80 %)
auto-immune disease
The most important autoantibody is
Thyroid Stimulating Immunoglobulin (TSI) or TSA
Others - (anti-TPO) (anti-TG)
Symetrical enlargement of the thyroid
Hyper secretion of thyroid hormones
Patients tend to be young women

11. Toxic Multinodular Goiter(TMG) (Plummer ds)
Characteristics
TMG is the next most common cause of hyperthyroidism - 20%
Caused by focal regions of hyper functioning follicular cells (
independent of TSH)
Due to mutation of the TSH receptor
Can be the result of chronic iodine deficiency
Excessive TSH stimulation induces
Focal hyperplasia
Subsequent necrosis and hemorrhage
Nodule formation
Cardiovascular manifestations tend to predominate

12. Toxic Single Adenoma (TSA) (Goetsch’s ds)
 Characteristics
TSA is a single hyper functioning follicular thyroid adenoma.
Benign monoclonal tumor that usually is larger than 2.5 cm
It is the cause in 5% of patients who are thyrotoxic
Nuclear Scintigraphy scan shows only a single hot nodule
TSH is suppressed by excess of thyroxines
So the rest of the thyroid gland is suppressed

13. Clinical Features of hyperthyroidism
 It is eight times more common in females.
 Sex M : F ratio
 Graves Disease 1: 5 to 1:10
 Toxic MNG 1: 2 to 1: 4
 Occurs in any age group.
 Age
Graves disease 20 to 40
Toxic MNG > 50 yrs
Toxic Single Adenoma 35 to 50.
 Clinical features can be grouped
 those related to hyperthyroidism
 Those that are specific to Graves disease

14. those related to hyperthyroidism

15. Specific to Graves Disease
 1. Diffuse painless and firm enlargement of thyroid gland
 2. Ophthalmopathy – Eye manifestations – 50% of cases
Classification of Eye Changes in Graves' Disease
 0) No signs or symptoms.
1) Only signs, no symptoms. (Signs limited to upper
lid retraction, stare, lid lag.)
2) Soft tissue involvement (symptoms and signs).
3) Proptosis (measured with Hertel exophthalmometer)
4) Extraocular muscle involvement.
5) Corneal involvement.
6 Sight loss (optic nerve involvement).

16. Eye Signs in Toxic Goitre
In early stages, may be unilateral but later may become bilateral.
 Order of appearance of signs
 Stellwag's sign : Absence of normal blinking—so staring look.
 Von Graefe`s sign : Upper eye lid lags behind the eye ball as the patient is asked to
look downwards.
 Dalrymphe's sign : Upper sclera is visible due to retraction of upper eye lid.
 Joffroy's sign : Absence wrinkling in the forehead on looking upwards with the face
inclined downwards.
 Moebius sign : Inability or failure to converge the eye balls
 Gifford's sign: Difficulty in eversion of the upper lid.

17. Specific to Graves Disease……..
 3. Thyroid dermopathy
 consists of thickening of the skin, particularly over the lower
tibia, due to accumulation of glycosaminoglycans
(pre tibial myxedema)
Is usually bilateral
 4. Thyroid Acropachy
 Thyroid acropachy is clubbing of fingers and toes in primary
thyrotoxicosis.

18. diagnosis
 Examinations, symptoms
 Thyroid blood tests
 Thyroid function tests TSH , T4,T3
 Thyrroid antibodies TSI, ANTI TPO, ANTI Tg
 Other — nonspecific laboratory findings.
low serum total, LDL, and (HDL) cholesterol concentrations
normochromic, normocytic anemia
Serum alkaline phosphatase

19. Diagnosis……………….
 Thyroid imaging
Radionuclide imaging
Size, shape & function of gland assessed
Increased uptake=“hot", less risk of malignancy,<5%
Decreased uptake=“cold" higher risk of
malignancy,15-20%
Ultrasound
CT/ MRI good for assessment of retrosternal extension.
 pathology

20. www.drsarma.in
Algorithm for Hyperthyroidism
Measure TSH and FT4
 TSH,  FT4
Measure FT3
Primary (T4)
Thyrotoxicosis
High
Pituitary Adenoma FNAC, N Scan
Normal
 TSH, FT4 N  TSH,  FT4 N TSH, FT4 N
T3 Toxicosis
Sub-clinical Hyper
Features of Grave’s
Yes
Rx. Grave’s
No
Single Adenoma, MNG
Low RAIU RAIU
Sub Acute Thyroiditis, I2, ↑ Thyroxine
F/u in 6-12 wks

21. MANAGEMENT
approaches
•Anti thyroid drugs,beta blockers
•Radioactive Iodine I131
•surgery

22. Choice Of Therapy
•Type of thyrotoxicosis
•Age of the patient
•Co existing medical illness
•Severity of thyrotoxicosis
•Goitre size
•Presence of ophtalmopathy
•Patient preference
Factors
influencing

23. ANTITHYROID DRUGS
 Indications for antithyroid drugs:
Patients with high likelihood of remission
the elderly or others with comorbidities increasing
surgical risk or with limited life expectancy
Toxicity in pregnant women
moderate to severe active Graves’
ophthalmopathy (GO)
Before surgery, to make the patient euthyroid
Soon after starting radioactive I131therapy for 6 to
12 weeks

24. Anti Thyroid Drugs (ATD)
 Medications known to inhbit thyroid hormone are
 Propylthrouracil
Drug class : thioamides
 Metimazole

25. How long to give ATD ?
 Most patients have improved symptoms in 2 weeks and become euthyroid
in about 6 weeks
 Check TSH and FT4 every 4 to 6 weeks
 In Graves, many go into remission after 12-18 months
 Once ATD therapy is discontinued, the patient should be monitored every
three months for the first year, and then annually
 40% experience recurrence in 1 yr.
 MNG and Toxic Adenoma will not get cured by ATD.

26. adjuvants
 Beta blockers
 Inhibit adrenergic effects
 Indications
Prompt control of symptoms;
treatment of choice for thyroiditis;
 first-line therapy before surgery, radioactive iodine, and antithyroid
drugs;
 Contraindications
Use with caution in older patients and in patients with pre-existing
heart disease, chronic obstructive pulmonary disease, or asthma
 Propranolol is the most commonly prescribed medication in doses of
about 20 to 40 mg four times daily

27. Adjuvants ….
 Iodides
 Block the conversion of T4to T3 and inhibit hormone release
 Indications
preoperatively when other medications are ineffective or
contraindicated;
to reduce gland vascularity before surgery for Graves’
disease
 during preg-nancy when antithyroid drugs are not tolerated;
 Complications
Paradoxical increases in hormone release with prolonged use;
 common side effects of sialadenitis, conjunctivitis, or acneform
rash;

28. RADIOIODINE THERAPY
 Radioactive iodine
 Concentrates in the thyroid gland and destroys thyroid tissue
 High cure rates with single-dose treatment (80 percent);
 treatment of choice for
 Graves’ disease in the United States,
Multi nodular goitre, toxic nodules in patients older than 40 years,
and
 In recurrent thyrotoxicosis
 It is effective, safe, and does not require hospitalization.
 Given orally as a single dose in a capsule or liquid form.

29. RADIOIODINE THERAPY………
 Drawbacks
 Delayed control of symptoms;
 post treatment hypothyroidism in majority of patients with Graves’
disease regardless of dosage (82 percent after 25 years);
 contraindicated in patients who are pregnant or breastfeeding;
 can cause transient neck soreness, flushing, and decreased taste;
radiation thyroiditis in 1 percent of patients;
 may exacerbate Graves’ ophthalmopathy;
 may require pre treatment with antithyroid drugs in older or cardiac
patients

30. Surgical Treatment
 Surgical treatment is reserved
 patient preference
 Pregnant women who can’t tolerate ATD
 child or adolescent intolerant of ATDs
 large goiter, with or without compressive symptoms
 severe Graves’ ophthalmopathy
 the presence of suspicious nodules

31. Preoperative Preparation
 Standard preparation
 make the patient euthyroid/ near euthyroid using antythyroid drugs
 Alternative method
 rapid control of thyroid status can be achieved with a combination of
thionamides, SSKI, dexamethasone (1 to 2 mg twice daily), and beta
blockers
very rapid control=> operation within a week
Lugol’s iodide solution or saturated potassium iodide( three
drops twice daily) for 7 to 10 days

32. SURGICAL TECHNIQUE
Extent of thyroidectomy
 controversial, and determined by the desired outcome
 Risk of recurrence Vs hypothyroid, and surgeons experience
 Total or near thyroidectomy
for patients with coexistent thyroid cancer, sever ophthalmopathy,
life treating reactions to antythyroid drugs
 Subtotal thyroidectomy is recommended for the rest
bilateral subtotal thyroidectomy in which 1–2 grams of thyroid tissue
is left on both sides.
Hartley Dunhill procedure

33. SURGICAL………..
 GRAVES DISEASE
 near-total or total thyroidectomy is the procedure of choice
 TMNG
 near- total or total thyroidectomy should be performed
 TOXIC ADENOMA
an ipsilateral thyroid lobectomy, or
 isthmusectomy
 In patients with coexisting eye disease,
 total thyroidectomy

34. Surgical options
Features
Control of toxicity
Return to euthyroid
state
Recurrence
Thyroid failure
Hypoparathyroidism
Followup
Total Thyroidectomy
Immediate
Immediate
None
100%
5%
Minimal
Subtotal
thyroidectomy
Immediate
Variable
5%
25%
1%
lifelong

35. Postoperative management
 Following surgery, thyroid hormone replacement should be started
 TSH should be measured every 1–2 months until stable, and then annually
 RAIT should be used for retreatment of persistent or recurrent
hyperthyroidism following inadequate surgery
 Following thyroidectomy, serum calcium hormone levels be measured, and
oral calcium supplementation be administered based on these results

36. novel minimally invasive therapies
 Percutaneous Ethanol Injection (PEI) for Nodules
 Injections of ethanol can be administered directly to toxic
thyroid nodules, cysts and large nontoxic thyroid nodules
 Ultrasound-Guided Laser Thermal Ablation (LTA) for
Nodules
 Percutaneous laser thermal ablation is used to reduce both
hyperfunctioning and compressive nodule

37. Treatments Under Investigation
 Arterial Embolization
 Indicated in patients with severe hyperthyroidism who cannot tolerate or
who prefer not to use conventional treatment methods
 The Novel Molecule
 a small-molecule antagonist that directly inhibits or prevents TSI antibodies from
activating the TSH receptor.
 The small-molecule antagonist has not yet been studied in clinical trials
 Therapeutic Peptides
 antagonistic peptides that interfere with the action of TSH receptor antibodies
as well as peptides that bind to TSH receptor antibodies, preventing them from
reacting with the TSH receptor

38. Choice of therapy
Diffuse toxic goitre
 over 45 years, radioiodine.
 under 45 years,
 surgery for the large goitre and
 anti-thyroid drugs or radioiodine
for the small goitre
 Toxic nodular goitre
 Surgery
 Toxic nodule
 Surgery or radioiodine(>45)
 Recurrent thyrotoxicosis after surgery
 radioiodine is the treatment of choice, but anti-
thyroid drugs may be used in young women
intending to havechildren. Further surgery has
little place.
8/22/2015managment of hyperthyroidism

40. Thyroid storm
 Is a life threatening emergency
 Characterized by sudden appearance of clinical signs of hyperthyroidism
due to the abrupt release of T4 and T3 into circulation.
 Mortality is as high as 25% to 30%.
 Commonly associated with Grave's disease.

41. Thyroid storm……….
 Predisposing conditions:
 Medical factors :
 Infection ,
 Fever
 Uncontrolled toxicity
 Irregular drug intake
 Pregnancy,
 Radio iodine therapy
 DKA.
Surgical factors
Anxious and nervous patient
before surgery,
Too much handling of gland just
before surgery.

42. Thyroid storm……….
 Clinical features :
 Fever ranges from 38 to 41°C
 Tachycardia: arrhythmias commonly atrial fibrillation
 CHF - initially high output failure, Later may go for Low output failure.
 Shock - cardiogenic/hypovolemic
 Electrolyte imbalance
 Hypo/hyperglycemia may also be present.
 Marked anxiety, agitation, psychosis.

43. TREATMENT

44. References
 HYPERTHYROIDISM AND OTHER CAUSES OF THYROTOXICOSIS:
MANAGEMENT GUIDELINES OF THE ATA AND AACE Baskin HJ, Cobin
RH, Duick DS, et al (American Association of Clinical
Endocrinologists) 2011
 Klein I, Becker D, Levey GS.Treatment of hyperthyroid disease. Ann
Int Med.1994;121:281-288.
 Schwartz’s Principles of Surgery, 9th ed.
 William’s Text Book Of Endocrinology, 11th ed.
 Bailey & Loves’ Short Practice of Surgery, 25th ed.
 Greenspan’s Basic & Clinical Endocrinology, 8th ed.
 Uptodate

45. Thank you

46. Tips for Coping with Hyperthyroidism
 Small measures can be taken to alleviate and reduce
hyperthyroidism symptoms
 Try to:
 Reduce stress by listening to music, taking a long bath or
meditating in a quiet place
 Avoid caffeine and other stimulants as they may worsen
certain symptoms
Ice packs on the throat can help to reduce inflammation
Stay away from refined foods, shellfish, wheat, and alcohol
 Avoid food and supplements containing iodine