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
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
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
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
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
39.
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.
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
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
