sendomet 1 semarang sept 2014

Clinical Problems
in Thyroid Disease

Asman Manaf

Sub division Endocrinology and Metabolism

Department of Medicine , Medical Faculty
University of Andalas / RSUP Dr M Jamil Padang
 Morphology of

Normal thyroid

unpalpable
invisible
 The role of
three hormones in
feedback mechanism
Graves’ disease

• autoimmune disease
• primary hyperthyroidism
• more frequent in female
Struma diffusa toxica ( Graves’ disease )
 Graves’ disease
Imbalance T supressor / Sel T helper

Th1
(IL-2, INF- γ, TNF-β) ↑ Th2 ↑
IL-5↑ IL-10↑ IL-13↑

IL-4↑

Activation of TSH receptors

and Antibodi production ↑
( Sel B )

Antigen-antibody rx
in thyroid gland ↑

Hypertrophy &
hyperfunction
of thyroid gland

Struma diffusa T3 / T4 serum ↑

 Factors That Alter Thyroxine
and Triiodothyronine Binding in Serum
Increased TBG Decreased TBG Binding inhibitors
Inherited Inherited Salicylates
Pregnancy Androgens Furosemide
Neonatal state Anabolic steroids Free fatty acids
Estrogens Glucocorticoids Phenytoin

Hepatitis Severe illness Carbamazepine
Porphyria Hepatic failure NSAIDs
(variable,
transient)
Heroin Nephrosis
Methadone Nicotinic acid Heparin
Mitotane L-Asparaginase
5-Fluorouracil
SERMS (e.g.,
tamoxifen,
raloxifene)
Perphanazine

TBG, T4-binding globulin; SERMS, selective estrogen receptor

modulators; NSAIDs, nonsteroidal anti-inflammatory drugs.
 Anti Thyroid Drugs (ATD )

◘ Thiouracil or Methimazole as the primary

therapy : the medication should be continued
for approximately 12–18 months,
then tapered or discontinued if the TSH
is normal at that time.

◘ Measurement of TRAb levels ( esp. in GD ) prior

to stopping ATD therapy is suggested, as it
aids in predicting which patients can be
weaned from the medication, with normal
levels indicating greater chance for remission.
 Graves’ disease
Imbalance T supressor / Sel T helper

Th1
(IL-2, INF- γ, TNF-β) ↑ Th2 ↑
IL-5↑ IL-10↑ IL-13↑

IL-4↑
Hipotalamus

Activation of TSH receptors

TRH ↓ and Antibodi production ↑
( Sel B )
propilthiourasil
Hipofisa Antigen-antibody rx
in thyroid gland ↑ methimazol
Anti Thy
roid Drugs
TSH ↓ Hypertrophiy & Hormogenesis
hyperfunction ( intrathyroid )↑
of thyroid gland

T3, T4 ↑
 Prior to initiating
antithyroid drug therapy for GD

It is suggested that patients have

a baseline complete blood count,
including white count with differential,

and,

a liver profile
including bilirubin and transaminases.
 Remission

 If euthyroid at least 1 yr after stopping th/.

 The probability of remission : 40 -50% ( after 12-18
mo. th/ )
 Lesser probability if :
– Severe hyperthyroidism
– Larger goiter
– Serum ratio of T3/ T4 > 20
– Serum antithyrotropin antibodi ↑

N Engl J Med 2005;352:905-17

 Relapse

 Usually in the first 3 – 6 month after treatment

 Then, recurrence will decrease after 1 – 2 yrs
 Generally, recurrence index will be 50-60%
 75% woman with Graves’ disease in remission,
will be relapse or thyroiditis during postpartum

N Engl J Med 2005;352:905-17

Struma nodosa toksika
 No remission in TMNG

◘ ATDs do not induce remission in patients with

nodular thyroid disease. Therefore,
discontinuation of treatment results in relapse

◘ Suggested that long-term methimazole

treatment of TMNG or TA be avoided, except in
some elderly or otherwise ill patients with limited
longevity who are able to be monitored regularly,
and, in patients who prefer this option.
Radio iodine treatment

 Internal radiation ( I131 )

 As an alternative treatment
 In USA: the first choice,
 In Europe : the second choice
( incl. Indonesia )
Post radioactive iodine therapy

● Follow-up within the first 1–2 months after

radioactive iodine therapy for GD should include
an assessment of free T4 and total T3

● If the patient remains thyrotoxic, biochemical

monitoring should be continued at 4–6 week
intervals.

● Hypothyroidism may occur from 4 weeks on, but

more commonly between 2 and 6 months,
 Thyroidectomy
◙ Whenever possible,
patients with GD undergoing
thyroidectomy should be rendered
euthyroid with methimazole.

◙ The patient should be adequately

treated with beta-blockade and
potassium iodide in the
immediate preoperative period.
 Post surgical treatment
◘ Following surgery for TMNG, thyroid hormone
replacement : started at a dose appropriate for
the patient’s weight (0.8 mcg/lb or 1.7 mcg/kg),
elderly patients needing somewhat less. TSH
should be measured every 1–2 months until
stable, and then annually.

◘ Following surgery for TA, TSH and estimated

free T4 levels should be obtained 4–6
weeks after surgery, and thyroid hormone
supplementation started if there is a
persistent rise in TSH above the normal range.
 Retreatment

◙ Radioactive iodine therapy

should be used for retreatment of
persistent or recurrent
hyperthyroidism following
inadequate surgery for TMNG or TA.
Post op. hypocalcemia

◙ Following thyroidectomy for TMNG, we

suggest that serum calcium or intact
parathyroid hormone levels be
measured, and that oral calcium and
calcitriol supplementation be
administered based on these results
 Subclinical
Hyperthyroidism
 Subclinical Hyperthyroidism:
When to Treat ?

Factor TSH (< 0.1 mU/L) TSH (0.1–0.5 mU/L)

Age > 65 Yes Consider treating

Age < 65 with comorbidities
Heart disease Yes Consider treating
Osteoporosis Yes No
Menopausal Consider treating Consider treating

Age < 65, asymptomatic Consider treating No

Nor,mal range :
TSH : 0,5-5 uU/ml ; T4 : 4-11 ug/ 100 mg ; T3 : 80-160 ng/ml
Thyroid Storm
Thyroid Storm : Emergency Case

A multimodality treatment approach to patients

with thyroid storm should be used, including

● beta-adrenergic blockade,
● antithyroid drug therapy,
● inorganic iodide,
● corti-costeroid therapy,
● aggressive cooling with acetaminophen
and cooling blankets,
● volume resuscitation,
● respiratory support and
● monitoring in an intensive care unit.
HYPOTHYROIDISM &
SUBCLINICAL
HYPOTHYROIDISM
 Grades of hypothyroidism
Overt Mild Subclinical

Sympt/signs obvious minimal none

Serum T4 low low/n normal
Serum T3 low normal normal
Serum TSH v. high m. high s. high
TSH resp TRH supra n. supra n. supra.n.
 PREVALENCE

◙ increased with age

◙ over 60 years , men: 5.0 % ; women:
◙ 13.6 % ( Framingham Study,1985 )
◙ more prevalent in women
◙ prevalence rate: males, 0.7 – 5.7 % ;
females, 3.0 – 13.6 %
◙ more prevalent in autoimmune disease
ec. type 1 diabetes mellitus, chronic active
hepatitis, Down syndr.
Type 1 DM & thyroiditis

 Approximately 10% of patients with

type 1 diabetes mellitus will develop
chronic thyroiditis during their lifetime,
which may lead to the insidious onset
of subclinical hypothyroidism.
 Reasons of
Screening and Aggressive Case Finding
for Hypothyroidism

 The condition is prevalent

 Important health problem
 Early diagnosis is not usually made
 Diagnosis is simple and accurate
 Treatment is cost effective and safe
DIAGNOSIS

- Subclinical hypothyroidism cannot

be identified on the basis of
symptoms and signs

- Diagnostic point: normal serum fT4

and moderately high serum TSH
Question : to treat or not to treat
Reasoning :

- frequently develop overt hypothyroidism,

TSH concentration will be a most powerful predictor
( Diez, 2004 )

- may decrease the size of goiter ( if present ) in 77 % of

patients ( Romaldini , 1996 )

- associated with coronary artery disease in older person

( Hak, 2000 ; Mya, 2002 )

- treatment has a beneficial effect on LDL level and

cardiovascular mortality ( Meier,2001 )
R/ Hypothyroidism

◘ Initial dose : ( levothyroxine )

TSH > 20 µU / ml : 50 – 75 µg / day
TSH > 44 µU / ml : 100 – 150 µg / day

◘ Average maintenance dose 100 – 200 µg / day :

control 90% of case
 Screening before pregnancy
Women with positive levels of serum TPOAb or with
a TSH greater than 2.5 mIU/L who are not being
treated with L-thyroxine should be monitored every 4
weeks in the first 20 weeks of pregnancy for the
development of hypothyroidism.

Overt untreated hypothyroidism during pregnancy

may adversely affect maternal and fetal
outcomes. These adverse outcomes include
increased incidences of spontaneous miscarriage,
preterm delivery, pre-eclampsia, maternal hypertensi
on, postpartum hemorrhage, low birth weight and
stillbirth, and impaired intellectual and psychomotor
development of the fetus
 Management of

Thyroid nodule
 history, physical, TSH

1
6

Algorhytm in evaluation of thyroid nodule ( s )

 SUMMARY
1. Functioning nodule R/ hyperthyroidism
TSH : low (TMNG , or TA )
Non functioning nod / US
2. TSH : low Close follow up
or Surgery
FNA ?
Hyper functioning nod. or not
3. FNA: benign /
Follow up or
Surgery
folicular neopl. /

FNA: malignant / susp paplillary / Surgery

4. Undeterminate / Hurthle cells

R/ for Clinical
No nodule / US
5. Elevated TSH
Or Subclinical
Hypothyroidism

No nodule / US
6. Normal TSH
No thyroid
problem
Assalamu ’alaikum