APPROACH TO THYROID DIORDERS

1. APPROACH TO A
PERSON WITH
ABNORMAL TSH
Dr. Ashutosh

2. INTRODUCTION
• The thyroid is distinctive amid the endocrine glands
owing to the large store of hormones it contains.
• The metabolic homeostasis in an adult is maintained
by the thyroid gland which is achieved through
secretion of the hormones, Thyroxine(T4) and
triiodothyronine(T3), regulated by thyroid stimulating
hormone (TSH) secreted by anterior pituitary.
• Thyroxine is obtained from thyroid and triiodothyronine
is formed by the conversion of fT4 to fT3.
• Normal T4 levels: Total-100nm/L, free- 20pmol/L, t1/2
7days
• Normal T3 levels: Total- 1.8nm/L, free- 5pmol/L, t1/2

3. • The hypothalamo-pituitary-thyroid axis regulates the
level of thyroid hormones in the blood by feedback
mechanisms.
• When the thyroid is stimulated by thyrotropin
hormone, it leads to increased levels of thyroid
hormones (fT3 and fT4).
• Increased levels of these hormones send signals to
the pituitary to stop the production of thyrotropin
hormone.
• On the contrary, the pituitary gland is stimulated if
there are low levels of fT3 and fT4 from the thyroid
until it reaches the normal level. This is called as the
negative feedback mechanism.

5. THYROID STIMULATING HORMONE
(THYROTROPIN)
• TSH is the major regulator for the growth and
functions of thyroid. In a healthy adult the rate of
production of TSH is within 100 to 200mU/day. In
normal serum, TSH is present at concentrations
between 0.4 and 4.2 mIU/L with a half life of 30mins.
• TSH is composed of an αsubunit of 14 kd (92 amino
acids) that is common to LH, follicle stimulating
hormone (FSH), hCG, and a specific βsubunit of 112
amino acids that is synthesized in thyrotrophs.
• In normal thyrotrophs and in thyrotroph tumors,
synthesis of αsubunit is in excess, indicating that the
quantity of βsubunit is rate limiting for TSH

6. • There is a linear inverse relationship between the
serum free T4 concentration and the log of the TSH,
making the serum TSH concentration an exquisitely
sensitive indicator of the thyroid state of patients with
an intact hypothalamic-pituitary axis.

7. Indications for TFT:
1. Decreased or increased
metabolism
2.Goitre on examination
3. Family history
High TSH
Hypothyroidism
Normal
Thyroid
disease
improbable
Low TSH
Hyperthyroidis
m
Order TSH and
fT4

8. CONDITIONS ASSOCIATED
WITH HIGH TSH

10. CONDITIONS WITH HIGH TSH
AND LOW FT4
• 1. Primary Hypothyroidism
• 2. Thyroid ablation/removal
• 3.Transient thyroiditis

11. HASHIMOTOS THYROIDITIS
• It is a chronic autoimmune thyroiditis which is the most
common cause of hypothyroidism.
• The patient may present with normal thyroid function
or overt or subclinical hypothyroidism.
• It occurs more in females than in males and increases
with age.
• Autoimmune hypothyroidism may be associated with a
goiter (Hashimoto’s, or goitrous thyroiditis) or, at the
later stages of the disease, minimal residual thyroid
tissue (atrophic thyroiditis)

12. CLINICAL MANIFESTATIONS
• The onset is usually insidious, and the patient may
become aware of symptoms only when euthyroidism
is restored.
• Patients with Hashimoto’s thyroiditis may present
because of goiter rather than symptoms of
hypothyroidism. The goiter may not be large, but it is
usually irregular and firm in consistency.
• Patients with atrophic thyroiditis or the late stage of
Hashimoto’s thyroiditis present with symptoms and
signs of hypothyroidism.

15. INVESTIGATIONS:
• As per the ATA/AACE guidelines, patients with
autoimmune thyroiditis can be diagnosed by following
tests:
oThyroid antibodies:
I. Anti-thyroglobulin antibodies (positive in 20-25%
patients)
II. Anti-microsomal/ anti-thyroid peroxidase antibodies
(TPOAb)
III. TSH receptor antibodies
oTotal T3

16. TREATMENT
• If there is no residual thyroid function, the daily
replacement dose of levothyroxine is usually 1.6-1.8
μg/kg body weight (typically 100–150 μg), ideally
taken at least 30 min before breakfast.
• Adult patients under 60 years old without evidence of
heart disease may be started on 50–100 μg
levothyroxine (T4) daily.
• The dose is adjusted on the basis of TSH levels, with
the goal of treatment being a normal TSH, ideally in
the lower half of the reference range.
• TSH responses are gradual and should be measured
about 2 months after instituting treatment or after any
subsequent change in levothyroxine dosage.

17. IODINE DEFICIENCY (ENDEMIC
GOITER)
• The term endemic goiter denotes any goiter that
occurs in a region where goiter is prevalent. It is
mainly due to iodine deficiency.
• Endemic goiter is also caused by exposure to
environmental goitrogens such as cassava root,
which contains a thiocyanate; vegetables of the
Cruciferae family (known as cruciferous
vegetables) (e.g., Brussels sprouts, cabbage, and
cauliflower); and milk from regions where
goitrogens are present in grass.

18. • Most abnormalities in iodine metabolism in patients
with endemic goiter are consistent with the expected
effects of iodine deficiency. The absolute iodine
uptake is normal or low.
• In areas of moderate iodine deficiency, the serum T4
concentration is usually in the lower range of normal;
in areas of severe deficiency, values are decreased.
• Nevertheless, most patients in these areas do not
appear to be in a hypothyroid state because of an
increase in the synthesis of T3 at the expense of T4.
TSH levels are typically in the upper range of normal.
• Low urinary iodine levels (<5mcg/dL) support
diagnosis of iodine deficiency.

19. • Although hypothyroidism due to iodine deficiency
can be treated with thyroxine, public health
measures to improve iodine intake should be
advocated to eliminate this problem. Iodized salt or
bread or a single bolus of oral or intramuscular
iodized oil have all been used successfully.
• Endemic goiter can be treated by the addition of
iodine to communal drinking water.
• Similarly, thyroid hormone usually has no effect on
long-standing goiter or on established mental or
skeletal changes, but it should be given in full-
replacement doses if there is evidence of
hypothyroidism. This is of paramount importance in
pregnant women.

20. ACUTE THYROIDITIS
• Acute thyroiditis is rare and due to suppurative
infection of the thyroid.
• The patient presents with thyroid pain, often referred
to the throat or ears, and a small, tender goiter that
may be asymmetric.
• Fever, dysphagia, and erythema over the thyroid are
common, as are systemic symptoms of a febrile
illness and lymphadenopathy.

21. • The erythrocyte sedimentation rate (ESR) and white
cell count are usually increased, but thyroid function is
normal.
• FNA biopsy shows infiltration by polymorphonuclear
leukocytes; culture of the sample can identify the
organism. Antibiotic treatment is guided initially by
Gram stain and, subsequently, by cultures of the FNA
biopsy.
• Surgery may be needed to drain an abscess, which
can be localized by CT scan or ultrasound. Tracheal
obstruction, septicemia, retropharyngeal abscess,
mediastinitis, and jugular venous thrombosis may
complicate acute thyroiditis but are uncommon with
prompt use of antibiotics.

22. SUBACUTE THYROIDITIS
• This is also termed de Quervain’s thyroiditis,
granulomatous thyroiditis, or viral thyroiditis.
• Many viruses have been implicated, including mumps,
coxsackie, influenza, adenoviruses, and echoviruses,
but attempts to identify the virus in an individual
patient are often unsuccessful and do not influence
management.
• The peak incidence occurs at 30–50 years, and
women are affected three times more frequently than
men.

23. • The patient usually presents with a painful and
enlarged thyroid, sometimes accompanied by fever.
• There may be features of thyrotoxicosis or
hypothyroidism, depending on the phase of the illness.
• Malaise and symptoms of an upper respiratory tract
infection may precede the thyroid-related features by
several weeks. In other patients, the onset is acute,
severe, and without obvious antecedent cause.
• Thyroid function tests characteristically evolve through
three distinct phases over about 6 months: (1)
thyrotoxic phase, (2) hypothyroid phase, and (3)
recovery phase.

24. • In the thyrotoxic phase, T4 and T3 levels are
increased, reflecting their discharge from the
damaged thyroid cells, and TSH is suppressed. The
T4/T3 ratio is greater than in Graves’ disease or
thyroid autonomy, in which T3 is often
disproportionately increased.
• The diagnosis is confirmed by a high ESR and low
uptake of radioiodine (<5%) or 99mTc pertechnetate.
• The white blood cell count may be increased, and
thyroid antibodies are negative. If the diagnosis is in
doubt, FNA biopsy may be useful.

25. MANAGEMENT
• Relatively large doses of aspirin (e.g., 600 mg every
4–6 h) or NSAIDs are sufficient to control symptoms in
many cases.
• If this treatment is inadequate, or if the patient has
marked local or systemic symptoms, glucocorticoids
should be given.
• The usual starting dose is 40–60 mg of prednisone,
depending on severity. The dose is gradually tapered
over 6–8 weeks, in response to improvement in
symptoms and the ESR.
• Thyroid function should be monitored every 2–4
weeks using TSH and unbound T4 levels.

26. SILENT THYROIDITIS
• Painless thyroiditis, or “silent” thyroiditis, occurs in
patients with underlying autoimmune thyroid disease
and has a clinical course similar to that of subacute
thyroiditis.
• The condition occurs in up to 5% of women 3–6
months after pregnancy and is then termed
postpartum thyroiditis.
• Typically, patients have a brief phase of thyrotoxicosis
lasting 2–4 weeks, followed by hypothyroidism for 4–
12 weeks, and then resolution; often, however, only
one phase is apparent. The condition is associated
with the presence of TPO antibodies antepartum, and
it is three times more common in women with type 1

27. • Glucocorticoid treatment is not indicated for silent
thyroiditis.
• Severe thyrotoxic symptoms can be managed with a
brief course of propranolol, 20–40 mg three or four
times daily.
• Thyroxine replacement may be needed for the
hypothyroid phase but should be withdrawn after 6–9
months, as recovery is the rule.
• Annual follow-up thereafter is recommended,
because a proportion of these individuals develop
permanent hypothyroidism. The condition may recur in
subsequent pregnancies.

28. CHRONIC THYROIDITIS
• The most common clinically apparent cause of chronic
thyroiditis is Hashimoto’s thyroiditis.
• Riedel’s thyroiditis is a rare disorder that typically
occurs in middle-aged women. It presents with an
insidious, painless goiter with local symptoms due to
compression of the esophagus, trachea, neck veins,
or recurrent laryngeal nerves. The goiter is hard, non-
tender, often asymmetric, and fixed, leading to
suspicion of a malignancy.
• Diagnosis requires open biopsy as FNA biopsy is
usually inadequate. Treatment is directed to surgical
relief of compressive symptoms. Tamoxifen may also
be beneficial.

29. CONDITIONS WITH HIGH TSH
AND HIGH FT4
• 1. Thyroid hormone resistance
• 2. TSH secreting adenoma

30. THYROID HORMONE RESISTANCE(RTH)
• Most patients with RTH have a mutation in the gene
encoding the thyroid hormone receptor β-subunit (TRβ)
that interferes with the capacity of that receptor to respond
normally to T3, usually by reducing its T3-binding affinity
• Patients with RTH usually are recognized because of
thyroid enlargement, which is present in about two thirds of
these individuals. Patients usually report a mixture of
symptoms of hyperthyroidism and hypothyroidism. With
respect to the heart, palpitations and tachycardia are more
common than a reduced heart rate; however, patients may
also demonstrate growth retardation and retarded skeletal
maturation.

31. • Abnormalities in neuropsychological development
exist, with an increased prevalence of attention deficit-
hyperactivity disorder, which is found in approximately
10% of people with RTH.
• Deafness in patients with RTH reflects the important
role of TRβ and thyroid hormone in the normal
development of auditory function.
• A reduced response to thyroid hormone is the
biochemical basis for the condition. However, the
laboratory results may be the first clear evidence that
a patient, otherwise thought to have hyperthyroidism,
has RTH. These tests show the unusual combination
of an increased fT4 accompanied by normal or slightly
increased TSH levels.

32. • Treatment is difficult because thyroid hormone
analogues that are designed to suppress TSH
and thereby relieve the hyperthyroxinemia may
lead to worsening of the cardiovascular
manifestations of the condition.
• Therapy with 3,5,3′-triiodothyroacetic acid
(TRIAC), a thyroid hormone analogue, has been
used in several patients.
• It suppresses the pituitary secretion of TSH but
not does not have any effect on peripheral thyroid
functions.

33. TSH SECRETING PITUITARY ADENOMA
• TSH-secreting pituitary adenoma is a rare cause of
thyrotoxicosis. It is characterized by the presence of an
inappropriately normal or increased TSH level in a patient
with hyperthyroidism, diffuse goiter, and elevated T4 and
T3 levels .
• Elevated levels of the α-subunit of TSH, released by the
TSH-secreting adenoma, support this diagnosis, which can
be confirmed by demonstrating the pituitary tumor on MRI
or CT scan.
• A combination of trans-sphenoidal surgery, sella irradiation,
and octreotide may be required to normalize TSH, because
many of these tumors are large and locally invasive at the
time of diagnosis. Radioiodine or antithyroid drugs can be
used to control thyrotoxicosis.

34. HIGH TSH WITH NORMAL FT4
• Subclinical hypothyroidism (TSH rarely above 15)
• Sick–euthyroid syndrome (recovery phase; will not persist
over 9m)
• Drugs like Metoclopramide (usually not above 10)
• Adrenal insufficiency (Expected to be more ill)

35. SUBCLINICAL
HYPOTHYROIDISM
• By definition, subclinical hypothyroidism refers to
biochemical evidence of thyroid hormone deficiency
(TSH levels are increased with normal fT3 and fT4
levels) in patients who have few or no apparent
clinical features of hypothyroidism.
• Regardless of the patients being asymptomatic, the
risks associated with the condition include
cardiovascular effects, progression to overt
hypothyroidism, hyperlipidemia and neuropsychiatric
effects.
• Two samples must be taken within a period of 2-3
months to differentiate from non-thyroid disease.

36. MANAGEMENT GUIDELINES:
1. If TSH> 10mU/L treat with levothyroxine
2. If TSH is between 4-10mU/L with positive TPO
antibodies, check TSH yearly, and if TPO
negative, check TSH every 3-5 years.
3. If patient is symptomatic and TSH is between
4-10mU/L , patient has to be started on
levothyroxine for 3-6 months, if his condition
improves, treatment can be continued.
4. Levothyroxine is also recommended if the
patient is a woman who wishes to conceive or
is pregnant.

37. • Patients with hypothalamic-pituitary dysfunction
may have clinical and chemical hypothyroidism but
low, normal, or even elevated serum TSH
concentrations.
• The explanation for this paradox is that the biologic
effectiveness of the circulating TSH is impaired due to
abnormal glycosylation secondary to reduced TRH
stimulation of the thyrotrophs.
• In adrenal insufficiency, TSH may be modestly
elevated but returns to normal with glucocorticoid
replacement. This may reflect glucocorticoid mediated
amelioration of Hashimoto’s thyroiditis.

38. HYPOTHYROIDISM IN
PREGNANCY
• Women with a history or high risk of hypothyroidism
should ensure that they are euthyroid prior to
conception and during early pregnancy because
maternal hypothyroidism may adversely affect fetal
neural development and cause preterm delivery.
• The presence of thyroid autoantibodies alone, in a
euthyroid patient, is also associated with miscarriage
and preterm delivery; it is unclear if levothyroxine
therapy improves outcomes.

39. • Thyroid function should be evaluated immediately
after pregnancy is confirmed and every 4 weeks
during the first half of the pregnancy, with less
frequent testing after 20 weeks’ gestation.
• The levothyroxine dose may need to be increased by
up to 50% during pregnancy, with a goal TSH of less
than 2.5 mIU/L during the first trimester and less than
3.0 mIU/L during the second and third trimesters. After
delivery, thyroxine doses typically return to pre-
pregnancy levels.
• Pregnant women should be counseled to separate
ingestion of prenatal vitamins and iron supplements
from levothyroxine by at least 4 h.

40. CONGENITAL HYPOTHYROIDISM
• Hypothyroidism occurs in about 1 in 4000 newborns. It
may be transient, especially if the mother has TSH-R
blocking antibodies or has received antithyroid drugs,
but permanent hypothyroidism occurs in the majority.
• Neonatal hypothyroidism is due to thyroid gland
dysgenesis in 80–85%, to inborn errors of thyroid
hormone synthesis in 10–15%, and is TSH-R
antibody-mediated in 5% of affected newborns.
• The developmental abnormalities are twice as
common in girls.

41. CLINICAL MANIFESTATIONS
• The majority of infants appear normal at birth, and
<10% are diagnosed based on clinical features, which
include prolonged jaundice, feeding problems,
hypotonia, enlarged tongue, delayed bone maturation,
and umbilical hernia.
• Importantly, permanent neurologic damage results if
treatment is delayed. Typical features of adult
hypothyroidism may also be present.
• Other congenital malformations, especially cardiac,
are four times more common in congenital
hypothyroidism

42. MANAGEMENT
• Because of the severe neurologic consequences of
untreated congenital hypothyroidism, neonatal
screening programs have been established. These
are generally based on measurement of TSH or T4
levels in heel-prick blood specimens.
• When the diagnosis is confirmed, T4 is instituted at a
dose of 10–15 μg/kg per day, and the dose is adjusted
by close monitoring of TSH levels. T4 requirements
are relatively great during the first year of life, and a
high circulating T4 level is usually needed to
normalize TSH.
• Early treatment with T4 results in normal IQ levels, but
subtle neurodevelopmental abnormalities may occur
in those with the most severe hypothyroidism at
diagnosis or when treatment is delayed or suboptimal.

43. MYXEDEMA COMA
• Myxedema coma still has a 20–40% mortality rate,
despite intensive treatment, and outcomes are
independent of the T4 and TSH levels.
• Clinical manifestations include reduced level of
consciousness, sometimes associated with seizures,
as well as the other features of hypothyroidism.
• Hypothermia can reach 23°C (74°F).
• There may be a history of treated hypothyroidism with
poor compliance, or the patient may be previously
undiagnosed.

44. • Myxedema coma almost always occurs in the elderly
and is usually precipitated by factors that impair
respiration, such as drugs (especially sedatives,
anesthetics, and antidepressants), pneumonia,
congestive heart failure, myocardial infarction,
gastrointestinal bleeding, or cerebrovascular
accidents.
• Sepsis should also be suspected. Exposure to cold
may also be a risk factor.
• Hypoventilation, leading to hypoxia and hypercapnia,
plays a major role in pathogenesis; hypoglycemia and
dilutional hyponatremia also contribute to the
development of myxedema coma.

45. MANAGEMENT
• Levothyroxine can initially be administered as a single
IV bolus of 500 μg, which serves as a loading dose.
Although further levothyroxine is not strictly necessary
for several days, it is usually continued at a dose of 50–
100 μg/d.
• If suitable IV preparation is not available, the same initial
dose of levothyroxine can be given by nasogastric tube
(although absorption may be impaired in myxedema).
• An alternative is to give liothyronine (T3) intravenously
or via nasogastric tube, in doses ranging from 10 to 25
μg every 8–12 h.
• Another option is to combine levothyroxine (200 μg)
and liothyronine (25 μg) as a single, initial IV bolus
followed by daily treatment with levothyroxine (50–100
μg/d) and liothyronine (10 μg every 8 h).

46. • Supportive therapy should be provided to correct any
associated metabolic disturbances.
• External warming is indicated only if the temperature is
<30°C, as it can result in cardiovascular collapse.
• Parenteral hydrocortisone (50 mg every 6 h) should be
administered, because there is impaired adrenal reserve in
profound hypothyroidism.
• Any precipitating factors should be treated, including the
early use of broad-spectrum antibiotics.
• Ventilatory support with regular blood gas analysis is
usually needed during the first 48 h.
• Hypertonic saline or IV glucose may be needed if there is
severe hyponatremia or hypoglycemia; hypotonic IV fluids
should be avoided because they may exacerbate water
retention secondary to reduced renal perfusion and
inappropriate vasopressin secretion.

47. Conditions associated with low TSH

49. GRAVES DISEASE
• Graves’ disease accounts for 60–80% of
thyrotoxicosis. The prevalence varies among
populations, reflecting genetic factors and iodine
intake (high iodine intake is associated with an
increased prevalence of Graves’ disease).
• Graves’ disease occurs in up to 2% of women but
is one-tenth as frequent in men. The disorder
rarely begins before adolescence and typically
occurs between 20 and 50 years of age; it also
occurs in the elderly.

51. • In Graves’ disease, the thyroid is usually diffusely
enlarged to two to three times its normal size. The
consistency is firm, but not nodular. There may be a
thrill or bruit, best detected at the inferolateral margins
of the thyroid lobes, due to the increased vascularity of
the gland and the hyperdynamic circulation.
• Lid retraction, causing a staring appearance, can
occur in any form of thyrotoxicosis and is the result of
sympathetic overactivity. However, Graves’ disease is
associated with specific eye signs that comprise
Graves’ ophthalmopathy .
• The earliest manifestations of ophthalmopathy are
usually a sensation of grittiness, eye discomfort, and
excess tearing.

52. • The most serious manifestation is compression of the
optic nerve at the apex of the orbit, leading to
papilledema; peripheral field defects; and, if left
untreated, permanent loss of vision.
• Thyroid dermopathy occurs in <5% of patients with
Graves’ disease, almost always in the presence of
moderate or severe ophthalmopathy. Although most
frequent over the anterior and lateral aspects of the
lower leg (hence the term pretibial myxedema), skin
changes can occur at other sites, particularly after
trauma.
• Thyroid acropachy refers to a form of clubbing found
in <1% of patients with Graves’ disease. It is so
strongly associated with thyroid dermopathy that an
alternative cause of clubbing should be sought in a
Graves’ patient without coincident skin and orbital
involvement.

54. MANAGEMENT
• The hyperthyroidism of Graves’ disease is treated by
reducing thyroid hormone synthesis, using antithyroid
drugs, or reducing the amount of thyroid tissue with
radioiodine (131I) treatment or by thyroidectomy.
• The main antithyroid drugs are the thionamides,
such as propylthiouracil, carbimazole, and the active
metabolite of the latter, methimazole.
• All inhibit the function of TPO, reducing oxidation and
organification of iodide. These drugs also reduce
thyroid antibody levels by mechanisms that remain
unclear, and they appear to enhance rates of
remission.

55. • The initial dose of carbimazole or methimazole is
usually 10–20 mg every 8 or 12 h, but once-daily
dosing is possible after euthyroidism is restored.
• Propylthiouracil is given at a dose of 100–200 mg
every 6–8 h, and divided doses are usually given
throughout the course.
• Thyroid function tests and clinical manifestations are
reviewed 4–6 weeks after starting treatment, and the
dose is titrated based on unbound T4 levels.
• Propranolol (20–40 mg every 6 h) or longer-acting
selective β1 receptor blockers such as atenolol may
be helpful to control adrenergic symptoms, especially
in the early stages before antithyroid drugs take effect.

56. • RADIOIODINE THERAPY: causes progressive
destruction of thyroid cells and can be used as initial
treatment or for relapses after a trial of antithyroid
drugs.
• 131I dosage generally ranges between 370 MBq (10
mCi) and 555 MBq(15 mCi).
• Subtotal or near-total thyroidectomy is an option for
patients who relapse after antithyroid drugs and prefer
this treatment to radioiodine.
• Careful control of thyrotoxicosis with antithyroid drugs,
followed by potassium iodide (3 drops SSKI orally tid),
is needed prior to surgery to avoid thyrotoxic crisis
and to reduce the vascularity of the gland.

57. THYROTOXIC CRISIS OR
THYROID STORM
• It is rare, and presents as a life- threatening
exacerbation of hyperthyroidism, accompanied by
fever, delirium, seizures, coma, vomiting, diarrhea,
and jaundice.
• The mortality rate due to cardiac failure, arrhythmia, or
hyperthermia is as high as 30%, even with treatment.
• Thyrotoxic crisis is usually precipitated by acute illness
(e.g., stroke, infection, trauma, diabetic ketoacidosis),
surgery (especially on the thyroid), or radioiodine
treatment of a patient with partially treated or
untreated hyperthyroidism.

58. • Management requires intensive monitoring and
supportive care, identification and treatment of the
precipitating cause, and measures that reduce thyroid
hormone synthesis.
• Large doses of propylthiouracil (500–1000 mg loading
dose and 250 mg every 4 h) should be given orally or
by nasogastric tube or per rectum.
• Methimazole can be used in doses up to 30 mg every
12 h
• One hour after the first dose of propylthiouracil, stable
iodide is given to block thyroid hormone synthesis via
the Wolff-Chaikoff effect (the delay allows the
antithyroid drug to prevent the excess iodine from
being incorporated into new hormone).

59. • A saturated solution of potassium iodide (5 drops
SSKI every 6 h) or, where available, ipodate or
iopanoic acid (500 mg per 12 h) may be given orally.
• Propranolol should also be given to reduce
tachycardia and other adrenergic manifestations (60–
80 mg PO every 4 h; or 2 mg IV every 4 h).
• Additional therapeutic measures include
glucocorticoids (e.g., hydrocortisone 300 mg IV bolus,
then 100 mg every 8 h), antibiotics if infection is
present, cooling, oxygen, and IV fluids.

60. SUBCLINICAL HYPERTHYROIDISM
• In this condition there are no signs or symptoms of
thyrotoxicosis but the serum TSH is subnormal
despite normal serum free thyroid hormone
concentrations.
• The diagnosis of subclinical hyperthyroidism requires
tests revealing several subnormal TSH concentration
results spaced months apart in the presence of normal
free T3 and T4 concentrations.
• Several studies have shown that suppressed TSH can
normalize spontaneously over several years,
particularly in patients without nodular goiter.

62. • In considering the decision for or against treatment of
persistently subnormal TSH concentrations (i.e., <0.1
mU/L with normal free thyroid hormone
concentrations), an evaluation should be made for
conditions that may benefit from treatment as well as
to determine the cause of the hyperthyroidism.
• On the other hand, patients with subclinical
hyperthyroidism due to toxic nodular goiter or a
solitary hyperfunctioning adenoma can often be
treated with a single dose of radioactive iodine with a
relatively low risk of subsequent hypothyroidism.

63. THYROTOXICOSIS FACTITIA
• Thyrotoxicosis that arises from the ingestion, usually
chronic, of excessive quantities of thyroid hormone
occurs typically in individuals with underlying
psychiatric disease, especially in paramedical
personnel who have access to thyroid hormone or in
patients for whom thyroid hormone medication has
been prescribed in the past. Usually, the patient is
aware of taking thyroid hormone but may adamantly
deny it.
• In the absence of preexisting disease of the thyroid,
the diagnosis is made from the combination of typical
thyrotoxic manifestations together with thyroid atrophy
and hypofunction.

64. • TSH levels are suppressed. Serum T4 concentrations
are increased unless the patient is taking T3, in which
case they are subnormal. Serum T3 concentrations
are increased in either case.
• Hypofunction of the thyroid gland is evidenced by the
subnormal values of RAIU. The presence of low,
rather than elevated, values of serum Tg is a clear
indication that the thyrotoxicosis results from
exogenous hormone rather than thyroid hyperfunction.
• Treatment of thyrotoxicosis factitia consists of
withdrawal of the offending medication. Psychiatric
consultation is often required.

65. IODIDE-INDUCED HYPERTHYROIDISM
• Administration of supplemental iodine to subjects with
endemic iodine deficiency goiter can result in iodine-
induced Graves’ disease. This response, termed
iodide- induced hyperthyroidism or the Jod-Basedow
effect.
• There are two major patterns of the underlying thyroid
disorder. In the first, which is common in older
individuals, a nodular goiter with areas of autonomous
function is present, and TRAbs are not detectable in
the blood.
• The second pattern occurs in younger individuals
with diffuse goiter, in whom stimulating TRAbs are
often present. These findings indicate that jod-
Basedow occurs in thyroid glands in which thyroid

66. • Iodide-induced hyperthyroidism is an important
disorder in areas of the world in which dietary iodine
intake is high.
• In regions in which iodine intake is marginal but overt
iodine deficiency is absent, moderate increments in
iodine intake may induce hyperthyroidism in patients
with autonomous thyroid nodules.
• Because nodular goiter is generally a disease of the
elderly, induction of the jod-Basedow phenomenon
can have serious consequences, because enrichment
of the thyroid with iodine forestalls administration of
131I and delays the response to anti-thyroid agents.
• Prevention of an acute exacerbation may be achieved
by pretreatment of at-risk subjects with methimazole
starting before exposure and for several weeks
afterward.

67. TRANSIENT GESTATIONAL THYROTOXICOSIS
• The syndrome of transient gestational thyrotoxicosis is
an exaggeration of the physiologic increase in thyroid
stimulation that occurs during the first trimester of
pregnancy.
• It is associated with high levels of hCG (100,000 to
200,000 U/L), similar to those found in twin
pregnancies, and is often accompanied by
hyperemesis.
• In most patients, the condition is self-limited, but in
rare circumstances, low doses of methimazole (≤10
mg/day) may be required for a few weeks until the
hCG falls spontaneously. It may be difficult to separate
this syndrome from early Graves’ disease, and a

68. HYDATIDIFORM MOLE
• Hydatidiform mole, elaborates differentially
glycosylated hCG molecules that also exhibit
crossover specificity for binding to the TSHR and can
induce variable degrees of thyroid overactivity.
• Some patients have clinically overt thyrotoxicosis;
however, clinical manifestations usually are not
prominent, and goiter is absent or minimal despite
laboratory evidence of a hyperthyroid state.
• The levels of free T4 or free T3 or both are increased,
and TSH values are suppressed.

69. • The reason for the discordance between the clinical
and the laboratory indices is not known, but it may be
related to the relatively short duration of thyroid
hormone excess.
• The possibility of a molar pregnancy should be
considered in a young woman with hyperthyroidism
and amenorrhea, because the appropriate therapy is
evacuation of the uterus.

70. SICK EUTHYROID
SYNDROME
• Any acute, severe illness can cause
abnormalities of circulating TSH or thyroid
hormone levels in the absence of underlying
thyroid disease, making these measurements
potentially misleading.
• The major cause of these hormonal changes
is the release of cytokines such as IL-6.
• Unless a thyroid disorder is strongly
suspected, the routine testing of thyroid
function should be avoided in acutely ill
patients.

71. • The most common hormone pattern in sick euthyroid
syndrome (SES) is a decrease in total and unbound
T3 levels (low T3 syndrome) with normal levels of T4
and TSH. The magnitude of the fall in T3 correlates
with the severity of the illness.
• T4 conversion to T3 via peripheral 5′ (outer ring)
deiodination is impaired, leading to increased reverse
T3 (rT3: 10-24 ng/dL). Since rT3 is metabolized by 5′
deiodination, its clearance is also reduced. Thus,
decreased clearance rather than increased production
is the major basis for increased rT3.
• Also, T4 is alternately metabolized to the hormonally
inactive T3 sulfate. It is generally assumed that this
low T3 state is adaptive, because it can be induced in
normal individuals by fasting.

72. • Very sick patients may exhibit a dramatic fall in total
T4 and T3 levels (low T4 syndrome).
• With decreased tissue perfusion, muscle and liver
expression of the type 3 deiodinase leads to
accelerated T4 and T3 metabolism. This state has a
poor prognosis.
• Another key factor in the fall in T4 levels is altered
binding to TBG.
• TSH levels may range from <0.1 mIU/L in very ill
patients, especially with dopamine or glucocorticoid
therapy, to >20 mIU/L during the recovery phase of
SES.
• The exact mechanisms underlying the subnormal TSH
seen in 10% of sick patients and the increased TSH
seen in 5% remain unclear but may be mediated by
cytokines including IL-12 and IL-18.

73. • The diagnosis of SES is challenging.
• Useful features to consider include previous history of
thyroid disease and thyroid function tests, evaluation
of the severity and time course of the patient’s acute
illness, documentation of medications that may affect
thyroid function or thyroid hormone levels, and
measurements of rT3 together with unbound thyroid
hormones and TSH.
• The diagnosis of SES is frequently presumptive, only
resolution of the test results with clinical recovery can
clearly establish this disorder.
• Treatment of SES with thyroid hormone (T4 and/or T3)
is controversial, but most authorities recommend
monitoring the patient’s thyroid function tests during
recovery, without administering thyroid hormone,
unless there is historic or clinical evidence suggestive
of hypothyroidism.

74. NON-TOXIC MULTINODULAR GOITRE
• MNG is more common in women than men and
increases in prevalence with age.
• Most patients with nontoxic MNG are asymptomatic
and euthyroid. MNG typically develops over many
years and is detected on routine physical examination,
when an individual notices an enlargement in the
neck, or as an incidental finding on imaging.
• If the goiter is large enough, it can ultimately lead to
compressive symptoms including difficulty swallowing,
respiratory distress (tracheal compression), or
plethora (venous congestion), but these symptoms are
uncommon.

75. • Sudden pain in an MNG is usually caused by
hemorrhage into a nodule but should raise the
possibility of invasive malignancy. Hoarseness,
reflecting laryngeal nerve involvement, also suggests
malignancy.
• On examination, thyroid architecture is distorted, and
multiple nodules of varying size can be appreciated.
• A TSH level should be measured to exclude
subclinical hyper- or hypothyroidism, but thyroid
function is usually normal.
• The risk of malignancy in MNG is similar to that in
solitary nodules. Ultrasonography can be used to
identify which nodules should be biopsied based on
sonographic features and size. For nodules with more
suspicious imaging characteristics (e.g.,
hypoechogenicity, microcalcifications, irregular
margins), biopsy is recommended when ≥1 cm.

76. • Most nontoxic MNGs can be managed conservatively.
T4 suppression is rarely effective for reducing goiter
size and introduces the risk of subclinical or overt
thyrotoxicosis, particularly if there is underlying
autonomy or if it develops during treatment.
• If levothyroxine is used, it should be started at low
doses (50 μg daily) and advanced gradually while
monitoring the TSH level to avoid excessive
suppression.
• Radioiodine is used with increasing frequency in
areas where large goiters are more prevalent because
it can decrease goiter size and may selectively ablate
regions of autonomy.
• When acute tracheal compression occurs,
glucocorticoid treatment or surgery may be needed.

77. TOXIC MULTINODULAR GOITRE
• In addition to features of goiter, the clinical
presentation of toxic MNG includes subclinical
hyperthyroidism or mild thyrotoxicosis.
• The patient is usually elderly and may present with
atrial fibrillation or palpitations, tachycardia,
nervousness, tremor, or weight loss.
• Recent exposure to iodine, from contrast dyes or other
sources, may precipitate or exacerbate thyrotoxicosis.
• The TSH level is low. The uncombined T4 level may
be normal or minimally increased; T3 is often elevated
to a greater degree than T4.

78. • Thyroid scan shows heterogeneous uptake with
multiple regions of increased and decreased uptake;
24-h uptake of radioiodine may not be increased but is
usually in the upper normal range.
• Prior to definitive treatment of the hyperthyroidism,
ultrasound imaging should be performed to assess the
presence of discrete nodules corresponding to areas
of decreased uptake (“cold” nodules).
• If present, FNA may be indicated based on
sonographic features and size cutoffs. The cytology
results, if indeterminate or suspicious, may direct the
therapy to surgery.

79. TREATMENT
• Antithyroid drugs normalize thyroid function and are
particularly useful in the elderly or ill patients with
limited lifespan.
• Radioiodine is generally the treatment of choice; it
treats areas of autonomy as well as decreasing the
mass of the goiter.
• Sometimes, however, a degree of autonomy remains,
presumably because multiple autonomous regions
emerge as soon as others are treated, and further
radioiodine treatment may be necessary.
• Surgery provides definitive treatment of underlying
thyrotoxicosis as well as goiter. Patients should be
rendered euthyroid using an antithyroid drug before
operation.

80. TOXIC ADENOMA
• A solitary, autonomously functioning thyroid nodule is
referred to as toxic adenoma.
• Thyrotoxicosis is usually mild. The disorder is
suggested by a subnormal TSH level; the presence of
the thyroid nodule, which is generally large enough to
be palpable; and the absence of clinical features
suggestive of Graves’ disease or other causes of
thyrotoxicosis.
• A thyroid scan provides a definitive diagnostic test,
demonstrating focal uptake in the hyperfunctioning
nodule and diminished uptake in the remainder of the
gland, as activity of the normal thyroid is suppressed.

81. • Radioiodine ablation is usually the treatment of
choice. Because normal thyroid function is
suppressed, 131I is concentrated in the
hyperfunctioning nodule with minimal uptake and
damage to normal thyroid tissue.
• Surgical resection is also effective and is usually
limited to enucleation of the adenoma or lobectomy,
thereby preserving thyroid function and minimizing risk
of hypoparathyroidism or damage to the recurrent
laryngeal nerves.
• Using ultrasound guidance, repeated ethanol
injections and percutaneous radiofrequency thermal
ablation have been used successfully in some centers
to ablate hyperfunctioning nodules.

82. AMIODARONE EFFECTS ON
THYROID FUNCTION
• Amiodarone is a commonly used type III
antiarrhythmic agent. It is structurally related to thyroid
hormone and contains 39% iodine by weight. Thus,
typical doses of amiodarone (200 mg/d) are
associated with very high iodine intake, leading to
greater than forty- fold increases in plasma and
urinary iodine levels.
• Amiodarone has the following effects on thyroid
function: (1) acute, transient suppression of thyroid
function; (2) hypothyroidism in patients susceptible to
the inhibitory effects of a high iodine load; and (3)
thyrotoxicosis that may be caused by either a Jod-
Basedow effect from the iodine load, in the setting of
MNG or incipient Graves’ disease, or a thyroiditis-like
condition.

83. • There are two major forms of AIT, although some
patients have features of both.
• Type 1 AIT is associated with an underlying thyroid
abnormality (preclinical Graves disease or nodular
goiter). Thyroid hormone synthesis becomes
excessive as a result of increased iodine exposure
(Jod-Basedow phenomenon).
• Type 2 AIT occurs in individuals with no intrinsic
thyroid abnormalities and is the result of drug-induced
lysosomal activation leading to destructive thyroiditis
with histiocyte accumulation in the thyroid; the
incidence rises as cumulative amiodarone dosage
increases.

84. • In AIT, the drug should be stopped, if possible,
although this is often impractical because of the
underlying cardiac disorder. High doses of antithyroid
drugs can be used in type 1 AIT but are often
ineffective.
• In type 2 AIT, oral contrast agents, such as sodium
ipodate (500 mg/d) or sodium tyropanoate (500 mg,
1–2 doses/d), rapidly reduce T4 and T3 levels,
decrease T4 → T3 conversion, and may block tissue
uptake of thyroid hormones.
• Glucocorticoids, as administered for subacute
thyroiditis, have modest benefit in type 2 AIT.
• Lithium blocks thyroid hormone release and can also
provide some benefit. Near-total thyroidectomy rapidly
decreases thyroid hormone levels and may be the
most effective long-term solution if the patient can
undergo the procedure safely.

87. REFERENCES
• Williams Textbook Of Endocrinology
• Harrisons Principles Of Internal
Medicine
• API : Progress In Medicine 2017