thyrotoxicosis: uncommon causes

3. • Abdulaziz .
• 3 year old boy case of congenital nephrotic
syndrome ,HIE, ESRD.thrombocytopenia.
• On multiple medication.
• Intially was hypothyroid on thyroxine then
euthyroid with no medication.
• Finally TFT showed:
• TSH: <0.005 → <0.005 → <0.005
• FT4: >100 → >100 → >100
• FT3: 17.8 → 9 → 7.
• TSH receptor Antibodies: positive.

4. • zainab .
• 3 year old girl case of intractable seizure
,HIE.
• On multiple medication.
• TFT showed:
• TSH: 2.3→ 1.7 →1.32 → 0.39
• FT4: 66 → 41 → 46 → 47.6
• Nuclear SCAN and uptake : normal

5. • wesam .
• 9 Month old boy case of :
Neurodegenerative disorder.
• On multiple medication.
• TFT showed:
• TSH: 0.2 → 8.7→1.5 → 0.64 → 0.08
• FT4: >100 → 28 → 39 → >100 → 52
• TSH receptor Antibodies: positive

6. Introduction
• Graves’ disease account for most of the
cases of thyrotoxicosis.
• there are more than 20 less common causes
of elevated free thyroid hormones.
• Most of these conditions are self-limited.
• Usually Lasting for for <8 wk.

7. ‘‘hyperthyroidism’’ Vs ‘‘thyrotoxicosis
•thyrotoxicosis refers to the manifestations of
excessive quantities of circulating thyroid
hormone.
•hyperthyroidism means that the thyroid
gland is functioning more than normal.
• Therefore, a hyperthyroid patient is
thyrotoxic, but a thyrotoxic patient need not
have an overactive thyroid and is therefore not
actually hyperthyroid.

8. Introduction
•Thyrotoxicosis :
high (free T4) and suppresed (TSH).
•T3 toxicosis :
free T4 normal, high (free T3) and TSH is low
•subclinical thyrotoxicosis
both free hormones are normal but TSH is low,

9. •Thyrotoxicosis is the syndrome caused by an
excess of free thyroid hormones.
•The symptoms and signs depend on :
1- the degree of elevation of the hormones.
2- the length of time that they have been
elevated
3- the rate at which the hormone levels rose.
4- individual variations of patients
manifestations.
Introduction

11. Decreased uptake of radioiodineIncreased uptake of radioiodine
Thyroiditis
Abscess: acute thyroiditis
Subacute thyroiditis
Silent thyroiditis
Graves’ disease
Toxic Multinodular goiter
Toxic adenoma
Postpartum thyroiditisNeonatal thyrotoxicosis
Neonatal Graves’ disease
Activated TSH receptor
TSI in milk
Traumatic thyroiditis
Radiation thyroiditis
Exogenous thyroid hormone
Thyrotoxicosis factitia
Thyrotoxicosis medicamentosa
Thyrotoxicosis insistiates
Hamburger thyrotoxicosis
Medication for weight loss
Excess TSH
Pituitary tumor
Resistance to thyroid hormone
Excess TSH-like material
Choriocarcinoma
Hydatidiform mole
Excess iodine (jod basedow)
Radiographic contrast
Amiodarone types I and II
Iodine supplementation
Increased uptake in abnormal site
Metastatic thyroid cancer
Struma ovarii
Lingual thyroid
Other :Lithium, Interferon, Interleukin
Denileukin diftitox, Leuprolide acetate
Marrow transplant

12. • very uncommon
• Pathophsiology :
Due to passive transplacental transfer of TSI
thyroid-stimulating antibodies from mother to
baby .
Neonatal Graves’ disease

13. •Premature closure of cranial sutures.
• reduced mentality.
•Diarrhea, vomiting, poor weight gain.
•exophthalmos may be seen.
• Arrhythmias and/or congestive heart failure.
Neonatal Graves’ disease

14. Neonatal Graves’ disease
Management:
•Careful monitoring of the fetal size and heart
rate and the size of the fetal thyroid .
•The presence of fetal goiter, tachycardia, and
intrauterine growth retardation suggests fetal
hyperthyroidism.
•TSH receptor antibodies should be obtained
during pregnancy.

15. •In high risk mothers, serum thyroid tests
should be performed on cord blood upon birth
and then measured monthly in the offspring
until 3 months of age.
•antithyroid drugs are administered to the
mother to control fetal Hyperthyroidism in
some patients.
Neonatal Graves’ disease

16. Activated TSH receptor
• also called familial non autoimmune hereditary
hyperthyroidism.
•rare condition
•an autosomal dominant .
•The cause is a mutation, usually substitution
of one base in the DNA responsible for the
production of the TSH receptor or the related G
protein complex.
• This mutation results in activation of the TSH-
receptor–G-protein–effector system complex.

17. •Patient usually hyperthyroid from birth.
• associated with preterm delivery and low
birth-weight
• No evidence of graves disease in the mother.
• no evidence of thyroid autoimmunity .
•no response to antithyroid medications.
• Treatment: total ablation of the gland, either
surgically or with RAI
Activated TSH receptor

18. TSI in milk
•transfer of thyroid-stimulating antibodies in the
mother’s milk.

19. •TSH-secreting pituitary tumors are rare.
•TSH-secreting adenoma have been
associated with both multiple endocrine
neoplasia type I and McCune–Albright
syndrome.
•The thyroid gland is palpably enlarged and
often multinodular because of sustained TSH
stimulation.
Excess TSH

20. •Visual field defects (classically bitemporal
hemianopia) are present in approximately
40%–50%.
•Treatment:
•The most effective therapy is transsphenoidal
resection of the pituitary tumor.
•External radiation.
• octeriotide and long-acting somatostatin
lanreotide analogs also effective.
Excess TSH

21. •In one case report .
•The TSH was secreted by an ectopic
nasopharyngeal pituitary tumor.
• that was identified when the patient
developed nasal obstruction.
.
Excess TSH

22. •Familial.
•an autosomal dominant pattern of inheritance.
•may represent forms of the syndrome of
generalized resistance to thyroid hormone .
•The syndrome is caused by a mutation in
THRB .
resistance to thyroid hormone RTH

23. •Criteria essential for the diagnosis of this
disorder include the following:
•evidence of increased peripheral metabolism,
• diffuse thyromegaly,
•Elevated free thyroid hormone levels,
•inappropriately elevated serum levels of TSH
•
•The TRH and T3 suppression tests may help
differentiate it from adenoma.
•A number of agents including L-T3, D-T4,
bromocryptine, and triiodothyroacetic acid
(Triac) have been advocated for treatment in
case of throtoxicosis.
pituitary resistance to thyroid hormone

24. •Trophoblastic disease and germ cell
tumors
•Hyperthyroidism can occur in adolcenent with
a hydatidiform mole or choriocarcinoma or in
male with testicular germ cell tumors.
•Human chorionic gonadotropin (hCG) is a
glycoprotein hormone that shares a common
a-subunit with TSH.
•hCG has confirmed thyroid-stimulating
activity when present at high concentrations in
serum
Excess TSH-Like Material

25. •Hydatidiform moles secrete large amounts of
hCG.
•Increased thyroid function in patients with
hydatidiform moles can occur in 25%–64% of
cases.
•but only 5% of cases have clinically significant
thyrotoxicosis.
•Therapy is directed against cause.
Thionamides are useful adjunctive therapy.
Excess TSH-Like Material and
Gestational

26. • Struma ovarii :
• is a teratoma of the ovary that is composed
primarily of thyroid epithelium which comprises
more than 50% of its structure .
• Most struma ovarii lesions are benign, and it
has been estimated that fewer than 3% are
malignant .
High Uptake in Ectopic Sites

27. •Treatment of struma ovarii causing
thyrotoxicosis is surgical excision.
• Antithyroid drugs can be used preoperatively
to ameliorate thyrotoxic symptoms and signs.
High Uptake in Ectopic Sites

28. •Thyroid cancer can cause thyrotoxicosis
through 3 mechanisms:
•first, when there is a large volume of
functioning cancer (usually of the follicular
type).
•second, when there are activated receptors
on the cancer cells
• third, when the cancer grows rapidly within
the thyroid, invading and destroying thyroid
follicles and releasing thyroid hormones
Thyrotoxicosis from Functioning Thyroid
Cancer

29. •there have been a few reports of elevated
thyroid function in patients with ectopic thyroid.
• Sites of ectopic thyroid include the tongue,
neck and abdomen .
•The treatment is surgical.
Thyrotoxicosis from Ectopic Thyroid.

30. •An inflammation of the thyroid gland.
•It Include a diverse group of disorders:
•Acute
•Hashimoto’s .
•Subacute.
• silent thyroiditis
•drug-induced,
•radiation-related.
Thyroiditis

31. •also known as autoimmune or chronic
lymphocytic thyroiditis .
•Or Hashitoxicosis
•the most common form of thyroiditis
•Biochemically and clinically, there is an initial
period of thyrotoxicosis secondary to the
release of thyroid hormones from the inflamed
gland.
Hashimoto’s thyroiditis

32. •thyrotoxic phase ranged from 31 to 168 days.
•This is followed by the development of
hypothyroidism or recovery.
•an eosinophil to monocyte ratio (Eo/Mo):
•below 0.2
•Eo/Mo multiplied by serum free T3 (pmol/l)
below 4.5
•Treatment of these disorders is symptomatic
Hashimoto’s thyroiditis

33. •also known as De Quervain’s or
granulomatous thyroiditis.
•This entity is rarely seen in children,
•The hallmark of this variant is a painful and
tender thyroid
•prodrome of myalgias, pharyngitis, low-grade
fever, and fatigue
•The most accepted etiology of subacute
thyroiditis is a viral illness.
subacute thyroiditis

34. •Pathophysiology :
•the destructive thyroiditis is caused by direct
viral infection of the gland
.or by the host’s response to the viral infection.
• is associated with several viruses, including:
• influenza virus,
•adenovirus,
• mumps virus,
•coxsackievirus..
•The erythrocyte sedimentation rate is
consistently elevated.
subacute thyroiditis

35. •Also called suppurative thyroiditis,
•It is rare.
•caused by Staphylococcus and Streptococcus
•The symptoms and signs are similar to those
of severe subacute thyroiditis with
thyrotoxicosis.
•Treatment : Drainage, culturing, and
appropriate antibiotics .
Acute thyroiditis

36. • occasionally in patient Graves' disease, who
is treated with radioiodine.
• develops thyroid pain and tenderness 5 to 10
days later.
• due to radiation-induced injury and necrosis
of thyroid follicular cells and associated
inflammation.
•usually mild and subside spontaneously in a
few days to one week.
Radiation thyroiditis

37. •Direct blunt or surgical trauma can cause
transient hyperthyroidism.
•This has been described after laryngectomy,
needle aspiration of the thyroid, and
parathyroidectomy
•Martial arts thyroiditis has been described
after a karate blow to the thyroid .
•The process is self-limited and resolves in
approximately 2 wk as the inflammation
subsides.
traumatic thyroiditis

38. •is a mild form of traumatic thyroiditis .
• It results from vigorous palpation of the
thyroid during physical exam.
•After manipulation of the gland during thyroid
biopsy.
Palpation thyroiditis

39. silent thyroiditis.
•Also called Painless thyroiditis.
•It is characterized primarily by transient
hyperthyroidism, followed sometimes by
hypothyroidism, and then recovery .
•It is considered a variant form of chronic
autoimmune thyroiditis.
•Also it could be secondary to medication.

40. •thyrotoxicosis factitia
•thyrotoxicosis medicamentosa
•Thyrotoxicosis insistiates
Thyrotoxicosis Attributable to Exogenous
Thyroid Hormones

41. • refers to a condition of thyrotoxicosis caused
by the ingestion of exogenous thyroid
hormone.
•It can be the result of mistaken ingestion of
excess drug, such as L-thyroxine
• or as a symptom of Munchausen syndrome.
thyrotoxicosis factitia

42. •The symptoms and sign: similar to those in
patients with hyperthyroidism from other
causes.
•No Exophthalmos or opthamopathy.
•Usually no goitre.
CLINICAL FEATURES

43. •Diagnosis depends on clinical suspicion
•biochemical thyrotoxicosis with high free T4
and/or free T3 and suppressed TSH .
•low uptake of radioiodine.
•serum thyroglobulin is usually low or
undetectable.
• antithyroglobulin antibodies should be
performed at the same time
•Some recommended to measure the
ratio of T4 to T3 to help make the diagnosis.
thyrotoxicosis factitia

44. •The source of thyroid might even be
unrecognized as in the case of diet pills that
contain thyroid hormones.
•Also it can be used in case of depression,
infertility or menstural problem.
•Exogenous Thyroid Hormones

45. •Patients with thyroid cancer prescribed
suppressive doses of thyroxine .
•Patients with goiter prescribed excessive
doses in an attempt to shrink the thyroid gland.
•Patients with a psychiatric disorder who may
take excessive doses of thyroid hormone.
thyrotoxicosis medicamentosa.

46. •iodine to food.
•Radiographic contrast.
•Drugs: Amiodarone.
Thyrotoxicosis Attributable to Excess
Iodine

47. •several outbreaks of thyrotoxicosis
attributable to thyroid gland being included
with neck trimmings that were used to make
meat.
ground beef
Hamburger thyrotoxicosis

48. Topical iodine preparations
Diiodohydroxyquinolone
Iodine tincture
Povidone iodine
Iodochlorohydroxyquinolone
Iodoform gauze
Solutions
Saturated potassium iodide (SSKI)
Lugol solution
Iodinated glycerol
Echothiopate iodide
Hydriodic acid syrup
Calcium iodide
Drugs
Amiodarone
Expectorants
Vitamins containing iodine
Iodochlorohydroxyquinolone
Diiodohydroxyquinolone
Potassium iodide
Benziodarone
Isopropamide iodide

49. Radiological contrast
agents
Diatrizoate
Ipanoic acid
Ipodate
Iothalamate
Metrizamide
Diatrozide

50. •is an effective antiarrhythmic medication
but it has several side effects, including effects
on thyroid function.
•It that contains 37 % iodine.
•Deiodination of amiodarone produces about
12 mg of free iodine daily when a patient
ingests 400 mg.
•Amiodarone is fat soluble and has a half-life
of many months.
Amiodarone

51. •The effect on thyroid function is somewhat
dependent on the quantity of iodine ingested.
• In regions of iodine deficiency amiodarone is
more likely to cause thyrotoxicosis,
•in iodine-sufficient regions hypothyroidism is
more likely.
Amiodarone

52. •Type 1 amiodarone–induced
thyrotoxicosis: there is increased synthesis
of thyroid hormone (usually in patients with a
preexisting nodular goiter),.
•The excess iodine from amiodarone provides
the raw material for the nodules to produce
excess thyroid hormones.
•type 2, which is attributable to destruction of
follicles producing a thyroiditis-like picture.
Amiodarone

53. •Iodine-induced thyrotoxicosis is also called
Jod Basedow disease.
•Usually an increase in plasma inorganic
iodine causes reduced trapping of iodine,
organification (Wolff–Chaikoff effect) and
reduced release of preformed thyroid
hormones
Amiodarone

54. •Treatment: Antithyroid medication such as
methimazole been effective
•Potassium perchlorate has been used as a
competitive inhibitor of trapping iodine by the
sodium–iodide symporter.
•Corticosteroids such as prednisone are
effective in the destructive type 2 syndrome.
• Thyroidectomy can be undertaken when
antithyroid therapy is ineffective.
Amiodarone

56. Thyrotoxicosis Attributable to Nonthyroid
Medications
•interferon-alpha.
• lithium,
•Interleukin-2
• leuprolide acetate

57. •interferon-alpha.
•.used for viral Hepatitis
•.The most common thyroid abnormality is the
development of de novo antithyroid antibodies
without clinical disease .
•Approximately 5 to 10 percent of patients
develop clinical thyroid disease,
•including painless thyroiditis, Hashimoto's
thyroiditis, or Graves' disease.

58. Lithium
• used for depression .
•lithium have an increased incidence of
hyperthyroidism.
•Mostly in form of painless thyroiditis .

59. Interleukin-2
•Used in Patients with metastatic cancer and
leukemia
•a syndrome mimicking painless thyroiditis
occurred in about 2 percent of the patients

60. Decreased uptake of radioiodineIncreased uptake of radioiodine
Thyroiditis
Abscess: acute thyroiditis
Subacute thyroiditis
Silent thyroiditis
Graves’ disease
Toxic Multinodular goiter
Toxic adenoma
Postpartum thyroiditisNeonatal thyrotoxicosis
Neonatal Graves’ disease
Activated TSH receptor
TSI in milk
Traumatic thyroiditis
Radiation thyroiditis
Exogenous thyroid
Thyrotoxicosis factitia
Thyrotoxicosis medicamentosa
Thyrotoxicosis insistiates
Hamburger thyrotoxicosis
Medication for weight loss
Excess TSH
Pituitary tumor
Excess TSH-like material
Choriocarcinoma
Hydatidiform mole
Excess iodine (jod basedow)
Radiographic contrast
Amiodarone types I and II
Iodine supplementation
Increased uptake in abnormal site
Metastatic thyroid cancer
Struma ovarii
Lingual thyroid
Other :Lithium, Interferon, Interleukin
Denileukin diftitox, Leuprolide acetate
Marrow transplant

61. PathogenesisEntity
TSH receptor-stimulating antibodiesGraves’ disease
Somatic gain-of-function mutations in
the TSH receptor or Gs
Toxic adenoma
Toxic multinodular goiter
Hyperthyroid thyroid carcinoma
Germline gain-of-function mutations in
the TSH receptor
Familial non-autoimmune
hyperthyroidism
Sporadic non-autoimmune
hyperthyroidism
Increased stimulation by inappropriate
TSH secretion
TSH secreting pituitary adenoma
Increased stimulation of the TSH
receptor by hCG
hCG-induced gestational
hyperthyroidism
TSH receptor mutation with increased
sensitivity to hCG
Familial hypersensitivity to hCG
Increased stimulation of the TSH
receptor by hCG
Trophoblast tumors (hydatiform mole,
choriocarcinoma)
Autonomous function of thyroid tissue
in ovarian teratoma
Struma ovarii
Increased synthesis of thyroid hormone
in autonomously functioning thyroid
Iodine-induced hyperthyroidism

64. • How should overt drug-induced thyrotoxicosis
be managed?
• Recommendation 88
• Beta-adrenergic blocking agents alone or in
combination with methimazole should be used to
treat overt iodine-induced hyperthyroidism.
• Recommendation 89
• Patients who develop thyrotoxicosis during therapy
with interferon-α or interleukin-2 should be
evaluated to determine etiology (thyroiditis vs. GD)
and treated accordingly

65. • Recommendation 90
• We suggest monitoring thyroid function tests before
and at 1 and 3 months following the initiation of
amiodarone therapy, and at 3–6-month intervals
thereafter.
• Recommendation 91
• We suggest testing to distinguish type 1 (iodine-
induced) from type 2 (thyroiditis) varieties of
amiodarone-induced thyrotoxicosis.

66. • Recommendation 92
• The decision to stop amiodarone in the setting of
thyrotoxicosis should be determined on an
individual basis in consultation with a cardiologist,
based on the presence or absence of effective
alternative antiarrhythmic therapy. 1/+00
• Recommendation 93
• Methimazole should be used to treat type 1
amiodarone-induced thyrotoxicosis and
corticosteroids should be used to treat type 2
amiodarone-induced thyrotoxicosis. 1/+00
•

67. • Recommendation 94
• Combined antithyroid drug and anti-inflammatory
therapy should be used to treat patients with overt
amiodarone-induced thyrotoxicosis who fail to
respond to single modality therapy, and patients in
whom the type of disease cannot be unequivocally
determined.

68. How should thyrotoxicosis due to
destructive thyroiditis be managed?
Recommendation 96
Patients with mild symptomatic subacute
thyroiditis should be treated initially with beta-
adrenergic-blocking drugs and nonsteroidal
anti-inflammatory agents. Those failing to
respond or those with moderate-to-severe
symptoms should be treated with
corticosteroids.

69. How should thyrotoxicosis due to unusual
causes be managed?
Recommendation 97
The diagnosis of TSH-secreting pituitary tumor
should be based on an inappropriately normal or
elevated serum TSH level associated with elevated
free T4 estimates and T3 concentrations, usually
associated with the presence of a pituitary tumor on
MRI and the absence of a family history or genetic
testing consistent with thyroid hormone resistance in
a thyrotoxic patient.

70. Recommendation 98
Patients with TSH-secreting pituitary adenomas
should undergo surgery performed by an
experienced pituitary surgeon.
Recommendation 99
Patients with struma ovarii should be treated initially
with surgical resection.
Recommendation 100
Treatment of hyperthyroidism due to
choriocarcinoma should include both methimazole
and treatment directed against the primary tumor.

71. •Prevalence of goiter and hypothyroidism was
observed high in patients with ESRD .
•Hyperthyroidism is rare in patients on dialysis
•The clinical diagnosis of hyperthyroidism in
ESRD may be delayed due to overlap of
symptoms.
• is not clear whether the excess iodine
stimulates the gland to a hyperactive state
(Jod-Basedow effect).
•Treatment:
• antithyroid,Surgery, I-131 ablation.
Gravs disease in ESRD on dialysis

73. .