thyrotoxicosis: uncommon causes

• 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.

• zainab .

• 3 year old girl case of intractable seizure

,HIE.


• TFT showed:

• TSH: 2.3→ 1.7 →1.32 → 0.39

• FT4: 66 → 41 → 46 → 47.6

• Nuclear SCAN and uptake : normal

• wesam .

• 9 Month old boy case of :

Neurodegenerative disorder.


• TFT showed:

• TSH: 0.2 → 8.7→1.5 → 0.64 → 0.08

• FT4: >100 → 28 → 39 → >100 → 52

• TSH receptor Antibodies: positive

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.

‘‘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.

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,

•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

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

• very uncommon

• Pathophsiology :

Due to passive transplacental transfer of TSI

thyroid-stimulating antibodies from mother to

baby .


•Premature closure of cranial sutures.

• reduced mentality.

•Diarrhea, vomiting, poor weight gain.

•exophthalmos may be seen.

• Arrhythmias and/or congestive heart failure.



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.

•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.



• 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.

•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


TSI in milk

•transfer of thyroid-stimulating antibodies in the

mother’s milk.

•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

•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

•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

•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

•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

•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

•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

• 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

•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

•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

•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.

•An inflammation of the thyroid gland.

•It Include a diverse group of disorders:

•Acute

•Hashimoto’s .

•Subacute.

• silent thyroiditis

•drug-induced,

•radiation-related.

Thyroiditis

•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

•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

•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

•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

•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

• 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.


•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

•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

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.

•thyrotoxicosis factitia

•thyrotoxicosis medicamentosa

•Thyrotoxicosis insistiates

Thyrotoxicosis Attributable to Exogenous

Thyroid Hormones

• 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

•The symptoms and sign: similar to those in

patients with hyperthyroidism from other

causes.

•No Exophthalmos or opthamopathy.

•Usually no goitre.

CLINICAL FEATURES

•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

•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

•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.

•iodine to food.

•Radiographic contrast.

•Drugs: Amiodarone.

Thyrotoxicosis Attributable to Excess

Iodine

•several outbreaks of thyrotoxicosis

attributable to thyroid gland being included

with neck trimmings that were used to make

meat.

ground beef


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

Radiological contrast

agents

Diatrizoate

Ipanoic acid

Ipodate

Iothalamate

Metrizamide

Diatrozide

•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

•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

•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

•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

•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

Thyrotoxicosis Attributable to Nonthyroid

Medications

•interferon-alpha.

• lithium,

•Interleukin-2

• leuprolide acetate

•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.

Lithium

• used for depression .

•lithium have an increased incidence of

hyperthyroidism.

•Mostly in form of painless thyroiditis .

Interleukin-2

•Used in Patients with metastatic cancer and

leukemia

•a syndrome mimicking painless thyroiditis

occurred in about 2 percent of the patients

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



TSI in milk

Traumatic thyroiditis


Exogenous thyroid

Thyrotoxicosis factitia

Thyrotoxicosis medicamentosa

Thyrotoxicosis insistiates


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

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

tissue after exposure to excessive

Iodine-induced hyperthyroidism

• 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.


• Patients who develop thyrotoxicosis during therapy

with interferon-α or interleukin-2 should be

evaluated to determine etiology (thyroiditis vs. GD)

and treated accordingly


• 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.


• We suggest testing to distinguish type 1 (iodine-

induced) from type 2 (thyroiditis) varieties of

amiodarone-induced thyrotoxicosis.


• 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


• 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

•


• 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.

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.

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.

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.

•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

.

Health & Medicine

thyrotoxicosis: uncommon causes