HYPERTHYROIDISM AND

HYPOTHYROIDISM

Luthfan Budi Purnomo

Subdivision of Endocrinology
Internal Medicine Department
School of Medicine Gadjah Mada University
Dr Sardjito Hospital Yogyakarta
2009
Kompetensi dokter umum

 Hipertiroid 3A
 Hipotiroid 1
 Tiroiditis 1

References

1. Basic Endocrinology Greenspan

2. Oxford Handbook of Endocrinology
and Diabetes
Introduction

 The terms of hyper- and hypothyroidism are

related to the function of thyroid gland
 Thyrotoxicosis is clinical syndrome that results
when tissues are exposed to high levels of
circulating thyroid hormones
 The function of thyroid gland is synthesis of
thyroid hormones: T4 (tetraiodothyronine/
thyroxine) and T3 (triiodothyronine)
Laboratory examination of thyroid function

 The function of the thyroid gland may be

evaluated in many different ways: 1. test of
thyroid hormones in blood, 2. evaluation of the
hypothalamic-pituitary-thyroid axis, 3.
assessment of iodine metabolism, 4. estimation
of gland size, 5. thyroid biopsy 6. observation
on peripheral tissue, and 7. measurement of
thyroid autoantibodies (Greenspan, 2004)
 TSH (thyroid stimulating hormone), T4
(thyroxine), T3 (triiodothyronine)
Physiologic effects of thyroid hormones
 Effects on fetal development (brain development, skeletal
maturation)
 Effects on oxygen consumption, heat production, and free radical
formation
 Cardiovascular effects (positive inotropic and chronotropic effects)
 Sympathetic effects (sensitivity to cathecolamine is markedly
increased)
 Pulmonary effects
 Hematopoietic effects (increased production of erythropoietin)
 Gastrointestinal effects (stimulated gut motility)
 Skeletal effects (stimulated bone turnover, bone resorption
 Neuromuscular effects
 Effects on lipid and carbohydrate metabolism
 Endocrine effects
Thyroid hormones regulation
Thyroid Hormone Synthesis

 Trapping of iodide, diffusion and transport to colloid

 Oxidation and iodination of tyrosine residues in
thyroglobulin
 Coupling of iodotyrosine molecules within thyroglobulin
 Proteolysis of thyroglobulin
 Deiodination of iodotyrosine
 High
Primary Subclinical Secondary
Hypofuncti Hypofunction Hyperfuncti
THYROTROPIN (TSH) LEVEL
on on

Normal

Normal
range

Pituitary Subclinical Primary

Low

Failure Hyperfunction Hyperfuncti

on

Low Normal High

THYROID HORMONE LEVEL
HYPERTHYROIDISM
HYPERTHYROIDISME

THYROTOXICOSIS
Hyperthyroidism: clinical signs and symptoms

 Primary hyperthyroidism: TSH decreases, FT4 or FT3

increases (low TSH concentration with normal FT4
concentration is named subclinical hyperthyroidism) with
increased iodine uptake
 Secondary hyperthyroidism: TSH increases, FT4 or FT3
increases, TRH decreases
 Tertiary hyperthyroidism: TSH increases, TRH
increases, and FT4 or FT3 increases
 The clinical manifestations of hyperthyroidism are
largely independent of it cause
Hyperthyroidism: clinical signs and symptoms

 Skin: warm, smooth, sweating increases, onycholysis,

hyperpigmentation, pruritus
 Eyes: lid lag (sclera can be seen above the iris as the
patient looks downward)
 Cardiovascular system: increased cardiac output,
tachycardia, atrial fibrillation (10-20%)
 Serum lipid: low total cholesterol, low HDL-C
 Respiratory system: dyspnea and dyspnea on exertion
(increased oxygen consumption and CO2 production,
respiratory muscle weakness)
 Gastrointestinal system: weight loss, increased gut
motility, hyperphagia, malabsorption, vomiting,
abnormality in liver function test
 Hyperthyroidism: clinical signs and symptoms

 Hematologic system: normochromic-normocytic anemia

 Genitourinary system: frequency, nocturia, in women high
serum estrogen concentrations, oligomenorrhea, anovulatory
infertility. In men high serum total testosterone
concentrations, gynecomastia, reduced libido, erectile
dysfunction
 Skeletal system: stimulation of bone resorption, osteoporosis
 Neuromuscular system: tremor, deep tendon reflexes are
hyperactive, hyperactivity, emotional lability, anxiety,
inability to concentrate, insomnia, hypokalemic periodic
paralysis
 Hyperglycemia: increased insulin secretion, antagonism to
peripheral action of insulin (increased gluconeogenesis, -
glycogenolysis, - intestinal glucose absorption)
Hyperthyroidism with a high radioiodine uptake

 Graves’ disease
 Hashitoxicosis (Hashimoto thyroiditis and
thyrotoxicosis)
 Toxic adenoma and toxic multinodular goiter
 Iodine-induced hyperthyroidism
 Trophoblastic disease and germ cell tumors
 TSH-mediated hyperthyroidism
Hyperthyroidism with a low radioiodine uptake
(Increased Thyroid Hormone non-hyperfunction)

 Subacute thyroiditis, silent & postpartum

thyroiditis
 Ectopic thyroid tissue: metastatic thyroid
carcinoma, struma ovarii (teratoma containing
thyroid tissue)
 Exogenous thyroid hormone: over treatment,
thyrotoxicosis factitia
Management of Hyperthyroidism

 Antithyroid drugs: carbimazol, PTU (the drug

of choice during pregnancy & lactation). Side
effects contain allergic reaction,
agranulocytosis, drug-induced hepatitis
 Beta adrenergic antagonists
 Radioiodine therapy (ablation)
 Surgery
 Thyroid Storm/Thyrotoxic Crisis
 Life threatening exacerbation of the manifestations
of thyrotoxicosis
 Precipitating factors: acute infection, surgery, post
partum, radiographic contrast agent, ATD withdrawn,
 Clinical signs: alteration in mental status, high fever,
tachycardia/tachyarrhythmias, severe clinical
hyperthyroid signs, vomiting, jaundice, diarrhoea,
multisystem decompensation
 Treatment: supportive, PTU, Sol lugol, beta adrenergic
antagonist
HYPOTHYROIDISM
 HYPOTHYROIDISM

 Hypothyroidism is the most common clinical

disorder of thyroid function
 Hypothyroidism may be primary or central
 Hypothyroidism is a syndrome manifested by a
collection of symptoms and signs that are
influenced by age, rate of development, and the
presence of other disorders
Hypothyroidism: cause

 Chronic autoimmune (Hashimoto’s) thyroiditis

 Iatrogenic disease: thyroidectomy, radioiodine
treatment, external radiation therapy
 Iodine
 Drugs: amiodarone, interferon alpha, IL-2
 Infiltrative disease: fibrous thyroiditis (Reidel’s
thyroiditis), hemochromatosis, scleroderma, leukemia
 Congenital
 Causes of Hypothyroidism
• Primary hypothyroidism
Destruction of thyroid tissue
Chronic autoimmune thyroiditis, radiation,
thyroidectomy, infiltrative disease
Defective thyroid hormone synthesis
iodine deficiency, drugs with antithyroid actions

• Central hypothyroidism: pituitary, hypothalamic

• Transient hypothyroidism
Silent thyroiditis, subacute thyroiditis, after
withdrawal of thyroid hormone therapy in euthyroid
patients
Hypothyroidism: laboratory findings

 Primary hypothyroidism: high serum TSH concentration

and low serum FT4 concentration (high serum TSH
concentration with normal serum FT4 and FT3
concentration is named subclinical hypothyroidism)
 Secondary hypothyroidism: low serum FT4 concentration
with serum TSH concentration that serum is not
appropriately elevated, high serum TRH concentration
 Tertiary (central) hypothyroidism: low serum FT4
concentration with low serum TSH concentration and low
serum TRH concentration
 Hypothyroidism: clinical signs and symptoms

 Age at onset, duration and severity of thyroid hormone

deficiency
 In infants and children: retardation of growth and brain
development, short stature and mental retardation
(cretinism)
 In adults: asymptomatic, overt hypothyroidism, mixedema
coma
 Generalized slowing of metabolic processes: fatigue, slow
movement and slow speech, cold intolerance, constipation,
weight gain, delayed relaxation of deep tendon reflexes,
bradycardia
 Coarse hair and skin, puffy facies, enlargement of the
tongue, hoarseness
Hypothyroidism: clinical manifestation

 Skin: cool, pale, dry roughness of the skin, decreased

sweating, coarse hair and hair loss, nonpitting edema
 Eyes: periorbital edema
 Cardiovascular system: decreased cardiac output,
decreased heart rate and contractility, hypertension
(increased peripheral resistance)
 Respiratory system: fatigue, dyspnea on exertion,
hypoventilation, sleep apnea (macroglossia)
 Gastroointestinal disorders: constipation, decreased
taste sensation, gastric atrophy
 Anemia
Hypothyroidism: clinical manifestation

 Reproductive system: in women oligo- or amenorrhea or

hypermenorrhea-menorrhagia, decreased fertility, early
abortion
 Neurological dysfunction: sleepiness, slow response to
question
 Myxedema coma
 Metabolic abnormalities: hyponatremia,
 Screening and case finding for hypothyroidism in
various patients and conditions

 Patients or conditions with low risk (prevalence <2%)

Adult and children at routine visits
Dementia Psychiatric patients Elderly
Hypercholesterolemia Sleep apnea
 Patients or conditions with moderate risk (prevalence 3-10%
Goiter or thyroid nodular disease
Lithium carbonate therapy Associated autoimmune disease
Graves’ ophthalmopathy Post partum women
 Patients or conditions with high risk (prevalence >10%)
Chronic autoimmune thyroiditis
Previous treatment for thyrotoxicosis
Previous high-dose neck radiation therapy
Suspected hypopituitarism Amiodarone therapy
Low risk TSH

Moderate and high risk TSH & FT4

Risk factors for mild thyroid failure
and progression to overt hypothyroidism

Female and age 50 or older

Previous therapy for hyperthyroidism
Long-term use of drugs affecting thyroid function
Hypercholesterolemia
Depression
Personal or family history of thyroid disease
?Personal or family history of other autoimmune disease
Smallridge RC. Postgrad Med 107: 143-152, 2000

Progression to clinically overt hypothyroidism, 2.6% each year if

TPO Ab are absent and 4.3% if the are present
A TSH level greater than 10 mIU/L predicts a higher rate of
progression, and a level of less than 6 mIU/L predict a lower
likehood of progression
Fatourechi V. Mayo Clin Proc 2009; 84: 65-71
 Raised thyroid stimulating hormone levels

Thyroid stimulating hormone Thyroid stimulating hormone Thyroid stimulating hormone

level >10 mU/l with or without level 5-10 mU/l with level 5-10 mU/l with
low free serum thyroxine low free serum thyroxine normal free serum thyroxine

Symptoms of hypothyroidism

Yes
No

3-6 months trial of thyroxine

Check status of thyroid peroxidase antibody

Symptom resolved?
Positive result Negative result

Yes No
Recheck thyroid Recheck thyroid
stimulating stimulating
Treat with thyroxine life Consider alternative hormone hormone level
long diagnosis level annually every three years

Vaidya B and Peacrce SHS. BMJ 2008; 337: 284-289

 MYXEDEMA COMA

 Is the ultimate stage of severe long-standing

hypothyroidsm, is an uncommon but potentially lethal
condition.
 Patients with myxedema coma are typically elderly
women who present during the winter months.
 Patients with hypothyroidism may exhibit a number of
physiologic alterations to compensate for the lack of
thyroid hormone. If these homeostatic mechanisms
are overwhelmed by factors such as infection, the
patient may decompensate into myxedema coma
 …MYXEDEMA COMA

 They often demonstrate classic symptoms of

hypothyroidism: fatigue; constipation; weight
gain; cold intolerance; a deep voice; coarse hair;
and dry, pale, cool skin.
 Physical Findings in Myxedema Coma

1. Altered mentation 7. Gastrointestinal

2. Alopecia Decreased motility
3. Bladder dystonia & distention Abdominal distension
4. Cardiovascular Paralytic ileus
1. Elevated diastolic blood Fecal impaction
pressure--early Myxedema megacolon-late
2. Hypotension--late 8. Hyperventilation
3. Bradycardia 9. Hypothermia
5. Delayed reflex relaxation 10.Myxedematous face
6. Dry, cool, doughy skin Generalized swelling
Macroglossia
Ptosis
Periorbital edema
Coarse, sparse hair
11.Nonpitting edema
Laboratory Abnormalities in Myxedema
Coma

Anemia
Elevated CPK
Elevated creatinine
Elevated transaminases
Hypercapnia
Hyperlipidemia
Hypoglycemia
Hyponatremia
Hypoxia
Leukopenia
Respiratory acidosis
 THYROIDITIS

 Inflammation of the thyroid gland: transient

thyrotoxicosis followed by hypothyroidism (overt
hypothyroidism: Hashimoto’s or atrophic thyroiditis)
 Types: chronic autoimmune (Hashimoto’s, atrophic),
silent thyroiditis, post partum, chronic fibrosis
(Riedel’s), pyogenic, sub-acute thyroiditis
(granulomatous, giant cell or de Quervain’s thyroiditis)
IODINE DEFICIENCY DISORDERS
(IDD)
IODINE DEFICIENCY DISORDERS (IDD)

Iodine has major role in the development of

physical and mental of children during pregnancy
The consequence of iodine deficiency beyond
endemic goiter and endemic cretinsim
 Spektrum GAKI
Fetus abortus, lahir mati
anomali kongenital
peningkatan kematian perinatal
peningkatan kematian anak
kretin endemi -gangguan mental
-bisu tuli
-diplegia spastik
-mata juling
kretin miksedematosa -cebol
-gangguan mental
defek psikomotor
Neonatus gondok neonatal, hipotiroid neonatal
Anak & gondok, hipotiroid juvenile, gangguan mental
remaja gangguan perkembangan fisik
Dewasa gondok dengan segala akibatnya, hipotiroid,
gangguan mental

Djokomoeljanto, 1974
 Pembesaran Kelenjar Gondok (Goiter)

Grade 0 tidak terabaidak lebih

Grade 1a tidak teraba atau bila teraba
tidak lebih besar dari normal
Grade 1b jelas teraba dan membesar,
tetapi tidak terlihat meskipun
kepala ditengadahkan
Grade II mudah dilihat, kepala posisi
biasa
Grade III terlihat dari jarak tertentu
Survei masyarakat dilakukan bila ditemukan ≥30% pada
anak sekolah (termasuk grade I)k
Bila gondok endemik >5% perlu perhatian
Bila gondok endemik >10% perlu pengobatan pencegahan
 Derajat Endemi
Endemi grade I (ringan)
bila nilai median ekskresi yodium urin
>50 ug I/g kreatinin atau median urin 5-9,9 ug/dl,
prevalensi gondok anak sekolah 5-20%

Endemi grade II (sedang)

bila nilai median ekskresi yodium urin
25-50 ug I/g kreatinin atau median 2-4,9
ug/dl, prevelensi gondok anak sekolah sampai 30%

Endemi grade III (berat)

bila median <25 ug I/g kreatinin atau <2 ug/dl,
prevalensi gondok anak sekolah >30%, prevalensi
kretin endemik 1-10%
 Diagnosis Kretin Endemik secara individu
Seorang yang lahir di daerah defisiensi yodium
berat dengan 2 atau lebih kombinasi gejala
ireversibel berikut: retardasi mental, kelainan
neuromotorik (gangguan bicara, cara berjalan
khas, refleks patologis dan refleks fisiologis
meninggi, mata juling, gangguan akibat kerusakan
batang otak, serta late walker), dan gangguan
pendengiaran (bilateral, tipe perseptif dan pada
nada tinggi)

Dengan atau tanpa hipotiroid

Thank You