The document discusses hypothyroidism, providing information on the thyroid gland anatomy and hormone synthesis, epidemiology and causes of hypothyroidism, clinical presentation of hypothyroidism, methods for diagnosing hypothyroidism including thyroid hormone tests and antibodies, treatment of hypothyroidism, and special considerations for thyroid dysfunction management in surgical patients. Epidemiology data presented found the prevalence of hypothyroidism is about 5% and increases with age, with some regional variations in iodine deficiency and goiter rates in Iran.

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Maryam Vasheghani , MD
Assistant Professor of Internal medicine _ Endocrinologist
National Research Institute of Tuberculosis and Lung Disease
Shahid Beheshti University of Medical Sciences, Tehran, Iran.
JULY 2015
HYPOTHYROIDISM

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AGENDA
• Thyroid Gland
 Anatomy
 Histology
 Thyroid Hormone Synthesis, Action and
Metabolism
• Hypothyroidism
 Epidemiology
 Clinical presentation
 Diagnosis
 Treatment
• Thyroid dysfunction management in
patient who is candidate for surgery
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Thyroid Gland
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Thyroid Gland Histology
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Thyroid Hormone Synthesis,
Metabolism, and Action
• I : IODINE TRAPPING
• Iodide uptake is a critical first step (NIS & Pendrin)
• II : OXIDATION & ORGANIFICATION
• The reactive iodine atom is added to selected tyrosyl
residues within Tg.
• III : COUPLING
• The iodotyrosines in Tg are then coupled via an ether
linkage in a reaction that is also catalyzed by TPO
• MIT + DIT = T3
• DIT + DIT = T4
• IV : STORAGE
• VI : RELEASE
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Regulation of Thyroid Hormone Synthesis
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Worldwide Iodine Nutrition
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HYPOTHYROIDISM
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DEFINITION
Hypothyroidism is a disorder with multiple
causes in which the thyroid fails to secrete an
adequate amount of thyroid hormone.
 The most common thyroid dysfunction.
Tissue resistance to thyroid hormone:Rare
• Nygaard B.Primary hypothyroidism.Am Fam Physician. 2015 Mar 15;91(6):359-60.PMID: 25822552
• Hennessey JV, Espaillat R. Subclinical hypothyroidism: a historical view and shifting prevalence. Int J Clin Pract. 2015
Jul;69(7):771-82. doi: 10.1111/ijcp.12619.
• Lane LC, CheethamT, Congenital hypothyroidism – what is new?Paediatrics and Child Health. 2015 Jul ;25( 7): 302-307.
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CLASSIFICATION
• There is different classification:
Congenital or Acquired
Primary, Secondary or Tertiary
Overt or Subclinical
Transient or Permanent
• Webb EA, Dattani MT. Understanding hypopituitarism. Paediatrics and Child Health.2015 Jul;25(7 (295-301.
• Doggui, Radhouene; El Atia, Jalila. Iodine deficiency: Physiological, clinical and epidemiological features, and pre-analytical considerations.Annals of Endocrinology . 2015Jul;
76( 1):59-66. © 2015.
• Huang, Chun-Jui; Jap, Tjin-Shing. A systematic review of genetic studies of thyroid disorders in Taiwan.Journal of the Chinese Medical Association. 2015March; 78( 3): 145-15
• Gong G, Basom J. Mattevada S, Onger F. Association of hypothyroidism with low-level arsenic exposure in rural West Texas. Environ Res.2015 Apr;138:154-60. doi:
10.1016/j.envres.
• Zimmermann, Michael B, Prof; Boelaert, Kristien, MD. Iodine deficiency and thyroid disorders.The Lancet Diabetes & Endocrinology.2015; 3( 4): 286-295.
• Peckham S,Lowery D, Spencer S . Are fluoride levels in drinking water associated with hypothyroidism prevalence in England? A large observational study of GP practice data
and fluoride levels in drinking water.
• J Epidemiol Community Health. 2015 Jul;69(7):619-24. doi: 10.1136/jech-2014-204971.
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ETHIOLOGY
Primary Secondary
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• Insufficient functioning thyroid tissue
 Autoimmune hypothyroidism
• Hashimoto's or atrophic thyroiditis
 Iatrogenic
• 131 I treatment, Thyroidectomy,
• External irradiation of neck
 Infiltrative destruction of thyroid tissue
• Amyloidosis, Sarcoidosis, Hemochromatosis,
Scleroderma, Cystinosis, Riedel’s thyroiditis
• Impaired thyroid hormone synthesis
 Iodine deficiency
 Overexpression of type 3 deiodinase in infantile
hemangioma and other tumors
 Drug
• Iodine excess (e.g. iodine-containing contrast
media and amiodarone), Lithium, Antithyroid
drugs, PAS, INF-α, Aminoglutethimide, TK
inhibitors (e.g., sunitinib)
• Hypopituitarism:
 Tumors
 Surgery
 Irradiation
 infiltrative disorders
 Sheehan’s syndrome
 Trauma
 genetic forms
• Isolated TSH deficiency
or inactivity
• Bexarotene treatment
• Hypothalamic disease:
 Tumors
 Trauma
 Infiltrative disorders
 Idiopathic

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ETHIOLOGY CONT…
Transient Congenital
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• Thyroiditis
 Silent or postpartum
 Sub-acute
• Withdrawal of supra-physiologic
thyroxin treatment
• Iatrogenic
 After 131I treatment or subtotal
thyroidectomy for Graves’ disease
• Hypopituitarism:
 Tumors, surgery or irradiation,
infiltrative disorders, Sheehan’s
syndrome, trauma, genetic forms
• Isolated TSH deficiency or
inactivity
• Bexarotene treatment
• Hypothalamic disease:
 Tumors, trauma, infiltrative
disorders, idiopathic

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EPIDEMIOLOGY
Dr. MVasheghani
• Congenital hypothyroidism occurs in about 1 in 4000 newborns.
• Primary hypothyroidism prevalence ~ 5% of individuals.
• Mild or subclinical hypothyroidism
 prevalence ~ 15% 6–8% of women (10% over the age of 60)
and 3% of men.
• More common in women. (F/M = 4/1)
• The prevalence of overt hypothyroidism increases with age.
• The annual risk of developing clinical hypothyroidism is about
4% when subclinical hypothyroidism is associated with positive
TPO antibodies.
• Secondary hypothyroidism is rare, representing less than 1% of
cases.

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Congenital Hypothyroidism
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• Rare
• Absent thyroid tissue or hereditary defects in
TH synthesis
• Mental retardation due to lack of T4
• It may be associated with:
 Autoimmune diseases (Diabetes Mellitus)
 Cardiomyopathy & CHD
 Galactorrhoea
 Muscular dystrophy + pseudohypertrophy (Kocher-
Debre-Semelaigne

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Department of Pediatrics, Division of Endocrinology, Oregon Health & Science University,
707 SW Gaines Street, Portland, OR, USA. Congenital hypothyroidism
Rastogi MV, LaFranchi SH - (2010)
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Prior to Therapy 7 months after therapy
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Diagnosis of CH
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1) Azizi F, Janghorbani M, Hatami H, editors. Epidemiology and Control of Common Diseases in Iran. 3rd Ed.Khosravi Publ; 2000. p. 123-39.
2) Azizi F, Sheikholeslam R, Hedayati M, Mirmiran P, Malekafzali H, Kimiagar M, et al. Sustainable control ofiodine deficiency in Iran: beneficial results of the implementation of
mandatory law on salt iodization. J EndocrinolInvest 2002; 25: 409-13.
3)Azizi F, Mehran L, Sheikholeslam R, Ordookhani A,Naghavi M, Hedayati M, et al. Sustainability of a wellmonitored salt iodization program in Iran: marked reduction in goiter
prevalence and eventual normalization of urinary iodine concentrations without alteration in iodine content of salt. J Endocrinol Invest 2008; 31: 422-31.
4) Delshad H, Amouzegar A, Mirmiran P, Mehran L, Azizi F. Eighteen years of continuously sustained elimination of iodine deficiency in the Islamic Republic of Iran: thevitality
of periodic monitoring. Thyroid 2012; 22: 415-21
5) Veisani Y, Sayehmiri K, Rezaeian S, Delpisheh A .Congenital Hypothyroidism Screening Program in Iran; a Systematic Review and Metaanalysis. Iran J Pediatr.,201DEC
2014December; 24(6): 665–672.
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• In 2001 vs 1996
 Total goiter rates were 13.9 vs 53.8%, (p<0.0001).
 Median (range) UIC in 2001 was 165 microg/l and in 1996 was 205 microg/l
(p<0.0001). 1
• The goiter rate in the country was 6.5% . The total goiter rate in Hamedan,
Zanjan, Kermanshah, Mazandaran, and Gilan provinces was over 10%.2
• According to Meta analysis the overall incidence of Congenital hypothyroidism
was 2/1000 in Iran (95% CI: .002 – .002).3
• Elevated TSH levels and low TSH values were found in 8.1% and 3.4% of the
participants respectively. Among those with increased serum TSH, 5.7% had
levels between 5.2 – 10 mIU/L and 2.4% had values greater than 10 mIU/L.4
• Congenital hypothyroidism is more prevalent in iran (2/1000 live births) .5
Epidemiology of Hypothyroidism in IRAN

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Karimi F, Kalantarhormozi MR, Dabbaghmanesh MH, Ranjbar Omrani G.Thyroid disorders and the prevalence of antithyroid
antibodies in Shiraz population Arch Iran Med. 2014 May;17(5):347-51. doi: 0141705/AIM.008.
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Karimi F, Kalantarhormozi MR, Dabbaghmanesh MH, Ranjbar Omrani G.Thyroid disorders and the prevalence of
antithyroid antibodies in Shiraz population Arch Iran Med. 2014 May;17(5):347-51. doi: 0141705/AIM.008.
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Thyroid Disease Spectrum
0 ≥105
TSH, µIU/mL
Subclinical Hypothyroidism
TSH >4.7 µIU/mL, Free T4 Normal
Overt Hypothyroidism
TSH >4.7 µIU/mL, Free T4 Low
Euthyroid
TSH 0.5-4.7 µIU/mL, Free T4 Normal
Hyperthyroidism
TSH <0.5 µIU/mL, Free T3/T4 Normal or Elevated
Braverman LE, et al. Werner & Ingbar’s The Thyroid. A Fundamental and Clinical Text. 8th ed. 2000.
Canaris GJ, et al. Arch Intern Med. 2000;160:526-534.
Vanderpump MP, et al. Clin Endocrinol (Oxf). 1995;43:55-68.Dr. MVasheghani

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EVALUATION
• History & Physical Examination
• Measurement of Thyroid Hormones
 TSH assays
 Total T4 and total T3
 Unbound thyroid hormones
 T3RU
• ↑ T3RU in hyperthyroidism and ↓ TBG
 Free T3 or free T4 index = total T4 or T3 concentration x
the thyroid hormone binding ratio (THBR)
• Tests to Determine the Etiology
 Antibodies against TPO and Tg ,TSI
 Serum Tg
• Radioiodine Uptake and Thyroid Scanning
• Thyroid Ultrasound
• Fine-Needle Aspiration (FNA) biopsyDr. MVasheghani 23

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Thyroid-Stimulating Hormone Assays
Ladenson PW, et al. Arch Intern Med. 2000;160:1573-1575.
Braverman LE, et al. Werner & Ingbar’s The Thyroid. A Fundamental and Clinical Text. 8th ed. 2000.
Zophel K, et al. Nuklearmedizin. 1999;38:150-155.Dr. MVasheghani
• Key test for diagnosis of hypothyroidism and hyperthyroidism
• TSH assay sensitivity has improved with subsequent test generations
 First generation: RIA
• Sensitivity: 1.0 µIU/mL
 Second generation: IRMA
• Sensitivity: 0.1 µIU/mL
 Third generation: ELISA
• Sensitivity: 0.03 µIU/mL
 Chemiluminescence immuno assay : CLIA
• Gold standard ,Sensitivity: 0.001 µIU/mL

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What the mind knows the eyes seeWhat the mind knows the eyes see
!!!!
• Other Autoimmune disease
• Rx. Grave’s Ophthalmopathy
• Family Hx. thyroid disease
• Neck irradiation therapy
• Previous Rx for thyrotoxicosis
• Autoimmune Thyroiditis
• Chronic urticaria
Order for TSH alone as a screen test
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• Psychiatric patients
• Elderly women / men
• Patients of OSA
• Hypercholesterolemia
• Lithium, Amiodarone
• Postpartum women
Caraccio N, et al. J Clin Endocrinol Metab. 2002;87:1533-1538.
Carmel R, et al. Arch Intern Med. 1982;142:1465-1469.
Perros P, et al. Diabetes Med. 1995;12:622-627.

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Screening for Disorders of Thyroid Function
Disorder Prevalence in Adults Screening Recommendation
Hypothyroidism 5–10%, women
0.5–2%, men
TSH; confirm with free T4
Screen women after age 35 and
every 5 years thereafter
Graves’ disease
1–3%, women
0.1%, men
TSH, free T4
Thyroid nodules and
neoplasia
2–5% palpable
>25% by ultrasound
Physical examination of thyroid
Fine-needle aspiration biopsy
Hyperparathyroidism
0.1–0.5%,
women > men
Serum calcium
PTH, if calcium is elevated
Assess comorbid conditions
Table 399-2 The Principle of Internal Medicine, Harrison 19th
editionDr. MVasheghani
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Autoimmune Hypothyroidism

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Hashimoto's thyroiditis (chronic autoimmune
thyroiditis) is the most common cause of
hypothyroidism in iodine-sufficient areas of
the world. It is characterized clinically by
gradual thyroid failure, goiter, or both, due to
autoimmune-mediated destruction of the
thyroid gland. Nearly all patients have high
serum concentrations of antibodies against
one or more thyroid antigens, lymphocytic
infiltration of the thyroid, which includes
thyroid-specific B and T cells, and apoptosis
of thyroid follicular cells.
Chronic Autoimmune Thyroiditis
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Grave’s Disease Hashimoto Disease
Postpartum thyroiditis
Silent thyroiditis
Drug induced thyroiditis
Spectrum of thyroid autoimmunity
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Possible precipitating factors
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• Genetic
• Gender: Women have more risk.
• Age: Elderly
• Infection
• Stress
• Humoral factors (sex steroids , pregnancy)
• Prior history of Graves disease or postpartum thyroid dysfunction
• Other autoimmune disease
 Pernicious anemia
 Type 1 Diabetes mellitus
• Family history of thyroid disease other autoimmune disease
• Laboratory evidence of hypercholesterolemia, elevated LFTs,
elevated CPK and LDH

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Pathogenesis
Molecular mimicry
Bystander activation
Thyroid cell expression of HLA Ag
Thyroid cell apoptosis
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• Thyroid auoantigenes
• Role of B cells
• The primary role of T cells
• Potential mechanism of thyroid
injury

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•The disease clusters in families, sometimes
alone and sometimes in combination with
Graves' disease
• It is more common in women.
• The concordance rate in monozygotic twins is
30 to 60 percent.
• It occurs with increased frequency in patients
with Down's and Turner's syndrome.
• There is an association, albeit relatively weak,
with certain HLA alleles.
• There is an association with certain alleles of
the gene for CTLA-4, a T-cell surface molecule
involved in T-cell activation
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TFT in Progressive Hypothyroidism
TSH
Moderate SevereMild
Normal Range
Free T4
Free T3
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The characteristic histopathological
abnormalities are profuse lymphocytic
infiltration, lymphoid germinal centers,
and destruction of thyroid follicular cells .
fibrosis and areas of follicular-cell
hyperplasia, presumably induced by TSH,
are also seen in patients with severe
disease. The intrathyroidal lymphocytes
are both T and B lymphocytes.
PATHOLOGY
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Clinical Features of Hypothyroidism
• Hypothyroidism is insidious in onset and the most of
symptoms or signs are nonspecific in nature, these
make it difficult to diagnose. Symptoms that are new,
progressive, or present in combination are more likely
to be due to hypothyroidism.
• Moreover, hypothyroidism S&S vary according to the
age at onset and disease severity.
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CURRENT CLINICAL PICTURE
• The prevalence of hypothyroid patients presenting
with minimal symptoms is increased, largely due to
the availability of sensitive and specific laboratory
tests that allow recognition of the primary form of the
disease long before severe symptoms have
developed.
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Figure 12-5 Frequency of hypothyroid symptoms
and signs (%) overt hypothyroidism and controls
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Causes of clinical S & S
• The mechanisms of S & S are:
Slowing of metabolic process
 Accumulation of matrix substance
• The clinical features of disease are the
consequence of:
 Thyroid hormone deficiency
Thyroid autoimmunity
Associated with signs or symptoms of other
autoimmune diseases, particularly Vitiligo, PA,
Addison’s disease, Alopecia areata, and T1DM
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Multisystem effects of Hypothyroidism
• General
Tiredness
Weakness and Fatigue
Cold Intolerance (Feeling cool)
Lethargy, Somnolence
Weight gain with poor appetite
• The weight gain is usually modest and due
mainly to fluid retention in the myxedematous
tissues.
• Typical features (myxedema) include a
puffy face with edematous eyelids and
nonpitting pretibial edema . 45
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Skin and Hair
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• Thickening, flayking and dryness of skin
 Decreased sweating
 Thinning of the epidermis
 Hyperkeratosis of the stratum corneum.
 Increased dermal glycosaminoglycan (myxedema)
 Content traps water, giving rise to skin thickening without pitting
• Dry, coarse hair, Alopecia
• Loss of lateral eyebrow hair (thinning of the outer third of the eyebrows)
• Pallor, often with a yellow tinge to the skin due to Carotenimia.
• Nail growth is retarded and brittle.
• Blood flow is diverted from the skin, producing cool extremities.
 Myxoedema, Malar flushes, Vitiligo

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Head and Neck
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• Impaired hearing due to Conductive
deafness
• Hoarse voice
• Thick, slurred (clumsy) speech and are
due to myxedematous infiltration of the
tongue and larynx, respectively.
• Ophthalmopathy occurs in about 5% of pts
with autoimmune hypothyroidism

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Cardiovascular
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• Dyspnea, Angina
• Decreased ventricular contractility, CHF
• Increased diastolic blood pressure
• Narrow pulse pressure
Reduced stroke volume
Increased peripheral resistance
• Bradycardia
• Peripheral non-pitting edema
• Pericardial effusions occur in up to 30% of patients but rarely
compromise cardiac function.
• Alterations in myosin heavy chain isoform expression have been
documented ,but cardiomyopathy is unusual.
• HyperlipIdemia, Xanthelsma

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Respiratory system
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Dr. MVasheghani
• Pulmonary function is generally normal.
• Dyspnea may be caused by
 Pleural effusion
 Impaired respiratory
 muscle function
 Diminished ventilatory drive
 Sleep apnea

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Gastro-intestinal Tract
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Dr. MVasheghani
• Gastro-intestine
 Constipation, fecal impaction (myxedema
megacolon).
 Ileus, Decreased GI motility, Gaseous distention
 Ascites
 Achlorhydria
 Elevations in the serum levels of CEA
 Malabsorption
• Hepatic
 Increased LDL / TC
 Elevated LDL + triglycerides
 Levels of aminotransaminases may be elevated
 The gallbladder contracts sluggishly and may be
distended

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Genito-Urinary system
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Dr. MVasheghani
• Renal
• Fluid retention and oedema
• Decreased GFR
• Reproductive system
• Infertility, ↑ Miscarriage
• Menometrorrhagia, oligomenorrhea or amenorrhea
• Impotence, ↑ Prolactin
• ↓ Libido both sexes
• Premature ovarian failure

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Musculoskeletal
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Dr. MVasheghani
• Muscle stiffness, cramps, pain,
weakness, myalgia
• Slow muscle-stretch reflexes,
muscle enlargement, atrophy
• Carpel tunnel syndrome
• arthralgias
• Pseudomyotonia
• Slow relaxation of DTR
• Arthralgias,

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Central Nervous System
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Dr. MVasheghani
• Memory and concentration impairment
• Depression with limited initiative and sociability.
• Cognitive deficits can range from mild lapses in
memory to delirium, dementia, seizures, psychosis,
and myxedema coma
• Cerebellar ataxia, myotonia, paresthesias
• Hashimoto’s encephalopathy has been defined as a
steroid-responsive syndrome associated with TPO
antibodies, myoclonus, and slow-wave activity on
electroencephalography

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Clinical Signs of Hypothyroidism
•Coarse Hair; Diffuse thinning of scalp hair
•The skin may be coarse, dry, pale or yellow and cool due to peripheral
vasoconstriction; Brritle nails
•Thinning of lateral 1/3 of eye brows (Queen Anne sign)
•Puffiness of eyes and face
Goiter (not in all cases), the thyroid gland may be normal in size,
diffusely enlarged, or atrophic, It may be soft and smooth with a lobular
texture, or firm and irregular with a variegated nodular texture ; cervical
incisional scars
•Low hoarse speech and slow movements; slow and dysarthric speech
•Bradycardia, pericardial effusion, diastolic hypertension, Non-pitting
edema (myxoedema), ↓ heart sound
•Delayed relaxation of DTR with a marked delay in the terminal
relaxation phase (Hang up reflex)
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Abnormal laboratory in hypothyroidism
• Anemia (25-50% of patients)
• Hyponautremia
• Hypercholesterolemia (90% of patients)
14% of patients hypercholesterolemia have hypothyroidism
• Abnormal LFT
• Elevated CPK and LDH
• Hyperprolactinemia
• Decreased GH secretion and action
• Schmidt syndrome (Primary adrenocortical insufficiency)
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Clinical features
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Pretibial Myxedema Myxedema with Carotinemia

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Pituitary Tumor – Secondary
Hypo
Normal Pituitary Fossa
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Massive Pericardial Effusion
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Feb1998
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Sep 1998 Dec1999

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Before Therapy After Therapy
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Before Therapy After Therapy

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Hypothyroidism and Depression
Have Many Common Features
Depression
• Sleep decrease
• Suicidal ideation
• Weight loss
• Appetite increase/
decrease
Nemeroff CB, J Clin Psychiatry. 1989;50(suppl):13-20.
• Bradycardia
• Cardiac and lipid
abnormalities
• Cold intolerance
• Delayed reflexes
• Goiter
• Hair and skin
changes
• Constipation
• Appetite decrease
• Decreased concentration
• Decreased libido
• Delusions
• Depressed mood
• Diminished interest
• Sleep increase
• Weight increase
• Fatigue
Hypothyroidism
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Classification
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• Established reference ranges for TSH levels is 0.5 to 4.5
mIU/L.
• A low free T4 level with a persistently elevated TSH level
represents overt primary hypothyroidism.
• A low-normal free T4 level with an elevated TSH level is
termed mild or subclinical primary hypothyroidism.
• Other uncommon causes of isolated TSH elevation
include:
 Recovery from severe systemic illness
Renal failure
Adrenal insufficiency.

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TFT ASSESSMENT
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Condition that affect TSH level
Low serum TSH
Dr. MVasheghani
Primary hyperthyroidism
Incomplete recovery of
hyperthyroidism
NTI
High level of hCG, early
pregnancy, molar pregnancy,
coriocarcinoma
Drugs: dopamine agonist, GC,
somatostatin analogs
Central hypothyroidism
 Primary hypothyroidism
 Recovery from NTI
 Drugs: dopamine antagonist,
amiodarone, OCG dye
 TSH-producing pituitary
adenoma
 Adrenal insufficiency
 Heterophilic antibody
interference
 Generalized thyroid hormone
resistant
High serum TSH

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• The underlying cause of primary hypothyroidism is usually
clinically obvious, and laboratory testing is unnecessary in
most cases.
• When confirmation is required (e.g., to convince a patient
the condition is permanent), serum antithyroid antibodies
may be assessed. Measurement of Anti-TPO Ab is a more
sensitive test than Anti-Tg Ab for this purpose.
• However, 10% of patients with histologically documented
autoimmune thyroiditis have no circulating antithyroid
antibodies. 70
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• When clinical findings suggest the possibility of secondary
hypothyroidism such as:
The presence of a sellar mass
Previous pituitary surgery or irradiation
Other pituitary axis hormone deficiencies
• The serum TSH and free T4 level must be assessed.
• In these settings, a low or even low-normal free T4 level
can confirm the diagnosis.
• The TSH level in patients with secondary hypothyroidism
can be low, normal, or even modestly elevated.
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Diagnosis
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Treatment
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Dr. MVasheghani
•The goals of thyroid hormone replacement therapy are:
To replace endogenous thyroid hormone production
To avoid iatrogenic thyrotoxicosis
To treat systemic complications of severe
hypothyroidism, rarely.
•Therapy with levothyroxine sodium products requires
individualized patient dosing:
Careful titration: use a formulation with consistent doses
Clinical evaluation: symptoms resolve more slowly than
TSH response
Laboratory monitoring: need consistent, sensitive TSH
measurements

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Treatment
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Dr. MVasheghani
• Treatment depends upon :
 Cause and severity of disease
 Patients age and weight
 Goiter size
 Comorbid states and treatment
 Cardiovascular health

75. 75
• LT4, LT3 or LT4+LT3
• LT4 therapy Choice
• LT4+LT3 therapy Sometimes
• Is there any place for liothyronine
alone as long-term replacement?
75
NO‼
Dr. MVasheghani

76. 76
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Dr. MVasheghani
1.6 micg/kg BW, at least 30 min before breakfast.
The goal of treatment being a normal TSH, ideally in the
lower half of the reference range.
TSH should be measured 4 - 8 week later.
Once an adequate dose has been established, the TSH
level should be checked annually.
In patients with secondary hypothyroidism, the serum
free T4 level should be monitored 2 to 4 weeks after the
thyroxine dose is started or adjusted, with a target free T4
level in the upper half of the reference range.
Clinical Hypothyroidism

77. 77
Thyroid hormone replacement
• Levothyroxine sodium is choice.
• It is well absorbed and 7 day half-life.
• Thyroxine is physiologically deiodinated to the more
biologically active T3 in peripheral tissues.
• Thyroxine has a narrow therapeutic index, and doses
differing by as little as 12% can have clinicalconsequences.
• Bioavailability may differ by as much as 12% among
different preparations. Consequently, adherence to a single
thyroxine formulation is advisable.
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Dr. MVasheghani
2004 AACE, TES, and ATA Joint Position Statement on the Use and
Interchangeability ofThyroxine Products

78. 78
78
Primary Hypothyroidism Rx. Algorithm
TSH >3.0 µIU/mL TSH <0.5 µIU/mL
Initial Levothyroxine Dose
Increase
Levothyroxine
Dose by
12.5 to 25 µg/d
Repeat TSH Test
6-8 Weeks
TSH 0.5- 2.0 µIU/mL
Symptoms Resolved
Measure TSH at 6 Months,
Then Annually or
When Symptomatic
Continue Dose Decrease
Levothyroxine
Dose by
12.5 to 25 µg/d
Singer PA, et al. JAMA. 1995;273:808-812.
Demers LM, Spencer CA, eds. The National Academy of
Clinical Biochemistry Web site. Available at:
http://www.nacb.org/lmpg/thyroid_lmpg.stm. Accessed
July 1, 2003.
Dr. MVasheghani

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CONT…
• In patients of normal body weight who are taking 200 g
of levothyroxine per day, an elevated TSH level :
Poor adherence to treatment.
Malabsorption (e.g., celiac disease, small-bowel surgery)
Drug:
• Estrogen or selective estrogen receptor modulator
therapy, Lovastatin, Amiodarone. PPI, TK inhibitors
 Thyroxine doses should be separated from these substances
by 8 hours or longer
Ingestion with a meal
Dr. MVasheghani
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80. 80
Interfrence with LT4 replacement
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81. 81
• The clinical effects of levothyroxine replacement
are slow to appear. Patients may not experience
full relief from symptoms until 3–6 months after
normal TSH levels are restored.
• patients who miss a dose can be advised to take
two doses of the skipped tablets at once.
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What is a Normal TSH?
• In their 2002 position statement, AACE used an
upper limit of normal for TSH of 3.0mIU/L
established in a population of patients carefully
screened for thyroid disease by the National
Academy of Biochemistry in 2002.
• However, in 2004 a statement was published in
JAMA maintaining that the upper limit of TSH
should remain at 4.5 mIU/L, rather than 3.0-3.5 as
some other organizations have suggested.
82
AACE MEDICAL GUIDELINES FOR CLINICAL PRACTICE FOR THE EVALUATION AND TREATMENT OF
HYPERTHYROIDISM AND HYPOTHYROIDISM. ENDOCRINE PRACTICE Vol 8 No. 6 2002
JAMA 2004; 291:228-238
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Complications
 Pseudotumor cerebri in children
• Idiosyncratic and occurs months after treatment has begun.
 Thyrotoxicosis usually accompany significant degrees of
overtreatment
 Bone mineral loss, especially in postmenopausal women
 Increase the risk of AF in older individuals, even a modestly excessive
thyroxine dose
 Exacerbate myocardial ischemia in patients with underlying CAD
 Coexisting adrenal insufficiency may be unmasked.
 Transient hair loss
 Acute sympathomimetic symptoms
83
Dr. MVasheghani

84. 84
Subclinical Hypothyroidism
• Subclinical hypothyroidism refers to biochemical
evidence of thyroid hormone deficiency .
• An isolated elevated TSH level with normal T3 and T4
levels
• It is important to confirm that any elevation of TSH is
sustained over a 3-month period before treatment is
given.
• There are no universally accepted recommendations for
the management of subclinical hypothyroidism.
• Treatment is administered by starting with a low dose of
levothyroxine (25–50 μg/d) with the goal of normalizing
TSH. 84
Dr. MVasheghani

85. 85
Subclinical Hypothyroidism
• Who should be treated?
 Patient is symptomatic
 TSH levels >=10 mU/L.
 TPO antibodies positive
 Woman who wishes to conceive or is pregnant
 Any evidence of heart disease
• Maintain TSH in normal range
• In patients not receiving Levothyroxine therapy,
check TSH every 3-6 months(annually) or when
symptoms occur 85
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86. 86
Special Treatment Considerations
• Women should ensure that they are euthyroid prior to
conception and during early pregnancy.
• The dose of levothyroxine may need to be increased:
 ↑ dose 50%(25-75%) during pregnancy
 Post-surgical or post-Iodine ablation
 Nephrotic syndrome due to rapid clearance of thyroid hormone
• The dose of levothyroxine may need to be decreased:
 ↓ Dose 20% in elderly patients
 Adults with known or suspected ischemic heart disease
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87. 87
Hypothyroidism & Pregnancy
• Fetal neural development delay or preterm delivery.
• The presence of thyroid autoantibodies alone, in a euthyroid
pt, is associated with miscarriage and preterm delivery.
• TFT should be evaluated immediately and every 4 w during
the first half of the pregnancy, then every 6–8 w depending on
whether LT4 dose adjustment is ongoing after 20 W gestation.
• The 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, LT4 doses return to pre-pregnancy levels.
• Pregnant women should be separate ingestion of prenatal
vitamins and iron supplements from LT4 by at least 4 h.
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Hypothyroidism & Heart Disease
• Elderly patients may require 20% less thyroxine
than younger patients.
• The starting dose of levothyroxine is 12.5–25 μg/d
with similar increments every 2–3 months until
TSH is normalized.
• In some patients, it may be impossible to achieve
full replacement despite optimal antianginal
treatment.
88
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Hypothyroidism & Surgery
• Emergency surgery is generally safe in
patients with untreated hypothyroidism.
• Elective or routine surgery in a hypothyroid
patient should be deferred until euthyroidism
is achieved.
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90. 90
Hypothyroidism Following Hemithyroidectomy
• The incidence & risk factors for hypothyroidism in
patients undergoing partial thyroid surgery
remains unclear. With reported incidence of b/w
6.5% & 45% and up to 65% in patient with head
and neck ca .
• Risk factors are the presence of :
Anti-TPO antibody
Thyroiditis in pathologyM
ultinodular goiter
Preoperative thyrotoxicosis
Thyroid remnant < 6 g
Elderly patients 90
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DAMAVAND MOUNTAIN
TEHRAN , IRAN