• First endocrine disorder treated by replacement with the
• Development of purified thyroid hormone preparationsmimic
the function of the normal thyroid gland with thyroid hormone
• Safe and well tolerated by most patients
• Thyroid glandthyroxine (T4) and triiodothyronine (T3).
• Autoimmune disorders of the thyroid glandglandular
destruction and hormone deficiency
• two lobes connected by an isthmus.
• Location:Anterior to the trachea between the cricoid cartilage and the
• 20 g in size, highly vascular, and soft in consistency.
• Four parathyroid glandsparathyroid hormone are located posterior
to each pole of the thyroid.
• The National Health and Nutrition Examination Survey
(NHANES 1999-2002) of 4392 individuals3.7%
hypothyroid. (defined as TSH levels exceeding 4.5
• World Health Organization (WHO) data from 130
countries taken from January 1994 through December
2006 found inadequate iodine nutrition in 30.6% of the
• WHOurinary iodine concentrations100 to 199 μg/L
in the general population.
• 150-249 μg/L in pregnant women.
• Age-related demographics:The frequency increases with
• Most prevalent in elderly populations-The Framingham
study found hypothyroidism (TSH > 10 mIU/L) in 5.9% of
women and 2.4% of men older than 60 years.
• Sex-related demographics:2 to 8 times higher in females.
• Race-related demographics:NHANES 1999-2002 whites
(5.1%) and Mexican Americans than in African Americans
• Iodine deficiencymore common in less-developed
• Out of an estimated world population of 5.8 billion in
different regions, 3.8% are estimated to be suffering
from iodine deficiency in some form, though only 12% is
affected by goitre.
• Areas of adequate iodine intake-Autoimmune thyroid
disease (Hashimoto disease).
• Prevalence of antibodies is higher in women and
increases with age.
Types of primary hypothyroidism include the following:
• Chronic lymphocytic (autoimmune) thyroiditis
• Postpartum thyroiditis
• Subacute (granulomatous) thyroiditis
• Drug-induced hypothyroidism
• Iatrogenic hypothyroidism
Chronic lymphocytic (autoimmune)
• Most frequent cause of acquired hypothyroidism
• Thyroid antigens as foreign chronic immune reaction
ensues resulting in lymphocytic infiltration of the gland
progressive destruction of functional thyroid tissue.
• Anti–thyroid peroxidase (anti-TPO) antibodies are the hallmark
of this disease.
• Antibody levels can vary over time.
• Absence of antibodies does not exclude the diagnosis
• Up to 10% of postpartum develop lymphocytic thyroiditis in the
2-12 months after delivery.
• Transient (2-4 months).
• Increased risk of permanent hypothyroidism or recurrence of
postpartum thyroiditis with future pregnancies.
• In a 12-year longitudinal study, Stuckey et al found that
hypothyroidism developed in 27 of 71 women (38%) who had a past
history of postpartum thyroid dysfunction (PPTD). In comparison,
only 14 of 338 women (4%) who had not had PPTD developed
Subacute granulomatous thyroiditis
• Also known as de Quervain disease,
• Relatively uncommon disease
• Most frequently middle-aged women.
• Low grade fever, thyroid pain, dysphagia, and elevated erythrocyte
sedimentation rate (ESR).
• inflammatory conditions or viral syndromes may be associated with
transient hyperthyroidism transient hypothyroidism.
• The following medications reportedly have the potential to cause
• Iodine excess (including iodine-containing contrast media and
• antithyroid drugs,
• p-aminosalicylic acid,
• tyrosine kinase inhibitors – Sunitinib, imatinib
• Radioactive iodine (I-131) for treatment of Graves disease results
in permanent hypothyroidism within 3-6 months after therapy.
• External neck irradiation (for head and neck neoplasms, breast
cancer, or Hodgkin disease)
• Thyroidectomy-approximately 15-30%
• Genome-wide association studies FOXE1 gene hypothyroidism.
• 10% of patients with congenital hypothyroidism have an error in
thyroid hormone synthesis.
• Mutations in the TPO gene appear to be the most common error of
hormone synthesis, causing failure to produce adequate amounts of
• Mutations in the TSHR and PAX8 genes congenital hypothyroidism
without goiter.[11, 12]
• Pendred syndrome mutation in the SLC26A4 gene defect in
the organification of iodine
congenital sensorineural hearing loss,
enlarged thyroid gland.
autosomal recessive manner.
• Autoimmune polyendocrinopathy
typeIAIRE genecharacterized by the presence of Addison
disease, hypoparathyroidism, and mucocutaneous candidiasis.
• Autoimmune polyendocrinopathy type 2 (Schmidt syndrome) is
associated with adrenal insufficiency and hypothyroidism
Iodine deficiency or excess
• Most common cause of hypothyroidism. Excess iodine can transiently
inhibit iodide organification and thyroid hormone synthesis (the
• Healthy individualsphysiologic escape from this effect. In patients
with iodine overloadsodium-iodide symporter shuts downallows
intracellular iodine levels to drop and hormone secretion to resume.
• The Wolff-Chiakoff effect is short-livedsodium-iodide symporter is
capable of rapidly downregulation.
• exposure to excess iodineprofound and sustained hypothyroidism
in individuals with abnormal thyroid glands.
Goitre can be classified as
per WHO classification
• Grade 0 – no goitre presence is found (the
thyroid impalpable and invisible)
• Grade 1 – neck thickening is present in result of
enlarged thyroid, palpable,not visible in normal
position of the neck.
• Grade 2 – neck swelling, visible when the neck is
in normal position, corresponding to enlarged
thyroid – found in palpation.
Central hypothyroidism[16, 17]
• Central hypothyroidismhypothalamic-pituitary axis is
damaged. The following potential causes should be
Pituitary adenoma-exerting pressure on normal
Tumors impinging on hypothalamus
Lymphocytic hypophysitis- cause death of cells.
History of brain or pituitary irradiation
• Drugs (eg, dopamine, prednisone, or opioids)-decreased TSH
• Congenital non goiterous hypothyroidism type 4Mutation in
theTSHB geneautosomal recessive pattern
• TRH resistanceTRHR geneautosomal recessive manner.
hypothyroidism and, unsurprisingly, have insensitivity to
• TRH deficiencymutation in the TRH geneautosomal recessive
• Menstrual disturbances,infertility
• Paresthesias, nerve entrapment syndromes
• Blurred vision
• Decreased hearing
• Fullness in the throat, hoarseness
Hashimoto thyroiditis is difficult to distinguish clinically, but the
following symptoms are more specific to this condition:
• Feeling of fullness in the throat
• Painless thyroid enlargement
• Transient neck pain, sore throat, or both
1.Tests of the Hypothalamic-Pituitary-Thyroid Axis
• TSH secretion: precise and specific indicator of the thyroid
• Normal range of the serum TSH:0.5 to 4.7 mU/L
• Diurnal variation of TSH secretion with peak values in the early
TSH as a screening test
• TSH-secreting pituitary tumor
• Thyroid hormone resistance
• Assay artifact
• 1ST trimester of pregnancy (due to hCG secretion),
• After treatment of hyperthyroidism
• Response to high doses of glucocorticoids or dopamine
• Low to high-normal TSH level, inappropriate for the low T4 level.
Sick Euthyroid Syndrome
• Acute, severe illness causes abnormalities of TSH or
thyroid hormone levels in the absence of underlying
• Major cause cytokines such as IL-6.
• M/C hormone patterndecrease in total and unbound
T3 levels (low T3 syndrome) with normal levels of T4 and
• Magnitude of the fall in T3 correlates with the severity of
• T4 conversion to T3 via peripheral deiodination is
impaired, leading to increased reverse T3 (rT3).
• Very sick patients :fall in total T4 and T3 levels (low T4
• TSH levels may range from <0.1 to >20 mIU/L
Diagnosis of SES
• Previous history of thyroid disease and TFT
• Evaluation of the patient's acute illness
• Measurements of Rt3 with unbound thyroid hormones
• Diagnosis of SES is presumptive
• Resolution of the test results with clinical recovery can
clearly establish this disorder.
• Wt loss of 2 to 4 kg
• Pulse rate increase
• Appetite improves, Constipation disappears
• Psychomotor activity increases
• Hoarseness ,changes in skin and hair improve last
PREGNANCY:Increase in serum TBG
• The mean increment in dose is 50μg/dayapparent
by the end of the first trimester, though may be
delayed to as late as the 6th month of gestation in
• A similar up-titration of thyroxine dose may be
required in women who are on estrogen preparations
including the oral contraceptive pill.
• TOC : Synthetic levothyroxine
• Most patients with postpartum thyroiditis
require treatment during the hypothyroid phase
• Long-term follow-up of patientsrisk of
• Subclinical hypothyroidism in pregnancy requires
• Co-existence of thyroid hormone deficiency and
• Important to replace glucocorticoid before starting
• Thyroxine therapy may lead to an increased
metabolism,increased demand of cortisol increasing
the likelihood of precipitating an adrenal crisis.
• Important to replace glucocorticoid before starting
• Monitoring of therapyserum T4 levels instead of
serum TSH levelssample should be collected prior to
ingesting the morning dose of thyroxine.
Ischemic heart disease:
• Thyroxine therapyimproves myocardial
function reduces peripheral vascular resistance
• Increases the myocardial oxygen demand
angina in 2% patients.
• Patients with pre-existing angina should ideally
undergo a cardiac evaluation prior to initiating
• Therapystarted at 25μg/day or even less and
increased no faster than at 4 weekly intervals.
Patients unable to take oral
• Intravenous thyroxine can be given in a dose
approximately 70% of the oral dose, which
reflects the fractional absorption of the oral
Persistently elevated TSH
despite thyroid hormone
• poor compliance- try ‘catch up’ when a physician
visit approachesfree T4 NORMAL,TSH
• Tissue-level unresponsiveness to thyroid
• Only 300 families have been identified with this
• Myxedema coma is a severe life threatening situation
• Most commonly occurs in individuals with undiagnosed
or untreated hypothyroidism who are subjected to an
external stress, such as low temperature, infection,
myocardial infarction, stroke.
• Respiratory depression,Bradycardia, Hypotension,
decreased intestinal motility, Hyponatremia, Altered
sensorium, Infections and Hypothermia.
• Most patients need ventilatoryat least 24-48
hoursmeasurement of arterial blood gases is
• Management includes maintaining of vital parameters
• Administration400 to 500 mcg of L-thyroxine through
nasogastric tube initially and subsequently 100 mcg/day.
• route is suboptimalconcerns of erratic
• Corticosteroids may be given along with assisted
ventilation and O2 administration.
• Hypothermiainsulating blankets.
• Persistently elevated TSH levels and free
thyroxine (T4) levels are not below normal
• May resolve on its own or remain unchanged.
• Rest of the patients proceed to develop overt
hypothyroidism (low free T4 and raised TSH
levels) within a few years.
• Patients with raised TSH elevations and
detectable anti-thyroid antibody
levelsincreased risk of developing overt
• mild hypothyroid symptoms
• subtle serum lipoprotein
• cardiac function abnormalities
• Progression to overt hypothyroidism5 to 20%
per year in patients with both mildly elevated
TSH levels and antithyroid antibodies.
Important clinical pointers when
monitoring thyroid replacement
• Serial TSH measurements in patients with an intact
• Important to keep in mind that changes in TSH levels lag
behind changes in thyroid hormone levels.
• Subsequent to adjustment of levothyroxine dosage, TSH
levels should be assessed only at least after four weeks.
• Changes in TSH levelsafter eight weeks of therapy with
thyroid hormone replacement.
• Adequacy of treatment in patients with pituitary
insufficiency measurements of free T4 and T3
• Increasing age is associated with declining
thyroid binding and serum albumin levels,dosage
requirementreduced by up to 20%.
• Elderly patientsannual monitoring for thyroid
function in order to avoid over replacement.
• Most hypothyroid patientstested annually for
TSH or free T4 levelsno data exists to support
• Stable maintenance dosage of levothyroxine is
achieved, it is adequate to maintain a euthyroid
state until the patient becomes 6o to 70 years
Potential adverse effects of
• Regular monitoring of serum TSH levelsmid-
normal serum TSH values ensuresis safe and
free from adverse events.
• In the event that thyroxinesuppressive
dosesafter carcinoma thyroid
surgerypotential adverse effectsskeletal and
• A TSH value of <0.1mU/lrisk factor for
left ventricular hypertrophy and
enhanced risk for ischemic heart disease.
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