HYPOTHYROIDISM

By Ketebu Blessing Wenghlayefa

 1. Which of the following is the
3. T3 is reliable in discriminating euthyroid
transporter responsible for the
from hypothyroid state
transport of iodine into the thyroid
True/False
cells against the concentration
gradient
a. Na iodine symporter 4..The following are clinical feautures of
b. K iodine symporter hypothyroidism except
c. I Cl antiport a. Menorrhagia
d. None of the above b. Bradycardia
c. Brittle nails
2. Subclinical hypothyroidism is
d. Scanty periods
characterized by
a. reduced TSH and normal levels 5. Myocardial infarction is a precipitant of
of t3 and t4 myxedema coma
b. Raised TSH and serum T True/False
3 and T4 concentrations are at
the lower end of the reference
range. 6.The thyroid gland located in the anterior
c. Raised TSH and t3 and t4 are at region of the neck spans from C4 to C7
the higher end of the reference True/False
range
d. Raised TSH and raised t3 and t4
7.Post sub-acute thyroiditis usually 11.Complete suppression of TSH should be
avoided because of risk of
occurs after a viral infection
a.Hyperventilation
True/False b. Seizures
c. Atrial fibrillation
8.What is responsible for the d. Osteoporosis
movement of the thyroid gland e. C and D
upon swallowing

9.Hypothyroidism is more common in males

True/False

10. Severe form of hypothyroidism is

termed
……………………………….
 OUTLINE
 INTRODUCTION
 EPIDEMIOLOGY
 FUNCTIONS OF THYROID HORMONES
 THYROID HORMONES SYNTHESIS
 PATHOPHYSIOLOGY OF HYPOTHYROIDISM
 CLINICAL FEAUTURES
 INVESTIGATIONS
 MANAGEMENT
 MYXEDEMA COMA
 INTRODUCTION

The thyroid gland is a butterfly-shaped organ located in the

anterior region of the neck at the level of C5 to T1 vertebrae. It is
found deep to the sternothyroid and sternohyoid muscles
Immediately inferior to the thyroid cartilage is found the cricoid
cartilage, below which the thyroid isthmus is located in the midline
The right and left lobes of the thyroid curve round the trachea
and the oesophagus in a posterolateral position and are partially
covered by the sternomastoid muscles 04
The thyroid is attached to the pretracheal fascia, which allows
it to move superiorly on swallowing
 Functions of thyroid hormones
• Thyroid hormones are important in the regulation of many functions
and aspects of the human body, such as temperature regulation, energy
levels, weight, hair, nail growth and more
• Thyroid hormones help with fetal brain development and function
• It helps with skeletal maturation
• It increases basal metabolic rate of the body
• Has inotropic and chronotropic effects
• Increases the body’s sensitivity to catecholamines
• It stimulates gut’s motility
● It metabolizes serum cholesterol
● It increases bone turnover and resorption
● Facilitates conversion of carotene to vitamin A
● Essential for the development and differentiation of cells
● Plays a role in thermal regulation
 DEFINITION

Hypothyroidism is a condition in which there is reduced level of

thyroid hormones circulating in the system either as a result of
underactivity of the thyroid gland which is “primary
hypothyroidism” or a disease of the hypothalamus or pituitary
“secondary hypothyroidism”. In sub-clinical hypothyroidism, serum
TSH is raised and serum T3 and T4 concentrations are at the
lower end of the reference range.
 EPIDEMIOLOGY

Primary hypothyroidism is one of the most common endocrine conditions, with

an overall UK prevalence of over 2% in women but under 0.1% in men.The
worldwide prevalence of subclinical hypothyroidism
varies from 1% to 10%.. Hypothyroidism is a common condition with various causes
but autoimmune disease (Hashimoto’s thyroiditis) and thyroid failure
following 131I or surgical treatment of thyrotoxicosis account for over 90%
of cases, except in areas where iodine defeciency is endemic. Women are
affected approximately six times more frequently than men
 SYNTHESIS OF THYROID HORMONES

The thyroid synthesizes two hormones:

Triiodothyronine (T3): Produced by the thyroid gland as well as in

other tissues, via the removal of iodine from Thyroxine (T4)
Tetraiodothyronine (T4): Produced by the thyroid gland under the
regulation of the pituitary gland and the hypothalamus. It is secreted
into the bloodstream and travels to organs such as the kidneys and
liver where it is converted into its active form – triiodothyronine
Thyroid hormone synthesis requires intact, functional and uninhibited Sodium-Iodide
Symporter (NIS), Thyroglobulin and the enzyme thyroid peroxidase
The synthesis of thyroid hormones involves six major steps:
1. Trapping: Active transport of iodide (I-) across the basement membrane into the
thyroid follicular cells. First, there is diffusion of iodide to the apex of the cells,
followed by transport of iodide into the colloid. This is the 1 st and rate-limiting
step
2. Organification: Oxidation of inorganic iodide to iodine and incorporation of
iodine into tyrosine residues within thyroglobulin molecules in the colloid
3. Coupling: Linking pairs of iodotyrosine molecules within thyroglobulin to form
iodothyronine. Combination of two DIT molecules to form tetraiodothyronine
(T4), while combination of MIT with DIT forms T3
4. Pinocytosis and then Proteolysis: Uptake of thyroglobulin from the colloid into
the follicular cells by endocytosis, fusion of the thyroglobulin with a lysosome
and proteolysis and release of T4, T3, DIT, MIT then into the circulation
5. Deiodination of iodotyrosines (DIT and MIT) to yield tyrosine, for conservation
and reuse of the liberated iodide
6. 5’-deiodination: Intrathyroidal 5’-deiodination of T4 to T3 (formed from
monodeiodination of T4 in the thyroid)
 PATHOPHYSIOLOGY
The most common cause of hypothyroidism is the inability of the thyroid gland to
produce a sufficient amount of thyroid hormone; however, less commonly pituitary
and hypothalamus may also result in thyroid dysfunction. The hypothalamus secretes
thyrotropin-releasing hormone (TRH) that stimulates the pituitary gland to produce
thyroid-stimulating hormone (TSH).
Thyroid-stimulating hormone stimulates the thyroid gland to produce and
secrete mainly T4 and smaller quantities of T3 and eventually, T4 is converted to T3
peripherally by 5'-deiodination. Levels of T3 majorly and T4, to some extent, in turn,
exert negative feedback on the production of TRH and TSH. Alteration in the
structure and function of any of these organs or pathways can result in
hypothyroidism.
 CAUSES OF HYPOTHYROIDISM
 Primary disease of thyroid
Congenital: Agenesis, Ectopic thyroid remnants
Defects of hormone synthesis: Iodine deficiency, Anti-thyroid drugs, Other drugs
(e.g. lithium, amiodarone, interferon)
Autoimmune: Atrophic thyroiditis, Hashimoto’s thyroiditis, Postpartum thyroiditis
Infective: Post-subacute thyroiditis
 Post-surgery
Post-irradiation: Radioactive iodine therapy, External neck irradiation, Infiltration,
Tumor
 Secondary (to hypothalamic–pituitary disease): Hypopituitarism, Isolated TSH
deficiency, hypothalamic diseases eg tumors, infiltrative diseases
 Peripheral resistance to thyroid hormone
 INVESTIGATIONS
 FBC
 Thyroid function test-
• TSH- ↑ in primary hypothyroidism
• slightly ↓ or Normal in secondary hypothyroidism due to lack of TSH from the
pituitary
• Free T4 =↓
• Note that T3 is not reliable in discriminating euthyroid from hypothyroid pts & may
not be necessary to measure
• Secondary hypothyroidism-↓T4, undetected TSH, T3 not indicated
 Thyroid antibodies- Antithyroid Peroxidase, Anti-Thyroglobulin, Anti-TSH Receptor
Ab (inhibitory)
 INVESTIGATIONS
 Lipid profile- Lipid profile is usually deranged
(Hypercholesterolaemia), which could reach fatal levels
 Serum cortisol level
 Aspartate transaminase, Creatine Kinase & Lactate
Dehydrogenase may be ↑ due to abnormal muscle metabolism
 Anaemia- Usually normocytic/normochromic in most cases. May
also be:
● -macrocytic= associated pernicious anaemia
● -microcytic =Iron deficiency due to menorrhagia
 Other investigations will depend on clinical situation- CXR,
ECG,ECHO
MANAGEMENT
Replacement therapy with levothyroxine (thyroxine, i.e. T4) is given for life.
The starting dose will depend upon the severity of the deficiency and on
the age and fitness of the patient, especially their cardiac performance:
100μg daily for the young and fit, 50μg (increasing to 100μg after 2–4
weeks) for the small, old or frail.
People with ischaemic heart disease require even lower initial doses,
especially if the hypothyroidism is severe and longstanding
Occasionally patients develop ‘thyrotoxic’ (hyperthyroid) symptoms despite

normal fT4 levels if the dose is increased too rapidly . 

 MONITORING
The aim is to restore T4 and TSH to well within the normal range.
Adequacy of replacement is assessed clinically and by thyroid
function tests after at least 6weeks on a steady dose.
25%
If serum TSH remains high, the 50%dose of T4 should be increased in
increments of 25–50μg, and the tests repeated at 6–8-week intervals
until TSH becomes normal, ideally in the lower third of the normal
range.
Note:Complete suppression of TSH should be avoided because of
the risk of atrial fibrillation and osteoporosis
 MXYEDEMA COMA

Severe hypothyroidism leading to:

↓mental status
Hypothermia
Bradycardia
Hypotension
Macroglossia
Pericardial effusion
and other symptoms related to slowing of function in multiple
organs
 Myxedema coma: precipitants

 Infection – fever may be absent

 Exposure to cold
 Drugs – especially sedatives/tranquilizers
 Myocardial infarction
 Cerebrovascular event
 May be a terminal event in patients with severe longstanding
hypothyroidism
 Myxedema coma: clinical features
 Altered Level of consciousness, ranging from drowsiness→coma;
occasionally- prominent psychotic features
 Focal or generalized seizures may occur
 Cardiovascular features- exertional dyspnoea, Hypotension, bradycardia,
non-pitting edema, rarely CCF, Pericardial effusion may be present
 Hypoventilation/Hypothermia
 Periorbital puffiness, macroglossia
 Skin is pale and cool, with a yellowish hue, can be rough and doughy
Peri-orbital puffiness
 Myxedema coma: Management

SUPPORTIVE
 Admit to ICU
 Passive rewarming for hypothermia
 Give warm humidified O2 by facemask
 Mechanical ventilation if ↓ventilating
 Correct hyponatraemia/hypoglycaemia
 Treat infection
 Myxedema coma: Management

SPECIFIC
 Thyroid hormone replacement
 IV L-thyroxine 200-400μg stat, then 50-100μg daily, until patient can
tolerate orally
 If no improvement is noted within 24-48h, IV Lio-T3 10-25μg 8hrly can
be given in addition
 Change to oral when patient can take orally
 IVFs should be given with caution as patient may have underlying
cardiovascular compromise
 Monitoring
Improvement is monitored by:
1. A rise in body temperature. The goal is to have a slow
rise in core temperature of 0.5⁰C per hour
2. Return to normal cerebral and respiratory function
THANK YOU