Thyroid Disorders

• Controls BMR calorigenesis
• Growth Rate
• Cell Differentiation
• CNS development
• Potentiates adrenergic sympathetic system

• T4 and T3 are secreted at ratio 20:1
• Both are transported in the blood bound to proteins
• Only the free fractions are active

BINDING PROTEINS

• Thyroxine Binding Globulin
  • High affinity
  • Low capacity
  • Binds 80% of T3 and T4
• Albumin
  • Low affinity
  • High concentration (capacity)
  • Binds 10% of T4 and 30% of T3
• Thyroxine-Binding Prealbumin (Transthyretin)
  • Binds 10% of T4
  • Little T3

• Family History
• Presence of other autoimmune conditions
• Smoking
• Infection e.g., Yersinia enterocolitica
• Stress
• Pregnancy

• The disorder results from production of autoantibody TSI
• TSI stimulates TSH receptors
• TSH receptor is expressed in the Follicular cells
• TSI acts as long-acting thyroid stimulants (LATS)
• Activates cells in longer and slower way than TSH
• Chronic stimulation leads to excessive T3 and T4 secretion

• Hyperactivity, Irritability
• Tremulousness
• Heat intolerance, sweating
• Unexplained weight loss
• Despite increased appetite

CVS

• Palpitations
• High output state
  • Wide pulse pressure
  • Bounding pulse
  • Aortic systolic murmur
• Arrhythmias
  • SVT
  • Atrial Fibrillation

SKIN

• Warm, moist skin
• Excessive sweating, heat intolerance
• Palmar erythema
• Onycholysis
• Diffuse hyperpigmentation
• Hair texture is fine, diffuse alopecia
• Pretibial myxedema
  • Indurated plaques (orange skin appearance)

GIT

• Reduced transit time
• Increased stool frequency
• Increased appetite

GUS

• Oligomenorrhea
• Amenorrhea
• Erectile dysfunction

EYES

• Lid retraction, causing starring appearance
• Lid lag
• Periorbital edema
• Chemosis
• Proptosis, exophthalmia
• Extent can be gauged using “NO SPECS” scheme

NO SPECS

1. No signs, no symptoms
2. Only signs, no symptoms
3. Soft tissue
4. Proptosis
5. Extra-ocular muscles
6. Corneal involvement
7. Sight loss

NECK

• The thyroid gland generally is diffusely enlarged and smooth
• A well-delineated pyramidal lobe may be appreciated upon careful palpation
• Thyroid bruits may be appreciated
• Rarely, thrills may be appreciated
• Thyroid nodules may be palpable

PSYCHIATRIC

• Restlessness
• Anxiety
• Irritability
• Insomnia
• Depression

• TSH is suppressed
• T3, T4 elevated
• If only T3, (T3 Toxicosis)
• Thyroid antibodies
  • TPO
  • TSI confirms it

Ultrasensitive (third-generation) TSH assays remain the best screening test for thyroid disorders. With the exception of TSH-induced hyperthyroidism, subnormal or suppressed TSH levels are seen in most patients with thyrotoxicosis.

Liver function test results should be obtained to monitor for liver toxicity caused by thioamides (antithyroid medications).

A complete blood count (CBC) with differential should be obtained at baseline and with the development of fever or symptoms of infection. Graves disease may be associated with normocytic anemia, low-normal to slightly depressed total white blood cell (WBC) count with relative lymphocytosis and monocytosis, and low-normal to slightly depressed platelet count. Thioamides may rarely cause severe hematologic side effects, but routine screening for these rare events is not cost-effective.

Radioactive iodine scanning and measurements of iodine uptake are useful in differentiating the causes of hyperthyroidism. In Graves disease, the radioactive iodine uptake is increased, and the uptake is diffusely distributed over the entire gland.

• Anxiety state
• Panic attacks
• Mania
• Phaeochromocytoma
• Malignancy

• Anti-thyroid Drugs
  • Thionamides
    • Propylthiouracil
    • Carbimazole
    • Methimazole
  • They inhibit TPO
  • PTU preferable in pregnancy less teratogenic
• Beta Blockers
• Anticoagulants, if there is AF
• Radioactive Iodine therapy
• Surgery

RADIOIODINE THERAPY

• Stop anti-thyroid drugs 1 week before
  • For optimal uptake
• Pregnancy and breastfeeding absolutely contraindicated
• But patients can conceive 6 months after
• Risk of cancer negligible
• Can be used safely in children

• Hyperthermia
• Delirium
• Seizures
• Coma
• Arrhythmias

• ICU support
• Identify and treat precipitating cause
• Large doses of PTU
• Lugol’s Iodine 1 hr after 1st dose of PTU
• IV Propranolol
• Dexamethasone
• Antibiotics
• Cooling blankets
• Oxygen
• IV Fluids for rehydration

• Fourth to fifth decade
• Female to Male ratio 4:1
• Cigarette smoking (modifiable risk factor)
• Treatment with radioactive iodine

• Graves’ disease (90%)
• Euthyroidism (6%)
• Hyperthyroidism – other causes (Toxic nodular goiter, Hashimoto’s thyroiditis (3%), Factitious hyperthyroidism, Thyroid malignancy)
• Hypothyroidism (1%)

Symptoms: Ocular

• Dry eyes
• Ocular redness and irritation
• Reduced vision
• Bulged eye
• Diplopia
• Eyelid edema
• Pain and pressure around the eye
• Field loss
• Dyschromatopsia

Clinical Features (Lid Signs)

1. Upper lid retraction (Dalrymple’s Sign)
   • Seen in 90% of cases
   • Gives frightened and staring looks
2. Lid lag (Von Graefe’s sign)
   • Seen in 50% of cases
   • Upper lid lags behind during down gaze
3. Fullness of lid (Enroth’s Sign)
   • Puffy odematous swelling
4. Difficulty in Lid Eversion (Gifford’s Sign)
   • Due to odematous lid swelling
5. Infrequent / Incomplete blinking (Stellwag’s Sign)
6. Presence of Glabellar furrows
7. Rosenbach's Sign: Fine tremors of the eyelids when closed.
8. Boston’s Sign: Jerky irregular movement of upper lid on downward gaze.
9. Kocher’s Sign: Increased lid retraction with visual fixation
10. Abadie Sign: Spasm of the levator palpebrae superioris muscle with retraction of the upper lid.
11. Riesman's Sign: Bruit heard over the closed eye with a stethoscope.

Clinical Features (Conjunctiva)

Chemosis and Deep Injection of Conjunctiva (Goldzeiher’s Sign)

Clinical Features (Pupil)

• Inequality of dilation of pupil
• Cowen’s Sign: Jerky pupillary constriction to light.
• Lowy’s Sign: Mydriasis with instillation of lower concentration of adrenaline.
• Knies’s sign: Unequal dilatation of pupil in dim light.

Clinical Features (EOM)

• Möbius Sign: Inability to converge.
• Ballet Sign: Restriction of one or more extraocular muscles. (40%)
• Jendrassik's Sign: Limitation of abduction and rotation of eyeballs.
• Suker’s Sign: Poor fixation on abduction.

• Antithyroids
• Stop smoking
• Artificial tears (e.g., 1% Methylcellulose Ointment)
• Dark glasses with side frames
• Sleep in upright posture to reduce periorbital edema

TREATMENT CONTINUED

• Tape eyelids shut
• Steroids
• Orbital decompression

• Iodine deficiency
• Autoimmune hypothyroidism (Hashimoto)
• Iatrogenic
  • Surgery
  • RAI
  • Drugs
• Congenital Hypothyroidism
• Dyshormonogenesis
• Infiltrative disorders
  • Amyloidosis
  • Sarcoidosis
  • Scleroderma
  • Reidel’s thyroiditis
• Secondary Hypothyroidism
  • Tumour, surgery, Sheehan’s
  • Hypothalamic disorders

Hashimoto’s Thyroiditis

• Chronic lymphocytic thyroiditis
• Probably the most common cause of hypothyroidism
• With (younger patients) or without goiter (older patients – atrophy gland after destruction by immunologic process)
• High titer of autoantibodies to thyroidal antigens (Thyroglobulin Ab, Thyroperoxidase Ab = TPO Ab = Antimicrosomal Ab = AMA)

SYMPTOMS

• Cold Intolerance
• Tiredness
• Poor memory, concentration
• Constipation
• Weight gain, despite poor appetite
• Hoarse voice
• Menorrhagia

SIGNS

• Dry skin
• Cool extremities
• Puffy face, hands and feet (Myxedema)
• Alopecia
• Bradycardia
• Delayed tendon reflex
• Carpal Tunnel Syndrome

Clinical Manifestations of Hypothyroidism

• Symptoms and signs vary in relation to the magnitude of the thyroid hormone deficiency, and the acuteness with which the deficiency develops.
• Less prominent clinically and better tolerated when gradual loss of thyroid function (as in most cases of primary hypothyroidism)
• Symptoms develop acutely after thyroidectomy or abrupt withdrawal of exogenous thyroid hormone

Skin

• Cool and pale skin - reduced blood flow
• Dry roughness of skin - the epidermis has an atrophied cellular layer and hyperkeratosis
• Decreased sweating - reduced calorigenesis and acinar gland secretion
• Generalized nonpitting edema (myxedema) in severe hypothyroidism - infiltration of the skin with glycosaminoglycans and associated water retention

Eyes

• Periorbital edema - as a manifestation of generalized nonpitting edema or Graves' ophthalmopathy.
• Graves' ophthalmopathy may persist or worsen when hypothyroidism develops after treatment of Graves' hyperthyroidism. Patients will have variable degrees of stare, protrusion of the eyes, and extraocular muscle weakness.

Cardiovascular System

• Bradycardia - reductions in heart rate
• Impaired muscular contractility
• Reduced cardiac output - decreased exercise capacity and shortness of breath during exercise
• ECG: low voltage of QRS complexes and P and T waves
• CXR: cardiomegaly - interstitial edema, myofibrillary swelling, LV dilatation, pericardial effusion
• Myxedema induces coronary artery disease ??
• CAD more common in patients with hypothyroidism
• Symptoms and signs of congestive heart failure are usually absent in patients who have no other cardiac disease
• Congestive heart failure or angina may worsen when hypothyroidism develops in patients with heart disease
• Hypertension - peripheral vascular resistance increased
• In normotensive patients, BP increases are small (<150/100 mmHg).
• The BP of patients with established hypertension may increase further with the development of hypothyroidism.

Respiratory System

• Fatigue, shortness of breath on exertion, and decreased exercise capacity - impaired respiratory function + cardiovascular disease
• Hypoventilation (shallow and slow respirations) - respiratory muscle weakness + reduced pulmonary responses to hypoxia and hypercapnia
• Obstructive sleep apnea - macroglossia

Gastrointestinal Disorders

• Constipation, even ileus - gut motility reduced
• Decreased taste sensation
• Gastric atrophy - presence of antiparietal cell antibodies. Pernicious anemia occurs in 10% of patients with hypothyroidism caused by chronic autoimmune thyroiditis.
• Weight gain - decreased metabolic rate + accumulation of fluid (nonpitting edema) that is rich in glycosaminoglycans
• Ascites, rare

Renal Function

• Decreased glomerular filtration rate (GFR - reduced)
• Impaired ability to excrete a water load
• The clearance of drugs (e.g., antiepileptic, anticoagulant, hypnotic, and opioid drugs) is decreased.
• Drug toxicity may occur if drug dosage is not reduced.
• During T4 replacement, drugs that are administered at effective doses in patients who are hypothyroid may become less effective.

Anemia

• Impaired hemoglobin synthesis - due to thyroxine deficiency
• Iron deficiency - increased iron loss with menorrhagia + impaired intestinal absorption of iron
• Folate deficiency - impaired intestinal absorption of folic acid
• Pernicious anemia - vitamin B12-deficient megaloblastic anemia

Reproductive Abnormalities

• Women with hypothyroidism may have either oligo- or amenorrhea or hypermenorrhea-menorrhagia.
• Decreased fertility
• Increased likelihood for early abortion
• Hyperprolactinemia may occur, and is occasionally sufficiently severe to cause amenorrhea or galactorrhea
• The serum sex hormone-binding globulin concentration may be low in hypothyroidism. This will lower serum total but not free sex hormone concentrations.

Neurological Dysfunction

• General depression of central nervous system function
• Sleepiness, inability to concentrate
• Sluggish thought processes
• Respond slowly to questions
• Less able to retrieve information from memory
• Agitated psychosis, rare (“myxedema madness”)
• PET: 23% reduction in cerebral blood flow and a 12% reduction in cerebral glucose metabolism

Neuromuscular Abnormalities

• A delay in the relaxation phase of deep tendon reflexes
• Carpal tunnel syndrome
• Paresthesia
• Asymptomatic elevation in serum CPK level to muscle hypertrophy (which may be accompanied by muscle cramps) to proximal muscle weakness to, in rare cases, rhabdomyolysis.

Metabolic Abnormalities

• Hyponatremia may result from a reduction in free water clearance
• Reversible increases in serum creatinine occur in 20 ~ 90% of hypothyroid patients
• Lipid clearance may be decreased, resulting in an elevation in the serum concentrations of free fatty acids and total and low-density lipoprotein cholesterol
• Plasma homocysteine concentrations are increased in some hypothyroid patients

TFT

• Elevated TSH
• T4 is low
• TPO elevated

• Replacement of Triiodothyroxine (T3): unsatisfactory due to rapid absorption, short half-life, and transient effect
• Levothyroxine (T4):
  • Converted to T3 intracellularly
  • Once daily, half-life: 7 days
  • Well-absorbed
  • Easily monitored by following serum TSH and T4 levels

• Sepsis
• Pneumonia
• Myocardial Infarction
• CCF (Congestive Cardiac Failure)
• CVA (Cerebrovascular Accident)
• Exposure to cold
• Hypoglycemia
• Electrolyte Imbalance

• Hypothermia
• Impaired sensorium
• Seizures

• Levothyroxine (Bolus)
• Supportive therapy
  • External warming
  • Space blanket
  • Steroids
  • Antibiotics
  • Ventilatory support
  • Hypertonic saline
  • IV Glucose