THYROTOXICOSIS

PRESENTER: EMIACU KENNETH

FACILITATOR: DR. FREDDIE KIBENGO
OUTLINE
• Anatomy and physiology
• Thyrotoxicosis
• Definition
• Epidemiology
• Etiology
• Pathogenesis
• Clinical features
• Investigations
• Treatment
• Thyroid storm
ANATOMY AND PHYSIOLOGY
• Thyroid gland is located immediately below the larynx on each side
and anterior to the trachea
• Weighs 15-20g in adults
• Secretes 2 major hormones; thyroxine(T4) and triiodothyronine(T3)
• 93% is T4 and 7% is T3
• Both these hormones increase body metabolic rate
• The gland also secretes calcitonin (involved in calcium metabolism)
ANATOMY AND PHYSIOLOGY
• 99% of T4 and T3 circulate bound to thyroxine-binding globulin(TBG)
• Only the free hormone is available for tissue action
• Thyroid secretion is primarily controlled by thyroid stimulating
hormone from the anterior pituitary gland
• Circulating T4 and T3 feed back on the pituitary gland to suppress TSH
production
ANATOMY AND PHYSIOLOGY
• Thyroid gland is of closed follicles (100-300 µm in diameter)
• Follicles are filled with secretory substance (colloid) and lined with
cuboidal epithelial cells that secrete into the interior of the follicles
• Thyroglobulin is the major constituent of colloid
• Once secretion has entered follicles, it must be absorbed into blood
through follicular epithelium
• Gland also contains C cells that secrete calcitonin
ANATOMY AND PHYSIOLOGY
IODINE METABOLISM
• Daily requirement is 0.1mg
• Sources: iodized salt (1 part of NaI to every 100,000 parts of NaCl),
fish, milk, and eggs
• In stomach and jejunum, iodine is converted to iodide and absorbed
into the bloodstream
• Iodide is actively transported into the thyroid follicular cells by an ATP
dependent process
• Thyroid is the storage site for >90% of the body’s iodine content
THYROID HORMONE SYNTHESIS
• Iodide trapping, involves active ATP dependent transport of iodide
across the thyrocyte basement membrane via the sodium-iodide
symporter
• Oxidation of iodide to iodine and iodination of tyrosine residues on
thyroglobulin (TG) to form monoiodotyrosines (MIT) and
diiodotyrosine (DIT)
• Coupling of 2 DIT molecules forms tetraiodotyrosine or thyroxine, and
1 DIT molecule with 1 MIT molecule to form 3,5,3’-triiodothyronine
THYROID HORMONE SYNTHESIS
• TG is hydrolyzed to release free iodothyronines (T3 and T4) and
mono- and diiodotyrosines following stimulation by TSH and engulfing
within the thyroid follicle
• The latter are de-iodinated in the 5th step to yield iodide, which is
reused in the thyrocyte.
THYROID HORMONE SYNTHESIS
THYROTOXICOSIS
• Refers to the clinical syndrome of hypermetabolism and hyperactivity
resulting from excessive quantities of the thyroid hormones
• Hyperthyroidism is used to denote sustained increased in thyroid
hormone biosynthesis and secretion by the thyroid gland
• While many patients with thyrotoxicosis have hyperthyroidism, it is
not so in others
EPIDEMIOLOGY
• The prevalence of overt hyperthyroidism ranges from 0.2% to 1.3% in
iodine sufficient parts of the world
• Incidence of hyperthyroidism was estimated at between 100 and 200
cases per 100,000 per year
• Prevalence of 2.7% in women and 0.23% in men taking into account
both established and possible causes (Whickam study)
• Affects 2-5% of all women at sometime, mainly between the ages of
20 and 40 years
• Grave’s disease accounts for 60-80% of thyrotoxicosis.
ETIOLOGY OF THYROTOXICOSIS
Primary hyperthyroidism Secondary hyperthyroidism
• Grave’s disease • TSH-secreting pituitary adenoma
• Toxic multinodular goiter • Excess human chorionic gonadotrophin (hCG):
• Toxic adenoma hyperemesis gravidarum, hCG-secreting
• Ectopic thyroid tissue: Functioning thyroid tumors. hCG has TSH activity
carcinoma metastases, Struma ovarii
• Drugs: iodine excess (Jod-basedow
phenomenon)
• Congenital: TSH-receptor mutation

Thyrotoxicosis without hyperthyroidism

• Silent and postpartum thyroiditis
• Subacute thyroiditis (de Quervain’s thyroiditis)
• Excess of thyroid hormone (thyrotoxicosis factitia)
• Other cause of thyroid destruction: amiodarone, radiation, infarction of adenoma
ETIOLOGY OF THYROTOXICOSIS
• 3 intrinsic thyroid disorders account for the majority of cases of
thyrotoxicosis:
Grave’s disease, toxic adenoma and toxic multinodular goiter
• Rarer causes include:
 viral thyroiditis (de Quervain’s), thyroiditis factitia,
drugs(amiodarone), metastatic differentiated thyroid carcinoma,
and TSH-secreting pituitary tumors
PATHOGENESIS OF THYROTOXICOSIS
• Grave’s disease:
 Commonest cause of thyrotoxicosis
 Female: male is 9:1
 Typical age: 40-60 years
 Results from IgG antibodies binding to TSH receptor and
stimulating thyroid hormone production but without negative
feedback
 IgG antibodies also bind to retro-orbital tissues producing T-cell
inflammatory response, cytokine release, fibroblast activation,
glycosaminoglycan accumulation hence infiltratory
ophthalmopathy
PATHOGENESIS OF THYROTOXICOSIS
• Toxic multinodular goiter: seen in elderly and iodine deficient areas.
There are nodules that secrete thyroid hormone. Patients are euthyroid
for many years before development of nodular autonomy
• Toxic adenoma: solitary nodule producing T3 and T4, and the rest of
the gland is suppressed
• Ectopic thyroid tissue: metastatic follicular thyroid cancer or Struma
ovarii (presence of significant amount of thyroid tissue > 50% in ovarian
tumors, typically monodermal teratomas.
• De Quervain’s thyroiditis: transient hyperthyroidism from acute
inflammation of the gland, usually from viral infection. Fever, malaise
and neck pain
PATHOGENESIS OF THYROTOXICOSIS
• Silent and postpartum thyroiditis: occurs in people with underlying
thyroid autoimmune disease. ‘Silent’ because it is ‘painless’
thyroiditis. Postpartum; 3-6 months after pregnancy. Usually
thyroperoxidase antibodies antepartum. 2-4 weeks of thyrotoxicosis
followed by 4-12 weeks of hypothyroidism.
• Exogenous: Jod-basedow syndrome (iodine excess); hyperthyroidism
following administration of iodine or iodide either as dietary
supplements or iodinated contrast for medical imaging.
• Drugs: amiodarone
CLINICAL FEATURES OF THYROTOXICOSIS
Symptoms Signs
• Hyperactivity, irritability, dysphoria • Tachycardia; atrial fibrillation in elderly
• Heat intolerance and sweating • Tremor
• Palpitations • Goiter
• Nervousness, fatigue, and weakness • Warm, moist skin
• Dyspnea • Muscle weakness, myopathy
• Weight loss with increased appetite • Hyperreflexia
• Diarrhea • Lid retraction or lag
• Polyuria • Gynecomastia
• Oligomenorrhea • Loss of libido
CLINICAL FEATURES OF THYROTOXICOSIS
CLINICAL FEATURES
OPHTHALMIC GRAVE’S DISEASE
• Lid retraction and lid lag; as a result of increased catecholamine
sensitivity of the levator palpebrae superioris and occurs in any form of
hyperthyroidism.
• Exophthalmos (proptosis/protruding eyeballs) and ophthalmoplegia
(limitation of eye movement); only occur in patients with Grave’s disease.
• Rx:
 correct thyroid dysfunction
 Mild ophthalmopathy; watchful waiting
 High dose IV glucocorticoids in severe cases
 Surgery; orbital decompression
GRADING OF EYE SIGNS OF GRAVE’S DISEASE
INVESTIGATIONS (LABORATORY)
• Thyroid function tests (TFTs)
 Serum TSH is suppressed (<0.05 µU/L)
 Serum free T4 and T3 are elevated, occasionally, T3 alone is
elevated (T3 toxicosis)
• Serum microsomal and thyroglobulin antibodies are present in cases
of Grave’s disease. TSH receptor antibodies are not measured
routinely
• FBC: mild normocytic anemia, mild neutropenia (Grave’s)
• Elevated ESR, Calcium levels, and LFTs
INVESTIGATIONS (IMAGING)
• Thyroid ultrasound: to assess for presence of nodules
• Isotope scan: to detect nodular disease (‘hot’ nodule), or subacute
thyroiditis
TREATMENT OF THYROTOXICOSIS
1) DRUGS
• Thionamides: inhibit thyroid peroxidase (carbimazole, methimazole,
propylthiouracil). 2 strategies of administration:
 Titration: E.g. carbimazole 20-40mg/24h PO for 4 weeks, reduce
according to TFTs every 1-2 months.
 Block-replace: Carbimazole + thyroxine simultaneously (less risk of
iatrogenic hypothyroidism).
 In Grave’s, maintain on either regimen for 12-18 months then withdraw.
 SE: Agranulocytosis (related to the dose of methimazole), methimazole
induced hepatotoxicity
TREATMENT OF THYROTOXICOSIS
• Beta-blockers: control cardiovascular and hyperadrenergic
manifestations of thyrotoxicosis. Propranolol is commonly used for
this purpose.
• Lithium: inhibits coupling of iodotyrosine residues. Dose; 300mg 8
hourly. Used when thionamides are contraindicated. Can cause
lithium toxicity.
• Potassium Perchlorate: inhibits iodine uptake by directly inhibiting
the sodium-iodide symporter. Dose; 500mg bd. Can normalize thyroid
function in about 4 weeks. SE; aplastic anemia and nephritic
syndrome.
TREATMENT OF THYROTOXICOSIS
• Iodine:
 At high concentrations, it blocks the release of pre-stored
hormone, decreases iodide transport, and prevent oxidation in the
follicular cells.
 This inhibition of thyroid metabolism by iodine is called the Wolf-
Chaikoff effect and is only transient.
 Available preparations; Lugol’s iodine (160mg/ml) 5 drops daily,
SSKI (saturated solution of Potassium iodide) (760mg/ml) 1 drop
daily, or collosol iodine.
TREATMENT OF THYROTOXICOSIS
1. Radioiodine (¹³¹I): most become hypothyroid post-treatment. CI;
pregnancy, lactation, caution in active hyperthyroidism as risk of
thyroid storm.
2. Thyroidectomy: carries risk of damage to recurrent laryngeal nerve
(voice hoarseness) and hypoparathyroidism. Patients may become
hypothyroid.
COMPLICATIONS
• Heart failure (dilated cardiomyopathy)
• Angina
• Atrial fibrillation
• Osteoporosis
• Ophthalmopathy
• Gynecomastia
• Thyroid storm
THYROID STORM OR CRISIS
• Endocrinological emergency
• Rare life threatening condition in which there is rapid deterioration of
thyrotoxicosis with hyperpyrexia, tachycardia, extreme restlessness,
and eventually delirium, coma and death.
• Precipitants: infection, trauma, MI, recent thyroid surgery or radio-
iodide therapy
• With careful management, it should no longer occur
THYROID STORM OR CRISIS
• Goals of treatment:
 Decrease thyroid synthesis
 Prevent release of already formed thyroid hormone
 Decrease its end organ effects
 Managing underlying precipitating condition or stressor
• 5 B’s: Block synthesis, block release, block conversion of T4 to T3,
Beta-blockers, and block enterohepatic circulation.
THYROID STORM OR CRISIS
• Treatment:
 ABCDE’s; prompt assessment, resuscitation, and stabilization
 large doses of carbimazole (20mg 8-hourly orally)
 propranolol (80 mg 12-hourly orally)
 potassium iodide (15mg 6 hourly orally)
 hydrocortisone (100mg IV 6-hourly to inhibit peripheral conversion
of T4 to T3)
 block enterohepatic circulation (cholestyramine)
REFERENCES
• Kumar and Clark, Essentials of clinical medicine, 6th Edition
• Harrison's Principles of Internal Medicine, 19th edition
• Davidson’s Principles and practice of medicine, 22nd Edition
• Oxford handbook of clinical medicine, 9th Edition
THANK YOU