The thyroid gland

Thyroid Crises (Thyroid storm)

Thyroid storm is an acute form of hyperthyroidism that results from
either unrecognized untreated or inadequately treated severe hyperthyroidism. It is a rare medical emergency, which has a mortality of 10% despite early recognition and treatment.
Precipitated by infection, trauma, surgery, or any other stressful condition.

Present with florid symptoms of hyperthyroidism with one or more of the following: fever, agitation confusion, psychosis, coma, tachycardia or atrial fibrillation, cardiovascular collapse
and shock.

Treatment of Thyroid Storm

Patients should be rehydrated

Give propranolol, either orally (80 mg 4 times daily) or intravenously (1–5 mg 4 times daily). It helps in controlling adrenergic symptoms and also reduces the peripheral conversion of T4 to T3 (propranolol only in high doses)

Sodium ipodate (500 mg per day orally) will restore serum T3 levels to normal in 48–72 hours (inhibits the release of thyroid hormones, and reduces the peripheral conversion of T4 to T3.
Dexamethasone (2 mg 4 times daily) also reduces the peripheral conversion of T4 to T3.
Oral carbimazole 40–60 mg daily should be given to inhibit the synthesis of new thyroid hormone.


If the patient is unconscious or uncooperative, carbimazole can be administered rectally with good effect.

Atrial fibrillation in thyrotoxicosis

Occurs in about 10% of patients with thyrotoxicosis. The incidence increases with age, so that almost half of all males with thyrotoxicosis over the age
of 60 are affected.

Characteristically and specifically, the ventricular rate is little influenced by digoxin, but responds to the addition of a β-blocker.
Thromboembolic complications are common in thyrotoxic atrial fibrillation so anticoagulation with warfarin is required, unless contraindicated.

Subclinical thyrotoxicosis

Serum TSH is undetectable or very low, and serum T3 and T4 are at the upper end of the normal range.
This is most often found in older patients with multinodular goitre.

These patients are at increased risk of atrial fibrillation and osteoporosis, and hence the consensus view is that they have mild thyrotoxicosis and require therapy, usually with 131I.
Otherwise, annual review is essential, as the conversion rate to overt thyrotoxicosis is about 5% each year.

Hypothyroidism

Hypothyroidism is a state of thyroid hormone deficiency.
Occurs at any age but is particularly common among the elderly,
10% of women and 6% of men > 65 are affected.
In all age group women are 6 times more frequently affected than men.


Causes
The most common cause of Primary hypothyroidism is
Autoimmune disease that usually results from Hashimoto's thyroiditis.
The 2nd most common cause is post-therapeutic hypothyroidism, following 131I , surgical treatment of thyrotoxicosis and goiter or overtreatment with antithyroid drugs. Both accounts for over 90% of causes, others are

Secondary hypothyroidism occurs when the hypothalamus produces insufficient thyrotropin-releasing hormone (TRH) or the pituitary produces insufficient TSH.

Clinical features of hypothyroidism

Symptoms and signs of primary hypothyroidism are often subtle and insidious.

It may manifest atypically in the elderly as confusion, anorexia, weight loss, incontinence, and decreased mobility.

The clinical presentation depends on the duration and severity of the disease.

A prolonged duration of Hypothyroidism, leads to the infiltration of many body tissues by

Mucopolysaccharides,

Hyaluronic acid
And chondroitin sulphate,
Resulting in a low-pitched voice and slurred speech due to a large tongue, poor hearing, and compression of the median nerve at the wrist (carpal tunnel synd with paresthesias of the hands).

Infiltration of the dermis gives rise to non pitting oedema (myxedema), which is most marked in the skin of the hands, feet, face and eyelids.










Resulting in periorbital and facial puffiness with dull facial expression combined with facial pallor due to vasoconstriction
anemia,
or a lemon-yellow tint of the skin caused by carotenaemia.

Other symptoms are

Clinical signs are

Investigations

In Primary hypothyroidism, the serum T4 is low and TSH is elevated, usually in excess of 20 mU/L.
Measurements of serum T3 are unhelpful since they do not discriminate reliably between euthyroidism and hypothyroidism.
Measurement of thyroid peroxidase antibodies although +ve in many different etiologies is some times helpful.


Other non-specific abnormalities are
Raised serum enzymes: creatine kinase, aspartate aminotransferase, lactate dehydrogenase (LDH)
Hypercholesterolemia
Anemia: normochromic normocytic or macrocytic
Hyponatremia
ECG classically demonstrates sinus bradycardia with low-voltage complexes and ST segment and T-wave changes.

Treatment

Is with levothyroxine(T) replacement.

In patients with known ischemic heart disease and elderly, thyroid hormone replacement should be introduced at
low dose 25 μg per day, and increased very slowly, to finally reach maintenance dose of 100–150 μg per day.

In younger patients, it is safe to initiate levothyroxine at a higher dose 100 μg per day.

Aim to maintain serum TSH within the reference range, to achieve this, serum T4 should be in the upper part of the normal range.

Levothyroxine has a half-life of

7 days so it should always be taken as a single daily dose, absorption is maximal when the dose is taken before bed and may be further optimized by taking vitamin C supplement.


At least 6 weeks should pass before repeating thyroid function tests and adjusting the dose, usually by 25 μg/day.

Measure thyroid function every 1–2 years once the dose of T4 is stabilized.

Patients feel better within 2–3 weeks. Reduction in weight and periorbital puffiness occurs quickly, but the restoration of skin and hair texture and resolution of any effusions may take 3–6 months.

Situations in which an adjustment of

the dose of T4 is necessary are
1- Pregnancy
• Increases concentration of serum thyroxine-binding globulin, require an increase in the dose of levothyroxine of approximately 25–50 μg daily, Inadequate maternal T4 therapy may be associated with impaired cognitive development in an unborn child.

2- Malabsorption

3- Drugs
• Drugs that Increase T4 clearance: Phenobarbital, phenytoin, carbamazepine, rifampicin, sertraline, chloroquine.
• Drugs Interfere with intestinal T4 absorption: colestyramine,
sucralfate, aluminium hydroxide, ferrous sulphate, dietary fibre supplements, calcium carbonate

SUBCLINICAL HYPOTHYROIDISM

Is elevated serum TSH in patients with absent or minimal symptoms of
hypothyroidism and normal serum levels of free T4.
It is relatively common; occurs in more than 15% of elderly women and 10% of elderly men.
In patients with serum TSH > 10 mU/L, there is a high likelihood of progression to overt hypothyroidism


These patients are also more likely
to have hypercholesterolemia and atherosclerosis. They should be treated with T4, even if they are asymptomatic. For patients with TSH levels between 4.5 and 10 mU/L, use of T4 is reasonable if symptoms of early hypothyroidism (eg, fatigue, depression) are present,
therapy is also indicated in pregnant and women who plan to become pregnant to avoid effects of hypothyroidism on the

pregnancy and fetal development. Patients should have annual measurement of serum TSH and free T4 to assess progress of the condition if untreated or to adjust the T4 dosage.

Non-thyroidal illness (‘sick euthyroidism’)

This presents with a low serum TSH, raised T4 and normal or low T3, in a patient with systemic illness who doesn't have clinical evidence of thyroid disease.

These abnormalities are due to

Decreased peripheral conversion of T4 to T3,
Altered levels of binding proteins
and their affinity for thyroid hormones,
Reduced secretion of TSH.

Myxedema coma

The condition usually occurs in patients with long-standing, undiagnosed hypothyroidism and is usually precipitated by infection, cerebrovascular disease, heart failure, trauma, or drug therapy.
It has a 50% mortality rate and needs urgent treatment.

Pathophysiology

long-standing hypothyroidism is associated with reduced metabolic rate and decreased oxygen consumption, which affects all body systems resulting in
Hypothermia,



Cardiac contractility is impaired, leading to reduced stroke volume, low cardiac output, bradycardia and hypotension and pericardial effusions.

Respiratory depression (Central),

Hypoventilation with CO2 retention.

Brain function is affected by

Reduction in oxygen delivery
Decreased glucose utilization
Reduced cerebral blood flow.


Rapid diagnosis based on clinical judgment, history, and physical examination is imperative, because
death is likely without rapid treatment.
So treatment must begin before biochemical confirmation of the
diagnosis.

Treatment

Maintenance of adequate airway is crucial, since most patients have depressed mental status with respiratory failure. Mechanical ventilation is usually required during the first 36-48 hours,
Intravenous injection of 20 μg triiodothyronine, (T3)/ 3 times daily until
there is sustained clinical improvement.



Or an intravenous loading dose of 300-600 micrograms of levothyroxine (T4) followed by a daily intravenous dose of 50-100 micrograms.

Corticosteroids are also given, because the possibility of central hypothyroidism usually cannot be initially ruled out.


Treat hypothermia with passive rewarming using ordinary blankets and a warm room. Active rewarming using external devices carries a risk of vasodilatation and worsening hypotension and should be avoided.

The precipitating factor should be rapidly treated.