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Synonyms: Myxoedema, lack of thyroid hormone, adult hypothyroidism.
German: Hypothyreose

1 Definition

Hypothyroidism is the most common thyroid disorder. This is a condition caused due to deficient or failure of the production of thyroid hormones by the thyroid gland. The thyroid is a butterfly shaped gland that lies in front of the trachea just below the larynx. It consists of the left and right lobes connected by a narrow isthmus and follows the movements of larynx in swallowing. The thyroid gland uses iodine to produce two hormones called thyroxin (T4) and triiodothyronine (T3). These hormones regulate the metabolism of the organism. The hormone levels produced by the thyroid gland is controlled in the context of the thyrotropic feedback control by the thyroid stimulating hormone (TSH) secreted by the pituitary gland. The pituitary secretion is in turn controlled by the releasing hormone TRH that is formed in the hypothalamus.

2 Epidemiology

Primary Hypothyroidism is very prevalent worldwide. It can be endemic in regions with severe iodine-deficiency. This disease is more frequent in women over the age of 40 years. In rare cases, hypothyroidism occurs in infants and children. Untreated hypothyroidism in infants may can cause brain damage and lead to mental retardation and developmental problems. Older adults, particularly those of over 60 years of age, have a higher incidence of subclinical disease.

3 Causes

  • Hashimoto's thyroiditis is the most common cause of hypothyroidism. This is a autoimmune disease that causes the destruction of the thyroid tissue. As a result, the thyroid gland cannot produce enough thyroid hormone.
  • Severe Iodine deficiency may cause hypothyroidism.
  • Exposure to high doses of radiation for the treatment of head and neck cancers. Radioactive iodine (RAI) treatment for Grave's disease may cause hypothyroidism.
  • Dyshormonogenesis is a autosomal recessive disease caused by peroxidase deficiency.
  • Postpartum thyroiditis: inflammation of the thyroid gland following pregnancy. Usually occurs in the first six months after delivery.
  • Massive Infantile Haemangioma: Severe hypothyroidism has been described in infants with massive haemangiomas. This is due to high levels of type 3 iodothyronine deiodinase in the haemangioma tissue. The deiodinase inactivates T4, thus leading to consumptive hypothyroidism.

4 Clinical Manifestations

The majority of clinical signs and symptoms results from a reduction in metabolic activity and deposition of glycosaminoglycans.

  • General Manifestations: generalized oedema, fatigue, lethargy, cold intolerance, weight gain, pitting oedema of lower extremities. The face is expressionless, puffi, pale and with yellow tinge. The voice is coarse and low-pitched. There is hair loss and the hair is brittle and dry. The skin is also scaly and dry. The nails are thick and brittle. Due to the thickening of the subcutaneous tissue the hands and feet appear broad.
  • Neurologic and Psychiatric manifestations: Headache, vertigo, Paresthesias, Carpal Tunnel Syndrome, delayed relaxation of deep tendon reflexes (intention tremor, nystagmus), cognitive deficits, depression and dementia. The most severe neurologic manifestation of hypothyroidism is myxedema coma.
  • Gastrointestinal manifestations: loss of apetite, constipation, gaseous distention and achlorhydria. Pernicious anemia is found in patients with autoimmune thyroid disease.
  • Cardiovascular system: the pulse rate and stroke volume are reduced, cardiac output is decreased to half the normal vaue, peripheral resistance is increased, heart is enlarged due to pericardial effusion and atherosclerosis. Elderly patients with coronary artery disease and hypothyroidism may encounter with angina pectoris, acute myocardial infarction, ventricular arrhythmias and congestive heart failure.
  • Respiratory System: the patients with hypothyroidism may present with dyspnea, obstructive sleep apnea and frequent respiratory infections. The pulmonary function tests may reveal decreased maximal breathing capacity, decreased diffusion capacity and decreased ventilatory drive.
  • Musculoskeletal system: muscle stiffness, weakness, cramps, mialgias, arthralgias, joint stiffness and effusions, Carpal Tunnel syndrome and delayed linear bone growth in children.
  • Reproductive system: females present with menstrual irregularities, infertility and anovulation. Males may present with gonadal dysfunctions. Children with juvenile hypothyroidism may present with precocious puberty.
  • Endocrine manifestations: pituitary macro adenoma, increase in serum prolactin levels, decrease in growth hormone secretion, decreased turnover rate of aldosterone and decreased renin activity.
  • Renal system: decreased urinary output, laboratory findings may show increased serum creatinine, proteinuria, hyperkalemia and increased plasma homocystein concentrations.
  • Haematopoietic system: mild anemia, the bone marrow is hypo plastic and the plasma and RBC turnover is decreased. Pernicious anemia, megaloblastic anemia (due to folic acid deficiency), some patients may present with leukopenia. Patients with hypothyroidism may also present with bleeding abnormalities such as bruising, menorrhagia and prolonged bleeding after injury or tooth extraction. The erythrocyte sedimentation rate maybe elevated.

5 Diagnosis

The diagnosis of hypothyroidism is based on the combination of symptoms and laboratory findings. In severe cases the diagnosis is straight forward. But in mild cases the diagnosis is rather difficult and a thorough evaluation of the history and the laboratory results must be made. Depending on the severity of the symptoms hypothyroidism is classified into three types.

  • Mild Hypothyroidism: the diagnosis in these patients is difficult because the symptoms are non-specific. the presence of mild hypothyroidism can be identified by the presence of family or personal history of thyroid disease or autoimmune disease. The measurement of circulating TSH could determine the condition.
  • Subclinical Hypothyroidism: mainly caused due to pituitary dysfunction. This type of hypothyroidism is rare. The laboratory findings show decreased or undetectable TSH and low T4 and T3. Usually seen in patients with hypothalamic or pituitary tumors. So a careful history evaluation is required.
  • Overt Hypothyroidism: The patient presents typically with all the general symptoms. In this case the diagnosis can be made directly and specially when the patient presents with hoarse voice along with other symptoms. If this condition is left untreated for prolonged period it might lead to a more severe and life-threatening condition called myxoedema coma. Usually occurs in elderly patients and presents with confusion, severe hypothermia, shock and coma.
  • Central Hypothyroidism: In central hypothyroidism (i.e. of pituitary of hypothalamic origin) measuring TSH concentrations alone isn't sufficient for the identification of affected patients. Decision making depends on the combination of TSH and FT4 concentrations:
    • Partial thyrotropic insufficiency: Here TSH levels are normal or low-normal, but FT4 concentrations are reduced.
    • Complete thyrotropic insufficiency: In this condition, which may result from more severe pituitary damage, both TSH and FT4 concentrations are reduced.

6 Laboratory findings

  • The serum TSH level is a very sensitive marker for the diagnosis of hypothyroidism. If the TSH level is elevated and the free T4 level is decreased then it is subject to primary hypothyroidism. If the TSH level is elevated with normal free T4 levels then it is subject to sub clinical hypothyroidism. If the both the TSH level and the free T4 levels are decreased then it suggests that the hypothyroidism is due to central cause at the pituitary or hypothalamic level rather than the thyroid gland.
  • The anti thyroid antibodies such as the anti-TPO and anti-TG are increased in patients with hypothyroidism.
  • The detection of anti-TSH receptor antibodies in pregnant woman indicates the risk of fetal and neo-natal transient hypothyroidism.
  • Fasting cholesterol and triglyceride maybe increased.
  • Ultrasonography of the neck in patients with hypothyroidism may reveal nodules or infiltrative disease. Other tests include radionuclide scan with iodine-123 or technitium-99 or direct visualization of the pituitary gland with magnetic resonance imaging (MRI).
  • Inherited disorders of thyroid function can be detected by evaluating the circulating and intrathyroidal thyroglobulin level.
  • The creatinin kinase maybe increased due to abnormal muscle membranes.

7 Treatment

  • If possible, the underlying cause should be treated.
  • In overt hypothyroidism and young and otherwise healthy patients thyroid hormone replacement with levothyroxine (L-T4) should be initiated. In elderly patients with history of coronary artery disease the full replacement dose should not be immediately administered. Rather, the dose should be adjusted according to clinical state and should keep the TSH level below 5 mIU/L and the free T4 concentration within its reference range. In this subgroup the initial dose should be low and increased every four to six weeks. In every case TSH and free T4 concentrations should be monitored regularly. Most patients (e.g. those suffering from autoimmune thyroiditis and being after thyroidectomy) require life-long treatment.
  • A subgroup of affected patients with persisting symptoms despite substution therapy with L-T4 (syndrome T) may benefit from combination therapy with L-T4 and liothyronine (L-T3). In the majority of hypothyroid patients a monotherapy with L-T4 is preferred, however, since it is simpler and cheaper and mostly results in an excellent quality of life.

Despite therapy with L-T4 and normal TSH concentration under substitution, about 10% of affected patients suffer from poor quality of life[1]. The causes for this condition, which is sometimes referred to as syndrome T, is unknown. Possible etiologies include (but are probably not limited to) an inadequate substitution dose (which doesn't hit the individual set point of thyroid homeostasis), an inadequate treatment modality (i.e. substitution with L-T4 alone, where concentrations of T3 and, possibly, non-classical thyroid hormones are reduced), immune phenomena and psychological factors[1][2][3].

8 Adverse effects of treatment

Long term treatment with levothyroxine can cause left ventricular hypertrophy, atrial fibrillation and increased risk of ischemic heart disease. This treatment could also result in decreased bone density especially in postmenopausal women. All adverse effects are dose-dependent and only observed in cases of (even slight) overdosage.

9 References

  1. 1.0 1.1 Wiersinga WM. Paradigm shifts in thyroid hormone replacement therapies for hypothyroidism. Nat Rev Endocrinol. 2014 Mar;10(3):164-74. doi: 10.1038/nrendo.2013.258. PMID 24419358.
  2. Dietrich JW, Midgley JEM, Hoermann R. Editorial: "Homeostasis and Allostasis of Thyroid Function". Front Endocrinol (Lausanne). 2018 Jun 5;9:287. doi: 10.3389/fendo.2018.00287. PMID 29922229
  3. Larisch R, Midgley JEM, Dietrich JW, Hoermann R. Symptomatic Relief is Related to Serum Free Triiodothyronine Concentrations during Follow-up in Levothyroxine-Treated Patients with Differentiated Thyroid Cancer. Exp Clin Endocrinol Diabetes. 2018 Sep;126(9):546-552. doi: 10.1055/s-0043-125064. PMID 29396968

10 Further reading

This page was last edited on 12 July 2019, at 17:21.

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