Thyroid gland secret thyroxine (T4) and triiodothyronine (T3) hormone which bind with alpha and beta receptors to act on the tissue. hypothyroid basically decrease thyroid hormone specifically T3 and T4. hypothyroid treatment should be initiated early in children, pregnant women, elder persons.person with hypothyroid play a pivotal role in metabolism, growth, chemical signal transmission in nerve conduction. hypothyroid women without treatment may go several adverse out-comes like miscarriage, interrupt fetal growth, mental retardation. so it is important to start hypothyroid treatment early.
Anatomy of thyroid gland
The thyroid is a Greek word that means shield form and consists of two lobs, located anterior to the trachea between the cricoid cartilage and the parasternal notch. The thyroid hormone starts at 11 weeks of gestation. Neural crest cells develop thyroid medullary C cell which secret calcitonin to reduce calcium levels, in addition, it is important for medullary cell carcinoma. Thyroid hormone development depends on the activation of transcription factors that activate various genes that act as the maturation of the thyroid gland.
Mutation in these genes leads to congenital hypothyroidism although Maternal thyroid may prevent developing hypothyroid during gestation. The thyroid gland consists of a follicular cell and it has basal and apical side basa side has TSH receptors that regulate thyroid hormone. When it stimulates follicular cell secret thyroglobulin which is metabolized further at the apical region and form thyroid hormone.
Regulation of thyroid axis
Hypothalamus secret thyrotropin-releasing hormone (TRH) which stimulate the Pituitary to secret thyrotropin stimulating hormone (TSH). Thyroid hormone act by negative feedback on the hypothalamus and pituitary to regulate hormone secretion.
Iodine metabolism and transport
The Iodine is an important role in hormone formation. it is bound with albumin and rest excreted in the urine. Iodine uptake through sodium iodide symporter (NIS) which is up or down-regulate when iodine levels are low or high respectively. Iodine deficiency is prevalent in central Africa, South America, and northern Asia. Selenium deficiency may contribute to further neurological manifestation. Iodine deficiency is the most common preventable mental disease. The RDA is 220 µg iodine per day.
Organification, coupling, storage, release: hypothyroid
Iodine enters into thyroid follicular cells and reaches to the apical membrane where it is oxidized by TPO hydrogen peroxide. This reaction adds iodine molecules to thyroglobulin and converted to T3 and T4.
The thyroid-stimulating hormone act by TSH-R activates adenylyl cyclase leading to an increase in the production of cyclic AMP. Mutation in receptors leads to grave’s disease and congenital hyperthyroidism. other factors that stimulate TSH are insulin-like growth factors, epidermal growth factor, transforming growth factor-beta. Iodine deficiency increases upregulates NIS to absorb iodine. Due to excess iodine inhibit organification this phenomenon called Wolf-Chaikoff effect
physical examination hypothyroid patient
Examination starts by thyroid itself then look for ophthalmopathy and dermopathy. Nack examination should start from the front, side, and back-sides and palpate by both thumbs. retrosternal goiter develops large venous dilatation and difficulty in breathing when both arms lifted upwards called Pemberton’s sign.
Laboratory evaluation for thyroid
Measurement of thyroid hormone
TSH levels change drastically so logically measure TSH whether normal, high, or low. Abnormal TSH finding must follow the T3 T4 measurement. But it is a highly protein-bound hormone and gives a false reading while some disease so should measure free T3 T4.
Test to determine the etiology of thyroid dysfunction
Autoimmune thyroid disease is easily detected by measuring TPO or TG antibody. TSH-R is the antibody that stimulates grave’s disease. Serum Tg levels are increased in all thyrotoxicosis except thyrotoxicosis factitia. Tg levels to see complete ablation or recurrent cancer.
Radioiodine uptake and thyroid scanning
thyroid gland selectively uptake radioisotopes of iodine 123 I, 125 I, 131 I, and 99m Tc pertechnetate, allow imaging of thyroid and quantification of radioactive tracer functional uptake. Grave’s disease characterized by increased tracer uptake and spread homogeneously. Thyroid scintigraphy is used to detect functioning or dysfunctional thyroid tissue. Functioning nodules never malignant.
Thyroid ultrasound for hypothyroid
It is important for the diagnosis and evaluation of a patient with nodular thyroid disease.
Iodine deficiency is a common cause of hypothyroidism in the world.
causes of hypothyroid
|Autoimmune hypothyroidism: hasimoto’s thyroiditis,atrophic thyroiditisIatrogenic: 131 I treatment ,thyroidectomyDrugs: excess iodine, lithium, InterferonCongenital hypothyroidism : absent glandIodine deficiencyInfiltrative disorders|
|Silent thyroiditisSubacute thyroiditisAfter iodine 131 treatment|
|Hypopituitarism: tumors, surgery, infiltrative disordersSheehan’s syndromeHypothalamic disease:Tumors , trauma|
Clinical manifestation of hypothyroid disease
|Tiredness,weakness,dry skin||Dry coarse skin ,cool peripheries|
|Feeling cold, hair loss||Puffy face, hand , feets|
|Difficulty concentrating and poor memory||Diffuse alopesia|
|Weight gain||Peripheral oedema|
|Hoarse voice, menorrhagia||Carpal tunnel syndrome|
|Paresthesia, impaired hearing||Serous cavity effusion|
Treatment of hypothyroid
The daily replacement dose of levothyroxine is 1.6µg /kg 30 minutes but before a meal. Adult patients without heart disease should be started on 50-100 µg levothyroxine daily. The dose is adjusted on the basis of TSH and the goal is to normal TSH. TSH should be measured 2 months after initial treatment and slow to appear any changes. Symptoms may not be relived after3-6 months of normal TSH and dose adjustment should be done 12.5 or25 µg increment.
Animal thyroid preparation is not recommended because it is not physiological. Triiodothyronine has been not benefited because the half-life is short so required 3-4 daily dosage.
Once TSH becomes a normal annual check-up should be required. The patient may not feel any changes after missing any dosage so sometimes leads to discontinuation.
A patient who takes >200µg of thyroxine per day with increased TSH level means they have not adhered to treatment.other causes of increased levothyroxine must be ruled out, malabsorption syndrome, oral estrogen, drugs, sucralfate, lovastatin, rifampin, phenytoin.
It refers to biochemical evidence of thyroid hormone deficiency in the patient have few or no symptoms. Levothyroxine is recommended if the patient gets pregnant, heart disease or TSH >10 mIU/L and symptomatic. Dosage should start 25-50 µg /d and goal to normalized TSH. If the drug not given then evaluate annually.
Special treatment consideration for hypothyroid
Pseudo tumor cerebri has associated with levothyroxine treatment.
Maternal hypothyroidism adversely affects fetal neuronal development and adverse gestational outcome. So, TSH levels keep to a normal level. The thyroid function should be monitored monthly once pregnancy is confirmed. Levothyroxine must be started and normalized TSH and dosage may be required up to 45% to normal dosage. And counseled to separate ingestion of vitamins, iron, and levothyroxine.
Elderly patients may require 20% less thyroxine than young. especially with coronary artery disease, the starting dosage of levothyroxine is 12.5-25 µg/d with the same increase every month till normal TSH . Emergency surgery is generally safe in hypothyroid patients but routine surgery may require euthyroidism.
Myxedema coma has a 20-40- mortality rate, despite intensive treatment. Clinical manifestation includes unconsciousness with seizures. hypothermia may reach up to 23*C and a history of poor compliance and hypothyroidism. An elderly patient is most commonly affects and precipitation occurs due to drugs that depressed the respiratory center, sepsis, cold exposure dilutional hyponatremia.
Levothyroxine can initially administer a single I.V. bolus of 200-400 µg, followed by 1.6 µg /kg/day. Levothyroxine can give by nasogastric tube but in myxedema coma, conversion T4 to t3 is impairing so direct T3 may give via nasogastric tube. T3 dosage load with 5-20 µg followed by 2.5-10 µg 8 hourly, with cardiovascular risk.
Supportive therapy should give to the patient. External warming if the temperature is <30 c as it can result in cardiovascular risk. Space blankets to further prevent heat loss. parenteral hydrocortisone (50mg every 6 hourly) should administered because the adrenal gland may be impaired. Broad-spectrum antibiotics for sepsis. The ventilator supports blood gas analysis for the first 48 hours. Hypertonic saline for severe hyponatremia and glucose drip for hypoglycemia. Drugs which is sedative to avoid and frequent monitoring of drug levels.
All infants born appeared normal but due to the routine investigation may find hypothyroidism. Clinical features include prolonged jaundice, feeding problem, hypotonia, enlarge tongue, delayed bone maturation, and umbilical hernia.
Diagnosis and treatment hypothyroid
Hypothyroidism occurs in about 1 in 4000 newborns. It may be due to the TSH –R antibody or has received anti-thyroid drugs. 80-85% is due to thyroid gland dysgenesis.
T4 (thyroxine) dosage is 10-15 µg/kg.
Thank you for reading my article.
Dr Manish Khokhar