DISORDERS OF ENDOCRINE FUNCTION: THE THYROID GLAND Flashcards

Question

What is Congenital Hypothyroidism?

Answer 1

Hypothyroidism occurs in about 1 in 4000 newborns. It may be transient if the mother has TSH-R blocking antibodies or has received antithyroid drugs Permanent hypothyroidism occurs in the majority. Neonatal hypothyroidism is due to Thyroid gland dysgenesis in 80 to 85%, Inborn errors of thyroid hormone synthesis in 10 to 15% TSH-R antibody-mediated in 5% of affected newborns. The developmental abnormalities are twice as common in girls. Mutations that cause congenital hypothyroidism are being increasingly recognized, but the vast majority remain idiopathic The majority of infants appear normal at birth, and <10% are diagnosed based on clinical features that includes: Prolonged jaundice Feeding problems Hypotonia Enlarged tongue Delayed bone maturation Umbilical hernia Permanent neurologic damage results if treatment is delayed. Typical features of adult hypothyroidism may also be present. Other congenital malformations, especially cardiac, are four times more common in congenital hypothyroidism

Answer 2

If untreated there is severe neurologic consequences Neonatal screening programs have been established in developed countries. They are based on measurement of TSH or T4 levels in heel-prick blood specimens. When the diagnosis is confirmed, T4 is instituted at a dose of 10 to 15 µg/kg per day and the dosage is adjusted by close monitoring of TSH levels. T4 requirements are relatively great during the first year of life, and a high circulating T4 level is usually needed to normalize TSH. Early treatment with T4 results in normal IQ levels, but subtle neurodevelopmental abnormalities may occur in those with the most severe hypothyroidism at diagnosis or when

Answer 3

Symptoms: Tiredness, weakness Dry skin Feeling cold Hair loss Difficulty concentrating and poor memory Constipation Weight gain with poor appetite Dyspnea Hoarse voice Menorrhagia (later oligomenorrhea or amenorrhea) Paresthesia Impaired hearing Signs: Dry coarse skin; Cool peripheral extremities Puffy face, hands, and feet (myxedema) Diffuse alopecia Bradycardia Peripheral edema Delayed tendon reflex relaxation Carpal tunnel syndrome Serous cavity effusions

Answer 4

Plasma TSH and fT4 or total T4 should be measured Slightly elevated plasma TSH with normal fT4: Suggest compensated hypothyroidism. Measure circulating thyroid antibodies to rule out autoimmune disorders Raised TSH with low fT4: Suggest primary hypothyroidism Low TSH with low fT4: Suggest secondary hypothyroidism (Pituitary or Hypothalamic) Raised TSH with raised/normal fT4 in the presence of hypothyroid symptoms: Suggest thyroid hormone resistance

Answer 5

Occasionally hypothyroid patients may present with hypothermia and stupor or coma, a condition termed ‘myxoedema coma’. Almost always occurs in the elderly and is usually precipitated by factors that impair respiration, such as: drugs (especially sedatives, anesthetics, antidepressants), pneumonia, congestive heart failure, myocardial infarction, gastrointestinal bleeding, or cerebrovascular accidents. Sepsis should also be suspected. Exposure to cold may also be a risk factor. Hypoventilation, leading to hypoxia and hypercapnia, plays a major role in pathogenesis; hypoglycemia and dilutional hyponatremia also contribute to the development of myxedema coma

Answer 6

Apart from the clinical features listed any unexplained biochemical changes should raise the suspicion of hypothyroidism Hypercholesterolaemia Elevated creatine kinase Hyponatraemia due to increase release of antidiuretic hormones Hyperprolactinaemia Plasma SHBG reduction Macrocytic anaemia Sometimes abnormal LFT and RFT may occur.

Answer 7

Biochemical diagnosis is quite straightforward decreased fT4 with a markedly increased TSH The disease often begins insidiously; in its early stages, the only abnormality may be an increased TSH, to which the failing gland responds by secreting enough T4 to keep the fT4 within the normal range (usually close to the lower end). In such cases, high titres of anti-thyroid antibodies provide supportive evidence of auto-immune thyroid disease.

Answer 8

Treatment is also simple and cheap Lifelong administration of sufficient thyroxine to normalise the plasma f T4 and TSH. Monitoring Treatment Abnormally high TSH indicates inadequate replacement or erratic compliance, whereas suppressed TSH suggests excessive replacement. T3 treatment is used where rapid onset of action is desired (eg. treatment of myxoedema coma) or where rapid reversal of overdosage is important (eg. treating hypothyroid patients with ischaemic heart disease). This is because of the rapid onset of action and shorter half-life of T3 compared to T4.

Answer 9

Clinical manifestations include: Reduced level of consciousness, Seizures, Features of hypothyroidism Hypothermia can reach 23°C (74°F). There may be a history of treated hypothyroidism with poor compliance, The patient may be previously undiagnosed This is a medical emergency that carries a high risk of mortality. Apart from T3 replacement, one needs to restore body temperature and correct electrolyte imbalance (typically hyponatraemia from water retention).

Answer 10

Hyperthyroidism causes sustained high plasma concentration of T3 and T4. There is often generalised increase in the metabolic rate, evidence of clinically by Heat intolerance Fine tremor Tachycardia Weight loss Tiredness Anxiety Sweating Diarrhea

Answer 11

The term thyrotoxicosis denotes the clinical, physiological, and biochemical findings that result when the tissues are exposed to excess thyroid hormone. It can arise in a variety of ways. It is essential to establish a specific diagnosis as this determines therapy choices and provides important information for the patient regarding prognosis. The term hyperthyroidism should be used to denote conditions in which hyperfunction of the thyroid leads to thyrotoxicosis.

Answer 12

Accounts for 60 to 80% of thyrotoxicosis Prevalence varies among populations, depending mainly on iodine intake (high iodine intake is associated with an increased prevalence of Graves' disease) More common in female than male Rarely begins before adolescence and typically occurs between 20 and 50 years of age, but it also occurs in the elderly It is an autoimmune disease with a varing degree of circulating antibodies such as anti-TPO, TSI May be associated with other autoimmune diseases such as type 1diabetes mellitus, adrenal insufficiency, pernicious anaemia

Answer 13

Primary hyperthyroidism Grave’s disease Toxic multinodular goitre Toxic Adenoma Thyroid carcinoma Metastatic thyroid carcinomas Activating mutation of the TSH receptor Activating mutation of Gsα (McCune-Albright syndrome) Administration of iodine to a patient with iodine deficiency (Jod-Basedow syndrome) TSH secreting tumours e.g. pituitary tumours, trophoblastic tumours Struma ovarii Thyrotoxicosis without hyperthyroidism Subacute thyroiditis Silent thyroiditis Other causes of thyroid destruction: amiodarone, radiation, infarction of adenoma Thyrotoxicosis factitia (self administration of thyroid hormones) Secondary hyperthyroidism TSH-secreting pituitary adenoma Thyroid hormone resistance syndrome: occasional patients may have features of thyrotoxicosis Chorionic gonadotropin-secreting tumors Gestational thyrotoxicosis

Answer 14

Symptoms Hyperactivity, irritability, dysphoria Dyspnea Heat intolerance and sweating Palpitations Fatigue and weakness Weight loss with increased appetite Diarrhea Thirst and Polyuria Pruritus Oligomenorrhea, loss of libido Signs: Sinus Tachycardia; atrial fibrillation in the elderly Hyperkinesia and hyperreflexia Fine Tremor Palma erthyma, oncolysis Goiter Warm, moist skin Hair loss Muscle weakness, proximal myopathy Periodic paralysis Congestive (high output) heart failure Chorea Pschosis Lid retraction or lag Gynecomastia

Answer 15

Thyroid Ophthalmopathy: Exophthalmos, due to lymphocytic infiltration and swelling of retro-orbital tissues of the eyes Thyroid Acropathy: A form of finger clubbing found in <1% of patients with Graves' disease. It is so strongly associated with thyroid dermopathy that an alternative cause of clubbing Thyroid Dermatopathy: Pretibial myxedema, localized thickening of the subcutaneous tissue over the shin

Answer 16

Diffuse goiter A feeling of grittiness and discomfort in the eye Retrobulbar pressure or pain, eyelid lag or retraction Periorbital edema, chemosis, scleral injection Exophthalmos (proptosis) Extraocular muscle dysfunction Exposure keratitis Optic neuropathy

Answer 17

Also known as de Quervain's thyroiditis A destructive thyroiditis resulting in release of preformed thyroid hormones There three subtypes: 1) Granulomatous or painful: a viral disease associated HLA-Bw35 2) Lymphocytic or silent and painless: autoimmune 3) Postpartum: autoimmune, occuring in 5-8% of pregnant women Associated with extremely elevated thyroid hormones Treatment is supportive

Answer 18

Either single or multiple Secrete thyroid hormone autonomously Nodules may be detected by uptake of radioactive iodine or technetium with suppression of uptake in the rest of the thyroid tissue Found mostly in adult patients, who present usually with artrial fibrillation Toxic multinodular goitre is also called Plummer’s disease

Answer 19

Jod-Basedow syndrome: excessive iodide intake Thyroid carcinoma: primary thyroid cancer that can be papillary, follicular, or anaplastic Metastatic thyroid carcinoma: metastasis from other organs to the thyroid causing hyper activity of the thyroid gland Struma ovarii: ectopic thyroid tissue found in dermoid cyst or ovarian carcinoma HCG secreting trophoblastic tumours: choriocarcinoma or molar pregnancy; HCG activate TSH receptor.

Answer 20

May occur with low or suppressed TSH but normal (usually high normal) plasma fT4 and fT3 May progress to full blown hyperthroidism May be associated with atrial fibrillation

Answer 21

Goiter refers to an enlarged thyroid gland. Biosynthetic defects, iodine deficiency, autoimmune disease, and nodular diseases can each lead to goiter, though by different mechanisms. Biosynthetic defects and iodine deficiency are associated with reduced efficiency of thyroid hormone synthesis, leading to increased TSH, which stimulates thyroid growth as a compensatory mechanism to overcome the block in hormone synthesis. Graves' disease and Hashimoto's thyroiditis are also associated with goiter. Nodular disease is characterized by the disordered growth of thyroid cells, often combined with the gradual development of fibrosis. Because the management of goiter depends on the etiology, the detection of thyroid enlargement on physical examination should prompt further evaluation to identify its cause. Thyroid function tests should be performed in all patients with goiter to exclude thyrotoxicosis or hypothyroidism

Answer 22

Either the plasma total or fT4 is abnormally raised without clinical evidence of thyroid disease May be transient or persist, with high, normal or low total or fT3 concentration

Answer 23

Under the influence of prolonged stimulation by TSH, the number of thyroid cells increases (cellular hyperplasia) and plasma thyroid hormone concentration are maintained at the expense of the development of goitre Iodide deficiency due to paraaminosalicylic acid, or partial deficiency of the enzymes involve in thyroid hormone synthesis

Answer 24

Any acute, severe illness can cause abnormalities of circulating TSH or thyroid hormone levels in the absence of underlying thyroid disease, making these measurements potentially misleading Any severe illness may be associated with low plasma total or fT4 concentration and may make the interpretation of thyroid function test extremely difficult Plasma TSH may be low, normal or high The assessment of TFT is deferred till patient has recovered from illness

Answer 25

Also known as thyrotoxic crisis, is an acute, life-threatening complication of hyperthyroidism. It is an exaggerated presentation of thyrotoxicosis. It comes with sudden multisystem involvement. The mortality associated with thyroid storm is estimated to be 8-25% despite modern advancements in its treatment and supportive measures. It is very important to recognize it early and start aggressive treatment to reduce mortality.

Answer 26

The precipitating factors are: Abrupt discontinuation of antithyroid medicine Thyroid surgery Non-thyroid surgery Trauma Acute illness like infections, diabetic ketoacidosis, acute myocardial infarction, cardiovascular accident, cardiac failure, drug reaction Parturition Recent use of Iodinated contrast medium Radioiodine therapy (rare) Burns Stroke Medication side effect e.g. amiodarone, anesthetics, salicylates.

Answer 27

Clinical presentation includes hyperpyrexia, dehydration, tachycardia, cardiac failure, CNS manifestation and GIT manifestation Thyroid function tests show high FT4/FT3 and low TSH. It is not necessary to have a very high level of thyroid hormone to cause thyroid storm. Other lab abnormalities may include hypercalcemia, hyperglycemia, abnormal LFTs, high or low white blood cell (WBC) count. It is a medical emergency associated with significant mortality and requires urgent treatment.

Answer 28

Plasma f T4 and f T3 are elevated, with TSH suppressed suggest hyperthyroidism Plasma f T4 is elevated, with normal TSH suggestive of Euththyroid thyroxinaemia Plasma f T4 is normal, f T3 is elevated with normal TSH suggestive of T3 toxicosis Presence of plasma antibodies TSI, anti-TPO suggest Grave’s disease

Answer 29

Hypercalceamia due to increased bone resorption Elevated alkaline phosphatase Hypercalciuria is also common Hypocholesterolaemia due to increased LDL clearance Hypokalaemia associated with hyperthyrotoxic periodic paralysis Plasma SHBG is increased Plasma creatine kinase may be increased because of thyrotoxic myopathy

Answer 30

Four factors alter thyroid function in pregnancy: 1. Transient increase in hCG during the first trimester, which stimulates the TSH-R 2. Estrogen-induced rise in TBG during the first trimester, which is sustained during pregnancy 3. Alterations in the immune system, leading to the onset, exacerbation, or amelioration of an underlying autoimmune thyroid disease 4. Increased urinary iodide excretion, which can cause impaired thyroid hormone production in areas of marginal iodine sufficiency Women with iodine intake (<50 µg/d) are most at risk of developing a goiter during pregnancy Iodine supplementation should be considered to prevent maternal and fetal hypothyroidism and the development of neonatal goiter. hCG-induced changes in thyroid function can result in transient gestational hyperthyroidism and/or hyperemesis gravidarum; characterized by severe nausea and vomiting and risk of volume depletion. Antithyroid drugs are rarely needed, and parenteral fluid replacement usually suffices until the condition resolves. Maternal hypothyroidism occurs in 2 to 3% of women of child-bearing age and is associated with increased risk of developmental delay in the offspring. Thyroid hormone requirements are increased by 25 to 50 µg/d during pregnancy