Lecture 17 (Endocrine)-Exam 6 Flashcards

Question

hypoparathyroidism clinical presentation * What are the cardiac findings?(4)

Answer 1

Cardiac findings may include a prolonged QT interval, hypotension, heart failure, and arrhythmia.

Answer 2

* The classic physical findings in patients with neuromuscular irritability due to latent tetany are Trousseau's and Chvostek's signs. * Other patients have less specific symptoms, such as fatigue, hyperirritability, anxiety, and depression, and some patients, even with severe hypocalcemia, have no neuromuscular symptoms.

Answer 3

Persistent hypocalcemia with a low or normal parathyroid hormone (PTH) level and hyperphosphatemia is, in the absence of hypomagnesemia, virtually diagnostic of hypoparathyroidism (PTH deficiency). * Triad of hypocalcemia, decreased intact PTH and increased phosphate

Answer 4

* Calcium sypplementation + activated Vit D supplementation (eg calcitriol) * Acute symptomatic hypocalcemia: IV calcium gluconate plus oral calcitriol

Answer 5

* Changes in teeth * Development of cataracts * Brain calcifications * Stunted growth and mental delay in children * Pernicious anemia, Addison’s disease, and Parkinson’s disease * Overtreatment with Vit. D and Ca can lead to hypercalcemia and cause kidney injury

Answer 6

* Albright’s hereditary osteodystrophy (AHO) – type Ia * Giving PTH does not cause a phosphate diuresis or increase serum calcium * Relative PTH resistance and hypocalcemia

Answer 7

* Albright's hereditary osteodystrophy is a form of osteodystrophy, and is classified as the phenotype of pseudohypoparathyroidism type 1A; this is a condition in which the body does not respond to parathyroid hormone. * Symptoms: Choroid plexus calcification, Full cheeks * Treatment: Phosphate binders, supplementary calcium

Answer 8

* Diagnostic method: calcium, phosphorus, PTH, Urine test for phosphorus and cyclic AMP * AHO is characterized by a round face, short stature with a stocky habitus, brachydactyly, subcutaneous ossification, and dental anomalies * Brachydactyly is a medical term which literally means 'short finger'

Answer 9

* Type Ia has the physical features and has low G8 alpha activity (in kidneys and some other tissues) * There may be resistance to other hormones also like TSH, glucagon, gonadotropins

Answer 10

* Short stature * Obesity * Round face * SQ ossifications * Brachydactyly

Answer 11

* Hypocalcemia, high PTH * Giving PTH does not cause an increase in urine cAMP * No physical features of AHO * No abnormality of G8 alpha in fibroblasts * The AHO physical features and PTH resistance but normal G8 alpha action

Answer 12

* There is renal resistance to PTH * Increased renal loss of calcium and impaired 1-α-hydroxylase, so there is less intestinal absorption of calcium and osteomalacia * Sometimes bone reacts to PTH but kidneys do not * Locus on chromosome 20q 13.3

Answer 13

The AHO physical features and PTH resistance but normal G8 alpha action

Answer 14

Giving PTH causes an increase in urine cAMP (cyclic adenosine monophosphate) but it does not cause an increase in urine phosphorus.

Answer 15

Cyclic Adenosine Monophosphate (cAMP) functions as an intracellular "second messenger" regulating the activity of intracellular enzymes or proteins in response to a variety of hormones (eg, parathyroid hormone). Urinary cAMP is elevated

Answer 16

* It does not have the special physical features of **Albright’s hereditary osteodystrophy** * Not familial * No resistance to PTH in bone cells and indeed you may see the bone changes of hyperparathyroidism

Answer 17

* Same physical features of AHO but normal calcium and PTH * No resistance to PTH * Curiously, when patients inherit the mutant G8 alpha gene from their fathers, they get PPHP, but when they inherit this mutant gene from their mothers, they have pseudohypoparathyroidism TYPE Ia.

Answer 18

* Primary hyperparathyroidism (PHPT) is a relatively common endocrine disorder, with prevalence estimates of one to seven cases per 1000 adults. * It is the most common cause of hypercalcemia, predominantly affecting elderly populations and W>M 3:1. * Primary hyperparathyroidism can occur at any age, but the great majority of cases occur in patients over the age of 50 to 65 years.

Answer 19

Parathyroid hormone (PTH) is one of the two major hormones modulating calcium and phosphate homeostasis, the other being calcitriol (1,25-dihydroxyvitamin D).

Answer 20

* The minute-to-minute regulation of serum ionized **calcium** is exclusively regulated through **PTH**, maintaining the concentration of this cation within a narrow range, through stimulation of renal tubular calcium reabsorption and bone resorption. * PTH secretion is, in turn, regulated by serum ionized calcium acting via an exquisitely sensitive calcium-sensing receptor (CaSR) on the surface of parathyroid cells.

Answer 21

hypercalcemia sings

Answer 22

* The most common clinical presentation of PHPT is Asymptomatic hypercalcemia. Also, PHPT should be considered in a patient with nephrolithiasis. * If hypercalcemia is confirmed, intact parathyroid hormone (PTH) should be measured concomitantly with the serum calcium (should be elevated)

Answer 23

When the PTH is only minimally elevated orwithin the normal range (but inappropriately normal given the patient's hypercalcemia), PHPT remains the most likely diagnosis, although familial hypocalciuric hypercalcemia (FHH), a rare disorder, is possible. * Triad: Hypercalcemia, increased intact PTH, decreased phosphate

Answer 24

Increased 24 hour urine calcium excretion

Answer 25

Patients with symptomatic primary hyperparathyroidism (PHPT) (nephrolithiasis, symptomatic hypercalcemia) should have **parathyroid surgery, which is the only definitive therapy**.

Answer 26

**Parathyroidectomy** is an effective therapy that cures the disease, decreases the risk of kidney stones, improves bone mineral density (BMD), and may decrease fracture risk and modestly improve some quality-of-life measurements. * Give Vit D and calcium supplementation to prevent hypocalemia

Answer 27

* Mild asymptomatic PHPT = Keep active to minimize resorption, and drink adequate fluids (Calciuresis) * Avoid thiazides, lithium, large dosages of Vit A and D and any calcium containing supplements * Bisphosphonates (Alendronate) -temporary measure to decrease serum calcium levels.

Answer 28

Bisphosphonates are a group of drugs that work by slowing bone loss. They reduce the risk of hip and spine fractures. Bone renewal is a slow process, but in many people an increase in bone density can be measured over five years of treatment. * Alendronate

Answer 29

The milk-alkali syndrome consists of the triad of hypercalcemia, metabolic alkalosis, and acute kidney injury associated with the ingestion of large amounts of calcium and absorbable alkali.

Answer 30

* Primary hypothyroidism (local) is characterized by a high serum TSH concentration and low serum free thyroxine (T4) concentration * Subclinical hypothyroidism is defined biochemically as a normal free T4 concentration in the presence of an elevated TSH concentration.

Answer 31

Secondary (central) hypothyroidism is characterized by a low serum T4 concentration and a serum TSH concentration that is not appropriately elevated.

Answer 32

* Present in 3-5% of US population * W>M 8:1, and more common in women with small body size at birth and during childhood

Answer 33

Most common cause of hypothyroidism in iodine-sufficient areas of the world. * Due to autoimmune-mediated destruction of the thyroid gland involving apoptosis of thyroid epithelial cells. May be present with or without goiter.

Answer 34

Nearly all patients have high serum concentrations of antibodies against one or more thyroid antigens; diffuse lymphocytic B and T cells infiltration of the thyroid; and follicular destruction.

Answer 35

* The cause of Hashimoto's thyroiditis is thought to be a combination of genetic susceptibility and environmental factors. * The familial association with Graves' disease and the fact that Graves' disease may sometimes evolve into Hashimoto's thyroiditis (and vice versa) indicate that the two disorders are closely related pathophysiologically, albeit not functionally.

Answer 36

* Has presence of antithyroid antibodies (TPO and/or Tg). * Approximately 10 to 15 percent of children with this disorder have negative anti-TPO and anti-Tg antibodies ("antibody-negative" autoimmune thyroiditis). * If autoimmune thyroiditis is suspected in a child with goiter despite negative antithyroid antibodies (with a family history of autoimmune thyroiditis or a finding of acquired hypothyroidism) ultrasonography may help establish this diagnosis.

Answer 37

* Decreased metabolic rate, fatigue, cold intolerance, dry thickened rough skin, constipation, weight gain despite decreased oral intake, menorrhagia, myxedema (eyelide and facial edema), weakness and lethargy * Goiter symptoms: hoarseness and dyspnea * Women may have galactorrhea

Answer 38

* Thyroid might be normal, enlarged (goiter), or atrophic (later in the diease course) * Bradycardia, decreased DTR, loss of 1/3 of eyebrows * Myxedema- nonpitting edema

Answer 39

* Normal thyroid: None just frequent labs * Overt hypothyroidism: Levothyroxine (Synthroid)

Answer 40

* Anti-Tg Ab * Anti-TPO Ab * Anti-TSHR Ab

Answer 41

* Tg is synthesized by follicular cells and secreted into the lumen of the thyroid follicle, where it is stored as colloid. * Patients with Hashimoto's thyroiditis or Graves' disease may have Tg antibodies, but Tg antibodies do not need to be measured to diagnose autoimmune thyroid disease.

Answer 42

However, thyroglobulin antibodies can interfere with the measurement of serum thyroglobulin, and they are therefore always assessed when monitoring serum thyroglobulin levels in patients with differentiated thyroid cancer. (Thyroglobulin is used for the detection of residual, recurrent, or metastatic disease.)

Answer 43

* TPO catalyzes the iodination of tyrosine residues of Tg to form monoiodotyrosine and diiodotyrosine. Nearly all patients with Hashimoto's thyroiditis have high serum concentrations of TPO antibodies. * Serum anti-TPO antibodies need not be measured in patients with overt primary hypothyroidism, because almost all have chronic autoimmune thyroiditis.

Answer 44

However, a test for anti-TPO antibodies may be useful to predict the likelihood of progression to permanent overt hypothyroidism in patients with subclinical hypothyroidism.

Answer 45

* Thyrotropin receptor antibodies (TRAbs) are classified as stimulating, blocking, or neutral. * Stimulating antibodies (thyroid-stimulating immunoglobulins, TSI) cause Graves' disease. * Thyroid receptor-blocking antibodies can cause hypothyroidism.

Answer 46

Some patients will have a mixture of both antibodies, and, depending on the relative titers of these antibodies, they may fluctuate between hyperthyroidism and hypothyroidism. Neutral antibodies bind the receptor but do not stimulate or block function.

Answer 47

* TSI assays measure only thyroid-stimulating antibodies * TSH receptor-binding inhibitor immunoglobulin (TBII or TBI) assays measure stimulating, blocking, and neutral antibodies.

Answer 48

Third-generation TSI assays have a sensitivity of 97 percent and a specificity of 99 percent for the diagnosis of Graves' disease

Answer 49

TSH * Excellent screening test * Released by pituitary, stimulates the thyroid to release T4/T3 * Elevated in Hypothyroidism, low in Hyperthyroidism Free T4 * Released by thyroid, needs to be converted to active form (T3) (about 80% converted) * Elevated in Hyperthyroidism, low in Hypothyroidism

Answer 50

Free T3 * The only thyroid hormone sensed by cells * Elevated in Hyperthyroidism, low in Hypothyroidism TRH (thyroid releasing hormone)

Answer 51

May help identify central hypothyroidism. If TSH is low and T3/T4 are low, may give TRH stimulation which will markedly raise TSH.

Answer 52

The treatment of choice for correction of hypothyroidism is synthetic thyroxine (T4,Levothyroxine). * T4 is a prohormone with very little intrinsic activity.

Answer 53

It is deiodinated in peripheral tissues to form T3, the active thyroid hormone. Approximately 70 to 80 percent of a dose of T4 is absorbed and, because the plasma half-life of T4 is long (seven days), once-daily treatment results in nearly constant serum T4 and triiodothyronine (T3) concentrations when a steady state is reached.

Answer 54

* TSH should be monitored every 4-6 weeks for treatment success * Crude thyroid is an option for those that do not want to wait - 2 weeks * Liothyronine (Synthetic T3) can also be used

Answer 55

* Changes in the T4 dose are based upon the person's TSH and T4 level. The dose may need to be increased if thyroid disease worsens, during pregnancy, if gastrointestinal conditions impair T4 absorption, or if the person gains weight. A high-fiber diet, calcium- or aluminum-containing antacids, and iron tablets can interfere with the absorption of T4 and should be taken at a different time of day. * The dose may need to be decreased as the person gets older, after childbirth, or if the person loses weight.

Answer 56

* Advanced age and heart disease — Thyroid hormone makes the heart work a bit harder. Therefore, a clinician may opt for more conservative T4 treatment in older adults and in people with coronary artery disease. * Metabolic Syndrome Complications – Hypercholesterolemia and hypertriglyceridemia are commonly see in hypothyroid patients

Answer 57

* Pregnancy — Women often need higher doses of T4 during pregnancy. Testing is usually recommended every four weeks, beginning after conception, until levels are stable, then once each trimester. After delivery, the woman's dose of T4 will need to be adjusted again, usually returning to the pre-pregnancy dose. * Surgery — Hypothyroidism can increase the risk of certain surgery-related complications; bowel function may be slow to recover, and infection may be overlooked if there is no fever. If preoperative blood tests reveal low thyroid hormone levels, nonemergency surgery is usually postponed until treatment has returned T4 levels to normal.

Answer 58

* Hyperthyroidism is more common in women than men (5:1 ratio). The overall prevalence of hyperthyroidism, which is approximately 1.3 percent, increases to 4 to 5 percent in older women. * Hyperthyroidism is also more common in smokers. * Graves' disease is seen most often in younger women, while toxic nodular goiter is more common in older women.

Answer 59

* Shake hands and note excessive warmth and sweating. * Look for fine tremor of outstretched hands and acropachy of the fingers (hyperthyroidism). * Examine the radial pulse (usually rapid and high-volume unless on a β -blocker). An irregularly irregular pulse is likely to indicate atrial fibrillation.

Answer 60

* Examine the thyroid and describe its size, surface and consistency. Listen for a thyroid bruit. * Look for evidence of thyroid eye disease. * Inspect the shins for pretibial myxedema

Answer 61

* Graves' disease is a syndrome that may consist of hyperthyroidism, goiter, thyroid eye disease (Graves' orbitopathy), and occasionally a dermatopathy referred to as pretibial or localized myxedema (PTM). * The terms Graves' disease and hyperthyroidism are not synonymous, because some patients may have orbitopathy but no hyperthyroidism, and there are many other causes of hyperthyroidism in addition to Graves' disease.

Answer 62

by autoantibodies to the thyrotropin receptor (TRAb) that activate the receptor, thereby stimulating thyroid hormone synthesis and secretion as well as thyroid growth (causing a diffuse goiter)

Answer 63

Exophthalmos, periorbital and conjunctival edema, limitation of eye movement, and infiltrative dermopathy (pretibial myxedema) occur only in patients with Graves' disease

Answer 64

* Acropachy is a dermopathy associated with Graves' disease. It is characterized by soft-tissue swelling of the hands and clubbing of the fingers. * Radiographic imaging of affected extremities typically demonstrates periostitis, most commonly the metacarpal bones. * Toxic nodular goiter does not cause the bulging eyes that can occur with Graves disease.

Answer 65

Graves disease results from production of thyroid-stimulating immunoglobulins (TSI) by stimulated B lymphocytes * Also known as autoantibodies to the thyrotropin receptor (TRAb) or TBII, or TBI

Answer 66

TSI’s bind to TSH receptors, cause hyperproduction of thyroid hormone. * As a result, hypervascularity develops leading to goiter formation * A new-onset ophthalmopathy develops

Answer 67

Primary hyperthyroidism is consistent with a low TSH, and a high free T4 and/or T3 blood test.

Answer 68

If TSH is elevated, and free T4 and T3 are high, an MRI of the pituitary gland is necessary to evaluate for central or TSH – induced hyperthyroidism.

Answer 69

* If TSH is low and T3 is high (but your free T4 is normal), the diagnosis is either Graves disease or a thyroid nodule that is producing too much hormone. * A radioactive iodine uptake scan can differentiate between these two diagnoses. Alternatively, taking too much T3 (called exogenous T3 ingestion) is another possibility.

Answer 70

* Anti-thyroid medicines reduce the amount of hormone your thyroid gland makes (Thionamides->Propylthiouracil or methimazole). Can be use -/+ of radioiodine or surgery. * Beta-blocker medicines help reduce the symptoms of hyperthyroidism. Beta-blockers can make you more comfortable until the thyroid imbalance is under control. * Calcium channel blockers can be used if BB are contraindicated

Answer 71

* Radioactive iodine (I-131) – Radioactive iodine comes in a pill or liquid you swallow. It destroys much of the thyroid gland causing Hypothyroidism * It can cause problems getting pregnant in the future or increase the risk of birth defects in future pregnancies.

Answer 72

* Radioactive iodine can make eye bulging worse in people with Graves' disease, especially if they smoke cigarettes. A steroid administration before radioactive iodine may help prevent bulging of the eyes. * Throwback from Radiology! Iodinated contrast should be avoided for two months before administration of iodine 131/123 * Reduces uptake of I-131 and makes it ineffective

Answer 73

Surgery – Surgery for those that fail medical therapy or those with malignancy. But surgery is the best choice in some cases.

Answer 74

Patient must wait at least 6 months before trying to get pregnant after being treated with radioactive iodine. * I-131 wipes out thyroid function, hypothyroidism in pregnancy can cause fetal complications. 6months timeframe allows work-up and stabilization of hormone level. During pregnancy, mother can develop hCG-mediated hyperthyroidism (Not Graves disease) * Can lead to pre-eclampsia, preterm labor or miscarriage * Does not require treatment if mild and is self-limiting

Answer 75

Severe symptoms of hCG-mediated hyperthyroidism and those with Graves disease will need thionamides (inhibit thyroid hormone synthesis) * **Propylthiouracil (PTU)** in the first trimester (less fetal malformations) * **Methimazole** in the second or third trimester (has longer half-life) * Patients can continue PTU throughout pregnancy, or switch to methimazole at 16 weeks * Methimazole may lead to an increased incidence of aplasia cutis, a fetal scalp defect. Avoid in first trimester.

Answer 76

Thyroid Storm = “hyperthyroidism on steroids”, can develop in patients with longstanding untreated hyperthyroidism (Graves' disease, toxic multinodular goiter, solitary toxic adenoma), but is often precipitated by an acute event such as thyroid or nonthyroidal surgery, trauma, infection, an acute iodine load, or parturition.

Answer 77

* The classical symptoms of thyroid storm include tachycardia, hyperpyrexia, central nervous system dysfunction (agitation, delirium, psychosis, stupor, or coma), and gastrointestinal symptoms (nausea, vomiting, abdominal pain). * Physical examination may reveal goiter, ophthalmopathy (in the presence of Graves' disease), lid lag, hand tremor, and warm and moist skin.

Answer 78

Thyroid function tests show hyperthyroidism (suppressed thyroid-stimulating hormone [TSH], elevated free thyroxine [T4] and triiodothyronine [T3]) generally comparable with that in patients with uncomplicated overt hyperthyroidism.

Answer 79

The diagnosis of thyroid storm is based upon the presence of severe and life-threatening symptoms (hyperpyrexia, cardiovascular dysfunction, altered mentation) in a patient with biochemical evidence of hyperthyroidism (elevation of free T4 and/or T3 and suppression of TSH)

Answer 80

* In addition to thionamides/BB/CCB/I-131, glucocorticoids and iodine solution (eg, saturated solution of potassium iodide [SSKI]) is used. * Don’t treat fever with ASA – can increase free T3/T4 concentration * ICU admission due to mortality rate of 10-30 percent.

Answer 81

* Beta blocker (propranolol) * Thionamide (PTU is preferred) * Iodine solution (1 hour after a thionamide is given) * Glucocorticoids (hydrocortisone) * Bile acid sequestrants (cholestyramine) may also be of benefit in severe cases to decrease enterohepatic recycling of thyroid hormones.

Answer 82

* Surgery for those that cannot get thionamides or those with obstructive goiter * Potassium perchlorate if iodine is contraindicated (ex: amiodarone induced or due to allergy)

Answer 83

* Inflammatory thyroid conditions that cause acute illness with severe thyroid pain (eg, subacute thyroiditis and infectious thyroiditis) * Or conditions in which there is no clinically evident inflammation and the illness is manifested primarily by thyroid dysfunction or goiter (eg, painless thyroiditis and fibrous [Riedel's] thyroiditis) * Incidence increased with diabetes (25%)

Answer 84

* Suppurative or infectious * Subacute painful (de Quervain’s, granulomatous, or giant cell) * Drug-induced (usually Amiodarone) * Chronic lymphocytic (Hashimoto) * Fibrous thyroiditis (Riedel)

Answer 85

* Caused by Staph. aureus * Tender Thyroid, fever, sore throat, overlying erythema * Leukocytosis and Elevated ESR * FNA with gram stain and culture * Treatment based on culture and surgical drainage ## Footnote Rare and nonviral

Answer 86

* Typically follows URI disease * Painful enlarge thyroid on exam * ESR is elevated and antithyroid antibody titers are low

Answer 87

* Both T3/T4 are elevated, TSH may be normal or low * Can last up to a year * Treatment is ASA with no steroids. BB and iodinated contrast products can reduce symptoms.

Answer 88

De Quervain's thyroiditis, also known as subacute granulomatous thyroiditis or giant cell thyroiditis, is a health condition involving the thyroid gland that usually resolves spontaneously without treatment.Patients with this disease go through different phases over weeks to months. Initially, they will be hyperthyroid and then transition to a brief euthyroid phase, followed by a hypothyroid phase, before eventually returning to being euthyroid

Answer 89

* Amiodarone induced (antiarrhythmic drug) which as 37% Iodine in it * Can mimic both hyper and hypothyroidism symptoms by increasing T4 by 20-40% during 1st month of taking the drug and reduces concentration of T3, therefore TSH will rise. * After 2-3 month, T4 and T3 and TSH levels normalize Stop the drug and find a replacement.

Answer 90

* Very rare form caused by development of dense fibrous tissue in the thyroid gland. May have other extraglandular fibrosis such as sclerosing cholangitis. * 80% are female * Asymmetric, painless, hard (woody) thyroid on palpation

Answer 91

* RAIU is decreased in the involved areas of thyroid with possible thyroid antibodies in nearly half of patient * Diagnosis is made via biopsy. * Resection vs tamoxifen, methotrexate, or steroids treatment is warranted. * Tamoxifen (selective estrogen receptor modulator (SERM) used often for breast cancer patients).