Endocrine Diseases

Endocrine Diseases

General Principles In Diagnosis of Endocrine Diseases

• Perform stimulatory tests if hypofunction is suspected and suppression tests if hyperfunction is suspected.
• Suppression tests suppress normal glands but not autonomous secretion (e.g., functioning neoplasm).
• Obtaining multiple or pooled samples of baseline specimens and drawing specimens from indwelling lines are often required to obtain optimal specimens.
• Patient preparation is particularly important for hormone studies, the results of which may be markedly affected by many factors such as stress, position, fasting state, time of day, preceding diet, and drug therapy; all of these should be recorded on the laboratory test requisition form and discussed with the laboratory before test ordering.
• Appropriate (e.g., frozen) and timely transportation to laboratory and preparation of specimen (e.g., separation of serum may be vital for some tests) are important.
• No single test adequately reflects the endocrine status in all conditions.

Tests of Thyroid Function

• Thyroid function tests are not indicated for screening programs without suspicion of thyroid disease (overall yield ~0.5%; varies from 0% in young men to 1% in women aged >40 yrs). Indicated in certain populations such as newborns (mandatory), those with strong family history of thyroid disease, elderly, women 4–8 wks postpartum, patients with autoimmune diseases (e.g., Addison's disease, type I diabetes mellitus). May be useful in some women aged >40 yrs with nonspecific complaints.
• Sensitive TSH complemented by free thyroxine index (FTI) are recommended tests for diagnosis and follow-up of most patients with thyroid disorders (Table 13-1).

Calcitonin

Use

• Basal fasting level may be increased in patients with medullary carcinoma of the thyroid even when no mass is palpable in the thyroid. Circadian rhythm with rise to peak after lunchtime. Basal level is normal in approximately one-third of medullary carcinoma cases.
• Basal calcitonin levels
• Levels >2000 pg/mL are almost always associated with medullary carcinoma of thyroid, with rare cases due to obvious renal failure or ectopic production of calcitonin.
• Levels of 500–2000 pg/mL generally indicate medullary carcinoma, renal failure, or ectopic production of calcitonin.
• Levels of 100–500 pg/mL should be interpreted cautiously with repeat assays and provocative tests; if these and repeat tests in 1–2 mos are still abnormal, some authors recommend total thyroidectomy.
• Normal basal levels: Males ≤19 pg/mL; females ≤14 pg/mL.
• Calcium infusion and/or pentagastrin injection are used as provocative tests in patients with normal basal levels for whom the index of suspicion is high, e.g., those with a

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family history of thyroid carcinoma, a calcified thyroid mass, pheochromocytoma, hyperparathyroidism, hypercalcemia, amyloid-containing metastatic carcinoma of unknown origin, or facial characteristics of the mucosal neuroma syndrome. Normally level should not rise above 0.2 ng/mL. Pentagastrin stimulation is more 18118f515s sensitive than calcium stimulation.

• To detect recurrence of medullary carcinoma or metastases after the primary tumor has been removed or to confirm complete removal of the tumor if basal calcitonin has been previously increased.

Increased in Some Patients with

• Carcinoma of lung, breast, islet cell, or ovary, and carcinoid due to ectopic production
• Hypercalcemia of any cause stimulating calcitonin production
• Z-E syndrome
• PA
• Acute or chronic thyroiditis
• Chronic renal failure

Perchlorate Washout Test

• Perchlorate is given 2–4 hrs after administration of I and RAIU is calculated before and at intervals after perchlorate administration.

Use

• Decreased uptake >10% from peak value is positive test indicating an organification defect as the cause of hypothyroidism. Free iodide is present within the thyroid in such patients. Perchlorate blocks the trapping mechanism, causing rapid discharge of iodine so that RAIU within the thyroid diminishes. Normal thyroid gland contains very little inorganic iodine.

Reverse Triiodothyronine (Rt

(Hormonally inactive isomer of T

Use

• Largely replaced by newer tests
• Usually increased in hyperthyroidism and increased serum TBG; often decreased in hypothyroidism but overlaps with normal range.
• Has been suggested to distinguish “sick thyroid” patients who are euthyroid (usually normal in euthyroid patients) from true hypothyroid cases, but serum TSH may be more reliable.

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Thyroid-Stimulating Hormone Sensitive (Thyrotropin; Tsh)

• (Hormone secreted by anterior pituitary; third- and fourth-generation assay detection limits are 0.01 mU/L and 0.001 mU/L, respectively)
• See Table 13-2, and Fig. 13-1.
• Euthyroid: 0.3–5.0 mU/L

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• Possible hypothyroid: >5.0 mU/L
• Possible hyperthyroid: <0.10 mU/L
• Borderline: 0.10–0.29 mU/L

Use

• Screening for euthyroidism—normal level in stable ambulatory patient not on interfering drugs excludes thyroid hormone excess or deficiency. Has been recommended as the initial test of thyroid function rather than T
• Screening is not recommended for asymptomatic persons without suspicion of thyroid disease or for hospital patients with acute medical or psychiatric illness.
• Initial screening and diagnosis for hyperthyroidism (decreased to undetectable levels except in rare TSH-secreting pituitary adenoma) and hypothyroidism

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• Second-generation or rate assay is required to determine TSH <0.10 mU/L.
• Especially useful in early or subclinical hypothyroidism before the patient develops clinical findings, goiter, or abnormalities of other thyroid tests
• Differentiation of primary (increased levels) from central (pituitary or hypothalamic) hypothyroidism (decreased levels)
• Monitor adequate thyroid hormone replacement therapy in primary hypothyroidism, although T may be mildly increased; up to 6–8 wks before TSH becomes normal. Serum TSH suppressed to normal level is the best monitor of dosage of thyroid hormone for treatment of hypothyroidism.
• Monitor adequate thyroid hormone therapy to suppress thyroid carcinoma (should suppress to <0.1 mU/L) or goiter or nodules (should suppress to subnormal levels). Third- or fourth-generation assays are required to allow closer titration to balance inhibition of functioning tumor against induced hyperthyroidism.
• Help differentiate euthyroid sick syndrome from primary hypothyroid patients. Sensitive TSH is only very slightly depressed in euthyroid sick patients but usually significantly depressed in true thyroid disorder.
• Replace TRH stimulation test in hyperthyroidism because most patients with euthyroid TSH level have a normal TSH response and patients with undetectable TSH level almost never respond to TRH stimulation
• In very early cases with only marginal elevation, the TRH stimulation test may be preferred.

May Not Be Useful

• As a single test to evaluate thyroid status of hospitalized or severely ill patients
• To monitor efficacy of thyroid ablation therapy for hyperthyroidism because TSH remains suppressed until T declines significantly; T or free T is test of choice.

Interferences

• Dopamine or high doses of glucocorticoids may cause false-normal values in primary hypothyroidism and may suppress TSH in nonthyroid illness.
• Presence of RF, human antimouse antibodies, and thyroid hormone autoantibodies may produce spurious results, especially in patients with autoimmune disorders (≤10%).

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Increased In

• Primary untreated hypothyroidism. Increase is proportionate to the degree of hypofunction, varying from 3× normal in mild cases to 100× normal in severe myxedema. A single determination is usually sufficient to establish the diagnosis.
• Patients with hypothyroidism receiving insufficient thyroid hormone replacement therapy
• Patients with Hashimoto's thyroiditis, including those with clinical hypothyroidism and about one-third of those patients who are clinically euthyroid
• Use of various drugs (e.g., amphetamine abuse)
• Iodine containing drugs (e.g., iopanoic acid, ipodate, amiodarone)
• Dopamine antagonists (e.g., metoclopramide, domperidone, chlorpromazine, haloperidol)
• Other conditions (test is not clinically useful)
• Iodide-deficiency goiter
• Iodide-induced goiter or lithium treatment
• External neck irradiation
• Post–subtotal thyroidectomy
• Neonatal period
• Thyrotoxicosis due to pituitary thyrotroph adenoma or pituitary resistance to thyroid hormone
• Euthyroid sick syndrome, recovery phase
• TSH antibodies
• Increased in first 2–3 days of life due to postnatal TSH surge

Decreased In

• Hyperthyroidism due to
• Toxic multinodular goiter
• Autonomously functioning thyroid adenoma
• Ophthalmopathy of euthyroid Graves' disease
• Treated Graves' disease
• Thyroiditis
• Extrathyroidal thyroid hormone source
• Factitious
• Overreplacement of thyroid hormone in treatment of hypothyroidism
• Secondary pituitary or hypothalamic hypothyroidism
• Euthyroid sick patients
• Acute psychiatric illness
• Severe dehydration
• Drug effect, especially large doses—use free T for evaluation
• Glucocorticoids, dopamine, dopamine agonists (bromocriptine), levodopa, T replacement therapy, apomorphine, pyridoxine; T may be normal or low.
• Antithyroid drug for thyrotoxicosis, especially early in treatment; T may be normal or low.
• Assay interference, e.g., antibodies to mouse IgG, autoimmune disease.
• First trimester of pregnancy

May Be Normal In

• Central hypothyroidism
• Recent rapid correction of hyperthyroidism or hypothyroidism
• Pregnancy
• Phenytoin therapy
• In absence of hypothalamic or pituitary disease, normal TSH excludes primary hypothyroidism

Thyroglobulin (Tg)

• (Cannot compare thyroglobulin values using different assays or assays from different laboratories)
• See Table 13-3.

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Use

• To assess the presence and possibly the extent of residual, recurrent, or metastatic follicular or papillary thyroid carcinoma after therapy. In patients with these carcinomas treated with total thyroidectomy or radioactive iodine and taking thyroid hormone therapy, Tg is undetectable if functional tumor is absent but detected by sensitive immunoassay if functional tumor is present. Tg correlates with tumor mass, with highest values in patients with metastases to bones and lungs.
• Diagnosis of factitious hyperthyroidism. Tg is very low or not detectable in factitious hyperthyroidism and high in all other types of hyperthyroidism (e.g., thyroiditis).
• Not recommended for initial diagnosis of thyroid carcinomas.
• Do not use in patients with preexisting thyroid disorders.
• Predict outcome of therapy for hyperthyroidism; higher remission rates in patients with lower Tg values. Failure to become normal after drug-induced remission suggests relapse after drugs are discontinued.
• Diagnosis of thyroid agenesis in newborn
• Presence in pleural effusions indicates metastatic differentiated thyroid cancer.

Interferences

• Thyroglobulin autoantibodies interferes with the test; patients' serum must always first be screened for these antibodies.

Increased In

• Most patients with differentiated thyroid carcinoma but not those with undifferentiated or medullary thyroid carcinomas
• Patients with hyperthyroidism; rapid decline after surgical treatment. Gradual decline after radioactive iodine treatment.
• Patients with subacute thyroiditis
• Some patients with nontoxic nodular goiter
• Patients with marked liver insufficiency

Decreased In

• Thyroid agenesis in newborn

Thyroid Autoantibody Tests

(Antimicrosomal [also called thyroid peroxidase] and antithyroglobulin autoantibodies)

Use

• Positive in almost all cases of Hashimoto's disease and ~80% of Graves' disease. Very high titer is pathognomonic of Hashimoto's thyroiditis but absence does not exclude Hashimoto's thyroiditis. Titer>1 to 1000 occurs virtually only in Graves' disease or Hashimoto's thyroiditis. Significant titer of microsome antibodies indicates Hashimoto's thyroiditis or postpartum thyroid dysfunction.
• To distinguish subacute thyroiditis from Hashimoto's thyroiditis, as antibodies are more common in the latter
• Hashimoto's thyroiditis is very unlikely cause of hypothyroidism in the absence of microsomal and Tg antibodies.
• Significant titer of microsomal and Tg antibodies in euthyroid patient with unilateral exophthalmos suggests the diagnosis of euthyroid Graves' disease.
• Occasionally useful to distinguish Graves' disease from toxic multinodular goiter when physical findings are not diagnostic.
• Graves' disease with elevated titers of antimicrosomal antibodies should direct surgeon to perform a more limited thyroidectomy to avoid late postthyroidectomy hypothyroidism.
• Results of Tg antibody test are less frequently positive than those of microsomal antibody test in autoimmune thyroid disease.
• Tg antibodies may interfere with assay for serum Tg.

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• Thyroid receptor antibody test mainly used in Graves' disease, especially as a predictor of relapse of hyperthyroidism.

Increased In

• Occasionally positive in papillary-follicular carcinoma of thyroid, subacute thyroiditis (briefly), lymphocytic (painless) thyroiditis (in ~60% of patients).
• Primary thyroid lymphoma often yields very high titers; should suggest need for biopsy in elderly patient with a firm, enlarging thyroid.
• Positive in 7% of normal population, reaching peak of 15% in females in sixth decade
• Other autoimmune diseases (e.g., PA, RA, SLE, myasthenia gravis)

Thyroid Uptake of Radioactive Iodine (Raiu)

• See Table 13-3.
• A tracer dose of I or I is administered orally, and the radioactivity over the thyroid is measured at specific time intervals (e.g., 2–6 hrs and again at 24 hrs). The percentage of administered iodine in the thyroid is an index of thyroid trapping and organification of iodide.
• Normal uptake is 9–19% in 1 hr; 7–25% in 6 hrs; 5–30% in 24 hrs. Varies with local iodine intake. 40–70% of administered dose is excreted in urine in 24 hrs. Technetium 99 ( Tc) is a measure of thyroid trapping only.

Use

• Detect hyperthyroidism associated with low RAIU, e.g., factitious hyperthyroidism, subacute thyroiditis, struma ovarii
• Evaluate use of radioactive iodine therapy
• Determine presence of an organification defect in thyroid hormone production
• T suppression test. Administration of T causes less suppression of RAIU in the hyperthyroid patient than in the normal person; has been replaced by the TRH stimulation test.

Contraindications:

pregnancy, lactation, childhood.

Interferences

• Not valid for 2–4 wks after administration of antithyroid drugs, thyroid hormone, or iodides; the effect of organic iodine (e.g., radiographic contrast media) may persist for a much longer time.
• Because of widespread dietary use of iodine in the United States, RAIU should not be used to evaluate euthyroid state.
• Increased by
• Withdrawal rebound (thyroid hormones, propylthiouracil)
• Increased iodine excretion (e.g., diuretic use, nephrotic syndrome, chronic diarrhea)
• Decreased iodine intake (salt restriction, iodine deficiency)

Increased (>12%) In

• Graves' disease (diffuse toxic goiter)
• Plummer's disease (toxic multinodular goiter)
• Toxic adenoma (uninodular goiter)
• Thyroiditis (early Hashimoto's disease; recovery stage of subacute thyroiditis)
• TSH excess
• TSH administration
• TSH production by pituitary tumor (TSH >4 µU/mL) or other neoplasm
• Defective thyroid hormone synthesis
• Thyrotropin-producing neoplasms (e.g., choriocarcinoma, hydatidiform mole, embryonal carcinoma of testis)

Decreased (<3%) In

• Hypothyroidism (tertiary, secondary, late primary)
• Thyroiditis (late Hashimoto's; active stage of subacute thyroiditis; RAIU does not usually respond to TSH administration)

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• Thyroid hormone administration (T or T
• Therapeutic
• Factitious (RAIU is augmented after TSH administration)*
• Antithyroid medication
• Iodine-induced hyperthyroidism (Jod-Basedow)†
• Radiographic contrast media, iodine-containing drugs, iodized salt
• Graves' disease with iodine excess
• Ectopic hypersecreting thyroid tissue
• Metastatic functioning thyroid carcinoma*
• Struma ovarii*
• Use of certain drugs (e.g., calcitonin, thyroglobulin, corticosteroids, dopamine)

Thyroxine (T ), Free (Ft

See Table 13-3.

Use

• Gives corrected values in patients in whom total T is altered because of changes in serum proteins or in binding sites, e.g.,
• Pregnancy
• Drug use (e.g., androgens, estrogens, birth control pills, phenytoin [Dilantin])
• Altered levels of serum proteins (e.g., nephrosis)
• Monitoring restoration to normal range is only laboratory criterion to estimate appropriate replacement dose of levothyroxine because 6–8 wks are required before TSH reflects these changes.

Increased In

• Hyperthyroidism
• Hypothyroidism treated with T
• Euthyroid sick syndrome
• Occasional patients with hydatidiform mole or choriocarcinoma with marked hCG elevations may show increased FT , suppressed TSH, and blunted TSH response to TRH stimulation. Values return to normal with effective treatment of trophoblastic disease. Severe dehydration (may be >6.0 ng/dL).

Decreased In

• Hypothyroidism
• Hypothyroidism treated with T
• Euthyroid sick syndrome

Thyroxine, Total (T

See Tables 13-2 and , and Fig. 13-1.

Use

Diagnosis of hyperthyroidism

Increased In

• Hyperthyroidism
• Pregnancy
• Drug effects (e.g., estrogens, birth control pills, d-thyroxine, thyroid extract, TSH, amiodarone, heroin, methadone, amphetamines, some radiopaque substances for radiographic studies [ipodate, iopanoic acid])
• Euthyroid sick syndrome
• Increase in TBG or abnormal T -binding prealbumin

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• Familial dysalbuminemic hyperthyroxinemia—albumin binds T but not T more avidly than normal, causing changes similar to thyrotoxicosis (total T ~20 µg/dL, normal thyroid-hormone-binding ratio, increased FTI) but patient is not clinically thyrotoxic.
• Serum T >20 µg/dL usually indicates true hyperthyroidism rather than increased TBG.
• May be found in euthyroid patients with increased serum TBG.
• Much higher in first 2 mos of life than in normal adults.

Decreased In

• Hypothyroidism
• Hypoproteinemia (e.g., nephrosis, cirrhosis)
• Use of certain drugs (phenytoin, T , testosterone, ACTH, corticosteroids)
• Euthyroid sick syndrome
• Decrease in TBG

Normal Levels May Be Found in Hyperthyroid Patients with

• T thyrotoxicosis
• Factitious hyperthyroidism due to T (Cytomel)
• Decreased binding capacity due to hypoproteinemia or ingestion of certain drugs (e.g., phenytoin, salicylates)

Interferences

Various drugs

Not Affected by

• Mercurial diuretics
• Nonthyroidal iodine

Thyroxine Index, Free (Fti; T

• American Thyroid Association now recommends the term thyroid hormone–binding ratios (THBR).
• See Table 13-4.

Use

• This index is the calculated product of T resin uptake and serum total T . It permits correction of misleading results of T and T determinations caused by conditions that alter the T -binding protein concentration (e.g., pregnancy, use of estrogens or birth control pills).

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Thyroxine-Binding Globulin (Tbg)

Use

• Diagnosis of genetic or idiopathic excess TBG
• Sometimes used for detection of recurrent or metastatic differentiated thyroid carcinoma, especially follicular type and cases in which patient has had an increased level due to carcinoma.
• Differentiation of increased/decreased total T or T concentrations due to changes in TBG from normal free T or T . Same purpose as T resin uptake and FTI (see above).

Increased In

• Pregnancy
• Use of certain drugs (e.g., estrogens, birth control pills, perphenazine [Trilafon], clofibrate, heroin, methadone)
• Estrogen-producing tumors
• Acute intermittent porphyria
• Acute or chronic active hepatitis
• Lymphocytic painless subacute thyroiditis
• Neonates

Decreased In

• Nephrosis and other causes of marked hypoproteinemia such as liver disease, severe illness, stress (T -binding-prealbumin also decreased)
• Deficiency of TBG, genetic or idiopathic
• Acromegaly (T -binding-prealbumin also decreased)
• Severe acidosis
• Use of certain drugs
• Androgens, anabolic steroids
• Glucocorticoids (T4-binding-prealbumin is increased)
• Testosterone-producing tumors

Decreased Binding of T and T Due to Drugs

• Salicylates
• Phenytoin
• Tolbutamide (Orinase), chlorpropamide (Diabinese)
• Penicillin, heparin, barbital
• An increased TBG is associated with increased serum T and decreased T resin uptake; a converse association exists for decreased TBG

Thyrotropin-Releasing Hormone (TRH) Stimulation Test

• See Fig. 13-2.
• Serum TSH is measured before and 20 mins after IV administration of TRH (usually 500 or 200 µg).
• Normal response: a significant rise from a basal level of ~1 µU/mL by 8 µU/mL at 20 mins and return to normal by 120 mins. Response is usually greater in women than in men.
• Primary hypothyroidism: an exaggerated rise of an already increased TSH level
• Secondary (pituitary) hypothyroidism: no rise in the decreased TSH level
• Hypothalamic hypothyroidism: low serum T and T and TSH levels, with a TRH response that may be exaggerated or normal or (most characteristically) with a peak delay of 45–60 mins.
• Hyperthyroidism: TRH administration does not cause a significant rise in serum TSH in hyperthyroid patients as it does in normal persons; a normal rise (>2 µU/mL) virtually excludes hyperthyroidism. Absent response may also occur in exophthalmic Graves' disease and nodular goiter.

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• Blunted response may occur in uremia, Cushing's syndrome, acromegaly, effect of certain drugs (corticosteroids, levodopa, ‘large amounts of salicylates).
• Response may also be suppressed in nonthyroidal conditions (e.g., starvation, renal failure, elevated levels of glucocorticoids, depression, some elderly patients).
• The TSH response to TRH is modified by T antithyroid drugs, corticosteroids, estrogens, and levodopa. Response is increased during pregnancy.

Use

• Interpretation must be based on clinical studies that exclude the pituitary gland as the site of the disease.
• Now largely replaced by TSH.
• Confirmation of hyperthyroidism when other test results are equivocal. Lack of response shows adequate therapy in patients receiving thyroid hormones to shrink thyroid nodules and goiters and during long-term treatment of thyroid carcinoma.
• Differentiation of two forms (whether or not due to tumor) of thyrotropin-induced hyperthyroidism
• May be particularly useful in T toxicosis cases in which the other tests are normal or in patients clinically suspected of hyperthyroidism with borderline serum T levels. TRH stimulation test is superior to the T suppression test of RAIU. Abnormal TSH response to TRH administration does not definitely establish the diagnosis of hyperthyroidism (because autonomous production of normal or slightly increased amounts of thyroid hormones causes pituitary suppression). TRH test may remain abnormal even after successful therapy of Graves' disease.
• Hyperthyroid patients in whom associated nonthyroid conditions result in only slight elevation of serum T and T
• Euthyroid Graves' disease patients presenting with only exophthalmos (unilateral or bilateral). TRH stimulation test may sometimes be normal in these patients, and T suppression test may be required
• Elderly patients with or without symptoms of hyperthyroidism may have serum T and T in upper normal range.

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• Euthyroid sick syndrome. Generally serum TSH is normal with a relatively normal TSH response to TRH.
• May help differentiate hypothalamic from pituitary hypothyroidism (see previous section)

Baseline TSH (µU/mL) Change in TSH 30 Mins after TRH Administration (µU/mL) Euthyroidism <10 >2 (95% of cases) Hyperthyroidism <10 <2 Primary hypothyroidism >10 >2 (exaggerated) Secondary hypothyroidism <10 <2 Tertiary hypothyroidism <10 >2 (delayed or exaggerated or normal)

Triiodothyronine (T

See Table 13-3 and Fig. 13-1.

Use

• Diagnosing T thyrotoxicosis (TSH is suppressed but T is normal) or cases in which FT is normal in presence of symptoms of hyperthyroidism
• Evaluating cases in which FT is borderline elevated
• Evaluating cases in which overlooking diagnosis of hyperthyroidism is very undesirable (e.g., unexplained atrial fibrillation)
• Monitoring the course of hyperthyroidism
• Monitoring T replacement therapy—is better than T or FT4 but TSH is preferred to both.
• Predicting outcome of antithyroid drug therapy in patients with Graves' disease
• Evaluating amiodarone-induced thyrotoxicosis
• Serum T parallels FT4; is early indicator of hyperthyroidism but TSH is better.
• Good biochemical indicator of severity of thyrotoxicity in hyperthyroidism
• Not recommended for diagnosis of hypothyroidism; decreased values have minimal clinical significance.
• May decrease by ≤25% in healthy older persons, whereas FT4 remains normal.
• Free T gives corrected values in patients in whom the total T is altered because of changes in serum proteins or in binding sites, e.g.,
• Pregnancy
• Drugs (e.g., androgens, estrogens, birth control pills, phenytoin)
• Altered levels of serum proteins (e.g., nephrosis)

Triiodothyronine (T ) Resin Uptake

See Table 13-4.

Use

• Measures unoccupied binding sites on TBG. Is not a measure of T
• Only with simultaneous measurement of serum T to calculate T to exclude the possibility that an increased T is due to an increase in T4-binding globulin. Measurement of serum T concentration should be done by RIA for diagnosis of hyperthyroidism.

Increased In

See causes of decreased serum TBG.

Decreased In

See causes of increased serum TBG.

Normal In

• Pregnancy with hyperthyroidism
• Nontoxic goiter
• Carcinoma of thyroid

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• Diabetes mellitus
• Addison's disease
• Anxiety
• Use of certain drugs (e.g., mercurials, iodine)

Variable In

Liver disease

Diseases of the Thyroid

See Table 13-3.

Carcinoma of Thyroid

• Medullary carcinoma
• Sporadic (noninherited) accounts for 80% of cases
• Familial accounts for 20% of cases
• MEN type I.
• Most are MEN type II.
• Familial non-MEN.
• Basal serum calcitonin may be increased in patients with medullary carcinoma of the thyroid.
• Serum Tg levels are increased in most patients with differentiated thyroid carcinoma but not in undifferentiated or medullary carcinoma. May not be increased with small occult differentiated carcinoma. May be useful to detect presence and possibly extent of residual, recurrent, or metastatic differentiated carcinoma. Increased levels may be found in patients with nontoxic nodular goiter; presence of autoantibodies interferes with the test.
• Serum CEA may be increased in medullary carcinoma and may correlate with tumor size or extent of disease.
• Serum LD, CEA, and Tg may be increased in advanced follicular carcinoma.
• Serum T3, T4, and TSH are almost always normal in untreated patients. Rarely, evidence of hyperthyroidism may be found with large masses of follicular carcinoma.
• Laboratory findings due to associated lesions (e.g., pheochromocytoma and parathyroid tumors) (10–20% of cases of medullary carcinoma of thyroid occur as part of MEN) and due to production of additional substances (e.g., ACTH, serotonin, histaminase) by medullary carcinoma
• RAIU is almost always normal.
• Radioactive scan of thyroid
• Needle biopsy of thyroid nodule

Euthyroid Sick Syndrome (Nonthyroidal Illness)

• (Wide variety of nonthyroidal acute and chronic conditions such as infection, liver disease, cancer, starvation, renal failure, heart failure, severe burns, trauma, and surgery may be associated with abnormal thyroid function tests in euthyroid patients, especially in aged persons; artifactual changes in thyroid tests are not included in euthyroid sick syndrome.)
• No single test is clearly diagnostic, especially in elderly and acutely or severely ill patients
• See Table 13-5.
• Initial change in all nonthyroidal illness patients is decreased T with increased rT . With increasing severity, serum T declines, producing low T –low T state.
• Increased T syndrome is most common (≤20%) in acute psychiatric admissions, especially in the presence of certain drugs (e.g., amphetamines, phencyclidine) and in old age (≤15% of elderly patients); increased values tend to decrease during first 2 wks after admission as patient improves. Is rarer in acutely ill patients (e.g., those with acute hepatitis).
• Increased serum T , FTI, and T
• TSH is usually normal in mild to moderate illness.

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• TRH test often is not useful due to flat TSH response commonly seen in melancholia patients.
• 50% of patients with hyperemesis gravidarum show elevated total and sometimes free T that persist until hyperemesis abates. Patients with symptomatic hyponatremia show transient increase until low sodium is corrected.
• Decreased T Syndrome
• Occurs in >50% of patients with severe or chronic illness.
• TSH is transiently increased (few days or weeks) during recovery.
• Low T syndrome is the most common. Occurs in most illnesses, starvation, and after surgery or trauma. T is decreased in ~70% of hospitalized patients without intrinsic thyroid disease and is normal in 20–30% of hypothyroid patients; therefore T testing is not indicated.
• Increased rT
• With progressive illness, tendency is for fall in total T and TBG with increase of free T4. Thus T uptake increases, and FTI tend to remain normal. A strong correlation is seen between low T (<3 µg/dL) and high mortality in hospitalized patients.
• Serum TSH is typically normal or slightly increased; TSH response to TRH is usually normal.

In Neonates

• Occurs in ~2.5% of newborns, particularly in association with prematurity, obstetrical or neonatal stress or illness, postmaturity.
• Decreased serum T4.
• Decreased serum T3.
• Normal serum TSH.
• By age of 1 mo, serum T is normal in 98% of these infants.
• By age of 4 mos, if T is still decreased, two-thirds of cases are due to genetic TBG deficiency.

Goiter, Neonatal

Due To

• Maternal ingestion of iodine (e.g., for thyroid disease, for asthma), propylthiouracil
• Inherited hypothyroidism (diminished ability to synthesize thyroid hormones)
• Neonatal hyperthyroidism

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• Dyshormonogenesis
• Hemangioma, lymphangioma