Thyroid hormone regulates a variety of biochemical reactions in virtually all tissues. Thus, ideally, the adequacy of hormonal supply should be assessed by the tissue responses rather than by parameters of thyroid gland activity or serum hormone concentration which are several steps removed from the site of thyroid hormone action. Unfortunately, the tissue responses (metabolic indices) are nonspecific because they are altered by a variety of physiologic and pathologic mechanisms unrelated to thyroid hormone deprivation or excess. The following review of biochemical and physiologic changes mediated by thyroid hormone has a dual purpose: (1) to outline some of the changes that may be used as clinical tests in the evaluation of the metabolic status, and (2) to point out the changes in various determinations commonly used in the diagnosis of a variety of nonthyroidal illnesses, which may be affected by the concomitant presence of thyroid hormone deficiency or excess.
The BMR has a long history in the evaluation of thyroid function. It measures the oxygen consumption under basal conditions of overnight fast and rest from mental and physical exertion. Since standard equipment for the measurement of BMR may not be readily available, it can be estimated from the oxygen consumed over a timed interval by analysis of samples of expired air.190 The test indirectly measures metabolic energy expenditure or heat production.
Results are expressed as the percentage of deviation from normal after appropriate corrections have been made for age, sex, and body surface area. Low values are suggestive of hypothyroidism, and high values reflect thyrotoxicosis. The various nonthyroidal illnesses and other factors affecting the BMR, including sources of errors, have been reviewed.191 Although this test is no longer a part of the routine diagnostic armamentarium, it is still useful in research.
Delay in the relaxation time of the deep tendon reflexes, visible to the experienced eye, occurs in hypothyroidism. Several instruments have been devised to quantitate various phases of the Achilles tendon reflex. Although normal values vary according to the phase of the tendon reflex measured, the apparatus used and individual laboratory standards, the approximate adult normal range for the half-relaxation time is 230-390 msec. Diurnal variation, differences with sex, and changes with age, cold exposure, fever, exercise, obesity, and pregnancy have been reported. However, the main reason for the failure of this test as a diagnostic measure of thyroid dysfunction is the large overlap with values obtained in euthyroid patients and alterations caused by nonthyroidal illnesses.192
Thyroid hormone induced changes in the cardiovascular system can be measured by noninvasive techniques. One such test measures the time interval between the onset of the electrocardiographic QRS complex (Q) and the arrival of the pulse wave at the brachial artery, detected by the Korotkoff sound (K) at the antecubital fossa.193 Related tests which determine the systolic time interval (STI) measure the preejection period (PEP), obtained by subtraction of the left ventricular ejection time (LVET) from the total electromechanical systole (Q-A2).194 The left ventricular ejection time (LVET) which is also affected by the thyroid status can be measured by the M mode echocardiogram195 (Figure 6-5). The PEP/LVET ratio is also useful in the assessment of thyroid hormone action in the cardiovascular system.196 As with other tests of thyroid hormone action, the principal deficiency of these measurements is their alteration in a variety of nonthyroidal illnesses.
| Figure 6-5: Simultaneous tracings of electrocardiogram (ECG), phonocardiogram, carotid pulse and echocardiogram. Measurements of the systolic pre-ejection period (PEP), isovolemic contraction time (ICT), left ventricular ejection time (LVET) and isovolumic relaxation time (IVRT) are indicated. (From I Kline, The thyroid, L.E. Braverman & R.D. Utiger (eds). 1991, J.B. Lippincot Co.) |
Thyroid hormone affects the function of a variety of peripheral tissues. Thus, hormone deficiency or excess may alter a number of determinations used in the diagnosis of illnesses unrelated to thyroid hormone dysfunction. Knowledge of the determinations which may be affected by thyroid hormone is important in the interpretation of laboratory data (Table 6-7).
Table 6-7.
Biochemical and Physiologic Changes Related to Thyroid Hormone Deficiency and Excess
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| Entity Measured | During Hypothyroidism | During Thyrotoxicosis |
| Metabolism of various substances and drugs Fractional turnover rate (antipyrine,197 dipyrone,198 PTU, and methimazole,197 albumin,199 low-density lipoproteins,200 cortisol,201,202 and Fe203,204 ) |
- | + |
Serum
|
- | + |
| Glutamic acid205 | N | + |
| Proteins | ||
| Albumin207 | - | - |
| Sex hormone- binding globulin14,208,209 | - | ++ |
| Ferritin210,211 | - | + |
| Low-density lipoproteins200 | - | + |
| Fibronectin212 | + | |
| Factor VIII-related antigen212 | + | |
| Tissue-plasminogen activator212 | + | |
| TBG83 | + | - |
| TBPA213 | N | - |
| Hormones | ||
| Insulin | ||
| Response to glucose214 | - | - |
| Response to glucagon215 | + | - |
| Estradiol-17ß216 , testosterone14,208,216 and gastrin217 | - or N | + |
| Parathyroid hormone concentration218,219 | + | - |
| Response to PTH administration219 | - | + |
| Calcitonin220 | - | + |
| Calcitonin response to Ca++ infusion221 | - | |
| Renin activity and aldosterone222,223 | - | + |
| Catecholamines224 and noradrenaline225 | + | + |
| Atrial naturetic peptide226,227 | - | + |
| Erythropoietin204 | N or - | + |
| LH216 | N or + | |
| Response to GnRH228 | + | N |
| Prolactin and response to stimulation with TRH, arginine, and chlorpromazine229,230 | + or N | - |
| Growth hormone | ||
| Response to insulin231,232 | - | N or - |
| Response to TRH233 | No change | |
| Epidermal growth factor234 | ||
| Enzymes | ||
| Creatine-phosphokinase,235,236 lactic dehydrogenase,236 and glutamic oxaloacetic transminase236 | + | - |
| Adenylate kinase237 | N | + |
| Dopamine ß-hydroxylase238 | + | - |
| Alkaline phosphatase219,239 a | a | + |
| Malic dehydrogenase240 | ++ | + |
| Angiotensin-converting enzyme,212,241 alanine aminotransferase,242 and glutathione S-transferase242,243 | N | + |
| Coenzyme Q10244 | ||
| Others | ||
| 1,25,OH-vitamin D3245 | - | |
| Carotene, vitamin A246 | ||
| cAMP,247 cGMP,248 and Fe203,249 | + N or - |
- N or + |
| K250 | - | |
| Na251 | - | |
| Mg252 | + | - |
| Ca219,253 | - | + |
| P218,219 | + | |
| Glucose | ||
| Concentration215,231 | - | + |
| Fractional turnover during iv tolerance test214 | - | |
| Insulin hypoglycemia231 | prolonged | |
| Bilirubin254,255 | +b | + |
| Creatinine256 | N or + | - |
| Creatine256 | N or + | + |
| Cholesterol,246,257 carotene,246,257 phospholipids and lethicin,246,257 and triglycerides257,258 | + | - |
| Lipoprotein (a)259 | + | - |
| Apolipoprotein B259 | + | - |
| Type IV collagen260 | + | + |
| Type III Pro-collagen 260 | - | + |
| Free fatty acids261 | + | |
| Carcinoembryonic antigen262 | + | |
| Osteocalcin220 | - | + |
| Urine | ||
| cAMP263 | - | + |
| after epinephrine infusion264 | No change | + |
| cGMP248 | N or - | + |
| Mg,252 | - | + |
| Creatinine256 | N | - |
| Creatine256 | N | + |
| Tyrosine206 | N or - | + |
| MIT (after) administration of 131IMIT265 | + | |
| Glutamic acid206 | N | ++ |
| Taurine266 | - | |
| Carnitine267 | - | + |
| Tyramine, tryptamine, and histamine268 | + | |
| 17-hydroxycorticoids and ketogenic steroids269 | - | + |
| Pyridinoline (PYD), deoxypyridinoline (DPD)270 | + | |
| Hydroxyproline,271 and hydroxylysyl glycoside272 | + | |
| Red blood cells | ||
| Fe203,249 | - | + |
| Na273 | N | + |
| Zn274 | N | - |
| Hemoglobin203,249 | - | - |
| Glucose-6-phosphate dehydrogenase activity275 | N or - | + |
| Reduced glutathione276 and carbonic anhydrase277 | + | - |
| Ca-ATPase activity278 | - | - |
| White blood cells | - | - |
| Alkaline phosphatase279 | ||
| ATP production in mitochondria280 | ?+ | - |
| Adipose tissue | N | - |
| cAMP247 | ||
| Lipoprotein lipase258 | ||
| Skeletal muscle | ||
| cAMP247 | + | |
| Sweat glands | - | + |
| Sweat electrolytes281 | + | N |
| Sebium excretion rate282 | - | N |
| Intestinal system and absorption | ||
| Basic electrical rhythm of the duodenum283 | - | + |
| Riboflavin absorption284 | -a | |
| Ca absorption285 | +a | - |
| Intestinal transit and fecal fat286,287 | - | |
| Pulmonary function and gas exchange | ||
| Dead space,288 hypoxic ventilatory drive,289 and arterial pO2288 | - | |
| Neurologic system and CSF | ||
| Relaxation time of deep tendon reflexes (phomotogram)290 | + | - |
| CSF proteins291 | + | |
| Cardiovascular and circulatory system | ||
| Timing of the arterial sounds (QKd)193 | + | - |
| Left ventricular ejection time (LVET), preejection period (PEP) ratio194 | - | - |
| ECG292,293 | ||
| Heart rate and QRS voltage | + | |
| Q-Tc interval | - | - |
| Pr interval | + | |
| T wave | Flat or inverted | Transient abnormalities |
| Common arrhythmias | Atrioventricular block | Atrial fibrillation |
| Bones | ||
| Osseous maturation (bone age by X-ray film)294,295 | Delayed (epiphysial dysgenesis) | Advanced |
| N = normal; + = increased; - = decreased. aIn children bIn neonates. |
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