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In this lecture, we're going to talk about thyroid and parathyroid testing. Now, before we begin, we need to kind of do a quick review of pituitary-hypothalamus axis. And then we're going to talk about the hypothalamic-pituitary-thyroid axis. Now remember, the hypothalamus has a number of releasing factors that go down to either the anterior pituitary or the posterior pituitary. And they trigger the release of those pituitary hormones.
From the posterior pituitary, we have two things-- antidiuretic hormone and oxytocin. From the anterior pituitary, we produce TSH, which we're going to talk about related to thyroid disease; ACTH for the adrenal cortex; FSH and LH in females and males-- the gonads; prolactin for breast; and growth hormone for multiple tissues in the body for growth and development of bone. So everything starts with releasing factors from these hypothalamus and then to the anterior pituitary.
Now in a lot of pituitary-hypothalamus axis, the more that produce the end product here, like T3-- that has a negative feedback on shutting down the release of the releasing factor from the hypothalamus. And that's what keeps all of these hormone levels in such tight control. |
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So this is an example more focusing on just the hypothalamic-pituitary-thyroid axis. In this case, you have thyrotropin-releasing hormone from the hypothalamus. That affects the pituitary to release thyroid-stimulating hormone. This has an effect on the thyroid gland to release and have the production of T4 and T3.
Now, the levels of T3 and T4, as they go up, they come back to the pituitary-- here's that negative-feedback loop-- and shut down the production of TSH. So as T3, T4 go up, that shuts down TSH. Then that will decrease T3, T4, which will then stimulate production as the levels get too low of more TSH. So it keeps these hormones down here in a very tight control. |
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• Synthesizes hormones from iodine and tyrosine (amino acid) • Iodine enters through alimentary tract • In thyroid gland, iodine incorporated into mono- and di-iodotyrosine, which are building blocks for active hormones - Thyroxine—T4 - Triiodothyronine—T3 |
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• Thyroxine (T4) • Triiodothyronine (T3) • Reverse T3 Now the only difference is the number of iodine molecules-- 1, 2 3, 4; 1, 2, 3. The only thing that separates the difference between T3 and reverse T3 is the location of that third iodine molecule. That's the only difference. |
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• More T4 than T3 in serum • T4 converted to T3 by removal of one iodine residue (in peripheral tissues) • T3 more significant physiologically—exerts majority of thyroidal hormone effects • T4 half-life = one week • T3 half-life = one day |
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Thyroid Hormone Circulation |
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• Thyroid hormones are bound to thyroid-binding globulin, albumin, or prealbumin in plasma - Free T4 is 0.03% of total T4 - Free T3 is 0.30% of total T3 • TBG is increased by estrogen, decreased by androgen |
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Most Common Thyroid Tests |
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• TSH—thyroid stimulating hormone—is best measure of thyroid function • Total T4 (thyroxine)—approximates the functional status of the thyroid gland • Total T3 (triiodothyronine)—measures active thyroid hormone • Free T4 (FT4)—measures physiologically active thyroid status • T3 uptake—labeled T3 binds to TBG—inversely proportional to amount of endogenous hormone already bound—amount of labeled T3 remaining is measured • Free Thyroxine Index (FTI or T7) - Serum total T4 x value of T3 uptake OR - Serum total T4 x T3 uptake/normal T3U uptake |
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Effects of Thyroid Hormones |
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• Control of oxygen consumption—measured by basal metabolic rate • Carbohydrate and protein metabolism • Mobilization of electrolytes • Conversion of carotene to vitamin A • Development of CNS (mechanism not well known) |
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Thyroid hormones affect synthesis, degradation, and intermediate metabolism of adipose tissue and circulating lipids • Hyperthyroidism - Degradation and excretion > synthesis • Low levels of cholesterol, phospholipids, triglycerides • Hypothyroidism - Slows catabolism > synthesis • High levels of cholesterol and triglycerides |
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• ↑ cholesterol, triglycerides • ↑ serum carotene • ↑ muscle enzymes • ↑ serum prolactin • Normochromic anemia • ↑ capillary fragility • ↑ spinal fluid protein • ↓ urinary excretion of 17- KS, 17-OHCS (adrenal) |
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• ↑ skin temp, pulse rate, pulse pressure • ↓ cholesterol, triglycerides • ↑ aminotransferases and alkaline phosphatase • Altered glucose insulin relationship • ↑ lymphocytes in diff • ↑ urinary calcium excretion |
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Hypothyroid (Myxedema) labs |
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• TSH ↑ (> 3x normal) - Exception: when hypothyroidism results from pituitary dysfunction • Serum T4 ↓ • T3 uptake ↓ • Serum T3 (no diagnostic value) - T3 normal in 20–30% of hypothyroid cases - T3 low in nonthyroid cases • Free Thyroxine Index ↓ |
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Hyperthyroid thyroid labs |
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• TSH ↓ • Serum T4 ↑ • Serum T3 ↑ • T3 uptake ↑ • Free T4 and Free Thyroxine Index ↑ ↑ • Subclass of hyperthyroidism: - T3 thyrotixicosis • Normal T4 and FTI, but ↑ T3 levels |
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Screening for Thyroid Disease |
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• Not recommended to screen all patients - The USPSTF concludes the evidence is insufficient to recommend for or against routine screening for thyroid disease in adults. • All females 50 years of age or older seeking medical care • All geriatric inpatients on admission, then every 5 years • Any patient >50 years old seeking treatment for other-than-minor illness, then every 5 years • All adults with newly diagnosed dyslipidemia |
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Now, we have a lot of effects here through the parathyroid, calcitonin. This is just kind of a schematic. It's kind of an introduction. What I want to get to is the effects of parathyroid hormone. |
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Effects of Parathyroid Hormone |
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• Mobilizes Ca and phosphate from bone • ↑ Phosphate excretion by ↓ renal phosphate reabsorption • ↓ Calcium excretion by ↑ renal calcium reabsorption • ↓ Renal H+ secretion, ↑ HCO3- excretion and Cl- retention • Enhances renal hydroxylation of vitamin D3 • ↑ Calcium absorption from gut, through effect on 1,25-(OH)2D3 |
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Parathyroid Laboratory Testing |
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• Parathyroid hormone (PTH) - C-terminal/midregion PTH—biologically nonfunctional— half-life 1–2 hours - N-terminal/intact PTH—active molecule—half-life of 5–10 minutes • Phosphorus—measured as phosphate • Calcium—both protein bound and free calcium (ionized) |
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• Exists in body in three forms - Bound to albumin: 50% - Complexed to phosphates: 3% - Free—ionized: 47% • Physiologically active form • If albumin is low, must correct calcium - (Ca – Alb) + 4 = corrected total calcium |
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Bone Metabolism Tests (Osteoblastic Activity) |
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• Hydroxyproline—serum and urine levels rise with increased bone resorption; used as an index of dissolution • Alkaline phosphatase—enzyme associated with osteocyte activity; used as an index of bone deposition • Osteocalcin—bone matrix protein; vitamin-K dependent protein that binds calcium • Osteoporosis assessed clinically by bone mineral density (BMD)—indicates how much calcium in bone (effective over long periods of time) • New bone-specific degradation products • -N-telopeptides (NTx) • From collagen fibers - Deoxypyridinoline dross links (Dpd) • Formed between collagen fibers • Repeat measurements effective in monitoring response to therapy after 2–3 months |
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Other Tests Involved in Calcium Metabolism |
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• Vitamin D and metabolites (increases absorption of dietary calcium and phosphorus) - 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) - 25 hydroxycholecalciferol (25-(OH)D3) • Calcitonin (inhibits osteoclasts so that calcium is laid down but not resorbed) - Since produced by thyroid (chief cells), measurement can help evaluate medullary CA of thyroid |
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Calcium metabolism testing |
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