Toxicants that Cause Goiter (9-Aug-1999)

Transcription

1 In: Veterinary Toxicology, V. Beasley (Ed.) Publisher: International Veterinary Information Service ( Ithaca, New York, USA. Toxicants that Cause Goiter (9-Aug-1999) V. Beasley Department of Veterinary Biosciences, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, USA. Chapter Sections Goitrogenic Substances Brassica and Related Genera Brassica spp. Goitrogenic Substances Specific Agents Major Species Usual Time of Onset Usual Duration (if survives) Iodine Horses Chronic Months Soybean (Glycine) (rare) Flax (See Toxicants that Inhibit the Function of Respiratory Pigments) linseed (Linum) Castor bean [See Plants that Affect the Gastrointestinal Tract, Lectins (Toxalbumins) ] (Ricinus) Sulfonamides (See Toxicants that Affect the Kidney) Full Table for Toxicants that Cause Goiter Introduction Goiter - Defined as any nonmalignant enlargement of the thyroid gland as a whole, may be accompanied by either hypo- or hyperthyroidism. the enlargement may be due to an increase in the amount of thyroid tissue (hyperplasia), or due to an increase in the amount of colloid causing a distension of acini. Inflammatory proliferation occurs less commonly. Hyperplastic goiter - Hyperplasia is the first morphologic response to iodine deficiency. With reduced thyroxine production the pituitary releases increased amounts of thyrotropic hormone, which is the stimulus for hyperplasia. Goitrogenic substances - Any substance which can lead to an increase in the size of the thyroid gland. Included in these are thiouracil (therapeutically used to treat hyperthyroidism), glucosinolates, cyanides, sulfocyanates, thiocyanates, and some sulfonamides. Certain plants are known to be goitrogenic when consumed. Included in these are soybeans and members of the Brassicas (cabbage, rape, kale, and turnips). Goitrogenic substances from these plants have been transmitted through the milk (glucosinolates). Cooking, heating, or processing (e.g., soybeans) destroys the goitrogenic substances in these plants. Glucosinolates are -D-thioglucoside glycosides found in members of the genus Brassica. The primary significance of glucosinolates in animal nutrition is that oils from these plants are occasionally used as protein supplements. The glucosinolates are hydrolyzed by the enzymes glucosinolase or thioglucosidase. The enzymes required for this activation are present in the plant and are produced by ruminal microorganisms. A major effect of the hydrolysis products of glucosinolates is inhibition of the thyroid gland. Antithyroid agents have 4 general effects: 1) they may interfere with iodine uptake by the thyroid gland (e.g., thiocyanate), 2) can interfere with tyrosine iodination, 3) suppress thyroxine secretion, or 4) function as a metabolic antagonist to thyroxine in the tissues. Colloid goiter (simple goiter) is characterized by enlargement and distension of the acini (which are filled with colloid). The colloid contains very little iodine and thyroxine, symptoms are those of hypothyroidism. Milder goitrogenic substances (e.g., soybeans) are likely to cause this type of goiter.

2 Iodine Deficiency Iodine deficiency results in hypothyroidism and goiter, especially affecting fetuses and neonates of deficient sows, cows, sheep, and goats. Primary iodine deficiency results from inadequate dietary intake of iodine. Conditioned iodine deficiency results from the ingestion of high levels of calcium or goitrogenic plants (e.g., members of the genus Brassica). Clinical Signs Iodine deficient cows have depressed reproductive function, e.g., increased anestrus. Cows, sheep, goats, and sows may resorb fetuses, abort, or produce stillborn or poorly viable offspring. Affected neonatal animals have complete or partial alopecia. Myxedema and decreased weight gain has been reported in piglets. Calves and lambs may have grossly enlarged thyroid glands. Death is common. Equine Goiter Due to Iodine Toxicosis Described (1968) in Thoroughbred mares and foals. Has been closely related to increased levels of iodine (due to the addition of dried seaweed). Measured dietary iodine levels were mg/day/mare. Iodine intake on a control farm (no evidence of thyroid enlargement) was estimated as mg/mare/day. Disease syndrome was predominately seen in foals; which were born weak and died in the early postnatal period. Thyroid glands were grossly enlarged. Several mares also had visible goiters. (Baker HJ, Lindsey JR. Equine goiter due to excess dietary iodide. J Am Vet Med Assoc 1968; 153: ) Other Goitrogens - Key Features Other goitrogens include: Soybeans (Glycine max) Of greater concern is trichloroethylene extracted soybean-oil-meal which exerts its effect on the bone marrow causing damage similar to that associated with bracken fern in cattle. Flax, linseed (Linum spp.) Of greater concern than the goitrogenic effect is the hydrogen cyanide content of flax (See Toxicants that Inhibit the Function of Cytochromes). Sulfonamides Of greater concern is the renal failure associated with sulfonamides. Castor bean (Ricinus).

3 Brassica and Related Genera, Brassica spp. (Rape - Canada - Cabbage, Kale, Mustards, Related Plants) B. hirta - White Mustard (Yellow) B. kaber - Charlock, Wild Mustard B. napobrassica - Rutabaga, Yellow Turnip, Swede Turnip B. napus - Rape (note rapeseed meal in brown in color) B. campestrus - Canola (note canola meal is yellow in color) B. oleracea var. acephala - Common Kale B. oleracea var. capitata - Cabbage B. oleraceai var. botrytis - Broccoli B. rapa - Turnip B. oleracea var. gemmifera - Brussel Sprouts B. nigra - Black Mustard B. juncea - Indian Mustard B. pekinensis - Chinese Cabbage Erysemum cheiranthoides - Wormseed Mustard Raphanus raphanastrum - Wild Radish Thlaspi arvense - Fanweed, Field Pennycress Barbarea vulgaris - Yellow Rocket, Wintercress Amoracia lapathifolia - Horseradish Major Species Usual Time of Onset Usual Duration (if survives) Full Table for Toxicants that Cause Goiter Horses Chronic Months Family - Cruciferae Images Brassica spp. Source: Cornell University, Poisonous Plants Informational Database ( - To view this image in full size go to the IVIS website at White mustard, yellow mustard, Brassica hirta - Google Image Search. - To view this image in full size go to the IVIS website at Charlock, wild mustard, Brassica kaber - Google Image Search. - To view this image in full size go to the IVIS website at Rutabaga, yellow turnip, swede turnip, Brassica napobrassica - Google Image Search. - To view this image in full size go to the IVIS website at Rape, Brassica napus - Google Image Search. - To view this image in full size go to the IVIS website at Canola, Brassica campestris - Google Image Search. - To view this image in full size go to the IVIS website at Common kale, Brassica oleracea var. acephala - Google Image Search. - To view this image in full size go to the IVIS website at Cabbage, Brassica oleracea var. capitata - Google Image Search. - To view this image in full size go to the IVIS website at Broccoli, Brassica oleracea var. botrytis - Google Image Search. - To view this image in full size go to the IVIS website at Turnip, Brassica rapa - Google Image Search. - To view this image in full size go to the IVIS website at Brussel sprouts, Brassica oleracea var. gemmifera - Google Image Search. - To view this image in full size go to the IVIS website at Black mustard, Brassica nigra - Google Image Search. - To view this image in full size go to the IVIS website at Indian mustard, Brassica juncea - Google Image Search. - To view this image in full size go to the IVIS website at Chinese cabbage, Brassica pekinensis - Google Image Search. - To view this image in full size go to the IVIS website at Wormseed mustard, Erysimum cheiranthoides - Google Image Search. - To view this image in full size go to the IVIS website at Wild radish, Raphanus raphanistrum - Google Image Search. - To view this image in full size go to the IVIS website at Fanweed, field pennycress, Thlaspi arvense - Google Image Search. - To view this image in full size go to the IVIS website at

4 Yellow rocket, wintercress, Barbarea vulgaris - Google Image Search. - To view this image in full size go to the IVIS website at Horseradish, Amoracia lapathifolia - Google Image Search. - To view this image in full size go to the IVIS website at Poisonous Principles Most serious problems arise from glucosinolates or their breakdown products. Glucosinolates are glycosides of B-D thioglucose. The aglycones of these compounds can yield an isothocyanate, thiocyanate, nitrile, or similar compound. Canola = at least some varieties such as Tower and Candle are reportedly low in glucosinolates and double zero varieties are low in both glucosinolates and erucic acid (B. campestrus) Isothiocyanate = causes severe gastroenteritis (B. hirta, B. kaber, B. napus, B. oleracea, B. nigra, B. juncea, Erysemum cheiranthoides, Raphanus raphanastrum, Thlaspi arvense, Barbarea vulgaris, Amoracia lapathifolia). Goitrogenic = due to goitrin (L-5-vinyl-2-thiooxazolidone), a breakdown product of glucosinolates. This compound inhibits incorporation of I into precursors of thyroxin and interferes with iodine secretion. Rapeseed or forage may cause thyroid enlargement, increased 131 I uptake by the thyroid, and decreased blood thyroid hormones in animals fed the milk of exposed lactating females. Placental transfer also can occur (B. napobrassica, B. napus, B. oleracea var. acephala, B. oleracea var. capitata, B. rapa, B. pekinensis) Hemolytic = due to S-methyl cysteine sulfoxide (B. napobrassica, B. oleracea var. gemmifera, B. napus, B. oleracea var. acephala, Thlaspi arvense) Nitrate = converted to nitrite in rumen (B. napus). Rapeseed may also cause pulmonary emphysema, reversible blindness, and hepatic necrosis which may be accompanied by photosensitization. The hepatic necrosis, as well as bile duct hyperplasia, and megalocytosis of the kidney tubular epithelium are believed to result from nitriles that may form from the glucosinolates in rapeseed meal (B. napus). Sources Forage and root brassicas are widely grown in Britain, and to a lesser extent in Canada, Sweden, and the USA to be used as winter feeds for cattle and sheep. Most serious economic problems in livestock seem to result from rapeseed meal. Note - Other glucosinolate-containing oil meals of minor economic importance include crambe, mustard, and limnanthes (meadow foam) meals. Glucosinolate Toxic Principles and Mechanisms of Action (Incompletely Worked Out)

5 Normal production of thyroxine from tyrosine Conversion of progoitrin to goitrin Susceptible Species Toxicity Poultry and swine fed raw rapeseed meal exhibit enlarged thyroids and growth depression. Liver hemorrhage in poultry fed rapeseed meal may be caused by nitrites. Swine may have enlarged livers when fed rapeseed meal. Levels of 5-10% rapeseed have been tolerated by nonruminants. Ruminants can tolerate 10% dietary rapeseed meal with no ill effects. "Double zero" varieties can be fed at much higher rates without reducing animal production.

6 Signs Problems of anemia and gastrointestinal upset are noted most often. Reproductive failure and goiter are more insidious. Scouring. Rumen stasis. Jaundice. Decreased milk production. Growth retardation. Poor conception, poor growth, enlarged thyroids; possibly due to antithyroid factors and anemia. Lesions Liver swollen, pale, or (in poultry fed rapeseed meal) hemorrhagic. Hepatic necrosis. Extensive hemosiderosis, e.g., spleen, kidney. Kidneys dark brown, renal tubular epithelial degeneration, hemosiderin deposition (hemolysis). Mustard Family, Cruciferae Wild Radish, Raphanus raphanistrum L. 1, upper part of plant with pods and flowers; 2, lower part of plant; 3, flower; 4, seedling plant; 5, pod with section. Annual or winter annual, reproducing by seeds. Stems erect, branching above, 1 to 3 feet (30 to 90 cm) tall, sparsely pubescent with stiff hairs, especially on lower parts. Leaves on lower stem with same type of pubescence, pinnately divided with a large rounded terminal segment. Upper leaves mostly undivided but with a few small segments. Flowers light yellow, shading into a whitish or purplish color, 1/2 inch (1.3 cm) in diameter, with 4 petals. Seed pods pithy and solid, 1 1/2 to 3 inches (3.8 to 7.5 cm) long, 1/8 inch (3mm) in diameter, at maturity breaking into segments containing seeds. Lower pods usually small and seedless. Seeds vary in size and shape but are usually oval, slightly flattened, light reddish-brown, and 3/16 inch (4.5 mm) in diameter. Found in small grain and flax crops, where it is serious; also common in wastelands. Pod segments containing seeds are hard to remove from seed grain.

7 Mustard Family, Cruciferae Field Pennycress, Thlaspi arvense L. 1, seed; 2, seed pod; 3, upper part of plant; 4, lower part of plant. Annual or winter annual, reproducing by seed. Stems, erect, 4 to 20 inches (10 to 50 cm) tall, simple or sometimes branched above, smooth throughout. Leaves alternate, simple, toothed, 1/2 to 2 inches (1.3 to 5 cm) long, clasping stem with earlike projections.. Flowers white with 4 petals, in racemes which lengthen greatly at maturity. Seed pod flat, circular, about 1/2 inch (1.3 cm) in diameter, 2-valved, broadly winged, with a deep, blunt notch at the top. Each pod contains several seeds. Seed dark reddish-brown to black, ovate in outline, flattened, about 1/16 inch (1.5mm) long with about 10 curved, granular ridges on each side. Found in small grains, legumes, and noncultivated areas. This weed imparts a bitter, garlicky flavor and odor to milk.

8 Mustard Family, Cruciferae Wild Mustard, Brassica Kaber (DC.) Wheeler. 1, lower part of plant; 2, upper part of plant; 3, leaf from upper part of stem; 4, flower cluster; 5, seed pods; 6, seed. Annual or winter annual, reproducing by seeds. Stems erect, branched near top, with a few bristly hairs. Leaves: lower ones irregularly lobed, toothed, with petioles and with bristly hairs; upper leaves smaller, often not lobed, alternate, with no petioles or short ones. Flowers conspicuous, with 4 yellow petals, in clusters at the end of branches. Seed pod slender, on a spreading stalk; 1 inch (2.5 cm) or more long, about 1/3 of length being an angular beak at the tip. Seeds round, black, bluish, or brown, smooth and hard, about 1/16 th inch (1.5mm) in diameter. Found commonly in grain fields and occasionally in other cultivated crops. A troublesome weed in many areas. Seeds live in the soil for many years. Also commonly known as charlock.

9 Mustard Family, Cruciferae Indian Mustard, Brassica juncea (L.) Coss. 1, seed pod; 2, lower leaf; 3, upper part of plant. Annual or winter annual with taproot. Stems smooth, erect, usually growing 2 to 3 feet (60 to 90 cm) tall. Leaves: upper ones short-petioled, lance-shaped, tapering gradually from a broad base; lower ones petioled, deeply lobed, leaf margins coarsely toothed. Flowers yellow, with 4 petals. Seed pods 1 to 2 inches long, tips conical. Seeds rounded, reddish-brown, surface pitted. Found in small grain and legume fields. Black Mustard, Brassica Nigra (L.) Koch. 4, seed pod; 5, lower leaf; 6, upper part of the plant. Annual, with taproot. Stems, erect, branched, growing commonly between 3 and 6 feet (0.9 and 1.8 m) tall; lower parts somewhat hairy. Leaves also somewhat hairy. Upper leaves narrow with elongated petiolelike base. Lower leaves petioled, divided, wth large terminal lobe, leaf margins fine-toothed. Flowers yellow, with 4 petals. Seed pods 1/2 to 3/4 inch (1.3 to 1.9 cm) long, lying along stem. Seeds somewhat oval, dark reddish-brown, their suface pitted. Found commonly in waste areas and fields.

10 Mustard Family, Cruciferae Yellow Rocket, Barbarea Vulgaris R. Br. 1, upper part of plant; 2, lower part of plant; 3, pods; 4, flower; 5, seed; 6, root. Winter annual, biennial, or perennial, reproducing by seed, taprooted. Stems numerous, growing from a crown, upright, 1 to 2 feet (30 to 60 cm) tall, branched near top, smooth, and angular or rided. Leaves pinnately divided; basal leaves have a large termianl lobe, are 2 to 8 inches (5 to 20 cm) long, and form a dense rosette; stem leaves become progessively shorter with top leaves about 1 inch (2.5 cm) long and less deeply lobed. Flowers bright lemon-yellow, 4-petaled (typical mustard flower), borne in spikelike racemes on end of each branch. Bloom in late April and early May. Pods about 1 inch (2.5 cm) long, about 3/32 inch (2.4 mm) in diameter, nearly square in cross section. Seeds light yellow to yellowish-brown, 1/32 inch (0.8 mm) long, ripening in May and early June. Found along roadsides, in pastures, and in timothy, clover, and alfalfa fields, where it matures before the crop is cut. Seeds live several years in the soil. Also known as winter cress. All rights reserved. This document is available on-line at Document No. A