Case History and Findings

For the past 7 years, tank-raised Lake Tanganyikan cichlids in a large-scale private spawning operation have acquired progressively-growing gray/pink lobular soft-tissue masses that protrude from under opercula. Fish are affected young, may otherwise appear clinically normal for months to years, and will even breed successfully. Economic loss occurs due to cosmetic deformity in large numbers of fish. Historically, some affected fish eventually become dyspneic, lethargic, develop body swellings, and gradually waste away.

The New York breeder of these fish has observed the sub-opercular masses in juveniles and adults of egg-scattering species of the genera Neolamprologous, Julidochromis, and Chalinochromis. Tanganyikan mouth-brooders, Lake Malawi cichlids, and Lake Victoria cichlids are generally unaffected, and may be housed with affected fish for prolonged periods without exhibiting growths. Juvenile fish of susceptible species purchased from other hatcheries often incur this problem in the breeders' tanks, without parallel development of the growths in the source population. Suspecting a thyroid disorder, select species have been receiving supplemental iodine for several years. Supplementation appears to decrease the incidence of sub-opercular masses in fry fish. Established growths are not abated by therapy.

Following the donation and humane sacrifice of two clinically affected fish, necropsy and histopathologic evaluation of tissues were performed. The microscopic appearance of a large sub-opercular mass from an adult Neolamprologous nigroventrus was consistent with adenomatous thyroid hyperplasia. In contrast, a grossly similar lesion in an adult male Neolamprologous forcifer was diagnosed as severe multifocal granulomatous thyroiditis with intralesional acid-fast bacterial rods. The bacilli were morphologically consistent with Mycobacterium sp. Attempts to culture and speciate acid-fast bacilli from eight additional fish from the colony were unsuccessful.

Including the 8 fish that were cultured, 10 fish of three different genera were sacrificed and necropsied. Findings included: thyroid hyperplasia(9), low numbers of visceral granulomas(3), pharyngitis/branchitis(3), hepatic lipidosis(2), granulomatous colitis with coccidia(2), intrahepatic or renal lipomas(2), muscle atrophy(1), ascites(1), hepatomegaly(1), and steatitis(1). Acid-fast bacilli could be identified histologically in only one of the visceral granulomas. In addition to pharyngeal thyroid hyperplasia, one fish had a nodule of well-differentiated thyroid tissue in a kidney, and a second larger encapsulated mass of thyroid tissue in the mid to caudal abdomen.

Goiter

Broadly defined, goiter is any focal or diffuse non-neoplastic thyroid enlargement. Therefore, causes of goiter in many species of animals and man can include:

1.  Epithelial hyperplasia, which refers to proliferation of the thyroid parenchyma.

2.  Colloid accumulation, which in some cases occurs secondary to long-term hyperplasia.

3.  Infiltrative disease, such as the mycobacterial infection in this case.

Mycobacteriosis in Fish

Mycobacteria are gram-positive, acid-fast non-motile non-encapsulated pleomorphic bacilli. The most common isolates in fish are Mycobacterium marinum and Mycobacterium fortuitum. Piscine tuberculosis is observed worldwide in both fresh and saltwater cultivated fish, and in wild marine fish. It has been demonstrated that both the fishes' environment and the fish themselves may serve as reservoirs of infection.

Clinical signs of mycobacteriosis in fish include emaciation, anorexia, dermal ulcerations, pigment alterations, fin rot, exophthalmos and deformities of the vertebral column or mandible. Diagnosis is by acid-fast staining of a cytologic preparation, culture on special media, or histopathology. PCR is available for M. fortuitum in this country, and recent paper from Israel reports detection of M. marium by polymerase chain reaction. At present, culture is usually necessary to speciate the organisms, and possibly to differentiate them from Nocardia asteroides. Attempts to treat affected fish with various antimicrobial agents have been less than universally successful. Standard recommendations are to cull affected fish whenever possible, and to decrease the density of stocking conditions to reduce stress and to reduce the spread of the agent by cannibalism. Both of the Mycobacterium species discussed harbor the potential for zoonotic disease in humans, especially in immunosuppressed individuals.

Thyroid Hyperplasia in Fish

Thyroid hyperplasia was first reported in brook trout in 1910. In most teleosts, normal thyroid tissue is diffuse, therefore hyperplastic glands were often initially confused with neoplasia. Thyroid hyperplasia can be caused by almost any process that results in decreased secretion of the thyroid hormones thyroxidine (T4), and triiodothyronine (T3). Decreased blood levels of thyroid hormones results in decreased inhibition at the level of the hypothalamus and pituitary, leading to increased secretion of thyroid stimulating hormone. Elevated blood levels of thyroid stimulating hormone in turn stimulate thyroid epithelial cell proliferation, and promote the release of stored colloid in the form of thyroid hormones. In fish, causes of decreased thyroid hormone secretion include:

1.  Decreased iodine intake. In food or water.

2.  Goitrogenic substances. In animals, these chemicals may decrease thyroid hormone production by interference with a number of different mechanisms, including: iodine uptake, thyroglobulin synthesis, thyroid hormone release, thyroid hormone deiodinization, and the acceleration of hepatic thyroid hormone metabolism.

Additionally, iodine excess and hereditary enzyme deficiencies have been identified as causes of thyroid hyperplasia in animals.

Summary and Conclusions

The identification of two separate disease processes responsible for identical gross lesions in the first two fish examined represented a unique presentation and posed diagnostic challenges. There were several conclusions and unanswered questions at the end of this case:

1.  From the limited amount of data (0.4% of the adult fish population sampled), the results suggest that the goiter problem within this colony is generally caused by thyroid hyperplasia rather than granulomatous thyroiditis.

2.  Mycobacteriosis most likely exists as an endemic infection in this colony that occasionally manifests as clinical disease within individual fish under certain circumstances.

3.  The sub-opercular thyroid proliferations are probably hyperplastic rather than neoplastic based upon tissue morphology and biologic behavior. Whether the additional thyroid growths observed in one of the fish represents neoplastic metastasis or multicentric hyperplasia is unknown.

4.  The pathogenesis the thyroid hyperplasia in this colony is undetermined. Causes to consider include insufficient iodine intake, the presence of goitrogenic substances in the food or water, and iodine toxicity. Further workup of this problem could include the measurement of iodine levels in the flesh, food, and water of supplemented fish versus appropriate controls, and a search for goitrogenic substances such as pesticide or fertilizer residues in the water supply.

References

1.  Lightner, D.V. & Fontaine, C.T. 1975. A Mycosis of the American Lobster, Homarus americanus, caused by Fusarium sp. Journal of Invertebrate Pathology 25, 239-245.

2.  Daoust, PY, Larson, BE, Johnson, GR. Mycobactedosis in yellow perch (perca flavacens) from two lakes in Alberta. Journal of Wildlife Diseases, 1989;25(l);31-37.

3.  Giawnni, R, et. al. Tuberculosis in marine tropical fishes in an aquarium. Journal of Wild Dis, 1980;16(2);l 61-168.

4.  Hedrick, RP, McDowell, T, Groff, J. Mycobacteriosis in cultured striped bass from California. Journal of Wildlife Diseases, 1987;23(3);391 -395.

5.  Hoover, KL. Hyperplastic thyroid lesions in fish. Natl Cancer Inst Monogr, 1984,65;275-289.

6.  Jubb, KVF, et.al. Pathology of Domestic Animal., Fourth Edition. Academic Press, In., 1993:315-321.

7.  Knibb, W et.al. Detection and identification of a pathogenic marine Mycobacterium from the European sea bass Dcentrarchus labrax using polymerase chain reaction and direct sequencing of 16S rDNA sequences. Mol Mar Biol Bitechnol, 1993;2(4);225-232.

8.  Mycobacterial infections of animals: pathology and pathogenesis. Laboratory Animal Science, 1995;45(4);334-351.

9.  Noga, EJ, Dykstra, MJ, Wright, JF. Chronic inflammatory cells with epithelial cell characteristics in teleost fishes.

10. Noga, EJ, Wright, JF, Pasarell, L. Some unusual features of Mycobacteriosis in the cichlid fish Oreochromis mossambicus. Journal of Comparative Pathology, 1990; 102; 335-344.

11. Nutrient Requirements of Fish. National Academy Press, 1993:21,39.

12. Pandey, AK, Batatacharya, L. Insecticide-induced inhibition of thyroid activity in the fish Oreochromis mossambicus and recovery in insecticide-free water. Funct Dev Morphol, 1991; 1 (4);l 5-19.

13. Ram, RN, Joy, KP, Sathyaneson, AG. Cythion-induced histophysiological changes in thyroid and thyratrophs of the teleost fish, Channa punctatus (Bloch). Ecotoxicol Environ Safety, 1989;1 7(3);272-278.

14. Ram, RN, Sathyanesan, AG. Histopathological changes in liver and thyroid of the teleost fish, Channa punctatus (Bloch), in response to ammonium sulfate fertilizer treatment. Ecotoxicol Environ Safety, 1987,13(2);185-190.

15. Ribelin, MigaW. Pathology of Fishes. University of Wisconsin Press, 1975:12,84-87.

16. Snieszko, SF. Mycobacteriosis (tuberculosis) of fishes. Fish Disease Leaflet 55, U.S. Fish and Wildlif. Service, 1978.

17. Stoskopf, MK Fish Medicine. W.B. Saunders Co., 1993: 12,43,215-216, 356-357,429,559-561, 815-816.

18. Timur, G, Roberts, RJ. The experimental pathogenesis of focal tuberculosis in the plaice (Pleuronectes platessa L.). Journal of Comparative Pathology, 1977;87(l);83-87.

19. vanDiujn, C Jr. Tuberculosis in fishes. J Small Anim Pract, 1981;22(6);391-411.