Abstract

We describe a case of overt primary hypothyroidism in a 26-year-old captive-born female western lowland gorilla. This animal presented with a long history of nonspecific clinical signs including weight gain, unsettled appetite, anxiety-like behavior, lethargy, and poor intraspecies interactions. Compared with clinically normal gorilla and human reference values, its thyroid-stimulating hormone (TSH) level (107 mIU/L) was markedly elevated, and its thyroxine (T₄) (<14.0 nmol/L) and free T₄ (5.0 pmol/L) levels were significantly lower. Oral supplementation with levothyroxine sodium was associated with weight reduction (-16%), and with an increase in its daily activity and interactions with the other members of the group. Levels of circulating TSH were monitored to access the effect of the levothyroxine supplementation on the thyroid homeostasis. TSH levels estimated by human-TSH assays seem to be a good indicator of thyroid function in gorillas. An initial dosage of 50 µg/day of levothyroxine, with increments of 25 µg/day at monthly intervals up to a dosage of 100 µg/day, is proposed as starting regimen for hypothyroid gorillas.

Introduction

Hypothyroidism, the most common disorder of thyroid function in humans, is associated with a wide range of subtle clinical signs.² The condition is uncommon in nonhuman primates. The most important diagnostic aid in the clinical evaluation of thyroid function in humans and dogs is the estimation of circulating thyroid-stimulating hormone (TSH).^3,13 Even though such assays are species-specific, TSH of some nonhuman primates can be detected by human-TSH assays.^1,9 We describe here the use of a human-TSH assay in the clinical investigation of hypothyroidism in a female western lowland gorilla (Gorilla gorilla gorilla).

Case Report

A 26-year-old captive-born female western lowland gorilla has been housed at the Metropolitan Toronto Zoo since 1974. The gorilla gave birth successfully 13 years ago, but has not displayed any further breeding activity. Various signs have been noticed by keepers over the last 3 years including weight gain, unsettled appetite, lethargy, anxiety-like behavior, and poor intraspecies interactions. In addition, a “head-holding” behavior has been observed regularly. No major illness has been recorded since its arrival, but bilateral swellings in the axillary areas were first reported in February 1995. On July 25, 1996, a general physical examination, including thoracic and abdominal radiographs, ultrasound, intradermal TB testing, and standard blood work was performed under general anesthesia. The only significant clinical finding was moderate obesity characterized by a 5.5% weight gain in the last 3 years, a somewhat distended abdomen, and an excessive amount of subcutaneous and abdominal fat revealed by ultrasonography. No fluid nor material could be retrieved from transcutaneous aspirations of the axillary swellings, which were later believed to be associated with the accumulation of fat. Levels of TSH, thyroxine (T₄), and free T₄ were determined (TSH using a microparticle enzyme immunoassay; T₄ using a fluorescence polarization immunoassay; and free T₄ using a microparticle enzyme immunoassay; Axsym®, Abbott Laboratories, Abbott Park, IL, USA). Frozen sera taken from the same animal in 1993, and from three clinically healthy adult gorillas were also analyzed (Table 1). Compared with the clinically normal gorilla, and human reference values, the TSH level of the affected animal was markedly elevated, and its T₄ and free T₄ levels were significantly lower. Similar changes were also present in the 1993 sample (Table 1). Based on these results, a tentative diagnosis of primary hypothyroidism was made, and oral supplementation with levothyroxine sodium (Synthroid, Knoll Pharma Inc., Markham, Ontario, Canada) was started on August 18, 1996 at 50 µg/day. This dose was progressively increased by 50 µg every 2 weeks, reaching a total of 200 µg/day on October 1, 1996. To monitor TSH levels, the gorilla was re-anesthetized 10 and 21 weeks after the first immobilization. After 10 weeks, TSH levels were below the reference range for humans, indicative of oversupplementation. Oral levothyroxine was consequently decreased to 88 µg/day and then 75 µg/day on October 25, 1996, and January 3, 1997 respectively. A 16% decrease in weight was observed during the 21-week period (from 93 kg on July 25, 1996, to 78 kg on December 20, 1996). This weight reduction was associated with obvious changes in its body conformation, mainly characterized by a decrease in abdominal size and by slimming of facial features. Although its actual food consumption could not be accurately determined, its appetite seemed to increase. Its daily activity, and interactions with the other members of the group also markedly increased, and several new behaviors, such as wrestling, playing, and “drumming,” have been reported since the beginning of the replacement therapy. As an unanticipated side effect, its hair coat has become quite rough and thrown up in whorls. Since hair growth anomalies have been described in human with thyrotoxicosis⁸ this change might have been due to oversupplementation of levothyroxine.

Table 1. Serum T₄, free T₄ levels, and TSH values in one hypothyroid and three euthyroid western lowland gorillas

^aMed-Chem Laboratories Limited, Scarborough, Ontario, Canada
^bAnimals with clinical signs compatible with hypothyroidism
^cAnimals clinically normal (euthyroid)
^dPre-levothyroxine supplementation
^eExcessive levothyroxine supplementation
T₄: Fluorescence polarization immunoassay; Axsym®, Abbot Laboratories, Abbott Park, IL, USA
Free T₄: Microparticle enzyme immunoassay: Axsym®, Abbot Laboratories, Abbott Park, IL, USA
TSH: Microparticle enzyme immunoassay: Axsym®, Abbot Laboratories, Abbott Park, IL, USA

Discussion

In humans, hypothyroidism is usually of thyroid origin (primary hypothyroidism), characterized by a low serum T₄, a high serum TSH, and the associated lack of T₄ negative feedback. Based on the clinical signs, the elevated TSH, the reduced T₄, and the therapeutic response, we believe that this gorilla is affected by overt primary hypothyroidism. TSH levels obtained from the three clinically normal gorillas were comparable to values reported in euthyroid humans, and the TSH values obtained for the hypothyroid gorilla markedly decreased following prolonged administration of oral levothyroxine. These findings indicate that the human-TSH assay used for this study is most likely valid for determination of gorilla-TSH levels. The relatively low T₄ and high TSH levels in the sample taken in 1993 indicate that the investigated animal had been hypothyroid for at least 2.5 years. The three gorillas used as control had a marginally elevated TSH compared to reference values for humans. However, since variation between species might exist, and since these animals do not show any clinical signs indicative of an endocrinopathy, the significance of this finding is unknown. Most hypothyroid humans show an increase in serum cholesterol.⁵ This was not the case in our animal; its serum cholesterol was low (3.31 mmol/L). Oral administration of levothyroxine produced a noticeable improvement of the animal’s physiological and psychological status. Monitoring of the serum TSH and T₄ every 6–8 weeks is recommended during the establishment of the replacement therapy.¹¹ In order to prevent iatrogenic hyperthyroidism, the goal of the treatment is to target a slightly high TSH level (between 10 and 20 mIU/L). The cause of the hypothyroidism observed in this gorilla remains undetermined. Primary hypothyroidism is not uncommon in older women,¹² secondary to autoimmune-mediated thyroiditis². No reproductive activity has been recorded in this female for several years. Since hypothyroidism has been associated with disturbance of the reproductive cycle,⁴ it is possible that its thyroid disorder may contribute to this reproductive inactivity. However, other factors such as sexual incompatibility with the present silverback and the presence of its daughter in the same group may have also contributed to its reduced sexual activity.

To our knowledge, cases of primary hypothyroidism have never been reported in gorillas. Primary hypothyroidism seems to be a rare event in nonhuman primates since only one case, described in a chimpanzee (Pan troglodytes), was found in a literature review.⁶ Considering the relatively high incidence of this condition in humans (between 0.1 to 0.7%),⁷ we believe that hypothyroidism is possibly underdiagnosed in nonhuman primates. Because of the nonspecific symptomatology of this condition, we advocate that a thyroid profile should be part of routine blood work in adult gorillas. TSH levels estimated by human-TSH assays seem to be a good indicator of thyroid function in gorillas, but results should be interpreted with caution since specificity could vary between different assays, laboratories, and species.¹⁰ In order to prevent iatrogenic thyrotoxicosis, slowly increasing dosages of thyroxine and monitoring of the serum TSH are advisable. An initial dosage of 50 µg/day of levothyroxine, with increments of 25 µg/day at monthly intervals up to a dosage of 100 µg/day, is proposed as starting regimen for hypothyroid gorillas.

Acknowledgments

We are grateful to the keepers of the African Pavilion, and volunteers of the Metropolitan Toronto Zoo. We also thank Dr. Nancy Behme for useful discussion.

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