Complications of Thyroidectomy in Cats: Postoperative Hypocalcemia

Surgical thyroidectomy is a highly effective treatment for hyperthyroidism in cats. While thyroidectomy is most often successful, it can be associated with significant morbidity and mortality (1-6).

Many potential complications are associated with thyroidectomy, including hypoparathyroidism, Horner's syndrome, laryngeal paralysis, and persistent or recurrent hyperthyroidism. The most serious complication is hypocalcemia, which develops after the parathyroid glands are injured, devascularized, or inadvertently removed in the course of bilateral thyroidectomy. Since only one parathyroid gland is required for maintenance of normocalcemia, hypoparathyroidism develops only in cats treated with bilateral thyroidectomy (4-6).

Pathogenesis of hypoparathyroidism (calcium crisis) after thyroidectomy
Hypocalcemia is the most serious complication associated with thyroidectomy. This adverse effect develops almost exclusively in hyperthyroid cats with bilateral thyroid disease who must have both thyroid lobes removed (bilateral or total thyroidectomy).

Under normal circumstances, the circulating calcium concentration is tightly regulated to remain within a narrow normal range, as calcium is required both for adequate muscle and nerve function. When circulating calcium falls, the parathyroid glands secrete parathyroid hormone (PTH), which leads to an increase in serum calcium concentration back to normal (7). PTH acts on several organs to increase calcium levels, including the intestinal tract, kidney, and bone.

A discussed in my recent blog post on thyroid and parathyroid anatomy, the 4 parathyroid glands are located within or around the cat’s thyroid gland (the prefix para is from Greek, meaning “at or to one side of, beside, side by side”). However, only the external parathyroid glands will be visible at time of thyroidectomy, whereas the internal parathyroid gland will be embedded within the tumor itself (Figure 1).

Figure 1: Identifying and preserving the external parathyroid gland in a hyperthyroid cat.
(Note: this cat has concurrent kidney disease, which led to secondary enlargement of the parathyroid gland, making it easier to find).

If the parathyroid glands are removed or damaged, the loss of parathyroid hormone secretion leads to a condition called hypoparathyroidism (the prefix hypo is again from Greek, meaning “under”). This leads to a low circulating calcium concentration which can progress to a hypocalcemia crisis due to hypoparathyroidism (7-10).

Clinical signs of hypoparathyroidism (calcium crisis) in cats
Hypocalcemia causes the major clinical manifestations of hypoparathyroidism by increasing the excitability of both the central and peripheral nervous systems (7-10).

Early signs of hypocalcemia due to iatrogenic hypoparathyroidism include anxiety, appetite loss, depression and weakness, twitching, muscle tremors, and facial itch (4-10). Later in the course of hypoparathyroidism, these signs can progress to tetany, collapse, and seizures—hence, the importance of monitoring serum calcium levels during the postoperative period.

Monitoring for hypoparathyroidism after thyroidectomy
After bilateral thyroidectomy, the serum calcium concentration should be monitored on a daily basis until it has stabilized within the normal range. In most cats with iatrogenic hypoparathyroidism, clinical signs associated with hypocalcemia will develop within 1 to 3 days of surgery, but it may take as long as 5 days in some cats (4-10).

Although mild hypocalcemia (6.5-7.5 mg/dl) is a common finding during this immediate postoperative period, laboratory evidence of hypocalcemia alone does not require treatment. However, if accompanying signs of muscle tremors, tetany, or convulsions develop, therapy with vitamin D and calcium is indicated (7-12).

Treating hypoparathyroidism 
If symptomatic hypocalcemia develops, the cat needs to be treated with large doses of calcium and vitamin D. Calcium is initially administered as an intravenous infusion, followed by daily oral administration. Large doses of oral vitamin D also need to be given daily to increase the intestinal absorption of calcium (7-12).  Supplementation with calcium and vitamin D may be needed for only a few days or for the rest of the cat’s life, depending on the extent of damage to the parathyroid glands.

Although hypoparathyroidism may be permanent in some cats, spontaneous recovery of parathyroid function usually occurs days to months after surgery. Therefore, in most cats with surgically-induced hypoparathyroidism, oral calcium and vitamin D supplementation can eventually be tapered and withdrawn (typically, after a few weeks of treatment).

In most cases, such transient hypoparathyroidism probably results from reversible parathyroid damage and ischemia incurred during surgery. Alternatively, accessory parathyroid tissue may secrete PTH and compensate for the damaged parathyroid glands to maintain normocalcemia, or accommodation of calcium-regulating mechanisms in the absence of PTH may occur (7,13).

Incidence of postoperative hypoparathyroidism
Several studies have evaluated the incidence of hypoparathyroidism after thyroidectomy in cats. In an early study (14), 4 out of 53 cats (7.5%) that had a total thyroidectomy performed with an intracapsular technique developed hypoparathyroidism.

A much higher rate was found in another study that compared the complication between different surgical techniques (15). In that study, extracapsular dissection resulted in an 82% incidence of hypocalcemia, whereas intracapsular dissection resulted in a 36% incidence of hypocalcemia. Staged bilateral thyroidectomy, in which two thyroidectomy procedures were performed a few weeks apart, resulted in an 11% incidence of hypocalcemia (15). However, another study found lower (and similar) rates of hypocalcemia between techniques—23% with a modified extracapsular technique and 33% with a modified intracapsular technique (16).

In the most recent study of thyroidectomy in cats, performed using the modified intracapsular dissection technique, a very low incidence of hypoparathyroidism was reported (17). In that study, only 5 (5.8%) of 86 cats developed postoperative hypocalcemia and none required permanent treatment with calcium and vitamin D.

Bottom Line

No matter which surgical technique is chosen, hypoparathyroidism will develop in a significant proportion of cats treated with bilateral thyroidectomy. However, the very low occurrence of postoperative hypocalcemia in some, but not all, studies suggests that surgeon experience may be the most important factor in determining the outcome for hyperthyroid cats undergoing thyroidectomy.

References:

1. Mooney CT, Peterson ME. Feline hyperthyroidism In: Mooney CT,Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association. 2012;92-110.
2. Baral RM, Peterson ME. Thyroid gland disorders In: Little SE, ed. The Cat: Clinical Medicine and Management. St. Louis: Elsevier Saunders, 2012;571-592.
3. Panciera DL, Peterson ME, Birchard, SJ: Diseases of the thyroid gland. In: Birchard SJ, Sherding RG (eds): Manual of Small Animal Practice (Third Edition), Philadelphia, Saunders Elsevier, pp 327-342, 2006.
4. Flanders JA. Surgical therapy of the thyroid. Veterinary Clinics of North America. Small Animal Practice 1994;24:607–621. 
5. Padgett S. Feline thyroid surgery. Veterinary Clinics of North America. Small Animal Practice 2002;32:851–859. 
6. Birchard, SJ. Thyroidectomy in the cat. Clinical Techniques in Small Animal Practice 2006;21:29-33. 
7. Baral RM. Disorders of calcium metabolism In: Little SE, ed. The Cat: Clinical Medicine and Management. St. Louis: Elsevier Saunders, 2012;625-642.
8. Peterson ME. Hypoparathyroidism, in Kirk RW (ed): Current Veterinary Therapy IX. Philadelphia, WB Saunders. 1986; 1039-1045.
9. Peterson ME. Hypoparathyroidism and other causes of hypocalcemia in cats, in Kirk RW (ed): Current Veterinary Therapy XI. Philadelphia, WB Saunders. 1992; 376-379.
10. Skelly BJ. Hypoparathyroidism In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Quedgeley, Gloucester: British Small Animal Veterinary Association. 2012;56-62.
11. Chew D, Nagode L. Treatment of hypoparathyroidism, in Bonagura JD (ed): Kirk’s Current Veterinary Therapy XIII. Philadelphia, WB Saunders. 2000; 340-345. 
12. Henderson AK, Mahony O. Hypoparathyroidism: treatment. Compend Contin Educ Vet 2005; April:280-287.  
13. Flanders JA, Neth S, Erb HN, et al. Functional analysis of ectopic parathyroid activity in cats. Am J Vet Res. 1991 Aug;52(8):1336-40.  
14. Birchard SJ, Peterson ME, Jacobson A. Surgical treatment of feline hyperthyroidism: Results of 85 cases. Journal of the American Animal Hospital Association 1984;20:705-709. 
15. Flanders JA, Harvey HJ, Erb HN. Feline thyroidectomy. A comparison of postoperative hypocalcemia associated with three different surgical techniques. Veterinary Surgery 1987;16:362–366. 
16. Welches CD, Scavelli TD, Matthiesen DT, Peterson ME. Occurrence of problems after three techniques of bilateral thyroidectomy in cats. Veterinary Surgery 1989;18:392-396. 
17. Naan EC, Kirpensteijn J, Kooistra HS, et al. Results of thyroidectomy in 101 cats with hyperthyroidism. Vet Surg 2006;35:287-293. 

Surgical Thyroidectomy in Cats: Thyroid and Parathyroid Anatomy

The thyroid gland, or simply the thyroid, in vertebrate anatomy, is one the largest endocrine glands. The thyroid is a very vascular organ located in the neck, just below the larynx or voice box. The thyroid gland secretes T4 and T3, the two main thyroid hormones.

The small parathyroid glands are located adjacent or embedded within the thyroid gland. These parathyroid glands secrete a hormone (parathyroid hormone or PTH) that regulates calcium levels in the body. If damaged or removed, a dangerous low serum calcium concentration can develop, leading to cramping and twitching of muscles or tetany (involuntary muscle contraction) and sometimes seizures.

Surgical removal of the thyroid glands is relatively straightforward. Successful, uncomplicated excision of unilateral or bilateral thyroid tumors, however, requires knowledge and preservation of the nervous, vascular, and other glandular structures surrounding the thyroid glands for a successful operation.

Normal Anatomy of the Feline Thyroid Gland

Location, size, color

Figure 1: Thyroid and parathyroid glands
of cat

The thyroid gland in the cat is divided into 2 lobes, which are located adjacent to the trachea (windpipe) and just distal to the larynx (voicebox). Each thyroid lobe lies on the lateral aspects of the trachea (windpipe) at first few tracheal rings. Each lobe is approximately 1-cm long, 3- to 5-mm wide, and 1-2 mm thick in the cat. The right thyroid may be located higher than the left, at the caudal aspect of the larynx (1-6).

The glands are closely adhered to the trachea and deep to the neck muscles — the sternohyoideus and sternothyroideus muscles (1-6). The normal thyroid gland is cream to tan in color. Each thyroid lobe is contained in a distinct capsule that can be bluntly separated from the gland. Small blood vessels are found on both the capsule surface and between the thyroid capsule and the gland itself.

In contrast to the human thyroid, where the thyroid lobes are connected by an isthmus, the feline thyroid gland does not have this connecting “bridge” between the two lobes of the thyroid (Figure 2).

Figure 2. Comparative anatomy of the human and feline thyroid gland. Note that cats lack the connecting bridge between the 2 thyroid lobes.

Blood supply
The principle blood supply to each thyroid lobe is the cranial thyroid artery, a branch of the common carotid artery (Figure 1). In contrast to dogs and humans, the caudal thyroid artery is absent in the cat (7). Venous drainage of the thyroid gland occurs through the cranial and caudal thyroid veins.

Surrounding structures
The right gland is closely associated with the structures of the carotid sheath (which contains the carotid artery, internal jugular vein, and vagosympathetic trunk). The recurrent laryngeal nerves pass dorsal to the thyroid glands. The left thyroid gland is closely associated with the esophagus, which lies dorsolateral to the gland and separates it from the carotid sheath. As discussed below, the parathyroid glands are located adjacent to or are embedded within the thyroid gland.

Ectopic thyroid tissue
As described above, the thyroid gland is normally located near the base of the larynx, lateral to the first few tracheal rings. During the few weeks of development of the fetus, the thyroid starts to form higher up, in the region of the cat’s tongue. As the fetus continues its development, thyroid tissue descends to its normal final resting place in the body, lower in the neck.

Sometimes descent of the thyroid gland is not complete and some (or all) thyroid tissue ends up remaining in the tongue. In other cases, the thyroid continues its descent too far and ectopic thyroid tissue ends up in the chest cavity.

In normal cats, the incidence of ectopic thyroid tissue is not known, but approximately 5% of hyperthyroid cats will have ectopic thyroid tissue found on thyroid scintigraphy. Therefore, this condition does not appear to be uncommon in cats.

Normal Anatomy of the Feline Parathyroid Glands

Location, size, color
The 4 parathyroid glands are intimately associated with the thyroid tissue. Two parathyroid glands are usually associated with each thyroid lobe (7).

Figure 3: Anatomy of the parathyroid glands of the cat

The external parathyroid gland usually lies in the loose fascia at the cranial (top) pole of each thyroid lobe (Figure 3). The external parathyroid glands are round and flat and are much smaller than the thyroid lobe (approximately 4 mm in diameter). They can be distinguished from the thyroid tissue by their lighter (white to tan) color and spherical shape. The internal parathyroid gland is usually embedded in the thyroid tissue itself and cannot be seen without dissection of the thyroid gland.

Blood supply
Like the thyroid gland, the blood supply to the parathyroid glands arises from the cranial thyroid artery (5,6,7).

Ectopic parathyroid tissue
A small percentage of cats have ectopic parathyroid tissue in the chest, similar to ectopic thyroid issue. It is not know if this tissue secretes parathyroid hormone, however, since one study found that this ectopic tissue was not capable of maintaining normal calcium levels immediately after removal of both the thyroid and parathyroid glands (8).

Bottom Line

The anatomy of the feline thyroid and parathyroid glands is extremely important when considering surgery to remove thyroid adenomas. Adjacent arteries, veins, and nerves (eg, carotid artery, internal jugular vein, vagosympathetic trunk, recurrent laryngeal nerve, esophagus) make the procedure complicated if the thyroid tumor is large, highly vascular, invasive, or malignant. 

Because of the highly vascular nature of the thyroid, operation carries the potential risk of hemorrhage, especially with larger thyroid tumors. Lastly, the intimate association of the parathyroid glands and the shared blood supply explains the risk of hypoparathyroidism leading to low calcium levels in hyperthyroid cats requiring bilateral thyroid gland surgery.

References:

1. Crile R. The comparative anatomy of the thyroid and adrenal glands in wild animals. Ohio Journal of Science 1937;37:42–61. 
2. Dyce KM, Sack WO, Wensing CJG. The endocrine glands. In: Dyce KM, Sack WO, Wensing CJG (eds): Textbook of Veterinary Anatomy. Philadelphia: WB Saunders, 1987;205–211. 
3. Waters DJ. Endocrine system. In: Hudson LC, Hamilton WP (eds): Atlas of Feline Anatomy for Veterinarians. Philadelphia: WB Saunders, 1993;127–134. 
4. Flanders JA. Surgical therapy of the thyroid. Veterinary Clinics of North America. Small Animal Practice 1994;24:607–621. 
5. Birchard, SJ. Thyroidectomy in the cat. Clinical Techniques in Small Animal Practice 2006;21, 29-33. 
6. Drost WT, Mattoon JS, Samii VF, et al. Computed tomographic densitometry of normal feline thyroid glands. Veterinary Radiology and Ultrasound 2004;45:112-116. 
7. Nicholas JS, Swingle WW. An experimental and morphological study of the parathyroid 
glands of the cat. American Journal of Anatomy 1925;34:469-508. 
8. Flanders JA, Neth S, Erb HN, et al. Functional analysis of ectopic parathyroid activity in cats. American Journal of Veterinary Research 1991;52:1336–1340. 

Overview of the Normal Endocrine System in Dogs and Cats

The endocrine system is the system of glands, each of which secretes a type of hormone into the bloodstream to regulate the body. While powerful, the endocrine organs are relatively small.

Most people find endocrinology very confusing. In order to illuminate the details of the endocrine system, we will be doing a series of blog posts explaining the basics. We have also set up a glossary of definitions of endocrine terms for your reference.

Hormones are chemical messengers that have many different functions. In the bloodstream, the hormones travel throughout the body. Their effects vary widely, and all are important for life. Some familiar examples of hormones include insulin, thyroid hormone, and cortisol. These hormones are important in the development of diabetes, hypo- and hyperthyroidism, and Cushing’s disease, respectively.

Human endocrine glands are essentially identical to dog and cat endocrine glands, both in structure and function. The endocrine glands include the pituitary gland, thyroid gland, parathyroid glands, pancreas, adrenal glands, ovaries, and testes.

Pituitary Gland

The pituitary gland is located near the center and bottom of the brain. It produces a number of critical hormones that control many parts of the body, including several other endocrine glands. Because of its central role, the pituitary gland is often referred to as the “master gland.”

Clinically, the most important of these hormones include growth hormone (GH), adrenocorticotropin (ACTH), thyroid-stimulating hormone (TSH), and antidiuretic hormone (ADH). Because the pituitary gland produces so many hormones, pituitary disease, most commonly pituitary tumors, may result in a variety of different conditions. The signs and symptoms of the disease depend on which pituitary hormones are affected.

Thyroid Gland

The thyroid gland is a two-lobed gland in the neck, located in front of the breathing airway (trachea) and below the Adam's apple. It produces two iodine-containing hormones, thyroxine (also called T4) and triiodothyronine (T3). In general, the thyroid hormones regulate metabolic rate, or the speed at which body processes “run.”

Thyroid disorders result from too little or too much T3 or T4. Symptoms of hypothyroidism (too little hormone) include decreased energy, lethargy, weight gain, dry skin, and hair loss. In young animals, hypothyroidism most commonly leads to stunted growth and dwarfism.

Hyperthyroidism (too much hormone) is common in cats. Common clinical signs include weight loss despite an increased appetite, nervousness, excitability, vomiting after eating, and increased thirst and urination.

Parathyroid Glands

The parathyroid glands are four small glands located adjacent or within the thyroid gland. These glands secrete parathyroid hormone (PTH). PTH helps maintain normal calcium and phosphorous levels in the body and is necessary for proper bone development.

If the parathyroids are removed during a thyroid operation, the blood PTH will fall (hypoparathyroidism). The blood calcium will then become dangerously low (hypocalcemia), causing neuromuscular signs of muscle spasms or twitches, tetany, or seizures.

A tumor of one of the parathyroid glands may cause the secretion or release too much PTH (hyperparathyroidism). The blood calcium will then become too high (hypercalcemia), causing increased thirst and urination, muscle weakness, and fatigue.

Endocrine Pancreas

The pancreas is an oblong, flattened gland located in the abdomen, adjacent to the stomach and small intestine. While it secretes digestive juices to aid in digestion, its endocrine function is to maintain healthy glucose (blood sugar) levels. If blood sugar is too high, such as after a meal, the pancreas secretes insulin. Insulin moves the sugar from the blood into the cells of the body, where it is used for energy. If blood sugar is too low, the pancreas releases glucagon. Glucagon releases sugar, stored in the liver as glycogen, back into the bloodstream.

Diabetes, an imbalance of blood sugar levels, is the major disorder of the pancreas. Diabetes occurs when the pancreas does not produce enough insulin or the body is resistant to the insulin in the blood. Without enough insulin to keep glucose moving through the metabolic process, the blood glucose level rises too high. Most dogs and cats with diabetes require insulin shots to do well, although some can be managed by a combination of diet or oral drugs.

A condition called hyperinsulinism is caused by too much insulin and leads to hypoglycemia (low blood sugar). This is most commonly seen when owners inadvertently overdose their diabetic dogs or cats with insulin. Less commonly, an insulinoma (insulin-secreting pancreatic tumor) will cause hypoglycemia. Symptoms of low blood sugar include anxiety, weakness, and seizures.

Adrenal Glands

The two adrenal glands are located on the top of each kidney. The adrenal glands essentially contain two separate endocrine organs. The outer portion or core of the adrenal gland is called the adrenal cortex. The inner portion of the gland is called the adrenal medulla. The hormones of the adrenal cortex are essential for life and the hormones of the adrenal medulla are not.

The adrenal cortex produces glucocorticoids (e.g., cortisol) that help the body control blood sugar, increase the burning of protein and fat, and respond to stressful stimuli, such as fever, major illness, and injury. The mineralocorticoids (e.g., aldosterone) control blood volume and help to regulate blood pressure by helping the kidneys hold on to sodium and water. Cushing’s syndrome (too much cortisol) and Addison’s disease (too little cortisol) are the two most common adrenal cortex disorders. Symptoms of Cushing’s syndrome generally include an increase in thirst and urination, enlarged abdomen, and hair loss on the trunk. Symptoms of Addison’s disease include poor appetite, weight loss, weakness, and vomiting.

The adrenal medulla produces epinephrine (adrenaline), which increases heart rate, opens airways to improve oxygen intake, and increases blood flow to muscles. The adrenal medulla usually secretes epinephrine when one is scared, excited, or under stress. The adrenal medulla also secretes norepinephrine, but this hormone is more related to maintaining normal activities as opposed to emergency reactions. Tumors of the adrenal medulla (called pheochromocytoma) may produce increased thirst and urination, increased heart rate, and restlessness.

Testes

As in humans, unneutered male dogs and cats have twin reproductive glands, called testes, which produce the hormone testosterone. Testosterone helps the young male develop and then maintain his sexual traits.

Ovaries

The female reproductive glands, the ovaries, produce estrogen and progesterone. These hormones are responsible for developing and maintaining female sexual traits, as well as maintaining a pregnancy. Along with certain pituitary hormones (i.e., luteinizing hormone [LH] and follicle-stimulating hormone [FSH]), they control the estrus cycle (a sort of “menstrual cycle” for animals, although animals do not menstruate).