Mimi, the Yorkshire terrier, was a mere five-pound pup when I first met her 15 years ago. She's had her problems since then. The occasional gimpy leg. A case of "dry eye." Dental issues common in toy breeds. As she reached her senior years, she developed senior difficulties. A touch of incontinence. A heart condition. She always rallied under the tender care of her owners but became increasingly frail as time passed. Right after Thanksgiving this year, Mimi ate some leftover turkey. Then she started to vomit. Then she stopped eating. When she arrived at my office on Monday afternoon, my first thought was a case of post-holiday gastroenteritis.
"Maybe the turkey disagreed with her," I suggested. I wasn't too worried. I see lots of dogs with upset tummies. Because of her age and delicate nature, I advised running basic blood work just to be sure. "We'll give subcutaneous fluids to re-hydrate her," I said, "then send her home with medication to settle her stomach and dietary recommendations. I'll call if the lab tests show any cause for concern," I added, walking them to the door.
The rest of the afternoon was busy with appointments. Tangerine, the dog with a wart on her tongue probably caused by Canine Oral Papilloma Virus. Charcoal, the lab with protein-losing nephropathy. A few annual physical exams. Five days of messages that had piled up over the holiday and phone calls waiting to be returned. When I finally came up for air, it was closing time. My assistants were ready to go home, my family was supposed to be at a school chorus rehearsal in ten minutes, and Mimi's blood work was sitting in my inbox. I grabbed the report, expecting to take a quick glance, and be on my way. My quick glance turned into a lingering look, then a sinking sigh.
Calcium is a substance essential to almost every system in the body. It plays a part in everything from muscle contraction, to hormone formation, to nerve conduction. In order for the body to function normally, calcium levels in the blood must be maintained in a very narrow range. This is done through a complex set of interactions regulated by parathyroid hormone (PTH), vitamin D, and calcitonin. Mimi's calcium levels were low...dangerously low. Technically called hypocalcemia, abnormally low calcium levels can lead to muscle tremors, incoordination, stiff gait, weakness, panting, facial rubbing due to a tingling sensation, vomiting, loss of appetite, seizures, and death. Perusing Mimi's report, I noticed significant abnormalities, most notably an elevated phosphorus and blood urea nitrogen. Clearly Mimi had a serious metabolic imbalance, but what was the cause? I called Mimi's owners, advising they immediately give her oral calcium supplements and return in the morning for further diagnostics and treatment. Then, gathering my children and a recent veterinary journal, I proceeded to our rehearsal where I reviewed the pathophysiology of hypocalcemia between songs.
The parathyroid glands, located alongside the thyroid in the neck, have specialized calcium receptors on their surface. A drop in serum calcium will stimulate the glands to secrete parathyroid hormone (PTH), which in turn prompts an increase in serum calcium by resorbing it from bone and via the kidneys, and by helping vitamin D to increase calcium absorption from the intestines. PTH also causes a decrease in serum phosphorus. In a condition know as primary hypoparathyroidism, the parathyroid glands do not make enough PTH. Calcium levels drop. Phosphorus levels rise. Could this be Mimi's diagnosis? It is an uncommon syndrome and Mimi's clinical symptoms were vague.
Her lab test results were also ambiguous, not fitting any one picture perfectly. Some parts were consistent with gastrointestinal bleeding, such as from a tumor or ulcer, other parts suggested kidney failure, maybe from antifreeze poisoning, and the possibility of laboratory error had to be considered. Confused? Don't feel badly. So was I. This stuff is complicated. In order to pin down the diagnosis, we had to run more tests. We would have a commercial veterinary reference lab measure her calcium levels, both total and ionized. This would eliminate any concerns about technical errors. We would also request a PTH level. If PTH was low, that would support the diagnosis of hypoparathyroidism.
Hypoparathyroidism can be caused by destruction of the parathyroids, via trauma or surgery. For example, the glands are sometimes damaged inadvertently during surgery for feline hyperthyroidism. Severely decreased magnesium levels can also result in hypoparathyroidism. But in dogs it is usually what we call idiopathic or immune-mediated. The body's immune system attacks its own glands and we don't know why. Although it can be seen at any age, it is most common in middle-aged dogs. Some texts report slightly greater prevalence in females. More cases have been reported in toy poodles, miniature schnauzers, German Shepherds, Labrador retrievers, and terrier breeds but any breed is susceptible. If an animal has normal kidney function, a presumptive diagnosis of hypoparathyroidism can be made if the patient has high phosphorus, low calcium, and other causes of hypocalcemia have been ruled out. For definitive diagnosis, PTH levels must be tested. Primary hypoparathyroidism is treatable but requires lifelong medication. It has a good prognosis if the owners are diligent.
Mimi had the low calcium and high phosphorus but there was serious question about her kidney function. Some tests that could indicate kidney failure were markedly elevated while others were close to normal.
"It's like we have half the pieces of the jigsaw puzzle," I told her owners, "but not enough to put it all together and figure out the big picture." The PTH level was going to take a few days to come back. In the meantime, we had the difficult situation of having to provide supportive care, not knowing for sure what the problem was, nor the prognosis. I talked to more specialists. The general consensus was that primary hypoparathyroidism was unlikely and that we might be dealing with a gastrointestinal tumor or an unusual presentation of kidney failure.
In a few days the lab report arrived by fax. Mimi's low calcium level was confirmed. No lab error there. Her PTH level? It was not too low. In fact, it was too high. Mimi didn't have hypoparathyroidism. She had hyperparathyroidism. To be specific she had renal secondary hyperparathyroidism. That's a mouthful, huh? What does it mean? It means that Mimi's kidneys were failing and this chronic failure had led to a complex cascade of events. Failing kidney function led to high serum phosphorus levels, which reduced production of calcitriol, which caused hypocalcemia, which caused increased PTH. Her parathyroid glands weren't underactive (hypo), they were overactive (hyper), putting out too much PTH. Don't try to understand the details. It takes me hours reviewing texts every time I need to handle a case like this.
The bottom line was that her underlying condition was kidney failure, with secondary hyperparathyroidism. There were things we could do to try to prolong her life but the long-term prognosis was guarded to poor. Mimi's family didn't want their elderly pup to go through a lot of poking and prodding. They wanted her with them, where she felt safe and loved. They decided to take a hospice approach and keep her home as long as they feel she is comfortable. Maybe she will pass peacefully at home, but if they decide she is suffering, we will help her gently on her way. My desk is still covered with the texts and journals I used to review this intricate biological system, with notes scrawled during conversations with specialists who helped to solve Mimi's puzzle. I only wish that when we finally put all the pieces together, we had found a happier answer.