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Transient diabetes mellitus and rapid remission following excision of a granulosa cell tumor in a dog

This case report describes a 14-year-old female Yorkshire Terrier with insulin-resistant diabetes mellitus secondary to a functional granulosa cell tumor, which achieved rapid and complete remission following ovariohysterectomy, highlighting that functional ovarian neoplasia should be considered a reversible cause of progesterone-mediated insulin resistance in intact female dogs.

Original authors: Sin-Wook Park, Seung-Jo Park, Keon Kim, Seong-Hyeon Baek, Woong-Bin Ro Ro, Chang-Min Lee

Published 2026-07-28

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CC BY 4.0

Original authors: Sin-Wook Park, Seung-Jo Park, Keon Kim, Seong-Hyeon Baek, Woong-Bin Ro Ro, Chang-Min Lee

Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). ✨ This is an AI-generated explanation of the paper below. It is not written or endorsed by the authors. For technical accuracy, refer to the original paper. Read full disclaimer

The Body's Sugar Switch: A Tale of Hormones and Glitches

Imagine your body is a bustling city where sugar (glucose) is the main fuel delivery truck. For the city to run smoothly, traffic lights called insulin tell the cells when to open their gates and let the sugar in. Usually, if the city has a sugar problem, it's because the traffic lights are broken or missing entirely, leaving the trucks stuck on the highway. This is what most people think of when they hear "diabetes."

But sometimes, the traffic lights aren't broken; they are just being ignored. This happens when something else in the city—like a hormonal signal—shouts "STOP!" so loudly that the cells refuse to open their gates, even though the insulin is working perfectly. This is called insulin resistance. In dogs, we know this can happen when a female dog goes through her natural heat cycle or gets a specific uterine infection, because their bodies naturally produce a hormone called progesterone that can temporarily jam the sugar gates.

However, there's a twist in the story: what if a tumor starts acting like a rogue hormone factory, flooding the body with these "STOP" signals even when the dog isn't supposed to be in heat? That is the mystery scientists set out to solve in this case report. They wanted to see if a specific type of ovarian tumor could trick a dog's body into thinking it was in a state of high progesterone, causing severe diabetes that could be cured simply by removing the tumor.

The Case of the Glitchy Yorkshire Terrier

Meet our patient: a 14-year-old Yorkshire Terrier named (let's call her) "The Sugar Stuck." She was a small dog, weighing just 6.2 kg, but she was acting like a giant water fountain. She was drinking and peeing non-stop, a classic sign that her body was drowning in sugar it couldn't use. When the vets checked her blood, they found a staggering 443 mg/dL of glucose (the normal range is 70–143 mg/dL). Her blood was so sweet it was spilling into her urine, and her "sugar memory" (a test called fructosamine) showed she had been high for a while.

The vets tried the standard fix: they gave her insulin, the key to open the sugar gates. But the keys didn't work. No matter how much insulin they gave her (up to 4 units a day), her sugar levels stayed stubbornly high, hovering between 350 mg/dL and the machine's maximum limit of 500 mg/dL. It was like trying to unlock a door that had been welded shut.

The Detective Work: Finding the Rogue Factory

The vets decided to look deeper. They used ultrasound to peek inside her belly. They saw a normal, tiny right ovary, but the left ovary? It had grown into a massive, cystic balloon, measuring 6.4 × 4.2 cm.

Here is where the plot thickened. The dog had reportedly been in heat about one month ago. Normally, after a heat cycle, a dog's body should have a structure called a "corpus luteum" that produces progesterone. But the ultrasound showed no such structure. Yet, a blood test revealed her progesterone levels were high (8.89 ng/mL), and her IGF-1 (a hormone that helps insulin resistance) was also sky-high at 456 ng/mL.

The vets realized something was wrong. The dog wasn't just in a normal post-heat phase; she had a tumor that was acting like a rogue hormone factory, pumping out progesterone and confusing her body. To be sure, they ran a CT scan to check for spread, found none, and then performed surgery to remove the ovaries and uterus (an OHE).

The Magic Moment: The Switch Flips Back

The moment the tumor was out, the story changed instantly. The tumor was confirmed to be a Granulosa Cell Tumor (GCT). Inside, the normal ovarian tissue was shriveled and atrophied, proving the tumor had taken over the whole show.

Three hours after the surgery, the dog's sugar was still high (387 mg/dL), so they gave her a tiny dose of insulin. But just five hours later, her sugar dropped to 156 mg/dL. By the next morning, her sugar was behaving itself. Within 24 hours, the vets stopped giving her insulin entirely. By day two, the sugar in her urine was gone.

Two weeks later, her "sugar memory" (fructosamine) had dropped to 266 μmol/L, well within the normal range. Four months later, she was still perfectly healthy with a blood sugar of 112 mg/dL. The diabetes hadn't just improved; it had vanished completely.

What This Means: The Tumor Was the Villain

This paper tells us that this dog's diabetes wasn't a permanent broken traffic light; it was a temporary jam caused by a tumor. The tumor was pumping out progesterone, which triggered the body to make too much growth hormone from the mammary tissue. This growth hormone acted like a shield, blocking insulin from doing its job.

The authors explain that while we know heat cycles and uterine infections can cause this kind of temporary diabetes, we rarely see it caused by an ovarian tumor. In this case, the tumor was the only source of the high progesterone, which is why the other ovary was shriveled and inactive. Once the tumor was removed, the "STOP" signal was silenced, the shield dropped, and the insulin could finally do its job again.

The paper suggests that if a female dog has diabetes that is hard to control with insulin, vets should check for ovarian tumors, not just infections. If the culprit is a tumor, removing it can lead to a rapid and complete cure, turning a "broken" sugar system back to normal in less than a day. It's a reminder that sometimes, the cure for a complex problem is as simple as taking out the source of the noise.

Technical Summary: Transient Diabetes Mellitus and Rapid Remission Following Excision of a Granulosa Cell Tumor in a Dog

Problem Statement
Canine diabetes mellitus (DM) is predominantly characterized by absolute insulin deficiency due to pancreatic $\beta$ -cell dysfunction. However, secondary DM driven by insulin resistance is a recognized but less common phenomenon, typically associated with obesity, hyperadrenocorticism, hypersomatotropism, or physiological diestrus. While progesterone-induced insulin resistance is well-documented in conditions like diestrus and pyometra, the association between clinically relevant, insulin-resistant DM and functional ovarian neoplasia—specifically granulosa cell tumors (GCTs)—remains poorly described in veterinary literature. This case addresses the diagnostic challenge of distinguishing tumor-driven hyperglycemia from physiological diestrus and investigates the potential for rapid diabetic remission following the surgical removal of a functional GCT.

Methodology
The study presents a detailed case report of a 14-year-old intact female Yorkshire Terrier (6.2 kg) presenting with polyuria, polydipsia, and severe hyperglycemia. The diagnostic workflow included:

Clinical and Laboratory Evaluation: Assessment of blood glucose, fructosamine, blood ketones, and urinalysis. Continuous glucose monitoring (FreeStyle Libre 2) was utilized to track glycemic trends.
Imaging: Abdominal ultrasonography and computed tomography (CT) were performed to characterize ovarian masses and rule out metastatic disease or local invasion.
Hormonal Profiling: Serial measurements of progesterone, anti-Müllerian hormone (AMH), estradiol, and insulin-like growth factor-1 (IGF-1) were conducted pre- and post-operatively.
Intervention: Despite initial insulin therapy (porcine lente insulin) and dose escalation, glycemic control remained poor. The patient underwent ovariohysterectomy (OHE).
Pathological Analysis: Histopathological examination of the excised mass confirmed the diagnosis. Immunohistochemistry was performed to rule out ectopic pancreatic islet cell tumors or functional neuroendocrine neoplasms (testing for glucagon and somatostatin).
Post-operative Monitoring: Blood glucose, fructosamine, and hormonal levels were monitored over a four-month period to assess remission.

Key Results

Pre-operative Status: The dog exhibited marked hyperglycemia (443 mg/dL), glucosuria (4+), and elevated fructosamine (338 $\mu$ mol/L) without significant ketoacidosis. Despite insulin therapy, glucose levels remained refractory (350–500 mg/dL).
Imaging and Hormonal Findings: Ultrasound and CT identified a large (approx. 6.4 cm), multilocular cystic mass on the left ovary, while the right ovary appeared small and inactive. Notably, serum progesterone was elevated (8.89 ng/mL) and IGF-1 was high (456 ng/mL), despite the absence of luteal structures on imaging and a reported estrus one month prior.
Pathology: Histopathology confirmed a granulosa cell tumor (GCT) with marked atrophy of the normal ovarian parenchyma and a complete absence of corpora lutea. Immunohistochemistry was negative for glucagon and somatostatin, confirming a primary ovarian origin.
Post-operative Outcome: Following OHE, the dog's glycemic control improved rapidly. Blood glucose dropped to 156 mg/dL within 5 hours of the last pre-operative insulin dose. Exogenous insulin was discontinued within 24 hours. By post-operative day 2, glucosuria resolved.
Long-term Remission: At 7 days post-op, fructosamine normalized (304 $\mu$ mol/L), and progesterone and IGF-1 levels dropped significantly (<0.05 ng/mL and 115 ng/mL, respectively). At the 4-month follow-up, the dog maintained normal fasting blood glucose (112 mg/dL) without insulin, confirming complete diabetic remission. Endocrine testing ruled out hypothyroidism and hyperadrenocorticism.

Significance and Claims
The authors claim that this case demonstrates that complete diabetic remission is achievable in dogs with functional ovarian GCTs following surgical excision. The study posits that the mechanism of insulin resistance was driven by a progesterone-mediated axis, where the tumor secreted progesterone, stimulating mammary tissue to produce growth hormone, which subsequently antagonized insulin action.

Key contributions of this work include:

Expanding the Etiology of Transient DM: The paper argues that functional ovarian neoplasia should be considered a distinct cause of progesterone-mediated insulin resistance in intact female dogs, alongside the more commonly recognized physiological diestrus and pyometra.
Differentiation from Physiological Diestrus: The case highlights that the absence of luteal structures on imaging, combined with histopathological evidence of ovarian atrophy and elevated progesterone, indicates a neoplastic rather than physiological source of the hormone.
Therapeutic Implication: The report suggests that in intact female dogs presenting with insulin-resistant hyperglycemia and an ovarian mass, timely surgical excision may offer a definitive therapeutic pathway to rapid diabetic remission, potentially avoiding the need for lifelong insulin therapy.

The authors maintain modesty regarding their claims, acknowledging limitations such as the lack of histopathological confirmation for the contralateral ovary and the absence of direct growth hormone or circulating gonadotropin measurements. Nevertheless, the rapid normalization of the endocrine profile and glycemic control strongly supports a tumor-driven etiology for the transient diabetes.