We hear some hormones ‘thrown around’ in conversation when we’re talking about different diseases - for example, calcitriol in our parathyroid disorder patients, or erythropoietin in our CKD patients.

But what are those hormones? And what do they do?

In the penultimate post in our endocrine series, we’re focusing on those specific hormones - and some very rare hormonal diseases you may have not yet encountered in your clinic!

Don’t forget - if you want to know more about nursing the endocrine patient, you can also pick up a handy guide to nursing the endocrine patient here.

Insulinoma

Insulinomas are tumours arising from the beta cells within the pancreas. The tumour secretes excessive amounts of insulin, resulting in periods of hypoglycaemia.

They are seen uncommonly in dogs, and very very rarely in cats.

Pathophysiology

Carbohydrates, fats, and proteins within food provide a source of energy for cells for up to around 8 hours.

After this time, the body relies on the liver to produce glucose. This is achieved initially by the breakdown of glycogen stores into glucose, and, after the glycogen stores are depleted, from:

• Fatty acids

• Amino acids (proteins)

• Lactate

• Glycerol (fat)

Blood glucose is regulated by the pancreatic beta cells. When blood glucose levels are high, insulin is secreted, which reduces blood glucose into the normal range by:

• Encouraging uptake of glucose into cells

• Promoting intake of glucose into the liver for storage as glycogen

The conversion of glycogen stores back into glucose for utilisation (glycogenolysis) is also stopped.

When blood glucose levels drop below normal, insulin secretion is inhibited.

When this negative feedback system is bypassed and insulin secretion continues (e.g. from a tumour), hypoglycaemia results.

The central nervous system relies on glucose for its normal function. Because of this, there are safety mechanisms in place to provide emergency supplies of glucose and allow the CNS to continue functioning.

When hypoglycaemia is detected, insulin secretion is suppressed, and the following counter-regulatory hormones are secreted to increase glucose levels rapidly:

• Cortisol

• Growth hormone (somatotropin)

• Glucagon

• Adrenaline

Clinical Signs

Insulinomas are most commonly seen in older dogs. Signs are episodic (as they are only seen when the tumour secretes insulin) and include periods of:

• Weakness

• Ataxia

• Muscle tremors

• Behavioural changes

• Collapse

• Seizures

These signs often resolve quickly, as the counter-regulatory hormones kick in and return blood glucose levels to normal.

Diagnostics

Measuring insulin and glucose levels is the first step in diagnosing an insulinoma. These samples should be paired (ie. taken at the same time) and run together, so an insulin:glucose ratio is obtained. This needs to be collected before any first aid treatment is given - i.e. before any glucose is administered.

We need to make sure we collect the samples at the time the patient is showing clinical signs. It’s also important to double-check your external laboratory’s sampling requirements (most want a plain, non-gel barrier tube) and spin/separate the sample down ASAP after collection, since leaving serum in contact with red blood cells continues to reduce glucose levels, affecting results.

Imaging is the next step in confirming a diagnosis. Insulinomas are usually very small nodules within the pancreas, and are best identified using abdominal ultrasound, or ideally CT if it is available.

Since many patients will have metastases in the lungs, thoracic radiographs or CT is also advised.

Treatment

Treatment is usually achieved with surgical removal of the tumour (partial pancreatectomy). Postoperative care includes:

• Monitoring the patient for any signs of pancreatitis, and providing treatment as necessary for this if present

• Monitoring the patient for the development of diabetes mellitus, which is a rare complication of aggressive pancreatic surgery

• Monitoring the patient for ongoing hypoglycaemia, and treating this as necessary if it persists

Medical management can also be attempted, but the disease is considered terminal. The veterinary nurse can provide an enormous amount of support to the client, and should discuss the following:

• Frequency of feeding - to provide a constant source of calories, avoiding spikes in glucose levels. At least 3-6 meals a day are advised.

• Minimising exercise and excitement - since these increase glucose utilisation, and reduce the release of glucose from the liver

• Spotting the signs of hypoglycaemia, and how to administer first aid for this at home

• Monitoring quality of life

When diet and exercise modification is not enough to control clinical signs, steroids (glucocorticoids) are administered. Glucocorticoids help to stimulate glycogen breakdown in the liver, making more glucose available - as well as causing insulin resistance.

Ongoing routine monitoring of blood glucose is not necessary, as home treatment is palliative. Clients may, however, check blood glucose at home if the patient is showing clinical signs - and the veterinary nurse is ideally placed to teach them how to do this.

Glucagonoma

Glucagonomas are very rare malignant tumours of the alpha cells within the pancreas. They cause excessive secretion of glucagon, a counter-regulatory hormone that increases blood glucose levels.

There have not been any feline glucagonomas reported, and the condition is mostly seen in middle-aged to older dogs.

Glucagonomas are associated with skin diseases - superficial necrolytic dermatitis (SND) has been seen in dogs with glucagonomas - also known as diabetic dermatopathy since some of these dogs will also develop diabetes mellitus.

Clinical Signs

The most common clinical signs seen in dogs with glucagonomas are:

• Dermatitis is most commonly seen around the footpads, between the digits, and on other pressure points such as the elbows and hocks

• Weight loss

• PU/PD

Diagnostics

On routine blood sampling, patients often have non-regenerative anaemia and elevated liver enzymes. Low urea and albumin are also often seen. If the patient is concurrently diabetic, hyperglycaemia and glucosuria will also be seen.

Biopsies of the skin lesions are recommended, to diagnose SND. Like insulinomas, abdominal ultrasonography or CT is also recommended to look for a pancreatic tumour and metastasis to surrounding organs such as the liver.

Treatment

The condition is treated surgically, with a partial pancreatectomy to remove the tumour. Postoperative care, like insulinoma patients, is aimed at identifying and treating any pancreatitis and managing blood glucose levels where necessary.

Amino acid solutions and high-quality dietary protein, alongside essential fatty acid and zinc supplementation, are used to treat the patient’s dermatological signs.

The prognosis for glucagonomas in dogs is considered poor, as in many cases, it is not diagnosed until an advanced stage when metastasis has already occurred.

Calcitriol

Calcitriol is bioactive Vitamin D and is a steroid hormone that plays a vital role in regulating calcium and phosphorus levels in the bloodstream. 

(It’s also known as 1,23(OH)2D3 - in case you’re ever looking for it on a lab form!)

Pathophysiology

Calcitriol is produced from Vitamin D3. In dogs and cats, D3 is obtained exclusively from the diet - since, unlike humans, they cannot synthesise it via their skin.

Calcitriol is formed via the following process:

• Vitamin D3 is converted to Vitamin D2 in the liver

• Vitamin D2 is transported via the bloodstream to the kidney

• Vitamin D2 is converted to calcitriol in the proximal renal tubules

The process is regulated by several methods to ensure excessive amounts are not produced. These include the release (or suppression of) parathyroid hormone levels, and the binding of calcitriol to proteins in the bloodstream to inactivate it.

The Role of Vitamin D

Vitamin D plays a key role in maintaining a normal calcium and phosphorus balance. It does this by:

• Stimulating absorption of calcium, phosphorus and magnesium in the GI tract

• Controlling renal calcium loss

It also plays a vital role in developing and maintaining the skeleton. Vitamin D deficiency results in softened bones in young patients, and osteomalacia in adults.

Vitamin D-Associated Diseases

Diseases associated with vitamin D include:

• Rickets (inadequate vitamin D levels resulting in softened/weak bones)

• Chronic kidney disease (as patients with CKD may be unable to synthesise calcitriol effectively in the kidney)

• Hypervitaminosis D toxicity (ingestion of high levels of vitamin D, commonly via the ingestion of psoriasis cream, leading to severe hypercalcaemia and potentially renal failure)

Erythropoietin

Erythropoietin or EPO is a hormone that plays a vital role in regulating red blood cell (RBC) production.

In adult animals, it is produced by interstitial cells between the tubules in the kidneys. In the foetus, it is produced within the liver.

Pathophysiology

EPO binds to RBC precursors in the bone marrow to regulate their production and survival. This causes an increase in the number of immature RBCs, which can then mature into reticulocytes (and then ultimately erythrocytes) and be released from the bone marrow into the bloodstream.

The secretion of EPO is a complex process and is regulated by tissue oxygen levels.

When inadequate numbers of RBCs are present, there is a lack of haemoglobin, and therefore less oxygen can be transported in the blood - leading to hypoxia. This is detected by the peritubular cells in the kidneys, and EPO secretion increases as a result.

The amount of EPO released varies depending on the severity of a patient’s anaemia, or the degree of hypoxia present. When oxygenation is adequate and RBC levels are sufficient, EPO secretion decreases to maintain a normal red blood cell level.

This is vital, since overproduction of RBCs increases blood viscosity, reducing its ability to circulate effectively and deliver oxygen to cells.

Diseases involving Erythropoietin

EPO is most classically thought of in 2 diseases - chronic kidney disease and polycythemia.

Chronic kidney disease patients are often not able to effectively produce EPO, leading to anaemia. In advanced CKD cases, supplementation with synthetic EPO (darbepoetin) and iron is often required. EPO injections are generally given weekly, alongside PCV measurement to assess the effectiveness of treatment and guide dosing. Iron injections are usually given alongside this every month, to help with RBC production.

EPO levels are used in the diagnosis and investigation of polycythemia - an increase in red blood cell levels. They help to determine whether it is a primary disease, or secondary. You can read more about polycythemia here.

Renin

Renin is another important hormone released by the kidney. It kicks off the RAAS - the renin-angiotensin-aldosterone system, which plays a vital role in regulating sodium and potassium levels, fluid balance, cardiac output and blood pressure.

Pathophysiology

Renin is secreted by specialised cells in the arterioles entering the glomerulus within the renal nephrons. These cells are known as juxtaglomerular cells.

It is released in response to:

• Systemic hypotension

• Decreased delivery of sodium to the distal renal tubules

The release of renin is inhibited when blood pressure is high, plasma sodium levels are high, volume overload is present, or angiotensin II is present (see below for more on this!).

Renin, as we’ve said, plays a key role in the RAAS. This is the method by which aldosterone is released from the adrenal gland. The system works like this:

1. Renin is released from the kidney

2. Renin converts angiotensinogen to angiotensin I in the liver

3. Angiotensin converting enzyme (ACE) then converts angiotensin I to angiotensin II

4. Angiotensin II acts on the adrenal cortex, stimulating it to produce aldosterone

5. Angiotensin II also acts on the pituitary gland, stimulating it to produce antidiuretic hormone (ADH).

This is important when it comes to treating patients with hypertension, cardiac failure and renal disease. By administering ACE inhibitors (e.g. benazepril), we can manipulate the RAAS, reducing blood pressure, cardiac afterload and blood volume.

Testing

Blood renin levels can be measured, but samples require specialised collection, handling and transport. A frozen EDTA plasma sample is generally required, which is shipped to the lab in a specialised frozen transport pack.

Gastrinoma

Gastrin is a hormone produced by G cells, which are located mostly within the stomach, though some are also present in the pancreas, duodenum and central nervous system. Gastrin has many functions, most notably:

• Stimulating the release of gastric acid, and

• Promoting the growth of the gastric mucosa.

Pathophysiology

A gastrinoma is a rare, malignant neuroendocrine tumour that can be seen either in the pancreas or in the duodenum. It causes excessive release of gastrin, resulting in excessive secretion of gastric acid, and thickening of the gastric mucosa. This leads to gastric ulceration, melena and a reduced ability to digest food and absorb nutrients.

Clinical Signs

Patients with gastrinomas present with:

• Anorexia

• Weight loss

• Vomiting

• Lethargy

• Abdominal pain

• Melena

• Haematochezia

If the patient has a perforated gastric ulcer, they may present acutely collapsed with signs of shock/sepsis, requiring prompt triage and stabilisation.

Diagnostics

Several abnormalities may be present on bloodwork, including anaemia, neutrophilia, hypoproteinaemia, increased urea, electrolyte and acid-base abnormalities and increased liver enzymes.

The condition is diagnosed by measuring gastrin levels on a fasted sample, and by performing abdominal imaging. Ultrasonography or CT may demonstrate a pancreatic or duodenal mass, as well as thickening of the gastric wall. Ulceration, thickening and erosions are commonly seen on endoscopy.

Treatment

Gastrinomas carry a poor prognosis and the treatment of choice is surgical removal, but due to the high risk of metastasis, it is rarely curative.

Medical management is achieved using antacids and gastroprotectants to protect the gastric lining against acid-associated damage. Agents commonly used include omeprazole or pantoprazole to reduce gastric acidity, and drugs such as sucralfate to treat ulceration or bleeding.

So that’s a recap of some of our less frequently-mentioned hormones and rare endocrine diseases! Have you ever seen any of these diseases in your patients? DM me on Instagram and let me know!