Case presentation
The patient (Figure 1) was a 6-year-old male neutered Domestic Short Hair feline that presented to the referral centre with diabetes mellitus. With subsequent testing, he was diagnosed with a pituitary adenoma, which was the cause for his hypersomatotropism, uncontrolled diabetes mellitus, acromegaly and hypertrophic cardiomyopathy. Hypersomatotropism is a state of excessive somatotropin, otherwise known as growth hormone, production. Somatotropin is made by somatotrophs, which are cells within the anterior pituitary gland. A state of excessive growth hormone can cause a condition called acromegaly, where soft tissue grows excessively and is characterised by a broadened face, protrusion of the mandible, large feet and organomegaly (Niessen, 2023).
Investigations
The cat was admitted for the first time to have a computed tomography scan of his head which showed a pituitary gland mass – suspected pituitary adenoma. He also had an abdominal ultrasound scan which showed generalised organomegaly, as well as diffuse enteropathy. He was taken for an echocardiogram which revealed hypertrophic cardiomyopathy, phenotype stage B2.
Stabilising treatment
The patient was started on furosemide (Frusol, 50 mg/5 ml solution: 0.6 ml orally once daily) as a result of increased filling pressures of the heart and clopidogrel (18.75 mg orally once daily) because of his thromboembolic risk. He was maintained on protamine zinc recombinant human insulin (Prozinc, four International Units subcutaneously every 12 hours) to manage his diabetes mellitus. After several weeks of stabilising treatment, he was admitted for a second time, to have the hypophysectomy surgery.
The surgery – hypophysectomy
During this procedure, the veterinary surgeons removed the hypophysis (pituitary gland) via a transsphenoidal (via the soft palate) approach. Within the veterinary field, it is not yet possible to remove only the neoplastic cells within the pituitary, so the whole hypophysis is removed. This results in the need to supplement certain hormones lifelong afterwards. To do this procedure safely, the patient was not allowed to move, so their depth of anaesthesia needed to be sufficient, and a head brace, which has pins that were tightened into their skull in front of both ears, was used. The patient was positioned in a sphynx-like position with their head up and bottom jaw pulled down to expose the soft palate. The surgeon then delicately removed the pituitary gland. Because of the unusual positioning of their head for surgery, and the possibility of the endotracheal tube being kinked, an armoured endotracheal tube was placed to prevent loss of the airway during surgery.
A post-operative computed tomography scan showed that the pituitary had been sufficiently removed but the patient had a small volume of post-operative haemorrhage within the nasopharynx. This is not a common finding in patients undergoing this surgery (Fenn et al, 2021).
Discussion of post-operative care
Patients having hypophysectomy surgery always return to the intensive care unit for close monitoring in the initial stages of recovery. This patient remained in the intensive care unit for 2 days for close monitoring of his blood glucose and electrolytes, and to allow for early identification of any post-operative complications.
One of the potential complications of performing surgery in the mouth is that haemorrhage from the surgical site can be aspirated, which occurred in this patient despite having a cuffed endotracheal tube. The patient was treated with oxygen therapy in the post-operative period because of an increased respiratory rate and effort likely as a result of aspiration of the blood seen in his nasopharynx. He was placed in a specialised oxygen cage (Figure 2) to facilitate delivery of a high percentage of oxygen while causing minimal stress to the patient. This method of oxygen therapy was chosen because it was the most stress-free provision of oxygen in a conscious cat we had access to, and it can be used for longer term oxygen provision than some other methods. Providing this oxygen supplementation supported the patient while he had aspiration pneumonia until the antibiotics had chance to take effect. On kennel-side T-FAST ultrasound scan he was seen to have bilateral B-lines, which indicated interstitial-alveolar fluid and can have a number of causes. A shred sign on his right side was also noted, which is the manifestation of having lung consolidation (Łobaczewski et al, 2021). These signs together were interpreted as a high likelihood that the patient had aspirated. An increased left atrium to aorta (LA:Ao) ratio was also seen, which indicated left atrium enlargement. In this patient with previously diagnosed cardiomyopathy, this finding caused great care to be taken with his fluid therapy as fluid overload in this patient was likely. These specialised oxygen delivery cages also control the kennel temperature, so active warming of the patient during the recovery phase was possible. The patient arrived in the intensive care unit at 36.0°C, so he was actively warmed until he was normothermic. As a result of being housed in the oxygen kennel, where the air is dry as a result of oxygen being piped in, and the risk of a transient decrease in tear production seen after this surgery, lubrication of his eyes with a tear substitute drop was vital to prevent corneal damage (Fenn et al, 2021). He was weaned off of oxygen therapy over the following 24 hours.
Blood glucose checks were performed with a handheld glucometer every 4 hours post-surgery throughout the first night; this is the current post-operative hypophysectomy protocol in the hospital to ensure blood glucose trends are well monitored. All hypophysectomy patients have a multi-lumen, long-term catheter placed into the jugular vein under anaesthesia to enable blood sampling without subsequent venepuncture (Figure 3). This is indicated because of the frequent nature of sampling in these patients during surgery and the post-operative period (Hurley, 2012). It is seen as an ethical intervention to facilitate vital blood sampling when compared with repeated venepuncture. He was started on a neutral insulin (Actrapid, Novo Nordisk Limited, 100 international units/ml) continuous rate infusion (CRI) to slowly bring down his blood glucose to an appropriate level before restarting his subcutaneous maintenance insulin. Immediately post-operatively his blood glucose was 30.3 mmol/l. To make up the neutral insulin CRI, 50 units of soluble neutral insulin were added to 500 ml of 0.9% sodium chloride, and 50 ml of the solution was run through the fluid giving set to allow the insulin to adsorb to the plastic. Doing this meant that the dose of insulin administered was what the patient would be receiving, as no further insulin should be adsorbed by the plastic. The starting rate for the insulin infusion was 0.5 ml/kg/hour as the patients' blood glucose was above 15 mmol/L, which should have decreased his blood glucose by 1–3 mmol/L per hour. The veterinary surgeon in charge of the case gave a detailed insulin plan depending on the patient's blood glucose results to enable the team to maintain a steady decrease in blood glucose. The blood glucose remained high, above 15 mmol/L, throughout the first night and the following morning it was still 26.8 mmol/L so Prozinc was started simultaneously with the insulin CRI to bring his blood glucose down. 1 international unit (IU) was given at 10am which brought his blood glucose down to 19.7 within 8 hours. A further 2 IU were administered after this and this brought the blood glucose down below 10 mmol/L, at which time the CRI rate was decreased by half. Six hours after this decrease, the patient's blood glucose was maintaining under 10 mmol/L so the insulin CRI was discontinued, and he was maintained solely on subcutaneous insulin. The patient was prescribed Prozinc insulin twice daily thereafter, the dose dependent on his blood glucose reading at that time. By 5 days post-surgery, the patient was maintaining his blood glucose sufficiently and he no longer required insulin therapy, which was the desired outcome from performing the surgery.
During the surgery the patient became bradycardic on the electrocardiogram, and subsequently a venous blood gas analysis was taken, which showed that the patient had become hyperkalaemic at 6.8 mmol/L (ref: 3.6–4.6 mmol/L). The anaesthesia team gave a one-off dose of neutral insulin at 0.25 IU/kg IV and calcium gluconate to stabilise and treat. Insulin shifts potassium into cells by stimulating the sodium/hydrogen antiporters on the surface of cell membranes; this subsequently causes activation of sodium/potassium ATPase, which results in potassium uptake by the cells (Li and Vinjayan, 2014). 10% calcium gluconate was administered slow intravenously at a dose of 2 ml/kg to protect against the potentially life-threatening effects of hyperkalaemia on heart rhythm, by stabilising the resting membrane potential of the heart muscle cells (McBride, 2017). The potassium normalised within 2 hours, and no further electrocardiogram changes were seen and the patient then maintained his own potassium thereafter. Hypokalaemia can be a consequence of giving a CRI of insulin, in which case supplemental potassium should be provided via intravenous fluid therapy or via oral supplements (Bollinger and Moore, 2015). As a result of this patient's risk of fluid overload, because of his diagnosed cardiomyopathy and his increased left atrium size after surgery, oral supplements would have been preferred over further fluid therapy, had they been required.
For the first two days after surgery venous blood gas analysis was performed every 6 hours as per the hospital protocol to check for electrolyte derangements. This was done by drawing samples from his central venous catheter. Once the blood serum potassium normalised, the patient then became hypernatraemic, which peaked at 161 mmol/L (ref: 140–153 mmol/L) but did not reach a sufficiently high level (165 mmol/L) to initiate treatment (Table 1). As this increase was likely because of increased free water loss associated with diabetes insipidus, the treatment would have been to continue desmopressin therapy and provide fluid therapy, to increase the volume of free water in the blood volume to dilute the sodium concentration (Del Magno et al, 2022). Encouraging these patients to eat and drink is of vital importance, as the sooner they do this for themselves, the sooner they can correct and maintain their own blood electrolyte concentrations (van Bokhorst et al, 2021). This patient always had water available and was also regularly offered water from the bowl. Despite this, he did not drink sufficiently, so water was added to his food to increase his uptake. This caused a reduction of his serum sodium levels back to within normal range over a few days. He was offered a wet diabetic cat food, which has a low carbohydrate, high protein content to reduce the considerable spike in blood glucose after eating (Frank et al, 2001). As is typical in these patients, he was ravenous. Marked polyphagia is a symptom of hypersomatotropism (Scudder and Church, 2024).
Table 1. The patient's blood values
| Blood gas values | Result | Reference range |
|---|---|---|
| pH | 7.376 | 7.350–7.470 |
| pCO2 | 38.2 mmHg | 37.0–47.0 |
| pO2 | 35.4 mmHg | 45.0–65.0 |
| Electrolyte values | ||
| K+ | 4.3 mmol/L | 3.6–4.6 |
| Na+ | 161 mmol/L | 140–153 |
| Ca2+ | 1.29 mmol/L | 1.28–1.43 |
| Cl- | 122 mmol/L | 106–120 |
| Metabolic values | ||
| Glucose | 14.5 mmol/L | 4.7–7.3 |
| Lactate | 0.4 mmol/L | 0.6–2.5 |
| tBil | 0 μmol/L | 0–2 |
Diabetes insipidus is defined as excretion of an abnormally large volume of dilute urine, which causes serum osmolality to increase. Diabetes insipidus usually presents after this surgery because of the lack of antidiuretic hormone being released, and the symptoms include polyuria, polydipsia and dehydration (Aroch et al, 2005). Antidiuretic hormone, otherwise known as vasopressin, is produced in the hypothalamus and stored in the posterior pituitary gland until it is released. The pituitary gland releases antidiuretic hormone when the body needs to retain water and it makes the kidneys produce more concentrated urine. As this cat no longer had a pituitary gland, it would not release antidiuretic hormone. This meant that after surgery water was not retained by the kidneys, causing polyuria. This often leads to patients becoming dehydrated, which causes sodium plasma concentrations to increase (Del Magno et al, 2022). Desmopressin spray (Desmopressin Acetate Trihydrate, Aspire Pharma, 10 mg/dose nasal spray solution) was used to mimic the endogenous antidiuretic hormone that was no longer secreted in this patient. Desmopressin was given as a drop on the conjunctiva, using each eye alternatively every dose to avoid irritation. Desmopressin is used as a lifelong treatment after surgery to prevent hypernatremia by controlling thirst and urination (Scudder and Church, 2024). These patients are commonly very thirsty, hence water was offered frequently in the initial stage of recovery. Monitoring his urine output by weighing his litter tray before and after urination was helpful to quantify his urine output and check the effectiveness of his drug therapy. It also helped to assess his likelihood of being volume overloaded, which was a concern because of his cardiomyopathy. His body weight was also closely monitored by weighing him every 4 hours while in the intensive care unit. An increase in body weight of over 10% during hospitalisation can be interpreted as fluid overload and is associated with increased mortality (Londono, 2019).
The cat was started on hydrocortisone (0.5 mg/kg/hr) given intravenously as a continuous rate infusion at first, which was started during surgery when the pituitary was first manipulated and then weaned to an oral version as the cat began to reliably eat. Hydrocortisone is required as a result of secondary adrenal insufficiency since having the pituitary gland removed. Amoxicillin clavulanic acid (Amoxy Clavulanic acid, 20 mg/kg every 8 hours) was commenced intravenously during surgery as a prophylactic medication to reduce the risk of surgical site infection. Levothyroxine (Leventa, MSD Animal Health, 15 mcg/kg two times a day) was given per os as a liquid treatment to prevent the cat from becoming hypothyroid. As the pituitary gland would no longer be producing thyroid stimulating hormone, this supplemental drug will be necessary for the rest of the patient's life (Scudder and Church, 2024). Furosemide (1 mg/kg two times a day) treatment was maintained orally to continue treatment of the patient's cardiomyopathy.
This patient was started on buprenorphine (Bupracare, Animalcare, 0.02 mg/kg every 6 hours) intravenously as an analgesic post-operatively. He did not appear in pain on the Feline Grimace Pain Score at any point (Figure 4); however, he was given pain relief for the first 48 hours after surgery to prevent any pain from occurring, which may have affected his ability to eat and drink. His defecation was monitored while he was hospitalised and he became constipated a few days after surgery, which was monitored and he was prescribed an enema to help relieve this.
Outcome and follow-up
This patient's procedure was successful and his pituitary mass was removed appropriately. He appeared to have entered diabetic remission before discharge, having not required insulin administration to control his blood glucose for two days. His cardiomyopathy was being suitably controlled and his owners were happy to monitor his respiration rate and effort.
Conclusions
Treatment of hypersomatotropism can be performed with a delicate surgical intervention to remove the pituitary gland. This approach is relatively novel and is an alternative for medical therapy with insulin or with pasireotide or cabergoline, and it has been shown to be an effective long-term solution for cats with hypersomatotropism (Fenn et al, 2021). Diabetic remission rates following the surgery have been reported as between 71–92% (Scudder and Church, 2024). There are a few hospitals that have veterinary surgeons trained to perform this technique. It requires intensive nursing care and monitoring postoperatively because of the endocrinological changes that occur; this patient was a perfect demonstration of this. This case was rewarding to nurse, as having knowledge of the physiology of the pituitary gland enabled the nurses to understand the patient's clinical signs and subsequent treatment plan.
KEY POINTS
- Monitoring of blood glucose and electrolytes, especially sodium and potassium, is vital for the post-operative management of these cases.
- Management of blood glucose is achieved using an insulin continuous rate infusion, before switching to subcutaneous insulin, and eventually the hope is that no insulin will be required.
- Central venous catheters are important for ethical repeated sampling from these cats.
- Intensive nursing care is necessary for the successful outcomes of these patients.
- Hypophysectomy is a novel procedure with high success rates for achieving diabetic remission in cats with hypersomatotropism.