34 Endocrine emergencies
The adrenal cortex produces corticosteroid hormones, including mineralocorticoids (primarily aldosterone) and glucocorticoids (primarily cortisol). Naturally occurring primary hypoadrenocorticism in dogs and cats is thought to be the result of immune-mediated destruction of both adrenal cortices and is the focus of this discussion. Secondary adrenocortical failure may also occur, either naturally due to diseases of the brain or as a result of chronic exogenous corticosteroid administration (i.e. iatrogenic causes).
Primary hypoadrenocorticism classically manifests with signs of both mineralocorticoid and glucocorticoid deficiency. Lack of aldosterone results in hyponatraemia (and hypochloraemia) with concurrent extracellular fluid volume depletion. Reduced cardiac output, systemic hypoperfusion and hypotension may ensue as a result of chronic renal fluid loss, acute gastrointestinal fluid loss and inadequate dietary intake. Reduced glomerular filtration rate (GFR) results in prerenal azotaemia. The aetiology of hyperkalaemia in primary hypoadrenocorticism is multifactorial and the most deleterious effects occur on cardiac function.
Cortisol affects almost every tissue in the body, and is significantly involved in haemodynamics and the cardiovascular system, metabolism, inflammation and immunological function, and gastrointestinal integrity. Its production increases during times of physiological stress. Lack of secretion may result in gastrointestinal signs, reduced mentation and activity levels, reduced energy metabolism and fasting hypoglycaemia, and especially impaired tolerance to stress.
Some dogs have atypical primary hypoadrenocorticism with only glucocorticoid insufficiency.
Clinical signs are nonspecific and variable in both nature and severity. Most dogs are chronically affected. However, owners may not have noticed more subtle abnormalities or may not have considered them significant. Thus some dogs are only presented for veterinary attention when they suffer an acute Addisonian crisis. Clinical signs reported in primary hypoadrenocorticism are listed in Box 34.1. These signs are vague and nonspecific and may also occur in a large number of other disorders. It is therefore essential to keep primary hypoadrenocorticism on the differential diagnosis list for all dogs presenting with any of these signs until a definitive diagnosis is made.
Presenting Signs and Case History
A 4-year-old female neutered bearded collie dog presented with a 3-day history of lethargy that had progressed to noticeable weakness, and occasional vomiting. Her owners reported that her appetite had been variable over the preceding 3 months and that she had had occasional episodes of diarrhoea. No other significant history was reported.
Clinical Tip
On presentation the dog was ambulatory but depressed. Cardiovascular examination revealed a heart rate of 80 beats per minute with mildly weak femoral pulses and even weaker dorsal pedal pulses. Mucous membranes were pink with a capillary refill time of 2 seconds, and the dog’s extremities were cool to the touch. Respiratory examination and abdominal palpation were unremarkable. Rectal temperature was mildly reduced (37.3°C). Electrocardiography was performed and the dog was found to be in sinus rhythm.
The dog’s cardiovascular examination was suggestive of moderate hypovolaemia and her apparently normal heart rate was therefore considered to be an inappropriate bradycardia. Together with her signalment and history, this finding prompted a very high index of suspicion for hypoadrenocorticism (Addison’s disease) with the bradycardia thought to be the result of hyperkalaemia and impaired response to endogenous catecholamines due to glucocorticoid deficiency.
An intravenous catheter was placed in a cephalic vein and blood obtained via the catheter for an emergency database. This revealed remarkable findings of moderate to severe hyponatraemia (128.5 mmol/l, reference range 140.0–153.0 mmol/l), moderate hyperkalaemia (7.0 mmol/l, reference range 3.6–4.6 mmol/l), mild hypoglycaemia (4.0 mmol/l, reference range 4.2–6.6 mmol/l), mild azotaemia (blood urea nitrogen 20 mmol/l, reference range 3–10 mmol/l; creatinine 250 µmol/l, reference range 50–140 µmol/l) and mild hyperphosphataemia (2.90 mmol/l, reference range 0.94–2.13 mmol/l). The sodium to potassium ratio was markedly reduced (18.4 : 1, normal range 27 : 1–40 : 1). Peripheral blood smear examination was considered remarkable due to an absence of a neutrophilia and lack of an obvious lymphopenia (i.e. absence of a stress leucogram); a subjective eosinophilia was not noted.
Clinical Tip
Clinical Tip
Although not identified in this case, bone marrow suppression due to hypocortisolism can result in anaemia that may be mild to moderate in severity. A normocytic normochromic non- or minimally regenerative anaemia is identified. However, manual packed cell volume (PCV) at presentation may also be affected by both haemoconcentration (increases PCV) and potentially also gastrointestinal blood loss (decreases PCV).
Clinical Tip
The findings of the emergency database strongly supported the suspected diagnosis of classic hypoadrenocorticism. The dog was started on intravenous 0.9% sodium chloride (normal, physiological saline). A conservative bolus of 20 ml/kg was administered over 20 minutes and a constant infusion of 6 ml/kg/hr was then provided. As the dog was clinically stable, an adrenocorticotrophic hormone (ACTH) stimulation test was performed over 1 hour prior to the administration of dexamethasone (0.5 mg/kg i.v. q 6). As hypoglycaemia was only mild, supplementation was not provided.
Clinical Tip
By the following day, the dog’s serum potassium concentration was within normal limits and only mild hyponatraemia persisted. The dog had made good clinical progress, becoming noticeably brighter and eating well without vomiting. She was started on oral mineralocorticoid (fludrocortisone 0.01 mg/kg p.o. q 12 hr) and glucocorticoid (prednisolone 0.2 mg/kg p.o. q 24 hr) supplementation and the results of the ACTH stimulation test received subsequently confirmed the suspected diagnosis (cortisol concentration both prior to and following administration of synthetic adrenocorticotrophin was less than 27.6 nmol/l).
The dog was discharged 3 days after initial presentation on oral medication as above. A good deal of time was spent educating the owner on the disease, including provision of a client education leaflet, and a comprehensive plan for on-going management was agreed. The owner was advised that the dog had a good prognosis with normal life expectancy as long as lifelong appropriate management was provided.
Clinical Tip
Both primary and secondary hypoadrenocorticism are considered rare in cats. Clinical signs and physical examination findings are nonspecific, and clinico-pathological findings are similar to those in dogs. An acute crisis is managed in the same way as it is in dogs; however, as is often the case, cats tend to take longer to show noticeable clinical improvement (3–5 days in cats versus a matter of hours often in dogs).
Diabetes mellitus is due to relative or absolute insulin deficiency and results in persistent fasting hyperglycaemia and glucosuria. Lack of insulin means that tissues are unable to take up glucose and are therefore in a state of glucose deficiency. Ketone bodies (acetoacetate, β-hydroxybutyrate and acetone) are derived from hepatic oxidation of free fatty acids and used as an energy source by multiple tissues during periods of glucose deficiency. However, excessive ketone body production, as occurs in uncontrolled diabetes mellitus, results in hyperketonaemia, ketosis and metabolic acidosis. In addition to insulin deficiency and resistance, counter-regulatory hormones (e.g. adrenaline (epinephrine), noradrenaline (norepinephrine), glucagon, cortisol) may also play a role in the pathogenesis.
There is a spectrum from ketonuric animals that are otherwise relatively well, appetent and without metabolic acidosis (diabetic ketosis) to those with severe metabolic acidosis and signs of systemic illness (diabetic ketoacidosis (DKA)). The majority of dogs and especially cats with diabetic ketosis or ketoacidosis have another concurrent disorder (Box 34.2) that may potentially increase counter-regulatory hormone production in addition to other associated adverse effects. DKA is diagnosed most often in middle-aged to older male cats and female dogs.
BOX 34.2 Common concurrent disorders in small animals with diabetic ketoacidosis
Obligatory osmotic diuresis, excessive renal and gastrointestinal water and electrolyte loss, severe metabolic acidosis, hyperosmolality, and dehydration and hypovolaemia are characteristic of DKA.
DKA is most often diagnosed in animals without a prior diagnosis of diabetes mellitus. These animals will have either been subclinical for the diabetes mellitus or tolerating their clinical signs until clinical decompensation occurs as a result of another disorder. Mortality is often related to the presence, nature and severity of a concurrent disorder.
The importance of having a very thorough and informed conversation with owners cannot be stressed enough following a diagnosis of DKA. Owners need to be made aware of the intensive and often prolonged management required in trying to stabilize patients with DKA. The clinical course can be highly unpredictable depending on the concurrent disorder and the cost implications of the management required should be stressed. Assuming it is possible to stabilize the patient, owners also need to be willing and able to provide lifelong care for a pet with diabetes mellitus, and again the practical and cost implications of this should be discussed, along with the possibility of recurrence of DKA; recurrence is more common in cats.
Animals with DKA require very comprehensive and intensive management and monitoring. These animals often have multiple metabolic, electrolyte and acid–base abnormalities, and frequently require not only insulin administration but also glucose, potassium and phosphorus supplementation. Multiple blood samples are required for regular monitoring and the use of a central venous catheter is often preferable both for patient welfare and ease of sampling. Prolonged inappetence is common and feeding tube placement may be necessary. Finally, extensive investigations may be required to identify any concurrent disorder(s).
With all of this in mind, the author is of the opinion that if finances allow, these cases should be referred for specialist care once the diagnosis is made. In the author’s experience, it can end up costing much more in terms of both patient welfare and financial expenses by attempting to manage these cases without adequate facilities or expertise and then having to refer due to poor response to treatment.
Animals with diabetic ketosis that remain relatively well and appetent require less intensive management than those with DKA and may be satisfactorily managed without referral. The reader is directed to other texts for information regarding the management of these cases.
Presenting Signs and Case History
A 7-year-old male entire Miniature Doberman Pinscher dog presented with a several day history of vomiting, polyuria/polydipsia, anorexia and progressive weight loss. He had also started to tremble on the day of presentation. No other significant history was reported.
On presentation the dog was ambulatory but markedly depressed. Cardiovascular examination revealed a heart rate of 160 beats per minute with no murmur heard. Femoral pulses were mildly hyperdynamic and dorsal pedal pulses were readily palpable; no pulse deficits were detected. Mucous membranes were pinker than normal with a capillary refill time of 1 second. The dog was panting but respiratory examination was appropriate for the rate and effort. Mild discomfort was detected on abdominal palpation and the urinary bladder was found to be small. The dog was mildly pyrexic (rectal temperature 39.4°C). Severe dehydration (estimated at 10%) was suspected on the basis of very dry oral mucous membranes and severely reduced skin turgor.
An intravenous catheter was placed in a cephalic vein and blood obtained via the catheter for an emergency database that showed a number of abnormalities. Manual PCV was 39% (reference range 37–55%); however, plasma total solids (TS) were significantly elevated (85 g/l, reference range 49–71 g/l). It was therefore suspected that the dog was anaemic but PCV was increased at presentation due to haemoconcentration. The dog was also found to be severely hyperglycaemic (blood glucose 29.6 mmol/l, reference range 4.20–6.60 mmol/l). The serum from one of the haematocrit tubes filled for PCV/TS measurement was therefore used to measure serum ketones (see Ch. 3) with a urine dipstick and was found to be strongly positive.
Mild to moderate azotaemia was identified (blood urea nitrogen 25 mmol/l, reference range 3–10 mmol/l; creatinine 300 µmol/l, reference range 50–140 µmol/l) that was suspected to be predominantly prerenal in origin. Serum electrolytes were included in the emergency database and the dog was found to be moderately hyponatraemic (132.0 mmol/l, reference range 140.0–153.0 mmol/l) before correction for glucose (Box 34.3) with a mild corrected hypochloraemia. Serum potassium concentration was within the normal range at presentation. Peripheral blood smear examination revealed a neutrophilic degenerate left shift (i.e. increased number of band neutrophils despite a subjectively normal total neutrophil count) and no obvious red blood cell regeneration. A serum SNAP® cPL™ Test (Idexx Reference Laboratories, Wetherby, UK) was performed to measure canine pancreas-specific lipase and found to be abnormal, suggesting acute pancreatitis.
BOX 34.3 Sodium in diabetic ketoacidosis
For several reasons, total body sodium content is almost always decreased in patients with DKA; however, serum sodium concentration is not representative of total body sodium.
In addition, insulin deficiency causes poor cellular uptake of glucose leading to increased extracellular (i.e. interstitial and intravascular) glucose concentration. This creates a transcellular osmotic gradient such that water moves out of the cells and causes a decrease in intravascular sodium concentration (pseudohyponatraemia). In general, for each 3.4 mmol/l increase in blood glucose concentration above the reference range, serum sodium concentration decreases by 1.0 mmol/l. Therefore, the corrected serum sodium concentration in this case example (Case example 2) was 132.0 + ((29.6 – 6.6)/3.4) = 138.7 mmol/l.
A urine sample was obtained prior to commencing fluid therapy via urethral catheterization performed using aseptic technique. Dipstick analysis revealed marked glucosuria and ketonuria, mild proteinuria and no haematuria. Urine specific gravity was found to be 1.060. Significant glucosuria will increase urine specific gravity measured using a refractometer (4+ glucosuria on dipstick analysis approximately increases specific gravity by 0.008 to 0.010) but even after correction for glucosuria, the specific gravity was still considered to be increased. This was consistent with prerenal azotaemia. Urinary sediment was considered benign but the sample was submitted for microbiology.
On the basis of the information available a diagnosis of DKA with acute pancreatitis was made. The dog was given a 10 ml/kg bolus of buffered lactate Ringer’s solution over 30 minutes and the rate then reduced to 6 ml/kg/hr to correct dehydration over 24 hr. Buprenorphine (0.02 mg/kg i.v. q 6 hr) was also administered.
Clinical Tip
A lengthy discussion was had with the dog’s owner about the diagnosis that had been made and the implications both in terms of short- and long-term management. The owner was both willing and felt able to provide lifelong management for the dog’s diabetes mellitus and given the need for 24-hour intensive care and frequent monitoring, it was decided to refer the dog for specialist care shortly after presentation.
Hypoparathyroidism is the most significant postoperative complication associated with bilateral thyroidectomy. It occurs if the parathyroid glands are either devascularized, or accidentally injured or removed. Mild postoperative hypocalcaemia is common following bilateral thyroidectomy but emergency treatment may be required if the cat becomes symptomatic.
Hypocalcaemia develops within 1–5 days following surgery and associated clinical signs may include anorexia, weakness, depression, vocalization, nervous/restless/aggressive behaviour, facial rubbing, ataxia, stiffness, muscle twitching or tremors, tetany and generalized seizures. Third eyelid prolapse may occur in cats and cardiovascular abnormalities may also be identified.
In the blood, calcium is found in three forms: ionized, protein bound and complexed (e.g. with phosphate, bicarbonate). Ionized calcium is the biologically active form and cats showing signs of hypocalcaemia will have reduced ionized calcium concentration. Clinical signs do not occur if ionized calcium concentration is normal. However, measurement of total rather than ionized calcium is more widely available. A correction formula involving albumin for conversion of total calcium to ionized calcium is no longer recommended for use and is definitely not valid in cats. Although total calcium may not reliably correlate with ionized calcium concentration, in a cat with appropriate clinical signs and measured total hypocalcaemia following bilateral thyroidectomy, it is reasonable to assume that ionized calcium will also be reduced and to instigate treatment immediately (Box 34.4). The severity of clinical signs should dictate the aggressiveness of the treatment provided.
BOX 34.4 Treatment of hypocalcaemia
Calcium gluconate 10% solution (100 mg calcium gluconate/ml, approximately 9 mg elemental calcium/ml): give 0.5–1.5 ml/kg i.v. bolus over 5–20 minutes, repeat until signs resolve
Calcium gluconate 10% solution: administer 0.3–0.6 ml/kg/hr constant rate infusion (CRI)
Calcium: 15–100 mg elemental calcium/kg q 24 hr (typically divided into 2–4 equal doses)
Serum calcium concentration should be monitored daily initially during hospitalization or more frequently as dictated by clinical status.
Calcium chloride can be used instead of calcium gluconate but carries a greater risk of significant tissue irritation if administered perivascularly and is therefore not preferred.
1 mg elemental calcium is equivalent to 11.2 mg calcium gluconate, 7.7 mg calcium lactate and 2.5 mg calcium carbonate.