Endocrine emergencies may produce severe secondary acid-base and hydroelectrolytic disorders. Hyper and hypoglycemia are also a common complications. The main objective of the emergency treatment is to prevent the severe sequels of tissue hypoxia, seizures and osmotic shifts over general and central nervous systems as a result of fluid and electrolytes imbalances. Expedite shock resuscitation and adequate correction of seizures, hydroelectrolytic and glucose balance are the corner stone of the therapeutic approach. Due to the possibility of SNC damage, in patients with > 48 hours of symptom presentation, it is very important to prevent plasmatic variations of osmolality larger than 3–4 mOsm/L/h.

Diabetic Ketoacidosis (DKA) and Hyperosmolar Hyperglycemic Syndrome (HHS)

Diabetic ketoacidosis and HSS share potentially fatal complications. Morbidity and mortality from these syndromes are related to the significance of metabolic disturbances, concomitant diseases and possible complications derived from improper therapy related to electrolytes and osmolality.

Diabetes mellitus results from the absence of insulin (type I) or insulin resistance (type II). Contributors diabetes type I development are amyloid deposit, chronic pancreatitis and pancreatic β cells vacuolization. Diabetes type II is the result of some factors like obesity, endogen or corticoid administration or hyperglycemic hormones. The four classic signs of decompensated diabetes mellitus are polyuria, polydipsia, polyphagia and weight lost.

Hyperosmolar hyperglycemic syndrome is characterized by severe hyperglycemia (> 600 mg/dl), absence or low presence of ketones and serum osmolality over 350 mOsm/kg. Comatose presentation is not common.

Between 69–92% of patients presented with DKA or HHS have a concomitant infection, pyometra, gastroenteritis, renal or hepatic failure, pancreatitis, hyperadrenocorticism, neoplasia and/or cardiac failure as precipitant causes. Corticosteroids, thiazides, sympathomimetic agents and progesterone (luteal phase, contraceptives) alter the carbohydrate metabolism and may cause a crisis.

The absolute or relative deficiency of insulin in combination with an increment in hyperglycemic hormones (glucagon, catecholamine, cortisol, growth hormone) increases glycogenolysis, gluconeogenesis rate, decreases glucose tissue extraction, activates lipid metabolism, fatty acid production and their hepatic metabolism into ketones. The absence of insulin activates the hormone-sensitive lipase increasing the production of free fatty acids (FFA). FFA could be utilized as a source of energy by many tissues, transforming them in to triglycerides by the liver or being totally metabolized into CO₂ and water. FFA could be also transformed in to ketone bodies (i.e., acetone, acetoacetic acid, and beta-hydroxybutyric acid) but this is limited in non-complicated diabetic patients. Development of ketoacidosis requires an increasing production of hyperglycemic hormones ("diabetogenic") secondary to an additional stressful insult such as concomitant disease. In addition of stimulating gluconeogenesis and glycogenolysis, these hormones augment protein catabolism releasing amino acids for the hepatic production of glucose while increasing lipolysis. The resulting FAA won't be used as a source of energy leading to the production of ketone bodies (KB). The accumulation of KB produces the classic DKA triad of hyperglycemia, ketonemia and acidosis, which is generally accompanied by ketonuria, glycosuria, and osmotic diuresis.

The reduction of glomerular filtration rate (GFR) diminishes secondary to dehydration and hypovolemia (due to glycosuria and osmotic diuresis) and concomitant diseases (shock, renal and/or cardiac failure) and will favor a marked increase of glycemia (glu > 600 mg/dl) and osmolality [osm = (Na + K) 2 + glu/18] (osm > 350 mOsm/kg) - main features of the HHS. The limited insulin concentration is able to inhibit lipolysis which limits ketosis in HHS but not to prevent hyperglycemia. Some patients, however, may display a combination of both syndromes (DKA + increased osmolality, or HHS + moderate ketosis).

Treatment

Rapidly stabilize the cardiovascular system and restore water and electrolyte loses before initiating insulin therapy. This will increase tissue perfusion and GFR reducing acidosis by promoting aerobic metabolism, liver metabolism of lactic acid and KB as well as the renal excretion of H⁺. Fluid therapy will reduce glycemia by 30–50% and hyperglycemic hormones facilitating the cellular response to insulin therapy. Fluid therapy will gradually reduce the osmolality by maintaining certain degree of hyperglycemia while normalizing natremia thus preventing cerebral edema. Serum glucose and electrolytes should be monitored every hour. Glycemia should be kept at a > 250 mg/dl during the first 4–6 hours, avoiding significant changes of > 100 mg GLU/dl/h or > 3–4 mOsm/l/h.

Dextrose 2.5% administration along with insulin titration may be needed to accomplish this therapeutic goal. Hyperkalemia and hyperphosphatemia are common; however, body depletion of these electrolytes is generally severe and fluid and insulin therapies tend to rapidly reduce their serum concentrations. Hyperkalemic patients should start fluid therapy with NaCl 0.9% until the GFR is restored and renal failure oligoanuria is ruled out. As long as K⁺ administration is ≤ 0.5 mEq/kg/h and renal function is normal, fluid therapy can be supplemented according to Table 1.

If signs of hypokalemia persist despite an aggressive K⁺ supplementation, hypomagnesaemia should be addressed by adding magnesium sulfate 0.75–1.0 mEq/kg/d CRI in 5% dextrose. Dosage should be gradually reduced by 50% in 3–5 days. Hypophosphatemia (< 1.5 mg/dL) may cause hemolysis and seizures; it is advisable to supplement 0.01–0.06 mmol/kg/h of potassium phosphate in NaCl 0.09% during the first 12–48 hours, (consider the additional source of potassium). One-quarter of the calculated base deficit of NaHCO₃ should be administered only if acidosis persist (pH < 7.0) after one hour fluid therapy.

Regular insulin administration should be started after 4–6 hours of fluids and only when [K⁺] is within a high-normal range. 2,2 U/kg (dogs) and 1,1 U/kg (cats) in 250 ml of NaCl 0,9% should be administered adjusting the infusion rate according to glycemia (Table 1).

Table 1

Adjustments for intravenously administered regular crystalline insulin, dextrose, and potassium.
Adapted from Boysen SR. Fluids and electrolyte therapy in endocrine disorders: diabetes mellitus and hypoadrenocorticism. Vet Clin North Am Small Pract. 2008;38(3):699-717.

Once the patient is able to eat, longer lasting acting insulin should be administered SC every 24 hours. Oral administration of lipoic acid (200 mg/kg/8 h), and chromium picolinate (200 µg/day) might help stabilizing serum glucose concentration by enhancement of the biological action of insulin. Ovariohysterectomy (OVH) could definitively resolve the occurrence of diabetes mellitus, and should be recommended to all affected intact bitches once they are clinically stable.

Hypoadrenocorticism (Addison Disease)

Hypoadrenocorticism is an uncommon disorder in dogs and rare in cats. Based on its origin, it can be characterized by a dual deficiency of mineralocorticoids and glucocorticoids, or just of glucocorticoids.

Clinical history will point out to PU/PD and GI episodes (emesis, diarrhea and melena), lethargy, weakness, and collapse, which could be all resolved by proper fluid therapy. However, the hydroelectrolytic disturbances, as well as the consequences of an inadequate therapy could risk the patient's life. Severe hypovolemic shock with bradycardia should prompt the suspicion of a potential hyperkalemia.

Blood work will typically show hyponatremia and hyperkalemia (Na/K < 27 suggestive; < 20 highly likely), hypochloremia, hypoglycemia, azotemia, acidosis (mild to severe), eosinophilia and absolute lymphocytosis. Prompt improvement of azotemia as a result of the fluid therapy will allow ruling out acute renal failure (ARF). Osmotic shifts secondary to hyponatremia could result in neurological signs (coma, seizures, stupor) before and/or during the treatment.

Conclusive diagnosis will be achieved by the corticotrophin test (dogs: 0.5 µg/kg/IV, max. 250 µg/kg; cats 125 µg/cat/IV). Plasma cortisol basal concentration (1 h post stimulation; 30 min in cats) of 2 µg/dL are considered diagnostic.

Treatment

The main objective of the treatment is to restore normovolemia and tissue perfusion. Shock resuscitation should be performed within the first 30 min. If chronic heart failure (CHF) is not present, the patient should start fluid therapy with NaCl 0.9% in bolus of 10–30 ml/kg/10 min until stabilization of the patient has been achieved. Once the patient is hemodynamically stable, fluid therapy should switch to NaCl 0.45%/dextrose 2.5% to prevent the risk of irreversible osmotic demyelination syndrome (hyponatremia > 48 h). Adjusting seric Na should always be < 10–12 mEq/L/24 h and 18 mEq/L/48 h. Should seizures arise, treatment should be far more aggressive considering that the risk of hyponatremic cerebral edema is greater than the potential presentation of a demyelination syndrome.

Generally, fluid therapy will be enough to correct the hyperkalemia. A slow infusion of calcium gluconate 10%, 0.5–1.0 ml/kg/IV should be administered to treat severe arrhythmias. Dextrose (2.5%), or in combination with insulin 0.2 U/kg/IV, followed by dextrose 5% IV CRI during 6 hours has proven to be effective to correct the hyperkalemia and hypoglycemia.

Dexamethasone 0.25–4.0 mg/kg during the first 3 hours of fluid therapy, will not only decrease the risk for demyelination, but also will address the deficit of glucocorticoids without interfering with the corticotropin test (prednisone, prednisolone, and hydrocortisone do interfere). Mineralocorticoids favor the rapid correction of the natremia and they should not be used during the first 48 hours of therapy.

Long-term supplementation should consist of fluorocortisone 0.2 mg/kg gradually increasing 0.05–0.1 mg/24 h until electrolytes have reached a stable concentration. Alternative therapy should incorporate DOCP 2 mg/kg/25 days + prednisone 0.22 mg/kg/day. Recommended DOCP dosages for cats are 12.5 mg/cat/day, or methyl prednisolone 10 mg/cat/3–4 weeks. During stressful events (surgery, traveling, etc.), prednisone therapeutic dosages should be increased 5–10 times.

References

1.  Boysen SR. Fluids and electrolyte therapy in endocrine disorders: diabetes mellitus and hypoadrenocorticism. Vet Clin North Am Small Pract. 2008;38(3):699–717.

2.  DiBartola S. Alteraciones del sodio y el agua: hipernatremia e hiponatremia. In: DiBartola SP, ed. Fluidoterapia, Electrolitos y Desequilibrios Ácido-Base en Pequeños Animales. 3ed ed. Barcelona, Spain: Multimédica Ediciones Veterinaria; 2007:45–78.

3.  DiBartola S, Autran de Morais H. Alteraciones del potasio: hipokalemia e hiperkalemia. In: DiBartola SP, ed. Fluidoterapia, Electrolitos y Desequilibrios Ácido-Base en Pequeños Animales. 3ed ed. Barcelona, Spain: Multimédica Ediciones Veterinaria; 2007;123–194.