Consider this Case , Emergency Medicine/Critical Care , Endocrinology

The ADR (Ain’t Doing Right) Dog: Endocrine Emergencies

The ADR (Ain’t Doing Right) Dog: Endocrine Emergencies
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Justine A. Lee, DVM, Diplomate ACVECC & ABT & Garret Pachtinger, VMD, Diplomate ACVECC
VETgirl, St. Paul, Minnesota

The first annual Today’s Veterinary Practice symposium—Insights from Experts—took place at the NAVC Conference 2016 in Orlando, Florida. This article reviews the information provided by Dr. Justine Lee and Dr. Garret Pachtinger in the session, Emergency Management of Hypoadrenocorticism. Stay tuned for more information on the 2017 NAVC Conference TVP symposium at tvpjournal.com and navc.com.

Lucky, a 6-year-old, 20-kg, female spayed, mixed-breed dog was presented due to a 1-week history of progressive “ADR” (ain’t doing right).

HISTORY

Lucky was presented to the emergency referral veterinary clinic because her primary care veterinarian was closed for the evening.

The owner reported that Lucky vomited in the car a week earlier when coming home from the groomer. Over the past week, Lucky’s appetite diminished but she seemed thirstier. Lucky had become progressively more lethargic and anorectic over the past 2 days.

Lucky was up-to-date on vaccines, receiving seasonal flea and tick medication and heartworm preventative, and healthy until a week ago.

PHYSICAL EXAMINATION

The physical examination findings for Lucky upon presentation to the referral facility are listed in Table 1. Doppler blood pressure measurement revealed that Lucky’s systolic blood pressure was 80 mm Hg.

T1609C08Table01

INITIAL DIAGNOSTICS

Due to the combination of Lucky’s dehydration and hypovolemia (based on poor pulse quality), a peripheral 18-gauge, 6-cm cephalic IV catheter was placed. A small amount of blood from the catheter hub was obtained for analysis of packed cell volume, total solids, blood urea nitrogen (Azostix, usa.healthcare.siemens.com), blood glucose, and venous blood gas/electrolytes. Laboratory results are listed in Table 2.

T1609C08Table02

Due to the severe hyperkalemia (see INITIAL DIAGNOSIS, Electrolyte Abnormalities), an electrocardiogram (ECG) was obtained immediately. A sinoventricular rhythm was observed, with absent P waves and widened QRS complexes (Figure 1). Typical ECG findings in hyperkalemic patients include bradycardia; tall, tented T waves; prolonged QRS intervals; prolonged PR intervals; absent P waves; and deviation of the ST segment.

FIGURE 1. Electrocardiogram showing sinoventricular rhythm, with absent P waves and widened QRS complexes. Courtesy Gordon Peddle, VMD, Diplomate ACVIM (Cardiology)

FIGURE 1. Electrocardiogram showing sinoventricular rhythm, with absent P waves and widened QRS complexes. Courtesy Gordon Peddle, VMD, Diplomate ACVIM (Cardiology)

Severe hyperkalemia

is a potentially life-threatening complication in a variety of conditions and, thus, emphasizes the importance of rapid evaluation and treatment.

INITIAL DIAGNOSIS

Electrolyte Abnormalities

Lucky’s sodium:potassium ratio was 16:1, which is most often seen in veterinary patients as a result of hypoadrenocorticism and mineralocorticoid deficiency. The hyperkalemia can potentially be life-threatening, resulting in severe arrhythmias. The hypoglycemia can result in clinical signs of weakness, tremors, vomiting, seizures, collapse, and death. Prompt treatment of the electrolyte abnormalities and hypoglycemia in this patient was imperative.

Dehydration & Hypovolemic Shock

This patient had both dehydration and hypovolemic shock. While the patient was only mildly bradycardiac, this was likely an inappropriate response to hypovolemia secondary to a life-threatening hyperkalemia. The presence of both dehydration and hypovolemia are likely due to both glucocorticoid and mineralocorticoid deficiencies.

Differential Diagnosis

Differential diagnosis—in addition to glucocorticoid/mineralocorticoid deficiencies—includes underlying metabolic conditions (eg, ascites, pericardial effusion, severe metabolic acidosis), gastrointestinal disease (eg, whipworm infection), acute kidney injury (AKI), neoplasia, trauma (eg, uroabdomen, rhabdomyolysis), and sepsis.1-6

INITIAL THERAPY

Therapy for Electrolyte Abnormalities

Hyperkalemia decreases resting potential, which makes it less negative and initially results in more hyperexcitable cells.7 To increase the normal threshold membrane potential, thereby normalizing the difference between the 2 potentials, a bolus of 50 mg/kg 10% calcium gluconate, delivered slowly over 15 minutes, was administered to Lucky.7

Alternatively, use of sodium bicarbonate or insulin:dextrose can be considered. Although calcium gluconate has the most rapid stabilizing effect in hyperkalemic patients, it does not address the hyperkalemia itself. Both sodium bicarbonate and insulin therapy result in a transient lowering of serum potassium, promoting its translocation from the extracellular to the intracellular fluid compartment (Figure 2).

FIGURE 2. The effects of potassium and calcium on the action potential. Reprinted with permission from DiBartola SP (ed). Disorders of potassium. Fluid Therapy in Small Animal Practice, 2nd ed. Philadelphia: WB Saunders, 2000.

FIGURE 2. The effects of potassium and calcium on the action potential. Reprinted with permission from DiBartola SP (ed). Disorders of potassium. Fluid Therapy in Small Animal Practice, 2nd ed. Philadelphia: WB Saunders, 2000.

Lucky received continuous ECG monitoring during calcium gluconate administration and until she was more cardiovascularly stable. It is important to remember that calcium gluconate does not directly affect potassium levels.

Therapy for Dehydration & Hypovolemic Shock

Lucky received an initial IV bolus of 0.5 g/kg dextrose (10 mL of 50% dextrose diluted in 20 mL of 0.9% saline) over 2 to 3 minutes to address the hypoglycemia. An additional bolus of 400 mL (20 mL/kg) of warmed lactated Ringer’s solution was administered over 15 minutes.

Ongoing Fluid Therapy

1. Replacement fluids: Lucky’s estimated dehydration was 5%. To correct this deficit over the next 8 hours, Lucky needed to receive fluids at a rate of 125 mL/H:

1000 mL (deficit)/8 H = 125 mL/H
20 kg (body weight) × 0.05 (dehydration) = 1000 mL fluid deficit

2. Maintenance fluids: Lucky also needed to concurrently receive maintenance fluids at a rate of 42 mL/H:

20 kg (body weight) × 50 mL Q 24 H = 1000 mL Q 24 H
1000 mL /24 H = 42 mL/H

More information on the dosage of 50 mL Q 24 H can be found at aaha.org/public_documents/professional/guidelines/fluidtherapy_guidlines_toolkit.pdf.

3. Ongoing losses: Ongoing losses (eg, vomiting, urinary losses) were estimated at 30 mL/H.

4. Crystalloid fluid therapy: Crystalloid fluid rate for the first 8 hours—after the initial fluid bolus—was calculated:

Replacement (125 mL/H) + maintenance (42 mL/H) + ongoing losses (30 mL/H)
= approximately 200 mL/H

Once the dehydration deficit had been replaced, the fluid rate was adjusted to reflect maintenance and ongoing losses. Based on blood glucose monitoring results, glucose supplementation (2.5%–5% dextrose supplementation) was adjusted to maintain normoglycemia.

Patient Monitoring

Reassessment of perfusion parameters showed improvement after the initial crystalloid and dextrose bolus, and Lucky was carefully and frequently assessed while receiving fluid therapy (Table 3). Blood glucose was measured Q 8 H in order to guide glucose supplementation.

T1609C08Table03

ADDITIONAL DIAGNOSTICS

While the patient was stabilized, further diagnostics were pursued, including a complete blood count (CBC), serum biochemical profile, urinalysis (Table 4), and baseline and resting cortisol levels.

T1609C08Table04

CBC results revealed:

  • Eosinophilia and lymphocytosis: May be due to glucocorticoid deficiency (eg, lack of a stress leukogram)1
  • Mild anemia: In the face of dehydration, may be due to gastrointestinal bleeding or anemia of chronic disease.

Biochemistry revealed:

  • Hypoglycemia: Rarely seen in adult dogs secondary to anorexia; may be due to glucocorticoid deficiency, insulinoma, iatrogenic insulin administration, hunting dog hypoglycemia, neoplasia, or sepsis
  • Electrolyte abnormalities, with a sodium:potassium ratio of 16:1
  • Azotemia: May be due to prerenal or primary AKI
  • Hypercalcemia: May be due to underlying metabolic disease (eg, hypoadrenocorticism, hyperparathyroidism), toxicosis (eg, cholecalciferol, calcipotriene), or neoplasia
  • Isosthenuria: May be due to medullary washout secondary to excessive sodium loss into the urine or underlying renal disease.

Lucky’s baseline cortisol (< 2 mcg/dL) was consistent with hypoadrenocorticism. Due to concern regarding the low baseline cortisol, a complete adrenocorticotropic hormone (ACTH) stimulation test was submitted. Both pre-ACTH (< 2 mcg/dL) and post-ACTH (< 2 mcg/dL) stimulation test results were consistent with hypoadrenocorticism.

DEFINITIVE DIAGNOSIS

Based on the baseline cortisol and ACTH stimulation tests, all the clinicopathologic tests were consistent with a diagnosis of hypoadrenocorticism. Additional diagnostics may include fecal testing (to rule out whipworms) and advanced diagnostic imaging, such as ultrasound (to rule out signs and disease, such as gastrointestinal bleeding, ascites, and neoplasia).

THERAPY FOR HYPOADRENOCORTICISM

Typical supportive therapies for the patient with hypoadrenocorticism include:8,9

  • Crystalloid fluids, along with dextrose supplementation as needed
  • Steroids, such as dexamethasone, due to lack of adequate glucocorticoid levels; other types of steroids (eg, prednisone, prednisolone, hydrocortisone) should not be used before diagnostic testing (eg, ACTH stimulation, baseline cortisol) because they interfere with the radioimmunoassay for glucocorticoid measurement
  • Gastric protectants, such as famotidine or pantoprazole, if gastric ulceration is suspected
  • Antiemetics, such as maropitant, dolasetron, ondansetron, or metoclopramide, if vomiting is present
  • Mineralocorticoids, such as desoxycorticosterone pivalate (DOCP) or fludrocortisone acetate (Florinef, bms.com), to help normalize electrolytes; they should be administered once the patient is stable, with life-threatening electrolyte abnormalities corrected, and can tolerate oral medication.

Lucky’s therapeutic approach included:

  1. Initial therapy for electrolyte abnormalities and arrhythmias (calcium gluconate), with continuous ECG monitoring
  2. Initial therapy for dehydration and hypovolemia (dextrose and fluid boluses, then fluid therapy)
  3. Rapid diagnosis of, and therapy for (Table 5), hypoadrenocorticism.

T1609C08Table05

Lucky’s hydration and hypovolemic state improved with fluid therapy and her blood pressure returned to normal after 2 crystalloid boluses. Within 12 hours, Lucky was eating and drinking, and her electrolyte abnormalities had resolved.

PROGNOSIS & FOLLOW-UP CARE

Lucky was discharged the day after presentation—once she was appropriately hydrated, her electrolytes were corrected, and she was eating and drinking voluntarily.

Lucky’s owner was instructed on the long-term management of hypoadrenocorticism, taught how to administer medications (including extra dosing during stressful events), and counseled to follow up with the veterinarian for long-term mineralocorticoid management (eg, DOCP).

The primary care veterinarian performed a recheck examination 3 days after discharge and noted that the physical examination and electrolyte findings were normal; follow-up was scheduled for 3 weeks later to recheck electrolytes and administer DOCP (Table 6).

T1609C08Table06

The owner was pleased with the outcome and rapid improvement in Lucky’s condition.

Overview of Hypoadrenocorticism

Pathophysiology

The adrenal gland is composed of an outer cortex and the inner medulla: The adrenal medulla, which is not affected in hypoadrenocorticism, secretes catecholamines, such as epinephrine and norepinephrine. Hypoadrenocorticism results from atrophy or destruction of the adrenal cortex, which is subdivided into 3 layers:

  • The outer layer—zona glomerulosa—is involved with synthesis and secretion of the mineralocorticoid hormone, aldosterone.
  • The middle layer—zona fasciculata—synthesizes glucocorticoids.
  • The inner layer—zona reticularis—produces adrenal sex steroids.

Primary versus Secondary Disease

Hypoadrenocorticism may be classified as primary or secondary8: Primary hypoadrenocorticism results from bilateral destruction of the adrenal cortices, presumed in most cases to result from immune-mediated destruction of the adrenal gland. Less common causes of primary hypoadrenocorticism include trauma (eg, surgical versus other), infections (eg, fungal or bacterial), neoplasia, or medical therapy (eg, mitotane, trilostane, ketoconazole, megestrol acetate).

 

Secondary hypoadrenocorticism results from lack of adrenal gland stimulation due to hypothalamic–pituitary–adrenal axis dysfunction, which most commonly results from inflammation, tumors, or trauma. Exogenous steroid administration may also suppress ACTH release, resulting in adrenal atrophy.

Signalment

With hypoadrenocorticism, certain breeds of dogs are over-represented, including standard poodles, Great Danes, Rottweilers, West Highland white terriers, Wheaten terriers, Leonbergers, Portuguese water dogs, Labrador retrievers, bearded collies, Old English sheepdogs, and standard schnauzers. Hypoadrenocorticism is also seen more often in young to middle-aged female dogs.11-18

Clinical Signs 

Pathophysiologic changes seen with hypoadrenocorticism are directly a result of glucocorticoid and mineralocorticoid deficiencies. Common clinical signs typically include lethargy, inappetence, vomiting, diarrhea, bradycardia, hypotension, weight loss, and, rarely, death.11

Clinical Findings

Clinicopathologic findings seen with hypoadrenocorticism include the failure to mount a stress leukogram (resulting in eosinophilia, lymphocytosis, and normal overall white blood cell and neutrophil count) and electrolyte abnormalities secondary to direct aldosterone effects (eg, hyperkalemia, hyponatremia, hypochloremia, metabolic acidosis).

Other common laboratory abnormalities include azotemia, isosthenuria (from osmotic diuresis secondary to sodium losses), hypoglycemia (due to impaired gluconeogenesis), hypercalcemia (due to altered renal excretion, reduced gastrointestinal absorption, and decreased resorption of calcium from bone), hypoalbuminemia, and hypocholesterolemia.11,12

Therapeutic Approach

Without treatment, hypoadrenocorticism can be life-threatening due to dehydration, hypovolemia, severe electrolyte derangements, and ongoing fluid losses. To ensure the best outcome, the hypoadrenocorticism state should be rapidly identified.

Treatment for the critically ill patient with hypoadrenocorticism should include symptomatic supportive care, aggressive fluid therapy, correction of electrolyte abnormalities and hypoglycemia, antiarrhythmic therapy (if needed), steroid administration, and mineralocorticoid supplementation, if needed. Appropriate use of steroids needs to be weighed so as not to impair diagnostic testing for baseline cortisol levels or for future ACTH stimulation tests.

IN SUMMARY

Clinicians should be able to rapidly recognize hypoadrenocorticism on the basis of history, signalment, clinical signs, and classic clinicopathologic testing. Rapid and appropriate diagnostic workup should be performed (eg, baseline cortisol, ACTH cortisol evaluation) to rule out other “look-alike” diseases, such as metabolic disorders (eg, renal disease, pancreatitis), toxicosis (eg, from ingestion of grapes, cholecalciferol), and infectious disease (eg, Leptospira infection, urinary tract infection, pyelonephritis).

While long-term management may be cumulatively expensive (eg, prednisone, periodic electrolyte monitoring, and mineralocorticoid supplementation), with medical management, the prognosis for hypoadrenocorticism is good to excellent.

ACTH = adrenocorticotropic hormone; AKI = acute kidney injury; CBC = complete blood count; ECG = electrocardiogram

T1609C09Fig03

Are you a busy veterinary professional that is constantly on the run and experiencing “time poverty”? Join VETgirl, a subscription-based podcast and webinar service offering RACE-approved, online veterinary CE. Founded by Dr. Justine Lee and Dr. Garret Pachtinger, VETgirl offers clinically relevant, practical online veterinary CE for just $199/year. With a VETgirl ELITE subscription, you receive 40+ hours of CE, all provided by board-certified veterinary specialists and experts. Learn more at JoinVETgirl.com and use the discount code TVP2016 for a 10% discount.

 

References

  1. DiBartola SP. Metabolic acid-base disorders. In DiBartola SP (ed): Fluid, Electrolyte, and Acid-Base Disorders, 3rd ed. St. Louis: Elsevier, 2006, pp 251-283.
  2. Peterson ME, Kintzer PP, Kass PH. Pretreatment clinical and laboratory findings in dogs with hypoadrenocorticism: 225 cases (1979-1993). JAVMA 1996; 208:85-91.
  3. DiBartola SP, Johnson SE, Davenport DJ, et al. Clinicopathologic findings resembling hypoadrenocorticism in dogs with primary gastrointestinal disease. JAVMA 1985; 187:60-63.
  4. Ruckstuhl N, Hoerauf A, Tomsa K, et al. Pseudohypoadrenocorticism in two Siberian huskies with gastrointestinal parasitoses. Schweiz Arch Tierheilkd 2002; 144:75-81.
  5. Graves TK, Schall WD, Refsal K, et al. Basal and ACTH-stimulated plasma aldosterone concentration are normal or increased in dogs with trichuriasis-associated pseudohypoadrenocorticism. J Vet Intern Med 1994;8:287-289.
  6. Willard MD, Fossum TW, Torrance A, et al. Hyponatremia and hyperkalemia associated with idiopathic or experimentally induced chylothorax in four dogs. JAVMA 1991; 199:353-358.
  7. DiBartola SP. Disorders of potassium. In DiBartola SP (ed): Fluid Therapy in Small Animal Practice, 2nd ed. Philadelphia: WB Saunders, 2000, pp 83-107.
  8. Kintzer PP, Peterson ME. Primary and secondary canine hypoadrenocorticism. Vet Clin North Am Small Anim Prac 1997; 27:349-357.
  9. Kintzer PP, Peterson ME. Treatment and long-term follow-up of 205 dogs with hypoadrenocorticism. J Vet Intern Med 1997; 11:43-49.
  10. Plumb DC. Plumb’s Veterinary Drug Handbook, 7th ed. Stockholm: Wiley-Blackwell, 2011.
  11. Lifton SJ, King LG, Zerbe CA. Glucocorticoid deficient hypoadrenocorticism in dogs: 18 cases (1986-1995). JAVMA 1996; 209:2076-2081.
  12. Peterson ME, Kintzer PP, Kass PH. Pretreatment clinical and laboratory findings in dogs with hypoadrenocorticism: 225 cases (1979-1993). JAVMA 1996; 208:85-91.
  13. Schaer M, Chen CL. A clinical survey of 48 dogs with adrenocortical hypofunction. JAAHA 1983; 19:443-452.
  14. Shaker E, Hurvitz A, Peterson M. Hypoadrenocorticism in a family of standard poodles. JAVMA 1988; 192:1091-1092.
  15. Famula TR, Belanger JM, Oberbauer AM. Heritability and complex segregation analysis of hypoadrenocorticism in the standard poodle. J Sm Anim Prac 2003; 442:2.
  16. Oberbauer AM, Benemann KS, Belanger JM, et al. Inheritance of hypoadrenocorticism in bearded collies. Am J Vet Res 2002; 63:643-647.
  17. Smallwood LJ, Barsanti JA. Hypoadrenocorticism in a family of Leonbergers. JAAHA 1995; 31:301-305.
  18. Burton S, Delay J, Holmes A, et al. Hypoadrenocorticism in young related Nova Scotia duck tolling retrievers. Can Vet J 1997; 38:231-234.

Author_J-LeeJustine A. Lee, DVM, Diplomate ACVECC & ABT, is the CEO and founder of VETgirl (vetgirlontherun.com), a subscription-based podcast and webinar service that offers RACE-approved online veterinary continuing education. She recently received the NAVC Speaker of the Year Award (2011, 2015, 2016) and is the author and editor of several veterinary textbooks, book chapters, and scientific publications. She completed her veterinary training at Cornell University, Angell Animal Medical Center (Boston), and University of Pennsylvania.

 

Author_G-PachtingerGarret Pachtinger, VMD, Diplomate ACVECC, is the COO and co-founder of VETgirl (vetgirlontherun.com). He is also a criticalist at the Veterinary Specialty & Referral Center in Levittown, Pennsylvania. He completed his veterinary training at University of Pennsylvania.

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id='input_6_10_5_label' >ZIP / Postal Code</label> </span><span class='ginput_right address_country' id='input_6_10_6_container' > <select name='input_10.6' id='input_6_10_6' aria-required="true"><option value='' selected='selected'></option><option value='Afghanistan' >Afghanistan</option><option value='Åland Islands' >Åland Islands</option><option value='Albania' >Albania</option><option value='Algeria' >Algeria</option><option value='American Samoa' >American Samoa</option><option value='Andorra' >Andorra</option><option value='Angola' >Angola</option><option value='Anguilla' >Anguilla</option><option value='Antarctica' >Antarctica</option><option value='Antigua and Barbuda' >Antigua and Barbuda</option><option value='Argentina' >Argentina</option><option value='Armenia' >Armenia</option><option value='Aruba' >Aruba</option><option value='Australia' >Australia</option><option value='Austria' >Austria</option><option value='Azerbaijan' >Azerbaijan</option><option value='Bahamas' >Bahamas</option><option value='Bahrain' >Bahrain</option><option value='Bangladesh' >Bangladesh</option><option value='Barbados' >Barbados</option><option value='Belarus' >Belarus</option><option value='Belgium' >Belgium</option><option value='Belize' >Belize</option><option value='Benin' >Benin</option><option value='Bermuda' >Bermuda</option><option value='Bhutan' >Bhutan</option><option value='Bolivia' >Bolivia</option><option value='Bonaire, Sint Eustatius and Saba' >Bonaire, Sint Eustatius and Saba</option><option value='Bosnia and Herzegovina' >Bosnia and Herzegovina</option><option value='Botswana' >Botswana</option><option value='Bouvet Island' >Bouvet Island</option><option value='Brazil' >Brazil</option><option value='British Indian Ocean Territory' >British Indian Ocean Territory</option><option value='Brunei Darussalam' >Brunei Darussalam</option><option value='Bulgaria' >Bulgaria</option><option value='Burkina Faso' >Burkina Faso</option><option value='Burundi' >Burundi</option><option value='Cambodia' >Cambodia</option><option value='Cameroon' >Cameroon</option><option value='Canada' >Canada</option><option value='Cape Verde' >Cape Verde</option><option value='Cayman Islands' >Cayman Islands</option><option value='Central African Republic' >Central African Republic</option><option value='Chad' >Chad</option><option value='Chile' >Chile</option><option value='China' >China</option><option value='Christmas Island' >Christmas Island</option><option value='Cocos Islands' >Cocos Islands</option><option value='Colombia' >Colombia</option><option value='Comoros' >Comoros</option><option value='Congo, Democratic Republic of the' >Congo, Democratic Republic of the</option><option value='Congo, Republic of the' >Congo, Republic of the</option><option value='Cook Islands' >Cook Islands</option><option value='Costa Rica' >Costa Rica</option><option value='Côte d&#039;Ivoire' >Côte d&#039;Ivoire</option><option value='Croatia' >Croatia</option><option value='Cuba' >Cuba</option><option value='Curaçao' >Curaçao</option><option value='Cyprus' >Cyprus</option><option value='Czech Republic' >Czech Republic</option><option value='Denmark' >Denmark</option><option value='Djibouti' >Djibouti</option><option value='Dominica' >Dominica</option><option value='Dominican Republic' >Dominican Republic</option><option value='Ecuador' >Ecuador</option><option value='Egypt' >Egypt</option><option value='El Salvador' >El Salvador</option><option value='Equatorial Guinea' >Equatorial Guinea</option><option value='Eritrea' >Eritrea</option><option value='Estonia' >Estonia</option><option value='Eswatini (Swaziland)' >Eswatini (Swaziland)</option><option value='Ethiopia' >Ethiopia</option><option value='Falkland Islands' >Falkland Islands</option><option value='Faroe Islands' >Faroe Islands</option><option value='Fiji' >Fiji</option><option value='Finland' >Finland</option><option value='France' >France</option><option value='French Guiana' >French Guiana</option><option value='French Polynesia' >French Polynesia</option><option value='French Southern Territories' >French Southern Territories</option><option value='Gabon' >Gabon</option><option value='Gambia' >Gambia</option><option value='Georgia' >Georgia</option><option value='Germany' >Germany</option><option value='Ghana' >Ghana</option><option value='Gibraltar' >Gibraltar</option><option value='Greece' >Greece</option><option value='Greenland' >Greenland</option><option value='Grenada' >Grenada</option><option value='Guadeloupe' >Guadeloupe</option><option value='Guam' >Guam</option><option value='Guatemala' >Guatemala</option><option value='Guernsey' >Guernsey</option><option value='Guinea' >Guinea</option><option value='Guinea-Bissau' >Guinea-Bissau</option><option value='Guyana' >Guyana</option><option value='Haiti' >Haiti</option><option value='Heard and McDonald Islands' >Heard and McDonald Islands</option><option value='Holy See' >Holy See</option><option value='Honduras' >Honduras</option><option value='Hong Kong' >Hong Kong</option><option value='Hungary' >Hungary</option><option value='Iceland' >Iceland</option><option value='India' >India</option><option value='Indonesia' >Indonesia</option><option value='Iran' >Iran</option><option value='Iraq' >Iraq</option><option value='Ireland' >Ireland</option><option value='Isle of Man' >Isle of Man</option><option value='Israel' >Israel</option><option value='Italy' >Italy</option><option value='Jamaica' >Jamaica</option><option value='Japan' >Japan</option><option value='Jersey' >Jersey</option><option value='Jordan' >Jordan</option><option value='Kazakhstan' >Kazakhstan</option><option value='Kenya' >Kenya</option><option value='Kiribati' >Kiribati</option><option value='Kuwait' >Kuwait</option><option value='Kyrgyzstan' >Kyrgyzstan</option><option value='Lao People&#039;s Democratic Republic' >Lao People&#039;s Democratic Republic</option><option value='Latvia' >Latvia</option><option value='Lebanon' >Lebanon</option><option value='Lesotho' >Lesotho</option><option value='Liberia' >Liberia</option><option value='Libya' >Libya</option><option value='Liechtenstein' >Liechtenstein</option><option value='Lithuania' >Lithuania</option><option value='Luxembourg' >Luxembourg</option><option value='Macau' >Macau</option><option value='Macedonia' >Macedonia</option><option value='Madagascar' >Madagascar</option><option value='Malawi' >Malawi</option><option value='Malaysia' >Malaysia</option><option value='Maldives' >Maldives</option><option value='Mali' >Mali</option><option value='Malta' >Malta</option><option value='Marshall Islands' >Marshall Islands</option><option value='Martinique' >Martinique</option><option value='Mauritania' >Mauritania</option><option value='Mauritius' >Mauritius</option><option value='Mayotte' >Mayotte</option><option value='Mexico' >Mexico</option><option value='Micronesia' >Micronesia</option><option value='Moldova' >Moldova</option><option value='Monaco' >Monaco</option><option value='Mongolia' >Mongolia</option><option value='Montenegro' >Montenegro</option><option value='Montserrat' >Montserrat</option><option value='Morocco' >Morocco</option><option value='Mozambique' >Mozambique</option><option value='Myanmar' >Myanmar</option><option value='Namibia' >Namibia</option><option value='Nauru' >Nauru</option><option value='Nepal' >Nepal</option><option value='Netherlands' >Netherlands</option><option value='New Caledonia' >New Caledonia</option><option value='New Zealand' >New Zealand</option><option value='Nicaragua' >Nicaragua</option><option value='Niger' >Niger</option><option value='Nigeria' >Nigeria</option><option value='Niue' >Niue</option><option value='Norfolk Island' >Norfolk Island</option><option value='North Korea' >North Korea</option><option value='Northern Mariana Islands' >Northern Mariana Islands</option><option value='Norway' >Norway</option><option value='Oman' >Oman</option><option value='Pakistan' >Pakistan</option><option value='Palau' >Palau</option><option value='Palestine, State of' >Palestine, State of</option><option value='Panama' >Panama</option><option value='Papua New Guinea' >Papua New Guinea</option><option value='Paraguay' >Paraguay</option><option value='Peru' >Peru</option><option value='Philippines' >Philippines</option><option value='Pitcairn' >Pitcairn</option><option value='Poland' >Poland</option><option value='Portugal' >Portugal</option><option value='Puerto Rico' >Puerto Rico</option><option value='Qatar' >Qatar</option><option value='Réunion' >Réunion</option><option value='Romania' >Romania</option><option value='Russia' >Russia</option><option value='Rwanda' >Rwanda</option><option value='Saint Barthélemy' >Saint Barthélemy</option><option value='Saint Helena' >Saint Helena</option><option value='Saint Kitts and Nevis' >Saint Kitts and Nevis</option><option value='Saint Lucia' >Saint Lucia</option><option value='Saint Martin' >Saint Martin</option><option value='Saint Pierre and Miquelon' >Saint Pierre and Miquelon</option><option value='Saint Vincent and the Grenadines' >Saint Vincent and the Grenadines</option><option value='Samoa' >Samoa</option><option value='San Marino' >San Marino</option><option value='Sao Tome and Principe' >Sao Tome and Principe</option><option value='Saudi Arabia' >Saudi Arabia</option><option value='Senegal' >Senegal</option><option value='Serbia' >Serbia</option><option value='Seychelles' >Seychelles</option><option value='Sierra Leone' >Sierra Leone</option><option value='Singapore' >Singapore</option><option value='Sint Maarten' >Sint Maarten</option><option value='Slovakia' >Slovakia</option><option value='Slovenia' >Slovenia</option><option value='Solomon Islands' >Solomon Islands</option><option value='Somalia' >Somalia</option><option value='South Africa' >South Africa</option><option value='South Georgia' >South Georgia</option><option value='South Korea' >South Korea</option><option value='South Sudan' >South Sudan</option><option value='Spain' >Spain</option><option value='Sri Lanka' >Sri Lanka</option><option value='Sudan' >Sudan</option><option value='Suriname' >Suriname</option><option value='Svalbard and Jan Mayen Islands' >Svalbard and Jan Mayen Islands</option><option value='Sweden' >Sweden</option><option value='Switzerland' >Switzerland</option><option value='Syria' >Syria</option><option value='Taiwan' >Taiwan</option><option value='Tajikistan' >Tajikistan</option><option value='Tanzania' >Tanzania</option><option value='Thailand' >Thailand</option><option value='Timor-Leste' >Timor-Leste</option><option value='Togo' >Togo</option><option value='Tokelau' >Tokelau</option><option value='Tonga' >Tonga</option><option value='Trinidad and Tobago' >Trinidad and Tobago</option><option value='Tunisia' >Tunisia</option><option value='Turkey' >Turkey</option><option value='Turkmenistan' >Turkmenistan</option><option value='Turks and Caicos Islands' >Turks and Caicos Islands</option><option value='Tuvalu' >Tuvalu</option><option value='Uganda' >Uganda</option><option value='Ukraine' >Ukraine</option><option value='United Arab Emirates' >United Arab Emirates</option><option value='United Kingdom' >United Kingdom</option><option value='United States' >United States</option><option value='Uruguay' >Uruguay</option><option value='US Minor Outlying Islands' >US Minor Outlying Islands</option><option value='Uzbekistan' >Uzbekistan</option><option value='Vanuatu' >Vanuatu</option><option value='Venezuela' >Venezuela</option><option value='Vietnam' >Vietnam</option><option value='Virgin Islands, British' >Virgin Islands, British</option><option value='Virgin Islands, U.S.' >Virgin Islands, U.S.</option><option value='Wallis and Futuna' >Wallis and Futuna</option><option value='Western Sahara' >Western Sahara</option><option value='Yemen' >Yemen</option><option value='Zambia' >Zambia</option><option value='Zimbabwe' >Zimbabwe</option></select> <label for='input_6_10_6' id='input_6_10_6_label' >Country</label> </span> <div class='gf_clear gf_clear_complex'></div> </div></li> </ul></div> <div class='gform_footer top_label'> <input type='submit' id='gform_submit_button_6' class='gform_button button' value='Sign Up' onclick='if(window["gf_submitting_6"]){return false;} window["gf_submitting_6"]=true; ' onkeypress='if( event.keyCode == 13 ){ if(window["gf_submitting_6"]){return false;} window["gf_submitting_6"]=true; jQuery("#gform_6").trigger("submit",[true]); }' /> <input type='hidden' class='gform_hidden' name='is_submit_6' value='1' /> <input type='hidden' class='gform_hidden' name='gform_submit' value='6' /> <input type='hidden' class='gform_hidden' name='gform_unique_id' value='' /> <input type='hidden' class='gform_hidden' name='state_6' value='WyJbXSIsIjNkNTNhNjhlOThlOGY4N2JlZWZiNTRmZDhlZDQ5OWI3Il0=' /> <input type='hidden' class='gform_hidden' name='gform_target_page_number_6' 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