T
Tenotomy
Thermography
Thermoregulation
Thrush
Thyroid hormones
Thyro-L - see Levothyroxine Sodium
TNF-alpha
Tramadol
Transporters - sugar/starch
TRH - thyrotropin-releasing hormone
TRH stimulation test
Triglycerides
Trilostane
Thermography
Thermoregulation
Thrush
Thyroid hormones
Thyro-L - see Levothyroxine Sodium
TNF-alpha
Tramadol
Transporters - sugar/starch
TRH - thyrotropin-releasing hormone
TRH stimulation test
Triglycerides
Trilostane
Tenotomy
BEFORE CONSIDERING A TENOTOMY, PLEASE ENSURE THAT EVERY ATTEMPT HAS BEEN MADE TO CARRY OUT A REALIGNING TRIM AND CORRECTLY SUPPORT THE FEET, AND TO REMOVE/TREAT THE CAUSE OF THE LAMINITIS. A TENOTOMY MAY BE A SALVAGE PROCEDURE AT BEST. MANY HORSES RECOVER FROM SIGNIFICANT DORSAL AND PALMAR ROTATION AND SINKING WITH REALIGNING TRIMMING. PLEASE SEE:
Laminitis and the Feet
How To Develop A Healthy Foot: Circulation Is It - Daisy Bicking
Tenotomy as a Treatment for Laminitis - O'Grady S
Morrison, Scott
Long-term Prognosis Using Deep Digital Flexor Tenotomy and Realignment Shoeing for Treatment of Chronic Laminitis
Journal of Equine Veterinary Science, 2011, Volume 31 , Issue 2 , 89 - 96
Eastman TG, Honnas CM, Hague BA, Moyer W, von der Rosen HD
Deep digital flexor tenotomy as a treatment for chronic laminitis in horses: 35 cases (1988-1997)
J Am Vet Med Assoc. 1999 Feb 15;214(4):517-9
BEFORE CONSIDERING A TENOTOMY, PLEASE ENSURE THAT EVERY ATTEMPT HAS BEEN MADE TO CARRY OUT A REALIGNING TRIM AND CORRECTLY SUPPORT THE FEET, AND TO REMOVE/TREAT THE CAUSE OF THE LAMINITIS. A TENOTOMY MAY BE A SALVAGE PROCEDURE AT BEST. MANY HORSES RECOVER FROM SIGNIFICANT DORSAL AND PALMAR ROTATION AND SINKING WITH REALIGNING TRIMMING. PLEASE SEE:
Laminitis and the Feet
How To Develop A Healthy Foot: Circulation Is It - Daisy Bicking
Tenotomy as a Treatment for Laminitis - O'Grady S
Morrison, Scott
Long-term Prognosis Using Deep Digital Flexor Tenotomy and Realignment Shoeing for Treatment of Chronic Laminitis
Journal of Equine Veterinary Science, 2011, Volume 31 , Issue 2 , 89 - 96
Eastman TG, Honnas CM, Hague BA, Moyer W, von der Rosen HD
Deep digital flexor tenotomy as a treatment for chronic laminitis in horses: 35 cases (1988-1997)
J Am Vet Med Assoc. 1999 Feb 15;214(4):517-9
Thermography
Thermography is an imaging technique which maps body surface temperature changes that could suggest inflammatory, circulatory or neurological abnormalities. It is increasingly being used to investigate lameness and may be useful in the diagnosis of laminitis. However, a controlled environment and strict protocol are required to accurately interpret images.
Soroko M, Howell K
Infrared Thermography: Current Applications in Equine Medicine
JEVS published online 22 Nov 2016
This review suggests that thermography is a useful complementary diagnostic tool in veterinary medicine, helping to find areas of abnormality and guide further diagnostic imaging or treatment, and is useful for monitoring response to treatment where inflammation is involved. However it suggests that using thermography to evaluate surface thermal patterns requires "a controlled environment and rigorous adherence to an imaging protocol to eliminate errors of interpretation", and that the specificity and sensitivity of thermography may be limited.
Turner TA
Thermography as an aid to the clinical lameness evaluation
Vet Clin North Am Equine Pract. 1991 Aug;7(2):311-38. (PubMed)
"Thermography has been shown to be a practical aid in the clinical evaluation of lameness. This modality specifically increases the accuracy of diagnosis. Thermography represents skin temperature, usually pictorially." "Noncontacting thermography, which detects infrared radiation, is the most accurate. In order to be accurate, thermography must be performed in a temperature-controlled, draft-free area. The area should be protected from sunlight to avoid erroneous heating of the skin, and the hair length should be uniform. Thermography detects heat before it is perceptible during routine physical examination; therefore, it is useful for early detection of laminitis, stress fractures, and tendinitis. It offers a noninvasive means of evaluating the blood supply to an injured part and offers one of the only reliable means to evaluate blood flow to the foot of horses with navicular syndrome." "Thermography is an excellent adjunct to clinical and radiographic examination. It is complementary to other imaging techniques such as ultrasonography and scintigraphy."
Recent research has found that variation in the position of the equipment does not have a significant effect on results, but that even a slight breeze can significantly effect results:
Blowing in the wind: how accurate is thermography of horses' legs? University of Veterinary Medicine Vienna - 2013
This paper concludes that thermography can assist with making a diagnosis (except in chronic cases) when used alongside other diagnostic methods e.g. radiography, ultrasonography, and scintigraphy:
Mehmet Alper ÇETİNKAYA, Alper DEMİRUTKU
Thermography in the assessment of equine lameness
Turk. J. Vet. Anim. Sci. 2012; 36(1): 43-48
The “ODD COUPLE” …The Professor and the Thermographer - Malcolm West - Thermal Inspection Services Pty. Ltd.
Understanding Winter Laminitis, Dr. Eleanor Kellon - Uckele Health & Nutrition 2012
Thermography helped to diagnose that front feet affected by repeated laminitis had a lower temperature than the hind feet.
Chapter 7 The Clinical Signs of Laminitis - Chris Pollitt - Equine Laminitis in Australia
Hoof temperatures of 30 degrees C for more than 24 hours during the developmental stage of carbohydrate overload laminitis can indicate impending laminitis.
See also Hoof wall surface temperature.
Soroko M, Howell K
Infrared Thermography: Current Applications in Equine Medicine
JEVS published online 22 Nov 2016
This review suggests that thermography is a useful complementary diagnostic tool in veterinary medicine, helping to find areas of abnormality and guide further diagnostic imaging or treatment, and is useful for monitoring response to treatment where inflammation is involved. However it suggests that using thermography to evaluate surface thermal patterns requires "a controlled environment and rigorous adherence to an imaging protocol to eliminate errors of interpretation", and that the specificity and sensitivity of thermography may be limited.
Turner TA
Thermography as an aid to the clinical lameness evaluation
Vet Clin North Am Equine Pract. 1991 Aug;7(2):311-38. (PubMed)
"Thermography has been shown to be a practical aid in the clinical evaluation of lameness. This modality specifically increases the accuracy of diagnosis. Thermography represents skin temperature, usually pictorially." "Noncontacting thermography, which detects infrared radiation, is the most accurate. In order to be accurate, thermography must be performed in a temperature-controlled, draft-free area. The area should be protected from sunlight to avoid erroneous heating of the skin, and the hair length should be uniform. Thermography detects heat before it is perceptible during routine physical examination; therefore, it is useful for early detection of laminitis, stress fractures, and tendinitis. It offers a noninvasive means of evaluating the blood supply to an injured part and offers one of the only reliable means to evaluate blood flow to the foot of horses with navicular syndrome." "Thermography is an excellent adjunct to clinical and radiographic examination. It is complementary to other imaging techniques such as ultrasonography and scintigraphy."
Recent research has found that variation in the position of the equipment does not have a significant effect on results, but that even a slight breeze can significantly effect results:
Blowing in the wind: how accurate is thermography of horses' legs? University of Veterinary Medicine Vienna - 2013
This paper concludes that thermography can assist with making a diagnosis (except in chronic cases) when used alongside other diagnostic methods e.g. radiography, ultrasonography, and scintigraphy:
Mehmet Alper ÇETİNKAYA, Alper DEMİRUTKU
Thermography in the assessment of equine lameness
Turk. J. Vet. Anim. Sci. 2012; 36(1): 43-48
The “ODD COUPLE” …The Professor and the Thermographer - Malcolm West - Thermal Inspection Services Pty. Ltd.
Understanding Winter Laminitis, Dr. Eleanor Kellon - Uckele Health & Nutrition 2012
Thermography helped to diagnose that front feet affected by repeated laminitis had a lower temperature than the hind feet.
Chapter 7 The Clinical Signs of Laminitis - Chris Pollitt - Equine Laminitis in Australia
Hoof temperatures of 30 degrees C for more than 24 hours during the developmental stage of carbohydrate overload laminitis can indicate impending laminitis.
See also Hoof wall surface temperature.
Thermoregulation
"Horses with PPID often have poor thermoregulation and patchy sweating associated with hirsutism. These patients are more comfortable with regular body clipping to minimize hirsutism and using blankets in the winter as needed."
Update on PPID in Horses Amy Bentz April 2017 DVM360
"Horses with PPID often have poor thermoregulation and patchy sweating associated with hirsutism. These patients are more comfortable with regular body clipping to minimize hirsutism and using blankets in the winter as needed."
Update on PPID in Horses Amy Bentz April 2017 DVM360
Thyroid hormones
The thyroid gland produces 2 principal hormones:
T3 = Tri-iodothyronine
T4 = Thyroxine
Secretion of thyroid hormones is regulated by the hypothalamus through a negative feedback loop. When blood levels of T3/T4 are low, the hypothalamus secretes TRH (Thyrotropin Releasing Hormone), which causes the pituitary gland to secrete TSH (Thyroid Stimulating Hormone or Thyrotropin), which stimulates the thyroid gland to secrete T3 and T4.
It used to be thought that laminitic ponies suffered from low thyroid hormone concentrations, but there is no evidence that thryoid problems cause EMS/IR or PPID. Thyroid hormones vary considerably in horses with EMS, but this is not the cause of their obesity.
Both hypothyroidism and hyperthyroidism are rare in horses. Low TH concentrations do not = hypothyroidism, TH concentrations are often low in sick horses, meaning that hypothyroidism can be diagnosed falsely. As well as illness, abnormal thyroid hormone concentrations can be caused by a high grain diet/meal, travelling and training stress.
To diagnose a thyroid disorder, a dynamic TRH stimulation test should be carried out, with T3 and T4 concentrations measured at 2 and 4 hours post TRH - a lack of increase in T3 and T4 in response to TRH would suggest thyroid disease.
Some drugs, e.g. Bute (phenylbutazone), glucocorticoid steroids and trrimethoprim-sulfonamide antibiotics can decrease thyroid hormone concentrations, therefore thyroid testing should not be carried out while such drugs are being administered.
Phenylbutazone decreases T4 thyroid hormone levels:
Sojka JE, Johnson MA, Bottoms GD
Serum triiodothyronine, total thyroxine, and free thyroxine concentrations in horses
Am J Vet Res. 1993 Jan;54(1):52-5
"Phenylbutazone given at a dosage of 4.4 mg/kg every 24 hours, for 7 days did significantly decrease resting T4 and fT4 concentrations, but did not significantly affect T3 concentrations in horses."
The Equine Manual - Higgins & Snyder 2013 p 652 Phenylbutazone is highly protein bound and can displace thyroid hormone from carrier proteins, leading to increased amounts of free thyroid hormone and consequent inhibition of the hypothalamus-pituitary-thyroid axis.
Breuhaus A
Thyroid Hormone and Thyrotropin Concentrations and Responses to Thyrotropin-Stimulating Hormone in Horses with PPID Compared with Age-Matched Normal Horses
Journal of Equine Veterinary Science Volume 75, April 2019, Pages 35-40 (Online 30 January 2019). https://doi.org/10.1016/j.jevs.2019.01.008
"To test the hypothesis that serum thyrotropin (TSH) concentrations are decreased in horses with PPID, baseline serum thyroid hormone and TSH concentrations, and responses to TSH-releasing hormone (TRH), were compared between 12 horses diagnosed as having PPID and 14 age-matched normal horses. Horses with PPID had resting serum concentrations of free thyroxine by equilibrium dialysis (fT4D) and TSH that were significantly lower than serum concentrations of fT4D and TSH in age-matched normal horses. Serum concentrations of total T4 and total and free triiodothyronine (T3) were also lower in horses with PPID compared with normal horses, but the differences did not reach statistical significance. Thyroid hormone and TSH responses to TRH administration were not different between horses with PPID and normal horses."
Breuhaus BA
Serum Thyroid Hormone and Thyrotropin Concentrations in Adult Horses as They Age
Journal of Equine Veterinary Science Volume 68, September 2018, Pages 21-25
The myth of equine hypothyroidism - Kenneth Marcella - DVM360 Nov 2011
The Thyroid - Dr Eleanor Kellon Nov 2014
Breuhaus BA
Disorders of the Equine Thyroid Gland
Vet Clin Equine 27 (2011) 115-128
Thyroid Disease Ch 161 Babetta Breuhaus - Current Therapy in Equine Medicine Vol 6
Thyroid Hormones and Equine Metabolic Syndrome - Dr. Christine King
Investigating suspected thyroid disorders - Liphook Equine Hospital
Thyroid secretary activity - Liphook Equine Hospital
Diagnosing Hypothyroidism in Horses - Dr Bryan Waldridge - KER
Thyroid Gland - Anatomy & Physiology - "WikiVet
Thyroid/Cushing's Disease - Les Sellnow - www.thehorse.com Feb 2005
Iodine and thyroid function
Iodine is necessary for the synthesis of T3 and T4, thyroid hormones that regulate metabolism. An increase in T3 or T4 leads to reduced TSH secretion and an increase in metabolic rate.
Both iodine excess and deficiency reduce the production of thyroid hormones, causing hypothyroidism and an increase in TSH production, leading to goiter (an increase in the size of the thyroid glands).
Symptoms: as well as goiter, excess iodine can cause abortion, foal mortality, hair loss. Iodine deficiency can cause foal abnormalities.
Urinary iodine content can give an indication of the amount of iodine being fed.
Iodine and selenium interact - high levels of iodine in the diet combined with low levels of selenium may cause thyroid tissue damage.
The iodine content of most horse feeds ranges from 0 to 2 mg/kg DM, depending on the iodine content of the soil.
Toxicity is usually the result of oversupplementation or eating feeds with high levels of iodine, e.g. kelp and seaweed, which can have iodine levels over 1,800 mg/kg DM.
Goitrogens can affect iodine uptake and are found in soya beans, linseed and brassicas (cabbage, kale, broccoli, cauliflower, swede, turnip).
The NRC Nutrient Requirements of Horses
Maximum tolerable concentration 5 mg/kg diet, although iodine toxicity has been reported at 40 mg/day.
Minimum recommendation 0.007 mg/kg BW or 3.5 mg/day for a 500 kg horse.
T3 = Tri-iodothyronine
T4 = Thyroxine
Secretion of thyroid hormones is regulated by the hypothalamus through a negative feedback loop. When blood levels of T3/T4 are low, the hypothalamus secretes TRH (Thyrotropin Releasing Hormone), which causes the pituitary gland to secrete TSH (Thyroid Stimulating Hormone or Thyrotropin), which stimulates the thyroid gland to secrete T3 and T4.
It used to be thought that laminitic ponies suffered from low thyroid hormone concentrations, but there is no evidence that thryoid problems cause EMS/IR or PPID. Thyroid hormones vary considerably in horses with EMS, but this is not the cause of their obesity.
Both hypothyroidism and hyperthyroidism are rare in horses. Low TH concentrations do not = hypothyroidism, TH concentrations are often low in sick horses, meaning that hypothyroidism can be diagnosed falsely. As well as illness, abnormal thyroid hormone concentrations can be caused by a high grain diet/meal, travelling and training stress.
To diagnose a thyroid disorder, a dynamic TRH stimulation test should be carried out, with T3 and T4 concentrations measured at 2 and 4 hours post TRH - a lack of increase in T3 and T4 in response to TRH would suggest thyroid disease.
Some drugs, e.g. Bute (phenylbutazone), glucocorticoid steroids and trrimethoprim-sulfonamide antibiotics can decrease thyroid hormone concentrations, therefore thyroid testing should not be carried out while such drugs are being administered.
Phenylbutazone decreases T4 thyroid hormone levels:
Sojka JE, Johnson MA, Bottoms GD
Serum triiodothyronine, total thyroxine, and free thyroxine concentrations in horses
Am J Vet Res. 1993 Jan;54(1):52-5
"Phenylbutazone given at a dosage of 4.4 mg/kg every 24 hours, for 7 days did significantly decrease resting T4 and fT4 concentrations, but did not significantly affect T3 concentrations in horses."
The Equine Manual - Higgins & Snyder 2013 p 652 Phenylbutazone is highly protein bound and can displace thyroid hormone from carrier proteins, leading to increased amounts of free thyroid hormone and consequent inhibition of the hypothalamus-pituitary-thyroid axis.
Breuhaus A
Thyroid Hormone and Thyrotropin Concentrations and Responses to Thyrotropin-Stimulating Hormone in Horses with PPID Compared with Age-Matched Normal Horses
Journal of Equine Veterinary Science Volume 75, April 2019, Pages 35-40 (Online 30 January 2019). https://doi.org/10.1016/j.jevs.2019.01.008
"To test the hypothesis that serum thyrotropin (TSH) concentrations are decreased in horses with PPID, baseline serum thyroid hormone and TSH concentrations, and responses to TSH-releasing hormone (TRH), were compared between 12 horses diagnosed as having PPID and 14 age-matched normal horses. Horses with PPID had resting serum concentrations of free thyroxine by equilibrium dialysis (fT4D) and TSH that were significantly lower than serum concentrations of fT4D and TSH in age-matched normal horses. Serum concentrations of total T4 and total and free triiodothyronine (T3) were also lower in horses with PPID compared with normal horses, but the differences did not reach statistical significance. Thyroid hormone and TSH responses to TRH administration were not different between horses with PPID and normal horses."
Breuhaus BA
Serum Thyroid Hormone and Thyrotropin Concentrations in Adult Horses as They Age
Journal of Equine Veterinary Science Volume 68, September 2018, Pages 21-25
The myth of equine hypothyroidism - Kenneth Marcella - DVM360 Nov 2011
The Thyroid - Dr Eleanor Kellon Nov 2014
Breuhaus BA
Disorders of the Equine Thyroid Gland
Vet Clin Equine 27 (2011) 115-128
Thyroid Disease Ch 161 Babetta Breuhaus - Current Therapy in Equine Medicine Vol 6
Thyroid Hormones and Equine Metabolic Syndrome - Dr. Christine King
Investigating suspected thyroid disorders - Liphook Equine Hospital
Thyroid secretary activity - Liphook Equine Hospital
Diagnosing Hypothyroidism in Horses - Dr Bryan Waldridge - KER
Thyroid Gland - Anatomy & Physiology - "WikiVet
Thyroid/Cushing's Disease - Les Sellnow - www.thehorse.com Feb 2005
Iodine and thyroid function
Iodine is necessary for the synthesis of T3 and T4, thyroid hormones that regulate metabolism. An increase in T3 or T4 leads to reduced TSH secretion and an increase in metabolic rate.
Both iodine excess and deficiency reduce the production of thyroid hormones, causing hypothyroidism and an increase in TSH production, leading to goiter (an increase in the size of the thyroid glands).
Symptoms: as well as goiter, excess iodine can cause abortion, foal mortality, hair loss. Iodine deficiency can cause foal abnormalities.
Urinary iodine content can give an indication of the amount of iodine being fed.
Iodine and selenium interact - high levels of iodine in the diet combined with low levels of selenium may cause thyroid tissue damage.
The iodine content of most horse feeds ranges from 0 to 2 mg/kg DM, depending on the iodine content of the soil.
Toxicity is usually the result of oversupplementation or eating feeds with high levels of iodine, e.g. kelp and seaweed, which can have iodine levels over 1,800 mg/kg DM.
Goitrogens can affect iodine uptake and are found in soya beans, linseed and brassicas (cabbage, kale, broccoli, cauliflower, swede, turnip).
The NRC Nutrient Requirements of Horses
Maximum tolerable concentration 5 mg/kg diet, although iodine toxicity has been reported at 40 mg/day.
Minimum recommendation 0.007 mg/kg BW or 3.5 mg/day for a 500 kg horse.
TNF-alpha (Tumour Necrosis Factor-alpha)
Lorenzo M, Fernández-Veledo S, Vila-Bedmar R, Garcia-Guerra L, De Alvaro C, Nieto-Vazquez I
Insulin resistance induced by tumor necrosis factor-α in myocytes and brown adipocytes
J ANIM SCI April 2008 vol. 86 no. 14 suppl E94-E104
Obesity is a risk factor for the development of insulin resistance. Adipose tissue secretes adipokines that may influence insulin sensitivity. TNF-alpha is overexpressed in adipose tissue of obese animals and humans and has been proposed as a link between obesity and insulin resistance.
Lorenzo M, Fernández-Veledo S, Vila-Bedmar R, Garcia-Guerra L, De Alvaro C, Nieto-Vazquez I
Insulin resistance induced by tumor necrosis factor-α in myocytes and brown adipocytes
J ANIM SCI April 2008 vol. 86 no. 14 suppl E94-E104
Obesity is a risk factor for the development of insulin resistance. Adipose tissue secretes adipokines that may influence insulin sensitivity. TNF-alpha is overexpressed in adipose tissue of obese animals and humans and has been proposed as a link between obesity and insulin resistance.
Tramadol
Guedes A, Knych H, Hood D
Plasma concentrations, analgesic and physiological assessments in horses with chronic laminitis treated with two doses of oral tramadol
Equine Vet J. 2016 Jul;48(4):528-31. doi: 10.1111/evj.12448. Epub 2015 May 21
Guedes A, Knych H, Hood D
Plasma concentrations, analgesic and physiological assessments in horses with chronic laminitis treated with two doses of oral tramadol
Equine Vet J. 2016 Jul;48(4):528-31. doi: 10.1111/evj.12448. Epub 2015 May 21
Transporters - sugar/starch
Ingested food enters the stomach and passes into the lumen of the small intestine. Sugars and starch are digested if necessary (broken down by enzymes to monosaccharides: glucose, fructose, galactose) and transported through the gut wall into enterocyte cells, then into the portal vein, which carries them to the liver.
The first membrane sugars have to cross - the membrane between the gut lumen (along which the ingested food passes) and the enterocyte cells - is called the apical membrane or brush border membrane. Glucose and galactose are actively transported across this border by Sodium Glucose Transporter 1(SGLT-1) (this requires energy - ATP). When the concentration of carbohydrates in the lumen is high, glucose, galactose and fructose can also be transported (facilitated transport) across the apical membrane by GLUT-2. Glucose Transporter 5 (GLUT-5) transports fructose (facilitated transport).
The second membrane sugars have to cross - the membrane between the enterocyte cells and the portal blood circulation - is called the basolateral membrane. Glucose, galactose and fructose leave the enterocyte facilitated by GLUT-2 transporters.
Advanced Nutrition and Human Metabolism - Gropper & Smith, 2013 p 72 good illustration of the transport of monosaccharides into enterocytes.
Drozdowski LA, Thomson ABR
Intestinal sugar transport
World J Gastroenterol. Mar 21, 2006; 12(11): 1657-1670
Carbohydrates in Exercise and Recovery - EAS Academy
Slide 7 - good graphic of sugar transportation across the gut wall.
Shirazi-Beechey, S.P., Moran, A.W., et al.
Influences of food constituents on gut health; glucose sensing and signaling; regulation of intestinal glucose transport
Proceedings of the Nutrition Society, 2011.70: p. 185–193 (ResearchGate)
Research in horses
Rapson JL MSc thesis Michigan State University 2015
Effects of age and diet on glucose and insulin dynamics in the horse
p 43
Daly K, Al-Rammahi M, Arora DK, Moran AW, Proudman CJ, Ninomiya Y, Shirazi-Beechey SP
Expression of sweet receptor components in equine small intestine: relevance to intestinal glucose transport
Am J Physiol Regul Integr Comp Physiol. 2012 Jul 15;303(2):R199-208. doi: 10.1152/ajpregu.00031.2012. Epub 2012 May 2
"Horses possess the ability to upregulate SGLT1 expression in response to increased dietary carbohydrates, and to enhance the capacity of the gut to absorb glucose."
Dyer J, Al-Rammahi M, Waterfall L, Salmon KS, Geor RJ, Bouré L, Edwards GB, Proudman CJ, Shirazi-Beechey SP
Adaptive response of equine intestinal Na+/glucose co-transporter (SGLT1) to an increase in dietary soluble carbohydrate
Pflugers Arch. 2009 Jun;458(2):419-30. doi: 10.1007/s00424-008-0620-4. Epub 2008 Dec 2
"Glucose transport rates, SGLT1 protein, and mRNA expression were all 2-fold higher in the jejunum and 3- to 5-fold higher in the ileum of horses maintained on a hydrolyzable carbohydrate-enriched diet compared to pasture forage." SGLT-1 expression increased in the duodenum and ileum as the carbohydrate content of the diet increased slowly from <1 g/kg bw to 6 g/kg bw.
Dyer J, Fernandez-Castaño Merediz E, Salmon KS, Proudman CJ, Edwards GB, Shirazi-Beechey SP
Molecular characterisation of carbohydrate digestion and absorption in equine small intestine
Equine Vet J. 2002 Jul;34(4):349-58
Ingested food enters the stomach and passes into the lumen of the small intestine. Sugars and starch are digested if necessary (broken down by enzymes to monosaccharides: glucose, fructose, galactose) and transported through the gut wall into enterocyte cells, then into the portal vein, which carries them to the liver.
The first membrane sugars have to cross - the membrane between the gut lumen (along which the ingested food passes) and the enterocyte cells - is called the apical membrane or brush border membrane. Glucose and galactose are actively transported across this border by Sodium Glucose Transporter 1(SGLT-1) (this requires energy - ATP). When the concentration of carbohydrates in the lumen is high, glucose, galactose and fructose can also be transported (facilitated transport) across the apical membrane by GLUT-2. Glucose Transporter 5 (GLUT-5) transports fructose (facilitated transport).
The second membrane sugars have to cross - the membrane between the enterocyte cells and the portal blood circulation - is called the basolateral membrane. Glucose, galactose and fructose leave the enterocyte facilitated by GLUT-2 transporters.
Advanced Nutrition and Human Metabolism - Gropper & Smith, 2013 p 72 good illustration of the transport of monosaccharides into enterocytes.
Drozdowski LA, Thomson ABR
Intestinal sugar transport
World J Gastroenterol. Mar 21, 2006; 12(11): 1657-1670
Carbohydrates in Exercise and Recovery - EAS Academy
Slide 7 - good graphic of sugar transportation across the gut wall.
Shirazi-Beechey, S.P., Moran, A.W., et al.
Influences of food constituents on gut health; glucose sensing and signaling; regulation of intestinal glucose transport
Proceedings of the Nutrition Society, 2011.70: p. 185–193 (ResearchGate)
Research in horses
Rapson JL MSc thesis Michigan State University 2015
Effects of age and diet on glucose and insulin dynamics in the horse
p 43
Daly K, Al-Rammahi M, Arora DK, Moran AW, Proudman CJ, Ninomiya Y, Shirazi-Beechey SP
Expression of sweet receptor components in equine small intestine: relevance to intestinal glucose transport
Am J Physiol Regul Integr Comp Physiol. 2012 Jul 15;303(2):R199-208. doi: 10.1152/ajpregu.00031.2012. Epub 2012 May 2
"Horses possess the ability to upregulate SGLT1 expression in response to increased dietary carbohydrates, and to enhance the capacity of the gut to absorb glucose."
Dyer J, Al-Rammahi M, Waterfall L, Salmon KS, Geor RJ, Bouré L, Edwards GB, Proudman CJ, Shirazi-Beechey SP
Adaptive response of equine intestinal Na+/glucose co-transporter (SGLT1) to an increase in dietary soluble carbohydrate
Pflugers Arch. 2009 Jun;458(2):419-30. doi: 10.1007/s00424-008-0620-4. Epub 2008 Dec 2
"Glucose transport rates, SGLT1 protein, and mRNA expression were all 2-fold higher in the jejunum and 3- to 5-fold higher in the ileum of horses maintained on a hydrolyzable carbohydrate-enriched diet compared to pasture forage." SGLT-1 expression increased in the duodenum and ileum as the carbohydrate content of the diet increased slowly from <1 g/kg bw to 6 g/kg bw.
Dyer J, Fernandez-Castaño Merediz E, Salmon KS, Proudman CJ, Edwards GB, Shirazi-Beechey SP
Molecular characterisation of carbohydrate digestion and absorption in equine small intestine
Equine Vet J. 2002 Jul;34(4):349-58
TRH - thyrotropin-releasing hormone
TRH stimulates the horse's pituitary gland to release POMC-derived peptides, including alpha-MSH from the pars intermedia and ACTH from the pars distalis - this may be caused by TRH's ability to decrease dopamine secretion. TRH also stimulates the secretion of prolactin and growth hormone from the pars distalis. TRH release is suppressed by TSH, thyroid hormones and glucocorticoids. TRH receptor RNA is expressed in both the pars distalis and pars intermedia of the horse.
Breuhaus A
Thyroid Hormone and Thyrotropin Concentrations and Responses to Thyrotropin-Stimulating Hormone in Horses with PPID Compared with Age-Matched Normal Horses
Journal of Equine Veterinary Science Volume 75, April 2019, Pages 35-40 (Online 30 January 2019). https://doi.org/10.1016/j.jevs.2019.01.008
"Thyroid hormone and TSH responses to TRH administration were not different between horses with PPID and normal horses. Normal serum thyroid hormone and TSH concentration responses to exogenous TRH administration support the theory that increased glucocorticoid activity in horses with PPID may exert prolonged tonic suppression, but not complete inhibition, of TRH and subsequent TSH release."
Breuhaus BA
Serum Thyroid Hormone and Thyrotropin Concentrations in Adult Horses as They Age
Journal of Equine Veterinary Science Volume 68, September 2018, Pages 21-25
Thompson DL, Arana-Valencia N
Thyrotropin Releasing Hormone: A Powerful Tripeptide with Diverse Effects in Horses
JEVS December 2017 Vol 59, Pages 7–13 (published online Sept 2017) (DeepDyve)
Domest Anim Endocrinol. 2013 May;44(4):204-12
Changes in plasma melanocyte-stimulating hormone, ACTH, prolactin, GH, LH, FSH, and thyroid-stimulating hormone in response to injection of sulpiride, thyrotropin-releasing hormone, or vehicle in insulin-sensitive and -insensitive mares
Arana-Valencia N, Thompson Jr DL, Mitcham PB
J Vet Intern Med. 2011 May-Jun;25(3):579-85
Seasonal changes in plasma adrenocorticotropic hormone and α-melanocyte-stimulating hormone in response to thyrotropin-releasing hormone in normal, aged horses
Funk RA, Stewart AJ, Wooldridge AA, Kwessi E, Kemppainen RJ, Behrend EN, Zhong Q, Johnson AK
Vet Clin North Am Equine Pract. 2011 Apr;27(1):1-17
Hypothalamic-pituitary gland axis function and dysfunction in horses
Hurcombe SD
Breuhaus A
Thyroid Hormone and Thyrotropin Concentrations and Responses to Thyrotropin-Stimulating Hormone in Horses with PPID Compared with Age-Matched Normal Horses
Journal of Equine Veterinary Science Volume 75, April 2019, Pages 35-40 (Online 30 January 2019). https://doi.org/10.1016/j.jevs.2019.01.008
"Thyroid hormone and TSH responses to TRH administration were not different between horses with PPID and normal horses. Normal serum thyroid hormone and TSH concentration responses to exogenous TRH administration support the theory that increased glucocorticoid activity in horses with PPID may exert prolonged tonic suppression, but not complete inhibition, of TRH and subsequent TSH release."
Breuhaus BA
Serum Thyroid Hormone and Thyrotropin Concentrations in Adult Horses as They Age
Journal of Equine Veterinary Science Volume 68, September 2018, Pages 21-25
Thompson DL, Arana-Valencia N
Thyrotropin Releasing Hormone: A Powerful Tripeptide with Diverse Effects in Horses
JEVS December 2017 Vol 59, Pages 7–13 (published online Sept 2017) (DeepDyve)
Domest Anim Endocrinol. 2013 May;44(4):204-12
Changes in plasma melanocyte-stimulating hormone, ACTH, prolactin, GH, LH, FSH, and thyroid-stimulating hormone in response to injection of sulpiride, thyrotropin-releasing hormone, or vehicle in insulin-sensitive and -insensitive mares
Arana-Valencia N, Thompson Jr DL, Mitcham PB
J Vet Intern Med. 2011 May-Jun;25(3):579-85
Seasonal changes in plasma adrenocorticotropic hormone and α-melanocyte-stimulating hormone in response to thyrotropin-releasing hormone in normal, aged horses
Funk RA, Stewart AJ, Wooldridge AA, Kwessi E, Kemppainen RJ, Behrend EN, Zhong Q, Johnson AK
Vet Clin North Am Equine Pract. 2011 Apr;27(1):1-17
Hypothalamic-pituitary gland axis function and dysfunction in horses
Hurcombe SD
TRH stimulation test
Source: Equine Endocrinology Group Recommendations for the Diagnosis and Treatment of PPID 2021
What is the TRH stimulation test?
Two tests are currently (2022) recommended for the diagnosis of PPID:
- baseline ACTH - used as the initial test for all suspected PPID cases, or only for moderate/advanced PPID cases;
- TRH stimulation of ACTH - used as the initial test for early PPID cases (e.g. when there are few or mild clinical signs or a horse is young), or when baseline ACTH has given an equivocal result, or a negative result when PPID is suspected.
Note that testing for PPID is only recommended if a horse shows clinical signs of PPID.
TRH stimulates pars intermedia activity, and the TRH stimulation of ACTH test relies upon horses with PPID producing higher amounts of ACTH than normal horses following an injection of thryotropin releasing hormone. However, in her 2014 webinar Is it PPID or is it EMS – Diagnosing Equine Endocrine Disease (see also Is it PPID or is it EMS?), Dianne McFarlane suggested that increased activity does not necessarily mean dysfunction - increased activity could be appropriate and not due to lack of dopaminergic inhibition.
The TRH stimulation of ACTH is a relatively new test, and research into the interpretation of results is ongoing.
In 2014 the sensitivity (true positives) and specificity (true negatives) were considered to be 88-95% and 71-91% respectively for the TRH stimulation of ACTH, suggesting that this test is more accurate than basal ACTH.
Two tests are currently (2022) recommended for the diagnosis of PPID:
- baseline ACTH - used as the initial test for all suspected PPID cases, or only for moderate/advanced PPID cases;
- TRH stimulation of ACTH - used as the initial test for early PPID cases (e.g. when there are few or mild clinical signs or a horse is young), or when baseline ACTH has given an equivocal result, or a negative result when PPID is suspected.
Note that testing for PPID is only recommended if a horse shows clinical signs of PPID.
TRH stimulates pars intermedia activity, and the TRH stimulation of ACTH test relies upon horses with PPID producing higher amounts of ACTH than normal horses following an injection of thryotropin releasing hormone. However, in her 2014 webinar Is it PPID or is it EMS – Diagnosing Equine Endocrine Disease (see also Is it PPID or is it EMS?), Dianne McFarlane suggested that increased activity does not necessarily mean dysfunction - increased activity could be appropriate and not due to lack of dopaminergic inhibition.
The TRH stimulation of ACTH is a relatively new test, and research into the interpretation of results is ongoing.
In 2014 the sensitivity (true positives) and specificity (true negatives) were considered to be 88-95% and 71-91% respectively for the TRH stimulation of ACTH, suggesting that this test is more accurate than basal ACTH.
TRH stimulation test protocol
The TRH stimulation test can be carried out at any time of day.
Although reference ranges have recently been suggested for the seasonal rise (Adams et al p 12 Equine Endocrinology Summit 2017), other researchers have not experienced similar results, so for the moment (2022) the TRH stimulation test should not be carried out between mid-July and mid-November, other than for identifying negative cases. See the Equine Endocrinology Group for updates.
Horses can be fed hay in the hours before the test but cereal feeds should not be fed within 12 hours of the test.
The TRH stimulation test can be carried out BEFORE an oral sugar test, but not within 12 hours AFTER an oral sugar test (Restifo et al. 2016). Note that horses suspected of having PPID should have insulin dysregulation assessed (by baseline insulin after eating hay or an oral sugar test), therefore the timing of carrying out an oral sugar test and TRH stimulation test in the same vet visit is important.
Ideally collect a basal ACTH sample into EDTA (purple topped) tubes (time 0).
Inject 1.0 mg of TRH** for horses >250 kg or 0.5 mg for ponies <250 kg intravenously. Note that transient side effects of coughing, Flehmen response, yawning, lip smacking and trembling may be seen, but no serious side effects have been reported.
Collect blood into EDTA (purple topped) tubes EXACTLY 10 MINUTES after TRH administration (time 10). Note the timing of the post-TRH blood collection is important and a 10 minute timer should be started as soon as the TRH is injected.
Both ACTH samples should be handled as for baseline ACTH samples:
Collect blood into EDTA (purple topped) tubes.
Keep samples cool at all times (using ice packs or a refrigerator, but ensure whole blood never comes into contact with ice/freezes as this can give falsely high results).
Centrifuge and separate the plasma. Note if plasma is separated by gravity, it must never be frozen - gravity-separated samples may give falsely high results.
Keep chilled (with ice packs) during transport to the testing laboratory (freezing is not necessary but may be desirable if samples may not reach the laboratory within 48 hours - but note samples must be separated by centrifugation before freezing, and avoid freeze-thaw cycles).
The TRH stimulation test can be carried out at any time of day.
Although reference ranges have recently been suggested for the seasonal rise (Adams et al p 12 Equine Endocrinology Summit 2017), other researchers have not experienced similar results, so for the moment (2022) the TRH stimulation test should not be carried out between mid-July and mid-November, other than for identifying negative cases. See the Equine Endocrinology Group for updates.
Horses can be fed hay in the hours before the test but cereal feeds should not be fed within 12 hours of the test.
The TRH stimulation test can be carried out BEFORE an oral sugar test, but not within 12 hours AFTER an oral sugar test (Restifo et al. 2016). Note that horses suspected of having PPID should have insulin dysregulation assessed (by baseline insulin after eating hay or an oral sugar test), therefore the timing of carrying out an oral sugar test and TRH stimulation test in the same vet visit is important.
Ideally collect a basal ACTH sample into EDTA (purple topped) tubes (time 0).
Inject 1.0 mg of TRH** for horses >250 kg or 0.5 mg for ponies <250 kg intravenously. Note that transient side effects of coughing, Flehmen response, yawning, lip smacking and trembling may be seen, but no serious side effects have been reported.
Collect blood into EDTA (purple topped) tubes EXACTLY 10 MINUTES after TRH administration (time 10). Note the timing of the post-TRH blood collection is important and a 10 minute timer should be started as soon as the TRH is injected.
Both ACTH samples should be handled as for baseline ACTH samples:
Collect blood into EDTA (purple topped) tubes.
Keep samples cool at all times (using ice packs or a refrigerator, but ensure whole blood never comes into contact with ice/freezes as this can give falsely high results).
Centrifuge and separate the plasma. Note if plasma is separated by gravity, it must never be frozen - gravity-separated samples may give falsely high results.
Keep chilled (with ice packs) during transport to the testing laboratory (freezing is not necessary but may be desirable if samples may not reach the laboratory within 48 hours - but note samples must be separated by centrifugation before freezing, and avoid freeze-thaw cycles).
Interpreting TRH stimulation test results
As at 2022, ACTH tested by CIA Immulite 2000XPI* 10 minutes after TRH injection between January and June (northern hemisphere) is considered likely to be:
negative for PPID if <100 pg/ml
positive for PPID if >200 pg/ml
equivocal if 100-200 pg/ml
and between July and December (northern hemisphere) is considered likely to be:
negative for PPID if <100 pg/ml
but the TRH stimulation test cannot be used to identify positive PPID cases between July and December.
*Note that different assays give different results, and therefore interpretation of results must be specific for the assay used.
The Laminitis Site recommends using a laboratory that uses Immulite 2000XPI (e.g. Liphook Equine Hospital in the UK) to facilitate interpretation of ACTH results.
PPID is progressive and difficult to diagnose in the early stages, therefore there will be a grey zone for testing in the early stages of the disease. Diagnosis should be based on history and clinical signs as well as diagnostic test results. Horses with clinical signs of PPID but negative test results should be retested and/or have treatment instigated.
As at 2022, ACTH tested by CIA Immulite 2000XPI* 10 minutes after TRH injection between January and June (northern hemisphere) is considered likely to be:
negative for PPID if <100 pg/ml
positive for PPID if >200 pg/ml
equivocal if 100-200 pg/ml
and between July and December (northern hemisphere) is considered likely to be:
negative for PPID if <100 pg/ml
but the TRH stimulation test cannot be used to identify positive PPID cases between July and December.
*Note that different assays give different results, and therefore interpretation of results must be specific for the assay used.
The Laminitis Site recommends using a laboratory that uses Immulite 2000XPI (e.g. Liphook Equine Hospital in the UK) to facilitate interpretation of ACTH results.
PPID is progressive and difficult to diagnose in the early stages, therefore there will be a grey zone for testing in the early stages of the disease. Diagnosis should be based on history and clinical signs as well as diagnostic test results. Horses with clinical signs of PPID but negative test results should be retested and/or have treatment instigated.
Source: Table 2 Equine Endocrinology Group Recommendations for the Diagnosis and Treatment of PPID 2021
TRH stimulation test research
Durham AE.
The effect of pergolide mesylate on adrenocorticotrophic hormone responses to exogenous thyrotropin releasing hormone in horses.
Vet J. 2022 Jul;285:105831. doi: 10.1016/j.tvjl.2022.105831. Epub 2022 Apr 25. PMID: 35477010.
Keywords: ACTH; Horse; PPID; Pergolide; TRH stimulation test.
Thane K, Uricchio C, Frank N.
Effect of early or late blood sampling on thyrotropin releasing hormone stimulation test results in horses.
J Vet Intern Med. published on line January 2022. doi: 10.1111/jvim.16362. PMID: 35049089. Open Access.
Kam YN, McKenzie K, Coyle M, Bertin F-R.
Repeatability of a thyrotropin-releasing hormone stimulation test for diagnosis of pituitary pars intermedia dysfunction in mature horses.
J Vet Intern Med. Nov/Dec 2021;35(6): 2885-2890. doi:10.1111/jvim.16281.
Hodge E, Kowalski A, Torcivia C, Lindborg S, Stefanovski D, Hart K, Frank N, van Eps A
Effect of thyrotropin-releasing hormone stimulation testing on the oral sugar test in horses when performed as a combined protocol
J Vet Intern Med. 2019 Sep;33(5):2272-2279. doi: 10.1111/jvim.15601. Epub 2019 Aug 20
"The results of this study support the use of combined testing for PPID and ID by performing the TRH stimulation test before the OST, although further validation of these findings in a cohort of horses with confirmed PPID and ID is recommended."
Adams AA, Siard MH, Reedy SE, Barker D, Elzinga S, Sanz MG, Cesar F, Lawson C, Tucker C, Mulholland M, Horohov DW, Urschel K, Ireland JL
Evaluating Seasonal Influences on Hormone Responses to a Diagnostic Test (Thyrotropin-Releasing Hormone Stimulation) Advocated for Early Diagnosis of Pituitary Pars Intermedia Dysfunction (PPID)
International Equine Endocrine Summit Jan 2017
Byrne DP, Secombe CJ, Tan RHH, Perara DI, Watts SP, Wearn J
Highly Variable Autumnal TRH-Stimulation Tests in Normal Horses at two Australian Locations
International Equine Endocrine Summit Jan 2017
Chapman AM, Ainsworth S, Keowen M, Fletcher J, Liu CC
Adrenocorticotropin Hormone Response to Varying Dosages of Thyrotropin Releasing Hormone in Normal Horses
International Equine Endocrine Summit Jan 2017
Restifo MM, Frank N, Hermida P, Sanchez-Londoño A
Effects of withholding feed on thyrotropin-releasing hormone stimulation test results and effects of combined testing on oral sugar test and thyrotropin-releasing hormone stimulation test results in horses
Am J Vet Res. 2016 Jul;77(7):738-48. doi: 10.2460/ajvr.77.7.738
Feeding or fasting beforehand made no difference to TRH stimulation of ACTH results.
TRH stimulation of ACTH results were significantly lower when carried out 60 minutes after an oral sugar test.
Current recommendations (2017) are that an oral sugar test and TRH stimulation of ACTH should not be carried out at the same time.
Goodale L, Frank N, Hermida P, D'Oench S
Evaluation of a thyrotropin-releasing hormone solution stored at room temperature for pituitary pars intermedia dysfunction testing in horses
Am J Vet Res. 2015 May;76(5):437-44. doi: 10.2460/ajvr.76.5.437
"Adverse effects associated with TRH administration included transient coughing and yawning."
"Results indicated that the TRH stimulation test should not be repeated within 24 hours, and cTRH solution stored at room temperature could be used to effectively perform TRH stimulation testing in horses."
Beech J, Boston R, Lindborg S
Comparison of cortisol and ACTH responses after administration of thyrotropin releasing hormone in normal horses and those with pituitary pars intermedia dysfunction
J Vet Intern Med. 2011 Nov-Dec;25(6):1431-8. doi: 10.1111/j.1939-1676.2011.00810.x. Epub 2011 Oct 7
"Measuring ACTH concentration after TRH administration appears superior to measuring cortisol concentration as a diagnostic test for PPID."
J Am Vet Med Assoc. 2011 May 15;238(10):1305-15.
α-Melanocyte--stimulating hormone and adrenocorticotropin concentrations in response to thyrotropin-releasing hormone and comparison with adrenocorticotropin concentration after domperidone administration in healthy horses and horses with pituitary pars intermedia dysfunction
Beech J, McFarlane D, Lindborg S, Sojka JE, Boston RC
"Results suggested that ACTH concentration in response to TRH administration was useful for the diagnosis of PPID in horses and appeared more accurate than response to domperidone administration. Use of an α-MSH concentration ≥ 30 or 50 pmol/L did not appear superior to use of an ACTH concentration ≥ 36 pg/mL for the diagnosis of PPID, either before or 30 minutes after TRH administration."
Journal of the American Veterinary Medical Association August 1, 2007, Vol. 231, No. 3, Pages 417-426
Adrenocorticotropin concentration following administration of thyrotropin-releasing hormone in healthy horses and those with pituitary pars intermedia dysfunction and pituitary gland hyperplasia
Beech J, Boston R, Lindborg S, Russell GE
"The ACTH response to TRH is a useful test for diagnosis of pituitary gland hyperplasia, particularly in horses in which baseline ACTH concentrations are within reference range."
Domest Anim Endocrinol. 2006 May;30(4):276-88. Epub 2005 Aug 9.
Alpha-melanocyte stimulating hormone release in response to thyrotropin releasing hormone in healthy horses, horses with pituitary pars intermedia dysfunction and equine pars intermedia explants.
McFarlane D, Beech J, Cribb A.
"We proposed that TRH directly stimulates the PI in normal and PPID-affected horses to release proopiomelanocortin (POMC) derived peptides. Using alpha-melanocyte stimulating hormone (alpha-MSH) as a marker of a PI response and ACTH as a marker of a PD response, we were able to demonstrate a marked increase in plasma concentration of alpha-MSH and a modest, but significant increase in ACTH after TRH treatment in normal horses. The ability of TRH to directly stimulate release of POMC peptides was confirmed using PI and PD tissue explants.... We conclude that TRH triggers the release of POMC-derived peptides from the PI through the direct stimulation of TRH receptors normally expressed on melanotropes."
Durham AE.
The effect of pergolide mesylate on adrenocorticotrophic hormone responses to exogenous thyrotropin releasing hormone in horses.
Vet J. 2022 Jul;285:105831. doi: 10.1016/j.tvjl.2022.105831. Epub 2022 Apr 25. PMID: 35477010.
Keywords: ACTH; Horse; PPID; Pergolide; TRH stimulation test.
Thane K, Uricchio C, Frank N.
Effect of early or late blood sampling on thyrotropin releasing hormone stimulation test results in horses.
J Vet Intern Med. published on line January 2022. doi: 10.1111/jvim.16362. PMID: 35049089. Open Access.
Kam YN, McKenzie K, Coyle M, Bertin F-R.
Repeatability of a thyrotropin-releasing hormone stimulation test for diagnosis of pituitary pars intermedia dysfunction in mature horses.
J Vet Intern Med. Nov/Dec 2021;35(6): 2885-2890. doi:10.1111/jvim.16281.
Hodge E, Kowalski A, Torcivia C, Lindborg S, Stefanovski D, Hart K, Frank N, van Eps A
Effect of thyrotropin-releasing hormone stimulation testing on the oral sugar test in horses when performed as a combined protocol
J Vet Intern Med. 2019 Sep;33(5):2272-2279. doi: 10.1111/jvim.15601. Epub 2019 Aug 20
"The results of this study support the use of combined testing for PPID and ID by performing the TRH stimulation test before the OST, although further validation of these findings in a cohort of horses with confirmed PPID and ID is recommended."
Adams AA, Siard MH, Reedy SE, Barker D, Elzinga S, Sanz MG, Cesar F, Lawson C, Tucker C, Mulholland M, Horohov DW, Urschel K, Ireland JL
Evaluating Seasonal Influences on Hormone Responses to a Diagnostic Test (Thyrotropin-Releasing Hormone Stimulation) Advocated for Early Diagnosis of Pituitary Pars Intermedia Dysfunction (PPID)
International Equine Endocrine Summit Jan 2017
Byrne DP, Secombe CJ, Tan RHH, Perara DI, Watts SP, Wearn J
Highly Variable Autumnal TRH-Stimulation Tests in Normal Horses at two Australian Locations
International Equine Endocrine Summit Jan 2017
Chapman AM, Ainsworth S, Keowen M, Fletcher J, Liu CC
Adrenocorticotropin Hormone Response to Varying Dosages of Thyrotropin Releasing Hormone in Normal Horses
International Equine Endocrine Summit Jan 2017
Restifo MM, Frank N, Hermida P, Sanchez-Londoño A
Effects of withholding feed on thyrotropin-releasing hormone stimulation test results and effects of combined testing on oral sugar test and thyrotropin-releasing hormone stimulation test results in horses
Am J Vet Res. 2016 Jul;77(7):738-48. doi: 10.2460/ajvr.77.7.738
Feeding or fasting beforehand made no difference to TRH stimulation of ACTH results.
TRH stimulation of ACTH results were significantly lower when carried out 60 minutes after an oral sugar test.
Current recommendations (2017) are that an oral sugar test and TRH stimulation of ACTH should not be carried out at the same time.
Goodale L, Frank N, Hermida P, D'Oench S
Evaluation of a thyrotropin-releasing hormone solution stored at room temperature for pituitary pars intermedia dysfunction testing in horses
Am J Vet Res. 2015 May;76(5):437-44. doi: 10.2460/ajvr.76.5.437
"Adverse effects associated with TRH administration included transient coughing and yawning."
"Results indicated that the TRH stimulation test should not be repeated within 24 hours, and cTRH solution stored at room temperature could be used to effectively perform TRH stimulation testing in horses."
Beech J, Boston R, Lindborg S
Comparison of cortisol and ACTH responses after administration of thyrotropin releasing hormone in normal horses and those with pituitary pars intermedia dysfunction
J Vet Intern Med. 2011 Nov-Dec;25(6):1431-8. doi: 10.1111/j.1939-1676.2011.00810.x. Epub 2011 Oct 7
"Measuring ACTH concentration after TRH administration appears superior to measuring cortisol concentration as a diagnostic test for PPID."
J Am Vet Med Assoc. 2011 May 15;238(10):1305-15.
α-Melanocyte--stimulating hormone and adrenocorticotropin concentrations in response to thyrotropin-releasing hormone and comparison with adrenocorticotropin concentration after domperidone administration in healthy horses and horses with pituitary pars intermedia dysfunction
Beech J, McFarlane D, Lindborg S, Sojka JE, Boston RC
"Results suggested that ACTH concentration in response to TRH administration was useful for the diagnosis of PPID in horses and appeared more accurate than response to domperidone administration. Use of an α-MSH concentration ≥ 30 or 50 pmol/L did not appear superior to use of an ACTH concentration ≥ 36 pg/mL for the diagnosis of PPID, either before or 30 minutes after TRH administration."
Journal of the American Veterinary Medical Association August 1, 2007, Vol. 231, No. 3, Pages 417-426
Adrenocorticotropin concentration following administration of thyrotropin-releasing hormone in healthy horses and those with pituitary pars intermedia dysfunction and pituitary gland hyperplasia
Beech J, Boston R, Lindborg S, Russell GE
"The ACTH response to TRH is a useful test for diagnosis of pituitary gland hyperplasia, particularly in horses in which baseline ACTH concentrations are within reference range."
Domest Anim Endocrinol. 2006 May;30(4):276-88. Epub 2005 Aug 9.
Alpha-melanocyte stimulating hormone release in response to thyrotropin releasing hormone in healthy horses, horses with pituitary pars intermedia dysfunction and equine pars intermedia explants.
McFarlane D, Beech J, Cribb A.
"We proposed that TRH directly stimulates the PI in normal and PPID-affected horses to release proopiomelanocortin (POMC) derived peptides. Using alpha-melanocyte stimulating hormone (alpha-MSH) as a marker of a PI response and ACTH as a marker of a PD response, we were able to demonstrate a marked increase in plasma concentration of alpha-MSH and a modest, but significant increase in ACTH after TRH treatment in normal horses. The ability of TRH to directly stimulate release of POMC peptides was confirmed using PI and PD tissue explants.... We conclude that TRH triggers the release of POMC-derived peptides from the PI through the direct stimulation of TRH receptors normally expressed on melanotropes."
Can the TRH stimulation test be used for monitoring response to treatment?
Although in 2013 the Equine Endocrinology Group's Recommendations for the Diagnosis and Treatment of Pituitary Pars Intermedia Dysfunction (PPID) suggested that "the test used to diagnose PPID (e.g., plasma ACTH concentration or TRH stimulation test) should be rechecked after 30 days to assess the response to treatment" and "a period of two months is required before conclusions should be drawn about changes in clinical signs", the 2021 Recommendations (Figure 6) only refer to monitoring baseline ACTH, doing so 1 to 3 months after starting treatment with pergolide, and then every 6 to 12 months.
Although in 2013 the Equine Endocrinology Group's Recommendations for the Diagnosis and Treatment of Pituitary Pars Intermedia Dysfunction (PPID) suggested that "the test used to diagnose PPID (e.g., plasma ACTH concentration or TRH stimulation test) should be rechecked after 30 days to assess the response to treatment" and "a period of two months is required before conclusions should be drawn about changes in clinical signs", the 2021 Recommendations (Figure 6) only refer to monitoring baseline ACTH, doing so 1 to 3 months after starting treatment with pergolide, and then every 6 to 12 months.
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Presenting at the 2nd European Equine Endocrinology Symposium in May 2014, Dr McFarlane (one of the researchers responsible for the EEG Recommendations) reported that when horses with PPID were treated with pergolide and retested using both resting ACTH and the TRH stimulation of ACTH every 4 weeks, resting ACTH levels dropped significantly after starting treatment, but TRH stimulation of ACTH results didn't drop until 20 weeks after treatment was started - in fact TRH stimulated ACTH rose significantly following the start of treatment with pergolide.
Dr McFarlane concluded that "further work should be performed to determine if provocative testing is necessary to adequately assess response to treatment". |
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General information
The TRH stimulation of cortisol is not considered to be diagnostic of PPID and should not be used (cortisol increases in both normal and PPID horses in response to TRH).
Testing two or more of the hormones produced in excess (alpha-MSH, beta-endorphin, CLIP, ACTH) might improve diagnostic accuracy of PPID, and profiling hormone levels against clinical signs might help to increase our understanding of PPID. As at 2022 generally only ACTH testing is widely available.
The TRH stimulation of cortisol is not considered to be diagnostic of PPID and should not be used (cortisol increases in both normal and PPID horses in response to TRH).
Testing two or more of the hormones produced in excess (alpha-MSH, beta-endorphin, CLIP, ACTH) might improve diagnostic accuracy of PPID, and profiling hormone levels against clinical signs might help to increase our understanding of PPID. As at 2022 generally only ACTH testing is widely available.
Triglycerides
Testing serum triglyceride concentrations may
To convert triglyceride levels (human):
Triglyceride mg/dl = mmol/l x 88.5
Triglyceride mmol/l = mg/dl ÷ 88.5
As at 2016, Liphook Equine Hospital is suggesting testing adiponectin for assessing obesity and possible laminitis risk, and does not suggest testing triglycerides as part of a laminitis risk panel. See Endocrinopathic Laminitis 2016. (However, there have also been problems with adiponectin assays (2020) - insulin and glucose likely remain the best blood tests for insulin dysregulation and EMS).
ECEIM Congress 2015. J Vet Intern Med. 2016 May-Jun;30(3):899–916. doi: 10.1111/jvim.13925.
Prospective Cohort Study Evaluating Risk Factors for the Development of Pasture‐Associated Laminitis in the UK
N.J. Menzies‐Gow, P.A. Harris, K. Potter, J. Elliott.
Triglyceride concentrations were not associated with laminitis development.
A15 Morphometric characteristics, insulin, leptin and triglyceride concentrations in obese Andalusian horses
T. Martin Gimenez, I. de Blas Giral, C.N. Aguirre Pascasio.
Triglycerides were significantly higher in obese Andalusian horses. BCS was significantly correlated with triglycerides. Triglycerides were correlated with waist:height and waist:length ratios. However, insulin was not associated with BCS.
Dunkel B, Wilford SA, Parkinson NJ, Ward C, Smith P, Grahame L, Brazil T, Schott HC 2nd.
Severe hypertriglyceridaemia in horses and ponies with endocrine disorders.
Equine Vet J. 2014 Jan;46(1):118-22. doi: 10.1111/evj.12089. Epub 2013 Jul 1. PMID: 23663085.
Severe hypertriglyceridaemia was considered to be serum triglyceride concentration >5.65 mmol/l. Histories of 3 horses and 4 ponies with severe hypertriglyceridaemia were analysed. 4 equids had weight loss, but in 3 equids the discovery of hypertriglyceridaemia was incidental. All equids were bright and alert with normal or increased appetites. Serum triglyceride concentrations ranged from 10.5 to 60.3 mmol/l. Other abnormalities included hyperglycaemia (6/7), suspected insulin resistance, mild to severe increases in hepatic enzyme activity, with moderate hepatic lipidosis confirmed histologically in 2 equids. 3/3 horses and 3/4 ponies were diagnosed with PPID based on clinical signs and basal ACTH concentration or dexamethasone suppression test results, and in 5 of these equids type 2 diabetes mellitus was confirmed. 1 pony had type 2 diabetes mellitus without PPID being diagnosed.
With treatment (pergolide and/or insulin) laboratory abnormalities improved in 4 equids. Treatment was not attempted for 1 horse. 2 ponies had poor or only partly effective treatment; however in one of these biochemical abnormalities persisted for 7 years without apparent ill effects.
"Conclusions and potential relevance: Horses and ponies may develop severe hypertriglyceridaemia secondary to endocrine disorders that are associated with insulin resistance. Hypertriglyceridaemia can resolve with treatment of the endocrinopathy. Although biochemical evidence of hepatic compromise was present, clinical abnormalities were not noted in these animals."
Testing serum triglyceride concentrations may
To convert triglyceride levels (human):
Triglyceride mg/dl = mmol/l x 88.5
Triglyceride mmol/l = mg/dl ÷ 88.5
As at 2016, Liphook Equine Hospital is suggesting testing adiponectin for assessing obesity and possible laminitis risk, and does not suggest testing triglycerides as part of a laminitis risk panel. See Endocrinopathic Laminitis 2016. (However, there have also been problems with adiponectin assays (2020) - insulin and glucose likely remain the best blood tests for insulin dysregulation and EMS).
ECEIM Congress 2015. J Vet Intern Med. 2016 May-Jun;30(3):899–916. doi: 10.1111/jvim.13925.
Prospective Cohort Study Evaluating Risk Factors for the Development of Pasture‐Associated Laminitis in the UK
N.J. Menzies‐Gow, P.A. Harris, K. Potter, J. Elliott.
Triglyceride concentrations were not associated with laminitis development.
A15 Morphometric characteristics, insulin, leptin and triglyceride concentrations in obese Andalusian horses
T. Martin Gimenez, I. de Blas Giral, C.N. Aguirre Pascasio.
Triglycerides were significantly higher in obese Andalusian horses. BCS was significantly correlated with triglycerides. Triglycerides were correlated with waist:height and waist:length ratios. However, insulin was not associated with BCS.
Dunkel B, Wilford SA, Parkinson NJ, Ward C, Smith P, Grahame L, Brazil T, Schott HC 2nd.
Severe hypertriglyceridaemia in horses and ponies with endocrine disorders.
Equine Vet J. 2014 Jan;46(1):118-22. doi: 10.1111/evj.12089. Epub 2013 Jul 1. PMID: 23663085.
Severe hypertriglyceridaemia was considered to be serum triglyceride concentration >5.65 mmol/l. Histories of 3 horses and 4 ponies with severe hypertriglyceridaemia were analysed. 4 equids had weight loss, but in 3 equids the discovery of hypertriglyceridaemia was incidental. All equids were bright and alert with normal or increased appetites. Serum triglyceride concentrations ranged from 10.5 to 60.3 mmol/l. Other abnormalities included hyperglycaemia (6/7), suspected insulin resistance, mild to severe increases in hepatic enzyme activity, with moderate hepatic lipidosis confirmed histologically in 2 equids. 3/3 horses and 3/4 ponies were diagnosed with PPID based on clinical signs and basal ACTH concentration or dexamethasone suppression test results, and in 5 of these equids type 2 diabetes mellitus was confirmed. 1 pony had type 2 diabetes mellitus without PPID being diagnosed.
With treatment (pergolide and/or insulin) laboratory abnormalities improved in 4 equids. Treatment was not attempted for 1 horse. 2 ponies had poor or only partly effective treatment; however in one of these biochemical abnormalities persisted for 7 years without apparent ill effects.
"Conclusions and potential relevance: Horses and ponies may develop severe hypertriglyceridaemia secondary to endocrine disorders that are associated with insulin resistance. Hypertriglyceridaemia can resolve with treatment of the endocrinopathy. Although biochemical evidence of hepatic compromise was present, clinical abnormalities were not noted in these animals."
Trilostane
Trilostane is a competitive inhibitor of the enzyme 3-beta hydroxysteroid dehydrogenase, and works by inhibiting corticosteroid synthesis in the adrenal glands, i.e. it inhibits the production of cortisol. It is commonly used for dogs with pituitary dependent hyperadrenocorticism.
Whilst pergolide is the treatment of choice for PPID, it may be that horses with PPID that develop adrenal hyperplasia (reported to be around 20% - these are likely to be advanced cases of PPID) could benefit from treatment with trilostane. McGowan and Neiger (2003) used an average dose of 0.5 mg/kg bodyweight trilostane. Nicholas Frank suggested that the recommended dosage for trilostane should now be 1.0 mg/kg once a day, given in the evening.
Management of Pituitary Pars Intermedia Dysfunction (PPID) - Nicholas Frank 2011
Abra Wright MSc Thesis 2009 (page 18)
Pharmacokinetics of Pergolide in normal mares
The Veterinarian Feb 2005
Diagnosis and Treatment of Equine Cushing's Syndrome
Catherine M McGowan
Equine vet. J. (2003) 35 (4) 414-418
Efficacy of trilostane for the treatment of equine Cushing's syndrome
McGowan CM, Neiger R
Whilst pergolide is the treatment of choice for PPID, it may be that horses with PPID that develop adrenal hyperplasia (reported to be around 20% - these are likely to be advanced cases of PPID) could benefit from treatment with trilostane. McGowan and Neiger (2003) used an average dose of 0.5 mg/kg bodyweight trilostane. Nicholas Frank suggested that the recommended dosage for trilostane should now be 1.0 mg/kg once a day, given in the evening.
Management of Pituitary Pars Intermedia Dysfunction (PPID) - Nicholas Frank 2011
Abra Wright MSc Thesis 2009 (page 18)
Pharmacokinetics of Pergolide in normal mares
The Veterinarian Feb 2005
Diagnosis and Treatment of Equine Cushing's Syndrome
Catherine M McGowan
Equine vet. J. (2003) 35 (4) 414-418
Efficacy of trilostane for the treatment of equine Cushing's syndrome
McGowan CM, Neiger R