Herp Endocrinology

Question 1

Describe the anatomy of the reptile thyroid gland.

What species have a single glands, which have paired, which have bridged?

Where is the thyroid located in various reptile taxa?

Answer 1

• Thyroid gland
  
  • Chelonians, snakes – single.
  • Lizards – single, bilobed, or paired.
  • Green iguanas, crocodilians – paired thyroid glands joined by a narrow bridge of tissue.
  • Location:
    
    • Snakes – ventral to trachea, cranial to heart, caudal to thymus.
    • Chelonians, lizards – ventral to trachea, near base of heart.
    • Nile crocodile – two asymmetric lobes on lateral sides of each bronchi, right close to where right bronchus enters lung, left close to bifurcation of trachea.
    • Tuatara – single, transversely elongate gland.
• Thyroid glands in reptiles are distinct from parathyroid glands (unlike mammals).
• Thyroid gland receives one of the largest relative blood supplies of any organ.
  
  • Dual arterial supplies on both sides.
  • Lacerta, Zantusia – superior thyroid arteries branch off external or internal carotids, respectively, and attach to lateral thyroids.
  • Inferior thyroid arteries attach to dorsal thyroid.
  • Medial thyroid vents drain into right tracheal or right internal jugular veins.
  • Thyroid gland is within a lymphatic sac, surrounded by lymph tissue.
  • Innervation from laryngeal branches of agus nerve, fine branches of cervical sympathetics.
  • Dense connective tissue capsule.
  • In mammals – thyroid also secretes calcitonin.
    
    • Reptiles – calcitonin is secreted by a separate gland (ultimobranchial gland).

Question 2

Describe the physiology of the reptile thyroid.

What hormone regulated T3, T4 production?

Which is the active form? Which is the storage form?

What taxa have the highest thyroid levels, which have the lowest?

What are the effects of thyroidectomy in lizards and in snakes?

What factors affec thyroid values?

What assays are used in reptiles to measure thyroid function?

Answer 2

• Thyroid function mediated via TRH from hypothalamus, TSH from pituitary.
  
  • TSH controls synthesis and release of T3, T4.
  • Dietary iodine is concentrated in follicular cells, convert iodide to iodine.
    
    • Molecules of iodine attach to tyrosine to form monoiodotyrosine MIT or diiodotyrosine DIT.
      
      • Coupled to form triiodothyronine (T3).
      • Or two DITs can couple to form tetraiodothyronine (thyroxine, T4).
      • Dependent on follicle production of thyroglobulin.
        
        • All of these molecules stored as colloid.
    • T4 accounts for ~80% thyroid hormones in thyroid gland and plasma.
      
      • Storage and transport form.
    • T3 is metabolically active form.
      
      • T4 converted to T3 in skeletal muscle, liver, brain, other target tissues by deiodination.
  • Snake thyroid levels generally lowest of reptiles, chelonians highest.
  • Sea turtles and other reptiles, most T4 bound to carrier proteins, only free T4 available for conversion to T3.
  • Free T4 is the most informative measure of thyroid function in reptiles.
    
    • Most publications measure total T4 due to lack of assays.
• HPT axis in reptiles:
  
  • Shedding, growth, development, reproduction, metabolic rate, nutrient assimilation and activity.
  • Thyroid activity may play a role in sexual behavior, gonad maturation depending on day length and temp.
  • Critical for bone growth and development.
    
    • T3 stimulates osteoblast and osteoclast activities.
  • Influences myocardial contractility and hemogynamics.
  • Low thyroid hormons inhibit activity and feeding, metabolic rate.
  • In lizards, thyroidectomy caused decreased or cessation in shedding.
  • Snakes – excess thyroxine caused shedding to cease, thyroidectomy increased shed frequency.
• Factors influencing thyroid values:
  
  • Age, sex, diurnal changes, seasonal changes, day length, shedding, illness, stress, breeding.
    
    • Chelonians – continuous illumination lead to decline in T4.
    • Chrysemys, Pseudemys, Trachemys have significantly higher thyroid values than other reptiles, females > males.
    • Thyroxine-bind protein – seasonal variation, major component of T4 transport.
  • Thyroid activity high during high temps, low during low temps.
    
    • Tropical species have higher thyroid values in cooler months.
    • T4 and T3 decline with stress.
• Thyroid testing
  
  • Mammals – basal total, free thyroxins (T4, fT4), T3, fT3, T3 suppression, TSH response, TRH stim tests.
    
    • High TSH, low T4 with accompanying symptoms dx for hypothyroidism.
    • Low TSH, high T4 – hyperthyroidism.
  • Reptiles – T3 usually not detectable with current tests.
    
    • T4 more commonly assayed.
    • Significant normal variations seen.
    • fT3 and fT4 circulate in minute concentrations in reptiles.
    • High-sensitive RIA validated for T4 concentrations in select spp of snakes.

Question 3

Describe the thyroid diseases of reptiles.

What conditions lead to goiter in reptiles?

What are the clinical signs of hypothyroidism? What are the two primary mechanisms?

What is the most common cause of hyperthyroidism in reptiles?

Answer 3

• Thyroid disease
  
  • Goiter – Hyperthyroid, euthyroid, or hypothyroid.
    
    • Hypertrophy/hyperplasia, malignancies, euthyroid sick syndrome, hypothyroidism.
    • Proliferative thyroid dz – adenomatous disease dt iodine deficiency or toxicity, goitrogenic substances, endocrine-disrupting compounds, trace vitamin and mineral deficiencies (vit A, Se, Fe, Zn in humans), autoimmune disease, genetics, age, temp, photoperiod.
  • Reptiles – most cases of hyperthyroidism assoc with thyroid neoplasia.
  • Euthyroid sick syndrome.
    
    • Food restriction can reduce thyroid hormones in chelonians and other reptiles.
      
      • Energy conservation during times of food deprivation and hibernation.
      • Cold-stunned sea turtles, fT4 usually undetectable.
  • Hypothyroidism.
    
    • Primary – idiopathic atrophy or lymphocytic thyroiditis.
    • Secondary – iodine deficiency.
    • Reptiles – iodine deficiency, toxicity, excessive amounts of goitrogenic food items.
      
      • Bok choy, broccoli, cabbage, cauliflower, kale, mustard seed, rapeseed, soybeans, turnips.
    • Low iodine -> decreased thyroxine -> increased TSH -> thyromegaly (goiter).
    • Potentially, hypothyroidism in galapagos and aldabra tortoises that were thought to have a higher metabolic requirement for iodine.
    • CS – anorexia, lethargy, myxedema of SQ tissues around head, neck, forelimbs.
  • Hyperthyroidism
    
    • Abnormally high metabolism due to high T3, T4.
    • Most commonly caused by hyperfunctional thyroid nodules (adenoma), malignant thyroid neoplasm, oversupplementation of exogenous thyroid hormone, increased TSH from pituitary dysfunction.
    • Current lab assays able to measure T4 by RIA in reptiles, but not validated.
    • Case in green iguana – palpable bilobed mass ventral cervical region, hyperactivity, polyphagia, weight loss.
      
      • Dx with elevated T4 compared to controls.
      • Excision curative, higto confirmed thyroid adenoma.
      • T4 returned to normal after surgery, suggesting incomplete removal or extraneous thyroid tissue.
    • Case of leopard gecko treated with radioactive I-131, became euthyroid for 5 mos posttreatment and resolution of clinical signs. Eventually died.
  • Misc thyroid conditions

Question 4

What is the ultimobrachial gland in reptiles?

What does it secrete? What are the functions of that hormone?

How does exoenous administration of that hormone affect iguanas and snakes?

Answer 4

• Ultimobranchial gland
  
  • UBG – derived from pharyngeal pouch epithelium
  • Secretes calcitonin CT from C-cells.
  • Separate from thyroid in nonmammalian verts.
    
    • Adult reptiles have one on left side or two, anterior to the heart.
    • Calcitonin – Ca and P homeostasis.
      
      • Salmon CT administration resulted in hypocalcemia and hypophosphatemia in iguanas and snakes (not seen with mammalian CT administration).
      • Calcitonin did not appear to influence Ca on long-term basis.
      • Functions of calcitoinin – neurotransmission, blood volume regulation, phosphate balance, promotion of bone calcification.
        
        • Regulated by serum Ca, elevated Ca results in secretion of CT.
          
          • CT inhibits Ca resorption from bone, acts in opposition to PTH to reduce serum Ca.

Question 5

Where are the parathyroid glands located in the various reptile taxa?

What hormone is excreted in the parathryoid?

What are the various calcium stores in the body?

What conditions stimulate PTH secretion?

Answer 5

• Parathyroid glands, vit D3, Ca homeostasis
  
  • Location – anterior pair assoc with carotid artery, posterior pair assoc with aortic arch.
    
    • Snakes – near mandibular ramus.
    • Iguanas – anterior PTGs at origin of internal and external carotids.
    • Chelonians – anterior within thymus, posterior caudal to aortic arch, cranial to heart.
    • Crocs – PTGs near common carotid artery.
  • Parenchyma – chief cells in cords, connective tissue with a capillary network.
    
    • Minute-to-minute Ca regulation.
    • Release PTH.
  • Ca storage.
    
    • Intracellularly in all tissues, extracellularly as brushite and hydroxyapatite (bone).
      
      • Skeletal bone – 99% total body calcium.
      • Protein bound and ionized fractions.
        
        • iCa – biologically active – muscle contraction, coagulation, enzyme activity, neural excitability, hormone release, membrane permeability.
          
          • Most accurate representation of Ca status.
      • Ca, Mg, P closely regulated by several hormones – PTH, vit D3, calcitonin, cortisol, and GIT, bone, kidneys.
        
        • Mg – cofactor in over 300 enzymatic reactions, required by all enzymatic reactions involving ATP.
        • P – structural component of ATP.
        • Hypomagnesemia can cause secondary hypocalcemia, will resist Ca supplementation until Mg is corrected.
      • Decreased Ca stimulates PTH -> increases Ca resorption from bone and kidney and increased GIT absorption.
      • Increased iCa decreases PTH.
      • Parathyroidectomy -> hypocalcemia, tetany.

Question 6

Describe the process of vitamin D metabolism in reptiles.

What are the two dietary forms and what sources do they come from?

Describe the pathway from provitamin D3 to the active 1,25 OH form.

What form of the vitamin is most commonly used for measuring Vit D status?

What role does vitamin and UVB supplementation play in reptiles?

Answer 6

• Vit D forms
  
  • Cholecalciferol – vit D3; animal sources.
  • Ergocalciferol – vit D2; plant sources.
  • Vit D can also be synthesized in skin.
  • Provitamin D3 (7-dehydrocholesterol, 7-DHC) – cholesterol-like precursor that is converted into previt D3 (cholecalciferol) by sunlight (UVB) and temp dependent isomerization.
    
    • PTH stimulates hydroxylation of cholecalciferol to 25-hydroxycholecalciferol (25-OH-D3) or calcidiol in the liver.
      
      • Major metabolite of vit D, storage form.
        
        • Then converted to 1, 25-hydroxycholecalciferol (1,25 OH-D3 or calcitiol) in kidney.
        • Calcitriol has short half life, active form of Vit D3. Ca homeostasis.
        • 1,25-OH-D3 – increases Ca, Mg, P intestinal absorption, increases renal calcium and P reabsorption, increases bone resorption.
  • Calcidiol – longer half life, more stable and reliable for determining vit D status.
    
    • Liquid chromatography/mass spect – gold standard > radioimmunoassay.
    • Sunlight determined to be superior to UVB lamps in Hermann’s tortoises.
    • Daily UVB lights (lamp) and gut loaded crickets with ViD supplementation and whole mice in diet restored and mainted vit D in monitors in another study.
    • There is considerable variation in requirements for vit D and UVB in reptiles.
    • Vit D plays a significant role in immune function.

Question 7

Describe hyperparathyroidism in reptiles.

What are the predisposing factors?

What are the typical clinical signs?

How is it treated?

How does renal secondary hyperparathyroidism occur?

Answer 7

• Hyperparathyroidism
  
  • Inadequate Ca or Vit D3 (nutritional or UVB) -> NSHP or chronic renal dz disrupting calcitriol and Ca/P homeostasis leading to RSHP.
    
    • Predisposing factors to NSHP – decreased dietary Ca, vit D3 deficiency, improper dietary Ca/P ratio, inadequate thermal provision, inadequate exposure to UVB.
    • CS – thickening and swelling of long bonds, mandibles, pathologic fractures, tetany, muscle fasciculations, hyperreflexia, constipation, cloacal or rectal prolapse, anorexia, stunted growth.
    • Tx – address life-threatening hypocalcemia and fractures, husbandry and nutritional supplementation (Ca) for months before recovery is complete.
      
      • Can supplement vit D3 IM followed by UVB.
    • RSHP – two mechanisms:
      
      • Impaired renal function leads to hyperphosphatemia.
        
        • Ca decreases, PTH secreted -> decreased Ca absorption from GIT.
      • Kidney disease results in relative or absolute deficiency of calcitriol.
        
        • Since Vit D3 neeed for absorption of Ca and P from GIT, leads to hypocalcemia -> PTH secretion.
          
          • Reduction in either iCa or calcitriol can lead to PTH sythenesis.
          • Results in osteomalacia, nephrotoxicity, metastatic mineralization.
          • Px is guarded – tx with fluid therapy, P binders, xanthine oxidase inhibitors, titrated calcitriol supplementation.
    • Excess administration of vit D3 can cause hypercalcemia and metastatic mineralization.
      
      • Also reported with hypovitaminosis D3, reduced neg feedback and excess PTH.
      • Supplementation with sunlight is safer.
    • Primary hyperparathyroidism usually dt functional adenoma or PTG carcinoma.
      
      • Parathyroidmegaly, significant osteomalacia.

Question 8

Where is the pancreas located in reptile species?

How does the endocrine arrangement of the pancreas differ in reptiles from other taxa?

How does the number of alpha cells differ from mammals?

Answer 8

• Pancreas
  
  • Location varies with reptile species.
    
    • Lizards – usually extended and trilobed.
      
      • One portion runs along bild duct toward GB, one portion runs to SI, thin limb runs to spleen.
      • Geckos have a diverticulum of pancreas tissue extending form the ventral portion that encircles the CBD and can enter hepatic parenchyma.
      • Large islets confined to dorsal lobe and splenic pancreas.
    • Snakes – pyramid shaped, attached to first portion of duodenum.
      
      • Pancreas, spleen, GB closely associated aka triad.
      • Some species have a splenic limb, not all.
      • Some snakes have a splenopancreas.
  • No segregation of alpha and beta cells in lizards and snakes (segregated in fish, birds, mammals).
  • In some species, insulin-immunoreactive (IR) cells located in the intestinal mucosa.
  • Chelonians – also variable, mesenteric border of duodenum or assoc with proximal spleen.
  • Pancreatic islets smaller, diffusely throughout the pancreas.
  • Marked segregation of alpha and beta cells.
  • Seasonal and repro cycles influence cell type and distribution.
  • Relative number of alpha cells > vs mammals, same with glucagon content.

Question 9

Describe pancreatitis in reptiles.

What are some of teh common pathologies?

What are some of the common etiologies?

Answer 9

• Pancreatitis
  
  • Inflammation of pancreas.
  • In reptiles – usually due to bacterial or metazoan parasite infection.
  • Acute necrotizing pancreatitis may also occur with trauma, abscesses or pyogranulomatous conditions, migrating helminthes, obstruction of pancreatic outflow ducts by masses or calculi.
  • Chronic – fibrosing pancreatitis common.
  • Tx – supportive – fluid therapy, assisted feeding, antimicrobials, pain management.
  • Obstruction of outflow of pancreatic duct may result in atrophy or autodigestion and necrosis.
  • Trematodes/nematodes
    
    • May migrate to pancreatic tissue, found on histo.
  • Cryptosporidiosis involving pancreas and biliary ducts reported in snakes.
  • Intranuclear coccidiosis in tortoises.
  • IBD in snakes – intracytoplasmic inclusions often within the pancreas.
  • Neoplasia – carcinomas, adenocarcinomas, islet cell tumors.

Question 10

Describe hyperglycemia in reptiles.

How is blood glucose controlled?

When should you consider investigating causes of hyperglycemia?

What disease conditions has it been seen with?

What is a classic disease of bearded dragons with hyperglycemia?

Answer 10

• Hyperglycemia
  
  • BG regulated by insulin and glucagon.
  • Nonspecific CS associated with hyperglycemia.
    
    • PE also nonspecific – loss of muscle, weakness, loss of righting reflex, stupor, depression, obesity.
    • Hibernation and reproduction may influence BG levels.
    • Serial sampling recommended to confirm true hyperglycemia.
    • Glucosuria may be seen with persistent hyperglycemia.
  • Variations in BG common due to variable metabolic rates, environmental influences and adaptations, relative insulin resistance.
  • Stress can increase BG.
  • Temperate reptiles usually have higher BG during breeding season.
  • May peak following emergence from hibernation in tortoises.
  • FW turtles have marked hyperglycemia when diving, related to increased anaerobic metabolism.
  • Hyperglycemia may be seen with starvation due to decreased production of insulin-like proteins in some species. Due to damage to beta cells.
  • BG > 300 mg/dL prompt further investigation.
  • Hyperglycemia reported with hepatic lipidosis, hepatic carcinoma, renal adenocarcinoma, chronic glomerulonephritis, interstitial nephritis, granulomatous pancreatitis, GI adenocarcinoma, pancreatic glucagonoma, gastric somatostatinoma, DM.
    
    • Gastric somatostatinoma (neuroendocrine gastric carcinoma) recently diagnosed in bearded dragons, arises from pylorus and mets.
      
      • Severe hyperglycemia in animals < 3 years old.
      • IHC – somatostatin reservours in the tissues.
        
        • Suppresses pancreatic secretion of insulin, lowers insulin receptor sensitivity,r esults in hyperglycemia.
  • Management
    
    • Diagnosis of underlying cause.
    • Most reported cases of hyperglycemia in reptiles are associated with malignancy.
    • Lizards and alligators are less sensitive to insulin than snakes or turtles.

Question 11

Discuss hypoglycemia in reptiles.

What diseases is it associated with?

What are typical signs?

Answer 11

• Hypoglycemia
  
  • Assoc with starvation, hepatobiliary dz, septicemia.
  • CS – weakness, depression, loss of righting reflex, mydriasis, tremors.
  • Insulinoma reported in a monitor.
    
    • Glucose measurements considered unremarkable.
    • Serum insulin was low compared to conspecifics.

Question 12

Where are the adrenal glands located in the various repile taxa?

What is the adrenal gland also referred to in reptiles?

What are the two types of cells and what hormones do they produce?

What is the primary stress hormone in reptiles?

How are stress hormones measured?

What adrenal diseases have been reported in reptiles?

Answer 12

• Adrenal glands
  
  • Paired, variable in color (yellow, pink, red).
  • Chelonians – craniomedial to kidneys.
  • Crocs – retroperitoneal, dorsolateral to gonads.
  • Squamates – within gonadal mesentery.
  • Blood supply includes venous portal system.
  • Medullary tissue is peripheral, cortical tissue is central.
  • Referred to as interrenal tissue.
    
    • Two cell types predominate – interrenal and chromaffin cells.
      
      • Interrenal cells secrete glucocorticoids (cortisol, corticosterone), chromaffin cells secrete catecholamines (epinephrine and norepinephrine).
        
        • Reinin-angiotensin system causes vasoconstriction, aldosterone release, increased BP.
        • Corticosterone primary glucocorticoid in amphibians, birds, reptiles.
        • Glucocorticoids subject to circadian rhythm, max during most active period.
        • Vary between males and females.
    • Physiologic stress response
      
      • Activation of SNS and HPA axis.
      • Acute measurement of catecholamines difficult, only available transiently.
      • HPA axis evaluation used to evaluate stress response.
        
        • Glucocorticoids metabolized by liver prior to exretion in urine and feces via bile.
        • Normally bound to carrier protein – corticosteroid-binding globulin.
          
          • Only free form (5-10%) biologically active.
      • Corticosterone and cortisol increase dramatically during stressful events, coordinated by the hypothalamus and anterior pituitary.
      • Baseline cortisol measured in reptiles.
        
        • Obtain sample shortly after capture.
        • Within 3 minutes.
        • Stress leukogram – heterophilia, lymphopenia.
        • Can affect granulation of hets and eos.
        • CK also increases.
        • Hyperglycemia in crocs and phidians.
        • Increased HCT, NA, Cl, K reported in aquatic chelonians with hyperosmotic stress.
        • Corticosterone can be measured in blood, feces, urine, saliva.
      • Sea turtles – significant elevations of corticosterone, excessively decreased thyroxine in stressed Kemp’s.
        
        • Significant decrease in corticosterone during recovery from cold-stunning.
      • Fecal glucocorticoid metabolite concentrations can be measured.
        
        • Easily collected, feedback free.
        • Reflect free, biologically active glucocorticoid concentrations in the blood, excellent predictor of stressor.
        • Measured via ELISA.
        • Handling stress induced only transient response.
        • Chronic stress from lack of enrichment/climbing in iguanas was observed.
      • Adrenal neoplasia reported in some spp.
        
        • Carcinomas, pheos, interrenal cell adenocarcinomas.
        • Highly malignant with mets.