Endocrinology Flashcards
What are the main products of pars intermedia?
POMC which can then be cleaved into :
- α MSH (main peptide),
- ACTH,
- ß lipotropin,
- ß endorphin and
- Corticotropin-like intermediate peptide (CLIP),
List the products of the cortex and medulla of the adrenal glands.
Medulla: related to the sympathetic nervous system; chromaffin cells secrete catecholamines (adrenaline, noradrenaline and dopamine)
Cortex:
- Z Glomerulosa - mineralocorticoids (aldosterone);
- Z Fasciculata - glucocorticoids (cortisol);
- Z Reticularis - sex steroids (mainly androgens)
What are the systemic effects of cortisol?
- Increases gluconeogenesis
- Mobilisation of amino acids for gluconeogenesis
- Decreased glucose utilisation
- Increased glucose concentrations
- Inhibits insulin actions on glucose uptake and lipogenesis
- Increases fat and amino acid mobilisation during stress
- Endogenous glucocorticoids are antiinflammatory and immunosuppressors
- Organ maturation.
Why do some premature foals have lower basal cortisol and higher ACTH levels?
17α-P450 is expressed 5 days before birth in normal foals so if premature this enzyme might limit cortisol production.
High ACTH is due to a lack of negative feedback.
# Define relative adrenal insufficiency (RAI) and critical illness-related corticosteroid insufficiency (CIRCI)
RAI: transient inadequate production of cortisol in relation an increased demand during periods of severe illness and stress (high ACTH:cortisol ratio).
CIRCI: promoted instead of RAI as it considers clinical findings; an exaggerated pro-inflammatory response from cortisol deficiency and tissue refractoriness to corticosteroids.
List serum biochemical abnormalities that might be seen with adrenal insufficiency.
May be normal or; hyponatremia, hypochloremia, hyperkalemia, hypoglycemia.
Differentiate primary versus secondary hypoadrenocorticism.
Primary: adrenocortical dysfunction leads to high plasma ACTH (rule out PPID) due to lack of negative feedback.
Secondary: increased use of exogenous glucocorticoids leads to low ACTH levels.
ACTH stimulation test involves what?
Baseline heparinised or plain blood for cortisol; administer 1iu/kg natural ACTH IM between 8-10am; take post ACTH blood samples 2 and 4 hours after ACTH administration. A functional adrenal gland results in 2-3fold increase in cortisol compared with baseline.
Treatment of hypoadrenocorticism involves:
Treatment with corticosteroids, ideally hydrocortisone or prednisolone at low doses.
What are the clinical signs of CIRCI in foals and recommended treatment protocol?
vasopressor-unresponsive hypotension, hypoglycaemia or persistent SIRS. (Ideally to ACTH stim test).
Tx: a short tapering therapy of hydrocortisone (1.3mg/kg/day IV divided in 4-6 bolus).
Where do pheochromocytomas arise?
Chromaffin cells of the adrenal medulla
Which catecholamines are produced by pheochromocytomas?
Adrenaline and noradrenaline.
What are the clinical signs of pheochromocytomas?
Intense adrenergic stimulation, may include: abdominal pain from haematomas or haemoperitoneum, GIT distension secondary to ileus, anxiety, tachycardia, tachypnoea, profuse sweating, muscle tremors, hyperthermia, dry and pale MM, increase CRT, ataxia and mydriasis.
What is the incidence of concurrent endocrine abnormalities or multiple endocrine neoplasia (MEN) in horses with pheochromocytoma?
73% had concurrent endocrine abnormalities and 21% of those had changes consistent with MEN.
What are the two cell types in the thyroid gland and what does each secrete?
Follicular cells secrete thyroxine (T4 - prohormone) and triiodothyronine (T3 - active hormone). These increase metabolic rate.
Neuroendocrine cells give rise to parafollicular cells that secrete calcitonin (important for calcium metabolism).
Which hormones stimulate and which hormones inhibit TSH?
TRH stimulates thyrotropes of the pars distalis to secrete TSH.
Dopamine and somatostatin released by the hypothalamus inhibit TSH secretion.
Are thyroid hormone levels higher in newborn foals or adults?
Approximately 10 fold higher in foals
What is the effect of lactation on thyroid hormone concentrations?
Serum T3 and T4 concentrations are higher in lactating mares cf non lactating.
What are the effects of feeding on thyroid hormone secretion?
- Soluble carbohydrates increase secretion of TH
- Energy deprivation inhibits deiodination of T4 to T3 to decrease T3 but increases rT3 concentrations (maybe to reduce metabolic rate and conserve energy)
- Starvation decreases leptin concentrations which have a flow-on effect to decrease TRH and therefore TSH; hence feed restriction decreases while caloric intake increases leptin concentrations and the same in THs.
Define non-thyroidal illness syndrome (NTIS) and the relative levels of T3 and T4.
NTIS is a reduction in T3 due to suppression of the HPTA from illnesses, systemic inflammation, stress and starvation. T4 can be normal, decreased or increased during NTIS.
cytokines (IL 1ß, IL 6, TNFα), corticosteroids and leptin may concern
Explain the TSH stimulation test, the TRH stimulation test
TSH stim: Baseline blood; inject 2.5-5iu of TSH IV and compare pre and 3-4h post TSH concentrations of THs. T4 should peak at 2.4 times baseline and T3 peak at 5 times baseline. An insufficient response is consistent with hypothyroidism (but decreases TH concentrations but doesn’t affect this test; dex blunts the TH response to the TSH stim test).
TRH stim: baseline blood; inject 1mg TRH IV and compare pre and 2-4h post TRH concentrations of THs. Both T3 and T4 should increase 2-3fold. An inadequate response occurs with primary (thyroid) or secondary (pituitary) hypothyroidism.
Differentiate primary from secondary hypothyroidism
Primary (thyroid): low TH, high TSH concentrations and a low response to TSH stimulation suggest thyroid gland dysfunction.
Secondary (pituitary): low TH with low or normal TSH concentration indicate hypothalamic or pituitary gland dysfunction.
Low THs and TSH whit normal response to TRH stimulation indicate hypothalamic dysfunction (tertiary hypothyroidism).
What effect do nitrates have on thyroid function in-utero?
Proposed as a possible mechanism for development of congenital hypothyroidism and dysmaturity (CH&D) in foals; nitrates cross the palcenta and impair foetal thyroid gland function. TH concentrations in foals with CH&D are low or within normal and their response to TSH is poor. Prognosis is poor. Gestation is often prolonged and they are often weak to stand, silky short coat with domed head, tendon laxity, incomplete ossification of cuboidal bones, flexural and angular limb deformities and rupture of the common digital extensor tendons.
What is the treatment for hyperthyroidism?
- Hemithyroidectomy if a unilateral tumour
- Glucocorticoids may alleviate signs
- Eliminate exposure to iodine-containing products.
- Potassium iodide 1g/day may improve signs.
- Propylthiouracil (PTU) 8mg/kg POq24h may be successful and can be decreased to EOD.
List the common thyroid tumours.
- Adenoma (most common), benign and not associated with thyroid function.
- Adenocarcinoma, malignant and can cause euthyroid, hypo or hyperthyroidism (systemic metastasis whit pituitary adenoma).
- Medullary carcinoma (C-cell or parafollicular cell tumour), usually unilateral.
- Multiple endocrine neoplasia (MEN), consider this when you see a tumour of the thyroid gland.
List the mechanisms of calcium reabsorption in the cortical thick ascending loop of henle and the distal convoluted tubules of the kidney.
CTAL: PTH mediated
- Increases Ca reabsorption (enhances the Na/K/2Cl cotransporter which creates the voltage gradient that enables paracellular reabsorption of Ca).
- Reduces phosphate reasbsoprtion
- Promotes calcitriol synthesis.
DCT:
- Increased Ca reabsorption in in his region is
transcellular mediated by epithelial calcium channels, calbindin, basolateral proteins and the vitamin D receptor.
What is the role of calcitonin?
It is secreted by the parafollicular cells of the thyroid gland in response to hypercalcaemia and it decreases calcium and phosphate levels by increasing urinary calcium and phosphate excretion and suppressing osteoclastic bone resorption.
What drives humoral hypercalcaemia of malignancy?
Secretion of parathyroid hormone related peptide.
What effect does blood pH have on Ca binding to albumin?
During acidosis Ca binding is reduced so ionised concentration is higher and during alkalosis Ca binding to albumin is increased so ionised concentration is lower; but in both states total calcium is unchanged.
What do you see with chronic excess and chronic deficiency of phosphorus?
Excess: clinical signs of calcium deficiency including osteodystrophia fibrosa or nutritional secondary hyperparathyroidism.
Deficiency: weight loss, weakness, depraved appetite, lameness and DOD.
Explain re-feeding syndrome
Occurs when re-feeding starved horses and begins with introduction of carbohydrates, specifically glucose which causes insulin release. Insulin prevents release of free fatty acids and causes an intracellular influx of glucose and selected electrolytes (potassium, magnesium and phosphorus), decreasing serum concentrations of these substances. Depletion of ATP results in RBC dysfunction and inability to release oxygen to tissues. Resultant heart, respiratory and kidney failure contribute to death - neurological signs may or may not occur concurrently.
List the clinical signs of hypocalcaemia
Anxiety, depression, synchronous diaphragmatic flutter, hyperexcitability, ataxia, stiff gait, tetany, muscle fasciculations and tremors, tachypnoea with flared nostrils, upper airway stridor, dyspnoea, dysphagia, hypersalivation, hyperhidrosis, ileus, seizures, hypotension, recumbency, collapse and death. tachycardias and cardiac arrhythmias may be present although bradycardia can occur in severe cases due to reduced myocardial contractility.
Explain synchronous diaphragmatic flutter
Occurs as a result of ionised hypocalcaemia or hypomagnesaemia. Depolarisation of the right atrium stimulates action potentials in the hyperexcitable phrenic nerve as it crosses over the surface of the heart, causing a rhythmic movement on the flank due to synchronous contraction of the diaphragm with the heartbeat.
What electrolytes are affected with hypoparathyroidism?
Hypocalcaemia, hyperphosphataemia and decreased serum PTH concentrations. Hypomagnesaemia is often present and may be the cause in secondary hypopaathyroidism.
