BL6 Testing Endocrine Function

• Endocrine disorder

  Hypofunction as a result of hyposecretion, atrophy, destruction etc.<|>Hyperfunction as a result of hypersecretion, loss of suppression, tumour, hyperplasia etc.
• Hormone abnormality

  Primary disease: Endocrine gland producing the hormone. Normally associated with increased or decreased secretory hormones.<|>Secondary disease: Disease of pituitary gland controlling the primary gland. Normally associated with increased or decreased trophic hormones<|>Tertiary disease: Disease of hypothalamus controlling the pituitary<|>End organ or quarternary disease: Inability of target tissue to respond to the hormone.
• Tests for Endocrine Functions

  • Direct measurement of hormone concentration
  • Dynamic Test (the use of an exogenous agent to manipulate the body's hormonal levels)
• Direct measurement of hormone concentration

  Basal serum hormone levels<|>Hormone measurement in the urine<|>Hormone measurement in the blood
• Dynamic Test

  Suppressive tests (for hormone excess)<|>Stimulation tests (for hormone deficiency)
• Insulin Hypoglycaemic Test (IHT)/Insulin Tolerance Test (ITT)

  1. Administration of insulin (0.15 U/Kg or 0.3 U/Kg) via IV after overnight fast

  2. Normal response: GH rises >20 mU/L (adult), cortisol rises by 200nmol/L - 550nnmol/L

  3. Contraindications: epilepsy, IHD/CVD, glycogen storage disease, severe long standing hypoadrenalism

  4. Signs of hypoglycaemia should be observed
• Glucagon Stimulation Test

  1. Administration of glucagon (IV) 0.01mg/kg after overnight fast

  2. Glucagon stimulates GH release

  3. Safer test than ITT for young children and infants
• Clonidine Stimulation Test

  1. Clonidine is administered orally and GH response in blood is measured

  2. Clonidine is a potent stimulus to GH release via GHRH secretion

  3. In hypopituitarism there was no change in growth-hormone concentrations
• Glucose Tolerance Test

  1. Administration of 75g oral glucose after overnight fast

  2. GH secretion is part of the counter-regulatory defence against hypoglycaemia and physiological GH secretion is inhibited by hyperglycaemia

  3. In acromegaly or gigantism fail to suppress GH after glucose intake is highly suggestive of GH excess
• Thyroid function test

  Serum measurement of TSH, T4, T3, TT4 and TT3 for diagnosis and monitoring response to therapy<|>Free T4 is better than total T4 for measuring thyroid hormone activity

  
• Primary and Subclinical Hypothyroidism

  Autoimmune hypothyroidism (Hashimoto thyroiditis), Iodine deficiency, Congenital, Drugs (Antithyroid, lithium, Iatrogenic)<|>Overt primary hypothyroidism: TSH of > 10 mU/L and T4 below the reference range<|>Subclinical hypothyroidism: TSH above the reference range with a normal T4 level
• Secondary Hypothyroidism

  Hypopituitarism (Tumours; Sheehans Syndrome)<|>First line TSH and T4 to identify secondary hypothyroidism<|>Measurement of other anterior pituitary hormones are useful in the diagnosis of hypopituitarism as a cause of secondary hypothyroidism
• Congenital hypothyroidism

  Condition resulting from an absent or under-developed thyroid gland<|>Measurement of filter paper blood spot TSH using sample collected within 2-8 days of birth<|>Confirmation of diagnosis: measurement of serum TSH and T4 in both mother and baby and TSH receptor ab in mother

  
• Laboratory value associated with Hypothyroidism

  • Primary Hypothyroidism: T4 Low, TSH High, TRH High
  • Secondary Hypothyroidism: T4 Low, TSH Low, TRH High
  • Tertiary Hypothyroidism: T4 Low, TSH Low, TRH Low
  • Subclinical Hypothyroidism: T4 Normal, TSH High, TRH Normal
• Primary Hyperthyroidism

  The single most important biochemical test is serum TSH (by a second or third generation TSH assay)<|>If the serum TSH concentration is within the reference range, T4 is increased then a diagnosis of hyperthyroidism is ruled out<|>TSH dependant causes of hyperthyroidism are rare, such as TSH producing tumours of the pituitary and Thyroid hormone resistance
• Laboratory value associated with Hyperthyroidism

  • Primary Hyperthyroidism (Grave's disease): T4 High, TSH Low, TRH Low
  • Secondary Hyperthyroidism (Pituitary adenoma): T4 High, TSH High, TRH Low
  • Tertiary Hyperthyroidism (Hypothalamic tumor): T4 High, TSH High, TRH High
• Hashimoto thyroiditis

  Most likely form of autoimmune thyroiditis if the patient has hypothyroidism (elevated TSH and low free T4 concentrations)
• Graves disease

  Has hyperthyroidism (low TSH and elevated free T4 concentrations)
• In many patients with hypothyroidism or hyperthyroidism, lymphocytes react against the thyroid

  
• Primary Hyperthyroidism

  • The single most important biochemical test is serum TSH (by a second or third generation TSH assay)
  • If the serum TSH concentration is within the reference range, T4 is increased then a diagnosis of hyperthyroidism is ruled out
  • TSH dependant causes of hyperthyroidism are rare, such as: TSH producing tumours of the pituitary, Thyroid hormone resistance
• Primary Hyperthyroidism

  • Grave's disease
• Secondary Hyperthyroidism

  • Pituitary adenoma
• Tertiary Hyperthyroidism

  • Hypothalamic tumor
• Hashimoto thyroiditis

  The most likely form of autoimmune thyroiditis if the patient has hypothyroidism (elevated TSH and low free T4 concentrations)
• Thyroid antibodies

  Thyroid peroxidase antibody and thyroglobulin antibody<|>Measuring levels may help diagnose the cause of the thyroid problem

  
• TSH receptor antibody (TSI)

  This antibody causes the thyroid to be overactive in Graves' Disease and congenital thyroidism
• Tests to determine the cause of thyroid dysfunction

  • Thyroid peroxidase antibodies
  • Thyroglobulin antibodies (TgAb)
  • TSH receptor antibodies
  • Thyroglobulin

  
• Thyroglobulin

  A protein produced by normal thyroid cells and thyroid cancer cells, used to monitor patients who have had surgery for thyroid cancer

  
• Screening for Cortisol Excess or Deficiency

  1. 24-hour urinary free cortisol

  2. Dexamethasone Suppression Test

  3. Synacthen test/ACTH stimulation of cortisol
• 24-hour urinary free cortisol

  Measures the total amount of cortisol excreted into the urine over a 24-hour period, not influenced by circadian rhythm
• Cushing's disease

  Caused by a pituitary gland tumor (usually benign) that over-secretes the hormone ACTH (thus overstimulating adrenal glands' cortisol production)
• Cushing's syndrome

  Refers to the signs and symptoms associated with excess cortisol in the body, regardless of the cause
• Dexamethasone Suppression Test

  1. A useful initial screening test for Cushing's syndrome/Cushing's disease

  2. Involves the measurement of plasma cortisol levels at 8 A.M. following the oral administration of 1 mg dexamethasone the previous midnight

  3. Normal response: After 48 hours serum cortisol is suppressed to <50 nmol/L (normal (170-700 nmol/L)
• Multiple Dose Dexamethasone suppression test (DST)

  1. Aids in the differential diagnosis of hypercortisolism in patients who do not suppress after an overnight Dexamethasone suppression text

  2. Consists of administration of Dexamethasone 0.5 mg every 6hrs for 48 hours followed by 2mg Dexamethasone every 6hrs for 48 hrs

  3. Cushing's syndrome: Low dose - no change in cortisol level, High dose - no change in cortisol level

  4. Cushing's Syndrome caused by pituitary tumor (Cushing's Disease): Low dose - no change, High dose - suppression
• Addison disease

  Cortisol deficiency
• ACTH Stimulation of Cortisol

  1. Also known as Synacthen stimulation test

  2. Measurement of serum cortisol before and after an injection of synthetic ACTH- failure to response suggests adrenal failure primary or secondary

  3. Normal response: Cortisol levels exceed 495 nmol/L (18μg/dL)

  4. A low plasma/serum cortisol that does not rise after synacthen administration (Short Synacthen test) confirms impaired adreno-cortical reserve

  5. If the impaired response persists after prolonged synacthen administration (Long Synacthen Test), primary adreno-cortical insufficiency is indicated

  6. In secondary hypoadrenalism, a delayed but normal cortisol response may be observed
• Prolactin

  Secretion is regulated primarily by the inhibitory action of dopamine, a major neurotransmitter secreted into the hypothalamic-pituitary portal system<|>The only prolactin releasing hormone known is TRH. Estrogen also stimulates prolactin release
• Pituitary tumours (Hyper condition)

  Serum prolactin values greater than 200 ng/ml are almost always associated with a prolactin-secreting pituitary tumor<|>The decline in serum prolactin in response to treatment with the dopaminergic agonist bromocriptine is usually dramatic in both functional or tumorous hyperprolactinemia
• Hypopituitarism

  Prolactin deficiency may occur with destructive lesions of the pituitary<|>The presence and severity of the pituitary injury can be assessed by measuring the serum prolactin and TSH response to TRH
• Serum FSH, LH

  Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) control reproductive function and the serum levels of testosterone and estradiol<|>Elevated FSH and LH levels are diagnostic of primary ovarian failure<|>Measuring FSH and LH as an abbreviated test following GnRH injection does not reliable in all cases<|>Functional suppression of FSH and LH in postmenopausal women would be strongly suggestive of pituitary pathology<|>In contrast, low values in young women without an increase in prolactin usually result from a functional disorder<|>Hypogonadism in men is suggested clinically by loss of libido, primary hypogonadism - chromosomal defects in the testes or acquired causes, secondary testicular failure - prolactin-producing tumor