Endocrine Tests

Endocrinology

The endocrine system (hormones) has different glands that release various hormones. This system, similar to the nervous system helps one part of the body (the gland) to communicate with another part of the body (the target cell) to perform different functions.. The endocrine glands are important for reproduction, metabolism, growth and other functions.

This system uses hormones to control and coordinate the body’s homeostasis and regulate reproduction, energy level, growth and development, and respond to various environmental stimuli.

ENDOCRINE TESTS

INDICATIONS

  1. To assess ACTH and cortisol reserve.
  2. To assess GH reserve in children with definite growth retardation and a subnormal growth hormone stimulation test.
  3. To differentiate Cushing’s syndrome from depression.
  4. To assess GH response in adults.

CONTRAINDICATIONS

Ischemic heart disease,

Epilepsy,

Untreated hypothyroidism,

9am Serum cortisol <3.625 µg/dL

PREPARATION

  • Overnight fasting is required. ECG must be normal and the patient’s weight known.
  • In peri-pubertal children (bone age > 10 years) priming is needed.
  • Calculate Actrapid Insulin dose,Oral oestrogens to be discontinued 6 weeks before the test.
  • 20% dextrose must be available for immediate administration.
  • Glucometer,6 grey top Vacutainers, 6 red or yellow top Vacutainers are required.

SIDE EFFECTS

Sweating, palpitations, loss of consciousness and rarely convulsions.

METHOD

  1. Insert I.V cannula, take baseline blood samples and then inject insulin I.V
  2. Take samples for GH, cortisol and glucose at 0, 30, 60, 90, and 120 minutes, flushing the cannula with saline between samples.
  3. Check glucose on glucometer every time a specimen is taken. At 30 minutes, if patient is not hypoglycemic, repeat the insulin dose. (This means prolonging sampling by 30 min).
  4. Adequate hypoglycemia is defined as glucose £40 mg/dl with symptoms.
  5. Reverse hypoglycaemia with simple oral treatment or I.V. 20% dextrose, or 1 mg I.M. glucagon and continue sampling.
  6. Once test completed, give supervised meal and ensure glucose is normal before discharging.

 

 

IMPORTANT NOTE ON ITT CORTISOL INTERPRETATION

The cortisol response to stress and to an ITT is highly variable. ITT is used as a surrogate for stress, assumes that if patients cannot produce atleast 13.59 µg/dL of cortisol during the ITT, that they might suffer an Addisonian crisis at times of stress. It also assumes that patients who produce >18.2 µg/dL cortisol during an ITT are very unlikely to have an Addisonian crisis at times of stress, and thus do not need regular cortisol replacement.

 

INTERPRETATION

  • The test cannot be interpreted unless hypoglycaemia <40 mg/dl is achieved.
  • Adequate cortisol response is defined as a rise of greater than 5.43 µg/dL to 18.2 µg/dL or above.
  • In Cushing’s syndrome there will be a rise of <5.07 µg/dL above the fluctuations of basal levels of cortisol.
  • As per European and Endo Society guidelines, severe GHD is defined as GH <3mcg/L and partial  as GH<5mcg/L.
  • In children a rise to >10 mcg/L (>39 mU/L) is considered normal. Appropriate priming is very important if they are peri-pubertal.
  • By consensus, children should have two different stimulatory tests before assigning a diagnosis of isolated GH deficiency (e.g. insulin, glucagon or GHRH-arginine tests) unless IGF-1 is decreased in which case one test may be considered adequate.

SENSITIVITY AND SPECIFICITY

If there is adequate hypoglycaemia and the patient is not hypothyroid then cortisol response is a good test of ACTH/adrenal reserve.

5-15% of normal people will show a suboptimal response as defined by these two criteria.

à20% of patients with Cushing’s syndrome will show a rise greater than 140 µg/dL but a rise of less than this is rare in depression or alcoholic pseudo-Cushing’s.

àGH responses are reduced in 20% of normal children and some small children whose peak GH is 3-6mcg/L(10-20mU/l) may benefit from GH replacement.

INDICATION

  1. To assess GH and ACTH/cortisol reserve, especially when insulin-induced hypoglycaemia is contraindicated.
  2. As a combination of glucagon test and metyrapone test when ITT is contraindicated.

CONTRAINDICATIONS

Pheochromocytoma or insulinoma.

Starvation >48 hours or glycogen storage diseases.

Severe hypocortisolaemia (9am cortisol <2 µg/dl).

Thyroxine deficiency as it may reduce GH and cortisol responses.

SIDE EFFECTS

Nausea is seen in about 30% of cases.

PREPARATION.

  • Fasting from midnight. There’s no need to be continually observed as hypoglycaemia is not provoked.
  • Oral oestrogens to be discontinued 6 weeks before the test
  • Calculate glucagon dose: adults: 1 mg, (1.5mg if > 90kg); children: 15 mcg/kg
  • 6 grey top Vacutainers and 6 red or yellow top Vacutainers

METHOD

  1. Insert an I.V cannula and take basal samples for glucose, cortisol and GH.
  2. Inject glucagon I.M. (the deltoid is a suitable site).
  3. Take further samples at 90, 120, 150 and 180 minutes.

INTERPRETATION

  • Adequate cortisol response is defined as a rise of > 5.0 µg/dL to above 12.68 µg/dL.
  • Severe GHD defined as GH <3mcg/L and partial GHD GH <5mcg/L

SENSITIVITY AND SPECIFICITY

This test is a slightly less reliable test of somatotroph and corticotroph function than the ITT, with a sensitivity of 71% and a specificity of 57% for adequate cortisol reserve if a peak cortisol cut-off of > 12.68 µg/dL is used.

It is a reasonable alternative in patients who cannot tolerate hypoglycaemia because of epilepsy, ischaemic heart disease or hypopituitarism (cortisol <3.6 µg/dL).

INDICATION

  1. To investigate possibility of gonadotrophin deficiency.
  2. In investigating precocious and delayed puberty.

PREPARATION

  • Overnight fast not necessary.
  • In women with a normal menstrual cycle the test should be performed in the follicular phase (day 3-7 of the cycle) as greater LH responses are observed later on in the cycle.
  • Larger dose or priming with LHRH may be necessary in suspected hypogonadism.
  • 100 mcg GnRH.
  • 3 red or yellow top Vacutainers – 7 ml

METHOD

  1. Insert I.V cannula and take baseline blood for LH, FSH and testosterone (M) or oestradiol (F).
  2. Inject GnRH I.V and flush cannula with saline.
  3. Take further samples for LH and FSH at 30 and 60 mins.

INTERPRETATION

  • The normal peak can occur at either 30 or 60 minutes. LH should exceed 10 IU/L and FSH should exceed 2 IU/l. An inadequate response may be an early indication of hypopituitarism.
  • Gonadotrophin deficiency is diagnosed on the basal levels rather than the dynamic response. In males this is based on low testosterone and in females low oestradiol in the absence of raised basal gonadotrophins.
  • Pre-pubertal children should have no response of LH or FSH to GnRH unless primed with sex steroids.

This test has a very low sensitivity and specificity for hypogonadotrophic hypogonadism. Serial investigations in patients with pituitary disease especially in those exposed to irradiation may give early indication of the development of hypopituitarism.

INDICATION

Assessment of all components of anterior pituitary function.

CONTRAINDICATIONS

Ischaemic heart disease.

Epilepsy.

Untreated hypothyroidism.

Serum cortisol <3.6 µg /dL.

SIDE EFFECTS

Sweating, palpitations, loss of consciousness and rarely convulsions.

TRH injection may cause transient symptoms of  metallic taste in the mouth, flushing or nausea.

PREPARATION

  • The patient should fast overnight, ECG must be normal.
  • In peri-pubertal children (bone age >10 years) priming is needed.
  • Calculate Actrapid Insulin dose.
  • TRH 200 mcg as slow I.V. injection.
  • GnRH – 100 mcg as I.V. bolus.
  • 100 ml 20% dextrose should be available for immediate administration.
  • Cannula, 18-20G.
  • Glucometer.
  • 6 grey top Vacutainers and 7 red or yellow top Vacutainers.
  • 500 ml of 0.9% saline to flush cannula.
  • 3 way tap to assist in drawing the samples.

STANDARD METHOD

  1. Insert I.V cannula and take baseline blood samples for Testosterone/Estradiol, Prolactin, Thyroxine, LH, FSH, TSH, GH, Cortisol (14 ml) and glucose (2 ml).
  2. Then at T = 0 inject insulin and GnRH as I.V boluses followed by the TRH I.V over 2 minutes.
  3. Take samples for LH, FSH, TSH, Prolactin, GH, Cortisol (7 ml) and glucose (2ml) at 30, 60 minutes and GH, Cortisol, Glucose at 90 and 120 minutes.
  4. Flush the cannula with saline between samples.
  1. At 30 minutes check blood glucose with Glucometer and repeat the insulin dose if not hypoglycaemic. Adequate hypoglycaemia is defined as glucose £40 mg/dl with symptoms.
  2. Hypoglycaemia should be reversed by giving I.V. 20% dextrose, or I.M. glucagon and continue sampling.
  1. Take further samples for GH, cortisol and glucose at 90 and 120 minutes. There must be at least 2 specimens following adequate hypoglycaemia.
  2. After the test completion, give supervised meal and ensure glucose is normal pre-discharge.

INDICATION

  1. As a screening test for Cushing’s syndrome, especially if the result of the overnight DST contradicts other investigations.
  2. This test may be used to differentiate PCOS and partial hydroxylase deficiencies (CAH) from autonomous androgen secreting tumours in women with high testosterone levels.

CONTRAINDICATIONS

Patients on enzyme inducing drugs (e.g. anti-convulsants) or suffering from malabsorption syndromes.

Patients taking estrogens (e.g. pregnancy, HRT or COCP).

Care in diabetes mellitus and patients who are psychologically unstable.

PREPARATION

  • This is usually an inpatient test with no particular patient preparation.
  • Stop all oral oestrogen therapy 6 weeks prior to test.

METHOD

  1. The patient takes 0.5 mg dexamethasone p.o. at strict6 hour intervals (i.e. 09:00h, 15:00h, 21:00h and 03:00h) for 48 hours.
  2. The cortisol & ACTH are measured at 09:00h (before the first dose of dexamethasone) on the first day (T=0h) of the test and at 48 hours later (6 hours after the last dose). Samples are taken in red or yellow top Vacutainers for cortisol and purple top tubes on icefor ACTH. The red or yellow topped sample can be used to measure SHBG and CBG if needed.
  3. A total of eight doses of dexamethasone should be written up (09:00h, 15:00h, 21:00h, 03:00h 09:00h, 15:00h, 21:00h and 03:00h ).

 

INTERPRETATION

  • If the 09:00h cortisol (T=48h) value is <1.8 µg/dl, the patient has shown appropriate suppression.
  • Failure to suppress is seen in the autonomous secretion of cortisol found in Cushing’s syndrome.
  • In virilisation from PCOS or partial hydroxylation deficiencies there will be complete/partial suppression of testosterone. This is not seen in ovarian or adrenal tumours.

SENSITIVITY AND SPECIFICITY

Sensitivity for Cushing’s syndrome is above 95% with a reported specificity of 70%. This test is more specific than the overnight suppression test with a lower false positive rate.

Failure of suppression in patients may be seen in patients with systemic illness, endogenous depression, or on enzyme inducing drugs e.g. phenytoin or rifampicin. The predictive value of all tests is falling as morbid obesity becomes more common.

INDICATION

  1. Patients with Cushing’s syndrome and high ACTH levels in whom there is no clear MRI evidence of definite pituitary source. The aim of this test is to differentiate pituitary from a non-pituitary source of ACTH and to attempt to lateralise a corticotroph adenoma prior to surgery though this test may not be reliable to lateralise.

INDICATION

  1. Patients with definite Cushing’s syndrome  but not sure of the source.
  2. ACTH-dependent Cushing’s syndrome could either be from a pituitary adenoma or from an ectopic source. This test is rarely used as the probability of picking up Cushing’s disease is  less than 70%.

FOR FURTHER DETAILS ON PREPARATION, METHOD, CONTRAINDICATIONS AND INTERPRETATION Contact Us

INDICATION

  1. Commonly used screening test for suspected Cushing’s syndrome in a patient when suspicion is low. when standard low dose dexamethasone suppression test is felt unnecessary.

INDICATION

  1. Assessment of control of Cushing’s syndrome while on medications like ketoconazone pre-operatively.
  2. Assessment of possibility of early recurrence of hypercortisolism in previously treated cushings disease.

INDICATION

  1. Establish correct dose and distribution of hydrocortisone replacement throughout the day.

INDICATION

  • Establish correct dose of prednisolone replacement throughout the day.
  • Low dose prednisolone is a once daily alternative to hydrocortisone in corticosteroid replacement therapy.
  • Prednisolone should be taken on waking in the morning and an 8 hour serum prednisolone level is performed to judge the adequacy of the dose.
  • Initial dose is 4mg before titrating according to the 8 hour level.

INDICATION

  1. This test is standard one for a clinical diagnosis of acromegaly.

INDICATION

  1. Useful for differential diagnosis of polyuria, whether central diabetes insipidus (CDI), nephrogenic diabetes insipidus (NDI) and primary polydipsia (PP).
  2. If in the basal state plasma osmolality > 295 mosmol/kg, plasma Na > 145 mmol/L and urine is hypotonic (< 300 mosmol/kg), PP is excluded and investigation goes straight to DDAVP (1-deamino-8-D-arginine vasopressin) administration.

INDICATION

Used when partial response to water deprivation test.

  1.  In  Partial Cranial Diabetes Insipidus: prompt improvement in thirst and polyuria is present.
  2. In Nephrogenic Diabetes Insipidus no effect is seen.
  3. In Primary Polydipsia decreased polyuria with no change in polydipsia.

INDICATION

  1. Used as a screening test. to diagnose hypoadrenalism both Addison’s disease (primary) and secondary hypoadrenalism (eg pituitary cause or previous steroid use)
  2. Simple test that is used as an alternative to insulin tolerance test to diagnose secondary hypoadrenalism caused by  pituitary hypofunction. However it is not reliable for early post-operative assessment of the hypothalamic-pituitary-adrenal axis as it can be falsely normal. In these situations pituitary dyanamic tests like ITT or Glucagon tests are to be used.
  3. More commonly it may also be used to assess if adrenals functionality is normal or not after a prolonged course of corticosteroids, or after after removal of a unilateral Cushing’s adrenal adenoma causing cushing’s syndrome.
  4. Diagnosis of classic forms of Congenital Adrenal Hyperplasia ( eg: 21-hydroxylase deficiency)
  5. Diagnosis of non-classical congenital adrenal hyperplasia and to differentiate from PCOS, the more common cause for hyperandrogenism in women particularly when the morning follicular-phase baseline 17-hydroxyprogesterone is >6.0 nmol/L.

INDICATIONS

It is an artificial form of  ACTH or adrenocorticotropic hormone which can be used in place of synacthen to assess adrenal reserves and to diagnose both Addison’s disease (primary) and secondary hypoadrenalism (eg pituitary cause or previous steroid use)

INDICATIONS

  1. When secondary Hypertension is suspected eg: Accelerated/ Drug resistant hypertension.
  2. Hypertension when associated with adrenal incidentaloma.
  3. Hypertension with hypokalaemia, (potassium is < 3.5 mmol/L).
  4. Family history of hyperaldosteronism or
  5. Hypertension at a young age < 30 years

INDICATION

  1. Once primary hyperaldosteronism has been confirmed biochemically, this invasive test will help the distinction between unilateral and bilateral disease.

PLASMA/URINE METANEPHRINE MEASUREMENT FOR PHAEOCHROMOCYTOMAS AND PARAGANGLIOMAS

INDICATION

  1. To diagnose excess secretion of catecholamines when patients present with possible secondary hypertension and when associated with symptoms like paroxysmal sweating, headaches, anxiety and hypertension.

INDICATION

  1. To diagnose excess secretion of catecholamines when patients present with possible secondary hypertension and when associated with symptoms like paroxysmal sweating, headaches, anxiety and hypertension.

INDICATION

  1. To exclude the diagnosis of phaeochromocytoma in patients with hypertension and borderline raised catecholamines or catecholamine metabolites.

INDICATION

The MIBG scan is a highly useful, qualitative nuclear medicine investigation used a method of locating the site of a phaeochromocytoma.after confirmed biochemical evidence for a tumour demonstrated by a raised urine or plasma catecholamines/metanephrines, This test is used along with  ultrasound, CT scanning, and, sometimes venous sampling.

It is useful particularly for extra-adrenal and metastatic or post operative residual phaeochromocytoma detection.

INDICATIONS

  1. When medullary carcinoma of thyroid is Suspected
  2. As screening test for families with medullary carcinoma of the thyroid.
  3. Patients with suspected MEN type 2.
  4. Patients with basal CT level < 11.8 ng/L in men and < 4.8 ng/L in women

INDICATIONS

  1. When calcitonin levels are low and suspected acalcitoninaemia.
  2. Patients with suspected MEN type 2.
  3. As screening test for families with medullary carcinoma of the thyroid.
  4. Patients with suspected MEN type 2 syndrome.

INDICATIONS

  1. When secondary Hypertension is suspected eg: Accelerated/ Drug resistant hypertension.
  2. Hypertension when associated with adrenal incidentaloma.
  3. Hypertension with hypokalaemia, (potassium is < 3.5 mmol/L).
  4. Family history of hyperaldosteronism or
  5. Hypertension at a young age < 30 years

INDICATION

  1. Investigation of thyroid nodule of over 1cm when palpable or found on ultrasound of other radiology tests. The prime aim of FNAC is to exclude malignancy.

INDICATIONS

  1. Suspected diabetes mellitus. in pregnant women or when  HbA1c is unreliable like in people with haemoglobinopathies or other situations.
  2. In acromegaly, to establish the diagnosis and to follow patients after treatment with surgery or irradiation.
  3. Suspected reactive hypoglycaemia when a prolonged OGTT is preferred.

INDICATION

  1. Patients with hypoglycemic symptoms when investigated for an insulinoma or post prandial (reactive) hypoglycemia  a prolonged (5 hour) oral glucose tolerance test is performed.

INDICATION

  1. Used to demonstrate fasting hypoglycaemia and diagnose insulinoma if not observed. spontaneously or after an overnight fast.

INDICATION

  1. Used by infertility centres with follicular tracking to demonstrate the capacity for ovulation using clomiphene, a selective oestrogen receptor modulator.
  2. Clomiphene works by preventing oestrogen binding at the hypothalamus and pituitary thereby blocking the negative feedback resulting in LH/FSH surge.

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