Diagnosis

Diagnosis of Growth Hormone Deficiency (GHD)

Tests

• Insulin tolerance test (aka insulin stress test)
• or glucagon stimulation test
• or GHRH arginine test
• or Macimorelin test (not yet widely available)

• They have severe GH deficiency, defined as a peak GH response of less than 9 mU/litre (3 ng/ml) during an insulin tolerance test or a cross-validated GH threshold in an equivalent test.
• They have a perceived impairment of quality of life (QoL), as demonstrated by a reported score of at least 11 in the disease-specific ‘Quality of life assessment of growth hormone deficiency in adults’ (QoL-AGHDA) questionnaire [link to questionnaire].
• They are already receiving treatment for any other pituitary hormone deficiencies as required.

Diagnosis of Cortisol Deficiency (aka hypoadrenalism / adrenal insufficiency)

Click here to view Treatment for Cortisol Deficiency

Tests

Your 9am cortisol level should be checked. If it is below 590nmol/L and you have symptoms, you need a dynamic test (also called a provocative/stimulation test): 

• Insulin tolerance test (aka insulin stress test) – best option
• Glucagon stimulation test (less reliable but acceptable)

The short synacthen test is not recommended.

The short synacthen test is very unreliable. A ‘normal’ result does not rule out cortisol deficiency. The Pituitary Foundation states: “Please note: for patients with symptoms that may suggest cortisol deficiency that a ‘pass’ on a SST, may not always mean that cortisol deficiency is excluded, and that with persisting symptoms, referral to an endocrinologist is recommended, where testing may be carried out with alternatives such as the glucagon test or insulin stress test.”
If your GP is reluctant, explain that if you have undiagnosed cortisol deficiency, you may suffer a life-threatening adrenal crisis.
Some patients find that if they buy the day curve cortisol test from a private lab and get an abnormal result, their GPs are more easily persuaded. Details on the Pituitary Foundation website.

Testing for Sex Hormone Deficiency

Click here to view Treatment for Sex Hormone Deficiency (Secondary Hypogonadism)

Your endocrinologist should test

• Estradiol/testosterone, sex hormone binding globulin (SHBG) early morning (usually 9am) and on more than one occasion
• Luteinising hormone, follicle stimulating hormone (LH/FSH).
• Prolactin – test on at least two occasions
  Men will be given a sperm count. A sperm count of less than 20 million per ml makes fertility problems more likely.

Possible problems

You may be told you do not have a pituitary or thalamopituitary problem if your LH/FSH levels are normal i.e.within the range (1.5-12.4 U/L). However, this is incorrect. The standard textbook Principles and Practice of Endocrinology and Metabolism, K L Becker states “In secondary hypogonadism, LH and FSH levels will be in the normal or subnormal range despite a low total or free testosterone level.”
You may also be told that if your testosterone levels are normal, you do not need testosterone replacement. However, your consultant may not realise that normal testosterone levels are age-related, and what is normal for a 90-year-old man may not be normal for you. See chart [link to C2 ‘Average Testosterone Levels by Age]

Note
Endobible gives a more detailed account of these tests and recommends also testing Thyroid stimulating hormone (TSH), free thyroxine, cortisol and growth hormone. cortisol and growth hormone, and doing a pituitary MRI urgently if the sight is affected. Hypogonadism diagnosis – investigation (endobible.com)

Diagnosing Thyroid Hormone Deficiency

Click here to view Treatment for Thyroid Hormone Deficiency (Hypothyroidism)

Tests

Thyroid-stimulating hormone (TSH). TSH is made in the pituitary gland and controls the balance of thyroid hormones — including T4 and T3 — in your blood. This is usually the first test you will receive to check for thyroid hormone imbalance.
Most of the time, thyroid hormone deficiency (hypothyroidism) is associated with a high TSH level, while thyroid hormone excess (hyperthyroidism) is associated with a low TSH level. However, it is different when thyroid deficiency is caused by pituitary dysfunction. According to the Cleveland Clinic ‘TSH levels may be normal or even slightly elevated in secondary hypothyroidism ‘[that is, hypothyroidism caused by the pituitary]. ‘For this reason, TSH levels are not reliable for diagnosing and assessing thyroid adequacy in these patients. If TSH is abnormal, your doctor may measure your thyroid hormones directly, including thyroxine (T4) and triiodothyronine (T3).
Normal TSH range for an adult: 0.40 – 4.50 mIU/mL (milli-international units per litre of blood).

T4: Thyroxine tests for hypothyroidism and hyperthyroidism, are used to monitor treatment of thyroid disorders. Low T4 is seen with hypothyroidism, whereas high T4 levels may indicate hyperthyroidism. Normal T4 range for an adult: 5.0 – 11.0 ug/dL (micrograms per decilitre of blood).

FT4: Free T4 or free thyroxine is a method of measuring T4 that eliminates the effect of proteins that naturally bind T4 and may prevent accurate measurement. Normal FT4 range for an adult: 0.9 – 1.7 ng/dL (nanograms per decilitre of blood).

T3: Triiodothyronine tests help diagnose hyperthyroidism or show how severe hyperthyroidism is. Low T3 levels can be seen in hypothyroidism, but this test is more often used to diagnose and manage hyperthyroidism, where T3 levels are high. Normal T3 range: 100 – 200 ng/dL (nanograms per decilitre of blood).

FT3: Free T3 or free triiodothyronine is a method of measuring T3 that eliminates the effect of proteins that naturally bind T3 and may prevent accurate measurement. Normal FT3 range: 2.3 – 4.1 pg/mL (picograms per millilitre of blood)

This information is taken from the Cleveland Clinic website. You can read more there about what tests may be done if the problem lies in thyroid gland itself rather than your pituitary gland.

Diagnosing Arginine Vasopressin Deficiency (AVD)

Click here to view Treatment for Arginine Vasopressin Deficiency (AVD) (Diabetes Insipidus)

Testing

An ADH test will help to diagnose diabetes insipidus, if your ADH level is low. High levels can indicate can help diagnose the syndrome of inappropriate diuretic hormone, or SIADH, a condition that occurs when the body makes too much ADH and retains excess water as a result. Abnormal ADH levels can be a sign of other illnesses. https://my.clevelandclinic.org/health/diseases/16618-diabetes-insipidus
A blood sample will be measured. Normal ADH levels are 1-5pg/mL (0.9-4.6 pmol/L).
You may be required to drink a large amount of water before the test, or to refrain from drinking for 4-6 hours.

Diagnosing Prolactin Abnormality

Click here to view Treatment for Prolactin Abnormality

Test

The prolactin test is a simple blood test which should be taken 3-4 hours after waking. You do not need to make any special preparations beforehand.
The normal ranges for prolactin in your blood are:

• Males: 2 to 18 nanograms per millilitre (ng/mL)
• Nonpregnant females: 2 to 29 ng/mL
• Pregnant females: 10 to 209 ng/mL

High prolactin may reflect a problem in your pituitary or hypothalamus, or liver disease.

This information is taken from the Medline Plus website.

FOUR MISTAKEN REASONS YOUR CONSULTANT MAY GIVE FOR REFUSING YOU A DYNAMIC TEST FOR GHD OR CORTISOL DEFICIENCY

1. “If the other pituitary hormones show no abnormality, there is no need to test for growth hormone deficiency.”
There is much research demonstrating that growth hormone deficiency is the most common pituitary defect after traumatic brain injury, and as such there will be many occasions when it is the only defect. As Vera Popovic’s 2005 paper says, “GH deficiency is very common in TBI, particularly isolated GHD” [1]. Richmond and Rogol’s standard textbook Growth Hormone Deficiency (2016) states “The most common isolated hormonal deficiency after traumatic brain injury (TBI) in both children and adults is growth hormone deficiency.” [2]
The incidence of GHD after TBI is reported in various studies as being between 10% and 63% [3]. Even if the 10% figure is nearer the truth it is clearly vital to exclude GHD as a possibility, given the devastating consequences if it is missed.

2. “If a scan of the pituitary shows no abnormality, there is no need to test.”
MRI scans are not normally used to exclude the need for dynamic testing, but to check for the presence of a pituitary tumour and to differentiate types of pituitary tumour. There is no research stating that an apparently normal pituitary MRI means there is no need to test biochemically. In fact, even in the case of microadenomas “Symptoms or signs of hypopituitarism may occur before a mass is evident on an MRI or CT scan” [4]
Anecdotally, at least two people who have approached Christopher Lane Trust have had ‘normal’ MRIs and then gone on to be diagnosed with severe GHD.

3. “If IGF-1 levels are normal, there is no need to test for GHD.”
Click here for a list prepared by Gareth Hamill of ten publications stating that in-range IGF-1 does not rule out growth hormone deficiency. As he says, this is by no means an exhaustive list.

4. “If the short synacthen test is normal, there is no need to test for secondary adrenal insufficiency.”
A review by D I Dorin (2003) finds the sensitivity of the SST for diagnosing secondary insufficiency to be only 57%-61% [5]. For this review the MEDLINE database was searched from 1966 to 2002 for all English-language papers related to the diagnosis of adrenal insufficiency. In other words the test misses 40% of patients. Moreover, Christopher Lane Trust has been in touch with three people who were badly failed by this test, two of whose stories can be found on the InvestinME website [6].

Finally a note about dynamic testing
The Insulin Tolerance Test is the gold standard dynamic test for GHD, and it also will diagnose secondary hypoadrenalism. However, it is unpleasant and sometimes risky, so used less these days. However the Glucagon Stimulation Test also diagnoses GHD and secondary hypoadrenalism and is considered an acceptable alternative. Also the Macimorelin test has recently appeared on the scene and since it is oral and only takes 90 minutes to do, may be less costly [7].
[1] GH deficiency as the most common pituitary defect after TBI: clinical implications. (medscape.com)
[2] Traumatic Brain Injury and Growth Hormone Deficiency | SpringerLink
[3] IJMS | Free Full-Text | Growth Hormone Deficiency Following Traumatic Brain Injury | HTML (mdpi.com)
[4] Hypopituitarism | NEJM
[5] Medline ® Abstract for Reference 23 of ‘Initial testing for adrenal insufficiency: Basal cortisol and the ACTH stimulation test’ – UpToDate
[6] Invest in ME Research – ME/CFS/PITUITARY AWARENESS CHRISTINE’S LEGACY
[7] https://www.pituitary.org.uk/news/2022/06/growth-hormone-deficiency-new-test-available-for-adults