Medicines in Pituitary Conditions

By Catherine Matheson, Jemma Campbell, Philip Newland-Jones, Pharmacists – University Hospital Southampton NHSFT

The body’s hormonal system is coordinated by a structure in the brain called the hypothalamus. The hypothalamus sends signals to the pituitary gland, which then releases hormones that act on all different areas of the body. The pituitary gland is made up of the anterior pituitary lobe and the posterior pituitary lobe.

The anterior pituitary lobe releases hormones that control: the thyroid gland, the reproductive system, the production of growth hormone and prolactin and how the body responds to stress. The posterior pituitary lobe releases oxytocin and a hormone that controls the body’s water balance.

In certain conditions, the pituitary gland can either produce too much or too little of some of these hormones. Hypopituitarism covers a range of conditions where low levels of some or all of these hormones are produced. Prolactinoma is an example where high levels of a hormone (prolactin) is produced.

Although this article will discuss common side effects, for a full list, please see the product information supplied with your medication. If you are experiencing any side effects or have any concerns, please seek advice from a healthcare professional.  If you would like to access patient information leaflets and further medicines information please go to www.medicines.org.uk

Thyroid Hormone

In pituitary disorders, hypothyroidism occurs when your pituitary gland does not secrete enough thyroid stimulating hormone (TSH) and therefore your thyroid gland is not told to release thyroid hormone (FT4) and (FT3). This leads to low levels of thyroid hormone in your blood.  Levothyroxine is commonly used to treat hypothyroidism and is the mainstay of therapy working by replacing thyroid hormone T4.

Levothyroxine (T4)

Good to know:

• Levothyroxine should be taken on an empty stomach, at least 30 minutes before food or other medications because it can severely reduce its absorption and effectiveness.
• If you take any medications containing calcium and iron or take any indigestion remedies, such as Gaviscon, these should not be taken until at least 4 hours after you take your levothyroxine.

What to look out for:

• Side effects from levothyroxine are rare and tend to be from over treatment. In these cases, you may experience symptoms such as sweating, a fast heart rate and diarrhoea. If this occurs, please discuss with your GP or endocrinology team.
• Signs that your thyroid hormone levels are not high enough can include tiredness, weight gain and feeling cold. This is not a side effect but could indicate that your dosage is too low.
• Usually, day-to-day changes in symptoms are unlikely to be related to your thyroxine treatment due to the long-acting nature of levothyroxine. However, persistent changes in symptoms may be related to thyroid hormone replacement issues.

Monitoring:

• It is important that when healthcare professionals are checking your thyroid levels that they check your FT4 level as well as TSH, as doses should be adjusted based on FT4 in those with pituitary conditions.
• Biotin is a supplement which can affect your blood test result when checking thyroid levels. It is important that if you take biotin, or any supplements that contain it, that you make sure that your healthcare professionals know that you take this so that they can interpret your blood results properly.

Liothyronine (T3)

• A small proportion of people may still have symptoms of hypothyroidism despite adequate replacement of T4 with levothyroxine.  In these circumstances your specialist endocrine team may suggest a trial of a combination of levothyroxine (T4) and Liothyronine (T3) although this is not recommended as routine practice.

Generic “non-branded” vs branded medicines:

• Every patient is different in how their body absorbs and processes medication, which means there might be a difference in how much drug there is available for the body to use compared to someone else. Levothyroxine is a narrow-therapeutic range drug, which means small changes in the dose can have an impact on its efficacy.
• Although drug manufacturers have to prove that the effectiveness of their levothyroxine tablets are comparable to other manufacturers (also known as generic), sometimes there can be slight differences. This can be due to, for example, other ingredients (excipients) used to make the tablet affecting the absorption of the drug, which can have a noticeable effect for some patients. Most patients are able to switch between levothyroxine products without experiencing any symptoms but in some cases, they may need to be maintained on a specific product.
• If you find that a particular manufacturer of levothyroxine tablets works better for you, or that you notice a difference when changing between levothyroxine products, you can speak to your community pharmacy to ask if they are able to order it in from a specific manufacturer for your prescription. Alternatively, you can ask your GP to prescribe a specific levothyroxine product. However, be aware that if this product is not available for your pharmacy to order, then they will not be able to supply you with an alternative. The best way to proceed is to discuss with your usual pharmacy and they can advise you on the best course of action.
• If you experience symptoms despite taking a specific brand of levothyroxine tablets, then levothyroxine liquid solution is an alternative option that can be tried.

Growth Hormone

Growth hormone (somatropin), as the name suggests, causes growth of the body. It is used in children and adults who do not produce enough growth hormone naturally. In children it is used to stimulate growth. In adults it is used to maintain weight, energy levels, bone health and to regulate the processing of protein, carbohydrates and fat in the body.

Somatropin

Good to know:

• Somatropin is given by injection daily to treat growth hormone deficiency and it is prescribed by brand.
• The different brands currently available are: Genotropin, Norditropin, Omnitrope, Saizen and Zomacton.
• The brand is mainly chosen based on cost-effectiveness and the type of device used to administer it. Generally, you will be prescribed the same brand each time. However, there are only slight differences in effect between the brands, so if it is necessary to change brands, because of medication shortages this should not be problematic.

What to look out for:

• Some of the side affects you could experience are usually related to over replacement of growth hormone.
• These can include high blood sugar levels, mild build-up of fluid in the legs, tingling in the hands and feet and some joint pain.

Monitoring:

• In order for us to monitor that you are receiving the right amount of growth hormone, we measure the amount of IGF-1. This is a protein which is produced by the liver in response to growth hormone and so it is a good way of telling how well the treatment is working.
• Growth hormone can affect thyroid hormone levels and so these may need monitoring during changes in treatment.

Other medication:

• If you are taking steroids for another condition, this can impact the effects of somatropin and vice versa. Steroid doses may need to be adjusted.
• Oral oestrogen replacement therapy can also affect somatropin and higher doses of somatropin may need to be given.
• Please ensure healthcare professionals are aware you are prescribed somatropin if they want to start you on steroids or oestrogen replacement therapy or they adjust doses of pre-existing prescriptions for these.
• As blood sugar levels can be affected, medication used to treat diabetes may need to be adjusted if you are taking them.

Sex Hormones

The key sex hormones – oestrogens, progestogens and testosterone are all produced in response to hormones released by the anterior pituitary gland called follicle-stimulating hormone (FSH) and luteinising hormone (LH). Amongst others, they are responsible for triggering puberty, menstruation, pregnancy and sperm production.

Hormone Replacement Therapy in women

If levels of oestrogens and progestogens are low, for example during the perimenopause and menopause, they can cause various symptoms that can be unpleasant. Hormone replacement therapy (HRT), consisting of oestrogens and/or progestogens can be given to manage these symptoms and also to help protect against osteoporosis.

Good to know:

• Oestrogens come as oral tablets, gels, transdermal patches and vaginal tablets.
• Progestogens come as tablets, intra-uterine coil or combined with oestrogen in a patch.
• If a woman has an intact uterus, then it is normally recommended to take progestogens as well as oestrogens to reduce the risk of endometrial cancer providing there are no other reasons to avoid therapy.

What to look out for:

• Common side effects include: fluid retention, breast tenderness, headaches, bloating, premenstrual syndrome symptoms and breakthrough bleeding. These can usually be managed by changing the type, route or dose of the HRT.
• There are more serious side effects associated with HRT. These include increased risk of blood clots, breast cancer and heart disease.
• However, various different factors can influence how high the risk of these side effects occurring is. These factors can include: what other medical conditions you may have, whether you are overweight, whether you are taking tablet or patch forms of HRT, age at which you started HRT or duration of taking HRT.
• Before starting HRT, you should have a discussion with your GP or specialist endocrine team to review the risks and benefits of HRT and choose the most appropriate formulation and type of therapy for you.

Other medication:

• Levels of oestrogens and progestogens can be affected by other medications. If you notice changes in your symptom control, please speak to a healthcare professional.
• Using patches instead of tablets can mean the hormone levels are less affected by other medication and vice versa, as tablets can increase the production of essential proteins in the liver.

Supply:

• There have been shortages of HRT products and various protocols were put in place so that pharmacies in certain circumstances could either change to another specified brand or change the amount supplied without needing to refer you back to your prescriber.
• At the time of writing, there are no active protocols in place for HRT.
• If you are encountering supply issues, there are equivalent alternatives available. Please speak to your GP about prescribing alternatives.

Hormone Replacement Therapy in men

Good to know:

Testosterone production occurs in the testes, but is driven by hormones secreted from the pituitary, follicle-stimulating hormone (FSH) and luteinising hormone (LH). Testosterone affects libido, erections, body hair, bone density and distribution of fat within the body, and less specifically can affect energy levels, mood, muscle strength.

• Testosterone therapy should only be used if there is evidence that there is not enough testosterone being produced or available to the body.
• Testosterone can be administered with gels or injections into the muscle, whilst there have been oral tablets and patches historically these are not commonly used in practice any more.
• Taking testosterone will reduce fertility by further reducing sperm production, if fertility is possible and desired then alternative treatments may be suggested.

What to look out for:

• We like to monitor your red blood cells, fat levels in the blood, ongoing testosterone levels and prostate blood markers called prostate specific antigen (PSA).
• We would ask those on therapy to watch for changes in urination flow rate, increased fluid retention in lower limbs or breathlessness, changes in breast tissue.
• Previously undiagnosed prostate cancer can sometimes be unearthed on starting testosterone.  If you are over 40, healthcare professionals will usually want to have a PSA level before starting therapy and ongoing monitoring after starting testosterone and may want to examine your prostate should you have symptoms suggestive of an enlarged prostate.
• If using testosterone gel, ensure hands are washed thoroughly after application, and avoid contact with clothing until the gel has completely dried.  Ensure you wait at least 2 hours before showering or swimming to ensure the dose is fully absorbed.

Other medication:

• If you take any medicine that affects your blood clotting (anticoagulants), then increased monitoring or adjustment may be needed when starting or stopping testosterone.
• If you take insulin or medicines called sulfonylureas (gliclazide/glipizide), then doses may need to be adjusted when starting or stopping testosterone, therefore increased glucose monitoring is advised.

Raised prolactin due to prolactinoma

Benign (non-cancerous) tumours on the pituitary that produce prolactin are called prolactinomas. The cause of these are unknown but they can occur in men and women. These are often treated with medications that include cabergoline, bromocriptine and quinagolide.

Cabergoline, bromocriptine and quinagolide

Good to know:

• These medications work by reducing the amount of prolactin produced by the pituitary gland which reduce the levels of prolactin and also reduce the size of the tumour.

What to look out for:

• You may find that these medications make you feel dizzy, cause nausea or headache. This can be reduced or prevented by either taking the tablets with food or taking them just before going to bed.
• A rare side effect to be aware of is impulse-control disorder where you may have a strong desire to gamble or have an increased sex drive. This usually stops when treatment is stopped. It is important that you are aware of this risk and that your friends and family are aware too so that this can be looked out for.
• At high doses for prolonged use there may be a risk of a rare side effect called fibrosis which can occur in heart valves or in the lungs. Your healthcare professional team will review the risk of this on a case by case basis, where additional investigations may be suggested.

Other medication:

• Some anti-depressants and anti-psychotics can cause raised prolactin levels, which can counteract the effects of the medications used to treat prolactinoma. Please make sure your healthcare professional is aware if you are taking any of these medications as doses may need to be adjusted.

Antidiuretic Hormone

Antidiuretic Hormone (ADH), also known as vasopressin, helps regulate the body’s water balance by affecting the reabsorption of water by the kidneys.

If there is a deficiency of ADH, this can lead to a condition called Arginine vasopressin deficiency (AVP-D) previously called diabetes insipidus, where your body loses too much water. To treat this deficiency, a manufactured version of ADH called desmopressin is given.

Desmopressin

Good to know:

• Desmopressin tablet, sublingual melts or nasal spray formulations are more commonly used but injections are available.
• Different formulations have different doses.

What to look out for:

• If you notice significant changes in how often you go to the toilet and how much urine you produce or how thirsty you feel, please seek medical advice as your dose may need to be adjusted.
• Other side effects can include nausea, headache and confusion.

Monitoring:

In order to make sure you are receiving the right dose of desmopressin, the amount of urine you are producing, how thirsty you feel, the levels of sodium in your blood, along with the concentration of your urine are monitored.

Other medication:

• Drugs that can also cause your body to retain water, for example some antidepressants, antipsychotics and certain painkillers, such as ibuprofen, can lead to retention of too much water.
• Paracetamol would be the best pain relief medication to try instead of ibuprofen.
• Diuretics cause your body to lose water. Please ensure healthcare professionals are aware you are on desmopressin if they want to start or adjust pre-existing prescriptions for diuretics.
• Imodium (loperamide), which is used to treat diarrhoea, slows the rate at which food passes through your gut, which can increase the amount of desmopressin you absorb, causing more water to be retained.

Steroids

Steroids made within the body, called glucocorticoids, are produced in the adrenal glands in response adrenocorticotropic hormone (ACTH) which is released from the pituitary.  Not being able to produce enough steroids yourself is called adrenal insufficiency (AI).  Steroids are essential and needed in the body to regulate appetite, blood glucose, metabolism and how your body responds to stress and illness.   If there are not enough steroids available to the body in those that are critically unwell then something called an adrenal crisis can occur which is life threatening, but reversible if treated appropriately with emergency steroids.

Good to know:

• Hydrocortisone and prednisolone are the mainstay of medicines that are used to replace steroid hormones in the body.
• Hydrocortisone is short acting and needs to be taken multiple times per day, whilst prednisolone is only given once daily in most circumstances.
• During illness or stress from physical trauma your body requires more steroids to respond and therefore doses need to be increased to cover during this time (termed sick day rules).
• Sick day rules will state that doses for hydrocortisone needs to be increased to at least 40mg daily in 2 to 4 divided doses, or prednisolone increased to at least 10mg daily in 1 to 2 divided doses until the acute illness or physical trauma has resolved.
• The dose should not be increased for a long duration to avoid signs and symptoms of over-replacement such as weight gain, increased appetite, skin thinning, decreased bone density.
• You should ensure that you have an emergency management injection kit available to you to use if adrenal crisis is suspected.  This should contain an intramuscular injection of hydrocortisone with water for injection (if needed), two needles and two 2ml syringes with written instructions/pictures on how to prepare and administer in an emergency.
• You should ensure that you carry an NHS steroid emergency card with you at all times which can be obtained from your healthcare professional team.
• Medical alert jewellery is advised to be worn (such as bracelets) and mobile phone medical IDs are advised to be set up – please speak to your healthcare professional team about how to do this if you are not sure.

Monitoring:

• Monitoring is often adjusted based on circumstances, where more frequent reviews may be needed at the point of diagnosis or during changes in personal circumstances.
• Monitor for any signs that you may be under- or over-replaced with steroids and report to your healthcare professional team.  Under-replacement may present as weight loss, decreased appetite, nausea, tiredness, muscle weakness.
• Doses may need to be adjusted depending on lifestyle factors such as shift working and travel or temporary increased demands on activities of daily living.
• We like to keep an eye on blood pressure, kidney function, diabetes markers (HbA1c), bone density and blood fat profile.

Other medication:

• Any medicine that affects the activity of liver enzymes can affect how your body handles your steroids.  This can be a large list of medicines, therefore when starting any new medicine, it is good practice to ask if this will affect your steroid doses from the healthcare professional prescribing the medicine.
• If your cortisol levels are checked as part of your care, these can be affected if you take oral oestrogens, it is important to inform your healthcare professional team that you are taking oral oestrogens.

Practicalities

Free NHS prescriptions

If you have an endocrine disorder, you could be entitled to free prescriptions if you have any of the following endocrine conditions:

• A form of hypoadrenalism which requires essential replacement therapy (e.g. Addison’s disease)
• Diabetes insipidus (AVP deficiency) and other forms of hypopituitarism
• Hypothyroidism that requires thyroid replacement therapy (myxoedema)
• Hypoparathyroidism

If you qualify for receiving free prescriptions, you need to apply for a medical exemption certificate – please speak to your GP surgery. If you are unsure, it is always worth speaking to your GP surgery or healthcare professional team.

Electronic repeat dispensing

Your GP can issue a batch of repeatable prescriptions that are sent electronically directly to your nominated pharmacy which can cover up to 12 months’ worth of prescriptions at one time. This means you do not need to contact your GP each month for a new prescription and your nominated pharmacy can start preparing your prescription in advance each month to avoid you needing to wait for medications to be ordered in. Your pharmacy may ask you if there have been any changes to your medications or your condition before supplying.

Emergency Supply

A pharmacist can supply medication without a prescription if it is felt that there is an immediate need for the medication, and it is not practical for a patient to obtain a prescription without undue delay. The medication being requested can only be supplied if you have been prescribed this before in the UK. This may be easier to obtain through your regular pharmacy as they will have a record of your recently dispensed medication, but it is not essential if, for example, you are on holiday. A maximum of 30 days can be supplied.

Supply of Essential Steroid Medication

There is no official limit on the quantity of medication that can be supplied on a prescription (except for controlled drugs) but generally 28 to 56 days are supplied at a time. The Society for Endocrinology advise having three months’ supply of essential steroid medication available in case you need to increase your dose as per sick day rule advice or there are supply shortages. In practice, it would be reasonable to have two monthly prescribing as long as you have a two-week surplus to ensure you can double your dose if you were to become unwell. Please speak to your GP if you feel you require an increased volume.