Bimonthly Growth Hormone Injections to Replace Daily Injections?

At the Annual ENDO 2017 meeting in Orlando, FL, Moore et al provided an update on somavaratan, the long acting recombinant human growth hormone being investigated for children and adults with growth hormone deficiency.

Current treatment for these patients is somewhat burdensome given the need for daily subcutaneous injections. Somavaratan provides the option for bimonthly injections.

At ENDO 2017, 3 year data was presented in children given somavaratan and the data is impressive.

The 3 year data is part of an ongoing extension study following a 6 month Phase 2 trial in which 64 patients received 5.0 mg/kg/month at various dosing schedules. Of those patients, 60 continued in an open label extension study (dose adjusted to 3.5 mg/kg given twice-monthly by the beginning of Year 2 of treatment).  At ENDO 2017, data from 30 of those patients who had completed 3 years of treatment were presented.

(Insulin-like growth factor standard deviation score (IGF-I SDS) increased from -1.7 ± 0.8 at baseline to 1.1 ± 1.6 at peak (3–5 days post-injection) and -0.2 ± 0.9 at trough (end of dosing cycle) in Year 3. Of the 30 patients, 8 had transient IGF-I SDS excursions > 2.0, of which 3 events were > 3.0 (range, 2.3–3.9).

Height velocity (HV) remained consistent at 8.5 ± 1.8, 8.5 ± 1.7, and 8.1 ± 1.5 cm/year, for years 1, 2, and 3 respectively.

Height-SDS increased from -2.6 ± 0.5 at baseline to -1.9 ± 0.6, -1.4 ± 0.7, and -1.0 ± 0.7 at years 1, 2, and 3, respectively.

Treatment-related adverse events were generally mild and transient.

In an exclusive interview with Rare Disease Report, one of the investigators of the study, Bradley Miller, MD, PhD, of the University of Minnesota Masonic Children’s Hospital, said that compliance is an issue with growth hormone replacement therapy and any options that can remove the daily injection requirements would likely be well received by both patients and clinicians.

A Phase 3 study is currently underway to comparing bimonthly somavaratan treatment with daily growth hormone treatments (NCT02339090).

Somavaratan is being developed by Versartis Inc

About Growth Hormone Deficiency 

Growth hormone deficiency occurs when the pituitary gland does not produce enough growth hormone, resulting in short stature, delayed or absent puberty, and changes in muscle mass, cholesterol levels, and bone strength. The condition can be congenital, structural (malformations in the brain) or acquired (resulting from trauma, infections, tumors, radiation therapy, or other causes).

Currently, the standard of care is subcutaneous injection of a biosynthetic recombinant human growth hormone (rhGH). The frequency of the injections is based on the patient’s level of growth hormone deficiency (ie, whether growth hormone is completely absent or some growth hormone is present), but most patients require daily administration.

The rhGH treatments are typically given until the child’s maximum growth potential is achieved, often requiring many years of treatment (and increasing the risk of poor compliance).

Reference

Moore WV, Fechner PY, Nguyan HJ, et al. Safety and Efficacy of Somavaratan (VRS-317), a Long-Acting Recombinant Human Growth Hormone (rhGH), in Children with Growth Hormone Deficiency (GHD): 3-Year Update of the Vertical & VISTA Trials (NCT01718041, NCT02068521). Presented at: ENDO 2017; Orlando, FL; April 1-4, 2017. Abstract OE31-1.

From http://www.raredr.com/news/bimonthly-growth-hormone

The Pituitary Gland: Small But Mighty

The pituitary gland works hard to keep you healthy, doing everything from ensuring proper bone and muscle growth to helping nursing mothers produce milk for their babies. Its functionality is even more remarkable when you consider the gland is the size of a pea.

“The pituitary is commonly referred to as the ‘master’ gland because it does so many important jobs in the body,” says Karen Frankwich, MD, a board-certified endocrinologist at Mission Hospital. “Not only does the pituitary make its own hormones, but it also triggers hormone production in other glands. The pituitary is aided in its job by the hypothalamus. This part of the brain is situated above the pituitary, and sends messages to the gland on when to release or stimulate production of necessary hormones.”

These hormones include:

  • Growth hormone, for healthy bone and muscle mass
  • Thyroid-stimulating hormone, which signals the thyroid to produce its hormones that govern metabolism and the body’s nervous system, among others
  • Follicle-stimulating and luteinizing hormones for healthy reproductive systems (including ovarian egg development in women and sperm formation in men, as well as estrogen and testosterone production)
  • Prolactin, for breast milk production in nursing mothers
  • Adrenocorticotropin (ACTH), which prompts the adrenal glands to produce the stress hormone cortisol. The proper amount of cortisol helps the body adapt to stressful situations by affecting the immune and nervous systems, blood sugar levels, blood pressure and metabolism.
  • Antidiuretic (ADH), which helps the kidneys control urine levels
  • Oxytocin, which can stimulate labor in pregnant women

The work of the pituitary gland can be affected by non-cancerous tumors called adenomas. “These tumors can affect hormone production, so you have too little or too much of a certain hormone,” Dr. Frankwich says. “Larger tumors that are more than 1 centimeter, called macroadenomas, can also put pressure on the area surrounding the gland, which can lead to vision problems and headaches. Because symptoms can vary depending on the hormone that is affected by a tumor, or sometimes there are no symptoms, adenomas can be difficult to pinpoint. General symptoms can include nausea, weight loss or gain, sluggishness or weakness, and changes in menstruation for women and sex drive for men.”

If there’s a suspected tumor, a doctor will usually run tests on a patient’s blood and urine, and possibly order a brain-imaging scan. An endocrinologist can help guide a patient on the best course of treatment, which could consist of surgery, medication, radiation therapy or careful monitoring of the tumor if it hasn’t caused major disruption.

“The pituitary gland is integral to a healthy, well-functioning body in so many ways,” Dr. Frankwich says. “It may not be a major organ you think about much, but it’s important to know how it works, and how it touches on so many aspects of your health.”

Learn more about Mission Hospital. Learn more about Dr. Frankwich.

From http://www.stjhs.org/HealthCalling/2016/December/The-Pituitary-Gland-Small-but-Mighty.aspx

Endocrine Society issues new guidelines on hypopituitarism

The Endocrine Society today issued a Clinical Practice Guideline that recommends treating insufficient hormone levels in individuals with hypopituitarism by replacing hormones at levels as close to the body’s natural patterns as possible.

The guideline, titled “Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline,” was published online and will appear in the November 2016 print issue of The Journal of Clinical Endocrinology & Metabolism (JCEM), a publication of the Endocrine Society.

Hypopituitarism, or pituitary insufficiency, occurs when the pituitary gland does not produce sufficient amounts of hormones–the chemical signals that regulate respiration, reproduction, growth, metabolism, sexual function and other important biological functions. The pituitary gland is often called the master gland because the hormones it produces impact many bodily functions. As a result, hypopituitarism can cause a range of symptoms, according to the Hormone Health Network.

The rare disorder can occur due to abnormal development or later in life as a result of a tumor, traumatic brain injury, hemorrhage or autoimmune condition, according to the Society’s

“Hypopituitarism can manifest as low levels of a variety of hormones, including cortisol, thyroid hormone, estrogen, testosterone and growth hormone,” said Maria Fleseriu, MD, FACE, of Oregon Health & Science University in Portland, OR. Fleseriu chaired the task force that developed the guideline. “The goal of treatment should be to restore hormone levels as close to healthy levels as possible The interactions between these hormones also are very important, and patients might require dose changes of one or more of the replacement hormones after starting or discontinuing another one.”

In recommending treatment options, the guideline task force followed the overriding principle of using hormone replacement therapy dose size and timing to mimic the body’s natural functioning as closely as possible.

Accurate and reliable measurements of hormones play a central role in diagnosing hypopituitarism and monitoring the effectiveness of treatments, Fleseriu said. Healthcare providers need to keep in mind technical considerations to ensure the testing procedure is as accurate as possible.

The guideline addresses special circumstances that may affect the treatment of patients with hypopituitarism, including pregnancy care, post-surgical care following pituitary or other operations, treatment in combination with anti-epilepsy medication, and care following pituitary apoplexy–a serious condition that occurs when there is bleeding into the gland or blood flow to it is blocked.

Recommendations from the guideline include:

  • Measurements of both free thyroxine and thyroid-stimulating hormone are needed to evaluate central hypothyroidism, a condition where the thyroid gland does not produce enough hormones because it isn’t stimulated by the pituitary gland.
  • People who have central hypothyroidism should be treated with levothyroxine in doses sufficient to raise levels of the thyroid hormone free thyroxine to the upper half of the reference range.
  • Growth hormone stimulation testing should be used to diagnose patients with suspected growth hormone deficiency.
  • People who have proven cases of growth hormone deficiency and no contraindications should be offered growth hormone replacement as a treatment option.
  • Premenopausal women who have central hypogonadism, a condition where the sex glands produce minimal amounts or no hormones, can undergo hormone treatment, provided there are no contraindications.
  • People producing abnormally large volumes of dilute urine should be tested for central diabetes insipidus–a rare condition that leads to frequent urination–by analyzing the concentration of their blood and urine.
  • For patients who have low levels of glucocorticoid hormones, hydrocortisone can be given in a daily single or divided dose.
  • All hypopituitarism patients should be instructed to obtain an emergency card, bracelet or necklace warning about the possibility of adrenal insufficiency.
  • Patients who are suspected of having an adrenal crisis due to secondary adrenal insufficiency should receive an immediate injection of 50 to 100 milligrams of hydrocortisone.
  • People who have central adrenal insufficiency should receive the lowest tolerable dose of hydrocortisone replacement on a long-term basis to reduce the risk of metabolic and cardiovascular disease.
Source:

The Endocrine Society

From http://www.news-medical.net/news/20161013/Endocrine-Society-issues-new-guidelines-on-hypopituitarism.aspx

Hypopituitarism – Deficiency in Pituitary Hormone Production

By Yolanda Smith, BPharm

Hypopituitarism is a health condition in which there is a reduction in the production of hormones by the pituitary gland.

The pituitary gland is located at the base of the brain and is responsible for the production of several hormones, including:

  • Adrenocorticotropic hormone (ACTH), which controls the production of the vital stress hormones cortisol and dehydroepiandrosterone (DHEA) in the adrenal gland
  • Thyroid stimulating hormone (TSH), which controls the production of hormones by the thyroid gland
  • Luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which control the secretion of the primary sex hormones and affect fertility
  • Growth hormone (GH), which regulates the growth processes in childhood and other metabolic processes throughout life
  • Prolactin (PRL), which facilitates the production of breast milk
  • Oxytocin, which is crucial during labor, childbirth and lactation
  • Antidiuretic hormone (ADH), also known as vasopressin, which regulates the retention of water and the blood pressure

An individual with hypopituitarism shows a deficiency in one or more of these hormones. This inevitably leads to abnormal body function, as an effect of the low levels of the hormone in the body, and may result in symptoms.

Causes

Hypopituitarism is most commonly due to the destruction, compression or inflammation of pituitary tissue by a brain tumor in that region. Other causes include:

  • Head injury
  • Infections such as tuberculosis
  • Ischemic or infarct injury
  • Radiation injury
  • Congenital and genetic causes
  • Infiltrative diseases such as sarcoidosis

Symptoms

General symptoms that are associated with pituitary hormone deficiency include:

  • Weakness and fatigue
  • Decreased appetite
  • Weight loss
  • Sensitivity to cold
  • Swollen facial features or body

There are also likely to be more specific symptoms according to the type of pituitary hormone deficiency, such as:

  • ACTH deficiency:
    • abdominal pain
    • low blood pressure
    • low serum sodium levels
    • skin pallor
  • TSH deficiency:
    • generalized body puffiness
    • sensitivity to cold
    • constipation
    • impaired memory and concentration
    • dry skin
    • anemia
  • LH and FSH deficiency:
    • reduction in libido
    • erectile dysfunction in men
    • abnormal menstrual periods
    • vaginal dryness in women
    • difficulty in conceiving
    • infertility.
  • GH deficiency:
    • slow growth
    • short height
    • an increase in body fat

Treatment

The first step in the treatment of hypopituitarism is to identify the cause of the condition.

Secondly, the hormones that are deficient must be identified. From this point, the appropriate treatment decisions can be made to promote optimal patient outcomes.

Hormone replacement therapy is the most common type of treatment for a patient with hypopituitarism.

This may involve supplementation of one or more hormones that are deficient, to reduce or correct the impact of the deficiency.

Follow Up

As hormone replacement therapy is expected to continue on a lifelong basis, it is important that patients have a good understanding of the therapy.

It is especially important to educate patients on what to do in case of particular circumstances that may change their hormone requirements.

For example, during periods of high stress, the demand for many hormones is increased, and the dose of hormone replacement may need to be adjusted accordingly.

It is recommended that patients have regular blood tests to monitor their hormone levels and ensure that they are in the normal range.

Patients should also carry medical identification, such as a medical bracelet or necklace, to show that they are affected by hypopituitarism and inform others about their hormone replacement needs and current treatment. This can help to meet their medical needs in case of any emergency.

Epidemiology

Hypopituitarism is a rare disorder that affects less than 200,000 individuals in the United States, with an incidence of 4.2 cases per 100,000 people per year.

The incidence is expected to be higher in certain subsets of the population, such as those that have suffered from a brain injury. Statistics in reference to these population groups have not yet been determined.

Reviewed by Dr Liji Thomas, MD.

References

From http://www.news-medical.net/health/Hypopituitarism-Deficiency-in-Pituitary-Hormone-Production.aspx

(For the General Public) Are there any advantages to human growth hormone?

Harvard Men’s Health Watch

Ask the doctor

Q. I’ve heard about the benefits of human growth hormone (HGH) for older individuals. Is this something I should try?

A. The benefits of HGH supplementation for older adults are unproven, and perhaps most telling is that these products have a negligible effect on HGH levels. In addition, there are concerns about potential side effects.

HGH comes in two forms: injections and pills. Since HGH injections are difficult to administer, pills are often preferred. Yet, these supplements do not actually contain HGH like injections do, because the hormone would quickly break down in the digestive tract. Instead, they contain amino acids that are absorbed by the body, which raises HGH levels. (They are also more expensive and can cost $100-plus for a month’s supply.)

HGH levels naturally decline as people age, which makes sense since our bodies stop growing during the late teenage years. So why would you need higher HGH levels later in life? The hype around HGH comes from a few studies that showed HGH injections can increase lean body mass and shrink body fat, which led to claims of HGH as an “anti-aging” hormone. However, the effects on strength and body weight are quite minimal. In addition, HGH can increase the amount of soft tissues in the body, which can lead to swelling, joint pain, carpal tunnel syndrome, and breast tenderness in men.

There is also a concern that HGH might promote cancer growth. (MaryO’Note:  I always mentioned this to doctors when I was diagnosed with kidney cancer.  Even though I couldn’t take HGH for the first 5 years after diagnosis, none of my doctors would confirm a connection between HGH and my cancer)

If you want to improve your strength, forget about HGH and increase your exercise. Some studies suggest this alone may be more effective than HGH supplementation for raising growth hormone levels in the body.

—William Kormos, MD
Editor in Chief, Harvard Men’s Health Watch

Originally published: July 2016

Adapted from http://www.health.harvard.edu/mens-health/are-there-any-advantages-to-human-growth-hormone

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