A Retrospective Review of 34 Cases of Pediatric Pituitary Adenoma

Abstract

Purpose

The purpose of this paper is to study invasiveness, tumor features and clinical symptoms of pediatric pituitary adenoma, and to discuss some inconclusive results in prior studies.

Methods

We retrospectively reviewed 34 cases of children (<20 year-old) who were pathologically diagnosed with pituitary adenoma and surgically treated from 2010 to 2017. Data of general information, clinical symptoms, invasive behaviors, surgery approaches, and tumor features were collected and analyzed.

Results

Sixteen boys and 18 girls aged from 12 to 19 years old were included. Prolactinoma was most suffered, followed by GH-, none- and ACTH-secreting pituitary adenoma. Invasive behaviors were observed frequently and suprasellar extensions were most found. Macroadenoma account 70% of all cases. Meanwhile, unlike prior studies, a significant raise of incidence on invasive tumor and pituitary adenoma apoplexy were observed. Craniotomy and transsphenoidal surgery were both applied with zero mortality. Nine cases occurred with transient hypopituitarism and diabetes insipidus. Three cases of tumor recurrence received secondary surgery or radiotherapy.

Conclusions

Invasive behaviors were more frequent than previous prediction. Craniotomy is worth considering for total tumor removal. Pituitary adenoma apoplexy needs further studies since its different features between children and adults in present study. Specialized care and teamwork of neurosurgeons, pediatricians, and endocrinologists are important.

Keywords

Pediatric pituitary adenoma Invasion Pituitary apoplexy Transsphenoidal surgery 

Growth Hormone: Improving Patients’ Lives and Boosting Mature Product Portfolios

Jul 07, 2017
Volume 37, Issue 7

easypod—an automated drug delivery device manufactured by Merck KGaA, Darmstadt, Germany for its recombinant human growth hormone, Saizen—is the only electronic, fully automated injection device for growth hormone therapy. Its features include automated dose delivery and prescription tracking, which records injection history and any missed injections, and allows patients to know when to change their cartridge by displaying how much medicine is left in the device.

Speaking to Pharm Exec, Merck KGaA’s Chief Operating Officer of Biopharma, Simon Sturge, outlines the device’s development and highlights its position in the context of a changing treatment-adherence landscape that could bring benefits both to patients and mature product portfolios.

PE: Are digital interventions in patient adherence becoming more of a focus at your company?

STURGE: Absolutely. We are a major player in the area of diabetes, for example, and as we all know, lifestyle has a huge impact on the outcome of diabetes. How much we as a company should be able to offer a whole package that helps to support the lifestyle changes needed is a very important element of us preventing or delaying the onset of diabetes. In other areas, many people who are sick have a degree of depression. There are excellent apps that are reimbursed in some countries to help treat depression, and those sorts of things should be offered as part of a solution. We believe it is an essential part of our business to look holistically at the patient and bring to that patient as many practical things as possible to help them overcome their disease.

However, innovative drugs are also at the core of what we do. A few years ago, we established a clear strategy of driving innovation in the area of specialty products. This has taken quite some time from an R&D perspective, but it is now coming to fruition, with a focus on the areas of oncology, immuno-oncology, and immunology. We have a number of exciting innovative products coming to market, and what we’re also seeing is substantial growth on the portfolio of our established products, one of which is our growth hormone, Saizen.

PE: How much did you incorporate patients’ adherence behaviors in developing easypod?

STURGE: Quite a few of our products are biotech products that need to be given via injection. Understanding the patient need around that product, how they inject, what the issues are, particularly for children, has helped drive our e-health and digital platform. We have a number of different applications around our growth hormone product, but the most sophisticated is easypod. The device sends administration data such as time and dose to the cloud via a mobile device or home network, and then shares that data with the treating physician or carer, to be able to understand the usage of that product.

There are digital ways that you can track people and their activities, of course, but what we’ve found is that you can’t beat having somebody almost living with a patient. In some circumstances we do that. We use an external group, and they send an observer to stay with a family for several days to really understand the practical issues that surround the use of the product. It’s those kinds of insights that really help to provide solutions that are practical and that address genuine issues that the patient wants to overcome.

Adherence in using an injectable product in a chronic environment can be very low, as low as 25%, but we’ve seen in controlled studies that with easypod that we can take that up to close to 90%.

[Ramy Sourial, growth hormone franchise director at Merck KGaA, Darmstadt, Germany, adds: We worked with patient organizations and healthcare providers at different stages of planning the device, and we used focus groups and market researchers to identify the needs. During development, we conduct regular tests to check that we are on the right track. And when the product is on the market, we continue to improve the device, even small things like designing covers and designing smaller needles.]

PE: Can this higher adherence be sustained in a real-world setting?

STURGE: We’re moving to very elegant devices, more universal devices; physicians and caregivers are becoming a lot more comfortable using the data that is generated. Where the big transition needs to take place is still with the payers. The NHS (National Health Service) is one of the most sophisticated providers in terms of understanding usage of products on a more holistic basis and has a willingness to work with the pharma industry on pricing and payment mechanisms that ultimately link efficacy with payment. As governments, payers, and the industry work more closely together, this will be of benefit to all parties and especially patients.

Our responsibility as a pharma company is broader than just supplying the drug. We have worked with the NHS on schemes where they only pay if the drug is used. If adherence levels are low, they don’t pay. In some of the pilot schemes with the NHS in a real-world setting, we were getting those adherence rates of close to 90%; we think that is quite achievable in everyday use. But there’s always things you can add, adding digital gains into these things to encourage children to use these devices on a daily basis; it’s a dynamic process and our aim is to try and maintain these increased adherence rates.

PE: What would you say are the remaining challenges in patient adherence?

STURGE: One of the biggest challenges we face is data privacy, the different data privacy laws country by country. If you end up having to develop software that has to be different in every country, it becomes less meaningful. Respecting and understanding data privacy but having a broader global alignment on data privacy laws in our industry will help everybody.

It will remain a sticking point for quite some time; it’s a highly complex and politically emotive subject, for very good reasons. But our concern isn’t around data privacy, per se—it’s consistency of the regulations thereof.

 

Julian Upton is Pharm Exec’s European and Online Editor. He can be reached at julian.upton@ubm.com

From http://www.pharmexec.com/improving-patients-lives-and-boosting-mature-product-portfolios

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

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