Pituitary Gland: Normal Function and Assessment

Abstract

This computer-based, interactive module introduces preclinical medical students to normal pituitary function and outlines its assessment. Solid understanding of these topics is requisite to learning clinical disorders of the pituitary.

Existing resources largely target learners at earlier or later stages of training; thus, we created this resource to address needs of medical students during a first- or second-year endocrine course. A module format was selected to promote interactive, independent learning.

Two cohorts of medical students completed the 40-minute module: 172 second-year students who had completed a year of basic sciences in the traditional curriculum and 180 foundation-phase students in a three-semester combined basic and clinical sciences curriculum (due to a change in the medical school curriculum at our institution). In both instances, the module was completed before start of clinical pituitary content. A static set of PowerPoint slides accompanied the module to facilitate note taking.

Test Your Knowledge slides were inserted to ensure grasp of key terms/concepts before moving to subsequent slides. A short question-and-answer session was held following module completion to clarify points of confusion. Students rated effectiveness of the module as 4.6 out of 5, commenting on its clarity, organization, high-yield nature, and utility in preparing for clinical material.

Faculty noted greater understanding of foundational pituitary principles and more engaging discussions. The percentage of pituitary-related questions answered correctly on the midterm exam increased.

Finally, success of the pituitary module prompted development of adrenal, thyroid, and parathyroid modules that now comprise the Endocrine Organs Introduction Series in our curriculum.

Citation

Kirk D, Smith KW. Pituitary gland: normal function and assessment. MedEdPORTAL Publications. 2016;12:10430. http://dx.doi.org/10.15766/mep_2374-8265.10430

Educational Objectives

After completing this module, the learner will be able to:

  1. Describe the normal function and regulation of the pituitary gland, including names and actions of the anterior and posterior pituitary hormones.
  2. Understand the basic approach to laboratory assessment of the pituitary.
  3. Differentiate between anterior and posterior pituitary origin, function, and regulation.
  4. List the hormones produced by the pituitary gland.
  5. Discuss for each pituitary hormone: hypothalamic stimulating/inhibiting factors and their clinical uses, basic physiologic function, and regulation (feedback loop).
  6. Describe factors that affect growth hormone levels.
  7. Understand the tests for growth hormone excess and deficiency.
  8. Define a primary versus secondary endocrine disorder.

Keywords

  • Endocrine, Endocrinology, Pituitary, Module, Preclinical Medical Education

More information at https://www.mededportal.org/publication/10430

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

Webinar: The Essentials: The Diagnosis and Treatment of Hypopituitarism

Presented By

John D. Carmichael, MD
Associate Professor of Clinical Medicine
Co-Director, USC Pituitary Center

After registering you will receive a confirmation email with details about joining the webinar.

Contact us at webinar@pituitary.org with any questions or suggestions.
Date: Thursday, June 30, 2016
Time: 11:00 AM Pacific Daylight Time, 2:00 PM Eastern Daylight Time

Webinar Description

This will be a case-based review of the causes, diagnosis and treatment of pituitary failure, focusing on the most common scenarios patients may encounter. We will review issues with hormonal testing unique to patients with pituitary disease, and the approach toward optimizing pituitary hormone replacement.

Presenter Bio

John CarmichaelDr. John Carmichael is the Co-Director of the USC Pituitary Center and Associate Professor of Clinical Medicine at the Keck School of Medicine at the University of Southern California. After earning a degree in biomedical ethics at Brown University, Dr. Carmichael graduated from the Medical College of Virginia in Richmond. He then completed internship and residency at Virginia Mason Medical Center in Seattle, Washington. He received his endocrinology fellowship training at NYU, where he received a research fellowship grant to conduct clinical trials devoted to growth hormone deficiency and acromegaly after his clinical fellowship. In 2006, he moved to Los Angeles to join the Pituitary Center at Cedars-Sinai Medical Center, where he cared for patients with pituitary disease, devised and conducted clinical trials, and taught medical students, residents, and endocrinology fellows. In 2014, he joined the faculty at the University of Southern California. He has authored several journal articles devoted to clinical pituitary medicine, book chapters covering hypopituitarism and hypothalamic disease, and sits on the editorial boards for Pituitary and Endocrine, Diabetes, and Metabolism Case Reports.

Surgery Preferred Option in Cushing’s Disease for Best Survival

Patients with Cushing’s disease who have been in remission for more than 10 years still have an increased mortality risk compared with the general population, says an international team of researchers, who found the risk of early death was particularly increased in those with Cushing’s and accompanying circulatory disease.

Richard N Clayton, MD, department of medicine, Keele University, Stoke-on-Trent, United Kingdom, showed that Cushing’s disease, which is characterized by increased secretion of adrenocorticotropic hormone by the anterior pituitary gland, is associated with an increased mortality risk of more than 60% and a median survival of around 40 years.

In patients who also had circulatory disease, the mortality risk was even higher, say Dr Clayton and colleagues.

However, patients who had undergone curative pituitary surgery had a long-term risk of death no different from that of the general population. US Endocrine Society guidelines published last August recommend that optimal treatment of Cushing’s syndrome involves direct surgical removal of the causal tumor.

But Dr Clayton and colleagues point out that even patients who undergo pituitary surgery will nevertheless “require lifelong follow-up at a center experienced in dealing with this condition, having regular checks for diabetes, hypertension, and other cardiovascular risk factors.”

The study was published online June 2 in Lancet Diabetes & Endocrinology.

In an accompanying editorial, Rosario Pivonello, MD, PhD, department of clinical medicine and surgery, section of endocrinology, University of Naples Federico II, Italy, and colleagues write that, although surgery is not suitable for all patients, “Prompt pituitary surgery might be the preferred treatment for Cushing’s disease to guarantee the best mortality outcome.”

Calling for further research to better understand why one treatment “has a better effect on mortality than another,” they state: “The results from this study might also motivate rapid interventions, cure, and long-term follow-up in patients with Cushing’s disease — even for a long time after hypercortisolism resolution.”

Studying Those Who Have Survived More Than 10 Years

Dr Clayton and colleagues explain that previous studies have explored mortality in patients with Cushing’s disease during either active disease or remission. But the outcome of patients in remission, especially long-term remission, is still a matter of debate, and assessing long-term survival has been limited by various methodological differences. To overcome some of these issues, they performed a retrospective analysis of case records from specialist referral centers in the United Kingdom, Denmark, the Netherlands, and New Zealand.

They identified 320 patients diagnosed with Cushing’s disease and cured for a minimum of 10 years at enrollment and had no relapses during the study period. The ratio of women to men was 3:1.

Median patient follow-up was 11.8 years, yielding a total of 3790 person-years of follow-up 10 years after cure. There was no difference in follow-up between countries. And as there were no significant demographic and clinical differences between men and women, the data were pooled.

During the study 16% of patients died. Median survival was 31 years for women and 28 years for men, at approximately 40 years following remission. The overall standardized mortality ratio (SMR) for all-cause mortality compared with the general population was 1.61 (P = .0001).

Patients with Cushing’s and circulatory disease had an SMR vs the general population of 2.72 (P < .0001), but deaths from cancer among those who had survived Cushing’s disease were not higher than the general population, at an SMR of 0.79 (P = .41).

Patients with Cushing’s and diabetes also had an increased mortality risk, at a hazard ratio (HR) of 2.82 (P < .0096) compared with the general population, while hypertension was not significantly associated with increased mortality, at an HR of 1.59 (P = .08).

There was also an association between mortality and number of treatments, at an HR of 1.77 for two vs one treatment (P = .08) and an HR of 2.6 for three vs one treatment (P = .02).

Pituitary Surgery Alone Associated With No Increased Risk of Death

Pituitary surgery performed as the first and only treatment was associated with an SMR vs the general population of 0.94 compared with an SMR of 2.58 for other patients (P < .0005).

Patients who had pituitary surgery only had a median survival of 31 years compared with 24 years if surgery had been required at any time (P = 0.03).

The research team states: “For patients who have been cured of Cushing’s disease for 10 years or more, treatment complexity and an increased number of treatments, reflecting disease that is more difficult to control, appears to negatively affect survival.”

“Pituitary surgery alone achieves a mortality outcome that is not different from the normal population and should be performed in a center of excellence,” they conclude.

However, in the editorial, Dr Pivonello and colleagues point out that the surgical approach “is not a treatment option for some patients, either because of contraindications (eg, severe clinical complications) or because of an absence of clear indication for surgery (eg, tumor is not completely removable by surgery).”

The authors and editorialist have reported no relevant financial relationships.

Lancet Diabetes Endocrinol. Published online June 2, 2016. Abstract, Editorial

From http://www.medscape.com/viewarticle/865073#vp_2

Pituitary tissue grown from human stem cells releases hormones in rats

Researchers have successfully used human stem cells to generate functional pituitary tissue that secretes hormones important for the body’s stress response as well as for its growth and reproductive functions. When transplanted into rats with hypopituitarism–a disease linked to dwarfism and premature aging in humans–the lab-grown pituitary cells promoted normal hormone release. The study, which lays the foundation for future preclinical work, appears June 14 in Stem Cell Reports, a publication of the International Society for Stem Cell Researchers.

“The current treatment options for patients suffering from hypopituitarism, a dysfunction of the pituitary gland, are far from optimal,” says first study author Bastian Zimmer of the Sloan Kettering Institute for Cancer Research. “Cell replacement could offer a more permanent therapeutic option with pluripotent stem cell-derived hormone-producing cells that functionally integrate and respond to positive and negative feedback from the body. Achieving such a long-term goal may lead to a potential cure, not only a treatment, for those patients.”

The pituitary gland is the master regulator of hormone production in the body, releasing hormones that play a key role in bone and tissue growth, metabolism, reproductive functions, and the stress response. Hypopituitarism can be caused by tumors, genetic defects, brain trauma, immune and infectious diseases, or radiation therapy. The consequences of pituitary dysfunction are wide ranging and particularly serious in children, who can suffer severe learning disabilities, growth and skeletal problems, as well as effects on puberty and sexual function.

Currently, patients with hypopituitarism must take expensive, lifelong hormone replacement therapies that poorly mimic the body’s complex patterns of hormone secretion that fluctuates with circadian rhythms and responds to feedback from other organs. By contrast, cell replacement therapies hold promise for permanently restoring natural patterns of hormone secretion while avoiding the need for costly, lifelong treatments.

Recently, scientists developed a procedure for generating pituitary cells from human pluripotent stem cells–an unlimited cell source for regenerative medicine–using organoid cultures that mimic the 3D organization of the developing pituitary gland. However, this approach is inefficient and complicated, relies on ill-defined cellular signals, lacks reproducibility, and is not scalable or suitable for clinical-grade cell manufacturing.

To address these limitations, Zimmer and senior study author Lorenz Studer of the Sloan Kettering Institute for Cancer Research developed a simple, efficient, and robust stem cell-based strategy for reliably producing a large number of diverse, functional pituitary cell types suitable for therapeutic use. Instead of mimicking the complex 3D organization of the developing pituitary gland, this approach relies on the precisely timed exposure of human pluripotent stem cells to a few specific cellular signals that are known to play an important role during embryonic development.

Exposure to these proteins triggered the stem cells to turn into different types of functional pituitary cells that released hormones important for bone and tissue growth (i.e., growth hormone), the stress response (i.e., adrenocorticotropic hormone), and reproductive functions (i.e., prolactin, follicle-stimulating hormone, and luteinizing hormone). Moreover, these stem cell-derived cells released different amounts of hormone in response to known feedback signals generated by other organs in the body.

To test the therapeutic potential of this approach, the researchers transplanted the stem cell-derived pituitary cells under the skin of rats whose pituitary gland had been surgical removed. The cell grafts not only secreted adrenocorticotropic hormone, prolactin, and follicle-stimulating hormone, but they also triggered appropriate hormonal responses in the kidneys.

The researchers were also able to control the relative composition of different hormonal cell types simply by exposing human pluripotent stem cells to different ratios of two proteins: fibroblast growth factor 8 and bone morphogenetic protein 2. This finding suggests their approach could be tailored to generate specific cell types for patients with different types of hypopituitarism. “For the broad application of stem cell-derived pituitary cells in the future, cell replacement therapy may need to be customized to the specific needs of a given patient population,” Zimmer says.

In future studies, the researchers plan to further improve the protocol to generate pure populations of various hormone-releasing cell types, enabling the production of grafts that are tailored to the needs of individual patients. They will also test this approach on more clinically relevant animal models that have pituitary damage caused by radiation therapy and receive grafts in or near the pituitary gland rather than under the skin. This research could have important implications for cancer survivors, given that hypopituitarism is one of the main causes of poor quality of life after brain radiation therapy.

“Our findings represent a first step in treating hypopituitarism, but that does not mean the disease will be cured permanently within the near future,” Zimmer says. “However, our work illustrates the promise of human pluripotent stem cells as it presents a direct path toward realizing the promise of regenerative medicine for certain hormonal disorders.”

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The researchers were supported by the New York State Stem Cell Science and the Starr Foundation. The work was further supported in part by the National Institutes of Health and the National Cancer Institute.

Stem Cell Reports, Zimmer et al.: “Derivation of diverse hormone-releasing pituitary cells from human pluripotent stem cells” http://www.cell.com/stem-cell-reports/fulltext/S2213-6711(16)30060-1

Stem Cell Reports, published by Cell Press for the International Society for Stem Cell Research (@ISSCR), is a monthly open-access forum communicating basic discoveries in stem cell research, in addition to translational and clinical studies. The journal focuses on shorter, single-point manuscripts that report original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. Visit http://www.cell.com/stem-cell-reports. To receive Cell Press media alerts, please contact press@cell.com.

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