Grant Liddle

Last updated April 04, 2019

Grant Winder Liddle (June 27, 1921 – June 29, 1989) was an American endocrinologist whose research focused largely on the hypothalamic–pituitary–adrenal axis. He was a professor at Vanderbilt University and chaired its Department of Medicine from 1968 to 1983.

The hypothalamic–pituitary–adrenal axis is a complex set of direct influences and feedback interactions among three components: the hypothalamus, the pituitary gland, and the adrenal glands.

Vanderbilt University is a private research university in Nashville, Tennessee. Founded in 1873, it was named in honor of New York shipping and rail magnate Cornelius Vanderbilt, who provided the school its initial $1-million endowment despite having never been to the South. Vanderbilt hoped that his gift and the greater work of the university would help to heal the sectional wounds inflicted by the Civil War.

Biography

Liddle was born on June 27, 1921, in American Fork, Utah. He attended the University of Utah, graduating in 1943, before moving to California to attend the UCSF School of Medicine.^[1] After graduating in 1948, he became a research fellow at the National Institutes of Health Metabolic Research Unit.^[2] From 1953 to 1956, he worked as a surgeon for the Section on Clinical Endocrinology at the National Heart, Lung, and Blood Institute. He left to join the faculty of the Vanderbilt University School of Medicine as chief of the school's Endocrine Service, and was appointed chairman of Vanderbilt's Department of Medicine in 1968.^[3] He held that role until 1983, when he had a stroke while driving and sustained numerous fractures from the crash.^[1] He died on June 29, 1989, in Nashville, Tennessee.^[4]

American Fork is a city in north-central Utah County, Utah, United States, at the foot of Mount Timpanogos in the Wasatch Range, north of Utah Lake. It is part of the Provo–Orem Metropolitan Statistical Area. The population was 28,326 in 2015, representing a nearly 20% growth since the 2000 census. The city has grown rapidly since the 1970s.

The University of Utah is a public research university in Salt Lake City, Utah, United States. As the state's flagship university, the university offers more than 100 undergraduate majors and more than 92 graduate degree programs. The university is classified among "R-1: Doctoral Universities – Highest Research Activity" with "selective" admissions. Graduate studies include the S.J. Quinney College of Law and the School of Medicine, Utah's first medical school. As of Fall 2015, there are 23,909 undergraduate students and 7,764 graduate students, for an enrollment total of 31,673.

The UCSF School of Medicine, is the medical school of the University of California, San Francisco, United States, and is located in San Francisco. Founded in 1864 by Hugh Toland, it is the oldest medical school in California and the western United States. The school is affiliated with the UCSF Medical Center, which was ranked in 2017 as the #1 hospital in California and the #5 in the United States. UCSF faculty have treated patients and trained residents since 1873 at the San Francisco General Hospital and for over 50 years at the San Francisco VA Medical Center.

Research

Liddle published 223 research papers throughout his career. Much of his research focused on the hypothalamic–pituitary–adrenal axis and diseases that can affect it. He was the first to show that Cushing's disease was caused primarily by an abnormality in the anterior pituitary rather than the adrenal glands. He also described Liddle's syndrome, a genetic syndrome causing high blood pressure.^[1] Liddle developed the dexamethasone suppression test for assessing adrenal function and the metyrapone test for pituitary reserve. He discovered a method for measuring aldosterone levels in urine and pioneered the use of spironolactone in the treatment of high blood pressure. He also discovered that certain cancers, especially of the lungs, can secrete ACTH, producing a paraneoplastic Cushing's syndrome.^[3] Based on his research into paraneoplastic syndromes, he coined the term "ectopic hormone secretion".^[5]

Cushing's disease is one cause of Cushing's syndrome characterised by increased secretion of adrenocorticotropic hormone (ACTH) from the anterior pituitary. This is most often as a result of a pituitary adenoma or due to excess production of hypothalamus CRH that stimulates the synthesis of cortisol by the adrenal glands. Pituitary adenomas are responsible for 80% of endogenous Cushing's syndrome, when excluding Cushing's syndrome from exogenously administered corticosteroids.

Anterior pituitary glandular, anterior lobe that, together with the posterior lobe, makes up the pituitary gland

A major organ of the endocrine system, the anterior pituitary, is the glandular, anterior lobe that together with the posterior lobe makes up the pituitary gland (hypophysis). The anterior pituitary regulates several physiological processes including stress, growth, reproduction and lactation. Proper functioning of the anterior pituitary and of the organs it regulates can often be ascertained via blood tests that measure hormone levels.

Adrenal gland endocrine gland that produces a variety of hormones

The adrenal glands are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex which produces steroid hormones and an inner medulla. The adrenal cortex itself is divided into three zones: the zona glomerulosa, the zona fasciculata and the zona reticularis.

Awards and honors

Liddle was elected to the National Academy of Sciences in 1981. He received the Endocrine Society's Distinguished Leadership Award in 1971 and the American College of Physicians' John Phillips Memorial Award in 1977.^[3] In 1983, the Vanderbilt University Medical Center established the Grant W. Liddle Award in his honor.^[6]

The National Academy of Sciences (NAS) is a United States nonprofit, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the National Academy of Medicine (NAM).

The Endocrine Society is a professional, international medical organization in the field of endocrinology and metabolism, founded in 1916 as The Association for the Study of Internal Secretions. The official name of the organization was changed to the Endocrine Society on January 1, 1952. It is a leading organization in the field and publishes four leading journals. It has more than 17,000 members from over 120 countries in medicine, molecular and cellular biology, biochemistry, physiology, genetics, immunology, education, industry, and allied health. The Society's mission is: "to advance excellence in endocrinology and promote its essential and integrative role in scientific discovery, medical practice, and human health."

The American College of Physicians (ACP) is a national organization of internists, who specialize in the diagnosis, treatment, and care of adults. With 154,000 members, ACP is the largest medical-specialty organization and second-largest physician group in the United States, after the American Medical Association. Its flagship journal, the Annals of Internal Medicine, is considered one of the five top medical journals in the United States and Britain.

Related Research Articles

Endocrinology is a branch of biology and medicine dealing with the endocrine system, its diseases, and its specific secretions known as hormones. It is also concerned with the integration of developmental events proliferation, growth, and differentiation, and the psychological or behavioral activities of metabolism, growth and development, tissue function, sleep, digestion, respiration, excretion, mood, stress, lactation, movement, reproduction, and sensory perception caused by hormones. Specializations include behavioral endocrinology and comparative endocrinology.

The endocrine system is a chemical messenger system consisting of hormones, the group of glands of an organism that secrete those hormones directly into the circulatory system to regulate the function of distant target organs, and the feedback loops which modulate hormone release so that homeostasis is maintained. In humans, the major endocrine glands are the thyroid gland and the adrenal glands. In vertebrates, the hypothalamus is the neural control center for all endocrine systems. The study of the endocrine system and its disorders is known as endocrinology. Endocrinology is a branch of internal medicine.

Cushings syndrome Adrenal gland overactivity

Cushing's syndrome is a collection of signs and symptoms due to prolonged exposure to cortisol. Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, a round red face, a fat lump between the shoulders, weak muscles, weak bones, acne, and fragile skin that heals poorly. Women may have more hair and irregular menstruation. Occasionally there may be changes in mood, headaches, and a chronic feeling of tiredness.

Posterior pituitary posterior lobe of the pituitary gland

The posterior pituitary is the posterior lobe of the pituitary gland which is part of the endocrine system. The posterior pituitary is not glandular as is the anterior pituitary. Instead, it is largely a collection of axonal projections from the hypothalamus that terminate behind the anterior pituitary, and serve as a site for the secretion of neurohypophysial hormones directly into the blood. The hypothalamic–neurohypophyseal system is composed of the hypothalamus, posterior pituitary, and these axonal projections.

Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones, primarily cortisol; but may also include impaired production of aldosterone, which regulates sodium conservation, potassium secretion, and water retention. Craving for salt or salty foods due to the urinary losses of sodium is common.

Metyrapone, sold under the brand name Metopirone, is a medication which is used in the diagnosis of adrenal insufficiency and occasionally in the treatment of Cushing's syndrome (hypercortisolism).

Pituitary adenomas are tumors that occur in the pituitary gland. Pituitary adenomas are generally divided into three categories dependent upon their biological functioning: benign adenoma, invasive adenoma, and carcinomas. Most adenomas are benign, approximately 35% are invasive and just 0.1% to 0.2% are carcinomas. Pituitary adenomas represent from 10% to 25% of all intracranial neoplasms and the estimated prevalence rate in the general population is approximately 17%.

Endocrine glands are glands of the endocrine system that secrete their products, hormones, directly into the blood rather than through a duct. The major glands of the endocrine system include the pineal gland, pituitary gland, pancreas, ovaries, testes, thyroid gland, parathyroid gland, hypothalamus and adrenal glands. The hypothalamus and pituitary gland are neuroendocrine organs.

Neuroendocrine cells are cells that receive neuronal input and, as a consequence of this input, release message molecules (hormones) into the blood. In this way they bring about an integration between the nervous system and the endocrine system, a process known as neuroendocrine integration. An example of a neuroendocrine cell is a cell of the adrenal medulla, which releases adrenaline to the blood. The adrenal medullary cells are controlled by the sympathetic division of the autonomic nervous system. These cells are modified postganglionic neurons. Autonomic nerve fibers lead directly to them from the central nervous system. The adrenal medullary hormones are kept in vesicles much in the same way neurotransmitters are kept in neuronal vesicles. Hormonal effects can last up to ten times longer than those of neurotransmitters. Sympathetic nerve fiber impulses stimulate the release of adrenal medullary hormones. In this way the sympathetic division of the autonomic nervous system and the medullary secretions function together.

Neuroendocrinology is the branch of biology which studies the interaction between the nervous system and the endocrine system, that is how the brain regulates the hormonal activity in the body. The nervous and endocrine systems often act together in a process called neuroendocrine integration, to regulate the physiological processes of the human body. Neuroendocrinology arose from the recognition that the brain, especially the hypothalamus, controls secretion of pituitary gland hormones, and has subsequently expanded to investigate numerous interconnections of the endocrine and nervous systems.

Liddles syndrome genetic disorder inherited in an autosomal dominant manner that is characterized by early, and frequently severe, high blood pressure

Liddle's syndrome, also called Liddle syndrome is a genetic disorder inherited in an autosomal dominant manner that is characterized by early, and frequently severe, high blood pressure associated with low plasma renin activity, metabolic alkalosis, low blood potassium, and normal to low levels of aldosterone. Liddle syndrome involves abnormal kidney function, with excess reabsorption of sodium and loss of potassium from the renal tubule, and is treated with a combination of low sodium diet and potassium-sparing diuretics. It is extremely rare, with fewer than 30 pedigrees or isolated cases having been reported worldwide as of 2008.

Pseudo-Cushing's syndrome is a medical condition in which patients display the signs, symptoms, and abnormal hormone levels seen in Cushing's syndrome. However, pseudo-Cushing's syndrome is not caused by a problem with the hypothalamic-pituitary-adrenal axis as Cushing's is; it is mainly an idiopathic condition, however a cushingoid appearance is sometimes linked to excessive alcohol consumption. Elevated levels of total cortisol can also be due to estrogen found in oral contraceptive pills that contain a mixture of estrogen and progesterone. Estrogen can cause an increase of cortisol-binding globulin and thereby cause the total cortisol level to be elevated.

George P. Chrousos is professor of Pediatrics and Endocrinology Emeritus and former chairman of the Department of Pediatrics at the Athens University Medical School, Greece. Earlier he was senior investigator, director of the Pediatric Endocrinology Section and Training Program, and chief of the Pediatric and Reproductive Endocrinology Branch of the National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH). He is also clinical professor of Pediatrics, Physiology and Biophysics at Georgetown University Medical School and distinguished visiting scientist, NICHD, NIH. Dr. Chrousos was the first general director of the Foundation of Biomedical Research of the Academy of Athens (2001–2002). He holds the UNESCO Chair on Adolescent Health Care, while he held the 2011 John Kluge Chair in Technology and Society, Library of Congress, Washington, D.C.

Frederic Crosby Bartter was an American endocrinologist best known for his work on hormones affecting the kidney and his discovery of syndrome of inappropriate antidiuretic hormone and Bartter syndrome. He had a separate interest in mushroom poisoning.

Hypothalamic disease is a disorder presenting primarily in the hypothalamus, which may be caused by damage resulting from malnutrition, including anorexia and bulimia eating disorders, genetic disorders, radiation, surgery, head trauma, lesion, tumour or other physical injury to the hypothalamus. The hypothalamus is the control center for several endocrine functions. Endocrine systems controlled by the hypothalamus are regulated by antidiuretic hormone (ADH), corticotropin-releasing hormone, gonadotropin-releasing hormone, growth hormone-releasing hormone, oxytocin, all of which are secreted by the hypothalamus. Damage to the hypothalamus may impact any of these hormones and the related endocrine systems. Many of these hypothalamic hormones act on the pituitary gland. Hypothalamic disease therefore affects the functioning of the pituitary and the target organs controlled by the pituitary, including the adrenal glands, ovaries and testes, and the thyroid gland.

Neena Betty Schwartz was an American endocrinologist and William Deering Professor of Endocrinology Emerita in the Department of Neurobiology at Northwestern University. She was best known for her work on female reproductive biology and the regulation of hormonal signaling pathways, particularly for the discovery of the signaling hormone inhibin. Schwartz was an active feminist advocate for women in science throughout her career; she was a founding member of the Association for Women in Science organization in 1971 and shared the founding presidency with Judith Pool. She also co-founded the Women in Endocrinology group under the auspices of the Endocrine Society, served terms as the president of the Endocrine Society and the Society for the Study of Reproduction, and was recognized for her exceptional mentorship of women scientists. In 2010, she wrote a memoir of her life in science, A Lab of My Own, in which she came out as lesbian.

Levoketoconazole, also known as (2S,4R)-ketoconazole, is a steroidogenesis inhibitor that is under development by Strongbridge Biopharma for the treatment of Cushing's syndrome. It is currently in phase III clinical trials for this indication. The drug is the levorotatory or (2S,4R) enantiomer of ketoconazole. It is expected to have greater potency, efficacy, and safety, including a lower risk of hepatotoxicity relative to racemic ketoconazole.

Claude Jean Migeon was a French pediatric endocrinologist who spent the majority of his career at the Johns Hopkins Hospital.

References

1 2 3 Christy, Nicholas P. (1993). "Grant W. Liddle". Transactions of the American Clinical and Climatological Association. 104: xliii–xlv.
↑ "Grant W. Liddle Biographical File". Eskind Biomedical Library, Vanderbilt University . Retrieved August 18, 2017.
1 2 3 "Grant W. Liddle". National Academy of Sciences . Retrieved August 18, 2017.
↑ "Grant W. Liddle, endocrinologist, dies in Nashville". Deseret News . June 30, 1989. Retrieved August 18, 2017.
↑ Loriaux, D. Lynn (2016). "Grant Liddle (1921–1989)". A Biographical History of Endocrinology. doi:10.1002/9781119205791.ch102.
↑ "Grant W. Liddle Award". Vanderbilt University Medical Center . Retrieved August 18, 2017.

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[tacca-1] 1 2 3 Christy, Nicholas P. (1993). "Grant W. Liddle". Transactions of the American Clinical and Climatological Association. 104: xliii–xlv.

[vanlib-2] "Grant W. Liddle Biographical File". Eskind Biomedical Library, Vanderbilt University . Retrieved August 18, 2017.

[nas-3] 1 2 3 "Grant W. Liddle". National Academy of Sciences . Retrieved August 18, 2017.

[4] "Grant W. Liddle, endocrinologist, dies in Nashville". Deseret News . June 30, 1989. Retrieved August 18, 2017.

[5] Loriaux, D. Lynn (2016). "Grant Liddle (1921–1989)". A Biographical History of Endocrinology. doi:10.1002/9781119205791.ch102.

[6] "Grant W. Liddle Award". Vanderbilt University Medical Center . Retrieved August 18, 2017.