PAINE #PANCE Pearl – Endocrine



Question

47yo man presents to your clinic to establish care. He has a history of resistant hypertension, DMII, and sleep apnea. Vital signs are BP-159/101, HR-74, RR-16, O2-100%, and temp-98.9. Physical examination is also significant for multiple bruises on the lower extremities.

  1. What would be the next step in the diagnosis of this patient?
  2. What else would you need to order to determine the cause of this patient’s condition?


Answer

The initial SCREENING test of choice for Cushing Syndrome is a low-dose dexamethasone overnight suppression test. For this, 1mg dexamethasone is given around midnight and a serum cortisol is measured at 8am. A positive result is cortisol level of 1.8 mcg/dL.

The CONFIRMATORY test of choice for Cushing Syndrome is a 24-hour urinary cortisol excretion. A positive finding would be levels that are 3x the upper limit of normal for the assay used.

Once the diagnosis is made, the cause of the hypersecretion needs to be determined. For this, ordering a serum ACTH and high dose dexamethasone suppression test will help differentiate the various causes of the hypersecretion.



References

  1. Findling JW, Raff H, Aron DC. The low-dose dexamethasone suppression test: a reevaluation in patients with Cushing’s syndrome. The Journal of clinical endocrinology and metabolism. 2004; 89(3):1222-6. [pubmed]
  2. Dichek HL, Nieman LK, Oldfield EH, Pass HI, Malley JD, Cutler GB. A comparison of the standard high dose dexamethasone suppression test and the overnight 8-mg dexamethasone suppression test for the differential diagnosis of adrenocorticotropin-dependent Cushing’s syndrome. The Journal of clinical endocrinology and metabolism. 1994; 78(2):418-22. [pubmed]

Ep-PAINE-nym



Addison’s Disease

Other Known Aliasesprimary adrenal insufficiency

Definitionautoimmune destruction of the adrenal cortex that produces cortisol

Clinical Significance In times of physiologic stress, the adrenal glands are unable to produce and secrete cortisol, which is a key hormone in the “fight-or-flight” response.  If the stress is significant (trauma, surgery, hemorrhage, etc.), then the patient can not mount a compensatory response to this stress and can have life-threatening consequences.

HistoryNamed after Thomas Addison (1793-1860), an English physician who received his medical doctorate from the University of Edinburgh Medical School in 1815. He was a house physician at Guy’s Hospital and established himself as a prolific teacher and lecturer, often attracting physicians from all over London. He first described his eponymous disease in a short note in the London Medical Gazette called “Anaemia – Disease of the Suprarenal Capsules”.  This was then followed up by the more well known article “On the Constitutional and Local Effects of Disease of the Suprarenal Capsule” in 1855, which is largely considered the beginning of the study of the adrenal glands.  The disease eponym was original given to Dr. Addison by the French physician, Armand Trousseau, after fierce debate among experts as to whether the disease actually existed.


References

  1. Firkin BG and Whitwirth JA.  Dictionary of Medical Eponyms. 2nd ed.  New York, NY; Parthenon Publishing Group. 1996.
  2. Bartolucci S, Forbis P.  Stedman’s Medical Eponyms.  2nd ed.  Baltimore, MD; LWW.  2005.
  3. Yee AJ, Pfiffner P. (2012).  Medical Eponyms (Version 1.4.2) [Mobile Application Software].  Retrieved http://itunes.apple.com.
  4. Whonamedit – dictionary of medical eponyms. http://www.whonamedit.com
  5. Up To Date. www.uptodate.com
  6. Pearce JM. Thomas Addison (1793-1860). Journal of the Royal Society of Medicine. 2004; 97(6):297-300. [pubmed]
  7. Addison T.  On the Constitutional and Local Effects of Disease of the Suprarenal Capsules.  1855.  London: Samuel Highley.

PAINE #PANCE Pearl – Endocrine



Question

47yo man presents to your clinic to establish care. He has a history of resistant hypertension, DMII, and sleep apnea. Vital signs are BP-159/101, HR-74, RR-16, O2-100%, and temp-98.9. Physical examination is also significant for multiple bruises on the lower extremities.

  1. What would be the next step in the diagnosis of this patient?
  2. What else would you need to order to determine the cause of this patient’s condition?

Ep-PAINE-nym



Cushing Disease/Syndrome

Other Known Aliaseshypercortisolism,

Definitionconstellation of signs and symptoms due to excessive cortisol. This can be caused by several different mechanism that affect the hypothalamus-pituitary-adrenal axis:

  • CRH secretion by hypothalamus
  • ACTH secretion by:
    • Anterior pituitary
    • Ectopic tumor
  • Cortisol secretion adrenal glands by:
    • Adrenal hyperplasia
    • Adrenal tumor
  • Exogenous administration of corticosteroids

Clinical Significance This is one of the more common endocrinologic pathologies you will see in clinical practice. Classic presentation includes obesity, abdominal striae, “moon face”, “buffalo hump”, and hirsutism. Diagnosis is made by obtaining a 24-hour urine cortisol measurement

HistoryNamed after Harvey Williams Cushing (1869-1939), who was an American surgeon and pioneering neurosurgeon of the early 20th century. He received his medical doctorate from Harvard Medical School in 1895. He completed his internship at Massachussets General Hospital and went on to do a surgical residency under William Halsted at John Hopkins Hospital. He trained under Kocher in England for several years before returning stateside and setting up practice in Baltimore. One of his greatest contributions to western medicine was his introduction of blood pressure management he learned from Scipione Riva-Rocci in Italy during his time in Europe.

At the age of 32, he achieved associate professor at Johns Hopkins Hospital and was placed in full charge of all surgery of the central nervous system. In 1912, he first described what would become his eponymous disease, but before he could publish it, he was called to serve during the first world war as the director for a field hospital in France for the British. It was during this appointment that he cared for a fatally wounded soldier by the name of Lt. Edward Revere Osler, son of William Osler. He formally published his findings on his eponymous disease in 1932 in an article entitled “The Basophil Adenoma of the Pituitary Body and Their Clinical Manifestations: Pituitary Basophilism”.

During his career, he was regarded as the world’s leading teacher of neurosurgeons for in the first decades of the 20th century and held professorships at Johns Hopkins Hospital, Brigham Hospital in Boston, Harvard Medical School, Yale School of Medicine, as well as honorary Fellowship in the Royal College of Surgeons. He also was awarded the 1926 Pulitzer Prize for Biography for his biography on the life of William Osler and was nominated for the Nobel Prize in Physiology or Medicine 28 times.

Cushing (far left) with Osler (second from right) and Kelley (second from left). Johns Hopkins Hospital. 1900.

References

  1. Firkin BG and Whitwirth JA.  Dictionary of Medical Eponyms. 2nd ed.  New York, NY; Parthenon Publishing Group. 1996.
  2. Bartolucci S, Forbis P.  Stedman’s Medical Eponyms.  2nd ed.  Baltimore, MD; LWW.  2005.
  3. Yee AJ, Pfiffner P. (2012).  Medical Eponyms (Version 1.4.2) [Mobile Application Software].  Retrieved http://itunes.apple.com.
  4. Whonamedit – dictionary of medical eponyms. http://www.whonamedit.com
  5. Up To Date. www.uptodate.com
  6. http://doc1.med.yale.edu/historical/cushing/hopkins.html
  7. Hansson N, Schlich T. “Highly qualified loser”? Harvey Cushing and the Nobel Prize. Journal of neurosurgery. 2015; 122(4):976-9. [pubmed]
  8. Cushing H. The basophil adenomas of the pituitary body. Annals of the Royal College of Surgeons of England. 1969; 44(4):180-1. [pubmed]
  9. Starling PH. The case of Edward Revere Osler. Journal of the Royal Army Medical Corps. 2003; 149(1):27-9. [pubmed]
  10. Ellis H. Harvey Cushing: Cushing’s disease. Journal of perioperative practice. 2012; 22(9):298-9. [pubmed]

PAINE #PANCE Pearl – Endocrine



Question

58yo male, with DMI controlled with insulin, has blood glucose measurements in the morning of 205-272 mg/dL for the past week.  He reports that his evening blood glucose measurements before bed range from 103-127 mg/dL.  What are two potential causes of these findings?



Answer

There are two potential causes of early morning hyperglycemia in a diabetic patient on insulin.

  1. Dawn Phenomenon
    1. Due to the early morning rise of cortisol, patients can experience an early morning hyperglycemia as a result
  2. Somogyi Phenomenon
    1. (as covered by last week’s Ep-PAINE-nym) This was theorized to occur as undetectable hypoglycemia while the patient was asleep and the resultant hyperglycemia from instrinsic protective mechanisms.

Ep-PAINE-nym



Somogyi Phenomenon

 

Other Known Aliasesposthypoglycemic hyperglycemia

 

Definitionrebounding hyperglycemia in the setting of a undetected hypoglycemic event

 

Image

 

Clinical Significance It had been hypothesized that patients who had a hypoglycemic event during sleep would have rebound hyperglycemia due to the protective mechanism of the body to counteract this.  This would result in an undetectable change that would cause hyperglycemia in the morning.  This hypothesis has been proven wrong by numerous studies, but it is still a favorite among endocrinologists to pimp their students on.

 

History – Named after Michael Somogyi (1883-1971), who was a Hungarian American biochemist and received his doctorate degree from the University of Budapest in 1914.  He took a position as professor of biochemistry in 1922 at the Washington University’s Medical School in St. Louis, where later that year the first child with diabetes was treated with an insulin prepared by Somogyi himself.  His career work revolved around diabetes and theorized that insulin itself could causes unstable diabetes.  He published this paper describing the phenomenon that bears his name in 1938 in the Weekly Bulletin of the St. Louis Medical Society entitled “Insulin as a cause of extreme hyperglycemia and instability”.  He also went on to develop the test for serum amylase to help diagnose acute pancreatitis.  Dr. Somogyi died from a stroke on July 21st, 1971.

 

Michael Somogyi early portrait cropped 01.03.002.tif


References

  1. Firkin BG and Whitwirth JA.  Dictionary of Medical Eponyms. 2nd ed.  New York, NY; Parthenon Publishing Group. 1996.
  2. Bartolucci S, Forbis P.  Stedman’s Medical Eponyms.  2nd ed.  Baltimore, MD; LWW.  2005.
  3. Yee AJ, Pfiffner P. (2012).  Medical Eponyms (Version 1.4.2) [Mobile Application Software].  Retrieved http://itunes.apple.com.
  4. Whonamedit – dictionary of medical eponyms. http://www.whonamedit.com
  5. Up To Date. www.uptodate.com
  6. M. Somogyi, “Insulin as a cause of extreme hyperglycemia and instability,” Weekly Bulletin of the St Louis Medical Society, 1938, 
  7. Tordjman KM, Havlin CE, Levandoski LA, White NH, Santiago JV, Cryer PE. Failure of nocturnal hypoglycemia to cause fasting hyperglycemia in patients with insulin-dependent diabetes mellitus. The New England journal of medicine. 1987; 317(25):1552-9. [pubmed]
  8. Hirsch IB, Smith LJ, Havlin CE, Shah SD, Clutter WE, Cryer PE. Failure of nocturnal hypoglycemia to cause daytime hyperglycemia in patients with IDDM. Diabetes care. 1990; 13(2):133-42. [pubmed]

PAINE #PANCE PEARL – Endocrine



Question

 

58yo male, with DMI controlled with insulin, has blood glucose measurements in the morning of 205-272 mg/dL for the past week.  He reports that his evening blood glucose measurements before bed range from 103-127 mg/dL.  What are two potential causes of these findings?