Tuesday, November 08, 2011

Today in Medical History

Among the important early researchers in X-rays were Professor Ivan Pulyui, Sir William Crookes, Johann Wilhelm Hittorf, Eugen Goldstein, Heinrich Hertz, Philipp Lenard, Hermann von Helmholtz, Nikola Tesla, Thomas Edison, Charles Glover Barkla, Max von Laue, and Wilhelm Conrad Röntgen.


Wilhelm Röntgen
On November 8, 1895, Wilhelm Conrad Röntgen, a German physics professor, began observing and further documenting X-rays while experimenting with Lenard and Crookes tubes. Röntgen, on December 28, 1895, wrote a preliminary report "On a new kind of ray: A preliminary communication". He submitted it to the Würzburg's Physical-Medical Society journal.[13] This was the first formal and public recognition of the categorization of X-rays. Röntgen referred to the radiation as "X", to indicate that it was an unknown type of radiation. The name stuck, although (over Röntgen's great objections), many of his colleagues suggested calling them Röntgen rays. They are still referred to as such in many languages, including German. Röntgen received the first Nobel Prize in Physics for his discovery.

There are conflicting accounts of his discovery because Röntgen had his lab notes burned after his death, but this is a likely reconstruction by his biographers.[14] Röntgen was investigating cathode rays with a fluorescent screen painted with barium platinocyanide and a Crookes tube which he had wrapped in black cardboard so the visible light from the tube wouldn't interfere. He noticed a faint green glow from the screen, about 1 meter away. The invisible rays coming from the tube to make the screen glow were passing through the cardboard. He found they could also pass through books and papers on his desk. Röntgen threw himself into investigating these unknown rays systematically. Two months after his initial discovery, he published his paper.

Röntgen discovered its medical use when he saw a picture of his wife's hand on a photographic plate formed due to X-rays. His wife's hand's photograph was the first ever photograph of a human body part using X-rays.


Johann Hittorf
Physicist Johann Hittorf (1824 – 1914) observed tubes with energy rays extending from a negative electrode. These rays produced a fluorescence when they hit the glass walls of the tubes. In 1876 the effect was named "cathode rays" by Eugen Goldstein, and today are known to be streams of electrons. Later, English physicist William Crookes investigated the effects of electric currents in gases at low pressure, and constructed what is called the Crookes tube. It is a glass cylinder mostly (but not completely) evacuated, containing electrodes for discharges of a high voltage electric current. He found, when he placed unexposed photographic plates near the tube, that some of them were flawed by shadows, though he did not investigate this effect. Crookes also noted that his cathode rays caused the glass walls of his tube to glow a dull blue colour. Crookes failed to realise that it wasn't actually the cathode rays that caused the blue glow, but the low-level X-rays produced when the cathode rays struck the glass.


Ivan Pulyui
In 1877 Ukranian-born Pulyui, a lecturer in experimental physics at the University of Vienna, constructed various designs of vacuum discharge tube to investigate their properties.[15] He continued his investigations when appointed professor at the Prague Polytechnic and in 1886 he found that that sealed photographic plates became dark when exposed to the emanations from the tubes. Early in 1896, just a few weeks after Röntgen published his first X-ray photograph, Pulyui published high-quality x-ray images in journals in Paris and London.[15] Although Pulyui had studied with Röntgen at the University of Strasbourg in the years 1873-75, his biographer Gaida (1997) asserts that his subsequent research was conducted independently.[15]

The first medical X-ray made in the United States was obtained using a discharge tube of Pulyui's design. In January 1896, on reading of Röntgen's discovery, Frank Austin of Dartmouth College tested all of the discharge tubes in the physics laboratory and found that only the Pulyui tube produced X-rays. This was a result of Pulyui's inclusion of an oblique "target" of mica, used for holding samples of fluorescent material, within the tube. On 3 February 1896 Gilman Frost, professor of medicine at the college, and his brother Edwin Frost, professor of physics, exposed the wrist of Eddie McCarthy, whom Edwin had treated some weeks earlier for a fracture, to the x-rays and collected the resulting image of the broken bone on gelatin photographic plates obtained from Howard Langill, a local photographer also interested in Röntgen's work.[16]


Nikola Tesla
In April 1887, Nikola Tesla began to investigate X-rays using high voltages and tubes of his own design, as well as Crookes tubes. From his technical publications, it is indicated that he invented and developed a special single-electrode X-ray tube [17] [18], which differed from other X-ray tubes in having no target electrode. The principle behind Tesla's device is called the Bremsstrahlung process, in which a high-energy secondary X-ray emission is produced when charged particles (such as electrons) pass through matter. By 1892, Tesla performed several such experiments, but he did not categorize the emissions as what were later called X-rays. Tesla generalized the phenomenon as radiant energy of "invisible" kinds.[19] [20] Tesla stated the facts of his methods concerning various experiments in his 1897 X-ray lecture [21] before the New York Academy of Sciences. Also in this lecture, Tesla stated the method of construction and safe operation of X-ray equipment. His X-ray experimentation by vacuum high field emissions also led him to alert the scientific community to the biological hazards associated with X-ray exposure.[22]


Fernando Sanford
X-rays were first generated and detected by Fernando Sanford (1854-1948), the foundation Professor of Physics at Stanford University, in 1891. From 1886 to 1888 he had studied in the Hermann Helmholtz laboratory in Berlin, where he became familiar with the cathode rays generated in vacuum tubes when a voltage was applied across separate electrodes, as previously studied by Heinrich Hertz and Philipp Lenard. His letter of January 6, 1893 (describing his discovery as "electric photography") to The Physical Review was duly published and an article entitled Without Lens or Light, Photographs Taken With Plate and Object in Darkness appeared in the San Francisco Examiner.[23]


Heinrich Hertz
In 1892, Heinrich Hertz began experimenting and demonstrated that cathode rays could penetrate very thin metal foil (such as aluminium). Philipp Lenard, a student of Heinrich Hertz, further researched this effect. He developed a version of the Crookes tube and studied the penetration by X-rays of various materials. Philipp Lenard, though, did not realize that he was producing X-rays. Hermann von Helmholtz formulated mathematical equations for X-rays. He postulated a dispersion theory before Röntgen made his discovery and announcement. It was formed on the basis of the electromagnetic theory of light (Wiedmann's Annalen, Vol. XLVIII). However, he did not work with actual X-rays.


Thomas Edison
Diagram of a water cooled X-ray tube. (simplified/outdated) In 1895, Thomas Edison investigated materials' ability to fluoresce when exposed to X-rays, and found that calcium tungstate was the most effective substance. Around March 1896, the fluoroscope he developed became the standard for medical X-ray examinations. Nevertheless, Edison dropped X-ray research around 1903 after the death of Clarence Madison Dally, one of his glassblowers. Dally had a habit of testing X-ray tubes on his hands, and acquired a cancer in them so tenacious that both arms were amputated in a futile attempt to save his life. "At the 1901 Pan-American Exposition in Buffalo, New York, an assassin shot President William McKinley twice at close range with a .32 caliber revolver." The first bullet was removed but the second remained lodged somewhere in his stomach. McKinley survived for some time and requested that Thomas Edison "rush an X-ray machine to Buffalo to find the stray bullet. It arrived but wasn't used . . . McKinley died of septic shock due to bacterial infection."[24]


The 20th century and beyond
Before the 20th century until the 1920s, X-rays were generated in cold cathode tubes, called Crookes tubes. These tubes had to contain a small quantity of gas (invariably air) as a current will not flow in such a tube if they are fully evacuated. One of the problems with early X-ray tubes is that the generated X-rays caused the glass to absorb the gas and consequently the efficiency quickly falls off. Larger and more frequently used tubes were provided with devices for restoring the air, known as 'softeners'. This often took the form of small side tube which contained a small piece of mica – a substance that traps comparatively large quantities of air within its structure. A small electrical heater heats the mica and causes it to release a small amount of air restoring the tube's efficiency. However the mica itself has a limited life and the restore process was consequently difficult to control.

In 1904, John Ambrose Fleming invented the thermionic diode valve (vacuum tube). This used a heated cathode which permitted current to flow in a vacuum. This idea was quickly applied x-ray tubes, and heated cathode x-ray tubes, called Coolidge tubes, replaced the troublesome cold cathode tubes by about 1920.

Two years later, physicist Charles Barkla discovered that X-rays could be scattered by gases, and that each element had a characteristic X-ray. He won the 1917 Nobel Prize in Physics for this discovery. Max von Laue, Paul Knipping and Walter Friedrich observed for the first time the diffraction of X-rays by crystals in 1912. This discovery, along with the early works of Paul Peter Ewald, William Henry Bragg and William Lawrence Bragg gave birth to the field of X-ray crystallography. The Coolidge tube was invented the following year by William D. Coolidge which permitted continuous production of X-rays; this type of tube is still in use today.

ROSAT image of X-ray fluorescence of, and occultation of the X-ray background by, the Moon. The use of X-rays for medical purposes (to develop into the field of radiation therapy) was pioneered by Major John Hall-Edwards in Birmingham, England. In 1908, he had to have his left arm amputated owing to the spread of X-ray dermatitis[1].

The X-ray microscope was invented in the 1950s.

The Chandra X-ray Observatory, launched on July 23, 1999, has been allowing the exploration of the very violent processes in the universe which produce X-rays. Unlike visible light, which is a relatively stable view of the universe, the X-ray universe is unstable, it features stars being torn apart by black holes, galactic collisions, and novas, neutron stars that build up layers of plasma that then explode into space.

An X-ray laser device was proposed as part of the Reagan Administration's Strategic Defense Initiative in the 1980s, but the first and only test of the device (a sort of laser "blaster", or death ray, powered by a thermonuclear explosion) gave inconclusive results. For technical and political reasons, the overall project (including the X-ray laser) was de-funded (though was later revived by the second Bush Administration as National Missile Defense using different technologies).

Saturday, November 05, 2011

What Is the Best Approach for the Evaluation and Management of Endocrine Incidentalomas?

Key points include:  Advances and more frequent use of diagnostic radiology have led to the increased prevalence of endocrine incidentalomas;  Pituitary, thyroid, and adrenal incidentalomas must be assessed for dysfunctional hormone secretion and malignant potential; Inpatient management of endocrine incidentalomas should include consultation of endocrine or surgical teams in cases of dysfunctional or malignant lesions; Post-discharge instructions shouldclearly delineate timelines for repeat imaging, laboratory testing, and subspecialist follow-up.

by Darlene Tad-y, MD, Section of Hospital Medicine, University of Colorado Denver

Benign adrenal gland tumors.

Case

A 54-year-old man with a history of hypertension treated with hydrocholorothiazide and Type 2 diabetes mellitus is admitted with abdominal pain and found to have an incidental 2.1-cm left adrenal mass on CT scan of the abdomen. He denies symptoms of headache, palpitations, weight gain, or muscle weakness. His exam is significant for mildly elevated blood pressure. What is the best approach for evaluation and management of this incidental finding?

Overview

Incidentalomas are mass lesions that are inadvertently discovered during radiolographic diagnostic testing or treatment for other clinical conditions that are unrelated to the incidental mass. In recent decades, improvements in radiographic diagnostic techniques and sensitivity have led to increasing discovery of incidental lesions that are often in the absence of clinical signs or symptoms.1 Three commonly discovered lesions by hospitalists are pituitary, thyroid, and adrenal incidentalomas.2 The concerns associated with these findings relate to the potential for dysfunctional hormone secretion or malignancy.

Patients found with pituitary incidentalomas can be susceptible to several types of adverse outcomes: hormonal hypersecretion, hypopituitarism, neurologic morbidity due to tumor size, and malignancy in rare cases. Thyroid incidentalomas are impalpable nodules discovered in the setting of ultrasound or cross-sectional neck scans, such as positron emission tomography (PET) scans. Discovery of a thyroid incidentaloma raises concern for thyroid malignancy.3 The increased use of abdominal ultrasound, CT scans, and MRI has fueled the growing incidence of adrenal incidentalomas (AIs).

The discovery of an endocrine incidentaloma in the inpatient setting warrants a systematic approach that includes both diagnostic and potentially therapeutic management. A hospitalist should consider an approach that includes (see Table 1):

click for large version
Table 1. General inpatient approach to endocrine incidentalomas
  1. Characterization of the incidentaloma, including clinical signs and symptoms, size, hormonal function, and malignant potential;
  2. Immediate management, including medical versus surgical treatment; and
  3. Post-discharge management, including monitoring.

Review of the Data

Pituitary incidentalomas. The prevalence of pituitary incidentalomas found by CT ranges from 3.7% to 20%, while the prevalence found by MRI approximates 10%. Autopsy studies have revealed a prevalence ranging from 1.5% to 26.7% for adenomas less than 10 mm, considered to be microadenomas. Broad categories of etiologies should be considered: pituitary adenoma, nonpituitary tumors, vascular lesions, infiltrative disorders, and others (see Table 2). The majority of pituitary adenomas secrete prolactin (30% to 40%) or are nonsecreting (30% to 40%). Adenomas secreting adrenocorticotropin hormone (ACTH, 2% to 10%), growth hormone (GH, 2% to 10%), thyroid-stimulating hormone (TSH, <1%), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) are much less common.2 Significant morbidity and premature mortality are associated with hyperprolactinemia, acromegaly (growth hormone excess), Cushing’s syndrome, and hyperthyroidism. Additionally, up to 41% of patients with macroadenomas were found to have varying degrees of hypopituitarism due to compression of the hypothalamus, the hypothalamic-pituitary stalk, or the pituitary itself.4

TABLE 2. DIFFERENTIAL DIAGNOSIS FOR PITUITARY INCIDENTALOMAS2,4,14

Pituitary adenoma:

  • Secreting: prolactin, growth hormone, ACTH, glycopeptides (LH, FSH, TSH, a-subunit)
  • Nonsecreting

Non-pituitary tumors:

  • Germ cell tumors
  • Craniopharyngioma
  • Meningioma
  • Metastatic disease

Vascular lesions:

  • Aneurysms
  • Hamartomas
  • Infarctions

Infiltrative:

  • Sarcoidosis
  • Histiocytosis
  • Lymphocytic hypophysitis
  • Eosinophilic granulomas

Other:

  • Rathke’s cleft cyst
  • Anatomic abnormalities

ACTH=adrenocorticotropin hormone, GH=growth hormone, TSH=thyroid-stimulating hormone (thyrotropin), LH=luteinizing hormone, FSH=follicle-stimulating hormone

Recently, the Endocrine Society released consensus recommendations to guide the evaluation and treatment of pituitary incidentalomas, which are included in the approach outlined below.5 A detailed history and physical examination should be obtained with specific inquiry as to signs and symptoms of hormonal excess and mass effect from the tumor. Examples of symptoms of hormone excess can include:

  • Prolactin: menstrual irregularity, anovulation, infertility, decreased libido, impotence, osteoporosis;
  • Growth hormone: high frequency of colonic polyps and colon cancer (chronic excess);
  • TSH: thyrotoxicosis, atrial fibrillation; and
  • ACTH: hypertension, osteoporosis, accelerated vascular disease.

Symptoms related to the mass effect of the tumor include visual field defects and hypopituitarism related to the deficient hormone, including:

  • FSH/LH: oligomenorrhea, decreased libido, infertility;
  • TSH: hypothyroidism (weight gain, constipation, cold intolerance);
  • ACTH: adrenal insufficiency (hypotension, hypoglycemia, weight loss); and
  • ADH: polyuria, polydypsia.

The size and location of the pituitary lesion must be assessed. Lesions greater than 10 mm are considered macroademonas, and their size will affect their management. If the lesion was initially identified by CT scan, an MRI is recommended to better evaluate it.5 If the MRI locates the incidentaloma abutting the optic nerve or chiasm, then the patient should undergo a formal visual field examination.

Indications for an inpatient surgical referral for treatment include: a lesion larger than 2 cm, evidence of mass effect such as visual field defects, neurologic compromise, opthalmoplegia, hypopituitarism, a tumor abutting the optic nerve or chiasm, pituitary apoplexy, and hypersecretion of hormones other than prolactin. Patients with prolactinomas warrant an inpatient endo-crinology consult and may need medical management with a dopamine agonist. Hormone replacement therapy can also be provided for patients with hypopituitarism.2,5

For patients who do not meet the criteria for inpatient surgical therapy, follow-up management must be arranged at the time of discharge. Clinical, laboratory assessment, and an MRI should be scheduled six months after the initial finding of the incidentaloma with the patient’s PCP or with an endocrinologist.5

Thyroid incidentalomas. The prevalence of thyroid nodules based on ultrasound studies ranges from 19% to 46%, with autopsy studies estimating an incidence of approximately 50%.2,6 Incidence of thyroid nodules also increases with age, as almost 60% of people over the age of 60 harbor a thyroid incidentaloma. The rate of malignancy in the general population has ranged between 8% and 24%; however, in the last decade, the rates have increased by 2.4 times as more sophisticated ultrasound techniques and liberal use of fine-needle aspiration (FNA) biopsies have detected subclinical disease.7,8

Etiologies for incidental thyroid nodules can be divided into benign and malignant causes. Benign etiologies include thyroid cyst (simple or complex), multinodular goiter, and Hashimoto’s thryoiditis, while malignant causes include papillary, medullary, follicular, Hurthle cell, and anaplastic carcinomas, thyroid lymphomas, and rare instances of metastatic cancers.2,3

Targeted history and physical examination helps to characterize the thyroid incidentaloma. Historical features, such as palpitations, weight loss, anxiety, new onset atrial fibrillation, or menstrual irregularities, coupled with tachycardia, tremors, proximal muscle weakness, and a palpable nodule aid in the diagnosis of hyperthyroidism. Findings such as a family history of thyroid cancer, symptoms of hoarseness or dysphagia, rapid growth of the nodule, environmental or history of head or neck irradiation along with physical findings of a hard, fixed nodule, or cervical lymphadenopathy increase the suspicion for malignancy.2,7

The functionality of the nodule can be assessed by checking TSH, free T3, and free T4 levels. Suppression of TSH (< 0.1 mU/L) with elevated levels of free T3 and T4 indicates nodule production of excess thyroid hormone and warrants thyroid scintography. Thyroid scintography will identify the nodule as “hot” (hyperfunctioning) or “cold” (nonfunctioning).2

Regardless of the radiographic modality that initially identified the thyroid incidentaloma, a dedicated thyroid high-resolution ultrasound should be ordered to assess the size, multiplicity (single or multinodular), location, and character (solid, cystic, or mixed).7

Recommendations for proceeding to FNA to evaluate for malignancy differ among subspecialty societies. Generally, nodules larger than 1 cm or nodules smaller than 1 cm with risk factors for malignancy should be referred for FNA.2,7

If diagnostic workup identifies a patient with hyperthyroidism due to an autonomously functional nodule or a nodule that may be at high risk for malignancy, it is appropriate to involve an endocrinologist and possibly a surgical subspecialist prior to discharge. Management of hyperthyroidism can include starting antithyroid agents (methimazole or propylthiouracil), radioactive iodine ablation, or referral for surgery.

Preparation for discharge of the patient whose incidentaloma is nonfunctional or does not appear to be malignant should include appointments to recheck thyroid hormone levels, including TSH as well as a thyroid ultrasound within one year of the initial discovery.

Adrenal incidentaloma. The prevalence of AIs found by CT of the abdomen ranges from 0.4% to 4%, while autopsy studies have found a prevalence of 1.4% to 9% with increasing prevalence with age.2,9,10 The majority of AIs are benign and nonfunctioning adenomas, in the absence of known malignancy. Other differential diagnoses include Cushing’s syndrome, pheochromocytoma, adrenocortical adenoma, aldosteronoma, and metastatic lesions.

Because functioning adrenal incidentalomas may be clinically silent, any patient found with an AI must undergo biochemical workup as part of their evaluation to assess for pheochromocytoma, Cushing’s syndrome, and if he or she has a history of hypertension or hyperaldosteronism (Conn’s syndrome). Table 3 outlines the approach for characterizing adrenal incidentalomas.2,11,12 An important point is that imaging studies are not useful in distinguishing a functioning versus nonfunctioning tumor but rather can help to discriminate malignant lesions.11

click for large version
Table 3. Characterization of the adrenal incidentaloma2,11

Inpatient surgical consult for resection is indicated if the patient is found to have pheochromocytoma, clinically apparent functioning adrenocortical adenoma, or a tumor size greater than 4 cm. Consultation with an endocrinologist is also recommended if biochemical tests are positive. If the diagnostic workup leads to suspicion for infection or metastatic disease, the patient should be referred for FNA.2,12

For patients whose lesions do not require surgical resection, repeat CT scan of the abdomen is recommended six months from the initial finding. Hospitalists should also arrange for the patient to repeat biochemical testing, including an overnight dexamethasone test.12,13

Back to the Case

The patient underwent biochemical testing and was found to have normal levels of plasma-free metanephrines, a plasma aldosterone, plasma renin activity ratio less than 20, and a serum cortisol level of 7 mg/dL after his overnight dexamethasone suppression test. The 24-hour urine collection for free cortisol revealed elevated levels of cortisol in the urine, and the ACTH level was low.

Endocrinology and endocrine surgery teams were consulted, and recommended surgical resection. After surgical resection of his tumor, the patient was started on glucocorticoid replacement and was discharged with a follow-up appointment with endocrinology.

Bottom Line

An inpatient approach to endocrine incidentalomas should include characterization of the clinical signs and symptoms, size, function, and malignant potential of the lesion. Based on this, inpatient surgical or medical management can be determined. Post-discharge management should include arrangements for surveillance testing and follow-up with appropriate subspecialists.

Dr. Tad-y is assistant professor of medicine and a hospitalist at the University of Colorado Denver.

KEY POINTS

  • Advances and more frequent use of diagnostic radiology have led to the increased prevalence of endocrine incidentalomas.
  • Pituitary, thyroid, and adrenal incidentalomas must be assessed for dysfunctional hormone secretion and malignant potential.
  • Inpatient management of endocrine incidentalomas should include consultation of endocrine or surgical teams in cases of dysfunctional or malignant lesions.
  • Post-discharge instructions should clearly delineate timelines for repeat imaging, laboratory testing, and subspecialist follow-up.

ADDITIONAL READING

  • Shirodkar M, Jabbour SA. Endocrine incidentalomas. Int J Clin Pract. 2008; 62:1423-1431.
  • Freda PU, Beckers AM, Katznelson L, et al. Pituitary incidentaloma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:894-904.
  • Iyer NG, Shaha AR, Silver CE, et al. Thyroid incidentalomas: to treat or not to treat. Eur Arch Otorhinolaryngol. 2010;267:1019-1026.
  • Zeiger MA, Siegelman SS, Hamrahian AH. Medical and surgical evaluation and treatment of adrenal incidentalomas. J Clin Endocrinol Metab. 2011;96:2004-2015.

References

  1. Aron DC, Howlett TA. Pituitary incidentalomas. Endocrinol Metab Clin North Am. 2000;29:205-221.
  2. Shirodkar M, Jabbour SA. Endocrine incidentalomas. Int J Clin Pract. 2008;62:1423-1431.
  3. Burguera B, Gharib H. Thyroid incidentalomas. Prevalence, diagnosis, significance, and management.Endocrinol Metab Clin North Am. 2000;29:187-203.
  4. Molitch ME. Nonfunctioning pituitary tumors and pituitary incidentalomas. Endocrinol Metab Clin North Am. 2008;37:151-171, xi.
  5. Freda PU, Beckers AM, Katznelson L, et al. Pituitary incidentaloma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:894-904.
  6. Gough J, Scott-Coombes D, Fausto Palazzo F. Thyroid incidentaloma: an evidence-based assessment of management strategy. World J Surg. 2008;32:1264-1268.
  7. Iyer NG, Shaha AR, Silver CE, et al. Thyroid incidentalomas: to treat or not to treat. Eur Arch Otorhinolaryngol. 2010;267:1019-1026.
  8. Jin J, Wilhelm SM, McHenry CR. Incidental thyroid nodule: patterns of diagnosis and rate of malignancy. Am J Surg. 2009;197:320-324.
  9. Davenport C, Liew L, Doherty B, et al. The prevalence of adrenal incidentaloma in routine clinical practice.Endocrine. 2011;40:80-83.
  10. Zeiger MA, Siegelman SS, Hamrahian AH. Medical and surgical evaluation and treatment of adrenal incidentalomas. J Clin Endocrinol Metab. 2011;96: 2004-2015.
  11. Zeiger MA, Thompson GB, Duh QY, et al. American Association of Clinical Endocrinologists and American Association of Endocrine Surgeons Medical Guidelines for the Management of Adrenal Incidentalomas: executive summary of recommendations. Endocr Pract. 2009;15:450-453.
  12. NIH state-of-the-science statement on management of the clinically inapparent adrenal mass (“incidentaloma”).NIH Consens State Sci Statements. 2002;19:1-25.
  13. Young WF. Clinical practice. The incidentally discovered adrenal mass. N Engl J Med. 2007;356:601-610.
  14. Chidiac RM, Aron DC. Incidentalomas. A disease of modern technology. Endocrinol Metab Clin North Am. 1997;26:233-253.

 

From http://www.the-hospitalist.org/details/article/1380161/What_Is_the_Best_Approach_for_the_Evaluation_and_Management_of_Endocrine_Inciden.html

Wednesday, November 02, 2011

Cushing's News

Something new of interest to Cushies most every day. Please note that there is a current backlog of about three weeks for submitted bios to be added to the website.

November 2, 2011:


 

Thursday, October 27, 2011

Effects of Hormone Stimulation on Brain Scans for Cushing's Disease

This study is currently recruiting participants.
Verified on August 2011 by National Institutes of Health Clinical Center (CC)

First Received on October 21, 2011.   No Changes Posted

Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by: National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT01459237

  Purpose

Background:

  • Cushing's disease can be caused by a tumor of the pituitary gland, a small gland about the size of a pea located at the base of the brain. These tumors produce high levels of hormones, which cause obesity, diabetes, and growth problems. The cure for this type of Cushing's disease is to have surgery that removes the tumor but leaves the pituitary gland alone. Currently, magnetic resonance imaging scans are the best way to find these tumors. However, many of these tumors do not show up on the scan.
  • Positron emission tomography (PET) scans use radioactive chemicals to light up parts of the body that are more active, such as tumors. Researchers want to try to make the small Cushing's disease tumors more active to help them show up on the scans. A special hormone will be given before the scan to make the tumors more active.

Objectives:

- To test the use of hormone stimulation to improve brain scans for Cushing's disease tumors.

Eligibility:

- Individuals at least 8 years of age who will be having surgery to remove Cushing's disease tumors.

Design:

  • Participants will be screened with a medical history, physical exam, blood and urine tests, and imaging studies.
  • They will have three brain scans before surgery. The first scan is a magnetic resonance imaging scan to show a full picture of the brain. The second and third scans are PET scans.
  • The first PET scan will be given without the special hormone. The second PET scan will be done more than 24 hours but less than 14 days after the first PET scan. The second PET scan will be given with the special hormone.
  • Participants will have tumor removal surgery through another study protocol....

Condition
Pituitary Neoplasm

Study Type: Observational
Official Title: Prospective Evaluation of the Effect of Corticotropin-Releasing Hormone Stimulation on 18F-Fludeoxyglucose High-Resolution Positron-Emission Tomography in Cushing's Disease


Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 30
Study Start Date: October 2011

Detailed Description:

Objective

Preoperative imaging identification and localization of adrenocorticotropin hormone (ACTH)-secreting pituitary adenomas is critical for the accurate diagnosis and the successful surgical treatment of Cushing's disease (CD). Unfortunately, over 40 percent of CD patients do not have a visible pituitary adenoma on magnetic resonance (MR)-imaging (the most sensitive imaging modality for ACTH-positive adenoma detection and localization). Lack of MR-imaging for diagnosis and to guide surgical resection results in significantly higher rates of surgical failure compared to cases associated with adenomas visible on MR-imaging. Because ACTH-adenomas are metabolically active compared to the surrounding pituitary gland, (18)F-fludeoxyglucose ((18)F-FDG) positron emission tomography (PET)-imaging in CD patients could be used to detect adenomas not detectable on MR-imaging. Moreover, corticotropin-releasing hormone (CRH) can be given to selectively increase the metabolic activity of ACTH-secreting pituitary adenomas to increase the likelihood of their detection and localization by (18)F -FDG PET-imaging. To determine the effect of CRH stimulation on (18)F-FDG uptake using PET-imaging in CD, we will perform (18)F-FDG high-resolution PET-imaging (with and without CRH stimulation) in CD patients.

Study Population

Thirty male and female CD patients 8 years and older will participate in this study.

Study Design

This is a single center trial to determine the effect of CRH stimulation on (18)F-FDG uptake in high-resolution PET-imaging of ACTH-adenomas in CD patients. CD patients will undergo (18)F-FDG high-resolution PET-imaging without CRH stimulation and (18)F-FDG high-resolution PET-imaging with intravenous CRH stimulation. The order of the PET scans will be randomized and the second PET scan will occur greater than 24 hours but less than 14 days after initial PET-imaging. For (18)F-FDG PET-imaging with CRH stimulation, intravenous (18)F-FDG will be given just before CRH administration. The PET images will be read by radiologists who are blinded to the administration of CRH. Within 12 weeks after completion of the last (18)F-FDG high-resolution PET-imaging scan, patients will undergo surgical resection of the pituitary adenoma. Surgical and histological confirmation of adenoma location will be used to assess the diagnostic and localization accuracy of PET-imaging and to compare to preoperative MR-imaging results in CD patients. Inferior petrosal sinus sampling (IPSS) results will be compared with imaging results and with surgical and histological findings.

Outcome Measures

The primary objective of this study is to determine the effect of CRH stimulation on (18)F-FDG uptake in high-resolution PET-imaging for CD. To assess and compare (18)F-FDG uptake without and with CRH stimulation, we will compare (18)F-FDG standardized uptake values (SUVs) in the region of interest (pituitary gland and pituitary adenoma). Secondary objectives include determining if CRH stimulation enhances detection of ACTH-adenomas as demonstrated on (18)F-FDG high-resolution PET-imaging and assessing the accuracy and sensitivity of (18)F-FDG high-resolution PET-imaging detection of ACTH-adenomas compared to MR-imaging. Measures to assess for these secondary objectives include comparing (18)F-FDG high-resolution PET-imaging (with and without CRH stimulation) detection to (1) MR-imaging detection of adenomas, (2) IPSS results, and (3) actual tumor location confirmed by histological findings to location predicted by PET- and MR-imaging within patients.

  Eligibility

Ages Eligible for Study:   8 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Criteria
  • INCLUSION CRITERIA:

To be eligible for entry into the study, patients must meet all the following criteria:

  1. Be 8 years of age or older and able to undergo PET-imaging without needing general anesthesia.
  2. Able to provide informed consent (or guardian is able to provide consent in case of minor).
  3. Clinical diagnosis of CD based on medical records.
  4. Medically able to undergo resection of pituitary adenoma and planning to undergo surgical resection of adenoma within 12 weeks of PET-imaging.
  5. Normal liver enzymes: tests should be completed within 14 days before injection of the radiopharmaceutical; SGOT, SGPT less than or equal to 5 times ULN; bilirubin less than or equal to 2 times ULN.

EXCLUSION CRITERIA:

Candidates will be excluded if they meet any of the following criteria:

  1. Pregnant or nursing women.
  2. Contraindication to MR-scanning, including pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pump, or shrapnel fragments
  3. Severe chronic renal insufficiency (glomerular filtration rate < 30 mL/min/1.73 m(2)), hepatorenal syndrome or post-liver transplantation.
  4. Elevated blood glucose level above 200 mg/dL on the day of the scan prior to (18)F-FDG administration.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01459237

Contacts

Contact: Patient Recruitment and Public Liaison Office (800) 411-1222 prpl@mail.cc.nih.gov
Contact: TTY 1-866-411-1010


Locations

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892

Wednesday, September 21, 2011

Today in Medical History

Synthesized Cortisone

In 1948, Edward Kendall and Philip Hench created the first of the many “miracle drugs," which were actually synthesized hormones, to treat rheumatoid arthritis and other diseases. Hench and Kendall, who each headed a medical department at the Mayo Clinic in Rochester, Minn., realized that the adrenal glands play an important role in rheumatoid arthritis. The two noticed that a woman with rheumatoid arthritis had a lessening of symptoms while she was pregnant, and they worked to discover what caused the change. They were able to isolate a hormone in the cortex, or outer part, of the adrenal glands, which they called cortisone.

On Sept. 21, 1948, Hench administered a synthesized version of cortisone developed by Kendall to a patient with arthritis. The two researchers were awarded the Nobel Prize in physiology or medicine in 1950 for their achievements.

Friday, September 09, 2011

Just like Cushing's?

P1478

Saturday, September 03, 2011

Today in Medical History

A Growing Knowledge

On this date in 1931, chemists discovered that the pituitary gland contains a hormone, hGH, that controls growth. Overactivity of the pituitary, which sits at the base of the brain, results in gigantism. Underactivity results in dwarfism.

The discovery in 1931 eventually led to physicians treating children suffering from a deficiency of the hormone by injections of hGH obtained from the pituitaries of cadavers. More recently, scientists have discovered a way to produce genetically engineered hGH in bacteria.

Thursday, August 18, 2011

Selective inferior petrosal sinus sampling without venous outflow diversion in the detection of a pituitary adenoma in Cushing’s syndrome

Lukas Andereggen, Gerhard Schroth, Jan Gralla, Rolf Seiler, Luigi Mariani, Jürgen Beck, Hans-Rudolf Widmer, Robert H. Andres, Emanuel Christ and Christoph Ozdoba

DOI: 10.1007/s00234-011-0915-6

Abstract

Introduction  

Conventional MRI may still be an inaccurate method for the non-invasive detection of a microadenoma in adrenocorticotropin (ACTH)-dependent Cushing’s syndrome (CS). Bilateral inferior petrosal sinus sampling (BIPSS) with ovine corticotropin-releasing hormone (oCRH) stimulation is an invasive, but accurate, intervention in the diagnostic armamentarium surrounding CS. Until now, there is a continuous controversial debate regarding lateralization data in detecting a microadenoma. Using BIPSS, we evaluated whether a highly selective placement of microcatheters without diversion of venous outflow might improve detection of pituitary microadenoma.

Methods  

We performed BIPSS in 23 patients that met clinical and biochemical criteria of CS and with equivocal MRI findings. For BIPSS, the femoral veins were catheterized bilaterally with a 6-F catheter and the inferior petrosal sinus bilaterally with a 2.7-F microcatheter. A third catheter was placed in the right femoral vein. Blood samples were collected from each catheter to determine ACTH blood concentration before and after oCRH stimulation.

Results  

In 21 patients, a central-to-peripheral ACTH gradient was found and the affected side determined. In 18 of 20 patients where transsphenoidal partial hypophysectomy was performed based on BIPSS findings, microadenoma was histologically confirmed. BIPSS had a sensitivity of 94% and a specificity of 67% after oCRH stimulation in detecting a microadenoma. Correct localization of the adenoma was achieved in all Cushing’s disease patients.

Conclusion  

BIPSS remains the gold standard in the detection of a microadenoma in CS. Our findings show that the selective placement of microcatheters without venous outflow diversion might further enhance better recognition to localize the pituitary tumor.

Keywords  Angiography, Digital subtraction – Cushing disease – Petrosal sinus sampling – Pituitary gland – Magnetic resonance imaging

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Tuesday, August 16, 2011

Johns Hopkins Pituitary Patient Day

Join us on September 24, 2011, for the 3rd Annual Patient Education Day at the Johns Hopkins Pituitary Center.

When: Saturday, September 24, 2011
Time: 9:00 a.m.
Location:
Johns Hopkins Mt. Washington Conference Center
5801 Smith Avenue,
Baltimore, MD 21209
map and directions

Patient Education Day Agenda:
9:00-9:30 AM REGISTRATION AND BREAKFAST
9:30-10:00 AM Introduction to Sellar Masses Gary Wand, MD
10:00-10:30 AM Neuro-ophthalmological issues in pituitary patients Prem Subramanian, MD
10:30-11:00 AM Medical therapy of pituitary disease Roberto Salvatori, MD
11:00-11:30 AM Surgical Therapy of Pituitary Tumors Alfredo Quinones-Hinojosa, MD
11:30-12:00 PM Approach to Large Invasive Tumors Gary Gallia, MD
12:00-12:30 PM Radiotherapy of pituitary masses Kirsten Redmond, MD
12:30-01:25 PM Lunch
1:30-03:00 PM

Breakout sessions:

  1. Medical therapy (Wand/Salvatori)
  2. Surgical therapy (Gallia/Quinones)
  3. Radiation therapy (Redmond/Lim)
  4. Vision issues (Subramanian)
To RSVP, please contact Colleen Hickson at 410-614-5887 by September 9, 2011.

For more information, contact the Johns Hopkins Pituitary Center at 410-955-GLAN (4526).