ADRENALS, PARATHYROIDS, THYMUS, PINEAL
Ed Friedlander, M.D., Pathologist
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Especially if you're looking for information on a disease with a name that you know, here are a couple of great places for you to go right now and use Medline, which will allow you to find every relevant current scientific publication. You owe it to yourself to learn to use this invaluable internet resource. Not only will you find some information immediately, but you'll have references to journal articles that you can obtain by interlibrary loan, plus the names of the world's foremost experts and their institutions.

Alternative (complementary) medicine has made real progress since my generally-unfavorable 1983 review. If you are interested in complementary medicine, then I would urge you to visit my new Alternative Medicine page. If you are looking for something on complementary medicine, please go first to the American Association of Naturopathic Physicians. And for your enjoyment... here are some of my old pathology exams for medical school undergraduates.

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Courtesy of CancerWEB

Endocrine
Taiwanese pathology site
Good place to go to practice

Endocrine
Photo Library of Pathology
U. of Tokushima

Mediastinum (Thymus)
Photo Library of Pathology
U. of Tokushima

Endocrine
Iowa Virtual Microscopy
Have fun

Endocrine
Utah cases for path students
Juliana Szakacs MD

Adrenal Exhibit
Virtual Pathology Museum
University of Connecticut

Endocrine
Photos, explanations, and quiz
Indiana U.

Adrenal
Nice case photos
Charam M. Ramnani MD

Endocrine
Brown Digital Pathology
Some nice cases

KCUMB Students
"Big Robbins" -- Endocrine
Lectures follow Textbook

QUIZBANK

STUDY OBJECTIVES

Mention the normal gross and microscopic anatomy of the adrenal glands, parathyroid glands, and thymus gland. Describe their origins within individuals, and their functions.

Define hypoadrenocorticism, mention the etiologies of the chronic and acute forms, and tell what each looks like clinically. Explain hyperpigmentation in some of these patients, and tell why they are at risk for sudden death.

Describe the etiologies of Cushing's syndrome, from the most to the least common. Tell what symptoms and signs should alert you, the physician, to the possibility of Cushingism. Explain Nelson's syndrome, and why it is becoming uncommon.

Define primary hyperaldosteronism and Conn's syndrome. Distinguish these from secondary hyperaldosteronism. Tell what symptoms and signs point to excess aldosterone, and explain the danger of treating these patients with "safe" diuretics.

Describe in detail the pathogenesis of congenital adrenal hyperplasia, and distinguish the most common salt-retaining and the most common salt-wasting form. Describe the forme fruste that we now believe is very common.

Describe the behavior of carcinomas of the adrenal cortex.

Discuss pheochromocytoma and neuroblastoma with respect to their names, locations, etiologies, catecholamine production, gross and microscopic appearances, clinical picture, and prognosis. Mention the "primitive neuroectodermal tumors" that look like neuroblastomas, and describe "spontaneous cures" of neuroblastoma. Provide an educated guess of how many of your classmates had a "neuroblastoma" at birth.

Describe in some depth the prevalence, etiologies, symptoms, signs and treatment of hyperparathyroidism. Explain how to tell parathyroid hyperplasia from parathyroid adenoma, and why anyone cares. Describe how and when hypoparathyroidism develops, why it is serious, and how to recognize it.

Describe how the size of the thymus gland changes with age. Define thymic hyperplasia and thymoma, tell what they look like, and mention the diseases with which they are associated.

List the components of the important anti-oncogene deletion syndromes MEN I, IIa, and IIb.

MAINTAIN A HIGH INDEX OF SUSPICION FOR ENDOCRINE DISEASE. This lecture ought to scare you.

Adrenal gland
"Pathology Outlines"
Nat Pernick MD, great site

Adrenal Histology
Ed's Histology Notes

Normal adrenal
Find it!
WebPath Photo

Adrenal histology
Point and click
WebPath Photo

Normal adrenals

WebPath Photo

Normal adrenals

WebPath Photo

One surprising fact about the adrenal gland is that, unlike many other organs, masses found here are seldom biopsied prior to excision. The radiology team will advise surgeons whether to remove particular masses. The one exception is biopsy to confirm metastatic disease in someone with a known cancer, usually in the lung (Arch. Surg. 144: 465, 2009).

THE ADRENAL CORTEX: "An organ essential to life." Pathology of the adrenal cortex: Arch. Path. Lab. Med. 132: 1263, 2008.

{11204}      adrenal and its nerve, normal
{11207}      adrenal and its nerve, normal
{11210}      adrenal and its nerve, histology, normal
{15035}      normal adrenal gland, showing zones (can you figure them out?)


Androstenedione (?)

{49431}      hyperplasia of adrenal cortex, etiology undisclosed
{09217}      adrenal cortical hyperplasia, etiology unknown

CONGENITAL ADRENAL HYPOPLASIA

Adrenal -- cytomegalic fetal cortex
Beckwith-Wiedemann, a poorly-understood
genetic illness. Wikimedia Commons

ECTOPIC ADRENAL CORTICAL TISSUE (sometimes ectopic adrenal medulla too)

HYPOADRENOCORTICISM ("Addisonism", etc.): Insufficient glucocorticoid (and usually insufficient mineralocorticoid) production. Reviews Lancet 361: 1881, 2003; NEJM 360: 2328, 2009.

{09223}      adrenal tuberculosis, gross
{25399}      tuberculosis of adrenal, histology
{27257}      tuberculosis of adrenal, histology

Adrenal atrophy in
treated addisonism
KCUMB Team

TB of the adrenal

WebPath Photo

{25394}      adrenal cortical atrophy (key says "hypoplasia", I doubt this)
{24607}      adrenal amyloidosis, gross
{15960}      cytomegalic inclusion disease, adrenal
{37216}      adrenal leukodystrophy ("Lorenzo's oil") case, gross brain
{37218}      adrenal leukodystrophy case, gross brain
{37221}      adrenal leukodystrophy case, histology brain
{37224}      adrenal leukodystrophy case, gross adrenal
{37225}      adrenal leukodystrophy case, histology adrenal

Adrenal amyloidosis

WebPath Photo

Adrenals
Atrophic, normal, hyperplastic
WebPath Photo

{09371}      Addison's disease; pigmentation and vitiligo (mother and daughter)
{09372}      Addison's disease, face
{09373}      Addison's disease, buccal pigmentation
{49438}      Addison's disease, pigmentation
{49439}      Addison's disease, pigmentation
{49440}      Addison's disease, atrophy of the adrenal gland

{24606}      Waterhouse-Friderichsen adrenal, gross
{09224}      adrenal hemorrhage, consistent with Waterhouse Friderichsen
{07570}      adrenal hemorrhage, gross, consistent with Waterhouse-Friderichsen syndrome

Waterhouse-Friderichsen
Patient photo
WebPath Photo

Waterhouse-Friderichsen
Cortex blood / necrotic, medulla (blue) spared
KCUMB Team

Waterhouse-Friderichsen

WebPath Photo

Waterhouse-Friderichsen

WebPath Photo

CUSHING'S SYNDROME: too much glucocorticoid. Review NEJM 332: 791, 1995.

{49441}      looks like an oat cell case; adrenal cortex is hyperplastic, and bears a metastasis

Both Cushing's disease and glucocorticoid-secreting adenomas are most common in women ages 15 to 45, but can hit anybody, anytime. (* Cushingism in kids and teens: NEJM 331: 629, 1994).

Symptoms and signs that should alert you to possible Cushingism:

{09367}      Cushingism, face
{09370}      Cushingism, face
{16109}      Cushing's syndrome
{16110}      Cushing's syndrome
{16112}      Cushing's syndrome "before"
{16111}      Cushing's syndrome "after"
{49426}      Cushingism, 40 y/o patient
{49427}      Cushingism
{49428}      Cushingism, hyperplastic adrenal cortex

PRIMARY HYPERALDOSTERONISM ("low-renin hyperaldosteronism"): too much mineralocorticoid (review: Postgrad. Med. 95(4): 199, March 1994; NEJM 339: 1820, 1999; Lancet 353: 1341, 1999; Surg. Clin. N.A. 84: 887, 2004; Lancet 371: 1921, 2008)

CONGENITAL ADRENAL HYPERPLASIA: autosomal-recessive virilization syndromes that, in their most severe forms, affect young children.

{49437}      adrenogenital syndrome 2 year old girl
{24450}      adrenogenital syndrome, virilized baby girl
{49432}      11-hydroxylase deficiency, 11 month old boy

ADRENAL CORTICAL ADENOMAS

{09220}      adrenal cortical adenoma, gross
{20312}      adrenal cortical adenoma, gross
{49436}      adrenal cortical adenoma, gross; this one produced Conn's syndrome
{10298}      adrenal cortical adenoma
{20315}      adrenal cortical adenoma, histology
{09221}      adrenal cortical adenoma, histology
{09222}      adrenal cortical adenoma, histology
{08964}      adrenal cortical adenoma, histology (hard to tell from normal cortex)
{09052}      adrenal cortical adenoma, electron micrograph; note tubular cristae in mitochondria (spaghetti instead of lasagna)
{09375}      effect of masculinizing adrenal cortical adenoma, "before"
{09374}      effect of masculinizing adrenal cortical adenoma, "after"
{49434}      gynecomastia in five-year old boy, feminizing adrenal cortical adenoma

Adrenal cortical adenoma
This was a cushingoma
WebPath Photo

Adrenal cortical adenoma
Urbana Atlas of Pathology

Adrenal cortical adenoma
This was a connoma
WebPath Photo

Adrenal cortical adenoma

WebPath Photo

{25412}      adrenal myelolipoma, gross
{49443}      adrenal myelolipoma, gross
{25413}      adrenal myelolipoma, histology

Adrenal myelolipoma
Pittsburgh Pathology Cases

ADRENAL CORTICAL CARCINOMA (Am. J. Clin. Path. 105: 76, 1996; J. Urol. 169: 5, 2003; J. Clin. Endo. Metab. 95: 4812, 2010)

Adrenal cortical carcinoma
Pittsburgh Pathology Cases

Adrenal cortical carcinoma
Pittsburgh Pathology Cases

Adrenal cortical carcinoma

WebPath Photo

Adrenal cortical carcinoma

WebPath Photo

Adrenal cortical carcinoma

WebPath Photo

{24087}      adrenal cortical carcinoma, gross
{40196}      adrenal cortical carcinoma
{24090}      adrenal cortical carcinoma, histology

Metastatic cancer in the adrenals

WebPath Photo

Cancer metastatic to the adrenal
AFIP
Wikimedia Commons

THE ADRENAL MEDULLA: "An organ not essential to life".

PHEOCHROMOCYTOMA ("paraganglioma", "pheo", formerly "ten percent tumor"; big NIH consensus review Ann. Int. Med. 134: 315, 2001; big review for pathologists Arch. Path. Lab. Med. 132: 1272, 2008).

{24716}      neuroblastoma, histology, good rosettes
{25420}      neuroblastoma, gross
{25422}      neuroblastoma, histology
{39049}      neuroblastoma, gross; probably an incidental finding in a newborn
{09009}      neuroblastoma, histology
{09232}      neuroblastoma, histology
{20046}      neuroblastoma, histology
{20047}      neuroblastoma, histology
{09011}      neuroblastoma, histology, good rosettes
{08963}      neuroblastoma histology (sorry, no good rosettes)
{25424}      ganglioneuroblastoma, histology
{25426}      ganglioneuroblastoma, histology
{24608}      ganglioneuroma, gross

Neuroblastoma rosette
AFIP
Wikimedia Commons

Child with neuroblastoma
AFIP
Wikimedia Commons

Neuroblastoma

WebPath Photo

Neuroblastoma

WebPath Photo

Neuroblastoma
WebPath Photo

Neuroblastoma
WebPath Photo

Neuroblastoma patient & family
Cindie and 10 y/o Derek Madsen
Pulitzer-Prize photoessay

INTRODUCTION TO ADRENAL TESTING

PARATHYROID GLANDS: ANATOMY AND PHYSIOLOGY

Parathyroid Exhibit
Virtual Pathology Museum
University of Connecticut

Parathyroids
"Pathology Outlines"
Nat Pernick MD

Normal parathyroid

WebPath Photo

Parathyroid Histology
Ed's Histology Notes

HYPERPARATHYROIDISM ("stone and bone disease"; review Mayo Clin. Proc. 77: 87, 2002; pathologists see Arch. Path. Lab. Med. 134: 1639, 2010)

Brown Tumor of Hyperparathyroidism
Pittsburg Illustrated Case

Brown tumor
Pittsburgh Pathology Cases

Brown tumor
WebPath Tutorial

Brown tumor
WebPath Tutorial

{10827}      parathyroid adenoma, histology

Parathyroid adenoma
Note rim of normal tissue
WebPath Photo

Parathyroid adenoma
Oxyphilic type
WebPath Photo

Nowadays, some folks talk about "just following" people with a parathyroid adenoma who doesn't have symptoms (Am. J. Med. 124: 911, 2011). I would demand surgery. If the serum parathormone level is more than three times the upper limit of normal, or there is a palpable neck mass, it's likely to be cancer and I don't think anyone would question the need to operate (Am. J. Surg. 202: 590, 2011).

Parathyroid carcinoma

WebPath Photo

Parathyroid carcinoma

WebPath Photo

{27260}      parathyroid hyperplasia (arrow sign helps)
{09271}      primary parathyroid hyperplasia, histology

Parathyroid hyperplasia

WebPath Photo

Parathyroid hyperplasia
You cannot tell this from adenoma by itself
WebPath Photo

Parathyroid hyperplasia
Note cell uniformity. Uremia.
KCUMB Team

HYPERCALCEMIA: Differential diagnosis for beginners. Review Postgrad. Med. 115: 69, 2004.

HYPOPARATHYROIDISM

Child with pseudo-pseudo-hypoparathyroidism
Courtesy of Mary Fay MD

THYMUS

Thymus Exhibit
Virtual Pathology Museum
University of Connecticut

Thymus Histology
Ed's Histology Notes

{14760}      normal kid's thymus; a=cortex, b=medulla, c=vessel
{13958}      Hassall's corpuscles stained for keratin (this appears to be normal thyroid)

{13952}      thymoma, gross
{25653}      thymoma, gross
{13955}      thymic tumor, possibly Hodgkin's
{49097}      malignant thymoma, gross

Thymoma
Pittsburgh Pathology Cases

Non-Invasive Thymoma
Pittsburgh Illustrated Case

PINEAL ("the third eye"): Tumors of the pineal are troublesome because of their location. In children, pineal tumors are likely to produce sexual precocity.

{03998}      normal pineal gland, anatomy
{02815}      normal pineal gland, gross
{01223}      normal pineal gland
{01239}      normal pineal gland histology, with brain sand
{05219}      pineal cyst, gross
{01711}      pineal germinoma, gross

Pineocytoma
Pittsburgh Pathology Cases

* THE MELATONIN BUSINESS: Older review Am. Fam. Phys. 57(8): 1783, 1998.

THE MAN

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