endocrine part i - bluedocs.duhs.duke.edu
TRANSCRIPT
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Endocrine Part I
Xiaoyin “Sara” Jiang, MD
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Outline
Endocrine I Thyroid
Parathyroids
MEN Syndromes
Endocrine II Pituitary
Pancreas
Adrenal
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Endocrine System
https://www.nlm.nih.gov/
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Endocrine System
https://www.nlm.nih.gov/
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Endocrine Basics
Endocrine signaling:
Molecules (hormones)
act on distant sites
Transported via blood
May show feedback
inhibition
Hormone carried by
blood
Hormone affects target
Tissue B
Hormone production by
Tissue A Downregulated
Hormone produced by
Tissue A
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Endocrine disease: Basics
1. Hormone overproduction
2. Hormone underproduction
3. Mass lesions (may also cause 1 or 2)
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Thyroid
Klatt, Edward C., MD, Robbins and Cotran Atlas of Pathology, Chapter 15, 387-408.e3 Copyright © 2015 Copyright © 2015, 2010, 2006 by Saunders, an imprint of Elsevier Inc.
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Thyroid
Klatt, Edward C., MD, Robbins and Cotran Atlas of Pathology, Chapter 15, 387-408.e3 Copyright © 2015 Copyright © 2015, 2010, 2006 by Saunders, an imprint of Elsevier Inc.
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Thyroid
Normal wt 15-20 g
May have Pyramidal
lobe
http://reference.medscape.com/article/835535-overview
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Normal Thyroid
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Normal Thyroid
Parafollicular C-cells
Normally not
visible by H&E
Calcitonin inhibits
bone resorption
Klatt, Edward C., MD, Robbins and Cotran Atlas of Pathology, Chapter 15, 387-408.e3 Copyright © 2015 Copyright © 2015, 2010, 2006 by Saunders, an imprint of Elsevier Inc.
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Thyroid
Thyroid hormones have
wide range of metabolic
effects
Generally increase basal
metabolic rate
Kumar, Vinay, MBBS, MD, FRCPath, Robbins Basic Pathology, Chapter 19, 715-763 Copyright © 2013 Copyright © 2013, 2007, 2003, 1997, 1992, 1987, 1981, 1976, 1971 by Saunders, an imprint of Elsevier Inc
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Thyroid Disease
Hyperthyroidism
Hypothyroidism
Mass Effects
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Hyperthyroidism
Kumar, Vinay, MBBS, MD, FRCPath, Robbins Basic Pathology, Chapter 19, 715-763 Copyright © 2013 Copyright © 2013, 2007, 2003, 1997, 1992, 1987, 1981, 1976, 1971 by Saunders, an imprint of Elsevier Inc.
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Thyrotoxicosis
Elevated T3 and T4
Hyperthyroidism: due to hyperfunction
of the thyroid gland (most common!)
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Thyrotoxicosis
Heat intolerance
Increased appetite, weight loss *
GI upset
Palpitations, tachycardia
Tremor, myopathy
Wide gaze
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Thyrotoxicosis
What is most useful
initial screening test?
Kumar, Vinay, MBBS, MD, FRCPath, Robbins Basic Pathology, Chapter 19, 715-763 Copyright © 2013 Copyright © 2013, 2007, 2003, 1997, 1992, 1987, 1981, 1976, 1971 by Saunders, an imprint of Elsevier Inc
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Thyrotoxicosis
What is most useful
initial screening test?
TSH
Kumar, Vinay, MBBS, MD, FRCPath, Robbins Basic Pathology, Chapter 19, 715-763 Copyright © 2013 Copyright © 2013, 2007, 2003, 1997, 1992, 1987, 1981, 1976, 1971 by Saunders, an imprint of Elsevier Inc
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Lab values
State Serum TSH Serum Free T4 Serum T3
Hyperthyroidism
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Lab values
State Serum TSH Serum Free T4 Serum T3
Hyperthyroidism
In most cases of hyperthyroidism, TSH low due to feedback inhibition – with
one exception!
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Lab values
State Serum TSH Serum Free T4 Serum T3
Hyperthyroidism
Hyperthyroidism w/ TSH-secreting pituitary adenoma
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Lab values
State Serum TSH Serum Free T4 Serum T3
Hyperthyroidism
Hyperthyroidism w/ TSH-secreting pituitary adenoma
Hyperthyroidism d/t T3 toxicosis Normal or
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Thyrotoxicosis
Primary
Diffuse toxic hyperplasia (Graves)
Hyperfunctioning goiter
Hyperfunctioning adenoma
Iodine-induced hyperthyroidism
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Graves
Maitra, Anirban, Robbins and Cotran Pathologic Basis of Disease, Chapter 24, 1073-1139 Copyright © 2015 Copyright © 2015, 2010, 2004, 1999, 1994, 1989, 1984, 1979, 1974 by Saunders, an imprint of Elsevier Inc.
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Graves
Maitra, Anirban, Robbins and Cotran Pathologic Basis of Disease, Chapter 24, 1073-1139 Copyright © 2015 Copyright © 2015, 2010, 2004, 1999, 1994, 1989, 1984, 1979, 1974 by Saunders, an imprint of Elsevier Inc.
Normal Thyroid Graves
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Thyrotoxicosis
Secondary
TSH-secreting pituitary adenoma *
Early Granulomatous thyroiditis (De Quervain)
Early Subacute lymphocytic thyroiditis
Struma ovarii
Factitious thyrotoxicosis
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Struma Ovarii
Prat, Jaime, Pathology of the Female Reproductive Tract, 29, 670-693 Copyright © 2014 Copyright © 2014, Elsevier Limited. All rights reserved
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Hypothyroidism
Infancy/Early Childhood: Cretinism
Short stature
Mental retardation
Myxedema
Sluggishness
Cold intolerant
Obesity
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Hypothyroidism
Most common cause worldwide?
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Hypothyroidism
Most common cause worldwide?
Iodine deficiency
http://www.flickr.com/photos/11939863@N08/3793288383/in/photostream/
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Hypothyroidism
Primary
Developmental/congenital
Autoimmune
Iodine deficiency
Iatrogenic Drugs
Surgery
Radiation
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Lab values
State Serum TSH Serum Free T4 Serum T3
Primary hypothyroidism NL or
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Hashimoto Thyroiditis
AKA Chronic Lymphocytic
Women >> Men
45- 65 yo
Autoimmune process caused by thyroid autoantigens
Presents with painless enlargement, hypothyroidism
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Hashimoto Thyroiditis
Normal Thyroid Normal Lymph Node
Chronic Lymphocytic Thyroiditis
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Granulomatous thyroiditis (De Quervain)
AKA “Painful” thyroiditis
Women > Men
30-50 yo
Most patients have preceding URI – viral process or immune response to virus?
Pain (esp. w/ swallowing) and fever
Early hyperthyroidism -> euthyroid -> hypothyroid
Usually self-limited 6-8 wks
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Granulomatous thyroiditis (De Quervain)
DeLellis, Ronald A., Diagnostic Surgical Pathology of the Head and Neck, Chapter 7, 563-646 Copyright © 2009 Copyright © 2009, 2001 by Saunders, an imprint of Elsevier Inc.
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Subacute lymphocytic
thyroiditis
AKA “silent” or “painless” thyroiditis
Middle-aged women
Subset post-partum
Painless neck mass
Early hyperthyroidism -> euthyroid
Minority progress to hypothyroidism
Usually self-limited 6-8 wks
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Hashimoto De Quervain Subacute lymphocytic
Early hyperthyroidism possible
More common in women
Painless Painful Painless
Chronic Self-limited
Lymphocytic infiltrate Granulomatous infiltrate Lymphocytic infiltrate
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Hypothyroidism
Secondary
Pituitary failure
Hypothalamic failure
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Lab values
State Serum TSH Serum Free T4 Serum T3
Primary hypothyroidism NL or
Hypothyroidism d/t pituitary dz
NL or
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Lab values
State Serum TSH Serum Free T4 Serum T3
Hyperthyroidism
Hyperthyroidism w/ TSH-secreting pituitary adenoma
Hyperthyroidism d/t T3 toxicosis Normal or
Primary hypothyroidism NL or
Hypothyroidism d/t pituitary dz
NL or
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https://www.nlm.nih.gov/exhibition/historicalanatomies/Images/1200_pixels/22womangoiter.jpg
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Thyroid masses
“Goiter”= nonspecific term for enlargement
Endemic – iodine deficiency
Sporadic – cause may be unclear
Kumar, Vinay, MBBS, MD, FRCPath, Robbins Basic Pathology, Chapter 19, 715-763 Copyright © 2013 Copyright © 2013, 2007, 2003, 1997, 1992, 1987, 1981, 1976, 1971 by Saunders, an imprint of Elsevier Inc.
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Sporadic goiter
More common in females, peaks in puberty or young adulthood
Can also be associated with excessive cruciferous vegetables
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Thyroid Nodules
Very common- found on exam or
incidentally (up to a third of patients on
Ultrasound!)
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Fine Needle Aspiration
First step in diagnosis for many nodules
~70% nodules benign on FNA
3-7% malignant
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Thyroid Nodules
Benign Malignant
Follicular adenoma Papillary Carcinoma
Multinodular goiter Follicular Carcinoma
Nodules in Hashimoto Poorly-Differentiated Carcinoma
Colloid nodule Anaplastic Carcinoma
Medullary Carcinoma
Metastases
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Colloid Nodule/Cyst
Left: Klatt, Edward C., MD, Robbins and Cotran Atlas of Pathology, Chapter 15, 387-408.e3 Copyright © 2015 Copyright © 2015, 2010, 2006 by Saunders, an imprint of Elsevier Inc. Right: Courtesy Dr. Simon Chiosea, UPMC
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Follicular Adenoma
Benign encapsulated tumor with
follicular cell differentiation
Most common thyroid neoplasm
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Follicular Adenoma
Left image: Klatt, Edward C., MD, Robbins and Cotran Atlas of Pathology, Chapter 15, 387-408.e3 Copyright © 2015 Copyright © 2015, 2010, 2006 by Saunders, an imprint of Elsevier Inc. Right image: Dr. Jiang
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Thyroid Carcinoma
~1.5% cancers in US
Papillary
Follicular
Anaplastic
Medullary
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Papillary thyroid carcinoma
Most common malignancy of the thyroid
Risk factors: Ionizing radiation
Size varies from microscopic (incidental microcarcinomas) to huge
Grossly most are solid, pale, firm
Less than 10% encapsulated
10-yr survival >95%
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Papillary Thyroid Carcinoma
Left: Klatt, Edward C., MD, Robbins and Cotran Atlas of Pathology, Chapter 15, 387-408.e3 Copyright © 2015 Copyright © 2015, 2010, 2006 by Saunders, an imprint of Elsevier Inc. Right: Dr. Jiang
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Papillary Thyroid Carcinoma
Psammoma bodies
Overlapping nuclei
“Orphan-Annie-eye” nuclei
Nuclear grooves
Pseudoinclusions
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Papillary Thyroid Carcinoma
Many variants: Follicular variant
Tall cell variant
Oncocytic variant
Clear cell variant
Diffuse sclerosing variant
Columnar variant
Insular solid variant
Cribriform morula variant
Warthin-like variant
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Poorly-differentiated
Carcinoma
AKA Insular
Follicular cell origin, partial loss of
differentiation
55-63yo
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Poorly-differentiated
Carcinoma
Chan, John K.C., Diagnostic Histopathology of Tumors, Chapter 18, 1177-1293 Copyright © 2013 Copyright © 2013 by Saunders, an imprint of Elsevier Inc.
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Poorly-differentiated Carcinoma
Chan, John K.C., Diagnostic Histopathology of Tumors, Chapter 18, 1177-1293 Copyright © 2013 Copyright © 2013 by Saunders, an imprint of Elsevier Inc.
Thyroglobulin IHC stain
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Anaplastic carcinoma
2% of thyroid malignancies, but 40% of deaths
Rapidly enlarging, bulky neck mass with invasion of adjacent structures
Likely arises as anaplastic transformation of differentiated thyroid carcinomas
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Anaplastic carcinoma
http://atlasgeneticsoncology.org/Tumors/Images/AnaCarciThyroidFig1.jpg
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Medullary carcinoma
Arises from C-cells
Most arise in mid to upper half of gland Greater concentration of C-cells
Two forms: Sporadic in about 80%, adults, solitary
Familial at younger age, multiple and bilateral, with C-cell hyperplasia MEN IIA and MEN IIB (RET mutation)
Five-year survival 70-80%
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Medullary carcinoma
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Medullary carcinoma
Calcitonin Immunostain
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Parathyroid
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Parathyroid Glands
Normal wt 25-40mg each
3rd and 4th pharyngeal pouches
Can migrate from upper thyroid to mediastinum
Can be ectopic within other organs like thyroid, thymus
http://reference.medscape.com/article/835535-overview
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Parathyroid
http://ars.els-cdn.com/content/image/
Chief cells Water clear cells Oxyphil nodule
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Intrathyroidal Parathyroid
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Hyperparathyroidism
Primary
Adenoma 85-95%
Hyperplasia
Carcinoma (<1%)
Secondary
Caused by anything
leading to low serum
Ca2+
Renal failure most
common
Wenig, Bruce M., MD, Atlas of Head and Neck Pathology, Chapter 31, 1477-1481.e1 Copyright © 2016 Copyright © 2016 by Elsevier, Inc. All rights reserved. Modified from www.netterimages.com . From Som PM, Curtin HD: Head and neck imaging, ed 5, Philadelphia, 2011, Elsevier, Fig. 41-93, p 2661.
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Hyperparathyroidism
Primary
Adenoma 85-95%
Hyperplasia
Carcinoma (<1%)
Secondary
Caused by anything
leading to low serum
Ca2+
Renal failure most
common
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Hyperparathyroidism
Bones
Stones
Groans
(Abdominal)
Overtones
(Psychiatric)
http://endocrinediseases.org/parathyroid/symptoms_summary.shtml
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Parathyroid Adenoma vs
Hyperplasia
80% or more of primary
hyperparathyroidism is caused by one
gland abnormality - adenoma
Problems
Locating gland
Determining status of other glands
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Parathyroid Adenoma
Wenig, Bruce M., MD, Atlas of Head and Neck Pathology, Chapter 33, 1494-1517.e3 Copyright © 2016 Copyright © 2016 by Elsevier, Inc. All rights reserved.
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Parathyroid Hyperplasia
Klatt, Edward C., MD, Robbins and Cotran Atlas of Pathology, Chapter 15, 387-408.e3 Copyright © 2015 Copyright © 2015, 2010, 2006 by Saunders, an imprint of Elsevier Inc.Q
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Parathyroid Carcinoma
Defined by:
Invasion of adjacent structures
Metastasis
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Hypoparathyroidism
Tetany: Chvostek & Trousseu signs
Mental status changes
Intracranial manifestations
Ocular disease: lens calcification, cataracts
Cardiovascular: characteristic prolongation of QT interval
Dental abnormalities if hypocalcemic in development
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Hypoparathyroidism
Most common cause: surgery Uncommon causes:
Autoimmune- autoimmune polyendocrine syndrome type 1 (APS1)- mutations in autoimmune regulator (AIRE) gene
Autosomal-dominant hypoparathyroidism- calcium-sensing receptor (CASR) gene mut.
Familial isolated hypoparathyroidism (FIH)
Congenital absence of parathyroids
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Multiple Endocrine Neoplasia (MEN)
Tumors at younger age
Multiple endocrine organ tumors
Can be multifocal within same organ
May be preceded by hyperplasia (ex C-cells)
More aggressive, may recur more often
than sporadic tumors
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MEN1
Autosomal dominant
MEN1 (11q13), tumor suppressor
3 “P”s
Pituitary Adenoma
Parathyroid hyperplasia
Pancreatic tumors Kumar, Vinay, MBBS, MD, FRCPath, Robbins Basic Pathology, Chapter 19, 715-763 Copyright © 2013 Copyright © 2013, 2007, 2003, 1997, 1992, 1987, 1981, 1976, 1971 by Saunders, an imprint of Elsevier Inc.
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MEN2
RET activating mutations
Autosomal dominant
2A: Thyroid - medullary CA
Adrenal pheochromocytomas
Parathyroid hyperplasia
2B: No parathyroid hyperplasia, ganglioneuromas and marfanoid habitus
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Multiple Endocrine Neoplasia (MEN)
MEN1 MEN2A MEN2B
Pituitary Adenoma Marfanoid body habitus
Parathyroid Hyperplasia Parathyroid Hyperplasia Mucosal Neuromas
Medullary Thyroid Ca Medullary Thyroid Ca
Pheochromocytoma Pheochromocytoma
Pancreatic tumors
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Multiple Endocrine Neoplasia (MEN)
MEN1 MEN2A MEN2B
Wermer syndrome Sipple syndrome
MEN1 gene RET RET
Pituitary Adenoma Marfanoid body habitus
Parathyroid Hyperplasia Parathyroid Hyperplasia Mucosal Neuromas
Medullary Thyroid Ca Medullary Thyroid Ca
Pheochromocytoma Pheochromocytoma
Pancreatic tumors