Endocrine Part I - bluedocs.duhs.duke.edu

Endocrine Part I

Xiaoyin “Sara” Jiang, MD

Outline

Endocrine I Thyroid

Parathyroids

MEN Syndromes

Endocrine II Pituitary

Pancreas

Adrenal

Endocrine System

https://www.nlm.nih.gov/

Endocrine System

https://www.nlm.nih.gov/

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

Endocrine disease: Basics

1. Hormone overproduction

2. Hormone underproduction

3. Mass lesions (may also cause 1 or 2)

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.

Thyroid


Thyroid

Normal wt 15-20 g

May have Pyramidal

lobe

http://reference.medscape.com/article/835535-overview

Normal Thyroid

Normal Thyroid

Parafollicular C-cells

Normally not

visible by H&E

Calcitonin inhibits

bone resorption


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

Thyroid Disease

Hyperthyroidism

Hypothyroidism

Mass Effects

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.

Thyrotoxicosis

Elevated T3 and T4

Hyperthyroidism: due to hyperfunction

of the thyroid gland (most common!)

Thyrotoxicosis

Heat intolerance

Increased appetite, weight loss *

GI upset

Palpitations, tachycardia

Tremor, myopathy

Wide gaze

Thyrotoxicosis

What is most useful

initial screening test?


Thyrotoxicosis

What is most useful

initial screening test?

TSH


Lab values

State Serum TSH Serum Free T4 Serum T3

Hyperthyroidism

Lab values


Hyperthyroidism

In most cases of hyperthyroidism, TSH low due to feedback inhibition – with

one exception!

Lab values


Hyperthyroidism

Hyperthyroidism w/ TSH-secreting pituitary adenoma

Lab values


Hyperthyroidism


Hyperthyroidism d/t T3 toxicosis Normal or

Thyrotoxicosis

Primary

Diffuse toxic hyperplasia (Graves)

Hyperfunctioning goiter

Hyperfunctioning adenoma

Iodine-induced hyperthyroidism

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.

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

Thyrotoxicosis

Secondary

TSH-secreting pituitary adenoma *

Early Granulomatous thyroiditis (De Quervain)

Early Subacute lymphocytic thyroiditis

Struma ovarii

Factitious thyrotoxicosis

Struma Ovarii

Prat, Jaime, Pathology of the Female Reproductive Tract, 29, 670-693 Copyright © 2014 Copyright © 2014, Elsevier Limited. All rights reserved

Hypothyroidism

Infancy/Early Childhood: Cretinism

Short stature

Mental retardation

Myxedema

Sluggishness

Cold intolerant

Obesity

Hypothyroidism

Most common cause worldwide?

Hypothyroidism

Most common cause worldwide?

Iodine deficiency

http://www.flickr.com/photos/11939863@N08/3793288383/in/photostream/

Hypothyroidism

Primary

Developmental/congenital

Autoimmune

Iodine deficiency

Iatrogenic Drugs

Surgery

Radiation

Lab values


Primary hypothyroidism NL or

Hashimoto Thyroiditis

AKA Chronic Lymphocytic

Women >> Men

45- 65 yo

Autoimmune process caused by thyroid autoantigens

Presents with painless enlargement, hypothyroidism

Hashimoto Thyroiditis

Normal Thyroid Normal Lymph Node

Chronic Lymphocytic Thyroiditis

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

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.

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

Hashimoto De Quervain Subacute lymphocytic

Early hyperthyroidism possible

More common in women

Painless Painful Painless

Chronic Self-limited

Lymphocytic infiltrate Granulomatous infiltrate Lymphocytic infiltrate

Hypothyroidism

Secondary

Pituitary failure

Hypothalamic failure

Lab values



Hypothyroidism d/t pituitary dz

NL or

Lab values


Hyperthyroidism


Hyperthyroidism d/t T3 toxicosis Normal or


Hypothyroidism d/t pituitary dz

NL or

https://www.nlm.nih.gov/exhibition/historicalanatomies/Images/1200_pixels/22womangoiter.jpg

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.

Sporadic goiter

More common in females, peaks in puberty or young adulthood

Can also be associated with excessive cruciferous vegetables

Thyroid Nodules

Very common- found on exam or

incidentally (up to a third of patients on

Ultrasound!)

Fine Needle Aspiration

First step in diagnosis for many nodules

~70% nodules benign on FNA

3-7% malignant

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

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

Follicular Adenoma

Benign encapsulated tumor with

follicular cell differentiation

Most common thyroid neoplasm

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

Thyroid Carcinoma

~1.5% cancers in US

Papillary

Follicular

Anaplastic

Medullary

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%

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


Psammoma bodies

Overlapping nuclei

“Orphan-Annie-eye” nuclei

Nuclear grooves

Pseudoinclusions


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

Poorly-differentiated

Carcinoma

AKA Insular

Follicular cell origin, partial loss of

differentiation

55-63yo

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.

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

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

Anaplastic carcinoma

http://atlasgeneticsoncology.org/Tumors/Images/AnaCarciThyroidFig1.jpg

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%

Medullary carcinoma

Medullary carcinoma

Calcitonin Immunostain

Parathyroid

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

Parathyroid

http://ars.els-cdn.com/content/image/

Chief cells Water clear cells Oxyphil nodule

Intrathyroidal Parathyroid

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.

Hyperparathyroidism

Primary

Adenoma 85-95%

Hyperplasia

Carcinoma (<1%)

Secondary

Caused by anything

leading to low serum

Ca2+

Renal failure most

common

Hyperparathyroidism

Bones

Stones

Groans

(Abdominal)

Overtones

(Psychiatric)

http://endocrinediseases.org/parathyroid/symptoms_summary.shtml

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

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.

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

Parathyroid Carcinoma

Defined by:

Invasion of adjacent structures

Metastasis

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

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

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

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.

MEN2

RET activating mutations

Autosomal dominant

2A: Thyroid - medullary CA

Adrenal pheochromocytomas

Parathyroid hyperplasia

2B: No parathyroid hyperplasia, ganglioneuromas and marfanoid habitus


MEN1 MEN2A MEN2B

Pituitary Adenoma Marfanoid body habitus

Parathyroid Hyperplasia Parathyroid Hyperplasia Mucosal Neuromas

Medullary Thyroid Ca Medullary Thyroid Ca

Pheochromocytoma Pheochromocytoma

Pancreatic tumors


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

Documents

Endocrine Part I - bluedocs.duhs.duke.edu