Department of Pathology

The Endocrine System

Part 1

Mark Lester Dalanon, MD July 11, 2023

Lecturer doc.mldalanon@gcm.edu.ph

 OUTLINE
01 Overview
03 Review Questions

02 Diseases of the Endocrine System

- Diseases of the Thyroid Gland 04 Reading Assignments
- Hyperthyroidism
- Diseases of the Pituitary Gland and - Hypothyroidism
Hypothalamus - Cretinism
- Pituitary Adenoma and - Myxedema
Hyperpituitarism - Thyroiditis
- Hashimoto’s Thyroiditis
- Hypopituitarism - Subacute Thyroiditis
- Posterior Pituitary Syndromes - Granulomatous Thyroiditis
- Hypothalamic Suprasellar - Graves Disease
Tumors - Goiter
- Diffuse Nontoxic Goiter
- Multinodular Goiter
- Neoplasm of the Thyroid
- Papillary Thyroid Carcinoma
- Follicular Carcinoma
- Medullary Carcima
- Undifferentiated or Anaplastic Carcinoma
01 Overview
 01 Overview: The Endocrine System
• Highly integrated and widely distributed
group of organs, called Glands
• Secretes molecules can be classified into
three types (on the basis of the distance
over which the signal acts)

• Autocrine

• Paracrine

• Endocrine

• Hormones, act on target cells that

are distant from their sites of
synthesis
01 Overview: Disorders of the Endocrine System
02
Disorders of the Pituitary
Gland & Hypothalamus
 02 Pituitary Gland
• Small, bean-shaped structure that lies at the base of the brain
within the sella turcica

• Two morphologically and functionally distinct components:

• Anterior lobe (adenohypophysis)

• constitutes about 80% of the gland

• produces trophic hormones that stimulate the

production of hormones from the thyroid, adrenal, and
other glands

• Posterior lobe (neurohypophysis)

• consists of modified glial cells (termed pituicytes) and

axonal processes extending from the hypothalamus

• Secretes oxytocin and antidiuretic hormone (ADH,

also called arginine vasopressin or AVP)
 02 Hypothalamus
• Structure deep within your brain

• Main link between the endocrine system and

the nervous system

• Helps manage body temperature, hunger

and thirst, mood, sex drive, blood pressure
and sleep

• Sends signals in the form of releasing

hormones to tell the anterior and posterior
pituitary when to release (secrete) its
hormones

• Produce hormones itself that are stored in

the posterior pituitary
 02 Pituitary Adenoma
• Most common cause of hyperpituitarism is an adenoma arising
in the anterior lobe

• Classified on the basis of:

• the hormones

• cell type–specific transcription factors that are expressed

by the tumor cells

Pituitary Adenoma on MRI Imaging

• Usually found in adults

• Peak incidence is from 35 to 60 years of age

Gross Appearance

• Designation (Based on the tumor size):

• Microadenomas

• less than 1 cm in diameter

• Macroadenomas

• exceed 1 cm in diameter
02 Classifications of Pituitary Adenomas
02 Classifications of Pituitary Adenomas
 02 Lactotroph Adenoma
• Prolactinoma is the most common

• Macroadenoma if the size of the tumor is >1cm

• Clinical Findings:

• Amenorrhea

• Galactorrhea

• Low Libido
Pituitary Adenoma on MRI Imaging
• Infertility (Due to decrease in GnRH)

• Bitemporal Hemianopia due to impingement of the

Optic Chiasm

• Treatment:

• Dopamine Agonist which shrinks the Prolactinoma

• Bromocriptine and Cabergoline

02 Bitemporal Hemianopia
02 Classifications of Pituitary Adenomas
 02 Acromegaly
• Excess Growth Hormone in Adults

• Gigantism is increased Growth Hormone in Children (Linear Bone Growth)

• Typically caused by Pituitary Adenoma (Somatotroph Adenoma)

• Clinical Findings:

• Large Tongue

• Deep voice

• Large Hands and Feet

• Impaired Glucose Tolerance (GH is a counter regulatory hormone of Insulin)

• Diagnosis

• Increase Serum IGF-1

• Failure to Suppress Serum GH follow Oral Glucose Test

• Pituitary Mass on MRI or CT Scan

• Treatment

• Resection

• Followed by Somatostatin Analogue (Octreotide) if not cured

• Potent Growth Hormone Inhibitor

02 Classifications of Pituitary Adenomas
 02 Cushing’s Syndrome
• Increased in CORTISOL level
Adrenal Adenoma

• EXOGENOUS Cause:

• Used of Steroids - Primary Cause of Decrease

Adrenocorticotropic Hormone (ACTH)

• ENDOGENOUS Causes:

• Cushing's Disease (70%) - Pituitary Adenoma

(Corticotroph Adenoma)

• Ectopic ACTH (15%) - Nonpituitary tissue secreting

ACTH (e.g. Small Lung Cell Cancer and Bronchial
Carcinoids)

• Adrenal (15%) - Adrenal Adenoma, Carcinoma, Nodular

Adrenal Hyperplasia
02 Cushing’s Syndrome: Clinical Features
02 Negative Feedback Loop: Hypothalamic–Pituitary–Adrenal (HPA) Axis
02 Negative Feedback Loop: Hypothalamic–Pituitary–Adrenal (HPA) axis
02 Negative Feedback Loop: Hypothalamic–Pituitary–Adrenal (HPA) axis
02 Negative Feedback Loop: Hypothalamic–Pituitary–Adrenal (HPA) axis
 02 Hypopituitarism
• Decreased secretion of ALL Pituitary Hormone

• 70% to 90% of ANTERIOR PITUITARY is destroyed before

it becomes clinically evident

• Causes:

• Nonsecreting Pituitary Adenoma

• Craniopharyngioma

• Sheehan’s Syndrome

• Empty Sella Syndrome

• Brain Injury and Hermorrhage

• Radiation

• Treatment:

• Substitution Therapy using Corticosteroids, Thyroxine,

Sex Steroids, Human Growth Hormone
 02 Hypopituitarism
• Sheehan’s Syndrome

• Ischemic infarct of the Pituitary following Postpartum Bleeding

• Usually presents with failure to Lactate due to absence in the secretion of Prolactin
 02 Posterior Pituitary Syndrome: Diabetes Insipidus
• Diabetes insipidus

• Anti-Diuretic Hormone (ADH) deficiency

• Excessive urination (polyuria) due to an

inability of the kidney to resorb water properly
from the urine

• Causes:

• Head trauma, tumors

• Inflammatory disorders of the

hypothalamus and pituitary

• Surgical complications
 02 Posterior Pituitary Syndrome: SIADH
• Syndrome of inappropriate ADH (SIADH) secretion

• Anti-Diuretic Hormone (ADH) excess

• Causes:

• Secretion of Ectopic ADH by Malignant neoplasms

• Particularly small-cell carcinoma of the lung)

• Most frequent causes

• Drugs that increase ADH secretion

• Variety of central nervous system disorders, including infections

and trauma

• Clinical manifestations
• Hyponatremia

• Cerebral edema

• Resultant neurologic dysfunction

• Blood volume remains normal

• Peripheral edema does not develop

 02 Hypothalamic Supracellar Tumors
• May induce hypofunction or hyperfunction of the anterior
pituitary, diabetes insipidus, or combinations of these
manifestations

• Most commonly implicated tumors are glioma and

craniopharyngioma

• Craniopharyngioma

• Arise from vestigial remnants of Rathke pouch

• Slow-growing tumors account for 1% to 5% of

intracranial tumors

• Bimodal age distribution

• Childhood (5 to 15 years) - first peak

• Adults 65 years of age or older - second peak

 02 Hypothalamic Supracellar Tumors
• Craniopharyngioma

• Symptoms

• Headaches

• Visual disturbances

• Growth retardation in children

• due to Pituitary hypofunction and GH

deficiency

• Gross Findings

• Lobular and cystic tumor with calcifications

• Cysts may contain dark "motor oil" fluid

composed of cholesterol and hemorrhage
02 Craniopharyngioma: Histologic Variants

Both variants have a good prognosis

03
Disorders of the
Thyroid Gland
 03 Thyroid Gland: Gross Anatomy
• Butterfly-shaped gland located anterior to the neck,
inferior to the Laryngeal Prominence (Adam’s apple)

• Important part of the endocrine system and plays a crucial

role in regulating metabolism and growth

• Consists of two connected lobes and the lower two thirds of

the lobes are connected by a thin band of tissue called the
Isthmus

• Pyramidal lobe

• Stretches up to the hyoid bone from the thyroid isthmus

• Presence of this lobe ranges in reported studies from

18.3% to 44.6%
 03 Thyroid Gland: Histology
• Thyroid follicles

• Majority of the thyroid gland is made of spherical structures called follicles

• Central cavity of a follicle is filled with a colloid composed of Thyroglobulin

• Thyroglobulin is glycoprotein that is a precursor and storage

molecule for thyroid hormones

• Two types of endocrine cells

• Thyroid follicular cells

• Secretory (glandular) epithelial cells surrounding a cavity filled with

a pink thyroglobulin

• Produce and secrete the hormones thyroxine and

triiodothyronine

• Parafollicular cells (C Cells)

• Primarily located in clusters between follicles but can also be a part

of the follicular wall

• Oval in shape and have lighter stained cytoplasm than follicular

cells

• Secrete Calcitonin
03 Hypothyroidism vs Hyperthyroidism: Signs and Symptoms

SLOWING things DOWN SPEEDING things UP

03 Hypothyroidism vs Hyperthyroidism: Laboratory Findings
 03 Hypothyroidism: Cretinism
• Severe Fetal Hypothyroidism

• Endemic Cretinism occurs when there is prevalent

Endemic Goiter (lack of dietary Iodine)

• Usually caused by Maternal Hypothyroidism

• Sporadic Cretinism is caused by defect in T4 formation

or developmental failure in thyroid formation.

Protruding Tongue
• Clinical Findings: (5 Ps)
Puffy Face

• Pot belly

• Puffy face

• Protruding Umbilicus

• Protuberant Tongue
Pot Belly Protruding Umbilicus
 03 Hypothyroidism: Myxedema
• Applied to hypothyroidism developing in the older child or adult

• Slowing of physical and mental activity

• Early symptoms include generalized fatigue, apathy, and mental
sluggishness
• May mimic depression
• Decreased sympathetic activity results in constipation and decreased
sweating

• Histologic Findings:
• Accumulation of matrix substances, glycosaminoglycans and
hyaluronic acid, in skin, subcutaneous tissue, and visceral sites

• Signs and Symptoms:

• Non-pitting edema

• Broadening and coarsening of facial features

• Enlargement of the tongue

• Deepening of the voice

 03 Hypothyroidism: Myxedema
• Laboratory Findings:

• Hypercholesterolemia should be assessed for

potential hypothyroidism

• Serum TSH level is the most sensitive

• Decreased in primary hypothyroidism as

a result of a loss of feedback

• Inhibition of TRH and TSH production by

the hypothalamus and pituitary

• T3 and T4 levels are decreased in individuals

with hypothyroidism of any origin except
Subclinical Hypothyroidism
 03 Thyroiditis: Hashimoto’s Thyroiditis
• Most common cause of Hypothyroidism

• Autoimmune Disorder

• Anti-TSH (Specific for Hashimoto’s Thyroiditis and

Graves Disease)

• Anti-Thyroid Peroxidase Antibodies

• Anti-Thyroglobulin Antibodies

• Associated with HLA-DR5 (Goitrous Form), HLA-DR3

(Atrophic Form)

• Increased risk of Non-Hodgkin’s Lymphoma

• Can cause Hyperthyroidism early in course due to

rupture of thyroid follicle releasing thyroid hormone into
the circulation
 03 Thyroiditis: Hashimoto’s Thyroiditis
• Histology:
Lymphocytic Infiltrates with Germinal Center

• Hürtle cells

• Lymphocytic infiltrates with Germinal Centers

• Clinical Findings:

• Moderately Enlarged and Non-Tender thyroid gland

Gross Appearance

Hürthle Cells
 03 Thyroiditis: Subacute Thyroiditis (de Quervain’s)
• Self limited Hypothyroidism
Foreign type body Giant Cell

• Usually following a Flu-like illness or Viral

Infection

• Clinical Findings: Normal Thyroid Follicles

• Elevated ESR

• Jaw pain

• Very tender Thyroid Gland

• May have episodes of Hyperthyroidism

early in course

• Histology:

• Granulomatous Inflammation
Fibrosis
 03 Thyroiditis: Riedel’s Thyroiditis
• Normal Thyroid gland is replaced by fibrous tissue
causing Hypothyroidism
Fibrosis Inflammatory Infiltrates

• Clinical Findings:

• Fixed, Hard (Rock-like), and Painless thyroid gland

• Histology:

• Prominent Inflammatory Infiltrates composed of Microscopic Appearance

Plasma Cells (mostly IgG-4 producing), Lymphocytes
and Macrophages aswell as numerous Eosinophils

• Treatment:

• Steroids

• Surgery if with compression symptoms

Gross Appearance
 03 Multinodular Goiter
• Most common disease of the Thyroid

• Iodine deficiency is most common cause worldwide

• Clinical Findings

• Diffuse or nodular enlargement with distorted outer

surface

• Histology

• Variable sized dilated follicles with flattened to

hyperplastic epithelium

• Treatment

• Thyroidectomy (very large goiters; > 80 - 100 mL)

• Radioiodine therapy

• Jod-Basedow Phenomenon

• Thyrotoxicosis due to rapid correction to Iodine

deficiency
 03 Grave’s Disease
• Autoimmune disease characterized by hyperthyroidism

• Type 2 hypersensitivity

• Due to circulating autoantibodies against thyrotropin

(TSH receptor)

• Disease often present in stressful situations such as Child

Birth

• Clinical Findings:

• Exophthalmus (Proptosis and Lid Retraction)

• Pretibial Myxedema (Only seen in Graves Disease)

03 Grave’s Disease

Exophthalmus (Proptosis and Lid Retraction) Pretibial Myxedema

 03 Thyroid Storm / Thyrotoxicosis
• Stress-Induced Catecholamine surge

• Seen in serious complication of Graves Disease and

other Hyperthyroid disorders

• Can lead to death due to Arrhythmia

 03 Thyroid Neoplasm: Papillary Thyroid Carcinoma (PTC)
• Most common type of Thyroid Cancer

• BRAFV600E is the most frequent mutation

• RET or NTRK1 proto-oncogene is seen in 30% of

all PTCs

• Diagnosis is based on nuclear features

• Carries Excellent prognosis

• Histology:

• Orphan Annie Eye - Nuclear Clearing

• Psammoma Bodies - Not specific since it can

be seen in other tumors

• Nuclear Grooves
Papillary Thyroid Carcinoma on Cytology
 03 Thyroid Neoplasm: Papillary Thyroid Carcinoma (PTC)
Orphan Annie Eye Nuclei

Nuclear Grooves or Coffee Bean Nuclei Psammoma Bodies

 03 Thyroid Neoplasm: Follicular Carcinoma
• Thyroid carcinoma with follicular differentiation but no
papillary nuclear features

• Second most common thyroid carcinoma (6 -

10%)

• Insufficient dietary iodine is a risk factor

• Diagnosis is based on capsular or vascular Gross Appearance

invasion but without papillary nuclear features

• Histology:

• Trabecular or solid pattern of follicles

• Capsular invasion and/or Vascular invasion

• Follicular Adenoma - If there’s no evidence of

capsular or vascular invasion
Microscopic Appearance
 03 Thyroid Neoplasm: Medullary Carcinoma
• Derived from the Parafollicular “C” Cells which Gross Appearance
produces Calcitonin

• Associated with MEN Types 2A and 2B

• Laboratory Findings:

• High serum Calcitonin and CEA levels

• Histology:

• Sheets of cells

Tumor Cells
• Amyloid Stroma Amyloid Deposits

Microscopic Appearance
 03 Thyroid Neoplasm: Undifferentiated or Anaplastic Carcinoma
• Rare
CT Scan Image
• Poor prognosis

• Common in Older patients

• Signs and Symptom:

• Rapidly Enlarging, Bulky Neck Mass

• Hoarseness

• Dysphagia

Microscopic Appearance
• Dyspnea

• Histology:

• Extensive tumor necrosis

• Marked nuclear pleomorphism

• High mitotic activity

Marked Pleomorphism
03 Review Question
 03 Review Questions
A 45-year-old man has felt a lump on the left side of his neck for 4 months. Physical
examination shows a non-tender nodule on the left lobe of the thyroid gland. An
adjacent cervical lymph node is enlarged and non-tender. Laboratory studies show no
thyroid autoantibodies in his serum, and the T4 and TSH levels are normal. A
thyroidectomy is performed; the figure shows the microscopic appearance of the
nodule. Which of the following etiologic factors is most likely to be involved in the
pathogenesis of the thyroid nodule in this patient?
A. Autoimmunity
B. Chronic dietary iodine deficiency
C. Consumption of goitrogens
D. RET gene mutation
E. Viral infection
 03 Review Questions
A 45-year-old man has felt a lump on the left side of his neck for 4 months. Physical
examination shows a non-tender nodule on the left lobe of the thyroid gland. An
adjacent cervical lymph node is enlarged and non-tender. Laboratory studies show no
thyroid autoantibodies in his serum, and the T4 and TSH levels are normal. A
thyroidectomy is performed; the figure shows the microscopic appearance of the
nodule. Which of the following etiologic factors is most likely to be involved in the
pathogenesis of the thyroid nodule in this patient?
A. Autoimmunity
B. Chronic dietary iodine deficiency
C. Consumption of goitrogens
D. RET gene mutation
E. Viral infection
 03 Papillary Thyroid Carcinoma (PTC)
• Most common type of Thyroid Cancer

• BRAFV600E is the most frequent mutation

• RET or NTRK1 proto-oncogene is seen in 30% of

all PTCs

• Diagnosis is based on nuclear features

• Carries Excellent prognosis

• Histology:

• Orphan Annie Eye - Nuclear Clearing

• Psammoma Bodies - Not specific since it can

be seen in other tumors

• Nuclear Grooves
Papillary Thyroid Carcinoma on Cytology
 03 Thyroid Neoplasm: Papillary Thyroid Carcinoma (PTC)
Orphan Annie Eye Nuclei

Nuclear Grooves or Coffee Bean Nuclei Psammoma Bodies

 Department of Pathology
The Endocrine System
Part 1
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