Pathology of endocrinopathies

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PATHOLOGY OF
ENDOCRINOPATHIES
Thyroid & Parathyroid Gland Disorders
Etiology • Pathogenesis • Morphology • Clinical features
MBBS Pathology | Class Presentation

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Learning Objectives
By the end of this presentation, students should be able to:
Define endocrinopathies and classify endocrine dysfunction.
Explain common causes and mechanisms of endocrine disease.
Describe the pathology of major thyroid disorders.
Compare hyperparathyroidism with hypoparathyroidism.
Recognize key microscopic findings and basic laboratory patterns.
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3.

Endocrinopathies: Definition & Types
Disorders caused by abnormal hormone production, transport, metabolism, or action.
Hyperfunction
Hypofunction
Hormone resistance
Excess hormone production or
secretion.
Example: Graves disease.
Insufficient hormone production.
Example: Hashimoto thyroiditis.
Target tissues respond
inadequately despite hormone
presence.
Example: insulin resistance.
Disease may originate in the endocrine gland (primary) or in its regulatory axis (secondary/tertiary).
Feedback loops, receptor signaling, and hormone clearance influence the clinical picture.
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4.

General Etiology & Pathogenesis
Common mechanisms shared by endocrine disorders
Autoimmune injury: immune-mediated destruction or receptor stimulation.
Genetic defects: altered hormone synthesis, receptors, or signaling pathways.
Tumors: adenoma or carcinoma may produce hormones or destroy normal tissue.
Nutritional factors: iodine deficiency impairs thyroid hormone synthesis.
Vascular injury, infection, surgery, radiation, and medications may damage glands.
Pathogenesis: abnormal hormone level → altered target-organ function → clinical manifestations.
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5.

Thyroid Gland: Overview
Follicular cells produce T4 and T3; parafollicular C cells produce calcitonin.
T3 / T4
TSH
Negative feedback
Regulate basal metabolic rate,
heat production, growth, and
development.
Pituitary hormone that stimulates
thyroid hormone synthesis and
gland growth.
T3/T4 suppress hypothalamic
TRH and pituitary TSH secretion.
Thyroid dysfunction is commonly assessed using TSH and free T4.
In primary disease, TSH generally changes inversely to free T4.
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6.

Goiter
Goiter means enlargement of the thyroid gland; it does not necessarily imply abnormal hormone levels.
Causes
Morphology
Iodine deficiency, Graves disease, thyroiditis, and
nodular thyroid disease.
Diffuse enlargement or multiple nodules. Microscopy
varies with the cause and stage.
Diffuse hyperplasia may show crowded follicles and papillary infoldings.
Colloid goiter shows enlarged follicles distended with colloid.
Clinical effects may include neck swelling, compression, or altered thyroid function.
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Graves Disease (Autoimmune Hyperthyroidism)
A common cause of diffuse hyperthyroidism
Pathogenesis: thyroid-stimulating immunoglobulins activate the TSH receptor.
Gross: diffuse, symmetrical enlargement with increased vascularity.
Microscopy: tall follicular cells, hyperplasia, papillary infoldings, and scalloped colloid.
Clinical features: weight loss, heat intolerance, tremor, tachycardia, and anxiety.
Associated findings: ophthalmopathy and, less commonly, pretibial myxedema.
Exam clue
Scalloped colloid + TSH-receptor antibodies
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8.

Hypothyroidism & Hashimoto Thyroiditis
Hashimoto thyroiditis is a major cause of primary hypothyroidism in iodine-sufficient regions.
Pathogenesis
Microscopy
Autoimmune lymphocytic injury progressively
damages thyroid follicles, reducing T4/T3 production.
Dense lymphocytes with germinal centers, follicular
destruction, and Hürthle (oxyphilic) cells.
Symptoms: fatigue, weight gain, cold intolerance, constipation, and slow heart rate.
Typical primary pattern: increased TSH with decreased free T4 in overt disease.
Anti-thyroid peroxidase antibodies are commonly present.
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9.

Other Important Thyroid Disorders
Recognize the classic pathology pattern
De Quervain (subacute) thyroiditis
Thyroid nodules
Often follows a viral-like illness; painful, tender thyroid.
Microscopy: granulomatous inflammation and
multinucleated giant cells.
May be benign or malignant; evaluate with clinical
assessment, ultrasound, and indicated fine-needle
aspiration.
Thyroiditis may cause a transient thyrotoxic phase followed by temporary hypothyroidism.
A thyroid nodule requires risk assessment; not every nodule is cancer.
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10.

Parathyroid Gland & PTH
PTH maintains extracellular calcium and phosphate balance.
Bone
Kidney
Intestine
Promotes bone resorption
indirectly through osteoblast
signaling when PTH is persistently
elevated.
Increases calcium reabsorption
and phosphate excretion;
stimulates active vitamin D
formation.
Active vitamin D increases
intestinal absorption of calcium
and phosphate.
PTH secretion rises when serum ionized calcium falls.
Interpret PTH together with calcium, phosphate, vitamin D, and renal function.
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Hyperparathyroidism
Excess PTH secretion; classify as primary, secondary, or tertiary.
Primary
Secondary
Tertiary
Most often a solitary adenoma;
causes high calcium with elevated or
inappropriately normal PTH.
Compensatory PTH elevation,
commonly due to chronic kidney
disease or vitamin D deficiency.
Autonomous PTH secretion after
prolonged secondary
hyperparathyroidism.
Morphology: adenoma or multigland hyperplasia; long-standing disease may affect bone.
Clinical features: nephrolithiasis, bone pain, fractures, constipation, and neurocognitive symptoms.
Classic skeletal lesion: osteitis fibrosa cystica; brown tumors may occur in severe disease.
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Hypoparathyroidism
Insufficient PTH leads to hypocalcemia and hyperphosphatemia.
Causes
Clinical features
Post-surgical parathyroid damage or removal;
autoimmune disease; less commonly congenital
disorders.
Paresthesia, muscle cramps, tetany, and seizures in
severe hypocalcemia.
Typical laboratory pattern: low PTH, low calcium, and high phosphate.
Chvostek and Trousseau signs may be present but are not fully specific.
Severe symptomatic hypocalcemia requires urgent medical treatment.
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13.

Laboratory Comparison
Typical patterns; interpret results in clinical context
Condition
TSH
Free T4
PTH / Calcium
Primary hyperthyroidism
Low
High
—
Primary hypothyroidism
High
Low
—
Primary hyperparathyroidism
—
—
PTH high or inappropriately
normal; Ca high
Hypoparathyroidism
—
—
PTH low; Ca low; phosphate
high
Note: Secondary hyperparathyroidism often has low/normal calcium and high PTH; phosphate varies with the cause.
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High-Yield Morphology: Exam Revision
Link the disease with its characteristic microscopic finding
Graves disease
Hashimoto thyroiditis
Follicular hyperplasia + scalloped colloid
Lymphocytes + germinal centers + Hürthle cells
De Quervain thyroiditis
Hyperparathyroidism
Granulomas + multinucleated giant cells
Bone resorption; osteitis fibrosa cystica in severe disease
Memory aid: Graves = scalloped colloid; Hashimoto = Hürthle cells; De Quervain = giant cells.
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Summary & Viva Questions
Quick review
What is an endocrinopathy? Name three mechanisms of endocrine dysfunction.
What causes Graves disease, and what is its characteristic microscopy?
What are the main microscopic features of Hashimoto thyroiditis?
Differentiate primary hyperparathyroidism from hypoparathyroidism using calcium and PTH.
Name two clinical consequences of severe hyperparathyroidism.
Suggested references: Robbins & Cotran Pathologic Basis of Disease; standard endocrinology and pathology texts.
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