Endocrine system, pathology in detail, lamane lang, from textbook mbbs 3rd yr

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Endocrine pathology (MBBS 3rd year) covers:

Pituitary gland
- Pituitary adenomas
- Hyperpituitarism: acromegaly, gigantism, Cushing disease
- Hypopituitarism
- Diabetes insipidus
Thyroid gland
- Goitre and thyroiditis
- Graves disease
- Hypothyroidism
- Thyroid tumors: papillary, follicular, medullary, and anaplastic carcinoma
Parathyroid glands
- Primary, secondary, and tertiary hyperparathyroidism
- Hypoparathyroidism
- Parathyroid adenoma and hyperplasia
Adrenal glands
- Cushing syndrome
- Primary hyperaldosteronism (Conn syndrome)
- Adrenal insufficiency (Addison disease)
- Pheochromocytoma
- Neuroblastoma and adrenal cortical tumors
Endocrine pancreas
- Diabetes mellitus type 1 and type 2
- Diabetic complications
- Pancreatic neuroendocrine tumors: insulinoma, gastrinoma, etc.
Multiple endocrine neoplasia
- MEN 1
- MEN 2A and MEN 2B

For MBBS pathology, the most exam-relevant approach for every disease is:

Definition -> causes/pathogenesis -> morphology (gross and microscopy) -> clinical features -> investigations -> complications.

I can explain each in simple language with pathology diagrams, histology points, and exam answers.

Which topic should I start in detail with?

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pituitary adenoma AND pathology

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pituitary gland disorders pathology Merck Manual Professional pituitary adenoma hypopituitarism diabetes insipidus

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pituitary adenoma histology uniform cells reticulin stain pathology

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Pituitary gland pathology - MBBS 3rd year

The pituitary gland is a small endocrine gland at the base of the brain, inside a bony space called the sella turcica. It is called the “master gland” because its hormones control thyroid, adrenal glands, ovaries, testes, growth, and lactation.

It has two parts:

Part	Main hormones	Main role
Anterior pituitary (adenohypophysis)	GH, PRL, ACTH, TSH, FSH, LH	Growth, lactation, adrenal, thyroid, reproductive functions
Posterior pituitary (neurohypophysis)	ADH and oxytocin	Water balance and uterine/milk-ejection functions

ADH and oxytocin are actually made in the hypothalamus and stored/released from posterior pituitary.

Hypothalamus controls the anterior pituitary using releasing and inhibiting hormones. Dopamine inhibits prolactin release.
Robbins & Kumar Basic Pathology, pp. 723-724.

1. Clinical effects of pituitary disease

Pituitary disease gives symptoms by three mechanisms:

A. Hormone excess

A functioning pituitary tumor produces excess hormone.

Examples:

Excess PRL -> galactorrhea, amenorrhea
Excess GH -> gigantism or acromegaly
Excess ACTH -> Cushing disease

B. Hormone deficiency

Destruction or compression of normal gland causes hypopituitarism.

C. Mass effect

A large tumor can compress nearby structures.

Important effects:

Headache
Bitemporal hemianopia: loss of outer half of visual field of both eyes due to optic chiasma compression
Nausea/vomiting from raised intracranial pressure
Compression of normal pituitary -> hypopituitarism

Pituitary apoplexy means sudden hemorrhage into a pituitary tumor. It causes sudden severe headache, visual disturbance, altered consciousness, and acute hormonal deficiency. It is an emergency.
Robbins & Kumar Basic Pathology, p. 724.

2. Pituitary adenoma / Pituitary neuroendocrine tumor (PitNET)

Definition

A pituitary adenoma is a benign neoplasm arising from anterior pituitary cells. Modern terminology calls it a pituitary neuroendocrine tumor (PitNET).

It is the commonest cause of hyperpituitarism.

Classification

According to size

Microadenoma: less than 1 cm
Macroadenoma: more than 1 cm

Macroadenomas commonly produce mass effects, such as headache and bitemporal hemianopia.

According to function

Functioning adenoma: secretes a hormone and produces a clinical syndrome
Nonfunctioning adenoma: does not produce clinically obvious hormone excess; usually presents late as a large mass
Silent adenoma: produces hormone demonstrable by immunohistochemistry but does not cause clinical hormonal excess

Pathogenesis

Most are caused by acquired mutations in tumor cells. A common molecular abnormality is mutation in GNAS, causing persistent activation of stimulatory G-protein signaling.

Simple mechanism:

GNAS mutation -> increased cAMP signaling -> increased cell proliferation + increased hormone synthesis

Some pituitary tumors occur in inherited syndromes, especially MEN 1.

Morphology of pituitary adenoma

Gross appearance

Usually soft, well-circumscribed tumor
May expand the sella turcica
Large tumors can compress the optic chiasma and normal pituitary tissue
Large tumors may invade nearby structures

Microscopy

The two classic points for exam:

Monomorphic cells
Tumor cells look very similar to each other, unlike the normal anterior pituitary which contains a mixed population of acidophils, basophils, and chromophobes.
Loss of reticulin network
Normal pituitary has a reticulin framework around cell nests. In adenoma, this framework is disrupted or absent.

One-line morphology answer: Pituitary adenoma shows a monotonous population of uniform pituitary cells with loss of normal reticulin architecture.

Robbins & Kumar Basic Pathology, pp. 725-728.

3. Functioning pituitary adenomas

A. Prolactinoma - lactotroph adenoma

This is a tumor of lactotroph cells that secretes excess prolactin.

Pathogenesis of symptoms

Prolactin inhibits hypothalamic GnRH.

High prolactin -> low GnRH -> low FSH/LH -> hypogonadism

Clinical features in females

Amenorrhea
Oligomenorrhea
Infertility
Galactorrhea: milk secretion not related to normal breastfeeding
Reduced libido

Clinical features in males

Reduced libido
Erectile dysfunction
Infertility
Decreased facial/body hair
Gynecomastia may occur
Often presents late with headache and visual problems because men may not notice hormonal symptoms early

Important point: stalk effect

Compression of the pituitary stalk reduces dopamine delivery from hypothalamus.

Since dopamine normally inhibits prolactin:

Pituitary stalk compression -> less dopamine -> increased prolactin

Thus, a nonfunctioning macroadenoma may produce a mild rise in prolactin without being a true prolactinoma.

B. Somatotroph adenoma - GH-producing adenoma

This tumor secretes excess growth hormone (GH). GH stimulates the liver and other tissues to produce IGF-1, which causes many growth effects.

GH excess -> increased IGF-1 -> abnormal tissue and bone growth

1. Gigantism

Occurs in children, before epiphyseal closure.

Features:

Marked increase in height
Long limbs
Generalized excessive growth

2. Acromegaly

Occurs in adults, after epiphyseal closure. Height cannot increase, so bones and soft tissues become thickened.

Clinical features:

Enlarged hands and feet
Ring and shoe size increase
Coarse facial features
Enlarged nose, lips, tongue
Prognathism: protruding lower jaw
Widely spaced teeth
Thick oily skin and sweating
Headache
Hypertension
Cardiomegaly and heart failure
Arthritis
Glucose intolerance or diabetes mellitus
Increased risk of colonic neoplasia

Diagnosis

Raised serum IGF-1
GH does not suppress after an oral glucose load
MRI of pituitary for tumor

Exam difference:

Gigantism	Acromegaly
Before epiphyseal closure	After epiphyseal closure
Increased height is prominent	Hands, feet, jaw, face enlarge
Child/adolescent	Adult

Robbins & Kumar Basic Pathology, pp. 726-727.

C. Corticotroph adenoma - ACTH-producing adenoma

This tumor secretes excess ACTH.

ACTH excess -> bilateral adrenal cortical hyperplasia -> cortisol excess

The cortisol excess caused specifically by a pituitary ACTH adenoma is called Cushing disease.

Cushing disease versus Cushing syndrome

Cushing syndrome: clinical state due to excess cortisol from any cause
Cushing disease: Cushing syndrome specifically due to a pituitary ACTH-secreting adenoma

Clinical features

Central obesity
Moon face
Buffalo hump
Thin skin and easy bruising
Purple abdominal striae
Proximal muscle weakness
Hypertension
Diabetes/glucose intolerance
Osteoporosis
Infections
Depression or mood changes
Menstrual irregularity
Hyperpigmentation may occur with high ACTH

Robbins & Kumar Basic Pathology, p. 727.

D. Thyrotroph adenoma - TSH-producing adenoma

Rare.

Produces excess TSH, causing:

Hyperthyroidism
Diffuse goitre
Palpitations, sweating, weight loss, tremor

E. Gonadotroph adenoma - FSH/LH-producing adenoma

Usually clinically nonfunctioning because the hormones released may not be biologically active.

Often presents as:

Macroadenoma
Headache
Bitemporal hemianopia
Hypopituitarism

4. Nonfunctioning pituitary adenoma

These do not produce a recognizable hormone-excess syndrome.

They are often detected late because they become large.

Clinical features

Headache
Bitemporal hemianopia
Hypopituitarism due to compression of normal gland
Mild hyperprolactinemia due to stalk effect

High-yield line: A nonfunctioning pituitary adenoma commonly presents with mass effect and hypopituitarism, not hormone excess.

5. Hypopituitarism

Definition

Hypopituitarism means decreased secretion of one or more anterior pituitary hormones.

Causes

1. Tumors and mass lesions

Most important cause:

Nonfunctioning pituitary macroadenoma

Other lesions:

Craniopharyngioma
Metastatic tumor
Hypothalamic tumor

2. Ischemic necrosis

Sheehan syndrome

Postpartum ischemic necrosis of anterior pituitary.

Why does it occur?

During pregnancy:

Anterior pituitary enlarges, mainly due to lactotroph hyperplasia.
Its blood supply does not increase proportionately.
Severe postpartum hemorrhage or hypotension causes ischemia.
Result: anterior pituitary necrosis.

Clinical features of Sheehan syndrome

Failure of lactation after delivery due to low prolactin
Amenorrhea
Loss of pubic and axillary hair
Weakness
Hypothyroidism
Adrenal insufficiency

3. Iatrogenic

Pituitary surgery
Radiotherapy

4. Inflammatory/infiltrative disease

Tuberculosis
Sarcoidosis
Autoimmune hypophysitis

5. Trauma

Head injury

6. Genetic causes

Rare developmental or transcription-factor abnormalities.

Clinical features according to deficient hormone

Hormone deficient	Main clinical effect
GH	Growth failure in children
FSH/LH	Infertility, amenorrhea, low libido, impotence
TSH	Secondary hypothyroidism
ACTH	Secondary adrenal insufficiency
PRL	Failure of postpartum lactation
MSH	Skin pallor

Important difference: primary vs secondary adrenal insufficiency

Feature	Primary adrenal insufficiency	Secondary adrenal insufficiency due to low ACTH
ACTH	High	Low
Skin pigmentation	Increased	Pallor/no hyperpigmentation
Aldosterone	Often low	Usually preserved

Robbins & Kumar Basic Pathology, pp. 728-729.

6. Posterior pituitary disorders

A. Central diabetes insipidus

Definition

Central diabetes insipidus is caused by deficiency of ADH, also called vasopressin.

Normal ADH action

ADH acts on renal collecting ducts and helps reabsorb water.

ADH -> water reabsorption -> concentrated urine

In ADH deficiency

Low ADH -> less water reabsorption -> large volume of dilute urine

Causes

Head trauma
Tumors of hypothalamus/pituitary
Neurosurgery involving pituitary or hypothalamus
Inflammatory disease
Idiopathic disease

Clinical features

Polyuria: excessive urine
Polydipsia: excessive thirst
Large volume of dilute urine
Low urine specific gravity
Hypernatremia
Increased serum osmolality
Severe dehydration if patient cannot access water

Central vs nephrogenic diabetes insipidus

Feature	Central DI	Nephrogenic DI
Basic defect	ADH deficiency	Kidney does not respond to ADH
ADH level	Low	Normal or high
Cause	Hypothalamus/posterior pituitary lesion	Renal tubular resistance
Response to desmopressin	Improves	Little or no improvement

Robbins & Kumar Basic Pathology, p. 729.

B. SIADH - syndrome of inappropriate ADH secretion

Here there is excess ADH, so excess water is retained.

Excess ADH -> water retention -> dilutional hyponatremia -> cerebral edema

Causes

Small-cell carcinoma of lung producing ectopic ADH
CNS disease
Lung disease
Hypothalamic/neurohypophyseal injury

Clinical features

Hyponatremia
Confusion
Seizures
Coma in severe cases
Cerebral edema
Usually no peripheral edema, despite increased total body water

7. Pituitary pathology - quick revision table

Disease	Main defect	Key clinical clue
Prolactinoma	High PRL	Amenorrhea + galactorrhea + infertility
Somatotroph adenoma	High GH/IGF-1	Acromegaly in adults; gigantism in children
Corticotroph adenoma	High ACTH	Cushing disease
Nonfunctioning adenoma	Mass effect	Headache + bitemporal hemianopia
Hypopituitarism	Low anterior pituitary hormones	Multiple hormonal deficiencies
Sheehan syndrome	Postpartum anterior pituitary necrosis	Failure to lactate after severe PPH
Central DI	Low ADH	Polyuria with dilute urine
SIADH	Excess ADH	Hyponatremia with neurologic symptoms

8. Very important viva questions

What is the most common cause of hyperpituitarism?
Anterior pituitary adenoma.
What is the most common functioning pituitary adenoma?
Prolactinoma.
What is the difference between Cushing disease and Cushing syndrome?
Cushing disease is due to a pituitary ACTH adenoma. Cushing syndrome is cortisol excess from any cause.
What visual defect occurs in pituitary macroadenoma?
Bitemporal hemianopia.
What are the two microscopic features of pituitary adenoma?
Cellular monomorphism and loss of reticulin network.
Why does Sheehan syndrome occur?
Postpartum hemorrhage/hypotension causes ischemic necrosis of the enlarged anterior pituitary.
Which pituitary part is more vulnerable in Sheehan syndrome?
Anterior pituitary.
What is central diabetes insipidus?
Polyuria due to ADH deficiency from hypothalamic or posterior pituitary disease.
What is pituitary apoplexy?
Acute hemorrhage into a pituitary tumor causing sudden expansion and possible acute adrenal insufficiency.

Textbook source: Robbins & Kumar Basic Pathology, Endocrine System chapter, pp. 723-729. Current clinical overview is consistent with the Merck pituitary disorders reference.

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thyroid disease pathology

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thyroid disorders pathology Graves Hashimoto thyroid carcinoma Merck Manual Professional

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Hashimoto thyroiditis histology Hürthle cells lymphoid follicles pathology

Bright-field light microscopy of thyroid tissue stained with Hematoxylin and Eosin demonstrates features of Hashimoto thyroiditis. The image shows diffuse lymphocytic infiltration with formation of large lymphoid follicles and well-demarcated germinal centers, consistent with chronic autoimmune thyroiditis. Residual thyroid follicles are small and atrophic, and follicular epithelial cells display prominent oxyphilic (Hurthle cell) change with abundant eosinophilic cytoplasm. Foci of squamous metaplasia and fibrous stromal expansion may be present, reflecting chronicity. The parenchymal architecture is disrupted by mononuclear cell infiltrates, including lymphocytes and plasma cells, with occasional residual colloid-containing follicles. These histologic features correlate with hypothyroid or fluctuating thyroid function and aid in distinguishing autoimmune thyroiditis from other thyroid disorders. Clinically, Hashimoto thyroiditis carries a risk for development of thyroid lymphoma, particularly extranodal marginal zone lymphoma; hence vigilance and multidisciplinary assessment are advised. This slide is a representative teaching example for pathology residents, endocrinology trainees, and head-and-neck oncologic surgeons. It is useful for differential diagnosis, immunohistochemical workup planning, and correlating histology with serology, imaging, and clinical presentation in autoimmune thyroid disease. This description supports researchers seeking biomarkers, educators designing case-based curricula, and clinicians integrating histology with ultrasound, fine-needle aspiration results, and serum antibodies to optimize patient management and therapeutic decisions.

$Light microscopy of thyroid tissue prepared with Hematoxylin and Eosin (H&E) staining shows features consistent with Hashimoto thyroiditis. The specimen arises from the thyroid gland in the cervical region. The slide demonstrates diffuse lymphocytic infiltration with formation of enlarged lymphoid follicles bearing prominent germinal centers, a hallmark of autoimmune thyroiditis. Interspersed are residual thyroid follicles that are small and atrophic, many lined by oncocytic (Hürthle) cells with abundant granular eosinophilic cytoplasm. The architectural disruption of normal thyroid parenchyma and the presence of germinal center-rich lymphoid infiltrates reflect chronic inflammation. These histologic features are classic for Hashimoto thyroiditis and are associated with an increased risk of secondary thyroid lymphoma, notably diffuse large B-cell lymphoma (DLBCL) comprising the majority of lymphomas in this setting, with mucosa-associated lymphoid tissue (MALT) lymphoma accounting for a smaller but meaningful fraction. The image highlights autoimmune etiologies and potential malignant transformation. Clinically, such histology supports autoimmune hypothyroidism in many patients and warrants surveillance for lymphoma development. Diagnostic significance includes correlation with serology (anti-thyroid peroxidase antibodies) and thyroid function tests, and may guide therapeutic decisions, including consideration of targeted biopsy in suspicious cases. These features aid educational teaching and differential diagnosis for pathology trainees in practice and research.$

Light microscopy of thyroid tissue prepared with Hematoxylin and Eosin (H&E) staining shows features consistent with Hashimoto thyroiditis. The specimen arises from the thyroid gland in the cervical region. The slide demonstrates diffuse lymphocytic infiltration with formation of enlarged lymphoid follicles bearing prominent germinal centers, a hallmark of autoimmune thyroiditis. Interspersed are residual thyroid follicles that are small and atrophic, many lined by oncocytic (Hürthle) cells with abundant granular eosinophilic cytoplasm. The architectural disruption of normal thyroid parenchyma and the presence of germinal center-rich lymphoid infiltrates reflect chronic inflammation. These histologic features are classic for Hashimoto thyroiditis and are associated with an increased risk of secondary thyroid lymphoma, notably diffuse large B-cell lymphoma (DLBCL) comprising the majority of lymphomas in this setting, with mucosa-associated lymphoid tissue (MALT) lymphoma accounting for a smaller but meaningful fraction. The image highlights autoimmune etiologies and potential malignant transformation. Clinically, such histology supports autoimmune hypothyroidism in many patients and warrants surveillance for lymphoma development. Diagnostic significance includes correlation with serology (anti-thyroid peroxidase antibodies) and thyroid function tests, and may guide therapeutic decisions, including consideration of targeted biopsy in suspicious cases. These features aid educational teaching and differential diagnosis for pathology trainees in practice and research.

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Thyroid gland pathology - MBBS 3rd year

The thyroid gland lies in the front of the neck, below the larynx. It has two lobes connected by an isthmus.

Its functional unit is the thyroid follicle.

Follicular cells make thyroid hormones: T3 and T4
Follicle lumen contains colloid, mainly thyroglobulin
Parafollicular or C cells make calcitonin

Normal axis

Hypothalamus (TRH) -> Pituitary (TSH) -> Thyroid gland (T3, T4)

T3 and T4 increase metabolic activity, heat production, growth, and development.

Main thyroid disorders

Hyperthyroidism
Hypothyroidism
Thyroiditis
- Hashimoto thyroiditis
- Subacute granulomatous thyroiditis
- Painless/postpartum thyroiditis
Goitre
Thyroid tumors
- Follicular adenoma
- Papillary carcinoma
- Follicular carcinoma
- Medullary carcinoma
- Anaplastic carcinoma

1. Hyperthyroidism / Thyrotoxicosis

Definition

Thyrotoxicosis means clinical effects of excess circulating thyroid hormone.

Hyperthyroidism means excessive production of T3/T4 by the thyroid gland itself.

Common causes

Graves disease - most common
Toxic multinodular goitre
Toxic adenoma
Thyroiditis, where preformed hormone leaks from damaged follicles
Rarely, TSH-secreting pituitary adenoma

Clinical features

Excess thyroid hormone causes a hypermetabolic state:

Weight loss despite increased appetite
Heat intolerance
Sweating
Warm, moist skin
Palpitations and tachycardia
Tremor
Anxiety, irritability
Hyperreflexia
Diarrhea
Proximal muscle weakness
Menstrual disturbances
In elderly patients: atrial fibrillation or heart failure may occur

Lab pattern in primary hyperthyroidism:

T3/T4 high + TSH low

Thyroid storm

Sudden severe thyrotoxicosis, often triggered by infection, surgery, trauma, or stopping antithyroid drugs.

Features:

High fever
Severe tachycardia/arrhythmia
Delirium or coma
Heart failure

It is a medical emergency.
Robbins & Kumar Basic Pathology, pp. 729-730.

2. Graves disease

Definition

Graves disease is an autoimmune disease causing diffuse enlargement and hyperfunction of the thyroid gland.

It is the commonest cause of hyperthyroidism.

Pathogenesis

The body makes TSH receptor-stimulating antibodies, also called thyroid-stimulating immunoglobulins.

These antibodies act like TSH:

TSH receptor antibody -> continuous stimulation of thyroid -> diffuse hyperplasia -> increased T3/T4

Although T3/T4 are high, actual pituitary TSH is low because of negative feedback.

Clinical triad

Hyperthyroidism
Diffuse goitre
Ophthalmopathy

Some cases also have pretibial myxedema.

Clinical features

Besides general hyperthyroid symptoms:

Diffuse, soft thyroid enlargement
Exophthalmos/proptosis
Lid lag and staring look
Diplopia due to eye muscle involvement
Pretibial myxedema: thickened skin over shins
Thyroid acropachy, rarely: clubbing and swelling of fingers

Why does exophthalmos occur?

Autoimmune T cells activate fibroblasts in orbital tissues.

This causes:

Glycosaminoglycan deposition
Edema
Fibrosis
Enlargement of extraocular muscles and retro-orbital tissue

Therefore, the eyeball is pushed forward.

Morphology

Gross

Diffuse, symmetrical enlargement of thyroid
Soft, fleshy, red-brown gland

Microscopy

Diffuse hypertrophy and hyperplasia of follicular cells
Follicular lining cells become tall and crowded
Papillary infoldings project into colloid
Colloid becomes pale and shows scalloped margins due to active resorption
Lymphoid infiltrate may be present

Important differentiation

Graves disease	Toxic multinodular goitre
Autoimmune	Usually due to long-standing nodular goitre
Diffuse enlargement	Multiple nodules
TSH receptor antibodies present	Antibodies usually absent
Ophthalmopathy common	Ophthalmopathy absent
Pretibial myxedema can occur	Absent

Robbins & Kumar Basic Pathology, pp. 732-733.

3. Hypothyroidism

Definition

Hypothyroidism means deficient production of thyroid hormones.

Causes

Primary hypothyroidism: problem is in thyroid gland

Hashimoto thyroiditis
Iodine deficiency
Surgical removal of thyroid
Radioiodine therapy
Drugs such as lithium
Congenital thyroid dysgenesis
Dyshormonogenesis

Secondary hypothyroidism: pituitary failure

Low TSH due to pituitary disease

Tertiary hypothyroidism: hypothalamic failure

Low TRH

Laboratory pattern

Type	T3/T4	TSH
Primary hypothyroidism	Low	High
Secondary/tertiary hypothyroidism	Low	Low or inappropriately normal

Clinical features in adults: myxedema

Fatigue and lethargy
Weight gain
Cold intolerance
Constipation
Dry, coarse skin
Puffy face
Hair loss
Slow speech and thinking
Depression
Bradycardia
Reduced cardiac output
Raised cholesterol
Menstrual irregularities
Hoarse voice

Myxedema results from deposition of hydrophilic glycosaminoglycans in skin and soft tissues. This causes non-pitting puffiness.

Congenital hypothyroidism

If untreated early in life, it causes:

Severe intellectual disability
Growth retardation
Short stature
Coarse facial features
Large protruding tongue
Umbilical hernia

Early diagnosis and treatment prevent permanent neurodevelopmental damage.
Robbins & Kumar Basic Pathology, pp. 730-731.

4. Thyroiditis

Thyroiditis means inflammation of the thyroid gland.

A. Hashimoto thyroiditis

Also called chronic lymphocytic thyroiditis.

Definition

An autoimmune disease in which immune cells progressively destroy thyroid follicles. It is a common cause of hypothyroidism where iodine intake is sufficient.

Usually occurs in middle-aged women.

Pathogenesis

Autoimmunity against thyroid antigens, especially:

Anti-thyroid peroxidase antibodies: anti-TPO
Anti-thyroglobulin antibodies

Main mechanisms of follicular cell destruction:

CD8+ cytotoxic T-cell-mediated injury
Cytokine-mediated damage
Antibody/complement-related injury

Autoimmune response -> follicular destruction -> reduced T3/T4 -> raised TSH -> hypothyroidism

Morphology

Gross

Usually diffuse, painless, symmetrical thyroid enlargement initially
In late stages, gland may become small and fibrotic

Microscopy - very important

Dense lymphocytic and plasma-cell infiltration
Lymphoid follicles with germinal centres
Atrophic thyroid follicles
Hürthle cell change
Interstitial fibrosis

Hürthle cells

These are injured follicular cells with:

Large size
Abundant granular eosinophilic cytoplasm
Many mitochondria

Hashimoto thyroiditis histology: lymphoid follicles with germinal centres, atrophic thyroid follicles, and Hürthle-cell change

Clinical features

Painless goitre
Gradually developing hypothyroidism
Fatigue and weight gain
Cold intolerance
Constipation
Raised anti-TPO antibody levels
May have a short early thyrotoxic phase due to leakage of stored hormones

Complications

Permanent hypothyroidism
Increased risk of B-cell lymphoma, especially MALT lymphoma of thyroid

One-line exam answer: Hashimoto thyroiditis is an autoimmune destruction of the thyroid characterized by lymphoid follicles with germinal centres, Hürthle-cell metaplasia, follicular atrophy, and fibrosis.

Robbins & Kumar Basic Pathology, pp. 731-732.

B. Subacute granulomatous thyroiditis

Also called de Quervain thyroiditis.

Cause

Usually follows a viral infection or postviral inflammatory reaction.

Clinical features

Painful, tender thyroid swelling
Fever and malaise
Neck pain may radiate to jaw or ear
Initially transient hyperthyroidism due to release of stored hormone
Later temporary hypothyroidism may occur
Usually recovers completely

Microscopy

Disruption of thyroid follicles
Colloid leakage
Granulomatous inflammation
Multinucleated giant cells surrounding colloid

Key difference from Hashimoto: de Quervain thyroiditis is painful and shows granulomas with giant cells. Hashimoto is painless and shows lymphoid follicles with Hürthle cells.

C. Painless/postpartum thyroiditis

Autoimmune thyroiditis
Painless thyroid enlargement
Often occurs postpartum in women
Transient hyperthyroid phase followed by hypothyroid phase
Lymphocytic infiltration but little/no Hürthle cell change compared with Hashimoto

5. Goitre

Definition

A goitre is enlargement of the thyroid gland.

It may occur in euthyroid, hypothyroid, or hyperthyroid states.

A. Diffuse nontoxic goitre

Mainly caused by iodine deficiency or impaired hormone synthesis.

Mechanism

Low thyroid hormone production -> increased TSH -> thyroid hyperplasia and enlargement

Initially, the gland enlarges diffusely.

B. Multinodular goitre

Repeated cycles of hyperplasia and involution lead to irregular nodules.

Morphology

Gross

Enlarged gland with multiple nodules
Areas of hemorrhage, cystic degeneration, fibrosis, and calcification may occur

Microscopy

Follicles vary in size
Some follicles are dilated and filled with colloid
Others are hyperplastic
Fibrosis, hemorrhage, and cystic changes may be seen

Multinodular goitre showing an enlarged nodular gland and colloid-filled follicles

Clinical features

Slowly enlarging neck mass
Usually euthyroid initially
Cosmetic concern
Compression symptoms in large goitre:
- Dysphagia
- Dyspnea
- Hoarseness
- Superior vena cava obstruction, rarely
May become toxic and cause hyperthyroidism: toxic multinodular goitre

Robbins & Kumar Basic Pathology, pp. 733-734.

6. Thyroid neoplasms

Important clinical clues suggesting malignancy in thyroid nodule

Solitary nodule
Nodule in male patient
Nodule in child or young person
History of neck irradiation
Rapid increase in size
Hoarseness or vocal cord palsy
Cervical lymph node enlargement
Cold nodule on radioactive iodine scan

The definitive assessment is by fine-needle aspiration cytology (FNAC) and, where required, histopathology.
Robbins & Kumar Basic Pathology, pp. 734-735.

A. Follicular adenoma

Definition

A benign, solitary tumor arising from thyroid follicular epithelium.

Morphology

Solitary, well-circumscribed, encapsulated lesion
Uniform follicles containing colloid
Compresses adjacent thyroid tissue
No capsular invasion
No vascular invasion

Important point

Follicular adenoma cannot be differentiated from follicular carcinoma by cytology alone because the diagnosis of carcinoma requires demonstration of capsular or vascular invasion.

Some may be toxic adenomas and produce excess thyroid hormone.

7. Thyroid carcinomas

Type	Cell of origin	Main spread	Key clue
Papillary carcinoma	Follicular cells	Lymphatics	Orphan Annie eye nuclei, nuclear grooves, psammoma bodies
Follicular carcinoma	Follicular cells	Blood	Capsular/vascular invasion
Medullary carcinoma	C cells	Lymph nodes/blood	Calcitonin, amyloid stroma, RET/MEN 2
Anaplastic carcinoma	Follicular cells	Local invasion/metastasis	Very aggressive tumor in elderly

A. Papillary thyroid carcinoma

This is the commonest thyroid carcinoma.

Risk factors

Ionizing radiation, especially in childhood
Genetic alterations involving:
- BRAF
- RET/PTC rearrangements
- NTRK fusions
- RAS mutations

Morphology

Gross

Solitary or multifocal tumor
May be well circumscribed or infiltrative

Microscopy - very important

Papillae with fibrovascular cores
Orphan Annie eye nuclei or ground-glass nuclei
Nuclear grooves
Intranuclear cytoplasmic inclusions
Psammoma bodies: laminated calcified bodies

Papillary thyroid carcinoma showing papillae and characteristic clear nuclei

Clinical features

Painless thyroid nodule
Usually euthyroid
Cervical lymph-node metastasis may be present
Spreads mainly by lymphatics

Prognosis

Generally excellent, especially in younger patients.

Most important diagnostic feature: nuclear characteristics, not necessarily papillary architecture.

Robbins & Kumar Basic Pathology, pp. 736-737.

B. Follicular thyroid carcinoma

Definition

Malignant tumor of follicular cells.

Pathogenesis

Often associated with:

RAS mutations
PI3K/AKT pathway mutations
PAX8-PPARG rearrangement

Morphology

It may look similar to follicular adenoma.

The diagnosis depends on:

Capsular invasion
Vascular invasion

A lesion with follicles but no capsular or vascular invasion is usually follicular adenoma, not carcinoma.

Spread

Spreads mainly through the bloodstream:

Bone
Lungs
Liver

Lymph-node spread is less common than in papillary carcinoma.

Viva point: Papillary carcinoma spreads through lymphatics. Follicular carcinoma spreads hematogenously.

C. Medullary thyroid carcinoma

Origin

Arises from parafollicular C cells, not from follicular cells.

C cells produce calcitonin.

Types

Sporadic
Familial, associated with MEN 2A and MEN 2B

Familial tumors are associated with germline RET mutations.

Morphology

Nests, trabeculae, or sheets of tumor cells
Amyloid deposits in stroma, derived from altered calcitonin molecules
Amyloid is Congo-red positive

Clinical features

Thyroid mass
Raised calcitonin
Diarrhea or flushing may occur due to hormone secretion
In MEN 2, evaluate for pheochromocytoma and hyperparathyroidism, depending on subtype

High-yield line: Medullary carcinoma arises from C cells, secretes calcitonin, shows amyloid in stroma, and may be associated with RET mutation/MEN 2.

D. Anaplastic thyroid carcinoma

Definition

An undifferentiated thyroid carcinoma. It is rare but extremely aggressive.

Usually occurs in elderly patients.

Clinical features

Rapidly enlarging neck mass
Dyspnea
Dysphagia
Hoarseness
Early local invasion
Distant metastasis

Morphology

Highly pleomorphic cells
Spindle cells and giant cells
Numerous mitoses
Necrosis
No useful thyroid differentiation

Prognosis

Very poor. Death may occur within months due to local compression or metastasis.

Quick revision: thyroid pathology

Disease	Key cause/pathogenesis	Key pathology finding	Important clue
Graves disease	TSH receptor-stimulating antibodies	Diffuse hyperplasia, scalloped colloid	Hyperthyroidism + eye signs
Hashimoto thyroiditis	Autoimmune follicular destruction	Lymphoid follicles, Hürthle cells	Painless goitre + hypothyroidism
de Quervain thyroiditis	Viral/postviral inflammation	Granulomas with giant cells	Painful tender thyroid
Multinodular goitre	Repeated TSH-driven hyperplasia/involution	Multiple nodules, colloid, hemorrhage, fibrosis	Large irregular thyroid
Follicular adenoma	Benign follicular neoplasm	Encapsulated follicular lesion	No invasion
Papillary carcinoma	BRAF/RET/NTRK pathway abnormalities	Orphan Annie nuclei, grooves, psammoma bodies	Lymphatic spread
Follicular carcinoma	RAS/PI3K pathway changes	Capsular/vascular invasion	Blood spread to bone/lung
Medullary carcinoma	C-cell tumor, RET in familial cases	Amyloid stroma	Calcitonin, MEN 2
Anaplastic carcinoma	Highly undifferentiated malignancy	Pleomorphism, giant cells, necrosis	Elderly, rapidly enlarging mass

Most asked viva questions

Most common thyroid carcinoma?
Papillary thyroid carcinoma.
Most common cause of hypothyroidism in iodine-sufficient areas?
Hashimoto thyroiditis.
Most common cause of hypothyroidism worldwide?
Iodine deficiency.
Characteristic cells of Hashimoto thyroiditis?
Hürthle cells.
Histological hallmark of papillary carcinoma?
Orphan Annie eye nuclei, nuclear grooves, intranuclear inclusions, and psammoma bodies.
How is follicular carcinoma distinguished from follicular adenoma?
By capsular and/or vascular invasion.
Which thyroid cancer spreads by blood?
Follicular carcinoma.
Which thyroid cancer is associated with calcitonin and amyloid?
Medullary thyroid carcinoma.
Which thyroid cancer is associated with MEN 2?
Medullary thyroid carcinoma.
Which thyroiditis is painful?
Subacute granulomatous/de Quervain thyroiditis.

Textbook source: Robbins & Kumar Basic Pathology, Endocrine System chapter, pp. 729-740.

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hyperparathyroidism pathology

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hyperparathyroidism hypoparathyroidism pathology Merck Manual Professional

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parathyroid adenoma histology normal rim pathology

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osteitis fibrosa cystica brown tumor hyperparathyroidism bone pathology

This histopathology image depicts an osteitis fibrosa cystica (brown tumor) within bone in the setting of hyperparathyroidism. The center shows a zone of bone resorption with loss of normal trabecular architecture, replaced by a fibrous, cellular stroma. The lesion is filled with fibrous tissue containing spindle-shaped fibroblasts and occasional osteoclast-type giant cells and hemorrhagic debris; the periphery demonstrates osteoid production forming an immature woven bone matrix with a fibrous dysplasia-like appearance. The overall pattern includes a mixture of radiating fibrous tissue and newly formed osteoid at the margins, which mimics fibrous dysplasia. The histologic spectrum reflects exuberant bone remodeling driven by excess parathyroid hormone, with interspersed areas of osteoclast resorption and fibrous tissue that may produce cystic spaces. Clinically, such brown tumors are part of osteitis fibrosa cystica and signal advanced hyperparathyroidism; identification on biopsy prompts evaluation of parathyroid function and calcium-phosphate homeostasis. Differential considerations include fibrous dysplasia, giant cell-rich lesions, and osseous metastases; however, the association with systemic hyperparathyroidism and parathyroid dysfunction supports the diagnosis. This image is relevant for medical students, pathology residents, and clinicians assessing metabolic bone disease, surgical planning, and educational case reviews.

$This anteroposterior (AP) radiograph of the right shoulder region demonstrates significant skeletal pathology of the clavicle. The image reveals a focal, expansile cystic lesion characterized by a well-defined area of radiolucency (decreased bone density) within the shaft of the clavicle. This lesion, consistent with osteitis fibrosa cystica (brown tumor), has caused marked thinning of the overlying cortical bone. A clear discontinuity in the cortical margin is visible through the lesion, signifying a pathologic fracture. The surrounding bone shows generalized osteopenia. This finding is a classic skeletal manifestation of primary hyperparathyroidism, where excessive parathyroid hormone leads to increased osteoclastic activity and the replacement of bone marrow with fibrous tissue and cystic vascular spaces.$

This anteroposterior (AP) radiograph of the right shoulder region demonstrates significant skeletal pathology of the clavicle. The image reveals a focal, expansile cystic lesion characterized by a well-defined area of radiolucency (decreased bone density) within the shaft of the clavicle. This lesion, consistent with osteitis fibrosa cystica (brown tumor), has caused marked thinning of the overlying cortical bone. A clear discontinuity in the cortical margin is visible through the lesion, signifying a pathologic fracture. The surrounding bone shows generalized osteopenia. This finding is a classic skeletal manifestation of primary hyperparathyroidism, where excessive parathyroid hormone leads to increased osteoclastic activity and the replacement of bone marrow with fibrous tissue and cystic vascular spaces.

This composite of diagnostic images illustrates systemic skeletal manifestations of primary hyperparathyroidism. Images (a) and (b) are axial and sagittal CT scans of the left knee, revealing a prominent osteolytic, cyst-like lesion within the patella. The lesion exhibits a polylobate internal structure, regular borders, significant cortical thinning, and localized erosion, characteristic of a brown tumor. Image (c) is a lateral skull radiograph (X-ray) demonstrating the classic 'salt-and-pepper' appearance of the cranial vault. This sign is produced by multiple small, diffuse, punctate lucencies caused by trabecular resorption and replacement with fibrous tissue. Together, these findings highlight the generalized demineralization and focal bone lesions associated with hyperparathyroid-induced osteitis fibrosa cystica. The educational focus is on identifying systemic radiologic correlates of parathyroid pathology beyond common oral manifestations.

Parathyroid gland pathology - MBBS 3rd year

The parathyroid glands are usually four small glands located behind the thyroid gland. Their main hormone is parathyroid hormone (PTH).

Main function of PTH

PTH maintains blood calcium level.

When blood calcium falls:

Low calcium -> increased PTH -> blood calcium rises

PTH raises blood calcium by:

Bone: increases bone resorption, releasing calcium.
Kidney: increases calcium reabsorption, so less calcium is lost in urine.
Kidney: increases phosphate excretion, so serum phosphate falls.
Vitamin D activation: activates vitamin D in kidney, increasing intestinal calcium absorption.

Net effect of PTH

Effect	Result
Serum calcium	Increased
Serum phosphate	Decreased
Urinary phosphate	Increased
Bone resorption	Increased

Robbins & Kumar Basic Pathology, p. 741.

1. Hyperparathyroidism

Definition

Hyperparathyroidism means excessive secretion of PTH.

This causes:

High PTH -> hypercalcemia + hypophosphatemia + increased bone resorption

There are three forms:

Primary hyperparathyroidism
Secondary hyperparathyroidism
Tertiary hyperparathyroidism

2. Primary hyperparathyroidism

Definition

Primary hyperparathyroidism is excess PTH secretion due to a problem within the parathyroid gland itself.

It is an important cause of hypercalcemia.

Causes

Cause	Approximate frequency
Parathyroid adenoma	85% to 95%
Parathyroid hyperplasia	5% to 10%
Parathyroid carcinoma	About 1%

A. Parathyroid adenoma

A parathyroid adenoma is a benign tumor of parathyroid cells. It usually affects one gland only.

Pathogenesis

Important molecular abnormalities:

Cyclin D1 overexpression
MEN1 mutation

Morphology

Gross

Solitary
Well-circumscribed
Soft, tan or reddish-brown nodule
Usually surrounded by a thin capsule
Other parathyroid glands are normal or atrophic due to suppression by high calcium

Microscopy

Mainly proliferation of chief cells
Little or absent stromal fat
A rim of compressed normal parathyroid tissue may be present at the edge
Mild nuclear pleomorphism, called endocrine atypia, may occur but does not mean cancer
Mitoses are rare

High-yield difference: Parathyroid adenoma is usually a single-gland lesion, while parathyroid hyperplasia usually involves multiple glands.

B. Parathyroid hyperplasia

In primary hyperparathyroidism, hyperplasia may be sporadic or part of MEN syndromes.

Morphology

Usually all four glands are enlarged
May be diffuse or nodular
Chief-cell hyperplasia is common
Stromal fat is reduced

Association

MEN 1
MEN 2A
Familial hyperparathyroidism

C. Parathyroid carcinoma

Very rare cause of primary hyperparathyroidism.

Clinical clue

It tends to produce very severe hypercalcemia and markedly elevated PTH.

Morphology

Large, firm gray-white mass
Thick fibrous capsule
Cells may look rather uniform, so cytology alone cannot reliably diagnose malignancy

Definitive evidence of carcinoma

Invasion into surrounding tissue
Vascular invasion
Metastasis

Do not diagnose parathyroid carcinoma only by pleomorphism. Invasion or metastasis is needed.

Clinical features of primary hyperparathyroidism

Many patients are found incidentally on serum calcium testing.

Classical mnemonic:

Stones, bones, abdominal groans, and psychic moans

1. Renal features: stones

Hypercalciuria
Renal stones: nephrolithiasis
Calcium deposition in kidney: nephrocalcinosis
Renal impairment in severe disease

2. Skeletal features: bones

Bone pain
Osteoporosis
Fractures
Osteitis fibrosa cystica
Brown tumors

3. Gastrointestinal features: abdominal groans

Constipation
Abdominal pain
Peptic ulcer disease
Pancreatitis, occasionally

4. Neuropsychiatric features: psychic moans

Fatigue
Weakness
Depression
Poor concentration
Confusion, especially in severe hypercalcemia

Laboratory findings

Investigation	Finding in primary hyperparathyroidism
PTH	High
Serum calcium	High
Serum phosphate	Low
Urinary calcium	Usually high
Alkaline phosphatase	May be high if bone disease is active

Bone pathology in hyperparathyroidism

PTH indirectly increases osteoclast activity. Continuous excess PTH causes bone resorption.

Osteitis fibrosa cystica

This is severe skeletal disease due to long-standing hyperparathyroidism.

Features:

Cortical bone thinning
Increased osteoclastic resorption
Marrow replaced by fibrous tissue
Hemorrhage and cyst-like spaces
Bone becomes weak and prone to fracture

Brown tumor

A brown tumor is not a true neoplasm.

It is a localized mass formed by:

Osteoclast-type giant cells
Fibrous tissue
Hemorrhage
Hemosiderin pigment, which gives the brown color

Brown tumor in hyperparathyroidism: fibrous tissue, giant cells, hemorrhage, and bone resorption

One-line answer: Brown tumors are giant-cell-rich, hemorrhagic lesions of osteitis fibrosa cystica caused by prolonged hyperparathyroidism.

Robbins & Kumar Basic Pathology, pp. 742-743.

3. Secondary hyperparathyroidism

Definition

Secondary hyperparathyroidism is compensatory PTH overproduction due to chronic hypocalcemia.

The parathyroid gland is initially normal but becomes hyperplastic because it is continuously stimulated.

Most common cause

Chronic kidney disease (CKD) is the most important cause.

Pathogenesis in chronic renal failure

In CKD:

Kidney cannot excrete phosphate properly
CKD -> phosphate retention -> high serum phosphate
Phosphate binds calcium
High phosphate -> low free calcium
Diseased kidneys cannot activate vitamin D adequately
Low active vitamin D -> reduced intestinal calcium absorption
Low calcium stimulates parathyroid glands
Low calcium -> increased PTH -> parathyroid hyperplasia

Simple flowchart

Chronic renal failure -> phosphate retention + low active vitamin D -> hypocalcemia -> increased PTH -> secondary hyperparathyroidism

Other causes

Vitamin D deficiency
Intestinal malabsorption
Low dietary calcium

Laboratory findings in renal secondary hyperparathyroidism

Investigation	Finding
PTH	High
Calcium	Low or normal
Phosphate	High in CKD
Vitamin D	Low
Alkaline phosphatase	Often high

Morphology

Usually involves all parathyroid glands
Diffuse or nodular chief-cell hyperplasia
Reduced fat in glands

Skeletal lesion

Long-standing secondary hyperparathyroidism due to CKD produces renal osteodystrophy.

It includes:

Osteitis fibrosa cystica
Osteomalacia due to vitamin D deficiency
Osteosclerosis
Growth retardation in children

4. Tertiary hyperparathyroidism

Definition

Tertiary hyperparathyroidism occurs when long-standing secondary hyperparathyroidism becomes autonomous.

The hyperplastic parathyroid glands start secreting PTH even after the original stimulus has improved, such as after renal transplantation.

Flowchart

Long-standing CKD -> secondary hyperparathyroidism -> persistent gland hyperplasia -> autonomous PTH secretion -> tertiary hyperparathyroidism

Laboratory findings

Condition	PTH	Calcium	Phosphate
Primary hyperparathyroidism	High	High	Low
Secondary HPT due to CKD	High	Low/normal	High
Tertiary hyperparathyroidism	Very high	High	Often high in CKD

5. Hypoparathyroidism

Definition

Hypoparathyroidism is decreased PTH secretion.

This produces:

Low PTH -> hypocalcemia + hyperphosphatemia

Causes

Accidental removal or damage during thyroid surgery
Most common acquired cause.
Autoimmune destruction of parathyroid glands
Congenital absence or underdevelopment
Example: DiGeorge syndrome
Radiation injury
Severe magnesium deficiency can impair PTH secretion/action

Clinical features

Symptoms are due to hypocalcemia causing increased neuromuscular excitability.

Tingling around mouth
Tingling in fingers and toes
Muscle cramps
Carpopedal spasm
Tetany
Seizures
Laryngospasm in severe cases

Clinical signs

Chvostek sign

Tapping over facial nerve causes twitching of facial muscles.

Trousseau sign

Inflating a blood-pressure cuff causes carpal spasm.

Laboratory findings

Investigation	Finding in hypoparathyroidism
PTH	Low
Serum calcium	Low
Serum phosphate	High
Alkaline phosphatase	Usually normal

The current Merck reference on hypoparathyroidism also describes hypocalcemia, hyperphosphatemia, paresthesia, cramps, and tetany as key findings.

Primary versus secondary hyperparathyroidism

Feature	Primary HPT	Secondary HPT
Basic problem	Autonomous parathyroid disease	Chronic low calcium stimulus
Common cause	Single parathyroid adenoma	Chronic kidney disease
PTH	High	High
Calcium	High	Low or normal
Phosphate	Low	High in CKD
Gland involvement	Usually one gland in adenoma	Usually all glands hyperplastic
Bone lesion	Osteitis fibrosa cystica, brown tumors	Renal osteodystrophy

Short notes for exams

Write a short note on parathyroid adenoma

Parathyroid adenoma is a benign neoplasm of chief cells and is the commonest cause of primary hyperparathyroidism. It is usually solitary and involves one parathyroid gland. Grossly, it is a well-circumscribed, soft tan nodule. Microscopically, it consists predominantly of chief cells with little stromal fat. A rim of compressed normal parathyroid tissue may be seen at the periphery. It causes increased PTH secretion, leading to hypercalcemia, hypophosphatemia, renal stones, bone resorption, osteoporosis, and osteitis fibrosa cystica.

Write a short note on secondary hyperparathyroidism

Secondary hyperparathyroidism is compensatory PTH excess caused by chronic hypocalcemia. The commonest cause is chronic kidney disease. Renal phosphate retention and decreased activation of vitamin D reduce serum calcium, which chronically stimulates all parathyroid glands. The glands show diffuse or nodular chief-cell hyperplasia. PTH is high, calcium is low or normal, and phosphate is typically high in chronic renal failure. Long-standing disease may cause renal osteodystrophy.

Viva questions

What is the main function of PTH?
To increase ionized serum calcium.
Commonest cause of primary hyperparathyroidism?
Parathyroid adenoma.
Commonest cause of secondary hyperparathyroidism?
Chronic kidney disease.
What is the difference between primary and tertiary hyperparathyroidism?
Primary is autonomous PTH secretion due to primary gland disease. Tertiary occurs when long-standing secondary hyperparathyroidism becomes autonomous.
What are brown tumors?
Giant-cell-rich, hemorrhagic lesions in severe hyperparathyroidism. They are not true tumors.
Which parathyroid cells produce PTH?
Chief cells.
Most common cause of acquired hypoparathyroidism?
Accidental damage/removal during thyroid surgery.
Laboratory findings in hypoparathyroidism?
Low PTH, low calcium, high phosphate.
Which gene is associated with familial parathyroid tumors?
MEN1.
What confirms parathyroid carcinoma?
Invasion of adjacent tissues or metastasis.

Textbook source: Robbins & Kumar Basic Pathology, Endocrine System chapter, pp. 741-744.

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