Endocrine Disorders Quiz

Endocrine Pathology II - Thyroid and Parathyroid Pathology

• The course is for Year 2 Pathology students
• The lecturer is Dr Helen Barrett
• The date of the lecture is January 10th, 2025

Learning Outcomes

• Identify the histological features of a normal thyroid gland
• List causes of hypo and hyperthyroidism
• Describe and illustrate pathological features of neoplastic and non-neoplastic thyroid lesions (including thyroiditis)
• Explain the usefulness and limitations of thyroid FNA
• Classify thyroid tumours and outline key clinical features and presentation
• List the aetiological factors in the development of thyroid carcinoma
• Identify the histological features of normal parathyroid glands
• List causes of hypo and hyperparathyroidism
• Discuss Multiple Endocrine Neoplasia (MEN)

Endocrine System

• Pure endocrine organs include the pituitary, thyroid, parathyroid, and adrenal glands
• Endocrine components are in mixed organs such as the pancreas, ovaries, and testes

Disease in Endocrine Organs

• Disease in endocrine organs often presents via hyperfunction, hypofunction, or enlargement/mass effect

Thyroid Gland

• Develops via the thyroglossal duct
• Typically weighs 20-25g
• Composed of two large lateral lobes connected by an isthmus
• Potential developmental anomalies include aplasia/hypoplasia (rare) and heterotopic thyroid tissue (in unusual locations) as well as thyroglossal duct cysts (near the hyoid bone)

Thyroid Gland - Histologically

• Follicular cells produce thyroid hormones
• Parafollicular (C) cells produce calcitonin
• T3 (triiodothyronine) is more active than T4 (thyroxine)
• Thyroid function tests include T4, T3, TSH, and antibodies to thyroid/thyroglobulin

Graves' Disease

• An autoimmune disorder causing hyperthyroidism
• Predominantly affects females (M:F = 1:5)
• Typically develops between the ages of 15 and 40
• Often has a familial tendency
• involves IgG autoantibodies targeting the TSH receptor, increasing thyroid hormone release
• Macroscopically, characterized by diffuse enlargement
• Microscopically, displays star-shaped follicles, reduced colloid, increased lymphocytes
• Clinical features include hyperthyroidism, exophthalmos (eye bulging), and potential dermopathy (pretibial myxedema)

Hyperthyroidism

• Primary causes include Graves' disease, toxic multinodular goitre, toxic adenoma, and toxic carcinoma
• Secondary causes include TSH-releasing pituitary adenomas (rare) and other thyroiditis types, as well as exogenous thyroxine ingestion, or struma ovarii (ovarian teratoma)
• Symptoms in elderly can include “apathetic hyperthyroidism” and worsened cardiac insufficiency
• Generalized symptoms include heat intolerance, weight loss despite increased appetite, tachycardia, palpitations, hypermotile GI symptoms, tremor, irritability, proximal muscle weakness
• "Thyroid storm" involves abrupt, severe hyperthyroidism, requiring medical emergency intervention, typically due to underlying Graves' disease

Hypothyroidism

• Primary causes include Hashimoto thyroiditis, iodine deficiency, and dyshormonogenic conditions (congenital synthesis defects)
• Secondary causes include pituitary/hypothalamic dysfunction
• Symptoms in adults generally include apathy, mental sluggishness, intolerance to cold, swelling of face/tongue, hoarseness, and myxedema
• Childhood symptoms include these adult symptoms, plus impaired skeletal development, intellectual disability, and cretinism

Hashimoto's Thyroiditis

• An autoimmune condition where the immune system attacks the thyroid
• Typically occurs in middle-aged individuals, with a predominance in females
• Histologically characterized by lymphocytic infiltration, with reactive germinal centers, and cellular changes in follicles
• Clinically, may begin as euthyroid, progress to hypothyroid, and rarely show transient hyperthyroidism (Hashitoxicosis).

Thyroiditis

• A group of disorders associated with thyroid inflammation
• Autoimmune forms like Graves' and Hashimoto's are common
• De Quervain's thyroiditis is subacute, granulomatous, often preceded by an upper RTI, and most patients recover euthyroid within 6-8 weeks, often presenting with sudden painful enlargement and fever

Thyroid Enlargement

• Common causes include simple/multinodular goitre (diffuse gland involvement, often not associated with abnormal function, potentially due to low iodine intake or goitrogens), hyperplastic nodules, thyroid cysts, and some thyroiditis cases

Thyroid Nodules

• Thyroid nodules are common
• Can be benign or malignant (primary/metastatic)
• Differential diagnoses include hyperplasia, neoplasms, and occasionally thyroiditis
• Evaluation usually involves clinical history/exam, blood tests, radiology (ultrasound, radionuclide imaging, rarely CT/MRI), and pathology/fine-needle aspiration biopsy (FNAB)
• FNAB categories range from non-diagnostic (Thy 1) to malignant (Thy 5); intermediate classifications are associated with further action (repeat scan, biopsy, etc)

Thyroid FNAs

• FNAs classify nodules into categories (Thy 1-5) for diagnosis
• Often performed under ultrasound guidance
• Diagnostic tool of choice, safe, cost-effective

Thyroid Neoplasms

• Benign neoplasms include follicular adenoma (encapsulated, firm, usually <5cm), other variants like Hurthle cell/oncocytic adenoma.
• Malignant neoplasms include papillary carcinoma, follicular carcinoma, medullary carcinoma, and anaplastic carcinoma

Papillary Carcinoma

• Most common thyroid cancer (~85%)
• Commonest age range 20-40, with a 4:1 female to male ratio
• Good prognosis, with a 98% 5-year survival rate
• Common favorable factors are: female sex, <20 years old, confined to the thyroid, well-differentiated cytologic morphology
• Often multifocal, with small whitish nodules, sometimes cystic
• Micro features include papillary architecture, pale/optic clear nuclei, overlapping nuclei, nuclear inclusions, nuclear grooves, psammoma bodies
• Has a propensity to spread/metastasize to draining lymphatics

Follicular Carcinoma

• Accounts for 10-15% of thyroid cancers
• Typically occurs in individuals aged 50-60, with a 3:1 female to male ratio
• Prognosis depends on invasion extent
• Can be minimally invasive (high survival rates) or widely invasive (lower survival rates)
• Usually presents as a slowly enlarging painless thyroid nodule
• Commonly spreads hematogenously, sometimes to bone marrow
• Often characterized by capsular or vascular invasion

Medullary Carcinoma

• Accounts for up to 5% of thyroid cancers
• A neuroendocrine neoplasm of parafollicular C cells
• Often secretes calcitonin
• Frequently associated with a distinctive amyloid stroma
• A familial component exists (30% of cases), often associated with MEN syndromes
• Typically presents macroscopically as single to multiple nodules; microscopically, shows variable appearances (solid, glandular, spindled cells)

Anaplastic Carcinoma

• Accounts for less than 5% of thyroid cancers
• Primarily affects elderly individuals
• Rapid growth into adjacent neck structures
• Macroscopically presents as hard, gritty masses
• Microscopically, characterized by undifferentiated, giant cells
• Poor prognosis, typically fatal within a year

Parathyroid Glands

• Derived from pharyngeal pouches
• Can be located elsewhere in the anterior mediastinum as well
• Typically 2-4 glands (some individuals may have fewer or more)
• Typically weigh 35-40 mg each
• Contains chief cells (functionally active; main cell type) and oxyphil cells (have a lesser role in function)

Parathyroid Hyperfunction

• Primary (most common cause): characterized by PTH overproduction, leading to hypercalcemia (high blood calcium levels)
• Causes include adenoma (75-80%); primary hyperplasia (10-15%); and rarely parathyroid carcinoma (<5%)
• Common symptoms include painful bones, renal stones, abdominal groans, and psychic moans, characterized by osteoporosis, kidney stones, gut upset, confusion/depression, and occasionally severe weakness
• Secondary: due to systemic factors—e.g., kidney insufficiency.
• Tertiary: results from long-term secondary hyperplasia.

Parathyroid Hypofunction

• Conditions leading to low PTH include surgical removal during thyroid procedures, congenital absence of the gland (e.g., DiGeorge syndrome), primary idiopathic atrophy, and familial hypoparathyroidism.
• Symptoms include hypocalcemia (low blood calcium levels), characterized by numbness, tingling, muscle cramps, seizures, and potentially other varied manifestations.

Multiple Endocrine Neoplasia (MEN)

• Familial diseases involving multiple endocrine glands, inherited predominantly as autosomal dominant traits.
• MEN type 1 (Wermer's): associated with parathyroid, pituitary, and pancreatic tumors.
• MEN type 2A (Sipple syndrome): characterized by medullary thyroid cancer, pheochromocytoma, and parathyroid disease.
• MEN type 2B: includes medullary thyroid cancer and pheochromocytoma, plus specific extra-endocrine manifestations such as ganglioneuromas and marfanoid habitus.
• Tumors arising in these syndromes generally occur earlier than sporadic cases, are often multifocal, and sometimes preceded by an asymptomatic hyperplasia stage.
• These have a higher recurrence rate than sporadic cases
• Germline RET mutation carriers are advised for prophylactic thyroidectomy.