neoplasms, hypothyroidism, parathyroid diseases

neoplasms, hypothyroidism, parathyroid diseases

How is hypothyroidism classified based on the level of dysfunction?

It is classified into primary (thyroid gland failure) and secondary (pituitary or hypothalamic failure).

Which drug used for cardiac arrhythmias is a known iatrogenic cause of hypothyroidism?

Amiodarone

What is the most common cause of neonatal hypothyroidism worldwide?

Iodine deficiency

In congenital hypothyroidism (cretinism), what are the 'six Ps' used to describe clinical manifestations?

Pot belly, Protruding umbilicus, Puffy face, Protruding tongue, Poor neurologic development, and Intellectual disability (formerly 'Poor neurologic development').

Which condition is defined as hypothyroidism developing in an older child or adult?

Myxedema

What life-threatening decompensated state of severe hypothyroidism classically presents in elderly patients?

Myxedema coma

What are the common triggers for a myxedema coma in a patient with stable hypothyroidism?

Stressful events such as infection, myocardial infarction, or stroke.

Which form of thyroiditis typically follows a viral infection and presents with a painful thyroid?

Subacute Granulomatous (de Quervain) thyroiditis

What is the most common cause of hypothyroidism in iodine-sufficient/developed countries?

Hashimoto thyroiditis (Autoimmune hypothyroidism)

Which $HLA$ subtypes are associated with an increased risk of Hashimoto thyroiditis?

HLA-DR3 and HLA-DR5

Patients with Hashimoto thyroiditis have a significantly increased risk of developing which malignancy?

Lymphoma (specifically marginal zone B-cell lymphoma).

What is the most sensitive autoimmune marker used for diagnosing Hashimoto thyroiditis?

Anti-thyroid peroxidase antibodies (Anti-TPO).

What is the other autoimmune marker?

Anti-thyroglobulin antibodies (Anti-Tg)

what are the histological features of Hashimoto thyroiditis?

• Mononuclear inflammatory infiltrate with germinal centres

• Atrophy of epithelium

• Metaplasia of cuboidal follicular epithelium → Hurthle cells with eosinophilic cytoplasm

Can be complicated by papillary carcinoma or lymphoma

What are the three primary immunologic mechanisms of thyroid destruction in Hashimoto thyroiditis?

• CD8 T-cell mediated destruction,

• CD4 T-cell/macrophage mediated destruction

• Antibody-dependent cell-mediated cytotoxicity.

Gross appearance in hashimoto’s

Diffuse enlargement of thyroid gland (may be localized in

certain cases).

Which rare form of thyroiditis is characterized by extensive fibrosis and a 'rock-hard' painless mass?

Riedel's thyroiditis (Riedel's struma)

Riedel's thyroiditis is associated with which systemic group of autoimmune fibrosing conditions?

IgG4-related diseases

In the context of hypothyroidism, what causes the characteristic periorbital and facial puffiness?

Accumulation of glycosaminoglycans in the interstitial tissue.

Are follicular adenomas considered precancerous lesions?

No, they are benign tumors and do not typically transform into carcinoma.

What is the 'gross' hallmark of a follicular thyroid adenoma?

A solitary, spherical, encapsulated lesion separated from normal tissue by a well-defined intact capsule.

what is this and what do u see?

Follicular thyroid adenoma

• Follicles resemble normal thyroid parenchyma

• Little variation in cell size/shape/morphology

They share the same histological features of

follicular carcinoma, but do not invade the

tumour capsule or surrounding blood vessels

Why is Fine Needle Aspiration (FNA) insufficient for differentiating between follicular adenoma and follicular carcinoma?

FNA cannot assess the presence of capsular or vascular invasion, which is the defining criterion for malignancy.

clinical features of follicular adenoma

✓Unilateral, painless masses that are discovered during a

routine physical examination

✓ Nonfunctioning adenomas take up less radioactive iodine

(cold nodules) than does normal thyroid parenchyma

✓A histopathologic examination (Not FNAC) for the intact

capsule is mandatory for a definitive diagnosis of adenomas

What radioactive iodine uptake pattern is typical for most thyroid adenomas?

They are typically 'cold' nodules (take up less iodine than normal parenchyma).

What is the most common subtype of thyroid carcinoma, accounting for over 85% of cases?

Papillary thyroid carcinoma

Which two gene mutations are most frequently associated with Papillary thyroid carcinoma?

RET and BRAF

histological characteristics of Papillary carcinoma?

• Branching papillae with fibro- vascular stalk and particularly nuclear features.

• orphan annie & nuclear grooves

• Nuclear elongation and intranuclear inclusions

• psammoma bodies are often present

Gross appearance of papillary carcinoma

cystic mass with papillary excrescences

tumour invades lymphatics within the thyroid to metastasise

Clinical features of papillary carcinoa

• asymptomatic thyroid nodules

• may be in cervical LN

• Not good prognosis in elderly

details on Follicular carcinoma

• second most common thyroid cancer

• cold nodules

• vascular invasion

• RAS mutations

• Mostly affects women 40-50s

Gross appearance of follicular carcinoma

• solid mass replacing thyroid lobe

• tumour has tan appearance

• small areas of haemorrhage and necrosis

histology of follicular carcinoma?

• the distinction from adenoma is dependant on presence of capsular/vascular invasion by the tumour

where does medullary carcinoma originate from?

parafollicular cells which secrete calcitonin

When does medullary carcinoma occur?

occurs in the setting of MEN IIA/IIB in young patients

two types of medullary carcinoma

sporadic

familial

gross appearance of medullary carcinoma?

• sporadic: single circumscribed but non-encapsulated, gray-tan mass

• familial: can have multiple foci and can be infiltrative

• large lesions → haemorrhage and necrosis

What are the familial type associated with?

multiple endocrine neoplasia syndrome

what is this? name 5 things you see

medullary carcinoma

• cells are solid and nest like, arranged in sheets

• polygonal/spindle shaped cells with round/oval nuclei

• variable nuclear pleomorphisms

• moderate eosinophilic/amphophilic cytoplasm

• amyloid deposition

Details on anaplastic carcinoma

• Undifferentiated tumours of follicular epithelium

• 65+ years.

• Most likely to be painful.

• Rapidly enlarging and infiltrative lesions with compression and invasion

Gene mutation for anaplastic carcinoma

p53

what does anaplastic carcinoma look like on ultrasound

• Calcifications, irregular borders, and invasion into surrounding tissues (may suggest malignancy)

What are the primary sites for hematogenous metastasis of Follicular thyroid carcinoma?

Lungs, bones, and liver.

Which cells in the parathyroid gland are responsible for secreting Parathyroid Hormone?

Chief cells

3 functions of PTH?

• increases serum calcium via bone resorption

• increases renal calcium reabsorption, phosphate excretion

• increases intestinal calcium absorption via vit D activation

main cause of primary hyperparathyroidism

parathyroid adenoma

pathogenesis of primary hyperparathyroidism

too much PTH → too much calcium + LOW phosphate

Clinical features of primary hyperparathyoidisim

bones, stones, groans and psychiatric overtones

(Osteitis fibrosa cystica, nephrolithiasis, GI symptoms, depression)

microscopy of parathyroid adenoma

• uniform chief cells

• minimal fat

• compressed rim of normal parathyroid

treatment for parathyroid adenoma

surgical removal

compare the histology of parathyroid hyperplasia and parathyroid carcinoma

In hyperplasia, there is increased cellularity and decreased fat.

In carcinoma, there is invasion into surrounding tissue as well as increased mitotic activity

main cause of Secondary Hyperparathyroidism

chronic renal failure, this is because chronic hypocalcaemia results in increased PTH as a compensatory mechanism

what can Secondary Hyperparathyroidism develop into?

renal osteodystrophy

or tertiary hyperparathyroidism

lab findings in Secondary Hyperparathyroidism

• increased PTH

• increased phosphate

• low/normal calcium

what are the 3 things that happen when the kidney fails?

1. phosphate accumulates (it’s also responsible for binding Ca)

2. Hypocalcaemia

3. PTH goes up

lab findings in hypoparathyroidism

• low PTH

• low calcium

• high phosphate

three causes of hypoparathyoidism

1. post-surgical

2. autoimmune (aps)

3. DiGeorge syndrome

clinical features of Hypoparathyroidism

• Tetany, Chvostek’s and Trousseau’s signs

• Seizures, arrhythmias

How to diagnose parathyroid disease

• PTH levels test

• calcium, phosphate and vitamin D blood tests

• renal function tests

• ultrasound/MRI/CT

Most common cause of primary hyperparathyroidism?

Parathyroid adenoma

name 3 complication of hyperparathyroidism

• Osteoporosis

• Nephrolithiasis

• Calciphylaxis (in renal failure)

name 3 complication of hypoparathyroidism

• Hypocalcemic seizures

• Arrhythmias

• Basal ganglia calcifications

what is multiple endocrine neoplasia and what is it a result of?

disorders where tumours involving multiple endocrine organs resulting from mutations in tumour supressor pathways

what are two major syndromes?

• MEN 1 → parathyroid + pituitary + pancreatic tumours

• MEN 2 → Medullary thyroid carcinoma + pheochromocytoma ±

hyperparathyroidism

what is the gene profile of MEN2?

1. Gene: RET on chromosome 10q11.2

2. RET = receptor tyrosine kinase proto-oncogene

3. Inheritance: Autosomal dominant