Endocrine Pathology II - Thyroid and Parathyroid Pathology PDF 2025

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Endocrine Pathology II - Thyroid and parathyroid pathology Class Year 2 Course Pathology Lecturer Dr Helen Barrett Date 10th January 2025 LEARNING OUTCOMES Identify histological features of the normal...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Endocrine Pathology II - Thyroid and parathyroid pathology Class Year 2 Course Pathology Lecturer Dr Helen Barrett Date 10th January 2025 LEARNING OUTCOMES Identify histological features of the normal thyroid gland List the 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 aetiological factors in the development of thyroid carcinoma Identify histological features of the normal parathyroid glands List causes of hypo and hyperparathyroidism ENDOCRINE SYSTEM Pure endocrine organs – Pituitary – Thyroid – Parathyroid – Adrenal Endocrine components in mixed organs – Pancreas – Ovary – Testis DISEASE IN ENDOCRINE ORGANS Usually comes to the attention via – Hyperfunction – Hypofunction – Enlargement / mass effect THYROID GLAND THYROID GLAND Develops via thyroglossal duct 20-25g 2 large lateral lobes joined by an isthmus Developmental anomalies Aplasia/hypoplasia (rare) Heterotopic thyroid tissue Thyroglossal duct cyst (hyoid bone region) THYROID GLAND Histologically Follicular cells – Thyroid hormones Parafollicular C cells – Calcitonin T3 (triiodothyronine) and T4 (thyroxine) T3 is more active form Thyroid function tests T4, T3, TSH, antibodies to thyroid, thyroglobulin SYMPTOMS OF THYROID DISEASE Hyperthyroidism Hypothyroidism Thyroid enlargement Generalised – goitre Localised – nodule Euthyroid – normal thyroid status HYPERTHYROIDISM Primary Graves’ disease Hyperfunctioning (toxic) multinodular goitre Hyperfunctioning (toxic) adenoma Hyperfunctioning (toxic) carcinoma Secondary TSH releasing pituitary adenoma (rare) Others Some types of thyroiditis Exogenous thyroxine Struma ovarii (ovarian teratoma with ectopic thyroid)  HYPERTHYROIDISM - SYMPTOMS Constitutional Elderly Heat intolerance ‘Apathic hyperthyroidism’ Weight loss despite increased Worsen cardiac insufficiency appetite CVS Tachycardia Palpitations ‘Thyroid storm’ GIT Abrupt, severe hyperthyroidism Hypermotile symptoms Medical emergency NS Usually in underlying Grave’s Tremor Irritability Often proximal muscle weakness  GRAVES’ DISEASE Autoimmune disorder with hyperthyroidism M:F = 1:5 Age 15-40 Familial tendency IgG autoantibody to TSH-receptor with TSH-like effect -> increased release of thyroid hormones  GRAVES’ DISEASE Macro Diffuse enlargement Micro Star shaped follicles Little colloid Increased lymphocytes GRAVES’ - CLINICAL FEATURES Hyperthyroidism +/- thyroid swelling Exophthalmus Swelling of the retro-orbital tissues leads to protrusion of the orbit ‘Lid lag’ due to hyperthyroidism per se Dermopathy (pretibial myxedema). HYPOTHYROIDISM Primary Hashimoto thyroiditis Iatrogenic (surgery and/or radioactive iodine, drugs) Iodine deficiency Dyshormonogenic (congenital synthesis defect) Secondary Pituitary / hypothalamic dysfunction HYPOTHYROIDISM - SYMPTOMS Adult onset Childhood onset Apathy Same as for adults Mental sluggish but also: Cold intolerance Impaired skeletal ‘Oedema’ of face, tongue development and some viscera Intellectual disability Hoarse ‘Cretinism’ ‘Myxoedema’ NB: Elderly HASHIMOTO’S THYROIDITIS Middle age, F>M Chronic thyroiditis Autoimmune – attacked by cytotoxic T lymphocytes (breakdown in self tolerance). Clinically: Euthyroid / hypothyroid, uncommonly hyperthyroid (Hashitoxicosis - transient)  HASHIMOTO’S THYROIDITIS Macro: Swollen in start, atrophy later Micro: Lymphocytic infiltration of the stroma with reactive germinal centres and oxyphilic change of follicular epithelium. THYROIDITIS Group of disorders All have some form of thyroid inflammation Most common are autoimmune thyroiditis Graves’ disease Hashimoto’s thyroiditis THYROIDITIS De Quervain’s Thyroiditis Subacute granulomatous thyroiditis F>M, most common between ages of 30 and 50. Viral aetiology – Majority of patients have a history of an upper RTI before onset. Most patients return to euthyroid state in 6- 8wks. Clinical sudden painful enlargement + fever THYROID ENLARGEMENT Simple / multinodular goitre Nodules: – Neoplasm – Hyperplastic nodule – Thyroid cyst Some cases of thyroiditis NB: Goitre in broadest sense refers to an enlarged thyroid gland – clinical term SIMPLE AND MULTINODULAR GOITRE Diffuse involvement of gland Gland bordering on too low function but Usually not associated with abnormal function SIMPLE AND MULTINODULAR GOITRE Endemic: Low iodine Decreased T3/T4 output ‘Goitrogens’ Non-endemic: Low iodine Synthesis defect Increased TSH level F>M Hypertrophy/hyperplasia of thyroid SIMPLE AND MULTINODULAR GOITRE Hyperplasia and hypertrophy of follicles Simple goitre involution T3/T4 low TSH ↓ TSH ↑ T3/T4 normal hyperplasia Fibrosis, haemosiderin, atrophy, hypertrophy/hyperplasia Multinodular goitre THYROID NODULES Thyroid nodules are common. Differential Dx: – Hyperplastic nodule – Neoplasm Benign / Malignant (primary / metastasis) – Rarely thyroiditis THYROID NODULES Approach to evaluation: ‘triple assessment’. – Clinical: History, change in size of lesion, clinical evaluation, blood tests – Radiology: Ultrasound – solid vs cystic, calcifications, size, vascularity Radionuclide imaging – classify nodules into “cold, warm and hot” Other imaging rarely used – CT / MRI – Pathology: FNABx THYROID NODULES Solitary* vs. multiple Young* vs. old ‘Cold’* vs. ‘hot’ Male* vs. female *These are features that would be more concerning for a neoplam THYROID NODULES Fine needle aspiration biopsy (FNAB): – Performed under ultrasound guidance for accuracy – Diagnostic tool of choice – safe, accurate and cost effective. THYROID FNA http://3.bp.blogspot.com/_taRFteuYyxE/TEC2poLuvgI/AAAAAAAAABM/gdsiwOvVrrk/s1600/fna+biopsy.jpg http://fitsweb.uchc.edu/student/selectives/Luzietti/images/thyroid/thyroid_fna_2.JPG THYROID FNA Categories Thy 1 – Non diagnostic Thy 2 – Non neoplastic Thyroiditis, hyperplastic nodule / colloid nodule Thy 3 – Neoplasm possible Follicular lesion (Thy 3f) – hyperplastic nodule, follicular neoplasm. Atypia (Thy 3a) Thy 4 – Suspicious of malignancy Thy 5 – Malignant  THYROID FNA FNA Malignant Colloid nodule Follicular lesion Papillary carcinoma or Medullary carcinoma other benign Anaplastic carcinoma Category - Thy2 Category – Thy3 Category – Thy4/5 Repeat US +/-FNA Excision? Excision (usually) Sign off THYROID NEOPLASMS Benign Malignant Follicular adenoma Papillary carcinoma Others (e.g. lipoma) Follicular carcinoma Medullary carcinoma Anaplastic carcinoma Others (e.g.lymphoma, metastases) FOLLICULAR ADENOMA Any age F>M Clinical euthyroid, sometimes toxic Macro Encapsulated, firm Usually M Predisposition Ionizing radiation exposure Iodine rich diet Genetic (medullary, MEN 2a or 2b) Nodules MALIGNANT THYROID TUMOURS Papillary carcinoma ~85% Follicular carcinoma 10-15% Medullary carcinoma 5% Anaplastic carcinoma rare Lymphoma rare Others (incl. metastases) rare PAPILLARY CARCINOMA Most common (~85% of thyroid ca) Any age, 20 - 40yrs F:M - 4:1 Good prognosis; 98% 5yr survival Favourable factors female sex stimulates parathyroid gland activity (hyperplasia of parathyroid glands) -> increased PTH secretion -> serum calcium remains near normal. HYPERPARATHYROIDISM Tertiary In a minority of patients, parathyroid activity becomes autonomous and excessive with resultant hypercalcaemia - Can be treated with parathyroidectomy. HYPERCALCAEMIA Signs and symptoms: “Painful bones, renal stones, abdominal groans and psychic moans” – Osteoporosis, osteitis fibrosa cystica. – Chronic renal insufficiency, renal stones. – Constipation, anorexia, nausea, vomiting, pancreatitis, peptic ulcer disease. – Altered concentration, depression, confusion, seizures. – Weakness and fatigue. – Aortic / mitral valve calcifications (cardiac manifestations). FEATURES OF HYPERPARATHYROIDISM PARATHYROID HYPOFUNCTION HYPOPARATHYROIDISM Surgical removal (inadvertently) during thyroidectomy – mistaken for lymph nodes Congenital absence (DiGeorge syndrome – along with thymic aplasia) Primary idiopathic atrophy (autoimmune) – antibodies against the Ca sensing receptors in parathyroid gland Familial hypoparathyroidism – Condition presents in childhood HYPOCALCAEMIA Signs and symptoms: – Numbness and tingling in the extremities and perioral region – Muscle cramps – Bronchospasm / laryngospasm / seizures – Chvostek’s sign (muscle spasms of mouth/eye/nose with tapping of the facial nerve) – Trousseau’s sign (carpal spasm with inflation of sphygmomanometer 20mmHg above systolic pressure) – Intra-cranial manifestations (parkinsonian like movement) – Cardiovascular manifestations – conduction defect with prolonged QT interval MULTIPLE ENDOCRINE NEOPLASIA (MEN) SYNDROMES MEN SYNDROMES ▪ Familial diseases associated with neoplasia or hyperplasia of several endocrine glands ▪ The disorders are inherited as autosomal dominant traits: ▪ MEN type 1 (Wermers syndrome) ▪ MEN type 2A ▪ MEN type 2B MEN SYNDROMES MEN type 1 (aka Wermer’s syndrome) – Hyperplasia or Neoplasia of: Parathyroid gland Pituitary (prolactinomas) Pancreatic islet cells “the 3 P’s” – Primary hyperparathyroidism most common manifestation. – Genetic defect: MEN1 gene (tumour suppressor gene) located at chromosome 11q13. MEN SYNDROMES MEN type 2 – two distinct groups but both have activating mutations of the RET proto-oncogene at chromosome 10q11.2 MEN type 2A (Sipple syndrome): – Characterised by: Medullary Carcinoma Phaechromocytoma Parathyroid hyperplasia MEN SYNDROMES ▪ Familial medullary thyroid cancer ▪ Variant of MEN 2A ▪ Strong predisposition to medullary thyroid cancer but not the other manifestations of MEN 2A Typically occurs at an older age & follows a more indolent course. MEN SYNDROMES ▪ MEN 2B: ▪ Characterized by: 1. Medullary carcinoma of thyroid. 2. Phaeochromocytoma. 3. Extra-endocrine manifestations: – ganglioneuromas of mucosal sites. – ‘Marfanoid habitus’ – long bones of axial skeleton. ▪ Do not get primary hyperparathyroidism MEN SYNDROMES Tumours occur at a younger age than sporadic neoplasms. Arise in multiple endocrine organs. Often multifocal. Tumours usually preceded by asymptomatic stage of endocrine hyperplasia. More aggressive and higher rate of recurrence than sporadic tumours. MEN SYNDROMES Any patient carrying a germline RET mutation is advised to have prophylactic thyroidectomy to prevent the inevitable development of medullary carcinoma. LEARNING OUTCOMES Identify histological features of the normal thyroid gland List the 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 aetiological factors in the development of thyroid carcinoma Identify histological features of the normal parathyroid glands List causes of hypo and hyperparathyroidism Discuss Multiple Endocrine Neoplasia THANK YOU