PA31.1-10 | Endocrine System — Glossary

Anterior pituitary hormone derived from POMC; stimulates cortisol and adrenal androgen secretion; elevated in primary adrenal insufficiency and Cushing disease.

Chronic primary adrenal insufficiency due to destruction of >90% of the adrenal cortex; features include hyperpigmentation, hypotension, hyponatraemia, hyperkalaemia.

Rare malignant tumour of the adrenal cortex; typically large (>100 g), with haemorrhage and necrosis; diagnosed histologically by Weiss criteria (≥3 of 9 features).

Proteins or lipids non-enzymatically modified by glucose; accumulate in diabetes and cause basement membrane thickening, crosslinking, and macrophage activation, driving microangiopathy.

Screening test for primary hyperaldosteronism; an ARR >30 with a suppressed renin strongly suggests autonomous aldosterone secretion.

In medullary carcinoma, amyloid consists of polymerized calcitonin precursor peptides deposited between tumor nests; stains with Congo red, shows apple-green birefringence under polarized light

A highly aggressive, undifferentiated thyroid carcinoma typically arising by dedifferentiation from differentiated thyroid carcinoma; uniformly fatal (median survival 3–6 months)

Autoantibodies against thyroid peroxidase; highly sensitive marker for Hashimoto thyroiditis; also positive in ~70% of Graves disease

A standardized 6-category reporting system for thyroid cytopathology (I = non-diagnostic, II = benign, III = atypia of undetermined significance, IV = follicular neoplasm, V = suspicious for malignancy, VI = malignant)

A point mutation (valine→glutamic acid at codon 600) in the BRAF serine/threonine kinase, found in ~60% of papillary thyroid carcinomas; activates the MAP kinase pathway

A non-neoplastic reactive bone lesion in hyperparathyroidism consisting of osteoclasts, fibroblasts, and hemosiderin (causing brown color); resolves after parathyroidectomy

The connecting peptide cleaved from proinsulin during insulin secretion; released in equimolar amounts with insulin; a marker of endogenous β-cell function, absent with exogenous insulin administration.

Carbohydrate antigen 19-9 (sialyl Lewis antigen); the primary serum tumour marker for PDAC; used for monitoring treatment response and detecting recurrence; not a valid screening or diagnostic tool alone.

A 32-amino acid peptide hormone secreted by thyroid C cells that lowers serum calcium by inhibiting osteoclasts; markedly elevated in medullary thyroid carcinoma and used as a serum tumor marker

Full-thickness penetration of the fibrous tumor capsule by neoplastic cells; the defining feature of follicular carcinoma (vs. adenoma)

Neuropathic joint destruction in diabetic neuropathy, typically involving the midfoot, characterised by bone fragmentation, subluxation, and deformity in a painless, insensate limb.

The predominant PTH-secreting cells of the parathyroid gland; small, polygonal, with round nuclei and pale granular cytoplasm; compose most parathyroid adenomas

Catecholamine-secreting cells of the adrenal medulla, derived from neural crest; turn brown with chromate fixation (chromaffin reaction); give rise to pheochromocytoma.

Gel-like substance stored in thyroid follicular lumen, consisting mainly of thyroglobulin; the source of stored T3/T4

Primary hyperaldosteronism due to an aldosterone-producing adrenal adenoma or bilateral adrenal hyperplasia; presents with hypertension, hypokalaemia, and suppressed plasma renin.

The principal glucocorticoid hormone synthesised by the zona fasciculata; regulates glucose homeostasis, anti-inflammatory responses, protein catabolism, and the stress response.

A palpable, non-tender gallbladder in the setting of obstructive jaundice; indicates malignant biliary obstruction (most commonly pancreatic head cancer) rather than gallstone disease.

Congenital or early-childhood hypothyroidism causing irreversible intellectual disability and growth retardation; caused by iodine deficiency or thyroid dysgenesis

Cushing syndrome caused specifically by an ACTH-secreting pituitary adenoma; bilateral adrenal cortical hyperplasia results; suppresses on high-dose but not low-dose DST.

Subacute granulomatous thyroiditis of probable viral aetiology; presents with painful thyroid, raised ESR, and characteristic 4-phase thyroid function evolution

The dense fibrous/collagenous reactive stroma produced by activated pancreatic stellate cells in PDAC; constitutes up to 90% of tumour volume and is a physical barrier to drug delivery.

A test using exogenous dexamethasone to assess HPA axis suppressibility; low-dose DST confirms Cushing syndrome, high-dose DST localises the cause.

A heterogeneous group of metabolic disorders characterised by chronic hyperglycaemia due to defects in insulin secretion, insulin action, or both.

An acute hyperglycaemic emergency characterised by absolute insulin deficiency, ketogenesis, metabolic acidosis (anion gap), and volume depletion; classic in Type 1 DM.

Nerve damage in DM; most commonly distal symmetrical sensorimotor polyneuropathy (glove-and-stocking pattern) due to sorbitol accumulation in Schwann cells and microangiopathy of vasa nervorum.

Microvascular complication of DM affecting the retina; progresses from non-proliferative (microaneurysms, haemorrhages, exudates) to proliferative (neovascularisation, vitreous haemorrhage).

Simultaneous dilatation of both the common bile duct and the main pancreatic duct on MRCP or ERCP; highly suggestive of a head-of-pancreas mass (PDAC or ampullary tumour) causing dual obstruction.

Congenital defect in any step of thyroid hormone synthesis (iodine trapping, organification, coupling, deiodination); causes familial goiter with hypothyroidism

Cushing syndrome caused by non-pituitary ACTH secretion, most often from small-cell lung carcinoma or carcinoid tumour; very high ACTH, does not suppress on high-dose DST.

PAS-positive hyaline deposits in the efferent arteriolar wall of renal glomeruli; virtually pathognomonic of diabetes mellitus (other diseases affect only the afferent arteriole).

A minimally invasive diagnostic procedure using a thin needle to aspirate cells from a thyroid nodule for cytological analysis

A benign, solitary, encapsulated thyroid neoplasm of follicular cells with an intact capsule and no evidence of invasion

The main cell type of the thyroid parenchyma; synthesises thyroglobulin, traps iodine, and produces T3/T4; its height reflects TSH stimulation level

Enlargement of the thyroid gland from any cause, regardless of functional status

Chronic autoimmune thyroiditis characterised by lymphocytic infiltrate with germinal centres, Hürthle cell metaplasia, and progressive hypothyroidism; most common autoimmune thyroid disease

Haemoglobin non-enzymatically glycated at the N-terminal valine of β-globin; reflects mean blood glucose over the preceding 8–12 weeks; threshold for DM diagnosis ≥6.5% (48 mmol/mol).

A family of cell-surface glycoproteins (class I and II) that present antigens to T cells; HLA-DR3 and HLA-DR4 confer susceptibility to Type 1 DM.

Pathognomonic feature of neuroblastoma; tumour cells clustered around a central core of neuropil (fibrillar processes) without a central vessel or lumen.

Metaplastic follicular cell with abundant granular eosinophilic cytoplasm (mitochondria-rich) and large irregular nucleus; classic in Hashimoto thyroiditis

Large thyroid follicular cells with abundant granular eosinophilic cytoplasm packed with mitochondria; seen in Hashimoto thyroiditis and some thyroid neoplasms (Hürthle cell adenoma/carcinoma)

A urinary dopamine metabolite elevated in neuroblastoma; used alongside VMA for biochemical diagnosis of catecholamine-secreting paediatric tumours.

An acute hyperglycaemic emergency of Type 2 DM characterised by extreme hyperglycaemia (>33 mmol/L), serum hyperosmolality (>320 mOsm/kg), severe dehydration, and absence of ketoacidosis.

An adrenal mass discovered incidentally on imaging performed for another reason; most are non-functional cortical adenomas; workup includes hormonal evaluation and size-based follow-up.

An impaired biological response to normal insulin concentrations in target tissues (liver, skeletal muscle, adipose tissue); the initiating metabolic defect in Type 2 DM.

A lymphocytic inflammatory infiltrate (predominantly CD8⁺ T cells) within and around the islets of Langerhans, the histological hallmark of active Type 1 DM.

A 37-amino acid peptide co-secreted with insulin by β cells; overproduction in Type 2 DM leads to islet amyloid deposition, contributing to β-cell loss.

Sudden iodine-excess-induced hyperthyroidism occurring in patients with underlying autonomous thyroid tissue (MNG, Graves susceptibility) when iodine supply is restored or supplemented

Rounded, PAS-positive, acellular mesangial nodules at the periphery of glomerular lobules; the pathognomonic lesion of diabetic nodular glomerulosclerosis.

The most frequently mutated oncogene in PDAC (>90%); codon 12 mutations provide constitutive activation of RAS-MAPK and PI3K-AKT proliferative signalling; the first and most prevalent genetic event in PDAC.

Deep, rapid, laboured breathing that compensates for metabolic acidosis by increasing CO₂ excretion; characteristic of DKA.

A thyroid carcinoma arising from parafollicular C cells, characterized by calcitonin secretion, amyloid stroma, and association with RET mutations/MEN2 syndromes

A tumor suppressor syndrome caused by germline MENIN gene mutation comprising parathyroid hyperplasia, anterior pituitary adenoma, and pancreatic islet cell tumor (Werner syndrome)

Autosomal dominant syndrome caused by RET proto-oncogene mutations; MEN2A includes pheochromocytoma, medullary thyroid carcinoma, and hyperparathyroidism.

A germline RET mutation syndrome comprising medullary thyroid carcinoma, bilateral pheochromocytoma, and parathyroid hyperplasia (Sipple syndrome)

A cluster of central obesity, hypertriglyceridaemia, low HDL, hypertension, and impaired fasting glucose that strongly predisposes to T2DM and cardiovascular disease.

Direct O-methylated metabolites of epinephrine and norepinephrine; plasma fractionated metanephrines are the most sensitive test for pheochromocytoma.

A monogenic, autosomal dominant form of diabetes caused by mutations in single genes regulating β-cell function; onset typically before age 25.

Irregular, nodular thyroid enlargement from repeated hyperplasia-involution cycles; most common thyroid disease globally; heterogeneous architecture with degenerative changes

Non-pitting dermal oedema caused by accumulation of glycosaminoglycans (dermatan sulphate, hyaluronic acid) in the dermis; hallmark of severe hypothyroidism; paradoxically also occurs in pretibial skin in Graves (pretibial myxoedema)

A transcription factor oncogene on chromosome 2p24; amplification (>10 copies) in neuroblastoma is the single most important adverse prognostic marker.

The commonest extracranial solid tumour of childhood; arises from adrenal medulla or sympathetic ganglia; composed of small round blue cells with Homer-Wright pseudorosettes.

Linear infoldings of the nuclear membrane seen in papillary thyroid carcinoma cells; appear as grooves or coffee-bean configurations on cross-section

Cytoplasmic invaginations into the nucleus appearing as sharply outlined eosinophilic round inclusions; characteristic of papillary thyroid carcinoma

Pathognomonic nuclear feature of papillary thyroid carcinoma — optically clear, pale, 'empty-looking' nuclei due to peripheral chromatin condensation

Severe bone disease caused by prolonged hyperparathyroidism; characterized by osteoclastic bone resorption, peritrabecular fibrosis, cysts, and brown tumors (von Recklinghausen disease of bone)

The precursor lesion of pancreatic ductal adenocarcinoma, graded PanIN-1 to PanIN-3; PanIN-1 carries KRAS mutations; PanIN-3 (carcinoma in situ) precedes invasive PDAC.

Projections of hyperplastic follicular epithelium into the follicular lumen in Graves disease; lack fibrovascular cores (unlike true papillae in papillary carcinoma)

Calcitonin-secreting cells of the thyroid derived from neural crest, scattered between follicles; the cell of origin of medullary thyroid carcinoma

Neuroendocrine cell dispersed between thyroid follicles; secretes calcitonin (calcium-lowering hormone); origin of medullary thyroid carcinoma

Chromosomal translocation t(2;3)(q13;p25) producing a PAX8-PPARγ fusion protein; characteristic of follicular thyroid carcinoma (30–35%)

Cancer cell infiltration along and around nerve sheaths; nearly universal in PDAC; correlates with back pain (coeliac plexus), poor surgical margins, and high recurrence rates.

Catecholamine-secreting tumour of adrenal medullary chromaffin cells; presents with paroxysmal hypertension, headache, sweating, palpitations; follows the rule of 10s.

Metabolic pathway activated by hyperglycaemia in which aldose reductase converts excess glucose to sorbitol, causing osmotic and oxidative stress in nerves, lens, and retinal pericytes.

Precursor protein cleaved in the anterior pituitary into ACTH, β-endorphin, and α-MSH; elevated in primary adrenal insufficiency, driving hyperpigmentation.

Subacute lymphocytic thyroiditis occurring within 1 year of delivery; immune rebound after pregnancy-related immunosuppression; typically self-limiting

Autonomous, non-feedback-regulated hypersecretion of PTH from parathyroid tissue; most commonly due to a chief cell adenoma; produces hypercalcemia, hypophosphatemia

Advanced stage of diabetic retinopathy characterised by VEGF-driven neovascularisation on the retinal surface and optic disc; risks vitreous haemorrhage and tractional retinal detachment.

Forward protrusion of the eyeball due to expansion of retroorbital contents; characteristic of Graves ophthalmopathy

Concentrically laminated, basophilic calcifications formed by calcification of necrotic tumor cells; strongly associated with papillary thyroid carcinoma (~40–50%)

A peptide secreted by certain tumors (e.g., squamous cell carcinoma of lung) that mimics PTH action on bone and kidney; causes humoral hypercalcemia of malignancy; intact PTH is suppressed in this condition

Diagnostic test measuring the fraction of administered radioactive iodine (123I) trapped by the thyroid at 24 hours; reflects iodine-trapping capacity and synthesis activity

Chromosomal rearrangement juxtaposing the RET receptor tyrosine kinase with a constitutively active promoter; found in ~20% of sporadic PTCs and is the predominant driver in radiation-induced and pediatric PTCs

Rare fibrosing thyroiditis characterised by dense paucicellular hyaline fibrosis extending into perithyroidal soft tissues; part of IgG4-related disease spectrum

Radiologic appearance of vertebral bodies with alternating dense (sclerotic) and lucent (resorbed) bands, seen in secondary hyperparathyroidism due to CKD; resembles the stripes of a rugby jersey

A mnemonic for pheochromocytoma: ~10% bilateral, ~10% extra-adrenal, ~10% familial, ~10% malignant, ~10% paediatric.

Peripheral pale vacuoles seen at the colloid–cell interface in actively stimulated thyroid (Graves); represents active endocytosis of colloid by follicular cells

Appropriate compensatory rise in PTH in response to chronic hypocalcemia or hyperphosphatemia; most commonly caused by CKD; all four glands enlarged

A tumour suppressor gene encoding a TGF-β pathway mediator; deleted in ~55% of PDAC; its loss predicts widespread haematogenous metastasis and poor surgical outcome.

Erosion of bone cortex at the periosteal surface due to PTH-driven osteoclast activation; pathognomonic finding along the radial aspect of the middle phalanges on hand X-ray in hyperparathyroidism

A test of adrenal reserve using synthetic ACTH (tetracosactide); primary adrenal insufficiency shows no cortisol rise; secondary insufficiency shows a blunted but eventual response.

Autonomous PTH hypersecretion developing after prolonged secondary hyperparathyroidism; produces hypercalcemia despite correction of the original stimulus

Large glycoprotein synthesised and secreted by follicular cells into the follicular lumen; serves as the scaffold for iodination and T3/T4 storage

A discrete lesion within the thyroid gland, radiologically distinct from surrounding parenchyma; ~5% are malignant

Enzyme on the apical membrane of follicular cells that catalyses iodination of tyrosine residues on thyroglobulin and coupling reactions to form T3/T4

Life-threatening exacerbation of thyrotoxicosis characterised by hyperpyrexia, tachyarrhythmia, altered consciousness, and cardiovascular collapse

Clinical state of excess thyroid hormone activity in peripheral tissues, regardless of the source (overproduction, passive leakage, or exogenous)

Thyroid enlargement associated with autonomous hormone overproduction causing hyperthyroidism; may be diffuse (Graves), multinodular (Plummer), or solitary (toxic adenoma)

Umbrella term for autoantibodies against TSHR; includes stimulating (TSI), blocking, and neutral antibodies

Recurrent superficial thrombophlebitis affecting different veins; a paraneoplastic sign of mucin-secreting adenocarcinomas (classically PDAC) caused by tumour mucin activating tissue factor.

Anterior pituitary glycoprotein hormone that binds TSHR on follicular cells to stimulate T3/T4 synthesis and secretion

IgG autoantibodies in Graves disease that bind and activate TSHR, mimicking TSH without being subject to negative feedback

Presence of tumor cell emboli within blood vessel lumina lined by endothelium, within or outside the tumor capsule; indicates follicular carcinoma

The principal urinary metabolite of catecholamines; elevated in pheochromocytoma and neuroblastoma; 24-hour urinary VMA is a standard biochemical screen.

Acute bilateral adrenal haemorrhage and infarction complicating overwhelming sepsis (classically Neisseria meningitidis); causes acute primary adrenal insufficiency.

A nine-feature histological scoring system for adrenocortical tumours; ≥3 features (including capsular invasion, vascular invasion, atypical mitoses, necrosis) indicates malignancy.

Acute inhibition of thyroid hormone synthesis by excess iodine; normal glands escape after 1–2 weeks, but Hashimoto patients may fail to escape → hypothyroidism

German for 'cell balls'; the characteristic nesting pattern of pheochromocytoma in which polygonal chromaffin cells are arranged in compact nests surrounded by a delicate vascular stroma.

The middle and largest zone of the adrenal cortex; secretes glucocorticoids (cortisol); regulated by ACTH; undergoes disuse atrophy with exogenous steroid therapy.

The outermost zone of the adrenal cortex; secretes mineralocorticoids (aldosterone); regulated by the renin-angiotensin system and serum potassium, not ACTH.

The innermost zone of the adrenal cortex; secretes adrenal androgens (DHEA, androstenedione); regulated by ACTH.

Pituitary-derived peptide from POMC that activates MC1R on melanocytes to increase melanin synthesis; responsible for hyperpigmentation in Addison disease.