Endocrine Pathology I - Pituitary and Adrenal Pathology PDF

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Endocrine Pathology I - Pituitary and adrenal pathology Class Year 2 Course Pathology Lecturer Dr Helen Barrett Date 10th January 2025 LEARNING OUTCOMES Describe feedback loops as they apply to endoc...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Endocrine Pathology I - Pituitary and adrenal pathology Class Year 2 Course Pathology Lecturer Dr Helen Barrett Date 10th January 2025 LEARNING OUTCOMES Describe feedback loops as they apply to endocrine organs Identify histological features of the normal pituitary gland List the causes of hyper and hypopituitarism Classify pituitary tumours Identify histological features of the normal adrenal gland Describe key clinical features and presentation of hypo and hyperadrenalism Outline and illustrate pathological features of adrenocortical and medullary lesions OVERVIEW – ENDOCRINE SYSTEM Integrated, widely distributed group of organs. Maintain metabolic equilibrium between various organs. Secreting chemical messengers (hormones) into the blood that regulate the activity in an organ. ENDOCRINE SYSTEM Pure endocrine organs Pituitary Thyroid Parathyroid Adrenal – Cortex & Medulla Endocrine components in mixed organs Pancreas Ovary Testis ENDOCRINE SYSTEM Endocrine glands are under complex regulatory control mechanisms with a variety of stimulatory and inhibitory signals Trophic releasing hormones Trophic hormones Feedback inhibition - Increased activity in the target tissue down regulates the activity of the gland secreting the stimulating hormone Release inhibiting hormones  ENDOCRINE FUNCTION Endocrine organ Upstream stimulation Hormone End organ DISEASE IN ENDOCRINE ORGANS Usually comes to attention via: Hyperfunction – excessive secretion of hormones Hypofunction – decreased secretion of hormones Enlargement / mass effect Functional Non functional ENDOCRINE HYPERFUNCTION Excessive secretion of hormones Hyperplasia or neoplasia of hormone secreting cells Secondary hyperfunction – increased stimulation / decreased feedback inhibition Ectopic hormone production  ENDOCRINE HYPERFUNCTION Endocrine organ Functioning lesion, eg tumour Ectopic hormone Increased upstream stimulation End organ ENDOCRINE HYPOFUNCTION Decreased secretion Primary hypofunction Congenital absence Hypoplasia Destruction of the gland Secondary hypofunction Absence of trophic hormones Pseudohypofunction Target organ receptors not functioning  ENDOCRINE HYPOFUNCTION Degeneration/destruction of organ Decreased upstream stimulation Defect receptor in end organ End organ PITUITARY GLAND PITUITARY GLAND 500mg 10-15mm Sella turcica 2 functionally separate components Anterior lobe, adenohypophysis derived from Rathke’s pouch Posterior lobe, neurohypophysis derived from 3rd ventricle ANTERIOR PITUITARY, 3 CELL TYPES Acidophils Chromophobes Basophils ANTERIOR PITUITARY HORMONES Growth Hormone (GH) Prolactin (PL) Thyroid Stimulating Hormone (TSH) Follicle Stimulating Hormone (FSH) Luteinising Hormone (LH) Adrenocorticotrophic Hormone (ACTH) (Melanocyte Stimulating Hormone (MSH)) HYPERPITUITARISM Functioning adenoma Most common pathology encountered Carcinoma Very rare Must show metastasis for diagnosis Very rarely other pathology (e.g. hyperplasia) PITUITARY ADENOMAS 10% primary intracranial neoplasms All ages (most common 40-60 yrs) Usually isolated disorder Rarely as part of MEN type 1 PITUITARY ADENOMAS Functional adenoma Prolactinoma 50% Somatotrophic adenoma 15% Adrenocorticotrophic adenoma 10% Gonadotrophic adenoma 4% Thyrotrophic travel down nerve axons to posterior pituitary -> released into circulation Influenced by plasma osmolality and volume POSTERIOR PITUITARY Syndrome of inappropriate ADH secretion (SIADH) Continued inappropriate production of ADH leads to excessive water reabsorption by kidneys and water overload. Causes hyponatraemia. POSTERIOR PITUITARY Decreased secretion of ADH causes Diabetes Insipidus: Kidneys unable to conserve water - polyuria and polydypsia Causes - Head injury/surgical, Neoplasm, Inflammation DDx: nephrogenic diabetes insipidus ADRENAL GLANDS ADRENAL GLANDS Left adrenal Right adrenal gland gland 4gm 4gm ADRENAL CORTEX Diet Androgens Mineralocorticoids (Aldosterone) Cholesterol Glucocorticoids (Cortisol) Acetate ADRENAL CORTEX Glucocorticoid hormones – Zona Fasiculata – Zona Reticularis Mineralocorticoids – Zona Glomerulosa Sex steroids – Zona Reticularis ADRENAL HYPERFUNCTION ADRENOCORTICAL HYPERFUNCTION Hypercortisolism (Cushing syndrome) Hyperaldosteronism Primary Secondary Adrenogenital syndromes ADRENOCORTICAL HYPERFUNCTION Hypercortisolism (Cushing syndrome) – Increased glucocorticoid levels – Exogenous OR Endogenous ADRENOCORTICAL HYPERFUNCTION Hypercortisolism (Cushing syndrome) Exogenous Iatrogenic (administration of glucocorticoids) Most common cause of Cushing Syndrome ADRENOCORTICAL HYPERFUNCTION Endogenous – 1°hypothalamic-pituitary diseases Pituitary disease (70-80% of cases) Pituitary adenoma [Cushing disease] – Adrenal causes Adenoma, carcinoma, nodular hyperplasia (10-20% of cases) – Paraneoplastic cause Secretion of ectopic ACTH by a neoplasm (small cell carcinoma, carcinoid tumours, medullary carcinomas of thyroid, islet cell tumours of pancreas)  Morphology of adrenal gland in hypercortisolism depends on the cause: – Cortical atrophy (exogenous glucocorticoids) – Diffuse / nodular hyperplasia – Adenoma / carcinoma CLINICAL FEATURES OF CUSHING SYNDROME Hypertension Weight gain (truncal obesity, buffalo hump) Moon face Decreased muscle mass (hypercortisolism → atrophy of fast twitch myofibers) Hyperglycaemia (glucocorticoids → gluconeogenesis and inhibit uptake of glucose by cells) – Glucosuria and polydipsia Fragile thin skin, easily bruised, cutaneous striae (catabolic effect of glucocorticoids on protein with loss of collagen) Osteoporosis (glucocorticoids induce bone resorption) Susceptibility to infections (glucocorticoids suppress immune system) Mental disturbances (mood swings, depression, psychosis) Hirsutism and menstrual abnormalities HYPERALDOSTERONISM Aldosterone – steroid hormone – acts on the renal distal tubules and collecting ducts – retention of sodium, secretion of potassium, increased water retention, and increased blood pressure HYPERALDOSTERONISM 1. Primary 2. Secondary (extra-adrenal) Na+ K+ Hypertension Aldosterone Hypokalaemia File:Renin-angiotensin-aldosterone system.png HYPERALDOSTERONISM Primary hyperaldosteronism Overproduction of aldosterone – Results in suppression of renin-angiotensin system → Decrease plasma renin Clinically – hypertension and hypokalemia Diagnosis - ↑ aldosterone and ↓ renin PRIMARY HYPERALDOSTERONISM Caused by: 1. Aldosterone producing adrenocortical neoplasm 80% of cases – adenoma (Conn syndrome) Conn syndrome: adults, midlife, F:M = 2:1 Small R, bright yellow adenoma 2. Adrenocortical hyperplasia (bilateral idiopathic hyperplasia) 3. Glucocorticoid-suppressible hyperaldosteronism (rare) Mutation resulting in hybrid glomerulosa cells responsive to ACTH PRIMARY HYPERALDOSTERONISM Treatment: – Adenoma: surgical removal – Hyperplasia: aldosterone antagonist (spironolactone) SECONDARY HYPERALDOSTERONISM ▪ Overproduction of aldosterone due to activation of the renin-angiotensin system ▪ Increased plasma renin ▪ Occurs in: ▪ Congestive heart failure. ▪ Decreased renal perfusion (renal artery stenosis). ▪ Hypoalbuminemia. ▪ Pregnancy (oestrogen-induced increases in plasma renin substrate). ▪ Treatment: correction of underlying cause ADRENOGENITAL SYNDROMES Disorders of sexual differentiation 1. primary gonadal disorders 2. primary adrenal disorders Two compounds secreted by adrenal cortex (dehydroepiandrosterone and androstenedione) converted to testosterone in peripheral tissues ADRENOGENITAL SYNDROMES Androgen adrenocortical neoplasm: – Carcinoma > adenoma Congenital adrenal hyperplasia: – Group of autosomal recessive disorders – Deficiency/lack of a particular enzyme involved in synthesis of cortical steroids (mostly cortisol) – Steroidogenesis channeled into increased production of androgens → virilisation – Deficiency in cortisol results in ACTH increase → adrenal hyperplasia – May impair aldosterone secretion ADRENOGENITAL SYNDROMES ▪ 21-Hydroxylase deficiency (90% of these cases) ▪ Converts progesterone to 11-deoxycorticosterone ▪ No mineralocorticoid and deficient cortisol synthesis ▪ Excess production of androgens ▪ Hyponatremia, hyperkalaemia inducing acidosis, hypotension, cardiovascular collapse and death ADRENAL HYPOFUNCTION ADRENAL INSUFFICIENCY Primary adrenocortical insufficiency: – Primary adrenal disease 1. Primary acute adrenocortical insufficiency (adrenal crisis) 2. Primary chronic adrenocortical insufficiency (Addison’s disease) Secondary adrenocortical insufficiency – Decreased stimulation due to deficiency of ACTH PRIMARY ACUTE ADRENOCORTICAL INSUFFICIENCY Acute adrenal crisis Occurs in: – Chronic adrenocortical insufficiency precipitated by any form of stress (infections, trauma, surgical procedures) which requires increased steroid output from the glands. – Patients on exogenous corticosteroids → rapid withdrawal or failure to increase steroid doses in response to stress. – Massive adrenal haemorrhage (anticoagulant therapy, post- surgical developing DIC, bacteremic infection). Manifested by intractable vomiting, abdominal pain, hypotension, coma, vascular collapse.  WATERHOUSE-FRIDERICHSEN SYNDROME Bilateral adrenal haemorrhage: – Neisseria meningitidis septicemia (Pseudomonas, pneumococci, staphylococci, or haemophilus influenzae) – Rapidly progressive hypotension -> shock – DIC (purpura of skin) Children > adults Clinical course abrupt and devastating Effectively treated with antibiotics if recognized promptly WATERHOUSE-FRIDERICHSEN SYNDROME PRIMARY CHRONIC ADRENOCORTICAL INSUFFICIENCY Addison disease Progressive destruction of adrenal cortex 90% cortex destroyed clinical manifestations Pathogenesis – 90% cases due to 1. Autoimmune adrenalitis (60-70% of cases) 2. Infections, particularly TB 3. Metastatic carcinoma  30% Autoimmune adrenalitis 70% Tuberculosis, metastatic carcinoma Carcinomas of lung/breast majority of cases 50% adrenal sole target 50% - [Polyglandular syndromes] other autoimmune diseases co-exist (e.g. hashimotos thyroiditis, pernicious anemia, DM type I, hypoparathyroidism) Frequency of adrenalitis increased with HLA-B8 and DR-3 (histocompatibility antigens) CLINICAL MANIFESTATIONS OF ADDISON DISEASE Progressive weakness Fatigability GI symptoms (Anorexia, N&V, weight loss) Hyperpigmentation of skin → ↑ACTH → stimulate melanocytes Hyperkalaemia, hyponatraemia, hypotension (aldosterone deficiency) Hypoglycaemia (glucocorticoid deficiency) Stresses → acute adrenal crisis SECONDARY ADRENOCORTICAL INSUFFICIENCY Hypothalamus Metastatic carcinoma, infection, infarction, irradiation Pituitary gland ACTH Manifestations differ to primary adrenocortical insufficiency as only cortisol and androgen levels are deficient whereas aldosterone is normal. No hyperpigmentation as ACTH is low Administration of ACTH exogenously -> no response in primary but with secondary -> prompt rise in cortisol ADRENOCORTICAL NEOPLASMS ADRENOCORTICAL NEOPLASMS Adenomas / Carcinomas F>M Age 30-50 Functional neoplasms may be responsible for any form of hyperadrenalism If functioning: high cortisol -> suppression of endogenous ACTH -> atrophic adjacent cortex and contralateral gland ADRENOCORTICAL ADENOMAS Most are clinically silent (incidental finding) Gross: – well circumscribed – virilism and hyperadrenalism) Usually >20cm when diagnosed Macro: poorly demarcated, necrosis, haemorrhage, cystic change Micro: range from well-differentiated cells to undifferentiated carcinoma Invade adrenal vein, vena cava and lymphatics Metastasize to regional LN, lungs or other viscera (bone mets uncommon) Median survival 2 years ADRENAL MYELOLIPOMA Benign entity Fat and haematopoietic cells Incidental findings May reach massive proportions ADRENAL MEDULLA ADRENAL MEDULLA Composed of: – Neuroendocrine cells (chromaffin cells) -> catecholamines – Sustentacular cells (supporting cells) Sympathetic nervous system -> chromaffin cells to secrete catecholamines – Increase rate and force of myocardial contractions and vasoconstriction ADRENAL MEDULLA Diseases of adrenal medulla: – Neoplasms of chromaffin cells (phaeochromocytoma) – Neuronal neoplasms (neuroblastomas, ganglion cell tumours) Neuroblastoma - sporadic but familial cases do occur; most common extracranial tumour of childhood PHAEOCHROMOCYTOMA Uncommon neoplasms Surgically correctable form of hypertension – 0.1%-0.3% of hypertensive patients “Rule of 10s” 10% extra-adrenal paraganglia (referred to as paragangliomas) (10% ->) >25% occur with familial syndromes (MEN syndromes, type I neurofibromatosis, von Hippel Lindau disease) 10% bilateral (~50% familial cases) 10% malignant (adrenal) vs. 20-40% extra-adrenal Histologically: small nests of polygonal/spindle cells referred to “Zellballen” PHAEOCHROMOCYTOMA As many as 25-30% of patients with phaeochromocytoma / paraganglioma harbour a germ line mutation (RET, NF1, VHL, succinate dehydrogenase complex – SDHB, SDHC, SDHD). PHAEOCHROMOCYTOMA Clinical features: – Hypertension, tachycardia, palpitations, headaches, sweating, tremor – Abdominal/chest pain – Sustained hypertension (two thirds cases) – Paroxysmal episodes of hypertension – exercise, stress, change in posture, palpation in region of tumour cause release of catecholamines – “Catecholamine cardiomyopathy” (myocardial instability and ventricular arrhythmias -> due to vasomotor constriction of myocardial circulation) PHAEOCHROMOCYTOMA Diagnosis: – 24 hour urinary collection of catecholamines and metabolites (e.g. VMA [vanillylmandelic acid] and metanephrines) Treatment: – Surgical excision after pre-operative and intra- operative medication with adrenergic blocking agents (prevent adrenal crisis) EXTRA-ADRENAL PARAGANGLIA TUMOURS Paragangliomas – Carotid body tumours (carotid body) – Chemodectomas (jugulotympanic body) 10-40% malignant (recur after resection) 10% metastasize widely 15-25% multicentric LEARNING OUTCOMES Describe feedback loops as they apply to endocrine organs Identify histological features of the normal pituitary gland List the causes of hyper and hypopituitarism Classify pituitary tumours Identify histological features of the normal adrenal gland Describe key clinical features and presentation of hypo and hyperadrenalism Classify adrenal tumours THANK YOU