Endocrinology Quiz on Hyperaldosteronism

Endocrine Pathology - Pituitary and Adrenal

• The endocrine system is an integrated, widely distributed group of organs maintaining metabolic equilibrium.
• Endocrine organs secrete hormones into the bloodstream to regulate organ activity.
• Pure endocrine organs include the pituitary, thyroid, parathyroid, and adrenal cortex/medulla.
• Endocrine components are found in mixed organs – pancreas, ovaries, and testes.
• Endocrine glands are regulated by complex mechanisms with stimulatory and inhibitory signals.
• The adrenal glands are located above each kidney, weighing approximately 4 grams each.
• The pituitary gland, or hypophysis, is located in the sella turcica, weighing 500mg and measuring 10-15mm in size.
• The pituitary consists of both an anterior, adenohypophysis, and posterior lobe, neurohypophysis, derived from Rathke's pouch and the 3rd ventricle, respectively.
• Multiple separate histological cell types exist in the anterior pituitary

Learning Outcomes

• Describe feedback loops in endocrine organs
• Identify histological features of the normal pituitary gland
• List causes of hyper and hypopituitarism
• Classify pituitary tumors
• Identify histological features of the normal adrenal gland
• Describe clinical features and presentation of hypo- and hyperadrenalism
• Outline and illustrate pathological features of adrenocortical and medullary lesions
• Classify adrenal tumors

Overview - Endocrine System

• The endocrine system is a group of organs that control metabolic balance between various organs.
• These organs secrete chemical messengers, hormones, into the bloodstream to regulate the activity of an organ.

Endocrine System (Types)

• Pure endocrine organs: pituitary, thyroid, parathyroid, adrenal (cortex & medulla).
• Endocrine components in mixed organs: pancreas, ovary, testis

Endocrine System (Feedback)

• Endocrine glands are under complex regulatory control with stimulatory and inhibitory signals.
• Trophic releasing hormones
• Trophic hormones
  • Increased activity in the target tissue downregulates the gland secreting the stimulating hormone.
• Release inhibiting hormones.

Feedback Regulation in the Endocrine System

• The hypothalamus (brain) regulates the pituitary gland.
• Hypothalamic factors (releasing and inhibiting) stimulate/inhibit the pituitary.
• Circulating hormones (from the pituitary) influence target tissues/organs.
• Feedback loops (positive and negative) maintain hormone levels.

Feedback Regulation of Thyroid Hormone

• TRH (thyrotropin-releasing hormone) from hypothalamus stimulates TSH (thyroid-stimulating hormone) release from the pituitary.
• TSH stimulates the thyroid to produce T4 and T3 (thyroid hormones).
• Increased levels of T4 and T3 inhibit TRH and TSH release, creating a negative feedback loop.

Feedback Regulation of Cortisol

• Stress triggers CRH (corticotropin-releasing hormone) from hypothalamus, activating ACTH (adrenocorticotropic hormone) in the pituitary
• ACTH stimulates the adrenal gland to produce cortisol
• Elevated cortisol inhibits CRH and ACTH release, creating a negative feedback loop

Endocrine Function

• Upstream stimulation triggers hormone secretion in the endocrine organ.
• The hormone acts upon an end-organ.

Disease in Endocrine Organs

• Typically recognized through hyperfunction (excessive hormone secretion), hypofunction (decreased hormone secretion), or enlargement/mass effect.

Endocrine Hyperfunction

• Excessive hormone secretion can result from
  • Hyperplasia or neoplasia of hormone-secreting cells
  • Increased stimulation/decreased feedback inhibition
  • Ectopic hormone production

Endocrine Hypofunction

• Decreased hormone secretion from
  • Primary hypofunction (congenital absence, hypoplasia, destruction of the gland)
  • Secondary hypofunction (absence of trophic hormones)
  • Pseudohypo function (target organ receptors not functioning)

Pituitary Gland

• 500mg weight, 10-15mm size
• Two functionally separate components: anterior (adenohypophysis) and posterior (neurohypophysis) lobes
• Anterior lobe (adenohypophysis): derived from Rathke's pouch
• Posterior lobe (neurohypophysis): derived from the 3rd ventricle

Pituitary Gland (Anatomy)

• Pituitary (hypophysis) is comprised of:
  • Paraventricular nucleus
  • Supraoptic nucleus
  • Infundibulum
  • Pars tuberalis
  • Pars nervosa
  • Pars distalis
  • Pars intermedia

Anterior Pituitary (Cell Types)

• Acidophils
• Chromophobes
• Basophils

Anterior Pituitary Hormones

• Growth Hormone (GH)
• Prolactin (PL)
• Thyroid Stimulating Hormone (TSH)
• Follicle Stimulating Hormone (FSH)
• Luteinizing Hormone (LH)
• Adrenocorticotrophic Hormone (ACTH)
• Melanocyte Stimulating Hormone (MSH)

Control of Anterior Pituitary

• Mostly controlled by hypothalamic positive stimulus except for Prolactin and Growth Hormone (partly)

Hyperpituitarism

• The most common pathology is a functioning adenoma
• Carcinoma is rare
• Adenomas often show no metastasis

Pituitary Adenomas

• 10% of primary intracranial neoplasms
• Commonly occur between ages 40-60
• Typically an isolated disorder, not part of MEN1

Pituitary Adenomas (Types)

• Functional adenomas: prolactinomas (50%), somatotropinomas (15%), adrenocorticotropinomas, gonadotropinomas (4%), thyrotropinomas(<1%)
• Non-functional adenomas (null-cell): 20%

Pituitary Adenomas (Symptoms)

• Hormone overproduction (prolactin, GH, ACTH, TSH, FSH/LH)
• Space-occupying effects (optical chiasm pressure, increased intracranial pressure, hormone deficiencies)

Prolactinoma

• Elevated prolactin levels
• Can manifest subtly with low libido, impotence in males, and amenorrhea, sterility & galactorrhea in females
• Local pressure effects can occur

How Can Prolactin Be Increased?

• Prolactinoma
• Pregnancy/Lactation
• Stalk compression

Growth Hormone (Somatotropic) Adenomas

• Often bihormonal (+PRL)
• Pre-pubertal: giantism
• Post-pubertal: acromegaly

Acromegaly (Symptoms)

• Appearance changes (prognathism, brow protrusion, broad nose/hands/feet, enlarged tongue)
• Other symptoms (carpal tunnel syndrome, glycosuria/diabetes, joint pain, deafness).

Other Adenomas

• ACTH-producing adenomas (usually microadenomas, silent Cushing's disease)
• Gonadotroph pituitary adenomas.
• Thyrotrophic adenomas (rare)
• Null-cell adenomas

Cushing's Disease

• Hypercortisolism due to excess ACTH from the pituitary.

Hypothalamic-Pituitary Diseases

• Primary hypothalamic-pituitary diseases
• Pituitary disease (70-80% of cases)
• Pituitary adenoma [Cushing's disease]
• Adrenal causes
• Adenoma, carcinoma, nodular hyperplasia
• Paraneoplastic cause
• Secretion of ectopic ACTH by a neoplasm

Hypothyroidism

• Decreased secretion of ADH leads to polyuria and polydipsia
• Primarily due to head injury/surgical trauma, neoplasia, or inflammation
• Differentiate to nephrogenic diabetes insipidus.

SIADH

• Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
• Excess ADH leads to excessive water reabsorption, resulting in water overload and hyponatremia.

Adrenal Cortex

• Structures: zona glomerulosa, zona fasciculata, zona reticularis
• Hormones: glucocorticoids (zona fasciculata and zona reticularis), mineralocorticoids (zona glomerulosa), androgens (zona reticularis)

Adrenocortical Hyperfunction

• Primary hyperaldosteronism: caused by aldosterone-producing adrenocortical neoplasms (Conn syndrome), adrenal cortical hyperplasia.
• Secondary hyperaldosteronism: Overproduction of aldosterone from activation of renin-angiotensin system.
• Adrenogenital syndrome: disorders of sexual differentiation (including congenital adrenal hyperplasia).

Adrenocortical Hyperfunction (Cushing Syndrome, causes)

• Hypercortisolism (elevated glucocorticoid levels), exogenous (iatrogenic administration of glucocorticoids) or endogenous (pituitary or adrenal disease; paraneoplastic causes).

Adrenocortical Hyperfunction (Clinical Features)

• Hypertension, weight gain (truncal obesity), buffalo hump, moon face; reduced muscle mass, hyperglycemia, glucosuria, polydipsia, fragile skin, striae.
• Susceptibility to infections, mental disturbances, hirsutism, and menstrual abnormalities.

Hyperaldosteronism

• Aldosterone acts on renal tubules and collecting ducts to retain sodium, increase water retention, and increase blood pressure.
• Primary hyperaldosteronism is overproduction of aldosterone (suppresses renin-angiotensin system) -> hypertension and hypokalemia.
• Diagnosis involves elevated aldosterone and reduced plasma renin.
• Common causes include adrenal adenoma (Conn syndrome), adrenal cortical hyperplasia.

Secondary Hyperaldosteronism

• Overproduction of aldosterone due to activation of the renin-angiotensin system.
• Occurs with heart failure, decreased renal perfusion (renal artery stenosis), hypoalbuminemia, and pregnancy.
• Treatment: correction of the underlying cause.

Adrenogenital Syndromes

• Disorders of sexual differentiation, primary gonadal or primary adrenal disorders.
• Two compounds secreted by the adrenal cortex (dehydroepiandrosterone and androstenedione). These are converted to testosterone in peripheral tissues

Adrenogenital Syndromes (Causes)

• Androgen adrenocortical neoplasm (carcinoma > adenoma)
• Congenital adrenal hyperplasia (group of autosomal recessive deficiency disorders resulting in increased androgen production leading to virilisation, deficiency in cortisol, high ACTH, adrenal hyperplasia).

Adrenogenital Syndromes (21-Hydroxylase Deficiency)

• Common cause of congenital adrenal hyperplasia (90% of cases)
• Results in insufficient mineralocorticoids and glucocorticoids and excess androgens → hyponatremia, hyperkalemia, acidosis, hypotension.

Adrenal Hypofunction

• Primary adrenocortical insufficiency (Addison's disease): primary adrenal disease
  • Primary acute : serious medical emergency due to stressors (infections, trauma, surgical procedures.
  • Primary chronic: autoimmune adrenalitis (60-70% of cases), infections, particularly TB, or metastatic carcinomas.

Adrenal Hypofunction (Clinical Manifestations)

• Progressive weakness, fatigue, GI symptoms (anorexia, N&V, weight loss), hyperpigmentation, hyperkalemia, hyponatremia, hypotension, hypoglycemia.
• Stress triggers acute adrenal crisis

Secondary Adrenocortical Insufficiency

• Decreased ACTH stimulation leading to reduced cortisol and androgen (but aldosterone is normal)

Adrenocortical Neoplasms

• Adenomas/Carcinomas
• Typically age 30-50, functional adenomas could be responsible for various hyperadrenalisms.
• High cortisol suppresses ACTH ->atrophy in adjacent cortex and contralateral glands
• Adenomas are mostly clinically silent but can be responsible for overproduction of hormones.
• Adrenocortical carcinomas are rare, usually over 20cm, poorly demarcated with necrosis, hemorrhage and cystic changes.

Adrenal Myelolipoma

• Benign tumor of the adrenal gland.
• Contains fat and hematopoietic cells.

Adrenal Medulla

• Composed of neuroendocrine chromaffin cells and sustentacular cells.
• Responds to the sympathetic nervous system by secreting catecholamines.

Adrenal Medulla Diseases

• Phaeochromocytoma: neoplasm of chromaffin cells (often, but not always, presenting with hypertension)
• Neuroblastomas / ganglion cell tumours: neuronal neoplasms common in childhood.

Phaeochromocytoma

• Uncommon neoplasm (0.1%-0.3% of hypertensive pts)
• 10%: extra-adrenal paraganglia
• 10%: bilateral (~50% of familial cases)
• 10%: malignant (adrenal vs. 20-40% extra-adrenal)
• ~25-30% of pts with a germline mutation in the succinate dehydrogenase complex (SDHB, SDHC, SDHD)
• "Rule of 10s"

Phaeochromocytoma (Clinical Features)

• Hypertension, tachycardia, palpitations, headaches, sweating, tremor, abdominal/chest pain, Paroxysmal hypertension episodes (exercise, stress, posture change).
• Catecholamine cardiomyopathy

Phaeochromocytoma (Diagnosis)

• 24-hour urinary collection of catecholamines and metabolites (e.g., VMA, metanephrines)

Extra-Adrenal Paraganglia Tumours

• Carotid body tumors, chemodectomas
• 10-40% malignant
• 10% metastasize widely
• 15-25% multicentric

Pituitary and Adrenal Pathologies: Learning Outcomes

• Describe feedback loops in endocrine organs
• Histological features of normal pituitary/adrenal glands
• Causes of hyper/hypo-pituitarism
• Pituitary tumor classification
• Clinical features of hypo/hyper-adrenalism
• Adrenal tumor classification.

Test your knowledge on primary and secondary hyperaldosteronism with this quiz. Explore symptoms, causes, and treatments related to adrenal gland disorders. Ideal for students of endocrinology or anyone interested in hormone regulation.