Endocrine Disorders PDF

Assessing the function of the endocrine system Pixabay.com 1. Overview of the Endocrine System Homeostasis System of control mechanisms The endocrine control Achieved by biochemical regulators ❖Hormones ❖Paracrine factors (e.g., prostaglandins) ❖Autocrine f...

Assessing the function of the endocrine system Pixabay.com 1. Overview of the Endocrine System Homeostasis System of control mechanisms The endocrine control Achieved by biochemical regulators ❖Hormones ❖Paracrine factors (e.g., prostaglandins) ❖Autocrine factors (e.g., interleukins) 1. Overview of the Endocrine System Larson, 2017 2. Types of Hormones Hormones are classified by structure: ❖Peptide or polypeptides Different sizes but same mechanism of function Pixabay.com E.g., insulin, GH, PTH, glucagon Water soluble ❖Amino acid derivative Synthesized by the thyroid gland (T4 and T3), and the adrenal medulla Water soluble (catecholamines) or lipid soluble ❖Steroid hormones All derived from cholesterol Not stored Lipid soluble (cortisol, aldosterone, testosterone, estrogen, and progesterone) 3. Negative Feedback in the Hypothalamus-Pituitary- Thyrotropin-releasing hormone (TRH), Endocrine Gland Axis (TSH) Used by the endocrine system to precisely regulate hormone “Thyroid gland” synthesis and release E.g., Thyroid hormone production “Thyroid hormones” 4. Disease Processes of the Endocrine System Diseases and disorders of the endocrine system are usually caused by: Tumours Inflammation Degenerative processes Genetic mutations Endocrine diseases can be: ▪ Primary (disease from target organ) ▪ Secondary (disease from hypothalamus- pituitary axis) ▪ Tertiary (tumour in hypothalamus or pituitary) ▪ “Ectopic” (hormone-secreting tumour in a part of the body) 5. Hypothalamus and Pituitary Glands Form a controlling unit Other endocrine glands Thyroid Adrenal Gonads ✓Direct control of physiological functions Lactation Growth and metabolism 5.1 Pituitary Gland Regulated by the hypothalamus Anterior pituitary ACTH, GH, prolactin, TSH, LH, and FSH Posterior pituitary ADH, oxytocin 5.1 Hypothalamus Hormones and Anterior Pituitary Regulation 5.1 Posterior Pituitary Hormones Antidiuretic hormone (ADH) Stimulated by: Increased plasma osmolality Blood volume depletion Stress and nausea Oxytocin ADH https://www.sciencedirect.com/topics/medicine-and-dentistry/posterior-pituitary 6. Clinical Disorders of the Pituitary Gland The consequence of pituitary disorders may be: ▪ Oversecretion Abnormal growth of cells in pituitary gland Increased production of tropic hormones by the hypothalamus Ectopic tumour ▪ Deficiency of hormones Posterior pituitary gland It usually involves more than one hormone E.g., tumours, trauma, infections, pituitary surgery Excess Pituitary Hormone Disorders 6.1 Excess Pituitary Hormone Disorders ADH Excess 1. Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) Secretion of high levels of ADH without stimulus ❖Causes: Ectopic tumours, tuberculosis, cystic fibrosis, trauma, use of drugs (e.g.., antidepressants), etc. ❖Consequences: Water retention (hyponatremia) Serum/urine osmolality? SIADH Water retention, kidneys keep excreting sodium ADH secretion ❖Symptoms: Thirst, weight gain, fatigue, anorexia, etc. (No edema!) ❖ Diagnosing SIADH Medical history and physical examination Laboratory tests: Measurements of electrolytes (hyponatremia) Serum (< 280 mOsm/Kg) and urine osmolality (> serum osmolality) Normal: renal, adrenal, and thyroid function test results 6.2 Excess Pituitary Hormone Disorders Growth Hormone (GH) ❖Normal growth Rapid growth (first 2 years) Steady growth (for around 9 years) Controlled by GH Growth spurt at puberty 6.2 Excess Pituitary Hormone Disorders 2. Growth Hormone excess Gigantism in children and adolescents Acromegaly in adults ❖Causes: Pituitary adenoma ❖Consequences Gigantism Acromegaly Cardiac hypertrophy, hypertension, atherosclerosis, type 2 diabetes, coarsening facial features ❖Diagnosing acromegaly Requires oral glucose tolerance test with GH measurement ▪ No GH suppression IGF-1 measurement ▪ Produced in response to GH Treatment: Surgery Radiation Synthetic analogues of somatostatin 6.3 Excess Pituitary Hormone - Other Disorders 3. Hyperprolactinemia Excess of prolactin (prolactinomas) ▪ Milk production in women ▪ Hypogonadism and erectile dysfunction in men 4. Adrenocorticotropic hormone (ACTH) excess Stimulates the adrenal cortex to produce glucocorticoids (stress) Excess of ACTH (Cushing syndrome) Deficit Disorders of the Pituitary Gland 6.4 Deficit Disorders of the Pituitary Gland ADH Decrease 1. Diabetes insipidus Low ADH Kidneys unable to retain water Increased excretion of water Plasma osmolality - urine osmolality Symptoms: Polyuria, nocturia, continuous thirst, and polydipsia Laboratory findings: Water restriction = no increase in urine osmolality 6.5 Deficit Disorders of the Pituitary Gland GH Decrease 2. Growth hormone deficiency Diminished GH secretion Occurs in children and in adults ❖Causes: Genetic mutations Tumours ❖Consequences https://www.momjunction.com/articles/children-dwarfism-types-symptoms-causes_00780340/ Children (e.g., growth failure, fasting hypoglycemia) Adults (E.g., increased body fat, decreased muscle bulk and strength) ❖ Tests for growth hormone deficiency A lack of GH response to stress of exercise or clonidine is diagnostic GH response to stimulation Insulin tolerance test (ITT) Induces hypoglycemia Arginine stimulation test Stimulates pituitary ❖Treatment Genetically engineered GH 7. Thyroid Gland Consists of ring-shaped follicles composed of follicular cells Follicular cells secrete thyroid hormones T3 (triiodothyronine) T4 (tetraiodothyronine or thyroxine) https://depositphotos.com/photos/thyroid.html Functions Neurologic development, oxygen consumption, heat production, growth, sexual maturity, metabolism of carbohydrates and proteins 7.1 Thyroid Hormones Essential for tissue maturation and metabolism Congenital hypothyroidism Thyroxine (T4) and Triiodothyronine (T3) Produced in thyroid gland with iodine atoms Peripheral tissues deiodinate T4 to produce 2/3 of circulating T3 (more biologically active) Most cells can deiodinate T4 T4 can be metabolized to reverse T3 (rT3) – inactive Most T3 and T4 are bound to proteins “Free” T3 and T4 are active 7.2 Regulation of Thyroid Hormone Secretion Hypothalamic – pituitary – thyroid axis Components: Thyrotropin-releasing hormone (TRH) Thyroid-stimulating hormone (TSH) Thyroid hormones Too much thyroid hormone – suppression of TSH Low thyroid hormone – high TSH 7.3 Goiter Enlarged thyroid gland May be associated with underproduction (hypothyroidism) and overproduction (hyperthyroidism) of thyroid hormones Associated with iodine deficiency Disorders of the Thyroid Gland 7.4 Disorders of Thyroid Underproduction – Hypothyroidism Usually due to primary hypothyroidism Decreased thyroid hormones, increased TSH Secondary Decreased TSH, decreased thyroid hormones Tertiary Decreased TRH Overproduction – Hyperthyroidism Commonly a primary disease 7.5 Deficit of Thyroid Hormones - Hypothyroidism Commonly develops slowly Causes: Autoimmune (thyroiditis - Hashimoto’s disease- >90%) Surgery for hyperthyroidism Transient hypothyroidism (e.g., lithium carbonate) TSH deficiency Congenital defects Severe iodine deficiency 7.5 Hypothyroidism- Signs and Symptoms Appearance: weight gain, coarse dry skin, hoarse voice, perhaps goiter Disposition: lethargic, depressed, cold intolerance Neuromuscular: altered tendon reflexes, muscle weakness Heart: slow pulse, reduced cardiac output ❖ Diagnosis of Hypothyroidism Primary hypothyroidism Failure of the thyroid gland (most common) Low thyroid hormones TSH measurement ? Elevation of TSH is diagnostic Secondary hypothyroidism Failure of the pituitary gland to secrete TSH Thyroid hormone level? TSH level? ❖ Treatment of Hypothyroidism Thyroid hormone replacement Therapy for life (T4) Important to monitor TSH concentrations Replacement of thyroid hormone in newborns will avert the development of symptoms Congenital hypothyroid disorders 7.6 Excess of Thyroid Hormones - Hyperthyroidism Overactivity of the thyroid glands Tissues are exposed to high levels of thyroid hormones Excess thyroid hormones increase the body's metabolism Primary Increased T3 and T4, decreased TSH Secondary (rare) and Tertiary Increased TSH with or without increased TRH 7.6 Excess of Thyroid Hormones - Hyperthyroidism Causes: Grave’s disease (most common) Antibodies bind to the TSH receptor on thyroid cells Solitary toxic adenoma Independent of TSH stimulation Thyroiditis Ingestion of excess T4 and/or T3 Exogenously administered iodine Toxic multinodular goiter 7.6 Excess of Thyroid Hormones - Hyperthyroidism Signs and Symptoms Appearance: weight loss despite appetite, sweating, tremor, possible goiter Disposition: agitated, nervous, heat intolerance, easy fatigability Heart: tachycardia Neuromuscular: muscle weakness and loss of muscle mass Eyes: upper lid retraction, exophthalmos ❖ Diagnosis of Hyperthyroidism Easily diagnosed Decreased TSH with an increased free T4 (fT4) concentration Presence of TSH-receptor antibodies Indicative of Grave’s disease (not diagnostic) Subclinical hyperthyroidism Low TSH and free T4 and T3 within the reference intervals Some patients are at increased risk of primary hyperthyroidism ❖ Treatment of Hyperthyroidism Three methods for the treatment of Grave’s disease: Antithyroid drugs Patients with higher likelihood of remission Radioiodine 131I ; irreversible treatment Permanent thyroid hormone replacement is expected Surgery Thyroidectomy (subtotal or total) 8. Hypothalamic-Pituitary-Adrenal Axis Overviews the interactive actions of neuroendocrine system Responsible for the control of reactions to stress Regulates digestion, immune system, mood, sexuality and energy storage utilization Wikimedia, 2024 https://www.frontiersin.org/journals/neurology/articles/10.3389/fne ur.2013.00021/full 8.1 Adrenal Glands Two adrenal glands Composed of cortex and medulla ❖Cortex Zona glomerulosa Zona fasciculata Zona reticularis Hormones include mineralocorticoids, glucocorticoids and the adrenal androgens ❖Medulla (part of sympathetic nervous system) Adrenaline, noradrenaline, and dopamine 8.2 Cortisol Major glucocorticoid Functions It regulates carbohydrate, protein and lipid metabolism Cortisol levels show diurnal variation Single serum measurement are of limited clinical value Affected by sleep-wake cycle Regulated by the hypothalamus and anterior pituitary gland 8.3 Aldosterone Major mineralocorticoid Functions Maintain extracellular fluid volume, regulate sodium and potassium Produced by the zona glomerulosa Controlled by the renin-angiotensin system 8.4 Adrenal Androgens Secretion of small amounts ACTH regulation Androstenedione, (DHEA), and DHEA sulfate are converted to sex hormones in gonads, skin, and adipose tissue Functions Females (important source of androgens) Males https://kids.frontiersin.org/articles/10.3389/frym.2020.554380 8.5 Adrenal Medulla Catecholamines Epinephrine (adrenaline) Norepinephrine (noradrenaline) Response to stresses “Fight or flight response” Traumatic injury, hypoxia, hypoglycemia 8.5.1 Adrenal Medulla Hormones Epinephrine (adrenaline) Increases heart rate Increases blood pressure Increases muscle strength Increases glucose metabolism Norepinephrine (noradrenaline) Increases rate of heart contractions Affects the brain Increases peripheral blood vessel resistance Alertness End of activity Stored and reused Excreted in the urine 8.6 Hormonal disorders of the Adrenal Cortex Alter development and homeostasis Decrease in secretion (e.g., Aldosterone – Addison’s disease) Increase in secretion (e.g., Cortisol - Cushing syndrome) Deficit Disorders of the Adrenal Gland 8.6.1 Adrenal Insufficiency Rare and potentially fatal Important signs Pigmentation and/or hyponatremia and dehydration – must be investigated Lack of mineralocorticoids – loss of sodium from ECF – loss of water Causes Primary Addison’s disease Secondary – use of corticosteroid suppression of the entire hypothalamic–pituitary– adrenocortical axis 8.6.1 Addison’s Disease Autoimmune mechanism More common in women than in men Laboratory results: low corticosteroid and mineralocorticoid levels with elevated ACTH levels Symptoms Only when more than 90% of the adrenal tissue is destroyed Weakness, easily fatigued, hyperpigmented skin, anorexia, nausea, vomiting, diarrhea Excess Disorders of the Adrenal Gland 8.6.2 Hyperfunction of the Adrenal Cortex Cortisol excess Prolonged exposure of tissues to cortisol or other corticosteroids Effects lead to Cushing’s syndrome ▪ Most commonly due to the use of steroid medications (iatrogenic Cushing’s syndrome) ▪ Tumours that secrete cortisol or ACTH ▪ Causes 8.6.2 Cushing’s Syndrome Symptoms Skin pigmentation Weight gain Increased body and Central obesity and growth of fat facial hair (moon face) Decreased immune Thinning scalp hair response Facial flush Purple striae Hyperglycemia Easy bruising Hypertension Laboratory considerations for Cushing’s disease Cortisol measurement (high in many conditions) ACTH measurement Help determine the cause  9. Hypothalamic–pituitary–gonadal axis Hypothalamic–pituitary–gonadal axis Gonadotrophin-releasing hormone (GnRH) Stimulates synthesis of gonadotrophins: LH and FSH Stimulate sex hormone secretion and reproduction Wikimedia Commons, 2024 https://commons.wikimedia.org/wiki/File:Hypothalamic%E2%80%93pit uitary%E2%80%93gonadal_axis.svg  9.1 Gonadal Function - Male Male gonadal function Testes: secrete testosterone and manufacture spermatozoa LH stimulates the development of Leydig cells and testosterone Sertoli cells are influenced by FSH Disorders of male sex hormones Hypogonadism Primary (testicular deficiency) Decrease in testosterone Increase in LH and FSH Secondary (defect in hypothalamus or pituitary) Decrease in LH and FSH 9.2 Gonadal Function - Female Estradiol is responsible for: Female secondary characteristics Stimulation of follicular growth Development of endometrium Normal hormonal control of the menstruation cycle FSH is released – follicular growth initiates Surge in LH- ovulation Follicle differentiates into corpus luteum – progesterone and estradiol Disorders of female sex hormones Subfertility, amenorrhea and oligomenorrhea Hirsutism Virilism 9.3 Subfertility The failure of a couple to conceive after 1 year of regular, unprotected intercourse Clinical history + physical examination Endocrine abnormalities Found in one-third of female patients Very rare in males No cause identified in some couples Endocrine examinations in females High progesterone in the middle of the luteal phase No further endocrine examination Low progesterone in the middle of the luteal phase No ovulation Women with irregular/absent menstruation or no ovulation Hormone measurements may be diagnostic Measures of estradiol (low) and gonadotrophin (high) (primary ovarian failure) Measures of prolactin and androgens