1. Basic laboratory tests in endocrinology Drahomíra Springer ÚKBLD VFN a 1.LF UK Praha

2. Hormones Hormones are chemical messengers secreted into blood or extracellular fluid by one cell that affect the functioning of other cells One hormone type usually affects only target cells. A target cell has receptors for the hormone

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4. Pineal gland It produces melatonin, a hormone that affects the modulation of wake/sleep patterns and photoperiodic (seasonal) functions Thymus located posterior to the sternum ater puberty begins to decrease in size the primary function is the processing and maturation of T- lymphocytes produces a hormone, thymosin, which stimulates the maturation of lymphocytes in other lymphatic organs

5. Endocrine action: the hormone is distributed in blood and binds to distant target cells. Paracrine action: the hormone acts locally by diffusing from its source to target cells in the neighborhood. Autocrine action: the hormone acts on the same cell that produced it. Hormonal pathway

6. Structural groups of hormons Peptides and proteins Peptides and proteins many protein hormones are synthesized as prohormones many protein hormones are synthesized as prohormones circulate unbound to other proteins, exception – IGF 1 circulate unbound to other proteins, exception – IGF 1 the halflife of circulating peptide hormones is only a few minutes the halflife of circulating peptide hormones is only a few minutes Steroids - derivatives of cholesterol Steroids - derivatives of cholesterol Glucocorticoids (cortisol), mineralocorticoids (aldosterone), androgens (testosterone), estrogens, (estradiol), progestogens (progesterone) Glucocorticoids (cortisol), mineralocorticoids (aldosterone), androgens (testosterone), estrogens, (estradiol), progestogens (progesterone) Amino acid derivatives Amino acid derivatives Thyroid hormones are basically a "double" tyrosine with the critical incorporation of 3 or 4 iodine atoms Thyroid hormones are basically a "double" tyrosine with the critical incorporation of 3 or 4 iodine atoms Catecholamines include epinephrine and norepinephrine, which are used as both hormones and neurotransmitters Catecholamines include epinephrine and norepinephrine, which are used as both hormones and neurotransmitters Fatty acid derivatives – Eicosanoids Fatty acid derivatives – Eicosanoids prostaglandins, prostacyclins, leukotrienes and thromboxanes prostaglandins, prostacyclins, leukotrienes and thromboxanes

7. Concentration of hormons Rate of production: Synthesis and secretion of hormones are mediated by positive and negative feedback circuits Rate of production: Synthesis and secretion of hormones are mediated by positive and negative feedback circuits Rate of delivery: high blood flow delivers more hormone than low blood flow to a target organ Rate of delivery: high blood flow delivers more hormone than low blood flow to a target organ Rate of degradation and elimination: Hormones are metabolized and secreted from the body through several routes. If a hormone's biological halflife is long, effective concentrations persist for some time after secretion ceases Rate of degradation and elimination: Hormones are metabolized and secreted from the body through several routes. If a hormone's biological halflife is long, effective concentrations persist for some time after secretion ceases

8. Hypothalamus Secrete hormones that strictly control secretion of hormones from the anterior pituitary Secrete hormones that strictly control secretion of hormones from the anterior pituitary They are referred to as releasing hormones and inhibiting hormones, reflecting their influence on anterior pituitary hormones. They are referred to as releasing hormones and inhibiting hormones, reflecting their influence on anterior pituitary hormones.

9. Pituitary gland anterior and posterior pituitary secrete a battery of hormones that collectively influence all cells and affect virtually all physiologic processes anterior and posterior pituitary secrete a battery of hormones that collectively influence all cells and affect virtually all physiologic processes

10. Anterior Pituitary HormoneMajor target organ(s)Major Physiologic Effects Growth Growth hormone Liver, adipose tissue Promotes growth (indirectly), control of protein, lipid and carbohydrate metabolism Thyroid-stimulating hormone Thyroid gland Stimulates secretion of thyroid hormones Adrenocorticotropic hormone Adrenal gland (cortex) Stimulates secretion of glucocorticoids Prolactin Mammary glandMilk production Luteinizing hormone Ovary and testis Control of reproductive function Follicle-stimulating hormone Ovary and testis Control of reproductive function

11. Posterior Pituitary HormoneMajor target organ(s) Major Physiologic Effects Antidiuretic hormone Kidney Conservation of body water Oxytocin Ovary Stimulates milk ejection and uterine contractions

12. Hypothalamus Pituitary Target Gland CNS inputs Hypothalamic hormones Intrapituitary cytokines Peripheral hormones Pituitary trophic hormones Secretion of pituitary hormones determined by - hypothalamic hormones - intrapituitary factors - peripheral feedback

13. Synthesis of Pituitary Hormones Cell type% in pituitary LHGonadotrophs5 - 10 FSH ProlactinLactotrophs10 - 25 TSHThyrotrophs5 - 15 GHSomatotrophs35 - 45 ACTHCorticotrophs1 - 2

14. Growth hormone role in stimulating body growth role in stimulating body growth stimulate the liver and other tissues to secrete IGF-I, resulting in bone growth stimulate the liver and other tissues to secrete IGF-I, resulting in bone growth important effect on protein, lipid and carbohydrate metabolism important effect on protein, lipid and carbohydrate metabolism

15. Growth hormone Protein metabolism Protein metabolism stimulates protein anabolism in many tissues stimulates protein anabolism in many tissues increases amino acid uptake and protein synthesis increases amino acid uptake and protein synthesis decreases oxidation of proteins. decreases oxidation of proteins. Fat metabolism Fat metabolism enhances the utilization of fat enhances the utilization of fat Carbohydrate metabolism Carbohydrate metabolism maintain blood glucose within a normal range maintain blood glucose within a normal range has anti-insulin activity, supresses the abilities of insulin to stimulate uptake of glucose in peripheral tissues and enhance glucose synthesis in the liver has anti-insulin activity, supresses the abilities of insulin to stimulate uptake of glucose in peripheral tissues and enhance glucose synthesis in the liver

16. Control of GH secretion  stress, exercise, nutrition, sleep and growth hormone itself Growth hormone-releasing hormone (GHRH) Growth hormone-releasing hormone (GHRH) hypothalamic peptide that stimulates both the synthesis and secretion of GH hypothalamic peptide that stimulates both the synthesis and secretion of GH Somatostatin (SS) Somatostatin (SS) peptide produced by several tissues in the body, including the hypothalamus peptide produced by several tissues in the body, including the hypothalamus inhibits GH release in response to GHRH and to other stimulatory factors such as low blood glucose concentration. inhibits GH release in response to GHRH and to other stimulatory factors such as low blood glucose concentration. Ghrelin Ghrelin peptide hormone secreted from the stomach peptide hormone secreted from the stomach stimulates secretion of growth hormone. stimulates secretion of growth hormone.

18. Disease States Deficiency in growth hormone or defects in its binding to receptor are seen as growth retardation or dwarfism. The manifestation of growth hormone deficiency depends upon the age of onset of the disorder and can result from either heritable or acquired disease. The effect of excessive secretion of growth hormone is also very dependent on the age of onset and is seen as two distinctive disorders: Giantism and Acromegaly

19. Giantism  Excessive growth hormone secretion that begins in young children or adolescents. It is a very rare disorder, usually resulting from a tumor of somatotropes  220-240 cm  Lower IQ  metabolic malfunctions

20. Acromegaly  excessive secretion of GH in adults  usually benign pituitary tumors  onset of this disorder occurring over several years  overgrowth of extremities, soft-tissue swelling, abnormalities in jaw structure and cardiac disease  excessive GH and IGF-I also lead to a number of metabolic derangements, including hyperglycemia.

21. IGF-1 insuline like growth factor – I stimulates proliferation of chondrocytes (cartilage cells), resulting in bone growth insuline like growth factor – I stimulates proliferation of chondrocytes (cartilage cells), resulting in bone growth key player in muscle growth, it stimulates both the differentiation and proliferation of myoblasts. It also stimulates amino acid uptake and protein synthesis in muscle and other tissues. key player in muscle growth, it stimulates both the differentiation and proliferation of myoblasts. It also stimulates amino acid uptake and protein synthesis in muscle and other tissues. Transport protein - IGFBP 3 Transport protein - IGFBP 3 Primary investigation for acromegaly and giantism diagnosis Primary investigation for acromegaly and giantism diagnosis

22. ACTH Adrenocorticotropic hormone Adrenocorticotropic hormone secreted from the anterior pituitary in response to corticotropin-releasing hormone (CRH) from the hypothalamus - response to stress secreted from the anterior pituitary in response to corticotropin-releasing hormone (CRH) from the hypothalamus - response to stress stimulates the adrenal cortex - secretion of glucocorticoids - cortisol stimulates the adrenal cortex - secretion of glucocorticoids - cortisol CRH is inhibited by glucocorticoids – negative feedback loop CRH is inhibited by glucocorticoids – negative feedback loop

24. Prolactin Secreted by the anterior pituitary under the control of prolactin inhibitory factor secreted by the hypothalamus levels rise during pregnancy and cause stimulation of milk production after childbirth elevated serum prolactin levels are the most common disorder of the hypothalamic-pituitary axis inhibits the release of other gonadotropic hormones Dopamine serves as the major prolactin-inhibiting factor Estrogens provide a positive control over prolactin synthesis and secretion

26. Macroprolactin Prolactin in human serum exists as multiple forms of different molecular sizes of which the predominant species (90%) is the monomeric form (MW - 22.5kD) Prolactin in human serum exists as multiple forms of different molecular sizes of which the predominant species (90%) is the monomeric form (MW - 22.5kD) In some individuals, however, the predominant circulating prolactin is the very high molecular weight form (macroprolactin, MW >100kD) In some individuals, however, the predominant circulating prolactin is the very high molecular weight form (macroprolactin, MW >100kD) This phenomenon, termed macroprolactinaemia, is a non- pathological cause of persistent, and often asymptomatic hyperprolactinaemia This phenomenon, termed macroprolactinaemia, is a non- pathological cause of persistent, and often asymptomatic hyperprolactinaemia A method for assessing prolactin recovery based on precipitation of macroprolactin by polyethylene glycol (PEG) has been proposed as a simple test for detection of macroprolactinaemia A method for assessing prolactin recovery based on precipitation of macroprolactin by polyethylene glycol (PEG) has been proposed as a simple test for detection of macroprolactinaemia

27. Hyperprolactinaemia relatively common disorder in humans condition - prolactin-secreting tumors and therapy with certain drugs Women amenorrhea -lack of menstrual cycles galactorrhea - excessive or spontaneous secretion of milk Men Hypogonadism decreased sex drive, impotence, decreased sperm production breast enlargement (gynecomastia), but very rarely produce milk.

28. TSH Thyroid-stimulating hormone, thyrotropin Thyroid-stimulating hormone, thyrotropin stimulates the thyroid gland to synthesize and release thyroid hormones stimulates the thyroid gland to synthesize and release thyroid hormones glycoprotein hormone composed of two subunits, non-covalently bound to one. The alpha subunit is also present FSH, LH and in the placental hormone chorionic gonadotropin. glycoprotein hormone composed of two subunits, non-covalently bound to one. The alpha subunit is also present FSH, LH and in the placental hormone chorionic gonadotropin.

29. Gonadotropins stimulate the gonads stimulate the gonads in men - the testes in men - the testes in women - the ovaries in women - the ovaries They are not necessary for life, but are essential for reproduction TSH, LH and FSH are large glycoproteins composed of  and  subunits TSH, LH and FSH are large glycoproteins composed of  and  subunits  subunit is identical in all three hormones  subunit is identical in all three hormones  subunit is unique and endows each hormone with the ability to bind its own receptor.  subunit is unique and endows each hormone with the ability to bind its own receptor.

30. FSH ovaries contain follicles, (fluid-filled sacs in which eggs grow) ovaries contain follicles, (fluid-filled sacs in which eggs grow) in the female, FSH stimulates a follicle to mature during each menstrual cycle in the female, FSH stimulates a follicle to mature during each menstrual cycle follicles mature in the ovary and continue to develop in the fallopian tube, which connects the ovary to the uterus follicles mature in the ovary and continue to develop in the fallopian tube, which connects the ovary to the uterus FSH is also critical for sperm production. It supports the function of Sertoli cells, which in turn support many aspects of sperm cell maturation FSH is also critical for sperm production. It supports the function of Sertoli cells, which in turn support many aspects of sperm cell maturation

31. LHLHLHLH Luteinizing hormone Luteinizing hormone Stimulates secretion of sex steroids from the gonads Stimulates secretion of sex steroids from the gonads In the testes - secretion of testosterone In the testes - secretion of testosterone in the ovary - secretion of estrogen in the ovary - secretion of estrogen ovulation of mature follicles on the ovary is induced by a large burst of LH secretion ovulation of mature follicles on the ovary is induced by a large burst of LH secretion LH is required for continued development and function of corpora lutea LH is required for continued development and function of corpora lutea

32. Measurement of anterior pituitary hormones 1.Baseline measurements ACTH (Cortisol 9am, 12mn), TSH (FT4), Prolactin, LH/FSH (Testosterone, Estradiol) 2.Dynamic function tests Why? -low pituitary hormone levels not diagnostic - normal levels do not exclude pituitary disease - pulsatile excretion + diurnal variation confuse interpretation of baseline levels - if baseline levels are high dynamic tests can aid in differential diagnosis Hypofunction  stimulation tests Hyperfunction  suppression tests

33. Types of pituitary adenomas Prolactinomas 50-55% Somatotroph 20-23% Gonadotroph < 5% Non-functional 20-25% Corticotroph 5-8% Thyrotroph < 1%

34. Thyroid

35. Thyroid Hormones Triiodothyronine (T3) Triiodothyronine (T3) Thyroxine (T4) Thyroxine (T4) Principal actions Principal actions Stimulate energy use Stimulate energy use Cardiac stimulation Cardiac stimulation Promote growth & development Promote growth & development

36. Neurons in the hypothalamus secrete thyroid releasing hormone (TRH), which stimulates cells in the anterior pituitary to secrete thyroid- stimulating hormone (TSH). TSH binds to receptors on epithelial cells in the thyroid gland, stimulating synthesis and secretion of thyroid hormones, which affect probably all cells in the body. When blood concentrations of thyroid hormones increase above a certain threshold, TRH-secreting neurons in the hypothalamus are inhibited and stop secreting TRH.

37. Calcitonin The major source of calcitonin is from the parafollicular or C cells in the thyroid gland The major source of calcitonin is from the parafollicular or C cells in the thyroid gland participate in calcium and phosphorus metabolism participate in calcium and phosphorus metabolism Bone: suppresses resorption of bone, releasing Ca and P into blood Bone: suppresses resorption of bone, releasing Ca and P into blood Kidney: Calcitonin inhibits tubular reabsorption Ca and P Kidney: Calcitonin inhibits tubular reabsorption Ca and P Elevated blood ionized calcium levels strongly stimulate calcitonin secretion Elevated blood ionized calcium levels strongly stimulate calcitonin secretion

38. DISORDERS OF THE THYROID HYPERFUNCTION: Hyperthyroidism HYPERFUNCTION: Hyperthyroidism HYPOFUNCTION: Hypothyroidism HYPOFUNCTION: Hypothyroidism Adult Adult Child Child GOITER: GOITER: Simple Simple Toxic Toxic

39. HYPERTHYROIDISM: Definition A state of hypermetabolism and hyperactivity of cardiovascular and neuromuscular systems induced by high levels of circulating T 3, T 4, or both. Major cause: Graves Disease Major cause: Graves Disease

40. Young to middle-aged adults Young to middle-aged adults Females more often affected Females more often affected Familial incidence Familial incidence GRAVES DISEASE: Prevalence

41. Behavior changes Behavior changes Goiter Goiter Ocular manifestations Ocular manifestations Insomnia, restlessness Insomnia, restlessness Palpitations, hand tremors, nervousness Palpitations, hand tremors, nervousness Increased body temperature Increased body temperature GRAVES DISEASE

42. Life threatening form of thyrotoxicosis. Life threatening form of thyrotoxicosis. Exagerated clinical features: Exagerated clinical features: Increased temperature Increased temperature Tachycardia and cardiac arrhythmias Tachycardia and cardiac arrhythmias Congestive heart failure Congestive heart failure Extreme restlessness, agitation, psychoses Extreme restlessness, agitation, psychoses Nausea and vomiting, severe diarrhea Nausea and vomiting, severe diarrhea GRAVES DISEASE: Thyroid Storm

43. Congenital: Cretinism Congenital: Cretinism Acquired Acquired Hashimoto thyroiditis Hashimoto thyroiditis Iodine deficiency or impeded utilization Iodine deficiency or impeded utilization Iatrogenic events: XRT, thyroidectomy Iatrogenic events: XRT, thyroidectomy Goitrogen ingestion Goitrogen ingestion Secondary (pituitary origin) Secondary (pituitary origin) HYPOTHYROIDISM: Etiology

44. Older age group (60s) Older age group (60s) Females more often affected Females more often affected Pregnant women Pregnant women HYPOTHYROIDISMHYPOTHYROIDISM

45. Decreased metabolism, reduced appetite Decreased metabolism, reduced appetite Slow mentation, speech, movement Slow mentation, speech, movement Goiter (optional) Goiter (optional) Skin cool and dry Skin cool and dry Weakness, lethargy, fatigability Weakness, lethargy, fatigability Intolerance to cold Intolerance to cold Deepened voice Deepened voice Hypercholesterolemia Hypercholesterolemia Menstrual irregularities Menstrual irregularities In advanced disease: MYXEDEMA In advanced disease: MYXEDEMA HYPOTHYROIDISMHYPOTHYROIDISM

46. GOITERGOITER Definition: Definition: Thyroid enlargement, with (toxic goiter) or without (simple goiter) increased hormone production. Thyroid enlargement, with (toxic goiter) or without (simple goiter) increased hormone production. Types of goiter: Types of goiter: Diffuse Diffuse Nodular Nodular Etiology: Etiology: Inflammatory process (thyroiditis) Inflammatory process (thyroiditis) Functional disorders Functional disorders Neoplasms Neoplasms

47. Etiology: autoimmune Etiology: autoimmune Prevalence: Prevalence: Females are more often affected Females are more often affected Disease in males is more severe Disease in males is more severe Clinical characteristics: Clinical characteristics: Thyroid enlargement Thyroid enlargement Symptoms of tracheal/esophageal compression Symptoms of tracheal/esophageal compression Malignant transformation risk: 5% Malignant transformation risk: 5% Association with other autoimmune diseases Association with other autoimmune diseases Hashimoto Thyroiditis

48. Benign tumors: Benign tumors: follicular adenomas follicular adenomas Malignant tumors: Malignant tumors: Papillary carcinoma Papillary carcinoma Follicular carcinoma Follicular carcinoma Anaplastic carcinoma Anaplastic carcinoma Medullary carcinoma Medullary carcinoma NeoplasmsNeoplasms

49. Parathyroid glands The 4 parathyroid glands (4x2 mm) are located near or attached to the back side of the thyroid gland The 4 parathyroid glands (4x2 mm) are located near or attached to the back side of the thyroid gland The glands synthesize and secrete parathyroid hormone that controls blood levels of calcium. The glands synthesize and secrete parathyroid hormone that controls blood levels of calcium. The structure of a parathyroid gland is distinctly different from a thyroid gland. The cells are arranged in rather dense cords or nests around abundant capillaries. The structure of a parathyroid gland is distinctly different from a thyroid gland. The cells are arranged in rather dense cords or nests around abundant capillaries.

50. Parathyroid hormone The most important endocrine regulator of Ca and P concentration in extracellular fluid The most important endocrine regulator of Ca and P concentration in extracellular fluid PTH is released in response to low extracellular concentrations of free calcium PTH is released in response to low extracellular concentrations of free calcium PTH has a circadian rhythm PTH has a circadian rhythm Max 14. – 16.h Max 14. – 16.h Min 8.h Min 8.h Sampling in ice, plasma or serum, -20 o C Sampling in ice, plasma or serum, -20 o C

51. Parathyroid hormone Mobilization of calcium from bone: stimulates osteoclasts to reabsorb bone mineral, liberating calcium into blood. Mobilization of calcium from bone: stimulates osteoclasts to reabsorb bone mineral, liberating calcium into blood. Enhancing absorption of calcium from the small intestine: PTH stimulates production of the active vitamin D. It induces synthesis of a calcium-binding protein Enhancing absorption of calcium from the small intestine: PTH stimulates production of the active vitamin D. It induces synthesis of a calcium-binding protein Suppression of calcium loss in urine Suppression of calcium loss in urine

53. Hyperparathyroidism Primary hyperparathyroidism Primary hyperparathyroidism most commonly due to a parathyroid tumor (adenoma) which secretes the hormone without proper regulation most commonly due to a parathyroid tumor (adenoma) which secretes the hormone without proper regulation chronic elevations Ca (hypercalcemia), kidney stones and decalcification of bone chronic elevations Ca (hypercalcemia), kidney stones and decalcification of bone Secondary hyperparathyroidism Secondary hyperparathyroidism kidney disease - unable to reabsorb Ca kidney disease - unable to reabsorb Ca inadequate nutrition – diets deficient in Ca or vitamin D, or which contain excessive phosphorus inadequate nutrition – diets deficient in Ca or vitamin D, or which contain excessive phosphorus decalcification of bone ("rubber bones„) decalcification of bone ("rubber bones„)

54. Adrenal glands Cortex Cortex Medulla Medulla

55. Adrenal gland Cortex (steroid hormon) Cortex (steroid hormon) glucocorticoids glucocorticoids mineralocorticoids mineralocorticoids From cholesterol - steroidogenesis From cholesterol - steroidogenesis Medulla ( derivates of aminoacids) Medulla ( derivates of aminoacids) epinephrine and norepinephrine epinephrine and norepinephrine

56. Adrenal medulla circulating epinephrine and norepinephrine released from the adrenal medulla have the same effects on target organs as direct stimulation by sympathetic nerves circulating epinephrine and norepinephrine released from the adrenal medulla have the same effects on target organs as direct stimulation by sympathetic nerves Increased rate and force of contraction of the heart muscle -epinephrine Increased rate and force of contraction of the heart muscle -epinephrine Constriction of blood vessels - norepinephrine, increase blood pressure Constriction of blood vessels - norepinephrine, increase blood pressure Dilation of bronchioles - assists in pulmonary ventilation Dilation of bronchioles - assists in pulmonary ventilation Stimulation of lipolysis in fat cells - energy production Stimulation of lipolysis in fat cells - energy production Increased metabolic rate: oxygen consumption and heat production increase throughout the body in response to epinephrine Increased metabolic rate: oxygen consumption and heat production increase throughout the body in response to epinephrine Dilation of the pupils Dilation of the pupils Inhibition of certain "non-essential" processes - gastrointestinal secretion and motor activity. Inhibition of certain "non-essential" processes - gastrointestinal secretion and motor activity.

57. Adrenal cortex Cortisol Cortisol circadian rhythm min. 12 mn, max. about 6 am circadian rhythm min. 12 mn, max. about 6 am,  by stress maintain normal concentrations of glucose in blood Stimulation of gluconeogenesis, particularly in the liver Mobilization of amino acids from extrahepatic tissues Inhibition of glucose uptake in muscle and adipose tissue Stimulation of fat breakdown in adipose tissue

58. Cortisol Effects on inflammation and immune function Glucocorticoids have potent anti-inflammatory and immunosuppressive properties glucocorticoids are also among the most frequently used drugs, and often prescribed for their anti-inflammatory and immunosuppressive properties

59. Aldosteron Mineralocorticoid Mineralocorticoid critical role in regulating concentrations of minerals - particularly Na and K - in extracellular fluids critical role in regulating concentrations of minerals - particularly Na and K - in extracellular fluids The major target is the distal tubule of the kidney, where it stimulates exchange of Na and K The major target is the distal tubule of the kidney, where it stimulates exchange of Na and K Increased resorption of sodium Increased resorption of sodium Increased resorption of water Increased resorption of water an osmotic effect directly related to increased resorption of Na an osmotic effect directly related to increased resorption of Na Increased renal excretion of K Increased renal excretion of K

60. Addison's disease hypoadrenocorticism hypoadrenocorticism this disease is a result of infectious disease (e.g. tuberculosis in humans) or autoimmune destruction of the adrenal cortex this disease is a result of infectious disease (e.g. tuberculosis in humans) or autoimmune destruction of the adrenal cortex cardiovascular disease, lethargy, diarrhea, and weakness. Aldosterone deficiency can be acutely life threatening due to disorders of electrolyte balance and cardiac function

61. Cushing’s Syndrome hyperadrenocorticism Excessive endogenous production of cortisol, which can result from a primary adrenal defect (ACTH-independent) or from excessive secretion of ACTH (ACTH-dependent) Administration of glucocorticoids for theraputic purposes. This is a common side- effect of these widely-used drugs.

62. Cholesterol Pregnenolon Progesteron 11deoxykortiko steron Kortikosteron 18 hydroxykorti kosteron Aldosteron 17 hydroxy pregnenolon 17 hydroxy progesteron 11 deoxykortizol Kortizol DHEA Androstendion Estradiol Testoste ron Desmoláza 21 hydroxyláza 11  hydroxyláza 18 hydroxyláza 21 hydroxyláza 11  hydroxyláza Steroidogenesis in adrenal gland

63. Pancreas The bulk of the pancreas is composed of pancreatic exocrine cells and their associated ducts. Embedded within this exocrine tissue are roughly one million small clusters of cells called the Islets of Langerhans, which are the endocrine cells of the pancreas

64. Islets of Langerhans only 1-2% of the mass of the pancreas only 1-2% of the mass of the pancreas Alpha cells (A cells) secrete glucagon. Alpha cells (A cells) secrete glucagon. Beta cells (B cells) produce insulin and are the most abundant of the islet cells Beta cells (B cells) produce insulin and are the most abundant of the islet cells Delta cells (D cells) secrete somatostatin Delta cells (D cells) secrete somatostatin F cells secrete pancreatic polypeptid (PP) F cells secrete pancreatic polypeptid (PP)

65. Pancreas Insulin and glucagon are critical participants in glucose homeostasis and serve as acute regulators of blood glucose concentration Insulin and glucagon are critical participants in glucose homeostasis and serve as acute regulators of blood glucose concentration A deficiency in insulin or deficits in insulin responsiveness lead to the disease diabetes mellitus A deficiency in insulin or deficits in insulin responsiveness lead to the disease diabetes mellitus

66. Glucose from the ingested lactose or sucrose is absorbed in the intestine and the level of glucose in blood rises Elevation of blood glucose concentration stimulates endocrine cells in the pancreas to release insulin Insulin has the major effect of facilitating entry of glucose into many cells of the body - as a result, blood glucose levels fall When the level of blood glucose falls sufficiently, the stimulus for insulin release disappears and insulin is no longer secreted

67. Insulin synthesized in significant quantities only in beta cells in the pancreas synthesized in significant quantities only in beta cells in the pancreas facilitates entry of glucose into muscle, adipose and several other tissues facilitates entry of glucose into muscle, adipose and several other tissues stimulates the liver to store glucose in the form of glycogen stimulates the liver to store glucose in the form of glycogen

69. Insulin and lipid metabolism Insulin promotes synthesis of fatty acids in the liver Insulin promotes synthesis of fatty acids in the liver Insulin inhibits breakdown of fat in adipose tissue Insulin inhibits breakdown of fat in adipose tissue Insulin facilitates entry of glucose into adipocytes and glucose can be used to synthesize glycerol Insulin facilitates entry of glucose into adipocytes and glucose can be used to synthesize glycerol indirectly stimulates accumulation of fat in adipose tissue indirectly stimulates accumulation of fat in adipose tissue

70. Types of DM Type 1 (IDDM) Insulin dependent Type 1 (IDDM) Insulin dependent Destruction of pancreatic beta cells Destruction of pancreatic beta cells No insulin produced No insulin produced Type 2 (NIDDM) Non-insulin dependent Type 2 (NIDDM) Non-insulin dependent Cells are less responsive to insulin Cells are less responsive to insulin Altered insulin secretion Altered insulin secretion

71. Glukagon Glucagon has a major role in maintaining normal concentrations of glucose in blood - increasing blood glucose levels Glucagon has a major role in maintaining normal concentrations of glucose in blood - increasing blood glucose levels Glucagon stimulates breakdown of glycogen stored in the liver Glucagon stimulates breakdown of glycogen stored in the liver Glucagon activates hepatic gluconeogenesis - non-hexose substrates such as amino acids are converted to glucose Glucagon activates hepatic gluconeogenesis - non-hexose substrates such as amino acids are converted to glucose Diseases associated with excessively high or low secretion of glucagon are rare Diseases associated with excessively high or low secretion of glucagon are rare

72. S omatostatin secreted by a broad range of tissues, including pancreas, intestinal tract and regions of the central nervous system outside the hypothalamus secreted by a broad range of tissues, including pancreas, intestinal tract and regions of the central nervous system outside the hypothalamus Somatostatin was named for its effect of inhibiting secretion of GH Somatostatin was named for its effect of inhibiting secretion of GH Somatostatin appears to act primarily in a paracrine manner to inhibit the secretion of both insulin and glucagon Somatostatin appears to act primarily in a paracrine manner to inhibit the secretion of both insulin and glucagon

73. Fertility

74. Ovarian Hormones Two classes of ovarian sex hormones: Estrogens and progestins The most important of the estrogens is estradiol The most important progestin is progesterone Estrogens: Promote proliferation and growth of sex related cells; cause secondary sexual characteristics Progestins: Important for preparation of the uterus for pregnancy and the breast for lactation

75. Estradiol Principal Function: cellular proliferation; growth of the tissues of sexual organs; growth of other tissues related to reproduction

76. Progesterone Residual cells within ovulated follicles proliferate to form corpora lutea, which secrete the steroid hormones progesterone and estradiol Residual cells within ovulated follicles proliferate to form corpora lutea, which secrete the steroid hormones progesterone and estradiol Progesterone is necessary for maintenance of pregnancy Progesterone is necessary for maintenance of pregnancy secreted by the corpus luteum secreted by the corpus luteum it prepares the uterus for the development of the fertilised egg it prepares the uterus for the development of the fertilised egg this is called the proliferative phase of the uterus since there is a proliferation of blood vessels in the uterine lining this is called the proliferative phase of the uterus since there is a proliferation of blood vessels in the uterine lining these blood vessels serve as a nutrient source for the developing embryo these blood vessels serve as a nutrient source for the developing embryo

77. Circulating levels (LH,FSH, Prog and Estradiol) Circulating levels (LH,FSH, Prog and Estradiol) 11428721 Day of menstrual cycle 10 20 30 40 50 LH and FSH (IU/L) LH FSH Progesterone ovulation 5 10 15 20 25 1850 1500 740 1100 370 Estradiol Estradiol (pmol/L) Progesterone (nmol/L)

79. Investigation of amenorrhoea

80. Causes of amenorrhoea physiological e.g prepuberty, pregnancy, lactation, post menopause physiological e.g prepuberty, pregnancy, lactation, post menopause anatomical e.g. absence of uterus anatomical e.g. absence of uterus structural endocrine disorders e.g. Kallman’s syndrome (congenital lack of GnRH), severe head injury, pituitary adenoma, Sheehan’s syndrome structural endocrine disorders e.g. Kallman’s syndrome (congenital lack of GnRH), severe head injury, pituitary adenoma, Sheehan’s syndrome functional endocrine disorders e.g. weight loss, anorexia nervosa, excessive exercise, stress functional endocrine disorders e.g. weight loss, anorexia nervosa, excessive exercise, stress all above result in decreased LH and FSH all above result in decreased LH and FSH

81. Causes of amenorrhoea premature ovarian failure (depletion of primordial oocytes) premature ovarian failure (depletion of primordial oocytes) associated with autoimmune disorders (Addison’s disease) associated with autoimmune disorders (Addison’s disease) also caused by radiation/cytotoxic drug therapy for Ca breast also caused by radiation/cytotoxic drug therapy for Ca breast increased LH and FSH seen increased LH and FSH seen

82. The menopause time of permanent cessation of menstruation time of permanent cessation of menstruation normally occurs between ages 40-55 yrs, average age of onset 49 - 51 yrs normally occurs between ages 40-55 yrs, average age of onset 49 - 51 yrs decline in follicles leads to lower estradiol decline in follicles leads to lower estradiol FSH levels rise progressively from 41 yrs to 47 yrs FSH levels rise progressively from 41 yrs to 47 yrs rise in FSH related to time of menopause rise in FSH related to time of menopause

83. Testosterone Androgen testosterone is primarily secreted in the testes of males and the ovaries of females Necessary for normal sperm development Libido Mental and physical energy Maintenance of muscle trophism

85. Infertility The failure to achieve pregnancy after one year of unprotected intercourse The failure to achieve pregnancy after one year of unprotected intercourse the consistent failure to carry a pregnancy to term the consistent failure to carry a pregnancy to term treatable condition; > 50% of couples can achieve pregnancy treatable condition; > 50% of couples can achieve pregnancy