The endocrine system(2)

1. The endocrine system(2) DrMaramAbdaljaleel, MD School of Medicine, University of Jordan

2. Parathyroid gland: • Parathyroid glands are composed mostly of chief cells which have secretory granules containing parathyroid hormone (PTH). • Parathyroid glands are key regulators of calcium homeostasis. • The activity of the parathyroid glands is controlled by the level of free (ionized) calcium in the blood(not by trophic hormones secreted by hypothalamus and pituitary ).

3. Normally, decreased levels of free calcium stimulate the synthesis and secretion of PTH, which has the following effects: • Increased renal tubular reabsorption of calcium • Increased urinary phosphate excretion • Increased conversion of vitamin D to its active form in the kidneys • Enhanced osteoclastic activity (bone resorption) • an increase in the blood level of free calcium inhibits PTH secretion from chief cells.

4. Tumors of the parathyroid glands usually come to attention because of excessive secretion of PTH, rather than mass effects.

5. Hyperparathyroidism: • Primary: autonomous, spontaneous overproduction of PTH • Secondary and tertiary :caused by progressive renal failure.

6. Parathyroid gland diseases • primary hyperparathyroidism is caused by: • Adenoma85% to 95% • Primary hyperplasia 5%to10% • Parathyroid carcinoma1% - The most common manifestation is an increase in serum calcium. - Characterized by painful bones, renal stones, abdominal pain, and depression

7. Figure 15-34 Parathyroid adenoma, microscopicAdjacent to it there is a rim of normal parathyroid

8. C- Hypoparathyroidism: causes: 1. Surgical removal of parathyroid glands during thyroidectomy (most common cause) 2, Congenital absence: in DiGeorge syndrome 3. Autoimmune hypoparathyroidism. Clinical manifestations: a. Increased neuromuscular irritability including muscle spasm and tingling . b. Cardiac arrythmias and seizure.

9. Adrenal gland Figure 15-38 Normal adrenal gland, gross Each normal gland weighs 4 to 6 g.

12. hyperadrenal clinical syndromes • Cushing syndrome, characterized by an excess of cortisol • Hyperaldosteronism, caused by an excess of mineralocorticoid • Adrenogenitalor virilizing syndromes, caused by an excess of androgens

13. Hypercortisolism---Cushing syndrome • Hypercortisolism (Cushing syndrome) is caused by elevated glucocorticoid levels. - In clinical practice, most cases are caused by the administration of exogenous glucocorticoids • The remaining cases are endogenous: • Primary hypothalamic-pituitary diseases associated with hypersecretion of ACTH (cushing disease),the most common endogenous cause of hypercortisolism. • Primary adrenal neoplasms (ACTH independent hypercortisolism- adenoma or carcinoma) and, rarely, primary cortical hyperplasia • paraneoplasticACTH production by tumors (small-cell lung cancer).

14. Clinical manifestations of Cushing syndrome • Hypertension • weight gain, • central obesity, • moon faces. • accumulation of fat in the posterior neck and back (“buffalo hump”). • skin is thin, fragile, and easily bruised; cutaneous striae - Hyperglycemia, glucosuria and polydipsia mimicking diabetes mellitus. - risk of infection. - Harsutismand menstrual abnormalities.

16. 2. Hyperaldosteronism; • Excessive levels of aldosterone causing sodium retention and potassium excretion, with resultant hypertension and hypokalemia. • Can be primary or secondary

17. Primary hyperaldosteronism • primary autonomous overproduction of aldosterone resultant suppression of the renin-angiotensin system and decreased plasma renin activity. • The causes of primary hyperaldosteronism are : • Bilateral idiopathic hyperaldosteronism: • bilateral nodular hyperplasia of the adrenal glands. • the most common cause of primary hyperaldosteronism (60%) • Adrenocortical neoplasm: • either an aldosterone-producing adenoma (the most common,35% of cases)or, rarely, an adrenocortical carcinoma. • Solitary aldosterone-secreting adenoma, is referredto as Conn syndrome. • familial hyperaldosteronism: rare

18. 2. Secondary type:aldosterone release due to activation of the renin-angiotensin system high levels of plasma renin. Causes: • Decreased renal perfusions. (renal artery stenosis) • Arterial hypervolemia (CHF, cirrhosis, nephrotic syndrome) • Pregnancy (caused by estrogen-induced increases in plasma renin)

19. 2-ADRENAL INSUFFICIENCY (hypofunction) • Primary: I-Acute Adrenocortical Insufficiency (adrenal crisis), caused by : a. Stress in patients with chronic adreno-cortical insufficiency. b. Rapid withdrawal of long term used exogenous steroid. c. Massive adrenal haemorrhage that destroy enough of the adrenal cortex sufficient to cause acute insufficiency.

20. 2. Primary Chronic Adrenocortical Insufficiency (Addison Disease): • Uncommon • resulting from progressive destruction of the adrenal cortex. • More than 90% of all cases are caused by a. Autoimmune adrenalitis: Accounts for 60% to 70% of cases and is the most common cause of primary adrenal insufficiency in developed countries. b. Infections : mainly tuberculosis. c. acquired immune deficiency syndrome (AIDS) d. Metastatic neoplasms involving the adrenal mainly carcinomas of the lung and breast.

21. Secondary Adrenocortical Insufficiency : caused by any disorder of the hypothalamus and pituitary that reduces the output of ACTH, such as: a. Metastatic cancer, b. Infection, c. Infarction, d. Irradiation,

22. Clinical Features do not appear until at least 90% of the adrenal cortex has been compromised. a. Progressive weakness and easy fatigability, b. Anorexia, nausea, vomiting, weight loss, diarrhea. c. Decreased aldosterone: hyperkalemia, hyponatremia, volume depletion, and hypotension.

23. d. In individuals with primary adrenal insufficiency increased levels of ACTH precursor hormone stimulate melanocytes, with resultant hyperpigmentation of the skin and mucosa by contrast hyperpigmentation is not seen in individuals with secondary adrenocortical insufficiency (no ACTH).

24. Multiple Endocrine Neoplasia (MEN) Syndromes

25. MEN syndromes: • group of inherited diseases • caused by proliferative lesions (hyperplasias, adenomas, and carcinomas) of multiple endocrine organs. • endocrine tumors arising in the context of MEN syndromes have certain distinctive features that are not shared with their sporadic counterparts: • These tumors occur at a younger age than that typical for sporadic cancers. • arise in multiple endocrine organs, either synchronously (at the same time) or metachronously (at different times).

26. Even in one organ, the tumors often are multifocal. • The tumors usually are preceded by an asymptomatic stage of endocrine hyperplasia involving the cell of origin of the tumor (pts with MEN-2 demonstrate C cell hyperplasia in the thyroid Adj to medullary thyroid carcinomas). • tumors are usually more aggressive with higher recurrence

27. MEN-1 syndrome • caused by germ line mutations in MEN1 tumor suppressor gene, which encodes a protein called Menin. • “3Ps”: parathyroid, pancreas, and pituitary. • Parathyroid: • Primary hyperparathyroidism is the most common manifestation of MEN-1 (80%–95% of patients) including hyperplasia and adenoma. • Pancreas: • Endocrine tumors of the pancreas are the leading cause of death in MEN-1. • Aggressive tumors with metastasis. • gastrinomasand insulinomas. • Pituitary: • prolactin-secreting macroadenoma(most common)

28. MEN TYPE 2 • activating (gain-of-function) mutations of the RET proto-oncogene at chromosomal locus 10q11.2. • MEN-2 is inherited in an autosomal dominant.

29. MEN-2A • Thyroid: • Medullary carcinoma of the thyroid (all untreated cases) • occur in the first 2 decades of life. • Multifocal • foci of C cell hyperplasia can be found in the adjacent thyroid. • Adrenal medulla: • Adrenal pheochromocytomasin 50% of patients • Parathyroid: • 10% to 20% of patients develop parathyroid gland hyperplasia

30. MEN2b: • medullary thyroid carcinomas: - multifocal and more aggressive than in MEN-2A • Pheochromocytomas MEN-2B has the following distinctive features: • Primary hyperparathyroidism does not develop in pts with MEN-2B. • Extraendocrine manifestations: • ganglioneuromasof mucosal sites (gastrointestinal tract, lips, tongue) • marfanoid habitus: long bones of the axial skeleton give an appearance resembling that in Marfan syndrome.

31. Before the advent of genetic testing, relatives of patients with the MEN-2 syndrome were screened with annual biochemical tests, which lacked sensitivity. • Now, routine genetic testing identifies RET mutation carriers earlier and more reliably in MEN-2 kindreds. • All individuals carrying germlineRET mutations are advised to have prophylactic thyroidectomy to prevent the inevitable development of medullary carcinomas

32. Thank you