adrenal and parathyroid glands Done by jehad abdel aziz

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1 prof. muhammed khammash adrenal and parathyroid glands Done by jehad abdel aziz The adrenal glands:- Anatomy:- The adrenal glands are flattened, yellowish structures that weigh less than 10g in the adult and are situated in the retroperitoneum, adjacent to the upper pole of the kidneys enclosed within the renal fascia. The right adrenal gland is pyramidal in shape and lies, in part, posterior to the inferior vena cava and lower border of the liver and anterior to the diaphragm. The left adrenal gland is crescent in shape and lies on the posterior abdominal wall behind the tail of the pancreas and medial to the upper pole of the left kidney. The blood supply to the adrenal glands come from branches of the aorta; the inferior phrenic and renal arteries. The right adrenal vein drains into the inferior vena cava, and the left adrenal vein drains into the renal vein. Histology:- The adrenal glands are made from an outer adrenal cortex and an inner adrenal medulla, the adrenal cortex is made of three layers:- - Zona glomerulosa which secrets aldosterone mineralcorticoids - Zona fasciculate which secrets cortisol glucocorticoids - Zona reticularis which secrets sex hormones; estrogens and androgens. The adrenal medulla is composed of chromaffin cells that contain catecholamine granules. And it is concerned with sympathetic stimulation and sympathetic regulating hormones; adrenaline, nore-adrenaline and dopamine. Regarding the origin of the adrenal cortex and medulla, the cortex is of mesodermal origin, and the medulla develops from cells of the neural crest. Page 1 of 16

2 The problems of the adrenal glands could be functional or nonfunctional, if there is increase secretion of one type of hormones we call it functional adrenal abnormalities, like for example; cortical tumors that arise from the cortex:- Cortisone secreting tumors-cushing s Syndrome Aldosterone secreting tumors- Conn s Syndrome Sex hormone secreting tumors- Virilisation or Feminization. When we say hyperplasia of the suprarenal gland; we mean increase in its size and function, and this can be primary from its own without any known reasons, or it can be secondary as a result of increase in the level of ACTH adrenocorticotropic hormone which is secreted from the pituitary gland, Mostly, the hyperplasia affects one layer of the cortex, the outer, or the middle or the innermost layer. Regarding the medulla; there is no hyperplasia in it, but there is a tumor secreting adrenaline or nore-adrenaline (Pheochromocytoma) Now we come to the most thing that we will see in the medical department; Cushing syndrome. Definition:- Cushing syndrome:- It s Excess of circulating cortisol that occurs as a result of endogenous steroid hypersecretion due to ACTH-dependent or ACTH-independent diseases or exogenous steroid medication iatrogenic which is the most common cause. We know that corticosteroids now interfere with treatment of so many diseases. And as a result of chronic intake and the high dose of corticosteroids, Cushing symptoms will start to appear. Causes of Cushing: - it could be:- Primary due to adrenal diseases for example: - Adenoma. Carcinoma. Primary adrenal hyperplasia ACTH independent. When we have adrenal adenoma, there will be excessive secretion of corticoids, and mostly it happens unilateral, but in primary adrenal hyperplasia; where the two glands will be affected Page 2 of 16

3 bilateral, also there will be hypersecretion of corticoids, and the reason of this primary hyperplasia is unknown. So hyperplasia could be secondary due to pituitary tumors or primary which is rare to happen. Secondary due to extra-adrenal diseases: - Primary pituitary micro-adenoma also known as Cushing disease, in which there is hypersecretion of ACTH and this ACTH producing adenomas are less sensitive to the feedback effects of the cortisol than are normal corticotrophs, so The adrenal glands in these patients characterized by bilateral nodular cortical hyperplasia. Non pituitary source; which is secretion of ectopic ACTH by nonendocrine tumors which in turn causes adrenal gland to release cortisol without the normal negative feedback loop: -E.g:- small cell carcinoma of the lung (the most common), fore gut carcinoid, Medullary CA of the thyroid and islet cell tumors of the pancreas. So if a patient comes to us having Cushing symptoms and he doesn t take corticosteroids, we must differentiate if its ACTH dependent or ACTH independent. The most common cause to Cushing syndrome is iatrogenic steroids and the second most common cause is Cushing disease. ACTH dependent:- 1. Pituitary microadenoma Cushing disease. 2. Ectopic ACTH secretion: ACTH independent:- Small cell carcinoma. Fore gut carcinoid. Medullary thyroid tumor. Pancreatic neuro-endocrine tumors. Adrenocortical Adenoma. Bilateral nodular hyperplasia. Adrenal carcinoma. The first who discovered Cushing syndrome was cushine and he thought that the only thing which causes this syndrome was adenoma. Page 3 of 16

4 ACTIONS of glucocorticoids:- Glucose metabolism so patients with Cushing syndrome have a decrease in glucose tolerance. So it goes toward the DM. Peripheral glucose utilization, it will increase in patients with Cushing. Lipid metabolism, there will be some changes in lipid metabolism in the body, more lipid distribution in the trunks. Cells of the immune system, Mediators of inflammation; in patients with Cushing, there will be decrease in the function of the mediators of the inflammation; the antibody formation and the complement. So patients with Cushing or steroid intake are more liable to operative or post operative infection. Bone and minerals metabolism, in patients with Cushing, there will be deprivation of the calcium in the bone. So these patients will complain of osteoporosis. Soft tissue and skeletal growth, there will be decrease of protein concentration in the muscle. So there will be weakness. Fluid and electrolytes homeostasis; in patients with Cushing there will be sodium retention, so they will complain of hypertension. C N System changes; psychological changes. Clinical presentation:- 1- Truncal Obesity. 2- Loss of connective tissue, so these patients are easy to get wounded and bruising, and easy to get hematoma or subcutaneous clot due to trauma. 3- Hirsutism and virlism and that s because one of the elements of steroids is sex hormones so with steroid intake there will be increase in the level of estrogens and testosterone so there will be decrease in the distribution of the hair. 4- Muscle weakness. 5- Osteoporosis; easy to fracture. 6- Hypertension. 7- Glucose intolerance. 8- Psychological changes, this will not happen unless the patient didn t receive treatment or the patient in advance and significant disease. Page 4 of 16

5 Progressive central obesity, hypertension and glucose intolerance are key features of Cushing syndrome, particularly when associated with facial plethora, moon face, and buffalo hump (dorsocervical fat pad). We can see the central obesity, moon face, telengectaisa, and striae (usually its purple). So Cushing syndrome takes a long time to occur, not weeks, but months or years, but if a patient presented to you with rapidly evolving Cushing picture and he is not taking steroid you should think of extra adrenal cause of this Cushing like for example; carcinoid tumor or lung CA or medullary Ca of thyroid. Investigations:- So after we take history of the patient and proved clinically that this patient is having Cushing symptoms we do Biochemical diagnosis. Biochemical diagnosis; there will be:- Persistent increase in cortisol concentration in the blood. Cortisol suppression by dexamethasone. Resistancy to insulin administration. Then we search for the cause: - Low ACTH = Adrenal disease. High ACTH = Extra- adrenal cause. As a summary:- Page 5 of 16

6 Signs/symptoms of Cushing s syndrome Dexamthasone Cortisol suppression NO YES Cushing syndrome Normal Check ACTH (plasma) Low ACTH normal or elevated ACTH Adrenal tumor ACTH dependent process Pituitary adenoma ectopic ACTH In ACTH dependent Cushing syndrome how can we differentiate between a pituitary and ectopic ACTH source? By administration of high dose of dexamethasone, if the cortisol is suppressed then its pituitary source but if no cortisol suppression happened then its ectopic ACTH source. Then we see anatomically to localize the site of this steroid; if its extra adrenal we must do MRI the best, or CT SCAN or skull x-ray in the past they used to do it and see if there is changes in sella turcica but it s not used now. If the cause and the history don t match with the pituitary then we go and investigate about the adrenals. And the best way to see the anatomy of the adrenals is to do CT SCAN and US Page 6 of 16

7 ultrasound is useful, or MRI but the most sensitive and accurate test is to do a CT SCAN to see if there is tumor or not. Sometimes the anatomy shows to us if there is a unilateral tumor or bilateral hyperplasia when we do ct scan and we need to emphasis if there is functioning in the right or left side; so we do something which is called SCintigraphy or radio-nucleotide isotope scan and that s mean we give the patient radio-active isotope in the blood and this isotope will go to the gland which we want to check, If the uptake of the radio-isotope by that gland is increased then we say there is hyperactivity suggestive of tumors. So when we are confused about which side is more functioning and CT scan is not helping us, we do radio isotope scan and the radio isotope that we use is Technetium99. So we give these patients cholesterol scan in which the cholesterol will stand on the technetium99 radio isotope then it will go to the suprarenal glands, thus we can determine which side is more functioning the left or the right side. We do this scan if there is doubt in the functioning side. We know that the adrenal gland takes the cholesterol from the blood and converts it to corticosteroid. When we think that the patient has ACTH source not from the pituitary, but from carcinoid tumor in the liver or pancreas, here the angiography maybe helpful which will show a tumor that takes too much supply So as a summary we make sure that there is a steroid in the blood by checking the biochemistry of the blood. Then we see if its ACTH dependent or ACTH in-dependent. Then we check for the anatomy; in the abdomen as we said the best test we do is CT scan and in the brain MRI, and rarely we do the radio isotope scan. Management:- If the patient has pituitary adenoma then we do microadrenolectomy. If the patient has hyperplasia we make sure that it s a hyperplasia by doing CT and technetium99 scan then the treatment by bilateral adrenolectomy. If the patient has solitary adenoma in the left or the right side we do unilateral adrenolectomy. Page 7 of 16

8 Perioperative care of Cushing patients: - As we said Cushing patients have osteoporosis thus they can easily get fractured when we move them to the OR, also they have problems in the tissue so they are more liable for infection, and more liable for soft-tissue trauma e.g; hematoma, also they have low immunity, and have glucose intolerance. So Cushing patient must be treated with more special care for preparation to operation than a patient who doesn t have Cushing. once you do the operation and remove the adenoma or the two adrenal glands, corticosteroids will come back to zero level abruptly, so the patient will have Adrenocortical shock or shut down because he is completed devoid of the steroid that he used to ( for example a 50normal level comes zero the patient will be shocked). So you have to deal with Cushing patient with a great care before the operation, and very gentle care in his tissue and skin and give him prophylaxis against infection and DVT as well as perioperative administration of steroids to keep its level high level, that s means the patient has a high level of corticosteroids so we keep this level during the operation and after the operation we continue in the high level of steroids then we decrease it over a week or when his body adapts the new level of steroids. So perioperative care is very important in patients with Cushing syndrome. Rare. Adrenocortical CA:- It could arise in any cell in the suprarenal cortex, mostly around 80% non functional so the problem with it is not the hormone which is secreted, but its mass effect so the patient may not present with symptoms of excess hormone like steroids or mineralocorticoids, but, mostly the symptoms are secondary to the mass effect. Any age, most of it in the 4-5 th decades. 60% to 80%: no important secretory function. Benign or Malignant? we don t know but sometimes when its functioning, mostly its locally malignant and doesn t spread hematologically except in very rare cases. The symptoms results from the mass effect or the malignant effect:- The symptoms which results from mass effect:- Page 8 of 16

9 Abdominal pain because the size of it is large in comparison with functional adenoma which is small in size and its effect by the hormones secreted. Low grade temperature. Weight loss and anorexia. Generalized weakness. Functional tumors present depending on their type of secretion. Treatment:- As we said if it s functional, mostly it s localized malignant and it s treated once diagnosed by surgery. And you have to go deeper and remove the tumor surgically by suprarenaladrenolectomy. Tumor Localization by CT scan. The response to radio and chemo therapy is low so the main type of the treatment is surgical excision of the supra renal gland. Definition:- Hyperaldoseteronsim:- Excessive levels of aldosterone cause sodium retention and potassium excretion with resultant hypertension and hypokalemia. Hyperaldoseteronsim could be primary or secondary; Primary hyperaldoseteronsim conn syndrome and it s caused by:- 1- Tumor (adenoma) the most common; 80% of the cases. 2- Primary Adrenocortical hyperplasia.15% of the cases. 3- Carcinoma. Conn syndrome occurs most frequently in middle adult life, and is more common in females than males (2:1) Or it can be secondary, in which aldosterone release occurs in response to activation of the rennin-angiotensin system, and its characterized by increased levels of plasma rennin and is encountered in conditions associated with:- 1- Decreased renal perfusion(renal artery stenosis) Page 9 of 16

10 2- Arterial hypovolemia and edema(congestive heart failure, cirrhosis, nephritic syndrome) 3- Pregnancy(caused by estrogen-induced increases in plasma renin) But as we said the most common cause to hyperaldoseteronsim is aldosterone secreting adenoma, and mostly it s a benign adenoma causing hypertension and Hypokalemia. We know that hypertension mainly occurs in elderly and people with atherosclerosis. So if a 30 years old patient comes to you with hypertension you should look for possible primary cause of this hypertension. And 1% of these patients (young and hypertensive) are due to suprarenal adenoma. Pathophysiology:- Aldosterone functions: - Promotes sodium absorption and secretion. Promotes water retention. Increase potassium secretion. Clinical presentations:- Moderate to severe hypertension. Hypokalemia. Hypernatremia. Muscle weakness. Malaise. Polyurea polydypsia. Investigations:- Blood : Hypokalemia Plasma aldosterone and you will find it persistently high. Urine : Increase urinary potassium Page 10 of 16

11 Imaging for diagnosis: U S. C T. M R I. Iodo-cholestrol isotope scan, to see where is the site of hyperfuctioning. We do sometimes something which is called Adrenal vein sampling, and that s when we have a very small adenoma(1mm) and we are not able to localize it, and the aldosterone is high. So this is done By Introducing a catheter in the femoral vein towards the inferior vena cava, then we take a sample of a blood from the left renal vein or vena cava, so the sample in which there is increase in the level of aldosterone is the side of hyperfunctioning adenoma. This patient is having conn syndrome due to adenoma. This patient was given isotope scan and we can clearly see the side which there is hyperfunctioning, the left side, also some of this isotope will go to the urinary bladder and some will go the reticuloendothelial system the liver contains the largest RES, so we can see the liver and urinary bladder. Treatment:- Conn disease is not a killing disease, usually the hypertension is mild and usually if you give the patient spironlactone (potassium sparing diuretics), he will improve. But because of the improvement in the surgical technique such as laparoscope, you can go and remove the adenoma with minimal incidence of mortality. Also by Adrenalectomy; if the cause was adenoma then we do unilateral adrenalectomy (laparoscopic), if the cause was unilateral hyperplasia then we do unilateral adrenalectomy(laparoscopic). Page 11 of 16

12 The most important diseases of the adrenal medulla are neoplasms, which include both neuronal neoplasms (including Neuroblastoma, ganglioneuroma, paraganglioma) and neoplasms composed of chromaffin cells (Pheochromocytomas). Pheochromocytoma:- Composed of chromaffin cells that secrete catecholamine s (norepinephrine,epinephrine) which are metabolized to VMA vanillylmandelic acid The most common tumor of the adrenal medulla in adults. 90% of Pheochromocytoma is adrenal and solitary; in one side. Mostly its benign adenoma. Average size is 5cm. 0.1% of patients investigated for hypertension, that means 0.1 of patients with HT the cause is Pheochromocytoma. Mostly secrets adrenaline. Usually it s discovered early because of the significant effect of catecholamines on tissues. Sometimes its described as the 10% tumor because 10% of pheochromocytomas arise in association with one of several familial syndromes, these include the MEN syndromes. 10% of pheochromocytomas are extra-adrenal usually occurs in sites where is sympathetic changes(paragangliomas). 10% of adrenal pheochromocytomas are bilateral. 10% of adrenal Pheochromocytomas are biologically malignant. 10% of Pheochromocytoma happens in children. Clinical features:- Symptoms may be sporadic and paroxysmal against a background of continuing high concentrations of catecholamines and chronic physiological changes such as hypovolaemia, For example a patient with mild hypertension encountered stress condition straining 4example and you know stress means adrenaline so the patient will go to a very high spike of hypertension. Always we have a high blood pressure comes as paroxysmal changes secondary to certain changes. Page 12 of 16

13 So patients usually complain of:- 1- Intermittent episodes of hypertension. 2- Headache. 3- Palpitations. 4- Sweating. These are the classic manifestations of Pheochromocytoma. Also patients may complain of pallor due to vasoconstriction, anxiety, chest pain and weakness due to excessive secretion of adrenaline. Attacks often occur spontaneously but may be precipitated by vigorous exercise, twisting and bending, Alcohol, tobacco and drugs: Anesthesia, phenothiazines & tricyclic antidepressants. Clinical associations:- Pheochromocytoma occurs in association with the following hereditary syndromes:- 1- MEN type 2 multiple endocrine neoplasia type2 which is an autosomal dominant disorder associated with an activating germ line mutation of the RET protooncogene on chemosome 10. The clinical features of MEN:-Pheochromocytoma (40%), medullary thyroid CA (95%), hyperparathyroidism (25%) 2- Neurofibromatosis type 1 von recklinghausen s disease :- it s an autosomal dominant disorder associated with an inactivating mutation of NF1 tumor suppressor gene on chromosome 17. And 10% of patients with neurofibromatosis may develop Pheochromocytoma. 3- Von hippel-lindau s disease: - this is an autosomal dominant disorder associated with inactivating mutation of the VHL tumor suppressor gene on chromosome 3. Investigations:- Many patients with Pheochromocytoma are misdiagnosed with psychosis because they are young, and having anxiety, palpitation, sweating, so we must do biochemical diagnosis like:- Page 13 of 16

14 1- Measurement of VMA van mandilic acid which is the end product of adrenaline, and nore-adrenaline in an acidified 24-hour urine collection. And they found that it s high in the urine around 60%. 2- Measurement of urinary catecholamines, 90% sensitive and specific. A patient with 24 hour urine of catecholamines which is more than the normal together with the history is suggestion of Pheochromocytoma. Anatomical localization of the tumor by: - US. CT scan. MRI. ¹²³I-MIBG metaidobenzylguanidine which is a norepinephrine analog that collected in adrenergic vesicles and, thus, in Pheochromocytoma. It s very useful; it will identify at least 90% of tumors including extra-adrenal diseases, multiple tumors and if there is metastases. Management :- Once we know the cause we do adrenolectomy, and as we said in Cushing syndrome, also here there are special perioperative precautions to patients with Pheochromocytoma, so we know that these patients have a high level of catecholamines and, thus significant stress may result, so they will end up with collapsed blood volume and collapsed blood vessels, so once we do the operation there will be sudden dilation of blood vessels, thus shock will produce. So it s very important to prepare the circulation of the patient before operation, so we give him α-blockers to dilate the blood vessels, intravenous fluid to cope with these dilated blood vessels, and this effect of α-blockers will decrease the effect of the sudden increment of adrenaline. So perioperative care is important to prevent the sudden increase in the level of adrenaline during the operation where is going to cause heart problems and ventricular fibrillations in adults, so dilations of blood vessels by α-blockers and enough IV fluid then we will precede to surgery. Parathyroid glands:- Anatomy:- Normal parathyroid glands are soft, usually oval in shape, they measure up to 6mm in length and each will weigh between 30 and 50 mg, most individuals will have four parathyroid glands; Page 14 of 16

15 approximately 10% of the population will have one or more supernumerary glands and some will have fewer than four glands. The superior parathyroid glands are located near the junction of the inferior thyroid artery and recurrent laryngeal nerve, usually superior to the artery and posterior to the nerve. The inferior parathyroid glands are located anterior to the recurrent laryngeal nerve at the lower pole of the thyroid lobe. Embryology:- The superior parathyroid glands develop from the fourth pharyngeal pouch, and the inferior parathyroid glands develop with the thymus from the third pharyngeal pouch. Histology:- The parathyroid gland has a thin fibrous capsule, and contains cells; chief and oxyphil cells, but the predominant cell type in the gland is the chief cell, which contains lipid and PTH parathyroid hormone which ¹controls the level of calcium in the blood and extracellular fluid. Also it ²effect on the kidney; which stimulates calcium reabsorption, inhibits phosphate reabsorption and stimulates the synthesis of vitamin D, also ³in bone; which stimulates resorption by increasing osteoclast activity and stimulates osteoblast activity. Primary hyperparathyroidism:- A sporadic (in elderly people more than 60 years) or familial disorder associated with hypercalcemia, elevated or inappropriately raised PTH levels and parathyroid gland enlargement. And it s caused by adenoma (85%), or hyperplasia (14%), or carcinoma (1%). Mostly it s discovered incidentally except in the rare cases where the PTH is very high and causes disturbances in calcium levels and causes significant symptoms. Clinical manifestations:- Asymptomatic. Renal disorders. Bone disorders. Musculosceletal. Gastrintestinal. Psychiatric. Page 15 of 16

16 Cardiovascular. Metabolic. Biochemical diagnosis:- Hypercalcemia. Hypophosphatemia and high plasma chloride levels are commonly found. Bone specific alkaline phosphatase may be elevated. Due to turn over of the calcium in the bone. Localization:- Ultra sound of the neck to see if there is any masses e.g; adenoma. CT scan. Technetium99 labeled Sestamibi (MIBI) isotope scans identify approximately 80% of abnormal parathyroid glands and can image mediastinal parathyroid tissue. Treatment:- Follow up. Surgery: Urinary calculi Reduced bone density Serum calcium >2.85 (normal 1.8 to 2.1) After we take history and we investigate, if its adenoma and occurs in elderly patient the treatment is by follow up because elderly people may be associated with poor surgical outcome. In some rare cases the patient presents with bone pathology and stones and peptic ulcer symptoms, psychological changes Or could it be due to secondary causes like renal failure. So when we say secondary it means the cause is from outside the gland, and thus the four glands will be affected, but when we say primary cause, only one gland will be affected. End of the lecture Done by jehad abdel aziz Page 16 of 16