ظظظ/ Omar Sami. Hussam Twaissi. Mousa Abbadi
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1 ظظظ/ 5 Omar Sami Hussam Twaissi Mousa Abbadi
2 The doctor started this lecture by revising what we have taken in lecture number four, I won t re-write these stuff as it becomes boring so often. This sheet won t be so long if I cut out the pictures which can be readily found in the slides. Throughout this lecture, we will take about two main categories, and thus the sheet will be of two sections: A- Different diseases of adrenal cortex and medulla. B- Adrenocortical tumors. Let s practise some medicine Section A Adrenogenital Syndromes Adrenogenital Syndromes, in general, refer to group of disorders caused by androgen excess, which may be caused due to various reasons two of which are primary gonadal disorders&primary adrenal disorders. Let s have a closer look at the adrenal ones Q: What can affect the adrenal gland and cause androgen excess? A: 1- Cushing syndrome may be the culprit in many cases; as the adrenal androgen formation, unlike the gonadal androgen formation, is regulated by ACTH, thus excessive secretion can present in combination with Cushing Syndrome. 2-However, Adrenocortical neoplasms and uncommon group of disorders collectively designated Congenital Adrenal Hyperplasia (CAH) may also contribute in the formation of this syndrome. More details on point 2: Adrenocortical neoplasams associated with symptoms of androgen excess are more likely to be carcinomas than adenomas.
3 Congenital Adrenal Hyperplasia represents a group of autosomal recessive disorders, charectarized by enzymatic defect in 21- Hydroxylase, 21-hydroxylase is required for the synthesis of cortisol and aldosterone, but not sex steroids; thus a deficiency of this enzyme reduces cortisol and adlosterone synthesis and shunts the common precursor into the sex steroid pathway. The second pathological condition in this lecture Acute and Chronic Adrenal Insufficiency Hypofunction or Insuficiency of the adrenal gland may be caused by either: a- Primary Adrenal disease. Primary Hypoadrenalism b- Decreased stimulation of the adrenals due to ACTH deficiency. Secondary Hypoadrenalism. And again, let s have a closer look at the Primary Adrenal Disease. Primary adrenocortical insufficiency may be Acutecalled Adrenal Crisis, or Chroniccalled Addison disease. Acute Adrenocortical Insufficiency Acute Adrenocortical Insufficiency occurs in the clinical settings listed below: - Sudden withdrawl of long term corticosteroid therapy: patients who are on exogenous corticosteroids are prone to develop adrenal crisis upon sudden withdrawal; as their atrophic adrenals are not capable of producing glucocorticoid hormones, which are important to manage stress conditions. - Stress in patients with underlying adrenal insufficiency:
4 Patients with chronic adrenocortical insufficiency may develop an acute crisis as they encounter severe stress, so called Acute on top of Chronic. - Massive Adrenal Hemorrhage: Massive hemorrhage may destroy enough of the adrenal cortex ta cause acute adrenocortical insufficiency, this condition may occur in patients maintained on anticoagulant treatment, postoperative patients who develop Disseminated Intravascular Coagulation, during pregnancy and those who suffer from overwhelming sepsis. - WaterHouse Friderichen syndrome: This catastrophic syndrome is classicaly associated with Neisseria meningitidis, and develop Septicemia which can trigger Acute Adrenocortical Insufficiency. Chronic Adrenocortical Insufficiency Or so calledaddison Disease, uncommon disorder resulting from progressive destruction of the adrenal cortex (Panhypoadrenalism), more than 90% of the all cases are attributable to one of four disorders: 1- Autoimmune adrenalitis: Accounts to 60-70% of all cases, as the name implies there is an autoimmune destruction of steroid-producing cells, and autoantibodies to to several key steriodogenic enzymes have been detected. Mutations in the autoimmune regulator gene (AIRE) on chromosome number 21 will cause what is known as Auto Immune Polyendocrine Syndrome(APS), charectarized by mucocutaneous candida,dental, skin and nailabnormalities. 2- Infections: Particularly TB and those produced by fungi. 3- AIDS:
5 Pateints with AIDS are at a higher risk for the development of adrenal insufficiency; due to higher risk to infections. 4- Metastatic Carcinoma: Remember that adrenal glands are a common site for metastasis from tumors in lungs and beasts. ** Secondary adrenocortical insufficiency: hyopathalamic or pituitary in origin. Clinical Features for patients with Addison s disease - GI complications include: nausea, diarrhoea, vomiting, constipation and abdominal pain. - Hyperpigmentation; due to excess ACTH which stimulates melanocytes, thus hyperpigmentation won t occur in low ACTH adrenal insufficiency, hence secondary hypoadrenalism. - Decreased mineral corticoid (Aldosterone): results in potassium retention, and sodium loss, with consequent hyperkalemia, hyponatremia, volume depletion and hypotension. - Hypoglycaemia; due to impaired gluconeogenesis as glucocorticoids are deficient. Section B Adrenocortical Neoplasms Adrenal neoplasms may be responsible for any of the various forms of hyperadrenalism. Functional adenomas are most commonly associated with hyperaldosteronism and with Cushing syndrome, yet
6 adrenocortical neoplasms (virilizing neoplasm) are more likely to be carcinomas. Adrenocortical adenomas are encountered as incidental findings at the time of autopsy, 1-2 cm s in diameter. Carcinomas, on the other hand, are rare, large, infiltrative and occur at any age. And remember that metastasis to the adrenals is more common than primary neoplasms of the adrenals. Adrenal medulla tumor (Pheochromocytoma) Pheochromocytomas are neoplasms composed of chromaffin cells, which, like their nonneoplastic counterparts, synthesize and release catecholamines. They lie under the rule of 10 s or the 10% tumor : - 10% extra-adrenal, which means that we can find the same tissue located at different locations, one of which is the neck and so called paraganglioma. - 10% bilateral (50% in familial cases) - 10% malignant (> in extra-adrenalsites) - 10% not associated with Hypertension. - 25% have germline mutations (RET in MEN-2,NF1,VHL, andothers) Q: What is the buzz word that should be carefully handled when dealing with pheochromocytomas? A: Paroxysmal episodes of Hypertension, which are described as an abrupt, precipitous elevation in blood pressure, palpitations and tachycardia. However, some general and inconclusive symptoms may also occur; such as headache, sweating and tremors. And upon Laboratory diagnosis: increased urinary catecholamines metabolites, vanillymandelic acid(vma) Neuroblastoma - Most common extracranial solid tumor of childhood, children under 3 years of age are the classical example.
7 - Can occur anywhere throughout the body, but abdominal masses are the mostcommon. - Most aresporadic. Multiple Endocrine Neoplasia Syndromes General features - Inherited disorders, proliferative of multiple endocrineorgans. - Younger agegroups. - They arise in multiple endocrine organs, either Synchronously (at the same time) or metachronously (at different times) in multiple organs. - Even in one organ, the tumors are multifocal. - Often preceded by asymptomatichyperplasia. - More aggressive than theirsporadic counterparts; which means that tumors which occur as a result of MEN syndromes are more aggressive than their sporadic counterparts. Multiple Endocrine Neoplasia Types Multiple Endocrine Neoplasia is subdivided to two distinct types according to the number of chromosome that was hit. Type 1: MEN type 1 is inherited in an autosomal dominant pattern. The gene (MEN1) is located at chromosome 11, which encodes for Menin Protein, which is a tumor suppressor gene; thus, inactivation of both alleles of the gene is believed to be the basis for tumorigenesis. Organs most commonly involved are the parathyroid, the pancreas, and the pituitary, the 3 Ps. Parathyroid: Primary hyperparathyroidism is the most common manifestation of MEN-1. Pancreas: Endocrine tumors of the pancreas are the leading cause of death in MEN-1. Pituitary
8 Type 2: MEN type 2 actually comprises two distinct groups of disorders, the molecular basis of which these disorders are categorized at, was not discussed in the lecture. It is related to chromosome Multiple Endocrine Neoplasia Type 2A: Organs commonly involved in MEN type 2A include: Thyroid:Medullary carcinoma of the thyroid develops in virtually all untreated cases. Adrenal medulla: Adrenal pheochromocytomas develop in 50% of the patients. Parathyroid: Approximately 10% to 20% of patients develop parathyroid gland hyperplasia with manifestations of primary hyperparathyroidism. - Multiple Endocrine Neoplasia Type 2B: Patients develop medullary thyroid carcinomas and pheochromocytomas. MEN-2B has the following distinctive features: Primary hyperparathyroidism does not develop in patients with MEN- 2B. Extraendocrine manifestations are characteristic in patients with MEN-2B; such as Marfanoid Body Habitus, Marfan syndrome like features, and Mucosal Neuromas found on lips and tongue. However, medullary Thyroid carcinoma and Pheochromocytoma occur in MEN-2B. Love is Wise Hatred Is Foolish
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