Endocrine Pathology
Dr. Mudhaffar F. AL-ChetachiThe endocrine system comprises two main components
i. The classical endocrine organs e.g. pituitary, thyroid, adrenal, parathyroid, islet’ of Langerhans in pancrease.ii. The diffuse endocrine system consist of cells dispersed singly or in small group throughout various non-endocrine organ including G.I.T. lung. Skin.An endocrine hormone is frequently carried by the blood from its site of release to its target. Increased activity of the target tissue often down-regulates the activity of the gland that secretes the stimulating hormone, a process known as feedback inhibition.
Several processes may disturb the normal activity of the endocrine system, including impaired synthesis or release of hormones, abnormal interactions between hormones and their target tissues, and abnormal responses of target organs to their hormones. Therefore; endocrine disease can be generally classified as
Classification of endocrine diseases
Diseases of underproduction or overproduction of hormones and their resulting biochemical and clinical consequence. Diseases associated with the development of mass lesions, which may be nonfunctional or may be associated with overproduction or underproduction of hormones. The study of endocrine disease requires integration of morphologic findings with biochemical measurements of the hormone levels.
The pituitary gland is a small , bean- shaped structure that lies at the base of the brain within the confines of the sella turcica. The pituitary is composed of two morphologically and functionally distinct components : the anterior lobe (adenohypophysis) and the posterior lobe (neurohypophysis). Diseases of the pituitary , accordingly , can be divided into those that primarily affect the anterior lobe and those that primarily affect the posterior lobe.
The pituitary gland and the hypothalamus
Hyperpituitarism : This disorder arises from excessive secretion of trophic hormones . It most often results from an anterior pituitary adenoma, but may also be caused by other pituitary and extra- pituitary lesions . Hypopitutarism : This is caused by deficiency of trophic hormones and results from a variety of destruc- tive processes, including ischemic injury, surgery or radiation and inflammatory reactions . Local mass effects : Among the earliest changes referable to mass effect are radiographic abnormalities of the sella turcica, including sellar expansion, bony erosion, and disruption of the diaphragma sellae. Because of the close proximity of the optic nerves and chiasm to the sells, expanding pituitary lesions often compress decussating fibers in the optic chiasm. This gives rise to visual field abnormalities, classically in the form of defects in the lateral (temporal) visual fields a so-called bitemporal hemianopsia.
Symptoms of pituitary disease can be divided into the following :
Pituitary Adenomas
The most common cause of hyperpituitarism is an adenoma arising in the anterior lobe. Pituitary adenomas are classified on the basis of hormone(s) produced by the neoplastic cells, which are detected by immunohistochemical stains performed on tissue sections Pituitary adenoma are divided into micro adenoma < 10mm diameter and macro adenoma > 10mm.Clinically diagnosed pituitary adenomas are responsible for about 10% of intracranial neoplasms, and usually found in adults, with a peak incidence from the 30s to the 50s.
Pituitary adenomas can be functional (i.e., associated with hormone excess and clinical manifestations thereof) or silent (i.e., immunohistochemical and / or ultrastructural demonstration of hormone production at the tissue level only, without clinical manifestations of hormone excess), or may be hormone negative, based on absence of immunohistochemical reactivity. Both functional and silent pituitary adenomas are usually composed of a single cell type and produce a single predominant hormone, although exceptions are known to occur. Some pituitary adenomas can secrete two hormones (growth hormone and prolactin being the most common combination); rarely, pituitary adenomas are plurihormonal. Most pituitary adenomas occur as isolated lesions. In about 3% of cases, however, adenomas are associated with multiple endocrine neoplasia type 1 (MEN-1) syndrome.
Microscopically, pituitary adenomas are composed of relatively uniform, polygonal cells arrayed in sheets cords, or papillae. Supporting connective tissue, or reticulin, is sparse, accounting for the soft, gelatinous consistency of many lesions. The nuclei of the neoplastic cells may be uniform or pleomorphic. Mitotic activity is usually scanty. This cellular monomorphism and the absence of a significant reticulin network distinguish pituitary adenomas from non-neoplastic anterior pituitary parenchyma.
Acromegaly (GH producing pituitary adenoma), illustrating the thickening of the nose and enlargement of the lower jaw
Note monomorphic population of cells with little - no nuclear atypia and clear cytoplasm (this one is chromophobic)
Pituitary adenoma
Clinical Manifestations of Pituitary Adenomas
Prolactinomas : amenorrhea, galactorrhea, loss of libido, and infertility. Growth homone (somatotroph cell) adenomas : gigantism (children), acromegaly (adults), impaired glucose tolerance, and diabetes mellitus. Corticotroph cell adenomas : Cushing syndrome, hyperpigmentation. All pituitary adenomas, particularly nonfunctioning adenomas, may be associated with mass effects and hypopituitarism.Posterior Pituitary Syndromes
1. Hormones are synthesized in hypothalamus and transported via axons to the posterior pituitary. Oxytocin induces uterine contraction during labor and ejection of milk from mammary alveoli Antidiuretic hormone (ADH , vasopressin ) promotes water retention through action on the renal collecting ducts 2. Syndrome of inappropriate ADH secretion SIADH is most commonly caused by ectopic production of ADH by various tumors especially small cell carcinoma of the lungB. SIADH results in retention of water with consequent dilutional hyponatremia reduced serum osmolality and Inability to dilute the urine 3. deficiency of ADH A. This results in diabetes insipidus is characterized by Polyuria with consequent dehydration and polydepsia Nonfunctioning pituitary tumors 1. Nonsecreting pituitary adenomamas are most often chromophobic A. Dysfunction results because of local pressure effect B. These tumors are clinically variable include hypopituitarism , headache , visual disturbances due to pressure on optic chiasm and palsies caused by cranial nerve damage.
Thyroid gland
The thyroid gland produces 3 hormones : 1. Thyroxine 2. Tri-iodothyronine : It is more potent . They are not present as free compounds but are constituents of thyroglobulin in the colloid . 3. Calcitonin : It is produced by the parafollicular cells. It is polypeptides which lower the conc. Of calcium in the blood by causing deposition of calcium in the bone .
The normal adult gland weights 20-40 gm, & consists of two lateral lobes connected by isthmus . Micro. : It consists of thyroid follicles lined by cuboidal epithelium & containing colloid.
This is the normal appearance of the thyroid gland on the anterior trachea of the neck. The thyroid gland has a right lobe and a left lobe connected by a narrow isthmus.
Hormone synthesis in the thyroid gland : 1. The follicular cells of the thyroid gland remove iodide from the plasma at a rate which is controlled by the plasma / gland iodide gradient & by TSH . 2. The iodide is oxidized to iodine. 3.The iodine is taken up by a tyrosine component of an intrathyroid globulin to produce mono-& di-iodotyrosine- this forms the colloid . 4. Two of these molecules condense to form thyroxine & tri-iodothyronine, which are coupled to globulin as thyroglobulin. 5. Thyroglobulin is hydrolysed & thyroid hormones are released into the circulation.
Congenital Anomaly of thyroid gland
The human thyroid originates embryologically from an evagination of pharyngeal epithelium with some cellular contribution, from lateral pharyngeal pouches. Progressive descent of the midline of the thyroid give rise to the thyroid glossal duct, which extend from the foramen cecum near the base of the tongue to the isthmus of the thyroid. Remnants of the tissue may persist along the course of this tract as lingual thyroid, thyroglossal cysts or nodules.Goiter It is an enlargement of part or whole of the thyroid . It may be diffuse or nodular & it may be associated with a deficient , normal , or excessive production of thyroid hormone.
Cross Multinodular goiter
Micro-Multinodular goiter
Functional disorders of thyroid gland
Types : 1. Nontoxic goiter : ( Simple goiter ) : a. Sporadic nontoxic b. parenchymatous c. Colloid goiter : Diffuse Nodular 2. Toxic goiter : I. Primary II. Secondary. Simple goiter The thyroid enlargement is a response to insufficient iodine intake resulting from a deficient of iodine in the soil & water. Endemic goiter may be prevented by the addition to the diet of minute amount of iodine as by the use of iodised salt. The condition occurs more commonly in females & is particularly likely to develop at a time when the thyroid gland is subjected to extra functional stress as in adolescence or pregnancy .
Sporadic goiter may occur due to : 1. Iodine deficiency due to improper dietary habits. 2. Dyshormogenesis due to one of a group of inherited defects of the process of thyroid hormone synthesis or secretion. 3. The action of substances which interfere with thyroid hormone synthesis e.g. the ingestion of certain plant foods containing goitrogenic substances.
Pathogenesis : Deficiency of iodine leads to diminish production of thyroid hormone which, in turn, causes increased out put of TSH from the pituitary gland, followed by increased activity of thyroid epithelium which become hyperplastic, Involution must occur if the gland is to return to a normal stage. Derangements in the normal balance of these functions may lead to functional & anatomical damage recognizable as goiter .
Gross : The thyroid gland is enlarged which may be diffuse or nodular. The cut surface is transluscent because of the colloid material. Degenerative changes are common & there may be haemorrhage, cyst formation, calcification & fibrosis. Many of these goiters reach an enormous size & they may show a retrosternal prolongation . Micro. : The goiter consists of a large distended follicles containing colloid & lined by a low cuboidal or flattened epithelium. In some cases of simple goiter the thyroid gland is composed of small follicles without excess of colloid accumulation. This variety is termed parenchymatous goiter .
Toxic goiterI. Primary thyrotoxicosis–Graves disease, Exophthalmic goiter:There is a moderate diffuse enlargement of thyroid gland occurring mostly in females below the age of 40 years , & associated with evidence of hyperfunction & eye signs. Complications : Pressure : Especially on the trachea & oesophagus, particularly when there is retrosternal extension . Haemorrhage : Into the nodules producing a rapid increase in size. This may increase the pressure symptoms to a dangerous degree & result in asphyxia. Toxic changes Malignancy : Carcinoma may develop in a very small percentage.
Aetiology : The actual stimulus for the hyperactivity of the thyroid gland is not very well known. Evidence points to an autoantibody to some cellular components of the thyroid gland which is called long-acting thyroid stimulator (LATS), It is possible that the globulin (which is IgG) acts against the normal inhibitor of mitoses in the thyroid gland. Thus the removal of mitotic inhibition could lead to hyperplasia followed by hyperfunction. Macro. : There is diffuse vascular & fleshy enlargement of the gland with lack of colloid seen on the cut surface . Micro. : It is characterized by : The lining epithelium of the thyroid follicles is hyperplastic, tall & columnar, with papillary processes projecting into the lumen of the follicles. The follicles are deficient in colloid & show scalloping of the colloid margins .
3. There is increased vascularity & lymphocytic infiltration with lymph follicle formation . Effects : 1. General metabolism : The BMR is raised with increased in the activity of body of body function e.g. weight loss & increased heat production with sweating 2. Cardiovascular : Tachycardia & raised cardiac output , this predispose to cardiac failure, especially when aterial fibrillation develop. 3. Neurological : Exaggeration in the variation of mood with tremor. 4. Eye signs : a. Exophthalmus b. Lid retraction .
II. Secondary thyrotoxicosis: Nodular toxic goiter : toxic change occurring in one or more nodules of a nodular colloid goiter.
Note papillary hyperplasia of follicular epithelium and scalloping of colloid
The thyroid in Graves’ diseaseHypothyroidism : It is due to deficiency of circulating levels of thyroid hormones. It may be : 1. Primary : due to disease of the thyroid. 2. Secondary : To hypopituitarism .
Severe primary hypothyroidism in adults gives rise to myxoedema, so called because of the characteristic thickening of the skin by mucoid material. The clinical features are the opposite of those of thyrotoxicosis i.e. a very slow heart rate & gain in weight. Most of symptoms can be explained as being due to deficient tissue oxidation throughout the body. In severe myxoedema the reduced metabolism may lead to hypothermia . Causes : a. Idiopathic atrophy of the gland b. Iodine deficiency c. Destruction of the gland by Hashimoto's thyroiditis & post thyroidectomy.
Critinism : The child with hypothyroidism at birth will become a critin. in other ward in critin thyroid function is deficient from birth. The characteristic features are : coarse puffy face, protruding tongue & abdomen & the general physical & mental inactivity . Inflammation of Thyroid (THYROIDITIS) A. Bacterial : 1. Acute thyroiditis : It is rare caused by bacterial infections e.g. staph or strepto which reach the thyroid gland by one of the following ways : haematogenous, lymphatic or direct from near by focus. Pathology : The gland is swollen & congested with interstitial inflammation . Results : 1. Resolution or 2. Suppuration with abscess formation .
2. Granulomatous thyroiditis : Specific granulomatous inflammation due to TB, sarcoidosis , syphilis (gumma ) may occur . B. Non-bacterial : 1. Hashimoto's thyroiditis : The disease process is due to autoimmunity which is produced by the release of thyroid follicle constituents into the interstitial tissue & formation of auto antibody against them. Sex : M : F 1 : 9 . Serological tests : There may be 3 circulating antibodies : a. Antithyroglobulin antibody b. Microsomal antibody : It is antibody against a lipoprotein of the membrane of the endoplasmic reticulum(microsome) of the thyroid epithelial cells.
Macro. : There is diffuse enlargement of the gland which is smooth, firm & lobulated. The cut surface is lobulated, pale with diminished or absent colloid. Micro. : a. Lymphoid infiltration with lymph follicle formation . b. Diffuse plasma cell infiltration c. Epithelial metaplasia with large eosinophilic thyroid epithelial cells --- Askanazy cells . d. Diminished colloid in the follicles . e. Increase fibrous tissue producing a lobulated pattern. Result : The patient might develop myxodema.
Hashimoto’s thyroiditis Note prominent lymphoid infiltrate with germinal centers and thyroid follicles with bright eosinophilic cytoplasm (Hurthle cell change)
2. Subacute Granulomatous thyroiditis “De Quervain” :* It is rare self-limiting disease presented by fever, pain in the throat & thyroid enlargement.* It is believed to be caused by a viral infection.* Microscopically, it show focal granulomatous inflammation with foreign body giant cells, often engulfing colloid material. 3. Riedel's thyroiditis :* It is very rare lesion of unknown etiology, characterized by enlargement of the thyroid by fibrous tissue, which extend to the surrounding neck structures * It is hard in consistency which clinically simulate a thyroid neoplasm * The presence of circulating antithyroid antibody in most patients suggests an autoimmune etiology.
4. Subacute lymphocytic thyroiditis * Often occurs following a pregnancy (post-partum thyroiditis) * It is typically painless.* Diffuse lymphoplasmacytic infiltration with G. center formation.* Hurthle cell changes is not seen* Thyroid auto a.b. is present.* It represent an early precursor form of Hashimoto’s thyroiditis.
Auto immune thyroid diseases
This group of disease “Hashimoto’s thyroiditis, primarymyxoedima, and Graves diseases are generally characterized by : 1. Lymphoid infiltration of thyroid tissue.2. Presence of circulating auto-a.b. to various component of thyroid follicular cells e.g. “anti-microsomal, anti-thyroglobulin, antisecond colloid a.g and anti-TSH receptor.3. There is a familial association between the thyroid autoimmune disease and other organ specific auto immne disease including Addison’s disease, type I. D.M. pernicious anaemia.Tumours of the thyroid gland
1. Benign and malignant thyroid tumour usually present clinically as solitary nodule and majority of them are cold on thyroid scan. 2. It can arise from both follicular epithelium and C cells where the majority are follicular adenoma while the malignant tumour of the follicular cells origin fall into two main group, papillary and follicular carcinoma which behave differently, while the medullary carcinoma arise from C cells.Thyroid adenomas
They are benign neoplasm derived from follicular epithelium. The criteria for adenoma are : Complete encapsulation Homogenous texture throughout Variation of tissue of adenoma from that outside the capsule. Compression of adjacent thyroid tissue.1. They are the commonest thyroid neoplasm presenting most frequently in women over 30 year as solitary nodules.2. Adenoma are usually encapsulated and compress the surrounding normal gland, hemorrhage, necrosis, fibrosis may occur.3. Histologically most show microfollicular pattern with little colloid storages “fetal colloid adenoma”. Some are composed of hurthle cell “Hurthle cell adenoma which consist of cell with abundant eosinophilic cytoplasm or “trabecular adenoma composed of cords or trabecular pattern and lastly, papillary form “papillary adenoma” which consist of papillary structure.4. It is often difficult distinguish clinically and histologically between adenoma and carcinoma in the absence of capsular and/or blood vessel invasion. Types of thyroid adenomas
Folicular adenoma of the thyroid. A solitary, well-circumscribed nodule is seen
Mic. Folicular adenoma well-differentiated folicles resemble normal thyroidHurthle cell adenoma. it composed of cells with abundant eosinophilic cytoplasm
Thyroid Carcinoma
Which include the following : Papillary carcenoma 70-85%. Follicular carcinoma 10-20%. Medullary carcinoma 5%. Anaplastic carcinoma 5%.Both genetic and environmental factors “exposure to ionizing radiation” are implicated in the pathogenesis of thyroid carcinoma.
Pathology of papillary carcinoma
1. It is predominant form of thyroid cancer and can occur at any age but most often in 3rd to 5th decade “20-40” year. With female proponderance 75-85%.2. Because papillary carcinoma have tendency for invading lymphatic they often appear multifocal tumour and regional L-node metastases are present at times of diagnosis in 50% of cases.3. Histologically the tumour is rarely encapsulated and it range from those that are predominantly papillary to those that are in some part follicular in appearance 30% (follicular variants), to lesion have equal part of papillary and follicular architecture all papillary carcinoma reveal some branching papillae which have fibrovascular stalk covered by single or multiple layer of cuboidal epithelium cells which range from well differentiated cells to anaplastic variety.4. The characteristic hall mark of papillary neoplasm can be found in cell nuclei “nuclear features” even in the absence of papillary architecture which include :a. Hypochromatic “empty” nuclei devoid of nucleoli giving rise to the designation ground glass “Orphan Annie eye”.b. Nuclear grooves.c. Eosinophilic intra nuclear inclusion from cytoplasmic invagination (pseudo-inclusion).5. Psammoma bodies usually with the core of papillae which are never found in follicular or medullary carcinoma.6. Area of sequamous metaplasia, Lymphocytic infiltrates may be found.
Micro-Papillary carcinoma
Micro. Papillary carcinoma Psammoma bodyMicro. Papillary carcinoma "Orphan Annie eye" clear nuclei
Follicular carcinoma
1. It composes 10-20% of all thyroid cancer and more common in female with peak incidence in fifth decade. 2. Distant blood borne metastasis occur particularly to bone and lung with poor prognosis. 3. Microscoplically most follicular carcinoma are composed of fairly uniform cells forming small follicles. Hurthle cell variant of follicular carcinoma may be seen. 4. F. carcinoma can be divided into two group a. widely invasive tumour which spread throughout normally gland. b. microscopic invasion of fibrous capsule and blood vessels.Follicular carcinoma of thyroid. (Intact capsule)
Follicular carcinoma of thyroid. (Capsular invasion)Medullary carcinoma
1. It account for 5-10% of thyroid cancer with 10-20% familial tendency forming part of MEN. II2. Sporadic type (80%) is usually unilateral and in old age “while the familial variant is usually bilateral and multifocal arising on background of c cell hyperplasia and occur before the age of 25 years.3. Histologically it consist of solid irregular group and cords of polygonal to spindle shaped cells which may form nests and even follicles.4. Calcitonin immunoreactivety, can be demonstrated in all cases. A cellular Amyloid deposits are present in the stroma.5. Spread by blood and lymphatic. It is neuroendocrine neoplasm derived from parafollicular C-cell(Medullary carcinoma of thyroid) The tumor contain amyloid Homogeneous extracellular material H and E stain
Anaplastic Carcinoma
Anaplastic carcinoma of the thyroid are among the most aggressive human neoplasms, Individuals with anaplastic carcinoma are older than those with other types of thyroid cancer, with a mean age of 65 years. About half of the patients have a history of multinodular goiter. Microscopically, these neoplasms are composed of highly anaplastic cells, which may take on several histologic patterns, including large pleomorphic giant cells, spindle cells with a sarcomatous appearance, mixed spindle and giant cell lesions and lastly small cells, resembling those seen in small-cell carcinomas at other sites.Parathyroid diseases
Parathyroid hormone: Secretion is not under pituitary control The parathyroid glands are responsive to plasma concentration of ionized calcium, decreased calcium concentration stimulates PTH production Hyperparathyroidism: 1.Primary hyperparathyroidism: is the most common cause of asymptomatic hypercalcemia.
Most often due to parathyroid adenoma , few cases are caused by primary parathyroid hyperplasia ,Carcinoma is rarely a cause. Parathyroid adenomas are solitary while hyperplasia is typically a multiglandular process. Less often the cause is production of PTH like hormone by non parathyroid malignant tumors such as bronchogenic squamous cell carcinoma.
Laboratory findings: Hypercalcemia & hypercalciuria Increased serum alkaline phosphatase Decreased serum phosphorus Increased serum PTH
Clinically: Skeletal manifestation: include bone resorption ,osteitis fibrosa cyctica and brown tumors. Metastatic calcification affecting various tissues especially the kidney (nephrocalcinosis) and renal stones Peptic ulcer .
Secondary hyperparathyroidism : Compensatory parathyroid hyperplasia occurs in response to decreased serum ionized calcium It is most often cause by renal failure ,malignancies are most important cause of symptomatic hypercalcemia which result from osteolytic metastasis or release of PTH related protein from non parathyroid tumors.
Hypoparathyroidism
The most common cause is accidental surgical excision during thyroidectomy ,In rare cases this disorder is associated with congenital thymic hypoplasia (DiGeorge Syndrome). Severe hypocalcaemia manifest clinically by increased neuromuscular excitability and tetany is characteristic .Type 1 diabetes is an autoimmune disease characterized by progressive destruction of islet β cells, leading to absolute insulin deficiency. Several immune mechanisms probably contribute to β-cell damage, including T cells, cytokines, and autoantibodies.
Type 2 diabetes has no autoimmune basis; instead, features central to its pathogenesis are insulin resistance and β-cell dysfunction, resulting in relative insulin deficiency.Obesity has an important relationship with insulin resistance (and hence, type 2 diabetes), probably mediated by cytokines released from adipose tissues (adipocytokines).
The Adrenal gland
Glucocorticoids "principally cortisone" which are synthesized primarily in the Zona fasciculata. Mineralo corticoids, the most important being aldosterone which is generated in the zona glomerulosa. Sex steroid "eostrogens and androgens", which are produced largely in the zona reticularis.
The adrenal glands are paired endocrine organs consisting of both cortex and medulla, which differ in their development, structure, and function. The cortex being mesodermal and the medulla of neural origin. The adrenal cortex synthesizes three different types of steroids :
The adrenal medulla is composed of chromaffin cells which synthesize and secrete catecholamines, mainly epinephrine.
Pathology of adrenal cortex
I-Adrenocortical hyperfunction "Hyperadrenalism" As there are three basic types of corticosteroid, elaborated by the adrenal cortex "glusocorticoids, mineralocorticoid, and sex steroids", So there are 3 distinctive hyper adrenal clinical syndromes."Cushing syndrome characterized by an excess cortisone. Hyperaldosteromism. Adrenogenital or virilizing syndrome characterized by excess androgen.
Causes of "Cushing syndrome"
This conditions is caused by any condition that produces an elevation in glucocorticoid levels.In clinical practice most cases of Cushing syndrome are caused by the administration of exogenous glucocorticoids. The remaining cases are endogenous and include the following: Primary hypothalamic-pituitary diseases associated with hyper secretion of ACTH "Cushing disease" account for 50%. Primary adrenocortical hyperplasia or neoplasia "10-20%". The secretion of ectopic ACTH by nonendocrine neoplasma e.i.g." oat cell carcinoma of lung, medullary thyroid carcinoma carcinoid tumour, islet cell tumour of the pancreas.
Various forms of Cushing syndrome
The Pathology of Cushing syndromeThe main lesions of cushing syndrome one found in the pituitary and a adrenal glands, in pituitary, the normal granular, basophilic cytoplasm of ACTH-producing cell in anterior pituitary is replaced by homogonous, lightly basophilic material, due to accumulation of intermediate keratin filaments in the cytoplasm. "Crooke hyaline change, while the adrenal glands show either, cortical atrophy, diffuse or nodular hyperplasia or adenoma and rarly a carcinoma.
Clinically cushing cyndrome manifested by : Systemic hypertension. Obesity of face, neck and trunk. Striae of the abdomin. Facial hair. Thin and wasting of skeletal muscles Increased tendency for bacterial infection.
The Pathology of Hyperaldosteronism
Excessive levels of aldosterone cause sodium retension and potassium excretion, with resultant hypertension and hypokalemia. Hyperaldosteronism may be primary "Conn syndrome" associated with aldosterone-secreting adenoma in one adrenal gland. Primary hyperaldosteronism indicate a primary autonomous over production of aldosterone with resultant suppression of the rennin-angiotensin system with decreased plasma rennin activity. Secondary hyperaldosteromsm due to an extraadrenal cause where aldosterone release occurs in response to activation of rennin-angiotensin system, where plasma rennin level increased in many condition like I. decreased renal perfusion renal artery stenosn n,
Secondary hyperaldosteronism due to an extraadrenal cause where aldosterone release occurs in response to activation of rennin-angiotensin system, where plasma rennin level increased in many condition like
decreased renal perfusion (renal artery stenosis). congestive heart failure, cirrhosis, nephrotic syndrome Pregnancy (oestrogen increase plasma rennin).
Pathology of adreno-genital syndromes
The adrenal cortex can secrete excess androgens in two setting a. adrenocortical neoplasma "usually virilizing carcinoma". b. congenital adrenal hyperplasia "CAH" Cong. Adrenal hyperplasia is a group of autosomal recessive disorders characterized by defects in steroid biosynthesis usually cortisol, the common subtype is caused by deficiency of the enzyme 21-hydroylase. Reduction in cortisol production causes a compensation increase in ACTH secretion, which in turn stimulate androgen production Androgens have virilizing effects includeMuscalinization in females (ambiguous genitalia, oligomenorrhoea, hirsutism. Precocious puberty in males. Hypotension with salt (sodium) wasting There is bilateral hyperplasia of adrenal cortex.
Adrenal insufficiency
Adrenal insufficiency "hypofunction" may be considered under the following headings :Primary acute adrenocortical insufficiency "adrenal crisis" Primary chronic adrenocorticol insufficiency addison disease. Secondary adrenocortical insufficiency and the following table summarize the types and cause of adrenocortical insufficiency.
Pathology of Addison Disease
It is rare disease caused by chronic destructive process in the adrenal cortex, it is characterized by :90% of the case are due to autoimmune process or T.B. minor case are due to amyloidosis, adrenal heamorrhage, metastatic tumor, heamochromatosis. The outstanding features are weakness, lethering, hypotension with anorexia and weight loss. Libido is usually diminished. Skin pigmentation particularly of the exposed part, external genitalia, scar
Pheochromocytoma
Are neoplasms composed of chromaffin cells which synthesize and release catecholamine which is associated with cotecholamine. Induced hypertension. 10% of pheo arise in association with one of several of familial syndromes like MEN 2 A and MEN 2 B, type I neurofibromatosis. 10% of pheo are extra adrenal occurring in sites such an carotid body, organ of Zukerkandl, and Called usually paraganglioma. 10% of adrenal plaeo are bilateral. 10% of adrenal pheo are biologically malignant. Microscopically phco are composed of polygonal to spindle shaped chromaffin cells and their supporting cells compartmentalized into small nests Zellballen by rich vascular network, the cytoplasm of neoplastic cell is granular, mitosis is scanty. Vascular and capsuler invasion may be seen in benign neoplasm, therefore the definitive diagnosis of malignancy in pheo is based exclusively on the presence of melastasis.Pheochromocytoma, demonstrating characteristic nests of cells (“Zellballen”) with abundant cytoplasm Extra-adrenal pheochromocytoma
Multiple Endocrine Neoplasia Syndromes
The MEN syndromes are group of inherited diseases resulting in proliferative lesions (hyperplasia, adenomas and carcinomas) of multiple endocrine organs in the same individual or in members of family. It is characterized by :These tumour, occur of a younger age than sporadic cancers. They arise in multiple endocrine organs,
Classification
I. MEN.I.Parathyroid (95%) where hyperparathyroidism arising from multinodular parathyroid hyperplasia is the most consistent feature of MEN I. Pancrease Endocrine tumours of the pancreas are the leading cause of death in MEN 1 eig Zollinger Ellision syndrome associated with gastrinoma and hypoglycemia related to insulinoma. Pituitary prolactin-secreting adenoma is most frequent manifestation rarely acromegaly develop.
2. MEN II a :this include : Medullary thyroid carcinoma which occur in the first decades of life.Pheochromocytoma occur in 50% of cases .Hyperparathyroidism, approximately a third of patient develop parathyroid hyperplasia .it has been linked to mutation on chromosome 10.3. MEN II b or “III” (sipples syndrome).This syndrome includes pheochromocytoma , medullary thyroid carcinoma and multiple mucocutaneous neuromas or ganglioneuromas .In contrast to MEN IIa it does not induce hyperparathyroidisim.. Its linked to different mutations in the ret oncogene compared to MEN IIa .