Endocrine SystemEndocrine System

It consists of two main componentsIt consists of two main components::

The The classicalclassical endocrine organs: pituitary, thyroid, endocrine organs: pituitary, thyroid, parathyroid, adrenal, islets of langerhans in pancreas, parathyroid, adrenal, islets of langerhans in pancreas, ovary, testis and pineal gland.ovary, testis and pineal gland.

The The diffusediffuse endocrine system: consists of cells scattered endocrine system: consists of cells scattered as single or small group of cells in various non-as single or small group of cells in various non-endocrine organs such as lung, GIT, skin. endocrine organs such as lung, GIT, skin.

The pituitary gland and hypothalamusThe pituitary gland and hypothalamus

The pituitary gland: The pituitary gland:

Wt. about 600 mg Wt. about 600 mg The pituitary gland consists of: The pituitary gland consists of: anterior pituitary(adenohypophysis)anterior pituitary(adenohypophysis) and and posterior pituitary (neurohypophysis).posterior pituitary (neurohypophysis). Anterior pituitaryAnterior pituitary secretes growth hormone, secretes growth hormone, prolactin, TSH, ACTH, FSH and LH .prolactin, TSH, ACTH, FSH and LH .Posterior pituitaryPosterior pituitary secretes oxytocin and secretes oxytocin andADH (vasopressin).ADH (vasopressin).

The normal microscopic appearance of the pituitary gland is The normal microscopic appearance of the pituitary gland is shown here. The adenohypophysis is at the right and the shown here. The adenohypophysis is at the right and the

neurohypophysis is at the left.neurohypophysis is at the left.

The normal microscopic appearance of the adenohypophysis is shown here.The normal microscopic appearance of the adenohypophysis is shown here. The adenohypophysis contains three major cell types: acidophils(40%), The adenohypophysis contains three major cell types: acidophils(40%), basophils(10%), and chromophobes(50%). The staining is variable, and to basophils(10%), and chromophobes(50%). The staining is variable, and to properly identify specific hormone secretion, immunohistochemical properly identify specific hormone secretion, immunohistochemical staining is necessary. A simplistic classification is as follows: staining is necessary. A simplistic classification is as follows:

The pink acidophilsThe pink acidophils secrete growth hormone secrete growth hormone (GH)(GH) and prolactin and prolactin (PRL)(PRL) The dark purple basophilsThe dark purple basophils secrete corticotrophin secrete corticotrophin (ACTH), (ACTH), thyroid thyroid

stimulating hormone stimulating hormone (TSH),(TSH), and gonadotrophins: follicle stimulating and gonadotrophins: follicle stimulating hormone-luteinizing hormone hormone-luteinizing hormone (FSH and LH)(FSH and LH)

The pale staining chromophobesThe pale staining chromophobes have few cytoplasmic granules, but may have few cytoplasmic granules, but may have secretory activity.have secretory activity.

Pathology of adenohypophysis Pathology of adenohypophysis (Tumors):(Tumors): Pituitary adenoma:Pituitary adenoma: most common lesion of anterior most common lesion of anterior

pituitary, it divided into microadenoma (<15 mm in diameter) pituitary, it divided into microadenoma (<15 mm in diameter) and macroadenoma (>15 mm in diameter).and macroadenoma (>15 mm in diameter).

Effects or clinical features:Effects or clinical features: Endocrine effect Endocrine effect due to hypersecretion of specific hormones.due to hypersecretion of specific hormones. Local pressure symptoms Local pressure symptoms of large tumor causing compression of large tumor causing compression

on surrounding structure, optic chiasma,optic nerve, causing on surrounding structure, optic chiasma,optic nerve, causing visual disturbancevisual disturbance

pressure atrophy pressure atrophy on adjacent normal gland lead to on adjacent normal gland lead to hypopituitarism.hypopituitarism.

Enlargement and erosion of the floor of the sella turcica are Enlargement and erosion of the floor of the sella turcica are common findings and important common findings and important radiological signsradiological signs. .

Pituitary adenoma.The circumscribed mass lesion present here in the sella turcica is a pituitary adenoma. Though pituitary adenomas are benign, they can produce problems either from a mass effect (usually visual problems from pressing on the optic chiasm and/or headaches) or from production of hormones such as prolactin or ACTH.

This is a microadenoma of the anterior pituitary. Such This is a microadenoma of the anterior pituitary. Such microadenomas may appear in 1 to 5% of adults. These microadenomas may appear in 1 to 5% of adults. These microadenomas rarely have a significant hormonal output that microadenomas rarely have a significant hormonal output that leads to clinical disease. leads to clinical disease.

The microscopic appearance of the pituitary adenoma is The microscopic appearance of the pituitary adenoma is shown here. Note the monotonous appearance of these small shown here. Note the monotonous appearance of these small round cells with small round nuclei and pink to blue round cells with small round nuclei and pink to blue cytoplasm. The cells may be arranged in nests or cords and cytoplasm. The cells may be arranged in nests or cords and endocrine tumors also have prominent vascularity. endocrine tumors also have prominent vascularity.

Other tumorsOther tumors

Pituitary carcinoma:Pituitary carcinoma: extremely rare extremely rare CraniopharyngiomaCraniopharyngioma : :Most patients with Most patients with

craniopharyngiomacraniopharyngioma are in the first or second are in the first or second decade of life.decade of life.

Its location is usually suprasellar, although it Its location is usually suprasellar, although it may occupy the sella as well may occupy the sella as well

Metastatic tumorsMetastatic tumors : :from breast, lung ,GIT.from breast, lung ,GIT. Posterior lobe is mostly affected, anterior lobePosterior lobe is mostly affected, anterior lobe rarely involved. rarely involved.

A craniopharyngiomaA craniopharyngioma is seen here at medium and high power. It is is seen here at medium and high power. It is derived from remnants of Rathke's pouch and forms an expanding mass derived from remnants of Rathke's pouch and forms an expanding mass arising in the sella turcica that erodes bone and infiltrates into arising in the sella turcica that erodes bone and infiltrates into surrounding structures. They are difficult to eradicate, even though they surrounding structures. They are difficult to eradicate, even though they are composed of histologically appearing squamoid and columnar are composed of histologically appearing squamoid and columnar epithelium lining cystic spaces filled with oily fluid. epithelium lining cystic spaces filled with oily fluid.

Other pathology;Other pathology;

Inflammatory conditionsInflammatory conditions Circulatory disturbances (Sheehan's Circulatory disturbances (Sheehan's

syndrome)syndrome)::

necrosis of anterior lobe due to severe post-necrosis of anterior lobe due to severe post-partum hemorrhage after labour and the partum hemorrhage after labour and the patient develop after that hypopituitarism. patient develop after that hypopituitarism.

Hyperfunction of adenohypophysisHyperfunction of adenohypophysis

Hypersecretion of Hypersecretion of GHGH: Acromegaly and : Acromegaly and gigantism.gigantism.

ACTHACTH: Cushing’s disease.: Cushing’s disease. ProlactinProlactin: hyperprolactinemia : hyperprolactinemia

Acromegaly and gigantism:Acromegaly and gigantism:

Cause: pituitary adenoma.Cause: pituitary adenoma. GigantismGigantism::

when hypersecretion of GHwhen hypersecretion of GH occur in children occur in children before closure of epiphysis result in before closure of epiphysis result in proportional increase in length and thickness proportional increase in length and thickness of bones with delayed in epiphyseal fusion. If of bones with delayed in epiphyseal fusion. If excess of GH persists after epiphyseal closure excess of GH persists after epiphyseal closure causing feature of acromegaly.causing feature of acromegaly.

Acromegaly:Acromegaly:

occur when hyper-secretion of GH occur after fusion occur when hyper-secretion of GH occur after fusion of epiphysis in adult.of epiphysis in adult.

clinical featuresclinical features; enlargement of extremities, over-; enlargement of extremities, over-growth of bone, and soft tissue, large hand and feet, growth of bone, and soft tissue, large hand and feet, enlargement of nose and lower jaw (prognathism), enlargement of nose and lower jaw (prognathism), cardiomegally, hypertension, D.M., osteoarthritis, cardiomegally, hypertension, D.M., osteoarthritis, kyphosis, increased sweating, 30-40% have hyper-kyphosis, increased sweating, 30-40% have hyper-prolactinaemia leading to galactorrhoea. prolactinaemia leading to galactorrhoea.

  

Cushing’s diseaseCushing’s disease::

hypersecretion of ACTHhypersecretion of ACTH result in adrenal result in adrenal gland hyperplasia with excessive secretion of gland hyperplasia with excessive secretion of glucocorticoids by adrenalsglucocorticoids by adrenals resulting in resulting in Cushing’s syndrome .Cushing’s syndrome .

Causes of ACTH hypersecretion:Causes of ACTH hypersecretion:

ACTH-cell adenomaACTH-cell adenoma. . ACTH-cell hyperplasia.ACTH-cell hyperplasia. Ectopic ACTH secretionEctopic ACTH secretion

HyperprolactinemiaHyperprolactinemia::

Causes:Causes:

1.1. Adenoma (prolactinoma). Adenoma (prolactinoma).

2.2. destructive lesion of hypothalamus.destructive lesion of hypothalamus.

3.3. drugs (methyldopa, phenothiazine). drugs (methyldopa, phenothiazine).

4.4. physiological type in pregnancy.physiological type in pregnancy.

In female it results in amenorrhea, infertility, In female it results in amenorrhea, infertility, galactorrhoea,galactorrhoea,

in men it is usually asymptomatic, may cause in men it is usually asymptomatic, may cause loss of libido, infertility, impotence. loss of libido, infertility, impotence.

Hypopituitarism:Hypopituitarism:

Causes:Causes:

1.1. Pituitary tumor with pressure atrophyPituitary tumor with pressure atrophy2.2. Sheehan’s syndrome in developing countriesSheehan’s syndrome in developing countries3.3. Pituitary surgery or radiotherapyPituitary surgery or radiotherapy4.4. TraumaTrauma5.5. Inflammation (tuberculosis, sarcoidosis, syphilis) Inflammation (tuberculosis, sarcoidosis, syphilis) 6.6. Autoimmune diseaseAutoimmune disease7.7. Histiocytosis XHistiocytosis X8.8. CraniopharyngiomaCraniopharyngioma9.9. Metastatic tumorsMetastatic tumors

Neurohypophysis:Neurohypophysis: ADH: reabsorption of water by renal tubules and ADH: reabsorption of water by renal tubules and

concentration of urine.concentration of urine. Its Its deficiencydeficiency causes causes diabetes insipidusdiabetes insipidus: polyuria, : polyuria,

polydipsia with diluted urine which differentiated it from polydipsia with diluted urine which differentiated it from psychogenic polydipsia. psychogenic polydipsia. CausesCauses:: head injury, surgical head injury, surgical trauma, destructive lesion of hypothalamus (sarcoidosis, trauma, destructive lesion of hypothalamus (sarcoidosis, histiocytosis-X), tumors, idiopathic.histiocytosis-X), tumors, idiopathic.

ExcessiveExcessive secretion of ADH cause secretion of ADH cause inappropriate secretioninappropriate secretion of ADH, water retention causing hyponatraemia, of ADH, water retention causing hyponatraemia, hypoosmolarity resulting in vomiting, muscle cramps, hypoosmolarity resulting in vomiting, muscle cramps, weakness, central edema which may lead to coma, death. weakness, central edema which may lead to coma, death. CausesCauses:: ectopic secretion of ADH by small cell CA. of the ectopic secretion of ADH by small cell CA. of the lung, pneumonia, head injury, meningitis, subarachnoid lung, pneumonia, head injury, meningitis, subarachnoid hemorrhage and idiopathic.hemorrhage and idiopathic.

Hypothalamus:Hypothalamus:

TumorsTumors: :

1.1. Gliomas and germinomas. Gliomas and germinomas.

2.2. GangliocytomaGangliocytoma

HistologicallyHistologically: this lesion is composed of a : this lesion is composed of a mixture of mature neurons, astrocytes, and mixture of mature neurons, astrocytes, and oligodendrocytes arranged with a varying oligodendrocytes arranged with a varying degree of organization. degree of organization.

Thyroid gland

Normal thyroid gland :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. The normal weight of the thyroid is 10 to 30 grams. It cannot easily be palpated on physical

examination .

Normal thyroid seen microscopically consists of follicles lined Normal thyroid seen microscopically consists of follicles lined by an epithelium and filled with colloid .This normal thyroid by an epithelium and filled with colloid .This normal thyroid follicle is lined by a cuboidal follicular epithelium with cells that follicle is lined by a cuboidal follicular epithelium with cells that can add or subtract colloid depending upon the degree of can add or subtract colloid depending upon the degree of stimulation from TSH (thyroid stimulating hormone) released by stimulation from TSH (thyroid stimulating hormone) released by the pituitary gland. As in all endocrine glands, the interstitium the pituitary gland. As in all endocrine glands, the interstitium has a rich vascular supply into which hormone is secreted. has a rich vascular supply into which hormone is secreted.

Congenital abnormalities:Congenital abnormalities:

1.1. Congenital absence of thyroid Congenital absence of thyroid (aplasia)(aplasia) causes causes cretinismcretinism..

2.2. Ectopic thyroid glandEctopic thyroid gland: lingual thyroid, along : lingual thyroid, along midline in neck: sublingual, suprahyoid, infrahyoid midline in neck: sublingual, suprahyoid, infrahyoid or lateral position in neck (lateral aberrant thyroid) or lateral position in neck (lateral aberrant thyroid) which always represent lymph node metastasis which always represent lymph node metastasis from thyroid carcinoma (usually papillary from thyroid carcinoma (usually papillary carcinoma) rather than ectobia. Rare sites carcinoma) rather than ectobia. Rare sites esophagus, larynx, trachea, soft tissues of the neck. esophagus, larynx, trachea, soft tissues of the neck.

3.3. Thyroglossal fistula and thyroglossal cystThyroglossal fistula and thyroglossal cyst in in midline of the neck lined by respiratory or midline of the neck lined by respiratory or squamous epithelium, contain thyroid tissue and squamous epithelium, contain thyroid tissue and lymphoid tissue in its wall.lymphoid tissue in its wall.

Thyroid diseases present either as thyroid enlargement Thyroid diseases present either as thyroid enlargement (goiter: diffuse or nodular)(goiter: diffuse or nodular) or as excess or as excess (Hyperthyroidism)(Hyperthyroidism) or or deficiency deficiency (hypothyroidism)(hypothyroidism) of thyroid hormones. of thyroid hormones.

Hyperthyroidism:Hyperthyroidism: Clinically called Clinically called thyrotoxicosisthyrotoxicosis due to due to hypersecretion of thyroid hormones and presents with signs of hypersecretion of thyroid hormones and presents with signs of hypermetabolism and excessive stimulation of the sympathetic hypermetabolism and excessive stimulation of the sympathetic system (patient present with weight loss, but increased system (patient present with weight loss, but increased sensitivity to circulatory adrenaline, and there is increased sensitivity to circulatory adrenaline, and there is increased appetite,patient is nervous, irritable with heat intolerance, appetite,patient is nervous, irritable with heat intolerance, excessive sweating, fine tremor, tachycardia, atrial fibrillation, excessive sweating, fine tremor, tachycardia, atrial fibrillation, which may lead to cardiac failure, eye signs include; lid-lag and which may lead to cardiac failure, eye signs include; lid-lag and lid-retraction.lid-retraction.

Causes:Causes:

1.1. Grave’s disease is the most common cause in Grave’s disease is the most common cause in

80-85% of cases.80-85% of cases.2.2. Toxic nodular goiter 10% of cases.Toxic nodular goiter 10% of cases.3.3. Thyroid adenoma 5-10% of cases.Thyroid adenoma 5-10% of cases.4.4. Other causes: Early Hashimoto’s thyroiditis, Other causes: Early Hashimoto’s thyroiditis,

pituitary adenoma secrete TSH, exogenous pituitary adenoma secrete TSH, exogenous thyroid hormone and large doses of iodine thyroid hormone and large doses of iodine give to patient with nontoxic nodular goitregive to patient with nontoxic nodular goitre

HypothyroidismHypothyroidism:: Deficiency of thyroid hormones in adult is Deficiency of thyroid hormones in adult is called called myxoedemamyxoedema and in infant and early childhood is called and in infant and early childhood is called cretinism.cretinism.

Myxedema:Myxedema: dry waxy swelling of the skin of the extremities and dry waxy swelling of the skin of the extremities and face. patient is lethargic, feel cold, with constipation, face. patient is lethargic, feel cold, with constipation, psychosis, skin and hair are dry, coarse facial feature due to psychosis, skin and hair are dry, coarse facial feature due to deposition of mucopolysaccharide in dermis, and there is deposition of mucopolysaccharide in dermis, and there is pain, parasthesia (involvement of nerves), voice is gruff pain, parasthesia (involvement of nerves), voice is gruff (involvement of larynx), increased weight, increased serum (involvement of larynx), increased weight, increased serum cholesterol, bradycardia, pericardial effusioncholesterol, bradycardia, pericardial effusion . .

Cretinism:Cretinism: mental retardation, dwarfism, coarse facial features, mental retardation, dwarfism, coarse facial features, a protruding tongue and umbilical hernia.a protruding tongue and umbilical hernia.

Causes of hypothyroidism:Causes of hypothyroidism:

1.1. Autoimmune thyroiditis such as Hashimoto’s thyroiditis Autoimmune thyroiditis such as Hashimoto’s thyroiditis (most common cause in adult) and primary myxoedema.(most common cause in adult) and primary myxoedema.

2.2. Congenital: aplasia or hypoplagia.Congenital: aplasia or hypoplagia.3.3. Iatrogenic: following thyroidectomy, radiation therapy.Iatrogenic: following thyroidectomy, radiation therapy.4.4. Secondary hypothyroidism due to hypopituitarism.Secondary hypothyroidism due to hypopituitarism.5.5. Severe iodine deficiency (in endemic areas).Severe iodine deficiency (in endemic areas).6.6. Dietary: goitrogenes in foodDietary: goitrogenes in food

7.7. Drugs: propylthyouracil, lithium.Drugs: propylthyouracil, lithium.

8.8. Genetic causes; include; dyshormogenetic goiter, due to Genetic causes; include; dyshormogenetic goiter, due to absence of enzymes involved in synthesis of thyroid absence of enzymes involved in synthesis of thyroid hormones.hormones.

Pendred’s syndrome (dyshormogenesis+deafness+mutismPendred’s syndrome (dyshormogenesis+deafness+mutism).).

Goiter:Goiter: is enlargement of the thyroid. It is either diffuse or is enlargement of the thyroid. It is either diffuse or nodular, nontoxic or toxic. nodular, nontoxic or toxic.

Nontoxic goiter Nontoxic goiter ::

Commonest lesion of thyroid gland, causing enlargement of Commonest lesion of thyroid gland, causing enlargement of thyroid as a compensatory hyperplasia by increase TSH due thyroid as a compensatory hyperplasia by increase TSH due to defect in the synthesis of thyroid hormones.to defect in the synthesis of thyroid hormones.

It is of two types:It is of two types:

1.1. Endemic goiterEndemic goiter

2.2. Sporadic goiter Sporadic goiter

Endemic goiterEndemic goiter:: Occurrence of nontoxic goiter in more than Occurrence of nontoxic goiter in more than 10% of population. It is always related to iodine deficiency.10% of population. It is always related to iodine deficiency.

Usually occurs in mountainous areas and areas remote from Usually occurs in mountainous areas and areas remote from

the sea, it is due to iodine deficiency in food and water, but its the sea, it is due to iodine deficiency in food and water, but its incidence has decreased upon introduction of ionized salt.incidence has decreased upon introduction of ionized salt.

Morphological features is the same for Morphological features is the same for sporadic and endemic goiter.sporadic and endemic goiter.

Nodular goiter This patient was euthyroid. This represents the most common cause for an

enlarged thyroid gland and the most common disease of the thyroid. MNG characterized by 1. Asymmetrical enlargement.2. Multiple nodules of variable size.3. Secondary degenerative changes: hemorrhage, fibrosis, cystic degeneration filled

with fluid, and calcification can be formed.

Microscopic features of nontoxic Microscopic features of nontoxic goiter:goiter:

Early stage,Early stage, diffuse hyperplasia of follicles with scanty colloid diffuse hyperplasia of follicles with scanty colloid (parenchymatous goiter), this is followed by accumulation of (parenchymatous goiter), this is followed by accumulation of colloid with involution of epithelium (colloid goiter).colloid with involution of epithelium (colloid goiter).

Later onLater on, nodules formation of variable size contain colloid , nodules formation of variable size contain colloid separated by fibrous tissue (multinodular colloid goiter) separated by fibrous tissue (multinodular colloid goiter) associated with degenerative changes: cystic changes, associated with degenerative changes: cystic changes, hemorrhage, fibrosis, calcification.hemorrhage, fibrosis, calcification.

Multinodular goiter: Different sized follicles some are dilated and lined by flattened epithelium (indicate inactivity), filled with colloid,others lined by normal or hyperplastic epith.

In some cases, one nodule prominently In some cases, one nodule prominently enlarged (dominant nodule) confused with enlarged (dominant nodule) confused with tumor. In some cases of long standing tumor. In some cases of long standing multinodular goiter especially in elderly, show multinodular goiter especially in elderly, show picture of hyperthyroidism (toxic nodular picture of hyperthyroidism (toxic nodular goiter).goiter).

Autoimmune thyroid diseasesAutoimmune thyroid diseases: :

These characterized by:These characterized by:1.1. Presence of circulating auto antibodies to thyroid Presence of circulating auto antibodies to thyroid

tissue.tissue.2.2. Lymphocytic infiltration with destruction of thyroid Lymphocytic infiltration with destruction of thyroid

tissue and formation of lymphoid follicles with tissue and formation of lymphoid follicles with germinal centers.germinal centers.

3.3. It may be associated with other autoimmune It may be associated with other autoimmune diseases such as Addison’s disease, D.M., SLE, diseases such as Addison’s disease, D.M., SLE, rheumatoid arthritis, pernicious anemia.rheumatoid arthritis, pernicious anemia.

they include:they include:

Hashimoto’s thyroiditisHashimoto’s thyroiditis: :

this disease due to presence of auto antibodies this disease due to presence of auto antibodies (antithyroglobulin, anti-microsomal antibody).(antithyroglobulin, anti-microsomal antibody).

Increase in HLA-DR5 and B5 suggests genetic Increase in HLA-DR5 and B5 suggests genetic predisposition.predisposition.

1-2% led to B-cell lymphoma. 1-2% led to B-cell lymphoma. Increase risk of papillary carcinoma. Increase risk of papillary carcinoma.

This symmetrically small thyroid gland demonstrates atrophy. This symmetrically small thyroid gland demonstrates atrophy. This patient was hypothyroid. This is the end result of This patient was hypothyroid. This is the end result of Hashimoto's thyroiditis. Initially, the thyroid is enlarged and Hashimoto's thyroiditis. Initially, the thyroid is enlarged and there may be transient hyperthyroidism, followed by a there may be transient hyperthyroidism, followed by a euthyroid state and then hypothyroidism with eventual atrophy euthyroid state and then hypothyroidism with eventual atrophy years later. years later.

Here is a low power microscopic view of a thyroid with Here is a low power microscopic view of a thyroid with Hashimoto's thyroiditis. Note the lymphoid follicle at the right Hashimoto's thyroiditis. Note the lymphoid follicle at the right center. This is an autoimmune disease and often center. This is an autoimmune disease and often antithyroglobulin and antimicrosomal antibodies can be antithyroglobulin and antimicrosomal antibodies can be detected. Other autoimmune diseases such as Addison's detected. Other autoimmune diseases such as Addison's disease or pernicious anemia may also be present. disease or pernicious anemia may also be present.

Hashimoto’s thyroiditis:1- Hürthle cells: large pink cells at the center and right 2- The lymphoid follicle with germinal center is at the left.

Grave’s diseaseGrave’s disease: :

It’s characterized by diffuse thyroid hyperplasia and It’s characterized by diffuse thyroid hyperplasia and hyperthyroidism (diffuse toxic goiter) hyperthyroidism (diffuse toxic goiter)

Its incidence increase in HLA-DR3 individuals Its incidence increase in HLA-DR3 individuals suggests genetic predisposition.suggests genetic predisposition.

It results from presence of autoantibodies to TSH It results from presence of autoantibodies to TSH receptors cause their activation and stimulate thyroid receptors cause their activation and stimulate thyroid hormone secretion causing hyperthyroidism. These hormone secretion causing hyperthyroidism. These antibodies are called thyroid stimulating antibodies are called thyroid stimulating immunoglobulin (TSI: stimulate thyroxin -T4 immunoglobulin (TSI: stimulate thyroxin -T4 synthesis). TGI lead to gland hyperplasia and synthesis). TGI lead to gland hyperplasia and enlargement . enlargement .

Grave’s disease (difuse toxic goiter)A diffusely enlarged thyroid gland associated with hyperthyroidism is known as Grave's disease. Note the infoldings of the hyperplastic epithelium line by tall columnar thyroid epithelium with clear vacuoles in the colloid next to the epithelium where the increased activity of the epithelium to produce increased thyroid hormone has led to scalloping out of the colloid .

Other autoimmune diseasesOther autoimmune diseases

Primary myxoedema.Primary myxoedema.

Lymphocytic thyroiditis.Lymphocytic thyroiditis.

Other type of thyroiditis:Other type of thyroiditis:

De Quervain’s thyroiditisDe Quervain’s thyroiditis(granulomatous, or (granulomatous, or subacute thyroiditis).subacute thyroiditis).

Riedel’s thyroiditisRiedel’s thyroiditis

DeQuervian’s thyroiditis: This is subacute granulomatous thyroiditis which probably follows a viral infection and leads to a painful enlarged thyroid. This disease is usually self-limited over weeks to months and the patients return to euthyroid state. Note the foreign body giant cells with destruction of thyroid follicles.

Riedel’s thyroiditisRiedel’s thyroiditis

Very rare disease of unknown etiology, Very rare disease of unknown etiology, characterized by extensive replacement of characterized by extensive replacement of thyroid tissue by dense fibrous tissue causing thyroid tissue by dense fibrous tissue causing hardness of the gland (stony hard) with hardness of the gland (stony hard) with extension of fibrous tissue outside the gland extension of fibrous tissue outside the gland cause fixation of thyroid to adjacent structures cause fixation of thyroid to adjacent structures (iron collar) such as: trachea, recurrent (iron collar) such as: trachea, recurrent laryngeal nerve (clinically mimic Carcinoma), laryngeal nerve (clinically mimic Carcinoma), some cases associated with retroperitoneal or some cases associated with retroperitoneal or mediastinal fibrosis mediastinal fibrosis

Thyroid tumors:Thyroid tumors:

1. 1. Tumors arise from follicular epithelial cells:Tumors arise from follicular epithelial cells: benign: benign: follicular adenomafollicular adenoma (majority of (majority of

thyroid tumor)thyroid tumor) malignant: malignant: follicular carcinoma, papillary follicular carcinoma, papillary

carcinoma and anaplastic carcinoma. carcinoma and anaplastic carcinoma.

2.2. Tumors arise from C cellsTumors arise from C cells: medullary : medullary carcinoma.carcinoma.

Follicular adenoma:Follicular adenoma: Commonest thyroid tumor mainly in females over 30 years. Adenoma Commonest thyroid tumor mainly in females over 30 years. Adenoma

usually presents with nonfunctioning (cold) nodule but may be cause usually presents with nonfunctioning (cold) nodule but may be cause hyperthyroidism (toxic adenoma) which is hot nodule on thyroid scan.hyperthyroidism (toxic adenoma) which is hot nodule on thyroid scan.

The nodule is painless, if large may produce local symptoms.The nodule is painless, if large may produce local symptoms. GrossGross:Adenoma usually solitary encapsulated nodule:Adenoma usually solitary encapsulated nodule (3-10 cm) and compressing surrounding thyroid tissue.(3-10 cm) and compressing surrounding thyroid tissue. Histopathological featuresHistopathological features: Adenoma consists of uniform follicles : Adenoma consists of uniform follicles

contain colloid, surrounded by fibrous capsule without capsular or contain colloid, surrounded by fibrous capsule without capsular or vascular invasion with or without nuclear pleomorphism or atypia vascular invasion with or without nuclear pleomorphism or atypia (endocrine atypia).(endocrine atypia).

Adenoma with microfollicles and little colloid called Adenoma with microfollicles and little colloid called fetal adenomafetal adenoma, , while those with macrofollicles filled with colloid called while those with macrofollicles filled with colloid called colloid colloid adenomaadenoma..

If it consists of Hürthle cells (If it consists of Hürthle cells (Hürthle cell adenomaHürthle cell adenoma).). All have the same behavior.All have the same behavior.

Follicular neoplasm ( follicular adenoma histologically) A solitary neoplasm that is surrounded by a thin white capsule. It is sometimes difficult to tell a well-differentiated follicular carcinoma from a follicular adenoma. Thus, patients with follicular neoplasms are treated with subtotal thyroidectomy just to be on the safe side.

Follicular adenomaNormal thyroid follicles appear at the lower right. The follicular adenoma is at the center to upper left. This adenoma is a well- differentiated neoplasm because it closely resemble normal tissue. The follicles of the adenoma contain colloid, but there is greater variability in size than normal.

Papillary carcinoma:Papillary carcinoma: All papillary tumors of thyroid are malignant, it is the commonest All papillary tumors of thyroid are malignant, it is the commonest

malignant tumor of the thyroid =80% of all carcinomas.malignant tumor of the thyroid =80% of all carcinomas. Occur most often in middle aged females. may be solitary or multifocal Occur most often in middle aged females. may be solitary or multifocal

within the gland. It may be well circumscribed and even encapsulated, within the gland. It may be well circumscribed and even encapsulated, or illdefined. or illdefined.

This tumor commonly metastasize by lymphatic rather than by blood, This tumor commonly metastasize by lymphatic rather than by blood, and lymph node metastasis in the neck present in about half of cases and lymph node metastasis in the neck present in about half of cases and the presence of cervical lymph node metastasis doesn’t affect the and the presence of cervical lymph node metastasis doesn’t affect the prognosis. prognosis.

PrognosisPrognosis is good; 10 year survival is 85%. Papillary carcinoma may is good; 10 year survival is 85%. Papillary carcinoma may be very small (occult) and patient present with cervical lymph node be very small (occult) and patient present with cervical lymph node metastasis (previously called lateral aberrant thyroid).metastasis (previously called lateral aberrant thyroid).

Histology:Histology: tumors have papillary structures with fibrovascular core tumors have papillary structures with fibrovascular core lined by cuboidal cells with characteristic nuclear features; clear or lined by cuboidal cells with characteristic nuclear features; clear or empty nuclei with ground glass or empty nuclei with ground glass or (Orphan Annie) (Orphan Annie) nuclei, nuclei, intranuclear pseudoinclusion and grooved nuclei.intranuclear pseudoinclusion and grooved nuclei.

Psammoma bodies: Psammoma bodies: concentrically calcified structures are often concentrically calcified structures are often present within the papillae.present within the papillae.

Variants?Variants?

Papillary carcinoma This neoplasm can be multifocal, as seen here, because of the propensity to invade lymphatics within thyroid, and lymph node metastases are common. The larger mass is cystic and contains papillary excresences.

This is the microscopic appearance of a papillary carcinoma of This is the microscopic appearance of a papillary carcinoma of the thyroid. The fronds of tissue have thin fibrovascular cores. the thyroid. The fronds of tissue have thin fibrovascular cores. The fronds have a papillary pattern. There is no such thing as a The fronds have a papillary pattern. There is no such thing as a papillary adenoma, and all papillary neoplasms of the thyroid papillary adenoma, and all papillary neoplasms of the thyroid should be considered malignant. should be considered malignant.

Papillary carcinoma This is another papillary carcinoma of thyroid. Note the small psammoma body in the center. The cells of the neoplasm have clear nuclei. Papillary carcinomas are indolent tumors that have a long survival, even with metastases. The most favorite site of metastasis is to local lymph nodes in the neck. In fact, some papillary carcinomas may first present as nodal metastases.

Follicular carcinoma:Follicular carcinoma:

15 % of all thyroid cancer, more common in endemic area(dietary 15 % of all thyroid cancer, more common in endemic area(dietary iodine deficiency), suggesting that, in some cases,nodular goiter iodine deficiency), suggesting that, in some cases,nodular goiter may predispose to ca. more in females, occurs in 5th decade(older may predispose to ca. more in females, occurs in 5th decade(older than papillary ca), blood metastasis is more than lymphatic than papillary ca), blood metastasis is more than lymphatic metastasis, especially to bone and lung.metastasis, especially to bone and lung.

Prognosis is poorer than papillary carcinoma, 5 year survival Prognosis is poorer than papillary carcinoma, 5 year survival 50%. 50%.

It is of two types:It is of two types:1.1. Microinvasive carcinoma (minimally invasive carcinoma)Microinvasive carcinoma (minimally invasive carcinoma)::

Encapsulated tumor and differentiated from follicular adenoma by Encapsulated tumor and differentiated from follicular adenoma by presence of fibrous capsular invasion and/or vascular invasion. presence of fibrous capsular invasion and/or vascular invasion. prognosis is good.prognosis is good.

2.2. Widely invasive carcinomaWidely invasive carcinoma:: Widely spread of tumor within Widely spread of tumor within thyroid gland and outside the gland with prominent blood vessels thyroid gland and outside the gland with prominent blood vessels invasion. prognosis is poor.invasion. prognosis is poor.

Medullary carcinoma:Medullary carcinoma: Neuroendocrine neoplasm, 5% of thyroid cancer, either Neuroendocrine neoplasm, 5% of thyroid cancer, either sporadic 80%sporadic 80%

or or familial 20%familial 20% as part of multiple endocrine neoplasia-type ІІA or B. as part of multiple endocrine neoplasia-type ІІA or B. Sporadic type is usually unilateral(solitary) and occurs in 5th-6th Sporadic type is usually unilateral(solitary) and occurs in 5th-6th

decade. decade. Familial type is usually bilateral and multifocal associated with C-cell Familial type is usually bilateral and multifocal associated with C-cell

hyperplasia; occurs in young adults and even in children. hyperplasia; occurs in young adults and even in children. Gross appearanceGross appearance: it is solitary nodule or multiple lesions ± : it is solitary nodule or multiple lesions ±

hemorrhage and necrosis.hemorrhage and necrosis. Histology:Histology: tumor consists of polygonal to spindle cells form nests, tumor consists of polygonal to spindle cells form nests,

cords or even follicles with cords or even follicles with amyloid depositionamyloid deposition in stroma. in stroma. Medullary carcinoma spread by both blood and lymphatic.Medullary carcinoma spread by both blood and lymphatic. Prognosis: familial type is more aggressive and fatal tumor especially Prognosis: familial type is more aggressive and fatal tumor especially

MEN-2B. MEN-2B. This tumor produce calcitonin and other hormones, e.g.: VIP.This tumor produce calcitonin and other hormones, e.g.: VIP.

Medullary carcinoma . At the center and to the right is a medullary carcinoma of thyroid. At the far right is pink hyaline material with the appearance of amyloid. These neoplasms are derived from the thyroid "C" cells and, therefore, have neuroendocrine features such as secretion of calcitonin.

Here the amyloid stroma of the medullary thyroid carcinoma has been Here the amyloid stroma of the medullary thyroid carcinoma has been stained with Congo red. Medullary carcinomas can be sporadic or stained with Congo red. Medullary carcinomas can be sporadic or familial. The familial kind are associated with multiple endocrine familial. The familial kind are associated with multiple endocrine neoplasia syndrome. neoplasia syndrome.

Anaplastic carcinoma:Anaplastic carcinoma:

Highly malignant tumor, form<5% of thyroid Highly malignant tumor, form<5% of thyroid carcinoma, mainly occurs in elderly women carcinoma, mainly occurs in elderly women usually present with short history and grow usually present with short history and grow rapidly, locally invasive and early metastasis rapidly, locally invasive and early metastasis by blood and lymphatics. Tumor is poorly by blood and lymphatics. Tumor is poorly differentiated with spindle and bizarre giant differentiated with spindle and bizarre giant cells represent poorly differentiated follicular cells represent poorly differentiated follicular or papillary carcinoma.or papillary carcinoma.

There is no resemblance to normal thyroid tissue-hence the There is no resemblance to normal thyroid tissue-hence the term "anaplastic" to characterize this thyroid carcinoma. Note term "anaplastic" to characterize this thyroid carcinoma. Note the elongated spindle cells.This is the most aggressive thyroid the elongated spindle cells.This is the most aggressive thyroid cancer, and luckily the least common. cancer, and luckily the least common.

Etiology of thyroid carcinoma:Etiology of thyroid carcinoma:

1.1. Iodine deficiency: May determine the type of tumor but not Iodine deficiency: May determine the type of tumor but not as causative agent. Follicular carcinoma more in endemic as causative agent. Follicular carcinoma more in endemic area where iodine is deficient (nodular goiter).area where iodine is deficient (nodular goiter).

2.2. Radiation: To head and neck in children for treatment of Radiation: To head and neck in children for treatment of lymphoma or other lesions (tonsillar enlargement, acne) lymphoma or other lesions (tonsillar enlargement, acne) may increase the risk for development of thyroid carcinoma may increase the risk for development of thyroid carcinoma especially papillary carcinoma. (Atomic bomb in Japan, especially papillary carcinoma. (Atomic bomb in Japan, Ionizing radiation in Chernobyl also increase inc. of Ionizing radiation in Chernobyl also increase inc. of papillary carcinoma).papillary carcinoma).

3.3. Chromosomal translocation, t(2;3) recently found in a Chromosomal translocation, t(2;3) recently found in a proportion of follicular carcinomas.proportion of follicular carcinomas.

4.4. RET protooncogen mutation presents in (95%) of MEN-II.RET protooncogen mutation presents in (95%) of MEN-II.5.5. Inactivating mutation of TP53 in anaplastic carcinoma.Inactivating mutation of TP53 in anaplastic carcinoma.

LymphomaLymphoma: :

Primary NLH of thyroid is B-cell lymphoma; mainly Primary NLH of thyroid is B-cell lymphoma; mainly in elderly patients.in elderly patients.

80% of cases are associated with Hashimoto’s 80% of cases are associated with Hashimoto’s disease.(1-2% of thyroiditis….).disease.(1-2% of thyroiditis….).

It’s usually of diffuse large cell type of follicular It’s usually of diffuse large cell type of follicular center cell and it’s regarded as MATL-lymphoma. center cell and it’s regarded as MATL-lymphoma. The cells of lymphoma infiltrate the thyroid follicles The cells of lymphoma infiltrate the thyroid follicles (lymphoepithelial lesion).(lymphoepithelial lesion).

It has poor prognosis.It has poor prognosis.

Solitary thyroid nodule:Solitary thyroid nodule:

Benign lesions: Adenomas or localized non Benign lesions: Adenomas or localized non neoplastic conditions (e.g., nodular hyperplasia , neoplastic conditions (e.g., nodular hyperplasia , simple cysts, or foci of thyroiditis).simple cysts, or foci of thyroiditis).

Carcinomas are uncommon Carcinomas are uncommon >>1%.1%.

Clinical criteria suggest neoplastic nodule:Clinical criteria suggest neoplastic nodule:

1. solitary.1. solitary.

2. solid.2. solid.

3. nodules in young patients.3. nodules in young patients.

4. in males.4. in males.

5. Cold. 5. Cold.

Definite dx. By FNAC AND HISTOLOGICAL Definite dx. By FNAC AND HISTOLOGICAL STUDY.STUDY.

Parathyroid glandsParathyroid glands

Parathyroid glandsParathyroid glands

They are 4 glands located on posterior surface They are 4 glands located on posterior surface of thyroid gland (3-4mm in size) consist of 2 of thyroid gland (3-4mm in size) consist of 2 types of cells:types of cells:

Chief cells.Chief cells. Oxyphil cells.Oxyphil cells. secretes PTH (parathyroid hormone) acts on secretes PTH (parathyroid hormone) acts on

bone and kidney to increase the Ca+2 level in bone and kidney to increase the Ca+2 level in blood.blood.

Hyperparathyroidism:Hyperparathyroidism:

Primary:Primary: excess secretion of PTH causing excess secretion of PTH causing hypercalcemia (one of most common endocrine hypercalcemia (one of most common endocrine disorders). MEN-1, 2Adisorders). MEN-1, 2A

Causes:Causes:

1.1. Single parathyroid adenoma : commonest cause(80-Single parathyroid adenoma : commonest cause(80-90%), solitary and encapsulated confined to single 90%), solitary and encapsulated confined to single gland (others are normal or shrunken).gland (others are normal or shrunken).

2.2. Primary hyperplasia(10-20%): all glands are Primary hyperplasia(10-20%): all glands are diffusely involved. diffusely involved.

3.3. Parathyroid carcinoma (less than 1% of cases). Parathyroid carcinoma (less than 1% of cases).

Clinical featuresClinical features

Painful bones:# due to osteoporosis or osteitis Painful bones:# due to osteoporosis or osteitis fibrosa cystica.fibrosa cystica.

Renal stones: polyuria, nephrocalcinosis. Renal stones: polyuria, nephrocalcinosis. Abdomnal goans: constipation, peptic ulcers, Abdomnal goans: constipation, peptic ulcers,

G.stones, pancreatitis…G.stones, pancreatitis… Psychic moans: depression, seizures.Psychic moans: depression, seizures.

Morphology:Morphology: Adenoma:Adenoma: soft, tan encapsulated nodule composed soft, tan encapsulated nodule composed

of uniform, polygonal chief cells with few nests of of uniform, polygonal chief cells with few nests of oxiphil cells), a rim of compressed parathyroid oxiphil cells), a rim of compressed parathyroid tissue separated by a fibrous capsule at the edge. tissue separated by a fibrous capsule at the edge. Adipose tissue is inconspicuous within the Adipose tissue is inconspicuous within the adenoma. adenoma.

No invasion or metastases.No invasion or metastases. Other organsOther organs: : skeletalskeletal; osteitis fibrosa cystica, ; osteitis fibrosa cystica,

brown tumor. brown tumor. RenalRenal; UT-stones, nephrocalcinosis. ; UT-stones, nephrocalcinosis. Metastatic calcification Metastatic calcification in stomach, lungs , in stomach, lungs , myocardium and blood vessels.myocardium and blood vessels.

Parathyroid adenoma:Parathyroid adenoma: which is the most common cause for which is the most common cause for primary hyperparathyroidism. A rim of normal parathyroid primary hyperparathyroidism. A rim of normal parathyroid tissue admixed with adipose tissue cells is compressed to the tissue admixed with adipose tissue cells is compressed to the right and lower edge of the adenoma. right and lower edge of the adenoma.

Parathyroid hyperplasiaParathyroid hyperplasia : Three and one-half glands have been : Three and one-half glands have been removed (only half the gland at the lower left is present). removed (only half the gland at the lower left is present). Parathyroid hyperplasia is the second most common form of Parathyroid hyperplasia is the second most common form of primary hyperparathyroidism, with parathyroid carcinoma the primary hyperparathyroidism, with parathyroid carcinoma the least common form. least common form.

Secondary hyperparathyroidism Secondary hyperparathyroidism

Causes:Causes:

1.1. Chronic renal failure.Chronic renal failure.

2.2. Malabsorption syndrome.Malabsorption syndrome.

3.3. Vitamin D deficiency.Vitamin D deficiency.

4.4. Pregnancy and lactation Pregnancy and lactation The glands are hyperplastic : diffuse or multinodular.The glands are hyperplastic : diffuse or multinodular.

in minority of patients parath. activity may become in minority of patients parath. activity may become autonomous and excesive with resultant autonomous and excesive with resultant hypercalcemia termed tertiary hyperparathyroidismhypercalcemia termed tertiary hyperparathyroidism

Hypoparathyroidism:Hypoparathyroidism:

Causes:Causes:1.1. Surgical removal of glands during Surgical removal of glands during

thyroidectomy.thyroidectomy.

2.2. DiGeorge syndrome: congenital aplasia of DiGeorge syndrome: congenital aplasia of thymus and parathyroid gland lead to thymus and parathyroid gland lead to decrease in T-cell number and decrease in T-cell number and hypocalcaemia seen in infant and children.hypocalcaemia seen in infant and children.

3.3. Autoimmune disease.Autoimmune disease.

Adrenal (Suprarenal) glandsAdrenal (Suprarenal) glands

AdrenalAdrenal (Suprarenal) gland: consists of cortex and medulla. (Suprarenal) gland: consists of cortex and medulla.

Each adult adrenal gland weighs from 4 to 6 grams.Each adult adrenal gland weighs from 4 to 6 grams.

Cortex:Cortex: is mesoderm in origin¸ yellow in color¸ consisting of is mesoderm in origin¸ yellow in color¸ consisting of three zones:three zones:

1.1. Outer:Outer: zona glomerulosa produce zona glomerulosa produce aldosterone.aldosterone.

2.2. Intermediate zone:Intermediate zone: zona fasciculata produce zona fasciculata produce glucocorticoids.glucocorticoids.

3.3. Inner zone:Inner zone: zona reticularis produce zona reticularis produce sex hormonessex hormones mostly mostly (androgen) and less estrogen.(androgen) and less estrogen.

Adrenal medulla:Adrenal medulla: i is neuroectoderm in origin, brown in color s neuroectoderm in origin, brown in color consisting of chromaffin cells, nerve fibers and sympathetic consisting of chromaffin cells, nerve fibers and sympathetic ganglion cells produces ganglion cells produces catecholaminescatecholamines (adrenaline and nor- (adrenaline and nor-adrenaline).adrenaline).

Normal adrenal glandNormal adrenal gland

Adrenal cortical tumors:Adrenal cortical tumors:

1. Adrenal adenoma:1. Adrenal adenoma:

is commonly seen in post partum examination as is commonly seen in post partum examination as small encapsulated yellow nodule¸ Unilateral or small encapsulated yellow nodule¸ Unilateral or bilateral, consists of cells similar to adrenal cortex, bilateral, consists of cells similar to adrenal cortex, the majority are non-functioning tumor¸ some are the majority are non-functioning tumor¸ some are functioning with excessive secretion of cortisol, functioning with excessive secretion of cortisol, aldosterone¸ and sex hormones.aldosterone¸ and sex hormones.

This adrenal gland removed surgically in a patient with Cushing's syndrome has been sectioned in half to reveal an adenoma. Some remaining atrophic adrenal is seen at the right. The adenoma is composed of yellow firm tissue just like adrenal cortex. This neoplasm is well-circumscribed. Histologically, it is composed of well-differentiated cells resembling cortical fasciculata zone. It is benign.

Microscopically, the adrenal cortical adenoma at the right resembles normal adrenal fasciculata. The capsule is at the left. There may be some cellular pleomorphism.

2. Cortical carcinoma:2. Cortical carcinoma:

Most important sign to distinguish between benign Most important sign to distinguish between benign and malignant cortical tumor is the presence of and malignant cortical tumor is the presence of metastasis.metastasis. Other signs include tumor >100gms, large Other signs include tumor >100gms, large non-functioning tumor and tumor secrets androgen non-functioning tumor and tumor secrets androgen are most likely to be malignant.are most likely to be malignant.

Histology: Histology: Very difficult to differentiate between Very difficult to differentiate between benign and malignant tumor on morphology alone but benign and malignant tumor on morphology alone but presence of high mitotic activity, necrosis, capsular presence of high mitotic activity, necrosis, capsular and vascular invasion, and marked anaplasia are more and vascular invasion, and marked anaplasia are more favorable signs of malignancy.favorable signs of malignancy.

This is a large adrenal cortical carcinoma which is displacing the left kidney downward. Such neoplasms are usually functional (secreting corticosteroids or sex steroids). They have a poor prognosis.

This high power microscopic appearance of an adrenal cortical This high power microscopic appearance of an adrenal cortical carcinoma demonstrates that the neoplasm closely resembles carcinoma demonstrates that the neoplasm closely resembles normal adrenal cortex. It is difficult to determine malignancy in normal adrenal cortex. It is difficult to determine malignancy in endocrine neoplasms based upon cytology alone. Thus, invasion endocrine neoplasms based upon cytology alone. Thus, invasion (as seen here in a vein) and metastases are the most reliable (as seen here in a vein) and metastases are the most reliable indicators. Luckily, most endocrine neoplasms are benign indicators. Luckily, most endocrine neoplasms are benign adenomas. adenomas.

Adrenocortical Adrenocortical hyperfunction: hyperfunction: It produces 3 main It produces 3 main syndromes:syndromes:

1.1. Cushing’s syndrome:Cushing’s syndrome: hypersecretion of hypersecretion of cortisol.cortisol.

2.2. Hyperaldosteronism: primary calledHyperaldosteronism: primary called Conn’s Conn’s syndrome.syndrome.

3.3. Adrenogenital syndrome:Adrenogenital syndrome: excessive excessive secretion of androgen.secretion of androgen.

Cushing’s syndrome:Cushing’s syndrome:

because of its effect on the metabolism results in many signs because of its effect on the metabolism results in many signs and symptoms. It occurs most commonly in women with and symptoms. It occurs most commonly in women with central (truncal) obesity, moon face, buffalo hump, muscle central (truncal) obesity, moon face, buffalo hump, muscle wasting of limbs with weakness, osteoporosis may cause wasting of limbs with weakness, osteoporosis may cause vertebral collapse, skin atrophy with bruising and striae, skin vertebral collapse, skin atrophy with bruising and striae, skin pigment(in extra-adrenal Cushing syndrome), hypertension, pigment(in extra-adrenal Cushing syndrome), hypertension, impaired GTT with hyperglycemia, glucosuria, wound healing impaired GTT with hyperglycemia, glucosuria, wound healing delayed, menstrual disorder, hirsutism, amenorrhea, and delayed, menstrual disorder, hirsutism, amenorrhea, and virilization, depression, psychosis.virilization, depression, psychosis.

Causes:Causes:1.1. Long term therapy by corticosteroidsLong term therapy by corticosteroids:(Iatrogenic):(Iatrogenic) is the most is the most

common cause e.g.: patients with rheumatoid arthritis or common cause e.g.: patients with rheumatoid arthritis or nephrotic syndrome.nephrotic syndrome.

2.2. Cushing’s diseaseCushing’s disease:: pituitary Cushing’s syndrome, due to pituitary Cushing’s syndrome, due to excessive secretion of ACTH by pituitary adenoma or excessive secretion of ACTH by pituitary adenoma or hyperplasia.hyperplasia.

3.3. Adrenal tumors and nodular hyperplasia(Adrenal)Adrenal tumors and nodular hyperplasia(Adrenal):: either either adenoma or carcinoma, adrenal tumors are commonest cause of adenoma or carcinoma, adrenal tumors are commonest cause of Cushing’s syndrome in children, especially carcinoma. Increase Cushing’s syndrome in children, especially carcinoma. Increase serum level of the glucocorticoids and ACTH secretion is serum level of the glucocorticoids and ACTH secretion is decrease due to feedback and this cause atrophy of contralateral decrease due to feedback and this cause atrophy of contralateral adrenal gland and tissue adjacent to tumor.adrenal gland and tissue adjacent to tumor.

4.4. Ectopic ACTH syndrome(paraneoplastic)Ectopic ACTH syndrome(paraneoplastic):: secretion of ACTH by secretion of ACTH by non-pituitary tumors such as: small cell carcinoma of lung, non-pituitary tumors such as: small cell carcinoma of lung, carcinoid tumor, and islet cell tumor of pancreas, both 2&4 carcinoid tumor, and islet cell tumor of pancreas, both 2&4 produce bilateral adrenal hyperplasia .produce bilateral adrenal hyperplasia .

Center = Normal Adrenal glandUpper=adrenal atrophy (Addison’s disease or long-term corticosteroid therapy)Lower=The adrenals with bilateral cortical hyperplasia. This could be due to a pituitary adenoma secreting ACTH (Cushing's disease), or Cushing's syndrome from ectopic ACTH production, or idiopathic.

HyperaldosteronismHyperaldosteronism:: primary or secondary.primary or secondary.

Primary hyperaldosteronism (Conn´s syndrome): Primary hyperaldosteronism (Conn´s syndrome):

causes:causes:

1.1. Adenoma of zona glomerulosa Adenoma of zona glomerulosa 80%80% of cases. of cases.

2.2. Bilateral hyperplasia of zona glomerulosa Bilateral hyperplasia of zona glomerulosa 15% of cases.15% of cases.

3.3. Carcinoma (rare).Carcinoma (rare).

Secondary hyperaldosteronism:Secondary hyperaldosteronism:..

excessive stimulation of renin-angiotensin system stimulates excessive stimulation of renin-angiotensin system stimulates aldosterone secretion.aldosterone secretion.

Causes:Causes:

1.1. Renal disease with renal ischemia.Renal disease with renal ischemia.

2.2. Heart failure with edema. Heart failure with edema.

3.3. Liver cirrhosis. Liver cirrhosis.

4.4. Renin secreting tumor (rare).Renin secreting tumor (rare).

* To differentiate secondary from primary type both * To differentiate secondary from primary type both plasma level of aldosterone and renin are high in plasma level of aldosterone and renin are high in secondary type.secondary type.

Adrenogenital syndrome:Adrenogenital syndrome:

Causes:Causes:

1.1. Adrenal tumors:Adrenal tumors: tumors with excessive secretion of tumors with excessive secretion of androgen cause virilism in females (hirsutism and clitoris androgen cause virilism in females (hirsutism and clitoris enlargement) and in males cause precocious puberty. These enlargement) and in males cause precocious puberty. These tumors are mostly carcinoma.tumors are mostly carcinoma.

2.2. Congenital adrenal hyperplasia:Congenital adrenal hyperplasia: it is rare inborn error of it is rare inborn error of metapolism, AR condition, enzyme deficiency involved in metapolism, AR condition, enzyme deficiency involved in synthesis of glucocorticoids this result in plasma reduction synthesis of glucocorticoids this result in plasma reduction of cortisol , hypersecretion of ACTH this in turn causes of cortisol , hypersecretion of ACTH this in turn causes bilateral adrenal hyperplasia with excess production of bilateral adrenal hyperplasia with excess production of androgen commonest type is 21-hydroxylase deficiency androgen commonest type is 21-hydroxylase deficiency cause virilism in female and in male lead to precocious cause virilism in female and in male lead to precocious puberty also there is decrease in synthesis of aldosterone.puberty also there is decrease in synthesis of aldosterone.

Adrenocortical hypofunction: Adrenocortical hypofunction: either acute or chronic.either acute or chronic.

Acute adrenocortical insufficiency: Acute adrenocortical insufficiency:

May occur in septicemia particularly in children with meningococcal May occur in septicemia particularly in children with meningococcal septicemia (Waterhouse-Friedrichsen syndrome) less commonly with other septicemia (Waterhouse-Friedrichsen syndrome) less commonly with other infections. Presentation with hypotensive shock, high level K, low level Na infections. Presentation with hypotensive shock, high level K, low level Na and glucose, hypotension, collapse and death, also patients have high fever and glucose, hypotension, collapse and death, also patients have high fever and skin rashes. Adrenal gland show hemorrhage with extensive necrosis and skin rashes. Adrenal gland show hemorrhage with extensive necrosis of cortex. of cortex.

other causes:other causes: Chronic adrenal insufficiency may be complicated by acute failure Chronic adrenal insufficiency may be complicated by acute failure

(Addisonian crisis) due to increase demand of cortisone as in infection or (Addisonian crisis) due to increase demand of cortisone as in infection or trauma.trauma.

Sudden withdrawal of corticosteroid TRT from patient with long term Sudden withdrawal of corticosteroid TRT from patient with long term therapy (tapering of therapy by corticosteroid is mandatory in those therapy (tapering of therapy by corticosteroid is mandatory in those patients).patients).

The patient with Waterhouse-Friderichsen syndrome has sepsis with DIC and marked purpura.

These adrenals are black-red from extensive hemorrhage in a patient with meningococcemia. This produces the Waterhouse-Friderichsen syndrome

This is the microscopic appearance of the adrenals with meningococcemia. There is marked hemorrhagic necrosis with acute adrenal insufficiency.

Chronic adrenocortical insufficiency (Addison's Chronic adrenocortical insufficiency (Addison's disease):disease):

Causes:Causes:1.1. Autoimmune adrenalitis:Autoimmune adrenalitis: commonest cause (75%), atrophy of commonest cause (75%), atrophy of

adrenal cortex with lymphocyte infiltration, medulla is adrenal cortex with lymphocyte infiltration, medulla is normal may be associated with autoimmune disease of normal may be associated with autoimmune disease of thyroid, DM and pernicious anemia.thyroid, DM and pernicious anemia.

2.2. Tuberculosis:Tuberculosis: second most common cause. Adrenal enlarged second most common cause. Adrenal enlarged with caseation and calcification medulla destroyed. Other with caseation and calcification medulla destroyed. Other infection: AIDS, histoplasmosis.infection: AIDS, histoplasmosis.

3.3. Amyloidosis.Amyloidosis.4.4. Metastatic tumor:Metastatic tumor: especially lung and breast carcinomas. especially lung and breast carcinomas.5.5. Sarcoidosis.Sarcoidosis.

Addison's disease (chronic) adrenocortical insufficiency. Here are Congo red stained deposits of amyloid in the

adrenal cortex. Amyloid may collect in adrenal as well as other organs.

Adrenal medulla:Adrenal medulla:

1.1. Pheochromocytoma:Pheochromocytoma: Tumor of adrenal medulla Tumor of adrenal medulla secretes catecholamines causing paroxysmal secretes catecholamines causing paroxysmal hypertension, palpitation, severe head ache, hypertension, palpitation, severe head ache, sweating, hyperglycemia, occur in young adults, it sweating, hyperglycemia, occur in young adults, it has rule of 10:has rule of 10:

10% bilateral.10% bilateral. 10% non-functioning.10% non-functioning. 10% in children.10% in children. 10% malignant.10% malignant. 10% familial (MEN-2).10% familial (MEN-2).

This large adrenal neoplasm has been sectioned in half. Note the grey-tan color of the tumor compared to the yellow cortex stretched around it and a small remnant of remaining adrenal at the lower right. This patient had episodic hypertension. This is a tumor arising in the adrenal medulla--a pheochromocytoma.

There is some residual adrenal cortical tissue at the lower center right, with the darker cells of pheochromocytoma seen above and to the left.

Neuroblastoma:Neuroblastoma: small round cell tumor of children small round cell tumor of children arises from primitive cells of sympathetic system. arises from primitive cells of sympathetic system. Commonly seen in children below 5 years old, Commonly seen in children below 5 years old, common site is adrenal medulla,other sites are common site is adrenal medulla,other sites are posterior mediastinum,retroperitoneum. it is highly posterior mediastinum,retroperitoneum. it is highly malignant tumor with lymph node metastasis and malignant tumor with lymph node metastasis and blood metastasis to the bone.blood metastasis to the bone.

Others:Others: Neurofibroma, ganglioneuroma, and Neurofibroma, ganglioneuroma, and myelolipoma.myelolipoma.

Neuroblastoma This is a microscopic appearance of neuroblastoma, which is one of the "small round blue cell" tumors. These neoplasms can reach a large size in the retroperitoneum before detection. They often contain areas of necrosis and calcification.