The Endocrine System
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Transcript of The Endocrine System
The Endocrine System
Pituitary Gland Clinical manifestations of pituitary disease Pituitary adenomas and hyperpituitarism
Prolactinomas Growth hormone cell (somatotroph) adenomas ACTH (corticotroph) adenomas Other anterior pituitary adenomas
Hypopituitarism Posterior pituitary syndromes Hypothalmic suprasellar tumors
Pituitary GlandAnterior pituitary
Somatotrophs – GHLactotrophs – prolactinCorticotrophs – ACTH, POMC, MSHThryotrophs – TSHGonadotrophs – FSH, LH
Posterior pituitary – axonal processes from hypothalamus:OxytocinADH
Clinical – Hyperpituitarism, Hypopituitarism, local mass effects – radiographic abnormalities of the sella turcica, visual field abnormalities, elevated intracranial pressure, pituitary apoplexy
Pituitary GlandHyperpituitarism – pituitary adenoma
Most common cause is adenoma arising in the anterior pituitaryClassified based on the hormone producedFunctional or nonfunctionalMicroadenoma < 1 cmMacroadenoma > 1 cmUsually soft, well-circumscribed30% invasive adenomas – no capsuleCellular monomorphism and the absence of a significant reticulin
network distinguish pituitary adenomas from non-neoplastic anterior pituitary parenchyma
Atypical adenomas – p53 mutations, aggressive
Pituitary GlandProlactinomas
Most frequent hyperfunctioning adenomaAmenorrhea, galactorrhea, loss of libido, infertilityTend to undergo dystrophic calcificationAny mass in the suprasellar department may disturb
the normal inhibitory influence of the hypothalamus (via dopamine secretion) on prolactin secretion resulting in hyperprolactinemia
Pituitary GlandSomatothroph adenoma
Second most commonGH stimulates the hepatic secretion of IGF-1
(somatomedin C)Gigantism or acromegalyFailure to suppress GH production in response to a glucose challenge is one of the most sensitive tests for acromegaly
Pituitary GlandCorticotroph adenoma
Cushing diseaseNelson syndrome
Gonotroph adenomaThyrotroph adenomaNonfunctioning pituitary adenomaPituitary carcinoma ( <1% of all pituitary tumors)
Pituitary GlandHypopituitarism
Decreased secretion of pituitary hormonesHypofunction when > 75% of pituitary is lost or absentCauses – Tumors and other mass lesions,
traumatic brain injury, subarachnoid hemorrhage, pituitary surgery or irradiation, pituitary apoplexy, ischemic necrosis and Sheehan syndrome, Rathke cleft cyst, empty sella syndrome, genetic defects, hypothalamic lesions, inflammatory or infections
Pituitary GlandPosterior pituitary syndromes
DISIADH
Hypothalamic suprasellar tumorsGliomasCraniopharygiomas
Thyroid Gland Hyperthyroidism Hypothyroidism
Cretinism Myxedema
Thyroiditis Hashimoto thyroiditis Subacute (granulomatous) thyroiditis Subacute lymphocytic (painless) thyroiditis
Graves disease Diffuse and multinodular goiters
Diffuse nontoxic (simple) goiter Multinodular goiter
Neoplasms of the thyroid Adenomas Carcinomas
Pathogenesis Papillary carcinonoma Follicular carcinoma Anaplastic (undifferentiated) carcinoma Medullary carcinoma
Congenital anomalies
Thyroid Gland Hyperthyroidism
Hypermetabolic state caused by elevated circulating levels of free T3 and T4
ThyrotoxicosisMost common forms:Diffuse hyperplasia associated with Graves
disease ( 85%)Hyperfunctional multinodular goiterHyperfunctional adenoma of the thyroid
Thyroid GLandClinical manifestations of hyperthyroidism
Hypermetabolic stateOveractivity of the sympathetic nervous systemWarm, flushed skinheat intoleranceSweatingWeight loss despite increased appetiteCardiac- tachycardia, palpitations, cardiomegaly,
arrhythmias,CHF,cardiomyopathyNeuromuscular – tremor, hyperactivity, emotional lability, anxiety, inability to
concentrate, insomnia, myopathyOcular – wide staring gaze, lid lagOsteoporosisThyroid stormApathetic hyperthyroidism
Thyroid GlandHypothyroidism
Causes-Primary – Thyroid dysgenesis, Thyroid
hormone resistance syndrome, postablative, Hashomoto’s thyroiditis, Iodine deficiency, drugs, dyshormonogenetic goiter
Penred syndrome (+hearing loss)
Secondary – Pituitary failure, Hypothalamic failure
Thyroid GlandClinical manifestations:
Cretinism – infancy or childhood, impaired development of the skeletal system and CNS, short stature and mental retardation
Myxedema- older child or adult, slowing of physical and mental activity, fatigue, apathy, mental sluggishness, decreased sympathetic activity, non-pitting edema due to accumulation of matrix substances, decreased cardiac output
Thyroid glandThyroiditis
Infectious- acute or chronicHashimoto – autoimmune; anti- thyroglobulin, anti-
thyroid peroxidase antibodies, Painless enlargement with hypothyroidism in a middle- aged woman, inflammatory infiltrate, germinal centers, Hurthle cells
Subacute (granulomatous or DeQuervain) - triggered by a viral infection, painful enlargement, transient
Subacute lymphocytic (painless) – also post- partum, variant of Hashimoto
Riedel – extensive fibrosis of thyroid and contiguous structures
Thyroid GlandGraves disease
HyperthyroidismInfiltrative ophthalmopathy exothalmosLocalized, infiltrative dermopathy pretibial
myxedemaAntibodies: Thyroid-stimulating immunoglobulin,
thyroid growth-stimulating immunoglobulin, TSH-binding inhibitor immunoglobulin
Diffuse hypertrophy and hyperplasia with tall, crowded follicular cells
Thyroid GlandDiffuse nontoxic (simple) goiter- colloid goiter, iodine deficiency, clinically euthyroid, sporadic usually related to substances that interfere with thyroid hormone synthesis, mass effects from enlarging size
Multinodular goiter- recurrent hyperplasia and involution from a long-standing simple goiter, mistaken for neoplasia, mass effects, occasionally toxic - hyperthyroidism
Thyroid glandNeoplasms
AdenomaCarcinoma
PapillaryFollicularAnaplasticMedullary
Congenital anomaly – Thyroglossal duct or cyst
Thyroid Gland Solitary nodules, in general, are likely to be neoplastic than are
multiple nodules Nodules in younger patients are more likely to be neoplastic
than are those in older patients Nodules in males are more likely to be neoplastic that are those
in females A history of radiation treatment to the head and neck region is
associated with an increased incidence of thyroid malignancy Functional nodules that take up radioactive iodine in imaging
studies (hot nodules) are significantly more likely to be benign than malignant
Thyroid Gland Adenomas
Follicular, capsule, functioning autonomy, TSH receptor signaling pathway mutations in toxic ademonas
Unilateral painless mass – usual presentation
Thyroid Gland Carcinomas
Papillary – 85% of cases, associated with prior radiation, Orphan Annie eyes nuclei, papillae, psammoma bodies
Follicular Anaplastic Medullary - MEN syndromes, calcitonin
Parathyroid Gland PTH
Increases renal tubular reabsorption of calcium, thereby conserving free calcium
Increases the conversion of vitamin D to its active dihydroxy from in the kidneys
Increases urinary phosphate excretion, thereby lowering serum phosphate levels
Augments gastrointestional calcium absorption Malignancy is the most common cause of clinically apparent
hypercalcemia Hyperparathyroidism is the most common cause of asymptomatic
hypercalcemia
Parathyroid Glands Hyperparathyroidism
Primary – adenoma ( 85-95%), hyperplasia, carcinoma Familial forms – MEN-1, MEN-2, Familial hypocalciuric hypercalcemia Cyclin D1gene inversions MEN1 mutations Clinical – “painful bones, renal stones, abdominal groans, psychic moans” Table 24-5 Causes of Hypercalcemia
Secondary – renal failure is most common Hypoparathyroidism – surgically induced, autoimmune, Ad, FIH,
congenital absence, tetany, Chvostek and Trousseau signs, mental status changes, intracranical calcifications, Prolonged QT, dental
Pseudohypoparathyroidism
The Endocrine Pancreas Diabetes mellitus
Diagnosis Classification Glucose homeostasis Pathogenesis of type 1 DM Pathogenesis of type 2 DM Monogenic forms of diabetes Pathogenesis of late complications of DM Morphology of diabetes and its late complications Clinical features of DM
Diabetes Mellitus Diagnosis
A random glucose > 200mg/d l, with classical signs and symptoms
Fasting glucose concentration > 126 mg/dl Abnormal oral glucose tolerance test ( glucose >200mg.dL 2
hours after a standard carbohydrate load “pre-diabetes”
Diabetes Mellitus Classification – Table 24-6 Glucose homeostasis
Glucose production in the liver Glucose uptake and utilization by peripheral tissues (primarily
muscle) Actions of insulin and counter-regulatory hormones
Most important stimulus for insulin synthesis and release is glucose itself
Insulin is the most potent anabolic hormone, increase the rate of glucose transport into certain cells in the body – striated muscles including cardiac and adipose, other cells – uptake is insulin dependent
Diabetes Mellitus Pathogenesis of Type I
Autoimmune disease in which islet destruction is caused primarily by immune effector cells reacting against endogenous Beta-cell antigens
HLA-DR3 or HLA-DR4 Viral infections Failure of self-tolerance in T cells Clinical manifestations begin after > 90% Beta cells are
destroyed
Diabetes Mellitus Pathogenesis of Type 2
Decreased response of the peripheral tissues to insulin Beta-cell dysfunction – manifested as inadequate insulin
secretion in the face of insulin resistance and hyperglycemia Obesity
Nonesterified fatty acids Adiokines Inflammation Peroxisome proliferator-activated receptor gamma Intrinsic predisposition to Beta-cell failure
Pathogenesis of Complications of DM Macrovascular disease – accelerated atherosclerosis Microvascular disease – retinopathy, nephropathy,
neuropathy Persistent hyperglycemia – Hemoglobin A1C
Pormation of advanced glycation end products Activation of protein kinase C Intracellular hyperglycemia and disturbances in polyol pathways
Morphology of DM and Complications Pancreas
Reduction in number and size of islets Leucocytic inflitrates in the islets Amyloid deposition , reduction in islet cell mass ( type 2) Increase in number and size of islets ( IDM)
Macrovascular disease Endothelial dysfunction, MI – most common cause of death, gangrene, hyaline arteriolosclerosis
Diabetic microangiopathy Diffuse thickening of basement membranes, leaky capillaries
Diabetic nephropathy Glomerular lesions – Thickening of GBM, increase in mesangial matrix, intercapillary
glomerulosclerosis ( Kimmelstiel-Wilson) Renal vascular Pyelonephritis
Diabetic ocular complications – chapter 29 Diabetic neuropathy – chapter 27
Clinical Features of DM Type 1
Polyuria, polydipsia, polyphagia Honeymoon period Catabolic state – glucose, fats, proteins DKA Table 24-7 Type 1 vs Type 2 DM
Clinical Features Type 2
Hyperosmolar nonketotic coma Complications
MI, Renal vascular insufficiency, strokes End-stage renal disease Visual impairment Distal symmetric polyneuropathy of lower extremities Autonomic neuropathy Increased susceptibility to infections: skin, TB, pneumonia,
pyelonephritis
The Endocrine Pancreas Pancreatic Endocrine Neoplasms
Hyperinsulinism (insulinoma) – persistent hypoglycemia Zollinger-Ellison syndrome (gastrinomas) – peptic ulceration Other rare pancreatic endocrine neoplasms
Alpha –cell tumors – increase glucagon Delta-cell tumors – somatostatinomas VIPoma Carcinoid
Adrenal Glands Adrenal cortex
Adrenocortical hyperfunction (hyperadrenalism) Hypercortisolism (Cushing syndrome) Primary hyperaldonsteronism Adrenogenital syndromes
Adrenocortical insufficiency Primary acute adrenocortical insufficiency Waterhouse-Friderichsen syndrome Primary chronic adrenocortical insufficiency (Addison disease) Secondary adrenocortical insufficiency
Adrenocortical neoplasms Other lesions of the adrenal
Adrenal medulla Pheochromocytoma
Adrenal Cortex Hypercortisolism ( Cushing syndrome)
Clinical features – Table 24-9 Any condition that produces elevated glucocorticoid levels Exogenous – administration of gluocorticoids Endogenous – ACTH-dependent, ACTH –independent
Table 24-8 Cushing disease – ACTH-producing pituitary microadenoma Secretion of ectopic ACTH Adrenal neoplasms
Adrenal Cortex Primary Hyperaldosteronism
Resultant suppression of renin-angiotensin system Decreased levels of renin Bilateral idipathic hyperaldosteronism Adrenocortical neoplasm Glucocorticoid-remediable hyperaldosteronism Hypertension – endothelial dysfunction Secondary caused by activation of renin-angiotensin system,
increased renin
Adrenal Cortex Adrenogenital syndrome
Neoplasms Congenital adrenal hyperplasia
21-hydroxylase deficiency Salt-wasting Simple virilizing ( ambiguous genitalia) Nonlassic or late-onset adrenal virilism
Adrenal Cortex Adrenocortical Insufficiency – Table 24-10 Acute adrenal cortical insufficiency
Crisis precipitated by any form of stress Rapid withdrawal of steroids or failure to increase dose with
acute stress Massive adrenal hemorrhage Weaknees, fatigue, hyperpigmentation (primary ), hyperkalemia,
hypomatremia, volume depletion, hypotension
Adrenal Medulla Paraganglion system Pheochromocytomas
Rule of 10s – sort of Extra-adrenal Bilateral Malignant No hypertension Familial
Multiple Endocrine Neoplasia Syndromes Multiple Endocrine Neoplasia, type 1 (Wermer syndrome)
Parathyroid, pancreas, pituitary, also gastrinomas Multiple Endocrine Neoplasia, type 2
MEN-2A (Sipple syndorme) Pheochromocytoma, medullary carcinoma, parathyroid hyperplasia
MEN -2B Neuromas, marfanoid habitus, similar to 2A withouf
hyperparathyroidism Familial Medullary thyroid cancer -RET mutations, prophylactic
thyroidectomy
Pineal Gland Pinealomas Germinomas