Download The Endocrine System

The Endocrine System
Pituitary Gland
 Clinical manifestations of pituitary disease
 Pituitary adenomas and hyperpituitarism
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Prolactinomas
Growth hormone cell (somatotroph) adenomas
ACTH (corticotroph) adenomas
Other anterior pituitary adenomas
 Hypopituitarism
 Posterior pituitary syndromes
 Hypothalmic suprasellar tumors
Pituitary Gland
Anterior pituitary
Somatotrophs – GH
Lactotrophs – prolactin
Corticotrophs – ACTH, POMC, MSH
Thryotrophs – TSH
Gonadotrophs – FSH, LH
Posterior pituitary – axonal processes from hypothalamus:
Oxytocin
ADH
Clinical – Hyperpituitarism, Hypopituitarism, local mass effects –
radiographic abnormalities of the sella turcica, visual field abnormalities,
elevated intracranial pressure, pituitary apoplexy
Pituitary Gland
Hyperpituitarism – pituitary adenoma
Most common cause is adenoma arising
in
the anterior pituitary
Classified based on the hormone
produced
Functional or nonfunctional
Microadenoma < 1 cm
Macroadenoma > 1 cm
Usually soft, well-circumscribed
30% invasive adenomas – no capsule
Cellular monomorphism and the absence of a significant reticulin
network distinguish pituitary adenomas from non-neoplastic anterior
pituitary parenchyma
Atypical adenomas – p53 mutations, aggressive
Pituitary Gland
Prolactinomas
Most frequent hyperfunctioning adenoma
Amenorrhea, galactorrhea, loss of libido,
infertility
Tend to undergo dystrophic calcification
Any mass in the suprasellar department may disturb
the normal inhibitory influence of the hypothalamus (via
dopamine secretion) on prolactin secretion resulting in
hyperprolactinemia
Pituitary Gland
Somatothroph adenoma
Second most common
GH stimulates the hepatic secretion of IGF-1
(somatomedin C)
Gigantism or acromegaly
Failure to suppress GH production in response to a
glucose challenge is one of the most sensitive tests
for acromegaly
Pituitary Gland
Corticotroph adenoma
Cushing disease
Nelson syndrome
Gonotroph adenoma
Thyrotroph adenoma
Nonfunctioning pituitary adenoma
Pituitary carcinoma ( <1% of all pituitary tumors)
Pituitary Gland
Hypopituitarism
Decreased secretion of pituitary
hormones
Hypofunction when > 75% of pituitary is lost or absent
Causes – 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 Gland
Posterior pituitary syndromes
DI
SIADH
Hypothalamic suprasellar tumors
Gliomas
Craniopharygiomas
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
Thyrotoxicosis
Most common forms:
Diffuse hyperplasia associated with
Graves disease ( 85%)
Hyperfunctional multinodular
goiter
Hyperfunctional adenoma of the
thyroid
Thyroid GLand
Clinical manifestations of hyperthyroidism
Hypermetabolic state
Overactivity of the sympathetic nervous system
Warm, flushed skin
heat intolerance
Sweating
Weight loss despite increased appetite
Cardiac- tachycardia, palpitations,
cardiomegaly,
arrhythmias,CHF,cardiomyopathy
Neuromuscular – tremor, hyperactivity,
emotional lability, anxiety, inability to concentrate, insomnia, myopathy
Ocular – wide staring gaze, lid lag
Osteoporosis
Thyroid storm
Apathetic hyperthyroidism
Thyroid Gland
Hypothyroidism
CausesPrimary – 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 Gland
Clinical 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 gland
Thyroiditis
Infectious- acute or chronic
Hashimoto – autoimmune; antithyroglobulin, 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 Gland
Graves disease
Hyperthyroidism
Infiltrative ophthalmopathy 
exothalmos
Localized, infiltrative dermopathy 
pretibial myxedema
Antibodies: Thyroid-stimulating
immunoglobulin, thyroid growth-stimulating
immunoglobulin, TSH-binding inhibitor immunoglobulin
Diffuse hypertrophy and hyperplasia with tall, crowded
follicular cells
Thyroid Gland
Diffuse 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 gland
Neoplasms
Adenoma
Carcinoma
Papillary
Follicular
Anaplastic
Medullary
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
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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
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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
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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
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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
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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
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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
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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
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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)
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Clinical features – Table 24-9
Any condition that produces elevated glucocorticoid levels
Exogenous – administration of gluocorticoids
Endogenous – ACTH-dependent, ACTH –independent
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Table 24-8
Cushing disease – ACTH-producing pituitary microadenoma
Secretion of ectopic ACTH
Adrenal neoplasms
Adrenal Cortex
 Primary Hyperaldosteronism
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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
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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