Endocrine Path Flashcards
A number of pathologies can disturb the
normal activity of the endocrine system.
¡ abnormal synthesis or release of hormones from endocrine (and sometimes non-endocrine) tissues ¡ abnormal responses to hormones by their target tissues and organs
Causes of hormone overproduction
hyperfunction
¡ Adenoma (most common)
¡ Acute inflammation
¡ Hyperplasia
¡ Cancer
Causes of hormone underproduction
hypofunction
¡ Autoimmune destruction (most common) ¡ Any process that destroys endocrine tissue l infarction, surgery, radiation, infection, etc. ¡ Decreased stimulation by neuroendocrine messengers ¡ Enzyme deficiency ¡ Neoplasia ¡ Congenital disorder
lactotrophs
prolactin
mammosomatotrophs
prolactin
GH
somatotroph
GH
lactotroph regulators
TRH
dopamine
mamosomatotrophs regulators
dopamine
GHRH
somatostatin
somatotroph regulators
GHRH
somatostatin
Hyperpituitarism
l adenoma (most common) l hyperplasia l cancer l non-pituitary tumors l hypothalamic disorders
Hypopituitarism
l destructive processes: ischemia, surgery,
radiation, inflammation
l nonfunctional adenomas that compress and
destroy functional pituitary tissue -most common
adult cause
hypothalamic disorders
-most common cause in children (craniopharyngioma)
Local mass effects
l expanding lesions near the sella turcica compress
the optic chiasm → visual field disturbances
-classically affect lateral (temporal) vision =
bitemporal hemianopsia
l signs and symptoms of elevated cranial pressure
-headache, nausea, vomiting
pituitary apoplexy
l acute hemorrhage into adenoma with rapid
lesion enlargement
l causes sudden onset of excruciating
headache, diplopia (due to pressure on
oculomotor nerves), and hypopituitarism
l surgical emergency (can lead to sudden
death)
Molecular features of pituitary
adenomas
¡ monoclonal in origin ¡ features of aggressive tumors l RAS-activating mutations l c-Myc overexpression ¡ MEN1 mutations uncommon in sporadic cases ¡ best characterized genetic abnormality = G-protein gene mutations
Prolactinoma
¡ produce increased serum levels of prolactin (hyperprolactinemia) ¡ most common hyperfunctioning pituitary tumor (~40%) -most (90%) are small, intrasellar tumors that rarely increase in size *efficient producers of prolactin
Prolactinoma:
Clinical Features
¡ most common in premenopausal women: amenorrhea and infertility -most commonly detected after discontinuation of oral contraceptives -less common: galactorrhea (80%), oligomenorrhea ¡ most tumors small at diagnosis ¡ most common in men: headaches and neurologic disturbances -less common: impotence, infertility, decreased libido -uncommon: galactorrhea and gynecomastia ¡ large size at diagnosis
Other causes of hyperprolactinemia…
¡ any process that interferes with dopamine secretion or delivery to the portal vessels of the anterior pituitary -nonfunctioning pituitary tumors that compress the pituitary stalk (known as “the stalk effect”) -hypothalamic neoplasms (e.g., craniopharyngiomas) -head trauma -medications ¡ pregnancy and breast-feeding ¡ renal failure -decreased clearance ¡ primary hypothyroidism -mild hyperprolactinemia may develop due to increased synthesis of thyrotropin-releasing hormone
Other causes of hyperprolactinemia…
¡ any process that interferes with dopamine secretion or delivery to the portal vessels of the anterior pituitary -nonfunctioning pituitary tumors that compress the pituitary stalk (known as “the stalk effect”) -hypothalamic neoplasms (e.g., craniopharyngiomas) -head trauma -medications ¡ pregnancy and breast-feeding ¡ renal failure -decreased clearance ¡ primary hypothyroidism -mild hyperprolactinemia may develop due to increased synthesis of thyrotropin-releasing hormone
Prolactinoma:
Diagnostic Features
¡ obtain serum prolactin level -because levels are pulsatile or can be affected by stress, repeat tests that show mild elevations ¡ rule out other causes using the -H&P -pregnancy test -assessments of thyroid and renal function ¡ confirm diagnosis with MRI
Prolactinoma biopsy
although biopsy is not necessary to diagnose prolactinomas, you should know that excised lesions show a tendency to undergo dystrophic calcification -psammoma bodies (microscopic calcifications) -pituitary stones (gross calcification of tumor mass)
Growth Hormone (Somatotroph) Adenomas
cause elevated levels of serum growth hormone (GH) -because the manifestations of excessive GH are subtle, these adenomas are usually quite large by the time they are diagnosed second most common type of hyperfunctioning pituitary adenoma
Growth Hormone (Somatotroph) Adenomas: Clinical Features
In adults, Acromegaly -Acro = tip, extremity, end In children and teenagers, gigantism
Growth Hormone (Somatotroph) Adenomas: Diagnostic Features
¡ elevated IGF-I levels
¡ autonomous secretion of growth hormone
-failure to suppress GH production in response to an
oral glucose load is one of the most sensitive tests
for acromegaly
¡ use H&P, etc. to exclude other causes of elevated
growth hormone
¡ Pituitary MRI with contrast material is the most
sensitive imaging study for determining the
source of excess growth hormone… usually
(>90% of cases) an adenoma is the cause.
Corticotroph Adenomas
Causes excess production of ACTH, leading to
adrenal hypersecretion of cortisol and the
development of hypercortisolism (Cushing disease)
Nelson Syndrome
Nelson Syndrome
a pre-existing corticotroph tumor grows rapidly after surgical removal of the adrenal glands hypercortisolism doesn’t develop, but mass effects occur hyperpigmentation common
Gonadotroph (LH- or FSH-producing)
Adenomas
difficult to recognize because they do not cause a recognizable clinical syndrome and hormone production varies considerably most common presentation: neurologic symptoms due to mass effects different effect than most adenomas: these usually cause hypofunction rather than hyperfunction (clonal cell population is non-functioning, and compresses normal functioning tissue) -men: reduced testosterone à decreased energy and libido -premenopausal women: amenorrhea
Sheehan syndrome (post-partum necrosis of the anterior pituitary)
¡ most common form of clinically
significant ischemic necrosis of the
pituitary
¡ know pathogenesis
Rathke’s Cyst
¡ reminder: anterior pituitary is embryologically derived from the Rathke pouch ¡ cysts accumulate proteinaceous fluid and expand, compromising the normal gland
Primary Empty Sella Syndrome
¡ due to defect in the diaphragma sella -allows arachnoid matter and CSF to herniate into the sella, compressing the pituitary ¡ risk groups: obese women with multiple pregnancies
Secondary Empty Sella Syndrome
a mass enlarges the sella, but it is
either surgically removed or
undergoes spontaneous necrosis,
leading to loss of pituitary function
Hypothalamic Disorders
¡ in contrast to diseases that involve the pituitary directly, these also diminish the secretion of ADH, resulting in diabetes insipidus ¡ in addition to tumors, inflammatory disorders and infections can also compromise the hypothalamus (e.g., sarcoidosis and tuberculous meningitis)
Hypopituitarism
the clinical manifestations of anterior pituitary hypofunction are determined by the specific hormones that are lacking… -GH deficiency: pituitary dwarfism *whereas achondroplastic dwarfism primarily affects the long bones, pituitary dwarfism is proportional
Diabetes Insipidus
condition characterized by excessive urination (polyuria) -kidneys cannot resorb water properly from urine *produce large volumes of dilute urine with low specific gravity results in excessive thirst and polydipsia
Central Diabetes Insipidus
originating from ADH deficiency causes: -head trauma -tumors -inflammatory disorders of the hypothalamus and pituitary surgery
Nephrogenic Diabetes Insipidus
results from tubular unresponsiveness to
circulating ADH
Syndrome of Inappropriate ADH
(SIADH) Secretion
ADH excess causes resorption of excessive amounts of free water, resulting in hyponatremia -leads to cerebral edema and neurologic dysfunction
Thyroid Function Tests
Serum TSH
-most valuable
Total serum T4
-represents T4 bound to TBG and free T4 (FT4)
*Interpret with caution: any change in TBG will
affect total serum T4, but not free T4 (which
is active form)
*↑TBG: estrogen
~pregnancy, oral contraceptives, HR
*↓TBG: anabolic steroids, nephrotic syndrome
Free serum T4 or T3
Radioactive iodine uptake
- 131I, 123I, or 99mTc
Thyroid Function Tests
Serum TSH
-most valuable
Total serum T4
-represents T4 bound to TBG and free T4 (FT4)
*Interpret with caution: any change in TBG will
affect total serum T4, but not free T4 (which
is active form)
*↑TBG: estrogen
~pregnancy, oral contraceptives, HR
*↓TBG: anabolic steroids, nephrotic syndrome
Free serum T4 or T3
Radioactive iodine uptake
- 131I, 123I, or 99mTc
Hypothyroidism
inadequate levels of thyroid hormone l primary hypothyroidism -intrinsic thyroid abnormality l secondary hypothyroidism -pituitary abnormality (↓TSH) l tertiary hypothyroidism (rare) -hypothalamic abnormality (↓TRH)
Causes of primary hypothyroidism
thyroprivic
goitrous
thyroprivic
(absence or loss of thyroid
parenchyma)
radiation
surgery (thyroidectomy)
goitrous
(enlargement of the thyroid due to
↑TSH)
iodine-deficiency
autoimmune (most common in iodine-sufficient
areas)
-Hashimoto thyroiditis most common (see below)
drugs
-intentional (e.g., methimazole, propylthiouracil)
-unintentional (e.g., lithium, p-aminosalicylic acid)
inborn errors of thyroid metabolism (uncommon)
Clinical Manifestations of
Hypothyroidism: Cretinism
¡ limited to neonates and children ¡ formerly most common in areas of endemic iodine-deficiency… now fairly restricted to inborn errors of thyroid metabolism and maternal hypothyroidism (before fetal thyroid develops)
Cretinism clinical features
l severe mental retardation -from the French chrétien (Christ-like), as afflicted individuals believed to be too mentally retarded to commit sin l short stature l coarse facial features, protruding tongue l umbilical hernia
Clinical Manifestations of
Hypothyroidism: Myxedema
clinical manifestations more severe
in younger patients, whereas they
develop insidiously in adults
Clinical Features: -initially: generalized fatigue, apathy, mental sluggishness *may mimic depression in early stages edema, broadening of facial features, enlarged tongue, voice deepens -due to accumulation of matrix substances (e.g., GAGs, hyaluronic acid) in skin, subcutaneous tissue, and visceral sites cold-intolerance; cool, pale skin slowed metabolism → overweight reduced cardiac output: breathlessness, ↓exercise capacity decreased sympathetic activity: constipation, ↓sweating
Hashimoto Thyroiditis
Chronic Lymphocytic Thyroiditis
¡ presented here as the prototype of
hypothyroid disorders
¡ autoimmune destruction of the thyroid
gland
¡ most common cause of hypothyroidism in
areas of the world where iodine levels are
sufficient
-most prevalent in 45-65 y.o. women (female
predominance 10-20:1), but also a major
cause of nonendemic goiter in children
Hashimoto Thyroiditis info
l genetic component to susceptibility
-concordance rate in monozygotic twins =
30-60%
-50% of asymptomatic 1st-degree relatives
have circulating antithyroid antibodies
l associated with chromosomal abnormalities
-Turner syndrome
*circulating antithyroid antibodies common
*~20% develop hypothyroidism that is clinically
indistinguishable from Hashimoto thyroiditis
-Down syndrome
*increased risk for Hashimoto thyroiditis and
hypothyroidism
Hashimoto Thyroiditis
Pathogenesis
immune system reacts against thyroid antigens
-anti-TSH receptor antibodies, antithyroglobulin,
antithyroid peroxidase
Hashimoto Thyroiditis Morphology
l diffuse enlargement of the thyroid
l fine-needle aspiration biopsies typified by Hürthle cells and heterogeneous population of
lymphocytes
-Hürthle cells = metaplastic response of
follicular epithelium to injury
*distinguished by eosinophilic, granular cytoplasm
Hashimoto Thyroiditis
Clinical Features
typical presentation: painless diffuse enlargement of the thyroid in middleaged woman demonstrating some degree of hypothyroidism -hypothyroidism develops gradually *in some cases, death of thyroid follicles releases thyroid hormone, causing transient thyrotoxicosis (“hashitoxicosis”)
Hyperthyroidism
¡ usually synonymous with thyrotoxicosis, a hypermetabolic state caused by elevated circulating levels of free T3 and T4 -primary hyperthyroidism *intrinsic thyroid abnormality -secondary hyperthyroidism *pituitary abnormality (↑TSH) -tertiary hyperthyroidism *hypothalamic abnormality (↑TRH)
Causes of primary hyperthyroidism
¡ diffuse hyperplasia of the thyroid associated with Graves disease - ~85% of cases… note that this “breaks the rule” for most common causes of endocrine hyperfunction ¡ hyperfunctional multinodular goiter ¡ hyperfunctional adenoma of the thyroid
