MT Notes Endocrine Flashcards
Pituitary disease clinical manifestations
-Hyperpituitarism
•Excess secretion of trophic hormones
•Caused by tumors, hypothalamic disorders
-Hypopituitarism
•Deficiency of trophic hormones
•Caused by ischemia, surgery, radiation, inflammation, tumor
-Local mass effects
•Sella turcica deformation
•Optic chiasm compression- bitemporal hemianopsia
•Increased intracranial pressure
Pituitary adenomas
-Functional adenomas •Associated with hormone excess •Classified based on hormone produced, ie lactotroph adenoma -Nonfunctional adenomas •Without hormone excess -Peak incidence 35-65 years -Nonfunctional tend to be larger when diagnosed •Microadenomas < 1 cm •Macroadenomas > 1cm
Lactotroph adenoma
-Prolactin-secreting adenoma •Increased serum prolactin- hyperprolactinemia -MC functional pituitary adenoma •30% of cases -Manifestations: •Amenorrhea (responsible for ¼ of cases) •Galactorrhea (milky nipple discharge) •Loss of libido •Infertility
Somatotroph adenoma
-Growth hormone-secreting adenoma
•2nd MC functioning pituitary adenoma
-Primary manifestations:
•Gigantism in children
•Acromegaly in adults (after epiphyseal closure- soft tissue affected)
•Effects may be subtle
•Leads to late diagnosis and relatively large tumor
-Also associated with:
•Gonadal dysfunction, diabetes mellitus, hypertension, arthritis, muscle weakness, congestive heart failure, GI cancers
Corticotroph adenomas
-Adrenocorticotrophic hormone (ACTH) secreting adenomas
•Leads to adrenal hypersecretion of cortisol
•Development of hypercortisolism (Cushing’s)
-Treated with removal of adrenal glands
•Can lead to large destructive pituitary adenomas
•Known as Nelson syndrome
Other anterior pituitary adenomas
-Gonadotroph adenomas
•Produce LH and FSH
•Inefficient production; effectively nonfunctioning
•Diagnosed by mass effect symptoms
-Thyrotroph adenomas
•Very rare
•Lead to hyperthyroidism
-Nonfunctioning adenomas
•25-30% of pituitary tumors
-Pituitary carcinoma
•Very rare
•Craniospinal or systemic metastasesHypopituitarism
-Decreased secretion of pituitary hormones
-Results from hypothalamic or pituitary disease:
•Tumors and other mass lesions
•Traumatic brain injury / subarachnoid hematoma
•Pituitary surgery or radiation
•Pituitary apoplexy
•Sudden hemorrhage into pituitary causing rapid expansion
•Ischemic necrosis of pituitary
•Sheehan’s syndrome
•AKA postpartum necrosis of anterior pituitary
•Obstetric hemorrhage causes vasoconstriction to enlarged pituitary
Hypopituitarism Causes (continued):
-Rathke cleft cyst
-Empty sella syndrome
•Any destruction of part or all of pituitary
•Primary: diaphragma sella defect allows CSF herniation into sella
•Secondary: Mass enlarges sella then is removed or undergoes infarction
•Hypothalamic lesions
•Interfere with hormone-releasing hormones
•Generally tumors, benign or malignant
•Inflammation / infection
•Genetic defects
Hypopituitarism
Manifestations:
- Growth failure in children (pituitary dwarfism)
- Gonadotropin deficiency -> amenorrhea, infertility, decreased libido
- Hypothyroidism, hypoadrenalism
- Failure of postpartum lactation
Posterior pituitary syndromes Manifestations involve ADH:
- Central diabetes insipidus
- Inadequate ADH production
- Syndrome of inappropriate ADH (SIADH)
- Excess secretion of ADH
- Increased blood volume
- Hyponatremia
Thyroid gland
- -Hyperthyroidism- hypermetabolic state caused by elevated circulating levels of free T3 and/ or T4
- Primary: Intrinsic thyroid abnormality
- Secondary: Due to external process such as TSH-secreting pituitary tumor
- MC causes:
- Diffuse hyperplasia of thyroid associated with Graves (85% of cases)
- Hyperfunctional multinodal goiter
- Hyperfunctional thyroid adenoma
Hyperthyroidism Clinical manifestations:
- Increase in BMR
- Warm and flushed skin
- Heat intolerance
- Sweating
- Weight loss despite increased appetite
- tachycardia
Hyperthyroidism Cardiac manifestations:
- Tachycardia, palpitations, cardiomegaly
- Congestive heart failure
- Fibrous changes
- Thyrotoxic / hyperthyroid cardiomyopathy- left ventricular dysfunction and “low output” heart failure
hyperthyroid sympathetic overactivity presentations
- Sympathetic overactivity
- Tremor, hyperactivity, emotional lability, anxiety, insomnia
- GI- hypermotility, diarrhea, decreased absorption
- Thyroid myopathy- proximal muscle weakness and atrophy
hyperthyroid ocular changes
- Wide, staring gaze and lid lag
- Due to sympathetic overstimulation of superior tarsal m.
- Thyroid ophthalmopathy occurs only in Graves
skeletal changes
osteoporosis and increased fracture risk
thyroid storm
- Abrupt onset of severe hyperthyroidism
- Medical emergency
- Untreated patients may die of cardiac arrhythmia
- MC in Graves
- Due to elevated catecholamine due to surgery, infection, other stress
- Fever, tachycardia common
apathetic hyperthyroidism
- Thyrotoxicosis symptoms may be blunted in older patients due to reduced response to thyroid hormones
- Often diagnosed incidentally during lab work-up for weight loss
hyperthyroidism diagnosis
- Serum TSH concentration is most diagnostic
- Free T4 usually elevated
- Radioactive iodine uptake determines etiology (graves, toxic adenoma, thyroiditis)
Hyperthyroidism: Graves Disease
Clinical triad:
-Hyperthyroidism associated with diffuse enlargement of thyroid gland
-Infiltrative ophthalmopathy with resultant exophthalmos
Protrusion of eyeball
-Localized dermopathy (pretibial myxedema)
-MC in women 20-40 years old
Hyperthyroidism:
Graves disease pathogenesis
Production of antibodies against thyroid proteins, especially TSH receptor
- MC thyroid-stimulating immunoglobulin (TSI)
- Mimics TSH and causes release of thyroid hormone
- Minority of patients may also have blocking antibodies leading to hypothyroidism
Goiter
- enlargement of thyroid gland
- Caused by impaired synthesis of thyroid hormone (MC iodine def.)
- TSH production increases to compensate
- Increased TSH causes hypertrophy of thyroid
- Hypertrophy is usually able to compensate and TH levels are normal
- Euthyroid metabolic state
Diffuse nontoxic (simple) goiter
- Enlargement of entire gland without nodularity
- AKA colloid goiter due to follicles filling with colloid
- Can be endemic (in areas of low iodine) or sporadic
Multinodular goiter
- Most longstanding simple goiter progresses to multinodular
- Due to recurrent episodes of enlargement and involution
- Produces most extreme thyroid enlargements
- Frequently mistaken for neoplasm
Hypothyroidism-
- condition caused by structural or functional derangement that
- interferes with TH production
- May affect up to 4% subclinically
- 10:1 Female:male ratio
- Results from defect anywhere in hypothalamic-pituitary-thyroid axis
Congenital hypothyroidism
- MC result of endemic iodine deficiency
- Other rare forms:
- Dyshormonogenetic goiter- inborn errors of thyroid metabolism
- Thyroid agenesis- complete absence of thyroid parenchyme
- Thyroid hypoplasia- genetic mutations causing reduced size
Autoimmune hypothyroidism
- MC cause in iodine-sufficient areas
- Majority of cases due to Hashimoto’s thyroiditis
- Autoantibodies produced against thyroid (anti-microsomal, antithyroid peroxidase, antithyroglobulin)
- May be associated with autoimmune polyendocrine syndrome
Iatrogenic hypothyroidism
- Caused by surgical or radiation-induced ablation
- Resection for treatment of hyperthyroidism, neoplasm can lead to hypothyroidism
- IV drugs can reduce thyroid function intentionally or as side effect
Cretinism
- hypothyroidism that develops in infancy or early childhood
-Manifestations:
-Mental retardation
Severity depends on maternal thyroid hormone levels
-Impaired skeletal, CNS development
-Short stature
-Coarse facial features
-Protruding tongue
-Umbilical hernia
Myxedema
- hypothyroidism developing in older children or adults
-Slowing of physical and mental activity
-May initially mimic depression
-Speech and intellectual functions slowed
-Cold intolerance
Overweight
-Decreased sympathetic activity
-Constipation, decreased sweating, cool pale skin
-Reduced cardiac output
-Shortness of breath, decreased exercise capacity
Cushing syndrome
-Elevated glucocorticoids
2 types:
1) Exogenous Cushing
2) Endogenous Cushing
Exogenous Cushing
Caused by administration of glucocorticoids (iatrogenic)
Accounts for vast majority of cases
2) Endogenous Cushing
2 forms:
- ACTH-dependent
- ACTH-independent
ACTH-dependent cushings
- adrenocorticotrophic hormones- released by anterior pituitary
- 70% ACTH-secreting pituitary microadenomas (“Cushing disease”). May also be pituitary macroadenoma or corticotroph cell hyperplasia
- 10% Ectopic ACTH secretion by non-pituitary tumors, MC small cell lung carcinoma
-ACTH-independent
- Primary adrenal neoplasms secrete glucocorticoids
- MC adrenal adenoma (10%) and carcinoma (5%)
- Elevated cortisol, low ACTH
cushings Hypercortisolism clinical mainfestations
- slow onset
- moon face
- buffalo hump
- fast twitch muscle atrophy
- 2ndary diabetes
- thin skin
- osteoporosis
primary hyperaldosteronism
- chronic
- suppression of renin-angiotensin pathway
- blood pressure elevation is MC manifestation
Primary hyperaldosteronism is caused by?
3 mechanisms:
1) bilateral idiopathic hyperaldosteronism (IHA)
2) adrenocortical neoplasm
3) glucocorticoid remediable hyperaldosteronism
bilateral idiopathic hyperaldosteronism
- Nodular hyperplasia of adrenal glands
- 60% of cases
- MC in older patients
- Characterized by relatively less severe hypertension
Adrenocortical neoplasm
- Either aldosterone-producing adenoma (MC) or carcinoma (rare)
- 35% of cases involve single adenoma (Conn syndrome)
- MC in middle-aged women
Glucocorticoid-remediable hyperaldosteronism
Uncommon genetic condition, suppressible by dexamethasone
secondary hyperaldosteronism
- Aldosterone released in response to high levels of angiotensin
- increased serum renin
Secondary Hyperaldosteronism Clinical manifestations
Hypertension (MC cause of secondary hypertension)
Left ventricular hypertrophy
Increased risk of stroke, MI
Hypokalemia
Congenital adrenal hyperplasia
-Lack of various enzymes involved in cortical steroid synthesis (cortisol)
Congenital adrenal hyperplasia 3 types:
1) salt wasting syndrome
2) Simple virilizing adrenogenital syndrome
3) non classic or late onset adrenal virilism
Salt-wasting syndrome
- Inability to convert progesterone to deoxycorticosterone due to lack of 21-hydroxylase
- Virtually no synthesis of mineralcorticoids
- Salt wasting, hyponatremia, hypokalemia
- Virilization
- Females diagnosed in womb
- Males not diagnosed until salt wasting crisis
Simple virilizing adrenogenital syndrome without salt wasting
- 21-Hydroxylase deficiency but with sufficient mineralcorticoid to spare salt
- Virilization
Nonclassic or late-onset adrenal virilism
- MC form
- Only partial 21-hydroxylase deficiency
- May be virtually asymptomatic
Adrenocortical insufficiency
- May be primary or secondary due to decreased ACTH
- 3 patterns:
1) Primary acute adrenocortical insufficiency (adrenal crisis)
2) Primary chronic adrenocortical insufficiency (Addison disease)
3) Secondary adrenocortical insuffiency
Primary chronic adrenocortical insufficiency (addisons disease)
- progressive destruction of adrenal cortex
- asymptomatic in 9-0%
addison’s disease (Primary chronic adrenocortical insufficiency) causes?
- autoimmune adrenalitis
- infection
- MC = TB
- metastatic neoplasm
- genetic causes
addison’s disease (Primary chronic adrenocortical insufficiency) Clinical manifestations:
- Early: progressive weakness and fatigability
- Gastrointestinal disturbances
- Hyperpigmentation of skin (only in primary form)
Pheochromocytoma
- Neoplasm composed of chromaffin cells
- Usually located in adrenal medulla
- Synthesize and release catecholamines, peptide hormones
- Rare cause of surgically correctable hypertension
- Clinical features- (“rule of tens”)
