Endocrine Flashcards
1
Q
Total T4 (thyroxine)
A
- elevated in most hyperthyroid patients and decreased in hypothyroidism
- <5% of hyperthyroid patients have normal T4 but elevated T3
- T4 is highly bound, so fluctuations in serum proteins limit the value of total T4 and total T3
- Bound to prealbumin (transthyretin) and thyroid binding globulin (TBG)
2
Q
Thyroglobulin increased by ___ and decreased by ___
A
- Increased by
- pregnancy
- oral contraceptives
- estrogen therapy
- active hepatitis
- hypothyroidism
- Decreased by
- hypoproteinemic states
- androgen therapy
- cortisol
3
Q
A
4
Q
T3 resin uptake (T3RU)
A
- no longer used
- in hyperthyroidism there is high T3 resin uptake and in hypothyroidism there is low T3 resin uptake
5
Q
Free T4 and free T3
A
Correlate well with clinical thyroid status
6
Q
Euthyroid sick syndrome
A
- Reverse T3 (rT3) is a metabolic product of T4 (most of which is metabolized to T3)
- rT3 is elevated
- T3 and T4 are low
- seen in patients with nonthyroidal systemic illness
7
Q
Thyroid releasing hormone (TRH)
A
- TRH stimulation test is used in evaluation of hypothyroidism
- In primary hypothyroidism there is exaggerated secretion of TSH in response to TRH
- An inappropriate TSH response to TRH suggests hypopituitarisim
8
Q
TSH (thyrotropin)
A
- best first line test for diagnosing hypo and hyperthyroidism
- TSH elevated in hypothyroidism
- Not as helpful in hypothalamic or pituitary dysfunction and neonatal screening
- fT4 indicated in these patients in addition to TSH
9
Q
Hyperthyroidism
- diagnosis
- disease
- labs
A
- Diagnosis
- low TSH
- high serum FT4
- when FT4 is normal despite a low TSH, free T3 should be measured to assess for T3 thyrotoxicosis
- Diseases
- Graves disease is most common cause
- toxic multinodular goiter
- toxic adenoma (Plummer syndrome)
- transient hyperthyroidism in various kinds of thyroiditis
- exogenous thyroxine
- pituitary adenoma
- thyroid carcinoma
- Labs
- thyroid stimulating immunoglobulin in Graves, aka long acting thyroid stimulating antibodies
- antimicrosomal antibodies (aka, TPO antibodies found in 60% of cases of Graves
- antithyroglobulin antibodies in 30% of cases of Graves
10
Q
Hypothyroidism
- diagnosis
- causes
A
- Elevated TSH and low free T4
- Causes
- Hashimoto thyroiditis is most common cause
- Thyroidectomy
- Lymphocytic and granulomatous thyroiditis (de Quervain)
- I-131 therapy
- radiation
- drugs (iodine, lithium, IL-2, alpha-IFN)
- Hashimoto characterized by anti tissue peroxidase and antithyroglobulin (>90%) antibodies
- TSI not identified in Hashimoto
11
Q
Neonatal hypothyroidism
A
- Caused by
- Most often caused by thyroid dysgenesis
- familial thyroid dyshormonogenesis
- peripheral hormone resistance (autosomal dominant Refetoff syndrome)
- hypopituitarism
- maternal factors (maternal autoantibodies and medications)
12
Q
Nonthyroidal illness syndrome (euthyroid sick syndrome)
A
- abnormal thyroid function tests in euthyroid person suffering from a nonthyroidal illness
- decreased T3 and T4
- increased rT3
- normal TSH
13
Q
Medications that affect thyroid hormones
A
- Amiodarone causes hypothyroidism in iodine rich parts of the world and hyperthyroidism in iodine poor parts of the world
- Lithium inhibits release of thyroxine resulting in hypothyroidism
14
Q
Effect of exogenous estrogen on thyroid hormones
A
- Increase circulating thyroid binding globulin (TBG)
- thus total thyroxine (T3 and T4) are elevated
- Free thyroxine and TSH remain normal
15
Q
Characteristics of cortisol secretion
A
- Diurnal variation
- trough around midnight
- peak at 8 AM
- depends on levels of cortisol binding globulin
- low 8 AM secretion suggests adrenal insufficiency
16
Q
Cushing syndrome
A
- Elevated serum cortisol
- loss of diurnal variation
- Low dose DST does not suppress cortisol
- High dose DST should suppress cortisol
17
Q
Urine free cortisol test
A
- 24 hour urine collection
- reflects free (unbound) serum cortisol
- independent of time of day
18
Q
Dexamethasone suppression test
A
- dexamethasone suppresses ACTH and cortisol in a normal patient
- abnormal suppression seen in Cushing syndrome, which includes Cushing disease
- low dose DST given in two forms
- rapid (overnight) DST
- standard (2 day) DST
- normal people have suppression of cortisol
- abnormal suppression confirms diagnosis of Cushing syndrome or pseudoCushing (severe stress, alcohol abuse, major depression)
- high dose DST determines if patient has Cushing syndrome or Cushing disease (pituitary adenoma)
- Suppression implies pituitary adenoma
- Nonsuppression means
- ectopic ACTH production by tumor OR
- primary adrenal hypercortisolism
- The above two diseases can be distinguished by plasma ACTH measurement
- low dose DST given in two forms
19
Q
Cortisol releasing hormone (CRH) stimulation test
A
- like high dose DST, is aimed at determining cause of Cushing syndrome
- exaggerated elevation of ACTH and cortisol suggests Cushing disease (pituitary adenoma)
- No response seen in adrenal tumor or ectopic ACTH
20
Q
Diagnosis of Cushing syndrome
A
- Persistent hypercortisolism
- Screening tests (positive test should be confirmed by repeat test)
- low dose DST
- 24 hour urinary free cortisol
- midnight salivary or serum cortisol
- Measure ACTH
- ACTH dependent Cushing is evaluated with bilateral inferior petrosal sinus sampling (BIPSS) OR high dose DST and/or CRH stimulation tests
- Imaging of pituitary lacks S and S when used in isolation
- ACTH independent Cushing requires adrenal imaging (also need to exclude surreptitious steroid administration)
21
Q
Etiology of Cushing syndrome
A
- Iatrogenic Cushing syndrome - administration of steroids for treatment of inflammatory disease - is most common cause
- noniatrogenic causes
- pituitary adenoma (Cushing disease) - usually microadenoma of basophilic cells (corticotrophs)
- adrenal gland abnormality
- adenoma
- carcinoma
- bilateral adrenal hyperplasia
- ectopic ACTH
- small cell lung CA
- lung carcinoid
- pancreatic endocrine tumors
- non-small lung CA
- thymic tumors
- medullary thyroid carcinoma
- breast carcinoma
22
Q
Effects of Cushing syndrome
A
- hyperglycemia
- hypoK
- protein catabolism
- osteoporosis
- centripetal fat deposition
- skin thinning with striae
23
Q
Illness that looks like Cushing clinically and chemically, but isn’t
A
- depression
- anorexia
- alcoholism
- pregnancy
24
Q
Diagnosis of Addison disease
A
Primary adrenal insufficiency
- low 8 AM serum cortisol and/or blunted increase in cortisol following cosyntropin stimulation
- ACTH guides further evaluation
- Elevated ACTH: primary adrenal insufficiency
- perform autoantibody studies and/or imaging
- Normal or low ACTH suggest secondary adrenal insufficiency, most likely related to pituitary pathology or exogenous glucocorticoid administration
- Elevated ACTH: primary adrenal insufficiency
25
Etiology of Addison disease
* Primary destruction of adrenal gland by granulomatous disease (TB)
* Autoimmunity
* Metastatic tumor
* Amyloid
* Bilateral hemorrhage (Waterhouse Friderichsen syndrome)
* Congenital diseases
* CAH
* Adrenoleukodystrophy
* Drugs
* ketoconazole etomidate
* mitotane
26
Addisonian crisis and other symptoms
1. AMS
2. hypotension (including postural)
3. hypoglycemia
4. hypoNa
5. hyperK
6. metabolic acidosis
7. fatigue
8. weight loss
9. weakness
10. mood alteration
11. skin hyperpigmentation
27
Secondary adrenal insufficiency
* exogenous steroids usually that lead to irreversible suppression of endogenous ACTH production
* not as severe as Addison disease because renin-angiotensin system maintains mineralcorticoid production
* hyperK is absent and hypoNa is mild
* hyperpigmentation is not seen
28
Conn syndrome
Hyperaldosteronism
* Usually due to an adrenal adenoma or bilateral adrenal hyperplasia
* secondary hyperaldosteronism is seenin hyperreninemic states such as renal artery stenosis or renin producing juxtaglomerular cell tumor of the kidney
* Results in
* HTN
* hypoK
* metabolic alkalosis
* ratio of plasma aldosterone concentration to plasma renin activity is considered best screening test; must be confirmed by a 24 hour urinary aldosterone level
29
congenital adrenal hyperplasia
* Etiology
* 21 hydroxylase deficiency is the most common cause
* 11 hydroxylase deficiency is second most common cause
* Native Americans and Yupic Eskimos
* gene for 21 hydroxylase is on 6p21.3 within the HLA complex
* compensatory increase in ACTH by the pituitary leads to increased production of steroid hormone precursors in the adrenal cortex
* Resulting adrenal hyperplasia causes
* salt wasting
* HTN
* virilization
* Increased 17 hydroxyprogesterone
* Decreased cortisol
* Increase ACTH
* Increased androgens
* Increased 17-ketosteroids
* Decreased aldosterone
30
31
Pituitary adenoma
* Hypersecretion of anterior pituitary is almost always caused by a pituitary adenoma
* Prolactinoma is most common
32
Pituitary hypofunction
* rarely involves a single hormone
* causes
* tumors impinging on pituitary gland (nonsecretory pituitary adenoma, craniopharyngioma)
* infarction (Sheehan syndrome, sickle cell anemia)
* sarcoidosis
* histiocytosis X
* hemochromatosis
* irradiation
* autoimmune destruction
33
Hypothalamic disorders and interruption of pituitary stalk
* All anterior pituitary hormones except prolactin are suppressed (i.e., "stalk effect")
* Hormones in anterior pituitary:
* somatotropes (GH)
* prolactins (PRL)
* gonadotropes(LH and FSH)
* corticotropes (ACTH)
* thyrotropes (TSH)
34
Growth hormone hyposecretion
* dwarfism in children
* adults are asymptomatic
* undetectable GH levels occur in healthy subjects and are not diagnostic of hyposecretion
* provocative testing is required performed by measuring GH in
* fasting state
* during sleep
* following exercise
* following insulin or arginine administration
35
Growth hormone hypersecretion
* gigantism in children
* acromegaly in adults
* IGF-1 consistently elevated in GH hypersecretion
* normal IGF-1 excludes GH excess
* markedly elevated GH from a random blood sample or a relatively normal level that fails to suppress with glucose administration can diagnose GH excess
36
Follicle stimulating hormone
* FSH assays can be useful in women \< 45 yo presenting with possible early menopause
* persistently elevated FSH suggests ovarian failure
37
Prolactin
- regulation
- causes of hyperPRL
- findings in hyperPRL
* does not have a dedicated stimulator for its release
* instead, the hypothalamus produces an inhibitor: **dopamine**
* if connection between hypothalamus and pituitary is severed, all anterior pituitary hormones decrease except prolactin, which markedly increases due to lack of inhibition
* HyperPRL
* **amenorrhea galactorrhea** syndrome in women
* **testicular atrophy, impotence, and gynecomastia** in men
* usually 2/2 prolactin secreting pituitary **adenoma**
* other causes
* **pregnancy**
* **lactation**
* **stalk compression**
* **macroprolactinemia**
* **phenothiazine** therapy
38
Diabetes insipidus
* Results from inadequate ADH activity
* Polyuria and polydipsia with low urine osmolarity and hyperNa
* Types
* Central DI
* inadequate ADH secretion caused by
* head trauma
* mass lesions involving pituitary
* X linked recessive familial form
* Nephrogenic DI
* renal tubules unresponsive to ADH
* Caused by
1. hyperCa
2. hypoK
3. very low protein diet
4. demeclocycline
5. lithium
6. relief of longstanding obstruction
7. familial
8. normal aging
* Confirmed by overnight water deprivation test followed by administration of ADH (vasopressin)
* in healthy people urine osmolarity progressively increases during water deprivation and administration of exogenous ADH has no additional effect on urine concentration
* In central DI there is failure to appropriately concentrate urine in response to dehydration and a rise in urine osmolarity in response to administered ADH
* In nephrogenic DI urine cannot be concentrated in either case (dehydration or with ADH admin)
39
Syndrome of inappropriate ADH (SIADH)
* hypoNa normovolemia
* urine sodium \> 20 mmol/L
* urine osmolarity \> 100 mOsm/kg
* Caused by
* tumors
* small cell carcinoma of the lung
* pancreatic adenocarcinoma
* intracranial tumors
* interstitial lung disease
* cerebral trauma
* chlorpropamide
