Endocrine Function II: Thyroid, Sex, and Gastrointestinal Hormones; Regulation of Calcium and Phosphorus Levels Flashcards
List three thyroid binding proteins
- Throxine binding globulin (TBG)
- Transthyretin (Thyroxine Binding Prealbmin) (TBPA)
- Albumin
Which thyroid hormone secreted in the greatest quantity?
T4 is the main secretory prodct
Which thyroid hormone is the most potent, biologically active?
T3
Describe the structure and clinical significance of increased levels of reverse T3
Biologically inactive form favored under stress
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List eight physiological effects of thyroid hormones
- Increased oxygen consumption
- Increases basal metabolic rate
- Stimulates heart rate/contraction
- Stimulates protein synthesis
- Stimulates all aspects of lipid metabolism
- Affects all aspects of CHO metabolism (4 “Gs”)
- Increases demands for vitamins and coenzymes
- Provides negative feedback to TRH and TSH
What is the cause of hyperthyroidism in Graves’ Disease?
Autoimmune etiology
- AutoAbs bind to TSH receptors in thyroid
- Body thinks it’s getting TSH but is fooled by Abs
What is the cause of hyperthyroidism in toxic multinodular goiters?
- Discrete portions of thyroid are not under normal feedback control
- No exophthalmopathy but still producing thyroid hormone
What is the cause of hyperthyroidism in solitary toxic adenoma?
- Patients have thyroid nodules that avidly concentrate injected radioactive iodine
- Benign tumor doesn’t respond to normal feedback control
Nodules that concentrate injected radioactive iodine
“Hot nodules”
What causes hyperthyroidism in subacute thyroiditis?
- Inflammation of the thyroid gland
- Appears to be viral in origin
- Follicles become inflamed and disrupted
What causes hyperthyroidism in iatrogenic symptoms?
Adverse mental or physical conditions caused by a medical procedure/physician
What causes hyperthyroidism in factitious symptoms?
- Disorders that aren’t genuine or natural
- Physical or psychological symptoms are produced under the voluntary control of the patient
What causes hyperthyroidism in TSH-dependent hyperthyroidism?
Caused by excess placental hormones (hCG) and TSH-secreting pituitary tumors (tertiary in hypothalamus)
List the symptoms associated w/ hyperthyroidism
- Heat intolerance
- Flushing
- Perspiration
- Increased appetite
- Weight loss
- Tachycardia
- SOB
- Nervousness
- Sometimes exophthalmopathy
TSH-independent hyperthyroidism
- T3 levels
- T4 levels
- TSH levels
- T3 levels: ↑
- T4 levels: ↑
- TSH levels: ↓
TSH-dependent (2°) hyperthyroidism
- T3 levels
- T4 levels
- TSH levels
- T3 levels: ↑
- T4 levels: ↑
- TSH levels: ↑
TSH-dependent (3°) hyperthyroidism
- T3 levels
- T4 levels
- TSH levels
- T3 levels: ↑
- T4 levels: ↑
- TSH levels: ↑
Primary hyperthyroidism (TSH-independent) diseases
- Graves’ disease
- Toxic multinodular goiter
- Solitary toxic adenoma
- Subacute (“painless”) thyroiditis
- Iatrogenic
- Factitious
What is the treatment for hyperthyroidism?
Any anti-thyroid drugs, radio-iodine ablation, or thyroidectomy
List the symptoms of hypothyroidism
- Cold intolerance
- Dry skin
- Decreased appetite
- Muscle weakness
- Slow heart rate
- Low BP
- Weight gain
- Hoarseness due to thickened vocal cords
- More common in women
What causes hypothyroidism?
- Diseases (commonly autoimmune) or treatments that destroy thyroid tissue or interefere w/ thyroid hormone biosynthesis
- Less often caused by secondary (pituitary) or tertiary (hypothalamic) disorders
Primary hypothyroidism diseases
- Adult hypothyroidism
- Cretinism (pluts endemic goiter)
- Hashimoto’s thyroiditis
Secondary hypothyroidsm disorders
Pituitary or hypothalamus disease/removal/destruction
What are the five causes of adult hypothyroidism?
- Intrinsic disease of the thyroid
- Total thyroidectomy
- Complete blockage or thyroid function by irradiation or an antithyroid drug
- Various diseases
- Myxedema causes face puffiness, doughy skin, subcutaneous emea
What is the cause of cretinism (neonatal hypothyroidism)
- Failure to develop thyroid gland in utero
- If mother receives anti-thyroid drugs or radioactive iodine during pregnancy
- If maternal antithyroid Abs cross placenta (results in mental retardation)
What is the cause of hypothyroidism due to iodine deficiency (endemic goiter)
- W/ little or no iodine, less hormone is made to provide negative feedback to TSH, which is continually trying to stimulate hormone production
- This eventually causes hyperplasia and large goiters
What causes Hashimoto’s thyroiditis?
- Most common cause of hypothyroidsm
- Autoimmune, chronic inflammatory disease of thyroid in
T-hleper cells stimulate B-lymphs to produce antithyroid Abs - Defect in organification, causing lymphocytic infiltration of thyroid
What causes secondary/tertiary hypothyroidism?
Any factor that affects TSH or TRF production
- Infection
- Surgical removal of pituitary or hypothalamus
- Trauma
- Cancer
- Autoimmune destruction of pituitary and/or hypothalamus
Primary hypothyroidism
- T3 levels
- T4 levels
- TSH levels
- T3 levels: ↓
- T4 levels: ↓
- TSH levels: ↑
- TRF (TRH) levels: ?
Secondary hypothyroidism
- T3 levels
- T4 levels
- TSH levels
- TRF (TRH) levels
- T3 levels: ↓
- T4 levels: ↓
- TSH levels: ↓
- TRF (TRH) levels: ?
Tertiary hypothyroidism
- T3 levels
- T4 levels
- TSH levels
- TRF (TRH) levels
- T3 levels: ↓
- T4 levels: ↓
- TSH levels: ↓
- TRF (TRH) levels: ?
Define euthyroidism
- Condition in which the serum total thyroid hormone concentrations are abnormal, WITHOUT evidence of clinical thyroid disease
- Reverse T3 levels are elevated until recovery
What causes euthyroidism?
- Pathogenesis is unknown
- May include decreased peripheral conversion of T4 to T3 and decreased binding of thyroid hormones to TBG
- Proinflammatory cytokines may be responsible for some of these changes
Diagnosis of euthyroidism vs. hypothyroidism
- Slight TSH elevation occurs during euthyroid recovery
- Elevation of TSH (> 30 mU/mL) indices true hypothyroidism
Euthyroidism
- T3 levels
- T4 levels
- TSH levels
- Reverse T3
- T3 levels: ↓
- T4 levels: ↓
- TSH levels: normal
- Reverse T3: ↑ (slight ↑ during recovery)
What is the TRH (TRF) stimulation test used for?
- To distinguish b/w 2° and 3° hypothyroidism
- Synthetic TRH is administered and TSH response is monitored
- If no TSH increase → 2°
- If significant TSH increase → 3°
What do the total T4/T3 assays measure?
Measure both free and bound hormone
What is the clinical use of total T3 test?
Use for diagnosis and monitoring of hyperthyroid patients w/ suppressed TSH levels and normal FT4 levels
This assay is the most sensitive and specific measure of thyroid activity
TSH
What is the clinical use of the thyroglobulin test?
- Primarily to monitor patients w/ FSH cancer (which would be increased)
- Storage form of thyroid hormone precursors
What is the clinical use of the T3 Uptake test w/ thryoid hormone binding ratio (THBR)?
- Clinical use is to directly or indirectly assess available TBG binding sites, but is not used to diagnose hyperthyroidism or hypothyroidism
- May be ordered if the patient has an abnormal total T4 or total T3 levels w/ normal TSH
- The “discrepancy” may be due to ↑ or ↓ TBG levels → patient’s thyroid is functioning just fine
What is the clinical use of total T4?
This test by itself, does not provide enough clinical information and must be reported in conjunction with the other thyroid tests
THBR
This test provides an approximation of the free hormone concentration in the presence of abnormal TBG levels as TBG or free hormone levels are not easily measured
What factors increase TBG levels?
- Pregnancy
- Estrogen replacement therapy
- Oral contraceptives
- Porphyria
- Hydatidiforme mole
- Heroine or methadone abuse
- Clofibrate
What factors decrease TBG levels?
- Androgens
- Anabolic steroids
- Nephrotic syndrome
- Cirrhosis
- Corticosteroids
- Cushing’s syndrome
- Acromegaly
How does the THBR differentiate true hypothyroidism or hyperthyroidism and states of ↑ or ↓ TBG concentrations w/ normal thyroid function
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Primary hyperthyroidism (thyroid problem)
- Total T3
- Total T4
- FT3
- FT4
- TSH
- THBR
- Total T3: ↑
- Total T4: ↑
- FT3: ↑
- FT4: ↑
- TSH: ↓
- THBR: ↓
Primary hypothyroidism (thyroid problem)
- Total T3
- Total T4
- FT3
- FT4
- TSH
- THBR
- Total T3: ↓
- Total T4: ↓
- FT3: ↓
- FT4: ↓
- TSH: ↑
- THBR: ↑
Secondary hyperthyroidism (pituitary problem)
- Total T3
- Total T4
- FT3
- FT4
- TSH
- THBR
- Total T3: ↑
- Total T4: ↑
- FT3: ↑
- FT4: ↑
- TSH: ↑
- THBR: ↓
Secondary hypothyroidism (pituitary problem)
- Total T3
- Total T4
- FT3
- FT4
- TSH
- THBR
- Total T3: ↓
- Total T4: ↓
- FT3: ↓
- FT4: ↓
- TSH: ↓
- THBR: ↑
Tertiary hyperthyroidism (hypothalamus problem)
- Total T3
- Total T4
- FT3
- FT4
- TSH
- THBR
- Total T3: ↑
- Total T4: ↑
- FT3: ↑
- FT4: ↑
- TSH: ↑
- THBR: ↑
Tertiary hypothyrodism (hypothalamus problem)
- Total T3
- Total T4
- FT3
- FT4
- TSH
- THBR
- Total T3: ↓
- Total T4: ↓
- FT3: ↓
- FT4: ↓
- TSH: ↓
- THBR: ↓
What is the specific diagnostic usefulness of the antithyroidglobulin Ab (TgAb)?
- Hashimoto’s thyroiditis >85% reactivity
- Graves’ Disease >30% reactivity
- Tumor marker for recurrence of thyroid cancer
What is the specific diagnostic usefulness of the thyroid peroxidase autoAb (TPOAb)?
- Hashimoto’s thyroiditis 100% reactivity
- Graves’ Disease 70-80% reactivity
- Ab itself may be cytotoxic to the thyroid
What is the specific diagnostic usefulness of the TSH receptor autoAb (TRAb)?
- Igs that bind to thyroid cell membranes at or near the TSH-receptor site
- Either cause hyperactivity of the thyroid (Graves’) or an inability for TSH to stimulate the thyroid (Hashimoto’s)
- Used for differential diagnosis of hyperthyroidism
- Used to predict fetal and neonatal thyroid dysfunction due to transplacental passage of maternal TRAb
- Used to predict the course of Graves’ disease patients on antithyroid drug therapy
of carbons present in estrane
18 carbons
of carbons present in androstane
19 carbons
of carbons present in pregnane
21 carbons
What is the analytical importance of the phenolic hydroxyl group on carbon #3 on estrane and its derivatives?
- Estrogens on carbon #3
- Androgens do not have this
Estrogen
- Biological effects
Primary and secondary sexual characteristics
Estrogen
- Site of production
Graafian follicle of ovaries
Estrogen
- Most potent, physiologically-active estrogen
Estradiol (E2)
- Evaluates ovarian fxn
Estrogen
- Major post-menopausal estrogen
Estrone (E1)
Estrogen
- Major estrogen produced during pregnancy
Estriol (E3)
- ↓ in fetal distress and measured to monitor progress of pregnancy
Estrogen production is stimulated by ____ and ____ from the anterior pituitary
FSH; LH
Estrogen
- Metabolic activities
- Increases protein synthesis (CBG, TBG)
- Increases production of HDL and VLDL
- Promotes development/maturation/fxn of female reproductive system
- Accelerates linear growth (height)
Describe the menstrual cycle w/ the rise and fall of estrogen, FSH, and LH
E2 (estradiol) removes negative feedback for FSH/LH which ↑ FSH and estrogen
What hormones are responsible for the menstrual cycel?
- GnRH
- FSH
- LH
- Estrogens
- Progesterone
GnRH
- Source
Hypothalamus
FSH
- Source
Pituitary
LH
- Source
Pituitary
Estrogens
- Source
Ovary (follicle)
Progesterone
- Source
Ovary (corpus luteum)
GnRH
- Function during menstrual cycle
Stimulates pituitary to secrete FSH and LH above a basal level
LH
- Function during menstrual cycle
- Surge of LH stimulates follicle to break open and discharge ovum and follicular fluid (containing estrogens)
- Follicle converted into corpus luteum, which secretes estrogens and gradually increasing amounts of progesterone
FSH
- Function during menstrual cycle
- Stimulates ovaries to develop mature follicles (w/ ova)
- Follicles produce increasing high levels of estrogens
Estrogens
- Function during menstural cycle
- Causes rapid grwoth of endometrium of uterus
- Causes breast sensitivity that often accompanies menstrual flow to disapear
- Rising level of estrogens have negative feedback effect on hypothalamus and GnRH
- GnRH output reduced, and secretion of FSH and LH inhibited
- Very high level of estrogens reverses effect on hypothalamus, stimulating it to suddenly release large doses of GnRH
- GnRH causes pituitary to release sudden surge of FSH and LH
Progesterone
- Function during menstrual cycle
- Causes endometrium to become thick, spongy, glandular, and receptive to a fertilized ovum (zygote)
- Causes breast engorgement (sensitive or painful)
- Has negative feedback on pituitary
- Causes a drop in LH production, which results in the degradation of the corpus luteum and a drop in progesterone and estrogen production
- Lack of progesterone initiates menstrual flow
What is the SPECIFIC biological effect of FSH in women?
Chooses an egg
What is the SPECIFIC biological effect of LH in women?
LH stimulates ovulation
Discuss the menstrual cycle according to the rise and and fall of estrogen, FSH, and LH
?
What is the clinical usefulness of continuously monitoring estriol levels urging pregnancy?
Indicates status of fetoplacental unit
- Need premature delivery if there’s a sharp decrease in levels
Historical method for measuring estrogen
Kober Reaction by GM-MS
Specific site of progesterone production in pregnant women
Placenta
Specific site of progesterone production in non-pregnant women
Ovarian corpus luteum
Three uses for progesterone measurement
- Detect ovulation
- Detect ovarian tumors
- Detect placental dysfunction
Physiological effects of progesterone
- Stimulates breast development
- Increases body temperature
- Prepares uterus for fertilized egg implantation
- Important for maintenance of pregnancy-
Function of progesterone that act in synergy w/ estrogen
- Build up thin endometrial lining
- Diminish muscular contractions
- Change quantity/consistency of cervical mucus to allow penetration/viability of sperm
Two physiological effects of hCG
- Produced by trophoblasts that become the placenta
- Stimulates progesterone production by corpus luteum
Why is the ß-subunit assayed for hCG?
α-subunit is identical to those of FSH, LH, and TSH
Four uses for the measurement of hCG
- Pregnancy testing
- Prediction of spontaneous abortion
- Detection of multiples
- Detection of follow-up of hCG-producing tumors (testes, ectopic, pregnancy, hydatidiform moles, choriocarcinoma, cancer of prostate, lung, and breast)
Two physiological effects of human placental lactogen (HPL)
- Stimulates mammary gland development
- Used to monitor conditions associated w/ decrease in functional placental tissue
Is estriol increased or decreased w/ Down Syndrome?
Decreased (fetal distress)
HPL is a ____ hormone that acts in concert w/ ____ to stimulate hormone production by corpus luteum
Protein; hCG
hCG is a ____ hormone consisting of α-subunit identical to FSH, LH, and TSH
Protein
Results from overgrowth of tissue that was to become the placenta
Hydatidiform mole
Partial and complete molar pregnancies are due to problems during ____
Fertilization
What are the 19-carbon androgen compounds responsible for?
- Differentiation and maturation of the reproductive organs
- Secondary sexual characteristics
- Increased muscle mass and long bone growth
Three physiological effects of androgens
- Differentiation and maturation of reproductive organs
- Secondary sexual characteristics
- Increased muscle mass and long bone growth
Two sites of production of androgens
?
Three male reproductive abnormalities
- Hypogonadotropic hypogonadism
- Hypergonadotropic hypogonadism
- Klinefelter’s syndrome
Hypogonadotropic hypogonadism
- Testosterone levels
- FSH levels
- LH levels
- Testosterone levels: ↓
- FSH levels: ↓
- LH levels: ↓
(Indicates pituitary problem)
Hypergonadotropic hypogonadism
- Testosterone levels
- FSH levels
- LH levels
- Testosterone levels: ↓ (no negative feedback)
- FSH levels: ↑↑
- LH levels: ↑↑
(Primary failure = small testes)
Klinfelter’s syndrome
- Testosterone levels
- FSH levels
- LH levels
?
What is the SPECIFIC biological effect of FSH in men?
Stimulates Leydig cells to produce testosterone and Sertoli cells to produce sperm
What is the SPECIFIC biological effect of LH in men?
Stimulates Leydig cells in testes to produce testosterone
What is the SPECIFIC biological effect of testosterone?
Stimulates Sertoli cells to produce sperm and negatively feeds back on the anterior pituitary pituitary and hypothalamus
What is the SPECIFIC biological effect of the Sertoli cells?
Produce inhibin that negatively feeds back on the anterior pituitary and hypothalamus
Feedback loop that exists among GnRH in the hypothalamus, LH and FSH in the anterior pituitary, Leydig and Sertoli cells in males
?
Vitamin D
- Biologically active form
Calcitriol aka 1,25-dihydroxycholecalciferaol (1,25-dihydroxy vitamin D)
Vitamin D
- Specific effects on the intestine, kidney, and bone
- Stimulates production of intestinal transport molecules specific for the absorption of Ca2+ and phosphorus
- Works w/ PTH to enhance bone resorption (osteoCLASTIC activity)
- Enhances renal reabsorption of Ca2+ and phosphorus
Vitamin D
- Net effect on blood calcium and phosphorus concentrations
To increase blood levels of both calcium and phosphorus
Vitamin D
- Three functions
- Stimulates production of intestinal transport molecules specific for the absorption of calcium and phosphorus
- Works w/ PTH to enhance bone RESORPTION (osteoCLASTIC activity)
- Enhances renal reABsorption of calcium and phosphorus
PTH
- Specific site of production
Parathyroid gland
PTH
- Specific stimulus for its release
Low ionized Ca2+ levels in blood
PTH
- Specific effects on the intestine, kidney, and bone
- ↑ intestinal absorption of Ca2+ and phosphorus by stimulating renal formation of calcitriol (indirect action)
- ↑ bone resorption (osteoCLASTIC activity)
- ↑ renal tubular reabsorption of Ca2+
- ↓ renal tubular reabsorption of phosphorus
PTH
- Net effect on blood Ca2+ and phosphorus concentrations
To increase blood levels of Ca2+ and decrease levels of phosphorus
Calcitonin
- Site of production
Synthesized in the parafollicular cells of the thyroid gland
- Hypermagnesemia increases its release
Calcitonin
- Specific effects on the intestine, kidney, and bone
Opposes vitamin D and PTH
- ↓ intestinal absorption of Ca2+ and phosphorus
- Inhibits bone resorption (has osteoBLASTIC activity)
- ↓ renal reabsorption of Ca2+ and phosphorus
Calcitonin
- Net effect on blood Ca2+ and phosphorus concentrations
Decrease both Ca2+ and phosphorus
Calcitonin
- Two functions
- Stimulate bone formation
- Enhance secretion of filtered Ca2+ and phosphorus
Hyperparathyroidism
- Most common cause
- Adenoma
- Hyperplasia
Hyperparathyroidism
- Consequences on renal and bone tissue due to hypercalcemia
Bone resorption as Ca2+ and phosphorus are released to the blood
Hyperparathyroidism
- Ca2+
- Phosphorus
- PTH
- ↑ Ca2+
- ↑ Phosphorus
- ↓ PTH
Hypoparathyroidism
- Most common primary cause
Surgical procedures
Hypoparathyroidism
- Blood/urine Ca2+
- Phosphorus
- ↓ blood Ca2+
- Urine Ca2+
- ↑ blood phosphorus
- Urine phosphorus
Hypervitaminosis
- Blood Ca2+ and phosphorus levels
Both are increased
List diseases associated w/ vitamin D deficiency?
- Cancer
- Autoimmune disease
- Lung disease
- Infections
- Schizophrenia
- Malabsorption diseases
Gastrin
- Specific site of production
Peptide hormone secreted by G-cells of stomach antrum (lower third) in response to contact w/ food
Gastrin
- Function
- Causes HCl production by parietal cells in stomach
- Causes negative feedback as pH ↓
List diseases that cause hypergastrinemia?
- Achlorhydria
- Pernicious anemia
- Gastrinomas
Syndrome associated w/ gastrinomas
Zollinger-Ellison Syndrome
Secretin
- Specific site of production
Secreted by duodenal and upper jejunal intestinal mucosa after contact w/ gastric HCl
Secretin
- Function
Stimulates pancreas and liver to secrete HCO3 to counteract stomach acidity
Cholecystokinin-pancreozymin (CCK-PZ)
- Specific site of production
Produced by upper intestinal mucosal cells after contact w/ peptones, fatty acids, and HCl entering duodenum
What causes CCK-PZ?
Gallbladder contraction and pancreatic enzyme secretion
What is the amine hormone derived from the hydroxylation and decarboxylation of tryptophan?
Serotonin
Serotonin
- Specific site of production
Synthesized primarily by the enterchromaffin cells located in the GI tract
Serotonin
- Two physiological effects
- Smooth muscle stimulation
- Vasoconstriction (elevates mood)
Syndrome associated w/ serotonin-producing tumors
Carcinoid syndrome
Urinary metabolite of serotonin commonly measured in the lab
24-hour collection for 5-HIAA
What are the placental hormones?
- hCG
- Progesterone
- HPL
What are the ovarian hormones?
- Estrogen
- Progesterone