Setting: office
CC: “I just feel so weak and tired.”
VS: R: 10 breaths/minute; BP: 135/94 mm Hg; P: 56 beats/minute; T: 96.8°F
HPI: A 48-year-old woman with progressively worsening fatigue and tiredness developing over the last several months comes to your office. She says she, “has gotten to the point where everything is a struggle.” She has also been gaining weight and suffering from constipation.
PMHX:
Depression
Dry skin
Medications:
Selective serotonin receptor inhibitor (SSRI)
Bupropion
Stool softeners
PE:
General: sad appearing, modestly obese, slumping on examination table
Cardiovascular: normal
Abdomen: no organomegaly, decreased bowel sounds diffusely
Neurological: decreased relaxation phase of reflexes
Skin: course, thick hair
Initial Orders:
CBC
CHEM-7
Thyroid function tests (TFTs): free thyroxine (T4), thyroid-stimulating hormone (TSH)
Calcium, magnesium levels
In office-based cases, advance the clock to the time and day when the test results all list “Report Available.”
Advance the clock 1 week to have the patient revisit.
Laboratory Test Results:
CBC: hematocrit 34%; mean corpuscular volume (MCV) 90 fL
CHEM-7: normal except sodium 132 mEq/L
Free T4: low
TSH: high
Calcium, magnesium levels: normal
Low T4 + High TSH = Hypothyroidism
Normocytic anemia is part of hypothyroidism.
T4 is anabolic. Without it, things do not grow—like red blood cells.
Low T4 causes low sodium level.
Low T4 impairs free water clearance.
The patient is certainly very happy to know she has a clear medical reason for her tiredness and possibly her depression.
The patient asks why she feels cold all the time, and why her temperature is low?
a. Pituitary insufficiency
b. Concomitant adrenal insufficiency
c. Because T4 directly stimulates heat production in cells
d. From the hyponatremia and anemia
Answer c. T4 directly stimulates heat production in cells
The metabolic rate of all mature cells in the body is under the direct control of thyroid hormone except for the adult brain, the spleen, and the uterus. We are 98.6°F even when the ambient temperature is lower than that because the rate of Na+/K+-ATPase in almost all bodily tissues is under the control of thyroid hormone. T4 controls the “thermostat” for the body. The patient’s inability to generate a faster rate of metabolism lowers her temperature and makes her feel colder.
Low T4: Bowels slow = Constipation
High T4: Bowels fast = Frequent bowel movements
Coarse, thick hair and dry skin are a routine finding in hypothyroidism.
Which of the following acts as a steroid hormone?
a. T4
b. TSH
c. Thyrotropin-releasing hormone (TRH)
d. Reverse triiodothyronine (T3)
Answer a. T4
T4 is produced from the amino acid tyrosine, but it has a steroid hormone mechanism of action. Steroid hormones have a receptor in the cytosol or the nucleus and work by creating new mRNA and new proteins. They are not stored in vesicles and they have protein carriers. T4 follows all these pathways in its mechanism of action. Reverse T3 is metabolically inactive, so it has no steroid effect. TSH and TRH are peptide hormones.
Peptide Hormones
• No protein carrier
• Short half-life
• Cell surface receptor
• Work through G-proteins and second messengers
Steroid hormones do not use G-proteins.
Orders:
Vital signs
Synthroid (levothyroxine) replacement
CHEM-7
Lipid panel (LDL, HDL, triglycerides)
Repeat vital signs only take 2 minutes to do and will automatically advance the clock.
VS: R: 12 breaths/minute; BP: 142/94 mm Hg; P: 54 beats/minute; T: 96.8°F
What is the mechanism of bradycardia in hypothyroidism?
a. T4 is needed for myocardial contractility.
b. T3 speeds conduction at the atrioventricular (AV) node.
c. T4 has a permissive effect on catecholamines.
d. Hypothyroidism causes involution or loss of sinoatrial (SA) node tissue.
Answer c. T4 has a permissive effect on catecholamines.
The root cause of bradycardia in hypothyroidism is the combined effect on catecholamines with T4. Without T4, there is a decreased effect of both norepinephrine and epinephrine at both the SA and AV node. In addition, hypothyroidism leads to a decreased metabolic requirement of almost all the cells in the body. Low T4 and low T3 levels mean the muscles use less oxygen and need less perfusion (Figure 3-4).
Figure 3-4. The hypothalamic−pituitary−thyroid axis. LATS, long-acting thyroid-stimulator; T3, triiodothyronine; T4, thyroxine; TBG, thyroid-binding globulin; TRH, thyrotropin-releasing hormone; TSH, thyrotropin; TSH-R, thyrotropin G-protein-coupled receptor. (Goldsmith LA, et al. Fitzpatrick’s Dermatology in General Medicine, 8th ed. [online] New York: McGraw-Hill; 2012.)
Hypothyroidism causes bradycardia because of loss of catecholamine stimulation on the heart as well as decreased demand from a “slower” running body. This is the same reason people gain weight with hypothyroidism.
T4 is converted to T3 in tissues.
T3 is much more active than T4.
Why is T3 more active than T4?
a. T3 is more protein bound.
b. T3 leaves plasma and enters the cell much more easily.
c. T4 has a shorter half-life.
d. Reverse T3 directly inhibits T4 tissue effect.
e. Reverse T3 is converted to T4.
Answer b. T3 leaves plasma and enters the cell much more easily.
T4 is converted to T3 by 5-iodinase at the level of the tissues peripherally to increase the metabolic activity of those tissues. T3 is less protein bound and therefore can enter the cell and be more active. This also gives T3 a shorter half-life. T4 is more protein bound and is therefore less active.
More Protein Binding = Less Activity
The patient returns in 1 week to report on the effect of thyroid hormone replacement and discuss laboratory test results:
CHEM-7: glucose 145 mg/dL
LDL and triglycerides: elevated
What explains these laboratory test results abnormalities?
a. Glucagonoma is often present with hypothyroidism.
b. Hypothyroid states require less fuel.
c. Hypothyroidism provokes diabetes.
d. The patient has thyroid hepatopathy.
Answer b. Hypothyroid states require less fuel.
If thyroid hormone controls so much of the metabolic activity of the body, it is logical that a slower body needs less fuel. If Na+/K+-ATPase is not sufficiently stimulated and the patient’s bowels, muscles, and heart do not do as much work, then the fuels, such as glucose and fats, build up. This is why hypothyroidism is associated with weight gain.
The patient has been taking levothyroxine for 1 week and reports a slight increase in energy and a brighter mood. There is no change in weight, skin, or BP. You schedule a 1-month follow-up appointment because changes with thyroid hormones are very slow. T4 needs time to take effect and changes in the levothyroxine dose should not be done more frequently than every 6 to 8 weeks.
Rapid increases in thyroid hormone dosing is dangerous in which of these?
a. Diabetes
b. Coronary disease
c. Stroke
d. Renal insufficiency
Answer b. Coronary disease
Thyroid hormone controls metabolic rate. Rapid increases in thyroid hormone increase metabolic activity and myocardial demand. Hyperthyroidism can provoke myocardial ischemia by increasing total body oxygen consumption rates.
Go slowly when increasing thyroid hormone replacement in patients with coronary disease.
Low thyroid hormone levels cause polysaccharides to accumulate in vessel walls, making them stiff. Stiff vessels cause hypertension.
The patient returns 6 weeks later feeling much improved. She feels more energetic and her constipation has resolved. Her weight has decreased by 6 lb (2.7 kg); her pulse rate is 65 beats/minute; her BP is 134/78 mm Hg; and her temperature is 97.4°F.
Orders:
T4 and TSH
Long-term hypothyroidism management is easy. If T4 is low and TSH is high, continue to increase the levothyroxine dose every 6 to 8 weeks. All symptoms will resolve.