AssessmentsHypothyroidism and thyroiditis: Clinical practice
USMLE® Step 1 style questions USMLE
USMLE® Step 2 style questions USMLE
68-year-old man is brought to the physician by his partner because of increasing forgetfulness over the last 5 weeks. The patient is unable to finish his daily crossword puzzles and often has to call his partner when he is at the grocery store to help remember the list. He has had an 8-lb weight gain over this same time period. The patient has chronic hypertension, which is well-controlled with lisinopril, and he has also recently started taking laxatives several times a week to relieve constipation. Temperature is 36.5°C (97.7°F), pulse is 57/min, blood pressure is 128/86 mm Hg, and BMI is 27 kg/m2. The patient is alert and oriented to time, place, and person. Physical examination shows dry skin and a slightly distended abdomen. There is no mucosal pallor and capillary refill is less than 2 seconds. Deep tendon reflexes are delayed in the upper and lower extremities. Further testing confirms the diagnosis. Which of the following is the most appropriate pharmacotherapy for this patient?
Content Reviewers:Rishi Desai, MD, MPH
The hypothalamus secretes thyrotropin releasing hormone, or TRH, and TRH stimulates the anterior pituitary to secrete thyroid-stimulating hormone, or TSH.
TSH then binds to TSH receptors, which makes the thyroid secrete thyroxine, or T4 and triiodothyronine, or T3, in the blood. But this is not a one-way street - there’s also negative feedback happening, meaning when thyroid hormone levels rise, that inhibits the production of TSH and TRH, halting further production of T3 and T4 - to keep everything in balance.
Normally, some thyroid hormones travel through the bloodstream bound to thyroid binding globulin, and some are in their free form. And the thyroid actually makes more T4 than T3, and that T4 is converted to the more potent T3 in the periphery.
Thyroid hormones then increase the rate of metabolism in all cells, so they make us think, move, and talk faster, and they also increase heat generation. They also activate the sympathetic nervous system, the part of the nervous system responsible for our ‘fight-or-flight’ response, increasing cardiac output.
So with hypothyroidism, it’s like the entire body is functioning in slow motion - but this happens gradually, so it can take years before symptoms are even recognized. These include weight gain despite a loss in appetite because of the lower basal metabolic rate; cold sensitivity because the body is producing less heat; and slower heart rate, mental slowness, lethargy, and constipation because of the decreased effect of thyroid hormones on the sympathetic nervous system.
With hypothyroidism, glycosaminoglycans also accumulate in the skin and soft tissues, causing myxedema, or swelling, and an enlarged swollen tongue. Individuals may also have a puffy face - like a person who’s just woken up, coarse hair, periorbital edema, as well as loss of hair in the lateral third of the eyebrow - which is called Queen Anne’s sign. There might also be muscle aches, and a delayed relaxation phase of the deep tendon reflexes. Hypothyroidism also causes menstrual irregularities in females, and erectile dysfunction in males.
These signs and symptoms should prompt obtaining serum levels of free T4 and TSH to confirm the diagnosis.
Now, hypothyroidism actually comes in two flavors: primary, meaning it is the result of a thyroid condition, and secondary, or central, in which case the problem is a decreased secretion of TSH or TRH.
Primary hypothyroidism is much more common, accounting for over 95% of cases – and blood tests show low levels of free T3 and T4, which signals the pituitary to produce more TSH, so a high TSH.
In high-income countries, the most common cause of primary hypothyroidism is Hashimoto’s thyroiditis.
Hashimoto’s is an autoimmune form of thyroiditis, where autoantibodies are directed against the thyroid gland, and, as a consequence, more and more thyroid tissue gets destroyed over time, resulting in chronic hypothyroidism. And when there’s an immune attack, there’s inflammation - this inflammation makes the thyroid gland enlarge, so that can result in a goiter on physical examination. Finally, blood work may show high levels of anti-thyroperoxidase, or anti-TPO antibodies in the serum.
Treatment for Hashimoto’s thyroiditis depends on whether or not hypothyroidism is present - in euthyroid patients, no treatment is required.
In patients with chronic hypothyroidism, however, treatment is lifelong substitution therapy with T4.
There are other kinds of thyroiditis that can also cause hypothyroidism.
Particularly, subacute thyroiditis, also called de Quervain’s thyroiditis - which is associated with an inflamed, painful thyroid gland, and flu-like symptoms like high fevers and muscle aches. It can occur after a viral infection, and develops in three phases: at first, the follicles get destroyed, so T3 and T4 spill out into the blood, creating a transient hyperthyroid state, with low TSH levels.
In some cases, after 6 to 8 weeks, the inflammation subsides on its own, and the thyroid follicles repair themselves, so thyroid function goes back to normal without any treatment. But sometimes, after the initial hyperthyroid phase, individuals become slightly hypothyroid, before eventually returning to normal thyroid function. The inflammation causes a high erythrocyte sedimentation rate or ESR, typically in the range of 60 to 100.
Another type of thyroiditis is postpartum thyroiditis, which affects some females 2 to 12 months after giving birth. One explanation is that the immune system is generally diminished during the pregnancy so that there’s no attack against the fetus. And then after childbirth, the immune system becomes more active again and at that time, it might mistakenly attack the thyroid gland.
Like subacute thyroiditis, there’s a hyperthyroid phase, followed by a hypothyroid phase which occurs around 5 to 7 months after childbirth, and finally there’s a return to normal thyroid function.
Both subacute thyroiditis and postpartum thyroiditis often cause minimal symptoms, and resolve on their own over 12 to 18 months. In those situations, only pain management is needed, and sometimes beta-blockers may be helpful during the hyperthyroid phase.
During the hypothyroid phase, asymptomatic individuals require no treatment, whereas those who develop symptoms should be treated with T4, for several months. Once they have a normal serum TSH value, confirming the recovery of their thyroid function, exogenous T4 can be stopped.
Occasionally, however, these diseases progress to permanent hypothyroidism - in which case, lifelong substitution therapy with T4 is necessary.
Ok now! Let’s switch gears and look at iatrogenic causes of primary hypothyroidism.
First off, hypothyroidism can occur following surgery or radioiodine treatment for hyperthyroidism - either because the surgery removes part or all of the thyroid gland or because radioiodine therapy damages too many follicular cells.
For example, hypothyroidism usually begins within two to four weeks after a total thyroidectomy - which is when the entire gland is surgically removed. By comparison, hypothyroidism usually begins up to a year after a subtotal thyroidectomy - which is when most - but not all - of the gland is removed.
With radioiodine treatment, a person swallows a capsule containing a small dose of Iodine-131-which emits radiation. Functional thyroid tissue loves iodine, and gobbles it up to make thyroid hormones, and the iodine destroys the follicles with radiation - like a Trojan horse.
Hypothyroidism can occur months to years following radioiodine treatment, and it’s based on the extent of the follicular damage.
Another cause is when individuals get neck radiation to treat a cancer in the neck region, and the thyroid becomes a collateral victim.
Hypothyroidism can also result from side effects of other medications - including antithyroid medicine, like methimazole and propil-tio-uracil, which are used to treat hyperthyroidism due to Graves’ disease. Other medications include lithium, which treats bipolar disorder, amiodarone, an antiarrhythmic, interferon alpha, as well as anti-cancer medications like tyrosine kinase inhibitors, an example being Sunitinib, and checkpoint inhibitors, like Nivolumab, Pembrolizumab and Ipilimumab.