✅ Endocrine Flashcards Preview

ENDOCRINE > ✅ Endocrine > Flashcards

Flashcards in ✅ Endocrine Deck (84)
Loading flashcards...

Altered TBG 🔽 🔼 concentration

More than 99% of the circulating thyroid hormone pool is bound to 3 major transport proteins:  TBG, transthyretin, and albumin.  Only the free (ie, unbound) thyroid hormones are biologically active.  Changes in binding protein levels can affect the total circulating pool of thyroid hormones, but if the hypothalamic-pituitary-thyroid axis is intact, free hormone levels are unchanged.

Increased TBG

  • Estrogens (eg, pregnancy, OCs, HRT) & estrogenic medications (eg, tamoxifen)
  • Acute hepatitis

High levels of estrogen (eg, pregnancy, oral contraceptive pills, hormone replacement therapy) increase the level of TBG by decreasing its catabolism and increasing its synthesis in the liver.  As the additional TBG binds more thyroid hormone, thyroid hormone production increases to maintain a euthyroid state.

Decreased TBG

  • Androgenic hormones
  • High-dose glucocorticoids/hypercortisolism
  • Hypoproteinemia (eg, nephrotic syndrome, starvation)
  • Chronic liver disease

Dx: Slight elevation in total T4 level (free T4 level would be expected to be normal).


🌋Thyroid nodule 

Palpable thyroid nodules are common, occurring in about 5% of all adults.  Thyroid sonography by itself cannot rule out malignancy in palpable nodules.

💉 FNA biopsy is recommended for any nodule greater than 1 cm in diameter that is solid and hypoechoic on ultrasonography and for any nodule 2 cm or greater that is mixed cystic-solid without worrisome sonographic characteristics. 

🔪 Biopsy may be appropriate for  smaller nodules (at least 5 mm in diameter) in patients with risk factors, such as a history of radiation exposure, a family or personal history of thyroid cancer, cervical lymphadenopathy, or suspicious ultrasound characteristics. FNA biopsy is not routinely recommended for thyroid nodules less than 1 cm in diameter.

☢ Radionucleotide imaging (scan): If a nodule takes up radiotracer, it is termed a “hot” nodule. Colloidal cysts and tumors do not take up tracer and are “cold” nodules. Therefore, “hot” nodules are more likely benign. Neurofibromas would also be “cold.” Definitive diagnosis can be made through needle aspiration.


Thyroid Cancer

Papillary Thyroid Cancer (most common thyroid epithelial malignancy) is characterized by slow spread into local tissues and regional lymph nodes.  Pathologic findings include large cells with ground glass cytoplasm; pale nuclei with inclusion bodies and central grooving; and grainy, lamellated calcifications known as psammoma bodies.  Lymph node involvement is common.  Tx: Surgical resection is the primary treatment for papillary thyroid cancer. 

Follicular Thyroid Cancer is the second most common thyroid epithelial malignancy (after papillary cancer) and has a peak incidence at age 40-60.  It typically presents with a firm thyroid nodule and is often discovered incidentally on examination or imaging for other purposes.  Thyroid scintigraphy usually shows a nonmetabolically active ("cold") nodule.

Diagnosis of FTC based on a limited tissue sample (eg, fine-needle biopsy) is not possible as the cytologic findings (large numbers of follicular cells arranged in microfollicles, clusters, and clumps, often categorized as "follicular neoplasm") are similar in both FTC and benign follicular adenomas.  However, in contrast to benign adenomas, FTC is characterized by invasion of the tumor capsule and/or blood vessels, a finding that is typically made on examination of a surgically excised nodule.  This invasion pattern accounts for the tendency of FTC to metastasize via hematogenous spread to distant tissues (eg, bone, lung).

Thyroglobulin (Tg) is the precursor to active thyroid hormones (T3 and T4) and is produced by normal thyroid tissue or differentiated (papillary or follicular) thyroid cancer.  Most Tg is stored in the thyroid gland, but some is released into the circulation.  Patients who have undergone a total thyroidectomy and radioactive iodine treatment should have no residual normal thyroid tissue; therefore, a rising Tg level in these patients is likely due to recurrent differentiated thyroid cancer.

Patients who have undergone thyroidectomy for differentiated thyroid cancer require levothyroxine (T4) supplementation for 2 reasons:

  • Levothyroxine replaces thyroid gland function.
  • Levothyroxine suppresses pituitary release of TSH (negative feedback).  Because TSH stimulates thyroid tissue growth, levothyroxine supplementation to suppress TSH (ie, by causing a mildly hyperthyroid state) may help prevent thyroid cancer recurrence.

In some patients, a "stimulated" Tg level can also be obtained to evaluate for recurrence.  This test measures the Tg level after withdrawing levothyroxine supplementation (to increase pituitary release of TSH) or after giving recombinant TSH.  If there is recurrent cancer, the increased TSH will cause increased Tg release from the cancer cells.




  • Serum TSH normally 0.5-5.0 µU/mL
  • Serum free T4 (thyroxine) normally 0.9-2.4 ng/dL [Suspected thyroid dysfunction with concern for pituitary dysfunction, or evidence of TSH abnormality]; 
  • Serum free T3 (triiodothryronine) normally 3.6-5.6 ng/L [Rarely used except when T3 thyrotoxicosis is suspected]

Thyroiditis describes thyroid hormone release from a damaged thyroid gland.  In thyroiditis, a decrease in 123I uptake will be observed.



  • Anxiety & insomnia
  • Palpitations
  • Heat intolerance
  • Increased perspiration
  • Weight loss without decreased appetite

Physical examination

  • Goiter
  • Hypertension
  • Tremors involving fingers/hands
  • Hyperreflexia
  • Proximal muscle weakness 💈 💺 (thyrotoxic myopathy)
  • Lid lag
  • Atrial fibrillation


High RAIU suggests de novo hormone synthesis due to Graves' disease (diffusely increased uptake) or toxic nodular disease (nodular uptake). 

Low RAIU suggests either release of preformed thyroid hormone (ie, thyroiditis) or exogenous thyroid hormone intake. 


☠ Thyrotoxicosis ❗ describes all forms of excess thyroid hormone, including both endogenous and exogenous causes.

  • weight loss, tachycardia, tremor, and lid retraction
  • Thyrotoxicosis can produce a number of 💔 cardiovascular complications directly through the effects of tri-iodothyronine (T3) on cardiac myocytes and blood vessels, as well as indirectly by increasing sensitivity to circulating catecholamines.  Generally, thyrotoxicosis causes positive inotropic and chronotropic effects, leading to a hyperdynamic cardiovascular state characterized by tachycardia, systolic hypertension, and widened pulse pressure💦.  Arrhythmias are common and may include sinus tachycardia, atrial fibrillation/flutter, and atrial and ventricular ectopy.  Valvular abnormalities such as mitral valve prolapse 🏀and mitral or tricuspid regurgitation are also associated.  Increased oxygen demand in thyrotoxicosis is due to increased cardiac output and increased systemic oxygen consumption; this can lead to anginal symptoms in patients with underlying coronary atherosclerosis.  ⚓Angina may also occur due to coronary vasospasm (especially in young female patients).  Thyrotoxicosis may also cause new-onset heart failure or decompensation of pre-existing heart failure.

Thyroid strom ⛈ (medical emergency): 

The presence of fever, severe tachycardia, congestive heart failure, and
CNS changes
(delirium, psychosis, seizure, or coma) help separate thyroid storm from uncomplicated hyperthyroidism. Other factors that point toward storm or impending
storm include atrial fibrillation, abdominal symptoms, jaundice, and the absence of a precipitating event. Even with treatment, the mortality of thyroid storm can be 10% to
20%, so admission to an intensive care unit for close monitoring is mandatory. Tx: Propranolol, methimazole, corticosteroids (if adrenal insuficency present).

Treatment includes beta blockers (eg, propranolol) for symptom control, thionamides (eg, propylthiouracil) to block new hormone synthesis, iodine solution to block thyroid hormone release (given at least an hour after propylthiouracil to prevent excess iodine incorporation into thyroid hormone), and glucocorticoids to decrease peripheral conversion of T4 to T3.

Atrial fibrillation (AF) is the most common supraventricular arrhythmia in hyperthyroidism, occurring in 5%-15% of patients.  Thyroid hormones cause an increase in beta-adrenergic receptor expression, which leads to an increase in sympathetic activity.

🎺 Beta blockers (eg, propranolol, atenolol) are recommended as initial therapy to control heart rate and hyperadrenergic symptoms.  In addition, propranolol decreases conversion of T4 to T3 in peripheral tissues.  The beta blocker should be initiated as soon as hyperthyroidism is diagnosed and should be continued until the hyperthyroidism is adequately treated with thionamides, radioiodine, and/or surgery.


Graves Disease

Graves' disease is an autoimmune disorder characterized by anti-thyroid antibodies, most prominently thyroid-stimulating immunoglobulin (TSI).  TSI binds to TSH receptors in the thyroid and triggers release of thyroid hormones, leading to thyrotoxicosis. 

Hyperthyroidism is associated with increased expression of beta-adrenergic receptors in various organs, and the subsequent hyperadrenergic state can cause:


  • Nervousness or emotional lability (99)
  • Increased sweating (91)
  • Heat intolerance (89)
  • Palpitations (89) [Tachycardia]
  • Fatigue (88)
  • Weight loss (85)
  • Hyperdefecation (33)
  • Menstrual irregularity (22)

Px: Examination of the thyroid may reveal the classic smooth, rubbery, firm goiter, often associated with a bruit...

  • Tachycardia or atrial fibrillation (100)
  • Goiter (99)
  • Tremor (97)
  • Proptosis of the eyes or extraocular muscle palsy (40)
  • Stare, lid lag, or signs of optic neuropathy (40)
  • Pretibial myxedema (NA)

Dx: Low TSH; elevated T3, and T4

*Thyroid receptor antibodies: Serum TSI, Serum TBII, Antithyroid peroxidase antibodies

123I uptake is diffusely 🔥 increased throughout the whole thyroid gland.  *Over activation of the TSH receptor in the thyroid gland increases the iodine-trapping mechanism in the follicle cells.

Elevated thyroglobulin is consistent with endogenous thyroid hormone release


Thioamides [propylthiouracil (PTU) and methimazole] may induce remission by blocking new thyroid hormone production via inhibition of the oxidation, organification and coupling steps (thyroid peroxidase) of thyroid hormone synthesis.  

PTU (but not methimazole) also inhibits peripheral conversion of T4 to T3. 

Cx: ❗ 🦴 Agranulocytosis is the most feared side effect, and is seen in approximately 0.3% of patients treated with antithyroid drugs.  It is caused by immune destruction of granulocytes, and most cases occur within 90 days of treatment.  Current recommendations state that once the patient complains of fever and sore throat, the antithyroid drug should be discontinued promptly and the WBC count measured.  A total WBC count less than 1,000/cubic mm warrants permanent discontinuation of the drug. 

Beta blockers (eg, propranolol, atenolol) are recommended as initial therapy to control heart rate and hyperadrenergic symptoms.

Radioactive iodine (RAI) therapy: RAI (131I) is taken up by the thyroid follicular cells in a manner similar to that of natural iodine, and the subsequent beta emission induces slow necrosis of the thyroid follicular cells.  This leads to clinical and biochemical resolution of hyperthyroidism over the subsequent 6-18 weeks (not rapidly).  The goal of RAI in Graves disease is to administer a sufficient dose of radiation to prevent recurrence of hyperthyroidism.  However, the diffuse uptake of radioiodine eventually leads to permanent hypothyroidism within months in >90% of patients.  Cx: Titers of TRAB increase significantly following RAI therapy, and RAI can cause worsening of ophthalmopathy.  For this reason, administration of 🌚 glucocorticoids with RAI is often advised to prevent complications in patients with mild ophthalmopathy.

Cx: Graves ophthalmopathy Proptosis and impaired extraocular motion (decreased convergence, diplopia).  Other common symptoms include irritation (eg, gritty or sandy sensation), redness, photophobia, pain, and tearing.  In Graves disease, thyrotropin (TSH) receptor autoantibodies (TRAB) stimulate thyroid hormone production, resulting in hyperthyroidism.  Thyroid hormone increases sensitivity to catecholamines, and thyrotoxicosis of any etiology may cause lid lag and retraction due to sympathetic activation and contraction of the superior tarsal muscle.  However, true exophthalmos with impaired extraocular motion is seen only in Graves disease and is due to T cell activation and stimulation of orbital fibroblasts and adipocytes by TRAB, resulting in orbital tissue expansion and lymphocytic infiltration.​



Toxic adenoma (TA), Multinodular Goiter (MNG)

TA and toxic multinodular goiter (MNG) are the second most common causes of hyperthyroidism and are most often caused by activating mutations in the TSH receptor.  These disorders are characterized by TSH-independent thyroid hormone secretion and focal (TA) or multifocal (MNG) follicular hyperplasia. 

Dx: Elevated RAIU 🔥 "hot nodule" which indicates endogenous production of thyroid hormones.


Initial treatment of TA and MNG includes a beta blocker to alleviate the symptoms of hyperthyroidism

Thionamide (eg, methimazole, propylthiouracil) to decrease thyroid hormone secretion.  Options for definitive management of TA include surgery and radioiodine ablation.

Radioactive iodine (RAI) therapy: RAI (131I): The radioisotope is taken up only by the autonomous thyroid tissue, and the function of the remaining normal tissue is usually adequate to prevent permanent hypothyroidism.

Cx: If left untreated, patients with hyperthyroidism can develop rapid bone loss leading to osteoporosis and increased risk of fracture.  Direct effects of the thyroid hormones cause increased osteoclastic bone resorption.  Patients can also develop hypercalcemia and hypercalciuria due to increased bone turnover.


Subacute thyroiditis (de Quervain's thyroiditis) ❄

Subacute (de Quervain, subacute granulomatous) thyroiditis is thought to be due to a postviral inflammatory process and is often preceded by an upper respiratory illness.

Characterized by fever, neck pain, and thyroid tenderness.  In most cases, hyperthyroid symptoms fade in <8 weeks as the thyroid gland becomes depleted of preformed hormone.

Thyrotoxicosis in subacute thyroiditis resolves spontaneously within a few weeks and may be followed by a hypothyroid phase lasting a few months.  Most patients eventually recover to a euthyroid state. 


  • Elevated ESR 
  • TSH triphasic (low, high, normal) over 2-4 mo
  • Elevated Serum thyroglobulin (3-40 ng/mL):  is consistent with endogenous thyroid hormone release

Tx: Symptomatic with 🎺beta blockers to control thyrotoxic symptoms and 🧯nonsteroidal anti-inflammatory drugs (NSAIDs) for pain relief.  🌑Glucocorticoids are used for severe thyroid pain not responding to NSAIDs.



Elevated thyroglobulin is consistent with endogenous thyroid hormone release

Decreased thyroglobulin suggests exogenous or factitious thyrotoxicosis.  




Pituitary Adenoma

Most TSH-secreting pituitary adenomas are macroadenomas

Patients with this condition typically have a goiter due to the effect of TSH on growth of the thyroid follicles.  However, they do NOT have the extrathyroidal manifestations of Graves disease such as infiltrative ophthalmopathy or pretibial myxedema. 

Laboratory testing shows a high concentration of circulating thyroid hormone with an elevated or inappropriately normal TSH

By contrast, patients with non-TSH-dependent hyperthyroidism (much more common) will have a suppressed TSH.

TSH is comprised of 2 subunits, an alpha-subunit (common to TSH, FSH, LH, and hCG) and a thyroid-specific beta-subunit.  Many TSH-secreting pituitary adenomas overproduce the alpha-subunit, and an elevated ratio of alpha-subunit to TSH suggests a pituitary adenoma.  These patients would have an elevated TSH, elevated free T4, and normal or increased RAIU.

Although the rarest of functional pituitary tumors, a TSH-producing adenoma can mimic Graves disease by causing hyperthyroidism with a diffuse goiter. A TSH-producing tumor does not cause infiltrative ophthalmopathy or pretibial myxedema, but these findings, helpful when present, are absent in over 50% of patients with Graves disease as well.


Pituitary tumor apoplexy

Generally a neurosurgical emergency. On occasion, hemorrhagic infarction of a pituitary adenoma may be less urgent, especially in the absence of associated mass effect, and can be managed with conservative follow-up monitoring. In the setting of local mass effect and severe headache, however, neurosurgical decompression of the pituitary gland is necessary. Urgent 🌑 glucocorticoid administration is often required because of acute adrenocorticotropic hormone deficiency. The leading cause of death in patients with pituitary tumor apoplexy is adrenal insufficiency.

fatigue, weight gain, and erectile dysfunction and the laboratory finding of hyponatremia suggest panhypopituitarism, ❗ headache is consistent with hemorrhage.


Tumors / Colloidal Cyst

Do not take up tracer and are “cold” nodules.

Neurofibromas would also be “cold.”

Definitive diagnosis can be made through needle aspiration.


Ddx: Hypothyroidism:

Serum TSH normally 0.5-5.0 µU/mL

Serum free T4 (thyroxine) normally 0.9-2.4 ng/dL [Suspected thyroid dysfunction with concern for pituitary dysfunction, or evidence of TSH abnormality]; 

Serum free T3 (triiodothryronine) normally 3.6-5.6 ng/L [Rarely used except when T3 thyrotoxicosis is suspected

Hx: Sluggish affect or depression, Fatigue, Cold intolerance, Constipation, Weight gain, Alopecia.

Px: Dry, coarse skin and hair, Periorbital puffiness, Bradycardia, Slow movements and speech, Hoarseness, Diastolic hypertension, Goiter, Loss of the lateral portion of the eyebrow (NA), Delayed deep tendon reflexes.

Hypothyroidism can cause additional metabolic abnormalities such as hyperlipidemia, hyponatremia and asymptomatic elevations of creatinine kinase (usually <10x normal) and serum transaminases (aspartate aminotransferase and alanine aminotransferase). 

Hypercholesteremia with high low-density lipoprotein (LDL) is due primarily to decreased surface LDL receptors (type 2a hyperlipidemia) and/or decreased LDL receptor activity.  Hypothyroidism can also decrease lipoprotein lipase activity to cause hypertriglyceridemia.

Dx: Low T3 and T4, along with elevated TSH from the pituitary due to loss of negative of feedback. Titers of anti-thyroglobulin antibodies or anti-microsomal antibodies can also be elevated. Brief periods of hyperthyroidism ("Hashitoxicosis") may also be seen during acute inflammation due to active destruction of thyroid follicles and release of pre-formed thyroid hormone.

Tx: Levothyroxine

Major drug interactions

↓ Levothyroxine absorption

  • Bile acid binding agents (eg, cholestyramine)
  • Iron, calcium, aluminum hydroxide
  • Proton pump inhibitors, sucralfate

↑ TBG concentration

  • Estrogen (oral), tamoxifen, raloxifene
  • Heroin, methadone

↓ TBG concentration

  • Androgens, glucocorticoids
  • Anabolic steroids
  • Slow-release nicotinic acid

↑ Thyroid hormone metabolism

  • Rifampin
  • Phenytoin
  • Carbamazepine

Most patients with hypothyroidism have an increased requirement for levothyroxine after starting oral estrogen (estrogen replacement therapy or oral contraceptives).  Oral estrogen formulations decrease clearance of thyroxine-binding globulin (TBG), leading to elevated TBG levels.  TBG is synthesized and sialylated in the liver.  Transdermal estrogen bypasses the liver and does not affect TBG levels.

Patients with normal thyroid function can readily increase thyroxine production to saturate the increased number of TBG binding sites, but hypothyroid patients are dependent on exogenous thyroid replacement and cannot compensate.  This results in decreased free thyroxine and increased TSH.  As a result, higher dosing of levothyroxine may be required.  A rise in estrogen levels is also one of the main reasons for higher levothyroxine requirements during pregnancy.


Myxedema coma is defined as severe hypothyroidism leading to decreased mental status, hypothermia, and other symptoms related to slowing of function in multiple organs.  Unprovoked hypothermia is a particularly important sign. Myxedema coma constitutes a medical emergency; treatment should be started immediately. Should laboratory results fail to support the diagnosis, treatment can be stopped.

An intravenous bolus of levothyroxine is given (500 μg loading dose), followed by daily intravenous doses (50-100 μg). Impaired adrenal reserve may accompany myxedema coma, so parenteral hydrocortisone is given concomitantly. Intravenous fluids are also needed but are less important than thyroxine and glucocorticoids; rewarming should be accomplished slowly, so as not to precipitate cardiac arrhythmias. If alveolar ventilation is compromised, then intubation may also be necessary. 


Hypothyroid myopathy 🍗

Hypothyroid myopathy occurs in over one third of patients with hypothyroidism, and can range from an asymptomatic elevation in CK to myalgias, muscle hypertrophy, proximal myopathy, and rhabdomyolysis.  Serum CK🍗 can be elevated for years before a patient develops clinical symptoms of hypothyroidism, and there is no clear correlation between the degree of CK elevation and severity of muscle disease.  Inflammatory markers (eg, erythrocyte sedimentation rate, C-reactive protein) may be normal or mildly elevated.

Dx: Initial testing should include TSH and free T4.  If thyroid studies are normal, additional testing, including serologic markers (eg, antinuclear antibodies, anti-Jo-1 antibodies) and muscle biopsy, may be needed to rule out other causes of myositis


Congenital Hypothyroidism 🚼

Clinical manifestations

  • Initially normal at birth
  • Symptoms develop after maternal T4 wanes:
    • Lethargy
    • Enlarged fontanelle
    • Protruding tongue
    • Umbilical hernia
    • Poor feeding
    • Constipation
    • Dry skin
    • Jaundice 


  • ↑ TSH & ↓ free T4 levels
  • Newborn screening


  • Levothyroxine

Jaundice, decreased activity, poor feeding, and hoarse cry are typical symptoms of congenital hypothyroidism.  However, most infants with hypothyroidism are asymptomatic and identified through newborn screening.  The most common cause of congenital hypothyroidism worldwide is thyroid dysgenesis (eg, aplasia, hypoplasia, ectopic gland).  Prompt recognition and thyroid hormone replacement (eg, levothyroxine) is necessary to prevent permanent neurodevelopmental injury.

The most common cause is thyroid dysgenesis (i.e., aplasia, hypoplasia, or ectopic gland), which has been incriminated in 85% of cases.  Other causes include inborn errors of thyroxin synthesis (10%), and transplacental maternal thyrotropin-receptor blocking antibodies (5%).  Infants initially appear normal at birth, but gradually develop apathy, weakness, hypotonia, large tongue, sluggish movement, abdominal bloating, and an umbilical hernia.  Other signs include pathologic jaundice, difficult breathing, noisy respiration, hypothermia, and refractory macrocytic anemia.  Infants initially appear normal due to the presence of moderate amounts of maternal hormones in the infant's circulation.  For this reason, screening is mandated in all states at birth to allow for the early detection, treatment, and consequent improvement of the prognosis.  Screening is done by measuring serum T4 and TSH levels.  The treatment is levothyroxine (initial dose of 10 mcg/kg, then titrated accordingly).


Subclinical Hypothyroidism

Defined as a serum thyroid-stimulating hormone (TSH) level greater than the reference range, with a concomitant serum free thyroxine (T4) level in the reference range. 

Hx: Patients typically have mild or no symptoms of hypothyroidism.

Tx: Treatment is recommended when serum TSH levels are greater than 10 µU/mL. Levothyroxine also may be considered for patients who have marked symptoms, have a goiter, are pregnant or are planning to become pregnant, or have positive serum thyroid peroxidase antibody titers.  

Monitor q1y


Iatrogenic Hypothyroidism

Hx: Suspected surreptitious (gain) ingestion of thyroid hormone or analogues. 

Dx: Excess thyroid hormone negatively feeds back on the pituitary, leading to decreased TSH.  This decrease in thyroid activity manifests as decreased 123I uptake, with thyroid gland atrophy.



Hashimoto disease (Chronic autoimmune thyroiditis) 

The most common cause of thyroiditis.  Generally seen in middle-aged women, this generally presents with a palpable goiter most often there is associated tenderness.

TSH high; free T3 and T4 normal. positive family history for hypothyroidism; TPO antibodies present; slowly progressive

Dx: Antithyroblobulin antibodies / Antithyroid peroxidase antibodies (anti-TPO)

Tx: Levothyroxine (T4), which should always be taken on an empty stomach 1 hour before or 2 to 3 hours after intake of food or other medications.


Thyroid lymphoma is uncommon, but the incidence is approximately 60 times greater in patients with preexisting chronic lymphocytic (Hashimoto) thyroiditis (ie, chronic hypothyroidism, positive antithyroid peroxidase antibody).  The typical presentation of thyroid lymphoma includes a rapidly enlarging, firm goiter associated with compressive symptoms (eg, dysphagia, hoarseness).  As with other lymphomas, patients may have systemic B symptoms (eg, fever, night sweats, weight loss).

Mild pain and tenderness may be present, and the gland is frequently fixed to the surrounding structures and does not move up when swallowing.  Retrosternal extension of the tumor is common and can result in venous compression with distended neck veins and facial plethora; raising the arms causes compression of the subclavian (and right internal jugular) vein between the clavicles and the enlarged thyroid, leading to more prominent venous distension and facial redness (Pemberton sign).

Inflammatory markers (eg, erythrocyte sedimentation rate) can be elevated but are nonspecific.  CT imaging typically reveals diffuse enlargement of the thyroid around the trachea (doughnut sign).  Core or excisional biopsy may be required, and flow cytometry can confirm monoclonal lymphoma cells.


Silent /Painless (lymphocytic) thyroiditis

Painless thyroiditis is associated with thyroid peroxidase autoantibodies and is considered a variant of chronic lymphocytic (Hashimoto) thyroiditis.  It is similar to postpartum thyroiditis but by definition excludes patients within a year of pregnancy.  

Hx: Painless

Dx: Following a self-limited hyperthyroid phase, patients often develop a hypothyroid phase, which may persist or return to a euthyroid state.  

In patients with subacute, silent, or postpartum thyroiditis or exposure to exogenous thyroid hormones, the radioactive iodine uptake ❄ (RAIU) will be very LOW (<5% at 24 hours), which indicates very little endogenous thyroid production.

Tx: Painless thyroiditis does not require specific therapy.  However, as hyperthyroidism causes adrenergic overstimulation, a beta blocker (eg, propranolol) may be prescribed to control symptoms, especially palpitations or tremulousness.


🤰🏼Postpartum thyroiditis

Patients can have a brief hyperthyroid phase due to release of preformed thyroid hormone but frequently have only mild, nonspecific symptoms (eg, anxiety, palpitations).  The subsequent hypothyroid phase (eg, fatigue, weight gain despite normal appetite, constipation) often brings patients to medical attention.  Examination typically shows a nontender goiter, bradycardia, diastolic hypertension, lower extremity edema, and other findings (eg, coarse facies, delayed deep tendon reflex relaxation).  In the hypothyroid phase, TSH will be elevated and free T4 levels will be low.  Other laboratory findings associated with hypothyroidism include hypercholesterolemia (due to thyroid effects on lipid metabolism) and hyponatremia.

Hx: A subset of painless autoimmune thyroiditis and can occur up to 12 months after parturition. It affects 5% to 8% of pregnant women in the United States and can recur with each pregnancy. 

Postpartum thyroiditis is similar to painless (silent) thyroiditis, but by convention the latter is not diagnosed within a year of childbirth.  Both may be considered variants of chronic lymphocytic (Hashimoto) thyroiditis and are associated with elevated titers of anti-thyroid peroxidase autoantibodies.  However, whereas Hashimoto thyroiditis frequently leads to permanent hypothyroidism, postpartum and painless thyroiditis are usually self-limited, and patients return to a euthyroid state over several months.

The disorder usually follows a classic course of approximately 6 weeks of thyrotoxicosis, a shorter period of euthyroidism, 4 to 6 weeks of hypothyroidism, and then restoration of euthyroidism.

Dx: TSH triphasic (low, high, normal) over 2-4 mo but often ultimately elevated; recent pregnancy.

Thyroiditis is associated with elevated serum free thyroxine (T4) and triiodothyronine (T3) levels and a low serum thyroid-stimulating hormone (TSH) level.


Iodine deficiency

TSH high; iodine-deficient area; rare in United States


Pituitary/hypothalamic mass or radiation

"Central hypothyroidism"

Hx: Headaches; most often a pituitary or sellar lesion noted on MRI/CT scan or evidence of prior pituitary surgery

Dx: TSH low or normal; free T4 low

Serum thyroglobulin

3-40 ng/mL

Suspected subacute thyroiditis or suspected surreptitious ingestion of thyroid hormone or analogues; followed as a tumor marker in patients with well-differentiated thyroid cancer


Pregnancy (treated)

Pregnancy is known to increase levothyroxine requirements in most patients receiving thyroid replacement therapy, and this expected increase should be anticipated by increasing the levothyroxine dose. This is typically increased in the first (and sometimes in the second) trimester of pregnancy, with a possible total increase of 30% to 50%, and an increase in levothyroxine dose in this range to maintain the thyroid-stimulating hormone (TSH) level between approximately 0.1 and 2.5 µU/mL is associated with fewer maternal and fetal complications. The fetus is largely dependent on transplacental transfer of maternal thyroid hormones during the first 12 weeks of gestation, and the presence of maternal subclinical or overt hypothyroidism may be associated with subsequent fetal neurocognitive impairment, increased risk of premature birth, low birth weight, increased miscarriage rate, and even an increased risk of fetal death. In pregnant women with hypothyroidism, thyroid function testing should be frequent, preferably every 4 weeks, to protect the health of mother and fetus and to avoid pregnancy complications.

TSH levels generally should range from 0.1 to 2.5 µU/mL (0.1-2.5 mU/L) in the first trimester, 0.2 to 3.0 µU/mL (0.2-3.0 mU/L) in the second trimester, and 0.3 to 3.0 µU/mL (0.3-3.0 mU/L) in the third trimester.


Subacute lymphocytic thyroiditis

Less common, and although an acute increase in thyroid size is seen, it is generally nontender.


Subacute granulomatous thyroiditis

Usually follows a viral illness and is also associated with a mildly painful gland.


Invasive fibrous thyroiditis

Presents as a gradually increasing gland that is firm, but is nontender.




Suppurative (infectious) thyroiditis

Rare, and is associated with fever, a swollen thyroid, and clinical manifestations of a bacterial illness.

The thyroid gland may be palpably enlarged due to abscess formation.  However, patients are usually euthyroid as the involvement of the thyroid gland is focal.


Euthyroid sick syndrome

This condition, often referred to as euthyroid sick syndrome, or "low T3 syndrome," is thought to be a result of decreased peripheral 5'-deiodination of T4 due to caloric deprivation, elevated glucocorticoid and inflammatory cytokine levels, and inhibitors of 5'monodeiodinase (eg, free fatty acids, certain medications).  There is a rough correlation between the severity of the underlying, non-thyroidal illness and the fall in T3 levels.  If the non-thyroidal illness continues, serum T4 and TSH levels may eventually decrease as well.

  • Low serum (total) T3
  • Normal serum (total) T4
  • Normal TSH

In the setting of acute illness (eg, ulcerative colitis flare treated with glucocorticoids).

T4 is produced exclusively in the thyroid gland, whereas T3 is produced mainly by peripheral conversion of T4 by deiodination.  ESS encompasses a variety of alterations in thyroid physiology, the most common of which is termed "low T3 syndrome" and is thought to be the result of decreased conversion of T4 to T3.  Factors in acute illness that inhibit peripheral deiodination include high endogenous cortisol levels, inflammatory cytokines (eg, tumor necrosis factor), starvation, and certain medications (eg, glucocorticoids, amiodarone).

TSH and T4 levels are often normal in ESS, although they also may fall in severe or prolonged cases; thus, ESS may represent a transient central hypothyroidism rather than a true euthyroid state.  In light of these changes, thyroid function tests must be interpreted with caution in acutely ill patients.  ESS does not usually require treatment, and abnormal results should be followed up with repeat testing once the patient has returned to baseline health.



Type 1 diabetes mellitus (T1DM) is primarily a disease of β-cell failure resulting in lack of circulating insulin; insulin sensitivity usually remains normal, with insulin doses required to treat patients being similar to a healthy individual's daily endogenous insulin production (30-60 U/day). 

Patients with type 1 diabetes are typically diagnosed at the time of disease onset based on the occurrence of symptomatic hyperglycemia or ketoacidosis. Since microvascular complications in patients with type 1 diabetes typically occur after the onset of puberty and/or 5 to 10 years after the initial diagnosis, screening for these complications is delayed until that time. Because patients with type 1 diabetes have a higher risk of early cardiovascular disease, screening is typically done early in the disease course. The American Diabetes Association (ADA) recommends that such patients have a fasting lipid panel performed after puberty or at diagnosis if the diagnosis is established after puberty.

The ADA recommends screening for nephropathy (such as a urine albumin-creatinine ratio) once a patient with type 1 diabetes is 10 years of age or older and has been diagnosed with diabetes for 5 or more years. The first dilated funduscopic examination should be obtained once the child is 10 years of age or older and has been diagnosed with type 1 diabetes for 3 to 5 years. This patient only needs a fasting lipid profile since she was diagnosed with type 1 diabetes 2 years ago and is postpubertal.