Central Hypothyroidism

History & Epidemiology of Central Hypothyroidism

Hypothyroidism may be defined as primary, secondary, or tertiary hypothyroidism. Primary hypothyroidism occurs when the thyroid gland does not produce enough thyroid hormone. Lack of iodine and Hashimoto thyroiditis are the 2 main causes of primary hypothyroidism.1 Secondary and tertiary hypothyroidism are also known as central hypothyroidism (CeH).

Central hypothyroidism occurs when there is a problem with the pituitary gland (secondary) or hypothalamus (tertiary) rather than with the thyroid gland itself. CeH affects approximately 1 in 16,000 to 1 in 100,000 people.2

In infants and children, central hypothyroidism may be caused by gene mutations or other issues such as2:

  • craniopharyngiomas (benign tumors of the pituitary gland)
  • past radiation treatment for cancer
  • traumatic delivery
  •  multiple pituitary hormone deficiency

Other causes of CeH include1,2:

  • genetic factors
  • treating primary hypothyroidism with too much thyroid hormone
  • empty sella syndrome (pituitary gland shrinks or flattens because of issues with the sella turcica)
  • inflammation
  • infiltrative causes, such as lymphoma
  • head injury
  • medication-related causes
  • Sheehan syndrome (damage to the mother’s pituitary gland during childbirth)
  • thyroid-releasing hormone resistance or deficiency
  • pituitary macroadenomas
  • pituitary surgery
  • past radiation treatment
  • head trauma

Central Hypothyroidism Diagnosis & Presentation

Central hypothyroidism symptoms include1,2:

  • intolerance to cold and decreased sweating
  • dry skin and hair
  • fatigue, drowsiness, and headache
  • constipation
  • muscle cramps
  • changes in sleep and menstrual cycles
  • unexplained weight gain, along with swelling or puffiness
  • anxiety, depression, or memory loss

Other symptoms may include low sodium, high cholesterol, heart failure, and QT interval prolongation.

Family history, including any problems with pregnancies, should be discussed. A complete list of medications, surgeries, and past medical problems should also be included.

Diagnostic Workup

A diagnosis of central hypothyroidism may be made when there is an abnormally low TSH along with below-normal thyroxine (T4) and triiodothyronine (T3).2 A thyroid-releasing hormone (TRH)-stimulation test may help identify pituitary or hypothalamic disease.2 This test would show a blunted or delayed TSH response to TRH. Other considerations that may be helpful in diagnosing central hypothyroidism include2:

  • first-degree relative with diagnosis of CeH
  • signs of hypothyroidism, including:
    • hearing loss
    • macroorchidism
    • delayed growth
  • lack of pituitary hormone secretion
  • high cholesterol
  • bradycardia
  • decreased body temperature
  • changes in echocardiogram

To rule out tumors, magnetic resonance imaging (MRI) may be performed.

The TSH level in patients with CeH may be normal, low, or high, whereas the TSH level in patients with primary hypothyroidism is usually greater than 4.5 mIU/L.

Patients with the following conditions should be screened for central hypothyroidism2:

  • hyperprolactinemia
  • acromegaly
  • diabetes insipidus
  • recurring headaches
  • changes in vision
  • newborns with:
    • hypotonia
    • prolonged jaundice
    • undescended testes
    • developmental delay

Screening for hypothyroidism in general is recommended by the American Thyroid Association starting at age 35. Screening should occur once every 5 years. People most at risk for hypothyroidism include those who1:

  • are pregnant
  • are women aged 60 years and older
  • have a past history of radiation to the head and neck
  • have autoimmune disorders
  • have type 1 diabetes
  • have a family history of hypothyroidism
  • have tested positive for thyroid peroxidase antibodies

Central Hypothyroidism Differential Diagnosis

Patients presenting with hypothyroidism should be evaluated for the possibility of the following1:

  • over-replacement of thyroid hormone
  • myxedema coma
  • anemia
  • infertility, dysmenorrhea, or erectile dysfunction
  • high cholesterol
  • depression
  • chronic fatigue syndrome
  • subacute thyroiditis
  • Riedel thyroiditis
  • lymphoma of the thyroid
  • deficiency of iodine
  • Addison disease

Management of Central Hypothyroidism

Central hypothyroidism treatment includes thyroid hormone replacement with levothyroxine. Pituitary hormone deficiencies should be treated with glucocorticoids. Adrenal crisis may occur in patients who are given levothyroxine without glucocorticoids.

Levothyroxine dosing is based on the individual. Infants and children typically need higher doses than adults because of growth and development.

Combination treatment with thyroxine (T4) and triiodothyronine (T3) has not been shown to offer any benefit in cognition, mood, or metabolism over treatment with T4 alone.

The starting dosage of levothyroxine for infants is 10 to 15 mcg/kg per day (for an infant weighing 3-4.5 kg).3

The typical adult dosage of levothyroxine is 1.6 mcg/kg per day. Adults aged 65 years and older and patients with atrial fibrillation or other cardiac issues may need a lower starting dose (around 1 mcg/kg daily).2,3

Monitoring Adverse Effects, Adverse Events, and Drug-Drug Interactions

Adults being treated with levothyroxine should have serum TSH and free T4 checked 6 to 8 weeks after starting treatment. They should also have TSH checked after any change in dosage. Patients with stable dosage may have labs checked every 6 to 12 months or whenever there is a change in symptoms of hypothyroidism.2,3

Pediatric patients with hypothyroidism should have serum TSH and total or free-T4 measured:

  • 2 to 4 weeks after starting treatment with levothyroxine
  • 2 weeks after dosage changes
  • every 3 to 12 months after dosage is stabilized and until the patient is done growing

Patients who are not compliant with dosing or have abnormal lab values may require more frequent testing. Assessment of mental and physical development and bone maturation should be performed at routine check-ups.3

Patients should be monitored for signs of over-replacement of thyroid hormone, including cardiac arrhythmias and decreased bone mineral density.3

Adverse effects of levothyroxine treatment include:

  • headache
  • heart arrhythmias
  • shortness of breath
  • weight loss
  • nervousness and irritability
  • insomnia
  • increased appetite
  • heat intolerance

Levothyroxine may interact with3:

  • bile acid sequestrants
  • beta blockers
  • phosphate binders, such as calcium carbonate
  • orlistat
  • proton pump inhibitors
  • clofibrate
  • salicylates
  • estrogens
  • methadone
  • 5-fluorouracil
  • tamoxifen
  • androgens
  • glucocorticoids
  • carbamazepine and phenobarbital
  • heparin
  • nonsteroidal anti-inflammatory drugs
  • rifampin
  • amiodarone and digoxin
  • certain antidepressants

References

1. Patil N, Rehman A, Jialal I. Hypothyroidism. In: StatPearls. NCBI Bookshelf version. StatPearls Publishing: 2022. Accessed September 19, 2022.

2. Persani L, Brabant G, Dattani M, Bonomi M, Feldt-Rasmussen et al. 2018 European Thyroid Association (ETA) Guidelines on the Diagnosis and Management of Central Hypothyroidism. July19, 2018. Accessed September 27, 2022.

3. U.S. Food and Drug Administration. Synthroid (levothyroxine sodium) tablets, for oral use. August 2022. Accessed September 19, 2022.

Author Bio

Jen Seabright, PharmD, is a freelance medical writer in Pittsburgh, PA.