2016 Endocrine Society Guidelines: Central Hypothyroidism

Central Hypothyroidism is a very rare cause of reduced thyroid production, mainly secondary to pituitary anomaly. Infections, tumors, cysts, autoimmunity, surgery and radiation are usually responsible for the abnormal TSH secretion by the pituitary gland.

Endocrine Society released guidelines on diagnosis and management of central hypothyroidism in November 2016. Please find below excerpts with slightly modified wording for easier and succinct reading.




Central Hypothyroidism (CH) is caused by insufficient TSH stimulation of a normal thyroid gland due to the inadequate secretion or action of TSH-releasing hormone (TRH) or TSH. Acquired CH is usually associated with other pituitary hormone deficiencies.

Approximately 50% of CH cases are caused by pituitary macroadenomas, whereas craniopharyngiomas are the most common extrasellar cause, especially in younger patients. The frequency of CH with nonfunctioning pituitary adenomas may reach 43% preoperatively and 57% postoperatively.

CH occurs in up to 65% of patients irradiated for brain tumors and up to half of patients irradiated for nasopharyngeal or paranasal sinus tumors. CH due to traumatic brain injuries or stroke may be increasing in prevalence as more patients survive these events.


  • We recommend measuring serum free T4 (fT4) and TSH to evaluate central hypothyroidism (CH). An FT4 level below the laboratory reference range in conjunction with a low, normal, or mildly elevated TSH in the setting of pituitary disease usually confirms a CH diagnosis.

  • In patients with pituitary disease and low-normal fT4 levels suspected to have mild CH, we suggest starting levothyroxine (LT4) if suggestive symptoms are present or following fT4 levels over time and starting treatment if the fT4 level decreases by 20% or more.

  • We suggest against using dynamic TSH-secretion testing to diagnose CH.


  • We recommend LT4 in doses sufficient to achieve serum fT4 levels in the mid-upper half of the reference range. Appropriate LT4 doses in CH average 1.6 μg/kg/d, with dose adjustments based on clinical context, age, and fT4 levels.

  • We suggest against treating CH with levotriiodothyronine (LT3), thyroid extracts, or other formulations of thyroid hormones.

  • We recommend against using serum TSH levels to adjust thyroid replacement dosing in patients with CH.

Hormone Interactions:

  • We suggest evaluating patients with CH for adrenal insufficiency (AI) before starting LT4 therapy. If this is not feasible, clinicians should prescribe empiric GC therapy in patients with CH who are starting L-T4 therapy until there is a definitive evaluation for AI.

  • We recommend that clinicians monitor euthyroid patients with growth hormone deficiency (GHD) who begin GH therapy for the risk of developing CH, and if fT4 levels decrease below the reference range, these patients should begin LT4 therapy. CH patients with GHD who are already receiving LT4 may require increased LT4 doses when they begin GH therapy to maintain fT4 levels within target ranges.

  • We suggest clinicians treat CH before performing GH stimulation testing because CH may impair the accurate diagnosis of GHD.

  • In patients with CH requiring changes in estrogen therapy, we recommend monitoring fT4 levels and adjusting LT4 doses to maintain fT4 levels within target ranges.

Cardiovascular Risk:

  • To avoid the possible long-term cardiovascular risks of insufficient or excess thyroid hormone treatment, clinicians should adjust LT4 doses to avoid low or elevated fT4 levels in CH. (Ungraded Good Practice Statement).


  • We recommend that clinicians monitor fT4 or tT4 levels every 4–6 weeks for women with CH who become pregnant, and that these women may require increased LT4 doses to maintain levels within target ranges for pregnancy.

J  C  E  M

Endocrine Society Guidelines

November 2016