Approach
The treatment of central hypothyroidism is thyroxine replacement, as well as a thorough assessment and management of the underlying pituitary pathology.[4][46] A specialist endocrine opinion should be sought urgently. Genetic analyses are recommended in congenital cases, and in cases of onset during childhood or at any age when central hypothyroidism remains unexplained.[3]
Treatment of concomitant adrenal insufficiency
It is important to assess and treat concomitant adrenal hormone deficiency before thyroxine replacement is initiated. Drugs of choice for the treatment of adrenal insufficiency include hydrocortisone and prednisolone. If thyroxine is replaced prior to untreated adrenal insufficiency, an acute adrenal crisis may result. Thus, if it is not feasible to assess adrenal function prior to initiating thyroxine replacement, prophylactic treatment with glucocorticoids should be considered.[1]
Thyroxine replacement
Levothyroxine, a synthetically derived levorotatory isomer of thyroxine, is used for thyroxine replacement therapy. The dose of levothyroxine in central hypothyroidism depends on its aetiology. Generally, treatment can be started with the full estimated dose requirement; however, in older people or in those with known coronary artery disease, it is recommended to start at a low dose of levothyroxine and gradually titrate to the full calculated dose, based on serum free thyroxine (T4) results, usually targeting the upper half of the reference range.[47][48][49] Further dose adjustments may be required in patients treated with growth hormone and/or oestrogen therapy.[50][51][52] The main potential adverse effect of levothyroxine therapy is overdose.
Absorption of levothyroxine can be impaired by malabsorptive disorders such as coeliac disease, inflammatory bowel disease, and lactose intolerance. Drugs that may impair levothyroxine absorption include iron, aluminium-containing antacids, calcium carbonate, phosphate binders, bile-acid sequestrants, and proton-pump inhibitors. Levothyroxine should be taken at least 4 hours before or after drugs that may interfere with absorption.[53]
Levothyroxine in combination with liothyronine (a synthetic form of triiodothyronine) is usually not considered, due to levothyroxine being the major component of thyroid hormone transfer across the blood-brain barrier.[54]
Treatment of pituitary tumours
Medical treatments of responsive tumours may include dopaminergic medications or somatostatin analogues. Prolactin-secreting pituitary adenomas are managed primarily with dopamine agonist therapy.[55][56]
Non-prolactin-secreting pituitary adenomas may be managed surgically, depending on tumour size, extent of invasion, and secretory function. Surgical resection may be performed via a trans-sphenoidal or trans-frontal approach.[57][58]
Radiotherapy is an effective treatment for residual or recurrent pituitary adenomas, with excellent rates of tumour control and normalisation of excess hormone secretion. Technical developments in the delivery of radiotherapy, including stereotactic radiosurgery, aim to reduce the amount of radiation delivered to normal brain tissue.[59]
Laboratory evaluation
Treatment should be monitored in an endocrine clinic setting. Levothyroxine dose titration should be based on the fasting serum free T4 value measured 24 hours after the last levothyroxine dose. Adequacy of treatment is usually re-assessed by clinical assessment and measurement of free T4 levels 4 to 6 weeks after a dose adjustment. Thyroid-stimulating hormone measurements are not interpretable in the management of central hypothyroidism and should not be monitored. It is important to note that clinical benefits of levothyroxine replacement may take longer than the biochemical restoration of serum free T4 levels. Titration of levothyroxine should aim to achieve serum free T4 levels to the mid to upper part of the reference range. Once stable, repeat measurements of serum free T4 levels may be performed annually.
Use of this content is subject to our disclaimer