History and exam

Key diagnostic factors

common

presence of risk factors

Key risk factors include multiple endocrine neoplasia (MEN) type I, head and neck irradiation, and traumatic brain injury.

weakness

Common finding in hypothyroidism, but non-specific.

fatigue

Common finding in hypothyroidism, but non-specific.

cold intolerance

May be present in severe hypothyroidism.

Other diagnostic factors

common

decreased memory

Forgetfulness may be present in severe hypothyroidism. Non-specific sign which may be mistaken for other conditions, such as dementia.

constipation

17% prevalence among those with primary hypothyroidism.[37]

muscle cramps

34% prevalence among those with primary hypothyroidism.[37]

weight gain

The result of both fluid retention and decreased metabolism. Weight gain is usually modest. Marked obesity is not characteristic of hypothyroidism.

depression

Depression can be a manifestation of hypothyroidism.

dry, coarse skin

May be present in severe hypothyroidism.

oligomenorrhoea/amenorrhoea

May result from hypothyroidism and/or accompanying hypogonadism.

bradycardia

Caused by a decrease in thyroid hormone.

reduced body and scalp hair

May be present in severe hypothyroidism.

delayed relaxation of deep tendon reflexes

May be present in severe hypothyroidism.

uncommon

hearing impairment

May be present in up to 85% of cases of hypothyroidism and may be due to changes in sensorineural, central, or conductive components.[36]

impassive facial expression

May be present in severe hypothyroidism.

diabetes insipidus (DI)

DI is caused by decreased secretion of antidiuretic hormone and is more frequently associated with hypothalamic pathologies. Lesions of the posterior pituitary rarely cause permanent DI.

headache

May be indicative of an intra- or suprasellar mass lesion.

diplopia

May be indicative of an intra- or suprasellar mass lesion.

decreased peripheral vision

A pituitary adenoma compressing on the optic chiasm may cause a bitemporal hemianopia.

atrophic breasts

Sign of gonadotrophin (follicle-stimulating hormone and LH) deficiency as a result of stalk effect associated with a pituitary mass.

galactorrhoea

Functional pituitary adenomas may result in an elevation of prolactin.[38]

moon facies

Cushingoid appearance may be seen in some patients with hypothyroidism.

buffalo hump

Cushingoid appearance may be seen in some patients with hypothyroidism.

Risk factors

strong

presence of pituitary mass lesions

Pituitary mass lesions, especially pituitary adenomas, are the most common cause of central hypothyroidism.[1] Other mass lesions include primary tumours, such as growth hormone (GH)- or adrenocorticotrophic hormone (ACTH)-secreting adenomas, as well as cysts, meningiomas, dysgerminomas, craniopharyngiomas, and tumour metastases to the pituitary gland.[5]

multiple endocrine neoplasia (MEN) type I

Conditions that increase the risk of pituitary tumours, such as MEN type I, are associated with an increased risk of central hypothyroidism.[17]

head and neck irradiation

The risk of central hypothyroidism associated with head and neck irradiation is dose-dependent.[1]

Following conventional irradiation (30-50 Gy) for pituitary tumours, the incidence of central hypothyroidism is observed in 3% to 6% of patients.[18] In another study of 312 patients who underwent irradiation for extracranial head and neck tumours, 5.4% developed symptomatic central hypothyroidism over a median latency of 4.8 years, and 20.3% developed asymptomatic central hypothyroidism. Freedom from asymptomatic central hypothyroidism decreased from 91% at 5 years to 78% at 10 years, with a similar decline reported for symptomatic central hypothyroidism.[19]

traumatic brain injury (TBI)

Central hypothyroidism has been observed in 10% to 30% of cases following TBI.[7][20]

weak

age between 5-15 years and 45-60 years (craniopharyngiomas)

Craniopharyngiomas have a bimodal age distribution with a peak typically between 5-15 years of age and a second peak in adults aged 45-60 years.[21] Some variability in age distributions is reported in the literature. For example, data from one US study suggest a slightly shorter initial peak (5-9 years of age) and a more delayed second peak (55-69 years of age).[22]

age 20-50 years (prolactinomas)

Prolactinomas occur most commonly in women aged between 20 and 50 years.[23]

age 40-80 years (non-functioning pituitary adenomas)

Non-functioning pituitary adenomas are most common in adults aged 40-80 years.[24][25]

sarcoidosis

Sarcoidosis affects the central nervous system in 5% to 16% of patients.[26]

Hypothalamic dysfunction and hypopituitarism are the most common neuroendocrine manifestations; however, isolated central hypothyroidism can also be rarely observed.[26]

histiocytosis

Hypothalamic/pituitary involvement is a well-described feature of Langerhans' cell histiocytosis (LCH).

Hypopituitarism has been reported in up to 20% of patients with LCH.[6] Evidence of central hypothyroidism arising from LCH involvement is mostly available as case reports.

haemochromatosis

Hypopituitarism, particularly hypogonadotrophic hypogonadism, is a prominent manifestation of iron storage disease.

Central hypothyroidism is generally not found until the later stages of haemochromatosis, at which time it is usually irreversible.

Sheehan syndrome (postnatal pituitary necrosis)

Sheehan syndrome occurs as a result of ischaemic pituitary necrosis due to postnatal haemorrhage and is associated with central hypothyroidism in the majority of cases.[27]

lymphocytic hypophysitis

Lymphocytic hypophysitis is a potential cause of hypopituitarism and most often occurs in late pregnancy or the early postnatal period.[28]

family history of central hypothyroidism

In this situation, central hypothyroidism is generally due to a homozygous mutation of thyroid-stimulating hormone (TSH), resulting in familial clustering of congenital central hypothyroidism. However, pituitary-selective genes encoding the thyrotropin-releasing hormone (TRH) receptor, the beta-subunit of TSH, and the immunoglobulin superfamily factor 1 (IGSF1) have been associated with isolated central hypothyroidism.[1][16] Mutations in IGSF1 and TBL1X (part of the thyroid hormone receptor complex) are X-linked causes of central hypothyroidism.[3]

anticonvulsant drugs

Thyroid dysfunction has been associated with short- and long-term use of anticonvulsant drugs in both children and adults.[1][29]

Anticonvulsant drugs, mostly those from older classes including carbamazepine and phenytoin, may promote increased metabolism of thyroid hormones and interfere with the hypothalamic-pituitary axis.[29]

A retrospective study of adults with epilepsy found that 21% of those treated with anticonvulsant drugs developed central hypothyroidism. Both carbamazepine and oxcarbazepine were associated with an increased risk of central hypothyroidism, particularly in women.[30]

Similarly, a case series found oxcarbazepine to be the cause of central hypothyroidism in three paediatric patients. Key symptoms included weight gain and fatigue. The authors of the case series recommended periodic thyroid function tests for all paediatric patients on anticonvulsant drugs to evaluate for possible central hypothyroidism.[31]

Use of this content is subject to our disclaimer