History and exam
Key diagnostic factors
common
weakness
Common finding in hypothyroidism, but nonspecific.
fatigue
Common finding in hypothyroidism, but nonspecific.
cold intolerance
May be present in severe hypothyroidism.
Other diagnostic factors
common
decreased memory
Forgetfulness may be present in severe hypothyroidism. Nonspecific 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.
oligomenorrhea/amenorrhea
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 gonadotropin (follicle-stimulating hormone and LH) deficiency as a result of stalk effect associated with a pituitary mass.
galactorrhea
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 tumors, such as growth hormone (GH)- or adrenocorticotropic hormone (ACTH)-secreting adenomas, as well as cysts, meningiomas, dysgerminomas, craniopharyngiomas, and tumor metastases to the pituitary gland.[5]
multiple endocrine neoplasia (MEN) type I
Conditions that increase the risk of pituitary tumors, 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 tumors, 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 tumors, 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]
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 ages 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 (nonfunctioning pituitary adenomas)
sarcoidosis
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.
hemochromatosis
Hypopituitarism, particularly hypogonadotropic hypogonadism, is a prominent manifestation of iron storage disease.
Central hypothyroidism is generally not found until the later stages of hemochromatosis, at which time it is usually irreversible.
Sheehan syndrome (postpartum pituitary necrosis)
Sheehan syndrome occurs as a result of ischemic pituitary necrosis due to postpartum hemorrhage 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 postpartum 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 receptor (TRH), 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 pediatric patients. Key symptoms included weight gain and fatigue. The authors of the case series recommended periodic thyroid function tests for all pediatric patients on anticonvulsant drugs to evaluate for possible central hypothyroidism.[31]
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