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Hypothyroidism Main page

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Primary hypothyroidism
Hashimoto's thyroiditis
Secondary hypothyroidism
Tertiary hypothyroidism

Differentiating different causes of hypothyroidism



History and symptoms

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mahshid Mir, M.D. [2]

Synonyms and keywords:Primary hypothyroidism; Secondary hypothyroidism; Tertiary hypothyroidism; Decrease thyroid hormone; Hypo-functioning thyroid


Thyroxine (T4) and triiodothyronine (T3) are produced from the thyroid gland. Thyroid hormones are important in regulating various body functions and their deficiencies are associated with different symptoms including decrease in energy metabolism, decreased appetite, cold intolerance, and lower basal body temperature (due to low basal metabolic rate).[1] Iodine deficiency is recognized as the most common cause of hypothyroidism world-wide. In developed countries and areas with sufficient iodine, the most common cause of hypothyroidism is chronic autoimmune thyroiditis (Hashimoto’s thyroiditis). Hashimoto’s thyroiditis has a higher prevalence in women than in men.[2][3] Signs and symptoms of hypothyroidism are mostly related to the magnitude of the thyroid hormone deficiency and the acuteness of the development of hormone deficiency.[4] However, the typical clinical manifestations of hypothyroidism may vary depending on the cause of hypothyroidism. Clinical scenario, if associated with secondary and tertiary hypothyroidism, may present other coexisting endocrine deficiencies such as hypogonadism and adrenal insufficiency that may mask the manifestations of hypothyroidism. Although the diagnosis of hypothyroidism is mainly a laboratory diagnosis, the coexisting conditions and wide variation in clinical presentation may make the diagnosis difficult.[5] On the other hand, subclinical hypothyroidism is mostly asymptomatic, but may transform to clinical hypothyroidism. Recent evidence has shown that subclinical hypothyroidism may lead to various complications, such as hyperlipidemia, increased risk of cardiovascular disease (even heart failure), somatic and neuromuscular symptoms, and infertility.[6][7]


The table below presents a classification of isolated thyroid disorders and its causes based on the classification:[8] [9][10][11]

Classification Origin of the defect Causes
Endogenous causes Exogenous causes
Thyroid Pituitary Hypothalamus Surgery or radiation Other causes
Primary hypothyroidism + - -
Transient hypothyroidism + + -
  • Major surgeries
Central Hypothyroidism Secondary


Pituitary originated

- + -


Hypothalamus originated

- - +

Differentiating different causes of hypothyroidism

Various kinds of hypothyroidism can be differentiated from each other on the basis of history and symptoms and laboratory findings:[1][3][5]

Disease History and symptoms Laboratory findings Additional findings
Fever Goiter Pain TSH Free T4 T3 T3RU Thyroglobin TRH TPOAb
Primary hypothyroidism Autoimmune + +/-


- N/ Normal N/ Normal
Thyroiditis + +/- + Normal Normal N/ Normal Normal
Others - +/- - Normal Normal N/ Normal Normal
Transient hypothyroidism +/- - +/- Normal Normal Normal Normal
Subclinical hypothyroidism - - - Normal Normal Normal Normal N/
  • Asymptomatic
Central Hypothyroidism Pituitary + - - N/ N/ N/ Normal Normal Normal
Hypothalamus + - - Normal Normal
Resistance to TSH/TRH - - - N/ N/ Normal Normal / Normal
  • Rare


  • According to the Endocrine Society and the European Society for Pediatric Endocrinology, screening for congenital hypothyroidism (cretinism) is recommended in all neonates. Screening is recommended because early detection of cretinism and early treatment will prevent the consequences of the disease which may be mental retardation.[12]
  • In a worldwide view of strategies, screening of cretinism is been held in many countries including the United States. The screening helped in detecting the newborn with hypothyroidism. These cases are around 2000 annually in the United States and 12,000 worldwide.[13]
  • The screening of cretinism can be performed through the following laboratory tests:[14][15]


Hypothyroidism diagnosis can be made based on the laboratory findings[8][9][10][11] although choice of best lab test uncertain[16].

History, signs, and symptoms suggestive of hypothyroidism
Measure FT4 and TSH
Normal FT4, Elevated TSH>5.5
Decresased level of FT4
Subclinical hypothyroidism
Elevated TSH > 5.5
Normal TSH level OR Decreased TSH level < 0.2
Check anti-thyroid autoantibodies and TPOAb
Check TRH
Normal or increased
Autoimmune thyroiditis
• Resistance to TSH
Iodine deficeincy
•Pituitary related hypothyroidism
•Hypothalamus related hypothyroidism

History and symptom

The common symptoms and signs of clinical hypothyroidism are listed in the table below. The appearance of symptoms depends on the degree of hypothyroidism severity: [17][18][19]

Symptoms Constituitional HEENT Neuromuscular Other findings
More common
Less common
  • Slowed speech and movements

Differentiating hypothyroidism from other diseases:

Hypothyroidism should be differentiated from other diseases causing hypopituitarism.[20][21][22][23][24][25][26]

Diseases Onset Manifestations Diagnosis
History and Symptoms Physical examination Laboratory findings Gold standard Imaging Other investigation findings
Trumatic delivery Lactation failure Menstrual irregularities Other features
Sheehan's syndrome Acute ++ ++ Oligo/amenorrhea Symptoms of:
  • Clinical diagnosis
  • Most senitive test: Low baseline prolactin levels w/o response to TRH
  • Sequential changes of pituitary enlargement followed by:
  • Shrinkage and necrosis leading to decreased sellar volume or empty sella
Lymphocytic hypophysitis Acute +/- + Oligo/amenorrhea
  • Retro-orbital or Bitemporal pain
  • Diffuse and homogeneous contrast enhancement
Assays for:
  • Anti-TPO
  • Anti-Tg Ab
Pituitary apoplexy Acute +/- ++ Oligo/amenorrhea Severe headache
  • Decreased levels of anterior pituitary hormones in blood.
  • CT scan without contrast: Hemorrhage on CT presents as a hyperdense lesion

Blood tests may be done to check:

Empty sella syndrome Chronic - + Oligo/amenorrhea
  • Decreased levels of pituitary hormones in blood.
Simmonds' disease/Pituitary cachexia Chronic +/- + Oligo/amenorrhea
  • Loss of body hair
  • Decreased levels of anterior pituitary hormones in blood.
  • Done to rule out any pituitary cause
Hypothyroidism Chronic +/- - Oligomenorrhea/menorrhagia
  • Dry skin
  • Hair loss
  • Normal/ low TSH
  • Rest of pituitary hormone levels WNL
  • Done to rule out any pituitary cause
  • Assays for anti-TPO and anti-Tg Ab
  • FNA biopsy
Hypogonadotropic hypogonadism Chronic - - Oligo/amenorrhea
  • Energy and mood changes
  • Done to rule out any pituitary cause
Hypoprolactinemia Chronic - + -
  • Puerperal agalactogenesis
  • No workup is necessary
  • Decreased prolactin levels
  • Done to rule out any pituitary cause
Panhypopituitarism Chronic - + Oligo/amenorrhea
  • All pituitary hormones decreased
  • Done to rule out any pituitary cause
Primary adrenal insufficiency/Addison's disease Chronic - - -
  • Abdominal CT
  • Abdominal CT
  • Anti-adrenal Ab testing
Menopause Chronic - +/- Oligo/amenorrhea Normal

Hypothyroidism must be differentiated from other causes of headache,polyuria and polydypsia.

Disease Causes Symptoms Diagnosis and treatment
SIADH SIADH is a syndrome characterized by excessive release of antidiuretic hormone (ADH or vasopressin) from the posterior pituitary gland or another source. The result is hyponatremia, and sometimes fluid overload
  • Urine sodium concentration>40mmol/litre
Cerebral salt wasting syndrome Cerebral salt wasting syndrome is defined as therenal loss of sodium during intracranial disease leading to hyponatremia and a decrease in extracellular fluid volume The patient is Treatment is
Adrenal insufficiency Adrenal insufficiency

Adrenal insufficiency can be

Common causes of primary adrenal insufficiency:

Chronic disease is characterized by

Acute addisonian crisis is characterized by:

The diagnosis of Addisons disease is made through rapid ACTH administration and measurement of cortisol.

The definitive diagnosis is the cosyntropin or ACTH stimulation test. Acortisol level is obtained before and after administering ACTH. A normal person should show a brisk rise in cortisol level after ACTH administration.

Management: The management of Addison disease involves:

Adrenal crisis:

Hypopituitarism Abnormality in anterior pituitary function

Etiology is as follows:

Signs and symptoms ofhypopituitarism vary, depending on the deficient

hormone and severity of the disorder,some of the symptoms may be as follows:

The treatment of permanent hypopituitarism consists of replacement of the peripheral hormones

Hypothyroidism Hypofunctioning of the thyroid gland due to multifactorial etiology ranging from congenital to autoimmune causes described below: Diagnosis of hypothyroidism is based on blood tests:
Psychogenic polydipsia Also called as primary polydipsia is characterized bypolyuria and polydipsia. Causes are: Evaluation ofpsychiatric patients with polydipsia requires an evaluation for other medical causes of polydipsia, polyuria,hyponatremia, and the syndrome of inappropriate secretion of antidiuretic hormone.
  • The management strategy inpsychiatric patients should include:


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