Hypothyroidism

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Hypothyroidism Main page
Patient Information
Overview
Classification Primary hypothyroidism Hashimoto's thyroiditis Secondary hypothyroidism Tertiary hypothyroidism
Differentiating different causes of hypothyroidism
Screening
Diagnosis
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

Overview

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). 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. 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. 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. 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.

Classification

The table below presents a classification of isolated thyroid disorders and its causes based on the classification:

Classification		Origin of the defect			Causes
					Endogenous causes	Exogenous causes
		Thyroid	Pituitary	Hypothalamus		Surgery or radiation	Other causes
Primary hypothyroidism		+	-	-	Congenital hypothyroidism Autoimmune (Hashimoto's) thyroiditis Resistance to TSH	After hyperthyroidism or thyroid cancer treatment: Thyroidectomy Radioiodine therapy Radiation for non-thyroid-related head and neck malignancies including lymphoma	Iodine deficeincy Drug induced thyroiditis Amiodarone Lithium Thionamide Interferon Sunitinib Rifampicin Thalidomide Acute infectious thyroiditis Trauma-induced
Transient hypothyroidism		+	+	-	Subacute (de Quervain’s) thyroiditis Postpartum thyroiditis	Major surgeries
Central Hypothyroidism	Secondary OR Pituitary originated	-	+	-	Pituitary mass lesions, especially pituitary adenomas Brain cysts and abscesses Meningiomas Dysgerminomas Metastatic tumors Craniopharyngiomas Pituitary apoplexy Sheehan syndrome (postpartum pituitary necrosis) Idiopathic isolated TSH deficiency Lymphocytic or granulomatous hypophysitis	Surgery of pituitary adenomas Radiation therapy to: Pituitary adenomas Other mass lesions near pituitary gland	Head trauma with injury to the stalk
	Tertiary OR Hypothalamus originated	-	-	+	Hemochromatosis Histiocytosis Developmental abnormalities Internal carotid aneurysms Other central nervous system (CNS) tumors Idiopathic isolated TRH deficiency	Radiation in high doses to: Brain Infratemporal Nasopharyngeal Oropharyngeal	Infections Tuberculosis Syphilis Toxoplasmosis Sarcoidosis

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:

Disease		History and symptoms			Laboratory findings							Additional findings
		Fever	Goiter	Pain	TSH	Free T4	T3	T3RU	Thyroglobin	TRH	TPOAb
Primary hypothyroidism	Autoimmune	+	+/- Diffuse	-	↑	↓	N/↓	Normal	N/↑	Normal	↑	May be accompanied by other autoimmune diseases
	Thyroiditis	+	+/-	+	↑	↓	Normal	Normal	N/↑	Normal	Normal	Infectious thyroiditis associated with neck pain
	Others	-	+/-	-	↑	↓	Normal	Normal	N/↑	Normal	Normal	History of hyperthyroidism Drug history
Transient hypothyroidism		+/-	-	+/-	↑	↑	Normal	Normal	↑	Normal	Normal	May present primarily with hyperthyroidism
Subclinical hypothyroidism		-	-	-	↑	Normal	Normal	Normal	↑	Normal	N/↑	Asymptomatic
Central Hypothyroidism	Pituitary	+	-	-	N/↓	N/↓	N/↓	↓	Normal	Normal	Normal	Other pituitary hormone deficiencies signs
	Hypothalamus	+	-	-				↑	Normal	↓	Normal	Other pituitary hormone deficiencies signs
Resistance to TSH/TRH		-	-	-	↑	N/↓	N/↓	Normal	Normal	↑/↓	Normal	Rare

Screening

• 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.
• 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.
• The screening of cretinism can be performed through the following laboratory tests:
  • Measuring the level of thyroxine hormone (T4)
  • Blood TSH assay
  • Both thyroxine and TSH levels

Diagnosis

Hypothyroidism diagnosis can be made based on the laboratory findings although choice of best lab test uncertain.

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

Increased

Normal

Normal or increased

Decreased

•Autoimmune thyroiditis • Resistance to TSH

•Iodine deficeincy •Thyroiditis

•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:

Symptoms	Constituitional	HEENT	Neuromuscular	Other findings
More common	Fatigue Cold intolerance Decreased sweating Hypothermia Coarse skin Weight gain	Hoarseness Goiter Fullness in the throat and neck	Depression Emotional lability Attention deficit	Macroglossia Obstructive sleep apnea Paresthesia Nerve entrapment syndromes (carpal tunnel syndrome) Blurred vision (central hypothyroidism)
Less common	Puffiness Hair loss Constipation Fever If accompanied by thyroiditis	Sore throat Periorbital edema	Slowed speech and movements	Pituitary hyperplasia followed by hyperprolactinemia Ataxia Myxedema coma (with non-pitting edema) Cardiomegaly Pericardial effusion Ascites Hyperlipidemia Galactorrhea Infertility

Differentiating hypothyroidism from other diseases:

Hypothyroidism should be differentiated from other diseases causing hypopituitarism.

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: Adrenal insufficiency Hypothyroidism	Breast tissue atrophy Decreased axillary and pubic hair growth	Pancytopenia Eosinophilia Hyponatremia Low fasting plasma glucose Decreased levels of anterior pituitary hormones in blood	Clinical diagnosis Most senitive test: Low baseline prolactin levels w/o response to TRH	CT/MRI: Sequential changes of pituitary enlargement followed by: Shrinkage and necrosis leading to decreased sellar volume or empty sella	Pituitary hormone stimulation tests (Metoclopramide and clomiphene citrate stimulation tests)
Lymphocytic hypophysitis	Acute	+/-	+	Oligo/amenorrhea	Associated with autoimmune conditions Generalized headache Retro-orbital or Bitemporal pain Mass lesion effect such as visual field defects	DI Autoimmune thyroiditis	Decreased pituitary hormones(Gonadotropins most common) Hyperprolactinemia(40%) GH excess	Pituitary biopsy: lymphocytic infiltration	CT & MRI: Features of a pituitary mass Diffuse and homogeneous contrast enhancement	Assays for: Anti-TPO Anti-Tg Ab
Pituitary apoplexy	Acute	+/-	++	Oligo/amenorrhea	Severe headache Nausea and vomiting Paralysis of eye muscles (diplopia) Changes in vision	Visual acuity defects CN palsies (nerves III, IV, V , and VI)	Decreased levels of anterior pituitary hormones in blood.	MRI	CT scan without contrast: Hemorrhage on CT presents as a hyperdense lesion MRI: If inconclusive CT	Blood tests may be done to check: PT/INR and aPTT Pituitary hormonal assay
Empty sella syndrome	Chronic	-	+	Oligo/amenorrhea	Erectile dysfunction Headache Low libido	Signs of raised intracranial pressure may be present Nipple discharge	Decreased levels of pituitary hormones in blood.	MRI	Empty sella containing CSF	Pituitary hormone stimulation tests (Metoclopramide and clomiphene citrate stimulation tests)
Simmonds' disease/Pituitary cachexia	Chronic	+/-	+	Oligo/amenorrhea	Cachexia Premature aging	Progressive emaciation Loss of body hair	Decreased levels of anterior pituitary hormones in blood.	MRI	Done to rule out any pituitary cause	Pituitary hormone stimulation tests (Metoclopramide and clomiphene citrate stimulation tests)
Hypothyroidism	Chronic	+/-	-	Oligomenorrhea/menorrhagia	Cold intolerance Constipation	Dry skin Bradycardia Hair loss Myxedema Delayed relaxation phase of deep tendon reflexes	Low T3,T4 Normal/ low TSH Rest of pituitary hormone levels WNL	TSH levels	Done to rule out any pituitary cause	Assays for anti-TPO and anti-Tg Ab FNA biopsy
Hypogonadotropic hypogonadism	Chronic	-	-	Oligo/amenorrhea	Hot flushes Energy and mood changes Decreased libido	Breast tissue atrophy Decreased maturation of vaginal mucosa	Low estrogen, testosterone High FSH/LH	FSH LH	Done to rule out any pituitary cause	Genetic tests  (karyotype) Measurement of total and free testosterone and 17-hydroxyprogesterone concentrations
Hypoprolactinemia	Chronic	-	+	-	Infertility Subfertiliy	Puerperal agalactogenesis	No workup is necessary	Decreased prolactin levels	Done to rule out any pituitary cause	Prolactin assay in 3rd trimester LH, FSH Thyrotropin and free thyroxine
Panhypopituitarism	Chronic	-	+	Oligo/amenorrhea	Polyuria Polydipsia Features of hypothyroidism and hypoadrenalism	Growth failure B/L hemianopsia Papilledema	All pituitary hormones decreased	MRI	Done to rule out any pituitary cause	Left hand and wrist radiograph for bone age
Primary adrenal insufficiency/Addison's disease	Chronic	-	-	-	Hypoglycemia Hypotension	Dehydration Hyperpigmentation loss of pubic and axillary hair	Hyponatremia with/without hyperkalemia Plasma renin activity to aldosterone ratio	Abdominal CT	Abdominal CT	Serum cortisol testing Serum ACTH testing Anti-adrenal Ab testing
Menopause	Chronic	-	+/-	Oligo/amenorrhea	Hot flashes Insomnia Weight gain and bloating Mood changes	Vaginal atrophy Loss of pelvic muscle tone	↑ FSH ↓ Estradiol and inhibin	FSH > LH	Normal	Endometrial biopsy

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	Nausea / vomiting Cramps Depressed mood Irritability Confusion Hallucinations Seizures, stupor or coma	Hyponatremia <135 mmol/l Effective serum osmolality<275mosm Urine sodium concentration>40mmol/litre Plasma uric acid <200;FeUrate>12% Absence of edematous disease likecardiac failure, liver cirrhosis,nephrotic syndrome. Normal adrenal and thyroid function
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 Trauma Tumor Hematoma	The patient is Hypovolemic Hyponatremic	Treatment is Hydration and Sodium replacement
Adrenal insufficiency	Adrenal insufficiency Mineralocorticoid deficiency is present. Secondary or tertiary adrenal insufficiency will have preservedmineralocorticoid function owing to separate feedback mechanisms Adrenal insufficiency can be Primary Secondary Tertiary Common causes of primary adrenal insufficiency: Autoimmune Iatrogenic Drugs Adrenal hemorrhage Cancer Infection Congenital Secondary adrenal insufficiency: ( Aldosterone) levels normal Most common causes are: Traumatic brain injury (TBI) Panhypopituitarism Tertiary adrenal insufficiency Exogenoussteroid administration is the most common cause of tertiary adrenal insufficiency	Fatigue Muscle weakness Loss of appetite Weight loss Abdominal pain Diarrhea Vomiting Chronic disease is characterized by Weight loss Sparse axillary hair Hyperpigmentation Orthostatic hypotension. Acute addisonian crisis is characterized by: Fever Hypotension	The diagnosis of Addisons disease is made through rapid ACTH administration and measurement of cortisol. Lab findings include: White blood cell count with moderate neutropenia Lymphocytosis Eosinophilia Hyperkalemia Hypoglycemia Hyponatremia Morning low plasma 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: Gluocorticoid Mineralocorticoid Sodium chloride replacement. Adrenal crisis: In adrenal crisis,measure cortisol level,then rapidly administer Fluids Hydrocortisone
Hypopituitarism	Abnormality in anterior pituitary function Etiology is as follows: Pituitary tumors Sellar tumors Head trauma Infection Empty sella Infiltration Idiopathic Congenital	Signs and symptoms ofhypopituitarism vary, depending on the deficient hormone and severity of the disorder,some of the symptoms may be as follows: Fatigue Weight loss Decreased libido Decreased appetite Facial puffiness Anemia Infertility Cold insensitivity. Amenorrha Inability to lactate in breast feeding women Decreased facial orbody hair in men Short stature in children	History andphysical examination, including visual field testing, are important. The treatment of permanent hypopituitarism consists of replacement of the peripheral hormones Hydrocortisone DHEA Thyroxine Testosterone or oestradiol Growth hormone Surgery and/or Radiotherapy to restore normal endocrine function and quality of life Life long monitoring of serum hormone levels and symptoms of hormone deficiency or excess is needed in these patients
Hypothyroidism	Hypofunctioning of the thyroid gland due to multifactorial etiology ranging from congenital to autoimmune causes described below: Congenital Autoimmune Drugs Post surgery Post radiation Infiltrative e.g., amyloid	Fatigue Constipation Dry skin Weight gain Cold intolerance Puffy face Hoarseness Muscle weakness Elevated blood cholesterol level Bradycardia Myopathy Depression Impaired memory	Diagnosis of hypothyroidism is based on blood tests: T3(triiodothyronine) T4(Thyroxine) and TSH (thyroid stimulating hormone). Signs and symptoms are neither sensitive nor specific for the diagnosis. TSH is the most sensitive tool for screening,diagnosis and treatment follow up, whenpituitary is normal. The drug of choice for treatment is Levothyroxine
Psychogenic polydipsia	Also called as primary polydipsia is characterized bypolyuria and polydipsia. Causes are: Adverse effect of a medication Traumaticbrain injury Psychiatric disorders such as schizophrenia Defect in the hypothalamus	Polyuria Polydipsia Confusion Lethargy Psychosis Seizures and Sometimes, even death	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: Fluid restriction andbehavioral and pharmacologic modalities. The water deprivation test is the gold standard test

References