Primary hypothyroidism

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Last reviewed: 2 Jun 2025

Last updated: 25 Apr 2025

Primary hypothyroidism usually presents with non-specific symptoms of fatigue, depression, constipation, and mild weight gain; physical examination may show dry skin, eyelid oedema, and bradycardia.

Elevated thyroid-stimulating hormone and low free thyroxine confirms diagnosis of overt primary hypothyroidism.

Commonly, disease is sub-clinical with minimal elevation of thyroid-stimulating hormone and normal thyroxine.

Treatment is with levothyroxine; starting dose depends on age and presence of co-existing cardiac disease.

Over-treatment is uncommon but can lead to iatrogenic hyperthyroidism.

Definition

Hypothyroidism is a clinical state resulting from underproduction of the thyroid hormones thyroxine (T4) and triiodothyronine (T3). Most cases are due to primary hypothyroidism, a failure of the thyroid gland to produce thyroid hormones. Overt primary hypothyroidism is defined as thyroid-stimulating hormone (TSH) concentrations above the reference range and free thyroxine concentrations below the reference range.[1] Secondary hypothyroidism is due to underproduction of TSH by the pituitary gland.[2] Sub-clinical hypothyroidism is a state of mild thyroid failure, with normal levels of T4 and T3, and minimal elevation of TSH; it is usually asymptomatic.[3] Myxoedema coma is a rare severe form of hypothyroidism that can lead to multi-organ failure.[2]

History and exam

Key diagnostic factors

presence of risk factors
non-specific symptoms

Full details

Other diagnostic factors

lethargy
constipation
weight gain
depression
menstrual irregularity
dry or coarse skin
change in voice
bradycardia
hypertension
delayed relaxation of tendon reflexes
cold sensitivity
coarse hair
eyelid oedema
goitre

Full details

Risk factors

iodine deficiency
female sex
middle age
family history of autoimmune thyroiditis
autoimmune disorders
treatment for thyroid disease
post-partum thyroiditis
Turner and Down syndromes
type 1 diabetes
radiotherapy to head and neck
infiltrative disease
iodine excess
exposure to pesticides
amiodarone use
lithium use
laryngectomy
treatment for multidrug-resistant tuberculosis (TB)

Full details

Diagnostic investigations

1st investigations to order

serum thyroid-stimulating hormone (TSH)

Full details

Investigations to consider

free serum thyroxine (T4)
antithyroid peroxidase antibodies (anti-TPOAbs)
FBC
fasting blood glucose
serum cholesterol

Full details

Treatment algorithm

ONGOING

confirmed overt primary hypothyroidism

sub-clinical hypothyroidism

Contributors

Authors

Wail Malaty, MD

Adjunct Clinical Professor

Department of Family Medicine

University of North Carolina

Chapel Hill

Disclosures

WM declares that he has no competing interests.

Peer reviewers

Sun Y. Lee, MD, MSc

Assistant Professor of Medicine

Boston University School of Medicine

Boston

Disclosures

SYL declares that she has no competing interests.

Salman Razvi, MD, FRCP

Consultant Endocrinologist

Queen Elizabeth Hospital

Gateshead

Disclosures

SR declares that he has no competing interests.

Lakdasa Premawardhana, MBBS, FRCP, FRCPE

Consultant Physician

Caerphilly Miners' Hospital

Caerphilly

Disclosures

LP declares that he has no competing interests.

Birte Nygaard, MD, PhD

Associated Professor

Consultant Endocrinologist

Herlev Hospital

University of Copenhagen

Denmark

Disclosures

BN declares that she has no competing interests.

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

Taylor PN, Medici MM, Hubalewska-Dydejczyk A, et al. Hypothyroidism. Lancet. 2024 Oct 5;404(10460):1347-64. Abstract

Alexander EK, Pearce EN, Brent GA, et al. 2017 guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid. 2017 Mar;27(3):315-89.Full text Abstract

American Association of Clinical Endocrinologists; American Thyroid Association. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract. 2012 Nov-Dec;18(6):988-1028.Full text Abstract

Jonklaas J, Bianco AC, Bauer AJ, et al. Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement. Thyroid. 2014 Dec;24(12):1670-751.Full text Abstract

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials
- Central or secondary hypothyroidism
- Depression
- Alzheimer's dementia
More Differentials
Guidelines
- Thyroid disease: assessment and management
- Subclinical hypothyroidism and hypothyroidism in pregnancy
More Guidelines
Patient information
Underactive thyroid
Underactive thyroid: questions to ask your doctor
More Patient information
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Primary hypothyroidism

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic investigations

1st investigations to order

Investigations to consider

Treatment algorithm

confirmed overt primary hypothyroidism

sub-clinical hypothyroidism

Contributors

Authors

Wail Malaty, MD

Disclosures

Peer reviewers

Sun Y. Lee, MD, MSc

Disclosures

Salman Razvi, MD, FRCP

Disclosures

Lakdasa Premawardhana, MBBS, FRCP, FRCPE

Disclosures

Birte Nygaard, MD, PhD

Disclosures

References

Key articles

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials

Guidelines

Patient information

Log in or subscribe to access all of BMJ Best Practice

Log in or subscribe to access all of BMJ Best Practice

Log in to access all of BMJ Best Practice