Hypothyroidism is a clinical endocrine condition defined by inadequate availability of thyroid hormones at the tissue level, resulting in reduced metabolic processes dependent on triiodothyronine (T3) and thyroxine (T4). In most cases, it is caused by a primary defect of the thyroid gland, characterised by reduced production of T4 and T3 and a compensatory increase in TSH, whereas in central forms the dysfunction originates in the pituitary gland or hypothalamus and TSH is low or inappropriately normal. Because thyroid hormones regulate oxygen consumption, thermogenesis, cardiovascular, neuromuscular and neuropsychiatric function, hypothyroidism can affect virtually every organ system, with a clinical spectrum ranging from mild and insidious forms to emergencies such as myxoedema coma.
Conceptually, hypothyroidism represents the common outcome of different pathogenetic mechanisms, including autoimmune destruction of the thyroid parenchyma, iodine deprivation, iatrogenic injury following surgery or radioactive iodine treatment, pharmacological interference with hormone synthesis and secretion, and transient conditions such as certain forms of thyroiditis. Diagnosis is based on an accurate biochemical assessment, integrated with identification of the aetiology and evaluation of systemic consequences. The standard treatment is replacement therapy with levothyroxine, personalised according to age, comorbidities and clinical context, with particular attention to cardiovascular safety and management in special conditions such as pregnancy, older age and concomitant disease.
Hypothyroidism is one of the most common endocrine disorders, and its distribution in the population depends substantially on the iodine status of the geographical area and on the prevalence of autoimmune diseases. In areas with sufficient iodine intake, the predominant cause is chronic autoimmune thyroiditis, whereas in areas with persistent iodine deficiency, hypothyroidism may represent the progression of endemic goitre and adaptive alterations in hormone synthesis. Prevalence estimates vary across studies and healthcare settings because many forms are oligosymptomatic and are identified through opportunistic TSH screening, whereas others become apparent at advanced stages or during periods of physiological stress, such as pregnancy and ageing. Frequency increases with age, and the female-to-male ratio is markedly imbalanced, consistently with the epidemiology of autoimmune thyroid diseases.
Among individual risk factors, a family history of thyroid autoimmunity and other autoimmune diseases increases the likelihood of developing clinical hypothyroidism, as does the presence of anti-thyroid peroxidase or anti-thyroglobulin autoantibodies in euthyroid individuals, which represents a marker of risk for progression over time. Conditions such as type 1 diabetes mellitus, coeliac disease, vitiligo, pernicious anaemia and other autoimmune endocrinopathies may coexist and increase the pre-test probability, making periodic monitoring of thyroid function reasonable. Autoimmune susceptibility results from a complex interaction between genetic predisposition and environmental factors, with potential roles for immune status, sex hormones, the microbiome and inflammatory triggers, whereas excessive iodine exposure may facilitate the clinical expression of thyroid autoimmunity in some individuals.
Iatrogenic factors represent an important category. Total or subtotal thyroidectomy for nodular or oncological disease causes permanent hypothyroidism when the residual thyroid mass is insufficient to ensure adequate hormone synthesis. Treatment with radioactive iodine for hyperthyroidism or selected thyroid disorders may also lead to delayed hypothyroidism through progressive damage to the thyroid parenchyma. Radiotherapy to the neck and upper mediastinum, used in oncology, is an additional risk factor for thyroid dysfunction over the medium to long term, requiring prolonged follow-up because hypothyroidism may develop years after exposure.
Medications are a clinically important determinant. Amiodarone and lithium may induce hypothyroidism through different mechanisms, respectively because of a high iodine load and interference with organification and deiodination, or because of alterations in hormone synthesis and release and facilitation of autoimmunity in predisposed individuals. Other medications and interfering substances may reduce absorption or increase levothyroxine requirements in patients already receiving treatment, destabilising the biochemical profile and promoting recurrence of symptoms. In oncology, immunotherapies may be associated with autoimmune thyroid dysfunction or destructive thyroiditis that progresses to permanent hypothyroidism, requiring structured endocrine surveillance within treatment pathways.
The risk of hypothyroidism also increases in conditions in which thyroid physiology or the availability of hormones and binding proteins changes substantially. During pregnancy, thyroid hormone requirements increase and thyroid function becomes particularly vulnerable in the presence of reduced reserve or autoimmunity. In the postpartum period, immunological changes may promote thyroiditis with hyperthyroid phases followed by hypothyroidism. In older adults, the clinical presentation may be attenuated and diagnosis is often guided by laboratory testing in the context of cardiovascular comorbidity and frailty, in which treatment must be initiated with particular caution.
Hypothyroidism results from reduced production or peripheral action of thyroid hormones, leading to insufficient activation of nuclear T3 receptors in target tissues and altered gene expression of numerous metabolic enzymes and transporters. Under physiological conditions, thyroid hormone synthesis requires adequate iodine intake, active transport of iodide into the thyrocyte, organification and iodination of thyroglobulin, formation of T4 and T3 and their controlled release, regulated by TSH. Tissue availability also depends on peripheral conversion of T4 into T3 through deiodinases and on the dynamics of transport and protein binding. Hypothyroidism develops when one or more of these steps are impaired or when central regulation fails to provide adequate stimulation of the gland.
From an aetiological perspective, the most frequent cause in iodine-sufficient areas is Hashimoto thyroiditis, in which loss of immunological tolerance leads to lymphocytic infiltration, autoantibody production and progressive destruction of the thyroid parenchyma. Pathogenesis integrates genetic predisposition, environmental signals and dysfunction of immune regulatory mechanisms, with fibrosis and reduction of functional thyroid mass as the final outcome. The process may progress slowly, with an initial compensated phase in which TSH rises to sustain T4 production, followed by a decompensated phase in which the thyroid no longer responds adequately and overt hypothyroidism develops. Fluctuations in thyroid function may occur during some phases, particularly in thyroiditis with a destructive component, before the condition stabilises into a persistent deficiency.
Iodine deficiency is the leading global cause of thyroid dysfunction in many areas of the world because iodine is the essential substrate for the synthesis of T4 and T3. When intake is insufficient, the hypothalamic-pituitary-thyroid axis increases TSH secretion to support iodine uptake and organification, promoting follicular hyperplasia and goitre as adaptive responses. When this adaptation is insufficient, hormone production becomes inadequate and clinical signs of hypothyroidism develop. At the opposite extreme, excess iodine may induce a transient reduction in hormone synthesis in predisposed individuals or facilitate autoimmunity, highlighting the narrow physiological range of iodine homeostasis and the ability of rapid changes to destabilise thyroid function.
Iatrogenic causes act by reducing thyroid mass or impairing thyroid function. After thyroidectomy or radioactive iodine treatment, hypothyroidism is the expected consequence of reduced thyroid tissue, whereas after neck radiotherapy the effect is often progressive and associated with vascular and fibrotic damage. Numerous medications interfere with thyroid physiology: amiodarone, which contains a large iodine load, may induce hypothyroidism through inhibition of organification and changes in peripheral deiodination, whereas lithium may inhibit hormone release and promote autoimmune dysfunction. Medications and gastrointestinal conditions may also reduce levothyroxine absorption, causing iatrogenic hypothyroidism in patients receiving replacement therapy when administration is incorrect or interfering substances are introduced without appropriate dose adjustment.
The pathophysiology explains the systemic nature of the syndrome. Reduced thyroid hormone levels decrease energy expenditure and thermogenesis, causing cold intolerance and weight gain, mainly due to fluid retention and reduced basal metabolic rate. At the cardiovascular level, T3 deficiency reduces inotropism and chronotropism, increases peripheral vascular resistance and may promote dyslipidaemia with elevated LDL cholesterol, contributing to long-term atherosclerotic risk. Neuromuscular manifestations include delayed reflexes, stiffness, cramps and reduced performance, whereas neuropsychiatric manifestations include cognitive slowing, somnolence and mood alterations. The skin and appendages become dry and fragile, with hair loss caused by reduced tissue turnover.
Hypothyroidism may cause hyponatraemia because of reduced free-water clearance and haemodynamic and neurohormonal changes, particularly in severe forms or in frail patients. Haematological manifestations may include normocytic or macrocytic anaemia and coexistence of autoimmune deficiencies, whereas reproductive effects include menstrual irregularities, anovulation and reduced fertility. In the most severe forms, the clinical extreme is myxoedema coma, in which hypothermia, hypoventilation, bradycardia and altered mental status reflect collapse of compensatory mechanisms, often precipitated by infection, sedative medications, cold exposure or acute events in individuals with unrecognised or untreated hypothyroidism.
The clinical presentation of hypothyroidism is often insidious and may progress slowly, with early symptoms initially attributed to stress, ageing or comorbidities. Interindividual variability depends on the rate at which hormone deficiency develops, age, the burden of concomitant disease and tissue sensitivity to thyroid hormones. In many situations, the distinguishing feature is not a single pathognomonic sign but the combination of systemic slowing, cold intolerance, cutaneous and neuromuscular changes and metabolic abnormalities, which become clinically meaningful within a consistent context.
During history taking, patients frequently report fatigue, somnolence, reduced exercise tolerance and a sensation of physical and mental slowing. Weight gain may be modest compared with expectations, but a sensation of swelling and fluid retention is common, together with reduced sweating and cold intolerance. Constipation, dry skin, brittle hair, hoarseness and reduced occupational performance are frequent. Women may develop menstrual irregularities, menorrhagia or oligomenorrhoea, reduced fertility and, during pregnancy, an increased risk of obstetric complications if hypothyroidism is not corrected. In some patients, neuropsychiatric symptoms predominate, with impaired concentration, cognitive slowing and depressed mood, which may be mistaken for primary disorders.
On physical examination, findings may include dry, cold skin, non-pitting oedema in some areas caused by glycosaminoglycan accumulation, a slowed facial appearance, macroglossia and slurred or thickened speech. Bradycardia and increased peripheral vascular resistance may cause elevated diastolic blood pressure or, in severe cases, hypotension due to reduced cardiac output. Deep tendon reflexes may show delayed relaxation, a classic but inconsistent sign. Goitre or palpable thyroid irregularities may be present in autoimmune or nodular forms, whereas after surgery or radioactive iodine treatment the thyroid may be absent or reduced in size. Physical examination should also assess for signs of pleural or pericardial effusion, which are more likely in severe, long-standing disease.
Cardiovascular manifestations include reduced exercise capacity, exertional dyspnoea, exercise intolerance and, in some cases, signs of heart failure, particularly in patients with pre-existing heart disease. Dyslipidaemia may be the first biochemical clue, with increased total and LDL cholesterol. In older patients, hypothyroidism may present with functional decline, instability, falls and worsening cognition, with less typical symptoms and a greater risk of attribution to geriatric frailty, making a rational laboratory assessment essential.
Neuromuscular manifestations include cramps, myalgia and stiffness, which may be accompanied by elevated creatine kinase levels. Peripheral neuropathy and carpal tunnel syndrome may occur because of tissue infiltration and alterations in connective tissue metabolism. Respiratory impairment, which is more typical of severe forms, may include hypoventilation and a reduced response to hypoxic and hypercapnic stimuli, particularly when obesity and obstructive sleep apnoea coexist, conditions in which hypothyroidism amplifies ventilatory dysfunction.
The most severe form is myxoedema coma, an endocrine emergency characterised by altered mental status, hypothermia, bradycardia, hypoventilation and multiorgan dysfunction. It is often precipitated by infection, cold exposure, sedative medications, stroke or heart failure in individuals with undiagnosed hypothyroidism or poor adherence to treatment. In this context, the clinical picture takes priority over laboratory confirmation because timely treatment determines prognosis and mortality remains high despite modern care.
Hypothyroidism should be suspected when symptoms and signs consistent with reduced systemic metabolism occur in a plausible clinical context. In practice, the pre-test probability increases in the presence of persistent fatigue, cold intolerance, constipation, dry skin, bradycardia, unexplained weight gain, mood changes or lipid abnormalities, particularly when there is a family history of thyroid disease or other autoimmune conditions. Clinicians should recognise that many manifestations are non-specific and that hypothyroidism may remain occult until an intercurrent condition, a change in treatment or a physiological event such as pregnancy increases thyroid hormone requirements.
Suspicion should be particularly strong in patients with a history of thyroidectomy, radioactive iodine treatment or neck radiotherapy, because hypothyroidism may be expected or may develop progressively, and failure to correct it affects quality of life and cardiovascular risk. Similarly, in patients receiving amiodarone or lithium, the onset of fatigue, bradycardia, cold intolerance or increased cholesterol should prompt rapid measurement of TSH and FT4 because the temporal relationship with treatment may be overlooked, especially in patients with heart disease or mood disorders who already have overlapping symptoms.
During pregnancy and the preconception period, the threshold for suspicion should be lower because even a moderate deficiency may have maternal and fetal implications. Women with positive thyroid antibodies, a history of thyroiditis or previous thyroid treatment require close monitoring, and the onset of compatible symptoms should prompt timely assessment. In the postpartum period, thyroiditis may begin with different functional phases and end in hypothyroidism, making it useful to correlate symptoms temporally with reproductive status.
Hypothyroidism should also be considered when suggestive laboratory abnormalities emerge. Increased LDL cholesterol, unexplained hyponatraemia, elevated creatine kinase or unexplained anaemia may represent indirect clues. In older or frail patients, in whom the classic presentation may be attenuated, otherwise unexplained functional decline, unexpected bradycardia or subacute cognitive deterioration warrants a basic thyroid assessment because correction of hypothyroidism may significantly improve the clinical trajectory.
The urgency of suspicion increases when symptoms suggest severe disease. Altered mental status, hypothermia, marked bradycardia, hypoventilation, diffuse oedema and signs of infection or another precipitating event should raise concern for myxoedema coma as a time-dependent diagnosis, in which the priority is to initiate treatment and intensive support while obtaining biochemical confirmation without delaying life-saving measures.
The diagnosis of hypothyroidism is based on a sequential approach integrating the clinical picture and laboratory testing, with the aim of confirming hormone deficiency, determining its anatomical level and identifying its aetiology. The most useful initial test in the general population is measurement of TSH, interpreted together with FT4. Elevated TSH with reduced FT4 defines overt primary hypothyroidism, whereas elevated TSH with FT4 within the reference range identifies subclinical hypothyroidism, a condition that requires confirmation and clinical contextualisation before treatment decisions are made. Reduced FT4 with low or inappropriately normal TSH suggests central hypothyroidism, a setting in which TSH is not a reliable indicator of severity and assessment must be extended to the other pituitary axes and neuroimaging.
The initial assessment requires attention to conditions that may transiently alter thyroid function or the interpretation of test results. Acute systemic illnesses may modify thyroid hormone metabolism and generate misleading biochemical patterns, whereas medications such as glucocorticoids, dopaminergic agents, amiodarone and biotin may interfere directly or indirectly with hormone secretion and immunometric assays. Therefore, in non-urgent cases, borderline values should be confirmed with repeat testing after a reasonable interval, together with a targeted clinical assessment and, when appropriate, thyroid autoantibody testing.
Aetiological definition in primary forms is often based on measurement of anti-TPO antibodies and anti-thyroglobulin antibodies, which support a diagnosis of autoimmune thyroiditis and help estimate the risk of progression over time. Thyroid ultrasonography is not a routine diagnostic test for every patient with hypothyroidism, but it is useful when goitre, nodules, chronic thyroiditis with structural abnormalities or suspicious palpation findings are present. In iatrogenic hypothyroidism, a history of thyroid surgery, radioactive iodine treatment or radiotherapy is often decisive and directly indicates the permanent nature of the deficiency.
When central hypothyroidism is suspected, the diagnostic pathway changes because the priority is to identify hypothalamic-pituitary disease potentially associated with multiple hormone deficiencies. In this setting, in addition to FT4 and TSH, the other pituitary axes should be assessed, particularly corticotroph function, because possible central adrenal insufficiency must be identified before levothyroxine replacement is initiated or increased. Levothyroxine may increase glucocorticoid requirements and precipitate an adrenal crisis in unprotected patients. Magnetic resonance imaging of the hypothalamic-pituitary region is the imaging modality of choice when central disease is strongly suspected, to identify adenomas, postoperative changes, hypophysitis, infiltrative lesions or abnormalities of the pituitary stalk.
Additional investigations depend on the clinical presentation. A lipid profile is useful for quantifying metabolic impact and monitoring the response to treatment. A complete blood count, electrolytes and creatine kinase may reveal systemic consequences such as anaemia, hyponatraemia or hypothyroid myopathy. In the presence of bradycardia, dyspnoea or signs of effusion, electrocardiography and echocardiography may document findings consistent with severe hypothyroidism. When myxoedema coma is suspected, investigations should include blood gas analysis, assessment for infection and intensive-care parameters, but diagnosis remains predominantly clinical, with confirmation by TSH and FT4 when available without delaying treatment.
The classification of hypothyroidism is clinically useful because it influences diagnosis, monitoring and treatment. The main distinction is between primary forms, in which the defect is located in the thyroid gland, and central forms, in which the defect originates in the pituitary gland or hypothalamus. In primary forms, TSH is elevated as a compensatory response to the fall in FT4, whereas in central forms TSH is not a reliable marker and severity is defined mainly by FT4 and the clinical picture. A further practical category includes iatrogenic forms following surgery, radioactive iodine treatment or radiotherapy, in which the likelihood of recovery is generally low and replacement therapy tends to be permanent, with selected exceptions in which sufficient residual thyroid function remains.
A second distinction concerns biochemical and clinical status. Overt hypothyroidism is defined by reduced FT4 with corresponding TSH abnormalities in primary forms and is more frequently associated with clinical symptoms and signs. Subclinical hypothyroidism is characterised by elevated TSH with FT4 within the reference range, a condition in which symptoms may be absent or non-specific and treatment decisions depend on TSH level, thyroid autoantibodies, age, symptoms, cardiovascular risk and special clinical contexts. This distinction is relevant because the prognostic implications and benefits of treatment are not equivalent in the two conditions.
From a temporal perspective, hypothyroidism may be transient or permanent. Destructive thyroiditis, some postpartum forms and conditions related to treatment or changes in immune status may cause hypothyroidism that resolves partially or completely, whereas chronic autoimmune thyroiditis and iatrogenic causes often progress to a stable deficiency. The distinction requires follow-up and reassessment because replacement therapy may be required for long periods even in potentially reversible conditions. A cautious withdrawal trial may be planned only when the clinical context allows it and appropriate safety criteria are met.
Clinical severity may be conceptually graded from mild forms, with modest symptoms and limited biochemical abnormalities, to severe forms. The clinical extreme is myxoedema coma, which does not correspond to true coma in every case but represents a spectrum of hypothyroid encephalopathy with hypothermia and multiorgan dysfunction. This condition requires rapid recognition and intensive treatment and is more frequent in older adults with long-standing untreated hypothyroidism and precipitating factors such as infection or central nervous system depressant medications.
Finally, classification according to physiological context and comorbidity is useful in practice because pregnancy, ischaemic heart disease, heart failure and geriatric frailty modify therapeutic targets and the rate of dose titration. In these settings, the same biochemical abnormality may require different strategies, and the safety of correction is as important as normalisation of laboratory parameters.
Treatment of hypothyroidism consists of replacement with levothyroxine (T4), which is considered the standard therapy because it restores a peripheral reservoir that can be converted into T3 and allows titration based on biochemical and clinical parameters. The aim is to normalise thyroid hormone availability in tissues, relieve symptoms and prevent metabolic and cardiovascular complications while avoiding overtreatment, which may promote arrhythmias, osteopenia and symptoms of iatrogenic thyrotoxicosis. Treatment must be individualised, taking into account age, body weight, pregnancy, cardiac comorbidity, severity of the deficiency and the expected duration of hypothyroidism.
In overt primary hypothyroidism, levothyroxine is generally initiated at a dose based on body weight and severity, but titration must be cautious in older patients or those with ischaemic heart disease, in whom a rapid increase may raise myocardial oxygen demand and precipitate angina or arrhythmias. In these patients, treatment is preferably started at lower doses with gradual increases and close clinical monitoring. In younger patients without cardiovascular comorbidity, the starting dose may be closer to the full replacement dose, with reassessment after several weeks because the half-life of T4 and equilibration of TSH require time before the true effect of treatment can be evaluated.
The method of administration is crucial for efficacy. Levothyroxine should be taken consistently, preferably on an empty stomach and separately from substances that reduce its absorption. Iron and calcium supplements, resins, some gastric acid-suppressive treatments and malabsorption disorders may require dose adjustments or alternative strategies. In patients with biochemical instability or impaired absorption, different formulations or gastroenterological assessment may be considered because apparently resistant hypothyroidism is often related to treatment interactions or suboptimal adherence rather than lack of efficacy.
In the treatment of subclinical hypothyroidism, the decision is not automatic and depends on the patient’s risk profile. Persistently elevated TSH, particularly above certain thresholds, the presence of anti-TPO antibodies, compatible symptoms, pregnancy or plans for conception and cardiovascular risk may support treatment, whereas a more conservative monitoring strategy may be appropriate in older adults with mildly elevated TSH to avoid overtreatment. The strategy must integrate the probability of progression, potential symptomatic benefit and the risk of adverse events, recognising that the evidence is not identical across age groups.
The use of liothyronine (T3) or combination therapy remains debated and requires rigorous patient selection. International guidance and consensus documents emphasise that levothyroxine remains the standard therapy and that a trial of combination treatment may be considered only in selected patients with persistent symptoms despite adequate biochemical control and after exclusion of alternative causes. In such cases, T3 monotherapy should be avoided, a time-limited trial should be established, clinical and biochemical parameters should be monitored and the risk-benefit balance should be critically reassessed, particularly in patients at risk of arrhythmia or osteoporosis.
In myxoedema coma, treatment is urgent and multidisciplinary and includes parenteral administration of thyroid hormones when indicated, ventilatory and haemodynamic support, correction of hypoglycaemia and hyponatraemia, treatment of the precipitating factor and glucocorticoid coverage until concomitant adrenal insufficiency has been excluded. In this setting, treatment is guided by clinical severity and the intensive-care context, with continuous monitoring and management of cardiac and infectious complications.
The purpose of follow-up in hypothyroidism is to ensure effective and safe replacement therapy, verify the stability of biochemical control, identify undertreatment or overtreatment early and manage conditions that alter levothyroxine requirements. After treatment initiation or a dose change, reassessment should occur after a sufficient interval for TSH to reach a new equilibrium, whereas in central forms monitoring is based mainly on FT4 and the clinical picture because TSH may remain uninformative. The target depends on age, comorbidities and clinical objectives, balancing symptom correction against prevention of adverse effects.
Periodic clinical assessment should investigate persistent symptoms of hypothyroidism, such as fatigue, somnolence, constipation and cold intolerance, as well as signs of excessive treatment, such as palpitations, tremor, insomnia, unintentional weight loss and irritability. In many cases, a discrepancy between laboratory values and symptoms requires broad clinical reasoning because mood disorders, anaemia, obstructive sleep apnoea and metabolic diseases may mimic or amplify symptoms. Follow-up should therefore include an integrated assessment and should not be limited to normalisation of TSH alone, particularly when symptoms persist despite an adequate biochemical profile.
A central component of monitoring is identification of factors that alter levothyroxine absorption and metabolism. Changes in gastric acid-suppressive treatment, introduction of iron or calcium supplements, dietary changes and gastrointestinal disorders may cause significant changes in requirements, whereas non-adherence or incorrect administration are frequent causes of instability. Follow-up should reconstruct the actual method of administration and co-administration with other treatments because targeted education may resolve most TSH fluctuations without inappropriate dose increases.
During pregnancy, follow-up should be more frequent because levothyroxine requirements tend to rise early and the time window for preventing fetal exposure to maternal hypothyroidism is narrow. In the postpartum period, the dose may need to be reduced and thyroid function may change if postpartum thyroiditis coexists. In older adults and patients with heart disease, monitoring should include careful assessment of cardiovascular symptoms and heart rhythm because vulnerability to the effects of excess thyroid hormone is greater and an excessively aggressive target may be harmful.
In central forms or in the presence of hypothalamic-pituitary disease, follow-up should be coordinated with assessment of the other endocrine axes and with imaging when indicated. Changes in concomitant replacement therapies may alter thyroid hormone requirements and vice versa, and management must maintain a safe sequence, particularly when corticotroph insufficiency coexists. In these settings, surveillance is not limited to the thyroid axis but concerns the overall endocrine balance and the neurological or ophthalmological complications of the underlying lesion.
The prognosis of hypothyroidism is generally favourable when the diagnosis is correct and replacement therapy with levothyroxine is appropriately initiated and monitored. In most patients, normalisation of thyroid hormone availability produces substantial recovery of energy, cognitive function and well-being, with a reduction in the risk of metabolic complications. However, prognosis depends on the aetiology, the duration of hypothyroidism before treatment, adherence to therapy and the presence of cardiovascular or neuropsychiatric comorbidities that may limit complete reversibility of symptoms.
Complications of untreated or undertreated hypothyroidism include persistent dyslipidaemia, increased long-term atherosclerotic risk, reduced cardiac function and possible development of serous effusions. In individuals of reproductive age, hypothyroidism may contribute to infertility and obstetric complications if unrecognised, whereas inadequate control during pregnancy may be associated with adverse maternal and fetal outcomes. Neuromuscular complications include hypothyroid myopathy and compressive neuropathies, which may cause functional impairment and chronic pain, whereas neuropsychiatric manifestations such as cognitive slowing and mood changes may persist when diagnosis is delayed or concomitant conditions are present.
The most severe complication is myxoedema coma, a rare but highly fatal event that typically occurs in older adults with severe, long-standing hypothyroidism, often precipitated by infection, cold exposure, trauma or depressant medications. Prevention depends on early recognition of hypothyroidism, continuity of treatment and timely management of intercurrent conditions. In treated patients, omission or prolonged interruption of therapy represents a tangible risk, particularly when social, cognitive or organisational barriers coexist, which is why management should also include education and support.
Another group of complications concerns overtreatment, which may be clinically insidious. Chronic excess levothyroxine may promote atrial fibrillation, worsen myocardial ischaemia, cause autonomic symptoms and accelerate bone loss, particularly in postmenopausal women and older adults. Prevention requires realistic targets, appropriate monitoring and cautious titration in at-risk patients. In patients with persistent symptoms despite TSH values within the reference range, the safest strategy is to reassess alternative causes and optimise administration, avoiding empirical dose increases that raise the risk of overdosage without ensuring benefit.
Overall, hypothyroidism is a condition with a substantial clinical impact because of its frequency and potential systemic consequences, but its course is favourable in the vast majority of cases when managed with accurate diagnosis, personalised replacement therapy, patient education and follow-up tailored to the clinical context.