Endocrine complications of COVID-19: diabetes, musculoskeletal, thyroid, pituitary, adrenal, and gonadal disorders

Abstract

COVID-19 is generally associated with both short- and long-term complications. It can affect multiple organ systems and lead to severe or prolonged organ dysfunction, including the endocrine system. It also places a substantial burden on individuals and the health-care system. Therefore, providing up-to-date information for health-care providers is valuable. In this review, we aim to consolidate the current literature regarding the endocrine complications of acute SARS-CoV-2 infection, with a particular focus on diabetes, calcium homeostasis, pituitary, thyroid, adrenal, and gonadal disorders. Although current therapeutic approaches for COVID-19 are mainly limited to antivirals, symptomatic therapies, and supportive care, advances in understanding the mechanisms of SARS-CoV-2 entry and immune responses may support a more effective and personalized approach to clinical care.

The SARS-CoV-2 infection manifests from mild to severe disease. It has caused widespread global morbidity and mortality since 2020. Our understanding of the pathophysiology of acute SARS-CoV-2 infection has meaningfully evolved since the beginning of the pandemic. To date, scientific advances in understanding the short- and long-term complications of COVID-19, alongside remarkable therapeutic and preventive strategies, have substantially reduced morbidity and mortality. The progression of acute SARS-CoV-2 infection to severe disease is primarily linked to underlying comorbidities. Angiotensin-converting enzyme 2 (ACE2) receptors on the surface of the host cells are the main route of SARS-CoV-2 entry into the cells. ACE2 expression is higher in certain comorbidities. Its expression correlates with severity of COVID-19 disease. Nevertheless, ACE2 provides protective roles against organ damage by neutralizing the unfavorable effects of the renin-angiotensin-aldosterone system (RAAS). Concurrently, reduction of ACE2 expression may attenuate SARS-CoV-2 entry and infection; however, it can increase activation of the renin-angiotensin-aldosterone system (by reducing conversion of angiotensin II to angiotensin 1-7 and increasing activation of transmembrane angiotensin type 1 or type 2 receptors) and subsequent tissue damage [1-4]. The host protease TMPRSS2 (transmembrane protease serine 2) and metalloprotease ADAM17 (A disintegrin and metalloproteinase domain-containing protein 17) potentiate the virus endocytosis. The expression of TMPRSS2 and ADAM17 is linked to the degree of organ involvement and COVID-19 severity too [5, 6].

SARS-CoV-2 can directly invade human tissues or indirectly damage organs through inflammation and cytokine production, impairing the function of multiple organ systems, including the endocrine system, which can lead to thyroid dysfunction, diabetes, and also impairment of adrenal, gonadal, pituitary, and hypothalamic function [2]. It causes hypercalcemia [7], hypocalcemia, other mineral disorders (hypophosphatemia, hypomagnesemia) [8], hypoparathyroidism [9], syndrome of inappropriate antidiuresis (SIADH) [10], and malfunction of neuroendocrine system [11] (Fig. 1).

Figure 1.

Endocrine and metabolic effects of SARS-CoV-2 infection: mechanisms and organ involvement. Angiotensin-converting enzyme 2 (ACE2) receptors are the major route of SARS-CoV-2 entry with the help of the host proteases, transmembrane protease serine 2 (TMPRSS2) and A disintegrin and metalloproteinase domain-containing protein 17 (ADAM17). The most common mechanisms of tissue damage include SARS-CoV-2 invasion, cytokine production, autoimmunity, and medication side effects. Impairment of adrenal, gonadal, pituitary, and hypothalamic function may occur in addition to thyroid dysfunction and diabetes. Hypocalcemia (not uncommon), hypercalcemia (rarely), and other mineral disorders (hypophosphatemia, hypomagnesemia) could be seen. Generated by FigureLabs AI.

This article will review our current knowledge about endocrine complications of COVID-19, with a main focus on the more common complications including diabetes, musculoskeletal, pituitary, adrenal, gonadal, and thyroid disorders. Essentially, any tissue that expresses ACE2 can be affected following acute SARS-CoV-2 infection. While more severe complications might be expected following severe COVID-19, the overall burden may be greatest among those with a history of mild-to-moderate illness, who represent the vast majority of patients.

Materials and methods

A comprehensive review of literature by authors was conducted to identify studies via PubMed and Google Scholar. The search was limited to English literature and included articles published between March 2020 and June 2026. The authors used standardized terms as mentioned in the title of Tables 1 to 5. The authors looked at the narrative reviews, systematic reviews, and meta-analyses. The full texts of selected articles cited in the reviews were assessed afterward.

Table 1.

Results of systematic reviews included studies with type 1 diabetes, type 2 diabetes, and COVID-19 listed in reverse order of year of publication between 2020 and 2026 using standardized terms, such as “T1D, T1DM, type 1 DM, or type 1 diabetes,” “T2D, T2DM, type 2 DM, or type 2 diabetes,” and “coronavirus, SARS-CoV-2, or COVID-19”

Author, journal (y)	No. of studies	Results
T1D or mixed T1D and T2D
Duaa A Rajeh, J Family Med Prim Care (2026) [22]	17/457 studies	Increased risks of DKA in COVID-19 patients and new-onset diabetes from Middle East and African countries. High mortality observed in patients with newly diagnosed T2D
Anouar Oudhini. Clin Immunol (2026) [23]	39/2544 studies	Positive correlation between SARS-CoV-2 infection and new autoimmune conditions (T1D, blistering diseases, systemic sclerosis, and vitiligo)
Jordan N Keels. Diabetes Obes Metab (2026) [24]	33/648 articles	Increased prevalence of diabetes (T2D or combined T1D and T2D or undefined) among adults after COVID-19
Ana M Gil. Semin Arthritis Rheum (2025) [25]	8/6280 studies	Acute SARS-CoV-2 infection associated with increased risks for 11 immune-mediated conditions (Behçet disease, spondyloarthritis, systemic sclerosis, systemic lupus erythematosus, polymyalgia rheumatica, psoriasis, rheumatoid arthritis, Sjögren syndrome, T1D in adults, vasculitis, and inflammatory bowel disease)
Emma Cocking. Diabetes Res Clin Pract (2025) [26]	12/1562 studies	COVID-19 associated with higher incidence of new-onset diabetes mellitus, mainly T2D
Ahmed El-Naas. Emerg Microbes Infect (2025) [15]	43/52 641 studies	COVID-19 and diabetes development (T1D and T2D) have a complex and multifactorial relationship, with an increased prevalence of diabetes following COVID-19 infection (T2D > T1D) SARS-CoV-2 infection significantly elevates risk of developing new-onset diabetes over time, with peak danger occurring within the first-year post infection Factors affecting diabetes onset are severity of infection, type of variant involved, comorbidities, and demographic factors (age and race)
Jingye Zhou. Front Endocrinol (2024) [27]	20/21 386 studies	COVID-19 infection associated with higher risk of new onset diabetes (male > female)
Dimitra Stathi. J Int Med Res (2023) [28]	20/564 studies	Potential link between COVID-19 and development or exacerbation of T1D. Acceleration of presentation or unmasking previously undiagnosed T1D is possible after COVID-19 infection
Meregildo-Rodriguez. F1000Res (2023) [29]	46/112 studies	Acute SARS-CoV-2 infection increases risk of DKA, severe DKA, DKA de novo, and ICU admissions in both sexes
D'Souza. JAMA Netw Open (2023) [30]	42/10 757 studies	Incidence of T1D and DKA in children and adolescents during COVID-19 pandemic is higher than before the pandemic
Masoud Rahmati. J Med Virol (2023) [31]	7/19 253 studies	Acute SARS-CoV-2 infection in children and adolescents may increase risk of new-onset T1D and DKA in pediatric group (higher T1D in patients age<18 years)
Yanping Han. Front Endocrinol (2022) [32]	22/4488 studies	Pediatric patients with T1D had an improved glucose levels and other continuous glucose monitoring metrics during and post lockdown for COVID-19
Ting Zhang. BMC Med (2022) [33]	9/7741 studies	Patients across all age groups and sexes experience an elevated incidence and relative risk for developing new-onset diabetes following COVID-19 infection
Charlotte E M Rugg-Gunn. JAMA Pediatr (2022) [34]	195/2565 articles	COVID-19 increases risk of DKA. 195 articles included for the final analysis (149/2565 articles plus 46 from previous review)
Anas Elgenidy. Pediatr Res (2023) [35]	24/151 studies	Incidence of DKA in newly diagnosed T1D children has increased during the pandemic and presented with a severe form
Masoud Rahmati. J Med Virol (2022) [36]	26/4344 studies	Significant increase in the incidence of childhood new-onset T1D during the first year of COVID-19 pandemic. There is also an increased in DKA, and severe DKA with elevated hyperglycemia and mean HbA1c.
Arman Shafiee. Diabetes Metab Syndr (2022) [37]	11/2419 studies	After comparing of COVID1-9 outcomes in patients with T1D and T2D, there was no significant differences in disease severity between type 1 and type 2 diabetes. Based on unadjusted data, the mortality of T1D was lower than T2D.
Lauren L O’Mahoney. Diabetes Obes Metab (2022) [38]	59/7372 studies	COVID-19 pandemic was associated with improvement of multiple outcomes of glycemic control in people with diabetes, including average glucose and time in range. Lockdown and pandemic had no detrimental effects on any of the glycemic outcomes
Osamah M Alfayez. Front Endocrinol (2022) [39]	20/372 studies	Increased risk of DKA and severe DKA among pediatric patients during the pandemic
Ifan Ali Wafa. Diabetes Metab J (2022) [40]	21/166 studies	Lockdown did not affect glycemic outcomes of diabetic patient negatively (no significant difference in HbA1c, random blood glucose, or time-below-range; significant improvement of time-in-range and time-above-range). Meta-analysis (17/166 studies) showed an increase in FBG from prelockdown to lockdown period (mean difference 3.47 mg/dL [1.22-5.730 mg/dL])
Jamie Hartmann-Boyce. Diabetes Care (2021) [41]	112/663 systematic reviews	No strong evidence on whether diabetes predisposes to acute SARS-CoV-2 infection. Diabetes increases risk of severe COVID-19 and higher blood glucose levels in diabetic patients were associated with worse COVID-19 outcomes. T1D associated with worse outcomes than T2D
Diabetol Metab Syndr (2021) [42]	33/767 studies	25 studies for T1D and 8 studies for T2D. T1D patients had improvement of glycemic parameters during COVID-19 lockdown but T2D individuals experienced short-term worsening in glycemic values
Diabetes Metab Syndr (2021) [43]	15/966 studies	Prevalence of T1DM in COVID-19 patients ∼ 0.15%-28.98%. Rate of COVID-19 in patients with T1D could be 0%-16.67%. The study populations are heterogeneous, and there are many limitations for assessing changes in incidence of T1D in COVID-19 patients

Abbreviations: DKA, diabetic ketoacidosis; FBG, fasting blood glucose; HbA_1c, glycated hemoglobin A_1c; T1D, type 1 diabetes, T2D, type 2 diabetes.

Table 5.

Results of systematic reviews about sexual health, gonads, fertility, and COVID-19 listed in reverse order of year of publication between 2020 and 2026 by using related terms, such as “gonad, hypogonadism, infertility, erectile dysfunction, menstruation” and “coronavirus, SARS-CoV-2, or COVID-19”

Author, journal (y)	No. of studies	Result
G Della Rosa. Int Urol Nephrol (2026) [141]	27/185 studies	The restriction of COVID-19 pandemic has been associated with psychosocial stress, which in turn correlates with reduced libido. There is also an association between COVID-19 infection (mostly long-COVID) and male sexual dysfunction or alteration of reproductive indices
Stefano Salciccia. Sci Rep (2024) [149]	18/214 studies	COVID-19 associated with reduced TT levels, particularly in patients with severe COVID. Normal LH levels probably rules out primary hypogonadism as underlying cause. TT levels could be an indicator of poor outcomes among COVID-19 patients
Kristina Groti Antonic. Clin Endocrinol (Oxf) (2024) [144]	Narrative reviews 12 studies about effects of testosterone on COVID-19 15 studies about Effects of COVID-19 on testosterone and male reproductive system	Men have experienced higher rates of severe disease and mortality from COVID-19 compared to women Severe SARS-CoV-2 infection leads to an acute and significant drop in serum testosterone levels in men Lowering testosterone or blocking androgen signaling in clinical trials did not improve COVID-19 outcomes in men
Riccardo Leni. World J Mens Health (2023) [151]	46/1331 studies	Although low testosterone after COVID-19 is reported, long-term follow-up is required to assess permanent effects. Moreover, men with low testosterone (hypogonadism) face significantly higher risk of worse outcomes (admission to ICU, longer hospitalization, and death). There is a complex relationship between COVID-19 and male reproductive function. Long-term effects of COVID-19 on gonadal function (testosterone level) and fertility are still unclear
L Stárka. Physiol Res (2021) [152]	Narrative review	Androgen may play role in pathogenesis of acute SARS-CoV-2 infection. Androgen may modify immunity or promote viral entry into cells. Current evidence is insufficient to conclude that COVID-19 causes permanent hypogonadism or infertility
Sulagna Dutta. Reprod Sci (2021) [153]	Narrative review	Testis can be potentially damaged by SARS-CoV-2 virus, which may lead to male infertility. ACE2/TMPRSS2 expression in testes, orchitis, inflammation, oxidative stress, hormonal alterations, and impaired spermatogenesis are possible mechanisms. Lack of SARS-CoV-2 in semen in early studies suggests that damage is more likely inflammatory than direct viral invasion

Abbreviations: ACE2, angiotensin-converting enzyme 2; ICU, intensive care unit; LH, luteinizing hormone; TMPRSS2, transmembrane protease serine 2; TT, total testosterone.

The selected studies of systematic reviews are nonrandomized studies and heterogeneous, which may introduce a risk of bias. The distinction among SARS-CoV-2 infection–related complications with and without prior vaccination was not pursued because of inconsistencies of studies and heterogeneity of population selection. The roles of post–SARS-CoV-2 sequelae and long-COVID were discussed separately. The authors’ approaches were based on the review questions and review-specific guidance to evaluate risk of bias and applicability. The number of articles, sample size, age, design of study, and outcomes are evaluated by authors. Several identified biases—including health-care access and the use of different medications—could technically affect the study outcomes. The results of the selected reviews are shown in Tables 1 to 5.

Diabetes

Acute SARS-CoV-2 infection has profoundly affected the onset, progression, management, and outcomes of diabetes. It can cause hyperglycemia and diabetes; indeed, a bidirectional relationship between diabetes and COVID-19 has been broadly recognized. On the other hand, diabetes and hyperglycemia are considered risk factors for COVID-19 severity and worse outcomes by modulating the immune responses and activating RAAS [12-14]. Moreover, differences in outcomes and risk factors—including SARS-CoV-2 variant, age, comorbidities, and vaccination status—may affect the incidence of post–COVID-19 diabetes across different countries [14, 15].

Although the effect of COVID-19 on the incidence of type 1 diabetes (T1D) is not consistent throughout the studies, the complications of T1D, such as diabetic ketoacidosis (DKA), hospitalization, and death, were higher during the pandemic [14-18]. However, changes in T1D incidence during the pandemic may reflect seasonal or transient trends and may not have been adequately evaluated in some studies [19]. In general, acute SARS-CoV-2 infection can trigger autoimmunity against pancreatic β cells, invade the pancreas, reduce insulin production, and increase insulin resistance by provoking cytokine storm and multiorgan dysfunction [14, 20, 21]. Consequently, an increase in T1D incidence would be anticipated, at least transiently (see Table 1).

The prevalence of new-onset diabetes was relatively higher during the pandemic (1.37% or 60 189 cases out of 4 395 528 COVID-19 patients), with higher numbers for T2D (0.84%) vs T1D (0.017%) and more prevalent in patients without a history of diabetes (94.8%) vs prediabetes (5.2%) as reported in a systematic review of 43 studies [15]. In addition, the risk of new-onset diabetes was higher in patients following COVID-19 (relative risk [RR] 1.41; 95% CI, 1.07-1.84) compared to controls in another systematic review and meta-analysis that included 12 studies [26].

In summary, an exaggerated immune response and the activation of the RAAS are the primary drivers behind the rising incidence and complications of diabetes following acute SARS-CoV-2 infection. Therefore, routinely evaluating patients after an acute SARS-CoV-2 infection is essential to rule out the development of diabetes. Moreover, alleviating the immune response, decreasing viral entry into host cells, and reducing RAAS activity are essential strategies to prevent severe COVID-19 complications. Furthermore, considering medications, such as metformin and dipeptidyl peptidase 4 (DPP-4) inhibitors, which are shown to be protective against COVID-19, would be reasonable. Metformin can affect viral entry by phosphorylating the ACE2 receptor, modulate the immune response, and reduce the risk of post–SARS-CoV-2 sequelae and long-COVID [14, 44, 45]. DPP-4 inhibitors may affect SARS-CoV-2 endocytosis, modify the immune response, and improve clinical conditions [46, 47].

And, last but not least, gestational diabetes (GDM) screening, management, and outcomes were affected during the pandemic. GDM has been reported as a maternal risk factor for severe COVID-19 [48]. In addition, there are situations during pregnancy including changes in hormonal and immune function, increased ACE2 and DPP4 expression, and expression of TMPRSS2 and ADAM17 in the placenta, which can technically increase risk of COVID-19 infection and severity [49-51]. On the contrary, COVID-19 was associated with an increase in GDM prevalence [52, 53]. Geographic disparities in GDM prevalence and possible increases in its incidence have also been reported during the pandemic [51, 54]. However, there was no strong correlation between GDM and history of prior COVID-19 infection in Taiwan [55]. Therefore, COVID-19 may have contributed to an increase in GDM prevalence, although changes in screening and detection methods could also account for the observed variations in prevalence and incidence. Finally, applying a novel method of diagnosing GDM would be reasonable to improve clinical care and outcomes of pregnancies, such as checking fasting plasma/blood glucose (FPG/FBG) plus oral glucose tolerance test (OGTT) or offering OGTT after screening with glycated hemoglobin A_1c (HbA_1c) or FPG [56].

Musculoskeletal system and calcium homeostasis

The COVID-19 pandemic could not have only affected the management of osteoporosis but also the incidence of fragility fracture. Reduced outdoor activity was associated with a lower incidence of minor fractures (eg, forearm) [57], whereas chronic cough increased the risk of vertebral compression fracture [58, 59]. In general, reduced physical activity, prolonged hospitalization, sarcopenia, medication side effects (particularly corticosteroids), and acute and chronic inflammation are contributing factors to impaired bone health following acute SARS-CoV-2 infection [59, 60]. In addition, changes in bone mineral density (BMD), hypocalcemia, and low vitamin D without enough parathyroid hormone (PTH) response are signs of disruptive bone metabolism among affected individuals with COVID-19. Furthermore, direct effects of SARS-CoV-2 on bone cells, dysregulation of cytokines, metabolic derangement, hypercoagulable state, and hypoxic injuries are known mechanisms for bone damage. Animal studies have shown that SARS-CoV-2 infection can cause acute bone loss, increased osteoclast number, and thinner growth plates [61, 62]. The increased osteoclastogenesis and trabecular bone damages can occur within 2 weeks post SARS-CoV-2 infection [63]. Lipopolysaccharide-induced acute lung injury in mice led to increased production of RANKL (receptor activator of nuclear factor κ B ligand) in bone marrow stromal cells, augmented bone resorption, and trabecular bone loss [64].

Moreover, exposure of osteoblast precursors (mesenchymal stem cells) to ancestral SARS-CoV-2 and Omicron strains increased interleukin-6 and RANKL expression but reduced RUNX2 (runt-related transcription factor 2) expression, alkaline phosphatase activity, and calcium and collagen deposition, suggesting that SARS-CoV-2 may inhibit osteoblast differentiation [65]. The proinflammatory state of acute SARS-CoV-2 infection and steroid usage can increase osteoclastogenesis and bone loss by mainly damaging trabecular bone [59-61, 63, 64]. Additionally, it has been shown that osteoprotegerin (OPG), a decoy receptor that blocks RANKL, was higher in acute COVID-19 and post–COVID-19 patients, especially frail individuals [66, 67]. Higher OPG also correlates with lower BMD and inflammation [66, 67]. This suggests that increased RANKL expression and osteoclastogenesis may be accompanied by a compensatory upregulation of OPG. In conclusion, COVID-19 can negatively affect osteoblast function and differentiation while promoting osteoclastogenesis, which leads to an impaired maintenance of bone remodeling, reduced BMD, and an increased incidence of fractures, especially vertebral fractures.

In terms of parathyroid function and calcium homeostasis, COVID-19 has been associated with hypocalcemia, hypoparathyroidism, and rarely hypercalcemia. A meta-analysis of 7 studies (2032 patients) reported that hypocalcemia occurred in almost 55% (23%-78%) of COVID-19 patients and was associated with poor outcomes [68]. The prevalence of hypocalcemia in COVID-19 patients may be even higher—up to 87.2%—depending on the definition used (ionized vs total serum calcium). It also correlates with disease severity, hospitalization, inflammatory response, coagulopathy, and mortality [69]. There are multiple pathophysiological mechanisms for hypocalcemia following acute SARS-CoV-2 infection, such as direct invasion of the parathyroid glands, vitamin D deficiency, malnutrition, hypoalbuminemia, alkalosis, and organ damages, especially renal and liver injuries. Furthermore, calcium-dependent mechanisms of SARS-CoV-2 entry into host cells and the binding of calcium to free unsaturated fatty acids, which are elevated in COVID-19 patients, are additional contributing factors to hypocalcemia [68, 69]. SARS-CoV-2 may invade the parathyroid glands [9], and lead to persistent primary hypoparathyroidism [70], or decompensation of preexisting primary hypoparathyroidism [71] and pseudohypoparathyroidism [72]. The other mechanisms for inadequate PTH response due to SARS-CoV-2 infection are vascular damage, thrombosis, hypoxia, immune responses, and changing the sensitivity of calcium-sensing receptors [73]. Accordingly, assessing parathyroid function, performing an autoimmune evaluation, and differentiating between functional and permanent parathyroid dysfunction are crucial to guide preventive strategies and long-term management.

The incidence of hypercalcemia in COVID-19 is rare but is associated with poorer survival in hospitalized patients [74]. Hypercalcemia in COVID-19 could be due to persistent or intense inflammatory responses [75, 76], granulomatous disorders, such as sarcoidosis [77], and granulomatous silicosis [78], immobilization and prolonged hospital stay [79], or rhabdomyolysis [80]. Immune dysregulation and a persistent inflammatory response are potential mechanisms for COVID-19–induced hypercalcemia, which may be alleviated by reducing cellular viral entry and optimizing anti-inflammatory therapies.

Thyroid disorders

Nonthyroidal illness syndrome (NTIS), thyroiditis, especially subacute thyroiditis (SAT), and new-onset autoimmune thyroid disorders, including hypothyroidism and hyperthyroidism, are seen following acute SARS-CoV-2 infection [81-83]. The severity of COVID-19 is positively correlated with the incidence of abnormal thyroid function tests (TFT) or thyroid dysfunction [82-84]. The odds ratio (OR) for abnormal TFTs was 3.77 in patients with severe COVID-19 compared with those with mild to moderate COVID-19 in a meta-analysis of 30 studies that included 3865 patients with COVID-19 [84]. Furthermore, thyroid hormone levels correlated with outcomes such as illness severity and mortality among hospitalized patients with moderate-to-severe COVID-19 [85].

NTIS is the most common thyroid abnormality associated with COVID-19, with an average prevalence of 26% (range, 5%-58%) [82, 83, 86]. The typical TFT pattern in NTIS includes low 3,5,3′-triiodothyronine (T3) levels with normal or suppressed thyrotropin (TSH) levels. Thyroiditis is another fairly common thyroid complication of COVID-19 that may manifest as SAT, painless thyroiditis, autoimmune thyroiditis, or atypical thyroiditis. COVID-19–associated subacute and painless thyroiditis are generally self-limited and may be underdiagnosed. The incidence of thyroiditis varies across different geographic areas because of underdiagnosis and differences in population susceptibility, infection severity, and treatment modalities [83]. The exposure of thyroid antigens, including extracellular, intracellular, or intrafollicular antigens, to the immune system following thyroiditis may increase the risk of autoimmunity. It has been reported that SARS-CoV-2 infection can promote thyroid autoimmunity by direct invasion or exaggerated immune responses. SARS-CoV-2 can also induce autoantibody production, initiate new-onset autoimmune conditions, or activate latent autoimmune disease. This may lead to an increased incidence of autoimmune thyroid disorders (Graves disease and Hashimoto thyroiditis) with transient or persistent thyroid dysfunction [82, 83, 86, 87]. Moreover, the effect of SARS-CoV-2 on the thyroid gland may contribute to persistent symptoms after recovery, referred to as long-COVID or the post-COVID condition [81-83]. Therefore, thyroid function testing should be considered in patients with clinical features suggestive of thyroid dysfunction during or following acute SARS-CoV-2 infection (Table 2).

Table 2.

Results of systematic reviews included studies that assessed the correlation between COVID-19 and thyroid disorders listed in reverse order of year of publication between 2020 and 2026 by using standardized terms, such as “thyroid, hypothyroidism, thyrotoxicosis, hyperthyroidism, Graves disease, thyroid eye disease, Graves ophthalmopathy, thyroiditis,” and “coronavirus, SARS-CoV-2, or COVID-19”

Author, journal (y)	No. of studies	Result
Luai Hommos. Microorganisms (2026) [88]	28/52 641 studies	COVID-19 is associated with thyroid disorders and long-term post–COVID-19 thyroid dysfunction, including SAT, thyrotoxicosis, hyperthyroidism, and hypothyroidism
İpek Dağdeviren. Clin Chim Acta (2026) [89]	13/4260 studies	Thyroid dysfunction—specifically decreased FT3 and total T3 levels—strongly correlates with increased severity and higher mortality rates in COVID-19 patients
Maryam Zarkesh. Int J Endocrinol Metab (2024) [90]	21/329 studies	COVID-19 is associated with abnormal thyroid function, such as reduction of TSH, T3, and T4. It can trigger de novo thyroid autoimmunity (positive thyroid antibodies), and degree of thyroid dysfunction correlates with severity of COVID-19
Kiana Ghafourian. BMC Infect Dis (2025) [91]	46/1349 articles (37 case reports and 9 case series)	Challenges for management of SAT secondary to COVID-19 are variability in onset, manifestations, and diagnostic investigations. However, most patient cases recovered and few developed hypothyroidism
Narges Anbardar. Front Endocrinol (2025) [83]	32/1185 studies	COVID-19 can lead to thyroid abnormalities, such as NTIS and thyroiditis
Anisha Panesar. Front Endocrinol (2025) [82]	55/1888 studies	SAT, NTIS, and new-onset autoimmune thyroid disorders are common thyroid abnormalities in COVID-19 patients. There is also an association between long COVID and thyroid dysfunction
Sadra Ashrafi. BMC Endocr Disord (2024) [86]	8/1256 studies	Thyroid dysfunction is common in COVID-19 patients, especially NTIS and thyrotoxicosis. A 26% pooled prevalence for NTIS and a 10% pooled prevalence for thyrotoxicosis among patients infected with SARS-CoV-2 were seen
Jiaqi Wei. Front Endocrinol (2023) [92]	8/2067 studies	COVID-19 can cause thyroid dysfunction. TSH and FT3 levels were significantly lower in patients with severe COVID-19 compared to those with mild COVID-19
I S Vamshidhar. J Family Med Prim Care (2023) [93]	19/886 studies	Correlation between COVID-19 and autoimmune thyroid diseases, at least temporarily. COVID-19 infections carry an increased long-term risk for incident thyroid dysfunction
Elahe Meftah. Front Endocrinol (2023) [94]	43/820 studies	No significant clinical differences (neck pain 69%, fever 54%, fatigue 34%, and palpitations 31%) between typical and post-COVID SAT. Almost 23% may develop hypothyroidism
Ziqi Li. Front Endocrinol (2023) [95]	41/705 studies	COVID-19 patients had low TSH/FT3 and high FT4. Thyroxine levels (TSH, FT3, and FT4), especially FT3, have correlation with COVID-19 severity
Mohammad Darvishi. Front Endocrinol (2022) [84]	30/467 studies	Prevalence of thyroid dysfunction in COVID-19 patients is up to 15% (6.2% in mild to moderate COVID-19, and 20.8% in severe to critical COVID-19). Thyroid dysfunction has positive correlation with COVID-19 severity
Hikmat Permana. Indian J Endocrinol Metab (2022) [96]	20/672 studies	Unspecified thyroid disorders (OR 2.92 [95% CI, 1.52-5.60]; P < .05) and hypothyroidism (OR 3.19 [95% CI, 2.00-5.06]; P < .05) correlate with poor COVID-19 outcomes. Hyperthyroidism may not correlate with poor outcomes (OR 2.09 [95% CI, 0.70-6.29]; P > .05)
Permana. Diabetes Metab Syndr (2022) [97]	20/672 studies	Preexisting thyroid disorders correlate with poor COVID1-9 outcomes (OR 2.87 [95% CI, 2.04-4.04]; P < .001), including severity of COVID-19, ICU admission, mortality, and hospitalization

Abbreviations: FT3, free 3,5,3′-triiodothyronine; FT4, free thyroxine; ICU, intensive care unit; NTIS, nonthyroidal illness syndrome; OR, odds ratio; SAT, subacute thyroiditis; T3, 3,5,3′-triiodothyronine; T4, thyroxine; TSH, thyrotropin.

COVID-19 can also alter the radiologic appearance of the thyroid gland. SARS-CoV-2 infection may cause ultrasonographic changes suggestive of thyroiditis, reduced thyroid attenuation measured in Hounsfield units on computed tomography (CT), decreased uptake on single-photon emission CT (SPECT) using technetium-99m (^99mTc), or increased uptake on 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron emission tomography integrated with CT (¹⁸F-FDG PET/CT) [98, 99]. It might transiently reduce thyroid volume during the recovery phase (2-7 months after COVID-19) [100, 101], which seems to be reversible in the later convalescent phase (8 months after COVID-19) [102].

Several mechanisms have been proposed to explain thyroid injury associated with COVID-19, including direct invasion by SARS-CoV-2 through ACE2 receptors expressed on thyroid follicular epithelial and endothelial cells [69, 70], induction or alteration of thyroid autoimmunity, disruption of the HPT axis by inflammatory responses, and other forms of neuroendocrine dysregulation [83, 88, 103]. Consequently, standalone therapy with current antivirals, such as nirmatrelvir/ritonavir, may be insufficient to fully mitigate SARS-CoV-2–mediated tissue injury. Combining these regimens with medications that suppress viral endocytosis and inflammatory cascades could offer enhanced tissue protection; potential candidate agents include spironolactone, DPP-4 inhibitors, fluvoxamine, and alternative antivirals, such as the CCR5 antagonist maraviroc [104-106].

Pituitary, adrenal, and gonadal diseases

Although ACE2 expression in the pituitary is low [107, 108], SARS-CoV-2 may affect pituitary function by invading hypothalamic and pituitary tissues [107-110]. SARS-CoV-2 could theoretically impair the hypothalamic-pituitary axis not only through direct invasion but also through exaggerated inflammatory responses. In addition, hypoxia, thrombosis, and endothelial damage secondary to COVID-19 may impair hypothalamic and pituitary function. SARS-CoV-2 can cause hypopituitarism, secondary adrenal insufficiency (AI), secondary hypogonadism, or other hormonal deficiencies [111, 112]. SIADH [10], hypophysitis [113], pituitary abscess [114], and pituitary apoplexy [115] have also been reported following acute SARS-CoV-2 infection. Central diabetes insipidus after COVID-19 is relatively rare and could be due to direct damage, IgG4-related hypophysitis (with growth hormone deficiency in a 4-year-old boy) [116] and lymphocytic infundibulo-neurohypophysitis (with positive anti-rabphilin-3A antibodies) [117] (Table 3).

Table 3.

Results of systematic and narrative reviews that covered studies about pituitary and COVID-19 listed in reverse order of year of publication between 2020 and 2026 by using standardized terms, such as “pituitary, hypopituitarism, hypophysitis, apoplexy” and “coronavirus, SARS-CoV-2, or COVID-19”

Author, journal (y)	No. of studies	Results
Sara Menotti. Pituitary (2024) systematic review [113]	7 reported cases of post–COVID-19 hypophysitis	Most patients developed symptoms 2-3 wk after infection. Headache, polyuria, and polydipsia were common. 85% had anterior and/or posterior hypopituitarism, MRI findings were variable, most were treated with glucocorticoids
Christina Hazzi. Ear Nose Throat J (2024) Case series and literature Review [118]	15 cases (3 cases + 12 published cases) of pituitary apoplexy	Possible association between COVID-19 and pituitary apoplexy. Coagulopathy, hemorrhage, or infarction of pituitary gland are explained mechanisms
Cristina Capatina. Best Pract Res Clin Endocrinol Metab (2023) narrative review [119]	6 reported cases of AVP deficiency	Hypopituitarism, pituitary apoplexy, hypophysitis, AVP deficiency (diabetes insipidus) and SIADH are reported following mainly severe SARS-CoV-2 infection, due to both acute and delayed effects on pituitary. Hypoxia, hypercoagulability, endothelial dysfunction, and autoimmune changes induced by COVID-19 infection may damage HPA axis. Hypophysitis or immune-mediated injury are possible mechanisms of AVP deficiency. Patients with acromegaly, Cushing disease, and hypopituitarism have higher risk of complications with COVID-19
Stefano Frara. Rev Endocr Metab Disord (2022) Narrative Review [120]	3 reported case outcomes of patients with known hypopituitarism and adrenal insufficiency	Hypopituitarism may increase risk of COVID-19 infection due to metabolic comorbidities (DM, obesity, and vertebral fractures). Acute SARS-CoV-2 infection may damage pituitary gland directly or indirectly. It may induce vascular events and lead to loss of pituitary function (hypopituitarism, pituitary apoplexy, adrenal insufficiency, hypogonadism, central DI)
Stefano Frara. Pituitary (2021) Narrative review [121]	6 pituitary apoplexy cases 6 hypopituitarism cases	Pituitary apoplexy (6 cases), hyponatremia due to SIADH (prevalence of hyponatremia 9.9%-51.7% in 6 studies), hypophysitis (no data following COVID-19), hypopituitarism (6 cases). Pituitary diseases (hypopituitarism and Cushing disease) or comorbidities such as diabetes may be a risk factor for severe COVID-19

Abbreviations: AVP, arginine vasopressin; DI, diabetes insipidus; DM, diabetes mellitus; HPA, hypothalamic-pituitary-adrenal; MRI, magnetic resonance imaging; SIADH, syndrome of inappropriate antidiuresis.

AI following COVID-19 is not uncommon, occurring in approximately 3.5% to 6.8% of patients with mild disease and 7% to 38.5% of patients with severe disease. It predominantly presents as central AI and is associated with disease severity [122-125]. Central AI is usually reversible [126]. However, primary AI is rare and may be caused by adrenal hemorrhage, adrenal infarction [127, 128], autoimmune adrenalitis, or unmasking Addison disease [129, 130]. It may be accompanied by other autoimmune diseases, such as thyroid disease [129, 131], vitiligo [131], or T1D [132]. It may unmask autoimmune polyendocrine syndrome type 2 [133]. It could be associated with antiphospholipid syndrome [127, 134]. The mechanisms of primary AI following COVID-19 include the direct effects of SARS-CoV-2, adrenalitis with immune infiltration, arteriolar necrosis within the adrenal parenchyma, lipid degeneration, and hemorrhage [135]. AI may increase the risks of COVID-19–related morbidity and mortality, as well as susceptibility to infection [124, 136-138]. This could be due not only to the direct and indirect effects of SARS-CoV-2 on pituitary and adrenal gland function but also to the effects of glucocorticoids on immune function, the challenges associated with managing AI during the pandemic, and variations in glucocorticoid dosing (Table 4).

Table 4.

Results of systematic reviews about adrenal disorders and COVID-19 listed in reverse order of year of publication between 2020 and 2026 by using standardized terms, such as “adrenal, adrenalitis, adrenal insufficiency” and “coronavirus, SARS-CoV-2, or COVID-19”

Author, journal (y)	No. of studies	Result
Alessia Cozzolino. Endocrine (2023) [139]	17 studies (7 studies on adrenal function, 5 studies in adrenal insufficiency, 5 studies in Cushing syndrome)	SARS-CoV-2 has adrenal tropism and may cause adrenal injury
Emre Durcan. Neuroimmunomodulation (2023) [140]	10 published studies (1085 cases) evaluating HPA axis function in COVID-19	COVID-19 may cause both primary and secondary adrenal insufficiency through direct viral, vascular, and immune-mediated mechanisms. Basal cortisol levels vary with disease severity, and diagnosis of adrenal insufficiency remains challenging because no consensus cortisol cutoff exists. Dynamic testing (particularly LDST) and repeated cortisol measurements may improve diagnostic accuracy. Patients with preexisting adrenal insufficiency require stress-dose glucocorticoids during COVID-19 illness
Yasir S Elhassan. Clin Endocrinol (Oxf) (2023) [128]	25 cases of COVID-19–related adrenal hemorrhage (19 bilateral; 13 infection-related, and 12 vaccine-related). 18 cases included in multicenter descriptive study (11 survey cases + 7 UK cases from systematic review)	Adrenal hemorrhage can occur following SARS-CoV-2 infection and vaccination. Infection-related cases showed higher mortality, whereas vaccine-related cases were commonly associated with immune thrombocytopenia or thrombosis and acute abdominal pain. Bilateral adrenal hemorrhage leads to adrenal insufficiency

Abbreviations: LDST, low dose synacthen test; UK, United Kingdom.

Current evidence highlights the effects of COVID-19 on gonadal function, sexual health, and fertility. COVID-19 has been associated with psychosocial stress, decreased libido, erectile dysfunction (ED), and alterations of the male reproductive system, especially in patients with long-COVID [141]. COVID-19 can increase the risk of ED, which could be a manifestation of long-COVID too. Endothelial dysfunction within the corpus cavernosum, injury to penile tissue, hypogonadism, psychosocial factors, and impaired pulmonary function are potential causes of ED [142-144]. SARS-CoV-2 may cause orchitis and reduce sperm count. It can damage Leydig cells thereby reducing testosterone production, impair Sertoli cells function thereby diminishing spermatogenesis, and induce systemic inflammation that results in endothelial dysfunction and thrombotic events [144, 145]. Hypogonadism may occur following COVID-19 but usually resolves over time [146]. This could be secondary to direct pituitary damage [125], suppression of the hypothalamic-pituitary-gonadal (HPG) axis following acute illness and inflammation, testicular damage [144], and impaired Leydig cell function or a reduction in the number of Leydig cells, as reflected by lower levels of the Leydig cell biomarker insulin-like peptide 3 [147].

Furthermore, the role of testosterone in promoting severe acute SARS-CoV-2 infection has not been fully elucidated. Increased COVID-19 mortality among men has been reported across different geographic areas. This raised a concern regarding the role of sex-related factors in the pathophysiology of SARS-CoV-2 infection. However, other contributing factors, such as behavior, occupation, comorbidities, socioeconomic status, and lifestyle, should be taken into account before emphasizing the role of testosterone in the progression of COVID-19 [148]. On the other hand, a meta-analysis of 18 studies reported that low total testosterone (TT) levels with normal luteinizing hormone (LH) levels were observed among patients with COVID-19 [149], suggesting that primary hypogonadism is unlikely to be the cause of low TT levels. In addition, antiandrogen medications did not significantly improve COVID-19 outcomes, and testosterone replacement therapy did not alter the incidence of COVID-19. Therefore, sex disparities in COVID-19 mortality are unlikely to be explained completely by sex-related factors and the hypothesis that acute SARS-CoV-2 infection impairs the HPG axis is more plausible [144, 150] (Table 5).

Although there are difficulties in diagnosing long-COVID, or post-COVID syndrome, because of symptom heterogeneity and multisystem involvement, a potential role for hypothalamic-pituitary axis dysfunction has been suggested. Consequently, assessing adrenal function with a low-dose adrenocorticotropin stimulation test, evaluating thyroid function and autoimmunity, and ruling out hypogonadotropic hypogonadism and growth hormone deficiency may be valuable [112, 154].

Endocrine complications of COVID-19 vaccination

Multiple COVID-19 vaccines with demonstrated efficacy and acceptable safety profiles have been developed and widely administered. Endocrine dysfunction reported following COVID-19 vaccination has mainly involved the thyroid gland, pancreas, pituitary gland, adrenal glands, and reproductive system. Several mechanisms have been proposed to explain these endocrine adverse events, including immune system hyperstimulation, autoimmune/inflammatory responses, and molecular mimicry, immune cross-reactivity, systemic inflammatory response, and transient cytokine release following vaccination [155].

The thyroid gland is the most reported endocrine organ affected following COVID-19 vaccination. Subacute thyroiditis has been reported most frequently (100 cases) [155], while Graves disease (64 cases), overt hypothyroidism (14 cases), and subclinical hypothyroidism (2 cases) were also observed [156].

Transient worsening of hyperglycemia has been reported in patients with both T1D and T2D following COVID-19 vaccination. Rarely, severe hyperglycemic emergencies, including DKA and hyperosmolar hyperglycemic state, have been reported [155].

Adrenal disorders, including adrenal hemorrhage and primary AI, have also been reported in isolated instances. Some reports of adrenal hemorrhage occurred in association with vaccine-induced immune thrombotic thrombocytopenia [156]. Pituitary diseases following COVID-19 vaccination include 23 reported cases, comprising hypophysitis (9 cases), pituitary apoplexy (6 cases), SIADH (5 cases), isolated adrenocorticotropin deficiency (2 cases), and pituitary tumor enlargement (1 case) [157].

Menstrual irregularities and disturbances have also been seen in women following COVID-19 vaccination, which not only cause discomfort but also raise concerns among women of reproductive age. The underlying mechanisms for menstrual irregularities following COVID-19 vaccination are complex. Alterations in the function of the endocrine and immune systems are widely recognized mechanisms [158]. However, the role of psychological stress, anxiety, and depression during the pandemic should not be ignored. Importantly, available evidence has not demonstrated a clinically meaningful adverse effect of COVID-19 vaccination on fertility in men and women [159-162]. Overall, the established benefits of COVID-19 vaccination in reducing severe COVID-19, hospitalization, and mortality substantially outweigh the risk of endocrine adverse events, which are rare and often transient. It is important for clinicians to recognize and evaluate endocrine abnormalities occurring after vaccination.

Conclusion

This review underscores the importance of careful evaluation of the endocrine system in COVID-19 patients, particularly in individuals with persistent long-COVID. Organs such as the pancreas, pituitary, thyroid, adrenal glands, gonads, and parathyroid glands are susceptible to direct invasion and indirect inflammatory responses associated with acute SARS-CoV-2 infection. Combining strong preventive measures with targeted therapeutic treatments is the most effective strategy to reduce both acute severity and the risk of long-COVID. Preventive strategies could be COVID-19 vaccines and practicing daily hygiene plans, and therapeutic approaches are applying medications that block virus entry into the host cell with antivirals. Finally, relying strictly on targeting the highly mutable viral spike protein has limitations. Therefore, to more effectively reduce SARS-CoV-2 entry into cells while simultaneously alleviating the damaging inflammatory responses, next-generation biomedical research is shifting toward dual-action therapies and host-directed strategies (see Fig. 1).

Abbreviations

ACE2

angiotensin-converting enzyme 2

ADAM17

A disintegrin and metalloproteinase domain-containing protein 17

AI

adrenal insufficiency

ALI

acute lung injury

BMD

bone mineral density

CT

computed tomography

DPP-4

dipeptidyl peptidase-4

ED

erectile dysfunction

FBG

fasting blood glucose

FPG

fasting plasma glucose

18F-FDG PET/CT

positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-D-glucose integrated with CT

GDM

gestational diabetes

HbA_1c

glycated hemoglobin A_1c

HPA

hypothalamic-pituitary-adrenal

HPG

hypothalamic-pituitary-gonadal

HPT

hypothalamic-pituitary-thyroid

IRR

incidence rate ratios

LH

luteinizing hormone

NTIS

nonthyroidal illness syndrome

OGTT

oral glucose tolerance test

OPG

osteoprotegerin

OR

odds ratio

PTH

parathyroid hormone

RAAS

renin-angiotensin-aldosterone system

RANKL

receptor activator of nuclear factor κ B ligand

RR

relative risk

RUNX2

runt-related transcription factor 2

SAT

subacute thyroiditis

SIADH

syndrome of inappropriate antidiuresis

SPECT

single-photon emission CT

T1D

type 1 diabetes

T2D

type 2 diabetes

TFT

thyroid function test

T3

3,5,3′-triiodothyronine

T4

thyroxine

TSH

thyrotropin

TMPRSS2

transmembrane protease serine 2

TT

total testosterone

Funding

There is no funding support for this project.

Author contributions

The authors reviewed the literature and wrote the manuscript.

Disclosures

The authors have declared that no conflict of interest exists.

Data availability

There are no other generated data for this project.