Network-based analyses of direct and indirect hypothyroidism multimorbidity associations found that thyroid cancer, larynx cancer, and hyperthyroidism — among others — have the strongest comorbidity connections with the disease. This is according to research published in the Journal of Clinical Endocrinology and Metabolism.

Investigators for a registry-based study conducted in Spain sought to construct a hypothyroidism comorbidity network among the general population in order to analyze both positive and negative associations with other prevalent, simultaneous chronic conditions.

The network analyses included 2 primary connective components: nodes, or chronic conditions, and edges, or coexistence of disease. Odds ratios (ORs) were calculated as the ratio between the odds of comorbidity in patients with hypothyroidism and the odds of comorbidity in patients with multimorbidity without hypothyroidism. Directional networks were also used to assess the temporal associations among diseases.

Overall, information for 3,135,948 adults with multimorbidity was extracted from the database; of those, 285,342 had hypothyroidism. After exclusion criteria were applied, the study population included 239,701 adults with hypothyroidism.


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Within undirected networks, investigators identified 31 nodes and 216 edges for hypothyroidism comorbidity. Across the global network, the average degree was 14; however, diseases in the hypothyroidism network were less connected, with an average degree of 7.

Several diseases were most strongly connected to hypothyroidism in directed network analyses. These included respiratory cancers (adjusted odds ratio [aOR], 2.48), congenital anomalies (aOR, 2.26), thyroid cancer (aOR, 2.13), hyperthyroidism (aOR, 1.66), and type 1 diabetes (aOR, 1.50). After adjusting for additional comorbidities, the association for some diseases was lost, indicating that these diseases were highly correlated with other conditions associated with hypothyroidism.

In sex-restricted analyses, the network for men was more populated than for women, with 20 nodes and 68 edges (vs 9 nodes and 14 edges). Minimally adjusted OR values indicated “more and stronger connections,” to mental health conditions like schizophrenia, obsessive compulsive disorder, and psychosis; cardiovascular conditions including tachycardia and heart failure; and neurologic conditions such as epilepsy and nervous system benign neoplasm.

Connections to thyroid cancer, multiple congenital anomaly, hyperthyroidism, larynx cancer, and goiter were also stronger in men compared with women.

Investigators were also able to assess which diseases were less frequently diagnosed when hypothyroidism was present. After adjustment, the strongest negative associations were for HIV (OR, 0.71) and tobacco abuse (OR, 0.77). Women had more complex networks for negative associations compared with men (9 nodes and 8 edges vs 4 nodes and 3 edges).

Study limitations include the use of electronic health records, an inability to rule out errors in diagnosis or disease coding, and the tendency of registry data to underestimate the prevalence of diseases.

Hypothyroidism…is frequently associated with other health problems,” the researchers concluded. “Comorbidities of hypothyroidism include most organ systems [and] comorbidity networks showed more and stronger connections in men. As most differences disappeared when we adjusted for other comorbidities, it suggested many of the interactions for men were indirect, due to their interrelationship with other chronic conditions.”

Reference

Moratalla-Navarro F, Moreno V, López-Simarro F, Aguado A. MorbiNet study. Hypothyroidism comorbidity networks in the adult general population. Published online December 15, 2020. J Clin Endocrinol Metab. doi: 10.1210/clinem/dgaa927