Lakhasly

Hypertension affects 26.4% of the global adult population remaining the leading preventable risk factor for premature death and disability worldwide (1, 2). Besides the majority of patients with primary (essential) hypertension, a subgroup of ~10% of patients is affected by secondary hypertension. Among the underlying diseases several are of endocrine origin and thyroidal impairments represent an even smaller percentage of the secondary hypertension cases; their incidence and form of presentation varies with age and studied population (3). Hypertension may be the initial clinical presentation for at least 15 endocrine disorders (4), including overt and subclinical hyperthyroidism and hypothyroidism. The correction of thyroid dysfunction may normalize blood pressure (BP) in most cases, therefore checking thyroid function is essential during the workup for hypertension.

Thyroid dysfunction, both hypo- and hyperthyroidism may increase the risk of hypertension (5, 6). Hypothyroidism should be considered as a graded phenomenon with a wide variety of clinical conditions from subclinical hypothyroidism to myxedema. Subclinical hypothyroidism is a combination of serum thyrotropin (TSH) above the upper reference limit and normal free thyroxine (fT4) and free triiodothyronine (fT3) levels (7). This definition is only applicable in the absence of other acute or chronic recent or ongoing severe illness, assuming a stable thyroid function weeks or more before the evaluation and a normally functioning hypothalamic-pituitary-thyroid axis. Overt hypothyroidism is characterized by an elevated TSH, usually above 10 mIU/L, in combination with reduced circulating fT4 and fT3 levels.

While the most common cause of hypothyroidism had been environmental iodine deficiency for centuries, the situation has changed and the population became iodine sufficient or only mildly deficient. Since then, the leading causes of hypothyroidism are chronic autoimmune thyroid diseases (AITDs). Hashimoto's thyroiditis is 5–10 times more common in women than in men, characterized by an increased prevalence with age (8, 9). In AITDs the thyroid gland is infiltrated by sensitized T lymphocytes, while circulating thyroid autoantibodies can be detected as a consequence of presumably inherited defect in immune surveillance. Furthermore, hypothyroidism may occur as a consequence of radioiodine or surgical treatment for hyperthyroidism, benign nodular thyroid disease or thyroid cancer, and after external beam radiation for head and neck malignancies. Pharmacological treatment, in most of the cases administration of the iodine-containing antiarrhythmic agent amiodarone, lithium, or immune response modulators, such as interferon alfa can result in the development of thyroiditis and thyroid dysfunction; relatively new iatrogenic causes of hypothyroidism are tyrosine kinase inhibitors and PD-1 inhibitors, sunitinib, and nivolumab, respectively. Sunitinib induces hypothyroidism via reduction of glandular vascularization and induction of type 3 deiodinase enzyme (9, 10). The mechanism by which nivolumab impairs the thyroid function is not entirely understood; the explanation might be a reduction in the immune tolerance to normal thyroid tissue antigens (11). Central causes of hypothyroidism are acquired or congenital of origin; pituitary or hypothalamic tumors (including craniopharyngiomas), inflammatory (lymphocytic or granulomatous hypophysitis) or infiltrative diseases, hemorrhagic necrosis (Sheehan's syndrome), or surgical and radiation treatment for pituitary or hypothalamic disease can stay in the background of insufficient production of bioactive TSH (9).

The reported prevalence rate of overt hypothyroidism is between 0.2 and 5.3% in Europe and 0.3–3.7% in the United States, most probably due to the differences in iodine intake (12). The incidence of subclinical hypothyroidism was found to be 7.5% in the Wickham study (13), while in the Colorado study 21% among women and 16% in men, respectively (14). The levels of circulating TSH and antithyroid autoantibodies increase with advancing age; according to the NHANES III data TSH levels above 4.5 mIU/L are present in 14% of the population aged 85 and above (8).

The most common causes of hyperthyroidism are autoimmune Graves' disease and multinodular goiter. Iatrogenic hyperthyroidism can be a consequence of iodine exposure during administration of iodine-containing drugs among which far the most important is amiodarone, or excess of levothyroxine replacement therapy. Immune response modulator therapy of cancers can lead to hypo- and less frequently hyperthyroidism (15). Subacute thyroiditis is a less frequent cause of hyperthyroidism. Iatrogenic subclinical hyperthyroidism is the declared aim of T4 therapy, and is a relatively frequent condition among patients with differentiated thyroid cancer after near-total thyroidectomy. Further, a few weeks of iatrogenic overt hypothyroidism is an alternative to recombinant TSH administration before radioiodine treatment and during follow-up, in accordance with international guidelines.

The prevalence of thyrotoxicosis among women is between 0.5 and 2%, a 10-fold female predominance is present. Subclinical hyperthyroidism is a condition of mild thyroid hormone excess defined by a serum TSH concentration below the lower reference limit and normal serum fT4 and fT3 concentrations. The same biochemical pattern may describe hypothalamic or pituitary disease, non-thyroidal illness, or the pharmacologic effect of TSH secretion inhibiting drugs. The prevalence of subclinical hyperthyroidism ranges from 0.5 to 6.3%, with the highest established prevalence in individuals over 65 years; approximately half of the affected patients are on levothyroxine substitution (16).

Other relatively common thyroid diseases as multinodular goiter with euthyroidism and differentiated thyroid cancer have sparse impact on the cardiovascular system, and especially, the development of hypertension; however, a recently published meta-analysis found that hypertension significantly increases the risk of development of thyroid cancer (17).