Hypothyroidism | Clinical Medicine

Hypothyroidism is characterized by low thyroid hormone levels, divided into primary (thyroid gland problem) and secondary (pituitary or hypothalamus problem). Primary hypothyroidism involves reduced production of T3 (triiodothyronine) and T4 (thyroxine). This can result from the destruction of thyroid follicular cells or insufficient iodine intake, which is the most common worldwide cause. When thyroid hormone levels are low, the hypothalamus increases TRH and the pituitary increases TSH. This is diagnostically important, as primary hypothyroidism presents with low T3/T4 and high TSH.

Primary hypothyroidism due to thyroid destruction can be autoimmune, infectious, or iatrogenic. Autoimmune causes include autoantibodies attacking thyroglobulin or thyroid peroxidase (TPO). Hashimoto's thyroiditis is the most common cause in the United States, characterized by anti-thyroglobulin antibodies and anti-TPO antibodies, leading to permanent hypothyroidism, often linked to HLA-DR3 or HLA-DR4 mutations. Postpartum thyroiditis involves anti-TPO antibodies triggered by pregnancy and is typically transient, resolving within a year. Ridel's thyroiditis is part of IgG4 systemic diseases, causing fibrosis of the thyroid gland, which can lead to hypothyroidism in about 30% of cases. It can also cause compression of nearby structures like the recurrent laryngeal nerve (leading to hoarseness), trachea (dyspnea, stridor), and esophagus (dysphagia).

Infectious thyroiditis, such as De Quervain's thyroiditis, is triggered by a viral upper respiratory tract infection, causing direct injury and destruction of thyroid follicular tissue. It presents with a painful thyroid, goiter, URTI symptoms, and an elevated ESR, and is also transient. Iatrogenic causes include thyroidectomy, which obviously leads to a lack of thyroid hormone. The Wolff-Chaikoff effect is another interesting iatrogenic cause, where excessively high iodine levels (e.g., from amiodarone or radioiodine therapy) paradoxically inhibit the thyroid peroxidase enzyme, preventing thyroid hormone synthesis.

Secondary hypothyroidism results from dysfunction of the hypothalamus or pituitary. If the hypothalamus cannot produce TRH or the pituitary cannot produce TSH, then the thyroid gland will not be stimulated to produce T3/T4. This results in both low TSH and low T3/T4 levels, a key diagnostic difference from primary hypothyroidism. Causes include pituitary macro-adenomas which can cause mass effects like headaches and bitemporal hemianopia by compressing the optic chiasm. Another cause is Sheehan's syndrome, a postpartum hemorrhage leading to severe hypovolemia, reduced blood pressure, poor pituitary perfusion, and subsequent necrosis of pituitary tissue, leading to a loss of multiple hormones including TSH.

Hypothyroidism presents with multi-system involvement due to widespread effects of thyroid hormone. Common findings include a goiter (enlargement of the thyroid gland), which can be painful (e.g., De Quervain's) or painless (e.g., Hashimoto's, iodine deficiency). Metabolic dysfunction manifests as weight gain due to reduced catabolism of fats and glycogen, and cold intolerance due to decreased heat production from inhibited sodium-potassium pumps. Hypothyroidism can also stimulate ADH production, leading to water reabsorption and hyponatremia. Central nervous system effects include lethargy, fatigue, depression, and delayed deep tendon reflexes (DTRs).

Cardiovascular effects include decreased beta-1 receptor sensitivity, leading to bradycardia and increased vasoconstriction, potentially causing diastolic hypertension. Reduced LDL receptor expression in the liver can lead to hyperlipidemia. Reproductive dysfunction can manifest as menstrual irregularities, infertility, and reduced libido due to altered prolactin, estrogen, and progesterone levels. Gastrointestinal issues include decreased GI motility, resulting in constipation. Integumentary system changes, particularly in primary hypothyroidism with elevated TSH, involve fibroblasts releasing glycosaminoglycans (GAGs) that retain water. This causes non-pitting edema like pre-tibial myxedema, periorbital edema, and carpal tunnel syndrome. Patients also experience dry skin, brittle hair/nails, and hair loss.

Myxedema coma is a life-threatening complication of chronic hypothyroidism intensified by a severe metabolic stressor (e.g., infection, surgery, hypothermia, non-compliance with levothyroxine). This excessive stress on a body unable to produce adequate thyroid hormone leads to a profound metabolic shutdown. Clinical features include severe hypothermia (body temperature <35°C), significant bradycardia, acute heart failure due to drastically reduced cardiac output and increased systemic vascular resistance, and severe hypoactive encephalopathy ranging from confusion to obtundation and coma. Myxedema (often pre-tibial) combined with these severe symptoms indicates a myxedema coma.

Diagnosis begins with thyroid function tests (TFTs), measuring TSH and T4. Low TSH and low T4 suggest secondary hypothyroidism, warranting a pituitary MRI to look for adenomas or infarction. In these cases, reverse T3 is not high, differentiating it from euthyroid sick syndrome (critically ill patients with low TSH, T4, T3 but high reverse T3). High TSH and low T4 indicate primary hypothyroidism. For primary hypothyroidism, check anti-TPO and anti-thyroglobulin antibodies (positive in Hashimoto's or postpartum thyroiditis). Other causes are identified through patient history (e.g., recent birth, viral URTI, painful goiter with elevated ESR, features of IgG4-related diseases, amiodarone/lithium use, thyroidectomy, radioiodine ablation, iodine deficiency). Subclinical hypothyroidism is characterized by high TSH and normal T4, usually treated when TSH is significantly elevated (e.g., >20). Treatment for hypothyroidism is primarily levothyroxine (Synthroid) to replace missing thyroid hormone, with dosage adjusted based on TSH levels. Myxedema coma requires urgent treatment with IV T4 and T3, warming measures, and often IV hydrocortisone until adrenal insufficiency is ruled out.